Rates of serious infections, opportunistic infections, inflammatory bowel disease, and malignancies in subjects receiving etanercept vs. controls from clinical trials in ankylosing spondylitis: a pooled analysis.

OBJECTIVES: Therapies involving anti-tumour necrosis factor are associated with increased risk of serious infections, opportunistic infections, and some types of malignancies in subjects with rheumatic diseases. However, limited data have been collected for subjects with ankylosing spondylitis (AS). The aim of this retrospective analysis of all sponsor-conducted trials was to examine the rates of serious infections, inflammatory bowel disease (IBD), malignancies, and non-malignant skin cancers during treatment in subjects with AS. METHOD: Data from five randomized controlled trials (one sulfasalazine-controlled, four placebo-controlled) and four open-label studies evaluating etanercept were pooled for analyses. All randomized subjects who received at least one dose of treatment were included in the study. RESULTS: Analyses included 1323 subjects (> 1500 subject-years of treatment). Rate ratios of serious infections and IBD events for etanercept vs. placebo/sulfasalazine during the double-blind studies were 2.19 [95% confidence interval (CI) 0.22-107.79] and 1.09 (95% CI 0.06-64.56), respectively. There were no reports of opportunistic infections. Using the Surveillance, Epidemiology and End Results database, the standardized incidence ratio for malignancies was 1.47 (95% CI 0.54-3.21). CONCLUSIONS: These data suggest that etanercept is well tolerated in subjects with AS. Despite the large number of patients, the 95% CI data all cross 1.0, limiting possible conclusions. No new safety signals were observed.

Sustained efficacy and safety, including patient-reported outcomes, with etanercept treatment over 5 years in patients with ankylosing spondylitis.

OBJECTIVES: To assess long-term safety and clinical efficacy of etanercept 25 mg subcutaneously twice weekly up to 5 years in subjects with ankylosing spondylitis (AS). METHODS: An open-label (OL), multicentre, phase 4, 156-week extension study of subjects with AS who had completed a 12-week randomised, placebo-controlled study (N=84; n=45 etanercept, n=39 placebo) followed by a 96-week OL study (n=81; n=42 etanercept/etanercept; n=39 placebo/etanercept); 59 subjects who completed the 96-week OL extension enrolled in the current OL trial and continued etanercept 25 mg BIW for an additional 156 weeks (total duration: 264 weeks, original etanercept group; 252 weeks, original placebo group). Safety was based on spontaneous reports of adverse events (AEs). Last observation carried forward was used for imputation of missing values. RESULTS: Thirty-seven of 59 subjects (63%) completed 5 years of etanercept treatment. Serious non infectious AEs and serious infections occurred at a rate of 0.17 and 0.03 events per subject years, respectively; inflammatory bowel disease and uveitis (including iritis and iridiocyclitis) occurred at 0.01 and 0.14, respectively. No cases of tuberculosis or opportunistic infections were reported. Assessment in Ankylosing Spondylitis (ASAS) responses and improvements in Bath Ankylosing Spondylitis Functional Index and spinal mobility were sustained from week 108 through week 264. CONCLUSIONS: Etanercept was well tolerated with no new safety signals detected in subjects with AS over 5 years. Clinical efficacy and improvements in function and mobility seen during the double-blind and first OL study were sustained. These results support etanercept therapy for the long-term management of this chronic disease.

Physician office laboratory education and training in primary care residency programs.

OBJECTIVE: To assess the status of office laboratory residency education and training in family practice, internal medicine, obstetrics and gynecology, and pediatric residency programs. DESIGN: A single mailed survey to 1299 residency programs from December 1992 to February 1993. PARTICIPANTS: Primary care residency directors from 507 (39%) of 1299 programs. INTERVENTIONS: A 27-item survey of residency-based office laboratory practices, education, training, and resources. MAIN OUTCOME MEASURES: Differences between specialties in provision and quantity of office laboratory education and training, presence of a residency-based office laboratory, laboratory classification under the Clinical Laboratory Improvement Amendments, and available laboratory tests. RESULTS: Of those responding, office laboratories were present in 89% of family practice, 19% of internal medicine, 29% of obstetrics and gynecology, and 24% of pediatrics residency programs. Laboratory training was available at 60% of family practice, 16% of internal medicine, 15% of obstetrics and gynecology, and 30% of pediatrics programs. The median number of hours of formal skills training was 10 hours for family practice residency programs but less than 2 hours for the other specialties. Only 25% of the programs reported educational assistance from pathologists. Merely 4% of the programs had postassessment examinations and 2% awarded certificates of achievement. A majority of family practice programs performed waivered tests and physician-performed microscopy tests, but moderately complex tests were performed in less than 50% of family practice programs. CONCLUSIONS: Family practice residency programs provide more office laboratory training for residents than other specialties. There is a need for improved residency training in the basics of office laboratory practice.

Laboratory planning and design.

The design of the laboratory should fit the institution or setting in such a manner that it is sensitive to the needs of those who work on it and who are served by it. At the same time, the design should provide for future flexibility and growth consistent with the anticipated needs of those who use its facilities. Although it is not possible to adequately cover in this article all the possibilities in laboratory planning and design, it is hoped that a little of the basic process of laboratory design can be conveyed to the reader, with encouragement to read further.