Investigation of a multi-biomarker disease activity score in rheumatoid arthritis by comparison with magnetic resonance imaging, computed tomography, ultrasonography, and radiography parameters of inflammation and damage.

OBJECTIVES: To investigate the multi-biomarker disease activity (MBDA) score by comparison with imaging findings in an investigator-initiated rheumatoid arthritis (RA) trial (HURRAH trial, NCT00696059). METHOD: Fifty-two patients with established RA initiated adalimumab treatment and had magnetic resonance imaging (MRI), ultrasonography (US), computed tomography (CT), and radiography performed at weeks 0, 26, and 52. Serum samples were analysed using MBDA score assays and associations between clinical measures, MBDA score, and imaging findings were investigated. RESULTS: The MBDA score correlated significantly with MRI synovitis (rho = 0.65, p < 0.001), MRI bone marrow oedema (rho = 0.36, p = 0.044), and US power Doppler (PD) score at week 26 (rho = 0.35, p = 0.039) but not at week 0 or week 52. In the 15 patients who had achieved a Disease Activity Score based on C-reactive protein (DAS28-CRP) < 2.6 at week 26, MRI and/or US detected subclinical inflammation and 13 (87%) had a moderate/high MBDA score. For the cohort with available data, none of the four patients in MBDA remission (score ≤ 25) at week 26 had progression of imaging damage from baseline to week 52 whereas progression was observed in three out of nine (33%) and seven out of 21 (33%) patients with moderate (30-44) and high (> 44) MBDA scores, respectively. CONCLUSIONS: In this cohort, the MBDA score correlated poorly with MRI/US inflammation. However, the MBDA score and MRI/US were generally concordant in showing signs of inflammation in most patients in clinical remission during anti-tumour necrosis factor (anti-TNF) therapy. MBDA scores were elevated in all patients with structural damage progression.

Pattern of bone erosion and bone proliferation in psoriatic arthritis hands: a high-resolution computed tomography and radiography follow-up study during adalimumab therapy.

OBJECTIVES: To investigate the pattern and development of bone erosion and proliferation in patients with psoriatic arthritis (PsA) during treatment with adalimumab, using high-resolution computed tomography (CT) and conventional radiography. METHOD: Forty-one biologic-naïve PsA patients were initiated with adalimumab 40 mg subcutaneously every other week. CT and radiography of the 2nd-5th metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints were conducted at baseline (n = 41) and after 24 weeks (n = 32). Changes in bone erosion and proliferation are described and the imaging modalities compared. RESULTS: Ninety percent of bone erosions detected by CT were located in the metacarpal heads, and most frequently in the 2nd-3rd MCP joints. Radial (37%) and ulnar (31%) surfaces were more frequently eroded than dorsal (10%) and palmar (22%) sites. Using CT, bone proliferations were located primarily on the sides of the distal part of the DIP joints (43% of all proliferations), but also proximally in DIP (17%) and MCP joints (27%). For bone erosions and proliferations, respectively, radiography showed a low sensitivity (17% and 26%), but a high specificity (98% and 95%) and accuracy (93% and 87%), with CT as the gold standard reference. Neither CT nor radiography revealed statistically significant changes in bone erosion or proliferation scores between baseline and follow-up. CONCLUSIONS: Patterns of bone erosion and proliferation in PsA hands were revealed in more detail by CT than by radiography. No overall progression or repair could be detected during adalimumab treatment with either of the methods.

Erosive progression is minimal, but erosion healing rare, in patients with rheumatoid arthritis treated with adalimumab. A 1 year investigator-initiated follow-up study using high-resolution computed tomography as the primary outcome measure.

OBJECTIVE: With computed tomography (CT) and radiography, to investigate if repair of bone erosions, defined as regression of erosion scores, occurs during adalimumab treatment of patients with rheumatoid arthritis (RA). METHODS: Fifty-two patients with RA, naïve to biological agents, with at least two low-grade radiographic erosions in the wrist or metacarpophalangeal (MCP) joints in the same (index) hand, initiated adalimumab 40 mg subcutaneously every other week. Thirty-five patients completed the study (median age 61 years (interquartile range 46-68), disease duration 8 years (3-15)). CT of the index wrist and MCP joints 2-5 and radiographs of hands and forefeet were obtained at baseline, 6 and 12 months. Images were evaluated by investigators blinded to chronology and clinical data, and assessed according to Sharp/van der Heijde (radiographs) and OMERACT RA MRI scoring (CT) methods. RESULTS: Disease activity score, C-reactive protein, tender and swollen joints count and Health Assessment Questionnaire score had all decreased at 6 and 12 months (wilcoxon signed-ranks test p<0.001). No significant change in any imaging parameters of joint destruction was observed at 6 and 12 months. High intrareader agreements were reached (mean intraobserver intraclass coefficients: 0.96 (CT) and 0.97 (radiography)). The number of patients with change scores exceeding the smallest detectable change (SDC) was comparable on CT and radiography, as were the proportions of patients progressing/regressing. Decreased erosion scores at 12 months were registered in 1.6% and 1.8% of sites assessed on CT and radiography, respectively. CONCLUSION: Repair of erosions in adalimumab-treated patients with RA is rare, but erosive regression, exceeding the SDC, on CT and radiography occurred. The very limited overall erosive progression supports the view that joint destruction is minimal during adalimumab treatment of patients with RA.

Susceptibility of upper-genital tract isolates from women with pelvic inflammatory disease to ampicillin, cefpodoxime, metronidazole, and doxycycline.

The antibiotics that are recommended for treatment of pelvic inflammatory disease (PID) in the outpatient setting are efficacious against Neisseria gonorrhoeae and Chlamydia trachomatis. The susceptibility of non-sexually transmitted pathogens to these agents has not been well studied. The mean inhibitory concentrations of ampicillin, cefpodoxime, metronidazole, and doxycycline were determined for 137 upper-genital tract isolates from 84 women with confirmed PID. Antibiotic resistance was noted in 16%, 9%, 93%, and 72% of the facultative and 0%, 11%, 10%, and 56% of the anaerobic bacteria when tested against ampicillin, cefpodoxime, metronidazole, and doxycycline, respectively. The authors conclude that doxycycline is limited to coverage of Chlamydia and that a single dose of another antibiotic may not be adequate to eradicate the non-sexually transmitted disease pathogens from the upper-genital tract. Additional clinical and microbiologic studies are needed to determine whether the current outpatient antibiotic regimens provide optimal coverage for the non-sexually transmitted pathogens that are associated with PID.

Introduction of the new Centers for Disease Control and Prevention group B streptococcal prevention guideline at a large West Coast health maintenance organization.

OBJECTIVE: Our purpose was to assess the impact of new consensus guidelines issued by the Centers for Disease Control and Prevention, The American College of Obstetricians and Gynecologists, and the American Academy of Pediatrics to prevent perinatal group B streptococcal disease. STUDY DESIGN: We performed a descriptive analysis and a before-and-after analysis of implementation of the group B streptococcal disease prevention guidelines among singleton-birth pregnancies in 2 Group Health Cooperative hospitals from October 1, 1995, through December 31, 1997. We studied the speed and completeness of implementation and the effect on pregnancy care practices including intrapartum antibiotic use, test ordering, and maternal and neonatal health. RESULTS: Guideline implementation occurred rapidly. The proportion of term pregnancies screened according to the guideline increased markedly, and overall intrapartum antibiotic use more than doubled. Among group B streptococci-positive women, intrapartum antibiotic prophylaxis increased from 24% before to 74% after guideline implementation. Median duration of treatment before delivery increased from 1.8 to 4.3 hours. The rate of rash did not increase, and there were no cases of anaphylaxis or pseudomembranous colitis. The proportion of infants undergoing evaluation decreased after implementation of the neonatal guidelines; among infants of group B streptococci-negative women, test ordering dropped by almost 40%. CONCLUSIONS: Implementation of the new guidelines is feasible and can be accomplished rapidly. The guidelines were associated with increased maternal intrapartum antibiotic use, particularly among women at highest risk, and with a decrease in laboratory use for infants.

Role of bacterial vaginosis-associated microorganisms in endometritis.

OBJECTIVE: Our goal was to define the role of bacterial vaginosis and bacterial vaginosis-associated microorganisms in endometritis. STUDY DESIGN: Endometrial biopsies were obtained for histologic and microbiologic study from 178 consecutive women with suspected pelvic inflammatory disease, and 85 of them underwent laparoscopy to diagnose salpingitis. RESULTS: Histologic endometritis was confirmed in 117 (65%) of the women. Among women who underwent laparoscopy, salpingitis was present in 68% of those with and 23% of those without endometritis. Some but not all bacterial vaginosis-associated microorganisms were linked with endometritis. By logistic regression analysis, after adjustment for bacterial vaginosis and isolation of Neisseria gonorrhoeae and Chlamydia trachomatis, endometritis was associated with endometrial N. gonorrhoeae (odds ratio 5.7, 95% confidence interval 1.8 to 17.5), C. trachomatis (odds ratio 4.8, 95% confidence interval 1.3 to 18.2), anaerobic gram-negative rods (odds ratio 2.6, 95% confidence interval 1.1 to 5.7), and nonwhite race (odds ratio 2.3, 95% confidence interval 1.1 to 4.8). CONCLUSIONS: The association of anaerobic gram-negative rods with endometritis, after adjustment for bacterial vaginosis, N. gonorrhoeae, and C. trachomatis, supports the role of these microorganisms in the etiology of histologic endometritis among women with clinically suspected pelvic inflammatory disease.