Efficient practices associated with diagnosis, treatment and management of fibromyalgia among primary care physicians.

OBJECTIVES: To describe beliefs and practice patterns of primary care physicians (PCPs) providing fibromyalgia (FM) care, and to characterize differences between PCPs who report being able to provide timely and beneficial care versus the remaining PCPs. METHODS: A mixed-methods approach including surveys followed by semi-structured focus groups among United States-based PCPs in seven cities was used. Post hoc, a composite threshold of timely and beneficial care, defined as PCPs reports of at least one-half of their patients achieving an 'acceptable' quality of life within one to four office visits after diagnosis, was created to compare subgroups. RESULTS: Forty-six per cent of PCPs reported some uncertainty when diagnosing FM. PCPs reported personally treating approximately two-thirds of their patients (63%), and reported an average of three dosage titrations. In a post hoc exploratory analysis, 42.5% of PCPs met a composite threshold of self-reported timely and beneficial FM care. These PCPs reported fewer office visits to confirm an FM diagnosis (2.7 versus 4.0 visits [P<0.01]) and more patients with 'significant improvement' (38% versus 23% [P<0.01]) after six months of treatment compared with the remaining PCPs. CONCLUSIONS: Physicians self-reported an inadequacy in diagnosing, treating and managing patients with FM in current practice. A subset of PCPs, however, perceived an ability to reach a definitive diagnosis and initiate treatment plans relatively sooner than the other respondents. If the perception of this subset can be confirmed with objective clinical outcomes, and these behaviours modelled, steps could be taken to improve FM care within the broader PCP setting.

A multicenter pilot study to estimate the prevalence of bovine and human coagulation antibodies in the general US population.

Antibodies to bovine and human coagulation proteins have been reported to develop in some patients receiving perioperative exposure to topical bovine thrombin. To estimate the prevalence of antihuman and antibovine thrombin and factor V antibodies in the general population, this multicenter pilot study in 278 participants was undertaken. Of the participants, 88% had no detectable antibodies by enzyme-linked immunosorbent assay (ELISA). Cumulatively 22 (7.9%) of 278 of the participants were positive for at least 1 of the antibovine antibodies and only 11 (4%) of 278 were positive for human thrombin antibodies. No participants had antihuman factor V/Va antibodies. Antibodies were found in 21% of participants with no history of surgery, transfusion, or pregnancy. In participants without a surgical history, thus a low likelihood of bovine thrombin exposure, 7.9% (9 of 114) had antibovine antibodies and 3.5% (4 of 114) had human antithrombin antibodies, suggesting that antibodies may arise from contact with antigenic sources other than bovine-derived thrombin.

Exogenous bovine thrombin as a biomarker of exposure and outcome.

Bovine thrombin has been used for more than 60 years as a surgical hemostat and sealant. Rare postsurgical events have been attributed to antibovine thrombin immunoglobulins cross-reacting with human homologs. In a literature review of 37 papers reporting safety outcomes in surgical patients, we extracted each paper for a quantitative measurement of bovine thrombin exposure and coagulopathic outcomes. We found that 59.5% of papers documented the commercial source of bovine thrombin and only 19% provided an estimate of exposure in units. Conventional tests for hypocoagulation were common (86%); however, only 9% of papers confirmed this inhibition as an isolated antibody. In addition, only 9% of papers cited a specific biomarker for thrombosis.

Efficacy and safety of erythropoiesis-stimulating proteins in myelodysplastic syndrome: a systematic review and meta-analysis.

OBJECTIVE: The objective was to assess the efficacy and safety of erythropoiesis-stimulating proteins (ESPs) in anemia of myelodysplastic syndrome (MDS). METHOD: A systematic review and meta-analysis was conducted covering English-language studies published from 1980 to December 2005. RESULTS: Fifty-nine studies qualified: five controlled trials (n = 354), all epoetin versus control (EvC); 51 epoetin single-arm studies (n = 1,650); and three darbepoetin single-arm studies (n = 102). In the EvC studies, epoetin patients demonstrated a significant advantage over controls in terms of hemoglobin (Hb) response (odds ratio, 5.2; 95% confidence interval, 2.5-10.8). Hb response was 48.1% in single-arm darbepoetin studies, 32.1% in epoetin single-arm studies, and 27.3% in EvC studies. Major Hb response averaged 38.8% in darbepoetin studies, 24.5% in epoetin single-arm studies, and 11.4% in EvC studies. Stratified analyses suggest that lower baseline erythropoietin levels, longer treatment durations, and concurrent iron may be associated with greater Hb response to ESPs. None of the analyzable predictors of Hb response (gender, baseline Hb, ESP type, and ESP duration) were significant in meta-regression analyses. In the few studies with quality-of-life measures, ESP groups attained a pre-post change (Functional Assessment of Cancer Therapy - Fatigue) that exceeded minimum clinically important differences. Selected adverse event rates did not differ between the epoetin and darbepoetin groups. CONCLUSION: Published studies suggest that ESPs are efficacious in anemia of MDS. Hb response appears higher in darbepoetin patients than in epoetin patients, and safety appears comparable, but darbepoetin data are sparse, and there are as yet no direct comparison studies.

Synthesis and structure-activity relationships of soluble 7-substituted 3-(3,5-dimethoxyphenyl)-1,6-naphthyridin-2-amines and related ureas as dual inhibitors of the fibroblast growth factor receptor-1 and vascular endothelial growth factor receptor-2 tyrosine kinases.

7-Substituted 3-aryl-1,6-naphthyridine-2,7-diamines and related 2-ureas are inhibitors of fibroblast growth factor receptor-1 (FGFR-1) and vascular endothelial growth factor receptor-2 (VEGFR-2). 3-(3,5-Dimethoxyphenyl) and 3-phenyl analogues were prepared from 7-acetamido-2-tert-butylureas by alkylation with benzyl omega-iodoalkyl ethers, debenzylation, and amination, followed by selective cleavage of the 7-N-acetamide. 3-(2,6-Dichlorophenyl) analogues were prepared from the 7-fluoro-2-amine by displacement with substituted alkylamines, followed by selective acylation of the resulting substituted naphthyridine-2,7-diamines with alkyl isocyanates. The 3-(3,5-dimethoxyphenyl) derivatives were low nanomolar inhibitors of both FGFR and VEGFR and were highly selective (>100-fold) over PDGFR and c-Src. Variations in the base strength or spatial position of the 7-side chain base had only small effects on the potency (<5-fold) or selectivity (<20-fold). The 3-(2,6-dichlorophenyl)-2-urea derivatives were slightly less active against VEGFR and less selective, being more effective against PDGFR (ca. 10-fold) and c-Src (ca. 500-fold). The 3-(3,5-dimethoxyphenyl)-1,6-naphthyridines were generally more potent than the corresponding pyrido[2,3-d]pyrimidines against both VEGFR and FGFR (2- to 20-fold), with only slightly increased PDGFR and c-Src activity. The 3-(3,5-dimethoxyphenyl)-1,6-naphthyridine 2-ureas were also low nanomolar inhibitors of the growth of human umbilical vein endothelial cells (HUVECs) stimulated by serum, FGF, or VEGF, at concentrations that did not affect the growth of representative tumor cell lines, and were more (3- to 65-fold) potent than the corresponding pyrido[2,3-d]pyrimidines.