A review of the efficacy, safety, and cost-effectiveness of COX-2 inhibitors for Africa and the Middle East region.

Despite an increasingly sophisticated understanding of pain mechanisms, acute and chronic pain remain undertreated throughout the world. This situation reflects the large gap that exists between evidence and practice in pain management and is typified by inappropriate use of nonsteroidal anti-inflammatory drugs (NSAIDs). The scientific evidence around these drugs continues to expand at a high rate, yet physicians are often unaware of best practice. To address this gap among physicians in Africa and the Middle East, an Expert Panel meeting was convened with representatives from the region. The principal objective of the meeting was to review the latest guidelines on the management of acute and chronic pain and to review the efficacy, safety, and cost-effectiveness of cyclooxygenase-2 (COX-2) inhibitors in these settings. The main outcome of this review process was a number of consensus statements concerning the definitions of acute and chronic pain, and the efficacy, safety and cost-effectiveness of traditional nonselective NSAIDs (nsNSAIDs) and selective COX-2 inhibitors (coxibs). The panel agreed that nsNSAIDs and coxibs are effective analgesics with similar efficacy for acute pain; for chronic musculoskeletal pain, NSAIDs are significantly more effective than either placebo or paracetamol. Coxibs offer important safety advantages over nsNSAIDs, including gastrointestinal safety and preservation of platelet function; notably, the cardiovascular safety of coxibs has been the subject of much recent debate. Furthermore, the panel agreed there is substantial evidence to indicate that cost savings can be achieved by using celecoxib in patients at moderate to high risk of gastrointestinal adverse events, even in countries with moderate healthcare expenditures.

Association and frequency of HLA-A, B and HLA-DR genes in south Tunisian patients with spondyloarthritis (SpA).

The aim of this study is to investigate the association of HLA-A, B and HLA-DR gene expression and to assess an association of additional HLA antigens besides HLA-B27 in south Tunisian patients with spondyloarthritis (SpA). Eighty-five patients diagnosed with ankylosing spondylitis (AS, n=68) and reactive arthrithis (ReA, n=17) were selected and compared with 100 healthy controls (HC). HLA class I antigens were typed serologically using microlymphocytotoxicity technique. HLA-DRB1* alleles were studied by polymerase chain reaction amplification with sequence-specific primers. The significance of differences between patients and controls was tested by chi-square analysis. We found significantly increased frequencies of HLA-A3 (30.6%; pC=0.04; OR=2.95), HLA-B27 (62.35%; pC=4.10(-17), OR=53.55), and HLA-DRB1*15 (17.2%; pC=0.026; RR=2.58) alleles in SpA patients compared to HC. The most frequent and strongest association was observed for HLA-B27 in AS (pC=6.6 ×10(-16), OR=52.23). When AS and ReA patients were analysed separately, HLA-DRB1*15 and HLA-A3 were increased only in AS (pC=0.01, OR=2.99 and pC=0.03, OR=3.14, respectively). In ReA patients, HLA-DRB1*04 (p=0.033, pC=NS, OR=2.89) was found to be the most common allele. By analysing the HLA-B27-negative subgroup, HLA-A3 and HLA-DRB1*15 expression was found to be dependent on the presence of HLA-B27. HLA-B27 expression was higher in male (45/53; 85%) as compared to female (8/53; 15%) patients (p=0.03). Apart from HLA-B27, HLA-A3 and HLA-DRB1*15 are the MHC class I and II alleles found most frequent in Tunisian patients with AS, whereas HLA-DRB1*04 was found most frequent in ReA patients. HLA-B27 is more frequent in male than in female patients.

Broad-range PCR, cloning and sequencing of the full 16S rRNA gene for detection of bacterial DNA in synovial fluid samples of Tunisian patients with reactive and undifferentiated arthritis.

INTRODUCTION: Broad-range rDNA PCR provides an alternative, cultivation-independent approach for identifying bacterial DNA in reactive and other form of arthritis. The aim of this study was to use broad-range rDNA PCR targeting the 16S rRNA gene in patients with reactive and other forms of arthritis and to screen for the presence of DNA from any given bacterial species in synovial fluid (SF) samples. METHODS: We examined the SF samples from a total of 27 patients consisting of patients with reactive arthritis (ReA) (n = 5), undifferentiated arthritis (UA) (n = 9), rheumatoid arthritis (n = 7), and osteoarthritis (n = 6) of which the latter two were used as controls. Using broad-range bacterial PCR amplifying a 1400 bp fragment from the 16S rRNA gene, we identified and sequenced at least 24 clones from each SF sample. To identify the corresponding bacteria, DNA sequences were compared to the EMBL (European Molecular Biology Laboratory) database. RESULTS: Bacterial DNA was identified in 20 of the 27 SF samples (74, 10%). Analysis of a large number of sequences revealed the presence of DNA from more than one single bacterial species in the SF of all patients studied. The nearly complete sequences of the 1400 bp were obtained for most of the detected species. DNA of bacterial species including Shigella species, Escherichia species, and other coli-form bacteria as well as opportunistic pathogens such as Stenotrophomonas maltophilia and Achromobacter xylosoxidans were shared in all arthritis patients. Among pathogens described to trigger ReA, DNA from Shigella sonnei was found in ReA and UA patients. We also detected DNA from rarely occurring human pathogens such as Aranicola species and Pantoea ananatis. We also found DNA from bacteria so far not described in human infections such as Bacillus niacini, Paenibacillus humicus, Diaphorobacter species and uncultured bacterium genera incertae sedis OP10. CONCLUSIONS: Broad-range PCR followed by cloning and sequencing the entire 16S rDNA, allowed the identification of the bacterial DNA environment in the SF samples of arthritic patients. We found a wide spectrum of bacteria including those known to be involved in ReA and others not previously associated with arthritis.

Distribution of HLA-B27 and its alleles in patients with reactive arthritis and with ankylosing spondylitis in Tunisia.

The purpose of the present study is to investigate the frequency of HLA-B27 and its alleles in reactive arthritis (ReA) and in ankylosing spondylitis (AS) in Tunisia. HLA-B27 alleles were typed by PCR amplification with sequence-specific primers. We studied 17 patients with ReA associated with urethritis or with gastrointestinal infection; 42 HLA-B27-positive patients with AS and 100 healthy controls. Eleven ReA patients (67.7%) were HLA-B27 positive. There was an increased frequencies of HLA-B27 (P = 7.76 x 10(-12), OR = 59.30) and a moderate increase of HLA-B51 (P = 0.015; OR = 4.91) alleles in ReA patients when compared with healthy controls. Four B27 subtypes were identified: B*2702, 05, 09 and B*2712. The distribution of these alleles in the ReA patients was 37.5% for B*2702 and B*2705. Only these two subtypes were detected in 18 (42.8%) and 24 (57.1%), respectively, of the AS patients. B*2709 and B*2712 were relatively rare in ReA patients and were identified in one case each. Our results showed a restricted number of HLA-B27 subtypes associated with ReA and AS. B*2702 and 2705 were common in ReA and AS patients.

Detection and frequency of Chlamydia trachomatis DNA in synovial samples from Tunisian patients with reactive arthritis and undifferentiated oligoarthritis.

We aimed to determine the frequency of Chlamydia trachomatis DNA in the synovial compartment of 34 arthritic patients. Chlamydia trachomatis DNA was detected using a nested PCR targeting the cryptic plasmid, the 16S rRNA gene and the outer membrane protein 1 gene. The presence of serum immunoglobulin (Ig)G and IgA antibodies against C. trachomatis was studied by a microimmunofluorescence assay and by an enzyme-linked immunosorbent assay, respectively. Synovial samples from 20 of 34 (59%) patients [nine with reactive arthritis (ReA), seven with undifferentiated oligoarthritis (UOA), two with rheumatoid arthritis and two with osteoarthritis] were positive for at least one C. trachomatis DNA sequence by nested PCR. The high sensitivity results most likely from the combination of a standardized automated MagNA Pure extraction method, PCR targeting three different C. trachomatis genes and the screening for C. trachomatis in synovial tissue and fluid samples. There was no correlation between the presence of C. trachomatis DNA in the joint and a Chlamydia-specific serologic response. Our data support that PCR is the method of choice to establish the diagnosis of Chlamydia-induced arthritis in patients with ReA. We suggest that this diagnosis might also be considered in C. trachomatis-positive patients previously classified as UOA.

Analysis of bacterial DNA in synovial tissue of Tunisian patients with reactive and undifferentiated arthritis by broad-range PCR, cloning and sequencing.

INTRODUCTION: Bacteria and/or their antigens have been implicated in the pathogenesis of reactive arthritis (ReA). Several studies have reported the presence of bacterial antigens and nucleic acids of bacteria other than those specified by diagnostic criteria for ReA in joint specimens from patients with ReA and various arthritides. The present study was conducted to detect any bacterial DNA and identify bacterial species that are present in the synovial tissue of Tunisian patients with reactive arthritis and undifferentiated arthritis (UA) using PCR, cloning and sequencing. METHODS: We examined synovial tissue samples from 28 patients: six patients with ReA and nine with UA, and a control group consisting of seven patients with rheumatoid arthritis and six with osteoarthritis (OA). Using broad-range bacterial PCR producing a 1,400-base-pair fragment from the 16S rRNA gene, at least 24 clones were sequenced for each synovial tissue sample. To identify the corresponding bacteria, DNA sequences were compared with sequences from the EMBL (European Molecular Biology Laboratory) database. RESULTS: Bacterial DNA was detected in 75% of the 28 synovial tissue samples. DNA from 68 various bacterial species were found in ReA and UA samples, whereas DNA from 12 bacteria were detected in control group samples. Most of the bacterial DNAs detected were from skin or intestinal bacteria. DNA from bacteria known to trigger ReA, such as Shigella flexneri and Shigella sonnei, were detected in ReA and UA samples of synovial tissue and not in control samples. DNA from various bacterial species detected in this study have not previously been found in synovial samples. CONCLUSION: This study is the first to use broad-range PCR targeting the full 16S rRNA gene for detection of bacterial DNA in synovial tissue. We detected DNA from a wide spectrum of bacterial species, including those known to be involved in ReA and others not previously associated with ReA or related arthritis. The pathogenic significance of some of these intrasynovial bacterial DNAs remains unclear.