Two major histocompatibility complex haplotypes influence susceptibility to sporadic inclusion body myositis: Critical evaluation of an association with HLA-DR3

Previous studies of sporadic inclusion body myositis (sIBM) have shown a strong association with HLA-DR3 and other components of the 8.1 ancestral haplotype (AH) (HLA-A1, B8, DR3), where the susceptibility locus has been mapped to the central major histocompatibility complex (MHC) region between HLA-DR and C4. Here, the association with HLA-DR3 and other genes in the central MHC and class II region was further investigated in a group of 42 sIBM patients and in an ethnically similar control group (n = 214), using single-nucleotide polymorphisms and microsatellite screening. HLA-DR3 (marking DRB1*0301 in Caucasians) was associated with sIBM (Fisher's test). However, among HLA-DR3-positive patients and controls, carriage of HLA-DR3 without microsatellite and single-nucleotide polymorphism alleles of the 8.1AH (HLA-A1, B8, DRB3*0101, DRB1*0301, DQB1*0201) was marginally less common in patients. Patients showed no increase in carriage of the 18.2AH (HLA-A30, B18, DRB3*0202, DRB1*0301, DQB1*0201) or HLA-DR3 without the central MHC of the 8.1AH, further arguing against HLA-DRB1 as the direct cause of susceptibility. Genes between HLA-DRB1 and HOX12 require further investigation. BTL-II lies in this region and is expressed in muscle. Carriage of allele 2 (exon 6) was more common in patients. BTL-II(E6)*2 is characteristic of the 35.2AH (HLA-A3, B35, DRB1*01) in Caucasians and HLA-DR1, BTL-II(E6)*2, HOX12*2, RAGE*2 was carried by several patients. The 8.1AH and 35.2AH may confer susceptibility to sIBM independently or share a critical allele

Patient-Controlled Analgesia Versus Conventional Intramuscular Injection: A Cost Effectiveness Analysis

Background. In previous studies comparing patient-controlled-analgesia and intramuscular pain management have been unable to provide conclusive evidence of the benefits of either method of postoperative pain control. Aim. The purpose of the study was to compare the efficacy and cost-effectiveness of intravenous patient-controlled-analgesia with intermittent intramuscular morphine for Chinese women in the first 24 hours following elective gynaecological surgery. Methods. A randomized control design was used. The main outcomes were level of pain and cost for the two types of pain management. Participants indicated their level of pain at rest and when deep breathing or coughing on a 100 mm Visual Analogue Scale, on seven occasions within 24 postoperative hours. Costs for the two types of pain management were based on the costs of equipment, drugs and nursing time. Results. A total of 125 women participated in the study. Mean pain level over the 24 hours in the patient-controlled-analgesia group was significantly lower than in the intramuscular group (P < 0•001). Mean pain level over the seven occasions for the patient-controlled-analgesia group was 11•83 points (95% CI 7•1416•52) lower when at rest and 11•73 points (95% CI 5•9617•50) lower during motion than the intramuscular group. Cost per patient was $81•10 (Hong Kong) higher for patient-controlled-analgesia than for intramuscular pain management. Women in the patient-controlled-analgesia group had significantly greater satisfaction with pain management than those in the intramuscular group (P < 0•001), but reported significantly more episodes of nausea (P < 0•05). Conclusions. While patient-controlled-analgesia was more costly, it was also more effective than conventional on-demand intramuscular opioid injections after laparotomy for gynaecological surgery