Randomized Controlled Trial of Tacrolimus Versus Microemulsified Cyclosporin (TMC) in Liver Transplantation: Poststudy Surveillance to 3 Years

The 1-year results of the tacrolimus versus microemulsified cyclosporin (TMC) study found a benefit with tacrolimus immunosuppression after primary liver transplants in adults with respect to freedom from graft loss and immunological failure. The integrity of the randomization process was preserved for a further 2 years for poststudy surveillance. The data after 3 years confirms the significant difference between tacrolimus and cyclosporin with tacrolimus less likely to meet the composite primary endpoint (log rank p = 0.01; relative risk 0.75; 95% CI 0.60-0.95; p = 0.016). However, freedom from death or retransplantation no longer achieves statistical significance (relative risk 0.79; 95% CI 0.62-1.02; p = 0.065). A total of 62.1% of patients randomized to tacrolimus were alive at 3 years with their original graft and still on their allocated study medication, as compared with only 41.6% in the cyclosporin limb (p < 0.001). No difference was detected between tacrolimus and cyclosporin in hepatitis-C-positive patients with the available data. The TMC study confirms after 3 years of follow-up the benefits of tacrolimus-based immunosuppression over cyclosporin using C(0) monitoring.     

Support for a tax increase to provide unrestricted access to an Alzheimer's disease medication: a survey of the general public in Canada

Background  

Public drug insurance plans provide limited reimbursement for Alzheimer's disease (AD) medications in many jurisdictions, including Canada and the United Kingdom. This study was conducted to assess Canadians' level of support for an increase in annual personal income taxes to fund a public program of unrestricted access to AD medications.     

A simplified prognostic scoring system for peptic ulcer perforation in developing countries.

BACKGROUND: Several complex prognostic scoring systems are available for abdominal sepsis. We constructed and assessed a simplified scoring system for peptic perforation, which can be easily used in developing countries. METHODS: One hundred and forty consecutive patients with perforated pre-pyloric or duodenal ulcer undergoing Graham's patch omentopexy closure were studied prospectively. Each factor was given a score based on its severity in accordance with the APACHE-II scoring system to construct the simplified prognostic (Jabalpur) scoring system, and multiple regression analysis was used to identify risk factors. This system was prospectively validated in the next 50 consecutive patients and compared to existing systems. RESULTS: The factors associated with mortality were age, presence of co-morbid illness, perforation-to-operation interval, preoperative shock, heart rate, and serum creatinine. The mean score in survivors (4.9) was less than that in those who died (12.5; p<0.0001). This scoring system compared favorably with other scoring systems. CONCLUSIONS: The Jabalpur scoring system is effective for prognostication in cases of peptic perforation. It is simple and user-friendly as it uses only six routinely documented clinical risk factors.     

Immunopathogenesis of hepatitis C virus infection

The interplay of viral characteristics and the host’s immunologic defense is responsible for the viral persistence and pathogenesis seen in chronic hepatitis C infection. The polyclonal and multispecific CD4 T-helper response seen in patients with chronic hepatitis C lacks the vigor and epitope specificity, compared with acutely infected patients. Although a dominant explanation for the weak antiviral response still eludes us, some potential explanations have been immunologic tolerance, not so favorable type 2 cytokine profile, and rapid replication rate. The emergence of cytotoxic T-lymphocyte escape variants, the consequence or the explanation for the high viral mutation rates, in addition to virally induced immune suppression, may be yet another explanation. However, the role of immune response in controlling viral replication disease pathogenesis, including autoimmune phenomenon, has been clearly demonstrated. Further research is required to increase our understanding of the various host and viral factors in viral persistence in order to develop successful vaccines.