The road to educational excellence is via instruc tional excellence, says this writer, who believes that to achieve it, teachers must design potent teaching strategies, evaluation techniques that consider stu dent welfare, and methods for positive reinforce ment.
Introduction: There is a crucial, universal need for non-interferon (IFN)-based therapy for chronic genotype 1 hepatitis C virus (HCV). To date, there is limited data on the use of an all-oral treatment regimen in the “real world” clinical setting, especially in patients with advanced fibrosis. Methods: Seventy-seven patients with chronic genotype 1 HCV were treated using an “off-label” combination of sofosbuvir, simeprevir, +/- ribavirin for 12 weeks. We collected data on patient demographics, viral response, laboratory values, and adverse events. The decision to treat patients for recurrent HCV was made by 1 of 6 transplant hepatologists. Patients were monitored with monthly clinic visits and lab testing every 2-4 weeks during treatment. Results: Of the seventy-seven patients, 46 (60%) were genotype 1a, 22 (29%) were genotype 1b, and 9 (11%) were undifferentiated. There were 49 males (64%). There were 46 Caucasians (60%) and 27 African Americans (35%), and 4 “Other” (5%). The average age was 58 years (range 28-73). Sixty-six patients (86%) had stage 3 or 4 fibrosis. Forty-seven patients (61%) were treatment-experienced and 27% were IFN-intolerant. Twenty-three patients (30%) were treated with ribavirin; all but one had ribavirin added at treatment initiation. Thirty-eight patients (49%) had a high viral load (defined as >800,000 IU/mL). Fourteen patients (18%) were decompensated by ascites or hepatocellular carcinoma and 5 (6%) were waitlisted for liver transplant (LT). Thirty-eight patients (49%) had a BMI >30, with 17% having a BMI >35. Forty-nine patients (89%) achieved an undetectable viral load by week 4 of therapy; of which 29% had an undetectable viral load by week 2 of treatment. To date, 36 patients (65%) have an undetectable viral load at the end of treatment. There were no serious adverse events reported and no patients have discontinued therapy to date. The most common side effects were fatigue, headache, and nausea. Hyperbilirubinemia, when present, was mild. Conclusion: Treatment of chronic genotype 1 HCV with an “off-label” combination of an all-oral regimen (simeprevir, sofosbuvir, +/- ribavirin) appears to be safe and well-tolerated in a cohort of patients with advanced fibrosis, significant obesity, high viral load, and previous treatment failure. While treatment was very effective in rendering patients viral load undetectable, with 90% of patients achieving a rapid virologic response (RVR), 12-week sustained virologic response (SVR-12) data is eagerly awaited and will be reported when available.
As part of an audit of clinical practice in an orthopaedic unit for elective surgery, a study was made of the causes of cancellation of operations. Despite careful liaison with general practitioners, and a booked admission policy, over 6% of patients were cancelled as unsuitable. The results of this study suggest that the number of cancellations on medical grounds would be reduced by closer liaison with general practitioners, and the establishment of preadmission clinics. Ensuring that only consultants book patients for surgery would also reduce the number of cancellations due to incorrect indications for surgery.
Transplanting blood group A, B, or O (ABO)-incompatible (ABO-I) liver grafts has resulted in lower patient and graft survival with an increased incidence of vascular and biliary complications and rejection. We report that, without modification of our standard immunosuppression protocol, crossing blood groups is an acceptable option for children requiring liver transplantation. In our study, ABO-I liver grafts -- regardless of recipient age -- have comparable long-term survival (mean follow-up of 3.25 yr) with ABO-compatible grafts without any difference in rejection, vascular or biliary complications. From January 1, 1999 to October 1, 2005, we studied 138 liver transplants in 121 children: 16 (13.2%) received an ABO incompatible liver allograft. One-year actuarial patient survival for ABO-matched grafts vs. ABO-I grafts was 93.0% and 100%, respectively, whereas graft survival was 83.4% and 92.3%. Additionally, 6 of 16 (37.5%) ABO-I transplanted children had 8 rejection episodes, whereas 47 patients (44.8%) had 121 rejection episodes in the ABO-compatible group. There were no vascular complications and 2 biliary strictures in the ABO-I group. Plasmapheresis was not used for pretransplantation desensitization and was only required in 1 posttransplantation recipient. No child was splenectomized. Six of the 16 children were older than 13 yr of age, suggesting the possibility of successfully expanding this technique to an older population. In conclusion, our outcomes may support the concept of using ABO-I grafts in a more elective setting associated with split and living donor liver transplants.
Objectives: The combination of simeprevir (SMV) and sofosbuvir (SOF) was found to be well-tolerated with high sustained virologic response (SVR) rates in patients with genotype 1 chronic hepatitis C in clinical trials. Previous experience with hepatitis C virus (HCV) therapy has shown that patient tolerability and treatment efficacy described in controlled clinical trials did not necessarily mirror the “real world” experience. The goal of this study was to define SVR rates in a “real world” analysis and to explore predictors of treatment response with SMV and SOF. Methods: This is a retrospective study examining the “real world” treatment of 170 patients with chronic HCV genotype 1 using the combination of SMV and SOF with or without ribavirin (RBV) for a fixed 12-week duration irrespective of prior interferon therapy, transplant status or fibrosis stage. Differences between SVR cohorts were analyzed by both intention-to-treat (ITT) and per protocol. Results: The vast majority of patients were genotype 1a, 77% were cirrhotic in the non-LT group, and 35% of the entire cohort was African-American. Combination treatment with SMV and SOF in genotype 1 chronic HCV patients achieved an overall SVR rate at 12 weeks after completion of therapy (SVR12) of 78% by ITT and 86% by per protocol (84% in non-liver transplant (LT) patients and 89% in post-LT recipients). The presence of hepatocellular carcinoma was found to be a significant negative predictor of SVR12, whereas an undetectable week eight VL was a significant positive predictor of SVR in the entire cohort. Conclusions: Our data confirm excellent SVR outcomes with favorable safety and tolerability profiles in patients who carry many traditional high-risk features for non-response, including post-LT recipients and patients with advanced liver disease.
