PubMed · 12491998
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R Gamundi. 1999. Protease sparing regimens.. https://pubmed.ncbi.nlm.nih.gov/12491998/
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Based on experimental work and clinical small studies, histidine-tryptophan-ketoglutarate (HTK) solution was found to be suitable not only for heart and kidney preservation but also for liver preservation. We decided, therefore, to use this preservation solution for clinical liver preservation in a prospective multi-centre trial. Enrolment to the study was from 1996 to 1999 in four European centres, and the results of 214 patients with HTK-preserved organs were analysed. Analysis showed a primary dysfunction (PDF) rate of 8.8%, with a primary non-function (PNF) rate of 2.3% and initial poor function (IPF) in 6.5%. Patient survival rate at 1 year was 83% and 1-year graft survival rate was 80%. In a univariate and a multivariate analysis PDF, early surgical complications and tendentiously severe infections (septicaemia, pneumonia, cholangitis) were identified as independent risk factors for graft and patient survival. Preservation with HTK can be regarded as an established alternative to preservation with University of Wisconsin (UW) solution when preservation times are short. Definitive assessment of the efficacy of preservation solutions requires further prospective randomised clinical trials that compare HTK and UW.
PURPOSE: To compare the clinical efficacy of leukotriene receptor antagonists with that of placebo, antihistamines, and nasal corticosteroids in patients with allergic rhinitis or nasal polyposis. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials of the effectiveness of leukotriene receptor antagonists in patients with rhinitis. Composite daily rhinitis symptom scores (as a percentage of the maximum score) and rhinitis-specific quality of life (unit scores ranging from 0 to 6) were pooled after assessing heterogeneity among studies. The pooled estimates were expressed as weighted mean differences between treatments in a random-effects model. We considered a difference of 10% in nasal score and 0.6 units in quality-of-life score to be clinically relevant. RESULTS: Of the 196 citations, 11 studies on seasonal allergic rhinitis were used in the analysis: eight evaluating leukotriene receptor antagonists alone or in combination with other treatments versus placebo or other treatments (n = 3924) and three evaluating leukotriene receptor antagonists plus an antihistamine (n = 80). Leukotriene receptor antagonists reduced mean daily rhinitis symptom scores (in absolute terms) 5% (95% confidence interval [CI]: 3% to 7%) more than did placebo. However, antihistamines improved the nasal symptoms score 2% (95% CI: 0% to 4%) more than did leukotriene receptor antagonists, and nasal corticosteroids improved the score 12% (95% CI: 5% to 18%) more than did leukotriene antagonists. Leukotriene receptor antagonists significantly improved rhinoconjunctivitis quality of life by 0.3 units (95% CI: 0.24 to 0.36 units) when compared with placebo. There were no randomized controlled trials evaluating the effect of leukotriene receptor antagonists on perennial allergic rhinitis or polyposis. CONCLUSION: Leukotriene receptor antagonists are modestly better than placebo, as effective as antihistamines, but less effective than nasal corticosteroids in improving symptoms and quality of life in patients with seasonal allergic rhinitis.
The therapeutic response among patients infected with hepatitis C virus (HCV) of genotype 1 remains suboptimal. We examined a large database of patients treated with combination therapy (ribavirin plus an interferon [IFN]). We hypothesized that the longer the duration that the virus load was rendered undetectable in serum, the better would be the probability of a sustained viral response (SVR). A model predicting SVR was generated; it included the following covariates: duration of continuous nondetectability of an HCV load in serum, estimated creatinine clearance, and whether the isolate was of genotype 1. The validation model demonstrated positive and negative predictive values as well as sensitivity and specificity exceeding 90%. The model predicted that patients infected with HCV genotype 1 require continuous nondetectability of virus load in serum for 36 and 32 weeks, to attain 90% and 80% probabilities, respectively, of a SVR. The average time to clear serum of genotype-1 virus was 30.4 weeks, which indicates that the 48-week duration of therapy provided a suboptimal probability of a SVR. For some patients, suboptimal therapy with pegylated IFN plus ribavirin may need to be of longer duration than the currently recommended 48 weeks. This hypothesis requires prospective validation.