Hepatitis C virus (HCV) diminishes health related quality of life (HRQOL), and it is now common to measure HRQOL in clinical trials. We sought to summarize the HRQOL data in HCV, and to establish the minimally clinically important difference (MCID) in HRQOL scores in HCV. We performed a systematic review to identify relevant studies, and converted HRQOL data from each study into clinically interpretable statistics. An expert panel used a modified Delphi technique to estimate the MCID in HCV. We found that patients with HCV scored lower than controls across all scales of the SF-36. Patients achieving sustained virological response (SVR) scored higher across all scales versus patients without SVR, especially in the physical health domains. HRQOL differences did not correspond with differences in liver histology or ALT levels. Based upon the published data, the expert panel C hronic hepatitis C virus (HCV) infection is a prevalent and expensive condition affecting 4 million people in the United States at a cost of over $700 million annually. 1 HCV leads to cirrhosis in up to 20% of those chronically infected 2 and is the primary indication for liver transplantation worldwide. 3 This economic burden is multiplied by the dramatic impact of HCV on health related quality of life (HRQOL) resulting from complications of advanced liver disease such as encephalopathy, variceal hemorrhage, ascites, and liver transplantation. 4-6 However, these end-stage complications are relatively rare compared with the vast majority of patients with HCV in the absence of clinically significant liver disease. Despite the previous consensus that this majority of patients has asymptomatic seropositivity, 7 evolving data now indicate that HCV itself may diminish HRQOL in the absence of advanced liver disease, [8][9][10][11][12][13][14][15][16][17][18][19][20] perhaps as a result of extrahepatic symptoms related to HCV, cognitive dysfunction related to HCV, or a negative synergy between HCV and comorbid psychosocial disorders. 10,21 As awareness grows of the HRQOL decrement from HCV and its clinical consequences, investigators have be- From the
Background— Previous studies have associated reduced hemoglobin levels with increased adverse events in heart failure. It is unclear, however, whether this relation is explained by underlying kidney disease, treatment differences, or associated comorbidity. Methods and Results— We examined the associations between hemoglobin level, kidney function, and risks of death and hospitalization in persons with chronic heart failure between 1996 and 2002 within a large, integrated, healthcare delivery system in northern California. Longitudinal outpatient hemoglobin and creatinine levels and clinical and treatment characteristics were obtained from health plan records. Glomerular filtration rate (GFR; mL · min −1 · 1.73 m −2 ) was estimated from the Modification of Diet in Renal Disease equation. Mortality data were obtained from state death files; heart failure admissions were identified by primary discharge diagnoses. Among 59 772 adults with heart failure, the mean age was 72 years and 46% were women. Compared with that for hemoglobin levels of 13.0 to 13.9 g/dL, the multivariable-adjusted risk of death increased with lower hemoglobin levels: an adjusted hazard ratio (HR) of 1.16 and 95% confidence interval (CI) of 1.11 to 1.21 for hemoglobin levels of 12.0 to 12.9 g/dL; HR, 1.50 and 95% CI, 1.44 to 1.57 for 11.0 to 11.9 g/dL; HR, 1.89 and 95% CI, 1.80 to 1.98 for 10.0 to 10.9; HR, 2.31 and 95% CI, 2.18 to 2.45 for 9.0 to 9.9; and HR, 3.48 and 95% CI, 3.25 to 3.73 for <9.0 g/dL. Hemoglobin levels ≥17.0 g/dL were associated with an increased risk of death (adjusted HR, 1.42; 95% CI, 1.24 to 1.63). Compared with those with a GFR ≥60 mL · min −1 · 1.73 m −2 , persons with a GFR <45 mL · min −1 · 1.73 m −2 had an increased mortality risk: adjusted HR, 1.39 and 95% CI, 1.34 to 1.44 for 30 to 44; HR, 2.28 and 95% CI, 2.19 to 2.39 for 15 to 29; HR, 3.26 and 95% CI, 3.05 to 3.49 for <15; and HR, 2.44 and 95% CI, 2.28 to 2.61 for those on dialysis. Relations were similar for the risk of hospitalization. The findings did not differ among patients with preserved or reduced systolic function, and hemoglobin level was an independent predictor of outcomes at all levels of kidney function. Conclusions— Very high (≥17 g/dL) or reduced (<13 g/dL) hemoglobin levels and chronic kidney disease independently predict substantially increased risks of death and hospitalization in heart failure, regardless of the level of systolic function. Randomized trials are needed to evaluate whether raising hemoglobin levels can improve outcomes in chronic heart failure.
Objective. To determine the potential for additive or synergistic effects of combination therapy with the selective anti-tumor necrosis factor ␣ agent etanercept and the anti-interleukin-1 agent anakinra.Methods. Two hundred forty-four patients in whom rheumatoid arthritis (RA) was active despite methotrexate therapy were treated with subcutaneous etanercept only (25 mg twice weekly), full-dosage etanercept (25 mg twice weekly) plus anakinra (100 mg/day), or half-dosage etanercept (25 mg once weekly) plus anakinra (100 mg/day) for 6 months in a double-blind study at 41 centers in the US. Patients had never previously received anticytokine therapy. Patient response was measured with the American College of Rheumatology (ACR) core set criteria, a health-related quality-of-life questionnaire, and the Disease Activity Score. Safety was assessed by the number of adverse events and clinical laboratory values. Plasma concentrations of both agents and antibody formation against both agents were also assessed.Results. Combination therapy with etanercept plus anakinra provided no treatment benefit over etanercept alone, regardless of the regimen, but was associated with an increased safety risk. Thirty-one percent of the patients treated with full-dosage etanercept plus anakinra achieved an ACR 50% response, compared with 41% of the patients treated with etanercept only. This result was not statistically significant (P ؍ 0.914). The incidence of serious infections (0% for etanercept alone, 3.7-7.4% for combination therapy), injection-site reactions, and neutropenia was increased with combination therapy. Combination therapy had no effect on the pharmacokinetics or immunogenicity of either agent.Conclusion. Combination therapy with etanercept and anakinra provides no added benefit and an increased risk compared with etanercept alone and is not recommended for the treatment of patients with RA.
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