Death certificates may lack accuracy and misclassify the cause of death. The validity of proxy-reported cause of death is not well established. The authors examined death records on 336 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study, a national cohort study of 30,239 community-dwelling US adults (2003-2010). Trained experts used study data, medical records, death certificates, and proxy reports to adjudicate causes of death. The authors computed agreement on cause of death from the death certificate, proxy, and adjudication, as well as sensitivity and specificity for certain diseases. Adjudicated cause of death had a higher rate of agreement with proxy reports (73%; Cohen's kappa (κ) statistic = 0.69) than with death certificates (61%; κ = 0.54). The agreement between proxy reports and adjudicators was better than agreement with death certificates for all disease-specific causes of death. Using the adjudicator assessments as the "gold standard," for disease-specific causes of death, proxy reports had similar or higher specificity and higher sensitivity (sensitivity = 50%-89%) than death certificates (sensitivity = 31%-81%). Proxy reports may be more concordant with adjudicated causes of death than with the causes of death listed on death certificates. In many settings, proxy reports may represent a better strategy for determining cause of death than reliance on death certificates.

No abstract

Health-related quality of life (HRQOL) is an important measure of the effects of chronic liver disease in affected patients that helps guide interventions to improve well-being. However, the relationship between HRQOL and survival in liver transplant candidates remains unclear. We examined whether the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores from the Short Form 36 (SF-36) Health Survey were associated with survival in liver transplant candidates. We administered the SF-36 questionnaire (version 2.0) to patients in the Pulmonary Vascular Complications of Liver Disease study, a multicenter prospective cohort of patients evaluated for liver transplantation in 7 academic centers in the United States between 2003 and 2006. Cox proportional hazards models were used with death as the primary outcome and adjustment for liver transplantation as a time-varying covariate. The mean age of the 252 participants was 54 6 10 years, 64% were male, and 94% were white. During the 422 person years of follow-up, 147 patients (58%) were listed, 75 patients (30%) underwent transplantation, 49 patients (19%) died, and 3 patients were lost to follow-up. Lower baseline PCS scores were associated with an increased mortality rate despite adjustments for age, gender, Model for End-Stage Liver Disease score, and liver transplantation (P for the trend ¼ 0.0001). The MCS score was not associated with mortality (P for the trend ¼ 0.53). In conclusion, PCS significantly predicts survival in liver transplant candidates, and interventions directed toward improving the physical status may be helpful in improving outcomes in liver transplant candidates. Liver Transpl 16:238-245,

Hepatopulmonary syndrome (HPS) results when chronic liver disease or portal hypertension causes intrapulmonary microvascular dilatation with hypoxemia. In experimental HPS, tumor necrosis factor alpha (TNF-␣) overproduction contributes to vasodilatation, which is improved by pentoxifylline, a TNF-␣ inhibitor. The effectiveness of pentoxifylline in humans is unknown. The aim of this open-label, single-arm clinical trial was to assess the efficacy and tolerability of pentoxifylline in patients with cirrhosis and advanced HPS undergoing liver transplantation evaluation. Nine adults with cirrhosis and moderate to severe HPS were enrolled. All patients had an initial 2-week titration to a target dose of pentoxifylline of 400 mg by mouth every 8 hours, which was continued for 6 weeks. Baseline and follow-up arterial blood gases and TNF-␣ levels were evaluated. Adverse effects and tolerability were assessed. The 9 patients had a mean age of 55 Ϯ 10 years, and 67% were female. The most common causes of cirrhosis were hepatitis C virus and alcohol (55%). The mean Model for End-Stage Liver Disease score was 11 (range, 6-19), and patients had advanced hypoxemia [mean partial pressure of arterial oxygen (PaO 2 ) ϭ 54 Ϯ 12 mm Hg, mean alveolar-arterial oxygen gradient (A-a PaO 2 ) ϭ 57 Ϯ 15 mm Hg]. Of the 9 patients enrolled, follow-up blood gases were done in 7. There was no significant change in PaO 2 (P ϭ 0.3) or A-a PaO 2 (P ϭ 0.3) with treatment. Pentoxifylline was poorly tolerated. Nausea (100%) and vomiting (56%) were the predominant side effects, and only a single patient was able to complete full-dose therapy. Treatment with pentoxifylline did not improve arterial oxygenation in advanced HPS, and tolerance was limited by gastrointestinal toxicity. Liver Transpl 14: [1199][1200][1201][1202][1203] 2008 Hepatopulmonary syndrome (HPS) results from intrapulmonary microvascular dilatation that impairs arterial oxygenation in the setting of cirrhosis or portal hypertension. 1 As many as 10%-20% of patients with cirrhosis being evaluated for orthotopic liver transplantation (OLT) have advanced HPS, 2 and mortality is greater in those with HPS than in those without HPS. 3 Currently, OLT is the only effective treatment, although postoperative mortality in HPS is increased with respect to patients with cirrhosis without HPS, with a 1-year survival of 68% to 80%. 4 Therefore, effective medical therapy for advanced HPS could improve both preoperative and postoperative mortality.Recent work in experimental models of HPS has revealed that both nitric oxide synthase-derived nitric oxide and heme oxygenase-derived carbon monoxide cause intrapulmonary vasodilatation. These alterations appear to be driven in part by tumor necrosis factor alpha (TNF-␣) modulation of pulmonary blood flow and intravascular monocyte accumulation. 5-7 PentoxifyllineAbbreviations: A-a PaO 2 , alveolar-arterial oxygen gradient; ALT, alanine aminotransferase; AST, aspartate aminotransferase; HCV, hepatitis C virus; HPS, hepatopulmonary syndrome; INR, internat...

HPS patients have a significant decline in SpO(2) over time compared to non-HPS patients, and therefore, pulse oximetry may be useful for monitoring cirrhotics for development or worsening of HPS. Presence of intrapulmonary vasodilation in the absence of hypoxemia does not appear to affect SpO(2) over time.