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Abstracts from Around the World
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2009;7:712–713
ABSTRACTS FROM AROUND THE WORLD Visit CGH online at www.cghjournal.org to link to these articles and additional articles of interest.
Proton Pump Inhibitors Do Not Help Control Asthma The American Lung Association Asthma Clinical Research Centers. Efficacy of esomeprazole for treatment of poorly controlled asthma. N Engl J Med 2009;360:1487–1499.
Summary. A link between gastroesophageal reflux (GER) and asthma has long been considered, and investigation for GER and/or empiric use of proton pump inhibitors for severe asthmatics with reflux symptoms is often undertaken. This double-blind multicenter trial randomized 412 patients with both inadequately controlled asthma despite inhaled corticosteroid use and minimal or no symptoms of GER to either 40 mg of esomeprazole twice daily or placebo. Patients were followed for 24 weeks with daily asthma diaries and spirometry performed once every 4 weeks. Ambulatory pH monitoring was performed to determine the presence or absence of GER. Reflux disease was self-reported in 19% of the placebo group and 10% of the treatment group. The primary outcome was the rate of episodes of poor asthma control based upon asthma diaries. No differences were detected in the number of episodes of poor asthma control between the two groups (2.3 and 2.5 per person year). There was also no treatment effect related to any outcome measurement. GER was identified by pH monitoring in 40% of these minimally symptomatic or asymptomatic patients, and its presence did not identify a subgroup that benefitted from proton pump inhibitor use. Editor’s comment. This trial demonstrated a high rate of GER among patients with asthma— 40%. Nevertheless, the use of high-dose esomeprazole neither reduced the rate of poorly controlled asthma episodes nor impacted any other measures, including respiratory function and quality of life. Furthermore, the presence of GER did not identify a subgroup who responded to acid suppression as well. At least for now, it seems the pendulum has swung away from the reflux-asthma link. ............................................................
Protease Inhibitor Therapy Augments Standard Treatment of Hepatitis C Virus McHutchison JG, Everson GT, Gordon SC, et al. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med 2009;360:1827–1838. Hézode C, Forestier N, Dusheiko G, et al. Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. N Engl J Med 2009;360:1839 –1850.
Summary. Therapy for hepatitis C virus (HCV) infection remains inadequate with only about half of patients infected with HCV genotype 1 achieving a sustained viro-
logic response (SVR) to standard peginterferon/ribavirin therapy. Preliminary studies with telaprevir, a specific inhibitor of the HCV serine protease, suggested virologic activity against HCV. Two parallel studies examined the efficacy of this agent involving various combinations of this agent with the current standard for therapy. In the first study, patients with HCV genotype 1 infection were randomized to 1 of 4 treatment groups: either to a control group that received peginterferon and ribavirin for 48 weeks and telaprevirmatched placebo for 12 weeks, or to 1 of 3 telaprevir groups that received telaprevir 1250 mg on the first day, followed by 750 mg every 8 hours, plus peginterferon and ribavirin at the same dose as the control group but at different durations, including 12 weeks, 24 weeks, and 48 weeks. The primary outcome was SVR 24 weeks after the end of therapy. SRV was shown in 41% of patients in the control group, and in 35%, 61%, and 67% of patients in the 12-week, 24-week, and 48-week treatment groups, respectively. In the parallel trial by Hézode et al, the first group received telaprevir/peginterferon/ribavirin for 12 weeks followed by peginterferon/ribavirin for an additional 12 weeks; the second group received 12 weeks of each regimen alone; and the third group received 12 weeks of telaprevir and 12 weeks of peginterferon without ribavirin. The control group received peginterferon and ribavirin for 48 weeks. SVR was documented in 46% of patients in the control group compared with 36% of patients in the group receiving telaprevir for 12 weeks followed by peginterferon without ribavirin for 12 weeks, 60% of patients in the group receiving telaprevir, peginterferon, and ribavirin for a total of 12 weeks, and 69% of patients in the group receiving telaprevir for 12 weeks followed by peginterferon and ribavirin for 12 additional weeks. Side effects from telaprevir were more common and included pruritus and rash; 12% of patients discontinued the study treatment in the telaprevir-based groups. Editor’s comment. We have heard about protease inhibitor therapy for HCV infection for some time, but now it appears to be imminent. These data suggest that the addition of telaprevir for at least 12 weeks improves the sustained virologic response rate for standard peginterferon ribavirin therapy. Ribavirin was again shown to be an important component of the treatment cocktail, and the more prolonged treatment with peginterferon/ ribavirin (24 weeks) was also associated with a higher SVR. Look for many other studies of this agent and new ones yet to come to determine which agent(s) and regimen(s) are most efficacious. The overall direction of therapy appears similar to those for HIV, in which multiple agents in various combinations will likely be used to enhance SVR.
July 2009
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Use of Blood Urea Nitrogen to Gauge Severity of Acute Pancreatitis: Simple and Accurate Wu BU, Johannes RS, Sun Z, et al. Early changes in blood urea nitrogen predict mortality in acute pancreatitis. Gastroenterology 2009;137:129 –135.
Summary. The importance of maintaining intravascular volume during the acute phase of severe pancreatitis is well established both in animal models and clinically. In addition, prior scoring systems have used creatinine, blood urea nitrogen (BUN), and hemoglobin (HGB) to assess prognosis. This study used a database of 69 US hospitals to identify all patients with a diagnosis of acute pancreatitis by ICD-9 codes over a 3-year period. The authors specifically examined the prognostic utility of serial measurement of BUN vs HGB in the early assessment of acute pancreatitis. Multivariable logistic regression was then used. They identified 5819 cases with at least 3 BUN/HGB measurements within the first 48 hours of admission. BUN levels were consistently higher among nonsurvivors than survivors during the first 48 hours of hospitalization, which was not found for HGB. For every 5 mg/dL increase in BUN during the first 24 hours, the odds ratio for mortality increased by 2.2%. Of the 6 routine laboratory tests used, BUN yielded the highest predictive value at admission and at 48 hours. Editor’s comment. This straightforward, well-done study confirms the importance of BUN as a prognostic marker in acute pancreatitis. BUN is widely available, inexpensive, and easy to use.
713
Additional Papers of Interest Jensen DM, Marcellin P, Freilich B, et al. Re-treatment of patients with chronic hepatitis C who do not respond to peginterferon-␣2b. Ann Intern Med 2009;150:528 – 540. Fogli L, Boschi S, Patrizi P, et al. Laparoscopic cholecystectomy without intraoperative cholangiography: audit of long-term results. J Laparoendosc Adv Surg Tech 2009;19:191–193. Marrelli D, Caruso S, Pedrazzani C, et al. CA19-9 serum levels in obstructive jaundice: clinical value in benign and malignant conditions. Am J Surg 2009 Apr 16 [Epub ahead of print]. Zeuzem S, Gane E, Liaw Y-F, et al. Baseline characteristics and early on-treatment response predict the outcomes of 2 years of telbivudine treatment of chronic hepatitis B. J Hepatol 2009;51:11–20. DeLeve LD, Valla D-C, Garcia-Tsao G. Vascular disorders of the liver. Hepatology 2009;49:1729 –1764. Khalid A, Zahid M, Finkelstein SD, et al. Pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts: a report of the PANDA study. Gastrointest Endosc 2009; 69:1095–1102. Ventrucci M, Pozzato P, Cipolla A, et al. Persistent elevation of serum CA19-9 with no evidence of malignant disease. Dig Liver Dis 2009;41:357–363. Chamberlain RS, Sakpal SV. A comprehensive review of single-incision laparoscopic surgery (SILS) and natural orifice transluminal endoscopic surgery (NOTES) techniques for cholecystectomy. J Gastrointest Surg 2009 May 2 [Epub ahead of print].
ABSTRACTS FROM AROUND THE WORLD Visit CGH online at www.cghjournal.org to link to these articles and additional articles of interest.
Proton Pump Inhibitors Do Not Help Control Asthma The American Lung Association Asthma Clinical Research Centers. Efficacy of esomeprazole for treatment of poorly controlled asthma. N Engl J Med 2009;360:1487–1499.
Summary. A link between gastroesophageal reflux (GER) and asthma has long been considered, and investigation for GER and/or empiric use of proton pump inhibitors for severe asthmatics with reflux symptoms is often undertaken. This double-blind multicenter trial randomized 412 patients with both inadequately controlled asthma despite inhaled corticosteroid use and minimal or no symptoms of GER to either 40 mg of esomeprazole twice daily or placebo. Patients were followed for 24 weeks with daily asthma diaries and spirometry performed once every 4 weeks. Ambulatory pH monitoring was performed to determine the presence or absence of GER. Reflux disease was self-reported in 19% of the placebo group and 10% of the treatment group. The primary outcome was the rate of episodes of poor asthma control based upon asthma diaries. No differences were detected in the number of episodes of poor asthma control between the two groups (2.3 and 2.5 per person year). There was also no treatment effect related to any outcome measurement. GER was identified by pH monitoring in 40% of these minimally symptomatic or asymptomatic patients, and its presence did not identify a subgroup that benefitted from proton pump inhibitor use. Editor’s comment. This trial demonstrated a high rate of GER among patients with asthma— 40%. Nevertheless, the use of high-dose esomeprazole neither reduced the rate of poorly controlled asthma episodes nor impacted any other measures, including respiratory function and quality of life. Furthermore, the presence of GER did not identify a subgroup who responded to acid suppression as well. At least for now, it seems the pendulum has swung away from the reflux-asthma link. ............................................................
Protease Inhibitor Therapy Augments Standard Treatment of Hepatitis C Virus McHutchison JG, Everson GT, Gordon SC, et al. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med 2009;360:1827–1838. Hézode C, Forestier N, Dusheiko G, et al. Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. N Engl J Med 2009;360:1839 –1850.
Summary. Therapy for hepatitis C virus (HCV) infection remains inadequate with only about half of patients infected with HCV genotype 1 achieving a sustained viro-
logic response (SVR) to standard peginterferon/ribavirin therapy. Preliminary studies with telaprevir, a specific inhibitor of the HCV serine protease, suggested virologic activity against HCV. Two parallel studies examined the efficacy of this agent involving various combinations of this agent with the current standard for therapy. In the first study, patients with HCV genotype 1 infection were randomized to 1 of 4 treatment groups: either to a control group that received peginterferon and ribavirin for 48 weeks and telaprevirmatched placebo for 12 weeks, or to 1 of 3 telaprevir groups that received telaprevir 1250 mg on the first day, followed by 750 mg every 8 hours, plus peginterferon and ribavirin at the same dose as the control group but at different durations, including 12 weeks, 24 weeks, and 48 weeks. The primary outcome was SVR 24 weeks after the end of therapy. SRV was shown in 41% of patients in the control group, and in 35%, 61%, and 67% of patients in the 12-week, 24-week, and 48-week treatment groups, respectively. In the parallel trial by Hézode et al, the first group received telaprevir/peginterferon/ribavirin for 12 weeks followed by peginterferon/ribavirin for an additional 12 weeks; the second group received 12 weeks of each regimen alone; and the third group received 12 weeks of telaprevir and 12 weeks of peginterferon without ribavirin. The control group received peginterferon and ribavirin for 48 weeks. SVR was documented in 46% of patients in the control group compared with 36% of patients in the group receiving telaprevir for 12 weeks followed by peginterferon without ribavirin for 12 weeks, 60% of patients in the group receiving telaprevir, peginterferon, and ribavirin for a total of 12 weeks, and 69% of patients in the group receiving telaprevir for 12 weeks followed by peginterferon and ribavirin for 12 additional weeks. Side effects from telaprevir were more common and included pruritus and rash; 12% of patients discontinued the study treatment in the telaprevir-based groups. Editor’s comment. We have heard about protease inhibitor therapy for HCV infection for some time, but now it appears to be imminent. These data suggest that the addition of telaprevir for at least 12 weeks improves the sustained virologic response rate for standard peginterferon ribavirin therapy. Ribavirin was again shown to be an important component of the treatment cocktail, and the more prolonged treatment with peginterferon/ ribavirin (24 weeks) was also associated with a higher SVR. Look for many other studies of this agent and new ones yet to come to determine which agent(s) and regimen(s) are most efficacious. The overall direction of therapy appears similar to those for HIV, in which multiple agents in various combinations will likely be used to enhance SVR.
July 2009
............................................................
Use of Blood Urea Nitrogen to Gauge Severity of Acute Pancreatitis: Simple and Accurate Wu BU, Johannes RS, Sun Z, et al. Early changes in blood urea nitrogen predict mortality in acute pancreatitis. Gastroenterology 2009;137:129 –135.
Summary. The importance of maintaining intravascular volume during the acute phase of severe pancreatitis is well established both in animal models and clinically. In addition, prior scoring systems have used creatinine, blood urea nitrogen (BUN), and hemoglobin (HGB) to assess prognosis. This study used a database of 69 US hospitals to identify all patients with a diagnosis of acute pancreatitis by ICD-9 codes over a 3-year period. The authors specifically examined the prognostic utility of serial measurement of BUN vs HGB in the early assessment of acute pancreatitis. Multivariable logistic regression was then used. They identified 5819 cases with at least 3 BUN/HGB measurements within the first 48 hours of admission. BUN levels were consistently higher among nonsurvivors than survivors during the first 48 hours of hospitalization, which was not found for HGB. For every 5 mg/dL increase in BUN during the first 24 hours, the odds ratio for mortality increased by 2.2%. Of the 6 routine laboratory tests used, BUN yielded the highest predictive value at admission and at 48 hours. Editor’s comment. This straightforward, well-done study confirms the importance of BUN as a prognostic marker in acute pancreatitis. BUN is widely available, inexpensive, and easy to use.
713
Additional Papers of Interest Jensen DM, Marcellin P, Freilich B, et al. Re-treatment of patients with chronic hepatitis C who do not respond to peginterferon-␣2b. Ann Intern Med 2009;150:528 – 540. Fogli L, Boschi S, Patrizi P, et al. Laparoscopic cholecystectomy without intraoperative cholangiography: audit of long-term results. J Laparoendosc Adv Surg Tech 2009;19:191–193. Marrelli D, Caruso S, Pedrazzani C, et al. CA19-9 serum levels in obstructive jaundice: clinical value in benign and malignant conditions. Am J Surg 2009 Apr 16 [Epub ahead of print]. Zeuzem S, Gane E, Liaw Y-F, et al. Baseline characteristics and early on-treatment response predict the outcomes of 2 years of telbivudine treatment of chronic hepatitis B. J Hepatol 2009;51:11–20. DeLeve LD, Valla D-C, Garcia-Tsao G. Vascular disorders of the liver. Hepatology 2009;49:1729 –1764. Khalid A, Zahid M, Finkelstein SD, et al. Pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts: a report of the PANDA study. Gastrointest Endosc 2009; 69:1095–1102. Ventrucci M, Pozzato P, Cipolla A, et al. Persistent elevation of serum CA19-9 with no evidence of malignant disease. Dig Liver Dis 2009;41:357–363. Chamberlain RS, Sakpal SV. A comprehensive review of single-incision laparoscopic surgery (SILS) and natural orifice transluminal endoscopic surgery (NOTES) techniques for cholecystectomy. J Gastrointest Surg 2009 May 2 [Epub ahead of print].