Field Performance of Cryopreserved Seed-derived Maize Plants.

BACKGROUND: Cryo-preservation of plant materials in liquid nitrogen (LN) has been described as a suitable technology to conserve genetic resources of several species. However, the potential effects of LN in the subsequent plant growth in the field should be studied before large-scale implementation of cryopreserved germplasm banks. OBJECTIVE: To describe the field performance of cryopreserved seed-derived maize adult plants. MATERIALS AND METHODS: Germination percentage and numbers of leaves and ears per plant, internodes in stems, middle - aged leaf length, plant height, ear traits and weight of 100 seeds were recorded. RESULTS: Statistically significant differences between adult plants derived from cryopreserved seeds and the control treatment were not observed (t-test, p=0.05). CONCLUSION: The results presented confirm at the phenotype level the effectiveness of maize seed cryostorage to preserve and regenerate true-to-type plants.

Practice patterns in screening for varices: an American survey.

BACKGROUND AND AIMS: Guidelines recommend screening for gastroesophageal varices. Regional studies suggest screening is underutilized, but information from across the United States is unavailable. We explored practice patterns and adherence to guidelines in a random sample of physicians and sought to define whether differences existed according to practice type, setting and years of practice. MATERIALS AND METHODS: Surveys were randomly sent to 600 gastroenterologists and hepatologists. Descriptive data is presented as percentage and comparisons were performed by chi-square analysis. Significance was defined at a p value <0.05. RESULTS: 180 completed surveys were returned. Mean age was 48.9+/-10 years and 87% were male. 50% were community-based and 74% had been in practice >10 years. 53% (78% hepatologists versus 45% of gastroenterologists) screened consistently (>75% of the time), (p<0.001). No differences in screening frequency were found according to practice setting or years in practice. 62% screened all cirrhotics whereas 38% screened based on clinical characteristics. In patients without gastroesophageal varices, 60% repeated esophagogastroduodenoscopy in 2-3 years. In those with small gastroesophageal varices, repeat esophagogastroduodenoscopy was recommended in 1-2 years by 73%. In patients with small and large varices, 40% and 54% of physicians respectively, recommended prophylaxis. 6% of physicians recommend prophylaxis regardless of the presence or size of varices. CONCLUSIONS: Screening for varices is under-implemented. Many screened based on clinical findings that have not been shown to reliably predict high-risk gastroesophageal varices. Continued education and removal of financial barriers to screening are central to increasing screening rates and improving patient outcomes.

Pharmacokinetics of butorphanol and evaluation of physiologic and behavioral effects after intravenous and intramuscular administration to neonatal foals.

BACKGROUND: Despite frequent clinical use, information about the pharmacokinetics (PK), clinical effects, and safety of butorphanol in foals is not available. OBJECTIVES: The purpose of this study was to determine the PK of butorphanol in neonatal foals after IV and IM administration; to determine whether administration of butorphanol results in physiologic or behavioral changes in neonatal foals; and to describe adverse effects associated with its use in neonatal foals. ANIMALS: Six healthy mixed breed pony foals between 3 and 12 days of age were used. METHODS: In a 3-way crossover design, foals received butorphanol (IV and IM, at 0.05 mg/kg) and IV saline (control group). Butorphanol concentrations were determined by high-performance liquid chromatography and analyzed using a noncompartmental PK model. Physiologic data were obtained at specified intervals after drug administration. Pedometers were used to evaluate locomotor activity. Behavioral data were obtained using a 2-hour real-time video recording. RESULTS: The terminal half-life of butorphanol was 2.1 hours and C0 was 33.2 +/- 12.1 ng/mL after IV injection. For IM injection, Cmax and Tmax were 20.1 +/- 3.5 ng/mL and 5.9 +/- 2.1 minutes, respectively. Bioavailability was 66.1 +/- 11.9%. There were minimal effects on vital signs. Foals that received butorphanol spent significantly more time nursing than control foals and appeared sedated. CONCLUSIONS AND CLINICAL IMPORTANCE: The disposition of butorphanol in neonatal foals differs from that in adult horses. The main behavioral effects after butorphanol administration to neonatal foals were sedation and increased feeding behavior.

Aspirin chemoprevention in patients with increased risk for colorectal cancer: a cost-effectiveness analysis.

BACKGROUND: Aspirin chemoprevention combined with colonoscopy screening is not cost-effective for the general population. However, the cost-effectiveness of aspirin in individuals with prior adenoma resection has not been evaluated. AIM: To evaluate the cost-effectiveness of aspirin chemoprevention alone and in combination with colonoscopy surveillance in patients with prior adenoma resection. METHODS: A model of the natural history of individuals with a history of endoscopic polypectomy was constructed. Four strategies were compared: (i) no intervention, (ii) routine colonoscopy surveillance, (iii) aspirin chemoprevention alone, and (iv) aspirin therapy combined with colonoscopy. RESULTS: Compared with no intervention, all other strategies were more costly but were associated with gains in years of life saved. Aspirin chemoprevention alone was associated with a gain of 0.0092 years, whereas routine colonoscopic surveillance and combination strategy were associated with further gains in years of life saved (0.0124 and 0.0138 years, respectively). Compared with no intervention, the incremental cost-effectiveness ratio of routine colonoscopy surveillance was $78,226 per year of life saved, and the incremental cost-effectiveness ratio of combination aspirin and colonoscopy was $60,942 per year of life saved. CONCLUSION: Aspirin chemoprevention combined with colonoscopic surveillance in post-polypectomy patients may be considered a cost-effective strategy.

Comparison of health-related quality of life preferences between physicians and cirrhotic patients: implications for cost-utility analyses in chronic liver disease.

Accurate assessment of utilities to calculate quality-adjusted life expectancy for medical interventions is needed in cirrhosis. To date, limited data exist in cirrhotics and are generally physician-assigned. Therefore, our aim was to determine utilities for six clinical scenarios in cirrhosis and to define if differences exist in utilities assigned by physicians versus patients. We administered a questionnaire to 83 physicians and 114 cirrhotics to obtain utilities using the time trade-off method for (1) compensated cirrhosis, (2) decompensated cirrhosis, (3) encephalopathy, (4) spontaneous bacterial peritonitis, (5) variceal bleeding, and (5) hepatocellular carcinoma. On a scale from 0 (death) to 1 (perfect health), mean utilities of physicians and patients were compared using the Student t test. One-way analysis of variance was used to compare the utilities between patients according to Child-Pugh class. Statistical significance was defined as a P value <0.05. The mean age of the physicians was 42 +/- 11, with 52% being male. The mean age of the patients was 52 +/- 9; with 59% male. The mean Child-Pugh score was 8 +/- 2 and HCV was the most common etiology (54%). The mean utilities for physicians and patients were as follows: CC, 0.78 vs. 0.88; DC, 0.55 vs. 0.74; E, 0.38 vs. 0.55; SBP, 0.33 vs. 0.45; VB, 0.27 vs. 0.40; and HCC, 0.19 vs. 0.30. All comparisons were statistically significant. Although physicians and patients assigned similar relative rankings to each health state, physicians assigned utilities were significantly different from those assigned by patients. These results suggest that studies that have used physician-assigned utilities do not accurately reflect patient preferences.

Suspected sphincter of Oddi dysfunction type II: empirical biliary sphincterotomy or manometry-guided therapy?

BACKGROUND AND STUDY AIMS: Sphincter of Oddi manometry is considered to be the gold standard for diagnosing sphincter of Oddi dysfunction (SOD). Elevated basal sphincter pressures are found in about half of the patients with findings consistent with biliary type II SOD, and most of these patients will symptomatically improve after endoscopic sphincterotomy. Since manometric sphincter evaluation is not widely available, a decision analysis was used to compare the overall costs and outcomes of manometry-directed therapy with "empirical" sphincterotomy in patients with suspected biliary type II SOD. PATIENTS AND METHODS: A decision analysis model was constructed using a software program. In a hypothetical cohort of 100 patients with suspected type II SOD, the following strategies were evaluated: a). endoscopic retrograde cholangiopancreatography (ERCP) with manometry followed by biliary sphincterotomy only if an elevated sphincter of Oddi basal pressure was found; and b). "empirical" biliary sphincterotomy without manometry. Data on the probability of an elevated sphincter of Oddi basal pressure at the time of ERCP in patients with suspected biliary SOD type II, the proportion of patients who improved after biliary sphincterotomy (with and without elevated basal pressures), the proportion of patients who improved without biliary sphincterotomy, complications, and death were obtained from the literature and from our center. The procedural and hospitalization costs represented the average Medicare reimbursement at our institution. The expected overall costs and numbers of patients improving with each strategy were compared.[nl] RESULTS: The strategy of ERCP with manometry resulted in total costs of US dollars 2790 per patient, whereas a strategy of "empirical" biliary sphincterotomy resulted in total costs of US dollars 2244. In a cohort of 100 patients with suspected SOD, 55 % of patients would be expected to improve if manometry were performed, compared to 60 % of patients improving with "empirical" biliary sphincterotomy. Univariate sensitivity analyses demonstrated that "empirical" biliary sphincterotomy continued to be a cost-saving strategy in comparison with ERCP with manometry as long as the probability of spontaneous improvement in patients with "normal" manometry was less than 41 %, the probability of complications associated with manometry was greater than 6 %, and the probability of complications due to biliary sphincterotomy was less than 19 %. CONCLUSIONS: For patients with suspected biliary SOD type II, empirical biliary sphincterotomy performed by experienced endoscopists appears to be cost-saving in comparison with a strategy based on the results of manometry.

Cost-effectiveness of hepatic venous pressure gradient measurements for prophylaxis of variceal re-bleeding.

BACKGROUND: Measurement of the hepatic venous pressure gradient may identify a sub-optimal response to drug prophylaxis in patients with a history of variceal bleeding. However, the cost-effectiveness of routine hepatic venous pressure gradient measurements to guide secondary prophylaxis has not been examined. METHODS: A Markov model was constructed using specialized software (DATA 3.5, Williamstown, MA, USA). Three strategies involved secondary prophylaxis without haemodynamic monitoring using beta-blockers alone, beta-blockers plus isosorbide mononitrate or endoscopic variceal ligation alone. Four strategies involved secondary prophylaxis with beta-blockers plus isosorbide mononitrate or beta-blockers alone, accompanied by one or two hepatic venous pressure gradient measurements to identify haemodynamic non-responders, who underwent endoscopic variceal ligation as an alternative. The total expected costs, variceal bleeding episodes and total deaths were calculated for each strategy over 3 years. RESULTS: The two most effective strategies were combination therapy alone and combination therapy with two hepatic venous pressure gradient measurements. The incremental cost-effectiveness ratio of the latter strategy was 136,700 dollars per year of life saved compared with combination therapy alone. The ratio improved as the time horizon was extended or the rates of variceal re-bleeding were increased. CONCLUSIONS: The cost-effectiveness of haemodynamic monitoring to guide secondary prophylaxis of recurrent variceal bleeding is highly dependent on local hepatic venous pressure gradient measurement costs, life expectancy and re-bleeding rates.

Hepatic venous pressure gradient measurements to assess response to primary prophylaxis in patients with cirrhosis: a decision analytical study.

BACKGROUND: The measurement of the hepatic venous pressure gradient may identify a suboptimal response to beta-blockers in patients with varices at risk for bleeding. However, the cost-effectiveness of routine hepatic venous pressure gradient measurements to guide primary prophylaxis has not been examined. METHODS: We used decision analysis to evaluate two hepatic venous pressure gradient measurement strategies relative to standard beta-blocker therapy in a hypothetical cohort of patients with high-risk varices: (i) hepatic venous pressure gradient measurement 4 weeks after the initiation of beta-blocker therapy; and (ii) hepatic venous pressure gradient measurement prior to and 4 weeks after the initiation of beta-blocker therapy. The total expected costs, variceal bleeding episodes and deaths were calculated over a 1-year time horizon. RESULTS: Beta-blocker therapy was associated with total costs of $1464, seven variceal bleeding episodes, one variceal bleeding episode-related death and 15 deaths. One hepatic venous pressure gradient measurement was associated with total costs of $5015, four variceal bleeding episodes, one variceal bleeding episode-related death and 15 deaths. Two hepatic venous pressure gradient measurements were associated with total costs of $8657, four episodes of variceal bleeding, one variceal bleeding episode-related death and 15 deaths. Compared with beta-blocker therapy alone, the incremental costs per variceal bleeding episode prevented and death averted were, respectively, $108 185 and $355 100 (one hepatic venous pressure gradient measurement) and $202 796 and $719 300 (two hepatic venous pressure gradient measurements). The results were sensitive to the time horizon of the analysis, the probability of bleeding whilst on beta-blockers and the cost of hepatic venous pressure gradient measurement. CONCLUSION: Hepatic venous pressure gradient measurement to guide primary prophylaxis is an expensive strategy for reducing variceal bleeding or death, especially in patients with limited life expectancy, such as those with advanced, decompensated cirrhosis.

Antibiotic prophylaxis prior to endoscopic retrograde cholangiopancreatography in patients with obstructive jaundice: is it worth the cost?

BACKGROUND: There are few published data concerning the economic impact of antibiotic prophylaxis prior to endoscopic retrograde cholangiopancreatography in the setting of biliary obstruction. AIM: To perform decision analysis to determine the costs of prophylaxis in patients undergoing endoscopic retrograde cholangiopancreatography for obstructive jaundice. METHODS: A decision analysis model was constructed. The probability of biliary sepsis, death and endoscopic retrograde cholangiopancreatography complications was obtained from the medical literature and from a retrospective analysis of our own experience. Costs were obtained from Medicare reimbursement at our institution. The strategies evaluated were endoscopic retrograde cholangiopancreatography with and without single-dose antibiotic prophylaxis. We compared the total costs, number of episodes of cholangitis and deaths associated with each strategy. RESULTS: Based on published data and the results of our retrospective analysis, the strategy of administering single-dose prophylactic antibiotics prior to endoscopic retrograde cholangiopancreatography in patients with obstructive jaundice resulted in lower total costs, fewer episodes of cholangitis and fewer deaths compared to a strategy of not administering antibiotics. The results were sensitive to the rates of cholangitis, cost of antibiotics and the cost of treating an episode of cholangitis. CONCLUSIONS: Antibiotic prophylaxis prior to endoscopic retrograde cholangiopancreatography results in fewer cases of cholangitis and is cost saving when compared to a strategy of no prophylaxis in patients with obstructive jaundice.

Barrett's oesophagus: a review of costs of the illness.

Barrett's oesophagus is a premalignant complication that occurs in approximately 10% of patients with gastro-oesophageal reflux disease (GORD). In patients with Barrett's oesophagus, the risk of adenocarcinoma of the oesophagus approaches 0.5% per patient-years. Therefore, practice guidelines have been developed that suggest screening patients with GORD, particularly those with long-standing symptoms and those aged > or =50 years for the presence of Barrett's metaplasia. These guidelines also suggest performing surveillance endoscopy for the development of dysplasia and/or cancer in patients found to harbour Barrett's oesophagus at initial screening with the frequency of subsequent endoscopies dictated by the presence and grade of dysplasia. In patients with high-grade dysplasia and/or early adenocarcinoma, oesophagectomy is curative. Given the important clinical and economic implications of GORD complicated by Barrett's oesophagus, we review the costs associated with screening, surveillance and treatment for this condition. Although the majority of physicians recommend and/or perform surveillance for dysplasia in the setting of Barrett's oesophagus, differences in endoscopic technique, surveillance intervals and cancer perception among practitioners influence total costs. In the US, it is estimated that a population-wide surveillance program could potentially result in a total cost of 289.9 million US dollars. The outpatient management of Barrett's oesophagus is estimated to cost 1241 US dollars per year with medication use alone accounting for over half of the total costs. Cost-effectiveness analyses have been performed to evaluate the economic impact and benefit of surveillance for dysplasia and/or cancer. Studies to date have utilised several outcome measures such as life-years gained, quality-adjusted life-years and cases of cancer detected. Therefore, the incremental cost-effectiveness ratios reported have varied greatly and are particularly sensitive to the prevalence of Barrett's oesophagus in patients with GORD and the incidence of adenocarcinoma. Further epidemiological and clinical studies are likely to further define the economic impact of Barrett's oesophagus as a complication of GORD.

Where do ERCP, endoscopic ultrasound, magnetic resonance cholangiopancreatography, and intraoperative cholangiography fit in the management of acute biliary pancreatitis? A decision analysis model.

OBJECTIVES: The role of ERCP in acute biliary pancreatitis (ABP) is controversial. Magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasonography (EUS) are modalities for bile duct visualization that could lower costs and prevent ERCP-related complications. We analyzed costs and examined the cost-effectiveness of these modalities to define their role in ABP. METHODS: A decision analysis model of ABP was constructed. The strategies evaluated were 1) ERCP, 2) MRCP followed by ERCP if positive for common bile duct stones (CBDS) or if biliary sepsis ensued, 3) EUS followed by ERCP if positive or if biliary sepsis ensued, and 4) observation with intraoperative cholangiography at the time of cholecystectomy with ERCP only if biliary sepsis ensued. We compared costs and performed cost-effectiveness analysis between strategies at probabilities of CBDS ranging from 0% to 100%. The outcome measures were total costs and costs per ABP death prevented. RESULTS: At probabilities of CBDS < 15%, observation with intraoperative cholangiography is the least expensive strategy, whereas EUS and ERCP are the least expensive strategies at probabilities of 15-58% and >58%, respectively. In terms of cost-effectiveness, at probabilities of CBDS of 7-45%, EUS is the most cost-effective alternative, and at a probability of >45% ERCP is the most cost-effective option. CONCLUSIONS: Total costs and cost-effectiveness ratios of these strategies in patients with ABP are highly dependent on the probability of CBDS.

Immunogenicity of hepatitis A vaccination in decompensated cirrhotic patients.

Hepatitis A virus (HAV) vaccination is recommended in chronic liver disease because of an increased morbidity and mortality associated with HAV superinfection. However, data regarding the efficacy of HAV vaccination in patients with advanced chronic liver disease is limited. We assessed the efficacy of a standard HAV vaccination schedule in decompensated chronic liver disease in comparison with compensated disease and defined clinical predictors associated with seroconversion. Eighty-four anti-HAV antibody-negative patients, 49 with compensated liver disease, and 35 with decompensated disease were enrolled. Seroconversion was measured by qualitative and quantitative anti-HAV antibody measurements 1 month after each vaccine dose, and univariate/multivariate analysis was performed to define clinical predictors associated with seroconversion. One month after the primary dose, 71.4% of patients with compensated liver disease had detectable anti-HAV antibody compared with 37.1% with decompensated liver disease (P <.05). One month after the booster dose, 98% of compensated patients seroconverted compared with 65.7% with decompensated disease (P <.05). The median serum antibody concentration in compensated liver disease was 76.4 mIU/mL at month 1 and 327.91 mIU/mL at month 7 compared with 20.0 mIU/mL and 102.57 mIU/mL, respectively, in decompensated disease. On multivariate analysis, Child-Pugh class was the only factor predicting response to vaccination. Seroconversion after HAV vaccination was significantly less common in decompensated liver disease and the presence of advanced disease (Child-Pugh class B/C) predicted a lower response rate. These findings indicate that the response to HAV vaccination in chronic liver disease is optimal when targeted to patients before the development of hepatic decompensation.

Surveillance colonoscopy or chemoprevention with COX-2 inhibitors in average-risk post-polypectomy patients: a decision analysis.

OBJECTIVES: Clinical trials are currently underway evaluating the efficacy of COX-2 inhibitors in decreasing the incidence of adenomas and colorectal carcinoma in 'average' risk individuals. AIM: To use decision analysis to compare the cost-effectiveness of celecoxib to surveillance colonoscopy in 'average' risk patients who had undergone prior adenoma resection. METHODS: A model of the natural history of adenomas after endoscopic polypectomy was constructed using probabilities from the literature. Cost estimates were obtained from available Medicare reimbursement rates and supplemented by the literature. Three strategies were evaluated: (i) no surveillance; (ii) colonoscopic surveillance; and (iii) celecoxib chemoprevention. We compared total costs and performed cost-effectiveness analysis between these strategies. The outcome measures were years of life saved and 'high-grade' adenoma prevented. Sensitivity analyses were performed on selected variables. RESULTS: Our base-case analysis assumed a 50% risk reduction in the incidence of adenomas among patients using celecoxib. No surveillance was associated with a cost of $1014 per patient, and colonoscopic surveillance with a cost of $1572 per patient, whereas celecoxib use was associated with a total cost of $11,503. Ten years after the index colonoscopy, 15% of patients in the no surveillance strategy developed 'high-grade' lesions compared to 13% of patients in the colonoscopic surveillance group and 6% in the celecoxib group. There was a small gain in years of life saved (0.006) favouring celecoxib over colonoscopic surveillance. The incremental cost-effectiveness ratio of celecoxib vs. colonoscopy was $141 871 per 'high-grade' adenoma prevented and $1,715,199 per year of life saved. The most important variables in determining the cost-effectiveness of celecoxib were its cost and its efficacy. CONCLUSION: Chemoprevention with COX-2 inhibitors in 'average-risk' postpolypectomy patients is a more expensive strategy compared to colonoscopic surveillance.

Congenital vascular lesions of the gastrointestinal tract: blue rubber bleb nevus and Klippel-Trenaunay syndromes.

We present two cases of hemangiomatosis of the gastrointestinal tract. The first case describes a 59-year-old patient with upper gastrointestinal hemorrhage due to the blue rubber bleb nevus syndrome. The second case illustrates a 26-year-old patient with recurrent rectal bleeding due to Klippel-Trenaunay syndrome. These two syndromes are distinct disorders characterized by cavernous hemangiomas of the skin, soft-tissue, bones, and viscera. In addition, we review the available literature on the epidemiology, transmission, clinical features, associated conditions, diagnosis, and treatment of these two disorders.

The use of screening and preventive therapies for gastroesophageal varices in patients referred for evaluation of orthotopic liver transplantation.

OBJECTIVE: Screening for varices has been recommended in patients with cirrhosis to prevent variceal hemorrhage (primary prophylaxis). In addition, therapy is recommended after the initial episode of variceal bleeding to prevent recurrence (secondary prophylaxis). However, the degree of adherence to these recommendations remains unclear. The purpose of our study was to determine whether these recommendations are being followed in patients presenting for evaluation of orthotopic liver transplantation. METHODS: One hundred twenty-five patients referred for liver transplantation were evaluated. Data regarding demographics, clinical information, relevant time intervals (diagnosis of cirrhosis to screening, screening to initial variceal bleeding, variceal bleeding to referral, diagnosis of cirrhosis to referral), screening strategies used, and implementation of primary or secondary prophylaxis was obtained. The differences among quantitative variables were analyzed with Student's t test. Qualitative variables were evaluated with the Mantel-Haenzel chi2 test or Fisher's exact test. Statistical significance was designated at p < 0.05. RESULTS: Our study found that 46% of patients presenting for evaluation of liver transplantation had screening endoscopy or radiological studies to detect the presence of varices. On the contrary, secondary prophylaxis was performed in all patients with a prior history of variceal hemorrhage. Screening for varices displayed no regional differences. CONCLUSIONS: In our cohort, screening for varices is not being consistently performed, thus delaying the timely implementation of primary prophylaxis. Therefore, the adherence to currently available practice guidelines and the education of physicians to implement screening in this patient population is an important goal.

Prevention in liver disease.

Prevention has become an important component of medical therapy for a variety of diseases. Preventive strategies in liver disease are relatively underdeveloped and have focused mainly on specific complications of chronic liver disease and vaccination for viral hepatitis. Although public health initiatives designed to prevent certain forms of liver disease are in place, they seem to be underutilized and their utility has not been evaluated. The development of a comprehensive approach using public health initiatives in conjunction with strategies by health care providers is important because of the potential for decreasing the human and health care costs associated with hepatic dysfunction. This article reviews the available literature regarding prevention for health care providers, includes a summary of ongoing public health initiatives, and suggests an approach to prevention in liver disease. It is intended to raise awareness and encourage implementation of preventive strategies in hepatology.