The unexplored role of sedentary time and physical activity in glucose and lipid metabolism-related placental mRNAs in pregnant women who are obese: the DALI lifestyle randomised controlled trial.

OBJECTIVE: We aimed to explore: (i) the association of sedentary time (ST) and physical activity (PA) during pregnancy with the placental expression of genes related to glucose and lipid metabolism in pregnant women who are obese; (ii) maternal metabolic factors mediating changes in these placental transcripts; and (iii) cord blood markers related to the mRNAs mediating neonatal adiposity. DESIGN: Multicentre randomised controlled trial. SETTING: Hospitals in nine European countries. POPULATION: A cohort of 112 pregnant women with placental tissue. METHODS: Both ST and moderate-to-vigorous PA (MVPA) levels were measured objectively using accelerometry at three time periods during pregnancy. MAIN OUTCOME MEASURES: Placental mRNAs (FATP2, FATP3, FABP4, GLUT1 and PPAR-γ) were measured with NanoString technology. Maternal and fetal metabolic markers and neonatal adiposity were assessed. RESULTS: Longer periods of ST, especially in early to middle pregnancy, was associated with lower placental FATP2 and FATP3 expression (P < 0.05), whereas MVPA at baseline was inversely associated with GLUT1 mRNA (P = 0.02). Although placental FATP2 and FATP3 expression were regulated by the insulin-glucose axis (P < 0.05), no maternal metabolic marker mediated the association of ST/MVPA with placental mRNAs (P > 0.05). Additionally, placental FATP2 expression was inversely associated with cord blood triglycerides and free fatty acids (FFAs; P < 0.01). No cord blood marker mediated neonatal adiposity except for cord blood leptin, which mediated the effects of PPAR-γ on neonatal sum of skinfolds (P < 0.05). CONCLUSIONS: In early to middle pregnancy, ST is associated with the expression of placental genes linked to lipid transport. PA is hardly related to transporter mRNAs. Strategies aimed at reducing sedentary behaviour during pregnancy could modulate placental gene expression, which may help to prevent unfavourable fetal and maternal pregnancy outcomes. TWEETABLE ABSTRACT: Reducing sedentary behaviour in pregnancy might modulate placental expression of genes related to lipid metabolism in women who are obese.

Hemostasis Techniques for Non-variceal Upper GI Hemorrhage: Beyond Injection and Cautery.

B. Nulsen D. M. Jensen.

Outcomes in Severe Upper GI Hemorrhage from Dieulafoy's Lesion with Monitoring of Arterial Blood Flow.

BACKGROUND: Dieulafoy's lesion (DL) is a rare but increasingly recognized cause of severe upper GI hemorrhage (SUGIH). There is little consensus regarding the endoscopic approach to management of bleeding from DL. AIMS: Our purposes were to compare 30-day outcomes of patients with SUGIH from DL with Doppler endoscopic probe (DEP) monitoring of blood flow and guided treatment versus standard visually guided hemostasis (VG). METHODS: Eighty-two consecutive DL patients with SUGIH were identified in a large CURE Hemostasis database from previous prospective cohort studies and two recent RCTs at two university-based medical centers. 30-day outcomes including rebleeding, surgery, angiography, death, and severe medical complications were compared between the two treatment groups. RESULTS: 40.2% of DL bleeds occurred in inpatients. 43.9% of patients had cardiovascular disease, and 48.7% were taking medications associated with bleeding. For the entire cohort, 41.3% (26/63) of patients treated with VG had a composite 30-day outcome as compared to 10.5% (2/19) of patients treated with DEP (p = 0.017). Rebleeding occurred within 30 days in 33.3% and 10.5% of those treated with VG and DEP, respectively (p = 0.051). After propensity score matching, the adjusted 30-day composite outcome occurred in 39.0% in the VG group compared to 2.6% in the DEP group (p < 0.001). Adjusted 30-day rebleeding occurred in 25.3% in the VG group versus 2.6% in the DEP group (p < 0.001). DISCUSSION: DL patients with SUGIH were frequently inpatients and had severe cardiovascular comorbidities and recurrent bleeding. Lesion arterial blood flow monitoring and obliteration are an effective way to treat bleeding from DL which reduces negative 30-day clinical outcomes.

Metabolic phenotypes of early gestational diabetes mellitus and their association with adverse pregnancy outcomes.

AIMS: To describe the metabolic phenotypes of early gestational diabetes mellitus and their association with adverse pregnancy outcomes. METHODS: We performed a post hoc analysis using data from the Vitamin D And Lifestyle Intervention for gestational diabetes prevention (DALI) trial conducted across nine European countries (2012-2014). In women with a BMI ≥29 kg/m2 , insulin resistance and secretion were estimated from the oral glucose tolerance test values performed before 20 weeks, using homeostatic model assessment of insulin resistance and Stumvoll first-phase indices, respectively. Women with early gestational diabetes, defined by the International Association of Diabetes and Pregnancy Study Groups criteria, were classified into three groups: GDM-R (above-median insulin resistance alone), GDM-S (below-median insulin secretion alone), and GDM-B (combination of both) and the few remaining women were excluded. RESULTS: Compared with women in the normal glucose tolerance group (n = 651), women in the GDM-R group (n = 143) had higher fasting and post-load glucose values and insulin levels, with a greater risk of having large-for-gestational age babies [adjusted odds ratio 3.30 (95% CI 1.50-7.50)] and caesarean section [adjusted odds ratio 2.30 (95% CI 1.20-4.40)]. Women in the GDM-S (n = 37) and GDM-B (n = 56) groups had comparable pregnancy outcomes with those in the normal glucose tolerance group. CONCLUSIONS: In overweight and obese women with early gestational diabetes, higher degree of insulin resistance alone was more likely to be associated with adverse pregnancy outcomes than lower insulin secretion alone or a combination of both.

Independent risk factors of 30-day outcomes in 1264 patients with peptic ulcer bleeding in the USA: large ulcers do worse.

BACKGROUND: Predictors of worse outcomes (rebleeding, surgery and death) of peptic ulcer bleeds (PUBs) are essential indicators because of significant morbidity and mortality rates of PUBs. However those have been infrequently reported since changes in medical therapy (PPI, proton pump inhibitors) and application of newer endoscopic haemostatic technique. AIMS: To determine: (i) independent risk factors for 30-day rebleeding, surgery, and death and (ii) whether ulcer size is an independent predictor of major outcomes in patients with severe PUB after successful endoscopic haemostasis and treatment with optimal medical (high dose IV PPI) vs. prior treatment (high dose IV histamine 2 antagonists - H2RAs). METHODS: A large prospectively followed population of patients hospitalised with severe PUBs between 1993 and 2011 at two US tertiary care academic medical centres, stratified by stigmata of recent haemorrhage (SRH) was studied. Using multivariable logistic regression analyses, independent risk factors for each outcome (rebleeding, surgery and death) up to 30 days were analysed. Effects for medical treatment (H2RA patients 1993-2005 vs. PPIs 2006-2011) were also analysed. RESULTS: A total of 1264 patients were included. For ulcers ≥10 mm, the odds of 30-day rebleeding increased 6% per each 10% increase in ulcer size (OR 1.06, 95% CI 1.02-1.10, P = 0.0053). Other risk factors for 30-day rebleeding were major SRH, in-patient start of bleeding, and prior GI bleeding. Major SRH and ulcer size≥10 mm were predictors of 30-day surgery. Risk factors for 30-day death were major SRH, in-patient bleeding, and any initial platelet transfusion or fresh frozen plasma transfusion ≥2 units. Among patients with major SRH and out-patient start of bleeding, larger ulcer size was also a risk factor for death (OR 1.08 per 10% increase in ulcer size, 95% CI 1.02-1.14, P = 0.0095). Ulcer size was a significant independent variable for both time periods. CONCLUSIONS: Ulcer size is a risk factor for worse outcomes after PUB and should be carefully recorded at initial endoscopy to improve patient triage and management.

Clinical impact of treatment timing for chronic hepatitis C infection: a decision model.

Recent advances in the treatment of hepatitis C virus (HCV) infection have led to the availability of both highly efficacious interferon-containing and interferon-sparing regimens. However, the use of such therapies faces restrictions due to high costs. For patients who are medically eligible to receive interferon, the choice between the two will likely be impacted by preferences surrounding interferon, severity of disease, coverage policies and out-of-pocket costs. We developed a decision model to quantify the trade-offs between immediate, interferon-containing therapy and delayed, interferon-free therapy for patients with chronic, genotype 1 HCV infection. We projected the quality-adjusted life expectancy stratified by the presence or absence of cirrhosis for four strategies: (i) no treatment; (ii) immediate, one-time treatment with an interferon-containing regimen; (iii) immediate treatment as above with the opportunity for retreatment in patients who fail to achieve sustained virologic response with interferon-free therapy in 1 year; and (iv) delayed therapy with interferon-free therapy in 1 year. When compared to one-time immediate treatment with the interferon-containing regimen, delayed treatment with the interferon-free regimen in 1 year resulted in longer life expectancy, with a 0.2 quality-adjusted life year (QALY) increase in noncirrhotic patients, and a 1.1 QALY increase in patients with cirrhosis. This superiority in health benefits was lost when wait time for interferon-free therapy was greater than 3-3.2 years. In this modelling analysis, interferon-free therapy resulted in superior health benefits compared to immediate therapy with interferon until wait time exceeded 3-3.2 years. Such data can inform decision-making regarding treatment initiation for HCV as healthcare financing evolves.

Glutamic acid decarboxylase autoantibody-positivity post-partum is associated with impaired ß-cell function in women with gestational diabetes mellitus.

AIMS: To investigate whether the presence of glutamic acid decarboxylase (GAD) autoantibodies post-partum in women with prior gestational diabetes mellitus was associated with changes in metabolic characteristics, including ß-cell function and insulin sensitivity. METHODS: During 1997-2010, 407 women with gestational diabetes mellitus were offered a 3-month post-partum follow-up including anthropometrics, serum lipid profile, HbA1c and GAD autoantibodies, as well as a 2-h oral glucose tolerance test (OGTT) with blood glucose, serum insulin and C-peptide at 0, 30 and 120 min. Indices of insulin sensitivity and insulin secretion were estimated to assess insulin secretion adjusted for insulin sensitivity, disposition index (DI). RESULTS: Twenty-two (5.4%) women were positive for GAD autoantibodies (GAD+ve) and the remainder (94.6%) were negative for GAD autoantibodies (GAD-ve). The two groups had similar age and prevalence of diabetes mellitus. Women who were GAD+ve had significantly higher 2-h OGTT glucose concentrations during their index-pregnancy (10.5 vs. 9.8 mmol/l, P = 0.001), higher fasting glucose (5.2 vs. 5.0 mmol/l, P = 0.02) and higher 2-h glucose (7.8 vs. 7.1 mmol/l, P = 0.05) post-partum. Fasting levels of C-peptide and insulin were lower in GAD+ve women compared with GAD-ve women (520 vs. 761 pmol/l, P = 0.02 and 33 vs. 53 pmol/l, P = 0.05) Indices of insulin sensitivity were similar in GAD+ve and GAD-ve women, whereas all estimates of DI were significantly reduced in GAD+ve women. CONCLUSION: GAD+ve women had higher glucose levels and impaired insulin secretion adjusted for insulin sensitivity (DI) compared with GAD-ve women. The combination of OGTT and GAD autoantibodies post-partum identify women with impaired ß-cell function. These women should be followed with special focus on development of Type 1 diabetes.

Infant twin mortality and hospitalisations after the perinatal period - a prospective cohort study from Guinea-Bissau.

OBJECTIVE: To examine mortality and hospitalisations among infant twins and singletons after the perinatal period in Guinea-Bissau. METHODS: The study was conducted from September 2009 to November 2012 by the Bandim Health Project (BHP). Newborn twins and unmatched singleton controls were included at the National Hospital Simão Mendes in the capital Bissau. Children were examined clinically at enrolment. Maternal, pregnancy and obstetric information was collected and HIV testing offered at birth. Follow-up occurred at home at 2, 6 and 12 months and through linkage with the paediatric admission register at the National Hospital. RESULTS: About 495 twins and 333 singletons were alive on day 7 after birth. In total, 36 twins and 12 singletons died during follow-up, the post-perinatal infant mortality rate being 91/1000 person-years for twins and 42/1000 for singletons (HR = 2.11, 95% CI: 1.09-4.07). In a multivariable analysis among twins only, birth weight <2000 g [3.32, (1.36-8.07)], death of the cotwin perinatally [2.54, (1.16-5.57)] and severe maternal illness during pregnancy [2.35, (1.00-5.51)] were significant risk factors for twin death. In the subgroup with available HIV status, maternal HIV infection was strongly associated with twin mortality [3.16, (1.24-8.05)]. Death occurred at home for 60% of twins and 67% of singletons. During follow-up, 90 first-time hospital admissions were registered, with similar rates observed for twins (139/1000) and singletons (143/1000) [0.97, (0.61-1.52)]. CONCLUSION: The post-perinatal infant mortality rate of twins was double that of singletons. No excess in twin hospitalisations was observed, possibly implying obstacles to hospital admission for twins in case of severe illness.

Metabolic effects of lifestyle intervention in obese pregnant women. Results from the randomized controlled trial 'Lifestyle in Pregnancy' (LiP).

AIMS: The Lifestyle in Pregnancy intervention in obese pregnant women resulted in significantly lower gestational weight gain compared with the control group, but without improvement in rates of clinical pregnancy complications. The impact of the lifestyle intervention on metabolic measurements in the study participants is now reported. METHODS: The Lifestyle in Pregnancy study was a randomized controlled trial among 360 obese women (BMI 30-45 kg/m²) who were allocated in early pregnancy to lifestyle interventions with diet counselling and physical activities or to the control group. Fasting blood samples, including plasma glucose, insulin, lipid profile and capillary blood glucose during a 2-h oral glucose tolerance test were carried out three times throughout pregnancy. Insulin resistance was estimated with the homeostasis model assessment of insulin resistance. RESULTS: Three hundred and four women (84%) were followed until delivery. Women in the intervention group had a significantly lower change in insulin resistance (HOMA-IR) from randomization to 28-30 weeks' gestation compared with control subjects (mean ± SD: 0.7 ± 1.3 vs. 1.0 ± 1.3, P = 0.02). Despite a significantly lower gestational weight gain in the intervention group, there was no difference between the groups with respect to total cholesterol, HDL, LDL or triglycerides. CONCLUSIONS: Lifestyle intervention in obese pregnant women resulted in attenuation of the physiologic pregnancy-induced insulin resistance. Despite restricted gestational weight gain, there were no changes in glucose or lipid metabolism between the groups.

Severe upper gastrointestinal hemorrhage from linear gastric ulcers in large hiatal hernias: a large prospective case series of Cameron ulcers.

We report a case series of all consecutive patients hospitalized in our two tertiary referral medical centers over the past 17 years for Cameron ulcers causing severe upper gastrointestinal hemorrhage (GIH) or severe obscure GIH. Cameron ulcers were diagnosed in 25 of the 3960 screened patients with severe upper GIH or severe obscure GIH (0.6 %). Of these, 21 patients had a prospective follow-up (median time 20.4 months [interquartile range: 8.5 - 31.8]). Patients were more often elderly women with chronic anemia, always had large hiatal hernias, and were usually referred for obscure GIH. Twelve of the 21 patients (57 %) were referred for surgery while being treated with high-dose proton pump inhibitors (PPIs). The other 9 patients (43 %) continued PPIs without any rebleeding during the follow-up. Cameron ulcers in large hiatal hernias are an uncommon cause of severe upper GIH. The choice of medical vs. surgical therapy should be individualized.

Pregestational body mass index is related to neonatal abdominal circumference at birth--a Danish population-based study.

OBJECTIVES: To examine the impact of maternal pregestational body mass index (BMI) and smoking on neonatal abdominal circumference (AC) and weight at birth. To define reference curves for birth AC and weight in offspring of healthy, nonsmoking, normal weight women. DESIGN: Population-based study. SETTING: Data from the Danish Medical Birth Registry. POPULATION: All live singletons without congenital malformations in Denmark 2004-10. METHODS: Data on 366,886 singletons at 35(+0) to 41(+6) weeks(+days) of gestation were extracted and analysed using multivariate linear regressions. MAIN OUTCOME MEASURES: Birth AC and weight in relation to pregestational maternal BMI, maternal smoking and medical conditions (any). RESULTS: Birth AC and weight increased with increasing pregestational BMI, and decreased with smoking (P < 0.0001). Reference curves were created for offspring of healthy, nonsmoking mothers with normal pregestational BMI. Mean AC ranged from 30.1 cm and 30.2 cm at 35 weeks of gestation to 33.9 cm and 34.1 cm at 41 weeks of gestation, for girls and boys, respectively. Mean birthweight ranged from 2581 and 2666 g at 35 weeks to 3705 and 3852 g at 41 weeks of gestation for girls and boys, respectively. Pregestational BMI correlated more to the Z score of birthweight than to the Z score of AC (P < 0.0001). CONCLUSION: Birth AC and weight are affected by maternal smoking status and pregestational BMI. Pregestational BMI correlated more to birthweight than to AC. Using data from healthy, nonsmoking mothers with normal pregestational BMI we have provided new reference curves for birth AC and birthweight.

A practical guide for the use of boceprevir and telaprevir for the treatment of hepatitis C.

The aim of this study is to review clinical trial data on the newly approved protease inhibitors boceprevir and telaprevir to develop consensus recommendations on the optimal use of these agents for the treatment of patients with chronic hepatitis C virus (HCV) infection. An expert panel of seven leading authorities in viral hepatitis was convened to establish and disseminate a practical guide on best practices for incorporating boceprevir and telaprevir into therapy for HCV infection in both treatment-naive and treatment-experienced patients. The topics covered include selecting candidates for boceprevir- or telaprevir-based treatments, predictors of response and early viral kinetics, response-guided therapy approaches, on-treatment management strategies to optimize the likelihood of response and minimize the risk of drug resistance, management of adverse effects during therapy and key considerations for special populations. The expert panel incorporated the best available clinical evidence into recommendations on how boceprevir and telaprevir should be used in the clinical setting. They indicated how treatment regimens may differ according to the baseline factors, such as presence of cirrhosis and when therapy may need to be modified or stopped altogether because of adverse events or poor virologic response. This practical guide will serve as a valuable resource for clinicians embarking on the new treatment paradigm of boceprevir or telaprevir in combination with peginterferon/ribavirin for chronic genotype 1 HCV infection.

The significance of gastric and duodenal histological ischemia reported on endoscopic biopsy.

Although frequently reported, it is unknown whether pathological reports of ischemia obtained from gastroduodenal biopsies suggest a diagnosis, prognosis or a requirement for additional evaluation. The aim of this study was to review the natural history, clinical presentation, endoscopic appearance, treatments, and major clinical outcomes of patients with gastroduodenal ischemia. A case series of 14 patients with variable etiologies (seven gastric and seven duodenal) was obtained from a search of our endoscopic pathological database for reports of histological ischemia. The results were as follows. The most common presentation was upper gastrointestinal bleeding (71 %). Half of the endoscopic lesions appeared very severe (large or circumferential lesions, exudative, pseudomembranous, black or pale mucosa). There were six cases of rebleeding (43 %) and four deaths (29 %). Computed tomography scanning was frequently used (12 cases, 86 %), but led to an underlying diagnosis in only three cases. In our series, patients with underlying vascular pathology have substantial 6-month mortality (29 %).

Cognitive function in adult offspring of women with Type 1 diabetes.

AIMS: Maternal diabetes may affect offspring cognitive function. The objective of the study was to evaluate cognitive function and potential predictors hereof in adult offspring of women with Type 1 diabetes. METHODS: We conducted a follow-up study of adult offspring of women with Type 1 diabetes (n = 158) and a reference group from the background population (n = 118). The main outcome measure was offspring cognitive function measured by global cognitive score, derived from Raven's Progressive Matrices and three verbal subtests from the Weschler Adult Intelligence Scale. RESULTS: Offspring of women with Type 1 diabetes obtained lower global cognitive scores (94.8 vs. 100.0, P = 0.004) than offspring from the background population. When adjusted for confounders, the groups no longer differed significantly (difference 0.4, 95% CI -3.3 to 4.). Positive predictors of cognitive function in offspring of women with diabetes were family social class, parental educational level, maternal diabetes duration, male gender and offspring age, whereas parity ≥ 1 and gestational age < 34 weeks were negative predictors. We found no association with maternal glycaemia during pregnancy or with neonatal hypoglycaemia. CONCLUSIONS: Impaired cognitive function in adult offspring of women with Type 1 diabetes compared with the background population apparently reflects differences with respect to well-known confounders. However, harmful effects of maternal hyperglycaemia may be mediated through delivery at < 34 weeks.

Factors associated with rapid and early virologic response to peginterferon alfa-2a/ribavirin treatment in HCV genotype 1 patients representative of the general chronic hepatitis C population.

Rapid virologic response (RVR) and complete early virologic response (cEVR) are associated with sustained virologic response to hepatitis C virus (HCV) therapy. We retrospectively examined baseline and on-treatment factors associated with RVR (HCV RNA undetectable at week 4) and cEVR (HCV RNA undetectable at week 12, regardless of week 4 response). The analysis comprised 1550 HCV genotype-1 patients from five clinical trials, including three enriched with difficult-to-treat populations, randomized to peginterferon alfa-2a 180 microg/week plus ribavirin 1000-1200 mg/day. Overall, 15.6% achieved RVR and 54.0% achieved cEVR. Baseline factors predictive of RVR were serum HCV RNA 3 x ULN (OR: 2.01; P < 0.0001), non-cirrhotic status (OR: 1.92; P = 0.0087), age 13 mg/kg/day was predictive of RVR (OR: 1.69; P = 0.005) and cEVR (OR: 1.24; P = 0.09), whereas peginterferon alfa-2a dose reduction was not. Greater decreases in haematologic parameters were observed in patients who achieved cEVR compared with patients who did not. In conclusion, several baseline and on-treatment factors were associated with RVR and cEVR to peginterferon alfa-2a plus ribavirin in difficult-to-treat HCV genotype-1 patients, providing important prognostic information on the antiviral response in a patient cohort that is reflective of the general chronic hepatitis C population.

Re-treatment of chronic hepatitis C patients after relapse: efficacy of peginterferon-alpha-2a (40 kDa) and ribavirin.

We conducted a randomized multinational study to determine whether 48 weeks of re-treatment with peginterferon-alpha-2a (40 kDa) plus ribavirin would induce a sustained virological response (SVR) in relapsed chronic hepatitis C patients. Patients who had previously relapsed during 24 weeks of untreated follow-up, after having achieved an end-of-treatment virological response with 24 weeks of peginterferon-alpha-2a (40 kDa)/ribavirin combination therapy, within a phase III trial, were studied. Although the recommended dosage was the same as that used at the end of the initial trial, adjustments were permitted. Data on serious adverse events, or adverse events that resulted in dose reductions or discontinuations, were collected. Following re-treatment, the overall SVR rate in the 64 patients was 55%. The SVR rates in patients infected with hepatitis C virus (HCV) genotype 1 and non-1 genotypes were 51% and 63%, respectively. Early (week 12) virological responses were seen in 39 patients (61%) and were predictive of an SVR. Re-treatment was well tolerated. The most frequent adverse events recorded were fatigue (5%) and abdominal pain (3%). Dosages of peginterferon-alpha-2a (40 kDa) and/or ribavirin were modified because of adverse events in 3% and 13% of patients, and because of laboratory abnormalities in 23% and 5% of patients, respectively. Thus, a 48-week course of peginterferon-alpha-2a (40 kDa) plus ribavirin induces an SVR in 55% of patients who relapsed during follow-up after 24 weeks of combination therapy. Physicians should not hesitate to offer re-treatment to patients who relapse after an initial, 24-week course of combination therapy, or who have prematurely stopped treatment because, for example, of laboratory abnormalities.

Cost-effectiveness of combination peginterferon alpha-2a and ribavirin compared with interferon alpha-2b and ribavirin in patients with chronic hepatitis C.

BACKGROUND: Sustained virological response (SVR) is the primary objective in the treatment of chronic hepatitis C (CHC). Results from a recent clinical trial of patients with previously untreated CHC demonstrate that the combination of peginterferon alpha-2a and ribavirin produces a greater SVR than interferon alpha-2b and ribavirin combination therapy. However, the cost-effectiveness of peginterferon alpha-2a plus ribavirin in the U.S. setting has not been investigated. METHODS: A Markov model was developed to investigate cost-effectiveness in patients with CHC using genotype to guide treatment duration. SVR and disease progression parameters were derived from the clinical trials and epidemiologic studies. The impact of treatment on life expectancy and costs were projected for a lifetime. Patients who had an SVR were assumed to remain virus-free for the rest of their lives. In genotype 1 patients, the SVRs were 46% for peginterferon alpha-2a plus ribavirin and 36% for interferon alpha-2b plus ribavirin. In genotype 2/3 patients, the SVRs were 76% for peginterferon alpha-2a plus ribavirin and 61% for interferon alpha-2b plus ribavirin. Quality of life and costs were based on estimates from the literature. All costs were based on published U.S. medical care costs and were adjusted to 2003 U.S. dollars. Costs and benefits beyond the first year were discounted at 3%. RESULTS: In genotype 1, peginterferon alpha-2a plus ribavirin increases quality-adjusted life expectancy (QALY) by 0.70 yr compared to interferon alpha-2b plus ribavirin, producing a cost-effectiveness ratio of $2,600 per QALY gained. In genotype 2/3 patients, peginterferon alpha-2a plus ribavirin increases QALY by 1.05 yr in comparison to interferon alpha-2b plus ribavirin. Peginterferon alpha-2a combination therapy in patients with HCV genotype 2 or 3 is dominant (more effective and cost saving) compared to interferon alpha-2b plus ribavirin. Results weighted by genotype prevalence (75% genotype 1; 25% genotype 2 or 3) also show that peginterferon alpha-2a plus ribavirin is dominant. Peginterferon alpha-2a and ribavirin remained cost-effective (below $16,500 per QALY gained) under sensitivity analyses on key clinical and cost parameters. CONCLUSION: Peginterferon alpha-2a in combination with ribavirin with duration of therapy based on genotype, is cost-effective compared with conventional interferon alpha-2b in combination with ribavirin when given to treatment-naïve adults with CHC.

Endoscopic treatment outcomes in watermelon stomach patients with and without portal hypertension.

BACKGROUND AND STUDY AIMS: Watermelon stomach is a source of recurrent gastrointestinal hemorrhage and anemia. The aims of this study were to describe the endoscopic appearance and treatment outcomes in watermelon stomach patients with and without portal hypertension. PATIENTS AND METHODS: All patients with watermelon stomach enrolled in a hemostasis research group's prospective studies from 1991 to 1999 were identified. Investigators collected data using standardized forms. Comparisons were made using the chi-squared test, Wilcoxon rank-sum test, and Wilcoxon signed-rank test. RESULTS: Twenty-six of 744 (4 %) consecutively enrolled patients with nonvariceal upper gastrointestinal hemorrhage had watermelon stomach as the cause. Eight of these 26 patients (31 %) also had portal hypertension. These patients had diffuse antral angiomas, as opposed to the classic linear arrays seen in those without portal hypertension. The demographic data and clinical presentations of the two groups were otherwise similar. Palliative endoscopic treatment was associated with a significant rise in hematocrit and a decrease in the need for blood transfusion or hospitalization in watermelon stomach patients with and without portal hypertension. CONCLUSIONS: Watermelon stomach patients with and without portal hypertension had similar clinical presentations. The endoscopic findings differed in that those with portal hypertension had more diffuse gastric angiomas. Bleeding was effectively palliated by endoscopic treatment, regardless of the presence of portal hypertension.