Biomedical subjects

A Andriulli

Publications and source records attributed to A Andriulli.

At least 19 recordsLinked to original sources

PubMed2006

Short-term treatment duration for HCV-2 and HCV-3 infected patients.

BACKGROUND: We have shown that 12-14 weeks treatment is effective in HCV-2 or -3 patients with undetectable HCV-RNA after 4 weeks of therapy (rapid virologic response). PATIENTS: To identify predictors of sustained virologic response, rapid virologic response and relapse following short treatment, we pooled data from the original Italian and Norwegian studies. Four hundreds and three patients were treated with PegIFN alpha-2b (1.0, n=281 or 1.5 microg/kg, n=122) and ribavirin (800-1200 mg) for 12-14 or 24 weeks, depending on negative or positive HCV-RNA at week 4. RESULTS: Sustained virologic response differed between cases with and without rapid virologic response (85% versus 62%, P<0.0001), mild and severe fibrosis (83% versus 67%, P=0.004), and HCV-2 and -3 (81% versus 73%, P=0.05). In a regression model, RVR (odds ratio 3.49, confidence interval 1.73-5.36) and mild fibrosis (odds ratio 2.91, confidence interval 1.57-5.38) independently predicted sustained virologic response. Rapid virologic response was obtained in 274 (68%) patients, 163/242 (67%) HCV-2, and 111/161 (69%) HCV-3. Patients with RVR had more frequently mild fibrosis (70% versus 54%, P=0.03), and high PegIFN dose (78% versus 64%, P=0.005). In a regression model, mild fibrosis independently predicted rapid virologic response (odds ratio 1.87, confidence interval 1.10-3.16). In rapid virologic response patients, sustained virologic response was achieved in 85% of both HCV-2 and -3. Virologic relapse was observed in 10.6% rapid virologic response patients and was more frequent among those with low ALT (14% versus 2%, P=0.04). CONCLUSION: In HCV-2 or -3, the HCV-RNA status after 4 weeks of therapy may guide treatment duration. HCV-2 and HCV-3 patients with severe fibrosis are less likely to experience both rapid virologic response and sustained virologic response, and more frequently relapse after a 12 or 14 weeks duration of antiviral therapy.

Adult↗

PubMed2006

Multidrug resistance 1 gene in inflammatory bowel disease: a meta-analysis.

The MDR1 gene is an attractive candidate gene for the pathogenesis of inflammatory bowel disease (IBD) and perhaps response to therapy, with evidences at both functional and genetic levels. Its product, the P-glycoprotein (P-gp) functions as a transmembrane efflux pump thus influencing disposition and response of many drugs, some of whom (i.e. glucocorticoids) central to IBD therapy. In addition P-gp is highly expressed in many epithelial surfaces, included gastrointestinal tract (G-I) with a putative role in decreasing the absorption of endogenous or exogenous toxins, and perhaps host-bacteria interaction. Many genetic variations of MDR1 gene has been described and in some instances evidences for different P-gp expression as well drugs metabolism have been provided. However data are often conflicting due to genetic heterogeneity and different methodologies employed. Perhaps the greatest piece of evidence of the physiological importance of P-gp in the G-I tract has come from the description of the mdr1 knock-out mice model, which develops a spontaneous colitis in a specific pathogen-free environment. Studies investigating MDR1 gene polymorphism and predisposition to IBD have also shown conflicting results, owing to the known difficulties in complex diseases, especially when the supposed genetic contribution is weak. In this study we have undertaken a meta-analysis of the available findings obtained with two SNPs polymorphism (C3435T and G2677T/A) in IBD; a significant association of 3435T allele and 3435TT genotype has been found with UC (OR = 1.17, P = 0.003 and OR = 1.36, P = 0.017, respectively). In contrast no association with CD and the G2677T/A polymorphism could be demonstrated.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Detection of abnormal lesions recorded by capsule endoscopy. A prospective study comparing endoscopist's and nurse's accuracy.

BACKGROUND AND STUDY AIM: Capsule endoscopy is a non-invasive technique for small bowel examination but its evaluation is time consuming. The aim of this study was to assess whether, following adequate training, an endoscopy nurse is capable of picking up all significant images without reducing the diagnostic accuracy of the procedure. PATIENTS AND METHODS: Between April 2003 and December 2004, a total of 41 consecutive capsule endoscopy studies were blindly reviewed by both an endoscopy nurse and an endoscopist. The two operators had to select all significant images independently and to complete a structured questionnaire. Thirty-nine capsule endoscopy examinations (two studies discharged for premature battery failure) were evaluated. The agreement between the two operators was calculated by kappa statistics (coefficient of agreement). RESULTS: Agreement was excellent for all kind of selected lesions (mean kappa>0.85); the agreement was complete (kappa=1) for site identification, active bleeding, stenosis and negative studies. The greater disagreement (kappa=0.77) was found in cases of subtle mucosal abnormalities (i.e. reduction of villi), which were over-estimated by the nurse. CONCLUSIONS: The preview recordings made by the nurse may increase the cost/effectiveness of the study, by considerably reducing the time needed for the endoscopist to make the final report (about 5-10 min), without compromising final diagnosis.

Capsule Endoscopy↗

PubMed2006

Survival of patients with early hepatocellular carcinoma treated by percutaneous alcohol injection.

BACKGROUND: Once small (<10 mm) nodules, suspicious for hepatocellular carcinoma, are detected in cirrhotics, the European Association for the Study of the Liver guidelines recommend to delay histological confirmation and treatment until they increase in size. AIM: To validate this policy by evaluating survival of 450 cirrhotics in Child-Pugh class A or B with unifocal 'early' hepatocellular carcinoma treated by percutaneous alcohol injection. METHODS: Patients were sorted by nodular size into three groups: < or =10 mm (n = 36, group A), >10 to < or = 20 mm (n = 142, group B) and >20 to < or = 30 mm (n = 272, group C). Overall and tumour-free survivals were estimated by Kaplan-Meier method. RESULTS: In groups A, B and C, mean follow-up was 33 +/- 26, 34 +/- 22 and 35 +/- 25 months (P = 0.89), mean survival time was 63 +/- 54, 57 +/- 48 and 62 +/- 66 months (P = 0.69) and mean tumour-free survival was 44 +/- 47, 46 +/- 58 and 41 +/- 68 months (P = 0.51), respectively. When patients were sorted by Child status, mean survival time was 76 +/- 82 and 38 +/- 29 months in Child A and B (P < 0.0001). CONCLUSIONS: The comparable survival of percutaneous alcohol injection-treated patients with single, early hepatocellular carcinoma sorted by nodular size supports the European Association for the Study of the Liver 'wait-and-see' policy for patients with lesions <10 mm, and suggests that allowing the nodules to grow prior to taking further diagnostic or therapeutic actions would not harm these patients.

Administration, Cutaneous↗

PubMed2006

Variants of OCTN1-2 cation transporter genes are associated with both Crohn's disease and ulcerative colitis.

BACKGROUND: Two variants in the organic cation transporter gene cluster have been recently reported to confer susceptibility to Crohn's disease (CD). AIM: To investigate these variants in CD and ulcerative colitis (UC), and their interaction with CARD15 gene and correlation to clinical subphenotypes. METHODS: Case-control association analysis was performed in 899 patients (444 CD and 455 UC) and 611 controls. The organic cation transporter gene cluster single nucleotide polymorphisms G207G-->C and 1672C-->T, the IGR2198a_1 single nucleotide polymorphism in the IBD5 locus, and the R702W, G908R and L1007finsC variants of CARD15 gene were genotyped by ABI-7700, restriction fragment length polymorphic analysis and multiplex pyrosequencing, respectively. RESULTS: The 1672TT and -207CC genotype frequencies were increased in both CD (OR = 1.5, P = 0.011; OR = 1.6, P = 0.002), and UC (OR = 1.5, P = 0.017; OR = 1.4, P = 0.033), respectively. Compared with controls, the TC haplotype frequency was increased in both CD (36% vs. 44%, P < or = 0.01) and UC (36% vs. 45%, P < or = 0.01). The frequency of the TC haplotype was 43% in CARD15-positive and 44% in CARD15-negative CD, respectively. Similar results were found in UC. In CD a significant association of the TC haplotype was found with presence of perianal fistulae (P = 0.007) and steno-fistulizing behaviour (P = 0.037). In UC, the TC haplotype was more frequent in patients with more extensive disease (P = 0.015), and those on immunosuppressives (P = 0.004). CONCLUSIONS: Organic cation transporter gene cluster variants may confer susceptibility to both CD and UC, and the TC haplotype may influence some clinical features of IBD, but does not interact with CARD15 variants.

Adult↗

PubMed2006

HLA and enteric antineuronal antibodies in patients with achalasia.

The aetiopathogenesis of primary achalasia is largely unknown, although an immunogenetic predisposition is suspected. To establish whether a correlation exists among possible aetiological factors, including class II human leucocyte antigen (HLA) alleles and autoantibodies to enteric neurones, and clinical features of patients with achalasia, a total of 60 patients and 200 healthy subjects were typed by high-resolution HLA-DQ and HLA-DR alleles. Circulating antineuronal antibodies were investigated by using indirect immunofluorescence on enteric neurones of rat ileum and colon and immunoblotting assay in a subset of achalasic patients and in all controls. The DQB1*0502 and DQB1*0601 alleles were significantly increased in patients with achalasia compared with controls (P < 0.03, P < 0.001, respectively). Moreover a negative correlation with the DQB1*0201 allele was found (P = 0.016). As a whole, 14 of 60 (23.3%) achalasia patients were carriers of HLA risk alleles, and 10 of 41 (24.4%) presented antineuronal antibodies. No significant correlation among HLA risk alleles, antineuronal antibodies and clinical features was found. In achalasia, no correlation exists among HLA alleles, antineuronal antibodies and clinical features. However, given the association between achalasia and HLA-DQ1, further research is needed to clarify the role of HLA antigens and antineuronal antibodies in this disease.

Age of Onset↗

PubMed2005

Ultrasonographic and biochemical parameters in the non-invasive evaluation of liver fibrosis in hepatitis C virus chronic hepatitis.

BACKGROUND: Prior studies suggest that platelet counts of <140 000/microL can discriminate patients with different stages of fibrosis. AIM: To determine the added value of abdominal ultrasound analysis of morphological liver features in increasing the diagnostic accuracy of platelet counts for the prediction of liver fibrosis at histology. METHODS: In a retrospective study, clinical records of 1143 chronic hepatitis C patients at their first presentation, naives to both liver biopsy and anti-viral treatment, were reviewed. Sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios of following indices were evaluated singularly or in combination: platelet counts <140 000/microL; nodular liver surface, spleen and portal vein size. RESULTS: All indices had specificity rate of > or =90% in excluding bridging fibrosis/cirrhosis, whereas sensitivity was acceptable (51%) for only platelet counts <140 000/microL. None of the ultrasonographic parameters singularly evaluated and reached an acceptable sensitivity rate. For ruling cirrhosis in or out, specificity rate was > or =82% for all tests, with the highest value reported by portal vein size. Low platelet counts plus nodular liver surface had the best sensitivity. CONCLUSIONS: No additional significant predictive value was given by adding ultrasonographic parameters to low platelet counts, whereas only a mild non-significant improvement in sensitivity was obtained combining platelet counts <140 000/microL with the presence of nodular liver surface. The platelet counts <140 000/microL showed the best predictive value for including both significant fibrosis and cirrhosis.

Chronic Disease↗

PubMed2005

Multiple intrahepatic vascular shunts causing hyperammoniaemic encephalopathy in a patient without liver cirrhosis.

The very rare case of a non-cirrhotic patient with multiple intrahepatic portosystemic and arteriosystemic vascular shunts, presenting with hyperammoniaemic type B encephalopathy and hypoalbuminaemia due to proteinuria, is reported. The correct diagnosis, suspected by abdominal ultrasound and colour-Doppler imaging, was confirmed by hepatic and superior mesenteric angiography. A comparison with the few similar cases existing in the literature is offered.

Aged↗

PubMed2005

Lamivudine therapy in chronic delta hepatitis: a multicentre randomized-controlled pilot study.

BACKGROUND: Delta virus (HDV)-related chronic hepatitis is difficult to treat. AIMS: To evaluate the efficacy of lamivudine 100 mg daily on serum HDV-RNA, hepatitis D virus antibodies and alanine aminotransferase levels, liver histology, and on hepatitis B surface antigen seroconversion. METHODS: Thirty-one hepatitis B surface antigen-positive, HDV-RNA-positive patients with ALT > or = 1.5 upper normal level and compensated liver disease were randomized (1:2 ratio) to placebo (group A, n = 11) or lamivudine (group B, n = 20) for 52 weeks; thereafter, all patients were given lamivudine for 52 weeks and followed up for 16 weeks. RESULTS: Twenty-five patients (81%) completed the study. No patient was HDV-RNA-negative at week 52; three patients (11%) were negative at week 104. Two of them remained HDV-RNA-negative at week 120, and one lost the hepatitis B surface antigen without seroconversion. Paired pre-treatment and week 104 liver biopsies were available from 19 patients: of which three of seven (43%) from group A and two of 12 patients (17%) from group B had a > or =2 point decrease in the Ishak necroinflammatory score. CONCLUSION: A sustained complete response was achieved in 8% of hepatitis D virus-infected patients treated with lamivudine and a partial histological response in 26% of them. Hepatitis D virus viraemia was unaffected, even in patients when hepatitis B virus replication was lowered by lamivudine therapy.

Adult↗

PubMed2005

Cytokine gene polymorphisms in gastric cancer patients from two Italian areas at high and low cancer prevalence.

Polymorphisms of interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL1-RN), and tumor necrosis factor-alpha (TNF-alpha) genes are supposed to be key determinants of gastric cancer risk. Our aim was to study the association between these polymorphisms and gastric cancer in two areas characterized by high (Pavia/Bologna, North Italy) and low (San Giovanni Rotondo, South Italy) gastric cancer prevalence. Genomic DNA was obtained from 216 healthy donors and 98 gastric cancer patients from Pavia and Bologna, and 146 healthy donors and 86 gastric cancer patients from San Giovanni Rotondo. Two SNP in IL-1beta (-511 C/T) and TNF-alpha (-308 G/A) as well as the VNTR polymorphism of IL-1RN locus were studied. A significant linkage disequilibrium was found between IL-1beta -511 and IL-1RN. Genotype and allele frequencies at the IL-1beta, IL-1RN, and TNF-alpha loci in gastric cancer cases were not significantly different from controls. An epistatic effect between IL-1beta -511 and IL-1RN was found with the IL-1beta -511C/IL-1RN*2 haplotype conferring a significant protection against the intestinal-type of gastric cancer in the Southern population. In conclusion, IL-1beta, IL1-RN, and TNF-alpha genotypes are not associated with gastric cancer in Italian patients. An epistatic interrelationship between IL-1beta -511 and IL-1RN confers protection against gastric cancer in low-risk Italian population.

Adolescent↗

PubMed2005

HLA-DRB1 alleles may influence disease phenotype in patients with inflammatory bowel disease: a critical reappraisal with review of the literature.

PURPOSE: The HLA region has been implicated in determining the disease susceptibility or the clinical phenotype of inflammatory bowel disease. The aim of this study was to assess the relation between HLA-DRB1 alleles with the clinical features of Crohn's disease and ulcerative colitis and the presence of anti-neutrophil cytoplasmic and anti-Saccharomyces cerevisiae antibodies. METHODS: Blood samples were obtained from 102 Crohn's disease patients, 114 ulcerative colitis patients, and 264 unrelated healthy controls. Anti-neutrophil cytoplasmics were detected by a standard immunofluorescence method, and anti-Saccharomyces cerevisiaes were examined by an enzyme-linked immunosorbent assay immunoglobulin G/immunoglobulin A commercial assay. HLA-DRB1 typing of 26 alleles was performed by polymerase chain reaction sequence-specific primes. Patients were phenotyped according to gender, disease location, extent, and behavior, surgical resection, need of steroid, and anti-neutrophil cytoplasmic/anti-Saccharomyces cerevisiae status. RESULTS: As a whole, after applying Bonferroni's correction for multiple comparisons, no significant association of HLA-DRB1 alleles with Crohn's disease or ulcerative colitis was found. After stratifying HLA-DRB1 alleles by clinical phenotypes of patients with ulcerative colitis, an excess of DRB1*1309*1320*1325*1329 allele (DR13) was found in conjunction with pancolitis (P < 0.0001), surgical resection (P < 0.0003), and extraintestinal manifestations (P < 0.0001). In Crohn's disease patients, an excess of DRB1*0304*0305*0307*0309 allele (DR3) was found in those with colonic disease (P < 0.0001) and patients with extraintestinal manifestations (P = 0.0003). This statistical association, however, emerged in only 3 of 114 patients with ulcerative colitis and in 3 of 102 patients with Crohn's disease. We found no association with the presence of anti-Saccharomyces cerevisiae or anti-neutrophil cytoplasmic. CONCLUSIONS: Some clinical features of Crohn's disease and ulcerative colitis may be influenced by specific HLA-DR alleles; in particular, in ulcerative colitis some alleles appear to segregate with more aggressive disease, whereas in Crohn's disease different alleles cosegregate in patients with colonic disease and extraintestinal manifestations.

Adolescent↗

PubMed2005

An optimized experimental protocol based on neuro-evolutionary algorithms application to the classification of dyspeptic patients and to the prediction of the effectiveness of their treatment.

OBJECTIVE: This paper aims to present a specific optimized experimental protocol (EP) for classification and/or prediction problems. The neuro-evolutionary algorithms on which it is based and its application with two selected real cases are described in detail. The first application addresses the problem of classifying the functional (FD) or organic (OD) forms of dyspepsia; the second relates to the problem of predicting the 6-month follow-up outcome of dyspeptic patients treated by helicobacter pylori (HP) eradication therapy. METHODS AND MATERIAL: The database built by the multicentre observational study, performed in Italy by the NUD-look Study Group, provided the material studied: a collection of data from 861 patients with previously uninvestigated dyspepsia, being referred for upper gastrointestinal endoscopy to 42 Italian Endoscopic Services. The proposed EP makes use of techniques based on advanced neuro-evolutionary systems (NESs) and is structured in phases and steps. The use of specific input selection (IS) and training and testing (T and T) techniques together with genetic doping (GenD) algorithm is described in detail, as well as the steps taken in the two benchmark and optimization protocol phases. RESULTS: In terms of accuracy results, a value of 79.64% was achieved during optimization, with mean benchmark values of 64.90% for the linear discriminant analysis (LDA) and 68.15% for the multi layer perceptron (MLP), for the classification task. A value of 88.61% was achieved during optimization for the prediction task, with mean benchmark values of 49.32% for the LDA and 70.05% for the MLP. CONCLUSIONS: The proposed EP has led to the construction of inductors that are viable and usable on medical data which is representative but highly not linear. In particular, for the classification problem, these new inductors may be effectively used on the basal examination data to support doctors in deciding whether to avoid endoscopic examinations; whereas, in the prediction problem, they may support doctors' decisions about the advisability of eradication therapy. In both cases the variables selected indicate the possibility of reducing the data collection effort and also of providing information that can be used for general investigations on symptom relevance.

Algorithms↗

PubMed2005

Idiopathic achalasia is not allelic to alacrima achalasia adrenal insufficiency syndrome at the ALADIN locus.

BACKGROUND: Evidence indicates that patients with familial achalasia associated with Allgrove or triple-A syndrome (i.e. alacrima, achalasia and adrenocorticotropin-resistant adrenal insufficiency with neurological impairment) have mutations of the alacrima achalasia adrenal insufficiency syndrome (AAAS) gene. AIM: The present study was aimed at identifying possible AAAS gene mutations in patients with established idiopathic non-familial achalasia. METHODS: Genomic DNA of 41 patients was isolated from peripheral blood cells using standard methods. The 16 exons of the AAAS gene (or ALADIN) were screened for mutations using the denaturing high-performance liquid chromatography method. RESULTS: Four heterozygous nucleotidic variations have been identified in patients with idiopathic achalasia, among which three were exonic conservative polymorphisms [i.e. D138D (GAT-->GAC), L227L (TTG-->CTG) and F285F (TTC-->TTT) in exons 5, 7 and 9, respectively]. The fourth nucleotidic variation was located in intron 13 (IVS14-23delT). All variants have been regarded as polymorphisms resulting in a normal ALADIN protein since they are either conservative or lying outside the consensus splice sites. CONCLUSIONS: Our data do not support a pathogenetic role for common AAAS gene mutations in patients with idiopathic achalasia as seen in Allgrove syndrome. These findings suggest the participation of different mechanisms in the pathogenesis of idiopathic achalasia.

Adult↗

PubMed2005

Causes of portal venous thrombosis in cirrhotic patients: the role of genetic and acquired factors.

OBJECTIVE AND METHODS: We compared frequencies of three common prothrombotic mutations (factor V Leiden, the G20210A mutation of the prothrombin gene, and homozygosity for C677T methylenetetrahydrofolate reductase) in 219 cirrhotic patients, 43 with and 176 without portal vein thrombosis (PVT). The following variables were related to PVT: prothrombin levels, platelet count, Child-Pugh classification, previous abdominal surgery, number of decompensation events, size of varices, red markers on varices, and sclerotherapy. All patients were followed up for a mean period of 18 months (range 10-30). RESULTS: Prothrombotic mutations were detected in 64 of the 219 cirrhotic patients (29.2%), at equal frequency in patients with or without PVT. At univariate analysis, PVT was associated with Child-Pugh classes B and C, signs of liver decompensation, large varices with red markings, sclerotherapy, and abdominal surgery. At multivariate analysis, PVT was associated with sclerotherapy [odds ratio (OR) 4.9, 95% confidence interval (CI) 2.2-11] and previous surgery (OR 2.8, 95% CI 1.2-6.3). The combination of the two acquired factors increased the risk of PVT, whereas the combination of local with genetic defects did not. Only a single patient with genetic thrombophilia and without PVT at inclusion developed the complication during follow-up, concomitantly with the development of hepatocellular carcinoma. CONCLUSION: In cirrhotic patients prothrombotic mutations by themselves are not causative of PVT. Sclerotherapy and previous abdominal surgery favour the development of two-thirds of cases of PVT; in the remaining cases the pathogenesis remains elusive.

Adult↗

PubMed2005

Multidrug resistance 1 gene polymorphisms are not associated with inflammatory bowel disease and response to therapy in Italian patients.

BACKGROUND: Host genetic factors may be important in determining not only disease susceptibility, but also disease behaviour and response to therapy in inflammatory bowel disease. Two polymorphisms (C3435T and G2677T/A) of the multidrug resistance 1 gene have been correlated with the altered P-glycoprotein expression and function in humans, and associated with predisposition to ulcerative colitis and Crohn's disease. AIM: To investigate the contribution of these polymorphisms to disease susceptibility and response to medical therapy. METHODS: A total of 946 inflammatory bowel disease patients (478 Crohn's disease, 272 males, mean age 43 +/- 14 years and 468 ulcerative colitis, 290 males, mean age 48 +/- 15 years) and 450 healthy controls were genotyped for the single nucleotide polymorphisms C3435T and G2677T/A. Patients were also classified on the basis of response to medical therapy (mesalazine, steroids, immunosuppressives and infliximab). RESULTS: Both single nucleotide polymorphisms were in Hardy-Weinberg equilibrium and significant linkage disequilibrium. No significant difference in the allele, genotype, and haplotype frequencies was found in both Crohn's disease and ulcerative colitis patients compared with the controls. No correlation with clinical features was found, except for a reduced frequency of extra-intestinal manifestations in Crohn's disease patients with the G2677T genotype (40%) compared with GG2677 and 2677TT genotypes (54% and 58%, respectively) (P = <0.02). No significant difference was also found after stratifying the patients on the basis of their response to medical therapy. CONCLUSION: The investigated polymorphisms of the multidrug resistance 1 gene have no significant role in disease susceptibility and response to medical therapy in our Italian population of inflammatory bowel disease patients.

Case-Control Studies↗

PubMed2005

A randomized controlled trial of pegylated interferon alpha-2a (40 KD) or interferon alpha-2a plus ribavirin and amantadine vs interferon alpha-2a and ribavirin in treatment-naïve patients with chronic hepatitis C.

We determined whether triple therapy comprising amantadine (AMA), ribavirin (RBV) and either peginterferon (PEG-IFN) alpha-2a or conventional IFN alpha-2a would improve sustained virological response (SVR) rates over dual therapy with IFN alpha-2a and RBV in patients with chronic HCV infection. A total of 362 treatment-naïve patients were randomized to 48 weeks of treatment with: PEG-IFN alpha-2a 180 microg/week (group A) or IFN alpha-2a 3 MU tiw (groups B and C). All patients received RBV 1000 or 1200 mg/day and those in groups A and B received AMA 200 mg/day. SVR was defined as an undetectable HCV RNA after 24 weeks of untreated follow-up. At the end of therapy, 74.4% (95% CI 0.66-0.82) of patients in group A were HCV RNA-negative compared with 42.5% (95% CI 0.33-0.50) of those in group B (P = 0.0001) and 48.8% (95% CI 0.40-0.56) of those in group C. SVR was achieved in a significantly greater proportion of patients in group A compared with groups B and C: 65.3% (95% CI 0.53-0.56), 33.3% (95% CI 0.25-0.41) and 44.6% (95% CI 0.36-0.53; P = 0.0001) respectively. In patients with genotype 1, SVR rates were 55.2, 22.8 and 28.8% with the three regimens respectively. Factors independently associated with SVR were HCV genotype 2 or 3, therapy with PEG-IFN, female gender and age. In treatment-naive patients with chronic hepatitis C, triple therapy with PEG-IFN alpha-2a, RBV and AMA produces higher SVR than dual or triple therapy with conventional IFN alpha-2a.

Adolescent↗

PubMed2005

Proton-pump inhibitors and outcome of endoscopic hemostasis in bleeding peptic ulcers: a series of meta-analyses.

OBJECTIVE: To perform meta-analyses of studies on outcome of bleeding ulcers of different proton-pump inhibitors (PPIs) regimens, after stratification of patients by endoscopic stigmata, and analysis of studies with and without endotherapy. METHODS: A total of 35 randomized trials comparing PPIs to placebo and/or H2-receptor antagonists (H2RAs) in 4,843 patients with high-risk endoscopic stigmata were retrieved. Outcomes were rebleeding, surgery, and mortality. RESULTS: Monotherapy with oral or bolus PPIs was superior to placebo and H2RAs in reducing rebleeding in both bleeders and nonbleeders at index endoscopy; the need for surgery was reduced only when compared to H2RAs. In nonbleeders, PPI monotherapy was as effective as a combination of endotherapy with H2RAs. A combination of endotherapy with PPIs was superior to monotherapy in reducing bleeding and surgery, and superior to endotherapy alone in minimizing rebleeding, but not surgery; the benefit was lost when confronted to endotherapy plus H2RAs, whether PPIs were given as infusion or bolus. By pooling data from studies comparing high doses of PPIs as continuous infusion versus regular doses as intermittent bolus, rebleeding, surgery, and mortality were not significantly different. CONCLUSIONS: Combination of endotherapy with either PPIs or H2RAs is indicated for nonbleeding ulcers at endoscopy with the intent to reduce rebleeding and surgery. Its value may extend to bleeding lesions, but current data are scanty. The benefit appears to be independent from route and doses of PPIs, as oral, bolus, or infusional methods are all effective.

Anti-Ulcer Agents↗

PubMed2004

Proton-pump inhibitors reduce the risk of uncomplicated peptic ulcer in elderly either acute or chronic users of aspirin/non-steroidal anti-inflammatory drugs.

BACKGROUND: Although administration of gastroprotective drugs may reduce the risk of peptic ulcers associated with the chronic use of non-steroidal anti-inflammatory drugs or aspirin, no consensus exists as to whether this co-therapy is effective for short-term prevention, particularly in old age. AIM: To evaluate the risk of peptic ulcer associated with acute and chronic non-steroidal anti-inflammatory drugs or aspirin therapy in elderly subjects, and the influence of antisecretory treatment on this risk. METHODS: The study included 676 elderly non-steroidal anti-inflammatory drugs or aspirin users and 2435 non-users who consecutively underwent upper gastrointestinal endoscopy. The use of non-steroidal anti-inflammatory drugs and/or aspirin as well as antisecretory drugs (H2-blockers and proton-pump inhibitors) was evaluated by a structured interview. Diagnosis of gastric and duodenal ulcer as well as Helicobacter pylori infection were carried out by endoscopy and histological examination of the gastric mucosa. RESULTS: About 47.3% of patients were acute and 52.7% chronic users of non-steroidal anti-inflammatory drugs or aspirin. The risk of peptic ulcer, adjusted for age, gender, H. pylori infection and antisecretory drug use was higher in acute (gastric ulcer: odds ratio, OR = 4.47, 95% CI: 3.19-6.26 and duodenal ulcer: OR = 2.39, 95% CI: 1.73-3.31) than chronic users (gastric ulcer: OR = 2.80, 95% CI: 1.97-3.99 and duodenal ulcer: OR = 1.68, 95% CI: 1.22-2.33). Proton-pump inhibitor treatment was associated with a reduced risk of peptic ulcer in both acute (OR = 0.70, 95% CI: 0.24-2.04) and chronic (OR = 0.32, 95% CI: 0.15-0.67) non-steroidal anti-inflammatory drugs/aspirin users. Conversely, concomitant treatment with H2-blockers was associated with a significantly higher risk of peptic ulcer both in acute (OR = 10.9, 95% CI: 3.87-30.9) and chronic (OR = 6.26, 95% CI: 2.56-15.3) non-steroidal anti-inflammatory drugs/aspirin users than non-users. Proton-pump inhibitor treatment resulted in an absolute risk reduction of peptic ulcer by 36.6% in acute and 34.6% in chronic non-steroidal anti-inflammatory drugs/aspirin users; indeed, the number needed to treat to avoid one peptic ulcer in elderly non-steroidal anti-inflammatory drugs/aspirin users was three both in acute and chronic users. CONCLUSIONS: These findings suggest that proton-pump inhibitor co-treatment is advisable in symptomatic elderly patients who need to be treated with non-steroidal anti-inflammatory drugs and/or aspirin for a short period of time.

Acute Disease↗