Biomedical subjects
P A Bonis
Publications and source records attributed to P A Bonis.
Interferon and ribavirin for patients with chronic hepatitis C who did not respond to previous interferon therapy: a meta-analysis of controlled and uncontrolled trials.
The efficacy of interferon (IFN) combined with ribavirin for the treatment of patients with hepatitis C who failed to respond to initial IFN therapy is not well established. The primary goal of this study was to perform a systematic review of the literature evaluating the efficacy of combination therapy in nonresponders. Studies were retrieved from MEDLINE, abstracts of scientific meetings, and review of the bibliographies of retrieved studies. Controlled trials were included in the primary analysis whereas uncontrolled trials and trials reported as abstracts were included for sensitivity analysis. The primary endpoints were biochemical and virologic response. A combined estimate of the odds ratio (OR) for each endpoint was obtained by using the random effects model. The number needed to treat (NNT) was calculated by taking the inverse of the pooled risk difference. Nine controlled trials (789 patients) were identified. Six months after treatment, the overall sustained biochemical and virologic responses to 24 weeks of combination therapy were 15.2% and 13.2% with a common OR of 3.8 (95% confidence interval [CI] 2.2-6.7) and 4.9 (95% CI 2.1-11.2) compared with patients treated with IFN monotherapy. The pooled risk difference for the sustained virologic response (SVR) to combination therapy was 7% (95% CI 2-13). The NNT was 14 (95% CI 8-50), suggesting that approximately 14 patients would need to be treated with 6 months of combination therapy for 1 patient to have a SVR. A number of variables were associated with a high response rate in individual studies. Sensitivity analysis of preliminary trials suggest a higher response rate with longer duration of therapy and non-type 1 genotypes.
Ringed esophagus: unclear relationship to gastroesophageal reflux disease.
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Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease.
BACKGROUND: Heartburn affects 25% of the adult population on a monthly basis and represents the core symptom of gastro-oesophageal reflux disease (GORD). Treatment is readily available and puts a large demand on healthcare budgets. Research in the past has focused largely on the treatment of oesophagitis. A majority of GORD patients show no endoscopic abnormalities and in daily practice most patients are treated empirically. OBJECTIVES: Summarise, quantify and compare the efficacy of the short-term use of proton pump inhibitors (PPI), H2-receptor antagonists (H2RA) and prokinetics in the empirical treatment of GORD and the treatment of endoscopy negative reflux disease (ENRD). SEARCH STRATEGY: Electronic searches were performed of the Cochrane Controlled Trials Register, MEDLINE and EMBASE. Bibliographies were screened. SELECTION CRITERIA: Included were randomised controlled trials focussing on symptomatic outcome after short-term treatment for GORD using proton pump inhibitors, H2-receptor antagonists or prokinetic agents. Participants had to be classifiable in the empirical treatment group (no endoscopy used in treatment allocation) or in the endoscopy negative reflux disease group (no endoscopic signs of erosive oesophagitis). DATA COLLECTION AND ANALYSIS: Data from included trials were extracted by two reviewers independently. The impact of interventions was expressed as relative risks (RR) together with 95% confidence intervals (95% CI). Meta-analysis was only performed if there were sufficient trials of similar comparisons reporting the same outcomes. Relative risks were combined for binary outcomes. MAIN RESULTS: Twenty-one trials were included: eleven in the empirical treatment group, seven in the ENRD group and three in both. In empirical treatment of GORD the RR for heartburn remission in placebo-controlled trials for PPI was 0.35 (1 trial, 95% CI 0.26 to 0.46), for H2RAs 0.77 (2 trials, 95% CI 0.60 to 0.99) and for prokinetics 0.86 (1 trial, 95% CI 0.73 to 1.01). In direct comparison PPIs were significantly (p<0.05) more effective than H2RAs (3 trials, RR 0.67, 95% CI 0.57 to 0.80) and prokinetic's (2 trials, RR 0.53, 95% CI 0.32 to 0.87). In treatment of ENRD, RR for heartburn remission for PPI versus placebo was 0.68 (4 trials, 95% CI 0.53 to 0.88) and for H2RA versus placebo was 0.84 (2 trials, 95% CI 0.74 to 0.95). The RR for PPI versus H2RA was 0.69 (2 trials, 95% CI 0.39 to 1.20) and versus prokinetic 0.72 (1 trial, 95% CI 0.56 to 0.92). REVIEWER'S CONCLUSIONS: The findings in this review suggest that antisecretory drugs are effective in the empirical treatment of complaints likely to originate from GORD and in treatment of ENRD and furthermore that PPIs are superior to H2RAs in empirical treatment of typical GORD symptoms.
Clinical outcomes after hepatitis C infection from contaminated anti-D immune globulin.
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Low-dose methotrexate in primary biliary cirrhosis.
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Methotrexate improves biochemical tests in patients with primary biliary cirrhosis who respond incompletely to ursodiol.
BACKGROUND & AIMS: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of presumed autoimmune etiology. Ursodeoxycholic acid (UDCA), methotrexate, and colchicine each have shown promise in its treatment. The value of combining 2 or 3 of these drugs is uncertain. The aim of this study was to determine whether addition of methotrexate to the treatment regimen improves results of liver biochemical tests in patients with antimitochondrial antibody-positive PBC who responded incompletely to treatment with UDCA and colchicine. METHODS: Methotrexate was added to the treatment regimen of 10 consecutive patients with antimitochondrial antibody-positive PBC who had an incomplete response to therapy with UDCA alone or in combination with colchicine. The primary end point was biochemical response. Symptoms and histological changes were also recorded. RESULTS: Addition of methotrexate to the UDCA plus colchicine regimen was associated with a significant reduction in serum alkaline phosphatase (ALP) levels beyond those found with UDCA and colchicine alone or in combination. Median ALP concentration was 389 IU (range, 247-1013 IU) at baseline, 300 IU (range, 155-467 IU) after treatment with UDCA plus colchicine, and 120 IU (range, 66-351 IU) after treatment with methotrexate. CONCLUSIONS: Addition of methotrexate to a regimen of UDCA and colchicine may be beneficial for patients with PBC who respond incompletely to treatment with UDCA and colchicine.
A predictive model for the development of hepatocellular carcinoma, liver failure, or liver transplantation for patients presenting to clinic with chronic hepatitis C.
OBJECTIVE: Chronic infection with hepatitis C may lead to the development of cirrhosis, liver failure, and hepatocellular carcinoma. However, not all patients progress to these endpoints. Ideally, clinicians could improve their capability of stratifying the risk and the time frame within which their patients will progress to these endpoints. The purpose of the present study was to construct statistical models predicting disease progression for individual patients. METHODS: Study endpoints were the development of hepatocellular carcinoma, liver transplantation, or death due to liver disease. The study cohort was 256 patients with hepatitis C acquired from either blood transfusion or use of intravenous drugs. During follow-up, 17 patients developed hepatocellular carcinoma, seven received liver transplantation, and 12 died from liver disease. RESULTS: On multivariate analysis a history of decompensation (relative risk [RR] 4.321, 95% confidence interval [CI] 1.777-10.511) and the serum albumin (RR 0.253, 95% CI 0.136-0.474) were independently associated with the study endpoints. Patients without a history of decompensation and with a serum albumin > or = 4.1 mg/dl had a 3.2% chance of developing the study endpoints within 5 yr. Patients with a history of decompensation and a serum albumin < 4.1 mg/dl had a 40% chance of developing a study endpoint within 5 yr. Baseline genotype and quantitative RNA were not associated with development of the clinical endpoints, with the exception of patients coinfected with two or more genotypes. CONCLUSION: Thus, the serum albumin and a history of decompensation are useful for predicting the development of hepatocellular carcinoma, liver transplantation, and death due to liver disease among patients with hepatitis C.
Correlation of biochemical response to interferon alfa with histological improvement in hepatitis C: a meta-analysis of diagnostic test characteristics.
The current goal of interferon treatment for chronic hepatitis C is to normalize alanine aminotransferase (ALT) and to eradicate detectable viral RNA. Many patients do not achieve this objective during treatment, and most do not sustain these outcomes after interferon is discontinued. However, biochemical or virological responses to interferon may not reflect accurately the histological consequences of therapy. The aim of this study was to determine the extent to which the biochemical measures reflect the histological outcomes in the treatment of hepatitis C with interferon alfa using a meta-analysis of diagnostic test characteristics. The data sources were English and non-English language studies retrieved from Medline (from 1966 to December 1995). The study selection included studies in which interferon alfa was used for treatment of chronic hepatitis C with liver biopsies performed before and after therapy. Data on histological and biochemical outcomes were extracted independently by two reviewers. Two separate criteria were used for defining histological response. When strict definitions of histological improvement were considered, histology improved in 28% (95% confidence interval [95% CI], 17%-43%) of patients after interferon treatment. The sensitivity and specificity of the ALT for determining histological change were 70% (95% CI, 56%-81%) and 66% (95% CI, 56%-75%), respectively. As many as 17% (95% CI, 9%-30%) of subjects with an abnormal ALT at the end of therapy may have improved histologically after interferon therapy. When less stringent definitions of histological improvement were considered, 62% (95% CI, 51%-72%) improved after therapy. The sensitivity and specificity of the ALT for determining histological change were 55% (95% CI, 44%-65%) and 75% (95% CI, 67%-81%), respectively. As many as 51% (95% CI, 38%-64%) may have improved, despite failure to normalize ALT. A substantial number of patients may improve histologically after interferon therapy. The significance of histological changes observed after interferon therapy must be weighed against the limitations of liver biopsy and the uncertain natural history of hepatitis C. Nevertheless, the ALT does not always reflect liver histology accurately after interferon alfa treatment and may underestimate histological improvement.
The challenge of irritable bowel syndrome.
Irritable bowel syndrome is a common disorder with symptom complexes that can include diarrhea, constipation, pain and bloating. After other disorders have been excluded, treatment should be directed at the predominant symptoms and gauged to their severity. A careful balance between a thoughtful investigation and the expense and dangers of overtesting must always be considered. Most patients continue to have persistent symptoms several years after the original diagnosis.
Abscesses in Crohn's disease: outcome of medical versus surgical treatment.
GOALS: To compare the long-term outcome of medical, percutaneous, and surgical treatment of abdominal and pelvic abscesses complicating Crohn's disease. STUDY: All patients with Crohn's disease and an abdominal abscess treated at one institution during a 10-year period were retrospectively identified. We reviewed hospital and outpatient records and contacted patients for telephone interviews. Outcome measures included abscess recurrence, subsequent surgery for Crohn's disease, and medications used at the time of most recent follow-up. RESULTS: Fifty-one subjects were identified, with a mean follow-up of 3.75 years. Fewer patients developed recurrent abscesses after initial surgical drainage and bowel resection (12%) than patients treated with medical therapy only or percutaneous drainage (56%) (p = 0.016). One half of the patients treated nonoperatively ultimately required surgery, whereas only 12% of those treated with initial surgery required reoperation during the follow-up period (p = 0.010). Most failures of nonoperative therapy occurred within 3 months. Medication use was similar between the treatment groups at the time of most recent follow-up. CONCLUSIONS: In this series, surgical management of abscesses in Crohn's disease was more effective than medical treatment or percutaneous drainage for prevention of abscess recurrence. However, nonoperative therapy prevented subsequent surgery in half of the patients and may be a reasonable treatment option for some patients.