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Biomedical subjects

Yves Benhamou

Publications and source records attributed to Yves Benhamou.

At least 37 records · Page 2Linked to original sources
PubMed2004

Special considerations in the initiation and management of antiretroviral therapy in individuals coinfected with HIV and hepatitis C.

BACKGROUND: Although hepatitis C (HCV) treatment efficacy has improved in recent years, the majority of HIV/HCV-coinfected individuals may not enjoy the full benefits of these treatments and appropriate HIV management is crucial. Evidence is accumulating regarding the impact of HIV/HCV coinfection on the response to, and safety and tolerability of, antiretroviral therapy (ART) in this population. METHODS: Computerized, English-language literature searches of MEDLINE and PubMed databases (January 1985 to May 2004) for studies of HIV and HCV infection in humans to examine critically (a) the impact of HCV on the HIV virologic and immunologic response to ART; (b) the safety and tolerability of ART in coinfected individuals; and (c) the relationship between immune suppression and immune restoration on hepatic injury. RESULTS: Three key messages emerged regarding the use of ART in HIV/HCV-coinfected individuals: (a) although HCV appeared to have no impact on HIV virologic response, the data are equivocal regarding immunologic response; (b) morbidities associated with HCV infection, such as insulin resistance, diabetes, mitochondrial dysfunction, and liver inflammation, are also associated toxicities of ART, and (c) both immune suppression and restoration can contribute to the onset and acceleration of HCV-related liver disease. CONCLUSIONS: The CD4 cell count threshold for initiating ART in HIV/HCV-coinfected patients may be higher because of the impact of immune suppression and restoration on the onset of HCV-associated liver disease and the possibility of a blunted immune response to ART at lower CD4 cell counts. Further, overlapping morbidity between HCV-related mitochondrial and metabolic disease manifestations and ART toxicities warrant careful attention by clinicians.

AIDS-Related Opportunistic Infections↗
PubMed2004

Overview of the diagnostic value of biochemical markers of liver fibrosis (FibroTest, HCV FibroSure) and necrosis (ActiTest) in patients with chronic hepatitis C.

SUMMARY: BACKGROUND: Recent studies strongly suggest that due to the limitations and risks of biopsy, as well as the improvement of the diagnostic accuracy of biochemical markers, liver biopsy should no longer be considered mandatory in patients with chronic hepatitis C. In 2001, FibroTest ActiTest (FT-AT), a panel of biochemical markers, was found to have high diagnostic value for fibrosis (FT range 0.00-1.00) and necroinflammatory histological activity (AT range 0.00-1.00). The aim was to summarize the diagnostic value of these tests from the scientific literature; to respond to frequently asked questions by performing original new analyses (including the range of diagnostic values, a comparison with other markers, the impact of genotype and viral load, and the diagnostic value in intermediate levels of injury); and to develop a system of conversion between the biochemical and biopsy estimates of liver injury. RESULTS: A total of 16 publications were identified. An integrated database was constructed using 1,570 individual data, to which applied analytical recommendations. The control group consisted of 300 prospectively studied blood donors. For the diagnosis of significant fibrosis by the METAVIR scoring system, the areas under the receiver operating characteristics curves (AUROC) ranged from 0.73 to 0.87. For the diagnosis of significant histological activity, the AUROCs ranged from 0.75 to 0.86. At a cut off of 0.31, the FT negative predictive value for excluding significant fibrosis (prevalence 0.31) was 91%. At a cut off of 0.36, the ActiTest negative predictive value for excluding significant necrosis (prevalence 0.41) was 85%. In three studies there was a direct comparison in the same patients of FT versus other biochemical markers, including hyaluronic acid, the Forns index, and the APRI index. All the comparisons favored FT (P < 0.05). There were no differences between the AUROCs of FT-AT according to genotype or viral load. The AUROCs of FT-AT for consecutive stages of fibrosis and grades of necrosis were the same for both moderate and extreme stages and grades. A conversion table was constructed between the continuous FT-AT values (0.00 to 1.00) and the expected semi-quantitative fibrosis stages (F0 to F4) and necrosis grades (A0 to A3). CONCLUSIONS: Based on these results, the use of the biochemical markers of liver fibrosis (FibroTest) and necrosis (ActiTest) can be recommended as an alternative to liver biopsy for the assessment of liver injury in patients with chronic hepatitis C. In clinical practice, liver biopsy should be recommended only as a second line test, i.e., in case of high risk of error of biochemical tests.

Journal Article↗
PubMed2004

Prospective analysis of discordant results between biochemical markers and biopsy in patients with chronic hepatitis C.

BACKGROUND: The FibroTest and ActiTest are noninvasive biochemical markers of liver injury that are intended for use as alternatives to liver biopsy in patients with chronic hepatitis C. The aims of this study were to assess the quality of biopsy and the prevalence of discordances between biopsy and markers, to identify factors associated with discordances, and to attribute these discordances to either markers or biopsy failure. METHODS: Fibrosis stage and activity grade were prospectively assessed on the same day by a liver biopsy and by markers. On the basis of risk factors for failure and independent endpoints, discordance was classified as being attributable to biopsy or to markers. RESULTS: Only 74 of 537 patients (14%) had a biopsy size > or =25 mm. Discordance was observed in 154 of 537 patients (29%), including 16% for fibrosis staging and 17% for activity grading. Steatosis, an inflammatory profile, and biopsy size were associated with discordance. Discordance was attributable to failure of markers in 13 patients (2.4%) and to biopsy failure in 97 (18%; P <0.001 vs Fibrotest and Actitest), and was nonattributable in 44 patients (8.2%). The most frequent failures attributable to markers were false negatives (1.3%) attributable to inflammation. The most frequent failures attributable to biopsy were false negatives of activity grading (10.1%) and of fibrosis staging (4.5%), both associated with smaller biopsy size and steatosis. False positives of fibrosis staging (3.5%) were associated with fragmented biopsies. CONCLUSION: In this series, the size of liver biopsy is adequate in only a minor proportion (approximately 14%) of patients with chronic hepatitis C. When biopsy and marker results are discordant, a reason can be identified in more than two-thirds of cases and, in those cases, biopsy failure is >7 times more common than diagnostic failure of markers.

Adult↗
PubMed2004

Antiretroviral therapy and HIV/hepatitis B virus coinfection.

Among human immunodeficiency virus (HIV)-infected individuals, the prevalence of hepatitis B surface antigen (HBsAg) seropositivity is approximately 10-fold higher than in the general population. HIV/hepatitis B virus (HBV)-coinfected patients have an increased risk of cirrhosis and liver-disease-related death. The strategy and management of anti-HBV therapy in HIV-infected persons must take into consideration both viral infections. Among HIV/HBV-coinfected patients, lamivudine promptly inhibits HBV replication. The emergence of resistance to lamivudine has been documented in HBV strains. Adefovir has been shown to be effective in the treatment of lamivudine-resistant HBV in HIV/HBV-coinfected patients. Tenofovir has recently been shown to have significant activity against both HIV and HBV. HBsAg seropositivity has been identified as an independent predictor of highly active antiretroviral therapy-related hepatotoxicity. However, further research is needed to determine the exact role of HBV and the mechanisms involved in antiretroviral-associated hepatotoxicity in HBV/HIV-coinfected patients.

Adenine↗
PubMed2004

Pegylated interferon alpha 2b and ribavirin in HIV/hepatitis C virus-co-infected non-responders and relapsers to IFN-based therapy.

BACKGROUND: Pegylated interferon alpha (PEG-IFN-alpha) and ribavirin is the most effective available treatment for chronic hepatitis C virus (HCV) infection. Its role in HIV/HCV-co-infected patients who have failed IFN-based therapy is unclear. OBJECTIVE: The aim of this study was to determine the safety and efficacy of this therapy in HIV/HCV-co-infected non-responders and relapsers. DESIGN: An open-label cohort study of 32 non-responders and relapsers to IFN (with or without ribavirin). Patients were treated for 48 weeks with PEG-IFN-alpha 2b and ribavirin. MAIN OUTCOME MEASURE: A sustained virological response (SVR) defined as a negative HCV-RNA level 24 weeks after the end of treatment. RESULTS: The mean age of the patients was 40 years; 78% were men, 67% had genotype 1, and 36% had bridging fibrosis or cirrhosis. The majority had a CD4 cell count greater than 200 cells/microl (97%) and an undetectable HIV-RNA level (81%). Fifteen patients (47%) withdrew because of adverse events, predominantly neuropsychiatric. In an intention-to-treat analysis, a SVR was observed in five patients (16%); 9% with genotype 1 versus 29% with genotype 3 and 33% with genotype 4 (P = NS). Additional, but statistically non-significant, univariate predictors of response were lower serum HCV-RNA (P = 0.07) and higher alanine aminotransferase levels (P = 0.055) at baseline. No patient with bridging fibrosis or cirrhosis responded. Treatment had a minimal impact on HIV parameters. CONCLUSION: PEG-IFN-alpha 2b and ribavirin is a potentially useful therapy in HIV/HCV-co-infected patients who have failed standard IFN-based regimens. Strategies to improve adherence are vital so as to maximize long-term response rates.

Adult↗
PubMed2004

Decreased frequencies of virus-specific T helper type 1 cells during interferon alpha plus ribavirin treatment in HIV-hepatitis C virus co-infection.

Anti-hepatitis C virus (HCV) treatment combining IFN-alpha and ribavirin (IFN+R) has still poorly defined effects on immune responses. Frequencies of T helper (Th) type 1 cells specific for HCV, cytomegalovirus (CMV) and HIV were measured in chronically HCV-infected patients with or without HIV co-infection during IFN+R treatment. Although scarce, peripheral blood HCV-specific Th1 cells did not change significantly, while frequencies of HIV and CMV-specific Th1 cells decreased in co-infected patients independently of CD4 cell count changes. This suggests that IFN+R therapy might compromise virus-specific immune defenses in immunosuppressed patients.

Antiviral Agents↗
PubMed2004

Clonal B cell populations in the blood and liver of patients with chronic hepatitis C virus infection.

OBJECTIVE: The association of hepatitis C virus (HCV) infection with type II mixed cryoglobulinemia is well established, but the role of HCV in B cell lymphoma remains controversial. The objective of this study was to determine the frequency of circulating and liver-infiltrating monoclonal B cells in patients with HCV infection. METHODS: One hundred sixty patients were studied prospectively, including 115 HCV-positive patients and 45 HCV-negative patients with other nonimmune chronic liver disease(s). B cell clonality was determined by DNA amplification of the IgH rearrangements, followed by polyacrylamide gel electrophoresis. RESULTS: A clonal B cell population was detected in the blood of 21 (26%) of 81 HCV-positive patients whose cryoglobulin status was known, including 12 of 25 patients with type II cryoglobulinemia, 2 of 12 patients with type III cryoglobulinemia, and 7 of 44 patients without cryoglobulins. A clonal IgH rearrangement was detected in 26 (32%) of 81 liver biopsy specimens from HCV- infected patients, including 16 patients with a circulating clonal population. A clonal B cell population was not observed in the blood of 40 patients with non-HCV liver diseases and was present in only 1 (3%) of 30 liver biopsy specimens. Logistic regression analysis showed that HCV-infected patients with clonal B cell proliferation in both the blood and liver were older (P = 0.004) and had longer duration of HCV infection (P = 0.009), higher serum cryoglobulin levels (P = 0.001) that were more frequently symptomatic (P < 0.03), and liver disease that was more severe than that in patients without a clonal B cell population in the blood or liver (P = 0.05). In 4 of 16 patients with a clonal B cell population in both the blood and liver, a definite B cell malignancy was finally diagnosed. CONCLUSION: Clonal B lymphocytes are frequently detected in the blood and liver of patients with chronic HCV infection, in the absence of overt B cell malignancy. These clones are usually, but not always, associated with the presence of type II cryoglobulins. A high percentage of patients with B cell clonality in both the blood and liver were finally diagnosed as having a definite B cell malignancy.

Adult↗
PubMed2004

Short-term antiviral efficacy of BILN 2061, a hepatitis C virus serine protease inhibitor, in hepatitis C genotype 1 patients.

BACKGROUND AND AIMS: Novel, potent, and well-tolerated hepatitis C virus (HCV) drugs are needed. BILN 2061 is a potent and specific inhibitor of HCV serine protease in vitro. Preclinical toxicology data and studies in healthy volunteers supported the administration of BILN 2061 to patients with HCV infection. METHODS: The antiviral efficacy, pharmacokinetics, and tolerability of 25, 200, and 500 mg BILN 2061 twice daily given as monotherapy for 2 days in 31 patients infected with chronic genotype 1 HCV infection and with minimal liver fibrosis (Ishak score of 0-2) were assessed in a placebo-controlled, double-blind pilot study. In 2 subsequent placebo-controlled studies of similar design, 200 mg BILN 2061 twice daily was administered for 2 days to 10 patients with advanced liver fibrosis (Ishak score of 3 or 4) and to 10 patients with compensated cirrhosis (Ishak score of 5 or 6). RESULTS: Viral RNA reductions of 2-3 log 10 copies/mL were achieved in most of the patients. There was a trend toward a higher number of patients receiving 500 mg BILN 2061 achieving a viral RNA reduction > or =3 log(10) copies/mL as compared with patients receiving 25 mg BILN 2061. Advanced fibrosis or compensated cirrhosis did not affect the antiviral efficacy of BILN 2061. BILN 2061 was well tolerated in all studies. CONCLUSIONS: BILN 2061 is a well-tolerated and very active compound that reduced serum viral RNA concentrations after 2 days of treatment in patients infected with genotype 1 HCV independent of the degree of fibrosis. Nevertheless, further clinical trials are on hold pending resolution of animal toxicity issues.

Antiviral Agents↗
PubMed2004

The renal tolerance of low-dose adefovir dipivoxil by lamivudine-resistant individuals co-infected with hepatitis B and HIV.

BACKGROUND: Adefovir (ADV), an orally administered nucleotide analogue active against hepadnaviruses, retroviruses and herpes viruses was shown to be effective in HIV-infected patients, but the prevalence of nephrotoxicity with doses of 60-120 mg/day was considered unacceptable. Recently, lower doses of ADV were shown to be effective for the treatment of HIV-1 patients with chronic lamivudine (LAM)-resistant hepatitis B. METHODS: In a cohort of 35 patients infected with both HIV-1 and LAM-resistant hepatitis B virus, we investigated the renal tolerance of a once-daily dose of ADV 10 mg over 52 weeks. Their mean baseline creatinine clearance was within the normal range (105 +/- 3 ml/min/1.73 m(2)). No patient had significant changes in renal function or electrolyte balance secondary to ADV treatment. RESULTS: Transient increases in serum creatinine, which resolved by the end of the study were noted in two patients and three developed proteinuria, which was felt to be unrelated to ADV treatment. The cohort's mean serum phosphate level, 2.45 +/- 0.09 mg/dl at baseline, did not change significantly under treatment (2.66 +/- 0.12 mg/dl at week 52, P = NS). CONCLUSIONS: Our study shows that ADV dosed at 10 mg/day for the treatment of LAM-resistant chronic hepatitis B in patients co-infected with HIV is not associated with renal tubular dysfunction or a significant change in renal function.

Adenine↗
PubMed2004

Long-term therapy with lamivudine in renal transplant recipients with chronic hepatitis B.

BACKGROUND: Lamivudine is a potent inhibitor of hepatitis B virus (HBV) replication. As other available HBV therapies, its efficacy is hampered by relapse after discontinuation and by the risk of viral breakthrough. A recent study suggests that pre-emptive lamivudine therapy improves survival in HBV renal transplants, but few data are available regarding its long-term use in this population. The clinical features, course and viral mutations associated with the emergence of viral resistance in this population have not been well studied. METHODS: We followed 14 consecutive renal transplant patients treated with lamivudine for chronic hepatitis B. Breakthrough was defined as the reappearance of HBV DNA by hybridization. In patients with breakthrough, lamivudine was always continued and patients were followed up monthly. Mutations associated with viral resistance were determined by sequencing the polymerase encoding gene at the beginning of treatment and at the time of breakthrough. RESULTS: The median duration of treatment was 64.5 months. Resistance to lamivudine appeared in eight patients (57%) after a median duration of treatment of 15 (9-24) months. During a 51 month follow-up after breakthrough, only three of eight patients had a flare-up with alanine aminotransferase levels more than 5 ULN, and no hepatic decompensation was observed. Analysis of HBV sequencing after breakthrough revealed specific resistance mutations in both the B and C domains of the polymerase (rtL180M/M204V, n = 5; rtM204I, n = 2). CONCLUSION: Lamivudine is a safe and effective treatment of active hepatitis B in renal transplant patients. Resistance to treatment is frequent but seems to have little clinical impact over the considered period. In our experience, the YMDD mutation accounts for most cases of virological escape in patients with good compliance.

Adult↗
PubMed2004

In vitro susceptibility of lamivudine-resistant hepatitis B virus to adefovir and tenofovir.

Emergence of lamivudine-resistant hepatitis B virus (HBV) is a major concern in human immunodeficiency virus (HIV) and HBV coinfected patients. Following selection of resistant mutants, hepatitis flare or rapid progression to cirrhosis may occur. Treatment of patients with new nucleotide analogues such as adefovir dipivoxil (ADV) or tenofovir disoproxil fumarate (TDF) has shown good efficacy in controlling wild-type or lamivudine-resistant HBV replication. The purpose of this study was to assess the in vitro efficacy of new nucleotide analogues on HBV strains isolated from lamivudine-treated patients. After purification of HBV DNA from patient sera, the whole HBV genome was PCR-amplified and cloned. Drug sensitivity was measured after transfection of the isolated full genomes into HepG2 cells and measurement of HBeAg, HBsAg and viral replication in the culture media under increasing drug concentrations. A wild-type strain isolated from an untreated patient served as control. In a clinical study of ADV (Gilead 460i study), seven of the 35 patients carried HBV strains with the triple lamivudine resistance-associated amino-acid changes rtV173L/L180M/M204V at baseline. Although all patients responded to ADV in this clinical study, the serum HBV reduction was lower in the seven patients with the triple mutation (median -3.3 log copies/ml) compared to the patients who had only the rtL180M/M204V mutations (median -4.1 log copies/ml) at week 48 (P=0.04, Mann-Whitney test). In our in vitro system, lamivudine IC50 on lamivudine-resistant HBV carrying amino-acid substitutions rtL180M and rtM204V within the polymerase encoding region increased by more than 16,000-fold (from 6 nM to over 100 microM) when compared to wild-type HBV. For ADV and TDF, comparison of wild-type and lamivudine-resistant HBV IC50 (rtL180M-M204V) showed, respectively, 2.85-fold (from 0.07 to 0.2 microM) and 3.3-fold (from 0.06 to 0.2 microM) increases, indicating a mild decrease of both drug activities, in vitro. At the ADV concentration of 0.1 microM, presence of the V173L mutation reduced the inhibition of HBsAg production from 50 to 30% (P<0.01) and the viral replication from 45 to 32% (P<0.01, Mann-Whitney). Conversely, tenofovir had similar potency on both HBV mutation profiles with 60% inhibition of HBsAg production and 45% inhibition of viral replication at 0.1 microM. Our study supports the high efficacy of ADV and TDF seen in patients after lamivudine breakthrough. The excellent activity of TDF on lamivudine-resistant virus independently of the resistance mutation profile offers an interesting treatment alternative to HIV-HBV coinfected patients.

Adenine↗
PubMed2003

Incidence and predictors of severe liver fibrosis in human immunodeficiency virus-infected patients with chronic hepatitis C: a European collaborative study.

A study was performed in 10 European health care centers in which 914 patients coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) who had elevated serum alanine aminotransferase (ALT) levels underwent liver biopsy during the period of 1992 through 2002. Overall, the METAVIR liver fibrosis stage was F0 in 10% of patients, F1 in 33%, F2 in 22%, F3 in 22%, and F4 in 13%. Predictors of severe liver fibrosis (METAVIR stage, F3 or F4) in multivariate analysis were age of >35 years (odds ratio [OR], 2.95; 95% confidence interval [CI], 2.08-4.18), alcohol consumption of >50 g/day (OR, 1.61; 95% CI, 1.1-2.35), and CD4+ T cell count of <500 cells/mm3 (OR, 1.43; 95% CI, 1.03-1.98). Forty-six percent of patients aged >40 years had severe liver fibrosis, compared with 15% of subjects aged <30 years. The use of antiretroviral therapy was not associated with the severity of liver fibrosis. In summary, severe liver fibrosis is frequently found in HCV-HIV-coinfected patients with elevated serum ALT levels, and its severity increases significantly with age. The rate of complications due to end-stage liver disease will inevitably increase in this population, for whom anti-HCV therapy should be considered a priority.

Adult↗
PubMed2003

Serum biochemical markers accurately predict liver fibrosis in HIV and hepatitis C virus co-infected patients.

OBJECTIVE: Liver biopsy, the gold standard for assessing hepatitis C virus (HCV)-related fibrosis, is invasive and prone to complications. Our aim was to determine the operating characteristics of a non-invasive index of biochemical markers for the prediction of fibrosis in patients with HIV/HCV co-infection. DESIGN: In a cross-sectional, cohort study in a French tertiary-care hospital 130 HIV/HCV-co-infected patients with a liver biopsy and serum were tested for markers of liver fibrosis. METHODS: An index incorporating age, sex, alpha(2)-macroglobulin, apolipoprotein A1, haptoglobin, bilirubin, and gamma-glutamyl-transpeptidase (GGT), derived using multivariate logistic regression, was compared with liver histology. HIV-specific indices including the CD4 cell count and HIV-RNA load were also constructed. The diagnostic values of the indices were compared using receiver operating characteristic (ROC) curves. MAIN OUTCOME MEASURE: Septal fibrosis (F2-F4) by the METAVIR classification. RESULTS: By multivariate analysis, the most informative markers were alpha(2)-macroglobulin, apolipoprotein A1, GGT, and sex. The area under the ROC curve of the five-marker index was 0.856 +/- 0.035; not significantly different from the HIV-specific indices. On a scale from zero to 1.00, the five-marker index had a positive predictive value of 86% for scores greater than 0.60, and a negative predictive value of 93% for scores of 0.20 or less. These thresholds could reduce the necessity for liver biopsy by 55% while maintaining an accuracy of 89%. CONCLUSION: An index including five biochemical markers accurately predicts significant fibrosis in patients with HIV/HCV co-infection, and may substantially reduce the necessity for liver biopsy.

Adult↗
PubMed2003

Prediction of liver histological lesions with biochemical markers in patients with chronic hepatitis B.

BACKGROUND AIMS: Liver biopsy is the gold standard for assessing hepatitis B virus (HBV)-related histology. The aim was to determine the diagnostic utility of noninvasive serum markers in patients with chronic hepatitis B. METHODS: The aminotransferases and indices including alpha(2)-macroglobulin, apolipoprotein A1, haptoglobin, gamma-glutamyl-transpeptidase (GGT), and total bilirubin (Fibrotest), and ALT (Actitest) were compared with liver histology. The primary outcomes were A2-A3 activity and F2-F4 fibrosis (METAVIR). RESULTS: Two hundred and nine patients were included. Forty-one patients (20%) had A2-A3 activity and 61 (29%) had F2-F4 fibrosis. AST and GGT (P<0.001) were independently associated with A2-A3 activity. AST, ALT, and Actitest accurately predicted activity ((areas under receiver operating characteristic (ROC) curves (AUROC), 0.81-0.82+/-0.04)); an AST or ALT< or =30IU/l excluded significant activity with 96% certainty. Fibrotest accurately predicted F2-F4 fibrosis (AUROC, 0.78+/-0.04). Fibrotest scores (range, 0-1.0) < or =0.20 and >0.80 had negative and positive predictive values of 92%, respectively. Restricting biopsy to patients with intermediate scores (>0.20 and < or =0.80) may prevent liver biopsies in 46% of patients while maintaining 92% accuracy. CONCLUSIONS: The aminotransferases and an index including five biochemical markers are accurate noninvasive markers of HBV-related activity and fibrosis, respectively.

Adult↗
PubMed2002

Truth survival in clinical research: an evidence-based requiem?

PURPOSE: Factors associated with the survival of truth of clinical conclusions in the medical literature are unknown. The authors hypothesized that conclusions derived from studies using better methodology should have a longer half-life. DATA SOURCES: MEDLINE and hand searches of journals with studies on cirrhosis and hepatitis. STUDY SELECTION: Original articles and meta-analyses published from 1945 to 1999 about cirrhosis or hepatitis in adults. DATA SYNTHESIS: In 2000, 285 of 474 conclusions (60%) were still considered to be true, 91 (19%) were considered to be obsolete, and 98 (21%) were considered to be false. The half-life of truth was 45 years. The 20-year survival of conclusions derived from meta-analysis was lower (57% +/- 10%) than that from nonrandomized studies (87% +/- 2%) (P < 0.001) or randomized trials (85% +/- 3%) (P < 0.001). The survival of conclusions was not different when studies of high methodologic quality were compared with those of low quality. In randomized trials, the 50-year survival rate was higher for 52 negative conclusions (68% +/- 13%) than for 118 positive conclusions (14% +/- 4%) (P < 0.001). CONCLUSIONS: Contrary to the authors' hypothesis, conclusions based on recognized, good methodology had no clear survival advantage. To better convince clinicians of the long-term utility of evidence-based medicine, better prognostic factors should be developed.

Clinical Trials as Topic↗