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Biomedical subjects

J Durant

Publications and source records attributed to J Durant.

At least 19 recordsLinked to original sources
PubMed2005

Treatment of imported malaria in adults: a multicentre study in France.

BACKGROUND: Data about anti-malarial drugs prescription practices in Europe and the safety of imported malaria treatments are scanty. In 1999, a French consensus development conference published guidelines for the prevention and treatment of imported P. falciparum malaria. The impact of these guidelines has not been evaluated. AIM: To investigate the impact of these guidelines on the prescription of anti-malarials, and to evaluate the incidence of acute drug events (ADEs) leading to discontinuation of treatment. DESIGN: Cross-sectional survey. METHODS: Members of the medical staff in 14 French infectious and tropical disease wards completed a standardized form for each patient treated for imported malaria in 2001. A propensity score matching technique was used to estimate the risk of ADEs leading to discontinuation of the regimen. RESULTS: In the 474 patients studied, quinine was the first-line anti-malarial most often prescribed. Only 3% of patients received halofantrine. Mefloquine was associated with a RR of 4.9 (95%CI 3.2-7.4, p < 0.00001) risk of discontinuation of treatment due to ADEs. DISCUSSION: The very limited use of halofantrine indicates that the main practice recommendations of the guidelines have been taken into account. Mefloquine was associated with a substantial risk of discontinuing the treatment because of ADEs. This is a serious limitation for the use of mefloquine in the treatment of out-patients with imported malaria.

Adult↗
PubMed2001

The population requirement for cataract extraction: a cross-sectional study.

PURPOSE: To examine the distribution in the population of indications for cataract extraction in order to relate demand for this procedure to the capacity for satisfying it. METHODS: An age-stratified random population sample of 2783 individuals aged 55 years and over was taken from inner-city, urban and rural areas of Avon and Somerset. The requirement for cataract extraction was estimated on the basis of measures of vision-related quality of life, refracted visual acuity, and application of the Oxford Clinical Cataract Classification and Grading System. Data were also collected concerning suitability for surgery, including relative contraindications to surgery and whether participants considered their eyesight bad enough to merit surgery. Three sets of composite indications were defined. RESULTS: Estimated prevalent requirements for cataract extraction for the three sets of composite criteria were: 29 per 1000 aged over 55 years (95% CI 20-41) for the most inclusive criterion; 17 per thousand (95% CI 10-27) for the intermediate criterion; and 7 per thousand (95% CI 3-14) for the most stringent criterion. These rates are equivalent to a national prevalent requirement for England of 384,000 for the most inclusive criterion. If the approximately 15% of individuals whose desire or fitness for surgery was questionable are removed from this estimate, the prevalent requirement, including the backlog from previous unsatisfied demand, becomes 325,000 individuals. CONCLUSIONS: The findings suggest only a modest imbalance between supply and demand for cataract surgery. In particular there was a very small prevalence of untreated severe cataract, less than the annual health service surgical capacity, suggesting that the current National Health Service surgical capacity is adequate for cases of severe cataract.

Age Distribution↗
PubMed2001

A case of gnathostomiasis in a European traveller returning from Mexico.

Hundreds of human cases of gnathostomiasis have recently been reported from Mexico, where the disease is becoming a public health problem. We report a case of gnathostomiasis in a French tourist returning from Mexico. Tourists travelling in endemic countries are at risk of gnathostomiasis and should be advised about the risks of eating raw fish as a suspected source of infection.

Adult↗
PubMed2000

Importance of protease inhibitor plasma levels in HIV-infected patients treated with genotypic-guided therapy: pharmacological data from the Viradapt Study.

OBJECTIVE: In a prospective randomized study, the impact of plasma protease inhibitor (PI) trough levels on changes in HIV RNA were assessed in patients treated with genotypic-guided therapy. METHODS: Patients failing combination therapy (HIV-1 RNA > 10,000 copies/ml, and at least 6 months of therapy with nucleoside analogues and 3 months with PI) were randomly assigned into two arms: control group (C) in which the treatment was modified according to the standard of care; genotypic group (G) in which the treatment was modified according to resistance mutation profiles. Serial PI plasma levels were performed in patients throughout the 12 month study. PI levels were determined by high performance liquid chromatography. 'Suboptimal' concentration (SOC) was defined as at least two PI plasma levels below 2 x IC95. Others were defined as 'optimal' concentration (OC). Patients were categorized into four groups: G1 (SOC/control); G2 (OC/control); G3 (SOC/genotype); G4 (OC/genotype). An intent-to-treat analysis was performed with viral load as the primary endpoint. RESULTS: A total of 81 patients [mean age 39.7 +/- 8 years, 59 men, 52.7% Centers for Disease Control and Prevention (CDC) stage C] were included in the pharmacological substudy. The two groups according to randomization arms were comparable in terms of risk factor, age, sex, previous treatments, baseline CD4 cell count, HIV-1 RNA and mean PI plasma concentrations. Linear regression analysis showed a significant relationship between PI concentration and HIV RNA in the plasma. OC and SOC were found in 67.9% (55/81) and 32.1% (26/81) of patients, respectively. Mean changes in HIV RNA from baseline at month 6 were: -0.23 +/- 0.29 log10 copies/ml (G1); -0.97 +/- 0.28 (G2); -0.68 +/- 0.37 (G3); -1.38 +/- 0.20 (G4). Multivariate analysis showed PI plasma concentrations to be an independent predictor of HIV-RNA evolution (P = 0.017). CONCLUSION: Multiple parameters determine the response to antiretroviral therapy and causes other than the development of drug resistance should be considered in the setting of therapeutic failure. Suboptimal concentrations of PI limit the response to antiretroviral therapy. Therapeutic drug monitoring of the PI plasma concentration may therefore prove useful in optimizing antiretroviral therapy.

Adult↗
PubMed2000

Economic evaluation of drug resistance genotyping for the adaptation of treatment in HIV-infected patients in the VIRADAPT study.

BACKGROUND: Costs of antiretroviral therapy for HIV-infected patients have increased at a time when most countries are attempting to contain health care costs. Part of this increase results from HIV drug resistance associated with virologic failure and a subsequent shift to more complex and costly therapies. Genotypic guided treatment is associated with better virologic outcome. However, it is not yet known whether it will be cost effective. METHODS: We present here an economic evaluation based on the results from the VIRADAPT study, a prospective, open-label, randomized trial comparing patients assigned to standard of care (n = 43), versus genotypic guided treatment (n = 64) for 6 months. Total follow-up for the extended trial was 1 year. Costs were computed from the viewpoint of the health care system. Hospitalization data were retrieved from the VIRADAPT study case report forms, costs were estimated from the cost of the corresponding diagnosis-related groups derived from the French national cost data base: these were actual costs and not charges. Data on the volume of tests prescribed, drugs, and clinic visits were retrieved from the VIRADAPT study database. The unit costs of tests and clinic visits were determined using the French national Social Security reimbursement price; costing of drugs used were based upon purchase price by either retail pharmacies or hospitals. Genotyping using TruGene HIV-1 assay was estimated at $500 per test from manufacturer's data (all figures in this paper are expressed in U.S. dollars). RESULTS: Total mean (standard deviation) yearly costs per patients were $20,412 (+/-$10, 129) in the standard of care group and $18,484 (+/-$9,652) in the genotyping group (p =.35). Drug costs represented 55% of total costs. There was a trend toward a decrease in drug costs in the genotyping arm (p =.07), the greatest reduction being in the decreased use of protease inhibitors in the genotyping arm. The additional expense of genotyping appeared to be offset by the savings obtained in drug costs. CONCLUSION: In our study, the cost of drug resistance testing is offset by a reduced use of protease inhibitors and their attendant costs. Although not reaching statistical significance, this trend in the reduction of drug costs and drug use presents a great interest for future trials.

Adult↗
PubMed2000

A right to know?

Explore the source record for details and available documents.

Euthanasia, Active, Voluntary↗
PubMed2000

Integrity of the NS5A (amino acid 2209 to 2248) region in hepatitis C virus 1b patients non-responsive to interferon therapy.

BACKGROUND/AIMS: In hepatitis C virus-1b, it has been suggested that an amino acid stretch (aa 2209-2248) of the carboxy terminal half of the non-structural 5A (NS5A) region participates in the response to interferon treatment. We tested the hypothesis that absence of mutations in the NS5A (aa 2209-2248) sequence is required for interferon resistance. We also investigated the importance of different HCV-1b isolates in interferon response in France. METHODS: We determined the NS5A sequences of 70 patients with chronic hepatitis C before IFN therapy and then compared them with HCV-J prototype sequence. The isolates were determined by NS5B sequencing, the "gold standard" method for genotyping and subtyping. Pre-therapeutic viral load was also measured. RESULTS: No sustained virological response was observed in the patients without amino acid substitutions in the NS5A (aa 2209-2248) sequence, and in the patients with HCV-J isolates. Viral load was significantly higher in the patients with no amino acid substitutions in the NS5A (aa 2209-2248) sequence. CONCLUSIONS: In HCV-lb infected patients, an HCV-J strain with no amino acid substitution in the NS5A (aa 2209 2248) region indicates a poor prognosis for response to IFN therapy. The low interferon response rate in HCV-lb infection in Europe is probably not due to a difference between isolates.

Alanine Transaminase↗
PubMed2000

Unusual cutaneous manifestations of miliary tuberculosis.

Cutaneous manifestations of miliary tuberculosis are extremely rare. We describe a 62-year-old woman with leukopenia who developed infiltrated dermal-hypodermal and ulcerative cutaneous lesions during the course of miliary tuberculosis. Miliary tuberculosis was diagnosed when Mycobacterium tuberculosis bacilli were isolated by cultures of the bronchoalveolar lavage fluid and blood and when acid-fast bacilli were detected on histopathologic examination of hepatic, pulmonary, and cutaneous biopsy specimens. With the increasing incidence of immunocompromised patients, unusual presentations of tuberculosis may be observed more often. Acute miliary tuberculosis of the skin is an exceptional manifestation that is due to acute hematogenous dissemination of M. tuberculosis to the skin. We describe a patient who had unusual cutaneous manifestations of miliary tuberculosis.

Female↗
PubMed2000

Persisting long-term benefit of genotype-guided treatment for HIV-infected patients failing HAART. The Viradapt Study: week 48 follow-up.

OBJECTIVE: We report the 12 months follow-up of the patients who participated in the Viradapt study. METHODS: A total of 108 HIV-infected patients failing antiretroviral (ARV) therapy (HIV RNA > 10,000 copies/ml, therapy > 6 months with nucleoside reverse transcriptase inhibitors, > 3 months with protease inhibitors (PIs) were randomized into two arms: standard of care in the control arm, and treatment according to the resistance mutations in the protease and reverse transcriptase genes in the study arm. After the first 6 months of the randomized study, open-label, genotype-guided treatment was offered in both arms. A multivariate analysis was performed to assess the predictive factors of treatment success (HIV RNA < 200 copies/ml). RESULTS: The two arms were comparable in terms of risk factors, age, sex, previous treatments, CD4 cell count and log10 HIV-1 RNA at baseline. At week 24, an interim combined analysis showed a statistically significant difference in the drop in viral load at months 3 and 6 (P = 0.015, repeated measures analysis of variance) in favour of the genotype group. Patients in both arms were then offered open-label genotyping. Genotype analysis was performed every 3 months, and treatment changes could accordingly be made. As some of the patients in the control arm had already progressed to months 9 or 12, only 69% (30/43) of these patients received genotype-guided treatment changes. In the genotype arm, the mean drop in HIV RNA of 1.15 log10 copies/ml, obtained at month 6, persisted at months 9 and 12 (1.15 log10 copies/ml +/- 0.17). In the control arm, an additional drop in HIV RNA to 0.98 log10 +/- 0.22 copies/ml was observed by month 12. In control patients receiving open-label genotype, the percentage of patients with HIV-1 RNA levels below detection limit (200 copies/ml) rose from 14% at month 6 to 30.5% at month 12. This percentage in the study arm remained stable at 31.3% and 30% at months 9 and 12, respectively. Genotype-guided therapy, primary protease mutations and PI plasma concentrations were significantly correlated with virological success. CONCLUSION: In this heavily pretreated patient population, genotype-guided therapy resulted in a sustained reduction in HIV RNA of greater than one log10 throughout a 1 year follow-up period. Performance of genotype-guided therapy may have contributed to the additional viral load reduction seen in patients in the control group who received open-label genotyping after the 6 months point. Multivariate analysis showed that the presence of primary protease mutations, performance of genotype-guided treatment changes and PI plasma concentrations independently affected virological response.

Anti-HIV Agents↗
PubMed1999

Worlds apart? The reception of genetically modified foods in Europe and the U.S.

Recent controversies about genetically modified foods in the United Kingdom and several other European countries highlight the apparent differences that exist in public opinion on this subject across the Atlantic. Why are people in the United States seemingly untroubled by a technology that causes Europeans so many difficulties? The results of survey research on public perceptions of biotechnology in Europe and the United States during 1996-1997, together with an analysis of press coverage and policy formation from 1984 to 1996, can help to answer this question.

Attitude↗
PubMed1999

Drug-resistance genotyping in HIV-1 therapy: the VIRADAPT randomised controlled trial.

BACKGROUND: Growing evidence has linked HIV-1 resistance mutations and drug failure. The use of genotypic-resistance analysis to assist therapeutic decision-making in patients failing therapy has not been investigated. We assessed the virological and immunological impact of genotypic-resistance testing. METHODS: We did a prospective, open, randomised, controlled study of HIV-1-infected patients in whom combination therapy was not successful. We randomly assigned patients standard care (control, n=43) or treatment according to the resistance mutations in protease and reverse-transcriptase genes (genotypic group, n=65). The major endpoint was the change in HIV-1 RNA viral load. Analysis was by intention to treat. FINDINGS: 108 patients were enrolled. All patients were similar for risk factors, age, sex, previous treatment, CD4-cell count (214/microL [SD14]) and log HIV-1 RNA viral load at baseline (4.7 copies/mL [0.1]). At month 3, the mean change in HIV-1 RNA was -1.04 log (0.14) in the study group compared with -0.46 log (0.17) in the control group (mean difference 0.58 log [95% CI 0.14-1.02], p=0.01). At month 6, changes were -1.15 (0.15) log copies/mL, and -0.67 (0.19) log copies/mL in the genotypic group and the control group, respectively (mean difference 0.48 log [0.01-0.97], p=0.05). Difference in the drop in viral load combined at 3 months and 6 months was significant (p=0.015). At month 3, HIV-1 RNA was lower than detection level (200 copies/mL) in 29% (19/65) of patients in the genotypic group versus 14% (6/43) in the control group (p=0.017). At month 6, the values were 32% (21/65) and 14% (6/43) (p=0.067) for the genotypic group and the control group, respectively. Therapy was generally well tolerated, with ten patients (six in the genotypic group, four in the control group) requiring toxic-effect-related drug modification. INTERPRETATION: We found genotypic-resistance testing to have a significant benefit on the virological response when choosing a therapeutic alternative. Further study of the use of genotypic-resistance testing in assisting clinical decision-making is warranted.

Acquired Immunodeficiency Syndrome↗
PubMed1999

[Imported dengue: study of 44 cases observed from 1994 to 1997 in 9 university hospital centers. Infectio-Sud-France group].

Imported dengue is increasingly observed in non endemic countries. We report a retrospective study of 44 cases of dengue fever diagnosed in nine french university hospitals between 1994 and 1997. The patients were aged between 13 and 67 years. Most of them were tourists and had been traveling for a few weeks, in French West Indies and French Guyana (18), South-East Asia (10), India (7) or Polynesia (4). Only, two contracted the disease in Africa. The onset of symptoms preceded the return or followed it within 7 days. The most frequent clinical presentation was a febrile and painful syndrome. Cutaneous manifestations (rash or macular exanthem) were observed in 59% of cases, digestive symptoms in 50%, pharyngitis and/or cough in 25%, microadenopathy in 20%, moderate mucous haemorrhagic manifestations in 16% and neuropsychiatric manifestations in 14%. The common biological abnormalities were thrombocytopenia (84%), leukopenia (59%), and elevated transminases (57%). The diagnosis, orientated by negativity of malaria smears, the knowledge of an epidemic in the visited country, or occurrence of similar cases in the entourage, were argued by serological results: presence of anti-DEN IgM in 25 cases, serological conversion (anti- DEN IgG) in 7 cases or very high seropositivity (anti-DEN IgG > 1/1280) in 12 cases. No virus isolation was obtained.

Adolescent↗
PubMed1998

Lack of influence of hepatitis G virus infection on alcohol-related hepatic lesions.

BACKGROUND: The purposes of this study were to analyse the prevalence and histologic impact of hepatitis G virus (HGV), a newly discovered virus, in alcoholic patients, a population known to be at risk for viral hepatitis. METHODS: One hundred and thirty-nine consecutive alcoholics admitted to our liver unit (106 men and 33 women; mean age, 47.1 +/- 10.9 years) were included in the study. All patients had consumed more than 60 g of ethanol per day for at least 1 year. One hundred healthy blood donors constituted a control group. Antibodies to HGV E2 protein and HGV-RNA testing by reverse transcription-polymerase chain reaction (RT-PCR) with primers derived from the NS5 coding region were performed in all serum samples. RESULTS: A significantly higher seroprevalence of anti-E2 antibodies was observed in alcoholic patients than in healthy blood donors (41 (29.5%) versus 8 (8%); P < 0.0001). Moreover, the prevalence of HGV-RNA was significantly higher in alcoholic patients (13 (9.3%) versus 1 (1%); P = 0.01). HGV-RNA and anti-HGV antibodies were never detected simultaneously. HGV viraemia was not associated with an increased risk of cirrhosis or hepatocarcinoma in alcoholic subjects. CONCLUSIONS: Our study reports a high prevalence of HGV in alcoholic patients. HGV infection does not modify or aggravate the course of alcoholic liver disease.

Case-Control Studies↗