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Biomedical subjects

W Burman

Publications and source records attributed to W Burman.

8 recordsLinked to original sources

CD4+ count-guided interruption of antiretroviral treatment.

BACKGROUND: Despite declines in morbidity and mortality with the use of combination antiretroviral therapy, its effectiveness is limited by adverse events, problems with adherence, and resistance of the human immunodeficiency virus (HIV). METHODS: We randomly assigned persons infected with HIV who had a CD4+ cell count of more than 350 per cubic millimeter to the continuous use of antiretroviral therapy (the viral suppression group) or the episodic use of antiretroviral therapy (the drug conservation group). Episodic use involved the deferral of therapy until the CD4+ count decreased to less than 250 per cubic millimeter and then the use of therapy until the CD4+ count increased to more than 350 per cubic millimeter. The primary end point was the development of an opportunistic disease or death from any cause. An important secondary end point was major cardiovascular, renal, or hepatic disease. RESULTS: A total of 5472 participants (2720 assigned to drug conservation and 2752 to viral suppression) were followed for an average of 16 months before the protocol was modified for the drug conservation group. At baseline, the median and nadir CD4+ counts were 597 per cubic millimeter and 250 per cubic millimeter, respectively, and 71.7% of participants had plasma HIV RNA levels of 400 copies or less per milliliter. Opportunistic disease or death from any cause occurred in 120 participants (3.3 events per 100 person-years) in the drug conservation group and 47 participants (1.3 per 100 person-years) in the viral suppression group (hazard ratio for the drug conservation group vs. the viral suppression group, 2.6; 95% confidence interval [CI], 1.9 to 3.7; P<0.001). Hazard ratios for death from any cause and for major cardiovascular, renal, and hepatic disease were 1.8 (95% CI, 1.2 to 2.9; P=0.007) and 1.7 (95% CI, 1.1 to 2.5; P=0.009), respectively. Adjustment for the latest CD4+ count and HIV RNA level (as time-updated covariates) reduced the hazard ratio for the primary end point from 2.6 to 1.5 (95% CI, 1.0 to 2.1). CONCLUSIONS: Episodic antiretroviral therapy guided by the CD4+ count, as used in our study, significantly increased the risk of opportunistic disease or death from any cause, as compared with continuous antiretroviral therapy, largely as a consequence of lowering the CD4+ cell count and increasing the viral load. Episodic antiretroviral therapy does not reduce the risk of adverse events that have been associated with antiretroviral therapy. (ClinicalTrials.gov number, NCT00027352 [ClinicalTrials.gov].).

AIDS-Related Opportunistic Infections↗

Pneumocystis carinii cytochrome b mutations are associated with atovaquone exposure in patients with AIDS.

This retrospective cohort study was conducted to determine whether Pneumocystis carinii cytochrome b gene mutations in patients with AIDS and P. carinii pneumonia (PCP) are associated with atovaquone exposure. Portions of the P. carinii cytochrome b genes that were obtained from 60 patients with AIDS and PCP from 6 medical centers between 1995 and 1999 were amplified and sequenced by using polymerase chain reaction. Fifteen patients with previous atovaquone prophylaxis or treatment exposure were matched with 45 patients with no atovaquone exposure. Cytochrome b coenzyme Q binding site mutations were observed in 33% of isolates from patients exposed to atovaquone, compared with 6% from those who were not (P=.018). There was no difference in survival 1 month after treatment between patients with or without cytochrome b mutations (P=.14). Thus, cytochrome b mutations are significantly more common in patients with AIDS and PCP with atovaquone exposure, but the clinical significance of these mutations remains unknown.

Acquired Immunodeficiency Syndrome↗

Pneumocystis carinii mutations are associated with duration of sulfa or sulfone prophylaxis exposure in AIDS patients.

This study was conducted to determine whether Pneumocystis carinii dyhydropteroate synthase (DHPS) gene mutations in AIDS patients with P. carinii pneumonia (PCP) are affected by duration of sulfa or sulfone prophylaxis and influence response to sulfa or sulfone therapy. The P. carinii DHPS genes from 97 AIDS patients with PCP between 1991 and 1999 from 4 medical centers were amplified, using polymerase chain reaction (PCR), and sequenced. Mutations were observed in 76% of isolates from patients exposed to sulfa or sulfone prophylaxis compared with 23% of isolates from patients not exposed (P=.001). Duration of prophylaxis increased the risk of mutations (relative risk [RR] for each exposure month, 1.06; P=.02). Twenty-eight percent of patients with mutations failed sulfa or sulfone treatment; mutations increased the risk of sulfa or sulfone treatment failure (RR, 2.1; P=0.01). Thus, an increased duration of sulfa or sulfone prophylaxis increases the chance of developing a P. carinii mutation. The majority of patients with mutations respond to sulfa or sulfone therapy.

Acquired Immunodeficiency Syndrome↗

Acquired rifamycin monoresistance in patients with HIV-related tuberculosis treated with once-weekly rifapentine and isoniazid. Tuberculosis Trials Consortium.

BACKGROUND: Rifapentine is a cyclopentyl-substituted rifamycin whose serum half-life is five times that of rifampin. The US Public Health Service Study 22 compared a once-weekly regimen of isoniazid and rifapentine with twice weekly isoniazid and rifampin in the continuation phase (the last 4 months) of treatment for pulmonary tuberculosis in HIV-seropositive and HIV-seronegative patients. This report concerns only the HIV-seropositive part of the trial, which has ended. The HIV-seronegative part will stop follow-up in 2001. METHODS: Adults with culture-positive, drug-susceptible pulmonary tuberculosis who completed 2 months of four-drug (isoniazid, rifampin, pyrazinamide, ethambutol) treatment (induction phase) were randomly assigned 900 mg isoniazid and 600 mg rifapentine once weekly, or 900 mg isoniazid and 600 mg rifampin twice weekly. All therapy was directly observed. Statistical analysis used univariate, Kaplan-Meier, and logistic and proportional hazards regression methods. FINDINGS: 71 HIV-seropositive patients were enrolled: 61 completed therapy and were assessed for relapse. Five of 30 patients in the once-weekly isoniazid/rifapentine group relapsed, compared with three of 31 patients in the twice-weekly isoniazid/rifampin group (log rank chi2=0.69, p=0.41). However, four of five relapses in the once-weekly isoniazid/rifapentine group had monoresistance to rifamycin, compared with none of three in the rifampin group (p=0.05). Patients who relapsed with rifamycin monoresistance were younger (median age 29 vs 41 years), had lower baseline CD4 cell counts (median 16 vs 144 microL), and were more likely to have extrapulmonary involvement (75% vs 18%, p=0.03) and concomitant therapy with antifungal agents (75% vs 9%, p=0.006). No rifamycin monoresistant relapse has occurred among 1004 HIV-seronegative patients enrolled to date. INTERPRETATION: Relapse with rifamycin monoresistant tuberculosis occurred among HIV-seropositive tuberculosis patients treated with a once-weekly isoniazid/rifapentine continuation-phase regimen. Until more effective regimens have been identified and assessed in clinical trials, HIV-seropositive people with tuberculosis should not be treated with a once-weekly isoniazid/rifapentine regimen.

AIDS-Related Opportunistic Infections↗

Comparable specificity of 2 commercial tuberculin reagents in persons at low risk for tuberculous infection.

CONTEXT: One or both commercial tuberculin skin test reagents (Aplisol and Tubersol) may have a high rate of false-positive reactions. OBJECTIVE: To compare the reaction size and specificity of skin testing with Aplisol, Tubersol, and the standard purified protein derivative (PPD-S1). DESIGN: Double-blind trial, conducted between May 14, 1997, and October28, 1997, in which each individual received 4 tuberculin skin reagents at sites assigned at random. SETTING: Health departments and universities in 6 US cities. PARTICIPANTS: A total of 1555 persons at low risk of latent tuberculosis infection. INTERVENTION: Simultaneous skin tests with Aplisol, Tubersol, PPD-S1, and either a second PPD-S1 or PPD-S2 (a proposed new standard). MAIN OUTCOME MEASURE: Reaction size at each injection site measured by 2 investigators blinded to type of reagent. RESULTS: Aplisol produced slightly larger reactions than Tubersol, but this difference did not significantly change skin test interpretation. The mean +/- SD reaction sizes were 3.4+/-4.2 mm with Aplisol, 2.1+/-3.2 mm with Tubersol, and 2.5+/-3.6 mm with PPD-S1. Assuming that all participants were uninfected and using a 10-mm cutoff, the specificities of the tests were high: Aplisol, 98.2%; Tubersol, 99.2%; and PPD-S1, 98.9%. Significant variability was not detected in interobserver, host, and lot-to-lot reagent comparisons. CONCLUSION: Using a cutoff of at least 10 mm, testing with 3 different PPD reagents resulted in similar numbers of uninfected persons being correctly classified.

Adult↗

Injury severity: better data through direct physician entry of anatomic injuries?

The authors compared the injury diagnoses and Injury Severity Scores (ISSs) generated by three data-collection and -coding methods, and examined the times needed and costs associated with the methods. One method involved direct electronic entry of injury data by a physician in the admitting area. Codes, severity scores, and times and costs varied significantly with the different methods, thus suggesting a need for further study of the derivation of injury severity codes.

Abbreviated Injury Scale↗

One man's meat.

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Ethiopia↗