RESUMEN
OBJECTIVE: Efficacy and safety of adefovir dipivoxil (adefovir) added to background antiretroviral therapy in advanced HIV disease. DESIGN: Randomized, double-blind, placebo-controlled multicenter trial. SETTING: Fifteen clinical trial units providing HIV primary care. PARTICIPANTS: Adults with CD4 cell count < or = 100 x 10(6)/l, or 101-200 x 10(6)/l with prior nadir < or = 50 x 10(6)/l. INTERVENTIONS: Oral adefovir or placebo 120 mg once daily. MAIN OUTCOME MEASURES: Survival, cytomegalovirus (CMV) disease, plasma HIV-RNA, CD4 cell count, grade 4 drug toxicity, permanent drug discontinuation due to toxicity. RESULTS: Among the 253 patients assigned adefovir and the 252 assigned placebo, respectively, 17 and 16 died (P = 0.88), and four and eight experienced CMV disease (P = 0.25). Mean change in log(10) plasma HIV-RNA in the adefovir and placebo groups, respectively, was 0.09 and -0.03 copies/ml at 6 months (P = 0.22) and 0.06 and -0.02 at 12 months (P = 0.87). Changes in CD4 cell counts were not different between groups. At 12 months the cumulative percent with proximal renal tubular dysfunction (PRTD) was 17% in the adefovir group and 0.4% in the placebo group (P < 0.0001, log rank test). Median time to resolution of PRTD was 15 weeks among patients assigned adefovir, and 16% of patients did not resolve completely 41 weeks after onset. More drug discontinuations occurred in the adefovir group than in the placebo group. CONCLUSIONS: No virologic or immunologic benefit was observed when adefovir was added to background antiretroviral therapy in advanced HIV disease, and adefovir was associated with considerable nephrotoxicity. This study does not support the use of adefovir for treatment of advanced HIV disease in pretreated patients.
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Adenina/análogos & derivados , Adenina/uso terapéutico , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1/fisiología , Organofosfonatos , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Adenina/efectos adversos , Fármacos Anti-VIH/efectos adversos , Recuento de Linfocito CD4 , Infecciones por Citomegalovirus/diagnóstico , Método Doble Ciego , Quimioterapia Combinada , Infecciones por VIH/inmunología , Infecciones por VIH/mortalidad , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Humanos , ARN Viral/sangre , Inhibidores de la Transcriptasa Inversa/efectos adversosRESUMEN
In 1906 the great San Francisco earthquake and fire destroyed much of the city. As we approach the 100-year anniversary of that event, a critical concern is the hazard posed by another such earthquake. In this article, we examine the assumptions presently used to compute the probability of occurrence of these earthquakes. We also present the results of a numerical simulation of interacting faults on the San Andreas system. Called Virtual California, this simulation can be used to compute the times, locations, and magnitudes of simulated earthquakes on the San Andreas fault in the vicinity of San Francisco. Of particular importance are results for the statistical distribution of recurrence times between great earthquakes, results that are difficult or impossible to obtain from a purely field-based approach.
Asunto(s)
Desastres , Predicción , Probabilidad , San FranciscoRESUMEN
Fourteen of 318 consecutive shoulder arthroscopies performed over 5 years were found to have a complete tear of the supraspinatus tendon with an intact superior glenohumeral joint capsule. All tears were surgically repaired into a bony trough in the greater tuberosity. All of these tears were found in the past 2 years, representing the last 155 arthroscopies performed. This would indicate that there were probably similar lesions that were missed in earlier cases. This represents a significant pitfall injury that may yield a negative arthrogram and may be overlooked in arthroscopic shoulder surgery unless close inspection of the bursal side of the rotator cuff is accomplished.
Asunto(s)
Lesiones del Manguito de los Rotadores , Lesiones del Hombro , Articulación del Hombro/patología , Traumatismos de los Tendones/cirugía , Artroscopía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Manguito de los Rotadores/cirugía , Traumatismos de los Tendones/epidemiología , Traumatismos de los Tendones/patología , Factores de TiempoRESUMEN
BACKGROUND: Several agents are effective in preventing Mycobacterium avium complex disease in patients with advanced human immunodeficiency virus (HIV) infection. However, there is uncertainty about whether prophylaxis should be continued in patients whose CD4+ cell counts have increased substantially with antiviral therapy. METHODS: We conducted a multicenter, double-blind, randomized trial of treatment with azithromycin (1200 mg weekly) as compared with placebo in HIV-infected patients whose CD4+ cell counts had increased from less than 50 to more than 100 per cubic millimeter in response to antiretroviral therapy. The primary end point was M. avium complex disease or bacterial pneumonia. RESULTS: A total of 520 patients entered the study; the median CD4+ cell count at entry was 230 per cubic millimeter. In 48 percent of the patients, the HIV RNA value was below the level of quantification. The median prior nadir CD4+ cell count was 23 per cubic millimeter, and 65 percent of the patients had had an acquired immunodeficiency syndrome-defining illness. During follow-up over a median period of 12 months, there were no episodes of confirmed M. avium complex disease in either group (95 percent confidence interval for the rate of disease in each group, 0 to 1.5 episodes per 100 person-years). Three patients in the azithromycin group (1.2 percent) and five in the placebo group (1.9 percent) had bacterial pneumonia (relative risk in the azithromycin group, 0.60; 95 percent confidence interval, 0.14 to 2.50; P=0.48). Neither the rate of progression of HIV disease nor the mortality rate differed significantly between the two groups. Adverse effects led to discontinuation of the study drug in 19 patients assigned to receive azithromycin (7.4 percent) and in 3 assigned to receive placebo (1.1 percent; relative risk, 6.6; P=0.002). CONCLUSIONS: Azithromycin prophylaxis can safely be withheld in HIV-infected patients whose CD4+ cell counts have increased to more than 100 cells per cubic millimeter in response to antiretroviral therapy.