RESUMO
Six-month regimens that include rifampin for the treatment of tuberculosis in patients without human immunodeficiency virus (HIV) infection are recommended because of low percentage of relapses. Whether a similar duration of therapy should be used to treat tuberculosis in HIV-infected patients is unclear. Six studies of patients with HIV-infection and 3 of patients without HIV infection were reviewed and compared. The studies differed in terms of design, eligibility criteria, site of disease, frequency of dosing, dose administration methods, and outcome definitions. Among HIV-infected patients, the following percentages were found: cure, 59.4%--97.1%; treatment success, 34.0%--100%; effective treatment, 29.4%--88.2%; and relapse, 0%--10%. In those without HIV infection, percentages were as follows: cure, 62.3%--88.0%; treatment success, 91.2%--98.8%; effective treatment, 70.6%--83.8%; and relapse, 0%--3.4%. Although the rate of relapse appeared to be higher in some studies of HIV-infected patients with tuberculosis, this review demonstrates the limitation in the use of relapse as the exclusive outcome of interest when comparing studies.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antituberculosos/uso terapêutico , Rifampina/uso terapêutico , Tuberculose/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Antituberculosos/administração & dosagem , Ensaios Clínicos como Assunto , Humanos , Seleção de Pacientes , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Projetos de Pesquisa , Rifampina/administração & dosagem , Resultado do Tratamento , Tuberculose/microbiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologiaRESUMO
Quantifying the relationship between changes in lipid variables and clinical endpoints has been difficult. We studied the predictive value of various lipid variables on three endpoints in the Program on the Surgical Control of the Hyperlipidemias (POSCH): overall mortality, coronary heart disease (CHD) mortality, and CHD mortality and confirmed nonfatal myocardial infarction (MI) combined. We measured lipid variables for the annual visits from baseline to 5 years for actual follow-up values, actual and percentage differences between baseline and follow-up values, as well as the parameters comparing baseline only to 5 years for actual differences, percentage differences, and the ratio of baseline to 5 years. The lipid variables included were total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, triglycerides, and the LDL cholesterol/HDL cholesterol ratio. The analytic method used was that of Cox regression, with age and sex as secondary covariates, and each lipid or ratio of lipids as the primary (univariate) covariate. As a result, 108 univariate Cox regressions were conducted. The combined findings for the control and the intervention groups are presented. The number of events for the combined group were: overall mortality, 190; CHD mortality, 119; and CHD mortality and confirmed nonfatal MI, 262. The highest hazard ratios were found for the lipid variable of the LDL cholesterol/HDL cholesterol ratio (e.g. 1.196 for a 1-unit increase). Only for the combined endpoint of CHD mortality and confirmed nonfatal MI was there a substantial number of statistically significant relationships (P<0.01) of lipid variables and parameters of assessment.
Assuntos
Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Lipídeos/sangue , Doenças Cardiovasculares/sangue , Doença das Coronárias/etiologia , Doença das Coronárias/mortalidade , Seguimentos , Humanos , Estudos Multicêntricos como Assunto , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/mortalidade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de RiscoRESUMO
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.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Azitromicina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/prevenção & controle , Adulto , Antibacterianos/efeitos adversos , Antibioticoprofilaxia/efeitos adversos , Azitromicina/efeitos adversos , Contagem de Linfócito CD4 , Progressão da Doença , Método Duplo-Cego , Feminino , Seguimentos , HIV/genética , Infecções por HIV/imunologia , Infecções por HIV/mortalidade , Humanos , Masculino , RNA Viral/sangueRESUMO
CONTEXT: Because of problems with adherence, toxicity, and increasing resistance associated with 6- to 12-month isoniazid regimens, an alternative short-course tuberculosis preventive regimen is needed. OBJECTIVE: To compare a 2-month regimen of daily rifampin and pyrazinamide with a 12-month regimen of daily isoniazid in preventing tuberculosis in persons with human immunodeficiency virus (HIV) infection. DESIGN: Randomized, open-label controlled trial conducted from September 1991 to May 1996, with follow-up through October 1997. SETTING: Outpatient clinics in the United States, Mexico, Haiti, and Brazil. PARTICIPANTS: A total of 1583 HIV-positive persons aged 13 years or older with a positive tuberculin skin test result. INTERVENTIONS: Patients were randomized to isoniazid, 300 mg/d, with pyridoxine hydrochloride for 12 months (n = 792) or rifampin, 600 mg/d, and pyrazinamide, 20 mg/kg per day, for 2 months (n = 791). MAIN OUTCOME MEASURES: The primary end point was culture-confirmed tuberculosis; secondary end points were proven or probable tuberculosis, adverse events, and death, compared by treatment group. RESULTS: Of patients assigned to rifampin and pyrazinamide, 80% completed the regimen compared with 69% assigned to isoniazid (P<.001). After a mean follow-up of 37 months, 19 patients (2.4%) assigned to rifampin and pyrazinamide and 26 (3.3%) assigned to isoniazid developed confirmed tuberculosis at rates of 0.8 and 1.1 per 100 person-years, respectively (risk ratio, 0.72 [95% confidence interval, 0.40-1.31]; P = .28). In multivariate analysis, there were no significant differences in rates for confirmed or probable tuberculosis (P = .83), HIV progression and/or death (P = .09), or overall adverse events (P = .27), although drug discontinuation was slightly higher in the rifampin and pyrazinamide group (P = .01). Neither regimen appeared to lead to the development of drug-resistant tuberculosis. CONCLUSIONS: Our data suggest that for preventing tuberculosis in HIV-infected patients, a daily 2-month regimen of rifampin and pyrazinamide is similar in safety and efficacy to a daily 12-month regimen of isoniazid. This shorter regimen offers practical advantages to both patients and tuberculosis control programs.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Antituberculosos/uso terapêutico , Infecções por HIV/microbiologia , Isoniazida/uso terapêutico , Pirazinamida/uso terapêutico , Rifampina/uso terapêutico , Tuberculose/prevenção & controle , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Adolescente , Adulto , Idoso , Antituberculosos/administração & dosagem , Antituberculosos/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Infecções por HIV/mortalidade , Humanos , Isoniazida/administração & dosagem , Isoniazida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Modelos de Riscos Proporcionais , Pirazinamida/administração & dosagem , Pirazinamida/efeitos adversos , Rifampina/administração & dosagem , Rifampina/efeitos adversos , Estatísticas não Paramétricas , Teste Tuberculínico , Tuberculose/diagnóstico , Tuberculose/mortalidadeRESUMO
SETTING: Mortality associated with human immunodeficiency virus (HIV) related multidrug-resistant tuberculosis (MDR-TB) is reduced with effective early therapy. Identifying predictors of, and effective regimens for, MDR-TB is critical. OBJECTIVE: A multicenter prospective study was initiated to 1) determine the demographic, behavioral, clinical and geographic risk factors associated with the occurrence of MDR-TB among HIV-infected patients, and 2) to evaluate the overall survival and clinical response of MDR-TB patients treated with specific drug regimens. METHODS: Patients were prospectively evaluated for MDR-TB. Information included history of prior treatment for tuberculosis, close contact with a known case of MDR-TB, and residence in a facility with known or suspected MDR-TB transmission. Patients with known MDR-TB, or those suspected to be at high risk, were offered enrollment in a treatment pilot study. Study drugs included levofloxacin and at least two additional drugs to which the patient's isolate was known, or most likely, to be susceptible. Survival was the primary endpoint. RESULTS: Complete data are available for 156 HIV-infected patients with confirmed tuberculosis. Sixteen (10%) had MDR-TB. Only a history of prior tuberculosis treatment was associated with MDR-TB in multivariate analysis (OR = 4.4, P < 0.02). Twelve patients with MDR-TB enrolled in the treatment pilot had a median CD4 cell count of 51/mm3. The cumulative probability of survival at one year was 75% (95% CI 50.5-99.5) and at 18 months, 65.6% (95% CI 38.1-93.1). Toxicity requiring discontinuation of medications occurred in two patients. CONCLUSIONS: A history of treatment for tuberculosis was the only predictor for MDR-TB in a cohort of HIV-infected patients with tuberculosis. In addition, this prospective study supports the results of prior retrospective studies that effective treatment impacts on mortality. Current second-line treatment, including high dose levofloxacin, appears to be reasonably well tolerated.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Adulto , Anti-Infecciosos/uso terapêutico , Antituberculosos/uso terapêutico , Distribuição de Qui-Quadrado , Resistência Microbiana a Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Levofloxacino , Modelos Logísticos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Ofloxacino/uso terapêutico , Projetos Piloto , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Pulmonar/epidemiologia , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: To assess the prevalence of tuberculosis (TB) or a positive skin test in healthcare workers (HCWs) providing services to human immunodeficiency virus (HIV)-infected individuals and to determine prospectively the incidence of new infections in this population. DESIGN: This prospective cohort study enrolled 1,014 HCWs working with HIV-infected populations from 10 metropolitan areas. Purified protein derivative (PPD) tuberculin skin tests were placed at baseline and every 6 months afterwards on those without a history of TB or a positive PPD. Demographic, occupational, and TB exposure data also were collected. SETTING: Outpatient clinics, hospitals, private practice offices, and drug treatment programs providing HIV-related healthcare and research programs. PARTICIPANTS: A voluntary sample of staff and volunteers from 16 Community Programs for Clinical Research on AIDS units. RESULTS: Factors related to prior TB or a positive skin test at baseline included being foreign-born, increased length of time in health care, living in New York City, or previous bacille Calmette-Guerin vaccination. The rate of PPD conversion was 1.8 per 100 person years of follow-up. No independent relation was found between the amount or type of contact with HIV-infected populations and the risk of TB infection. CONCLUSION: These data provide some reassurance that caring for HIV-infected patients is not related to an increased rate of TB infection among HCWs in these settings.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/transmissão , Pessoal de Saúde/estatística & dados numéricos , Transmissão de Doença Infecciosa do Paciente para o Profissional , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/transmissão , Adulto , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
This study examined whether adding levofloxacin to a standard four-drug regimen improved the 8-week culture response and compared effectiveness of 9 versus 6 months of intermittent therapy for human immunodeficiency virus-related pansusceptible pulmonary tuberculosis. Patients were randomized to receive either four or five drugs, the fifth being levofloxacin. Patients who completed induction therapy were randomized to complete 9 versus 6 months of intermittent therapy with isoniazid and rifampin. In the randomized induction phase, 97.3% of patients in the four-drug group and 95.8% in the five-drug group had sputum culture conversion at 8 weeks (P = 1.00). In the continuation phase, one patient (2%) assigned to 9 months and two patients (3.9%) assigned to 6 months of therapy had treatment failure/relapse (P = 1.00). In conclusion, this study showed that levofloxacin added no benefit to a highly effective, largely intermittent, four-drug induction regimen. Both 9 and 6 months of intermittent therapy were associated with low treatment failure/relapse rates.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antituberculosos/uso terapêutico , Levofloxacino , Ofloxacino/uso terapêutico , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Antituberculosos/administração & dosagem , Esquema de Medicação , Quimioterapia Combinada , Etambutol/administração & dosagem , Etambutol/uso terapêutico , Feminino , Humanos , Isoniazida/administração & dosagem , Isoniazida/uso terapêutico , Masculino , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Ofloxacino/administração & dosagem , Pirazinamida/administração & dosagem , Pirazinamida/uso terapêutico , Recidiva , Rifampina/administração & dosagem , Rifampina/uso terapêutico , Escarro/microbiologia , Resultado do TratamentoRESUMO
OBJECTIVE: To characterize the susceptibility to levofloxacin of clinical isolates of Mycobacterium tuberculosis (MTB) obtained from patients with HIV-related tuberculosis and to characterize the molecular genetics of levofloxacin resistance. DESIGN AND METHODS: Isolates from culture-positive patients in a United States multicenter trial of HIV-related TB were tested for susceptibility to levofloxacin by minimum inhibitory concentration (MIC) determinations in Bactec 7H12 broth. Automated sequencing of the resistance determining region of gyrA was performed. RESULTS: Of the 135 baseline MTB isolates tested, 134 (99%; 95% exact binomial confidence interval, 95.9-99.9%) were susceptible to levofloxacin with an MIC < or = 1.0 microg/ml. We identified a previously unrecognized mis-sense mutation occurring at codon 88 of gyrA in a levofloxacin mono-resistant MTB isolate obtained from a patient with AIDS who had received ofloxacin for 8 months prior to the diagnosis of tuberculosis. CONCLUSIONS: Clinical MTB isolates from HIV-infected patients were generally susceptible to levofloxacin. However, the identification of a clinical isolate with mono-resistance to levofloxacin highlights the need for circumspection in the use of fluoroquinolones in the setting of potential HIV-related tuberculosis and for monitoring of rates of resistance of MTB isolates to fluoroquinolones.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Anti-Infecciosos/uso terapêutico , Levofloxacino , Mycobacterium tuberculosis/efeitos dos fármacos , Ofloxacino/uso terapêutico , Tuberculose/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/patologia , Antibióticos Antituberculose/administração & dosagem , Antibióticos Antituberculose/uso terapêutico , Antituberculosos/administração & dosagem , Antituberculosos/uso terapêutico , Resistência Microbiana a Medicamentos/genética , Quimioterapia Combinada , Etambutol/administração & dosagem , Etambutol/uso terapêutico , Humanos , Técnicas In Vitro , Isoniazida/administração & dosagem , Isoniazida/uso terapêutico , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Pirazinamida/administração & dosagem , Pirazinamida/uso terapêutico , Rifampina/administração & dosagem , Rifampina/uso terapêutico , Escarro/microbiologia , Tuberculose/complicações , Tuberculose/microbiologiaRESUMO
Losses to follow-up in clinical trials-patients for whom we do not know if the outcome of interest has occurred-can bias study results. If we investigate extreme case scenarios and find the study results do not change much, impact is negligible. If not, we may need to interpret the study's results with caution. At issue is how much caution do we need? We describe a graphical approach to assess the potential impact of losses to follow-up on the validity of study results. One can create the graphs using design estimates and interim or final data. We give two examples using design parameters and another example modelled after observed data from clinical trials conducted by the Terry Beirn Community Programs for Clinical Research on AIDS. The examples illustrate that tolerable levels of losses to follow-up change depending on the overall outcome and direction of differential losses.
Assuntos
Ensaios Clínicos como Assunto/estatística & dados numéricos , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Viés , Ensaios Clínicos como Assunto/normas , Humanos , Modelos Estatísticos , Projetos de Pesquisa , Tamanho da Amostra , Resultado do TratamentoRESUMO
Our aim was to evaluate the effect of human immunodeficiency virus (HIV) disease stage on chest radiographic (CXR) findings among patients with HIV-related pulmonary tuberculosis (TB). Data are from a prospective multicenter treatment trial for HIV-related TB. Baseline CXR findings and CD4+ lymphocyte counts were compared among patients with HIV-related TB. Data from published studies describing CXR findings in HIV-infected patients were reviewed and a pooled-data analysis was conducted. Of 135 patients with culture-confirmed HIV-related TB, 128 had both CXR and CD4+ lymphocyte data. CD4+ lymphocyte counts of < 200/mm3 (n = 98) were significantly associated with hilar/mediastinal adenopathy on CXR (30%, vs. 7% with counts > or = 200/mm3; P = .01); counts of > or = 200/mm3 (n = 30) more frequently were associated with cavitation (20% vs. 7%; P = .08). Analyses of these results, pooled with other published data, confirmed these findings. This study demonstrates associations of certain CXR findings with HIV disease stage. Knowledge of the degree of immunosuppression is important when evaluating CXR findings in HIV-infected patients.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS , Contagem de Linfócito CD4 , Pulmão/diagnóstico por imagem , Tuberculose Pulmonar/diagnóstico por imagem , Adolescente , Adulto , Idoso , Feminino , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Derrame Pleural/diagnóstico , Estudos Prospectivos , Radiografia , Índice de Gravidade de Doença , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/tratamento farmacológicoRESUMO
BACKGROUND: Patients with human immunodeficiency virus (HIV) infection and latent tuberculosis are at substantial risk for the development of active tuberculosis. As a public health measure, prophylactic treatment with isoniazid has been suggested for HIV-infected persons who have anergy and are in groups with a high prevalence of tuberculosis. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial of six months of prophylactic isoniazid treatment in HIV-infected patients with anergy who have risk factors for tuberculosis infection. The primary end point was culture-confirmed tuberculosis. RESULTS: The study was conducted from November 1991 through June 1996. Over 90 percent of the patients had two or more risk factors for tuberculosis infection, and nearly 75 percent of patients were from greater New York City. After a mean follow-up of 33 months, tuberculosis was diagnosed in only 6 of 257 patients in the placebo group and 3 of 260 patients in the isoniazid group (risk ratio, 0.48; 95 percent confidence interval, 0.12 to 1.91; P=0.30). There were no significant differences between the two groups with regard to death, death or the progression of HIV disease, or adverse events. CONCLUSIONS: Even in HIV-infected patients with anergy and multiple risk factors for latent tuberculosis infection, the rate of development of active tuberculosis is low. This finding does not support the use of isoniazid prophylaxis in high-risk patients with HIV infection and anergy unless they have been exposed to active tuberculosis.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Antituberculosos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Isoniazida/uso terapêutico , Tuberculose Pulmonar/prevenção & controle , Adulto , Antituberculosos/efeitos adversos , Método Duplo-Cego , Feminino , Infecções por HIV/imunologia , Humanos , Isoniazida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do TratamentoRESUMO
Infection with human immunodeficiency virus (HIV) has been associated with increased rates of single- and multidrug-resistant (MDR) tuberculosis in the New York City area. In order to examine the relationship of HIV infection to drug-resistant tuberculosis in other selected regions of the United States, we established a registry of cases of culture-proven tuberculosis. Data were collected from sites participating in an NIH-funded, community-based HIV clinical trials group. All cases of tuberculosis, regardless of HIV status, which occurred between January 1992 and June 1994 were recorded. Overall, 1,373 cases of tuberculosis were evaluated, including 425 from the New York City area, and 948 from seven other metropolitan areas. The overall prevalence of resistance to one or more drugs was 20.4%, and 5.6% of isolates were resistant to both isoniazid and rifampin (MDR). In the New York City area, HIV-infected patients were significantly more likely than persons not known to be HIV-infected, to have resistance to at least one drug (37% versus 19%) and MDR (19% versus 6%). In other geographic areas, overall drug resistance was 16%, and only 2.2% of isolates were MDR. In multiple logistic regression analyses, HIV infection was shown to be a risk factor for drug-resistant tuberculosis, independent of geographic location, history of prior therapy, age, and race. We concluded that HIV infection is associated with increased rates of resistance to antituberculosis drugs in both the New York City area and other geographic areas. MDR tuberculosis is occurring predominantly in the New York City area and is highly correlated with HIV infection.
Assuntos
Antituberculosos/uso terapêutico , Infecções por HIV/complicações , Tuberculose Resistente a Múltiplos Medicamentos/etiologia , Adolescente , Adulto , Ensaios Clínicos como Assunto , Feminino , Pessoas Mal Alojadas , Homossexualidade , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Prevalência , Sistema de Registros , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Pulmonar/prevenção & controle , Estados Unidos/epidemiologia , População UrbanaRESUMO
The purpose of this study was to examine the effects of aspirin use on mortality and morbidity rates in a subset of the control group of the Program on the Surgical Control of the Hyperlipidemias (POSCH) that was stratified by cigarette smoking status at the time of randomization. The clinical impact of aspirin intake in cigarette smokers and former cigarette smokers has not been well studied. POSCH was a randomized, controlled, clinical trial designed to ascertain the effects of lipid modification by the partial ileal bypass operation on clinical end-points and arteriographic changes in postmyocardial infarction subjects with hypercholesterolemia. Cohorts of cigarette smokers in the diet-control group were evaluated for overall and atherosclerotic coronary heart disease (ACHD) mortality rates and recurrent confirmed nonfatal myocardial infarction rates. In current cigarette smokers at baseline (n = 90) with a mean follow-up of 8.3 years, the overall mortality rate was 45.2% in patients with no aspirin use and 10.4% in patients who reported even infrequent aspirin use (relative risk = 4.3, 95% confidence interval (CI) = 2.4 to 10.6, p < 0.001). For ACHD mortality in this cohort, the relative risk was 17.1 (35.7% vs 2.1%, 95% CI = 1.4 to 125.0, p < 0.001); for the combined end-point of ACHD mortality and nonfatal myocardial infarction, the relative risk was 2.4 (40.5% vs 16.7%, 95% CI = 1.2 to 5.1, p = 0.018).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Aspirina/uso terapêutico , Infarto do Miocárdio/mortalidade , Fumar/mortalidade , Estudos de Coortes , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/mortalidade , Feminino , Seguimentos , Humanos , Hipercolesterolemia/cirurgia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Recidiva , Análise de Regressão , Fatores de Risco , Fumar/epidemiologia , Abandono do Hábito de FumarRESUMO
In this study we estimated occurrence of the booster effect in a population infected with the human immunodeficiency virus (HIV) and assessed the relation between the booster effect, T-lymphocyte CD4 cell counts, tuberculosis risk categories, and HIV exposure categories. Patients were recruited from 13 participating sites of the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). A two-stage tuberculin skin test was applied to 709 HIV-infected patients using the Mantoux method. An induration reading < 5 mm on the first test and > or = 5 on the second skin test defined the booster effect. Overall, 18 patients, or 2.7% (95% confidence interval, 1.6 to 4.2) experienced the booster effect. Boosted responses were seen in eight (2.1%) anergic patients, six (4.5%) nonanergic patients, and four (2.5%) with anergy status unknown. Boosting was noted in 1 of the 131 women enrolled. Age, race, CD4 cell count, injection drug use, anergy status, tuberculosis risk categories, and HIV exposure categories were not predictive of boosting. The booster effect occurs in a small percentage of HIV-infected patients tested, thus identifying small numbers of patients with latent tuberculosis infection. The two-stage procedure is probably of limited value in the diagnosis of latent tuberculosis in HIV-infected persons.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Teste Tuberculínico/métodos , Tuberculose Pulmonar/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Adulto , Reações Falso-Negativas , Feminino , Humanos , Masculino , Fatores de Risco , Sensibilidade e Especificidade , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/epidemiologiaRESUMO
The Program on the Surgical Control of the Hyperlipidemias (POSCH) was a secondary atherosclerosis intervention trial employing partial ileal bypass surgery as the intervention modality. For this report, we analyzed 105 subgroups in 35 variables in POSCH, chosen predominantly for their potential relationship to the risk of atherosclerotic coronary heart disease (ACHD). We defined potential differential effects as those with: (1) an absolute z-value > or = 2.0 for the subgroup, if the absolute z-value for the overall effect was < 2.0; and (2) an absolute z-value > or = 3.0 for the subgroup and a relative risk < or = 0.5, if the absolute z-value for the overall effect was > or = 2.0. For each of three major POSCH endpoints of overall mortality, ACHD mortality and ACHD mortality or confirmed nonfatal myocardial infarction, we found seven subgroups with a differential risk reduction in the surgery group as compared to the control group. Allowing for identical subgroups for more than one endpoint, there were 13 individual subgroups with differential effects. Of these, seven demonstrated internal consistency across endpoints, and five of these seven displaced external consistency with known ACHD risk factors and for biological plausibility: triglyceride concentration > or = 200 mg/dl; cigarette smoking; overt or borderline diabetes mellitus; a Minnesota ECG Q-QS code of 1-1; and obesity. A greater risk reduction, in comparison to the overall treatment effect, by the reduction of a single risk factor, hypercholesterolemia, in patients with at least two major ACHD risk factors was a provocative and an hypothesis-generating outcome of this analysis. The clinical implications of this finding may lead to more aggressive cholesterol intervention in patients with multiple ACHD risk factors.
Assuntos
Doença da Artéria Coronariana/mortalidade , Hiperlipidemias/cirurgia , Derivação Jejunoileal , Mortalidade , Infarto do Miocárdio/epidemiologia , Adulto , Antropometria , Colesterol/sangue , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde , Modelos de Riscos Proporcionais , Estudos Prospectivos , Risco , Estados Unidos/epidemiologiaRESUMO
Although myocardial ischemia causes angina pectoris, angina and the severity of coronary artery stenosis in individuals do not correlate. However, changes in anginal status over time correlated with changes in the severity of coronary artery stenosis as determined by repeated coronary arteriograms has not been previously studied. Coronary arteriograms, done both at entry into the Program on the Surgical Control of the Hyperlipidemias (POSCH) and 3 years later, were blindly graded for changes in overall severity of coronary artery stenosis according to protocol by the POSCH Arteriography Review Committee. Arteriographic and clinical data from 376 control subjects (347 men, 29 women) were analyzed. There was no statistically significant relation over a long-term (3 year) period between the absence, presence, development, or disappearance of angina pectoris and changes in coronary artery stenosis severity as determined by coronary arteriography.
Assuntos
Angina Pectoris/etiologia , Doença das Coronárias/complicações , Análise de Variância , Angina Pectoris/fisiopatologia , Pressão Sanguínea/fisiologia , Angiografia Coronária , Doença das Coronárias/fisiopatologia , Teste de Esforço , Feminino , Seguimentos , Frequência Cardíaca/fisiologia , Humanos , Hiperlipidemias/sangue , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de DoençaRESUMO
Pyrimethamine, 25 mg thrice weekly, was evaluated as primary prophylaxis for toxoplasmic encephalitis (TE) in a double-blind, randomized clinical trial in patients with human immunodeficiency virus (HIV) disease, absolute CD4 lymphocyte count of < 200/microL (or prior AIDS-defining opportunistic infection), and the presence of serum IgG to Toxoplasma gondii. Leucovorin was coadministered only for hematologic toxicity. There was a significantly higher death rate among patients receiving pyrimethamine (relative risk [RR], 2.5; 95% confidence interval [CI], 1.3-4.8; P = .006), even after adjusting for factors predictive of survival. The TE event rate was low in both treatment groups (not significant). Only 1 of 218 patients taking trimethoprim-sulfamethoxazole but 7 of 117 taking aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia developed TE (adjusted RR for the trimethoprim-sulfamethoxazole group, 0.16; 95% CI, 0.01-1.79; P = .14). Thus, for HIV-infected patients receiving trimethoprim-sulfamethoxazole, additional prophylaxis for TE appears unnecessary.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções por HIV/complicações , Pirimetamina/efeitos adversos , Toxoplasmose Cerebral/prevenção & controle , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/mortalidadeRESUMO
The Program on the Surgical Control of the Hyperlipidemias (POSCH) was a randomized controlled clinical trial designed to ascertain whether cholesterol lowering induced by the partial ileal bypass operation would favorably affect overall mortality and the mortality and morbidity due to coronary heart disease. The trial results provided strong clinical and coronary arteriographic support for the beneficial effects of lipid modification for the reduction of atherosclerosis progression. At the same time, the surgery-assigned group experienced diarrhea and an increased incidence of kidney stones and gallstones compared to the control-assigned group. Identical quality of life determinations were performed in the POSCH study population shortly before disclosure of the trial results to the patients and shortly thereafter. The purpose of this dual assessment was to evaluate the effect of knowledge of outcomes on the patients' subjective evaluation of quality of life. The primary instrument utilized for analysis of the perception of quality of life in POSCH was the McMasters Health Index Questionnaire (MHIQ). In addition, four study-specific questions were asked of the trial patients. The results for the MHIQ before disclosure of trial results showed a difference (p = 0.07) favoring the control-assigned group (diet-treated), for the social function index of the MHIQ. After disclosure of the trial results, the difference was larger (p < 0.05). For the four study-specific questions, all differences favored the control-assigned group (p < 0.01) before and after disclosure of the trial results, with the exception of satisfaction with randomization allocation in the surgery-assigned group (p = 0.08). The intragroup MHIQ indices before and after disclosure of the trial results showed no suggestive significant differences, except in the surgery-assigned group, in which there was an improvement in the emotional function index after disclosure of the trial results (p = 0.03). The intragroup responses to the study-specific questions before and after disclosure of the trial results again showed no significant differences, except in the surgery-assigned group, in which there was an improvement in patient satisfaction with randomization allocation after disclosure of the trial results (p = 0.04).(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Atitude Frente a Saúde , Hiperlipidemias/cirurgia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Colesterol/sangue , Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/mortalidade , Doença das Coronárias/prevenção & controle , Feminino , Humanos , Hiperlipidemias/psicologia , Derivação Jejunoileal/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mortalidade , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Radiografia , Inquéritos e Questionários , Resultado do Tratamento , Estados UnidosRESUMO
BACKGROUND: Serum creatinine has been reported in previous studies to be a prognostic indicator for overall mortality, in particular in a hypertensive population. METHODS: The Program on the Surgical Control of the Hyperlipidemias (POSCH) was a randomized, controlled clinical trial. All patients had survived a single myocardial infarction, were normotensive, were not obese, were not having heart failure, and were free of diabetes mellitus and renal disease at entry into the study. POSCH had followed its control group patients (N = 417) for a minimum of 7.0 years. In this group, a prospective post hoc analysis of the relationship of baseline serum creatinine with subsequent overall and atherosclerotic coronary heart disease mortality was performed. RESULTS: The baseline serum creatinine values in the control group patients ranged from 0.7 to 1.9 mg/dL (60 to 170 mumol/L), and were found to be independent predictors (P < .01) of both overall mortality and atherosclerotic coronary heart disease mortality. Each 0.1 mg/dL (9 mumol/L) increment in the baseline serum creatinine increased the relative risk for subsequent overall mortality by 36% and the relative risk for subsequent atherosclerotic coronary heart disease mortality by 47%. CONCLUSIONS: These results demonstrate that a serum creatinine value, obtained in normotensive, nonobese, normoglycemic survivors of a myocardial infarction without preexistent renal disease or heart failure, provides independent prognostic information regarding subsequent overall and atherosclerotic coronary heart disease mortality.
Assuntos
Doença da Artéria Coronariana/mortalidade , Creatinina/sangue , Infarto do Miocárdio/sangue , Adulto , Pressão Sanguínea , Causas de Morte , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/fisiopatologia , Feminino , Seguimentos , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/fisiopatologia , Prognóstico , Estudos Prospectivos , Fatores de RiscoRESUMO
This study correlated plasma lipid values with angiographic evidence of progression to complete coronary occlusion. Baseline triglycerides (TGs), total cholesterol (Chol), high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, and HDL/LDL and HDL/Chol ratios were compared with coronary angiograms taken at baseline, 3 and 5 years in a prospective angiographic study. Results were from part of the multicenter trial of plasma lipid reduction in patients after a single myocardial infarction (POSCH). Comparison of patient's baseline lipids in the absence or presence of a new total coronary occlusion at 3 years showed a significant difference (p = 0.01) in TGs of 197 +/- 147 versus 250 +/- 162 mg/dl (p = 0.02) and VLDL of 30 +/- 23 (n = 284) versus 40 +/- 30 (n = 49) mg/dl. Stratification by the mean HDL/Chol ratio (16%) demonstrated that baseline TG levels were significantly increased in patients with a new coronary occlusion by 3 years despite a higher HDL/Chol ratio. When measured at the 3-year visit, plasma TG (176 +/- 91 versus 212 +/- 146 mg/dl; p = 0.02) and VLDL (28 +/- 18 versus 35 +/- 29 mg/dl; p = 0.04) were significantly elevated in the presence of a new 3-year coronary occlusion. Stratification by the mean HDL/Chol ratio (16%) demonstrated that 3-year TG levels increased significantly in patients with a new 3-year coronary occlusion despite a higher HDL/Chol ratio.(ABSTRACT TRUNCATED AT 250 WORDS)