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1.
Community Dent Health ; 33(4): 274-280, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28537364

RESUMO

OBJECTIVE: To test the psychometric properties of the Oral Health Literacy Adult Questionnaire (OHL-AQ) in English. The OHL-AQ was designed to test functional oral health literacy in general populations and was initially validated in Iran. METHODS: The instrument was administered to 405 adult subjects (mean age 45 (SD 16) years and 67% female) attending the 2014 Minnesota State Fair. The OHL-AQ is composed of 17 items measuring four conceptual dimensions: reading comprehension, numeracy, listening, and decision-making. Participants selected the best answer for written or verbally administered items and entered answers on an electronic tablet. Item responses for each individual were combined into a summary score (range 0-17) with higher scores indicating better oral health literacy. Score dimensionality, reliability, and validity were investigated. RESULTS: For dimensionality, both exploratory factor analysis and a parallel analysis yielded evidence for scale unidimensionality. Reliability was sufficient indicated by a Cronbach's alpha ⟩0.74. Validity of scores was supported by "small" and "medium" effect sizes for construct validity. "Small" effect sizes were observed for global oral health self-report, OHIP-5 scores, treatment urgency, and having a regular dentist. "Medium" effect sizes were seen for presence of dentures, number of natural teeth present, and educational level. CONCLUSIONS: Dimensionality, reliability and validity of the English version of the OHL-AQ in a general adult English-speaking population is supported, providing sufficient psychometric properties in an important target population of the instrument.


Assuntos
Letramento em Saúde , Saúde Bucal , Psicometria , Inquéritos e Questionários , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Minnesota , Reprodutibilidade dos Testes
2.
Rev. Soc. Boliv. Pediatr ; 49(1): 34-34, 2010.
Artigo em Espanhol | LILACS | ID: lil-652522

RESUMO

El estudio identifica factores predictivos de infección o de complicaciones en pacientes pediátricos con neutropenia febril (NF), establece puntos clínicos decorte y destaca la importancia de la impresión clínica inicial y 24 horas de observación.


Assuntos
Neutropenia/prevenção & controle , Neutropenia/terapia
3.
AIDS Care ; 18(6): 544-9, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16831780

RESUMO

We undertook a retrospective medical chart review of HIV-infected adolescents referred to a Southern US urban comprehensive adolescent HIV clinic between 1992 and 2003 to describe the psychosocial profile of adolescents infected with HIV via high-risk behaviours.Ninety-one adolescents (59 females, 32 males, 95% African-American, median age 17 years) were identified. Common reasons for initial HIV testing included routine prenatal screening (20%), clinical symptoms suggestive of HIV (20%), and recognized risk-related behaviours (20%). Findings included a history of unstable housing in the previous year (27%), running away (29%), knowing someone with HIV (36%), parental substance abuse (reported by youth, 46%), parental abandonment/neglect (30%), high substance use rates (marijuana 33%, tobacco 27%), current/prior STDs (60%), and involvement with the juvenile justice system or incarceration (41%). Sexual abuse/assault was reported by 41%. Previous depression was reported in 15% with approximately half reporting prior hospitalization. An additional 12% of the cohort had current clinical depressive symptoms. We conclude that infections with HIV via high-risk behaviours during adolescence occur in youth with multiple psychosocial stressors. Targeted prevention efforts to reduce these underlying stressors may decrease new adolescent infection. HIV-infected youth are best served in a comprehensive care environment with immediate access to medical care, social work, and psychology/psychiatry services.


Assuntos
Infecções por HIV/psicologia , Adolescente , Adulto , Negro ou Afro-Americano , Feminino , Humanos , Acontecimentos que Mudam a Vida , Masculino , Estudos Retrospectivos , Fatores de Risco , Assunção de Riscos , Comportamento Sexual/psicologia , Comportamento Sexual/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Sexo sem Proteção/estatística & dados numéricos , Saúde da População Urbana
5.
AIDS Care ; 16 Suppl 1: S121-36, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15736825

RESUMO

This paper describes the research challenges involved in measuring costs in economic evaluations of patients who are coping simultaneously with HIV/AIDS and co-occurring mental health and substance abuse disorders-especially in multi-site studies. We describe the general issues that arise in measuring costs for this population and suggest some operational solutions for their resolution, drawing from our experience in a recent multi-site health services research study focused on this population. We show that while reliance on patient self-report data may be unavoidable to provide a common denominator in multi-site studies, there are also some practical ways of improving the accuracy of such data and the cost estimates that result from them. We also provide readers with a means for securing the data collection instruments developed for the cost component of this study in the hope that these may serve as templates for researchers doing similar work.


Assuntos
Infecções por HIV/economia , Transtornos Mentais/economia , Análise Custo-Benefício , Diagnóstico Duplo (Psiquiatria) , Feminino , Infecções por HIV/terapia , Custos de Cuidados de Saúde , Humanos , Masculino , Estudos Multicêntricos como Assunto , Transtornos Relacionados ao Uso de Substâncias/economia
6.
AIDS Care ; 13(5): 617-29, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11571008

RESUMO

This study examined the association between two components of the Health Belief Model (perceived vulnerability and barriers) and adherence to antiretroviral therapy (ART) among children who are HIV-infected. The parents/caregivers of 30 children (mean age = 5.21, SD = 3.18) who were HIV-infected and who were on active ART were surveyed to assess current methods of adherence assessment and educational efforts within the institution. All participants (except one) were African American and reported low monthly family incomes (M = $869.45, SD = $832.63). Assessment instruments included measures of perceived vulnerability, caregiver-reported adherence and perceived barriers, and objective measures of adherence (clinical pill count; electronic measurement). The results failed to demonstrate a significant relationship between parental perceived vulnerability, perceived barriers and adherence to antiretroviral medications. Methods of assessing adherence provided significantly discrepant estimates of adherence. Results are discussed in terms of implications for patient care and for future research in this area. The addition of behavioural and motivational components to traditional educational approaches may positively impact treatment results.


Assuntos
Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/tratamento farmacológico , Cooperação do Paciente , Adolescente , Adulto , Idoso , Análise de Variância , Cuidadores , Criança , Pré-Escolar , Feminino , Nível de Saúde , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Recusa do Paciente ao Tratamento
7.
Cancer Chemother Pharmacol ; 47(6): 467-72, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11459198

RESUMO

PURPOSE: The use of trimethoprim/sulfamethoxazole in the prevention of Pneumocystis carinii pneumonia in patients with acute lymphoblastic leukemia (ALL) may cause undesirable adverse effects: fungal overgrowth, neutropenia, and drug resistance. A possible alternative is atovaquone, a hydroxynaphthoquinone with anti-Pneumocystis carinii activity. However, it is not known if atovaquone alters the disposition or adverse effects of antileukemic drugs. METHODS: Using a crossover study design, we compared the pharmacokinetics of etoposide and its CYP3A4-formed catechol metabolite when given as a 300 mg/m2 i.v. infusion following daily atovaquone versus trimethoprim/sulfamethoxazole in nine patients. RESULTS: The area under the concentration time curve (AUC) of etoposide, etoposide catechol and the catechol to etoposide AUC ratio were slightly higher (a median of 8.6%, 28.4%, and 25.9%) following atovaquone as compared to trimethoprim/sulfamethoxazole (P=0.055, P= 0.031 and P=0.023), respectively. In vitro analysis in human liver microsomes showed modest inhibition of etoposide catechol formation in the presence of atovaquone. Using uptake of 3H-vinblastine in L-MDR1 cells, atovaquone was shown to inhibit P-glycoprotein with an apparent Ki of 95.6 microM. CONCLUSIONS: Although the effect of atovaquone on etoposide disposition was modest, in light of the fact that the risk of etoposide-related secondary acute myeloid leukemia has been linked to minor changes in schedule and concurrent therapy, we suggest caution with the simultaneous administration of atovaquone and etoposide, particularly if used with other CYP3A4/P-glycoprotein substrates.


Assuntos
Antifúngicos/farmacologia , Antineoplásicos Fitogênicos/farmacocinética , Etoposídeo/farmacocinética , Linfoma não Hodgkin/metabolismo , Naftoquinonas/farmacologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Combinação Trimetoprima e Sulfametoxazol/farmacologia , Adolescente , Área Sob a Curva , Atovaquona , Criança , Pré-Escolar , Estudos Cross-Over , Interações Medicamentosas , Feminino , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Projetos Piloto , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
8.
Clin Infect Dis ; 32(10): 1456-62, 2001 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-11317247

RESUMO

Two cases of Bacillus cereus meningitis in immunocompromised children at our hospital within a 2-month period prompted us to review B. cereus--related invasive disease. We identified 12 patients with B. cereus isolated in blood cultures from September 1988 through August 2000 at our institution. Three of these patients also had B. cereus isolated from CSF specimens; 1 additional patient had possible CNS involvement (33%, group A), whereas 8 patients had no evidence of CNS involvement (67%, group B). Patients in group A were more likely to have neutropenia at the onset of sepsis and were more likely to have an unfavorable outcome. They were also more likely to have received intrathecal chemotherapy in the week before the onset of their illness. Two patients from group A died. One survived with severe sequelae. The fourth patient had mild sequelae at follow-up. No sequelae or deaths occurred among patients in group B. In patients with unfavorable outcomes, the interval from the time of recognition of illness to irreversible damage or death was short, which demonstrates a need for increased awareness, early diagnosis, and more-effective therapy, particularly that which addresses B. cereus toxins.


Assuntos
Bacillus cereus/isolamento & purificação , Bacteriemia/epidemiologia , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Hospedeiro Imunocomprometido , Meningites Bacterianas/epidemiologia , Adolescente , Adulto , Bacteriemia/microbiologia , Sangue/microbiologia , Líquido Cefalorraquidiano/microbiologia , Criança , Pré-Escolar , Meios de Cultura , Feminino , Humanos , Masculino , Meningites Bacterianas/microbiologia
9.
Pediatr Radiol ; 31(3): 144-52, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11297075

RESUMO

BACKGROUND: Invasive pulmonary aspergillosis is fulminant and often fatal in immunosuppressed patients. Percutaneous biopsy may select patients who could benefit from surgical resection. OBJECTIVE: We sought to determine the accuracy of percutaneous biopsy for pediatric invasive pulmonary aspergillosis. MATERIALS AND METHODS: We retrospectively reviewed 28 imaging-guided percutaneous biopsies of the lungs of 24 children with suspected pulmonary aspergillosis. Twenty-two were being treated for malignancy and two for congenital immunodeficiency; 15 had received bone-marrow transplants. The accuracy of the percutaneous lung biopsy was determined by subsequent surgical resection, autopsy, or clinical course. RESULTS: Histopathological studies showed ten biopsy specimens with septate hyphae, indicating a mold, and seven with Aspergillus flavus colonies in culture. The remaining 18 biopsies revealed no fungi. No patient had progressive aspergillosis after negative biopsy. Invasive pulmonary mold was detected by percutaneous biopsy with 100% (10/10) sensitivity and 100% (18/18) specificity. Percutaneous biopsy results influenced the surgical decision in 86% (24 of 28) of the cases. Bleeding complicated the biopsy in 46% (13/28) and hastened one death. CONCLUSION: Percutaneous biopsy of the lung is an accurate technique for the diagnosis of invasive pulmonary aspergillosis and correctly determines which immunosuppressed pediatric patients would benefit from therapeutic pulmonary resection.


Assuntos
Aspergilose/patologia , Aspergillus flavus , Biópsia por Agulha , Pneumopatias Fúngicas/patologia , Infecções Oportunistas/patologia , Tomografia Computadorizada por Raios X , Criança , Seguimentos , Humanos , Pulmão/patologia , Valor Preditivo dos Testes , Estudos Retrospectivos
10.
Clin Infect Dis ; 32(1): 36-43, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11112678

RESUMO

Empiric oral antibiotic therapy for febrile neutropenic cancer patients has been suggested as a means to decrease hospitalization, but the safety of this approach has not been adequately studied in children. We compared continued iv antibiotic therapy with switching treatment to orally administered cefixime in a group of selected febrile neutropenic children for whom blood cultures were sterile after 48 h of incubation. Two hundred episodes of febrile neutropenia were studied (156 patients), and 100 episodes were randomized to receive each treatment. Failure to respond to therapy was defined by documented or suspected bacterial infection, recurrent fever, or discontinuation of assigned therapy for any reason before neutropenia resolved. Rates of treatment failure were similar in the oral cefixime group (28%) and in the iv antibiotic group (27%; P=1.0). Results support the safety of oral cefixime therapy for low-risk febrile neutropenic children, a therapeutic approach that would facilitate earlier outpatient management and decrease the costs of treatment.


Assuntos
Cefixima/uso terapêutico , Cefalosporinas/uso terapêutico , Febre/complicações , Neoplasias/complicações , Neutropenia/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Antibacterianos/administração & dosagem , Cefixima/administração & dosagem , Cefixima/efeitos adversos , Cefalosporinas/administração & dosagem , Cefalosporinas/efeitos adversos , Criança , Pré-Escolar , Qualidade de Produtos para o Consumidor , Feminino , Humanos , Lactente , Injeções Intravenosas , Masculino , Neutropenia/complicações , Falha de Tratamento
12.
Clin Infect Dis ; 31(2): 451-7, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10987704

RESUMO

Candidal meningitis is a rare disease that is seen most frequently in neonates, neurosurgical patients, and the immunocompromised host. We describe a series of 12 children with cancer (all of whom had leukemia) who had candidal meningitis develop. Univariate analysis revealed that duration of fever, antibiotic therapy, and profound neutropenia and use of total parenteral nutrition were significantly associated (P<.05) with candidal meningitis in children with cancer, compared with matched control subjects. Only duration of profound neutropenia (P=.08) and use of total parenteral nutrition (P=.06) approached significance in the multivariate analysis. One species of Candida, Candida tropicalis, was responsible for 11 of the 12 cases, indicating increased pathogenicity of this organism in CNS disease. The cases were invariably fatal, supporting aggressive treatment of candidal meningitis in immunocompromised patients and further study of the prevention, diagnosis, and management of C. tropicalis meningitis.


Assuntos
Candida/isolamento & purificação , Candidíase/etiologia , Hospedeiro Imunocomprometido , Leucemia/complicações , Meningite Fúngica/etiologia , Antifúngicos/uso terapêutico , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Candidíase/mortalidade , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Meningite Fúngica/tratamento farmacológico , Meningite Fúngica/microbiologia , Meningite Fúngica/mortalidade , Fatores de Risco
13.
J Infect Dis ; 181(5): 1817-21, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10823792

RESUMO

Pneumococcal antibody levels surrounding systemic pneumococcal illness (SPI) were measured in children infected with human immunodeficiency virus (HIV). Archived serum samples were collected from 28 HIV-infected children who had 34 cases of SPI, caused by pneumococcal groups 4, 6, 9, 14, 19, and 23. Serum samples collected within 23 weeks before and 13 weeks after the SPI were assayed by ELISA for antipneumococcal polysaccharide (PnPs) IgG antibody to 6 representative pneumococcal serotypes. There was a wide range (0. 16-30.80 microg/mL) of pre-SPI anti-PnPs antibody levels to the presumed infecting serotypes, with a geometric mean level of 0.83 microg/mL (n=34). Seventy-six percent of the antibody values were <2.0 microg/mL, and 95% were <5.0 microg/mL. Homologous seroresponses (>/=4-fold rise in anti-PnPs antibody) were detected in only 4 (27%) of 15 paired serum samples. Heterologous, noninfecting group seroresponses were detected frequently (72%) in the paired serum samples from these 4 homologous group seroresponders.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/imunologia , Anticorpos Antibacterianos/sangue , Infecções por HIV/imunologia , Imunoglobulina G/sangue , Infecções Pneumocócicas/imunologia , Infecções Oportunistas Relacionadas com a AIDS/sangue , Bacteriemia/sangue , Bacteriemia/imunologia , Criança , Ensaio de Imunoadsorção Enzimática , Infecções por HIV/sangue , Humanos , Prontuários Médicos , Infecções Pneumocócicas/sangue , Polissacarídeos Bacterianos/imunologia
14.
N Engl J Med ; 341(25): 1874-81, 1999 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-10601506

RESUMO

BACKGROUND: Consistent long-term viral suppression has been difficult to achieve in children with human immunodeficiency virus type 1 (HIV-1) infection. We tested the safety and antiviral efficacy of a novel combination consisting of efavirenz, nelfinavir, and one or more nucleoside reverse-transcriptase inhibitors in 57 children previously treated with only nucleoside reverse-transcriptase inhibitors. METHODS: The children were monitored for 48 weeks after the initiation of therapy. We assessed plasma concentrations of efavirenz and nelfinavir, plasma HIV-1 RNA levels, and lymphocyte subpopulations. RESULTS: At base line, the 57 HIV-1-infected children (age range, 3.8 to 16.8 years) had a median of 699 CD4 cells per cubic millimeter and 10,000 copies of HIV-1 RNA per milliliter of plasma. The most common treatment-related effects of at least moderate severity were rash (in 30 percent of children), diarrhea (in 18 percent), neutropenia (in 12 percent), and biochemical abnormalities (in 12 percent). Serious side effects were uncommon. The mean values for the area under the curve for efavirenz and nelfinavir corresponded to expected values. In an intention-to-treat analysis, 76 percent of children had plasma HIV-1 RNA levels of less than 400 copies per milliliter after 48 weeks of therapy and 63 percent had levels of less than 50 copies per milliliter. A high plasma HIV-1 RNA level at base line significantly decreased the likelihood that plasma levels of HIV-1 RNA would become undetectable during treatment. CONCLUSIONS: In HIV-1-infected children who were previously treated with nucleoside reverse-transcriptase inhibitors, the combination of efavirenz, nelfinavir, and nucleoside reverse-transcriptase inhibitors was generally well tolerated and had a potent and sustained antiviral effect.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV-1 , Nelfinavir/uso terapêutico , Oxazinas/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Adolescente , Alcinos , Benzoxazinas , Contagem de Linfócito CD4 , Criança , Pré-Escolar , Ciclopropanos , Quimioterapia Combinada , Feminino , Infecções por HIV/virologia , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/farmacocinética , HIV-1/isolamento & purificação , Humanos , Masculino , Nelfinavir/efeitos adversos , Nelfinavir/farmacocinética , Oxazinas/efeitos adversos , Oxazinas/farmacocinética , RNA Viral/sangue , Inibidores da Transcriptase Reversa/efeitos adversos , Inibidores da Transcriptase Reversa/farmacocinética
15.
J Infect Dis ; 180(6): 1844-50, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10558940

RESUMO

Systemic and intracellular pharmacokinetics of zidovudine were determined for 28 human immunodeficiency virus type 1-infected pregnant women and their newborn infants. Plasma zidovudine and intracellular zidovudine monophosphate and triphosphate concentrations were determined in serial maternal samples and cord blood at delivery. Higher levels of cord blood zidovudine were associated with lower maternal zidovudine clearance and longer infusion times. Median levels of zidovudine monophosphate and triphosphate in maternal (1556 and 67 fmol/106 cells) and cord (1464 and 70 fmol/106 cells) blood were similar but highly variable. Intersubject pharmacokinetic variability for zidovudine is substantial, but intravenous therapy provides plasma concentrations and intracellular zidovudine triphosphate levels consistent with high antiviral activity. The substantial amount of intracellular zidovudine triphosphate in cord blood provides an explanation for the clinical success of zidovudine in reducing vertical transmission. Studies of simpler oral regimens of zidovudine can now be evaluated regarding the ability to achieve these pharmacologic end points associated with highly effective parenteral therapy.


Assuntos
Fármacos Anti-HIV/farmacocinética , Infecções por HIV/tratamento farmacológico , HIV-1 , Complicações Infecciosas na Gravidez/tratamento farmacológico , Zidovudina/farmacocinética , Adolescente , Adulto , Fármacos Anti-HIV/sangue , Fármacos Anti-HIV/uso terapêutico , Didesoxinucleotídeos , Feminino , Sangue Fetal/química , Sangue Fetal/virologia , Infecções por HIV/sangue , Infecções por HIV/transmissão , Infecções por HIV/virologia , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Fosforilação , Gravidez , Complicações Infecciosas na Gravidez/virologia , Inibidores da Transcriptase Reversa/sangue , Inibidores da Transcriptase Reversa/farmacocinética , Inibidores da Transcriptase Reversa/uso terapêutico , Nucleotídeos de Timina/sangue , Zidovudina/análogos & derivados , Zidovudina/sangue , Zidovudina/uso terapêutico
16.
Clin Infect Dis ; 29(5): 1210-9, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10524965

RESUMO

A retrospective review of medical records, microbiology and pathology laboratory records, and nosocomial infection surveillance data was undertaken to describe the experience with culture-documented aspergillus infection in pediatric cancer patients at our facility. Sixty-six patients were identified from a 34-year period. The most common underlying diagnosis was leukemia. Risk factors included neutropenia, immunosuppression, and prior antibiotic therapy. On the basis of clinical presentation, 23 patients were believed to have disseminated disease and 43 to have localized disease. The lung was the most frequently affected organ. Despite aggressive medical and surgical management, overall mortality was 85% within the first year after diagnosis. Patients who presented with disease in sites other than the lungs fared better than patients with initial pulmonary involvement (P=.0014). Aspergillosis continues to be associated with poor outcome. Development of improved medical and adjuvant therapies, including surgery, is warranted.


Assuntos
Aspergilose/etiologia , Neoplasias/complicações , Adolescente , Aspergilose/tratamento farmacológico , Doenças Ósseas Infecciosas/etiologia , Criança , Pré-Escolar , Dermatomicoses/etiologia , Feminino , Humanos , Lactente , Masculino , Doenças dos Seios Paranasais/etiologia , Estudos Retrospectivos
17.
Nat Med ; 5(9): 1048-51, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10470083

RESUMO

Dideoxynucleosides, which are potent inhibitors of HIV reverse transcriptase and other viral DNA polymerases, are a common component of highly active anti-retroviral therapy (HAART) (ref. 1). Six reverse transcriptase inhibitors have been approved for human use: azidothymidine; 2'3'-dideoxycytidine; 2'3'-dideoxyinosine; 2', 3'-didehydro-3'deoxythymidine; 2',3'-dideoxy-3'-thiacytidine; and 4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-++ +metha nol. Although drug-resistant HIV strains resulting from genetic mutation have emerged in patients treated with HAART (ref. 1), some patients show signs of drug resistance in the absence of drug-resistant viruses. In our study of alternative or additional mechanisms of resistance operating during antiviral therapy, overexpression and amplification of the MRP4 gene correlated with ATP-dependent efflux of PMEA (9-(2-phosphonylmethoxyethyl)adenine) and azidothymidine monophosphate from cells and, thus, with resistance to these drugs. Overexpression of MRP4 mRNA and MRP4 protein severely impaired the antiviral efficacy of PMEA, azidothymidine and other nucleoside analogs. Increased resistance to PMEA and amplification of the MRP4 gene correlated with enhanced drug efflux; transfer of chromosome 13 containing the amplified MRP4 gene conferred resistance to PMEA. MRP4 is the first transporter, to our knowledge, directly linked to the efflux of nucleoside monophosphate analogs from mammalian cells.


Assuntos
Fármacos Anti-HIV/farmacologia , Proteínas de Transporte/metabolismo , HIV-1/efeitos dos fármacos , Nucleosídeos/farmacologia , Organofosfonatos , Linfócitos T/efeitos dos fármacos , Adenina/análogos & derivados , Adenina/farmacocinética , Adenina/farmacologia , Fármacos Anti-HIV/farmacocinética , Proteínas de Transporte/genética , Linhagem Celular , Resistência Microbiana a Medicamentos , Amplificação de Genes/genética , Dosagem de Genes , Expressão Gênica , Genes Dominantes/genética , Humanos , Células Híbridas/efeitos dos fármacos , Células Híbridas/metabolismo , Concentração Inibidora 50 , Proteínas de Membrana Transportadoras , Nucleosídeos/farmacocinética , Fenótipo , RNA Mensageiro/análise , RNA Mensageiro/genética , Inibidores da Transcriptase Reversa/farmacocinética , Inibidores da Transcriptase Reversa/farmacologia , Linfócitos T/metabolismo , Zidovudina/farmacocinética , Zidovudina/farmacologia
18.
Health Serv Res ; 34(3): 791-806, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10445903

RESUMO

OBJECTIVE: To examine lifetime and current psychiatric comorbidity measures as predictors of drug abuse treatment retention, and to test the generalizability of results across treatment agencies in diverse settings and with varying practices. DATA SOURCES/STUDY SETTING: The national Drug Abuse Treatment Outcome Studies (DATOS), a longitudinal study of clients from 96 treatment agencies in 11 U.S. cities. STUDY DESIGN: The design is naturalistic and uses longitudinal analysis of treatment retention in long-term residential, outpatient drug-free, and outpatient methadone treatment modalities; client background (including psychiatric comorbidity) and program service provision are predictors. Clinical thresholds for adequate treatment retention were 90 days for long-term residential and outpatient drug-free, and 360 days for outpatient methadone. Psychiatric indicators included lifetime DSM-III-R diagnoses of depression/anxiety and antisocial personality, and dimensional measures of current symptoms for depression and hostility. DATA COLLECTION/EXTRACTION METHODS: Data include structured interviews with clients, a survey of treatment program administrators, and program discharge records. PRINCIPAL FINDINGS: Dimensional measures of current psychiatric symptoms emerged as better predictors than lifetime DSM-III-R diagnoses. In addition, the predictive association of hostility with retention varied significantly across treatment agencies, both in the long-term residential and outpatient drug-free modalities. Other notable findings were that on-site mental health services in long-term residential programs were associated with better retention for clients with symptoms of hostility. CONCLUSIONS: Assessment issues and stability of results across programs are important considerations for treatment research and practice.


Assuntos
Comorbidade , Transtornos Mentais/diagnóstico , Centros de Tratamento de Abuso de Substâncias , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Resultado do Tratamento , Adulto , Demografia , Feminino , Humanos , Entrevista Psicológica , Estudos Longitudinais , Masculino , Cooperação do Paciente/etnologia , Cooperação do Paciente/estatística & dados numéricos , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Prognóstico , Análise de Regressão , Fatores Socioeconômicos , Estados Unidos
19.
JAMA ; 281(2): 151-7, 1999 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-9917118

RESUMO

CONTEXT: With the success of zidovudine chemoprophylaxis for prevention of perinatal transmission of the human immunodeficiency virus (HIV), an increasing number of HIV-exposed but uninfected children will have in utero exposure to zidovudine and other antiretroviral drugs. OBJECTIVE: To evaluate the long-term effects of in utero exposure to zidovudine vs placebo among a randomized cohort of uninfected children. DESIGN: Prospective cohort study based on data collected during Pediatric AIDS Clinical Trials Group Protocol 076, a perinatal zidovudine HIV prevention trial, and Protocol 219, a long-term observational protocol. SETTING: Pediatric research clinics in the United States. PATIENTS: Two hundred thirty-four uninfected children born to 230 HIV-infected women enrolled in Protocol 076 and followed up through February 28, 1997, in Protocol 219 (122 in the zidovudine group and 112 in the placebo group). MAIN OUTCOME MEASURES: Physical growth measurements, immunologic parameters, cognitive/developmental function, occurrence of neoplasms, and mortality data assessed every 6 months for children younger than 24 months and yearly thereafter or as clinically indicated. Baseline echocardiogram and funduscopic evaluations were collected before 36 months of age. RESULTS: Median age of children at time of last follow-up visit was 4.2 years (range, 3.2-5.6 years). There were no significant differences between children exposed to zidovudine and those who received placebo in terms of sequential data on lymphocyte subsets; weight, height, and head circumference z scores; and cognitive/developmental function. No deaths or malignancies occurred. Two children (both exposed to zidovudine) are being followed up for abnormal, unexplained ophthalmic findings. One child exposed to zidovudine had a mild cardiomyopathy on echocardiogram at the age of 48 months; the child is clinically asymptomatic. CONCLUSIONS: No adverse effects were observed in HIV-uninfected children with in utero and neonatal exposure to zidovudine followed up for as long as 5.6 years. Continued prospective evaluations of children born to HIV-infected women who are exposed to antiretroviral or immunotherapeutic agents are critical to assess the long-term safety of interventions that prevent perinatal HIV transmission.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/prevenção & controle , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/prevenção & controle , Efeitos Tardios da Exposição Pré-Natal , Inibidores da Transcriptase Reversa/uso terapêutico , Zidovudina/uso terapêutico , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos , Desenvolvimento Infantil , Pré-Escolar , Ecocardiografia , Feminino , Crescimento , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Resultado da Gravidez , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Testes Visuais
20.
Drug Alcohol Depend ; 57(2): 167-74, 1999 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-10617100

RESUMO

Our objective was to examine the cost of long-term residential (LTR) and outpatient drug-free (ODF) treatments for cocaine-dependent patients participating in the Drug Abuse Treatment Outcome Studies (DATOS), calculate the tangible cost of crime to society, and determine treatment benefits. Subjects were 502 cocaine-dependent patients selected from a national and naturalistic nonexperimental evaluation of community-based treatment. Financial data were available for programs from 10 US cities where the subjects received treatment between 1991 and 1993. Treatment costs were estimated from the 1992 National Drug Abuse Treatment Unit Survey (NDATUS), and tangible costs of crime were estimated from reports of illegal acts committed before, during, and after treatment. Sensitivity analyses examined results for three methods of estimating the costs of crime and cost-benefit ratios. Results showed that cocaine-dependent patients treated in both LTR and ODF programs had reductions in costs of crime from before to after treatment. LTR patients had the highest levels and costs of crime before treatment, had the greatest amount of crime cost reductions in the year after treatment, and yielded the greatest net benefits. Cost-benefit ratios for both treatment modalities provided evidence of significant returns on treatment investments for cocaine addiction.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/economia , Crime/economia , Tratamento Domiciliar/economia , Adulto , Transtornos Relacionados ao Uso de Cocaína/reabilitação , Análise Custo-Benefício/economia , Análise Custo-Benefício/estatística & dados numéricos , Crime/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tratamento Domiciliar/normas , Centros de Tratamento de Abuso de Substâncias/economia , Centros de Tratamento de Abuso de Substâncias/normas
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