RESUMO
BACKGROUND: Rifamycin SV is under development for treatment of travelers' diarrhea (TD) in a new oral formulation, Rifamycin SV MMX (RIF-MMX; Santarus Inc., San Diego, CA, USA), which targets its delivery to the colon, making it a unique rifamycin drug. METHODS: This was a randomized, double-blind, phase 3 study of adult travelers to Mexico or Guatemala experiencing acute diarrhea. A total of 264 patients received RIF-MMX (2 × 200 mg twice daily for 3 days, n = 199) or placebo (n = 65) in a 3 : 1 ratio. The primary endpoint was the length of time between the administration of first dose of study drug and passage of the last unformed stool (TLUS; after which clinical cure was declared). Other endpoints included eradication of pathogens from the stools, pathogen minimum inhibitory concentration (MIC), and adverse events (AEs). RESULTS: TLUS was significantly shorter in the RIF-MMX group (median: 46.0 hours) compared with placebo (median: 68.0 hours; p = 0.0008) and a larger percentage of RIF-MMX treated patients (81.4%) achieved clinical cure compared with placebo patients (56.9%). TLUS was significantly shorter in the subgroups of patients with enteroaggregative, enterotoxigenic, or diffusely adherent Escherichia coli infections (p = 0.0035) with nonsignificant activity against invasive bacteria (p = 0.3804). Overall pathogen eradication rates were numerically higher in the RIF-MMX group (67.0%) compared with placebo (54.8%) but the difference did not reach significance (p = 0.0836). In vitro resistance to rifamycin SV was observed in some bacteria remaining after treatment of patients with RIF-MMX but was not associated with lower efficacy in them. AEs appeared to be more frequent with placebo (38.5%) than with RIF-MMX (29.6%). CONCLUSIONS: RIF-MMX shortened the duration of TD in patients with a broad range of pathogens and was well tolerated. The unique pharmacokinetic properties of the drug offer evidence that TD pathogens work at the level of the colon.
Assuntos
Diarreia/tratamento farmacológico , Infecções por Escherichia coli/tratamento farmacológico , Fármacos Gastrointestinais/administração & dosagem , Rifamicinas/administração & dosagem , Viagem , Administração Oral , Adulto , Diarreia/microbiologia , Diarreia/prevenção & controle , Método Duplo-Cego , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/prevenção & controle , Feminino , Guatemala , Humanos , Masculino , México , Rifaximina , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: The purpose of this study was to compare gadobenate dimeglumine-enhanced MR angiography and unenhanced time-of-flight MR angiography for the detection of significant peripheral arterial occlusive disease using digital subtraction angiography as our reference standard. SUBJECTS AND METHODS: Two hundred seventy-two patients underwent MR angiography and digital subtraction angiography of the iliofemoral arteries. MR angiography was performed before (2D time-of-flight acquisitions) and after (spoiled gradient-echo acquisitions) the administration of 0.1 mmol/kg of gadobenate dimeglumine at 1-2 mL/s. Contrast-enhanced MR angiography and digital subtraction angiography of the calf arteries were performed in 241 of 272 participants. Images were evaluated on-site and by four blinded reviewers (three for MR angiography, one for digital subtraction angiography). Comparative diagnostic performance for the detection of significant (> or = 51% vessel lumen narrowing) disease was evaluated using the McNemar test and generalized estimating equations. Interobserver agreement was assessed with generalized kappa statistics. The chi-square test was used to compare technical failure rates. RESULTS: Digital subtraction angiography confirmed significant disease (597 stenoses, 386 occlusions) in 983 iliofemoral segments. The sensitivity (54-80.9%), specificity (89.7-95.3%), and accuracy (85-87.5%) of contrast-enhanced MR angiography for the detection of significant iliofemoral disease were significantly (p < 0.001, all reviewers) better than those of time-of-flight MR angiography (33.2-62.8%, 74.3-88.9%, and 68-77.3%, respectively). Similar diagnostic performance was obtained for the calf arteries. The technical failure rate with contrast-enhanced MR angiography (2.5-3.4%) was similar to that of digital subtraction angiography (1.4%) and significantly (p < 0.001) lower than that of time-of-flight MR angiography (6.2-18.0%). Significantly better reproducibility (p < 0.001) was obtained with contrast-enhanced MR angiography (82% vs 65.2% agreement; kappa = 0.66 vs 0.45). CONCLUSION: Improved diagnostic performance and reproducibility are achievable with gadobenate dimeglumine-enhanced MR angiography in patients with peripheral arterial occlusive disease.
Assuntos
Arteriopatias Oclusivas/diagnóstico , Aumento da Imagem/métodos , Angiografia por Ressonância Magnética/métodos , Meglumina/análogos & derivados , Compostos Organometálicos/uso terapêutico , Doenças Vasculares Periféricas/diagnóstico , Coxa da Perna/irrigação sanguínea , Coxa da Perna/patologia , Adulto , Idoso , Meios de Contraste , Europa (Continente) , Feminino , Humanos , Masculino , Meglumina/uso terapêutico , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , América do SulRESUMO
UNLABELLED: BACKGROUND; AIDS-related stigma is one of the biggest obstacles in the fight to prevent HIV transmission. Since stigma deters people from seeking treatment or getting tested for HIV, determining the factors that underpin AIDS-related stigmatization may be key to finding new ways to improve care and support for people living with HIV/AIDS (PLWHA) and to reduce new infections. SETTING: The town of Lucea and surrounding communities in the parish of Hanover, Jamaica. METHOD: Cross-sectional questionnaire survey of 195 individuals from health centers and households in Hanover. RESULTS: Of the 195 respondents, 28 percent felt the names of HIV-positive people should be public information. We found three constructs (avoidant behavior, social contact stigma, and blame stigma) that underpin stigmatization of PLWHA. The factors that influence avoidance behavior were education and being married. The factors associated with social contact stigma were being married and having no acquaintance with PLWHA. The factor that influenced blame stigma was not owning a home. CONCLUSION: Public health campaigns to reduce stigmatization must address individuals on the basis of their socio-demographic characteristics. A critical appraisal of current anti-stigma measures is warranted, and appropriate anti-stigma interventions are needed. Interventions with community members should address the social context of stigma, particularly the arenas of community norms, through education, information, and legislative measures to promote interaction with, and positive attitudes toward, PLWHA.