Comparative effectiveness of immediate antiretroviral therapy versus CD4-based initiation in HIV-positive individuals in high-income countries: observational cohort study.

BACKGROUND Recommendations have differed nationally and internationally with respect to the best time to start antiretroviral therapy (ART). We compared effectiveness of three strategies for initiation of ART in high-income countries for HIV-positive individuals who do not have AIDS: immediate initiation, initiation at a CD4 count less than 500 cells per μL, and initiation at a CD4 count less than 350 cells per μL. METHODS We used data from the HIV-CAUSAL Collaboration of cohort studies in Europe and the USA. We included 55 826 individuals aged 18 years or older who were diagnosed with HIV-1 infection between January, 2000, and September, 2013, had not started ART, did not have AIDS, and had CD4 count and HIV-RNA viral load measurements within 6 months of HIV diagnosis. We estimated relative risks of death and of death or AIDS-defining illness, mean survival time, the proportion of individuals in need of ART, and the proportion of individuals with HIV-RNA viral load less than 50 copies per mL, as would have been recorded under each ART initiation strategy after 7 years of HIV diagnosis. We used the parametric g-formula to adjust for baseline and time-varying confounders. FINDINGS Median CD4 count at diagnosis of HIV infection was 376 cells per μL (IQR 222-551). Compared with immediate initiation, the estimated relative risk of death was 1·02 (95% CI 1·01-1·02) when ART was started at a CD4 count less than 500 cells per μL, and 1·06 (1·04-1·08) with initiation at a CD4 count less than 350 cells per μL. Corresponding estimates for death or AIDS-defining illness were 1·06 (1·06-1·07) and 1·20 (1·17-1·23), respectively. Compared with immediate initiation, the mean survival time at 7 years with a strategy of initiation at a CD4 count less than 500 cells per μL was 2 days shorter (95% CI 1-2) and at a CD4 count less than 350 cells per μL was 5 days shorter (4-6). 7 years after diagnosis of HIV, 100%, 98·7% (95% CI 98·6-98·7), and 92·6% (92·2-92·9) of individuals would have been in need of ART with immediate initiation, initiation at a CD4 count less than 500 cells per μL, and initiation at a CD4 count less than 350 cells per μL, respectively. Corresponding proportions of individuals with HIV-RNA viral load less than 50 copies per mL at 7 years were 87·3% (87·3-88·6), 87·4% (87·4-88·6), and 83·8% (83·6-84·9). INTERPRETATION The benefits of immediate initiation of ART, such as prolonged survival and AIDS-free survival and increased virological suppression, were small in this high-income setting with relatively low CD4 count at HIV diagnosis. The estimated beneficial effect on AIDS is less than in recently reported randomised trials. Increasing rates of HIV testing might be as important as a policy of early initiation of ART. FUNDING National Institutes of Health.

Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage.

Mycobacterium tuberculosis strains of the Beijing lineage are globally distributed and are associated with the massive spread of multidrug-resistant (MDR) tuberculosis in Eurasia. Here we reconstructed the biogeographical structure and evolutionary history of this lineage by genetic analysis of 4,987 isolates from 99 countries and whole-genome sequencing of 110 representative isolates. We show that this lineage initially originated in the Far East, from where it radiated worldwide in several waves. We detected successive increases in population size for this pathogen over the last 200 years, practically coinciding with the Industrial Revolution, the First World War and HIV epidemics. Two MDR clones of this lineage started to spread throughout central Asia and Russia concomitantly with the collapse of the public health system in the former Soviet Union. Mutations identified in genes putatively under positive selection and associated with virulence might have favored the expansion of the most successful branches of the lineage.

Microbiota Promotes Chronic Pulmonary Inflammation by Enhancing IL-17A and Autoantibodies

RATIONALE Changes in the pulmonary microbiota are associated with progressive respiratory diseases including chronic obstructive pulmonary disease. Whether there is a causal relationship between these changes and disease progression remains unknown. OBJECTIVE To investigate the link between an altered microbiota and disease, we utilized a model of chronic lung inflammation in specific pathogen free (SPF) mice and mice depleted of microbiota by antibiotic treatment or devoid of a microbiota (axenic). METHODS Mice were challenged with LPS/elastase intranasally over 4 weeks, resulting in a chronically inflamed and damaged lung. The ensuing cellular infiltration, histological damage and decline in lung function were quantified. MEASUREMENTS AND MAIN RESULTS Similar to human disease, the composition of the pulmonary microbiota was altered in disease animals. We found that the microbiota richness and diversity were decreased in LPS/Elastase-treated mice, with an increased representation of the genera Pseudomonas, Lactobacillus and a reduction in Prevotella. Moreover, the microbiota was implicated in disease development as mice depleted of microbiota exhibited an improvement in lung function, reduction in airway inflammation, decrease in lymphoid neogenesis and auto-reactive antibody responses. The absence of microbial cues also markedly decreased the production of IL-17A, whilst intranasal transfer of fluid enriched with the pulmonary microbiota isolated from diseased mice enhanced IL-17A production in the lungs of antibiotic treated or axenic recipients. Finally, in mice harboring a microbiota, neutralizing IL-17A dampened inflammation and restored lung function. CONCLUSIONS Collectively, our data indicate that host-microbial cross-talk promotes inflammation and could underlie the chronicity of inflammatory lung diseases.

Total disc arthroplasty versus anterior cervical interbody fusion: use of the Spine Tango registry to supplement the evidence from randomized control trials.

BACKGROUND CONTEXT Several randomized controlled trials (RCTs) have compared patient outcomes of anterior (cervical) interbody fusion (AIF) with those of total disc arthroplasty (TDA). Because RCTs have known limitations with regard to their external validity, the comparative effectiveness of the two therapies in daily practice remains unknown. PURPOSE This study aimed to compare patient-reported outcomes after TDA versus AIF based on data from an international spine registry. STUDY DESIGN AND SETTING A retrospective analysis of registry data was carried out. PATIENT SAMPLE Inclusion criteria were degenerative disc or disc herniation of the cervical spine treated by single-level TDA or AIF, no previous surgery, and a Core Outcome Measures Index (COMI) completed at baseline and at least 3 months' follow-up. Overall, 987 patients were identified. OUTCOME MEASURES Neck and arm pain relief and COMI score improvement were the outcome measures. METHODS Three separate analyses were performed to compare TDA and AIF surgical outcomes: (1) mimicking an RCT setting, with admission criteria typical of those in published RCTs, a 1:1 matched analysis was carried out in 739 patients; (2) an analysis was performed on 248 patients outside the classic RCT spectrum, that is, with one or more typical RCT exclusion criteria; (3) a subgroup analysis of all patients with additional follow-up longer than 2 years (n=149). RESULTS Matching resulted in 190 pairs with an average follow-up of 17 months that had no residual significant differences for any patient characteristics. Small but statistically significant differences in outcome were observed in favor of TDA, which are potentially clinically relevant. Subgroup analyses of atypical patients and of patients with longer-term follow-up showed no significant differences in outcome between the treatments. CONCLUSIONS The results of this observational study were in accordance with those of the published RCTs, suggesting substantial pain reduction both after AIF and TDA, with slightly greater benefit after arthroplasty. The analysis of atypical patients suggested that, in patients outside the spectrum of clinical trials, both surgical interventions appeared to work to a similar extent to that shown for the cohort in the matched study. Also, in the longer-term perspective, both therapies resulted in similar benefits to the patients.

Chronostratigraphy on sediment core CRP-2 from the Ross Sea, Antarctica

Strontium isotope stratigraphy was used to date 16 discrete horizons within the CRP-2/2A drillhole. Reworked Quaternary (<1.7 Ma) and possible Pliocene (<2.4 Ma) sediments overlie a major sequence boundary at 25.92 meters below sea floor (mbsf). This hiatus is estimated to account for c. 16 Myr of missing section. Early Miocene to ?earliest Oligocene (c. 18.6 to >31 Ma) deposits below this boundary were cut by multiple erosion surfaces of uncertain duration. Strontium isotope ages are combined with 40Ar/39Ar dates, diatom and calcareous nannofossil datum and a palaeomagnetic polarity zonation, to produce an age model for the core.

Todo lo que querés saber como hacerse un aborto con pastillas

El misoprostol es un remedio que las mujeres de todo el mundo usan para hacerse el aborto ellas mismas en su casa de manera segura hasta la semana 12 de embarazo cumplida. Es fácil de usar, y casi todas las mujeres pueden usarlo sin problemas. Desde la semana 13 de embarazo en adelante, ningún aborto es seguro si se hace fuera del hospital. La información de este manual es para que entre todas podamos reducir los riesgos y daños de los abortos inseguros. Es información útil para personas que no tienen ninguna capacitación, y también para personas que sí tienen algo de capacitación médica formal

Lineamientos estratégicos para la garantía de prestaciones prioritarias en materia de salud sexual y reproductiva

El presente documento contiene un conjunto de lineamientos cuyo objetivo central es servir como una herramienta orientadora a la formulación de prestaciones prioritarias e integrales en SSR y para identificar estrategias efectivas, de modo que estas prestaciones se incorporen en las políticas y sistemas de salud con solidez y sustentabilidad. También estos lineamientos tienen como propósito contribuir a impulsar o fortalecer la integración de la SSR como un eje estratégico en los procesos de cambios de los sistemas de salud desde una perspectiva que entiende la participación y la construcción de consensos como dimensiones clave de esos procesos. Este eje estratégico puede ser utilizado como un «centinela» para evaluar el adecuado funcionamiento de sistemas de salud basados en la promoción y prevención para el diseño e implementación de cambios. Este documento no pretende ser una manual. Es una guía para orientar las decisiones políticas y técnicas que deberá ser necesariamente adaptada a los contextos de cada país, dado que todo proceso de diseño e implementación de una política pública depende estrechamente del sistema administrativo, la tendencia política del gobierno, las características de los recursos físicos y humanos disponibles, y el marco normativo que regula el sistema de salud.1 Por ello, la imagen de una «ruta crítica» expresa el sentido político estratégico que esta guía pretende ofrecer.

Cuando el Estado no dice todo: la relación entre la rendición de cuentas gubernamental y el monitoreo ciudadano en el caso uruguayo

Presentación en la 4ta. Conferencia Regional del CLACAI. Reafirmando el legado de Cairo: Aborto legal y seguro. Lima, 21 y 22 de Agosto de 2014

Investigación sobre aborto en América Latina y El Caribe : una agenda renovada para informar políticas públicas e incidencia

Esta publicación es un estado del arte que reúne el conocimiento disponible, producido en América Latina en el período 2009 a 2014. Aborda diversos aspectos de los temas más relevantes de la investigación sobre aborto inducido, desde una revisión crítica de resultados y metodologías, que apunta a identificar tendencias y resultados notables en cada temática, así como a reseñar sugerencias que podrían fortalecer el enfoque o el abordaje del tema, a identificar los vacíos o las lagunas de conocimiento en cada temática y, sobre todo, a ofrecer insumos para la elaboración de una agenda de investigación en la región, la cual oriente el trabajo de la comunidad de investigadores/as y activistas y responda a la demanda de producción de información confiable basada en evidencias, lo cual fortalecerá acciones de incidencia informada.

Mujeres y aborto

Este capítulo pertenece a la publicación "Investigación sobre aborto en América Latina y El Caribe : una agenda renovada para informar políticas públicas e incidencia", es un estado del arte que reúne el conocimiento disponible, producido en América Latina en el período 2009 a 2014. Aborda diversos aspectos de los temas más relevantes de la investigación sobre aborto inducido, desde una revisión crítica de resultados y metodologías, que apunta a identificar tendencias y resultados notables en cada temática