The long-term effectiveness of generic adult fixed-dose combination antiretroviral therapy for HIV-infected Ugandan children

Background

Access to pediatric antiretroviral formulations is increasing in resource-limited countries, however adult FDCs are still commonly used by antiretroviral therapy (ART) programs.

Objective

To describe long-term effectiveness of using adult FDC of d4T+3TC+NVP (Triomune) in children for HIV treatment.

Methods

Clinical, immunologic, and virologic outcomes of HIV-infected ART-naïve children aged six months to 12 years, were evaluated up to 96 weeks post-ART initiation.

Results

From March 2004 to June 2006, 104 children were followed with a median age of 5.4 years, median CD4 cell percent and HIV-1 RNA were 11.0% (IQR 6.7–13.9) and 348,846copies/mL (IQR 160,941–681,313) respectively at baseline. Using Kaplan-Meir estimates, 75% of children had undetectable viral loads (<400copies/mL) at 96weeks of ART. Children with a baseline CD4 cell percent >15% were 3 times more likely to achieve viral load <400copies/mL than those with baseline CD4 cell percent <5% after adjusting for baseline age {aHR = 3.03 (1.10–8.32), p=0.03}; no difference was found among those with CD4 cell percent >5–14.9% and <5%.

Conclusion

Treatment with generic adult FDC for HIV-infected Ugandan children led to sustained clinical, immunologic and virologic response during 96 weeks of ART. Early initiation of ART is key to achieving virological success.     

The effect of maternal age on chromosomal anomaly rate and spectrum in recurrent miscarriage

STUDY QUESTION: Is there any effect of maternal age on chromosomal anomaly rate and spectrum in recurrent miscarriage? SUMMARY ANSWER: There was no significant difference in the chromosome abnormality rate between sporadic and recurrent miscarriage but the chromosome abnormality rate increased significantly with maternal age. WHAT IS KNOWN ALREADY: About 50-70% of non-recurrent miscarriages occur because of a chromosomal anomaly, but no agreement about the effect of either maternal age or the number of previous miscarriages on the chromosomal anomaly rate has been reached. STUDY DESIGN, SIZE, DURATION: A retrospective cohort of 353 miscarriages successfully karyotyped in the same center between 2002 and 2011, grouped according to the number of miscarriages and maternal age. PARTICIPANTS/MATERIALS, SETTING, METHODS: Among the 353 women, 153 were below 35 years (73 with sporadic, 48 with two and 32 with recurrent miscarriage) and 200 were 35 years or more (81 with sporadic, 55 with two and 64 with recurrent miscarriage). The chromosomal anomaly rate and the anomaly spectrum were compared between sporadic and recurrent miscarriage, within the two maternal age groups, using the chi-square test and the Bonferroni correction for all the P-values. Risk of chromosomal anomaly was estimated for maternal age, number of miscarriages and previous live births by multivariate binary logistic regression analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Sporadic and recurrent miscarriage did not show significantly different chromosomal anomaly rates (68 versus 60%) and maternal age was the only statistically significant predictor of the chromosomal anomaly risk we identified. Some trends were observed in the chromosomal anomaly spectrum when sporadic was compared with recurrent miscarriage: recurrent miscarriage exhibited a decrease in viable trisomies (37 versus 11%) and an increase in non-viable trisomies (38 versus 57%) in women >35 years, together with an increase in unbalanced structural anomalies (4.9 versus 29%) in younger women. LIMITATION, REASONS FOR CAUTION: The mixed origin of our study population, and the limited number of recurrent miscarriages, particularly in the younger group, limits statistical power to detect differences. WIDER IMPLICATIONS OF THE FINDINGS: The most commonly observed chromosomal anomaly type in recurrent miscarriage depends on maternal age: non-viable autosomal trisomies in older women and unbalanced structural anomalies in younger women. When a chromosomal anomaly is identified as the cause of miscarriage, additional maternal evaluation may be avoided. STUDY FUNDING/COMPETING INTERESTS: No competing interests declared.     

退行性腰椎侧凸与骨质疏松症的关系探讨

目的探讨退行性腰椎侧凸（degenerativelumbarscoliosis,DIS）与骨质疏松症（osteoporosis,OP）两者之间的关系。方法选取2006年6月-2010年6月来我院就诊的DIS患者58例及对照组（非腰椎侧凸的腰痛患者）58例,对DIS组Cobb’s角进行测量,并采用双能x线吸收法检测两组患者腰椎（k～L4）、股骨颈、股骨粗隆和Ward’s三角区骨密度T值,分析患者年龄、Cobb’s角与骨密度T值的相关性。结果DIS组平均骨密度T值为-2．7±1．8,合并OP45例,发病率为77．59％;对照组平均骨密度T值为-1．3±1．0,合并OP8例,发病率为13．79％,两组比较有显著性差异（P〈0．05）。相关分析显示,DIS患者T值与年龄呈正相关（r=-0．318,P〈0．01）,与侧凸Cobb’s角无关。结论OP是DLS发病的危险因素,同时年龄越大OP程度越重,但与DLS进展程度无关。临床DLS治疗时要考虑到OP的影响。     

Cell-Autonomous Inactivation of the Reelin Pathway Impairs Adult Neurogenesis in the Hippocampus

Adult hippocampal neurogenesis is thought to be essential for learning and memory, and has been implicated in the pathogenesis of several disorders. Although recent studies have identified key factors regulating neuroprogenitor proliferation in the adult hippocampus, the mechanisms that control the migration and integration of adult-born neurons into circuits are largely unknown. Reelin is an extracellular matrix protein that is vital for neuronal development. Activation of the Reelin cascade leads to phosphorylation of Disabled-1, an adaptor protein required for Reelin signaling. Here we used transgenic mouse and retroviral reporters along with Reelin signaling gain-of-function and loss-of-function studies to show that the Reelin pathway regulates migration and dendritic development of adult-generated hippocampal neurons. Whereas overexpression of Reelin accelerated dendritic maturation, inactivation of the Reelin signaling pathway specifically in adult neuroprogenitor cells resulted in aberrant migration, decreased dendrite development, formation of ectopic dendrites in the hilus, and the establishment of aberrant circuits. Our findings support a cell-autonomous and critical role for the Reelin pathway in regulating dendritic development and the integration of adult-generated granule cells and point to this pathway as a key regulator of adult neurogenesis. Moreover, our data reveal a novel role of the Reelin cascade in adult brain function with potential implications for the pathogenesis of several neurological and psychiatric disorders.     

Social inequalities in the association between partner/marital status and health among workers in Spain

The objectives of this study are to examine the association between partner/marital status and several health outcomes among workers and to assess whether it depends on gender and occupational social class. The sample was composed of all workers aged 21-64 years interviewed in the 2006 Spanish National Health Survey (8563 men and 5881 women). Partner/marital status had seven categories: married and living with the spouse (reference category), married and not living with the spouse, cohabiting, single and living with parents, single and not living with parents, separated/divorced and widowed. Four health outcomes were analysed: self-perceived health status, mental health, psychiatric drugs consumption and hypertension. Multiple logistic regression models stratified by sex and social class were fitted. Female manual workers who were cohabiting were more likely to report poor self-perceived health status, poor mental health status, psychiatric medication consumption and hypertension than their married and living with the spouse counterparts. In that group the prevalence of poor health outcomes was even higher when compared with single people. Among male non-manual workers, being married and not living with the spouse was associated with poor self-perceived health status, poor mental health status and hypertension. There were almost no differences in health between being married and the rest of partner/marital status categories for different combinations of gender and social class and, even, some groups of single people reported better health outcomes than people who were married. Our results show no evidence that being married and living with the spouse is unequivocally linked to better health status among Spanish workers. They emphasize the importance of not only considering marital status, but also partner status, as well as the role of gender, social class and the sociocultural context in the analysis of the association between family characteristics and health.     

Racial/ethnic residential segregation: framing the context of health risk and health disparities

An increasing body of public health literature links patterns of racial/ethnic residential segregation to health status and health disparities. Despite substantial new empirical work, meaningful understanding of the pathways through which segregation operates to influence health remains elusive. The literature on segregation and health was appraised with an emphasis on select conceptual, methodological, and analytical issues. Recommendations for advancing the next generation of racial/ethnic residential segregation and health research will require closer attention to sharpening the methodology of measuring segregation, testing mediating pathways and effect modification, incorporating stronger test of causality, exploring factors of resilience in segregated areas, applying a life-course perspective, broadening the scope of the investigation of segregation to include nativity status in blacks and other racial/ethnic groups, and linking segregation measures with biological data.