Changing the conversation: applying a health equity framework to maternal mortality reviews.

The risk of maternal death in the United States is higher than peer nations and is rising and varies dramatically by the race and place of residence of the woman. Critical efforts to reduce maternal mortality include patient risk stratification and system-level quality improvement efforts targeting specific aspects of clinical care. These efforts are important for addressing the causes of an individual's risk, but research to date suggests that individual risk factors alone do not adequately explain between-group disparities in pregnancy-related death by race, ethnicity, or geography. The holistic review and multidisciplinary makeup of maternal mortality review committees make them well positioned to fill knowledge gaps about the drivers of racial and geographic inequity in maternal death. However, committees may lack the conceptual framework, contextual data, and evidence base needed to identify community-based contributing factors to death and, when appropriate, to make recommendations for future action. By incorporating a multileveled, theory-grounded framework for causes of health inequity, along with indicators of the community vital signs, the social and community context in which women live, work, and seek health care, maternal mortality review committees may identify novel underlying factors at the community level that enhance understanding of racial and geographic inequity in maternal mortality. By considering evidence-informed community and regional resources and policies for addressing these factors, novel prevention recommendations, including recommendations that extend outside the realm of the formal health care system, may emerge.

Plasma Micronutrient Concentrations Are Altered by Antiretroviral Therapy and Lipid-Based Nutrient Supplements in Lactating HIV-Infected Malawian Women.

BACKGROUND: Little is known about the influence of antiretroviral therapy with or without micronutrient supplementation on the micronutrient concentrations of HIV-infected lactating women in resource-constrained settings. OBJECTIVE: We examined associations of highly active antiretroviral therapy (HAART) and lipid-based nutrient supplements (LNS) with concentrations of selected micronutrients in HIV-infected Malawian women at 24 wk postpartum. METHODS: Plasma micronutrient concentrations were measured in a subsample (n = 690) of Breastfeeding, Antiretrovirals, and Nutrition (BAN) study participants who were randomly assigned at delivery to receive HAART, LNS, HAART+LNS, or no HAART/no LNS (control). HAART consisted of protease inhibitor-based triple therapy. LNS (140 g/d) met energy and micronutrient requirements of lactation. Multivariable linear regression tested the association of HAART and LNS, plus their interaction, with micronutrient concentrations, controlling for season, baseline viral load, and baseline CD4 count. RESULTS: We found significant HAART by LNS interactions for folate (P = 0.051), vitamin B-12 (P < 0.001), and transferrin receptors (TfRs) (P = 0.085). HAART was associated with lower folate (with LNS: -27%, P < 0.001; without LNS: -12%, P = 0.040) and higher TfR concentrations (with LNS: +14%, P = 0.004; without LNS: +28%, P < 0.001), indicating iron deficiency. LNS increased folate (with HAART: +17%, P = 0.037; without HAART: +39%, P < 0.001) and decreased TfR concentrations (with HAART only: -12%, P = 0.023). HAART was associated with lower vitamin B-12 concentrations only when LNS was present (-18%, P = 0.001), whereas LNS increased vitamin B-12 only when no HAART was present (+27%, P < 0.001). HAART, but not LNS, was associated with higher retinol-binding protein (RBP; +10%, P = 0.007). We detected no association of HAART or LNS with selenium, ferritin, or hemoglobin. CONCLUSION: The association of HAART with lower folate, iron deficiency, and higher RBP plus the attenuation of LNS effects on folate and vitamin B-12 when combined with HAART has implications for the health of lactating HIV-infected women taking HAART in prevention of mother-to-child transmission programs. This trial was registered at clinicaltrials.gov as NCT00164736.

Thalamo-cortical connectivity: what can diffusion tractography tell us about reading difficulties in children?

Reading is an essential skill in modern society, but many people have deficits in the decoding and word recognition aspects of reading, a difficulty often referred to as dyslexia. The primary focus of neuroimaging studies to date in dyslexia has been on cortical regions; however, subcortical regions may also be important for explaining this disability. Here, we used diffusion tensor imaging to examine the association between thalamo-cortical connectivity and children's reading ability in 20 children with typically developed reading ability (age range 8-17/10-17 years old from two imaging centers) and 19 children with developmental dyslexia (DYS) (age range 9-17/9-16 years old). To measure thalamo-cortical connections, the structural images were segmented into cortical and subcortical anatomical regions that were used as target and seed regions in the probabilistic tractography analysis. Abnormal thalamic connectivity was found in the dyslexic group in the sensorimotor and lateral prefrontal cortices. These results suggest that the thalamus may play a key role in reading behavior by mediating the functions of task-specific cortical regions; such findings lay the foundation for future studies to investigate further neurobiological anomalies in the development of thalamo-cortical connectivity in DYS.

Evaluation of using routine infant immunization visits to identify and follow-up HIV-exposed infants and their mothers in Tanzania.

BACKGROUND: Without treatment, approximately half of HIV-infected infants die by age 2 years, and 80% die before age 5 years. Early identification of HIV-infected and HIV-exposed infants provides opportunities for life-saving interventions. We evaluated integration of HIV-related services with routine infant immunization in Tanzania. METHODS: During April 2009 to March 2010, at 4 urban and 4 rural sites, mothers' HIV status was determined at first-month immunization using antenatal cards. HIV-exposed infants were offered HIV testing and follow-up care. Impact of integrated service delivery was assessed by comparing average monthly vaccine doses administered during the study period and a 2-year baseline period; acceptance was assessed by interviewing mothers and service providers. FINDINGS: During 7569 visits, 308 HIV-exposed infants were identified and registered; of these, 290 (94%) were tested, 15 (5%) were HIV infected. At urban sites, first-month vaccine doses remained stable (+2% for pentavalent vaccine and -4% for polio vaccine), and vaccine doses given later in life (pentavalent, polio, and measles) increased 12%, 8%, and 11%, respectively. At rural sites, first-month vaccine doses decreased 33% and 35% and vaccine doses given later in life decreased 23%, 28%, and 28%. Mothers and service providers generally favored integrated services; however, HIV-related stigma and inadequate confidentiality controls of HIV testing were identified, particularly at rural sites. INTERPRETATION: Integration of HIV-related services at immunization visits identified HIV-exposed infants, HIV-infected infants, and HIV-infected mothers; however, decreases in vaccine doses administered at rural sites were concerning. HIV-related service integration with immunization visits needs careful monitoring to ensure optimum vaccine delivery.

Caffeine intake and its association with urinary incontinence in United States men: results from National Health and Nutrition Examination Surveys 2005-2006 and 2007-2008.

PURPOSE: Epidemiological studies in women have revealed an association between caffeine intake and urinary incontinence, although evidence among men is limited. Therefore, we evaluated the association between caffeine intake and urinary incontinence in United States men. MATERIALS AND METHODS: Data were used from male NHANES (National Health and Nutrition Examination Surveys) 2005-2006 and 2007-2008 participants. Urinary incontinence was defined using a standard questionnaire with Incontinence Severity Index scores 3 or greater categorized as moderate to severe. Structured dietary recall was used to determine caffeine consumption (mg per day), water intake (gm per day) and total dietary moisture (gm per day). Stepwise multivariable logistic regression models were used to assess the association between caffeine intake at or above the 75th and 90th percentiles and moderate to severe urinary incontinence, controlling for potential confounders, urinary incontinence risk factors and prostate conditions in men age 40 years or older. RESULTS: Of the 5,297 men 3,960 (75%) were 20 years old or older with complete data. Among these men the prevalence of any urinary incontinence was 12.9% and moderate to severe urinary incontinence was 4.4%. Mean caffeine intake was 169 mg per day. Caffeine intake at the upper 75th percentile (234 mg or more daily) and 90th percentile (392 mg or more per day) was significantly associated with having moderate to severe urinary incontinence (1.72, 95% 1.18-2.49 and 2.08, 95% 1.15-3.77, respectively). In addition, after adjusting for prostate conditions, the effect size for the association between caffeine intake and moderate to severe urinary incontinence remained. CONCLUSIONS: Caffeine consumption equivalent to approximately 2 cups of coffee daily (250 mg) is significantly associated with moderate to severe urinary incontinence in United States men. Our findings support the further study of caffeine modification in men with urinary incontinence.

Discovery of pyrazolo[1,5-a]pyrimidine-based CHK1 inhibitors: a template-based approach--part 2.

Previous efforts by our group have established pyrazolo[1,5-a]pyrimidine as a viable core for the development of potent and selective CDK inhibitors. As part of an effort to utilize the pyrazolo[1,5-a]pyrimidine core as a template for the design and synthesis of potent and selective kinase inhibitors, we focused on a key regulator in the cell cycle progression, CHK1. Continued SAR development of the pyrazolo[1,5-a]pyrimidine core at the C5 and C6 positions, in conjunction with previously disclosed SAR at the C3 and C7 positions, led to the discovery of potent and selective CHK1 inhibitors.

Discovery of pyrazolo[1,5-a]pyrimidine-based CHK1 inhibitors: a template-based approach--part 1.

The synthesis and hit-to-lead SAR development of a pyrazolo[1,5-a]pyrimidine hit 4 is described leading to a series of potent, selective CHK1 inhibitors such as compound 17r. In the Letter, the further utility of the pyrazolo[1,5-a]pyrimidine template for the development of potent, selective kinase inhibitors is detailed.