New Insights Into Gestational Glucose Metabolism: Lessons Learned From 21st Century Approaches

Pregnancy presents a unique physiological challenge that requires changes coordinated by placentally and non–placentally derived hormones to prepare the mother for the metabolic stress presented by fetal development and to ensure appropriate nutrient allocation between mother and fetus. Of particular importance is the maintenance of normal glucose metabolism during pregnancy. Here, we describe physiological changes in glucose metabolism during pregnancy and highlight new insights into these adaptations that have emerged over the past decade using novel methodologies, specifically genome-wide association studies (GWAS) and metabolomics. While GWAS have identified some novel associations with metabolic traits during pregnancy, the majority of the findings overlap with those observed in nonpregnant populations and individuals with type 2 diabetes (T2D). Metabolomics studies have provided new insight into key metabolites involved in gestational diabetes mellitus (GDM). Both of these approaches have suggested that a strong link exists between GDM and T2D. Most recently, a role of the gut microbiome in pregnancy has been observed, with changes in the microbiome during the third trimester having metabolic consequences for the mother. In this Perspectives in Diabetes article, we highlight how these new data have broadened our understanding of gestational metabolism, and emphasize the importance of future studies to elucidate differences between GDM and T2D.     

Chemoprevention of colorectal cancer with nonsteroidal anti‐inflammatory drugs

Colorectal carcinoma is one of the commonest solid organ tumors in the world and its prevalence appears to be increasing in Asia. Recently, there has been much interest in various chemotherapeutic agents for the management of this condition, in particular nonsteroidal anti‐inflammatory drugs (NSAIDs). There is a large amount of data that suggest traditional NSAIDs, as well as the new cyclooxygenase (COX)‐2 selective inhibitors such as rofecoxib and celecoxib, have a role in the setting of primary and secondary prevention, and adjuvant therapy of both sporadic colorectal carcinoma and familial adenomatous polyposis. This review examines some of this data, as well as the potential problems and limitations of using these agents, particularly in light of the recent withdrawal of rofecoxib.     

Optimizing CT for the evaluation of vestibular aqueduct enlargement:Inter-rater reproducibility and predictive value of reformatted CT measurements

Enlarged vestibular aqueduct(EVA), the most frequent identifiable cause of congenital hearing loss, is evaluated with high-definition multidetector CT in the axial plane. Our purpose was to determine which reformatted CT measurements are most reproducible. Seven multiplanar reformatted images were created for each of the 64 temporal bones in patients with EVA. Intraclass correlation coefficients(ICC) were used to assess inter-observer variability, and both linear regression and ROC analyses were used to compare the measurements with severity of hearing loss, as assessed by pure tone audiometry. All seven measurements had excellent inter-observer variability, with average-measure ICC ranging from 0.92 to 0.98. There was no statistically significant correlation between the radiologic degree of aqueduct enlargement and severity of hearing loss using any of the seven measurements; ROC analyses revealed areas under the curves ranging from 0.57 to 0.73. Optimal accuracy was obtained with a threshold of 1.75 mm as measured at the aqueductal aperture in the P€oschl plane, with sensitivity of 0.75 and specificity of0.63. Although the radiologic measurement may not serve as a reliable tool for assessing severity of EVA, P€oschl plane reformatting has proven to be better than conventional axial acquisition plane for identifying patients with clinically significant hearing loss.     

A New Model for Catalyzing Translational Science: The Early Stage Investigator Mentored Research Scholar Program in HIV Vaccines

Engagement of early stage investigators (ESIs) in the search for a safe and effective vaccine is critical to the success of this highly challenging endeavor. In the wake of disappointing results from a large‐scale efficacy trial, the HIV Vaccine Trials Network (HVTN) and Center for HIV/AIDS Vaccine Immunology (CHAVI) developed a novel mentored research program focused on the translation of findings from nonhuman primate studies to human trials of experimental vaccines. From 2008 to 2011, 14 ESI Scholars were selected from 42 complete applications. Post program surveys and tracked outcomes suggest that the combination of flexible funding, transdisciplinary mentorship, and structured training and networking promoted the scientific contributions and career development of promising ESIs. Embedding a multicomponent research program within collaborative clinical trial networks and research consortia is a promising strategy to attract and retain early career investigators and catalyze important translational science.     

Cost-effectiveness of hydroxyurea in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia

The Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH) demonstrated the efficacy of hydroxyurea in reducing the rate of painful crises compared to placebo. We used resource utilization data collected in the MSH to determine the cost-effectiveness of hydroxyurea. The MSH was a randomized, placebo-controlled double-blind clinical trial involving 299 patients at 21 sites. The primary outcome, visit to a medical facility, was one of the criteria to define occurrence of painful crisis. Cost estimates were applied to all outpatient and emergency department visits and inpatient hospital stays that were classified as a crisis. Other resources for which cost estimates were applied included hospitalization for chest syndrome, analgesics received, hydroxyurea dosing, laboratory testing, and clinic visits for management of patient care. Annualized differential costs were calculated between hydroxyurea- and placebo-receiving patients. Hospitalization for painful crisis accounted for the majority of costs in both arms of the study, with an annual mean of $12,160 (95% CI: $9,440, $14,880) for hydroxyurea and $17,290 (95% CI: $13,010, $21,570) for placebo. The difference in means was $5,130 (95% CI: $60, $10,200; P = 0.048). Chest syndrome was the next largest cost with a mean difference of $830 (95% CI: $-340, $2,000; P = 0.16). The hydroxyurea arm was also associated with lower costs for emergency department visits, transfusion, and use of opiate analgesics. In total, the annual average cost per patient receiving hydroxyurea was $16,810 (95% CI: $13,350, $20,270) and the annual average costs per patient receiving placebo was $22,020 (95% CI: $17,340, $26,710). The difference in means was $5,210 (95% CI: $-610, $11,030; P = 0.21). The cost of hydroxyurea with the more intensive monitoring required when using this drug appears to be more than offset by decreased costs for medical care of painful crisis and analgesic use. Although the total cost difference was not significant statistically, these results suggest that hydroxyurea therapy is cost-effective compared to placebo in the management of adult patients with sickle cell anemia. If hydroxyurea can prevent development of chronic organ damage, long-term savings may be even greater.