Retrospective-prospective study of safety and efficacy of sofosbuvir-based direct-acting antivirals in HIV/HCV-coinfected participants with decompensated liver disease pre– or post–liver transplant

Direct-acting antiviral (DAA) therapy has transformed the management of human immunodeficiency virus (HIV) and hepatitis C (HCV) coinfected patients with advanced liver disease. STOP-Coinfection was a multicenter prospective and retrospective, open-label study using sofosbuvir-based DAA therapy to treat HIV/HCV-coinfected participants pre– or post–liver transplant (LT). Sixty-eight participants with end-stage liver disease (Child-Turcotte-Pugh score ≥7 and Model for End-Stage Liver Disease score 6–29) were enrolled, 26 had hepatocellular carcinoma. Forty-two participants were treated pre–LT and 26 post–LT. All participants completed therapy without need for dose reduction or transfusion; eight required two or more courses of therapy. Ninety-three percent achieved a sustained virologic response and DAA therapy was well tolerated. Despite HCV cure, 12 end-stage liver disease participants required subsequent LT, 7 for decompensated liver disease. Thirteen participants died, 10 with decompensated liver disease pre–LT and three post–LT. Overall, transplant free survival was 42.8% at 4 years and post–LT survival was 87.9% at 5 years. We conclude that sofosbuvir-based DAA therapy is safe and highly effective in HCV-HIV patients with decompensated liver disease and post–LT, with post–LT survival rates comparable to other indications. This removes one of the last barriers to liver transplantation in this challenging cohort of recipients.     

Selecting a Medical School Advisor

Having an advisor offers medical students many advantages, including increased likelihood of matching into their top choices. Interestingly, students who choose emergency medicine (EM) as a specialty are more likely to seek advising. However, finding and optimally utilizing an EM faculty advisor is often challenging for the medical student. In this article, we tackle the different ways to seek advising, including the ‘virtual advisor program’ implemented by the Society for Academic Emergency Medicine, the ‘e-Advisor Program’ instigated by the Clerkship Director in EM Group, the ‘member exclusive mentorship program’ of the Emergency Medicine Residency Association, as well as peer-based mentoring. More so, we discuss the consensus recommendations developed by the Student Advising Task Force to guide both students planning to apply to EM and their advisors to ensure high-caliber advising.     

Overweight concerns and body dissatisfaction among third-grade children: the impacts of ethnicity and socioeconomic status

OBJECTIVE: To examine the prevalence of overweight concerns and body dissatisfaction among third-grade girls and boys and the influences of ethnicity and socioeconomic status (SES). STUDY DESIGN: Nine hundred sixty-nine children (mean age, 8.5 years) attending 13 northern California public elementary schools completed assessments of overweight concerns, body dissatisfaction, and desired shape, height, and weight. RESULTS: The sample was 44% white, 21% Latino, 19% non-Filipino Asian American, 8% Filipino, and 5% African American. Twenty-six percent of boys and 35% of girls reported wanting to lose weight, and 17% of boys and 24% of girls reported dieting to lose weight. Among girls, Latinas and African Americans reported significantly more overweight concerns than Asian Americans and Filipinas, and Latinas reported significantly more overweight concerns than whites. White and Latina girls also reported greater body dissatisfaction than Asian American girls. Some differences persisted even after controlling for actual body fatness. Higher SES African American girls reported significantly more overweight concerns than lower SES African American girls, but higher SES white girls reported less overweight concerns than lower SES white girls. CONCLUSION: Overweight concerns and body dissatisfaction are highly prevalent among third-grade girls and boys, across ethnicity and SES. Young Latina and African American girls manifest equivalent or higher levels of disordered eating attitudes and behaviors as white and Asian American girls.     

Do adolescent smokers experience withdrawal effects when deprived of nicotine?

This is the first controlled prospective study of the effects of nicotine deprivation in adolescent smokers. Heart rate and subjective withdrawal symptoms were measured over an 8-hr period while participants smoked normally. Seven days later, participants were randomized to wear a 15-mg (16-hr) nicotine patch or a placebo patch for 8 hr, and they refrained from smoking during the session. Those wearing the placebo experienced a decrease in heart rate across sessions and an increase in subjective measures of nicotine withdrawal. Those wearing the active patch also reported significant increases for some subjective symptoms. Expectancy effects were also observed. The findings indicate that adolescent smokers experience subjective and objective changes when deprived of nicotine. As in previous research with adults, expectancies concerning the effects of nicotine replacement also influenced perceptions of withdrawal.     

Stanford GEMS phase 2 obesity prevention trial for low-income African-American girls: design and sample baseline characteristics

OBJECTIVE: African-American girls and women are at high risk of obesity and its associated morbidities. Few studies have tested obesity prevention strategies specifically designed for African-American girls. This report describes the design and baseline findings of the Stanford GEMS (Girls health Enrichment Multi-site Studies) trial to test the effect of a two-year community- and family-based intervention to reduce weight gain in low-income, pre-adolescent African-American girls. DESIGN: Randomized controlled trial with measurements scheduled in girls' homes at baseline, 6, 12, 18 and 24 month post-randomization. SETTING: Low-income areas of Oakland, CA. PARTICIPANTS: Eight, nine and ten year old African-American girls and their parents/caregivers. INTERVENTIONS: Girls are randomized to a culturally-tailored after-school dance program and a home/family-based intervention to reduce screen media use versus an information-based community health education Active-Placebo Comparison intervention. Interventions last for 2 years for each participant. MAIN OUTCOME MEASURE: Change in body mass index over the two-year study. RESULTS: Recruitment and enrollment successfully produced a predominately low-socioeconomic status sample. Two-hundred sixty one (261) families were randomized. One girl per family is randomly chosen for the analysis sample. Randomization produced comparable experimental groups with only a few statistically significant differences. The sample had a mean body mass index (BMI) at the 74 th percentile on the 2000 CDC BMI reference, and one-third of the analysis sample had a BMI at the 95th percentile or above. Average fasting total cholesterol and LDL cholesterol were above NCEP thresholds for borderline high classifications. Girls averaged low levels of moderate to vigorous physical activity, more than 3 h per day of screen media use, and diets high in energy from fat. CONCLUSIONS: The Stanford GEMS trial is testing the benefits of culturally-tailored after-school dance and screen-time reduction interventions for obesity prevention in low-income, pre-adolescent African-American girls.     

In vitro evidence of two-component system phosphorylation between the Mycobacterium tuberculosis TrcR/TrcS proteins

Two-component regulatory proteins, histidine kinases and response regulators, function in bacteria as sensing and adaptive factors in response to a wide range of environmental stimuli. Conserved histidine and glycine regions of histidine kinase sensor proteins were used to design degenerate oligonucleotide primers for amplification of DNA fragments from Mycobacterium tuberculosis. Two adjacent genes, trcR and trcS, which encode a response regulator and a histidine kinase, respectively, have been identified. Full-length and truncated TrcR and TrcS proteins have been expressed in Escherichia coli. Difficulties in expressing recombinant full-length TrcS and a truncated N -terminal form of TrcS reveal that the transmembrane domains are toxic to E. coli. Overexpressed truncated C-terminal transmitter domains of TrcS have been autophosphorylated in vitro and have transphosphorylated both the full-length recombinant TrcR protein and the N -terminal receiver/regulator domain of TrcR. In vitro autophosphorylation of TrcS requires the presence of Mn2+or Ca2+as a divalent cation cofactor and subsequent transphosphorylation of TrcR is evident in the presence of TrcS-phosphate and Ca2+. Transphosphorylation between these two proteins provides evidence that these M. tuberculosis genes encode functional two-component system regulatory proteins that are members of a signal transduction circuit.