Accurate dry weight assessment: reducing the incidence of hypertension and cardiac disease in patients on hemodialysis.

Hypertension is a major cause of cardiac disease in patients on hemodialysis (HD) and is most commonly due to hypervolemia. Removal of excess water during HD can successfully normalize blood pressure, but its success depends on an accurate assessment of dry weight. This article reviews the literature concerning hypertension in patients on HD and proposes that increased attention by dialysis staff to assessing dry weight may reduce the incidence of hypertension and cardiac disease in these patients.     

Gammadelta T cell-induced hyaluronan production by epithelial cells regulates inflammation

Nonhealing wounds are a major complication of diseases such as diabetes and rheumatoid arthritis. For efficient tissue repair, inflammatory cells must infiltrate into the damaged tissue to orchestrate wound closure. Hyaluronan is involved in the inflammation associated with wound repair and binds the surface of leukocytes infiltrating damaged sites. Skin gammadelta T cells play specialized roles in keratinocyte proliferation during wound repair. Here, we show that gammadelta T cells are required for hyaluronan deposition in the extracellular matrix (ECM) and subsequent macrophage infiltration into wound sites. We describe a novel mechanism of control in which gammadelta T cell-derived keratinocyte growth factors induce epithelial cell production of hyaluronan. In turn, hyaluronan recruits macrophages to the site of damage. These results demonstrate a novel function for skin gammadelta T cells in inflammation and provide a new perspective on T cell regulation of ECM molecules.     

Pharmacokinetic interactions of maraviroc with darunavir-ritonavir, etravirine, and etravirine-darunavir-ritonavir in healthy volunteers: results of two drug interaction trials

The effects of darunavir-ritonavir at 600 and 100 mg twice daily (b.i.d.) alone, 200 mg of etravirine b.i.d. alone, or 600 and 100 mg of darunavir-ritonavir b.i.d. with 200 mg etravirine b.i.d. at steady state on the steady-state pharmacokinetics of maraviroc, and vice versa, in healthy volunteers were investigated in two phase I, randomized, two-period crossover studies. Safety and tolerability were also assessed. Coadministration of 150 mg maraviroc b.i.d. with darunavir-ritonavir increased the area under the plasma concentration-time curve from 0 to 12 h (AUC12) for maraviroc 4.05-fold relative to 150 mg of maraviroc b.i.d. alone. Coadministration of 300 mg maraviroc b.i.d. with etravirine decreased the maraviroc AUC12 by 53% relative to 300 mg maraviroc b.i.d. alone. Coadministration of 150 mg maraviroc b.i.d. with etravirine-darunavir-ritonavir increased the maraviroc AUC12 3.10-fold relative to 150 mg maraviroc b.i.d. alone. Maraviroc did not significantly affect the pharmacokinetics of etravirine, darunavir, or ritonavir. Short-term coadministration of maraviroc with darunavir-ritonavir, etravirine, or both was generally well tolerated, with no safety issues reported in either trial. Maraviroc can be coadministered with darunavir-ritonavir, etravirine, or etravirine-darunavir-ritonavir. Maraviroc should be dosed at 600 mg b.i.d. with etravirine in the absence of a potent inhibitor of cytochrome P450 3A (CYP3A) (i.e., a boosted protease inhibitor) or at 150 mg b.i.d. when coadministered with darunavir-ritonavir with or without etravirine.     

Room air resuscitation of the depressed newborn: a systematic review and meta-analysis

Understanding of the potential dangers of hyperoxia in the newborn is growing. Several studies have examined the use of room air for the resuscitation of newborns. OBJECTIVE: To assess the effects of room air resuscitation versus 100% oxygen resuscitation on mortality at 1 week and 1 month in asphyxiated newborn infants. STUDY DESIGN: Systematic review and meta-analysis of seven randomized and quasi-randomised controlled trials comparing room air and 100% oxygen resuscitation of newborn infants. RESULTS: Compared to the 100% oxygen resuscitation group, neonates in the room air resuscitation group had a lower mortality both in the first week of life (odds ratio 0.70, 95% CI 0.50, 0.98) and at 1 month and beyond (odds ratio 0.63, 95% CI 0.42, 0.94). The incidence of severe hypoxic ischemic encephalopathy (Stage II and Stage III) was similar between the two groups. CONCLUSION: This meta-analysis supports the hypothesis that room air is superior to 100% oxygen as the initial choice for resuscitating clinically depressed newborns as it may result in a lower mortality rate. However, adequately powered studies of long-term neurodevelopmental outcomes are not yet available.     

Getting it right: Australian primiparas' views about breastfeeding: A quasi-experimental study

BACKGROUND: The study documented Australian primigravidas' perceptions about breastfeeding. OBJECTIVES: To examine women's perspectives of their breastfeeding experiences during the first 12 weeks postpartum. DESIGN: A Journal was introduced to an intervention group (n=149) attending prenatal classes at a private hospital at 36 antenatal weeks. Using quantitative data at two days and 12 weeks postpartum, the intervention group was compared with a control group (n=154) that delivered at the same hospital. Qualitative data were also collected about the women's perceptions about breastfeeding to further illuminate their experience. Qualitative data from 203 women at two days postpartum and 252 women at 12 weeks postpartum represented the combined comments from the intervention and control groups. PARTICIPANTS: Participants were recruited as part of a randomised controlled trial of the effects of a Breastfeeding Journal on breastfeeding prevalence, self-efficacy, support, and influence from conflicting advice. The convenience sample of middle class, well-educated primiparous women from a Western Australian hospital had given birth to a singleton infant that was greater than 34 weeks gestation. METHODS: An open-ended question on a questionnaire sought mothers' comments about their breastfeeding experiences. Data were analysed using inductive content analysis. FINDINGS: These mothers described trying to 'get breastfeeding right'. Getting it right included enhancing factors, factors with mixed effect, and negative factors. CONCLUSIONS: Middle class mothers share breastfeeding perceptions with women in more vulnerable groups, including encountering conflicting and unhelpful advice and feeding pressures from health care professionals, family, and community members.     

Susceptibilities of Genotype 1a, 1b,and 3 Hepatitis C Virus Variants to the NS5A Inhibitor Elbasvir

Elbasvir is an investigational NS5A inhibitor with in vitro activity against multiple HCV genotypes. Antiviral activity of elbasvir was measured in replicons derived from wild-type or resistant variants of genotypes 1a, 1b, and 3. The barrier to resistance was assessed by the number of resistant colonies selected by exposure to various elbasvir concentrations. In a phase 1b dose-escalating study, virologic responses were determined in 48 noncirrhotic adult men with chronic genotype 1 or 3 infections randomized to placebo or elbasvir from 5 to 50 mg (genotype 1) or 10 to 100 mg (genotype 3) once daily for 5 days. The NS5A gene was sequenced from plasma specimens obtained before, during, and after treatment. Elbasvir suppressed the emergence of resistance-associated variants (RAVs) in vitro in a dose-dependent manner. Variants selected by exposure to high elbasvir concentrations typically encoded multiple amino acid substitutions (most commonly involving loci 30, 31, and 93), conferring high-level elbasvir resistance. In the monotherapy study, patients with genotype 1b had greater reductions in HCV RNA levels than patients with genotype 1a at all elbasvir doses; responses in patients with genotype 3 were generally less pronounced than for genotype 1, particularly at lower elbasvir doses. M28T, Q30R, L31V, and Y93H in genotype 1a, L31V and Y93H in genotype 1b, and A30K, L31F, and Y93H in genotype 3 were the predominant RAVs selected by elbasvir monotherapy. Virologic findings in patients were consistent with the preclinical observations. NS5A-RAVs emerged most often at amino acid positions 28, 30, 31, and 93 in both the laboratory and clinical trial. (The MK-8742 P002 trial has been registered at ClinicalTrials.gov under identifier {"type":"clinical-trial","attrs":{"text":"NCT01532973","term_id":"NCT01532973"}}NCT01532973.)