Pharmacokinetic interaction between ethinyl estradiol, norethindrone and darunavir with low-dose ritonavir in healthy women

BACKGROUND: An open-label, randomized, crossover study was performed to investigate the effect of multiple doses of darunavir co-administered with low-dose ritonavir (DRV/r) on the steady-state pharmacokinetics of the oral contraceptives ethinyl estradiol (EE) and norethindrone (NE) (commercial name of the combined drug Ortho-Novum 1/35) in 19 HIV-negative healthy women. METHODS: In session 1, participants received 35 microg EE and 1.0 mg NE from days 1 to 21. In session 2, participants received the same oral contraceptive treatment as in session 1 on days 1 to 21 plus DRV/r (600 mg/100 mg twice daily) on days 1 to 14. Pharmacokinetic assessments were performed on day 14 for each session. RESULTS: Steady-state systemic exposure to EE and NE decreased when DRV/r was co-administered, based on the ratio of least square means of the minimum plasma concentration (Cmin), the maximum plasma concentration (Cmax), and the area under the curve (AUC24h) of EE (which decreased by 62%, 32% and 44%, respectively) and NE (which decreased by 30%, 10% and 14%, respectively) compared with administration of EE and NE alone. Five participants discontinued the study due to grade 2 cutaneous events, as required per protocol, during treatment with EE and NE in combination with DRV/r. There were no clinically relevant findings for laboratory and cardiovascular parameters. CONCLUSIONS: The pharmacokinetic interaction observed here is considered to be clinically relevant as EE concentrations are considerably reduced when DRV/r is co-administered with EE and NE. Alternative or additional contraceptive measures should be used when oestrogen-based contraceptives are co-administered with DRV/r.     

Mutational analysis using Sanger and next generation sequencing in sporadic spindle cell hemangiomas: A study of 19 cases

Spindle cell hemangioma (SCH) is a distinct vascular soft ‐ tissue lesion characterized by cavernous blood vessels and a spindle cell component mainly occurring in the distal extremities of young adults. The majority of cases harbor heterozygous mutations in IDH1/2 sporadically or rarely in association with Maffucci syndrome. However, based on mosaicism and accordingly a low percentage of lesional cells harboring a mutant allele, detection can be challenging. We tested 19 sporadic SCHs by Sanger sequencing, multiplex ligation‐dependent probe amplification (MLPA), conventional next generation sequencing (NGS), and NGS using a single molecule molecular inversion probes (smMIP) ‐ based library preparation to compare their diagnostic value. Out of 10 cases tested by Sanger sequencing and 2 analyzed using MLPA, 4 and 1, respectively, revealed a mutation in IDH1 (p.R132C). The 7 remaining negative cases and additional 6 cases were investigated using smMIP/NGS, showing hot spot mutations in IDH1 (p.R132C) (8 cases) and IDH2 (3 cases; twice p.R172S and once p.R172G, respectively). One case was negative. Owing to insufficient DNA quality and insufficient coverage, 2 cases were excluded. In total, in 16 out of 17 cases successfully tested, an IDH1/2 mutation was found. Given that IDH1/2 mutations were absent in 161 other vascular lesions tested by smMIP/NGS, the mutation can be considered as highly specific for SCH.     

Impact of Rotavirus Vaccine on Premature Infants

Infants born preterm are at a higher risk of complications and hospitalization in cases of rotavirus diarrhea than children born at term. We evaluated the impact of a rotavirus vaccination campaign (May 2007 to May 2010) on hospitalizations for rotavirus gastroenteritis in a population of children under 3 years old born prematurely (before 37 weeks of gestation) in the Brest University Hospital birth zone. Active surveillance from 2002 to 2006 and a prospective collection of hospitalizations for rotavirus diarrhea were initiated in the pediatric units of Brest University Hospital until May 2010. Numbers of hospitalizations for rotavirus diarrhea among the population of children born prematurely, before and after the start of the vaccination program, were compared using a Poisson regression model controlling for epidemic-to-epidemic variation. A total of 217 premature infants were vaccinated from 2007 to 2010. Vaccine coverage for a complete course of three doses was 41.9%. The vaccine safety in premature infants was similar to that in term infants. The vaccination program led to a division by a factor of 2.6 (95% confidence interval [CI], 1.3 to 5.2) in the number of hospitalizations for rotavirus diarrhea during the first two epidemic seasons following vaccine introduction and by a factor of 11 (95% CI, 3.5 to 34.8) during the third season. We observed significant effectiveness of the pentavalent rotavirus vaccine on the number of hospitalizations in a population of prematurely born infants younger than 3 years of age. A multicenter national study would provide better assessment of this impact. (This study [Impact of Systematic Infants Vaccination Against Rotavirus on Gastroenteritis Hospitalization: a Prospective Study in Brest District, France (IVANHOE)] has been registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT00740935","term_id":"NCT00740935"}}NCT00740935.)     

CHILD DISRUPTIVE BEHAVIOR AND PARENTING EFFICACY: A COMPARISON OF THE EFFECTS OF TWO MODELS OF INSIGHTS

In this article, we investigate the effectiveness of INSIGHTS into Children's Temperament (INSIGHTS), a temperament-based preventive intervention, in reducing the disruptive behavior problems of young children from low-income, urban families. Results indicate that children enrolled in INSIGHTS evidenced a decrease in disruptive behavior problems over the course of the intervention, with children with high maintenance temperaments evidencing the most rapid rates of decline. In addition, children in a collaborative version of the program with joint parent and teacher sessions demonstrated more rapid decreases in disruptive behavior than children in a parallel version with separate parent and teacher sessions. Furthermore, high maintenance children in the collaborative intervention evidenced lower levels of disruptive behaviors at the end of the intervention than their peers in the parallel version. Increases in parenting efficacy appeared to be the mechanism through which INSIGHTS reduced child disruptive behavior.     

Unpacking the racial disparity in HIV rates: the effect of race on risky sexual behavior among Black young men who have sex with men (YMSM)

The purpose of this study is to evaluate the large disparity in HIV prevalence rates between young Black and White Americans, including young men who have sex with men (YMSM). Research focusing on individual behaviors has proven insufficient to explain the disproportionately high rate of HIV among Black YMSM. The purpose of the present study was to gain a greater understanding of the pronounced racial disparity in HIV by evaluating whether YMSM are more likely to engage in risky sexual behaviors as a function of their partner’s race. Participants included 117 YMSM from a longitudinal study evaluating lesbian, gay, bisexual, and transgender youth (ages 16–20 at baseline), who reported characteristics and risk behaviors of up to 9 sexual partners over an 18-month period. Results indicated that participants were less likely to have unprotected sex with Black partners, and this finding was not driven by a response bias (i.e., Black YMSM did not appear to be minimizing their reports of unprotected sex). Furthermore, there was support for the hypothesis that participants’ sexual networks were partially determined by their race insofar as sexual partnerships were much more likely to be intra-racial (as opposed to interracial). It is possible that dyad- and sexual network-level factors may be needed to understand racial disparities in HIV among YMSM.     

“I think that everybody should be involved”: What informs experiences of shared decision-making in supporting people living with schizophrenia spectrum disorders?

ObjectiveTo identify facilitators and barriers associated with shared decision-making (SDM) in Australians affected by schizophrenia spectrum disorders.MethodsWe surveyed 78 participants with lived experience and held 12 in-depth interviews, including seven carers.ResultsA multiple linear regression model identified two independent variables significantly associated with degree of SDM: Personal Wellbeing Index scores (ß = .32, t = 3.3, p = .001) and treatment satisfaction rating (ß =.46, t = 4.7, p < .001), indicating that higher personal wellbeing and higher treatment satisfaction were significantly related to higher degree of SDM. Two key themes were identified through interview data: a complex pathway to SDM and impacts on wellbeing. Sub-themes included: self and carer characteristics, holistic care, education and knowledge, and power balance. Generally, participants reported a desire for SDM, noting that healthcare professionals inconsistently involve them in treatment decisions.ConclusionSDM is associated with treatment satisfaction and personal wellbeing among people living with schizophrenia spectrum disorders, but can be difficult to implement due to a range of challenges.Practice implicationsThere is a need to improve SDM in this population by decreasing stigma and discrimination, balancing power in consultations, increasing access to holistic treatment, and improving education and knowledge.