Caregiver Predictions of Their 3- to 6-Year-Old Child Who Stutters' Communication Attitude.

PURPOSE: Caregivers share critical insight during their child's stuttering evaluation; yet, there have been no empirical studies evaluating whether caregivers provide similar accounts of their 3- to 6-year-old child's communication attitude compared to their child's self-report. This study examined caregiver- and child-reported communication attitude and assessed potential moderators of more comparable caregiver and child ratings (i.e., caregiver confidence, caregiver-child conflict, observer-rated stuttering severity). METHOD: One hundred thirteen children who stutter ages 3 through 6 years and a primary caregiver were recruited from clinical settings across the United States. Children completed the Communication Attitude Test for Preschool and Kindergarten Children Who Stutter (KiddyCAT) and three speaking samples, which were recorded to assess observer-rated stuttering severity using the Stuttering Severity Instrument-Fourth Edition. Caregivers predicted their child's communication attitude (C-KiddyCAT) and provided a confidence rating for their prediction. Caregivers also rated caregiver-child conflict using the Child-Parent Relationship Scale-Short Form (CPRS-SF). Multiple regression was used to (a) evaluate whether caregiver C-KiddyCAT scores predicted child KiddyCAT scores and (b) assess potential moderators of the relationship between C-KiddyCAT and KiddyCAT scores. RESULTS: Caregiver ratings of their child's communication attitude (C-KiddyCAT) predicted child communication attitude ratings (KiddyCAT). A significant interaction between caregiver-child conflict (CPRS-SF) and caregiver ratings of their child's communication attitude (C-KiddyCAT) suggested caregiver-child conflict changed the underlying relationship between C-KiddyCAT and KiddyCAT scores, such that low conflict resulted in more similar C-KiddyCAT and KiddyCAT scores. Neither caregiver confidence nor observer-rated stuttering severity influenced the relationship between C-KiddyCAT and KiddyCAT scores. CONCLUSIONS: Although many caregivers predicted communication attitude ratings that closely aligned with their child's report, some caregiver-child dyads provided divergent ratings. Clinicians should interpret caregiver predictions of their child's communication attitude within the context of their full evaluation and the caregiver-child relationship. Assessing both self-reported communication attitude and caregiver predictions of their child's communication attitude provides a meaningful starting point to counseling caregivers about cognitive components of stuttering for preschool- and kindergarten-age children who stutter.

Correction to: What's Happening During Home Visits? Exploring the Relationship of Home Visiting Content and Dosage to Parenting Outcomes.

The article "What's Happening During Home Visits? Exploring the Relationship of Home Visiting Content and Dosage to Parenting Outcomes", written by Peggy Nygren, Beth Green, Katie Winters and Anna Rockhill, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 13 June 2018 without open access.

What's Happening During Home Visits? Exploring the Relationship of Home Visiting Content and Dosage to Parenting Outcomes.

Introduction Research has documented modest positive impacts of early childhood home visiting programs. However, understanding more about what home visitors do during visits and how much time they spend on specific topics may provide insight into the variability in effectiveness of services. Methods Outcome data were collected via parent survey at program enrollment and 12 months from 123 women in three MIECHV-funded home visiting models. Home visitors completed weekly home visit content and activity logs. Results Families received an average of 28 visits during the study (3.1 visits per month). Of ten content areas, the three most often discussed were early childhood development, physical care of children, and the parent-child-relationship. Multivariate regression models were used to explore the association of home visit dosage, home visit content and cumulative risk factors on parenting outcomes. Women whose visits were focused more on parenting topics reported lower parenting-related stress at follow-up compared to those whose visits had less parenting content. Additionally, higher-risk women who received greater numbers of home visits showed larger reductions in their attitudes about harsh punishment over time, compared to high-risk women with fewer home visits. Discussion Receiving home visits that emphasize parenting content may contribute to reduced parenting-related stress. For high-risk women in particular, receiving more visits overall may be important to achieving positive outcomes. Implications for practice include working to engage and retain high-risk families. Future home visiting research calls for improved methods for collecting data on content/activity during visits, the necessity for long-term follow-up, and testing for the effectiveness of varied and flexible visit schedules/content focus for women and families with trauma exposure.

Effect of food on the pharmacokinetics and pharmacodynamics of R1663, an oral factor Xa inhibitor, in healthy male volunteers.

AIMS: To explore the effect of food intake on the relative bioavailability of R1663 and on its pharmacodynamic effects (prothrombin time (PT) and activated partial thromboplastin time (aPTT)) after a single oral dose of 200 mg. METHODS: This was a prospective, open-label, randomized, two-way crossover study. Eight healthy male volunteers received R1663 on two occasions, after a high fat/high calorie breakfast and after an overnight fast of 10 h, with a 7-day washout between doses. Blood was sampled up to 48 h for the pharmacokinetic and pharmacodynamic evaluation of R1663. Pharmacokinetic parameters (area under the plasma concentration-time curve from Time 0 extrapolated to infinity (AUC(0-∞)) and maximal concentration (C(max)) as well as pharmacodynamic parameters (area under the effect curve over 48 h (AUE(0-48)) and maximal effect (E(max)) were determined on both occasions. Geometric mean ratios fed/ fasted (GMR) and 90% confidence intervals (CI) were calculated for AUC(0-∞) and C(max) of R1663 and AUE(0-48) and E(max) of PT and aPTT. RESULTS: Following food intake, C(max) was reduced by 10% with CI extended outside the bioequivalence range (GMR, 0.90; CI 0.72 - 1.13). R1663 t(max) was delayed in the fed state (4 h) as compared to the fasted state (1 h). There was no significant food effect on R1663 AUC(0-∞) (GMR, 1.09; CI 0.97 - 1.24). Although the Emax of PT showed statistically significant reduction with food, the 90% CIs for Emax and AUE(0-48) of PT and aPTT were all contained within the bioequivalence range (0.80 - 1.25). CONCLUSIONS: These findings will allow the administration of R1663 without regard to food in the upcoming trials.

Safety, pharmacokinetics and pharmacodynamics of multiple ascending doses of R1663, an oral factor Xa inhibitor, in healthy young subjects coupled with exploration of influence of gender and age.

This study investigated the safety, pharmacokinetics and pharmacodynamics of multiple oral doses of R1663, a factor Xa inhibitor, and explored the influence of age and gender on pharmacokinetics and pharmacodynamics of R1663. This was a single-blind, randomised, placebo-controlled, dose escalation study in 48 healthy male volunteers aged 18 to 44 years. R1663 doses up to 300 mg twice daily or 400 mg once daily were administered for seven days. The exploration of gender and age effect was carried out in separate cohorts of eight male and eight female volunteers aged 45 to 65 years. Multiple oral doses of R1663 were safe and well tolerated. Pharmacokinetics was linear and showed moderate variability. Plasma concentrations peaked at 3 hour. Terminal half-life at steady state was 3-5 hours. Accumulation of R1663 was minimal. R1663 prolonged clotting times, inhibited thrombin generation (peak height and endogenous thrombin potential [ETP]) and anti-factor Xa activity in a concentration-dependent manner without increasing bleeding time. Pharmacodynamic parameters were strongly correlated to R1663 plasma concentrations. The inhibition was more pronounced on peak height (IC50 = 194 ng/ml) than on ETP (2790 ng/ml). Pharmacokinetics and pharmacodynamics of R1663 appeared not to be substantially affected by age or gender but remained to be confirmed in larger clinical trials including older patients. Meanwhile, dose adjustments based on age and gender are not anticipated.

Crossover dose escalation study to assess safety, pharmacokinetics, and pharmacodynamics of single doses of R1663, an oral factor Xa inhibitor, in healthy male volunteers.

This study investigated the safety, pharmacokinetics, and pharmacodynamics of single oral doses of R1663, a factor Xa inhibitor, in healthy volunteers. It was a single-blind, randomized, crossover, placebo-controlled, dose escalation study in 33 healthy male volunteers aged 18 to 45 years. Each volunteer was dosed on 3 occasions with R1663 or placebo. Single oral doses of R1663 were safe and well tolerated. R1663 did not affect bleeding time. Pharmacodynamic effects (prothrombin time [PT], activated partial thromboplastin time [aPTT]), parameters of thrombogram, and anti-factor Xa activity) and plasma concentrations of R1663 were dose-dependent and showed low to moderate (<40%) intersubject and intrasubject variability. Maximum factor Xa inhibition was achieved 3 hours post dose (time to maximum concentration of R1663): clotting times were prolonged up to 2.5-fold, whereas endogenous thrombin potential (ETP) and peak height were decreased by 48% and 85% from their baseline values, respectively. Pharmacodynamic parameters were strongly correlated to R1663 plasma concentrations, with IC50 values of 182 and 2680 ng/mL for peak height and ETP, respectively. Oral doses of R1663 up to 480 mg were well tolerated, with predictable pharmacodynamics and pharmacokinetics. R1663 prolonged clotting times (PT, aPTT) and inhibited thrombin generation without increasing bleeding time.

Unexpected Hepatotoxicity of Rifampin and Saquinavir/Ritonavir in Healthy Male Volunteers.

OBJECTIVES: Rifampin is a potent inducer of the cytochrome P450 3A4 isoenzyme (CYP3A4) that metabolizes most protease inhibitor (PI) antiretrovirals. This study was designed to evaluate the steady-state pharmacokinetics and tolerability of the coadministration of the PIs saquinavir and ritonavir (a CYP3A4 inhibitor used as a pharmacoenhancer of other PIs) and rifampin when coadministered in healthy HIV-negative volunteers. METHODS: In an open-label, randomized, one sequence, two-period crossover study involving 28 healthy HIV-negative volunteers, arm 1 was randomized to receive saquinavir/ritonavir 1000/100 mg twice daily while arm 2 received rifampin 600 mg once daily for 14 days. Both arms were then to receive concomitant saquinavir/ritonavir and rifampin for 2 additional weeks. Vital signs, electrocardiography, laboratory analyses, and blood levels of total saquinavir, ritonavir, rifampin, and desacetyl-rifampin, the primary metabolite of rifampin, were measured. RESULTS: In arm 1, 10/14 (71%) and, in arm 2, 11/14 (79%) participants completed the first study phase; eight participants in arm 1 and nine in arm 2 went on to receive both saquinavir/ritonavir and rifampin. Following substantial elevations (>/= grade 2) in hepatic transaminases in participants receiving the coadministered agents, the study was discontinued prematurely. Two participants in arm 1 displayed moderate elevations after five and four doses of rifampin, respectively. In arm 2, all participants experienced severe elevations within 4 days of initiating saquinavir/ritonavir. Clinical symptoms (e.g., nausea, vomiting, abdominal pain, and headache) were more common and severe in arm 2. Clinical symptoms abated and transaminases normalized following drug discontinuation. Limited pharmacokinetic data suggest a possible relationship between transaminase elevation and elevated rifampin and desacetyl-rifampin concentrations. CONCLUSIONS: Although not confirmed in HIV-infected patients, the data indicate that rifampin should not be coadministered with saquinavir/ritonavir.