Randomized, placebo controlled phase I trial of the safety, pharmacokinetics, pharmacodynamics and acceptability of a 90 day tenofovir plus levonorgestrel vaginal ring used continuously or cyclically in women: The CONRAD 138 study.

Multipurpose prevention technologies (MPTs), which prevent sexually transmitted infection(s) and unintended pregnancy, are highly desirable to women. In this randomized, placebo-controlled, phase I study, women used a placebo or tenofovir (TFV) and levonorgestrel (LNG) intravaginal ring (IVR), either continuously or cyclically (three, 28-day cycles with a 3 day interruption in between each cycle), for 90 days. Sixty-eight women were screened; 47 were randomized to 4 arms: TFV/LNG or placebo IVRs used continuously or cyclically (4:4:1:1). Safety was assessed by adverse events and changes from baseline in mucosal histology and immune mediators. TFV concentrations were evaluated in multiple compartments. LNG concentration was determined in serum. Modeled TFV pharmacodynamic antiviral activity was evaluated in vaginal and rectal fluids and cervicovaginal tissue ex vivo. LNG pharmacodynamics was assessed with cervical mucus quality and anovulation. All IVRs were safe with no serious adverse events nor significant changes in genital tract histology, immune cell density or secreted soluble proteins from baseline. Median vaginal fluid TFV concentrations were >500 ng/mg throughout 90d. TFV-diphosphate tissue concentrations exceeded 1,000 fmol/mg within 72hrs of IVR insertion. Mean serum LNG concentrations exceeded 200 pg/mL within 2h of TFV/LNG use, decreasing quickly after IVR removal. Vaginal fluid of women using TFV-containing IVRs had significantly greater inhibitory activity (87-98% versus 10% at baseline; p<0.01) against HIV replication in vitro. There was a >10-fold reduction in HIV p24 antigen production from ectocervical tissues after TFV/LNG exposure. TFV/LNG IVR users had significantly higher rates of anovulation, lower Insler scores and poorer/abnormal cervical mucus sperm penetration. Most TFV/LNG IVR users reported no change in menstrual cycles or fewer days of and/or lighter bleeding. All IVRs were safe. Active rings delivered high TFV concentrations locally. LNG caused changes in cervical mucus, sperm penetration, and ovulation compatible with contraceptive efficacy. Trial registration: ClinicalTrials.gov #NCT03279120.

Reliability of the beighton score and impact of generalized joint mobility and resting scapular position on Median Neurodynamic Test 1.

INTRODUCTION: There is a lack of understanding of the impact of generalized joint mobility, joint hypermobility, and resting scapular position on neurodynamic testing of the median nerve. The objectives of the study were to determine: 1) the reliability of the Beighton score (BS) with and without the cutoff score for general joint hypermobility (GJH); 2) if there are differences in the Median Neurodynamic Test 1 (MNT 1) based on the Beighton cutoff score for GJH; 3) if there are differences in the MNT 1 based on an assessment of resting scapular position; 4) if there are relationships between the BS with and without the cutoff score for GJH, resting scapular position, and MNT 1. METHODS: Testing was performed by two testers at two-time intervals at least 1 week apart. The population of interest was healthy asymptomatic adults. The outcome measures included the BS, resting scapular position, and MNT 1. RESULTS: Intraclass correlation coefficients (ICC2,1) were 0.52 for intertester reliability at visit 1 and 0.86 at visit 2, with intratester reliability of 0.88 for Tester 1 and 0.71 for Tester 2 for the BS. Intertester prevalence-adjusted bias-adjusted kappa (PABAK) values for the Beighton GJH cutoff scores were 0.80-0.84 and 0.80 to 0.92 for intratester reliability. There were no statistically significant differences or relationships for any of the other variables of interest. CONCLUSION: Joint mobility and resting scapular position are not confounding variables when performing MNT 1 in an asymptomatic population.

Agreement and Reliability of Median Neurodynamic Test 1 and Resting Scapular Position.

OBJECTIVE: The purposes of this study were to determine whether there are differences between the dominant and nondominant arms for the Median Neurodynamic Test 1 (MNT 1); whether there are differences between men and women on the MNT 1; the reliability of an assessment of resting scapular position; the reliability of the MNT 1; and the frequency and percentage of sensory responses that are present during the MNT 1 in the asymptomatic population. METHODS: This was a reliability and agreement study. It included asymptomatic students enrolled in the college of health professions and the college of nursing at a university. The Mann-Whitney U was used to determine whether there were any differences between the dominant and nondominant sides and between sexes for elbow extension range of motion and for sensory responses on the numeric pain rating scale when performing the MNT 1. A χ2 analysis was used to determine whether there were any differences between sexes and between dominant and nondominant upper extremities for sensory-response location, sensory-response type, and structural differentiation for raters 1 and 2. The intraclass correlation coefficient (ICC2,3) was used to determine the intertester and intratester reliability for the degrees of elbow extension attained during testing. RESULTS: Reliability for degrees of elbow extension and strength of the sensory response was excellent (ICC2,3 ˃ 0.75) and substantial (κ ≥ 0.68), respectively. Resting scapular position and all other components of the MNT 1 demonstrated statistically significant side-to-side differences and κ values ranging from 0.23 to 0.88. CONCLUSION: Elbow extension and magnitude of sensory response are reliable components of the MNT 1 that are not different between the dominant and nondominant sides in the asymptomatic population.

Using multiple methods to assess learning and outcomes in an online degree-granting dental hygiene program.

Program evaluation is a necessary component of curricular change and innovation. It ascertains whether an innovation has met benchmarks and contributes to the body of knowledge about educational methodologies and supports the use of evidence-based practice in teaching. Education researchers argue that rigorous program evaluation should utilize a mixed-method approach, triangulating both qualitative and quantitative methods to understand program effectiveness. This approach was used to evaluate the University of Michigan Dental Hygiene Degree Completion E-Learning (online) Program. Quantitative data included time spent on coursework, grades, publications, course evaluation results, and survey responses. Qualitative data included student and faculty responses in focus groups and on surveys as well as students' portfolio reflections. The results showed the program was academically rigorous, fostering students' ability to connect theory with practice and apply evidence-based practice principles. These results also demonstrated that the students had learned to critically reflect on their practice and develop expanded professional identities; going beyond the role of clinician, they began to see themselves as educators, advocates, and researchers. This evaluation model is easily adaptable and is applicable to any health science or other professional degree program. This study also raised important questions regarding the effect of meta-reflection on student confidence and professional behavior.

Using online program development to foster curricular change and innovation.

Distance education offers an opportunity to catalyze sweeping curricular change. Faculty members of the University of Michigan Dental Hygiene Program spent eighteen months researching best practices, planning outcomes and courses, and implementing an e-learning (online) dental hygiene degree completion program. The result is a collaborative and portfolio-integrated program that focuses on the development of reflective practitioners and leaders in the profession. A team-based, systems-oriented model for production, implementation, and evaluation has been critical to the program's success. The models and best practices on which this program was founded are described. Also provided is a framework of strategies for development, including the utilization of backward course design, which can be used in many areas of professional education.