Facilitators and barriers to adolescent participation in a TB clinical trial.

The inclusion of adolescents in TB drug trials is essential for the development of safe, child-friendly regimens for the prevention and treatment of TB. TB Trials Consortium Study 31/AIDS Clinical Trials Group A5349 (S31/A5349) enrolled adolescents as young as 12 years old. We assessed investigator and coordinator described facilitators and barriers to adolescent recruitment, enrollment, and retention.Interviews were conducted with six investigators from sites that enrolled adolescent participants and six investigators from non-enrolling sites. Additionally, two focus groups were conducted with study coordinators from enrolling sites and two focus groups with non-enrolling sites. Discussions were transcribed, analyzed, summarized, and summaries were reviewed by Community Research Advisors Group members and research group representatives for content validity.Investigators and coordinators attributed the successful enrollment of adolescents to the establishment and cultivation of external partnerships, flexibility to accommodate adolescents' schedules, staff engagement, recruitment from multiple locations, dedicated recruitment staff working onsite to access potential participants, creation of youth-friendly environments, and effective communications. Non-enrolling sites were mainly hindered by regulations. Suggestions for improvement in future trials focused on study planning and site preparations.Proactive partnerships and collaboration with institutions serving adolescents helped identify and reduce barriers to their inclusion in this trial..

M-mode echocardiographic evaluation of fetal and infant hearts: longitudinal follow-up study from intrauterine life to year one.

OBJECTIVE: Our purpose was to evaluate cardiac variables, including right and left end-diastolic and end-systolic dimensions by use of M-mode echocardiography during fetal, neonatal (transitional), and infancy periods to understand hemodynamic adaptation during these periods. STUDY DESIGN: Fifty-three fetuses were enrolled in this study. Echocardiography evaluations were started as early as the sixteenth week of gestation and were repeated every 4 to 6 weeks until term, on postnatal days 1 and 2, and at 6 weeks, 6 months, and 12 months of age. End-diastolic and end-systolic measurements were made according to published standards. Mean and SEM for each of the end-diastolic and end-systolic measurements were calculated for each of 11 study periods. Data were analyzed by one-way analysis of variance, corrected for repeated measures, and in the case of right and left ventricular differences paired t tests were used for significance. RESULTS: Left ventricular end-diastolic and end-systolic correlated positively with advancing age (R2 = 0.93, p < 0.0001), right ventricular end-diastolic also correlated with advancing age (R2 = = 0.361, p < 0.05), and right ventricular end-diastolic was significantly larger than left ventricular end-diastolic in utero (p < 0.01), whereas the opposite was true after birth (p < 0.0001). Heart rate significantly decreased with advancing age (p < 0.001), whereas ejection fraction for either the right or the left ventricle did not change significantly with advancing age. CONCLUSION: This suggests that under basal conditions the ventricles can meet the increased demands in cardiac output by increasing ventricular dimensions without having to increase contractility reserve.

Maternal right hypogastric artery blood flow during normal pregnancy and 6 weeks postpartum.

OBJECTIVE: To document and quantify the temporal hemodynamic changes occurring in the pelvic circulation in normal human pregnancy, and to compare these changes with those found 6 weeks postpartum. METHODS: Thirty-three patients had color pulsed Doppler evaluation of the right hypogastric artery six times during pregnancy and once 6 weeks postpartum. Pulsed Doppler waveforms were digitized to assess the time velocity integral (area under the Doppler curve = TVI) and the peak flow velocity (maximum velocity = PFV). The diameter of the vessel was determined during systole using high-resolution two-dimensional ultrasound from a longitudinal plane. A quantitative estimate of the blood flow through this vessel was calculated by multiplying the TVI by the calculated cross-sectional area of the vessel. RESULTS: The cross-sectional area and the indexed volume of blood flow per minute of the hypogastric artery were significantly greater during pregnancy compared with the postpartum value. The estimated vascular resistance index was significantly decreased during pregnancy. Time velocity integral was significantly lower at the initial study compared with the postpartum value. CONCLUSION: The hypogastric artery undergoes significant hemodynamic changes during pregnancy when compared to the postpartum period. Furthermore, the pelvic circulation displays these changes early in gestation.

Longitudinal quantitation of middle cerebral artery blood flow in normal human fetuses.

OBJECTIVES: We attempted to quantify noninvasively blood flow of the middle cerebral artery in human fetuses during five distinct periods. STUDY DESIGN: Twenty normal fetuses had color pulsed Doppler ultrasonography of the middle cerebral artery. A total of 68 studies were successfully done and are reported. The Doppler sample was placed as parallel to the direction of the vessel flow as possible. All waveforms were recorded on a strip chart at a preset speed of 100 mm/sec. Six Doppler waveforms were digitized for the time velocity integral (area under the curve is equal to time velocity integral) and averaged. Middle cerebral blood flow was obtained by multiplying the time velocity integral of the Doppler curve by the cross-sectional area of the vessel. The combined cardiac output was obtained by adding the right and left ventricular outputs, which were obtained by multiplying the time velocity integrals by the area of the corresponding annuli. Analysis of variance for repeated measurements was used to determine significance. RESULTS: The diameter of the middle cerebral artery, the time velocity integral, and the peak flow velocity of the Doppler waveform increased significantly with advancing gestational age. Blood flow to the middle cerebral artery ranged from 23 ml/min at 19 weeks to 133 ml/min at term. Resistivity index values were not correlated with advancing gestational age. The percent of the cardiac output to one of the two middle cerebral arteries remained constant throughout gestation with a range between 3% and 7%. CONCLUSIONS: (1) Time velocity integral, peak flow velocity, diameter, and blood flow of the middle cerebral artery increased significantly with gestational age; (2) the percent of the total cardiac output to the middle cerebral artery does not significantly change with gestational age.

Quantitative assessment of human fetal renal blood flow.

OBJECTIVE: Our purpose was to longitudinally quantify human fetal renal blood flow. STUDY DESIGN: Twenty-two normal fetuses underwent a color-pulsed Doppler evaluation of the renal artery. The Doppler waveforms were digitized to assess the velocity-time integral. The size of the vessel was determined during systole with color high-resolution two-dimensional ultrasonography. Renal blood flow was estimated by multiplying the time-velocity integral (i.e., area under the curve) by the area of the renal artery. The combined cardiac output was calculated by adding right and left inflow Doppler-derived volumes. RESULTS: Renal artery size, peak flow velocity, time-velocity integral, and renal blood flow significantly increased with advancing gestational age. The resistivity indexes, such as the systolic/diastolic ratio or the Pourcelot index of the fetal renal artery, did not significantly change with advancing gestational age. The pulsatility index, however, was correlated with gestational age. The percentage of the combined cardiac output to the fetal kidney remained constant throughout gestation. CONCLUSIONS: Color pulsed Doppler can be used to visualize small and deep vascular structures in the human fetus. Renal blood flow increased with advancing gestational age. This increase seems to be related to the increase in the combined cardiac output.