ABSTRACT
Background: Observing medication ingestion through self-recorded videos (video directly observed therapy [VDOT]) has been shown to be a cost-effective alternative to in-person directly observed therapy (DOT) for monitoring adherence to treatment for tuberculosis disease. VDOT could be a useful tool to monitor short-course latent tuberculosis infection (LTBI) treatment. Methods: We conducted a prospective randomized controlled trial comparing VDOT (intervention) and clinic-based DOT (control) among patients newly diagnosed with LTBI who agreed to a once-weekly 3-month treatment regimen of isoniazid and rifapentine. Study outcomes were treatment completion and patient satisfaction. We also assessed costs. Pre- and posttreatment interviews were conducted. Results: Between March 2016 and December 2019, 130 participants were assigned to VDOT (n = 68) or DOT (n = 62). Treatment completion (73.5% vs 69.4%, P = .70) and satisfaction with treatment monitoring (92.1% vs 86.7%, P = .39) were slightly higher in the intervention group than the control group, but neither was statistically significant. VDOT cost less per patient (median, $230; range, $182-$393) vs DOT (median, $312; range, $246-$592) if participants used their own smartphone. Conclusions: While both groups reported high treatment satisfaction, VDOT was not associated with higher LTBI treatment completion. However, VDOT cost less than DOT. Volunteer bias might have reduced the observed effect since patients opposed to any treatment monitoring could have opted for alternative unobserved regimens. Given similar outcomes and lower cost, VDOT may be useful for treatment monitoring when in-person observation is prohibited or unavailable (eg, during a respiratory disease outbreak). The trial was registered at the National Institutes of Health (ClinicalTrials.gov NTC02641106). Clinical Trials Registration: ClinicalTrials.gov NTC02641106; registered 24 October 2016.
ABSTRACT
Neuroplasticity is a fundamental property of the respiratory control system, enabling critical adaptations in breathing to meet the challenges, but little is known whether neonates express neuroplasticity similar to adults. We tested the hypothesis that, similar to adults, tyrosine receptor kinase B (TrkB) or adenosine A2a receptor activation in neonates are independently sufficient to elicit respiratory motor facilitation, and that co-induction of TrkB and A2a receptor-dependent plasticity undermines respiratory motor facilitation. TrkB receptor activation with 7,8-dihydroxyflavone (DHF) in neonatal brainstem-spinal cord preparations induced a long-lasting increase in respiratory motor output in 55 % of preparations, whereas adenosine A2a receptor activation with CGS21680 only sporadically induced respiratory motor plasticity. CGS21680 and DHF co-application prevented DHF-dependent respiratory motor facilitation, whereas co-application of MSX-3 (adenosine A2a receptor antagonist) and DHF more rapidly induced respiratory motor plasticity. Collectively, these data suggest that mechanisms underlying respiratory neuroplasticity may be only partially operational in early neonatal life, and that adenosine A2a receptor activation undermines TrkB-induced respiratory plasticity.
