New drugs to target different pathways in pulmonary hypertension has resulted in increased combination therapy, but details of this use in infants are not well described. In this large multicenter database study, we describe the pharmacoepidemiology of combination pulmonary vasodilator therapy in critically ill infants.

We identified inborn infants discharged home from a Pediatrix neonatal ICU from 1997 to 2020 exposed to inhaled nitric oxide, sildenafil, epoprostenol, or bosentan for greater than two consecutive days. We compared clinical variables and drug utilisation between infants receiving simultaneous combination and monotherapy. We reported each combination’s frequency, timing, and duration and graphically represented drug use over time.

Of the 7681 infants that met inclusion criteria, 664 (9%) received combination therapy. These infants had a lower median gestational age and birth weight, were more likely to have cardiac and pulmonary anomalies, receive cardiorespiratory support, and had higher in-hospital mortality than those receiving monotherapy. Inhaled nitric oxide and sildenafil were most frequently used, and utilisation of combination and monotherapy for all drugs increased over time. Inhaled nitric oxide and epoprostenol were used in infants with a higher gestational age, earlier postnatal age, and shorter duration than sildenafil and bosentan. Dual therapy with inhaled nitric oxide and sildenafil was the most common combination therapy.

Our study revealed an increased use of combination pulmonary vasodilator therapy, favouring inhaled nitric oxide and sildenafil, yet with considerable practice variation. Further research is needed to determine the optimal combination, sequence, dosing, and disease-specific indications for combination therapy.

Understanding the factors contributing to optimal cognitive function throughout the aging process is essential to better understand successful cognitive aging. Processing speed is an age sensitive cognitive domain that usually declines early in the aging process; however, this cognitive skill is essential for other cognitive tasks and everyday functioning. Evaluating brain network interactions in cognitively healthy older adults can help us understand how brain characteristics variations affect cognitive functioning. Functional connections among groups of brain areas give insight into the brain’s organization, and the cognitive effects of aging may relate to this large-scale organization. To follow-up on our prior work, we sought to replicate our findings regarding network segregation’s relationship with processing speed. In order to address possible influences of node location or network membership we replicated the analysis across 4 different node sets.

Data were acquired as part of a multi-center study of 85+ cognitively normal individuals, the McKnight Brain Aging Registry (MBAR). For this analysis, we included 146 community-dwelling, cognitively unimpaired older adults, ages 85-99, who had undergone structural and BOLD resting state MRI scans and a battery of neuropsychological tests. Exploratory factor analysis identified the processing speed factor of interest. We preprocessed BOLD scans using fmriprep, Ciftify, and XCPEngine algorithms. We used 4 different sets of connectivity-based parcellation: 1)MBAR data used to define nodes and Power (2011) atlas used to determine node network membership, 2) Younger adults data used to define nodes (Chan 2014) and Power (2011) atlas used to determine node network membership, 3) Older adults data from a different study (Han 2018) used to define nodes and Power (2011) atlas used to determine node network membership, and 4) MBAR data used to define nodes and MBAR data based community detection used to determine node network membership.

Segregation (balance of within-network and between-network connections) was measured within the association system and three wellcharacterized networks: Default Mode Network (DMN), Cingulo-Opercular Network (CON), and Fronto-Parietal Network (FPN). Correlation between processing speed and association system and networks was performed for all 4 node sets.

We replicated prior work and found the segregation of both the cortical association system, the segregation of FPN and DMN had a consistent relationship with processing speed across all node sets (association system range of correlations: r=.294 to .342, FPN: r=.254 to .272, DMN: r=.263 to .273). Additionally, compared to parcellations created with older adults, the parcellation created based on younger individuals showed attenuated and less robust findings as those with older adults (association system r=.263, FPN r=.255, DMN r=.263).

This study shows that network segregation of the oldest-old brain is closely linked with processing speed and this relationship is replicable across different node sets created with varied datasets. This work adds to the growing body of knowledge about age-related dedifferentiation by demonstrating replicability and consistency of the finding that as essential cognitive skill, processing speed, is associated with differentiated functional networks even in very old individuals experiencing successful cognitive aging.

Inductive reasoning training has been found to be particularly effective at improving inductive reasoning, with some evidence of improved everyday functioning and driving. Telehealth may be useful for increasing access to, reducing time and travel burdens of, and reducing the need for physical spaces for cognitive training. On the other hand, telehealth increases technology burden. The present study investigated the feasibility and effectiveness of implementing an inductive reasoning training program, designed to mimic the inductive reasoning arm used in a large multi-site clinical trial (Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE)), via telehealth (using Zoom and Canvas as delivery platforms).

31 older adult participants (mean age = 71.2, range = 65-85; mean education = 15.5, range = 13-18; 64.5% female; 87.1% white) received 10-sessions of telehealth-delivered inductive reasoning training over 5 weeks. Comparison groups (inductive reasoning trained and no-contact controls) were culled from the in-person ACTIVE trial via propensity matching. All participants completed three pretest and posttest inductive reasoning measures (Word Series, Letter Series, Letter Sets), as well as a posttest measure assessing participant perceptions of the telehealth intervention. In addition, at the end of each of the ten training sessions, participants received a final inductive reasoning assessment.

Telehealth participants provided high levels of endorsement suggesting that the telehealth training program was useful, reliable, easy to use and interact on, and employed a useable interface. Participants were generally satisfied with the training program. With regard to performance, telehealth participants demonstrated greater gains than untrained controls on Letter Series [F(1, 116) = 9.81, p = 0.002, partial eta-squared = 0.084] and Letter Sets [F(1, 116) = 8.69, p = 0.004, partial eta-squared = 0.074], but did not differ in improvement on Word Series [F(1, 116) = 1.145, p = 0.287, partial eta-squared = 0.010]. Furthermore, telehealth participants evinced similar inductive reasoning gains as matched inperson inductive reasoning trained participants on Letter Series [F(1, 116) = 1.24, p = 0.226, partial eta-squared = 0.01] and Letter Sets [F(1, 116) = 1.29, p = 0.259, partial eta-squared = 0.01], but demonstrated fewer gains in Word Series performance [F(1, 116) = 25.681, p = < 0.001, partial eta-squared = 0.181]. On the end-of-session reasoning tests, telehealth-trained participants showed a similar general pattern of improvement across the ten training sessions and did not differ significantly from in-person trained comparison participants.

Cognitive training via telehealth evinced similar gains across nearly all measures as its in-person counterpart. However, telehealth also led to substantial challenges regarding the telehealth training platform. Despite these challenges, participants reported perceiving increased competence with computer use, peripherals (mice, trackpad), and videoconferencing. These may be ancillary benefits of such training and may be maximized if more age-friendly learning management systems are investigated. Overall, this study suggests that telehealth delivery may be a viable form of cognitive training in inductive reasoning, and future studies could increase performance gains by optimizing the online training platform for older adults.

The introduction of transoral robotic surgery into routine management of patients is complex. It involves organisational, logistical and clinical challenges. This study presents our experience of implementing such a programme and provides a blueprint for other centres willing to establish similar services.

Implementation of the robotic surgery programme focused on several key domains: training, logistics, governance, multidisciplinary team awareness, pre-operative imaging, anaesthesia, post-operative care, finance, patient selection and consent. Programme outcomes were evaluated by assessing operative outcomes of the first 117 procedures performed.

The success of the transoral robotic surgery programme has been possible because of the scrupulous planning phase before the first procedure, and the time invested on team awareness and training.

Implementation of a new transoral robotic surgery service has led to: the development of a dedicated transoral robotic surgery patient care protocol, the performance of progressively more complex procedures, the inclusion of transoral robotic surgery training and the establishment of several research projects.

Real-life decisions are often complex because they involve making sequential choices that constrain future options. We have previously shown that to render such multi-step decisions manageable, people ‘prune’ (i.e. selectively disregard) branches of decision trees that contain negative outcomes. We have theorized that sub-optimal pruning contributes to depression by promoting an oversampling of branches that result in unsavoury outcomes, which results in a negatively-biased valuation of the world. However, no study has tested this theory in depressed individuals.

Thirty unmedicated depressed and 31 healthy participants were administered a sequential reinforcement-based decision-making task to determine pruning behaviours, and completed measures of depression and anxiety. Computational, Bayesian and frequentist analyses examined group differences in task performance and relationships between pruning and depressive symptoms.

Consistent with prior findings, participants robustly pruned branches of decision trees that began with large losses, regardless of the potential utility of those branches. However, there was no group difference in pruning behaviours. Further, there was no relationship between pruning and levels of depression/anxiety.

We found no evidence that sub-optimal pruning is evident in depression. Future research could determine whether maladaptive pruning behaviours are observable in specific sub-groups of depressed patients (e.g. in treatment-resistant individuals), or whether misuse of other heuristics may contribute to depression.

Serotonin (5-HT) is thought to be critical for affect regulation in the brain and many antidepressants are thought to primarily work by altering 5-HT levels. However there has not been a validated means of directly imaging of endogenous 5-HT levels in humans. The main aims of this project are to image the effect of Citalopram on brain endogenous 5-HT levels and to determine the relationship between brain 5-HT and affect regulation.

Thirteen healthy volunteers (mean age 50.9yrs, range 35–63) underwent two Positron Emission Tomography (PET) scans with [11C]-CUMI, a highly selective 5-HT1A agonist radioligand. Subjects received either a slow intravenous infusion of citalopram 10mg or saline starting 45 minutes before each PET scan in a randomized design. All subjects had a functional MRI emotion processing task (block design) known to activate the amygdala on a separate day.

The citalopram infusion induced 6–11% increases in [11C]-CUMI binding potential in anterior cingulate, insula and cortical brain regions (p < 0.05 corrected for repeated measures).

BOLD response to fearful vs neutral faces in the left amygdala inversely correlated with baseline dorsal raphe BP (Pearson r2 =−0.90, p < 0.001) and directly correlated with dorsal raphe BP changes (r2=0.51, p = 0.07).

The increase in [11C]CUMI-101 availability would be consistent with a decrease in endogenous 5-HT availability in certain terminal regions. The relationship between brain emotion processing and [11C]-CUMI binding in the raphe indicates the 5-HT levels at presynaptic receptors regulate emotional processing and suggests presynaptic 5-HT as a treatment target for affective disorders.