Outcomes for Pediatric Oncology and Hematopoietic Stem Cell Transplantation Patients Who Undergo Tracheostomy Placement: A Pediatric Health information System Database Cohort Study, 2009-2020.

OBJECTIVES: To describe the epidemiology, surgical complications, and long-term outcomes after tracheostomy in pediatric oncology and/or hematopoietic stem cell transplantation (HSCT) patients in U.S. Children's Hospitals. DESIGN: Retrospective cohort from the Pediatric Health information System (PHIS) database, 2009-2020. SETTING: The PHIS dataset incorporates data from 48 pediatric hospitals in the Children's Hospital Association. PATIENTS: Patients 0-21 years old with an oncologic diagnosis and/or underwent HSCT, received a tracheostomy, and were discharged from hospital between January 1, 2009, and December 31, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 1061 patients included in the dataset, and 217 (20.5%) had undergone HSCT. The annual prevalence in tracheostomy usage did not change over the study period. The majority of patients (62.2%) underwent tracheostomy early (< 30 d) in the admission and those who underwent the procedure later (> 90 d) had a significant increase in mortality (52.6% vs. 17.6%; p < 0.001) and mechanical ventilation (MV) at discharge (51.9% vs. 24.5%; p < 0.001) compared with the early tracheostomy patients. Complications reported included tracheostomy site bleeding (< 1%) and infection (24%). The overall rate of MV at discharge was 32.6% and significantly associated with chronic lung (adjusted odds ratio [OR], 1.54; 95% CI, 1.03-2.32) and acute lung disease (OR, 2.18; 95% CI, 1.19-3.98). The overall rate of mortality was 19.6% within the cohort and significantly associated with HSCT (OR, 5.45; 95% CI, 3.88-7.70), diagnosis of sepsis (OR, 2.09; 95% CI, 1.28-3.41), and requirement for renal replacement therapy (OR, 2.76; 95% CI, 1.58-4,83). CONCLUSIONS: This study demonstrated a static prevalence of tracheostomy placement in the cohort population relative to the increasing trends in other reported groups. Regardless of underlying diagnosis, the study patients incurred substantial morbidity and mortality. However, tracheostomy specific complication rates were comparable with that of the general pediatric population and were not associated with increased odds of mortality within this population.

Outcomes for Children With Pulmonary Hypertension Undergoing Tracheostomy Placement: A Multi-Institutional Analysis.

OBJECTIVES: To describe epidemiology, interventions, outcomes, and the health services experience for a cohort of children with pulmonary hypertension (PH) who underwent tracheostomy placement and to identify risk factors for inhospital mortality and 30-day readmissions. DESIGN: Retrospective cohort study of the Pediatric Health Information System database. SETTING: Thirty-seven freestanding U.S. children's hospitals. PATIENTS: Patients 31 days to 21 years old who were discharged from the hospital between January 1, 2009, and December 31, 2017, with a diagnosis of primary or secondary PH, and who underwent tracheostomy placement. Outcomes were examined over a 2-year period from the time of discharge from the index encounter. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 793 patients with PH who underwent tracheostomy placement. The overall inhospital mortality rate was 23.7%. Secondary PH due to congenital heart disease (CHD) was significantly associated with overall inhospital mortality (adjusted odds ratio [OR], 2.36; 95% CI, 1.38-4.04). The rate of 30-day readmissions for patients over the 2-year follow-up period was 33.3%. Tracheostomy during the index encounter and the diagnosis of secondary PH due to CHD were significantly associated with lower rates of 30-day readmissions (adjusted OR, 0.34; 95% CI, 0.19-0.61; and adjusted OR, 0.43; 95% CI, 0.24-0.77, respectively). CONCLUSIONS: In the context of expanding utilization of tracheostomy and long-term ventilation, children with PH are among the highest risk cohorts for extended and repeated hospitalization and death. Tracheostomy placement during the index encounter was associated with fewer 30-day readmissions over the 2-year follow-up period. Further understanding of which subgroups may benefit from earlier intervention and which subgroups are at highest risk may offer important clinical insight when considering optimal timing of tracheostomy and may enhance informed decision-making for all stakeholders.

Visiting Jack: Mixed Methods Evaluation of a Virtual Home Visit Curriculum With a Child With Medical Complexity.

BACKGROUND: There are limited training opportunities for pediatricians in caring for children with medical complexity (CMC) in the home and community. Prior studies have described a lack of comfort caring for CMC among pediatric residents. OBJECTIVE: 1) To evaluate the impact of participation in a virtual home visit curriculum on pediatric residents' confidence, knowledge, and application of knowledge in complex care; 2) to explore changes in perspectives relating to the care of CMC after participation in the curriculum. METHODS: This was a prospective pre-post intervention study in 2019 with first-year pediatric residents, using quantitative and qualitative methods. The intervention, co-created with a family partner, was an online video-based curriculum followed by an in-person seminar. Pre- and postassessments were compared using paired t tests. Follow-up interviews and focus groups were performed 5 to 8 weeks after training. Transcripts were analyzed using inductive thematic analysis. RESULTS: Twenty-four residents (100%) participated. Residents reported increased confidence in all aspects of complex care presented in the curriculum, with significant increase in knowledge and application of knowledge (all P < .001). Twelve residents (50%) participated in a follow-up interview or focus group. Four themes were identified: 1) recognizing prior attitudes toward complexity, 2) new mental framework for complex care at home, 3) drivers of behavior change, and 4) commitment to change practice. CONCLUSIONS: Participation in this curriculum was associated with increased confidence, knowledge, and application of knowledge in complex care outside of the hospital. Qualitative findings align with transformative learning theory, lending insight into effective approaches to complex care training.

Differential effects of motor cortical excitability and plasticity in young and old individuals: a Transcranial Magnetic Stimulation (TMS) study.

Aging is associated with changes in the motor system that, over time, can lead to functional impairments and contribute negatively to the ability to recover after brain damage. Unfortunately, there are still many questions surrounding the physiological mechanisms underlying these impairments. We examined cortico-spinal excitability and plasticity in a young cohort (age range: 19-31) and an elderly cohort (age range: 47-73) of healthy right-handed individuals using navigated transcranial magnetic stimulation (nTMS). Subjects were evaluated with a combination of physiological [motor evoked potentials (MEPs), motor threshold (MT), intracortical inhibition (ICI), intracortical facilitation (ICF), and silent period (SP)] and behavioral [reaction time (RT), pinch force, 9 hole peg task (HPT)] measures at baseline and following one session of low-frequency (1 Hz) navigated repetitive TMS (rTMS) to the right (non-dominant) hemisphere. In the young cohort, the inhibitory effect of 1 Hz rTMS was significantly in the right hemisphere and a significant facilitatory effect was noted in the unstimulated hemisphere. Conversely, in the elderly cohort, we report only a trend toward a facilitatory effect in the unstimulated hemisphere, suggesting reduced cortical plasticity and interhemispheric communication. To this effect, we show that significant differences in hemispheric cortico-spinal excitability were present in the elderly cohort at baseline, with significantly reduced cortico-spinal excitability in the right hemisphere as compared to the left hemisphere. A correlation analysis revealed no significant relationship between cortical thickness of the selected region of interest (ROI) and MEPs in either young or old subjects prior to and following rTMS. When combined with our preliminary results, further research into this topic could lead to the development of neurophysiological markers pertinent to the diagnosis, prognosis, and treatment of neurological diseases characterized by monohemispheric damage and lateralized motor deficits.

Differentiation of motor cortical representation of hand muscles by navigated mapping of optimal TMS current directions in healthy subjects.

The precision of navigated transcranial magnetic stimulation (TMS) to map the human primary motor cortex may be effected by the direction of TMS-induced current in the brain as determined by the orientation of the stimulation coil. In this study, the authors investigated the effect of current directionality on motor output mapping using navigated brain stimulation. The goal of this study was to determine the optimal coil orientation (and, thus, induced brain current) to activate hand musculature representations relative to each subject's unique neuroanatomical landmarks. The authors studied motor output maps for the first dorsal interosseous, abductor pollicis brevis, and abductor digiti minimi muscles in 10 normal volunteers. Monopolar current pulses were delivered through a figure-of-eight-shaped TMS coil, and motor evoked potentials were recorded using electromyography. At each targeted brain region, the authors systematically rotated the TMS coil to determine the direction of induced current in the brain for induction of the largest motor evoked potentials. These optimal current directions were expressed as an angle relative to each subject's central sulcus. Consistency of the optimal current direction was assessed by repeating the entire mapping procedure on two different occasions across subjects. The authors demonstrate that systematic optimization of current direction as guided by MRI-based neuronavigation improves the resolution of cortical output motor mapping with TMS.

Insights on the neural basis of motor plasticity induced by theta burst stimulation from TMS-EEG.

Transcranial magnetic stimulation (TMS) is a useful tool to induce and measure plasticity in the human brain. However, the cortical effects are generally indirectly evaluated with motor-evoked potentials (MEPs) reflective of modulation of cortico-spinal excitability. In this study, we aim to provide direct measures of cortical plasticity by combining TMS with electroencephalography (EEG). Continuous theta-burst stimulation (cTBS) was applied over the primary motor cortex (M1) of young healthy adults, and we measured modulation of (i) MEPs, (ii) TMS-induced EEG evoked potentials (TEPs), (iii) TMS-induced EEG synchronization and (iv) eyes-closed resting EEG. Our results show the expected cTBS-induced decrease in MEP size, which we found to be paralleled by a modulation of a combination of TEPs. Furthermore, we found that cTBS increased the power in the theta band of eyes-closed resting EEG, whereas it decreased single-pulse TMS-induced power in the theta and alpha bands. In addition, cTBS decreased the power in the beta band of eyes-closed resting EEG, whereas it increased single-pulse TMS-induced power in the beta band. We suggest that cTBS acts by modulating the phase alignment between already active oscillators; it synchronizes low-frequency (theta and/or alpha) oscillators and desynchronizes high-frequency (beta) oscillators. These results provide novel insight into the cortical effects of cTBS and could be useful for exploring cTBS-induced plasticity outside of the motor cortex.

Transcranial magnetic stimulation: a historical evaluation and future prognosis of therapeutically relevant ethical concerns.

Transcranial Magnetic Stimulation (TMS) is a non-invasive neurostimulatory and neuromodulatory technique increasingly used in clinical and research practices around the world. Historically, the ethical considerations guiding the therapeutic practice of TMS were largely concerned with aspects of subject safety in clinical trials. While safety remains of paramount importance, the recent US Food and Drug Administration approval of the Neuronetics NeuroStar TMS device for the treatment of specific medication-resistant depression has raised a number of additional ethical concerns, including marketing, off-label use and technician certification. This article provides an overview of the history of TMS and highlights the ethical questions that are likely arise as the therapeutic use of TMS continues to expand.

An improved yeast transformation method for the generation of very large human antibody libraries.

Antibody library selection by yeast display technology is an efficient and highly sensitive method to identify binders to target antigens. This powerful selection tool, however, is often hampered by the typically modest size of yeast libraries (approximately 10(7)) due to the limited yeast transformation efficiency, and the full potential of the yeast display technology for antibody discovery and engineering can only be realized if it can be coupled with a mean to generate very large yeast libraries. We describe here a yeast transformation method by electroporation that allows for the efficient generation of large antibody libraries up to 10(10) in size. Multiple components and conditions including CaCl(2), MgCl(2), sucrose, sorbitol, lithium acetate, dithiothreitol, electroporation voltage, DNA input and cell volume have been tested to identify the best combination. By applying this developed protocol, we have constructed a 1.4 x 10(10) human spleen antibody library essentially in 1 day with a transformation efficiency of 1-1.5 x 10(8) transformants/microg vector DNA. Taken together, we have developed a highly efficient yeast transformation method that enables the generation of very large and productive human antibody libraries for antibody discovery, and we are now routinely making 10(9) libraries in a day for antibody engineering purposes.