What Information Do Clinicians Deem Important for Counseling Parents Facing Extremely Early Deliveries?: Results from an Online Survey.

OBJECTIVE: The study aimed to better understand how neonatology and maternal fetal medicine (MFM) physicians convey information during antenatal counseling that requires facilitating shared decision-making with parents facing options of resuscitation versus comfort care after extremely early delivery STUDY DESIGN: Attending physicians at US centers with both Neo and MFM fellowships were invited to answer an original online survey about antenatal counseling for extremely early newborns. The survey assessed information conveyed, processes for facilitating shared decision-making (reported separately), and clinical experiences. Neonatology and MFM responses were compared. Multivariable logistic regression analyzed topics often and seldom discussed by specialty groups with respect to respondents' clinical experience and resuscitation option preferences at different gestational weeks. RESULTS: In total, 74 MFM and 167 neonatologists representing 94% of the 81 centers surveyed responded. Grouped by specialty, respondents were similar in counseling experience and distribution of allowing choices between resuscitation and no resuscitation for delivery at specific weeks of gestational ages. MFM versus neonatology reported similar rates of discussing long-term health and developmental concerns and differed in all other categories of topics. Neonatologists were less likely than MFM to discuss caregiver impacts (odds ratio [OR]: 0.14, 95% confidence interval [CI]: 0.11-0.18, p < 0.001) and comfort care details (OR: 0.19, 95% CI: 0.15-0.25, p < 0.001). Conversely, neonatology versus MFM respondents more frequently reported "usually" discussing topics pertaining to parenting in the NICU (OR: 1.5, 95% CI: 1.2-1.8, p < 0.001) and those regarding stabilizing interventions in the delivery room (OR: 1.8, 95% CI: 1.4-2.2, p < 0.001). Compared with less-experienced respondents, those with 17 years' or more of clinical experience had greater likelihood in both specialties to say they "usually" discussed otherwise infrequently reported topics pertaining to caregiver impacts. CONCLUSION: Parents require information to make difficult decisions for their extremely early newborns. Our findings endorse the value of co-consultation by MFM and neonatology clinicians and of trainee education on antenatal consultation education to support these families. KEY POINTS: · Neonatology versus MFM counselors provide complementary information.. · More experience was linked to discussing some topics.. · Co-consultation and trainee education is supported.. · What information parents value requires study..

How do Clinicians View the Process of Shared Decision-Making with Parents Facing Extremely Early Deliveries? Results from an Online Survey.

OBJECTIVE: The objective of this study was to better understand how neonatology (Neo) and maternal-fetal medicine (MFM) physicians approach the process of shared decision-making (SDM) with parents facing extremely premature (<25 weeks estimated gestational age) delivery during antenatal counseling. STUDY DESIGN: Attending physicians at U.S. centers with both Neo and MFM fellowships were invited to answer an original online survey about antenatal counseling for extremely early newborns. Preferences for conveying information are reported elsewhere. Here, we report clinicians' self-assessments of their ability to engage in deliberations and decision-making and perceptions of what is important to parents in the SDM process. Multivariable logistic regression analyzed respondents' views with respect to individual characteristics, such as specialty, gender, and years of clinical experience. RESULTS: In total, 74 MFMs and 167 Neos representing 94% of the 81 centers surveyed responded. Neos versus MFMs reported repeat visits with parents less often (<0.001) and agreed that parents were more likely to have made delivery room decisions before they counseled them less often (p < 0.001). Respondents reported regularly achieving most goals of SDM, with the exception of providing spiritual support. Most respondents reported that spiritual and religious views, risk to an infant's survival, and the infant's quality of life were important to parental decision-making, while a physician's own personal choice and family political views were reported as less important. While many barriers to SDM exist, respondents rated language barriers and family views that differ from those of a provider as the most difficult barriers to overcome. CONCLUSION: This study provides insights into how consultants from different specialties and demographic groups facilitate SDM, thereby informing future efforts for improving counseling and engaging in SDM with parents facing extremely early deliveries and supporting evidence-based training for these complex communication skills. KEY POINTS: · Perceptions differed by specialty and demographics.. · Parents' spiritual needs were infrequently met.. · Barriers to shared decision-making exist..

A Bronx Dad's Tale.

In this narrative medicine essay, a neonatologist through the complex forces of intensive care physician, son, and ethicist grapples with the impending loss of his father and ultimately understanding his father's demand for autonomy in deciding his care.

Assessment of a shortened informed consent form for pediatric research: a pilot study.

BACKGROUND: Inherent to clinical research is the informed consent process, with the informed consent form (ICF), a key component of human participant protections. We wished to examine whether a shortened and simplified ICF, accompanied by an appendix, improved participant understanding of a study compared with a conventional ICF. METHODS: A shortened ICF was developed from an existing conventional ICF for a neonatal study. Either the shortened or conventional ICF was randomly distributed to members of two parental advocacy groups. Participants answered survey questions about the form they received. RESULTS: Thirty-one out of forty-one (76%) parents in the shortened ICF and 28/41 (68%) in the conventional ICF group responded. Significantly more parents in the shortened ICF group found their form "short and to the point". Although they also stated that the shortened ICF did not provide enough information, there were no significant differences between groups measuring the understanding of key study components. CONCLUSION: A shortened ICF did not impact the understanding of the clinical trial. It will be important to compare the shortened and conventional forms in actual clinical trials.

Variability of Care Practices for Extremely Early Deliveries.

OBJECTIVES: Assess temporal changes, intercenter variability, and birthing person (BP) factors relating to interventions for extremely early deliveries. METHODS: Retrospective study of BPs and newborns delivered from 22-24 completed weeks at 13 US centers from 2011-2020. Rates of neonatology consultation, antenatal corticosteroids, cesarean delivery, live birth, attempted resuscitation (AR), and survival were assessed by epoch, center, and gestational age. RESULTS: 2028 BPs delivering 2327 newborns were included. Rates increased in epoch 2-at 22 weeks: neonatology consultation (37.6 vs 64.3%, P < .001), corticosteroids (11.4 vs 29.5%, P < .001), live birth (66.2 vs 78.6%, P < .001), AR (20.1 vs 36.9%, P < .001), overall survival (3.0 vs 8.9%, P = .005); and at 23 weeks: neonatology consultation (73.0 vs 80.5%, P = .02), corticosteroids (63.7 vs 83.7%, P < .001), cesarean delivery (28.0 vs 44.7%, P < .001), live birth (88.1 vs 95.1%, P < .001), AR (67.7 vs 85.2%, P < .001), survival (28.8 vs 41.6%, P < .001). Over time, intercenter variability increased at 22 weeks for corticosteroids (interquartile range 18.0 vs 42.0, P = .014) and decreased at 23 for neonatology consultation (interquartile range 23.0 vs 5.2, P = .045). In BP-level multivariate analysis, AR was associated with increasing gestational age and birth weight, Black BP race, previous premature delivery, and delivery center. CONCLUSIONS: Intervention rates for extremely early newborns increased and intercenter variability changed over time. In BP-level analysis, factors significantly associated with AR included Black BP race, previous premature delivery, and center.

Safety and efficacy of a home nasogastric monitoring program for premature infants.

BACKGROUND: A novel home monitoring program, in which premature infants are cared for at home with a nasogastric tube in place prior to achievement of full oral feeding, was evaluated. The program combines a digital, fully EMR-integrated, virtual daily rounding platform with direct provider video and telephone contact. METHODS: A case-control study was performed evaluating infants < 34 weeks' gestation who were followed in our program. A historical control group, was created by matching 2 : 1 based on gestational age±6 days, retroactively. RESULT: 15 patients discharged in the program were compared with 30 controls. The home cohort gained an average of 30 g/day compared with the in-hospital group at 27g/day (p = 0.325). The home group required a mean of 5.9±2.9 days to full oral feeding once discharged, not different from the control group at 5.4±3.7 days (p = 0.606). The percentage of oral feeds for the home cohort, however, increased at a rate of 12.2%before discharge compared to rising 57%at home (p < 0.001). The control group spent an additional 8.1±3.9 days in the hospital after reaching criteria. There were no reported adverse events or readmissions. CONCLUSION: Premature infants can safely advance oral feeds using a home monitoring program. While at home, infants gained weight similarly to their inpatient controls, yet gained full oral skills at a significantly faster rate compared to when they were in the hospital.

Somatosensory response properties of excitatory and inhibitory neurons in rat motor cortex.

In sensory cortical networks, peripheral inputs differentially activate excitatory and inhibitory neurons. Inhibitory neurons typically have larger responses and broader receptive field tuning compared with excitatory neurons. These differences are thought to underlie the powerful feedforward inhibition that occurs in response to sensory input. In the motor cortex, as in the somatosensory cortex, cutaneous and proprioceptive somatosensory inputs, generated before and during movement, strongly and dynamically modulate the activity of motor neurons involved in a movement and ultimately shape cortical command. Human studies suggest that somatosensory inputs modulate motor cortical activity in a center excitation, surround inhibition manner such that input from the activated muscle excites motor cortical neurons that project to it, whereas somatosensory input from nearby, nonactivated muscles inhibit these neurons. A key prediction of this hypothesis is that inhibitory and excitatory motor cortical neurons respond differently to somatosensory inputs. We tested this prediction with the use of multisite extracellular recordings in anesthetized rats. We found that fast-spiking (presumably inhibitory) neurons respond to tactile and proprioceptive inputs at shorter latencies and larger response magnitudes compared with regular-spiking (presumably excitatory) neurons. In contrast, we found no differences in the receptive field size of these neuronal populations. Strikingly, all fast-spiking neuron pairs analyzed with cross-correlation analysis displayed common excitation, which was significantly more prevalent than common excitation for regular-spiking neuron pairs. These findings suggest that somatosensory inputs preferentially evoke feedforward inhibition in the motor cortex. We suggest that this provides a mechanism for dynamic selection of motor cortical modules during voluntary movements.

Autocrine activation of neuronal NMDA receptors by aspartate mediates dopamine- and cAMP-induced CREB-dependent gene transcription.

cAMP can stimulate the transcription of many activity-dependent genes via activation of the transcription factor, cAMP response element-binding protein (CREB). However, in mouse cortical neuron cultures, prior to synaptogenesis, neither cAMP nor dopamine, which acts via cAMP, stimulated CREB-dependent gene transcription when NR2B-containing NMDA receptors (NMDARs) were blocked. Stimulation of transcription by cAMP was potentiated by inhibitors of excitatory amino acid uptake, suggesting a role for extracellular glutamate or aspartate in cAMP-induced transcription. Aspartate was identified as the extracellular messenger: enzymatic scavenging of l-aspartate, but not glutamate, blocked stimulation of CREB-dependent gene transcription by cAMP; moreover, cAMP induced aspartate but not glutamate release. Together, these results suggest that cAMP acts via an autocrine or paracrine pathway to release aspartate, which activates NR2B-containing NMDARs, leading to Ca(2+) entry and activation of transcription. This cAMP/aspartate/NMDAR signaling pathway may mediate the effects of transmitters such as dopamine on axon growth and synaptogenesis in developing neurons or on synaptic plasticity in mature neural networks.

Abnormal anterior pretectal nucleus activity contributes to central pain syndrome.

Central pain syndrome (CPS) is a debilitating condition that affects a large number of patients with a primary lesion or dysfunction in the CNS, most commonly due to spinal cord injury, stroke, and multiple sclerosis lesions. The pathophysiological processes underlying the development and maintenance of CPS are poorly understood. We have recently shown, in an animal model of CPS, that neurons in the posterior thalamic nucleus (PO) have increased spontaneous and evoked activity. We also demonstrated that these changes are due to suppressed inhibitory inputs from the zona incerta (ZI). The anterior pretectal nucleus (APT) is a diencephalic nucleus that projects on both the PO and ZI, suggesting that it might be involved in the pathophysiology of CPS. Here we test the hypothesis that CPS is associated with abnormal APT activity by recording single units from APT in anesthetized rats with CPS resulting from spinal cord lesions. The firing rate of APT neurons was increased in spinal-lesioned animals, compared with sham-operated controls. This increase was due to a selective increase in firing of tonic neurons that project to and inhibit ZI and an increase in bursts in fast bursting and slow rhythmic neurons. We also show that, in normal animals, suppressing APT results in increased PO spontaneous activity and evoked responses in a subpopulation of PO neurons. Taken together, these findings suggest that APT regulates ZI inputs to PO and that enhanced APT activity during CPS contributes to the abnormally high activity of PO neurons in CPS.

Visitation restrictions: is it right and how do we support families in the NICU during COVID-19?

Although the COVID-19 pandemic has largely not clinically affected infants in neonatal intensive care units around the globe, it has affected how care is provided. Most hospitals, including their NICUs, have significantly reduced parental and family visitation privileges. From an ethical perspective, this restriction of parental visitation in settings where infectious risk is difficult to understand. No matter what the right thing to do is, NICUs are currently having to support families of their patients via different mechanisms. In this perspective, we discuss ways NICUs can support parents and families when they are home and when they are in the NICU as well as provide infants the support needed when family members are not able to visit.

Failure of Ca2+-activated, CREB-dependent transcription in astrocytes.

Astrocytes participate in signaling via Ca(2+) transients that spread from cell to cell across a multicellular syncytium. The effect, if any, of these Ca(2+) waves on the transcription of Ca(2+)/cAMP-regulatory element binding protein (CREB)-dependent genes is not known. We report here that, unlike neurons, increasing intracellular Ca(2+) in cultured mouse cortical astrocytes failed to activate CREB-dependent transcription, even though CREB was phosphorylated at serine 133. In contrast, both CREB phosphorylation and CREB-dependent transcription were robustly stimulated by increasing cAMP. The failure of Ca(2+)-activated transcription in astrocytes was correlated with the absence of CaMKIV, a Ca(2+)-dependent protein kinase required for Ca(2+)-stimulated gene transcription in neurons. The inability of Ca(2+) to signal via CaMKIV may insulate CREB-dependent gene transcription in astrocytes from activation by Ca(2+) waves.

Academic achievement and employment in young adults with end-stage kidney disease.

BACKGROUND: Young adults with end-stage kidney disease (ESKD) are at a pivotal stage of life: progressing through education, seeking employment and developing relationships. We set out to explore how ESKD impacts education and employment attainment in a matched UK and USA patient cohort. Moreover, we aimed to determine if there were significant differences in reported perceptions of impact. DESIGN: A mixed methods design combining previously validated quantitative questionnaire surveys and qualitative semi-structured interviews. PARTICIPANTS: Young people with ESKD aged 18-30 years (N = 27), attending single-centre follow-up in Oxford, UK were matched with 27 comparable young people aged 19-30 years, under follow-up in Denver, USA. Twelve of these patients from Denver were selected for interview. MEASUREMENTS: Self-report questionnaires surveyed patient demographics, educational and employment achievement and experiences. Questionnaire categorical data for matched pairs were analysed using Bowker's test of symmetry. Sequential flow analyses of interview content delineated perception patterns through thematic coding. RESULTS: Sixty percent of non-student Oxford participants were employed compared with 41% in Denver (p = 0.023). Forty-four percent of Oxford patients compared with 52% in Denver, reported illness had made it difficult to gain employment (p = 0.88). In Oxford, 32% completed high school as their highest educational achievement, versus 68% in Denver (p = 0.22). Qualitative themes included fatigue, self-esteem loss, social isolation and low mood. The impact of dialysis and poor understanding from educators/employers resulted in lost work time, and/or limited educational attainment. CONCLUSION: ESKD profoundly impacts on education and employment of young adults in the United States and United Kingdom, generating substantial barriers. Poor understanding appears prevalent amongst educators and employers. Healthcare providers must recognise these problems and invest resources towards tailored support in order to improve associated psychosocial and clinical outcomes.

Unilateral pediatric "do not attempt resuscitation" orders: the pros, the cons, and a proposed approach.

A unilateral do not attempt resuscitation (DNAR) order is written by a physician without permission or assent from the patient or the patient's surrogate decision-maker. Potential justifications for the use of DNAR orders in pediatrics include the belief that attempted resuscitation offers no benefit to the patient or that the burdens would far outweigh the potential benefits. Another consideration is the patient's right to mercy, not to be made to undergo potentially painful interventions very unlikely to benefit the patient, and the physician's parallel obligation not to perform such interventions. Unilateral DNAR orders might be motivated in part by the moral distress caregivers sometimes experience when feeling forced by parents to participate in interventions that they believe are useless or cruel. Furthermore, some physicians believe that making these decisions without parental approval could spare parents needless additional emotional pain or a sense of guilt from making such a decision, particularly when imminent death is unavoidable. There are, however, several risks inherent in unilateral DNAR orders, such as overestimating one's ability to prognosticate or giving undue weight to the physician's values over those of parents, particularly with regard to predicted disability and quality of life. The law on the question of unilateral DNAR varies among states, and readers are encouraged to learn the law where they practice. Arguments in favor of, and opposed to, the use of unilateral DNAR orders are presented. In some settings, particularly when death is imminent regardless of whether resuscitation is attempted, unilateral DNAR orders should be viewed as an ethically permissible approach.

Impact of end-stage kidney disease on academic achievement and employment in young adults: a mixed methods study.

PURPOSE: Young adult kidney patients are at an important stage of development when end-stage kidney disease (ESKD) may adversely influence progress in education and employment. This study is designed to assess the impact of ESKD on education and employment outcomes in young adults. METHOD: This cross-sectional study was a mixed methods design. Education and career achievements in young adults with ESKD were recorded quantitatively using a questionnaire survey (n = 57): 14 of 57 representative participants were subsequently selected for semistructured interview. RESULTS: Questionnaire survey was conducted in 57 young adults (median age 25): 8.8% (n = 5) were predialysis; 14.0% (n = 8) dialysis; and 78.9% (n = 45) were kidney transplant recipients. Median school-leaving age was 16 (interquartile range = 15-19). Of 57 young adults, 10 (17.5%) were still studying, 43 (75.4%) had completed education, 34 (59.7%) were employed (23 full time and 11 part time), and 19 (33.3%) were unemployed. Twenty-seven of 45 transplanted patients were employed (60.0%). Of these 27, 21 were full time (77.8%). Five of eight dialysis patients were employed: only one of eight was full-time employed (12.5%). Themes impacting on education and employment included low energy levels, time missed, loss of self-esteem, and feelings of loneliness and isolation, which may progress to depression and recreational drug use. Lack of understanding from educators and employers resulting in lost work, and career ambitions changed or limited because of dialysis. CONCLUSIONS: Dialysis has a major negative impact on education and reduced employment rates of young adults. There is a general lack of understanding among educators and employers of the impact of ESKD. Low energy levels, lack of self-esteem, and depression are key factors. There is a need for health care providers to recognize this issue and invest in supporting young adults with ESKD.

Zona incerta: a role in central pain.

Central pain syndrome (CPS) is a debilitating condition that affects a large number of patients with a primary lesion or dysfunction in the CNS. Despite its discovery over a century ago, the pathophysiological processes underlying the development and maintenance of CPS are poorly understood. We recently demonstrated that activity in the posterior thalamus (PO) is tightly regulated by inhibitory inputs from zona incerta (ZI). Here we test the hypothesis that CPS is associated with abnormal inhibitory regulation of PO by ZI. We recorded single units from ZI and PO in animals with CPS resulting from spinal cord lesions. Consistent with our hypothesis, the spontaneous firing rate and somatosensory evoked responses of ZI neurons were lower in lesioned animals compared with sham-operated controls. In PO, neurons recorded from lesioned rats exhibited significantly higher spontaneous firing rates and greater responses to noxious and innocuous stimuli applied to the hindpaw and to the face. These changes were not associated with increased afferent drive from the spinal trigeminal nucleus or changes in the ventroposterior thalamus. Thus CPS can result from suppressed inputs from the inhibitory nucleus zona incerta to the posterior thalamus.

Ca(2+)-dependent regulation of TrkB expression in neurons.

The neurotrophin brain-derived neurotrophic factor (BDNF), via activation of its receptor, tyrosine receptor kinase B (trkB), regulates a wide variety of cellular processes in the nervous system, including neuron survival and synaptic plasticity. Although the expression of BDNF is known to be Ca2+-dependent, the regulation of trkB expression has not been extensively studied. Here we report that depolarization of cultured mouse cortical neurons increased the expression of the full-length, catalytically active isoform of trkB without affecting expression of the truncated isoform. This increase in protein expression was accompanied by increased levels of transcripts encoding full-length, but not truncated, trkB. Depolarization also regulated transcription of the gene, TRKB, via entry of Ca2+ through voltage-gated Ca2+ channels and subsequent activation of Ca2+-responsive elements in the two TRKB promoters. Using transient transfection of neurons with TRKB promoter-luciferase constructs, we found that Ca2+ inhibited the upstream promoter P1 but activated the downstream promoter P2. Ca2+-dependent stimulation of TRKB expression requires two adjacent, non-identical CRE sites located within P2. The coordinated regulation of BDNF and trkB by Ca2+ may play a role in activity-dependent survival and synaptic plasticity by enhancing BDNF signaling in electrically active neurons.