Motivations for and against Participation in Neonatal Research: Insights from Interviews of Diverse Parents Approached for Neonatal Research in the US.

OBJECTIVE: To describe parents' motivations for and against participation in neonatal research, including the views of those who declined participation. STUDY DESIGN: We performed 44 semi-structured, qualitative interviews of parents approached for neonatal research. Here we describe their motivations for and against participation. RESULTS: Altruism was an important reason parents chose to participate. Some hoped participation in research would benefit their infant. Burdens of participation to the family, such as transportation to follow up (distinct from risks/burdens to the infant), were often deciding factors among those who declined participation. Perceived risks to the infant were reasons against participation, but parents often did not differentiate between baseline risks and incremental risk of study participation. Concerns regarding their infant being treated like a "guinea pig" were common among those who declined. Finally, historical abuses and institutional racism were reported as important concerns by some research decliners from minoritized populations. CONCLUSIONS: Within a diverse sample of parents approached to enroll their infant in neonatal research, motivations for and against participation emerged, which may be targets of future interventions. These motivations included reasons for participation which we may hope to encourage, such as altruism. They also included reasons against participation, which we may hope to, as feasible, eliminate, mitigate, or at least acknowledge. These findings can help clinical trialists, regulators, and funders attempting to improve neonatal research recruitment processes.

Interpersonal Influences on the Choice to Treat Nausea during Pregnancy with Medication or Cannabis.

OBJECTIVE: This study aimed to better understand the interpersonal influences on a pregnant individual's decision of how to treat nausea and vomiting during pregnancy using a qualitative approach. STUDY DESIGN: A semistructured interview guide was developed to assess pregnancy symptoms, decision-making regarding treating nausea, and interpersonal influences on treatment decisions. Interviews were conducted with 17 individuals enrolled in a neuroimaging and behavioral study of prenatal exposure to cannabis who used medication and/or cannabis to treat symptoms associated with pregnancy. RESULTS: Interviews revealed four groups of stakeholders who influenced participant decision-making: medical providers, partners, family, and friends. Influence was categorized as either positive, negative, neutral, or absent (if not discussed or participant chose not to disclose). Those in the medication group reported only positive or neutral feedback from friends, family, partners, and providers. In contrast, the cannabis group participants reported positive feedback from friends, mixed feedback from family and partners, and negative feedback from providers, which was often felt to be stigmatizing. Many in the cannabis group also reported varying feedback from different medical providers. While the cannabis group frequently reported eliciting feedback from friends, family, and partners, the medication group often did not. CONCLUSION: Medication group participants reported entirely positive feedback from providers and often did not mention any feedback at all from partners, family, and friends. Cannabis group participants reported much more varied feedback, both positive and negative, from a variety of interpersonal contacts and sometimes decided to conceal their treatment choice after receiving or fearing negative feedback. We recommend further research into the health outcomes of pregnant patients who chose not to discuss their treatment decisions with providers, family, partners, or friends. We also suggest further study of possible reasons behind a lack of disclosure, including fear of stigma and/or legal consequences. KEY POINTS: · Providers, partners, family, friends gave feedback.. · Medication group got positive feedback.. · Cannabis group stigmatized by providers.. · Cannabis group got mixed feedback..

Apigenin restores endothelial function by ameliorating oxidative stress, reverses aortic stiffening, and mitigates vascular inflammation with aging.

We assessed the efficacy of oral supplementation with the flavanoid apigenin on arterial function during aging and identified critical mechanisms of action. Young (6 mo) and old (27 mo) C57BL/6N mice (model of arterial aging) consumed drinking water containing vehicle (0.2% carboxymethylcellulose; 10 young and 7 old) or apigenin (0.5 mg/mL in vehicle; 10 young and 9 old) for 6 wk. In vehicle-treated animals, isolated carotid artery endothelium-dependent dilation (EDD), bioassay of endothelial function, was impaired in old versus young (70% ± 9% vs. 92% ± 1%, P < 0.0001) due to reduced nitric oxide (NO) bioavailability. Old mice had greater arterial reactive oxygen species (ROS) production and oxidative stress (higher nitrotyrosine) associated with greater nicotinamide adenine dinucleotide phosphate oxidase (oxidant enzyme) and lower superoxide dismutase 1 and 2 (antioxidant enzymes); ex vivo administration of Tempol (antioxidant) restored EDD to young levels, indicating ROS-mediated suppression of EDD. Old animals also had greater aortic stiffness as indicated by higher aortic pulse wave velocity (PWV, 434 ± 9 vs. 346 ± 5 cm/s, P < 0.0001) due to greater intrinsic aortic wall stiffness associated with lower elastin levels and higher collagen, advanced glycation end products (AGEs), and proinflammatory cytokine abundance. In old mice, apigenin restored EDD (96% ± 2%) by increasing NO bioavailability, normalized arterial ROS, oxidative stress, and antioxidant expression, and abolished ROS inhibition of EDD. Moreover, apigenin prevented foam cell formation in vitro (initiating step in atherosclerosis) and mitigated age-associated aortic stiffening (PWV 373 ± 5 cm/s) by normalizing aortic intrinsic wall stiffness, collagen, elastin, AGEs, and inflammation. Thus, apigenin is a promising therapeutic for arterial aging.NEW & NOTEWORTHY Our study provides novel evidence that oral apigenin supplementation can reverse two clinically important indicators of arterial dysfunction with age, namely, vascular endothelial dysfunction and large elastic artery stiffening, and prevents foam cell formation in an established cell culture model of early atherosclerosis. Importantly, our results provide extensive insight into the biological mechanisms of apigenin action, including increased nitric oxide bioavailability, normalization of age-related increases in arterial ROS production and oxidative stress, reversal of age-associated aortic intrinsic mechanical wall stiffening and adverse remodeling of the extracellular matrix, and suppression of vascular inflammation. Given that apigenin is commercially available as a dietary supplement in humans, these preclinical findings provide the experimental basis for future translational studies assessing the potential of apigenin to treat arterial dysfunction and reduce cardiovascular disease risk with aging.

Family Responses to Different Types of Clinician Empathy Expression in Pediatric Care Conferences.

Background: Clinician empathy positively impacts patient outcomes. Few studies have assessed the effects of different types of empathic expression. Objective: To describe how families respond when clinicians express empathy in different ways. Design: Prospective, mixed-methods cohort. Setting/Subjects: English and interpreted pediatric inpatient care conferences at a U.S. quaternary hospital between January 1, 2018 and January 1, 2021. Measurements: Directed content analysis of clinician empathic statements and family responses. Results: Of 29 patient-family dyads, 11 (39%) used language interpretation. In response to 80 clinician empathic statements, families expressed agreement or shared more 84% (67/80) of the time. Families shared more about their perspective in response to explore statements 71.4% (10/14) of the time, in response to validate statements 61% (17/28) of the time, and in response to respect/support statements 39% (11/28) of the time. Conclusion: Certain types of empathic statements may be more effective at prompting families to share more about their perspective, a key element of shared decision-making.

Experiences and preferences for learning about neonatal research: insights from parent interviews.

INTRODUCTION: Parents struggle with being asked to participate in neonatal research. Past work has largely failed to include views of minoritized parents, low-socioeconomic status parents, and those who declined research. We aimed to describe parents' preferences related to learning about eligibility for neonatal research. METHODS: Qualitative interviews of parents who were asked to enroll their infant in neonatal research. Themes related to parental experiences and preferences for learning about neonatal research were identified using content analysis. RESULTS: Many parents desired greater involvement of their clinical team. Emotions at the time of recruitment were critically important to parents' experience, where were deeply impacted by interpersonal relationships with research staff. DISCUSSION: Increased involvement of the clinical team and greater sensitivity to the stressors around parent and infant conditions at the time of recruitment for neonatal research should be considered by those attempting to improve recruitment for neonatal research.

Empathy Expression in Interpreted and Noninterpreted Care Conferences of Seriously Ill Children.

BACKGROUND AND OBJECTIVES: Clinician empathy is associated with improved communication and clinical outcomes. We hypothesized that, when clinicians express empathy, families are more likely to deepen discussions, and that clinicians express less empathy in care conferences with language interpretation. METHODS: Prospective, mixed methods cohort study of English and interpreted audio-recorded transcripts of care conferences for pediatric patients with serious illness hospitalized at a single urban, quaternary medical institution between January 2018 and January 2021. Directed content analysis identified empathic opportunities, clinician empathetic statements or missed opportunities, and family responses. Clinician empathic statements were "buried" if immediately followed by more clinician medical talk. Descriptive analyses summarized demographics and codes. χ2 analyses summarized differences among language interpretation and family responses. RESULTS: Twenty-nine patient-family dyads participated. Twenty-two (81%) family members were female. Eleven (39%) used language interpretation (8 Spanish, 2 Vietnamese, 1 Somali). Families created 210 empathic opportunities. Clinicians responded with unburied empathy 80 times (38%, no differences for English versus interpreted care conferences, P = .88). When clinicians buried empathy or missed empathic opportunities, families responded with alliance (agreement, gratitude, or emotional deepening) 14% and 15% of the time, respectively. When clinicians responded with unburied empathy, families responded with alliance 83% of the time (P < .01). CONCLUSIONS: Our study suggests that clinician empathic expression does not differ when language interpretation is used in pediatric care conferences. Clinicians often miss opportunities to express empathy, or they bury it by medical talk. Although unburied empathy created opportunities for relationship-building and family-sharing, buried empathy negatively impacted these domains similarly to no empathic expression.

Parent Perspectives on the Child Experience of Pediatric Home Ventilation via Tracheostomy.

BACKGROUND AND OBJECTIVE: Parents facing the decision of whether to initiate pediatric mechanical ventilation via tracheostomy ("home ventilation") report wanting information about what to expect for life at home for their child. The study objective is to explore parent descriptions of the child experience of home ventilation to increase awareness for clinicians in the inpatient setting caring for these children. METHODS: Semistructured interviews were conducted using purposive sampling of parents with children who initiated home ventilation within the previous 5 years from 3 geographically diverse academic medical centers. RESULTS: We interviewed 21 families from 3 geographic regions in the United States. About 75% of children had respiratory failure in the first year of life, 80% had medical complexity, and half had severe neurologic impairment. Five domains emerged regarding parent perceptions of their child's experience of home ventilation: (1) health and well-being; (2) development; (3) adaptation; (4) mobility and travel; and (5) relationships. Within each domain, several themes were identified. For each theme, there was a positive and negative subtheme to illustrate how the child's experience was modified by home ventilation. Parent descriptions were generally positive, however, in all domains and to varying degrees, parents expressed negative aspects of home ventilation. CONCLUSIONS: By providing information about the realistic experiences of children using home ventilation, clinicians can support families in the inpatient setting as they face this complex decision. Balanced information about home ventilation is critical to enhancing clinician counseling so that families may benefit from the perspectives of experienced parents.

Home values and experiences navigation track (HomeVENT): Supporting decisions about pediatric home ventilation.

Objective: To pilot feasibility and acceptability of HomeVENT, a systematic approach to family-clinician decision-making about pediatric home ventilation. Methods: Parents and clinicians of children facing home ventilation decisions were enrolled at 3 centers using a pre/post cohort design. Family interventions included: 1) a website describing the experiences of families who previously chose for and against home ventilation 2) a Question Prompt List (QPL); 3) in-depth interviews exploring home life and values. Clinician HomeVENT intervention included a structured team meeting reviewing treatment options in light of the family's home life and values. All participants were interviewed one month after the decision. Results: We enrolled 30 families and 34 clinicians. Most Usual Care (14/15) but fewer Intervention (10/15) families elected for home ventilation. Families reported the website helped them consider different treatment options, the QPL promoted discussion within the family and with the team, and the interview helped them realize how home ventilation might change their daily life. Clinicians reported the team meeting helped clarify prognosis and prioritize treatment options. Conclusions: The HomeVENT pilot was feasible and acceptable. Innovation: This systematic approach to pediatric home ventilation decisions prioritizes family values and is a novel method to increase the rigor of shared decision-making in a rushed clinical environment.

"What Would Give Her the Best Life?": Understanding Why Families Decline Pediatric Home Ventilation.

Background: Families who must decide about pediatric home ventilation rely on the clinicians who counsel them for guidance. Most studies about pediatric home ventilation decisions focus on families who opt for this intervention, leaving much unknown about the families who decline. Objective: To describe the rationales of families who decline home ventilation. Design: Semi-structured interview study. Setting/Subjects: We interviewed 16 families in hospitals across 3 U.S. states, identified by their clinicians as previously deciding to not pursue home ventilation via tracheostomy within the past five years. Measurements: Targeted content and narrative analyses were used to understand family intentions and reasons for declining. Results: The clinical and social context varied among the 16 families in this study. Families' intentions in saying "no" fell into two categories: (1) definitive "No": Families who stood firm on in their decision and (2) contingent "No": Families who may consider this in the future. Families described four reasons why their child did not receive home ventilation: (1) concern about medical impacts, (2) concern about physical and/or communication restrictions, (3) concern that there would be no clear health benefit, and (4) concern about no clear meaningful life. Most families mentioned all four reasons, but concern about no clear meaningful life predominated. Conclusions: Though these families did not see home ventilation as an appropriate option, each reported a complex interplay of intentions behind and reasons for declining. Clinicians who counsel families about home ventilation could share the reasons that families commonly decline this intervention to facilitate a balanced discussion.

Validation of a Process for Shared Decision-Making in Pediatrics.

OBJECTIVE: We sought to confirm, refute, or modify a 4-step process for implementing shared decision-making (SDM) in pediatrics that involves determining 1) if the decision includes >1 medically reasonable option; 2) if one option has a favorable medical benefit-burden ratio compared to other options; and 3) parents' preferences regarding the options; then 4) calibrating the SDM approach based on other relevant decision characteristics. METHODS: We videotaped a purposive sample of pediatric inpatient and outpatient encounters at a single US children's hospital. Clinicians from 7 clinical services (craniofacial, neonatology, oncology, pulmonary, pediatric intensive care, hospital medicine, and sports medicine) were eligible. English-speaking parents of children who participated in inpatient family care conferences or outpatient problem-oriented encounters with participating clinicians were eligible. We conducted individual postencounter interviews with clinician and parent participants utilizing video-stimulated recall to facilitate reflection of decision-making that occurred during the encounter. We utilized direct content analysis with open coding of interview transcripts to determine the salience of the 4-step SDM process and identify themes that confirmed, refuted, or modified this process. RESULTS: We videotaped 30 encounters and conducted 53 interviews. We found that clinicians' and parents' experiences of decision-making confirmed each SDM step. However, there was variation in the interpretation of each step and a need for flexibility in implementing the process depending on specific decisional contexts. CONCLUSIONS: The 4-step SDM process for pediatrics appears to be salient and may benefit from further guidance about the interpretation of each step and contextual factors that support a modified approach.

Exploring the Biocompatibility of Near-IR CuInSexS2-x/ZnS Quantum Dots for Deep-Tissue Bioimaging.

Near-infrared (NIR) emitting quantum dots (QDs) with emission in the biological transparency windows (NIR-I: 650-950 nm and NIR-II: 1000-1350 nm) are promising candidates for deep-tissue bioimaging. However, they typically contain toxic heavy metals such as cadmium, mercury, arsenic, or lead. We report on the biocompatibility of high brightness CuInSexS2-x/ZnS (CISeS/ZnS) QDs with a tunable emission covering the visible to NIR (550-1300 nm peak emission) and quantify the transmission of their photoluminescence through multiple biological components to evaluate their use as imaging agents. In general, CISeS/ZnS QDs were less cytotoxic to mouse fibroblast cells when compared with commercial CdSe/ZnS and InP/ZnS QDs. Surprisingly, InP/ZnS QDs significantly upregulated expression of apoptotic genes in mouse fibroblast cells, while cells exposed to CISeS/ZnS QDs did not. These findings provide insight into biocompatibility and cytotoxicity of CISeS/ZnS QDs that could be used for bioimaging.