Racial and Ethnic Disparity in Approach for Pediatric Intensive Care Unit Research Participation.

Importance: While disparities in consent rates for research have been reported in multiple adult and pediatric settings, limited data informing enrollment in pediatric intensive care unit (PICU) research are available. Acute care settings such as the PICU present unique challenges for study enrollment, given the highly stressful and emotional environment for caregivers and the time-sensitive nature of the studies. Objective: To determine whether race and ethnicity, language, religion, and Social Deprivation Index (SDI) were associated with disparate approach and consent rates in PICU research. Design, Setting, and Participants: This retrospective cohort study was performed at the Children's Hospital of Philadelphia PICU between July 1, 2011, and December 31, 2021. Participants included patients eligible for studies requiring prospective consent. Data were analyzed from February 2 to July 26, 2022. Exposure: Exposures included race and ethnicity (Black, Hispanic, White, and other), language (Arabic, English, Spanish, and other), religion (Christian, Jewish, Muslim, none, and other), and SDI (composite of multiple socioeconomic indicators). Main Outcomes and Measures: Multivariable regressions separately tested associations between the 4 exposures (race and ethnicity, language, religion, and SDI) and 3 outcomes (rates of approach among eligible patients, consent among eligible patients, and consent among those approached). The degree to which reduced rates of approach mediated the association between lower consent in Black children was also assessed. Results: Of 3154 children included in the study (median age, 6 [IQR, 1.9-12.5] years; 1691 [53.6%] male), rates of approach and consent were lower for Black and Hispanic families and those of other races, speakers of Arabic and other languages, Muslim families, and those with worse SDI. Among children approached for research, lower consent odds persisted for those of Black race (unadjusted odds ratio [OR], 0.73 [95% CI, 0.55-0.97]; adjusted OR, 0.68 [95% CI, 0.49-0.93]) relative to White race. Mediation analysis revealed that 51.0% (95% CI, 11.8%-90.2%) of the reduced odds of consent for Black individuals was mediated by lower probability of approach. Conclusions and Relevance: In this cohort study of consent rates for PICU research, multiple sociodemographic factors were associated with lower rates of consent, partly attributable to disparate rates of approach. These findings suggest opportunities for reducing disparities in PICU research participation.

Shifting Trends in Diagnosis of Asthma, Bronchiolitis, and Viral Pneumonia in Young Children.

Over the last decade, there have been widespread efforts to reduce non-evidence-based therapies for viral bronchiolitis. We question whether this change in practice has inadvertently impacted the diagnosis and management of other pediatric lower-respiratory-tract illnesses. We used the Pediatric Health Information System (PHIS) and logistic regression to describe trends in relative diagnosis frequency of bronchiolitis, viral pneumonia, and reactive airway disease (RAD)/asthma as well as systemic corticosteroid use among children of the age range 1 to 4 years over a 10-year period. Among 169,207 children, the relative frequency of asthma/RAD diagnoses declined over a 10-year period, while bronchiolitis and viral pneumonia diagnoses increased among children of the age range 1 to 3 years and 2 to 4 years, respectively. Frequency of systemic corticosteroid use declined. We question whether the observed shift in diagnosis from asthma/RAD to bronchiolitis or viral pneumonia is reflective of true disease pathophysiology or if it represents an unintended consequence of campaigns surrounding bronchiolitis.

Determinants of Blood Culture Use in Critically Ill Children: A Multicenter Qualitative Study.

Blood cultures are fundamental in diagnosing and treating sepsis in the pediatric intensive care unit (PICU), but practices vary widely. Overuse can lead to false positive results and unnecessary antibiotics. Specific factors underlying decisions about blood culture use and overuse are unknown. Therefore, we aimed to identify perceived determinants of blood culture use in the PICU. Methods: We conducted semistructured interviews of clinicians (M.D., D.O., R.N., N.P., P.A.) from 6 PICUs who had participated in a quality improvement collaborative about blood culture practices. We developed interview questions by combining elements of the Consolidated Framework for Implementation Research and behavioral economics. We conducted telephone interviews, open-coded the transcripts, and used modified content analysis to determine key themes and mapped themes to elements of Consolidated Framework for Implementation Research and behavioral economics. Results: We reached thematic saturation in 24 interviews. Seven core themes emerged across 3 Consolidated Framework for Implementation Research domains: individual characteristics [personal belief in the importance of blood cultures, the perception that blood cultures are a low-risk test]; inner setting [adherence to site-specific usual practices, site-specific overall approach to PICU care (collaborative versus hierarchical), influence of non-PICU clinicians on blood culture decisions]; and outer setting [patient-specific risk factors, sepsis guidelines]. In addition, outcome bias, default bias, and loss aversion emerged as salient behavioral economics concepts. Conclusions: Determinants of blood culture use include individual clinician characteristics, inner setting, and outer setting, as well as default bias, outcome bias, and loss aversion. These determinants will now inform the development of candidate strategies to optimize culture practices.

Why the Maternal Medication List Matters: Neonatal Toxicity From Combined Serotonergic Exposures.

Serotonergic medications are used for the prevention and treatment of depression during pregnancy. Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors (SNRIs) can cause poor neonatal adaptation, which has been attributed to withdrawal versus toxicity. Bupropion, a norepinephrine-dopamine reuptake inhibitor, is often used as an adjunctive agent to selective serotonin reuptake inhibitors or SNRIs for refractory depression. Quetiapine, an atypical antipsychotic, may also be used in more complex cases. When combined with serotonergic drugs, bupropion and quetiapine are associated with increased risk of serotonin syndrome in adults. We describe a neonate exposed to venlafaxine (an SNRI), bupropion, and quetiapine in utero who presented nearly immediately after birth with encephalopathy and abnormal movements. The severity and rapidity of symptoms may be attributable to potentiation of venlafaxine's serotonergic effects by bupropion and quetiapine. Neonatal providers should be aware of maternal medications and prepare for possible adverse effects, particularly from common psychotropic exposures.

In Their Own Words: Caregiver and Patient Perspectives on Stressors, Resources, and Recommendations in Craniofacial Microsomia Care.

This study describes stressors, resources, and recommendations related to craniofacial microsomia (CFM) care from the perspective of caregivers of children with CFM and adults with CFM to inform improved quality of healthcare delivery. A mixed method design was used with fixed-response and open-ended questions from an online survey in English. The survey included demographics, CFM phenotypic information, and items about CFM-related experiences across settings. Themes were identified by qualitative analysis of responses to open-ended questions. Respondents (n = 51) included caregivers (n = 42; 90% mothers) and adults with CFM (n = 9; 78% female), who had a mean age of 45 ±â€Š6 years. Most children were male (71%) with an average age of 7 ±â€Š4 years. Respondents were primarily white (80%), non-Hispanic (89%), from the United States (82%), had a college degree (80%), and had private health insurance (80%). Reflecting the high rate of microtia (84%) in the sample, themes centered on the impact of hearing difficulties across settings with related language concerns. Negative social experiences were frequently described and school needs outlined. Multiple medical stressors were identified and corresponding suggestions included: providers need to be better informed about CFM, treatment coordination among specialists, and preference for a family-centered approach with reassurance, empathy, and clear communication. Advice offered to others with CFM included positive coping strategies. Overall, caregivers' and patients' responses reflected the complexity of CFM treatment. Incorporating these perspectives into routine CFM care has the potential to reduce family distress while improving their healthcare.

Transcription Activation Domains of the Yeast Factors Met4 and Ino2: Tandem Activation Domains with Properties Similar to the Yeast Gcn4 Activator.

Eukaryotic transcription activation domains (ADs) are intrinsically disordered polypeptides that typically interact with coactivator complexes, leading to stimulation of transcription initiation, elongation, and chromatin modifications. Here we examined the properties of two strong and conserved yeast ADs: Met4 and Ino2. Both factors have tandem ADs that were identified by conserved sequence and functional studies. While the AD function of both factors depended on hydrophobic residues, Ino2 further required key conserved acidic and polar residues for optimal function. Binding studies showed that the ADs bound multiple Med15 activator-binding domains (ABDs) with similar orders of micromolar affinity and similar but distinct thermodynamic properties. Protein cross-linking data show that no unique complex was formed upon Met4-Med15 binding. Rather, we observed heterogeneous AD-ABD contacts with nearly every possible AD-ABD combination. Many of these properties are similar to those observed with yeast activator Gcn4, which forms a large heterogeneous, dynamic, and fuzzy complex with Med15. We suggest that this molecular behavior is common among eukaryotic activators.

Healthcare and psychosocial experiences of individuals with craniofacial microsomia: Patient and caregivers perspectives.

OBJECTIVE: Craniofacial microsomia (CFM) is primarily characterized by underdevelopment of the ear and mandible, with several additional possible congenital anomalies. Despite the potential burden of care and impact of CFM on multiple domains of functioning, few studies have investigated patient and caregiver perspectives. The objective of this study was to explore the diagnostic, treatment-related, and early psychosocial experiences of families with CFM with the aim of optimizing future healthcare delivery. METHODS: Forty-two caregivers and nine adults with CFM responded to an online mixed-methods survey. Descriptive statistics and qualitative methods were used for the analysis. RESULTS: Survey respondents reported high rates of subspecialty evaluations, surgeries, and participation in therapies. Some participants reported receiving inaccurate or incomplete information about CFM and experienced confusion about etiology. Communication about CFM among family members included mostly positive messages. Self-awareness of facial differences began at a mean age of three years and teasing at mean age six, with 43% of individuals four years or older reporting teasing. Teasing often involved name-calling and frequent reactions were ignoring and negative emotional responses. Participants ranked "understanding diagnosis and treatment" as a top priority for future research and had the most questions about etiology and treatment guidance. CONCLUSIONS: The survey results on the healthcare and psychosocial experiences from birth through adulthood of individuals with CFM reinforce the need for ongoing psychological assessment and intervention. Healthcare provision could be improved through establishing diagnostic criteria and standardized treatment guidelines, as well as continued investigation of CFM etiology.