Trial of Erythropoietin for Hypoxic-Ischemic Encephalopathy in Newborns.

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy is an important cause of death as well as long-term disability in survivors. Erythropoietin has been hypothesized to have neuroprotective effects in infants with hypoxic-ischemic encephalopathy, but its effects on neurodevelopmental outcomes when given in conjunction with therapeutic hypothermia are unknown. METHODS: In a multicenter, double-blind, randomized, placebo-controlled trial, we assigned 501 infants born at 36 weeks or more of gestation with moderate or severe hypoxic-ischemic encephalopathy to receive erythropoietin or placebo, in conjunction with standard therapeutic hypothermia. Erythropoietin (1000 U per kilogram of body weight) or saline placebo was administered intravenously within 26 hours after birth, as well as at 2, 3, 4, and 7 days of age. The primary outcome was death or neurodevelopmental impairment at 22 to 36 months of age. Neurodevelopmental impairment was defined as cerebral palsy, a Gross Motor Function Classification System level of at least 1 (on a scale of 0 [normal] to 5 [most impaired]), or a cognitive score of less than 90 (which corresponds to 0.67 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition. RESULTS: Of 500 infants in the modified intention-to-treat analysis, 257 received erythropoietin and 243 received placebo. The incidence of death or neurodevelopmental impairment was 52.5% in the erythropoietin group and 49.5% in the placebo group (relative risk, 1.03; 95% confidence interval [CI], 0.86 to 1.24; P = 0.74). The mean number of serious adverse events per child was higher in the erythropoietin group than in the placebo group (0.86 vs. 0.67; relative risk, 1.26; 95% CI, 1.01 to 1.57). CONCLUSIONS: The administration of erythropoietin to newborns undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy did not result in a lower risk of death or neurodevelopmental impairment than placebo and was associated with a higher rate of serious adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT02811263.).

Resource and Service Use after Discharge Among Infants 22-25 Weeks Estimated Gestational Age at the First High-Risk Infant Follow-Up Visit in California.

OBJECTIVE: To examine resource and service use after discharge among infants born extraordinarily preterm in California who attended high-risk infant follow-up (HRIF) clinic by 12 months corrected age. STUDY DESIGN: We included infants born 2010-2017 between 22 + 0/7 and 25 + 6/7 weeks' gestational age in the California Perinatal Quality Care Collaborative and California Perinatal Quality Care Collaborative-California Children's Services HRIF databases. We evaluated rates of hospitalization, surgeries, medications, equipment, medical service and special service use, and referrals. We examined factors associated with receiving ≥ 2 medical services, and ≥ 1 special service. RESULTS: A total of 3941 of 5284 infants received a HRIF visit by 12 months corrected age. Infants born at earlier gestational ages used more medications, equipment, medical services, and special services and had higher rates of referral to medical and special services at the first HRIF visit. Infants with major morbidity, surgery, caregiver concerns, and mothers with more years of education had higher odds of receiving ≥ 2 medical services. Infants with Black maternal race, younger maternal age, female sex, and discharge from lower level neonatal intensive care units (NICUs) had lower odds of receiving ≥ 2 medical services. Infants with more educated mothers, multiple gestation, major morbidity, surgery, caregiver concerns, and discharge from lower level NICUs had increased odds of receiving a special service. CONCLUSIONS: Infants born extraordinarily preterm have substantial resource use after discharge. High resource utilization was associated with maternal/sociodemographic factors and expected clinical factors. Early functional and service use information is valuable to parents and underscores the need for NICU providers to appropriately prepare and refer families.

Risk of Adverse Perinatal Outcomes Among African-born Black Women in California, 2011-2020.

BACKGROUND: African-born women have a lower risk of preterm birth and small for gestational age (SGA) birth compared with United States-born Black women, however variation by country of origin is overlooked. Additionally, the extent that nativity disparities in adverse perinatal outcomes to Black women are explained by individual-level factors remains unclear. METHODS: We conducted a population-based study of nonanomalous singleton live births to United States- and African-born Black women in California from 2011 to 2020 (n = 194,320). We used age-adjusted Poisson regression models to estimate the risk of preterm birth and SGA and reported risk ratios (RR) and 95% confidence intervals (CI). Decomposition using Monte Carlo integration of the g-formula computed the percentage of disparities in adverse outcomes between United States- and African-born women explained by individual-level factors. RESULTS: Eritrean women (RR = 0.4; 95% CI = 0.3, 0.5) had the largest differences in risk of preterm birth and Cameroonian women (RR = 0.5; 95% CI = 0.3, 0.6) in SGA birth, compared with United States-born Black women. Ghanaian women had smaller differences in risk of preterm birth (RR = 0.8; 95% CI = 0.7, 1.0) and SGA (RR = 0.9; 95% CI = 0.8, 1.1) compared with United States-born women. Overall, we estimate that absolute differences in socio-demographic and clinical factors contributed to 32% of nativity-based disparities in the risk of preterm birth and 26% of disparities in SGA. CONCLUSIONS: We observed heterogeneity in risk of adverse perinatal outcomes for African- compared with United States-born Black women, suggesting that nativity disparities in adverse perinatal outcomes were not fully explained by differences in individual-level factors.

Homelessness and Type 2 Diabetes: A Qualitative Study of Facilitators and Barriers to Self-Management and Medication Adherence.

PURPOSE: In this study, we explore the barriers and facilitators to diabetes medication adherence and self-management for people with type 2 diabetes who have experienced homelessness. METHODS: We conducted five focus groups and two interviews with 26 participants. Our multi-disciplinary analysis team utilized principles of grounded theory and conducted thematic analysis with an inductive, iterative process to identify central themes. RESULTS: The majority of participants identified as Black/African American and over half stayed in shelters or had no steady place to stay at enrollment. Three key themes emerged regarding medication adherence and diabetes self-management for people who have experienced homelessness: personal autonomy and security, predictability and stability, and supportive, knowledgeable relationships (both social and medical). We define personal autonomy and security as individual agency and choice when making decisions related to one's health and well-being as well as protection from risk or harm to one's physical or psychological well-being, belongings, or means of income. Predictability and stability take place through the development of a system of connections and routines built over time where individuals can reliably adopt and maintain diabetes self-management activities. Supportive, knowledgeable relationships include medical and social relationships that offer encouragement, information, and hands-on care promoting diabetes self-management and connection to clinical care and resources. Participants also highlighted a "domino effect" where a cascade of events negatively and consequently impacted their health and well-being. We describe the interactions of these themes, the intersection of structural vulnerability and individual social risks, and resulting impacts on medication adherence and diabetes self-management. CONCLUSIONS: Our findings highlight the structural vulnerabilities impacting people experiencing homelessness and identify inflection points of opportunity at structural and individual levels to strengthen diabetes medication adherence and self-management. This understanding can inform policy change and future tailored diabetes interventions.

Water restriction increases oxidation of endogenous amino acids in house sparrows (Passer domesticus).

Animals can cope with dehydration in a myriad of ways, both behaviorally and physiologically. The oxidation of protein produces more metabolic water per kilojoule than that of fat or carbohydrate, and it is well established that birds increase protein catabolism in response to high rates of water loss. However, the fate of amino acids mobilized in response to water restriction has not been explicitly determined. While protein catabolism releases bound water, we hypothesized that water-restricted birds would also oxidize the resulting amino acids, producing additional water as a product of oxidative phosphorylation. To test this, we fed captive house sparrows (Passer domesticus) 13C-labeled leucine for 9 weeks to label endogenous proteins. We conducted weekly trials during which we measured the physiological response to water restriction as changes in lean mass, fat mass, metabolism and the enrichment of 13C in exhaled CO2 (δ13Cbreath). If water-restricted birds catabolized proteins and oxidized the resulting amino acids, we expected to simultaneously observe greater lean mass loss and elevated δ13Cbreath relative to control birds. We found that water-restricted birds catabolized more lean tissue and also had enriched δ13Cbreath in response to water restriction, supporting our hypothesis. δ13Cbreath, however, varied with metabolic rate and the length of the water restriction period, suggesting that birds may spare protein when water balance can be achieved using other physiological strategies.

Betamethasone treatment-to-delivery interval, retreatment, and severe intraventricular hemorrhage in infants <28 weeks' gestation.

BACKGROUND: Antenatal corticosteroids decrease the incidence of severe intraventricular hemorrhage (grades 3, 4) in preterm infants. It is unclear whether their beneficial effects on intraventricular hemorrhage wane with time (as occurs in neonatal respiratory distress) and if repeat courses can restore this effect. Previous randomized controlled trials of betamethasone retreatment found no benefit on severe intraventricular hemorrhage rates. However, the trials may have included an insufficient number of infants at risk for intraventricular hemorrhage to be able to adequately address this question. Severe intraventricular hemorrhages occur almost exclusively in infants born at <28 weeks' gestation, whereas only 7% (0%-16%) of the retreatment trials' populations were <28 weeks' gestation. OBJECTIVE: This study aimed to determine if the risk for severe intraventricular hemorrhage in infants delivered at <28 weeks' gestation increases when the betamethasone treatment-to-delivery interval increases beyond 9 days and to determine if betamethasone retreatment before delivery decreases the rate of hemorrhage. STUDY DESIGN: This was an observational study that examined the incidence of intraventricular hemorrhage before (epoch 1) and after (epoch 2) a practice change that encouraged obstetricians to retreat pregnant women still at high risk for delivery before 28 weeks' gestation when >9 days elapsed from the first dose of betamethasone. Multivariable analyses with logistic regression using generalized estimating equation techniques were conducted to examine the rates of intraventricular hemorrhage among 410 infants <28 weeks' gestation who were either delivered between 1 to 9 days (n=290) after the first 2-dose betamethasone course or ≥10 days (and eligible for retreatment) after the first course (n=120). RESULTS: After adjusting for potential confounding variables, infants who were delivered ≥10 days after a single betamethasone course had an increased risk for either severe intraventricular hemorrhage alone or the combined outcome severe intraventricular hemorrhage or death before 4 days (odds ratio, 2.8; 95% confidence interval, 1.2-6.6) when compared with infants who were delivered between 1 and 9 days after betamethasone. Among the 120 infants who were delivered ≥10 days after the first dose of betamethasone, 64 (53%) received a second or retreatment course of antenatal betamethasone. The severe intraventricular hemorrhage rate in infants whose mothers received a second or retreatment course of betamethasone was similar to the rate among infants who delivered within 1 to 9 days and significantly lower than among those who delivered ≥10 days without retreatment (odds ratio, 0.10; 95% confidence interval, 0.02-0.65). Following the change in guidelines, the rate of retreatment in infants who were delivered ≥10 days after the first betamethasone course (and before 28 weeks) increased from epoch 1 to epoch 2 (25% to 87%; P<.001) and the rate of severe intraventricular hemorrhage decreased from 22% to 0% (P<.001). In contrast, the rate of severe intraventricular hemorrhage among infants who were delivered 1 to 9 days after the initial betamethasone dose (who were not eligible for retreatment) did not change between epochs 1 and 2 (12% and 11%, respectively). CONCLUSION: Although betamethasone's benefits on severe intraventricular hemorrhage appear to wane after the first dose, retreatment with a second course seems to restore its beneficial effects. Encouraging earlier retreatment of women at high risk for delivery before 28 weeks was associated with a lower rate of severe intraventricular hemorrhages among infants delivered at <28 weeks' gestation.

Families as partners in neonatal neuro-critical care programs.

Parents of neonates with neurologic conditions face a specific breadth of emotional, logistical, and social challenges, including difficulties coping with prognostic uncertainty, the need to make complex medical decisions, and navigating new hopes and fears. These challenges place parents in a vulnerable position and at risk of developing mental health issues, which can interfere with bonding and caring for their neonate, as well as compromise their neonate's long-term neurodevelopment. To optimize neurologic and developmental outcomes, emerging neonatal neuro-critical care (NNCC) programs must concurrently attend to the unique needs of the developing newborn brain and of his/her parents. This can only be accomplished by embracing a family-centered care environment-one which prioritizes effective parent-clinician communication, longitudinal parent support, and parents as equitable partners in clinical care. NNCC programs offer a multifaceted approach to critical care for neonates at-risk for neurodevelopmental impairments, integrating expertise in neonatology and neurology. This review highlights evidence-based strategies to guide NNCC programs in developing a family-partnered approach to care, including primary staffing models; staff communication, implicit bias, and cultural competency trainings; comprehensive and tailored caregiver training; single-family rooms; flexible visitation policies; colocalized neonatal and maternal care; uniform mental health screenings; follow-up care referrals; and connections to peer support. IMPACT: Parents of neonates with neurologic conditions are at high-risk for experiencing mental health issues, which can adversely impact the parent-neonate relationship and long-term neurodevelopmental outcomes of their neonates. While guidelines to promote families as partners in the neonatal intensive care unit (NICU) have been developed, no protocols integrate the unique needs of parents in neonatal neurologic populations. A holistic approach that makes families true partners in the care of their neonate with a neurologic condition in the NICU has the potential to improve mental and physical well-being for both parents and neonates.

Parent and staff perceptions of racism in a single-center neonatal intensive care unit.

IMPACT: In alignment with previous literature, NICU parents reported experiencing racism and NICU staff reported witnessing racism in the NICU. Our study also uniquely describes personal experiences with racism by staff in the NICU. NICU staff reported witnessing and experiencing racism more often than parents reported. Black staff reported witnessing and experiencing more racism than white staff. Differences in reporting is likely influenced by variations in lived experience, social identities, psychological safety, and levels of awareness. Future studies are necessary to prevent and accurately measure racism in the NICU.

Neuroprotective therapies in the NICU in preterm infants: present and future (Neonatal Neurocritical Care Series).

The survival of preterm infants has steadily improved thanks to advances in perinatal and neonatal intensive clinical care. The focus is now on finding ways to improve morbidities, especially neurological outcomes. Although antenatal steroids and magnesium for preterm infants have become routine therapies, studies have mainly demonstrated short-term benefits for antenatal steroid therapy but limited evidence for impact on long-term neurodevelopmental outcomes. Further advances in neuroprotective and neurorestorative therapies, improved neuromonitoring modalities to optimize recruitment in trials, and improved biomarkers to assess the response to treatment are essential. Among the most promising agents, multipotential stem cells, immunomodulation, and anti-inflammatory therapies can improve neural outcomes in preclinical studies and are the subject of considerable ongoing research. In the meantime, bundles of care protecting and nurturing the brain in the neonatal intensive care unit and beyond should be widely implemented in an effort to limit injury and promote neuroplasticity. IMPACT: With improved survival of preterm infants due to improved antenatal and neonatal care, our focus must now be to improve long-term neurological and neurodevelopmental outcomes. This review details the multifactorial pathogenesis of preterm brain injury and neuroprotective strategies in use at present, including antenatal care, seizure management and non-pharmacological NICU care. We discuss treatment strategies that are being evaluated as potential interventions to improve the neurodevelopmental outcomes of infants born prematurely.

Evaluating the Implementation and Clinical Effectiveness of an Innovative Digital First Care Model for Behavioral Health Using the RE-AIM Framework: Quantitative Evaluation.

BACKGROUND: In the United States, innovation is needed to address the increasing need for mental health care services and widen the patient-to-provider ratio. Despite the benefits of digital mental health interventions (DMHIs), they have not been effective in addressing patients' behavioral health challenges as stand-alone treatments. OBJECTIVE: This study evaluates the implementation and effectiveness of precision behavioral health (PBH), a digital-first behavioral health care model embedded within routine primary care that refers patients to an ecosystem of evidence-based DMHIs with strategically placed human support. METHODS: Patient demographic information, triage visit outcomes, multidimensional patient-reported outcome measure, enrollment, and engagement with the DMHIs were analyzed using data from the electronic health record and vendor-reported data files. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework was used to evaluate the implementation and clinical effectiveness outcomes of PBH. RESULTS: PBH had a 47.58% reach rate, defined as patients accepting the PBH referral from their behavioral health integrated clinician. PBH patients had high DMHI registration rates (79.62%), high activation rates (76.54%), and high retention rates at 15 days (57.69%) and 30 days (44.58%) compared to literature benchmarks. In total, 74.01% (n=168) of patients showed clinical improvement, 22.47% (n=51) showed no clinical change, and 3.52% (n=8) showed clinical deterioration in symptoms. PBH had high adoption rates, with behavioral health integrated clinicians referring on average 4.35 (SD 0.46) patients to PBH per month and 90%-100% of clinicians (n=12) consistently referring at least 1 patient to PBH each month. A third (32%, n=1114) of patients were offered PBH as a treatment option during their triage visit. CONCLUSIONS: PBH as a care model with evidence-based DMHIs, human support for patients, and integration within routine settings offers a credible service to support patients with mild to moderate mental health challenges. This type of model has the potential to address real-life access to care problems faced by health care settings.

Almond Can Be Infected by Plum Pox Virus-D Isolate Penn4 and Is a Transmission-Competent Host.

Although it is currently eradicated from the United States, Plum pox virus (PPV) poses an ongoing threat to U.S. stone fruit production. Although almond (Prunus dulcis) is known to be largely resistant to PPV, there is conflicting evidence about its potential to serve as an asymptomatic reservoir host for the virus and thus serve as a potential route of entry. Here, we demonstrate that both Tuono and Texas Mission cultivars can be infected by the U.S. isolate PPV Dideron (D) Penn4 and that Tuono is a transmission-competent host, capable of serving as a source of inoculum for aphid transmission of the virus. These findings have important implications for efforts to keep PPV out of the United States and highlight the need for additional research to test the susceptibility of almond to other PPV-D isolates.

Structural Racism Operationalized via Adverse Social Events in a Single-Center Neonatal Intensive Care Unit.

OBJECTIVE: To evaluate structural racism in the neonatal intensive care unit (NICU) by determining if differences in adverse social events occur by racialized groups. STUDY DESIGN: Retrospective cohort study of 3290 infants hospitalized in a single center NICU between 2017 and 2019 in the Racial and Ethnic Justice in Outcomes in Neonatal Intensive Care (REJOICE) study. Demographics and adverse social events including infant urine toxicology screening, child protective services (CPS) referrals, behavioral contracts, and security emergency response calls were collected from electronic medical records. Logistic regression models were fit to test the association of race/ethnicity and adverse social events, adjusting for length of stay. Racial/ethnic groups were compared with a White referent group. RESULTS: There were 205 families (6.2%) that experienced an adverse social event. Black families were more likely to have experienced a CPS referral and a urine toxicology screen (OR, 3.6; 95% CI, 2.2-6.1 and OR, 2.2; 95% CI, 1.4-3.5). American Indian and Alaskan Native families were also more likely to experience CPS referrals and urine toxicology screens (OR, 15.8; 95% CI, 6.9-36.0 an OR, 7.6; 95% CI, 3.4-17.2). Black families were more likely to experience behavioral contracts and security emergency response calls. Latinx families had a similar risk of adverse events, and Asian families were less likely to experience adverse events. CONCLUSIONS: We found racial inequities in adverse social events in a single-center NICU. Investigation of generalizability is necessary to develop widespread strategies to address institutional and societal structural racism and to prevent adverse social events.

Structural racism is associated with adverse postnatal outcomes among Black preterm infants.

BACKGROUND: Structural racism contributes to racial disparities in adverse perinatal outcomes. We sought to determine if structural racism is associated with adverse outcomes among Black preterm infants postnatally. METHODS: Observational cohort study of 13,321 Black birthing people who delivered preterm (gestational age 22-36 weeks) in California in 2011-2017 using a statewide birth cohort database and the American Community Survey. Racial and income segregation was quantified by the Index of Concentration at the Extremes (ICE) scores. Multivariable generalized estimating equations regression models were fit to test the association between ICE scores and adverse postnatal outcomes: frequent acute care visits, readmissions, and pre- and post-discharge death, adjusting for infant and birthing person characteristics and social factors. RESULTS: Black birthing people who delivered preterm in the least privileged ICE tertiles were more likely to have infants who experienced frequent acute care visits (crude risk ratio [cRR] 1.3 95% CI 1.2-1.4), readmissions (cRR 1.1 95% CI 1.0-1.2), and post-discharge death (cRR 1.9 95% CI 1.2-3.1) in their first year compared to those in the privileged tertile. Results did not differ significantly after adjusting for infant or birthing person characteristics. CONCLUSION: Structural racism contributes to adverse outcomes for Black preterm infants after hospital discharge. IMPACT STATEMENT: Structural racism, measured by racial and income segregation, was associated with adverse postnatal outcomes among Black preterm infants including frequent acute care visits, rehospitalizations, and death after hospital discharge. This study extends our understanding of the impact of structural racism on the health of Black preterm infants beyond the perinatal period and provides reinforcement to the concept of structural racism contributing to racial disparities in poor postnatal outcomes for preterm infants. Identifying structural racism as a primary cause of racial disparities in the postnatal period is necessary to prioritize and implement appropriate structural interventions to improve outcomes.

Neuroprotective therapies in the NICU in term infants: present and future.

Outcomes of neonatal encephalopathy (NE) have improved since the widespread implementation of therapeutic hypothermia (TH) in high-resource settings. While TH for NE in term and near-term infants has proven beneficial, 30-50% of infants with moderate-to-severe NE treated with TH still suffer death or significant impairments. There is therefore a critical need to find additional pharmacological and non-pharmacological interventions that improve the outcomes for these children. There are many potential candidates; however, it is unclear whether these interventions have additional benefits when used with TH. Although primary and delayed (secondary) brain injury starting in the latent phase after HI are major contributors to neurodisability, the very late evolving effects of tertiary brain injury likely require different interventions targeting neurorestoration. Clinical trials of seizure management and neuroprotection bundles are needed, in addition to current trials combining erythropoietin, stem cells, and melatonin with TH. IMPACT: The widespread use of therapeutic hypothermia (TH) in the treatment of neonatal encephalopathy (NE) has reduced the associated morbidity and mortality. However, 30-50% of infants with moderate-to-severe NE treated with TH still suffer death or significant impairments. This review details the pathophysiology of NE along with the evidence for the use of TH and other beneficial neuroprotective strategies used in term infants. We also discuss treatment strategies undergoing evaluation at present as potential adjuvant treatments to TH in NE.

Estimating the effect of timing of earned income tax credit refunds on perinatal outcomes: a quasi-experimental study of California births.

BACKGROUND: The largest poverty alleviation program in the US is the earned income tax credit (EITC), providing $60 billion to over 25 million families annually. While research has shown positive impacts of EITC receipt in pregnancy, there is little evidence on whether the timing of receipt may lead to differences in pregnancy outcomes. We used a quasi-experimental difference-in-differences design, taking advantage of EITC tax disbursement each spring to examine whether trimester of receipt was associated with perinatal outcomes. METHODS: We conducted a difference-in-differences analysis of California linked birth certificate and hospital discharge records. The sample was drawn from the linked CA birth certificate and discharge records from 2007-2012 (N = 2,740,707). To predict eligibility, we created a probabilistic algorithm in the Panel Study of Income Dynamics and applied it to the CA data. Primary outcome measures included preterm birth, small-for-gestational age (SGA), gestational diabetes, and gestational hypertension/preeclampsia. RESULTS: Eligibility for EITC receipt during the third trimester was associated with a lower risk of preterm birth compared with preconception. Eligibility for receipt in the preconception period resulted in improved gestational hypertension and SGA. CONCLUSION: This analysis offers a novel method to impute EITC eligibility using a probabilistic algorithm in a data set with richer sociodemographic information relative to the clinical and administrative data sets from which outcomes are drawn. These results could be used to determine the optimal intervention time point for future income supplementation policies. Future work should examine frequent income supplementation such as the minimum wage or basic income programs.

Isavuconazonium or posaconazole for antifungal prophylaxis in patients with acute myeloid leukemia.

BACKGROUND: Invasive fungal infection (IFI) prophylaxis is recommended in patients with acute myeloid leukemia (AML) during induction chemotherapy. Posaconazole (POSA) is the recommended agent of choice; however, this medication can be associated with QTc prolongation, hepatotoxicity, and drug-drug interactions. Furthermore, there is conflicting evidence for the role of isavuconazole (ISAV) in this setting as an alternative to POSA. OBJECTIVE: The primary objective of this study was to evaluate the use of ISAV prophylaxis for primary IFI prevention in patients with AML undergoing induction. Additionally, the study investigated the use of ISAV trough concentration monitoring and compared these results to the efficacy of POSA therapeutic drug monitoring (TDM). Other secondary objectives included assessing the rates of toxicities associated with either prophylactic agent. This study analyzed the impact these toxicities had on patient outcomes by examining the need to hold or discontinue therapy. The final endpoint considered the efficacy associated with multiple dosing strategies employed at the study institution. Specifically, this included the use of loading doses or foregoing these when initiating prophylaxis. METHODS: This was a retrospective, single-center, cohort study. Patients included in this study were adults with AML admitted to Duke University Hospital between June 30, 2016 and June 30, 2021, who received induction chemotherapy and primary IFI prophylaxis for at least 7 days. Exclusion criteria included patients who received concomitant antifungal agents and patients who received antifungal agents as secondary prophylaxis. RESULTS: 241 patients met inclusion criteria with 12 (4.98%) participants in the ISAV group and 229 (95.02%) participants in the POSA group. The IFI incidence in the POSA group was 14.5%, while the ISAV group did not have any occurrences of IFI. No significant difference was found in the rate of IFI occurrence between the two treatment groups (p = 0.3805). Furthermore, it was demonstrated that the use of a loading dose when initiating prophylaxis could impact rates of IFI for this patient population. CONCLUSION: Due to no difference in incidence, patient specific factors such as concomitant medications and baseline QTc should influence the choice between prophylactic agent.

Intrinsic and extrinsic factors influencing Populus water use: A literature review.

Poplars (Populus L. spp.) are versatile, productive trees that are used in environmental systems worldwide to provide a variety of benefits. Though poplars are recognized for their elevated water use, summaries of existing data on poplar water use, its influencing factors, and the methodologies used to measure it, are lacking. We sought to 1) summarize the sap flow methodologies used to quantify poplar water use, 2) review sap flow-derived water use data reported in the literature for Populus hybrids and non-hybrids, and 3) assess the effects of different intrinsic factors (plant variables) and extrinsic factors (environmental variables) on poplar water use. We identified 133 articles containing information on the methodologies used to measure poplar sap flow. Of these, the thermal dissipation method was used in a majority (55%) of the studies. Poplar water use data were reported in 51 of the articles, with studies taking place in 13 countries, and representing the time period of 1992-2018. Hybrids were studied in 18 articles and included 17 genotypes, while non-hybrids were studied in 33 articles, and included eight species. Hybrid poplar water use ranged from 0.7 to 11.3 mm day-1, with an overall mean of 2.7 ± 0.3 mm day-1. Non-hybrid water use ranged from 0.2 to 19.5 mm day-1 with an average of 2.8 ± 0.4 mm day-1. Hybrid poplar water use differed significantly among hybrid types, tree age classes, and water availability classes, and non-hybrid water use was significantly different among species, experimental context, and water availability classes. While we focused on poplar water use measured by sap flow methodologies, this review builds the foundation for a comprehensive summary of available poplar water use information that has been reported in the literature. Our results on the factors influencing poplar water use can be used to aid in the decision-making process when designing poplar-based environmental systems such as remediation, bioenergy, and agroforestry systems.

Leveraging Implementation Science to Integrate Digital Mental Health Interventions as part of Routine Care in a Practice Research Network.

The supply / demand issue in behavioral health care is a well-established fact, and the mental health toll of the COVID-19 pandemic continues to add challenges to an already taxed system. Existing healthcare models are not set up to adequately address the increasing mental health related needs. As such, innovative models are needed to provide patients with access to appropriate, evidence-based behavioral health care within routine clinical care. This paper introduces Precision Behavioral Health (PBH) as an example of such a model. PBH is an innovative, digital first care delivery model that provides an ecosystem of evidence-based digital mental health interventions to patients as a frontline behavioral health treatment within routine care in a large multispecialty group medical center in the United States. This paper describes the implementation of PBH within a practice research network set-up as part of an integrated behavioral health department. We will present how our team leveraged the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance; "What is RE-AIM?," n.d.) implementation science framework, which emphasizes the design, dissemination, and implementation processes at the individual, staff, and organizational levels, to prioritize key implementation constructs to enhance the successful integration of PBH within routine care. We describe how each of these constructs were operationalized to aid data gathering for rapid evaluation and lessons learned. We discuss the benefits of these types of initiatives across multiple stakeholders including patients, providers, organizations, payers, and digital intervention vendors.

Disparities and Early Engagement Associated with the 18- to 36-Month High-Risk Infant Follow-Up Visit among Very Low Birthweight Infants in California.

OBJECTIVE: To determine follow-up rates for the high-risk infant follow-up (HRIF) visit at 18-36 months among infants with very low birthweights and identify factors associated with completion. STUDY DESIGN: We completed a retrospective cohort study using linked California Perinatal Quality of Care Collaborative neonatal intensive care unit, California Perinatal Quality of Care Collaborative California Children's Services HRIF, and Vital Statistics Birth Cohort databases. We identified maternal, sociodemographic, neonatal, clinical, and HRIF program level factors associated with the 18- to 36-month follow-up using multivariable Poisson regression. RESULTS: From 2010 to 2015, among 19 284 infants with very low birthweight expected to attend at least 1 visit at 18-36 months, 10 249 (53%) attended. On multivariable analysis, factors independently associated with attendance at an 18- to 36-month visit included estimated gestational age (relative risk [RR], 1.21; 95% CI, 1.15-1.26; <26 weeks vs ≥31 weeks), maternal education (RR, 1.09; 95% CI, 1.06-1.12; college degree or more vs high school), distance from clinic (RR, 0.92; 95% CI, 0.89-0.97; fourth quartile vs first quartile), and Black non-Hispanic race vs White race (RR, 0.88; 95% CI, 0.84-0.92). However, completion of an initial HRIF visit within the first 12 months was the factor most strongly associated with completion of an 18- to 36-month visit (RR, 6.47; 95% CI, 5.91-7.08). CONCLUSIONS: In a California very low birthweight cohort, maternal education, race, and distance from the clinic were associated with sustained HRIF participation, but attendance at a visit by 12 months was the most significantly associated factor. These findings highlight the importance of early engagement with all families to ensure equitable follow-through for children born preterm.

Long-term cognitive outcomes in term newborns with watershed injury caused by neonatal encephalopathy.

BACKGROUND: We previously reported that increasing severity of watershed (WS) injury in neonatal magnetic resonance imaging (MRI) is associated with worse language outcomes in early childhood. In the present study, we investigated the relationship between neonatal injury patterns and cognitive profile in adolescents with neonatal encephalopathy. METHODS: Term neonates with encephalopathy were prospectively enrolled and imaged using brain MRI from 1999 to 2008. Neonatal brain injury was scored according to the degree of injury in WS and basal ganglia/thalamus (BG/T) areas. The children underwent a neurocognitive assessment and follow-up brain MRI at the age of 10-16 years. The relationship between neonatal brain injury patterns and adolescent cognitive outcomes was assessed. RESULTS: In a cohort of 16 children, neonatal MRI showed WS injury in 7, BG/T injury in 2, and normal imaging in 7. Children with WS injury had lower estimated overall cognitive ability than those with normal imaging. Increasing WS injury score was associated with decreasing estimated overall cognitive ability, Perceptual Reasoning Index, and digit span score. CONCLUSIONS: Children with the WS injury are at an increased risk of having problems in long-term intellectual ability. These cognitive outcomes may underlie early language difficulties seen in children with neonatal WS injury. IMPACT: Adolescents with a history of neonatal encephalopathy and watershed pattern of injury on neonatal brain magnetic resonance imaging (MRI) had lower overall cognitive ability, perceptual reasoning skills, and auditory working memory than those with normal neonatal imaging. Children with post-neonatal epilepsy and cerebral palsy had the worst cognitive outcomes. Watershed pattern of injury confers high long-term differences in intellectual ability.