Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design.

IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of four cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n = 10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n = 6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n = 6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n = 600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. CONCLUSIONS AND RELEVANCE: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design.

Importance: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. Observations: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's RE searching COV ID to E nhance R ecovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of five cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study ( n =10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n=6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n=6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n=600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. Conclusions and Relevance: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions. Clinical Trialsgov Identifier: Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT05172011.

Advocating For a Culture of Support for Lactating Medical Residents in Hawai'i.

Lactating medical residents face unique barriers due to intense clinical work schedules, limited support in the clinic and hospital workspaces, and competing pressures between career development and childcare. The objective of this project was to explore the perceived culture of breastfeeding support among medical trainees and design an action plan to improve support for lactating residents in Hawai'i. Resident and faculty representatives from the Hawai'i Residency Programs and the University of Hawai'i John A Burns School of Medicine participated in an 8 month national learning collaborative to review the existing resident lactation policy and resident perception of lactation support. In a pre-survey, the majority of residents (88%) agreed that 20-30 minutes every 2-3 hours should be allowed to express milk but only 18% felt comfortable asking for a change in schedule to accommodate time to pump. An action plan was created with the following objectives: (1) revamping the existing policy to address protected pumping times, lactation spaces, and responsibilities of administration, faculty, and residents; (2) improving lactation space through uniform provision of educational material on available facilities and efficiency tips for new parents, and (3) improving awareness of the unique challenges lactating residents face and empowering faculty and trainees to advocate for lactating residents through department and educational presentations. Medical residents in Hawai'i recognize the importance of breastfeeding but perceive a lack of support in the workplace. A comprehensive action plan to revamp the resident lactation policy and improve faculty and resident education may foster an increased culture of lactation support and healthy development of the physician workforce.

Hawai'i IDeA Center for Pediatric and Adolescent Clinical Trials.

As one of 17 clinical sites of the Environmental influences on Child Health Outcomes (ECHO) IDeA States Pediatric Clinical Trials Network (ISPCTN), the Hawai'i IDeA Center for Pediatric and Adolescent Clinical Trials (HIPACT) was established in 2016 to participate in community-valued and scientifically-valid multi-center pediatric clinical trials to improve health and well-being of diverse multi-ethnic populations of Hawai'i. Hawai'i is home to large populations of diverse rural and underserved populations, including indigenous Hawaiian communities and immigrant populations of Pacific Islanders and Asians. Many of these communities experience significant health disparities, made worse by their geographic isolation and many socio-economic factors. In addition to providing opportunities for children and their families to participate in clinical trials, HIPACT's goal is to provide opportunities for junior faculty of the John A. Burns School of Medicine (JABSOM), University of Hawai'i at Manoa, to acquire knowledge about and to develop skills in clinical trials. HIPACT's partners include the Hawai'i Pacific Health with Kapi'olani Medical Center for Women and Children, and Waianae Coast Comprehensive Health Center. HIPACT builds on the experiences gained through partnerships with the Mountain West IDeA Clinical and Translational Research-Infrastructure Network, and Research Centers in Minority Institutions Translational Research Network. Apart from participating in ECHO ISPCTN-sponsored studies, HIPACT junior faculty serve as committee members, Working Group leaders, Protocol Study Principal Investigators (PI) and site study PIs with ECHO ISPCTN. Through participation in ECHO ISPCTN, HIPACT has successfully increased the number of pediatric and maternal-fetal medicine faculty involved in the conduct of clinical trials.

Zika Virus: Relevance to the State of Hawai'i.

Zika virus (ZIKV) is spread among human populations primarily through the bite of Aedes mosquitoes. While most ZIKV infections are asymptomatic or cause self-limited symptoms, the major concerns are its association with Guillain-Barré Syndrome and fetal microcephaly together with other birth defects, known as congenital Zika syndrome (CZS). This article reviews the confirmed Zika cases in the continental United States (U.S.) and Hawai'i thus far, as well as literature of Zika research relevant to Hawai'i. The first case of CZS within the U.S. was reported in Hawai'i, highlighting the unique position of Hawai'i for emerging and re-emerging infectious diseases. Recent studies of the Zika outbreak in Florida demonstrate the key role of Ae. aegypti mosquito in transmission; continuous and proactive vector surveillance in Hawai'i is warranted. Additionally, an updated interim pregnancy guidance for pregnant women with possible ZIKV exposure was summarized. Due to recent decline of ZIKV transmission in the Americas, the risk of ZIKV importation to Hawai'i has been greatly reduced. However, given the presence of Aedes mosquitoes, climate condition, and status of Hawai'i as a travel destination and foreign import market, public health officials and healthcare providers should remain vigilant for a potential outbreak of mosquito-borne diseases in the future.

Outcomes of inborn and transported extremely premature very-low-birthweight infants in Hawai'i.

BACKGROUND: Delivery of premature infants outside tertiary care centers is not always preventable. The aim of this study was to compare rates of survival and common morbidities in extremely premature babies transported to a level III facility versus those born at the level III center. METHODS: Retrospective chart review was performed on all neonates born at ≤ 28 weeks of gestation with birthweight ≤ 1500 g who were admitted to the Newborn Intensive Care Unit at Kapi'olani Medical Center for Women and Children (KMCWC) between 1 January 2000 and 31 December 2005. Infants were divided into two groups, those born at KMCWC (Inborn) and those born at level I institutions and subsequently transported (Transport) to KMCWC. RESULTS: A total of 394 neonates met the study criteria; 349 were inborn while 45 were transported. Survival rates were identical for both groups. However, the Transport group survivors displayed a significantly longer mean length of stay and higher rate of severe retinopathy of prematurity than those in the Inborn group (P ≤ 0.01). CONCLUSION: Identical rates of survival in both groups suggest that community medical professionals are providing satisfactory care to stabilize critical neonates without reducing their chances of survival. However, increased length of stay and higher rate of retinopathy of prematurity in the Transport group suggest that differences in medical management during the first few hours of life may adversely affect outcomes.

Improving transitional care in Hawaii: opening communication between community-based and tertiary-care healthcare providers.

The goal of the Holomua Project is to improve transitional care between community health centers and tertiary care facilities through healthcare IT for, thereby improving care for vulnerable populations in Hawaii. Individual interviews, cluster interviews and roundtable discussions were conducted with healthcare providers in these facilities to examine transitional care processes, identify existing challenges and make recommendations that improve transitional care.

Severe bronchiolitis and respiratory syncytial virus among young children in Hawaii.

BACKGROUND: Lower respiratory tract infections are a leading cause of hospitalization and mortality among children worldwide. Our objective was to describe the incidence and epidemiology of severe bronchiolitis, respiratory syncytial virus (RSV), and pneumonia among children in Hawaii. METHODS: Retrospective analysis of the patient-linked hospital discharge data associated with bronchiolitis, RSV, and pneumonia among Hawaii residents younger than 5 years of age during 1997 through 2004 using the Hawaii State Inpatient Database. RESULTS: During 1997 through 2004, the average annual incidence rates for bronchiolitis, RSV, and pneumonia were 3.8, 2.7, and 6.8 per 1000 children younger than 5 years, respectively. The incidence of each condition was higher for infants younger than 1 year (15.1, 9.8, and 15.9 per 1000 infants, respectively) than the incidence for children 1-4 years of age, and higher for boys compared with girls. The incidence of each condition was highest among Native Hawaiian and other Pacific Islander children compared with children of other race groups living in Hawaii. Most hospitalizations occurred during the months of October through February. Estimated median hospital charges were $4806 (bronchiolitis), $5465 (RSV) and $5240 (pneumonia), with overall average annual charges of $11.5 million. CONCLUSION: The incidence and hospitalization rates for bronchiolitis, RSV, and pneumonia among children younger than 5 years of age in Hawaii were low; the corresponding hospitalization rates were lower than those for the general U.S. population. However, the hospitalization rates for each condition among Hawaiian and other Pacific Islander children were much higher than those for other race groups or for the U.S. population.

The research subject advocate at the University of Hawai'i Clinical Research Center: an added resource for protection of human subjects.

In early 2001 the National Institutes of Health (NIH) created the Research Subject Advocate (RSA) position as an additional resource for human subjects protection at NIH-funded Clinical Research Centers (CRCs) to enhance the protection of human subjects participating in clinical research studies. The purpose of this article is to describe the RSA position in the context of clinical research, with a particular emphasis upon the role of the RSA in one of the five CRCs funded by the NIH Research Centers in Minority Institutions (RCMI) program. Through participation in protocol development, informed consent procedures, study implementation and follow-up with adverse events, the RSA works closely with research investigators and their staff to protect study participants. The RSA also conducts workshops, training and education sessions, and consultation with investigators to foster enhanced communication and adherence to ethical standards and safety regulations. Although it is too early to provide substantive evidence of positive outcomes, this article seeks to illuminate the value of the RSA position in ensuring that safety of research participants is accorded the highest priority at CRCs. Based upon initial results, we conclude that the RSA is an effective mechanism for achieving the NIH's goal of maintaining the utmost scrutiny of protocols involving human subjects.

The research subject advocate at minority Clinical Research Centers: an added resource for protection of human subjects.

In early 2001, the National Institutes of Health (NIH) created the research subject advocate (RSA) position as an additional resource for human subjects protection at NIH-funded Clinical Research Centers (CRCs) to enhance the protection of human participants in clinical research studies. We describe the RSA position in the context of clinical research, with a particular emphasis on the role of the RSA in two of the five CRCs funded by the NIH Research Centers in Minority Institutions (RCMI) program. Through participation in protocol development, informed consent procedures, study implementation and follow-up with adverse events, the RSA works closely with research investigators and their staff to protect study participants. The RSA also conducts workshops, training and education sessions, and consultation with investigators to foster enhanced communication and adherence to ethical standards and safety regulations. Although we cannot yet provide substantive evidence of positive outcomes, this article illuminates the value of the RSA position in ensuring that safety of research participants is accorded the highest priority at CRCs. On the basis of initial results, we conclude that the RSA is an effective mechanism for achieving the NIH goal of maintaining the utmost scrutiny of protocols involving human subjects.

Lavage administration of dilute surfactant in a piglet model of meconium aspiration.

Maldistribution of exogenous surfactant may preclude any clinical response in acute lung injury associated with surfactant dysfunction. Our previous studies have shown the effectiveness of surfactant lavage after homogenous lung injury. The present study utilizes a histologically confirmed non-homogeneous lung injury model induced by saline lung-lavage followed by meconium injected into a mainstem bronchus. Piglets were then treated with Infasurf or Exosurf by lavage (I-LAVAGE, n = 7; E-LAVAGE, n = 5) or bolus (I-BOLUS, n = 8; E-BOLUS, n = 5), or went untreated (CONTROL, n = 4). Lavage administration utilized a dilute surfactant (35 ml/kg; 4 mg phospholipid/ml) instilled into the lung, followed by gravity drainage. The retained doses of the respective surfactant in the lavage and bolus groups were similar. Results showed that the surfactant distribution was more uniform in the lavage groups compared to the bolus groups. Significant and consistent increases in PaO2 were observed in the lavage groups compared to the bolus groups and the controls. PaO2 (mmHg) at 240 min posttreatment: I-LAVAGE = 297 +/- 54, E-LAVAGE = 280 +/- 57; I-BOLUS = 139 +/- 31; E-BOLUS = 152 +/- 29; C = 119 +/- 73 (mean +/- SEM). Other improved pulmonary function parameters favored lavage administration. We conclude that better surfactant distribution achieved by lavage administration can be more effective than bolus administration in this type of non-homogeneous lung injury.

Six years and counting: the NIH-funded Clinical Research Center of Hawaii.

The CRC was developed in 1995 to make Hawaii a site of innovative, progressive research. Since then, the numbers of researchers and publications supported by the CRC have increased. In the next several years, the CRC will expand further into Hawaii's research community and apply for GCRC status, a strategy that will attract even more resources and investigators to JABSOM.