Best Practices for Conducting Clinical Trials With Indigenous Children in the United States.

We provide guidance for conducting clinical trials with Indigenous children in the United States. We drew on extant literature and our experience to describe 3 best practices for the ethical and effective conduct of clinical trials with Indigenous children. Case examples of pediatric research conducted with American Indian, Alaska Native, and Native Hawaiian communities are provided to illustrate these practices. Ethical and effective clinical trials with Indigenous children require early and sustained community engagement, building capacity for Indigenous research, and supporting community oversight and ownership of research. Effective engagement requires equity, trust, shared interests, and mutual benefit among partners over time. Capacity building should prioritize developing Indigenous researchers. Supporting community oversight and ownership of research means that investigators should plan for data-sharing agreements, return or destruction of data, and multiple regulatory approvals. Indigenous children must be included in clinical trials to reduce health disparities and improve health outcomes in these pediatric populations. Establishment of the Environmental Influences on Child Health Outcomes Institutional Development Award States Pediatric Clinical Trials Network (ECHO ISPCTN) in 2016 creates a unique and timely opportunity to increase Indigenous children's participation in state-of-the-art clinical trials.

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.

Changes in antidepressant medications prescribing trends in children and adolescents in Hawai'i following the FDA black box warning.

OBJECTIVES: To study prescribing trends for antidepressants in Hawai'i following the FDA black box warning regarding the possible risk of suicide in children and adolescents. We also explored relationships between changes in prescribing trends and patient and provider characteristics. STUDY DESIGN: Analysis of an existing insurance data set of prescriptions to children and adolescents within the State of Hawai'i. STUDY POPULATION: Children and adolescents under 18-years-old insured through the largest (>60%) third-party insurance company in the state. RESULTS: Our results showed variations in changes in prescribing trends for different selective serotonin reuptake inhibitors (SSRIs) following the FDA black box warning. SSRIs with more evidence-based research supporting their safety and efficacy were least affected as were those that were less implicated by the FDA analysis of the possible link between SSRIs and Suicidality. Trends were apparent for all age groups examined and for both females and males. CONCLUSIONS: Changes in prescribing patterns of psychiatric medications for children and adolescents in Hawai'i were identified. Differing patterns have evolved since 2003 following the series of concerns raised regarding SSRIs and suicidality in children and adolescents.

The role of translational research in addressing health disparities: a conceptual framework.

Translational research has tremendous potential as a tool to reduce health disparities in the United States, but a lack of common understanding about the scope of this dynamic, multidisciplinary approach to research has limited its use. The term "translational research" is often associated with the phrase "bench to bedside," but the expedited movement of biomedical advances from the laboratory to clinical trials is only the first phase of the translational process. The second phase of translation, wherein innovations are moved from the bedside to real-world practice, is equally important, but it receives far less attention. Due in part to this imbalance, tremendous amounts of money and effort are spent expanding the boundaries of understanding and investigating the molecular underpinnings of disease and illness, while far fewer resources are devoted to improving the mechanisms by which those advances will be used to actually improve health outcomes. To foster awareness of the complete translational process and understanding of its value, we have developed two complementary models that provide a unifying conceptual framework for translational research. Specifically, these models integrate many elements of the National Institutes of Health roadmap for the future of medical research and provide a salient conceptualization of how a wide range of research endeavors from different disciplines can be used harmoniously to make progress toward achieving two overarching goals of Healthy People 2010--increasing the quality and years of healthy life and eliminating health disparities.

Addressing health disparities through multi-institutional, multidisciplinary collaboratories.

The national research leadership has recently become aware of the tremendous potential of translational research as an approach to address health disparities. The Research Centers in Minority Institutions (RCMI) Translational Research Network (RTRN) is a research network that supports multi-institutional, multidisciplinary collaboration with a focus on key diseases and conditions for which disproportionately adverse racial and ethnic health disparities exist. The RTRN is designed to facilitate the movement of scientific advances across the translational research spectrum by providing researchers at different institutions with the infrastructure and tools necessary to collaborate on interdisciplinary and transdisciplinary research projects relating to specific health outcomes for which major racial/ethnic disparities exist. In the past, the difficulty of overcoming the restrictions imposed by time and space have made it difficult to carry out this type of large-scale, multilevel collaboration efficiently. To address this formidable challenge, the RTRN will deploy a translational research cluster system that uses "cyber workspaces" to bring researchers with similar interests together by using online collaboratory technology. These virtual meeting environments will provide a number of tools, including videoconferences (seminars, works in progress, meetings); project management tools (WebCT, Microsoft Share Point); and posting areas for projects, concepts, and other research and educational activities. This technology will help enhance access to resources across institutions with a common mission, minimize many of the logistical hurdles that impede intellectual exchange, streamline the planning and implementation of innovative interdisciplinary research, and assess the use of protocols and practices to assist researchers in interacting across and within cyber workspaces.

Self identity through Ho'oponopono as adjunctive therapy for hypertension management.

OBJECTIVE: Self Identity through Ho'oponopono is a step-by-step problem-solving approach to identify and relieve stress. The objective of this study was to determine if Self Identity through Ho'oponopono along with standard medical therapy might better control hypertension than standard therapy alone. DESIGN, SETTING, PARTICIPANTS: Twenty-three Asian, Hawaiian, and other Pacific Islanders from a local community in Hawaii participated in a longitudinal design comparing pre- and post-intervention measures of blood pressure. INTERVENTION: Participants attended a half-day class on Self Identity through Ho'oponopono to learn ways to create balance and correct stress through an understanding of their own self identity. Participants learned processes to care for themselves through repentance, forgiveness, and transmutation and how to apply the processes in their daily lives. MAIN OUTCOME MEASURES: Repeated blood pressure measurements were compared before and after the intervention using generalized estimating equations; two spirituality questionnaires were administered before and after the intervention and analyzed with paired RESULTS: Systolic blood pressure decreased after the intervention, averaging 11.86 mm Hg below pre-intervention levels. Diastolic blood pressure decreased by 5.44 mm Hg. Spirituality scores significantly increased after the intervention. CONCLUSIONS: Self Identity through Ho'oponopono was associated with a statistically and clinically significant reduction in mean blood pressure. Spirituality scores increased after the intervention. We conclude that Self Identity through Ho'oponopono may be an effective adjunctive therapy for hypertension. Further research is needed to validate these preliminary findings.

Hawaii cohort study of serum micronutrient concentrations and clearance of incident oncogenic human papillomavirus infection of the cervix.

The degree to which the resolution of human papillomavirus (HPV) infection parallels exposure to other factors, particularly those related to nutritional status, is a relatively unexplored area of research. We established a cohort of women for long-term follow-up to examine the association of serum retinol, carotenoid, and tocopherol concentrations with the clearance of incident cervical HPV infection. Interviews and biological specimens were obtained at baseline and at 4-month intervals. At each visit, a cervical cell specimen for HPV DNA analysis and cytology and a fasting blood sample to measure micronutrient levels were collected. A Cox proportional hazards model was used to study the relationship between clearance of 189 incident (type-specific) oncogenic HPV infections and the levels of 20 serum micronutrients among 122 women. Higher circulating levels of trans-zeaxanthin, total trans-lutein/zeaxanthin, cryptoxanthin (total and beta), total trans-lycopene and cis-lycopene, carotene (alpha, beta, and total), and total carotenoids were associated with a significant decrease in the clearance time of type-specific HPV infection, particularly during the early stages of infection (120 days) was not significantly associated with circulating levels of carotenoids or tocopherols. Results from this investigation support an association of micronutrients with the rapid clearance of incident oncogenic HPV infection of the uterine cervix.

Traumatic brain injury: outcomes from rural and urban locations over a 5-year period (Part 1).

The national death rates from rural trauma are disproportionately higher compared to urban areas. Traumatic brain injury is a major cause of hospital admissions in Hawai'i. This is the first in a two part series to explore this significant public health concern. Data on traumatic brain injuries from 2000-2004 was obtained from 2 sources. Male gender, alcohol use, and lack of protective devices resulted in higher rates of injury. Rates of severe injury were higher in young adults, the elderly, and in rural locations, but rural mortality rates here did not differ compared to urban settings. The greatest potential to reduce morbidity and mortality resides in the formulation and implementation of preventive strategies.

Use of provider delivered complementary and alternative therapies in Hawai'i: results of the Hawai'i Health Survey.

BACKGROUND: Provider delivered complementary and alternative medicine (CAM) is used increasingly as a treatment option. Nevertheless, data related to the prevalence of provider delivered CAM (or PDCAM) use in diverse racial and ethnic populations is limited. The purpose of this investigation was to describe the use of provider delivered CAM in Hawaiian, Asian, and other Pacific Island populations in Hawai'i. The investigation was undertaken to test the hypothesis that a significant difference existed in the use of provider delivered CAM in Hawai'i because of the cultural diversity existing within the population. METHODS: The data were collected through the Hawai'i Health Survey (HHS). The HHS was administered by telephone among 5,000 stratified, randomly selected households, representing each of the Hawaiian Islands. Data were collected on all members of sample households. The sample population was statistically adjusted to represent the population of Hawai'i. RESULTS: Several factors emerged that may indicate increased use of provider delivered CAM. Most provider delivered CAM users are more educated, have incomes 200% or more above the poverty line, and reported either good or very good health status. Among respondents with poor health status, 60.4% have used provider delivered CAM. Those with a body mass index indicating that they were overweight also reported a high level of provider delivered CAM use (51.4%). Similar percentages of both women and men use provider delivered CAM, while the youngest and oldest respondents reported the least use of provider delivered CAM. Whites (60.0%) and Koreans (56.6%) reported the highest percentage of use of provider delivered CAM, while African Americans (35.5%) and Filipinos (37. 1%) reported the lowest percentage. The majority of people without health insurance report provider delivered CAM use (53. 7%). The highest portion of people who have usedanyalternative health care service is found among those whose pain severely interferes with normal work (78.3%). CONCLUSIONS The use of provider delivered CAM was found to be significantly greater in Hawaii compared with the mainland. Our results suggest the need for additional investigation of provider delivered CAM use in specific ethnic subpopulations.

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.

Oral health disparities and periodontal disease in Asian and Pacific Island populations.

INTRODUCTION: While oral health disparities exist in many ethnic groups in Hawaii, the challenge of developing research and intervention programs is hampered by the lack of a dental school and adequate state resources. OBJECTIVE: To use a collaboration model to establish a mentoring relationship with a research-intensive school of dentistry to reduce oral health disparities in Hawaii. METHODS: Collaborative interactions with the University of Hawaii School of Medicine (UH) and the University of North Carolina School of Dentistry at Chapel Hill (UNC) included bimonthly teleconferences, on-site planning and mentoring sessions, yearly conferences in Hawaii open to the community using UNC faculty, and on-site skills training sessions. The community was asked to participate in determining priorities for research through focus-group interactions. Two pilot investigations were also conducted. RESULTS: Both universities have been awarded grants to fund activities to support the combined intellectual and physical resources of multiple private, public, and community organizations to achieve the goal of improving the oral health status of the people of Hawaii. As a result of initial planning, two related grants have been submitted (one approved, one disapproved) to fund pilot studies on the oral health status of mothers and their babies in a rural community. These studies include both UH and UNC investigators. CONCLUSIONS: Health disparities occur among diverse ethnic groups in Hawaii, and links between general health and oral health continue to emerge. In spite of obstacles to designing effective research and intervention programs in Hawaii, UH fostered a collaborative relationship with a premiere dental research institution to develop competence in clinical research, conduct pilot studies, and obtain extramural funding for comprehensive studies. Direct involvement of community representatives in the research process is integral to the success of such studies and will continue to serve as the foundation of our community-based participatory research. The network partners have accomplished their primary goal of developing culturally appropriate methods for assessing determinants of oral health, oral health-related quality of life, and health outcomes in Asians and Pacific Islanders.

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.

Anal human papillomavirus infection in women and its relationship with cervical infection.

Human papillomavirus (HPV), the primary cause of cervical cancer, is also associated with the development of anal cancer. Relatively little is known about the epidemiology of anal HPV infection among healthy females and its relationship to cervical infection. We sought to characterize anal HPV infection in a cohort of adult women in Hawaii. Overall, 27% (372 of 1,378) of women were positive for anal HPV DNA at baseline compared with 29% (692 of 2,372) with cervical HPV DNA. Among women with paired anal and cervical samples, anal infection without accompanying cervical infection was observed in 14% (190 of 1,363). Concurrent anal and cervical HPV infections were observed in 13% (178 of 1,363) of women. Women with cervical HPV infection had >3-fold increased risk of concurrent anal infection. Concurrent anal and cervical HPV infection was most prevalent among the youngest women and steadily decreased through age 50 years. By contrast, the prevalence of anal infection alone remained relatively steady in all age groups. Compared with cervical infections, the overall distribution of HPV genotypes in the anus was more heterogeneous and included a greater proportion of nononcogenic types. A high degree of genotype-specific concordance was observed among concurrent anal and cervical infections, indicating a common source of infection. Nevertheless, the association of anal intercourse with anal HPV infection was limited to those women without accompanying cervical infection. The relationship of anal to cervical infection as described in this study has implications for the development of anal malignancies in women.

Improving Hawaiian and Filipino involvement in clinical research opportunities: qualitative findings from Hawai'i.

OBJECTIVE: Investigate the barriers to participation in medical research that involves Asian and Pacific Islander (API) populations in Hawai'i. PARTICIPANTS: Fifty people (27 Filipinos, 23 Hawaiian/Pacific Islanders) in five different communities on Oahu. DESIGN: Nine focus groups with an ethnically matched moderator were held to explore people's feelings, problems, and recommendations regarding medical research. Sessions were audiotaped, transcribed, and qualitatively analyzed with the constant comparison method. RESULTS: Only 12% of study participants said that they absolutely would not participate in a clinical study. Most agreed that research is vital. Filipino participants were more optimistic about the safety and value of joining in medical research. Hawaiian groups were more hesitant and fearful. Reasons for nonparticipation included negative feelings about the purpose and intent of clinical trials and language and cultural barriers. Suggestions on how to encourage API populations to participate in research investigations included improving peoples' understanding of the benefits to family and community. Hawaiian and Filipino groups differed only slightly in their assessments of the type of research needed in their communities. CONCLUSIONS: Recruitment campaigns must improve people's awareness of the process of informed consent, research safeguards, and benefits to family and community. Attention should focus on K-12 health education to use members of the younger generations to access and educate elders, involving persons with medical research experience as a recruitment resource, returning results to study participants, and increasing the number of healthcare professionals and researchers that are culturally and linguistically matched to the community.

Growth in clinical research productivity and funding at the University of Hawaii's John A. Burns School of Medicine: the past 10 years.

Over the last ten years, faculty at the John A. Burns School of Medicine (JABSOM) and the University of Hawaii (UH) have been actively engaged in ongoing efforts to increase the quantity and improve the quality of biomedical research in the State of Hawaii. JABSOM's Clinical Research Center (CRC), funded in 1995 by the National Center for Research Resources (NCRR) and the Research Centers in Minority Institutions (RCMI) of the National Institutes of Health, has provided research infrastructure that has been essential to these efforts. The CRC and other JABSOM departments and affiliated programs have collaborated with public and private entities within the community, particularly in the area of health, related to diverse racial and ethnic populations. This paper sets forth a number of the significant indicators of research progress, as illustrated primarily through CRC support for various research activities conducted at JABSOM.

The Clinical Research Center of Hawaii: a nine year progress report.

The UH-CRC is an NIH minority funded infrastructure program at the University of Hawaii in partnership with Hawaii Pacific Health, now in its ninth year. The main purpose of the UH-CRC is to foster clinical research at UH in order to improve the health of the citizens of Hawaii, particularly those who suffer disproportionately from disorders affecting these communities. This status report documents the continued success and progress of the Center Manuscripts published or in press have increased from an average of 43 in years 1-3 to 54 in years 4-6 to 84 for years 7-9. Actual dollars received per year ranged from 1-7 million dollars the first 6 years, but reached 8-22 million dollars the last three years. This status report also documents the mandate for this clinical research infrastructure program to compete successfully for mainstream funding status by 2010.

Addressing oral health disparities in settings without a research-intensive dental school: collaborative strategies.

Research suggests that oral health is linked to systemic health, and those with poor oral health are potentially at greater risk for important diseases, including cardiovascular disease, stroke, diabetes mellitus, and adverse pregnancy outcomes. Asians and Pacific Islanders (APIs) in Hawaii have high rates of many such diseases. Studies in children in Hawaii have revealed disparities in dental health; for example, API children have significantly higher rates of cavities than other groups. Hence, conducting further study is vital in adults, particularly APIs, to assess oral health and its correlation to overall health outcomes. Given the lack of a dental school and the lack of fluoridated water in the state, the University of Hawaii's John A. Burns School of Medicine (ABSOM) has identified the need to assume a leadership role in creating effective community-based oral health research and treatment programs. With the support of the National Institute of Dental and Craniofacial Research, JABSOM fostered a collaborative relationship with the University of North Carolina at Chapel Hill School of Dentistry, a premiere research-intensive dental school, the Waimanalo Health Center, and the Hawaii State Department of Health. This partnership has worked together to implement a community-based approach to performing research designed to illuminate disparities and develop innovative strategies to promote oral health in Hawaii's diverse populations. We hope that this collaborative, culturally competent approach may serve as a model for use in other settings without a research-intensive dental school.

The relationship between ethnicity and obesity in Asian and Pacific Islander populations: a literature review.

The purpose of this literature review is to explore the potential relationship between ethnicity and obesity, and obesity-related risks, with a particular emphasis on disparities between Asian and Pacific Islander populations. We conducted a comprehensive search of available medical literature related to the rise of obesity in the United States, factors contributing to obesity, evidence-based clinical guidelines, and obesity and related risks as they occur in Hawaii. In conducting this search, we sought to illuminate obesity rates in Asians and Pacific Islanders in connection with various factors, such as diet and lifestyle, acculturation, and body image, as they occur in diverse cultural contexts. We found that the rates of obesity and related risks were highest in Native Hawaiians and Samoans. Based upon our review of the literature, we conclude that further research is necessary to address the relationship between ethnicity and obesity risk factors in Asian and Pacific Islander populations.

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.