Alaska sentinel surveillance study of Helicobacter pylori isolates from Alaska Native persons from 2000 to 2008

Helicobacter pylori infection is more common in Alaska Native persons than in the general U.S. population, with seroprevalence to H. pylori approaching 75%. Previous studies in Alaska have demonstrated elevated proportions of antimicrobial resistance among H. pylori isolates. We analyzed H. pylori data from the Centers for Disease Control and Prevention's sentinel surveillance in Alaska from January 2000 to December 2008 to determine the proportion of culture-positive biopsy specimens with antimicrobial resistance from Alaska Native persons undergoing endoscopy. The aim of the present study was to monitor antimicrobial resistance of H. pylori isolates over time and by region in Alaska Native persons. Susceptibility testing of H. pylori isolates to metronidazole, clarithromycin, amoxicillin, and tetracycline was performed using agar dilution. Susceptibility testing for levofloxacin was performed by Etest. Overall, 45% (532/1,181) of persons undergoing upper endoscopy were culture positive for H. pylori. Metronidazole resistance was demonstrated in isolates from 222/531 (42%) persons, clarithromycin resistance in 159/531 (30%) persons, amoxicillin resistance in 10/531 (2%) persons, and levofloxacin resistance in 30/155 (19%) persons; no tetracycline resistance was documented. The prevalence of metronidazole, clarithromycin, and levofloxacin resistance varied by region. Female patients were more likely than male patients to demonstrate metronidazole (P < 0.05) and clarithromycin (P < 0.05) resistance. No substantial change in the proportion of persons with resistant isolates was observed over time. Resistance to metronidazole, clarithromycin, and levofloxacin is more common among H. pylori isolates from Alaska Native persons than those from elsewhere in the United States.     

Resequencing of the human major histocompatibility complex in patients with rheumatoid arthritis and healthy controls in Alaska Natives of Southeast Alaska

High prevalence and severity of rheumatoid arthritis (RA) with an early age of onset have previously been described in Alaska Native and American Indian (AN/AI) populations. The contribution of HLA-DRB1 alleles encoding a similar amino acid sequence, referred to as the shared epitope (SE), to RA risk is well recognized in multiple populations worldwide. DRB1*1402 allele is the major SE-encoding allele in AN/AI populations. However, DRB1*1402 is highly prevalent in healthy Alaska Natives of Southeast Alaska (AN), with no significant difference from RA patients, indicating this allele alone is not informative for defining genetic risk and non-human leukocyte antigen (non-HLA) genes are likely important in AN. We sought to deep resequence the human major histocompatibility complex (MHC) to characterize the single-nucleotide polymorphism (SNP) haplotypes within this region in RA cases and controls in AN. Approximately 99 kb of the MHC was resequenced with 95 amplicons throughout this region. Thirty-four cases and 74 controls were examined. A total of 696 SNPs were discovered from 85 of the selected 95 amplicons. Disease association signals were detected for nine of the 95 amplicons analyzed. Increased risk of RA was associated with five amplicons in the class I, class II or class III region and resistance to disease with four amplicons in the class I region. Our results indicate that non-HLA MHC genes and/or unknown exogenous factors likely modulate risk of RA in the AN population.     

High Prevalence of Helicobacter pylori in the Alaska Native Population and Association with Low Serum Ferritin Levels in Young Adults

Iron deficiency anemia is a common public health problem in the Alaska Native population. Yet, a clear etiology has eluded researchers for decades. Previous studies suggested a link between Helicobacter pylori infection, gastrointestinal blood loss due to hemorrhagic gastritis, and generalized iron deficiency anemia in adult Alaska Natives. Therefore, we examined the association between the prevalence of H. pylori-specific immunoglobulin G (IgG) and serum ferritin levels, a marker of iron deficiency. A random sample of 2,080 serum samples from Alaska Native residents drawn between 1980 and 1986 from residents in 13 regions was selected, and the samples were stratified by age, sex, and region. Overall, 75% were positive for H. pylori-specific IgG. The rate of H. pylori seropositivity increased with age; by age 14 years, 78% of the residents were positive. There were no gender differences in H. pylori seropositivity. However, marked regional differences were observed. Serum ferritin levels of <12 ng/ml were found most commonly among persons <20 years of age and among women of childbearing age. A significant association between low serum ferritin levels and prevalence of H. pylori-specific IgG was found, particularly for people aged less than 20 years. H. pylori may be a factor contributing to the iron deficiency anemia in the Alaska Native population.     

Limited efficacy of a Haemophilus influenzae type b conjugate vaccine in Alaska Native infants. The Alaska H. influenzae Vaccine Study Group

BACKGROUND. The prevention of invasive Haemophilus influenzae type b disease requires a vaccine that is effective when administered during the first six months of life. The infants of Alaska Natives are at particularly high risk of invasive H. influenzae type b disease. METHODS. To evaluate the protective efficacy of a H. influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine (polyribosylribitol phosphate-diphtheria toxoid [PRP-D]), we enrolled 2102 Alaska Native infants in a randomized, double-blind, placebo-controlled trial in which either the vaccine or a saline placebo was administered at approximately two, four, and six months of age. RESULTS. After 3969 subject-years of follow-up and 32 episodes of H. influenzae type b disease, the overall incidence of invasive disease was not reduced significantly in the vaccinated subjects (6.0 cases per 1000 patient-years), as compared with the placebo controls (9.6) or with other Alaska Native infants (6.0). After one, two, or three doses there was no significant protective efficacy with the vaccine; after three doses the efficacy was only 35 percent (95 percent confidence interval, -57 to 73). The lack of efficacy was not related to the age at onset of disease, age at immunization, type of disease, degree of Alaska Native heritage, time after immunization, or year of the study. Levels of H. influenzae type b anticapsular antibody in recipients of the vaccine became significantly higher than levels in those who received placebo only after the second and third doses. Even after the third dose, only 48 percent of the vaccinated infants had antibody levels of more than 0.1 microgram per milliliter (geometric mean titer, 0.18). Antibody responses did not vary with the level of maternally acquired antibody, degree of Alaska Native ancestry, or age at time of the first or second immunizations, but they increased with increasing age at time of the third dose (P less than 0.001). CONCLUSIONS. We found no evidence that the PRP-D vaccine provides significant protection, at least for Alaska Native infants, against invasive diseases caused by H. influenzae type b. The ineffectiveness of the vaccine paralleled its limited immunogenicity.     

Bone mineral density of American Indian and Alaska Native women compared with non-Hispanic white women: results from the Women's Health Initiative Study

OBJECTIVE: To compare bone mineral density (BMD) of American Indian/Alaska Native (AI/AN) women with that of non-Hispanic white women. DESIGN: This cross-sectional study compared mean BMD between AI/AN women and a random sample of non-Hispanic white women matched on geographic region in the Women's Health Initiative Study, a prospective study of postmenopausal women. We analyzed baseline BMD measurements for the total hip, spine, and whole body from 139 AI/AN women and 1,431 non-Hispanic white women. RESULTS: Unadjusted mean spine and whole body BMDs were not significantly different between the two races. Controlling for age, education, and hormone therapy use, adjusted mean BMD was similar by race among women who were underweight, normal, or obese. We found a significant interaction of race by body mass index on spine (P = 0.003) and whole body (P = 0.0003) BMD; thus, analyses were stratified by body mass index. Overweight AI/AN women had slightly lower adjusted mean whole body and spine BMD than overweight non-Hispanic white women (whole body: 0.97 vs 1.03 g/cm, P = 0.02; spine: 0.96 versus 1.03 g/cm, P = 0.001). Among extremely obese (body mass index: > or =40.0 kg/m) women, adjusted mean total hip BMD was higher in the AI/AN women (1.07 vs 0.97 g/cm, respectively, P = 0.03). CONCLUSIONS: Overall, AI/AN and non-Hispanic white women had similar BMDs. This study suggests that extremely obese AI/AN women may have higher BMD at certain skeletal sites compared with extremely obese non-Hispanic white women. However, these results need to be confirmed by additional research.     

Genomic cloud computing: legal and ethical points to consider

The biggest challenge in twenty-first century data-intensive genomic science, is developing vast computer infrastructure and advanced software tools to perform comprehensive analyses of genomic data sets for biomedical research and clinical practice. Researchers are increasingly turning to cloud computing both as a solution to integrate data from genomics, systems biology and biomedical data mining and as an approach to analyze data to solve biomedical problems. Although cloud computing provides several benefits such as lower costs and greater efficiency, it also raises legal and ethical issues. In this article, we discuss three key ‘points to consider'' (data control; data security, confidentiality and transfer; and accountability) based on a preliminary review of several publicly available cloud service providers'' Terms of Service. These ‘points to consider'' should be borne in mind by genomic research organizations when negotiating legal arrangements to store genomic data on a large commercial cloud service provider''s servers. Diligent genomic cloud computing means leveraging security standards and evaluation processes as a means to protect data and entails many of the same good practices that researchers should always consider in securing their local infrastructure.     

High prevalence of Helicobacter pylori in the Alaska native population and association with low serum ferritin levels in young adults

Iron deficiency anemia is a common public health problem in the Alaska Native population. Yet, a clear etiology has eluded researchers for decades. Previous studies suggested a link between Helicobacter pylori infection, gastrointestinal blood loss due to hemorrhagic gastritis, and generalized iron deficiency anemia in adult Alaska Natives. Therefore, we examined the association between the prevalence of H. pylori-specific immunoglobulin G (IgG) and serum ferritin levels, a marker of iron deficiency. A random sample of 2,080 serum samples from Alaska Native residents drawn between 1980 and 1986 from residents in 13 regions was selected, and the samples were stratified by age, sex, and region. Overall, 75% were positive for H. pylori-specific IgG. The rate of H. pylori seropositivity increased with age; by age 14 years, 78% of the residents were positive. There were no gender differences in H. pylori seropositivity. However, marked regional differences were observed. Serum ferritin levels of <12 ng/ml were found most commonly among persons <20 years of age and among women of childbearing age. A significant association between low serum ferritin levels and prevalence of H. pylori-specific IgG was found, particularly for people aged less than 20 years. H. pylori may be a factor contributing to the iron deficiency anemia in the Alaska Native population.     

Stakeholder engagement: a key component of integrating genomic information into electronic health records

Integrating genomic information into clinical care and the electronic health record can facilitate personalized medicine through genetically guided clinical decision support. Stakeholder involvement is critical to the success of these implementation efforts. Prior work on implementation of clinical information systems provides broad guidance to inform effective engagement strategies. We add to this evidence-based recommendations that are specific to issues at the intersection of genomics and the electronic health record. We describe stakeholder engagement strategies employed by the Electronic Medical Records and Genomics Network, a national consortium of US research institutions funded by the National Human Genome Research Institute to develop, disseminate, and apply approaches that combine genomic and electronic health record data. Through select examples drawn from sites of the Electronic Medical Records and Genomics Network, we illustrate a continuum of engagement strategies to inform genomic integration into commercial and homegrown electronic health records across a range of health-care settings. We frame engagement as activities to consult, involve, and partner with key stakeholder groups throughout specific phases of health information technology implementation. Our aim is to provide insights into engagement strategies to guide genomic integration based on our unique network experiences and lessons learned within the broader context of implementation research in biomedical informatics. On the basis of our collective experience, we describe key stakeholder practices, challenges, and considerations for successful genomic integration to support personalized medicine.Genet Med15 10, 792–801.     

Understanding the burden of trauma and victimization among American Indian and Alaska native elders: historical trauma as an element of poly-victimization

ABSTRACT

Research on recognition of adverse childhood experiences (ACEs) and poly-victimization has transformed our understanding of violence and trauma exposure. Both concepts point to the importance of understanding the cumulative burden of trauma and the interconnections among forms of violence and abuse. However, there has been little conceptualization about what these two constructs mean for American Indian and Alaska Native (AI/AN) individuals, families, and communities, and even less attention to the experiences of AI/AN elders. This paper summarizes prior work on adverse childhood experiences and poly-victimization, addresses the limitations of past research on these issues, and expands these constructs to include concepts of historical trauma in order to better understand victimization and trauma among AI/AN elders. We call for the integration of historical trauma into the poly-victimization framework for AI/AN communities in order to more accurately capture the true burden of victimization among AI/AN peoples. Future research, prevention, and intervention can better incorporate historical trauma and we provide suggestions for doing so, including adding items on historical trauma to poly-victimization surveys and creating programs to promote cultural connectedness.     

Biomarker feedback intervention for smoking cessation among Alaska Native pregnant women: Randomized pilot study

Objective

There is some evidence for biomarker feedback when combined with cessation counseling for reducing smoking in pregnancy. This randomized controlled pilot study evaluated feasibility and potential efficacy of a social-cognitive theory (SCT)-based biomarker feedback intervention among pregnant Alaska Native (AN) smokers.

Stakeholder engagement in policy development: challenges and opportunities for human genomics

Along with rapid advances in human genomics, policies governing genomic data and clinical technologies have proliferated. Stakeholder engagement is widely lauded as an important methodology for improving clinical, scientific, and public health policy decision making. The purpose of this paper is to examine how stakeholder engagement is used to develop policies in genomics research and public health areas, as well as to identify future priorities for conducting evidence-based stakeholder engagements. We focus on exemplars in biobanking and newborn screening to illustrate a variety of current stakeholder engagement in policy-making efforts. Each setting provides an important context for examining the methods of obtaining and integrating informed stakeholder voices into the policy-making process. While many organizations have an interest in engaging stakeholders with regard to genomic policy issues, there is broad divergence with respect to the stakeholders involved, the purpose of engagements, when stakeholders are engaged during policy development, methods of engagement, and the outcomes reported. Stakeholder engagement in genomics policy development is still at a nascent stage. Several challenges of using stakeholder engagement as a tool for genomics policy development remain, and little evidence regarding how to best incorporate stakeholder feedback into policy-making processes is currently available.     

Rebuilding trust: a community,multiagency, state,and university partnership to improve behavioral health care for American Indian Youth,their families,and communities

American Indian/Alaska Native youth represent the strength and survival of many Nations and Tribes. However, the aftermath of colonialism has resulted in numerous health disparities and challenges for Native youth, including the highest rate of suicide in the United States. With the aims of elucidating the causes of behavioral health disparities, eliminating them, and improving behavioral health care for Native youth, a partnership of providers, community members, and university faculty and staff completed a comprehensive literature review, conducted advisory meetings with 71 American Indian youth, parents, and elders, surveyed 25 service providers, and engaged in ongoing consultation with traditional practitioners. Results from the multiple sources were synthesized and are reported with 20 policy, provider, and research recommendations that recognize the importance of moving beyond exclusive reliance on western models of care and that seek to foster transformation of individuals, families, communities, behavioral health service systems of care, and social structures. © 2011 Wiley Periodicals, Inc.     

Dynamics of Helicobacter pylori-specific immunoglobulin G for 2 years after successful eradication of Helicobacter pylori infection in an American Indian and Alaska Native population

Helicobacter pylori antibodies were measured over 24 months in American Indian and Alaska Native persons who cleared their infections. Two months after treatment, 82% of H. pylori-negative persons remained seropositive. While there were declines in H. pylori antibodies for 12 months, after 24 months 71% of persons remained seropositive.     

Opportunities and challenges for the integration of massively parallel genomic sequencing into clinical practice: lessons from the ClinSeq project

PurposeThe debate surrounding the return of results from high-throughput genomic interrogation encompasses many important issues including ethics, law, economics, and social policy. As well, the debate is also informed by the molecular, genetic, and clinical foundations of the emerging field of clinical genomics, which is based on this new technology. This article outlines the main biomedical considerations of sequencing technologies and demonstrates some of the early clinical experiences with the technology to enable the debate to stay focused on real-world practicalities.MethodsThese experiences are based on early data from the ClinSeq project, which is a project to pilot the use of massively parallel sequencing in a clinical research context with a major aim to develop modes of returning results to individual subjects.ResultsThe study has enrolled >900 subjects and generated exome sequence data on 572 subjects. These data are beginning to be interpreted and returned to the subjects, which provides examples of the potential usefulness and pitfalls of clinical genomics.ConclusionThere are numerous genetic results that can be readily derived from a genome including rare, high-penetrance traits, and carrier states. However, much work needs to be done to develop the tools and resources for genomic interpretation. The main lesson learned is that a genome sequence may be better considered as a health-care resource, rather than a test, one that can be interpreted and used over the lifetime of the patient.Genet Med 2012:14(4):393–398     

Health equity in the implementation of genomics and precision medicine: A public health imperative

Recent reviews have emphasized the need for a health equity agenda in genomics research. To ensure that genomic discoveries can lead to improved health outcomes for all segments of the population, a health equity agenda needs to go beyond research studies. Advances in genomics and precision medicine have led to an increasing number of evidence-based applications that can reduce morbidity and mortality for millions of people (tier 1). Studies have shown lower implementation rates for selected diseases with tier 1 applications (familial hypercholesterolemia, Lynch syndrome, hereditary breast and ovarian cancer) among racial and ethnic minority groups, rural communities, uninsured or underinsured people, and those with lower education and income. We make the case that a public health agenda is needed to address disparities in implementation of genomics and precision medicine. Public health actions can be centered on population-specific needs and outcomes assessment, policy and evidence development, and assurance of delivery of effective and ethical interventions. Crucial public health activities also include engaging communities, building coalitions, improving genetic health literacy, and building a diverse workforce. Without concerted public health action, further advances in genomics with potentially broad applications could lead to further widening of health disparities in the next decade.     

Integrating Massively Parallel Sequencing into Diagnostic Workflows and Managing the Annotation and Clinical Interpretation Challenge

Massively parallel sequencing has become a powerful tool for the clinical management of patients with applications in diagnosis, guidance of treatment, prediction of drug response, and carrier screening. A considerable challenge for the clinical implementation of these technologies is the management of the vast amount of sequence data generated, in particular the annotation and clinical interpretation of genomic variants. Here, we describe annotation steps that can be automated and common strategies employed for variant prioritization. The definition of best practice standards for variant annotation and prioritization is still ongoing; at present, there is limited consensus regarding an optimal clinical sequencing pipeline. We provide considerations to help define these. For the first time, clinical genetics and genomics is not limited by our ability to sequence, but our ability to clinically interpret and use genomic information in health management. We argue that the development of standardized variant annotation and interpretation approaches and software tools implementing these warrants further support. As we gain a better understanding of the significance of genomic variation through research, patients will be able to benefit from the full scope that these technologies offer.     

Meeting the needs of regional minority groups: the University of Washington's programs to increase the American Indian and Alaskan native physician workforce.

Minority populations in the United States are growing rapidly, but physician workforce diversity has not kept pace with the needs of underserved communities. Minorities comprised 26.4% of the population in 1995; by 2050, these groups will comprise nearly half. Medical schools must enlist greater numbers of minority physicians and train all physicians to provide culturally responsive care. The University of Washington School of Medicine (UWSOM) is the nation's only medical school that serves a five-state region (Washington, Wyoming, Alaska, Montana, and Idaho). Its mission addresses the need to serve the region, rectify primary care shortages, and meet increasing regional demands for underserved populations. The UWSOM Native American Center of Excellence (NACOE) was established as one important way to respond to this charge. The authors describe pipeline and minority recruitment programs at UWSOM, focusing on the NACOE and other activities to recruit American Indian/Alaskan Native (AI/AN) applicants to medical schools. These programs have increased the numbers of AI/AN medical students; developed the Indian Health Pathway; worked to prepare students to provide culturally responsive care for AI/AN communities; researched health disparities specific to AI/AN populations; provided retention programs and services to ensure successful completion of medical training; developed mentorship networks; and provided faculty-development programs to increase entry of AI/AN physicians into academia. Challenges lie ahead. Barriers to the pipeline will continue to plague students, and inadequate federal funding will have a significant and negative impact on achieving needed physician-workforce diversity. Medical schools must play a larger role in resolving these, and continue to provide pipeline programs, retention programs, and minority faculty development that can make a difference.     

后基因组时代的生物芯片技术

生命科学研究已进入后基因组时代,当前最重要的任务之一是对人类基因的注释与确认。基因芯片、蛋白质芯片及芯片实验室在揭示基因功能中将发挥重要作用。同时。生物芯片技术为系统生物学的发展提供大量数据,并成为系统生物学研究强有力的工具,为最终破解基因功能指明了方向。     

COVID-19: risk accumulation among biologically and socially vulnerable older populations

Emerging data show that the health and economic impacts of COVID-19 are being disproportionately borne by individuals who are not only biologically, but also socially vulnerable. Based on preliminary data from Sweden and other reports, in this paper we propose a conceptual framework whereby different factors related to biological and social vulnerability may explain the specific COVID-19 burden among older people. There is already some evidence showing large social disparities in the prevention, treatment, prognosis and/or long-term consequences of COVID-19. The remaining question is to what extent these affect older adults specifically. We provide the rationale to address this question with scientific methods and proper study designs, where the interplay between individuals’ biomedical status and their social environment is the focus. Only through interdisciplinary research integrating biological, clinical and social data will we be able to provide new insights into the SARS-CoV-2 pandemic and inform actions aimed at reducing older adults’ vulnerability to COVID-19 or other similar pandemics in the future.