Causes and Disparities in Death Rates Among Urban American Indian and Alaska Native Populations, 1999-2009.

OBJECTIVES: To characterize the leading causes of death for the urban American Indian/Alaska Native (AI/AN) population and compare with urban White and rural AI/AN populations. METHODS: We linked Indian Health Service patient registration records with the National Death Index to reduce racial misclassification in death certificate data. We calculated age-adjusted urban AI/AN death rates for the period 1999-2009 and compared those with corresponding urban White and rural AI/AN death rates. RESULTS: The top-5 leading causes of death among urban AI/AN persons were heart disease, cancer, unintentional injury, diabetes, and chronic liver disease and cirrhosis. Compared with urban White persons, urban AI/AN persons experienced significantly higher death rates for all top-5 leading causes. The largest disparities were for diabetes and chronic liver disease and cirrhosis. In general, urban and rural AI/AN persons had the same leading causes of death, although urban AI/AN persons had lower death rates for most conditions. CONCLUSIONS: Urban AI/AN persons experience significant disparities in death rates compared with their White counterparts. Public health and clinical interventions should target urban AI/AN persons to address behaviors and conditions contributing to health disparities.

Immunization information systems to increase vaccination rates: a community guide systematic review.

CONTEXT: Immunizations are the most effective way to reduce incidence of vaccine-preventable diseases. Immunization information systems (IISs) are confidential, population-based, computerized databases that record all vaccination doses administered by participating providers to people residing within a given geopolitical area. They facilitate consolidation of vaccination histories for use by health care providers in determining appropriate client vaccinations. Immunization information systems also provide aggregate data on immunizations for use in monitoring coverage and program operations and to guide public health action. EVIDENCE ACQUISITION: Methods for conducting systematic reviews for the Guide to Community Preventive Services were used to assess the effectiveness of IISs. Reviewed evidence examined changes in vaccination rates in client populations or described expanded IIS capabilities related to improving vaccinations. The literature search identified 108 published articles and 132 conference abstracts describing or evaluating the use of IISs in different assessment categories. EVIDENCE SYNTHESIS: Studies described or evaluated IIS capabilities to (1) create or support effective interventions to increase vaccination rates, such as client reminder and recall, provider assessment and feedback, and provider reminders; (2) determine client vaccination status to inform decisions by clinicians, health care systems, and schools; (3) guide public health responses to outbreaks of vaccine-preventable disease; (4) inform assessments of vaccination coverage, missed vaccination opportunities, invalid dose administration, and disparities; and (5) facilitate vaccine management and accountability. CONCLUSIONS: Findings from 240 articles and abstracts demonstrate IIS capabilities and actions in increasing vaccination rates with the goal of reducing vaccine-preventable disease.

Pneumonia and influenza mortality among American Indian and Alaska Native people, 1990-2009.

OBJECTIVES: We compared pneumonia and influenza death rates among American Indian/Alaska Native (AI/AN) people with rates among Whites and examined geographic differences in pneumonia and influenza death rates for AI/AN persons. METHODS: We adjusted National Vital Statistics Surveillance mortality data for racial misclassification of AI/AN people through linkages with Indian Health Service (IHS) registration records. Pneumonia and influenza deaths were defined as those who died from 1990 through 1998 and 1999 through 2009 according to codes for pneumonia and influenza from the International Classification of Diseases, 9th and 10th Revision, respectively. We limited the analysis to IHS Contract Health Service Delivery Area counties, and compared pneumonia and influenza death rates between AI/ANs and Whites by calculating rate ratios for the 2 periods. RESULTS: Compared with Whites, the pneumonia and influenza death rate for AI/AN persons in both periods was significantly higher. AI/AN populations in the Alaska, Northern Plains, and Southwest regions had rates more than 2 times higher than those of Whites. The pneumonia and influenza death rate for AI/AN populations decreased from 39.6 in 1999 to 2003 to 33.9 in 2004 to 2009. CONCLUSIONS: Although progress has been made in reducing pneumonia and influenza mortality, disparities between AI/AN persons and Whites persist. Strategies to improve vaccination coverage and address risk factors that contribute to pneumonia and influenza mortality are needed.

Sharing lessons learned from COVID-19 vaccine introductions: a global community forum for countries.

To optimize the efficient introduction and deployment of COVID-19 vaccines across the globe during the COVID-19 pandemic, in April 2021 WHO launched a new process and tools for countries to rapidly review the early phase of countries' COVID-19 vaccine introduction. This methodology is called the COVID-19 vaccination intra-action review, also known as mini COVID-19 vaccine post-introduction evaluation (mini-cPIE). As of November 2022, 46 mini-cPIEs had been conducted. In collaboration with Project ECHO, WHO convened and facilitated real-time experience sharing and peer-learning among countries following their mini-cPIEs through a virtual global real-time learning forum. This five-session clinic series was attended by 736 participants from 129 countries. Based on post-session feedback surveys, when asked about the utility of the sessions, half of the participants said that sessions led them to review national guidelines and protocols or make other changes to their health systems. The post-series survey sent following the end of the clinic series showed that at least eight countries subsequently conducted a mini-cPIE after participating in the clinics, and participants from at least nine countries indicated the experience shared by peer countries on the clinic largely benefited their COVID-19 vaccine introduction and deployment. In this article, we highlight the benefits and importance of creating a global experience-sharing forum for countries to connect and share pertinent learnings in real-time during an international public health emergency. Moving forward, it is critical to foster a culture of individual and collective learning within and between countries during public health emergencies, with WHO playing an important convening role.

Validation of algorithm to identify American Indian/Alaska Native pregnant women at risk from pandemic H1N1 influenza.

Pregnant women and American Indian and Alaska Native people are at elevated risk of severe disease and mortality from 2009 pandemic influenza A/H1N1. We validated an electronic health record-based algorithm used by Indian Health Service to identify pregnant women in near real-time surveillance of pandemic influenza A/H1N1. We randomly selected a stratified sample of 515 patients at 3 Indian Health Service-funded hospitals with varied characteristics. With comprehensive review of patients' electronic health records as the gold standard, we calculated the positive predictive value and sensitivity of the pregnancy algorithm. The sensitivity of the algorithm at individual hospitals ranged from 94.1-96.0%. Positive predictive value ranged from 94.4-98.3%. Despite differences among hospitals on key characteristics, the pregnancy algorithm performed nearly equivalently with high positive predictive value and sensitivity at all facilities. It may prove helpful for surveillance during future epidemics and for targeting interventions for pregnant women and infants.

The regulation of AMPK signaling in a natural state of profound metabolic rate depression.

In response to energy stress (and elevated AMP), the AMP-activated protein kinase (AMPK) coordinates the restoration of energy homeostasis. We determined that AMPK is activated in a model system (desert snail Otala lactea) during a physiological state of profound metabolic rate depression (estivation) in the absence of a rise in AMP. Kinetic characterization indicated a strong increase in AMPK activity and phosphorylation in estivation, consistent with an increase in P-Ser428 LKB, an established regulator of AMPK. Accordingly, approximately 2-fold increases in AMPKalpha1 protein and activity were observed with LKB1 immunoprecipitates from estivating snails. In vitro studies determined that AMPK in crude extracts was activated in the presence of cGMP and deactivated in conditions that permitted protein phosphatase type-2A (PP2A) activity. Furthermore, AMPKalpha1 protein and activity increased in PKG immunoprecipitates from estivating tissues, suggesting a novel role for PKG in the regulation of AMPK in vivo. We evaluated several downstream targets of AMPK. Acetyl-CoA carboxylase (ACC) activity was strongly inhibited in estivation, consistent with increased P-Ser79 content, and in vitro stimulation of AMPK negated citrate's ability to stimulate ACC aggregation. Analysis of other targets revealed a strong decrease in PPARgamma-coactivator 1alpha expression in both tissues, which was related to decreased gluconeogenic protein expression in hepatic tissue, but no changes in mitochondrial biogenesis markers in muscle. We concluded that AMPK activation in O. lactea aids in facilitating the suppression of anabolic pathways, without necessarily activating ATP-generating catabolism.

Regulation of global protein translation and protein degradation in aerobic dormancy.

We hypothesized that protein turnover would be substantially suppressed during estivation in the land snail, Otala lactea, as part of a wholesale move to conserve ATP in the hypometabolic state, and that decreased rates of protein synthesis and degradation would be mediated by altering the phosphorylation state of key proteins. Rates of protein translation, measured in vitro, decreased by approximately 80% in extracts of foot muscle and hepatopancreas after 2 days of estivation, and this reduction was associated with strong increases in the phosphorylation of ribosomal factors, eIF2 alpha and eEF2, as well as decreased phosphorylation of 4E-BP1. Reductions in levels of markers of ribosomal biogenesis and a tissue-specific reduction in the phosphorylation state of eIF4E and eIF4GI were also evident after 14 days of estivation. Activity of the 20S proteasome decreased by 60-80% after 2 days of estivation and this decrease was mediated by protein kinase G in vitro, whereas protein phosphatase 2A activated the proteasome. Levels of protein carbonyls did not change in snail tissues during estivation whereas the expression heat shock proteins increased, suggesting that protein resistance to damage is enhanced in estivation. In conclusion, protein synthesis and degradation rates were coordinately suppressed during estivation in O. lactea and this is associated with the phosphorylation of ribosomal initiation and elongation factors and the 20S proteasome.

Pandemic influenza preparedness and vulnerable populations in tribal communities.

American Indian and Alaska Native (AIAN) governments are sovereign entities with inherent authority to establish and administer public health programs within their communities and will be critical partners in national efforts to prepare for pandemic influenza. Within AIAN communities, some subpopulations will be particularly vulnerable during an influenza pandemic because of their underlying health conditions, whereas others will be at increased risk because of limited access to prevention or treatment interventions.We outline potential issues to consider in identifying and providing appropriate services for selected vulnerable populations within tribal communities. We also highlight pandemic influenza preparedness resources available to tribal leaders and their partners in state and local health departments, academia, community-based organizations, and the private sector.

A pathway to developing and testing quality measures aimed at improving adult vaccination rates in the United States.

Despite recommendations for vaccinating adults and widespread availability of immunization services (e.g., pharmacy venues, workplace wellness clinics), vaccination rates in the United States remain low. The U.S. National Adult Immunization Plan identified the development of quality measures as a priority and key strategy to address low adult vaccination coverage rates. The use of quality measures can provide incentives for increased utilization of preventive services. To address the lack of adult immunization measures, the National Adult and Influenza Immunization Summit, a coalition of adult immunization partners led by the Immunization Action Coalition, Centers for Disease Control and Prevention, and National Vaccine Program Office, spearheaded efforts to (1) identify gaps and priorities in adult immunization quality performance measurement; (2) explore feasibility of data collection on adult immunizations through pilot testing and engaging stakeholders; and (3) develop and test quality measure specifications. This paper outlines the process by which a public-private partnership drove the development of two adult immunization performance measures-an adult immunization status measure for influenza, tetanus and diphtheria (Td) and/or tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap), herpes zoster and pneumococcal vaccines, and a prenatal immunization status measure for influenza and Tdap vaccinations in pregnant women. These measures have recently been added to the 2019 Healthcare Effectiveness Data and Information Set (HEDIS®), a widely used set of performance measures reportable by private health plans.

Status of influenza and pneumococcal vaccination among older American Indians and Alaska Natives.

OBJECTIVES: We sought to estimate the influenza and pneumococcal vaccination coverage among older American Indian and Alaska Native (AIAN) adults nationally and the impact of sociodemographic factors, variations by geographic region, and access to services on vaccination coverage. METHODS: We obtained our sample of 1981 AIAN and 179845 White respondents 65 years and older from Behavioral Risk Factor Surveillance System data from 2003 to 2005. Logistic regression provided predictive marginal vaccination coverage for each covariate and adjusted for demographic characteristics and access to care. RESULTS: Unadjusted influenza coverage estimates were similar between AIAN and White respondents (68.1% vs 69.5%), but pneumococcal vaccination was lower among AIAN respondents (58.1% vs 67.2%; P<.01). After multivariable adjustment for sociodemographic characteristics, self-reported coverage for both vaccines was statistically similar between AIAN and White adults. CONCLUSIONS: Although there was no disparity in influenza coverage, pneumococcal coverage was lower among AIAN than among White respondents, probably because of sociodemographic risk factors. Regional variation indicates a need to monitor coverage and target interventions to reduce disparities within geographically and culturally diverse subpopulations of AIAN persons.

Promoting Adult Immunization Using Population-Based Data for a Composite Measure.

INTRODUCTION: A composite adult immunization status measure is currently under consideration for adoption into the Healthcare Effectiveness Data and Information Set. This paper complements the Healthcare Effectiveness Data and Information Set health plan-level measure testing efforts by examining use of survey-based self-reported vaccination data to assess composite adult immunization coverage and identify limitations to using survey data to measure progress. METHODS: The 2015 National Health Interview Survey data were used in 2017 to calculate estimates for a composite of selected vaccines routinely recommended for adults aged ≥19 years, overall and in three age groups: 19-59, 60-64, and ≥65 years for tetanus and diphtheria toxoids (Td); tetanus toxoid; reduced diphtheria toxoid; and tetanus, diphtheria, acellular pertussis vaccine (Tdap); and herpes zoster, pneumococcal, and influenza vaccines. RESULTS: Composite coverage for adults aged ≥19 years including receipt of Tdap in the past 10 years and influenza vaccination was 11.9%, ranging from 6.3% in adults aged 60-64 years to 13.7% in adults aged 19-59 years. Excluding influenza, composite coverage was 20.7%, ranging from 8.1% (adults aged 60-64 years) to 25.2% (adults aged 19-59 years). In a composite including any Td-containing vaccine in the past 10 years, coverage including influenza vaccination for adults aged ≥19 years was 23.4%, ranging from 12.6% (adults aged 60-64 years) to 25.7% (adults aged 19-59 years). Excluding influenza, composite coverage was 51.4%, ranging from 15.8% (adults aged 60-64 years) to 63.0% (adults aged 19-59 years). CONCLUSIONS: Survey-based vaccination data may under- or over-estimate coverage, but most adults require at least one additional vaccination by any metric. A composite measure provides a single focal point to promote adherence to standards of care.

Akt and its downstream targets play key roles in mediating dormancy in land snails.

Estivation, a state of aerobic dormancy, facilitates survival during adverse environmental conditions and is characterized at the molecular level by regulatory protein phosphorylation. The Akt (protein kinase B) signaling pathway regulates diverse responses in cells and the present study analyzes its role in the estivating desert snail Otala lactea. Kinetic analysis (maximal velocity, substrate affinities) determined that Akt was activated in tissues of estivating snails and Western blotting and in vitro incubations promoting changes to Akt phosphorylation state both confirmed that higher amounts of active (phosphorylated Ser473) Akt were present during estivation. Akt protein stability was also enhanced during estivation as assessed from urea denaturation studies. Multiple downstream targets of Akt were differentially regulated during estivation. Estivating animals showed elevated levels of phosphorylated FOXO3a (Ser253) and BAD (Ser136), no change in mTOR (Ser2481 and Ser2448), and reduced amounts of phosphorylated glycogen synthase kinase-3 (GSK-3) beta subunit (Ser9). Kinetic analysis of GSK-3 showed 1.5-1.7 fold higher activities in estivating snails coupled with increased GSK-3 substrate affinities in hepatopancreas. The data suggest an active role for Akt signaling during estivation emphasizing anti-apoptotic actions but uncoupling growth/proliferation actions to help achieve life extension on a limited energy budget.

Human Papillomavirus Vaccine Uptake: Increase for American Indian Adolescents, 2013-2015.

INTRODUCTION: Although Indian Health Service, tribally-operated, and urban Indian (I/T/U) healthcare facilities have higher human papillomavirus (HPV) vaccine series initiation and completion rates among adolescent patients aged 13-17 years than the general U.S. population, challenges remain. I/T/U facilities have lower coverage for HPV vaccine first dose compared with coverage for other adolescent vaccines, and HPV vaccine series completion rates are lower than initiation rates. Researchers aimed to assist I/T/U facilities in identifying interventions to increase HPV vaccination series initiation and completion rates. STUDY DESIGN: Best practice and intervention I/T/U healthcare facilities were identified based on baseline adolescent HPV vaccine coverage data. Healthcare professionals were interviewed about barriers and facilitators to HPV vaccination. Researchers used responses and evidence-based practices to identify and assist facilities in implementing interventions to increase adolescent HPV vaccine series initiation and completion. Coverage and interview data were collected from June 2013 to June 2015; data were analyzed in 2015. SETTING/PARTICIPANTS: I/T/U healthcare facilities located within five Indian Health Service regions. INTERVENTION: Interventions included analyzing and providing feedback on facility vaccine coverage data, educating providers about HPV vaccine, expanding access to HPV vaccine, and establishing or expanding reminder recall and education efforts. MAIN OUTCOME MEASURES: Impact of evidence-based strategies and best practices to support HPV vaccination. RESULTS: Mean baseline first dose coverage with HPV vaccine at best practice facilities was 78% compared with 46% at intervention facilities. Mean third dose coverage was 48% at best practice facilities versus 19% at intervention facilities. Intervention facilities implemented multiple low-cost, evidence-based strategies and best practices to increase vaccine coverage. At baseline, most facilities used electronic provider reminders, had standing orders in place for administering HPV vaccine, and administered tetanus, diphtheria, and acellular pertussis and HPV vaccines during the same visit. At intervention sites, mean coverage for HPV initiation and completion increased by 24% and 22%, respectively. CONCLUSIONS: A tailored multifaceted approach addressing vaccine delivery processes and patient and provider education may increase HPV vaccine coverage.

Endocrine therapy for breast cancer prevention in high-risk women: clinical and economic considerations.

The global burden of breast cancer highlights the need for primary prevention strategies that demonstrate both favorable clinical benefit/risk profile and good value for money. Endocrine therapy with selective estrogen-receptor modulators (SERMs) or aromatase inhibitors (AIs) has been associated with a favorable clinical benefit/risk profile in the prevention of breast cancer in women at high risk of developing the disease. The available endocrine therapy strategies differ in terms of their relative reductions of breast cancer risk, potential side effects, and upfront drug acquisition costs, among others. This review highlights the clinical trials of SERMs and AIs for the primary prevention of breast cancer, and the cost-effectiveness /cost-utility studies that have examined their "value for money" in various health care jurisdictions.

Meeting the Challenges of Immunizing Adults.

The overall burden of illness from diseases for which vaccines are available disproportionately falls on adults. Adults are recommended to receive vaccinations based on their age, underlying medical conditions, lifestyle, prior vaccinations, and other considerations. Updated vaccine recommendations from CDC are published annually in the U.S. Adult Immunization Schedule. Vaccine use among U.S. adults is low. Although receipt of a provider (physician or other vaccinating healthcare provider) recommendation is a key predictor of vaccination, more often consumers report not receiving vaccine recommendations at healthcare provider visits. Although providers support the benefits of vaccination, they also report several barriers to vaccinating adults, including the cost of providing vaccination services, inadequate or inconsistent payment for vaccines and vaccine administration, and acute medical care taking precedence over preventive services. Despite these challenges, a number of strategies have been demonstrated to substantially improve adult vaccine coverage, including patient and provider reminders and standing orders for vaccination. Providers are encouraged to incorporate routine assessment of their adult patients' vaccination needs during all clinical encounters to ensure patients receive recommendations for needed vaccines and are either offered needed vaccines or referred for vaccination.

Meeting the Challenges of Immunizing Adults.

The overall burden of illness from diseases for which vaccines are available disproportionately falls on adults. Adults are recommended to receive vaccinations based on their age, underlying medical conditions, lifestyle, prior vaccinations, and other considerations. Updated vaccine recommendations from CDC are published annually in the U.S. Adult Immunization Schedule. Vaccine use among U.S. adults is low. Although receipt of a provider (physician or other vaccinating healthcare provider) recommendation is a key predictor of vaccination, more often consumers report not receiving vaccine recommendations at healthcare provider visits. Although providers support the benefits of vaccination, they also report several barriers to vaccinating adults, including the cost of providing vaccination services, inadequate or inconsistent payment for vaccines and vaccine administration, and acute medical care taking precedence over preventive services. Despite these challenges, a number of strategies have been demonstrated to substantially improve adult vaccine coverage, including patient and provider reminders and standing orders for vaccination. Providers are encouraged to incorporate routine assessment of their adult patients' vaccination needs during all clinical encounters to ensure patients receive recommendations for needed vaccines and are either offered needed vaccines or referred for vaccination.