Lower respiratory tract infection hospitalizations among American Indian/Alaska Native adults, Indian Health Service and Alaska Region, 1998-2014.

OBJECTIVES: This study describes the changes in lower respiratory tract infection (LRTI) rates from 1998 to 2014 among hospitalized American Indian/Alaska Native (AI/AN) adults residing in Alaska and other Indian Health Service (IHS) regions. METHODS: Age-adjusted hospital discharge rates and rate ratios were calculated from the IHS Direct and Contract Health Services Inpatient Dataset, IHS National Patient Information Reporting System for AI/AN adults ≥18 years, hospitalized at an IHS-operated, tribally operated, or contract hospital with an LRTI-associated diagnosis during 1998-2014. RESULTS: Overall, there were 13 733 LRTI-associated hospitalizations in Alaska (1998-2014), with an age-adjusted rate of 13.7/1000 adults. Among non-Alaska (non-AK) AI/AN, there were a total of 79 170 hospitalizations, with a rate of 8.6/1000 adults. In the pre-PCV7 and pre-PCV13 periods, LRTI rates were higher in Alaska (AK) AI/AN (12.4 and 14.1, respectively) when compared to non-AK AI/AN (10.1 and 9.1, respectively) (P < 0.0001). In the post-PCV7 and post-PCV13 periods, LRTI rates were also higher in AK (13.5 and 15.0, respectively) compared to non-AK (9.2 and 7.3, respectively) (P < 0.0001). CONCLUSIONS: Over the study period, a 26% increase in rates of LRTI among adult AI/AN residing in AK compared with a 38% decrease in rates among AI/AN residing in non-AK were observed. This disparity is likely due to a variety of factors such as tobacco use, crowding, etc. Strategies to reduce LRTI in AI/AN adults are needed.

Electronic Health Record Reminders for Chlamydia Screening in an American Indian Population.

OBJECTIVES: Indian Health Service (IHS) screening rates for Chlamydia trachomatis are lower than national rates of chlamydia screening in the Southwest. We describe and evaluate the effect of a public health intervention consisting of electronic health record (EHR) reminders to alert health care providers to screen for chlamydia at an IHS facility. We also conducted an awareness presentation among health care providers on chlamydia screening. METHODS: We conducted our intervention from November 1, 2013, through October 31, 2015, at an IHS facility in the Southwest. We implemented algorithms that queried database values to assess chlamydia screening performance in 6 clinical departments. We presented data on the screening performance of clinical departments and health care providers (de-identified) in the awareness presentations. We re-queried database values 1 and 2 years after implementation of the EHR reminder intervention to evaluate before-and-after screening rates, comparing data among all patients and among female patients only. RESULTS: We found small, sustained relative increases in chlamydia screening rates during the 2012-2015 evaluation period: 20.8% pre-intervention to 24.9% and 24.2% one and two years postintervention, respectively, across all patients; 32.3% preintervention to 36.6% and 35.6% one and two years postintervention, respectively, among female patients. Increases in clinical department-specific screening rates varied and were most prominent in internal medicine (35.8% preintervention to peak 65.8% postintervention). The 1 clinic (obstetrics-gynecology) that did not receive an awareness presentation showed a consistent downward trend in screening rates, although absolute rates were consistently higher in that clinic than in other clinics. CONCLUSIONS: Awareness presentations that offer feedback to health care providers on screening performance, heighten provider awareness of the importance of chlamydia screening, and promote development of novel provider-initiated screening protocols may help to increase screening rates when combined with EHR reminders.

Cancers Associated with Human Papillomavirus in American Indian and Alaska Native Populations - United States, 2013-2017.

Human papillomavirus (HPV) causes most cervical cancers and some cancers of the penis, vulva, vagina, oropharynx, and anus. Cervical precancers can be detected through screening. HPV vaccination with the 9-valent HPV vaccine (9vHPV) can prevent approximately 92% of HPV-attributable cancers (1).* Previous studies have shown lower incidence of HPV-associated cancers in non-Hispanic American Indian and Alaska Native (AI/AN) populations compared with other racial subgroups (2); however, these rates might have been underestimated as a result of racial misclassification. Previous studies have shown that cancer registry data corrected for racial misclassification resulted in more accurate cancer incidence estimates for AI/AN populations (3,4). In addition, regional variations in cancer incidence among AI/AN populations suggest that nationally aggregated data might not adequately describe cancer outcomes within these populations (5). These variations might, in part, result from geographic disparities in the use of health services, such as cancer screening or vaccination (6). CDC analyzed data for 2013-2017 from central cancer registries linked with the Indian Health Service (IHS) patient registration database to assess the incidence of HPV-associated cancers and to estimate the number of cancers caused by HPV among AI/AN populations overall and by region. During 2013-2017, an estimated 1,030 HPV-associated cancers were reported in AI/AN populations. Of these cancers, 740 (72%) were determined to be attributable to HPV types targeted by 9vHPV; the majority were cervical cancers in females and oropharyngeal cancers in males. These data can help identify regions where AI/AN populations have disproportionately high rates of HPV-associated cancers and inform targeted regional vaccination and screening programs in AI/AN communities.

Hepatitis C in pregnant American Indian and Alaska native women; 2003-2015.

Recent reports have found a rise in Hepatitis C virus (HCV) infection in reproductive age women in the USA. Surveillance data suggests one group that is at increased risk of HCV infection is the American Indian and Alaska Native population (AI/AN). Using the National Center for Health Statistics (NCHS) birth certificate and the Indian Health Services, Tribal, and Urban Indian (IHS) databases, we evaluated reported cases of HCV infection in pregnant women between 2003 and 2015. In the NCHS database, 38 regions consistently reported HCV infection. The percentage of mothers who were known to have HCV infection increased between 2011 and 2015 in both the AI/AN population (0.57% to 1.19%, p < 0.001) and the non-AI/AN population (0.21% to 0.36%, p < 0.001). The IHS database confirmed these results. Individuals with hepatitis B infection or intravenous drug use (IDU) had significantly higher odds of HCV infection (OR 16.4 and 17.6, respectively). In total, 62% of HCV-positive women did not have IDU recorded. This study demonstrates a significant increase in the proportion of pregnant women infected with HCV between 2003 and 2015. This increase was greater in AI/AN women than non-AI/AN women. This highlights the need for HCV screening and prevention in pregnant AI/AN women.

Transmission of hepatitis C virus associated with surgical procedures - New Jersey 2010 and Wisconsin 2011.

Incidents of health care-associated hepatitis C virus (HCV) transmission that resulted from breaches in injection safety and infection prevention practices have been previously documented. During 2010 and 2011, separate, unrelated, occurrences of HCV infections in New Jersey and Wisconsin associated with surgical procedures were investigated to determine sources of HCV and mechanisms of HCV transmission. Molecular analyses of HCV strains and epidemiologic investigations indicated that transmission likely resulted from breaches of infection prevention practices. Health care and public health professionals should consider health care-associated transmission when evaluating acute HCV infections.

Secondhand tobacco smoke: a source of lead exposure in US children and adolescents.

OBJECTIVES: We evaluated the relationship between secondhand tobacco smoke (SHS) exposure and blood lead levels in US children and adolescents. METHODS: We analyzed data from 6830 participants aged 3-19 years in the National Health and Nutrition Examination Survey (1999-2004) who were not active smokers and for whom SHS exposure information and blood lead measurements were available. RESULTS: After multivariable adjustment, participants in the highest quartile of serum cotinine (≥ 0.44 µg/L) had 28% (95% confidence interval = 21%, 36%) higher blood lead levels than had those in the lowest quartile (< 0.03 µg/L). Similarly, blood lead levels were 14% and 24% higher in children who lived with 1 or with 2 or more smokers, respectively, than they were in children living with no smokers. Among participants for whom lead dust information was available, the associations between SHS and blood lead levels were similar before and after adjustment for lead dust concentrations. CONCLUSIONS: SHS may contribute to increased blood lead levels in US children. Lead dust does not appear to mediate this association, suggesting inhalation as a major pathway of exposure. Eliminating SHS exposure could reduce lead exposure in children.

ER stress response during the differentiation of H9 cells induced by retinoic acid.

Endoplasmic reticulum (ER) stress occurs during early embryonic development. The aim of this study is to determine whether ER stress occurs during human embryonic stem cell differentiation induced by retinoic acid (RA). H9 human embryonic stem cells were subjected to RA treatment for up to 29days to induce differentiation. HEK293 cells were treated with RA as a control. The results demonstrate that several ER stress-responsive genes are differentially regulated in H9 and HEK293 cells in response to 5days of RA treatment. GRP78/Bip was upregulated in H9 cells but downregulated in HEK293 cells. eIF2α was downregulated in H9 cells but not in HEK293 cells. Phosphorylation of eIF2α was downregulated in H9 cells but upregulated in HEK293 cells. XBP-1 was downregulated immediately after RA treatment in H9 cells, but its downregulation was much slower in HEK293 cells. Additionally, two ER-resident E3 ubiquitin ligases, gp78 and Hrd1, were both upregulated in H9 cells following 5 days of exposure to RA. Moreover, the protein Bcl2 was undetectable in H9 cells and H9-derived cells but was expressed in HEK293 cells, and it expression in the two types of cells was unaltered by RA treatment. In H9 cells treated with RA for 29 days, GRP78/Bip, XBP-1 and Bcl2 were all upregulated. These results suggest that ER stress is involved in H9 cell differentiation induced by RA.

AAA ATPase p97/valosin-containing protein interacts with gp78, a ubiquitin ligase for endoplasmic reticulum-associated degradation.

Endoplasmic reticulum-associated degradation (ERAD) is a protein quality control mechanism that eliminates unwanted proteins from the endoplasmic reticulum (ER) through a ubiquitin-dependent proteasomal degradation pathway. gp78 is a previously described ER membrane-anchored ubiquitin ligase (E3) involved in ubiquitination of ER proteins. AAA ATPase (ATPase associated with various cellular activities) p97/valosin-containing protein (VCP) subsequently dislodges the ubiquitinated proteins from the ER and chaperones them to the cytosol, where they undergo proteasomal degradation. We now report that gp78 physically interacts with p97/VCP and enhances p97/VCP-polyubiquitin association. The enhanced association correlates with decreases in ER stress-induced accumulation of polyubiquitinated proteins. This effect is abolished when the p97/VCP-interacting domain of gp78 is removed. Further, using ERAD substrate CD3delta, gp78 consistently enhances p97/VCP-CD3delta binding and facilitates CD3delta degradation. Moreover, inhibition of endogenous gp78 expression by RNA interference markedly increases the levels of total polyubiquitinated proteins, including CD3delta, and abrogates VCP-CD3delta interactions. The gp78 mutant with deletion of its p97/VCP-interacting domain fails to increase CD3delta degradation and leads to accumulation of polyubiquitinated CD3delta, suggesting a failure in delivering ubiquitinated CD3delta for degradation. These data suggest that gp78-p97/VCP interaction may represent one way of coupling ubiquitination with retrotranslocation and degradation of ERAD substrates.