Volume 11, Issue 41 October 15, 2019

CDC Science Clips: Volume 11, Issue 41, October 15, 2019

Science Clips is produced weekly to enhance awareness of emerging scientific knowledge for the public health community. Each article features an Altmetric Attention scoreexternal icon to track social and mainstream media mentions!

  1. CDC Public Health Grand Rounds
    • Health Disparities – Individuals with Intellectual Disabilities
      1. [No abstract]

      2. Contraceptive use at last intercourse among reproductive-aged women with disabilities: an analysis of population-based data from seven statesexternal icon
        Haynes RM, Boulet SL, Fox MH, Carroll DD, Courtney-Long E, Warner L.
        Contraception. 2018 Jun;97(6):538-545.
        OBJECTIVE: To assess patterns of contraceptive use at last intercourse among women with physical or cognitive disabilities compared to women without disabilities. STUDY DESIGN: We analyzed responses to 12 reproductive health questions added by seven states to their 2013 Behavioral Risk Factor Surveillance System questionnaire. Using responses from female respondents 18-50 years of age, we performed multinomial regression to calculate estimates of contraceptive use among women at risk for unintended pregnancy by disability status and type, adjusted for age, race/ethnicity, marital status, education, health insurance status, and parity. RESULTS: Women with disabilities had similar rates of sexual activity as women without disabilities (90.0% vs. 90.6%, p=.76). Of 5995 reproductive-aged women at risk for unintended pregnancy, 1025 (17.1%) reported one or more disabilities. Contraceptive use at last intercourse was reported by 744 (70.1%) of women with disabilities compared with 3805 (74.3%) of those without disabilities (p=.22). Among women using contraception, women with disabilities used male or female permanent contraception more often than women without disabilities (333 [29.6%] versus 1337 [23.1%], p<.05). Moderately effective contraceptive (injection, oral contraceptive, patch, or ring) use occurred less frequently among women with cognitive (13.1%, n=89) or independent living (13.9%, n=40) disabilities compared to women without disabilities (22.2%, n=946, p<.05). CONCLUSIONS: The overall prevalence of sexual activity and contraceptive use was similar for women with and without physical or cognitive disabilities. Method use at last intercourse varied based on presence and type of disability, especially for use of permanent contraception. IMPLICATIONS: Although women with disabilities were sexually active and used contraception at similar rates as women without disabilities, contraception use varied by disability type, suggesting the importance of this factor in reproductive health decision-making among patients and providers, and the value of further research to identify reasons why this occurs.

      3. Health disparities of adults with intellectual disabilities: what do we know? What do we do?external icon
        Krahn GL, Fox MH.
        J Appl Res Intellect Disabil. 2014 Sep;27(5):431-46.
        BACKGROUND: Recent attention to health of people with intellectual disabilities has used a health disparities framework. Building on historical context, the paper summarizes what is known about health disparities from reports and research and provide direction on what to do to reduce these disparities among adults with intellectual disabilities. METHODS: The present authors examined literature from 2002 to 2011 on health disparities and people with disabilities looking for broad themes on documenting disparities and on research approaches and methods. RESULTS: Multiple countries published reports on health of people with intellectual disabilities. Researchers summarized existing research within a health disparities framework. A number of promising methodologies are identified such as health services research, health indicators, enhanced surveillance and mixed-methods. CONCLUSIONS: Strategies to reduce health disparities include use of data to educate decision makers, attention to social determinants and a life-course model and emphasis on leveraging inclusion in mainstream services where possible.

      4. A cascade of disparities: health and health care access for people with intellectual disabilitiesexternal icon
        Krahn GL, Hammond L, Turner A.
        Ment Retard Dev Disabil Res Rev. 2006 ;12(1):70-82.
        People with ID represent approximately 2% of the population and, as a group, experience poorer health than the general population. This article presents recent conceptualizations that begin to disentangle health from disability, summarizes the literature from 1999 to 2005 in terms of the cascade of disparities, reviews intervention issues and promising practices, and provides recommendations for future action and research. The reconceptualization of health and disability examines health disparity in terms of the determinants of health (genetic, social circumstances, environment, individual behaviors, health care access) and types of health conditions (associated, comorbid, secondary). The literature is summarized in terms of a cascade of disparities experienced by people with ID, including a higher prevalence of adverse conditions, inadequate attention to care needs, inadequate focus on health promotion, and inadequate access to quality health care services. Promising practices are reviewed from the perspective of persons with ID, providers of care and services, and policies that influence systems of care. Recommendations across multiple countries and organizations are synthesized as guidelines to direct future action. They call for promoting principles of early identification, inclusion, and self-determination of people with ID; reducing the occurrence and impact of associated, comorbid, and secondary conditions; empowering caregivers and family members; promoting healthy behaviors in people with ID; and ensuring equitable access to quality health care by people with ID. Their broadscale implementations would begin to reduce the health disparity experienced by people with ID.

      5. Using Medicaid data to characterize persons with intellectual and developmental disabilities in five U.S. statesexternal icon
        McDermott S, Royer J, Cope T, Lindgren S, Momany E, Lee JC, McDuffie MJ, Lauer E, Kurtz S, Armour BS.
        Am J Intellect Dev Disabil. 2018 Jul;123(4):371-381.
        This project sought to identify Medicaid members with intellectual and developmental disabilities (IDD) in five states (Delaware, Iowa, Massachusetts, New York, and South Carolina) to develop a cohort for subsequent analyses of medical conditions and service utilization. We estimated that over 300,000 Medicaid members in these states had IDD. All members with diagnostic codes for IDD were identified and the three most frequent diagnoses were unspecified intellectual disability, autism or pervasive developmental disorder, and cerebral palsy. The percentage of Medicaid members with IDD ranged from 2.3% in New York to 4.2% in South Carolina. Identifying and characterizing people with IDD is a first step that could guide public health promotion efforts for this population.

      6. INTRODUCTION: Ambulatory care sensitive conditions (ACSCs) can be seen as failure of access or management in primary care settings. Identifying factors associated with ACSCs for individuals with an Intellectual Disability (ID) provide insight into potential interventions. METHOD: To assess the association between emergency department (ED) ACSC visits and a number of demographic and health characteristics of South Carolina Medicaid members with ID. A retrospective cohort of adults with ID was followed from 2001 to 2011. Using ICD-9-CM codes, four ID subgroups, totalling 14 650 members, were studied. RESULTS: There were 106 919 ED visits, with 21 214 visits (19.8%) classified as ACSC. Of those, 82.9% were treated and released from EDs with costs averaging $578 per visit. People with mild and unspecified ID averaged greater than one ED visit per member year. Those with Down syndrome and other genetic cause ID had the lowest rates of ED visits but the highest percentage of ACSC ED visits that resulted in inpatient hospitalisation (26.6% vs. an average of 16.8% for other subgroups). When compared with other residential types, those residing at home with no health support services had the highest ED visit rate and were most likely to be discharged back to the community following an ED visit (85.2%). Adults residing in a nursing home had lower rates of ED visits but were most likely to be admitted to the hospital (38.9%) following an ED visit. Epilepsy and convulsions were the leading cause (29.6%) of ACSC ED visits across all subgroups and residential settings. CONCLUSION: Prevention of ACSC ED visits may be possible by targeting adults with ID who live at home without health support services.

      7. Using all-payer claims data for health surveillance of people with intellectual and developmental disabilitiesexternal icon
        Phillips KG, Houtenville AJ, Reichard A.
        J Intellect Disabil Res. 2019 Apr;63(4):327-337.
        BACKGROUND: To address limitations and challenges associated with current health surveillance of people with intellectual and developmental disabilities (IDD), this study investigates the use of all-payer claims data to identify and characterise this population. METHOD: All-payer claims data from 2010 to 2014 were used to study people with IDD in New Hampshire. Starting with the Centers for Medicare and Medicaid Services’ algorithm, IDD was defined using ICD-9 diagnosis codes. Additional ICD-9 codes for developmental disabilities were included to build the knowledge base begun by recent research conducted on Medicaid claimants in five other states. RESULTS: Findings showed the enhanced algorithm offers a replicable and feasible way to conduct health surveillance of people with IDD at the state level. CONCLUSION: Substantive and significant differences between Medicaid and commercial claimants suggest that using all-payer claims provides a richer and more complete method for health surveillance of people with IDD.

      8. A longitudinal assessment of adherence to breast and cervical cancer screening recommendations among women with and without intellectual disabilityexternal icon
        Xu X, McDermott SW, Mann JR, Hardin JW, Deroche CB, Carroll DD, Courtney-Long EA.
        Prev Med. 2017 Jul;100:167-172.
        Each year in the United States, about 4000 deaths are attributed to cervical cancer, and over 40,000 deaths are attributed to breast cancer (U.S. Cancer Statistics Working Group, 2015). The purpose of this study was to identify predictors of full, partial, and no screening for breast and cervical cancer among women with and without intellectual disability (ID) who are within the age group for screening recommended by the U.S. Preventive Service Task Force (USPSTF), while accounting for changes in recommendations over the study period. Women with ID and an age matched comparison group of women without ID were identified using merged South Carolina Medicaid and Medicare files from 2000 to 2010. The sample consisted of 9406 and 16,806 women for mammography screening and Papanicolaou (Pap) testing adherence, respectively. We estimated multinomial logistic regression models and determined that women with ID were significantly less likely than women without ID to be fully adherent compared to no screening with mammography recommendations (adjusted odds ratio [AOR]: 0.63, 95% confidence interval [CI] 0.55-0.72), and Pap testing recommendations (AOR: 0.17, 95% CI 0.16-0.19). For the 70% of women with ID for whom we had residential information, those who lived in a group home, medical facility, or supervised community living setting were more likely to be fully adherent with both preventive services than those living alone or with family members. For both outcomes, women residing in a supervised nonmedical community living setting had the highest odds of full adherence, adjusting for other covariates.

  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. Public health practitioners need quick and easy access to reliable surveillance data to monitor states’ progress over time, compare benchmarks nationally or among states, and make strategic decisions about priorities and resources. Data, Trends, and Maps (DTM) at is a free, online interactive database that houses and displays data on nutrition, physical activity, breastfeeding, and obesity that practitioners can use for public health action. Created in 2015 by the Centers for Disease Control and Prevention’s (CDC) Division of Nutrition, Physical Activity, and Obesity, DTM was updated and relaunched in April 2017 with the capability to customize and download data sets directly; DTM also has other user-friendly features, such as visualization options. Since its relaunch, DTM has received more than 386,000 page views from approximately 110,000 unique visitors. However, the potential exists for more widespread use of DTM if more public health practitioners understood what the site offered and how others have used it in the field. Here, we explain how public health practitioners can explore the most recent state-level data on nutrition, physical activity, breastfeeding, and obesity and use this data to inform programmatic and policy efforts to prevent and control chronic diseases. We demonstrate 3 different ways practitioners can visualize data (ie, Explore by Location, Explore by Topic, and the Open Data Portal) and present 3 real-world examples to highlight DTM’s utility as a public health tool.

      2. [No abstract]

      3. Modeling the health and budgetary impacts of a team-based hypertension care intervention that includes pharmacistsexternal icon
        Overwyk KJ, Dehmer SP, Roy K, Maciosek MV, Hong Y, Baker-Goering MM, Loustalot F, Singleton CM, Ritchey MD.
        Med Care. 2019 Sep 18.
        OBJECTIVE: The objective of this study was to assess the potential health and budgetary impacts of implementing a pharmacist-involved team-based hypertension management model in the United States. RESEARCH DESIGN: In 2017, we evaluated a pharmacist-involved team-based care intervention among 3 targeted groups using a microsimulation model designed to estimate cardiovascular event incidence and associated health care spending in a cross-section of individuals representative of the US population: implementing it among patients with (1) newly diagnosed hypertension, (2) persistently (>/=1 year) uncontrolled blood pressure (BP), or (3) treated, yet persistently uncontrolled BP-and report outcomes over 5 and 20 years. We describe the spending thresholds for each intervention strategy to achieve budget neutrality in 5 years from a payer’s perspective. RESULTS: Offering this intervention could prevent 22.9-36.8 million person-years of uncontrolled BP and 77,200-230,900 heart attacks and strokes in 5 years (83.8-174.8 million and 393,200-922,900 in 20 years, respectively). Health and economic benefits strongly favored groups 2 and 3. Assuming an intervention cost of $525 per enrollee, the intervention generates 5-year budgetary cost-savings only for Medicare among groups 2 and 3. To achieve budget neutrality in 5 years across all groups, intervention costs per person need to be around $35 for Medicaid, $180 for private insurance, and $335 for Medicare enrollees. CONCLUSIONS: Adopting a pharmacist-involved team-based hypertension model could substantially improve BP control and cardiovascular outcomes in the United States. Net cost-savings among groups 2 and 3 make a compelling case for Medicare, but favorable economics may also be possible for private insurers, particularly if innovations could moderately lower the cost of delivering an effective intervention.

    • Communicable Diseases
      1. Severe human metapneumovirus and group A Streptococcus pneumonia in an immunocompetent adultexternal icon
        Biggs HM, Van Beneden CA, Kurkjian K, Kobayashi M, Peret TC, Watson JT, Schneider E, Gerber SI, Ravishankar J.
        Clin Infect Dis. 2019 Sep 29.
        An immunocompetent adult with asthma developed severe human metapneumovirus (HMPV) illness complicated by group A Streptococcus coinfection, progressing to ARDS and shock. Several coworkers had less severe HMPV infection. HMPV can cause severe respiratory illness in healthy adults and should be considered as a potential cause of community respiratory outbreaks.

      2. Progress toward rubella and congenital rubella syndrome control and elimination – worldwide, 2000-2018external icon
        Grant GB, Desai S, Dumolard L, Kretsinger K, Reef SE.
        MMWR Morb Mortal Wkly Rep. 2019 Oct 4;68(39):855-859.
        Rubella is a leading cause of vaccine-preventable birth defects. Although rubella virus infection usually causes a mild febrile rash illness in children and adults, infection during pregnancy, especially during the first trimester, can result in miscarriage, fetal death, stillbirth, or a constellation of birth defects known as congenital rubella syndrome (CRS). A single dose of rubella-containing vaccine (RCV) can provide lifelong protection (1). In 2011, the World Health Organization (WHO) updated guidance on the use of RCV and recommended capitalizing on the accelerated measles elimination activities as an opportunity to introduce RCV (1). The Global Vaccine Action Plan 2011-2020 (GVAP) includes a target to achieve elimination of rubella in at least five of the six WHO regions by 2020 (2). This report on the progress toward rubella and CRS control and elimination updates the 2017 report (3), summarizing global progress toward the control and elimination of rubella and CRS from 2000 (the initiation of accelerated measles control activities) and 2012 (the initiation of accelerated rubella control activities) to 2018 (the most recent data) using WHO immunization and surveillance data. Among WHO Member States,* the number with RCV in their immunization schedules has increased from 99 (52% of 191) in 2000 to 168 (87% of 194) in 2018(dagger); 69% of the world’s infants were vaccinated against rubella in 2018. Rubella elimination has been verified in 81 (42%) countries. To make further progress to control and eliminate rubella, and to reduce the equity gap, introduction of RCV in all countries is important. Likewise, countries that have introduced RCV can achieve and maintain elimination with high vaccination coverage and surveillance for rubella and CRS. The two WHO regions that have not established an elimination goal (African [AFR] and Eastern Mediterranean [EMR]) should consider establishing a goal.( section sign).

      3. Janibacter species with evidence of genomic polymorphism isolated from resected heart valve in a patient with aortic stenosisexternal icon
        Malania L, Bai Y, Khanipov K, Tsereteli M, Metreveli M, Tsereteli D, Sidamonidze K, Imnadze P, Fofanov Y, Kosoy M.
        Infect Dis Rep. 2019 Sep 18;11(2):8132.
        The authors report isolation and identification of two strains of bacteria belonging to the genus Janibacter from a human patient with aortic stenosis from a rural area of the country of Georgia. The microorganisms were isolated from aortic heart valve. Two isolates with slightly distinct colony morphologies were harvested after sub-culturing from an original agar plate. Preliminary identification of the isolates is based on amplification and sequencing of a fragment of 16SrRNA. Whole genome sequencing was performed using the Illumina MiSeq instrument. Both isolates were identified as undistinguished strains of the genus Janibacter. Characterization of whole genome sequences of each culture has revealed a 15% difference in gene profile between the cultures and confirmed that both strains belong to the genus Janibacter with the closest match to J. terrae. Genomic comparison of cultures of Janibacter obtained from human cases and from environmental sources presents a promising direction for evaluating a role of these bacteria as human pathogens.

      4. Introduction: Hospital-based surveillance programs only capture people presenting to facilities and may underestimate disease burden. We conducted a healthcare utilisation survey to characterise healthcare-seeking behaviour among people with common infectious syndromes in the catchment areas of two sentinel surveillance hospitals in Johannesburg, South Africa. Methods: A cross-sectional survey was conducted within three regions of Johannesburg from August to November 2015. Premises were randomly selected from an enumerated list with data collected on household demographics and selected syndromes using a structured questionnaire. Fisher’s exact or chi-square tests were used to determine association of characteristics among different regions. Results: Of 3650 selected coordinates, 3358 were eligible dwellings and 2930 (87%) households with 9850 individuals participated. Four percent of participants (431/9850) reported influenza-like illness (ILI) in the last 30 days; equal numbers of participants (0.2%, 20/9850) reported pneumonia or tuberculosis symptoms in the last year and <1% reported diarrhoea or meningitis symptoms. Sixty eight percent (295/431) of participants who reported ILI, 75% (6/8) of children with diarrhoea and all participants who reported pneumonia (20), tuberculosis (20) or meningitis (6) sought healthcare. For all syndromes most sought care at registered healthcare providers. Of these only 10% (24/237) attended sentinel hospitals, predominantly those that lived closer to the hospitals. In contrast, of patients with meningitis, 50% (3/6) sought care at sentinel hospitals. Conclusion: Patterns of seeking healthcare differed by syndrome and distance from facilities. Surveillance programs are still relevant in collecting information on infectious syndromes and reflect a proportion of the hospital’s catchment area.

      5. CONTEXT: An estimated 21% of non-U.S.-born persons in the United States have a reactive tuberculin skin test (TST) and are at risk of progressing to TB disease. The effectiveness of strategies by healthcare facilities to improve targeted TB infection testing and linkage to care among this population is unclear. EVIDENCE ACQUISITION: Following Cochrane guidelines, we searched several sources to identify studies that assessed strategies directed at healthcare providers and/or non-U.S.-born patients in U.S. healthcare facilities. EVIDENCE SYNTHESIS: Seven studies were eligible. In a randomized controlled trial (RCT), patients with reactive TST who received reminders for follow-up appointments were more likely to attend appointments (risk ratio, RR = 1.05, 95% confidence interval 1.00-1.10), but rates of return in a quasi-RCT study using patient reminders did not significantly differ between study arms (P = 0.520). Patient-provider language concordance in a retrospective cohort study did not increase provider referrals for testing (P = 0.121) or patient testing uptake (P = 0.159). Of three studies evaluating pre and post multifaceted interventions, two increased TB infection testing (from 0% to 77%, p < .001 and RR 2.28, 1.08-4.80) and one increased provider referrals for TST (RR 24.6, 3.5-174). In another pre-post study, electronic reminders to providers increased reading of TSTs (RR 2.84, 1.53-5.25), but only to 25%. All seven studies were at high risk of bias. CONCLUSIONS: Multifaceted strategies targeting providers may improve targeted TB infection testing in non-U.S.-born populations visiting U.S. healthcare facilities; uncertainties exist due to low-quality evidence. Additional high-quality studies on this topic are needed.

      6. Urine lipoarabinomannan (LAM) and antimicrobial usage in seriously-ill HIV-infected patients with sputum smear-negative pulmonary tuberculosisexternal icon
        Mthiyane T, Peter J, Allen J, Connolly C, Davids M, Rustomjee R, Holtz TH, Malinga L, Dheda K.
        J Thorac Dis. 2019 Aug;11(8):3505-3514.
        Background: Based on current WHO guidelines, hospitalized tuberculosis (TB) and HIV co-infected patients with CD4 count <100 cells/mm(3) who are urine lipoarabinomannan (LAM) positive should be initiated on TB treatment. This recommendation is conditional, and data are limited in sputum smear-negative patients from TB endemic countries where the LAM test is largely inaccessible. Other potential benefits of LAM, including reduction in antibiotic usage have, hitherto, not been explored. Methods: We consecutively enrolled newly-admitted seriously-ill HIV-infected patients (n=187) with suspected TB from three hospitals in KwaZulu-Natal, South Africa. All patients were empirically treated for TB as per the WHO 2007 smear-negative TB algorithm (patients untreated for TB were not recruited). Bio-banked urine, donated prior to anti-TB treatment, was tested for TB-infection using a commercially available LAM-ELISA test. TB sputum and blood cultures were performed. Results: Data from 156 patients containing CD4 count, urine-LAM, sputum and blood culture results were analysed. Mean age was 37 years, median CD4-count was 75 cells/mm(3) [interquartile range (IQR), 34-169 cells/mm(3)], 54/156 (34.6%) were sputum culture-positive, 12/54 (22.2%) blood-culture positive, and 53/156 (34.0%) LAM-positive. Thus, LAM sensitivity was 55.6% (30/54). The study design did not allow for calculation of specificity. Urine-LAM positivity was associated with low CD4 count (P=0.002). Ninety-point-six percent (48/53) of LAM-positive patients received antibiotics [15/48 (31.3%), 23/48 (47.9%) and 10/48 (20.8%) received one, two or three different antibiotics respectively], while the duration of antibiotic therapy was more than 5 days in 26 of 46 (56.5%) patients. Conclusions: Urine LAM testing in sputum smear-negative severely-ill hospitalized patients with TB-HIV co-infection and advanced immunosuppression, offered an immediate rule-in diagnosis in one-third of empirically treated patients. Moreover, LAM, by providing a rapid alternative diagnosis, could potentially reduce antibiotic overusage in such patients thereby reducing health-care costs and facilitating antibiotic stewardship.

      7. Integrated HIV surveillance finds recent adult hepatitis B virus (HBV) transmission and intermediate HBV prevalence among military in uncharacterized Caribbean countryexternal icon
        O’Connor SM, Mixson-Hayden T, Ganova-Raeva L, Djibo DA, Brown M, Xia GL, Kamili S, Jacobs M, Dong M, Thomas AG, Bulterys M, Hale B.
        PLoS One. 2019 ;14(10):e0222835.
        BACKGROUND: Guyana expanded its HIV response in 2005 but the epidemiology of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections has not been characterized. METHODS: The 2011 Seroprevalence and Behavioral Epidemiology Risk Survey for HIV and STIs collected biologic specimens with demographic and behavioral data from a representative sample of Guyana military personnel. Diagnostics included commercial serum: HIV antibody; total antibody to hepatitis B core (anti-HBc); IgM anti-HBc; hepatitis B surface antigen (HBsAg); anti-HBs; antibody to HCV with confirmatory testing; and HBV DNA sequencing with S gene fragment phylogenetic analysis. Chi-square, p-values and prevalence ratios determined statistical significance. RESULTS: Among 480 participants providing serologic specimens, 176 (36.7%) tested anti-HBc-positive. Overall, 19 (4.0%) participants tested HBsAg-positive; 17 (89.5%) of the HBsAg-positive participants also had detectable anti-HBc, including 1 (5.3%) IgM anti-HBc-positive male. Four (6.8%) females with available HBV testing were HBsAg-positive, all aged 23-29 years. Sixteen (16, 84.2%) HBsAg-positive participants had sufficient specimen for DNA testing. All 16 had detectable HBV DNA, 4 with viral load >2x104IU/ml. Sequencing found: 12 genotype (gt) A1 with 99.9% genetic identity between 1 IgM anti-HBc-positive and 1 anti-HBc-negative; 2 gtD1; and 2 with insufficient specimen. No statistically significant associations between risk factors and HBV infection were identified. CONCLUSIONS: Integrated HIV surveillance identified likely recent adult HBV transmission, current HBV infection among females of reproductive age, moderate HBV infection prevalence (all gtA1 and D1), no HCV infections and low HIV frequency among Guyana military personnel. Integrated HIV surveillance helped characterize HBV and HCV epidemiology, including probable recent transmission, prompting targeted responses to control ongoing HBV transmission and examination of hepatitis B vaccine policies.

      8. Extended prophylaxis with nevirapine does not affect growth in HIV-exposed infantsexternal icon
        Onyango-Makumbi C, Owora AH, Mwiru RS, Mwatha A, Young AM, Moodley D, Coovadia HM, Stranix-Chibanda L, Manji K, Maldonado Y, Richardson P, Andrew P, George K, Fawzi W, Fowler MG.
        J Acquir Immune Defic Syndr. 2019 Sep 13.
        BACKGROUND: Effects of prolonged nevirapine prophylaxis exposure on growth among HIV-exposed uninfected (HEU) infants are unknown. This study examines the impact of extended nevirapine prophylaxis from 6 weeks to 6 months on the growth of HEU infants followed for 18 months and also identifies correlates of incident wasting, stunting, underweight, and low head circumference in the HPTN 046 trial. METHODS: Intention-to-treat analysis examined the effect of extended nevirapine exposure on: weight-for-age Z-score (WAZ), length-for-age Z-score (LAZ), weight-for-length Z-score (WLZ) and head circumference-for-age (HCZ). Multivariable linear mixed-effects and Cox proportional hazard models were used to compare growth outcomes between the study arms and identify correlates of incident adverse growth outcomes, respectively. RESULTS: Compared to placebo, extended prophylactic nevirapine given daily from 6 weeks to 6 months did not affect growth in HEU breastfeeding (BF) infants over time (treatment x time: p>.05). However, overall growth declined over time (time effect: p<.01) when compared to WHO general population norms. Male sex was associated with higher risk of all adverse growth outcomes (p<.05), while short BF duration was associated with wasting (p=.03). Maternal ART exposure was protective against underweight (p=.02). Zimbabwe tended to have worse growth outcomes especially stunting, compared to South Africa, Uganda and Tanzania (p<.05). CONCLUSION: It is reassuring that prolonged exposure to nevirapine for prevention-of- maternal-to-child HIV transmission does not restrict growth. However, targeted interventions are needed to improve growth outcomes among at-risk HEU infants (i.e. male sex, short BF duration, lack of maternal ART exposure, and resident in Zimbabwe).

      9. Postinfectious irritable bowel syndrome after Campylobacter infectionexternal icon
        Scallan Walter EJ, Crim SM, Bruce BB, Griffin PM.
        Am J Gastroenterol. 2019 Oct;114(10):1649-1656.
        OBJECTIVES: Postinfectious irritable bowel syndrome (PI-IBS) is an important sequela of Campylobacter infection. Our goal is to estimate the incidence of Campylobacter-associated PI-IBS in the United States. METHODS: Data from January 1, 2010 to December 31, 2014, were obtained from the MarketScan Research Commercial Claims and Encounters Database. We identified patients with an encounter that included an International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code for “intestinal infection due to Campylobacter” (008.43) and individually matched them (on age group, sex, and length of enrollment) to a group of persons without a diagnosed Campylobacter infection (non-cases). The primary outcome of interest was a new diagnosis of IBS (International Classification of Diseases, Ninth Revision, Clinical Modification 564.1). RESULTS: Our final matched cohort included 4,143 cases and 20,491 non-cases. At 1 year, the incidence rate of IBS was 33.1 and 5.9 per 1,000 among cases and non-cases, respectively, with an unadjusted risk ratio of 5.6 (95% confidence interval [CI]: 4.3-7.3). After adjusting for healthcare utilization, the Cox proportional hazard ratio was 4.6 (95% CI: 3.5-6.1). Excluding those who received an IBS diagnosis within 90 days, the 1-year incidence rate of IBS was 16.7 and 3.9 per 1,000 among cases and non-cases, respectively, with an unadjusted risk ratio of 4.3 (95% CI: 3.0-6.2). DISCUSSION: Persons with a Campylobacter infection have a much higher risk of developing IBS compared with those not diagnosed with Campylobacter infection. The burden of Campylobacter-associated PI-IBS should be considered when assessing the overall impact of Campylobacter infections.

      10. Quantifying how different clinical presentations, levels of severity, and healthcare attendance shape the burden of influenza-associated illness: A modeling study from South Africaexternal icon
        Tempia S, Walaza S, Moyes J, Cohen AL, McMorrow ML, Treurnicht FK, Hellferscee O, Wolter N, von Gottberg A, Nguweneza A, McAnerney JM, Dawood H, Variava E, Madhi SA, Cohen C.
        Clin Infect Dis. 2019 Aug 30;69(6):1036-1048.
        BACKGROUND: Burden estimates of medically and nonmedically attended influenza-associated illness across syndromes and levels of severity are lacking. METHODS: We estimated the national burden of medically and nonmedically attended influenza-associated illness among individuals with different clinical presentations (all-respiratory, all-circulatory, and nonrespiratory/noncirculatory) and levels of severity (mild, fatal, and severe, nonfatal) using a combination of case-based (from laboratory-confirmed influenza surveillance) and ecological studies, as well as data from healthcare utilization surveys in South Africa during 2013-2015. In addition, we compared estimates of medically attended influenza-associated respiratory illness, obtained from case-based and ecological studies. Rates were reported per 100 000 individuals in the population. RESULTS: The estimated mean annual number of influenza-associated illness episodes was 10 737 847 (19.8% of 54 096 705 inhabitants). Of these episodes, 10 598 138 (98.7%) were mild, 128 173 (1.2%) were severe, nonfatal, and 11 536 (0.1%) were fatal. There were 2 718 140 (25.6%) mild, 56 226 (43.9%) severe, nonfatal, and 4945 (42.8%) medically attended should be after fatal episodes. Influenza-associated respiratory illness accounted for 99.2% (10 576 146) of any mild, 65.5% (83 941) of any severe, nonfatal, and 33.7% (3893) of any fatal illnesses. Ecological and case-based estimates of medically attended, influenza-associated, respiratory mild (rates: ecological, 1778.8, vs case-based, 1703.3; difference, 4.4%), severe, nonfatal (rates: ecological, 88.6, vs case-based, 75.3; difference, 15.0%), and fatal (rates: ecological, 3.8, vs case-based, 3.5; difference, 8.4%) illnesses were similar. CONCLUSIONS: There was a substantial burden of influenza-associated symptomatic illness, including severe, nonfatal and fatal illnesses, and a large proportion was nonmedically attended. Estimates, including only influenza-associated respiratory illness, substantially underestimated influenza-associated, severe, nonfatal and fatal illnesses. Ecological and case-based estimates were found to be similar for the compared categories.

      11. Three years of progress towards achieving hepatitis C elimination in the country of Georgia, April 2015 – March 2018external icon
        Tsertsvadze T, Gamkrelidze A, Chkhartishvili N, Abutidze A, Sharvadze L, Kerashvili V, Butsashvili M, Metreveli D, Gvinjilia L, Shadaker S, Nasrullah M, Adamia E, Zeuzem S, Afdhal N, Arora S, Thornton K, Skaggs B, Kuchuloria T, Lagvilava M, Sergeenko D, Averhoff F.
        Clin Infect Dis. 2019 Sep 29.
        BACKGROUND: In April 2015, in collaboration with U.S. CDC and Gilead Sciences, Georgia embarked on the world’s first hepatitis C elimination program. We aimed to assess progress towards elimination targets after three years since the beginning of the elimination program. METHODS: We constructed an HCV care cascade for adults in Georgia, based on the estimated 150,000 persons age >/= 18 years with active HCV infection. All patients who were screened or entered the treatment program during April 2015 – March 2018 were included in the analysis. Data on the number of persons screened for HCV was extracted from the national HCV screening database. For treatment component we utilized data from the Georgia National HCV treatment program database. Available treatment options included sofosbuvir (SOF) and ledipasvir/sofosbuvir (LDV/SOF) based regimens. RESULTS: Since April 2015, a cumulative 974,817 adults were screened for HCV antibodies, 86,624 persons tested positive, of which 61,925 underwent HCV confirmatory testing. Among estimated 150,000 adults living with chronic hepatitis C in Georgia, 52,856 (35.1%) were diagnosed, 45,334 (30.2%) initiated treatment with DAA, and 29,090 (19.4%) achieved sustained virologic response (SVR). Overall 37,256 persons were eligible for SVR assessment, of these only 29,620 (79.5%) returned for evaluation. In the per-protocol analysis, SVR rate achieved was 98.2% (29,090/29,620), and 78.1% (29,090/37,256) in the intent-to-treat analysis. CONCLUSIONS: Georgia has made substantial progress in the path towards eliminating hepatitis C. Scaling-up testing and diagnosis, along with effective linkage to treatment services are needed to achieve the goal of elimination.

      12. Influenza and tuberculosis co-infection: A systematic reviewexternal icon
        Walaza S, Cohen C, Tempia S, Moyes J, Nguweneza A, Madhi SA, McMorrow M, Cohen AL.
        Influenza Other Respir Viruses. 2019 Sep 30.
        INTRODUCTION: There are limited data on risk of severe disease or outcomes in patients with influenza and pulmonary tuberculosis (PTB) co-infection compared to those with single infection. METHODS: We conducted a systematic review of published literature on the interaction of influenza viruses and PTB. Studies were eligible for inclusion if they presented data on prevalence, disease association, presentation or severity of laboratory-confirmed influenza among clinically diagnosed or laboratory-confirmed PTB cases. We searched eight databases from inception until December 2018. Summary characteristics of each study were extracted, and a narrative summary was presented. Cohort or case-control studies were assessed for potential bias using the Newcastle-Ottawa scale. RESULTS: We assessed 5154 abstracts, reviewed 146 manuscripts and included 19 studies fulfilling selection criteria (13 human and six animal). Of seven studies reporting on the possible effect of the underlying PTB disease in patients with influenza, three of four analytical studies reported no association with disease severity of influenza infection in those with PTB, whilst one study reported PTB as a risk factor for influenza-associated hospitalization. An association between influenza infection and PTB disease was found in three of five analytical studies; whereas the two other studies reported a high frequency of PTB disease progression and complications among patients with seasonal influenza co-infection. CONCLUSION: Human analytical studies of an association between co-infection and severe influenza- or PTB-associated disease or increased prevalence of influenza co-infection in individuals’ hospitalized for PTB were not conclusive. Data are limited from large, high-quality, analytical epidemiological studies with laboratory-confirmed endpoints.

      13. OBJECTIVE: Emergency departments (EDs) are critical settings for hepatitis C care in the United States. We assessed trends and characteristics of hepatitis C-associated ED visits during 2006-2014. METHODS: We used data from the 2006-2014 Nationwide Emergency Department Sample to estimate numbers, rates, and costs of hepatitis C-associated ED visits, defined by either first-listed diagnosis of hepatitis C or all-listed diagnosis of hepatitis C. We assessed trends by demographic characteristics, liver disease severity, and patients’ disposition by using joinpoint analysis, and we calculated the average annual percentage change (AAPC) from 2006 to 2014. RESULTS: During 2006-2014, the rate per 100 000 visits of first-listed and all-listed hepatitis C-associated ED visits increased significantly from 10.1 to 25.4 (AAPC = 13.0%; P < .001) and from 484.4 to 631.6 (AAPC = 3.4%; P < .001), respectively. Approximately 70% of these visits were made by persons born during 1945-1965 (baby boomers); 30% of visits were made by Medicare beneficiaries and 40% by Medicaid beneficiaries. Significant rate increases were among visits by baby boomers (first-listed: AAPC = 13.8%; all-listed: AAPC = 2.6%), persons born after 1965 (first-listed: AAPC = 14.3%; all-listed: AAPC = 9.2%), Medicare beneficiaries (first-listed: AAPC = 18.0%; all-listed: AAPC = 3.9%), and persons hospitalized after ED visits (first-listed: AAPC = 20.0%; all-listed: AAPC = 2.3%; all P < .001). Increasing proportions of compensated cirrhosis were among visits by baby boomers (first-listed: AAPC = 11.5%; all-listed: AAPC = 6.3%). Annual hepatitis C-associated total ED costs increased by 400.0% (first-listed) and 192.0% (all-listed) during 2006-2014. CONCLUSION: Public health efforts are needed to address the growing burden of hepatitis C care in the ED.

    • Disease Reservoirs and Vectors
      1. The area in and around Chicago, IL, is a hotspot of West Nile virus activity. The discovery of a Culex pipiens form molestus Forskl population in Chicago in 2009 added to speculation that offspring from hybridization between Cx. pipiens f. pipiens L. and f. molestus could show a preference for feeding on humans. We collected blood-fed female mosquitoes (N = 1,023) from eight residential sites and one public park site in Chicago in July and August 2012. Bloodmeal analysis using the COI (cytochrome c oxidase subunit I) gene was performed to ascertain host choice. Almost all (99%) bloodmeals came from birds, with American Robins (Turdus migratorius L.) and House Sparrows (Passer domesticus L.) making up the largest percentage (74% combined). A forage ratio analysis comparing bird species fed upon and available bird species based on point count surveys indicated Northern Cardinals (Cardinalis cardinalis) and American Robins (Turdus migratorius) appeared to be over-utilized, whereas several species were under-utilized. Two human bloodmeals came from Culex pipiens complex mosquitoes. Admixture and population genetic analyses were conducted with 15 microsatellite loci on head and thorax DNA from the collected blood-fed mosquitoes. A modest amount of hybridization was detected between Cx. pipiens f. pipiens and f. molestus, as well as between f. pipiens and Cx. quinquefasciatus Say. Several pure Cx. quinquefasciatus individuals were noted at the two Trumbull Park sites. Our data suggest that Cx. pipiens complex mosquitoes in the Chicago area are not highly introgressed with f. molestus and appear to utilize avian hosts.

    • Environmental Health
      1. The association of urinary organophosphate ester metabolites and self-reported personal care and household product use among pregnant women in Puerto Ricoexternal icon
        Ingle ME, Watkins D, Rosario Z, Velez Vega CM, Huerta-Montanez G, Calafat AM, Ospina M, Cordero JF, Alshawabkeh A, Meeker JD.
        Environ Res. 2019 Sep 23;179(Pt A):108756.
        BACKGROUND: Organophosphate esters (OPEs) are widely detected among U.S. pregnant women. OPEs, some of which are present in nail polish, have been associated with adverse reproductive health outcomes. More research is needed to investigate associations with OPEs and personal care products (PCP) use. METHODS: Pregnant women (18-40 years) were recruited from two hospitals and five prenatal clinics in Northern Puerto Rico (n=148 women) between 2011 and 2015. Concentrations of bis(2-chloroethyl) phosphate (BCEtP), bis(1-chloro-2-propyl) phosphate (BCPP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), di-n-butyl phosphate (DNBP), di-benzyl phosphate (DBzP), di-cresyl phosphate (DCP), DPHP, and 2,3,4,5-tetrabromobenzoic acid (TBBA) were measured twice during pregnancy. Participants completed questionnaires on PCP and household products (HP) use. Associations among products and metabolite concentrations (n=296 observations) were assessed using linear mixed models. RESULTS: BCEtP, BCPP, BDCPP and DPHP were detected frequently (>/=77%). Correlations among metabolites (0.16</=r</=0.35) and Intraclass correlation coefficients (ICCs) (0.03</=ICC</=0.34) were weak-to-moderate. Suntan lotion was associated with a 110% increase in BDCPP. DPHP increased with perfume (51%) and nail polish (49%) use. BCPP increased 46% with pesticide use in home. CONCLUSION: Biomarkers of OPEs were often detected among pregnant women. Associations with PCP and HP use suggest OPEs may be used in such products, specifically in perfume and nail polish. Further investigation into these products is warranted.

    • Food Safety
      1. Salmonella serotypes: A novel measure of association with foodborne transmissionexternal icon
        Luvsansharav UO, Vieira A, Bennett S, Huang J, Healy JM, Hoekstra RM, Bruce BB, Cole D.
        Foodborne Pathog Dis. 2019 Sep 30.
        Most nontyphoidal Salmonella (NTS) illnesses in the United States are thought to be foodborne. However, transmission routes likely vary among the different serotypes. We developed a relative ranking of NTS serotypes according to the strength of their association with foodborne transmission. We used Laboratory-based Enteric Disease Surveillance data to estimate the proportion of infections for each Salmonella serotype reported from 1998 to 2015 and Foodborne Disease Outbreak Surveillance System data to calculate the proportion of foodborne outbreak-associated Salmonella illnesses caused by each serotype. We calculated the ratios of these proportions to create a foodborne relatedness (FBR) measure for each serotype. Of the top 20 serotypes, Saintpaul (2.14), Heidelberg (1.61), and Berta (1.48) had the highest FBR measures; Mississippi (0.01), Bareilly (0.13), and Paratyphi B variant L(+) tartrate(+) (0.20) had the lowest. The FBRs for the three most prevalent serotypes were 1.22 for Enteritidis, 0.77 for Typhimurium, and 1.16 for Newport. This method provides a quantitative approach to estimating the relative differences in the likelihood that an illness caused by a particular serotype was transmitted by food, which may aid in tailoring strategies to prevent Salmonella illnesses and guide future research into serotype-specific source attribution.

      2. Onsite investigation at a mail-order hatchery following a multistate Salmonella illness outbreak linked to live poultry – United States, 2018external icon
        Robertson SA, Sidge JL, Koski L, Hardy MC, Stevenson L, Signs K, Stobierski MG, Bidol S, Donovan D, Soehnlen M, Jones K, Robeson S, Hambley A, Stefanovsky L, Brandenburg J, Hise K, Tolar B, Nichols MC, Basler C.
        Poult Sci. 2019 Oct 3.
        Centers for Disease Control and Prevention (CDC), health departments, and other state and federal partners have linked contact with live poultry to 70 human Salmonella outbreaks in the United States from 2000 to 2017, which resulted in a total of 4,794 illnesses, 894 hospitalizations, and 7 deaths. During human salmonellosis outbreaks environmental sampling is rarely conducted as part of the outbreak investigation. CDC was contacted by state health officials on June 12, 2018, to provide support during an investigation of risk factors for Salmonella infections linked to live poultry originating at a mail-order hatchery. From January 1, 2018, to June 15, 2018, 13 human Salmonella infections in multiple states were attributed to exposure to live poultry from a single hatchery. Two serotypes of Salmonella were associated with these infections, Salmonella Enteritidis and Salmonella Litchfield. Molecular subtyping of the S. Enteritidis clinical isolates revealed they were closely related genetically (within 0 to 9 alleles) by core genome multi-locus sequence typing (cgMLST) to isolates obtained from environmental samples taken from hatchery shipping containers received at retail outlets. Environmental sampling and onsite investigation of practices was conducted at the mail-order hatchery during an investigation on June 19, 2018. A total of 45 environmental samples were collected, and 4 (9%) grew Salmonella. A chick box liner from a box in the pre-shipping area yielded an isolate closely related to the S. Enteritidis outbreak strain (within 1 to 9 alleles by cgMLST). The onsite investigation revealed lapses in biosecurity, sanitation, quality assurance, and education of consumers. Review of Salmonella serotype testing performed by the hatchery revealed that the number of samples and type of samples collected monthly varied. Also, S. Enteritidis was identified at the hatchery every year since testing began in 2016. Recommendations to the hatchery for biosecurity, testing, and sanitation measures were made to help reduce burden of Salmonella in the hatchery and breeding flocks, thereby reducing the occurrence of human illness.

    • Health Disparities
      1. [No abstract]

      2. Disparities in cancer incidence and trends among American Indians and Alaska Natives in the United States, 2010-2015external icon
        Melkonian SC, Jim MA, Haverkamp D, Wiggins CL, McCollum J, White MC, Kaur JS, Espey DK.
        Cancer Epidemiol Biomarkers Prev. 2019 Oct;28(10):1604-1611.
        BACKGROUND: Cancer incidence rates for American Indian and Alaska Native (AI/AN) populations vary by geographic region in the United States. The purpose of this study is to examine cancer incidence rates and trends in the AI/AN population compared with the non-Hispanic white population in the United States for the years 2010 to 2015. METHODS: Cases diagnosed during 2010 to 2015 were identified from population-based cancer registries and linked with the Indian Health Service (IHS) patient registration databases to describe cancer incidence rates in non-Hispanic AI/AN persons compared with non-Hispanic whites (whites) living in IHS purchased/referred care delivery area counties. Age-adjusted rates were calculated for the 15 most common cancer sites, expressed per 100,000 per year. Incidence rates are presented overall as well as by region. Trends were estimated using joinpoint regression analyses. RESULTS: Lung and colorectal cancer incidence rates were nearly 20% to 2.5 times higher in AI/AN males and nearly 20% to nearly 3 times higher in AI/AN females compared with whites in the Northern Plains, Southern Plains, Pacific Coast, and Alaska. Cancers of the liver, kidney, and stomach were significantly higher in the AI/AN compared with the white population in all regions. We observed more significant decreases in cancer incidence rates in the white population compared with the AI/AN population. CONCLUSIONS: Findings demonstrate the importance of examining cancer disparities between AI/AN and white populations. Disparities have widened for lung, female breast, and liver cancers. IMPACT: These findings highlight opportunities for targeted public health interventions to reduce AI/AN cancer incidence.

    • Health Economics
      1. A cost-effectiveness analysis of antenatal influenza vaccination among HIV-infected and HIV-uninfected pregnant women in South Africaexternal icon
        Biggerstaff M, Cohen C, Reed C, Tempia S, McMorrow ML, Walaza S, Moyes J, Treurnicht FK, Cohen AL, Hutchinson P, Stoecker C, Steinberg J.
        Vaccine. 2019 Sep 28.
        BACKGROUND: Pregnant women and infants are at increased risk of severe disease from influenza. Antenatal influenza vaccination is safe and can reduce the risk of illness for women and their infants. We evaluated for South Africa the health effects of antenatal influenza vaccination among pregnant women and their infants aged <6 months old and assessed its cost-effectiveness. METHODS: We constructed a decision tree model to simulate the population of pregnant women and infants aged <6 months in South Africa using TreeAge Pro Suite 2015. The model evaluated the change in societal costs and outcomes associated with a vaccination campaign that prioritized HIV-infected over HIV-uninfected pregnant women compared with no vaccination. We also examined the impacts of a campaign without prioritization. Upper and lower 90% uncertainty intervals (90% UI) were generated using probabilistic sensitivity analysis on 10000 Monte Carlo simulations. The cost-effectiveness threshold was set to the 2015 per capita gross domestic product of South Africa, US$5724. RESULTS: Antenatal vaccination with prioritization averted 9070 (90% UI: 7407-11217) total cases of influenza among pregnant women and infants, including 411 (90% UI: 305-546) hospitalizations and 30 (90% UI: 22-40) deaths. This corresponds to an averted fraction of 13.5% (90% UI: 9.0-20.5%). Vaccinating without prioritization averted 7801 (90% UI: 6465-9527) cases of influenza, including 335 (90% UI: 254-440) hospitalizations and 24 (90% UI: 18-31) deaths. This corresponds to an averted fraction of 11.6% (90% UI: 7.8-17.4%). Vaccinating the cohort of pregnant women with prioritization had societal cost of $4689 (90% UI: $3128-$7294) per Quality Adjusted Life Year (QALY) gained while vaccinating without prioritization had a cost of $5924 (90% UI: $3992-$9056) per QALY. CONCLUSIONS: Antenatal influenza vaccination campaigns in South Africa would reduce the impact of influenza and could be cost-effective.

      2. OBJECTIVE: While diabetic ketoacidosis (DKA) is common in youth at the onset of the diabetes, the excess costs associated with DKA are unknown. We aimed to quantify the health care services use and medical care costs related to the presence of DKA at diagnosis of diabetes. RESEARCH DESIGN AND METHODS: We analyzed data from the U.S. MarketScan claims database for 4,988 enrollees aged 3-19 years insured in private fee-for-service plans and newly diagnosed with diabetes during 2010-2016. Youth with and without DKA at diabetes diagnosis were compared for mean health care service use (outpatient, office, emergency room, and inpatient visits) and medical costs (outpatient, inpatient, prescription drugs, and total) for 60 days prior to and 60 days after diabetes diagnosis. A two-part model using generalized linear regression and logistic regression was used to estimate medical costs, controlling for age, sex, rurality, health plan, year, presence of hypoglycemia, and chronic pulmonary condition. All costs were adjusted to 2016 dollars. RESULTS: At diabetes diagnosis, 42% of youth had DKA. In the 60 days prior to diabetes diagnosis, youth with DKA at diagnosis had less health services usage (e.g., number of outpatient visits: -1.17; P < 0.001) and lower total medical costs (-$635; P < 0.001) compared with youth without DKA at diagnosis. In the 60 days after diagnosis, youth with DKA had significantly greater health care services use and health care costs ($6,522) compared with those without DKA. CONCLUSIONS: Among youth with newly diagnosed diabetes, DKA at diagnosis is associated with significantly higher use of health care services and medical costs.

      3. Estimating costs of implementing stroke systems of care and data-driven improvements in the Paul Coverdell National Acute Stroke Programexternal icon
        Yarnoff B, Khavjou O, Elmi J, Lowe-Beasley K, Bradley C, Amoozegar J, Wachtmeister D, Tzeng J, Chapel JM, Teixeira-Poit S.
        Prev Chronic Dis. 2019 Oct 3;16:E134.
        PURPOSE AND OBJECTIVES: We evaluated the costs of implementing coordinated systems of stroke care by state health departments from 2012 through 2015 to help policy makers and planners gain a sense of the potential return on investments in establishing a stroke care quality improvement (QI) program. INTERVENTION APPROACH: State health departments funded by the Paul Coverdell National Acute Stroke Program (PCNASP) implemented activities to support the start and proficient use of hospital stroke registries statewide and coordinate data-driven QI efforts. These efforts were aimed at improving the treatment and transition of stroke patients from prehospital emergency medical services (EMS) to in-hospital care and postacute care facilities. Health departments provided technical assistance and data to support hospitals, EMS agencies, and posthospital care agencies to carry out small, rapid, incremental QI efforts to produce more effective and efficient stroke care practices. EVALUATION METHODS: Six of the 11 PCNASP-funded state health departments in the United States volunteered to collect and report programmatic costs associated with implementing the components of stroke systems of care. Six health departments reported costs paid directly by Centers for Disease Control and Prevention-provided funds, 5 also reported their own in-kind contributions, and 4 compiled data from a sample of their partners’ estimated costs of resources, such as staff time, involved in program implementation. Costs were analyzed separately for PCNASP-funded expenditures and in-kind contributions by the health department by resource category and program activity. In-kind contributions by partners were also analyzed separately. RESULTS: PCNASP-funded expenditures ranged from $790,123 to $1,298,160 across the 6 health departments for the 3-year funding period. In-kind contributions ranged from $5,805 to $1,394,097. Partner contributions (n = 22) ranged from $3,912 to $362,868. IMPLICATIONS FOR PUBLIC HEALTH: Our evaluation reports costs for multiple state health departments and their partners for implementing components of stroke systems of care in the United States. Although there are limitations, our findings represent key estimates that can guide future program planning and efforts to achieve sustainability.

    • Healthcare Associated Infections
      1. An Introduction to STRIVEexternal icon
        Bell MR, Kuhar DT.
        Ann Intern Med. 2019 Oct 1;171(7_Supplement):S1.

        [No abstract]

      2. Potential fifth clade of Candida auris, Iran, 2018external icon
        Chow NA, de Groot T, Badali H, Abastabar M, Chiller TM, Meis JF.
        Emerg Infect Dis. 2019 Sep;25(9):1780-1781.
        Four major clades of Candida auris have been described, and all infections have clustered in these 4 clades. We identified an isolate representative of a potential fifth clade, separated from the other clades by >200,000 single-nucleotide polymorphisms, in a patient in Iran who had never traveled outside the country.

      3. The first two cases of Candida auris in The Netherlandsexternal icon
        Vogelzang EH, Weersink AJ, van Mansfeld R, Chow NA, Meis JF, van Dijk K.
        J Fungi (Basel). 2019 Sep 30;5(4).
        Candida auris is a rapidly emerging multidrug-resistant pathogenic yeast. In recent years, an increasing number of C. auris invasive infections and colonized patients have been reported, and C. auris has been associated with hospital outbreaks worldwide, mainly in intensive care units (ICUs). Here, we describe the first two cases of C. auris in The Netherlands. Both cases were treated in a healthcare facility in India prior to admission. The patients were routinely placed in contact precautions in a single room after admission, which is common practice in The Netherlands for patients with hospitalization outside The Netherlands. No transmission of C. auris was noticed in both hospitals. Routine admission screening both for multidrug-resistant (MDR) bacteria and MDR yeasts should be considered for patients admitted from foreign hospitals or countries with reported C. auris transmission.

    • Immunity and Immunization
      1. OBJECTIVE: To identify number of children who received live vaccines outside recommended intervals between doses and calculate corrective revaccination costs. METHODS: We analyzed >1.6 million vaccination records for children aged 12months through 6years from six immunization information system (IIS) Sentinel Sites from 2014-15 when live attenuated influenza vaccine (LAIV, FluMist(R) Quadrivalent) was recommended for use, and from 2016-17, when not recommended for use. Depending on the vaccine, insufficient intervals between live vaccine doses are less than 24 or 28days from a preceding live vaccine dose. Private and public purchase costs of vaccines were used to determine revaccination costs of live vaccine doses administered during the live vaccine conflict interval. Measles, mumps, rubella (MMR), varicella, combined MMRV, and LAIV were live vaccines evaluated in this study. RESULTS: Among 946,659 children who received at least one live vaccine dose from 2014-15, 4,873 (0.5%) received at least one dose too soon after a prior live vaccine (revaccination cost, $786,413) with a median conflict interval of 16days. Among 704,591 children who received at least one live vaccine dose from 2016-17, 1,001 (0.1%) received at least one dose too soon after a prior live vaccine (revaccination cost, $181,565) with a median conflict interval of 14days. The live vaccine most frequently administered outside of the recommended intervals was LAIV from 2014-15, and varicella from 2016-17. CONCLUSIONS: Live vaccine interval errors were rare (0.5%), indicating an adherence to recommendations. If all invalid doses were corrected by revaccination over the two time periods, the cost within the IIS Sentinel Sites would be nearly one million dollars. Provider awareness about live vaccine conflicts, especially with LAIV, could prevent errors, and utilization of clinical decision support functionality within IISs and Electronic Health Record Systems can facilitate better vaccination practices.

      2. Invasive disease potential of Streptococcus pneumoniae serotypes before and after 10-valent pneumococcal conjugate vaccine introduction in a rural area, southern Mozambiqueexternal icon
        Massora S, Lessa FC, Moiane B, Pimenta FC, Mucavele H, Chauque A, Cossa A, Verani JR, Tembe N, da Gloria Carvalho M, Munoz-Almagro C, Sigauque B.
        Vaccine. 2019 Sep 28.
        BACKGROUND: Invasive pneumococcal disease (IPD) is a significant cause of morbidity and mortality among children worldwide. In April 2013, Mozambique introduced 10-valent PCV (PCV10) into the National Expanded Program on immunization using a three-dose schedule at 2, 3, and 4months of age. We aimed to evaluate the invasive disease potential of pneumococcal serotypes among children in our region before and after PCV10 introduction. METHODS: We used data from ongoing population-based surveillance for IPD and cross-sectional pneumococcal carriage surveys among children aged<5years in Manhia, Mozambique. To determine the invasive disease potential for each serotype pre- and post-PCV10 introduction, odds ratios (OR) and 95% confidence intervals (95% CI) were calculated comparing serotype-specific prevalence in IPD and in carriage. For each serotype, OR and 95% CI>1 indicated high invasive disease potential and OR and 95% CI<1 indicated low invasive disease potential. RESULTS: In the pre-PCV10 period, 524 pneumococcal isolates were obtained from 411 colonized children and IPD cases were detected in 40 children. In the post-PCV10 period, 540 pneumococcal isolates were obtained from 507 colonized children and IPD cases were detected in 30 children. The most prevalent serotypes causing IPD pre-PCV10 were 6A (17.5%), 6B (15.0%), 14 (12.5%), 23F (10.0%) and 19F (7.5%), and post-PCV10 were 6A (36.7%), 13 (10%), 1 (10.0%), 6B (6.7%) and 19A (6.7%). Serotypes associated with high invasive disease potential pre-PCV10 included 1 (OR:22.3 [95% CI 2.0; 251.2]), 6B (OR:3.1 [95% CI 1.2; 8.1]), 14 (OR: 3.4 [95% CI 1.2; 9.8]) and post-PCV10 included serotype 6A (OR:6.1[95% CI 2.7; 13.5]). CONCLUSION: The number of serotypes with high invasive disease potential decreased after PCV10 introduction. Serotype 6A, which is not included in PCV10, was the most common cause of IPD throughout the study and showed a high invasive potential in the post-PCV10 period.

      3. Introduction: Vaccination is one of the most successful and cost-effective public health interventions. Although vaccines undergo extensive safety and efficacy evaluations prior to licensure, vaccine safety assessment post-licensure is essential for detecting rare and longer-term adverse events (AEs) and maintaining public confidence in vaccines and recommended immunization programs. Despite the proven effect of vaccines to save lives and prevent disease and overwhelming evidence of vaccines’ safety and societal benefit, like any drug, no vaccine can be considered as completely safe and completely effective. New vaccines continue to be introduced and require rapid safety assessment post-licensure through pharmacovigilance reports as well as epidemiologic studies to investigate any potential safety signals. Areas covered: We discuss selected challenges for conducting pharmacovigilance and epidemiologic studies of AEs after vaccination in the United States using the post-licensure safety surveillance infrastructure of the Centers for Disease Control and Prevention (CDC). Expert opinion: The availability of specific post-licensure surveillance systems to monitor and study AEs after vaccination such as the Vaccine Adverse Event Reporting System, the Vaccine Safety Datalink, and the Clinical Immunization Safety Assessment Project, each with its unique set of strengths and limitations, provide a harmonized and supportive approach to meet several of these barriers.

      4. Association of rotavirus vaccination with inpatient and emergency department visits among children seeking care for acute gastroenteritis, 2010-2016external icon
        Payne DC, Englund JA, Weinberg GA, Halasa NB, Boom JA, Staat MA, Selvarangan R, Azimi PH, Klein EJ, Szilagyi PG, Chappell J, Sahni LC, McNeal M, Harrison CJ, Moffatt ME, Johnston SH, Mijatovic-Rustempasic S, Esona MD, Tate JE, Curns AT, Wikswo ME, Sulemana I, Bowen MD, Parashar UD.
        JAMA Netw Open. 2019 Sep 4;2(9):e1912242.
        Importance: Rotavirus vaccines have been recommended for universal US infant immunization for more than 10 years, and understanding their effectiveness is key to the continued success of the US rotavirus vaccine immunization program. Objective: To assess the association of RotaTeq (RV5) and Rotarix (RV1) with inpatient and emergency department (ED) visits for rotavirus infection. Design, Setting, and Participants: This case-control vaccine effectiveness study was performed at inpatient and ED clinical settings in 7 US pediatric medical institutions from November 1, 2009, through June 30, 2016. Children younger than 5 years seeking medical care for acute gastroenteritis were enrolled. Clinical and epidemiologic data, vaccination verification, and results of stool sample tests for laboratory-confirmed rotavirus were collected. Data were analyzed from November 1, 2009, through June 30, 2016. Main Outcomes and Measures: Rotavirus vaccine effectiveness for preventing rotavirus-associated inpatient and ED visits over time for each licensed vaccine, stratified by clinical severity and age. Results: Among the 10 813 children included (5927 boys [54.8%] and 4886 girls [45.2%]; median [range] age, 21 [8-59] months), RV5 and RV1 analyses found that compared with controls, rotavirus-positive cases were more often white (RV5, 535 [62.2%] vs 3310 [57.7%]; RV1, 163 [43.1%] vs 864 [35.1%]), privately insured (RV5, 620 [72.1%] vs 4388 [76.5%]; RV1, 305 [80.7%] vs 2140 [87.0%]), and older (median [range] age for RV5, 26 [8-59] months vs 21 [8-59] months; median [range] age for RV1, 22 [8-59] months vs 19 [8-59] months) but did not differ by sex. Among 1193 rotavirus-positive cases and 9620 rotavirus-negative controls, at least 1 dose of any rotavirus vaccine was 82% (95% CI, 77%-86%) protective against rotavirus-associated inpatient visits and 75% (95% CI, 71%-79%) protective against rotavirus-associated ED visits. No statistically significant difference during this 7-year period was observed for either rotavirus vaccine. Vaccine effectiveness against inpatient and ED visits was 81% (95% CI, 78%-84%) for RV5 (3 doses) and 78% (95% CI, 72%-82%) for RV1 (2 doses) among the study population. A mixed course of both vaccines provided 86% (95% CI, 74%-93%) protection. Rotavirus patients who were not vaccinated had severe infections 4 times more often than those who were vaccinated (74 of 426 [17.4%] vs 28 of 605 [4.6%]; P < .001), and any dose of rotavirus vaccine was 65% (95% CI, 56%-73%) effective against mild infections, 81% (95% CI, 76%-84%) against moderate infections, and 91% (95% CI, 85%-95%) against severe infections. Conclusions and Relevance: Evidence from this large postlicensure study of rotavirus vaccine performance in the United States from 2010 to 2016 suggests that RV5 and RV1 rotavirus vaccines continue to perform well, particularly in preventing inpatient visits and severe infections and among younger children.

      5. Home-based records and vaccination appointment stickers as parental reminders to reduce vaccination dropout in Indonesia: A cluster-randomized controlled trialexternal icon
        Wallace AS, Peetosutan K, Untung A, Ricardo M, Yosephine P, Wannemuehler K, Brown DW, McFarland DA, Orenstein WA, Rosenberg ES, Omer SB, Daniels D.
        Vaccine. 2019 Sep 26.
        INTRODUCTION: Limited evidence is available about the effectiveness of strategies to remind caregivers when to bring children back for future vaccinations in low- and middle-income country settings. We evaluated the effectiveness of two reminder strategies based on home-based vaccination records (HBR) in Indonesia. METHODS: In this cluster-randomized controlled trial involving 3616 children <1year of age, 90 health facilities were randomly assigned to either a control group or one of two intervention groups: (1) HBR-only group, where healthcare workers provided an HBR to any child without an HBR during a vaccination visit and instructed the caregiver to keep it at home between visits, or (2) HBR+sticker group, where, in addition to HBR provision, healthcare workers placed vaccination appointment reminder stickers on the HBR. The primary outcome was receipt of the third dose of diphtheria-tetanus-pertussis-containing vaccine (DTPcv3) within 7months and the secondary outcome was receipt of a timely DTPcv3 dose. RESULTS: Control group DTPcv3 coverage was 81%. In intention-to-treat analysis, neither intervention group had significantly different DTPcv3 coverage compared with the control group (RR=0.94, 95% confidence interval [CI] 0.87; 1.02 for HBR-only group; RR=0.97, 95% CI 0.90; 1.04 for HBR+sticker group) by study end. However, children in the HBR+sticker group were 50% more likely to have received a DTPcv3 vaccination (RR=1.46, 95% CI 1.02, 2.09) within 60days of DTPcv1 vaccination, compared with children in the control group; children in the HBR-only group were not more likely to have done so (RR=1.05, 95% CI 0.71, 1.55). DISCUSSION: Reminder stickers had an immediate effect on coverage by improving the proportion of children who received a timely DTPcv3 dose but no effect on the proportion who received DTPcv3 after 7months. Coupling reminder stickers with strategies to address other reasons why children do not return for vaccination visits should be further explored.

      6. Influenza vaccination coverage among registered nurses in China during 2017-2018: An internet panel surveyexternal icon
        Yu J, Ren X, Ye C, Tian K, Feng L, Song Y, Cowling BJ, Li Z.
        Vaccines (Basel). 2019 Sep 29;7(4).
        Influenza vaccination is recommended for nurses in China but is not mandatory or offered free of charge. The main objective of this study was to determine influenza vaccination coverage and the principal factors influencing influenza vaccination among nurses in China. During 22 March-1 April 2018, we conducted an opt-in internet panel survey among registered nurses in China. Respondents were recruited from an internet-based training platform for nurses. Among 22,888 nurses invited to participate, 4706 responded, and 4153 were valid respondents. Overall, 257 (6%) nurses reported receiving the seasonal influenza vaccine during the 2017/2018 season. Vaccination coverage was highest among nurses working in Beijing (10%, p < 0.001) and nurses working in primary care (12%, p = 0.023). The top three reasons for not being vaccinated were lack of time (28%), not knowing where and when to get vaccinated (14%), and lack of confidence in the vaccine’s effectiveness (12%). Overall, 41% of nurses reported experiencing at least one episode of influenza-like illness (ILI) during the 2017/2018 season; 87% of nurses kept working while sick, and 25% of nurses reported ever recommending influenza vaccination to patients. Compared with nurses who did not receive influenza vaccination in the 2017/2018 season, nurses who received influenza vaccination were more likely to recommend influenza vaccination to patients (67% vs. 22%, p < 0.001). Influenza vaccination coverage among nurses was low, and only a small proportion recommended influenza vaccine to patients. Our findings highlight the need for a multipronged strategy to increase influenza vaccination among nurses in China.

    • Informatics
      1. Building workforce capacity for effective use of health information systems: Evaluation of a blended eLearning course in Namibia and Tanzaniaexternal icon
        Rudd KE, Puttkammer N, Antilla J, Richards J, Heffron M, Tolentino H, Jacobs DJ, KatjiuanJo P, Prybylski D, Shepard M, Kumalija JC, Katuma HL, Leon BK, Mgonja NG, Santas XM.
        Int J Med Inform. 2019 Aug 10;131:103945.
        BACKGROUND: Electronic health information systems (HIS) are critical components of national health systems, and have been identified as a key element in the development and strengthening of health systems globally. Novel approaches are needed to effectively and efficiently train health care workers on the use of HIS. One such approach is the use of digital eLearning programs, either alone or blended with face-to-face learning activities. METHODS: We developed a novel blended eLearning course based on an in-person HIS training package previously developed by the United States Centers for Disease Control and Prevention. We then conducted a pilot implementation of the eLearning course in Namibia and Tanzania. RESULTS: The blended eLearning pilot program enrolled 131 people, 72 (55%) from Namibia and 59 (45%) from Tanzania. The majority of enrollees were female (n = 88, 67%) and were nurses (n=66, 50%). Of the 131 people who participated in the in-person orientation, 95 (73%) completed some or all of the eLearning modules. Across all three modules, the mean score on the post-test was significantly greater than on the pre-test (p<0.001). When comparing results from previous in-person workshops and the blended eLearning course, we found that participants experienced strong learning gains in both, although learning gains were somewhat greater in the in-person course. Blended eLearning course participants reported good to very good satisfaction with the overall content of the course and with the eLearning modules (3.5 and 3.6 out of 5-point Likert scale). We estimate that the total cost per participant is 2.2-3.4 times greater for the in-person course (estimated cost USD $980) than for the blended eLearning course (estimated cost USD $287-$437). CONCLUSION: A blended eLearning course is an effective method with which to train healthcare workers in the basic features of HIS, and the cost is up to 3.4 times less expensive than for an in-person course with similar content.

    • Injury and Violence
      1. Surveillance for violent deaths – National Violent Death Reporting System, 32 States, 2016external icon
        Ertl A, Sheats KJ, Petrosky E, Betz CJ, Yuan K, Fowler KA.
        MMWR Surveill Summ. 2019 Oct 4;68(9):1-36.
        PROBLEM/CONDITION: In 2016, approximately 65,000 persons died in the United States as a result of violence-related injuries. This report summarizes data from CDC’s National Violent Death Reporting System (NVDRS) regarding violent deaths from 32 U.S. states for 2016. Results are reported by sex, age group, race/ethnicity, type of location where injured, method of injury, circumstances of injury, and other selected characteristics. PERIOD COVERED: 2016. DESCRIPTION OF SYSTEM: NVDRS collects data regarding violent deaths obtained from death certificates, coroner/medical examiner reports, law enforcement reports, and secondary sources (e.g., child fatality review team data, Supplementary Homicide Reports, hospital data, and crime laboratory data). This report includes data collected from 32 states for 2016 (Alaska, Arizona, Colorado, Connecticut, Georgia, Hawaii, Illinois, Indiana, Iowa, Kansas, Kentucky, Maine, Maryland, Massachusetts, Michigan, Minnesota, New Hampshire, New Jersey, New Mexico, New York, North Carolina, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, Utah, Vermont, Virginia, Washington, and Wisconsin). NVDRS collates information for each death and links deaths that are related (e.g., multiple homicides, homicide followed by suicide, or multiple suicides) into a single incident. RESULTS: For 2016, NVDRS captured 40,374 fatal incidents involving 41,466 deaths in the 32 states included in this report. The majority (62.3%) of deaths were suicides, followed by homicides (24.9%), deaths of undetermined intent (10.8%), legal intervention deaths (1.2%) (i.e., deaths caused by law enforcement and other persons with legal authority to use deadly force acting in the line of duty, excluding legal executions), and unintentional firearm deaths (<1.0%). (The term legal intervention is a classification incorporated into the International Classification of Diseases, Tenth Revision [ICD-10] and does not denote the lawfulness or legality of the circumstances surrounding a death caused by law enforcement.) Demographic patterns varied by manner of death. Suicide rates were highest among males, non-Hispanic American Indians/Alaska Natives, non-Hispanic whites, adults aged 45-64 years, and men aged >/=75 years. The most common method of injury was a firearm among males and poisoning among females. Suicides were most often preceded by a mental health, intimate partner, substance abuse, or physical health problem or a recent or impending crisis during the previous or upcoming 2 weeks. Homicide rates were highest among males and persons aged <1 year and 15-44 years. Among males, non-Hispanic blacks accounted for most homicides and had the highest rate of any racial/ethnic group. The most common method of injury was a firearm. Homicides were most often precipitated by an argument or conflict, occurred in conjunction with another crime, or for females, were related to intimate partner violence. When the relationship between a homicide victim and a suspected perpetrator was known, the suspect was most frequently an acquaintance/friend among males and a current or former intimate partner among females. Legal intervention death rates were highest among men aged 20-44 years, and the rate among non-Hispanic black males was three times the rate among non-Hispanic white males. Precipitating circumstances for legal intervention deaths most frequently were an alleged criminal activity in progress, reported use of a weapon by the victim in the incident, a mental health or substance abuse problem (other than alcohol abuse), an argument or conflict, or a recent or impending crisis. Unintentional firearm deaths were more frequent among males, non-Hispanic whites, and persons aged 15-24 years. These deaths most often occurred while the shooter was playing with a firearm and most often were precipitated by a person unintentionally pulling the trigger or mistakenly thinking the firearm was unloaded. Rates of deaths of undetermined intent were highest among males, particularly non-Hispanic black and American Indian/Alaska Native males, and adults aged 25-64 years. Substance abuse, mental health problems, physical health problems, and a recent or impending crisis were the most common circumstances preceding deaths of undetermined intent. In 2016, a total of 3,655 youths aged 10-24 years died by suicide. The majority of these decedents were male, non-Hispanic white, and aged 18-24 years. Most decedents aged 10-17 years died by hanging/strangulation/suffocation (49.3%), followed by a firearm (40.4%), and suicides among this age group were most often precipitated by mental health, family relationship, and school problems. Most suicides among decedents aged 18-24 years were by a firearm (46.2%), followed by hanging/strangulation/suffocation (37.4%), and were precipitated by mental health, substance abuse, intimate partner, and family problems. A recent crisis, an argument or conflict, or both were common precipitating circumstances among all youth suicide decedents. INTERPRETATION: This report provides a detailed summary of data from NVDRS for 2016. Suicides rates were highest among non-Hispanic American Indian/Alaska Native and white males, whereas homicide rates were highest among non-Hispanic black males. Mental health problems, intimate partner problems, interpersonal conflicts, and acute life stressors were primary precipitating events for multiple types of violent deaths, including suicides among youths aged 10-24 years. PUBLIC HEALTH ACTION: NVDRS data are used to monitor the occurrence of violence-related fatal injuries and assist public health authorities in the development, implementation, and evaluation of programs and policies to reduce and prevent violent deaths. For example, Utah VDRS data were used to help identify suicide risk factors among youths aged 10-17 years, Rhode Island VDRS suicide data were analyzed to identify precipitating circumstances of youth suicides over a 10-year period, and Kansas VDRS data were used by the Kansas Youth Suicide Prevention Task Force. In 2019, NVDRS expanded data collection to include all 50 states, Puerto Rico, and the District of Columbia. This expansion is essential to public health efforts to reduce violent deaths.

    • Laboratory Sciences
      1. Zika virus enhances monocyte adhesion and transmigration favoring viral dissemination to neural cellsexternal icon
        Ayala-Nunez NV, Follain G, Delalande F, Hirschler A, Partiot E, Hale GL, Bollweg BC, Roels J, Chazal M, Bakoa F, Carocci M, Bourdoulous S, Faklaris O, Zaki SR, Eckly A, Uring-Lambert B, Doussau F, Cianferani S, Carapito C, Jacobs FM, Jouvenet N, Goetz JG, Gaudin R.
        Nat Commun. 2019 Sep 27;10(1):4430.
        Zika virus (ZIKV) invades and persists in the central nervous system (CNS), causing severe neurological diseases. However the virus journey, from the bloodstream to tissues through a mature endothelium, remains unclear. Here, we show that ZIKV-infected monocytes represent suitable carriers for viral dissemination to the CNS using human primary monocytes, cerebral organoids derived from embryonic stem cells, organotypic mouse cerebellar slices, a xenotypic human-zebrafish model, and human fetus brain samples. We find that ZIKV-exposed monocytes exhibit higher expression of adhesion molecules, and higher abilities to attach onto the vessel wall and transmigrate across endothelia. This phenotype is associated to enhanced monocyte-mediated ZIKV dissemination to neural cells. Together, our data show that ZIKV manipulates the monocyte adhesive properties and enhances monocyte transmigration and viral dissemination to neural cells. Monocyte transmigration may represent an important mechanism required for viral tissue invasion and persistence that could be specifically targeted for therapeutic intervention.

      2. Field performance of two methods for detection of poliovirus in wastewater samples, Mexico 2016-2017external icon
        Estivariz CF, Perez-Sanchez EE, Bahena A, Burns CC, Gary HE, Garcia-Lozano H, Rey-Benito G, Penaranda S, Castillo-Montufar KV, Nava-Acosta RS, Meschke JS, Oberste MS, Lopez-Martinez I, Diaz-Quinonez JA.
        Food Environ Virol. 2019 Sep 30.
        To enhance our ability to monitor poliovirus circulation and certify eradication, we evaluated the performance of the bag-mediated filtration system (BMFS) against the two-phase separation (TPS) method for concentrating wastewater samples for poliovirus detection. Sequential samples were collected at two sites in Mexico; one L was collected by grab and ~ 5 L were collected and filtered in situ with the BMFS. In the laboratory, 500 mL collected by grab were concentrated using TPS and the sample contained in the filter of the BMFS was eluted without secondary concentration. Concentrates were tested for the presence of poliovirus and non-poliovirus enterovirus (NPEV) using Global Poliovirus Laboratory Network standard procedures. Between February 16, 2016, and April 18, 2017, 125 pairs of samples were obtained. Collectors spent an average (+/- standard deviation) of 4.3 +/- 2.2 min collecting the TPS sample versus 73.5 +/- 30.5 min collecting and filtering the BMFS sample. Laboratory processing required an estimated 5 h for concentration by TPS and 3.5 h for elution. Sabin 1 poliovirus was detected in 37 [30%] samples with the TPS versus 24 [19%] samples with the BMFS (McNemar’s mid p value = 0.004). Sabin 3 poliovirus was detected in 59 [47%] versus 49 (39%) samples (p = 0.043), and NPEV was detected in 67 [54%] versus 40 [32%] samples (p < 0.001). The BMFS method without secondary concentration did not perform as well as the TPS method for detecting Sabin poliovirus and NPEV. Further studies are needed to guide the selection of cost-effective environmental surveillance methods for the polio endgame.

      3. Acrylonitrile butadiene styrene (ABS) and polycarbonate (PC) filaments three-dimensional (3-D) printer emissions-induced cell toxicityexternal icon
        Farcas MT, Stefaniak AB, Knepp AK, Bowers L, Mandler WK, Kashon M, Jackson SR, Stueckle TA, Sisler JD, Friend SA, Qi C, Hammond DR, Thomas TA, Matheson J, Castranova V, Qian Y.
        Toxicol Lett. 2019 Sep 25;317:1-12.
        During extrusion of some polymers, fused filament fabrication (FFF) 3-D printers emit billions of particles per minute and numerous organic compounds. The scope of this study was to evaluate FFF 3-D printer emission-induced toxicity in human small airway epithelial cells (SAEC). Emissions were generated from a commercially available 3-D printer inside a chamber, while operating for 1.5h with acrylonitrile butadiene styrene (ABS) or polycarbonate (PC) filaments, and collected in cell culture medium. Characterization of the culture medium revealed that repeat print runs with an identical filament yield various amounts of particles and organic compounds. Mean particle sizes in cell culture medium were 201+/-18nm and 202+/-8nm for PC and ABS, respectively. At 24h post-exposure, both PC and ABS emissions induced a dose dependent significant cytotoxicity, oxidative stress, apoptosis, necrosis, and production of pro-inflammatory cytokines and chemokines in SAEC. Though the emissions may not completely represent all possible exposure scenarios, this study indicate that the FFF could induce toxicological effects. Further studies are needed to quantify the detected chemicals in the emissions and their corresponding toxicological effects.

      4. HSV-2 is a neurotropic virus that causes a persistent, lifelong infection that increases risk for other sexually transmitted infections. The vaginal epithelium is the first line of defense against HSV-2 and coordinates the immune response through the secretion of immune mediators, including the proinflammatory cytokine IL-36gamma. Previously, we showed that IL-36gamma treatment promoted transient polymorphonuclear cell infiltration to the vaginal cavity and protected against lethal HSV-2 challenge. In this report, we reveal that IL-36gamma specifically induces transient neutrophil infiltration but does not impact monocyte and macrophage recruitment. Using IL-36gamma(-/-) mice in a lethal HSV-2 challenge model, we show that neutrophil counts are significantly reduced at 1 and 2 d postinfection and that KC-mediated mature neutrophil recruitment is impaired in IL-36gamma(-/-) mice. Additionally, IL-36gamma(-/-) mice develop genital disease more rapidly, have significantly reduced survival time, and exhibit an increased incidence of hind limb paralysis that is linked to productive HSV-2 infection in the brain stem. IL-36gamma(-/-) mice also exhibit a significant delay in clearance of the virus from the vaginal epithelium and a more rapid spread of HSV-2 to the spinal cord, bladder, and colon. We further show that the decreased survival time and increased virus spread observed in IL-36gamma(-/-) mice are not neutrophil-dependent, suggesting that IL-36gamma may function to limit HSV-2 spread in the nervous system. Ultimately, we demonstrate that IL-36gamma is a key regulator of neutrophil recruitment in the vaginal microenvironment and may function to limit HSV-2 neuroinvasion.

      5. ICTV virus taxonomy profile: Caliciviridaeexternal icon
        Vinje J, Estes MK, Esteves P, Green KY, Katayama K, Knowles NJ, L’Homme Y, Martella V, Vennema H, White PA.
        J Gen Virol. 2019 Oct 1.
        The family Caliciviridae includes viruses with single-stranded, positive-sense RNA genomes of 7.4-8.3 kb. The most clinically important representatives are human noroviruses, which are a leading cause of acute gastroenteritis in humans. Virions are non-enveloped with icosahedral symmetry. Members of seven genera infect mammals (Lagovirus, Norovirus, Nebovirus, Recovirus, Sapovirus, Valovirus and Vesivirus), members of two genera infect birds (Bavovirus and Nacovirus), and members of two genera infect fish (Minovirus and Salovirus). This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Caliciviridae, which is available at

      6. Identification of Gram negative non-fermentative bacteria: How hard can it be?external icon
        Whistler T, Sangwichian O, Jorakate P, Sawatwong P, Surin U, Piralam B, Thamthitiwat S, Promkong C, Peruski L.
        PLoS Negl Trop Dis. 2019 Sep 30;13(9):e0007729.
        INTRODUCTION: The prevalence of bacteremia caused by Gram negative non-fermentative (GNNF) bacteria has been increasing globally over the past decade. Many studies have investigated their epidemiology but focus on the common GNNF including Pseudomonas aeruginosa and Acinetobacter baumannii. Knowledge of the uncommon GNNF bacteremias is very limited. This study explores invasive bloodstream infection GNNF isolates that were initially unidentified after testing with standard microbiological techniques. All isolations were made during laboratory-based surveillance activities in two rural provinces of Thailand between 2006 and 2014. METHODS: A subset of GNNF clinical isolates (204/947), not identified by standard manual biochemical methodologies were run on the BD Phoenix automated identification and susceptibility testing system. If an organism was not identified (12/204) DNA was extracted for whole genome sequencing (WGS) on a MiSeq platform and data analysis performed using 3 web-based platforms: Taxonomer, CGE KmerFinder and One Codex. RESULTS: The BD Phoenix automated identification system recognized 92% (187/204) of the GNNF isolates, and because of their taxonomic complexity and high phenotypic similarity 37% (69/187) were only identified to the genus level. Five isolates grew too slowly for identification. Antimicrobial sensitivity (AST) data was not obtained for 93/187 (50%) identified isolates either because of their slow growth or their taxa were not in the AST database associated with the instrument. WGS identified the 12 remaining unknowns, four to genus level only. CONCLUSION: The GNNF bacteria are of increasing concern in the clinical setting, and our inability to identify these organisms and determine their AST profiles will impede treatment. Databases for automated identification systems and sequencing annotation need to be improved so that opportunistic organisms are better covered.

      7. Evaluation of tobacco smoke and diet as sources of exposure to two heterocyclic aromatic amines for the U.S. population: NHANES 2013-2014external icon
        Zhang L, Wang L, Li Y, Xia Y, Chang CM, Xia B, Sosnoff CS, Pine BN, deCastro BR, Blount BC.
        Cancer Epidemiol Biomarkers Prev. 2019 Oct 1.
        BACKGROUND: Heterocyclic aromatic amines (HAAs) are a group of hazardous substances produced during combustion of tobacco or high-temperature cooking of meats. 2-Amino-9H-pyrido[2,3-b]indole (AalphaC) is a major carcinogenic HAAs in tobacco smoke. METHODS: Urinary AalphaC, used as a marker of AalphaC exposure, was analyzed on spot urine samples from adult participants of the 2013-2014 cycle of the National Health and Nutrition Examination Survey (NHANES; N=1,792). AalphaC was measured using isotope-dilution liquid chromatography-tandem mass spectrometry. Exclusive combusted tobacco smokers were differentiated from non-users of tobacco products through both self-report and serum cotinine data. RESULTS: Among exclusive smokers, sample-weighted median urinary AalphaC was 40 times higher than non-users. Sample-weighted regression models showed that urinary AalphaC increased significantly with serum cotinine among both exclusive tobacco users and non-users with second-hand smoke exposure. Among non-users, eating beef cooked at high temperature was associated with a significant increase in urinary AalphaC, while consuming vegetables was associated with decreased AalphaC. In addition, smoking one-half pack of cigarettes per day was associated with a significant increase of 23.6 pg AalphaC/mL calculated at geometric mean of AalphaC, controlling for potential confounders. In comparison, increase in AalphaC attributable to consuming the 99th percentile of beef cooked at high temperature was 0.99 pg AalphaC/mL. CONCLUSIONS: Both exclusive smokers and non-users of tobacco in the general U.S. population are exposed to AalphaC from tobacco smoke, with additional, lesser contributions from certain dietary components. IMPACT: AalphaC is an important biomarker that is associated with tobacco smoke exposure.

    • Maternal and Child Health
      1. Trisomy 13 and 18-prevalence and mortality – A multi-registry population based analysisexternal icon
        Goel N, Morris JK, Tucker D, de Walle HE, Bakker MK, Kancherla V, Marengo L, Canfield MA, Kallen K, Lelong N, Camelo JL, Stallings EB, Jones AM, Nance A, Huynh MP, Martinez-Fernandez ML, Sipek A, Pierini A, Nembhard WN, Goetz D, Rissmann A, Groisman B, Luna-Munoz L, Szabova E, Lapchenko S, Zarante I, Hurtado-Villa P, Martinez LE, Tagliabue G, Landau D, Gatt M, Dastgiri S, Morgan M.
        Am J Med Genet A. 2019 Sep 30.
        The aim of the study is to determine the prevalence, outcomes, and survival (among live births [LB]), in pregnancies diagnosed with trisomy 13 (T13) and 18 (T18), by congenital anomaly register and region. Twenty-four population- and hospital-based birth defects surveillance registers from 18 countries, contributed data on T13 and T18 between 1974 and 2014 using a common data-reporting protocol. The mean total birth prevalence (i.e., LB, stillbirths, and elective termination of pregnancy for fetal anomalies [ETOPFA]) in the registers with ETOPFA (n = 15) for T13 was 1.68 (95% CI 1.3-2.06), and for T18 was 4.08 (95% CI 3.01-5.15), per 10,000 births. The prevalence varied among the various registers. The mean prevalence among LB in all registers for T13 was 0.55 (95%CI 0.38-0.72), and for T18 was 1.07 (95% CI 0.77-1.38), per 10,000 births. The median mortality in the first week of life was 48% for T13 and 42% for T18, across all registers, half of which occurred on the first day of life. Across 16 registers with complete 1-year follow-up, mortality in first year of life was 87% for T13 and 88% for T18. This study provides an international perspective on prevalence and mortality of T13 and T18. Overall outcomes and survival among LB were poor with about half of live born infants not surviving first week of life; nevertheless about 10% survived the first year of life. Prevalence and outcomes varied by country and termination policies. The study highlights the variation in screening, data collection, and reporting practices for these conditions.

      2. Designation of neonatal levels of care: a review of state regulatory and monitoring policiesexternal icon
        Kroelinger CD, Okoroh EM, Goodman DA, Lasswell SM, Barfield WD.
        J Perinatol. 2019 Sep 30.
        OBJECTIVE: Summarize policies on levels of neonatal care designation among 50 states and District of Columbia (DC). STUDY DESIGN: Systematic review of publicly available, web-based information on levels of neonatal care designation policies for each state/DC. Information on designating authorities, designation oversight, licensure requirement, and ongoing monitoring for designated levels of care abstracted from 2019 published rules, statutes, and regulations. RESULT: Thirty-one (61%) of 50 states/DC had designated authority policies for neonatal levels of care. Fourteen (27%) incorporated oversight of neonatal levels of care into the licensure process. Among jurisdictions with designated authority, 25 (81%) used a state agency and 15 (48%) had direct oversight. Twenty-two (71%) of 31 states with a designating authority required ongoing monitoring, 14 (64%) used both hospital reporting and site visits for monitoring with only ten requiring site visits. CONCLUSIONS: Limited direct oversight influences regulation of regionalized systems, potentially impacting facility service monitoring and consequent management of vulnerable infants.

      3. National population-based estimates for major birth defects, 2010-2014external icon
        Mai CT, Isenburg JL, Canfield MA, Meyer RE, Correa A, Alverson CJ, Lupo PJ, Riehle-Colarusso T, Cho SJ, Aggarwal D, Kirby RS.
        Birth Defects Res. 2019 Oct 3.
        BACKGROUND: Using the National Birth Defects Prevention Network (NBDPN) annual data report, U.S. national prevalence estimates for major birth defects are developed based on birth cohort 2010-2014. METHODS: Data from 39 U.S. population-based birth defects surveillance programs (16 active case-finding, 10 passive case-finding with case confirmation, and 13 passive without case confirmation) were used to calculate pooled prevalence estimates for major defects by case-finding approach. Fourteen active case-finding programs including at least live birth and stillbirth pregnancy outcomes monitoring approximately one million births annually were used to develop national prevalence estimates, adjusted for maternal race/ethnicity (for all conditions examined) and maternal age (trisomies and gastroschisis). These calculations used a similar methodology to the previous estimates to examine changes over time. RESULTS: The adjusted national birth prevalence estimates per 10,000 live births ranged from 0.62 for interrupted aortic arch to 16.87 for clubfoot, and 19.93 for the 12 critical congenital heart defects combined. While the birth prevalence of most birth defects studied remained relatively stable over 15 years, an increasing prevalence was observed for gastroschisis and Down syndrome. Additionally, the prevalence for atrioventricular septal defect, tetralogy of Fallot, omphalocele, and trisomy 18 increased in this period compared to the previous periods. Active case-finding programs generally had higher prevalence rates for most defects examined, most notably for anencephaly, anophthalmia/microphthalmia, trisomy 13, and trisomy 18. CONCLUSION: National estimates of birth defects prevalence provide data for monitoring trends and understanding the impact of these conditions. Increasing prevalence rates observed for selected conditions warrant further examination.

      4. Clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescentsexternal icon
        Wolraich ML, Hagan JF, Allan C, Chan E, Davison D, Earls M, Evans SW, Flinn SK, Froehlich T, Frost J, Holbrook JR, Lehmann CU, Lessin HR, Okechukwu K, Pierce KL, Winner JD, Zurhellen W.
        Pediatrics. 2019 Oct;144(4).
        Attention-deficit/hyperactivity disorder (ADHD) is 1 of the most common neurobehavioral disorders of childhood and can profoundly affect children’s academic achievement, well-being, and social interactions. The American Academy of Pediatrics first published clinical recommendations for evaluation and diagnosis of pediatric ADHD in 2000; recommendations for treatment followed in 2001. The guidelines were revised in 2011 and published with an accompanying process of care algorithm (PoCA) providing discrete and manageable steps by which clinicians could fulfill the clinical guideline’s recommendations. Since the release of the 2011 guideline, the Diagnostic and Statistical Manual of Mental Disorders has been revised to the fifth edition, and new ADHD-related research has been published. These publications do not support dramatic changes to the previous recommendations. Therefore, only incremental updates have been made in this guideline revision, including the addition of a key action statement related to diagnosis and treatment of comorbid conditions in children and adolescents with ADHD. The accompanying process of care algorithm has also been updated to assist in implementing the guideline recommendations. Throughout the process of revising the guideline and algorithm, numerous systemic barriers were identified that restrict and/or hamper pediatric clinicians’ ability to adopt their recommendations. Therefore, the subcommittee created a companion article (available in the Supplemental Information) on systemic barriers to the care of children and adolescents with ADHD, which identifies the major systemic-level barriers and presents recommendations to address those barriers; in this article, we support the recommendations of the clinical practice guideline and accompanying process of care algorithm.

      5. Prevalence and trends of developmental disabilities among children in the United States: 2009-2017external icon
        Zablotsky B, Black LI, Maenner MJ, Schieve LA, Danielson ML, Bitsko RH, Blumberg SJ, Kogan MD, Boyle CA.
        Pediatrics. 2019 Oct;144(4).
        OBJECTIVES: To study the national prevalence of 10 developmental disabilities in US children aged 3 to 17 years and explore changes over time by associated demographic and socioeconomic characteristics, using the National Health Interview Survey. METHODS: Data come from the 2009 to 2017 National Health Interview Survey, a nationally representative survey of the civilian noninstitutionalized population. Parents reported physician or other health care professional diagnoses of attention-deficit/hyperactivity disorder; autism spectrum disorder; blindness; cerebral palsy; moderate to profound hearing loss; learning disability; intellectual disability; seizures; stuttering or stammering; and other developmental delays. Weighted percentages for each of the selected developmental disabilities and any developmental disability were calculated and stratified by demographic and socioeconomic characteristics. RESULTS: From 2009 to 2011 and 2015 to 2017, there were overall significant increases in the prevalence of any developmental disability (16.2%-17.8%, P < .001), attention-deficit/hyperactivity disorder (8.5%-9.5%, P < .01), autism spectrum disorder (1.1%-2.5%, P < .001), and intellectual disability (0.9%-1.2%, P < .05), but a significant decrease for any other developmental delay (4.7%-4.1%, P < .05). The prevalence of any developmental disability increased among boys, older children, non-Hispanic white and Hispanic children, children with private insurance only, children with birth weight >/=2500 g, and children living in urban areas and with less-educated mothers. CONCLUSIONS: The prevalence of developmental disability among US children aged 3 to 17 years increased between 2009 and 2017. Changes by demographic and socioeconomic subgroups may be related to improvements in awareness and access to health care.

    • Medicine
      1. PAs and NPs have broad prescribing authority in the United States, yet little is known about how the quality of their prescribing practices compares with that of physicians. The quality of prescribing practices of physicians, PAs, and NPs was investigated through a serial cross-sectional analysis of the 2006-2012 National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS). Ambulatory care services in physician offices, hospital EDs, and outpatient departments were evaluated using a nationally representative sample of patient visits to physicians, PAs, and NPs. Main outcome measures were 13 validated outpatient quality indicators focused on pharmacologic management of chronic diseases and appropriate medication use. The study sampled 701,499 patient visits during the study period, representing about 8.3 billion visits nationwide. Physicians were the primary provider for 96.8% of all outpatient visits examined; PAs and NPs each accounted for 1.6% of these visits. The proportion of eligible visits in which quality standards were met ranged from 34.1% (angiotensin-converting enzyme inhibitor use for patients with heart failure) to 89.5% (avoidance of inappropriate medications in older adults). The median overall performance across all indicators was 58.7%. On unadjusted analyses, differences in quality of care between PAs, NPs, and physicians for each indicator did not consistently favor one practitioner type over others. After adjustment for potentially confounding patient and provider characteristics, the quality of prescribing by PAs and NPs was similar to the care delivered by physicians for 10 of the 13 indicators evaluated, and no consistent directional association was found between provider type and indicator fulfillment for the remaining measures. Although significant shortfalls exist in the quality of ambulatory prescribing across all practitioner types, the quality of care delivered by PAs, NPs, and physicians was generally comparable.(1).

    • Occupational Safety and Health
      1. Associations between adiposity measures and 25-hydroxyvitamin D among police officersexternal icon
        Gu JK, Charles LE, Millen AE, Violanti JM, Ma CC, Jenkins E, Andrew ME.
        Am J Hum Biol. 2019 Sep;31(5):e23274.
        OBJECTIVE: Studies show that serum levels of 25-hydroxyvitamin D (25(OH)D), a biomarker for vitamin D status, are lower in persons with higher adiposity levels and that police officers have been found to have a high prevalence of obesity. The purpose of this study was to examine relationships between several adiposity measures and 25(OH)D, and also compare those measures to determine the best one that predicts insufficiency of 25(OH)D (<20 ng/mL) among police officers in the Northeast area of the United States. METHODS: Participants were 281 police officers (71.5% men) from the Buffalo Cardio-Metabolic Occupational Police Stress Study (2011-2016). Associations of body mass index (BMI), abdominal height (AbHt), waist circumference (WC), WC-to-height ratio (WCHtR), percent body fat (PBF), and fat mass index (FMI) with 25(OH)D were obtained using multiple regression models after adjustment for age, race/ethnicity, season, multivitamin supplement use, and high-density lipoprotein cholesterol. The area under the curve (AUC) was used to evaluate the predictive ability of each adiposity measure to identify insufficient 25(OH)D concentrations. RESULTS: The prevalence of obesity (BMI >/= 30) was 50.7% in men and 21.3% in women. Mean levels of 25(OH)D were 32.4 ng/mL in men and 34.4 ng/mL in women. After adjustment for covariates, PBF and FMI among men were inversely associated with 25(OH)D: PBF (beta +/- SE = -2.40 +/- 1.01, P = .018); FMI (-2.21 +/- 0.93, .018). Among women, no adiposity measure was associated with 25(OH)D. PBF was the best predictor of insufficient 25(OH)D concentrations regardless of gender (AUC = 0.878). CONCLUSION: Adiposity measures were inversely associated with 25(OH)D, but differed between female and male officers.

      2. Biomechanical modeling of deep squatting: Effects of the interface contact between posterior thigh and shankexternal icon
        Wu JZ, Sinsel EW, Carey RE, Zheng L, Warren CM, Breloff SP.
        J Biomech. 2019 Sep 13:109333.
        Epidemiological studies indicate that occupational activities that require extended deep knee flexion or kneeling are associated with a higher prevalence of knee osteoarthritis. In many sport activities, such as a catcher in a baseball or a softball game, athletes have to make repetitive deep squatting motions, which have been associated with the development of osteochondritis dissecans. Excessive deep knee flexion postures may cause excessive loading in the knee joint. In deep knee flexion postures, the posterior aspect of the shank will contact the posterior thigh, resulting in a compressive force within the soft tissues. The current study was aimed at analyzing the effects of the posterior thigh/shank contact on the joint loading during deep knee flexion in a natural knee. An existing, whole body model with detailed anatomical components of the knee (AnyBody) has been adopted and modified for this study. The effects of the posterior thigh/shank contact were evaluated by comparing the results of the inverse dynamic analysis for two scenarios: with and without the posterior thigh/shank contact force. Our results showed that, in a deep squatting posture (knee flexion 120+ degrees), the posterior thigh/shank contact helps reduce the patellofemoral (PF) and tibiofemoral (TF) normal contact forces by 42% and 57%, respectively.

    • Public Health Leadership and Management
      1. BACKGROUND: Quality improvement collaboratives (QICs) have been used to improve health care for decades. Evidence on QIC effectiveness has been reported, but systematic reviews to date have little information from low- and middle-income countries (LMICs). OBJECTIVE: To assess the effectiveness of QICs in LMICs. METHODS: We conducted a systematic review following Cochrane methods, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for quality of evidence grading, and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement for reporting. We searched published and unpublished studies between 1969 and March 2019 from LMICs. We included papers that compared usual practice with QICs alone or combined with other interventions. Pairs of reviewers independently selected and assessed the risk of bias and extracted data of included studies. To estimate strategy effectiveness from a single study comparison, we used the median effect size (MES) in the comparison for outcomes in the same outcome group. The primary analysis evaluated each strategy group with a weighted median and interquartile range (IQR) of MES values. In secondary analyses, standard random-effects meta-analysis was used to estimate the weighted mean MES and 95% confidence interval (CI) of the mean MES of each strategy group. This review is registered with PROSPERO (International Prospective Register of Systematic Reviews): CRD42017078108. RESULTS: Twenty-nine studies were included; most (21/29, 72.4%) were interrupted time series studies. Evidence quality was generally low to very low. Among studies involving health facility-based health care providers (HCPs), for “QIC only”, effectiveness varied widely across outcome groups and tended to have little effect for patient health outcomes (median MES less than 2 percentage points for percentage and continuous outcomes). For “QIC plus training”, effectiveness might be very high for patient health outcomes (for continuous outcomes, median MES 111.6 percentage points, range: 96.0 to 127.1) and HCP practice outcomes (median MES 52.4 to 63.4 percentage points for continuous and percentage outcomes, respectively). The only study of lay HCPs, which used “QIC plus training”, showed no effect on patient care-seeking behaviors (MES -0.9 percentage points), moderate effects on non-care-seeking patient behaviors (MES 18.7 percentage points), and very large effects on HCP practice outcomes (MES 50.4 percentage points). CONCLUSIONS: The effectiveness of QICs varied considerably in LMICs. QICs combined with other invention components, such as training, tended to be more effective than QICs alone. The low evidence quality and large effect sizes for QIC plus training justify additional high-quality studies assessing this approach in LMICs.

    • Substance Use and Abuse
      1. Biochemical verification of tobacco use and abstinence: 2019 updateexternal icon
        Benowitz NL, Bernert JT, Foulds J, Hecht SS, Jacob P, Jarvis MJ, Joseph A, Oncken C, Piper ME.
        Nicotine Tob Res. 2019 Oct 1.
        BACKGROUND: The changing prevalence and patterns of tobacco use, the advent of novel nicotine delivery devices, and the development of new biomarkers prompted an update of the 2002 Society for Research on Nicotine and Tobacco (SRNT) report on whether and how to apply biomarker verification for tobacco use and abstinence. METHODS: The SRNT Treatment Research Network convened a group of investigators with expertise in tobacco biomarkers to update the recommendations of the 2002 SNRT Biochemical Verification Report. RESULTS: Biochemical verification of tobacco use and abstinence increases scientific rigor and is recommended in clinical trials of smoking cessation, when feasible. Sources, appropriate biospecimens, cutpoints, time of detection windows and analytic methods for carbon monoxide, cotinine (including over the counter tests), total nicotine equivalents, minor tobacco alkaloids, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol are reviewed, as well as biochemical approaches to distinguishing cigarette smoking from use of electronic nicotine delivery devices (ENDS). CONCLUSIONS: Recommendations are provided for whether and how to use biochemical verification of tobacco use and abstinence. Guidelines are provided on which biomarkers to use, which biospecimens to use, optimal cutpoints, time windows to detection, and methodology for biochemical verifications. Use of combinations of biomarkers is recommended for assessment of ENDS use. IMPLICATIONS: Biochemical verification increases scientific rigor, but there are drawbacks that need to be assessed to determine whether the benefits of biochemical verification outweigh the costs, including the cost of the assays, the feasibility of sample collection, the ability to draw clear conclusions based on the duration of abstinence, and the variability of the assay within the study population. This paper provides updated recommendations from the 2002 SRNT report on whether and how to use biochemical markers in determining tobacco use and abstinence.

      2. Flavored tobacco product use among middle and high school students – United States, 2014-2018external icon
        Cullen KA, Liu ST, Bernat JK, Slavit WI, Tynan MA, King BA, Neff LJ.
        MMWR Morb Mortal Wkly Rep. 2019 Oct 4;68(39):839-844.
        The 2009 Family Smoking Prevention and Tobacco Control Act prohibits the inclusion of characterizing flavors (e.g., candy or fruit) other than tobacco and menthol in cigarettes; however, characterizing flavors are not currently prohibited in other tobacco products at the federal level.* Flavored tobacco products can appeal to youths and young adults and influence initiation and establishment of tobacco-use patterns (1). The Food and Drug Administration (FDA) and CDC analyzed data from the 2014-2018 National Youth Tobacco Surveys (NYTS) to determine prevalence of current (past 30-day) use of flavored tobacco products, including electronic cigarettes (e-cigarettes), hookah tobacco, cigars, pipe tobacco, smokeless tobacco, bidis, and menthol cigarettes among U.S. middle school (grades 6-8) and high school (grades 9-12) students. In 2018, an estimated 3.15 million (64.1%) youth tobacco product users currently used one or more flavored tobacco products, compared with 3.26 million (70.0%) in 2014. Despite this overall decrease in use of flavored tobacco products, current use of flavored e-cigarettes increased among high school students during 2014-2018; among middle school students, current use of flavored e-cigarettes increased during 2015-2018, following a decrease during 2014-2015. During 2014-2018, current use of flavored hookah tobacco decreased among middle and high school students; current use of flavored smokeless tobacco, cigars, pipe tobacco, and menthol cigarettes decreased among high school students. Full implementation of comprehensive tobacco prevention and control strategies, coupled with regulation of tobacco products by FDA, can help prevent and reduce use of tobacco products, including flavored tobacco products, among U.S. youths (2,3).

      3. E-cigarette product use, or vaping, among persons with associated lung injury – Illinois and Wisconsin, April-September 2019external icon
        Ghinai I, Pray IW, Navon L, O’Laughlin K, Saathoff-Huber L, Hoots B, Kimball A, Tenforde MW, Chevinsky JR, Layer M, Ezike N, Meiman J, Layden JE.
        MMWR Morb Mortal Wkly Rep. 2019 Oct 4;68(39):865-869.
        In July 2019, the Illinois Department of Public Health and the Wisconsin Department of Health Services launched a coordinated epidemiologic investigation after receiving reports of several cases of lung injury in previously healthy persons who reported electronic cigarette (e-cigarette) use, or vaping (1). This report describes features of e-cigarette product use by patients in Illinois and Wisconsin. Detailed patient interviews were conducted by telephone, in person, or via the Internet with 86 (68%) of 127 patients. Overall, 75 (87%) of 86 interviewed patients reported using e-cigarette products containing tetrahydrocannabinol (THC), and 61 (71%) reported using nicotine-containing products. Numerous products and brand names were identified by patients. Nearly all (96%) THC-containing products reported were packaged, prefilled cartridges, and 89% were primarily acquired from informal sources (e.g., friends, family members, illicit dealers, or off the street). In contrast, 77% of nicotine-containing products were sold as prefilled cartridges, and 83% were obtained from commercial vendors. The precise source of this outbreak is currently unknown (2); however, the predominant use of prefilled THC-containing cartridges among patients with lung injury associated with e-cigarette use suggests that they play an important role. While this investigation is ongoing, CDC recommends that persons consider refraining from using e-cigarette, or vaping, products, particularly those containing THC. Given the diversity of products reported and frequency of patients using both THC- and nicotine-containing e-cigarette products, additional methods such as product testing and traceback could help identify the specific cause of this outbreak.

      4. An examination of concurrent opioid and benzodiazepine prescribing in 9 states, 2015external icon
        Guy GP, Zhang K, Halpin J, Sargent W.
        Am J Prev Med. 2019 Sep 27.
        INTRODUCTION: Concurrent prescribing of opioids and benzodiazepines is discouraged by evidence-based clinical guidelines because of the known risks of taking these medications in combination. METHODS: This study analyzed concurrent opioid and benzodiazepine prescribing in 9 states using the 2015 Prescription Behavior Surveillance System, a multistate database of de-identified prescription drug monitoring program data. Concurrent prescribing rates were examined among individuals with both an opioid and a benzodiazepine prescription. Among patients with concurrent prescribing, total days of opioid supply, daily dosage of opioids, and total days of concurrent prescriptions were examined. Analyses were stratified by whether concurrent prescribing was from a single prescriber or multiple prescribers. Opioid prescribing and concurrent opioid and benzodiazepine prescribing rates were examined by age and sex. Analyses were conducted in 2018. RESULTS: Among 19,977,642 patients that were prescribed an opioid, 21.6% (4,324,092) were also prescribed a benzodiazepine, of which 54.9% (2,375,219) had concurrent prescriptions. More than half of patients with concurrent opioids and benzodiazepines received prescriptions from 2 or more distinct prescribers. Mean total opioid days, daily opioid dosage, and days of concurrent prescribing were higher among patients when multiple prescribers were involved compared with concurrent prescriptions from the same prescriber. Concurrent prescribing was more common among adults aged >/=50 years and female patients. CONCLUSIONS: Public health interventions are needed to reduce concurrent prescribing of opioids and benzodiazepines. Evidence-based guidelines can help reduce concurrent prescribing when one prescriber is involved, and utilization of prescription drug monitoring programs and improved care coordination could help address concurrent prescribing when multiple prescribers are involved.

      5. Hepatitis C virus (HCV) is transmitted primarily through parenteral exposures to infectious blood or body fluids that contain blood (e.g., via injection drug use, needle stick injuries) (1). In the last 10 years, increases in HCV infection in the general U.S. population (1) and among pregnant women (2) are attributed to a surge in injection drug use associated with the opioid crisis. Opioid use disorders among pregnant women have increased (3), and approximately 68% of pregnant women with HCV infection have opioid use disorder (4). National trends in HCV infection among pregnant women by opioid use disorder status have not been reported to date. CDC analyzed hospital discharge data from the 2000-2015 Healthcare Cost and Utilization Project (HCUP) to determine whether HCV infection trends differ by opioid use disorder status at delivery. During this period, the national rate of HCV infection among women giving birth increased >400%, from 0.8 to 4.1 per 1,000 deliveries. Among women with opioid use disorder, rates of HCV infection increased 148%, from 87.4 to 216.9 per 1,000 deliveries, and among those without opioid use disorder, rates increased 271%, although the rates in this group were much lower, increasing from 0.7 to 2.6 per 1,000 deliveries. These findings align with prior ecological data linking hepatitis C increases with the opioid crisis (2). Treatment of opioid use disorder should include screening and referral for related conditions such as HCV infection.

      6. Designing traceable opioid material kits to improve laboratory testing during the U.S. opioid overdose crisisexternal icon
        Mojica MA, Carter MD, Isenberg SL, Pirkle JL, Hamelin EI, Shaner RL, Seymour C, Sheppard CI, Baldwin GT, Johnson RC.
        Toxicol Lett. 2019 Sep 24.
        In 2017, the U.S. Department of Health and Human Services and the White House declared a public health emergency to address the opioid crisis (Hargan, 2017). On average, 192 Americans died from drug overdoses each day in 2017; 130 (67%) of those died specifically because of opioids (Scholl et al., 2019). Since 2013, there have been significant increases in overdose deaths involving synthetic opioids – particularly those involving illicitly-manufactured fentanyl. The U.S. Drug Enforcement Administration (DEA) estimates that 75% of all opioid identifications are illicit fentanyls (DEA, 2018b). Laboratories are routinely asked to confirm which fentanyl or other opioids are involved in an overdose or encountered by first responders. It is critical to identify and classify the types of drugs involved in an overdose, how often they are involved, and how that involvement may change over time. Health care providers, public health professionals, and law enforcement officers need to know which opioids are in use to treat, monitor, and investigate fatal and non-fatal overdoses. By knowing which drugs are present, appropriate prevention and response activities can be implemented. Laboratory testing is available for clinically used and widely recognized opioids. However, there has been a rapid expansion in new illicit opioids, particularly fentanyl analogs that may not be addressed by current laboratory capabilities. In order to test for these new opioids, laboratories require reference standards for the large number of possible fentanyls. To address this need, the Centers for Disease Control and Prevention (CDC) developed the Traceable Opioid Material( section sign) Kits product line, which provides over 150 opioid reference standards, including over 100 fentanyl analogs. These kits were designed to dramatically increase laboratory capability to confirm which opioids are on the streets and causing deaths. The kits are free to U.S based laboratories in the public, private, clinical, law enforcement, research, and public health domains.

      7. Characteristics of a multistate outbreak of lung injury associated with e-cigarette use, or vaping – United States, 2019external icon
        Perrine CG, Pickens CM, Boehmer TK, King BA, Jones CM, DeSisto CL, Duca LM, Lekiachvili A, Kenemer B, Shamout M, Landen MG, Lynfield R, Ghinai I, Heinzerling A, Lewis N, Pray IW, Tanz LJ, Patel A, Briss PA.
        MMWR Morb Mortal Wkly Rep. 2019 Oct 4;68(39):860-864.
        Electronic cigarettes (e-cigarettes), also called vapes, e-hookas, vape pens, tank systems, mods, and electronic nicotine delivery systems (ENDS), are electronic devices that produce an aerosol by heating a liquid typically containing nicotine, flavorings, and other additives; users inhale this aerosol into their lungs (1). E-cigarettes also can be used to deliver tetrahydrocannabinol (THC), the principal psychoactive component of cannabis (1). Use of e-cigarettes is commonly called vaping. Lung injury associated with e-cigarette use, or vaping, has recently been reported in most states (2-4). CDC, the Food and Drug Administration (FDA), state and local health departments, and others are investigating this outbreak. This report provides data on patterns of the outbreak and characteristics of patients, including sex, age, and selected substances used in e-cigarette, or vaping, products reported to CDC as part of this ongoing multistate investigation. As of September 24, 2019, 46 state health departments and one territorial health department had reported 805 patients with cases of lung injury associated with use of e-cigarette, or vaping, products to CDC. Sixty-nine percent of patients were males, and the median age was 23 years (range = 13-72 years). To date, 12 deaths have been confirmed in 10 states. Among 514 patients with information on substances used in e-cigarettes, or vaping products, in the 30 days preceding symptom onset, 76.9% reported using THC-containing products, and 56.8% reported using nicotine-containing products; 36.0% reported exclusive use of THC-containing products, and 16.0% reported exclusive use of nicotine-containing products. The specific chemical exposure(s) causing the outbreak is currently unknown. While this investigation is ongoing, CDC recommends that persons consider refraining from using e-cigarette, or vaping, products, particularly those containing THC. CDC will continue to work in collaboration with FDA and state and local partners to investigate cases and advise and alert the public on the investigation as additional information becomes available.

      8. Are there hardened smokers in low- and middle-income countries? Findings from the Global Adult Tobacco Surveyexternal icon
        Yin S, Ahluwalia IB, Krishna P, Mbulo L, Arrazola RA.
        Tob Induc Dis. 2019 ;17(February).
        Introduction: Hardened smokers are those who do not want to quit, or find it very difficult to quit. This study assessed the prevalence and predictors of hardened smokers in 19 low- and middle-income countries (LMICs).

    • Vital Statistics
      1. Evaluation of approaches to strengthen civil registration and vital statistics systems: A systematic review and synthesis of policies in 25 countriesexternal icon
        Suthar AB, Khalifa A, Yin S, Wenz K, Ma Fat D, Mills SL, Nichols E, AbouZahr C, Mrkic S.
        PLoS Med. 2019 Sep;16(9):e1002929.
        BACKGROUND: Civil registration and vital statistics (CRVS) systems play a key role in upholding human rights and generating data for health and good governance. They also can help monitor progress in achieving the United Nations Sustainable Development Goals. Although many countries have made substantial progress in strengthening their CRVS systems, most low- and middle-income countries still have underdeveloped systems. The objective of this systematic review is to identify national policies that can help countries strengthen their systems. METHODS AND FINDINGS: The ABI/INFORM, Embase, JSTOR, PubMed, and WHO Index Medicus databases were systematically searched for policies to improve birth and/or death registration on 24 January 2017. Global stakeholders were also contacted for relevant grey literature. For the purposes of this review, policies were categorised as supply, demand, incentive, penalty, or combination (i.e., at least two of the preceding policy approaches). Quantitative results on changes in vital event registration rates were presented for individual comparative articles. Qualitative systematic review methodology, including meta-ethnography, was used for qualitative syntheses on operational considerations encompassing acceptability to recipients and staff, human resource requirements, information technology or infrastructure requirements, costs to the health system, unintended effects, facilitators, and barriers. This study is registered with PROSPERO, number CRD42018085768. Thirty-five articles documenting experience in implementing policies to improve birth and/or death registration were identified. Although 25 countries representing all global regions (Africa, the Americas, Southeast Asia, the Western Pacific, Europe, and the Eastern Mediterranean) were reflected, there were limited countries from the Eastern Mediterranean and Europe regions. Twenty-four articles reported policy effects on birth and/or death registration. Twenty-one of the 24 articles found that the change in registration rate after the policy was positive, with two supply and one penalty articles being the exceptions. The qualitative syntheses identified 15 operational considerations across all policy categories. Human and financial resource requirements were not quantified. The primary limitation of this systematic review was the threat of publication bias wherein many countries may not have documented their experience; this threat is most concerning for policies that had neutral or negative effects. CONCLUSIONS: Our systematic review suggests that combination policy approaches, consisting of at least a supply and demand component, were consistently associated with improved registration rates in different geographical contexts. Operational considerations should be interpreted based on health system, governance, and sociocultural context. More evaluations and research are needed from the Eastern Mediterranean and Europe regions. Further research and evaluation are also needed to estimate the human and financial resource requirements required for different policies.

    • Zoonotic and Vectorborne Diseases
      1. Evaluation of infection prevention and control readiness at frontline health care facilities in high-risk districts bordering Ebola virus disease-affected areas in the Democratic Republic of the Congo – Uganda, 2018external icon
        Biedron C, Lyman M, Stuckey MJ, Homsy J, Lamorde M, Luvsansharav UO, Wilson K, Gomes D, Omuut W, Okware S, Semanda JN, Kiggundu R, Bulwadda D, Brown V, Nelson LJ, Driwale A, Fagan R, Park BJ, Smith RM.
        MMWR Morb Mortal Wkly Rep. 2019 Oct 4;68(39):851-854.
        Infection prevention and control (IPC) in health care facilities is essential to protecting patients, visitors, and health care personnel from the spread of infectious diseases, including Ebola virus disease (Ebola). Patients with suspected Ebola are typically referred to specialized Ebola treatment units (ETUs), which have strict isolation and IPC protocols, for testing and treatment (1,2). However, in settings where contact tracing is inadequate, Ebola patients might first seek care at general health care facilities, which often have insufficient IPC capacity (3-6). Before 2014-2016, most Ebola outbreaks occurred in rural or nonurban communities, and the role of health care facilities as amplification points, while recognized, was limited (7,8). In contrast to these earlier outbreaks, the 2014-2016 West Africa Ebola outbreak occurred in densely populated urban areas where access to health care facilities was better, but contact tracing was generally inadequate (8). Patients with unrecognized Ebola who sought care at health care facilities with inadequate IPC initiated multiple chains of transmission, which amplified the epidemic to an extent not seen in previous Ebola outbreaks (3-5,7). Implementation of robust IPC practices in general health care facilities was critical to ending health care-associated transmission (8). In August 2018, when an Ebola outbreak was recognized in the Democratic Republic of the Congo (DRC), neighboring countries began preparing for possible introduction of Ebola, with a focus on IPC. Baseline IPC assessments conducted in frontline health care facilities in high-risk districts in Uganda found IPC gaps in screening, isolation, and notification. Based on findings, additional funds were provided for IPC, a training curriculum was developed, and other corrective actions were taken. Ebola preparedness efforts should include activities to ensure that frontline health care facilities have the IPC capacity to rapidly identify suspected Ebola cases and refer such patients for treatment to protect patients, staff members, and visitors.

      2. Better surveillance to protect mothers and infants from Zikaexternal icon
        Gilboa SM, Gregory CJ, Honein MA.
        Lancet Infect Dis. 2019 Oct;19(10):1047-1048.

        [No abstract]

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DISCLAIMER: Articles listed in the CDC Science Clips are selected by the Stephen B. Thacker CDC Library to provide current awareness of the public health literature. An article's inclusion does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.

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