Volume 12, Issue 10, March 23, 2020

CDC Science Clips: Volume 12, Issue 10, March 24, 2020

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!

This week Science Clips is pleased to feature articles on the topic of p-Values.

The American Statistical Association released a statement on p-Values and statistical inference in 2016, catalyzing conversations about statistical applications and literacy throughout the scientific community. In March 2019, The American Statistician released a special issue containing an introductory editorial that expanded from the 2016 statement and provided more specific guidance for using p-Values and “statistical significance” in analyses and reports. Following the introduction were 43 articles to offer p-Value complements, supplements, and replacements, as well as guidance for presenting statistical results in scientific reports.

There is no consensus in the statistical community about the best methods to move forward, although there is consensus that it is time to reconsider current usage of p-values in the scientific literature. This Science Clips compilation comprises the American Statistical Association statements, select articles from the special issue of The American Statistician, and public health research articles that applied supplemental measures to p-Values. This compilation does not endorse these particular methods, but rather highlights the variety of methods for researchers to consider in order to adopt the American Statistical Association’s latest recommendations.

  1. Key Scientific Articles in Featured Topic Areas
    Subject matter experts decide what topic to feature, and articles are selected from the last 3 to 6 months of published literature. Key topic coincides monthly with other CDC products (e.g. Vital Signs).
    • Statistics as Topic - p-Values
      1. The ASA statement on p-values: Context, process, and purposeexternal icon
        Wasserstein RL, Lazar NA.
        Am Stat. 2016 2016/04/02;70(2):129-133.

      2. Phthalate Exposure and Breast Cancer Incidence: A Danish Nationwide Cohort Studyexternal icon
        Ahern TP, Broe A, Lash TL, Cronin-Fenton DP, Ulrichsen SP, Christiansen PM, Cole BF, Tamimi RM, Sorensen HT, Damkier P.
        J Clin Oncol. 2019 Jul 20;37(21):1800-1809.
        PURPOSE: Phthalate exposure is ubiquitous and especially high among users of drug products formulated with phthalates. Some phthalates mimic estradiol and may promote breast cancer. Existing epidemiologic studies on this topic are small, mostly not prospective, and have given inconsistent results. We estimated associations between longitudinal phthalate exposures and breast cancer risk in a Danish nationwide cohort, using redeemed prescriptions for phthalate-containing drug products to measure exposure. METHODS: We ascertained the phthalate content of drugs marketed in Denmark using an internal Danish Medicines Agency ingredient database. We enrolled a Danish nationwide cohort of 1.12 million women at risk for a first cancer diagnosis on January 1, 2005. By combining drug ingredient data with the Danish National Prescription registry, we characterized annual, cumulative phthalate exposure through redeemed prescriptions. We then fit multivariable Cox regression models to estimate associations between phthalate exposures and incident invasive breast carcinoma according to tumor estrogen receptor status. RESULTS: Over 9.99 million woman-years of follow-up, most phthalate exposures were not associated with breast cancer incidence. High-level dibutyl phthalate exposure (>/= 10,000 cumulative mg) was associated with an approximately two-fold increase in the rate of estrogen receptor-positive breast cancer (hazard ratio, 1.9; 95% CI, 1.1 to 3.5), consistent with in vitro evidence for an estrogenic effect of this compound. Lower levels of dibutyl phthalate exposure were not associated with breast cancer incidence. CONCLUSION: Our results suggest that women should avoid high-level exposure to dibutyl phthalate, such as through long-term treatment with pharmaceuticals formulated with dibutyl phthalate.

      3. Three recommendations for improving the use of p-valuesexternal icon
        Benjamin DJ, Berger JO.
        Am Stat. 2019 2019/03/29;73(sup1):186-191.
        Researchers commonly use p-values to answer the question: How strongly does the evidence favor the alternative hypothesis relative to the null hypothesis? p-Values themselves do not directly answer this question and are often misinterpreted in ways that lead to overstating the evidence against the null hypothesis. Even in the post p<0.05 era, however, it is quite possible that p-values will continue to be widely reported and used to assess the strength of evidence (if for no other reason than the widespread availability and use of statistical software that routinely produces p-values and thereby implicitly advocates for their use). If so, the potential for misinterpretation will persist. In this article, we recommend three practices that would help researchers more accurately interpret p-values. Each of the three recommended practices involves interpreting p-values in light of their corresponding Bayes factor bound, which is the largest odds in favor of the alternative hypothesis relative to the null hypothesis that is consistent with the observed data. The Bayes factor bound generally indicates that a given p-value provides weaker evidence against the null hypothesis than typically assumed. We therefore believe that our recommendations can guard against some of the most harmful p-value misinterpretations. In research communities that are deeply attached to reliance on p<0.05, our recommendations will serve as initial steps away from this attachment. We emphasize that our recommendations are intended merely as initial, temporary steps and that many further steps will need to be taken to reach the ultimate destination: a holistic interpretation of statistical evidence that fully conforms to the principles laid out in the ASA statement on statistical significance and p-values.

      4. An introduction to second-generation p-valuesexternal icon
        Blume JD, Greevy R, Welty VF, Smith JR, Dupont WD.
        Am Stat. 2019 2019/03/29;73(sup1):157-167.
        Second generation p-values preserve the simplicity that has made p-values popular while resolving critical flaws that promote misinterpretation of data, distraction by trivial effects, and unreproducible assessments of data. The second-generation p-value (SGPV) is an extension that formally accounts for scientific relevance by using a composite null hypothesis that captures null and scientifically trivial effects. Because the majority of spurious findings are small effects that are technically nonnull but practically indistinguishable from the null, the second-generation approach greatly reduces the likelihood of a false discovery. SGPVs promote transparency, rigor and reproducibility of scientific results by a priori identifying which candidate hypotheses are practically meaningful and by providing a more reliable statistical summary of when the data are compatible with the candidate hypotheses or null hypotheses, or when the data are inconclusive. We illustrate the importance of these advances using a dataset of 247,000 single-nucleotide polymorphisms, i.e., genetic markers that are potentially associated with prostate cancer.

      5. BACKGROUND: Cryptosporidium is a leading cause of moderate-to-severe diarrhea (MSD) in young children in Africa. We examined factors associated with Cryptosporidium infection in MSD cases enrolled at the rural western Kenya Global Enteric Multicenter Study (GEMS) site from 2008-2012. METHODOLOGY/PRINCIPAL FINDINGS: At health facility enrollment, stool samples were tested for enteric pathogens and data on clinical, environmental, and behavioral characteristics collected. Each child's health status was recorded at 60-day follow-up. Data were analyzed using logistic regression. Of the 1,778 children with MSD enrolled as cases in the GEMS-Kenya case-control study, 11% had Cryptosporidium detected in stool by enzyme immunoassay; in a genotyped subset, 81% were C. hominis. Among MSD cases, being an infant, having mucus in stool, and having prolonged/persistent duration diarrhea were associated with being Cryptosporidium-positive. Both boiling drinking water and using rainwater as the main drinking water source were protective factors for being Cryptosporidium-positive. At follow-up, Cryptosporidium-positive cases had increased odds of being stunted (adjusted odds ratio [aOR] = 1.65, 95% CI: 1.06-2.57), underweight (aOR = 2.08, 95% CI: 1.34-3.22), or wasted (aOR = 2.04, 95% CI: 1.21-3.43), and had significantly larger negative changes in height- and weight-for-age z-scores from enrollment. CONCLUSIONS/SIGNIFICANCE: Cryptosporidium contributes significantly to diarrheal illness in young children in western Kenya. Advances in point of care detection, prevention/control approaches, effective water treatment technologies, and clinical management options for children with cryptosporidiosis are needed.

      6. A proposed hybrid effect size plus p-value criterion: Empirical evidence supporting its useexternal icon
        Goodman WM, Spruill SE, Komaroff E.
        Am Stat. 2019 2019/03/29;73(sup1):168-185.
        When the editors of Basic and Applied Social Psychology effectively banned the use of null hypothesis significance testing (NHST) from articles published in their journal, it set off a fire-storm of discussions both supporting the decision and defending the utility of NHST in scientific research. At the heart of NHST is the p-value which is the probability of obtaining an effect equal to or more extreme than the one observed in the sample data, given the null hypothesis and other model assumptions. Although this is conceptually different from the probability of the null hypothesis being true, given the sample, p-values nonetheless can provide evidential information, toward making an inference about a parameter. Applying a 10,000-case simulation described in this article, the authors found that p-values' inferential signals to either reject or not reject a null hypothesis about the mean (α=0.05) were consistent for almost 70% of the cases with the parameter's true location for the sampled-from population. Success increases if a hybrid decision criterion, minimum effect size plus p-value (MESP), is used. Here, rejecting the null also requires the difference of the observed statistic from the exact null to be meaningfully large or practically significant, in the researcher's judgment and experience. The simulation compares performances of several methods: from p-value and/or effect size-based, to confidence-interval based, under various conditions of true location of the mean, test power, and comparative sizes of the meaningful distance and population variability. For any inference procedure that outputs a binary indicator, like flagging whether a p-value is significant, the output of one single experiment is not sufficient evidence for a definitive conclusion. Yet, if a tool like MESP generates a relatively reliable signal and is used knowledgeably as part of a research process, it can provide useful information.

      7. The present note explores sources of misplaced criticisms of P-values, such as conflicting definitions of significance levels and P-values in authoritative sources, and the consequent misinterpretation of P-values as error probabilities. It then discusses several properties of P-values that have been presented as fatal flaws: That P-values exhibit extreme variation across samples (and thus are unreliable), confound effect size with sample size, are sensitive to sample size, and depend on investigator sampling intentions. These properties are often criticized from a likelihood or Bayesian framework, yet they are exactly the properties P-values should exhibit when they are constructed and interpreted correctly within their originating framework. Other common criticisms are that P-values force users to focus on irrelevant hypotheses and overstate evidence against those hypotheses. These problems are not however properties of P-values but are faults of researchers who focus on null hypotheses and overstate evidence based on misperceptions that p=0.05 represents enough evidence to reject hypotheses. Those problems are easily seen without use of Bayesian concepts by translating the observed P-value p into the Shannon information (S-value or surprisal) log2(p).

      8. Why most published research findings are falseexternal icon
        Ioannidis JP.
        PLoS Med. 2005 Aug;2(8):e124.
        There is increasing concern that most current published research findings are false. The probability that a research claim is true may depend on study power and bias, the number of other studies on the same question, and, importantly, the ratio of true to no relationships among the relationships probed in each scientific field. In this framework, a research finding is less likely to be true when the studies conducted in a field are smaller; when effect sizes are smaller; when there is a greater number and lesser preselection of tested relationships; where there is greater flexibility in designs, definitions, outcomes, and analytical modes; when there is greater financial and other interest and prejudice; and when more teams are involved in a scientific field in chase of statistical significance. Simulations show that for most study designs and settings, it is more likely for a research claim to be false than true. Moreover, for many current scientific fields, claimed research findings may often be simply accurate measures of the prevailing bias. In this essay, I discuss the implications of these problems for the conduct and interpretation of research.

      9. Sensitivity analysis in observational research: Introducing the e-valueexternal icon
        VanderWeele TJ, Ding P.
        Ann Intern Med. 2017 ;167(4):268-274.
        Sensitivity analysis is useful in assessing how robust an association is to potential unmeasured or uncontrolled confounding. This article introduces a new measure called the "E-value," which is related to the evidence for causality in observational studies that are potentially subject to confounding. The E-value is defined as the minimum strength of association, on the risk ratio scale, that an unmeasured confounder would need to have with both the treatment and the outcome to fully explain away a specific treatment–outcome association, conditional on the measured covariates. A large E-value implies that considerable unmeasured confounding would be needed to explain away an effect estimate. A small E-value implies little unmeasured confounding would be needed to explain away an effect estimate. The authors propose that in all observational studies intended to produce evidence for causality, the E-value be reported or some other sensitivity analysis be used. They suggest calculating the E-value for both the observed association estimate (after adjustments for measured confounders) and the limit of the confidence interval closest to the null. If this were to become standard practice, the ability of the scientific community to assess evidence from observational studies would improve considerably, and ultimately, science would be strengthened.

      10. Moving to a world beyond "p < 0.05"external icon
        Wasserstein RL, Schirm AL, Lazar NA.
        Am Stat. 2019 2019/03/29;73(sup1):1-19.

      11. A crisis of validity has emerged from three related crises of science, that is, the crises of statistical significance and complete randomization, of replication, and of reproducibility. Guinnessometrics takes commonplace assumptions and methods of statistical science and stands them on their head, from little p-values to unstructured Big Data. Guinnessometrics focuses instead on the substantive significance which emerges from a small series of independent and economical yet balanced and repeated experiments. Originally developed and market-tested by William S. Gosset aka Student in his job as Head Experimental Brewer at the Guinness Brewery in Dublin, Gosset's economic and common sense approach to statistical inference and scientific method has been unwisely neglected. In many areas of science and life, the 10 principles of Guinnessometrics or G-values outlined here can help. Other things equal, the larger the G-values, the better the science and judgment. By now a colleague, neighbor, or YouTube junkie has probably shown you one of those wacky psychology experiments in a video involving a gorilla, and testing the limits of human cognition. In one video, a person wearing a gorilla suit suddenly appears on the scene among humans, who are themselves engaged in some ordinary, mundane activity such as passing a basketball. The funny thing is, prankster researchers have discovered, when observers are asked to think about the mundane activity (such as by counting the number of observed passes of a basketball), the unexpected gorilla is frequently unseen (for discussion see Kahneman 2011). The gorilla is invisible. People don't see it.

  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. OBJECTIVE: To report U.S. national population-based rates and trends in diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) among adults, in both the emergency department (ED) and inpatient setting. RESEARCH DESIGN AND METHODS: We analyzed data from 1 January 2006 through 30 September 2015 from the Nationwide Emergency Department Sample and National Inpatient Sample to characterize ED visits and inpatient admissions with DKA and HHS. We used corresponding year cross-sectional survey data from the National Health Interview Survey to estimate the number of adults >/=18 years with diagnosed diabetes to calculate population-based rates for DKA and HHS in both ED and inpatient settings. Linear trends from 2009 to 2015 were assessed using Joinpoint software. RESULTS: In 2014, there were a total of 184,255 and 27,532 events for DKA and HHS, respectively. The majority of DKA events occurred in young adults aged 18-44 years (61.7%) and in adults with type 1 diabetes (70.6%), while HHS events were more prominent in middle-aged adults 45-64 years (47.5%) and in adults with type 2 diabetes (88.1%). Approximately 40% of the hyperglycemic events were in lower-income populations. Overall, event rates for DKA significantly increased from 2009 to 2015 in both ED (annual percentage change [APC] 13.5%) and inpatient settings (APC 8.3%). A similar trend was seen for HHS (APC 16.5% in ED and 6.3% in inpatient). The increase was in all age groups and in both men and women. CONCLUSIONS: Causes of increased rates of hyperglycemic events are unknown. More detailed data are needed to investigate the etiology and determine prevention strategies.

      2. Kidney function surveillance in the National Spina Bifida Patient Registry: A retrospective cohort studyexternal icon
        Chu DI, Liu T, Patel P, Routh JC, Ouyang L, Baum MA, Cheng EY, Yerkes EB, Isakova T.
        J Urol. 2020 Mar 6:101097ju0000000000001010.
        PURPOSE: Chronic kidney disease affects 25-50% of patients with spina bifida. Guidelines recommend kidney function surveillance in these patients, but practice patterns are unknown. Variations in kidney function surveillance were assessed across patients with spina bifida, with the hypothesis that the treating clinic and spina bifida type would be associated with kidney function surveillance. MATERIALS AND METHODS: A retrospective cohort study was conducted from 2013-2018 within the National Spina Bifida Patient Registry in the United States. Follow-up was anchored at the 2013 visit. Participants with either an outcome event within 2 years of follow-up or >2 years of follow-up without an outcome event were included. Primary outcome was kidney function surveillance, defined as at least one renal ultrasound and serum creatinine within 2 years of follow-up. Primary exposures were clinic and spina bifida type, which were analyzed with covariates including sociodemographic and clinical characteristics in logistic regression models for their association with the outcome. Sensitivity analyses were performed using different kidney function surveillance definitions. RESULTS: Of 8351 total patients, 5445 were included, with median 3.0 years' follow-up. Across 23 treating clinics, kidney function surveillance rates averaged 62% (range 6-100%). In multivariable models, kidney function surveillance was associated with clinic, younger age, functional lesion level, non-ambulatory status, and prior bladder augmentation. Treating clinic remained a significant predictor of kidney function surveillance in all sensitivity analyses. CONCLUSIONS: Within the National Spina Bifida Patient Registry, wide variation exists in practice of kidney function surveillance across treating clinics, despite adjustment for key patient characteristics.

      3. Incidence and public health burden of sunburn among beachgoers in the United Statesexternal icon
        DeFlorio-Barker S, Holman D, Landolfi R, Arnold BF, Colford JM, Weisberg SB, Schiff KC, Sams EA, Wade TJ.
        Prev Med. 2020 Mar 3:106047.
        The beach environment creates many barriers to effective sun protection, putting beachgoers at risk for sunburn, a well-established risk factor for skin cancer. Our objective was to estimate incidence of sunburn among beachgoers and evaluate the relationship between sunburn incidence and sun-protective behaviors. A secondary analysis, of prospective cohorts at 12 locations within the U.S. from 2003 to 2009 (n=75,614), were pooled to evaluate sunburn incidence 10-12days after the beach visit. Behavioral and environmental conditions were cross-tabulated with sunburn incidence. Multivariable logistic regression was used to estimate the association between new sunburn and sun-protective behaviors. Overall, 13.1% of beachgoers reported sunburn. Those aged 13-18years (16.5%), whites (16.0%), and those at beach locations along the Eastern Seaboard (16.1%), had the highest incidence of sunburn. For those spending >/=5h in the sun, the use of multiple types of sun protection reduced odds of sunburn by 55% relative to those who used no sun protection (Odds Ratio=0.45 (95% Confidence Interval:0.27-0.77)) after adjusting for skin type, age, and race. Acute health effects of sunburn tend to be mild and self-limiting, but potential long-term health consequences are more serious and costly. Efforts to encourage and support proper sun-protective behaviors, and increase access to shade, protective clothing, and sunscreen, can help prevent sunburn and reduce skin cancer risk among beachgoers.

      4. Annual Report to the Nation on the Status of Cancer, part II: Progress toward Healthy People 2020 objectives for 4 common cancersexternal icon
        Henley SJ, Thomas CC, Lewis DR, Ward EM, Islami F, Wu M, Weir HK, Scott S, Sherman RL, Ma J, Kohler BA, Cronin K, Jemal A, Benard VB, Richardson LC.
        Cancer. 2020 Mar 12.
        BACKGROUND: The Centers for Disease Control and Prevention, the American Cancer Society, the National Cancer Institute, and the North American Association of Central Cancer Registries collaborate to provide annual updates on cancer occurrence and trends in the United States and to address a special topic of interest. Part I of this report focuses on national cancer statistics, and part 2 characterizes progress in achieving select Healthy People 2020 cancer objectives. METHODS: For this report, the authors selected objectives-including death rates, cancer screening, and major risk factors-related to 4 common cancers (lung, colorectal, female breast, and prostate). Baseline values, recent values, and the percentage change from baseline to recent values were examined overall and by select sociodemographic characteristics. Data from national surveillance systems were obtained from the Healthy People 2020 website. RESULTS: Targets for death rates were met overall and in most sociodemographic groups, but not among males, blacks, or individuals in rural areas, although these groups did experience larger decreases in rates compared with other groups. During 2007 through 2017, cancer death rates decreased 15% overall, ranging from -4% (rural) to -22% (metropolitan). Targets for breast and colorectal cancer screening were not yet met overall or in any sociodemographic groups except those with the highest educational attainment, whereas lung cancer screening was generally low (<10%). Targets were not yet met overall for cigarette smoking, recent smoking cessation, excessive alcohol use, or obesity but were met for secondhand smoke exposure and physical activity. Some sociodemographic groups did not meet targets or had less improvement than others toward reaching objectives. CONCLUSIONS: Monitoring trends in cancer risk factors, screening test use, and mortality can help assess the progress made toward decreasing the cancer burden in the United States. Although many interventions to reduce cancer risk factors and promote healthy behaviors are proven to work, they may not be equitably applied or work well in every community. Implementing cancer prevention and control interventions that are sustainable, focused, and culturally appropriate may boost success in communities with the greatest need, ensuring that all Americans can access a path to long, healthy, cancer-free lives.

      5. Vital Signs: Colorectal cancer screening test use - United States, 2018external icon
        Joseph DA, King JB, Dowling NF, Thomas CC, Richardson LC.
        MMWR Morb Mortal Wkly Rep. 2020 Mar 13;69(10):253-259.
        BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer death in the United States of cancers that affect both men and women. Despite strong evidence that screening for CRC reduces incidence and mortality, CRC screening prevalence is below the national target. This report describes current CRC screening prevalence by age, various demographic factors, and state. METHODS: Data from the 2018 Behavioral Risk Factor Surveillance System survey were analyzed to estimate the percentages of adults aged 50-75 years who reported CRC screening consistent with the United States Preventive Services Task Force recommendation. RESULTS: In 2018, 68.8% of adults were up to date with CRC screening. The percentage up to date was 79.2% among respondents aged 65-75 years and 63.3% among those aged 50-64 years. CRC screening prevalence was lowest among persons aged 50-54 years (50.0%) and increased with age. Among respondents aged 50-64 years, CRC screening prevalence was lowest among persons without health insurance (32.6%) and highest among those with reported annual household income of >/=$75,000 (70.8%). Among respondents aged 65-75 years, CRC screening prevalence was lowest among those without a regular health care provider (45.6%), and highest among those with reported annual household income >/=$75,000 (87.1%). Among states, CRC screening prevalence was highest in Massachusetts (76.5%) and lowest in Wyoming (57.8%). DISCUSSION: CRC screening prevalence is lower among adults aged 50-64 years, although most reported having a health care provider and health insurance. Concerted efforts are needed to inform persons aged <50 years about the benefit of screening so that screening can start at age 50 years.

      6. Human papillomavirus (HPV) types among Alaska native women attending a colposcopy clinic in Anchorage, Alaska, 2009-2011external icon
        Murphy NJ, Bulkow LR, Steinau M, Dunne EF, Meites E, Markowitz LE, Unger ER, Hennessy TW.
        Infect Agent Cancer. 2020 ;15:13.
        Background: The first HPV vaccines licensed targeted two HPV types responsible for most cervical cancers. A 9-valent vaccine (9vHPV), targeting 5 additional types, was introduced in 2016 and is currently the only HPV vaccine available in the United States. Previous studies demonstrated high rates of HPV infection in Alaska Native (AN) women. We sought to measure prevalence of high risk HPV types in AN women undergoing colposcopy and to determine those preventable by vaccination. Methods: For this cross-sectional study, we recruited women who were undergoing colposcopy for clinical indications at Alaska Native Medical Center to obtain cervical brush biopsy samples. Specimens were shipped to Atlanta, Georgia for DNA extraction, HPV detection, and typing using L1 PCR with type-specific hybridization to detect 37 HPV types. Results: Four hundred eighty eight specimens from 489 women were tested. At least one HPV type was found in 458 (94%) specimens. Of 458 participants who were HPV positive, 332 (72%) had two or more types. At least one type targeted by 9vHPV was detected in 95% of participants with CIN 3 (21/22), 82% with CIN 2 (37/45), and 65% with CIN 1 (119/184). (p < 0.001) HPV 16 or 18 were detected in 77% (17/22) with CIN 3, 53% (24/45) with CIN 2, and 36% (67/184) with CIN 1. (p < 0.001). Conclusions: A substantial proportion of AN women attending colposcopy clinic had evidence of HPV 16/18 infection, as well as other high risk types targeted by 9vHPV. At least one 9vHPV type was detected in 62% of the participants overall, and 95% of participants with CIN3. AN women are expected to benefit from vaccination against HPV 16/18, and will have greater benefit from 9vHPV. Information from this study could be used to develop public health strategies to increase vaccine uptake, or to track HPV genotype prevalence over time.

      7. PURPOSE: The objective of this study was to examine frequent mental distress (FMD) by demographics, chronic conditions, and health risk factors among Illinois adults. DESIGN: Descriptive analyses included chi(2) and pairwise t tests to examine how FMD status differed by selected characteristics and Cox proportional hazards regression analysis to examine the association between FMD and chronic conditions and risk factors. SETTING: Illinois Behavioral Risk Factor Surveillance System, 2011 to 2017 (n = 37 312). PARTICIPANTS: Adults who self-report FMD (n = 3455) were included. MEASURES: Prevalence of high blood pressure, coronary heart disease, chronic obstructive pulmonary disease, arthritis, asthma, high blood cholesterol, cancer, kidney disease, stroke, diabetes, weight status, physical activity status, smoking status, and drinking status. RESULTS: A significantly higher FMD prevalence was found among females (11.7%; 95% confidence interval [CI]: 11.1-12.4), non-Hispanic blacks (13.4, 95% CI: 11.9-15.0), adults with less than a high school degree (14.4%; 95% CI: 12.6-16.3), adults with an annual income of less than $15 000 (21.4%; 95% CI: 19.4-23.5), and adults with a disability (23.3%, 95% CI: 21.9-24.7). Adjusted prevalence of FMD was significantly higher among adults for 8 of 10 chronic conditions and 4 of 5 health risk factors studied. CONCLUSIONS: Social stigmas related to depression and anxiety may lead to the underreporting of FMD. Chronic disease management programs in Illinois should consider integrating mental health services.

      8. Eye care among US adults at high risk for vision loss in the United States in 2002 and 2017external icon
        Saydah SH, Gerzoff RB, Saaddine JB, Zhang X, Cotch MF.
        JAMA Ophthalmol. 2020 Mar 12.
        Importance: Timely eye care can prevent unnecessary vision loss. Objectives: To estimate the number of US adults 18 years or older at high risk for vision loss in 2017 and to evaluate use of eye care services in 2017 compared with 2002. Design, Setting, and Participants: This survey study used data from the 2002 (n = 30920) and 2017 (n = 32886) National Health Interview Survey, an annual, cross-sectional, nationally representative sample of US noninstitutionalized civilians. Analysis excluded respondents younger than 18 years and those who were blind or unable to see. Covariates included age, sex, race/ethnicity, marital status, educational level, income-to-poverty ratio, health insurance status, diabetes diagnosis, vision or eye problems, and US region of residence. Main Outcomes and Measures: Three self-reported measures were visiting an eye care professional in the past 12 months, receiving a dilated eye examination in the past 12 months, and needing but being unable to afford eyeglasses in the past 12 months. Adults at high risk for vision loss included those who were 65 years or older, self-reported a diabetes diagnosis, or had vision or eye problems. Multivariable logistic regression models incorporating sampling weights were used to investigate associations between measures and covariates. Temporal comparisons between 2002 and 2017 were derived from estimates standardized to the US 2010 census population. Results: Among 30 920 individuals in 2002, 16.0% were 65 years or older, and 52.0% were female; among 32 886 individuals in 2017, 20.0% were 65 years or older, and 51.8% were female. In 2017, more than 93 million US adults (37.9%; 95% CI, 37.0%-38.7%) were at high risk for vision loss compared with almost 65 million (31.5%; 95% CI, 30.7%-32.3%) in 2002, a difference of 6.4 (95% CI, 5.2-7.6) percentage points. Use of eye care services improved (56.9% [95% CI, 55.7%-58.7%] reported visiting an eye care professional annually, and 59.8% [95% CI, 58.6%-61.0%] reported receiving a dilated eye examination), but 8.7% (95% CI, 8.0%-9.5%) said they could not afford eyeglasses (compared with 51.1% [95% CI, 49.9%-52.3%], 52.4% [95% CI, 51.2%-53.6%], and 8.3% [95% CI, 7.7%-8.9%], respectively, in 2002). In 2017, individuals with lower income compared with high income were more likely to report eyeglasses as unaffordable (13.6% [95% CI, 11.6%-15.9%] compared with 5.7% [95% CI, 4.9%-6.6%]). Conclusions and Relevance: Compared with data from 2002, more US adults were at high risk for vision loss in 2017. Although more adults used eye care, a larger proportion reported eyeglasses as unaffordable. Focusing resources on populations at high risk for vision loss, increasing awareness of the importance of eye care, and making eyeglasses more affordable could promote eye health, preserve vision, and reduce disparities.

    • Communicable Diseases
      1. A phylogenetic analysis of HCV transmission, relapse, and reinfection among people who inject drugs receiving opioid agonist therapyexternal icon
        Akiyama MJ, Lipsey D, Ganova-Raeva L, Punkova L, Agyemang L, Sue A, Ramachandran S, Khudyakov Y, Litwin AH.
        J Infect Dis. 2020 Mar 9.
        BACKGROUND: Understanding hepatitis C virus (HCV) transmission among people who inject drugs (PWID) is essential for HCV elimination. We aimed to differentiate reinfections from treatment failures and to identify transmission linkages and associated factors in a cohort of PWID receiving opioid agonist therapy (OAT). METHODS: We analyzed baseline and follow-up specimens from 150 PWID from three OAT clinics in the Bronx, NY. NGS data from the hypervariable region 1 of HCV were analyzed using Global Hepatitis Outbreak and Surveillance Technology. RESULTS: There were three transmission linkages between study participants. Nine participants did not achieve sustained virologic response (SVR): seven had follow-up specimens with similar sequences to baseline and two passed away. Four additional participants achieved SVR but became viremic at later follow-up: two were reinfected with different strains, one had a late treatment failure, and one was transiently viremic 17 months post-treatment. All transmission linkages were from the same OAT clinic and involved spousal or common-law partnerships. CONCLUSION: This study highlights the use of next generation sequencing (NGS) as an important tool for identifying viral transmission and to help distinguish relapse and reinfection among PWID. Results reinforce the need for harm reduction interventions among couples and those who report ongoing risk factors following SVR.

      2. A mobile application to monitor mode, content and duration of health navigation services for people living with HIV in Guatemalaexternal icon
        Alvis-Estrada JP, Davis DA, Guevara KG, Santa Luce RL, Loya-Montiel MI, Northbrook S, Barrington C.
        AIDS Care. 2020 Mar 4:1-6.
        Health navigation is increasingly being used to support people living with HIV, but timely monitoring of navigation is challenging due to the burden of reporting a high volume of diverse activities. We designed a mobile application (app) for navigators to report their interactions with men who have sex with men living with HIV (n = 374), including: (1) mode of support; (2) content; and (3) duration. We assessed sociodemographic and behavioral characteristics of the study sample and calculated monitoring system indicators. We also conducted qualitative interviews with navigators (n = 7) and used thematic analysis to assess app acceptability and usability. From January 2017 to June 2018, 95.3% of participants interacted with their navigator at least one time and 4281 reports were recorded by nine navigators. The median number of interactions per participant was 10 (range: 1-46). The majority of interactions (71.6%) occurred remotely. Most frequently covered topics included: appointment reminders (36.9%), employment (19.9%), and family (15.5%). Navigators indicated that the system was easy to use, but some did not use it in real time as intended. Timely access to navigator data enabled feedback and continuous training. These data can also facilitate analysis of intensity and content of interactions to improve tailoring and sustainability.

      3. HIV clinical outcomes have not been fully assessed by place of birth at the national level. We analyzed the Medical Monitoring Project data, an annual cross-sectional survey designed to produce nationally representative estimates on adults with diagnosed HIV in the United States, collected during 2015-2017 (n = 7617). We compared sociodemographic, behavioral, and clinical outcomes by place of birth using Rao-Scott chi-square tests (P < .05). Overall, 13.6% of adults with diagnosed HIV were non-US-born. During the past 12 months, a higher percentage of non-US-born than US-born adults, respectively, were prescribed ART (89.4% vs. 84.1%), retained in care (87.1% vs. 80.0%), virally suppressed at the last test (77.2% vs. 70.9%), and had sustained viral suppression (70.9% vs. 63.3%). A lower percentage of non-US-born adults reported binge drinking (13.0% vs. 16.1%), using non-injection drugs (15.3% vs. 31.7%), and suffering from depression (15.9% vs. 23.3%) or anxiety (10.0% vs. 20.2%). A significantly higher percentage of non-US-born adults had Ryan White HIV/AIDS Program (RWHAP) coverage (54.4% vs. 43.1%) and attended a RWHAP-funded health care facility (73.9% vs. 66.6%). Factors contributing to better HIV clinical outcomes among non-US-born persons may include access to RWHAP coverage, lower levels of substance use, and better mental health.

      4. BACKGROUND: National chlamydia case rate trends are difficult to interpret due to biases from partial screening coverage, imperfect diagnostic tests, and under-reporting. We examined the extent to which these time-varying biases could influence reported annual chlamydia case rates. METHODS: Annual reported case rates among women aged 15 through 24 years from 2000 through 2017 were obtained from the CDC's National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention AtlasPlus tool. Estimates of reporting completeness, diagnostic test sensitivity and specificity, and screening coverage were derived from literature review and expert opinion. We adjusted annual reported case rates for incomplete reporting, imperfect diagnostic tests, and partial screening coverage through a series of corrections, and calculated annual adjusted case rates of correctly diagnosed chlamydia. RESULTS: Adjusted chlamydia case rates among young women were higher than reported case rates throughout the study period. Reported case rates increased over the study period, but adjusted rates declined from 12,900 to 7,900 cases per 100,000 person-years between 2000 and 2007. After 2007, adjusted case rates declined to 7,500 cases per 100,000 person-years in 2017. Bias from partial screening coverage had a larger impact on case rate magnitude and trend shape than bias from imperfect diagnostic tests or under-reporting. CONCLUSIONS: Reported chlamydia case rates may be substantially lower than true chlamydia case rates due to incomplete reporting, imperfect diagnostic tests, and partial screening coverage. Because the magnitude of these biases has declined over time, the differences between reported and adjusted case rates has narrowed, revealing a sharp decline in adjusted case rates even as reported case rates have risen. The decline in adjusted case rates suggests that the rise in reported case rates should not be interpreted strictly as increasing chlamydia incidence, as the observed rise can be explained by improvements in screening coverage, diagnostic tests, and reporting.

      5. High levels of HIV-1 drug resistance in children who acquired HIV infection through mother to child transmission in the era of option B+, Haiti, 2013 to 2014external icon
        Louis FJ, Segaren N, Desinor O, Beard RS, Jean-Louis R, Chang J, Boisson S, Hulland EN, Wagar N, DeVos J, Francois K, Buteau J, Boncy J, Marston BJ, Domercant JW, Yang C, Charles M.
        Pediatr Infect Dis J. 2019 May;38(5):503-507.
        BACKGROUND: The main objective of this study was to determine the frequency and patterns of HIV drug resistance-associated mutations among children under 18 months of age born to HIV-1-positive mothers enrolled in the prevention of mother-to-child transmission services in Haiti. METHODS: Between January 1, 2013 and December 31, 2014, HIV-positive remnant dried blood spots collected from children under 18 months of age for Early Infant Diagnosis at the National Public Health Laboratory were used for HIV-1 genotyping. HIV drug resistance mutations were analyzed using the Stanford Drug Resistance HIVdb program. RESULTS: Of the 3555 dried blood spots collected for Early Infant Diagnosis, 360 (10.1%) were HIV-positive and 355 were available for genotyping. Of these, 304 (85.6%) were successfully genotyped and 217 (71.4%) had >/=1 drug resistance mutation. Mutations conferring resistance to nucleoside reverse transcriptase inhibitor (NRTIs) and non-NRTIs were present in 40.5% (123) and 69.1% (210), respectively. The most frequent mutations were K103N/S (48.0%), M184V (37.5%), G190A/S (15.1%), and Y181C/G/V (14.1%). Predicted drug resistance analysis revealed that 68.8% of the children had high-level resistance to non-NRTIs and 11.5% had intermediate to high-level resistance to abacavir. CONCLUSIONS: This study showed high rates of resistance to NRTIs and non-NRTIs among newly HIV-diagnosed children in Haiti, suggesting that in the era of "Option B+" (initiation of lifelong combination antiretroviral therapy to pregnant women with HIV), the majority of children who acquire HIV infection through mother-to-child transmission of HIV have resistant HIV. These results have led the National HIV Program to revise the pediatric guidelines to include protease inhibitors in first-line regimens for all HIV-positive newborns.

      6. Understanding the HIV epidemic among MSM in Baltimore: a modelling study estimating the impact of past HIV interventions and who acquired and contributed to infectionsexternal icon
        Silhol R, Boily MC, Dimitrov D, German D, Flynn C, Farley JE, Gelman M, Hughes JP, Donnell D, Adeyeye A, Remien RH, Beyrer C, Paz-Bailey G, Wejnert C, Mitchell KM.
        J Acquir Immune Defic Syndr. 2020 Mar 3.
        INTRODUCTION: Men who have sex with men (MSM) in the United States (US) are disproportionately affected by HIV. We estimated the impact of past interventions and contribution of different population groups to incident MSM HIV infections. SETTING: Baltimore, US METHODS:: We used a deterministic model, parameterised and calibrated to demographic and epidemic Baltimore MSM data, to estimate the fraction of HIV infections among MSM averted by condoms and antiretroviral therapy (ART) over 1984-2017 and the fraction of infections acquired and transmission contributed by MSM from different demographic groups and disease and care continuum stages over 10-year periods from 1988 to 2017, using population attributable fractions (PAFs). RESULTS: Condom use and ART averted 19% (95% uncertainty interval: 14-25%) and 23% (15-31%) of HIV infections that would have occurred since 1984 and 1996, respectively. Over 2008-2017, 46% (41-52%) of incident infections were acquired by, and 35% (27-49%) of transmissions contributed by MSM aged 18-24 years old (who constitute 27% of all MSM, 19% of HIV+ MSM). MSM with undiagnosed HIV infection, those with diagnosed infection but not in care, and those on ART contributed to 41% (31-54%), 46% (25-56%), and 14% (7-28%) of transmissions, respectively. CONCLUSION: Condoms and ART have modestly impacted the HIV epidemic among Baltimore MSM to date. Interventions reaching MSM with diagnosed infection who are not in care should be implemented since the largest percentage of HIV transmissions among Baltimore MSM are attributed to this group.

      7. BACKGROUND: Expedited partner therapy (EPT) is commonly provided by prescription, however, the efficacy of this modality is unknown. We examined whether EPT prescriptions are filled when the cost barrier is removed. METHODS: To track EPT prescription fill rates, we used single-use pharmacy vouchers that covered the cost of azithromycin, 1-gram (chlamydia treatment). We recruited clinical sites to distribute vouchers to patients with chlamydia who would receive an EPT prescription under clinic policies. When distributing vouchers, sites recorded and retained: voucher unique identifier, sex and age of index patient, distribution date, and whether partner name was written on the EPT prescription. Pharmacists receiving vouchers entered the identifier, sex and age of presenting person, and redemption date into a standard pharmacy claim transmission system. Data for redeemed vouchers were retrieved from an industry portal and linked with data retained at clinical sites. RESULTS: Thirty-two clinical sites distributed 931 vouchers during 9/2017-01/2019; 382 (41%) were redeemed. Vouchers distributed to patients </=18 years (49/163; 30%) were less likely to be redeemed compared to those distributed to patients >18 years (322/736; 44%; p=0.001). Just over half of vouchers were redeemed the same day (195/351; 56%) and </=1 mile from the clinical site (188/349; 54%). After excluding an outlier site, vouchers accompanied by EPT prescriptions including a partner name (15/27; 56%) were more likely to be redeemed than those lacking a name (83/244; 34%; p=0.03). CONCLUSIONS: Less than half of EPT prescriptions were filled, even when medication was free. Whenever possible, EPT should be provided as drug-in-hand.

      8. Evaluation of the National STD Curriculum: Reach, utilization, and engagementexternal icon
        Snoeyenbos Newman G, Bauer K, Karpenko A, Unruh KT, Johnston C, Marrazzo JM, Workowski KA, Spach DH.
        Sex Transm Dis. 2020 Mar 5.
        BACKGROUND: With increasing rates of sexually transmitted infections (STIs) in the United States, there is a critical need to educate health professionals on the prevention, diagnosis, and treatment of STIs. The National STD Curriculum (NSTDC, is a free, online curriculum, funded by the Centers for Disease Control and Prevention (CDC). The purpose of this paper is to evaluate the reach, utilization, and engagement of users with the curriculum. METHODS: Data on NSTDC utilization was collected for 24 months after the February 1, 2017 launch. For all users, Google Analytics was used to determine total number of users, geographic location, age and sex, and average session duration. For registered users, additional data analysis included work-role, demographics, and completion of self-study modules, check-on-learning questions, and question banks. User satisfaction was measured on a 5-point Likert scale. RESULTS: During the evaluation period, 136,270 individual users accessed the NSTDC, including 24,652 registered users. Among all registered users, 10,660 (43.2%) were registered nurses, 2,810 (11.4%) physicians, 4,942 (20.1%) Advanced Practice Nurses and Physician Assistants, and 6,213 (25.2%) non-clinicians. Among registered users, 18,533 (75.2%) completed at least 1 module, 7,898 (32.0%) completed all 7 modules, and 19,804 (80.4%) answered optional check-on-learning questions. Median satisfaction with the content was (5) Very Satisfied (IQR 4-5). CONCLUSIONS: The NSTDC is a free, guideline-based, online curriculum with novel dual-functionality that has achieved extensive reach with a broad array of health professionals who engage deeply with the material. The wide usage of NSTDC demonstrates the need for high-quality, unbiased, free content in user-focused formats.

    • Disease Reservoirs and Vectors
      1. Background and Objectives: Vector-borne bacterial diseases represent a substantial public health burden and rodents have been recognized as important reservoir hosts for many zoonotic pathogens. This study investigates bacterial pathogens in a small mammal community of the southwestern United States of America. Methods: A total of 473 samples from 13 wild rodent and 1 lagomorph species were tested for pathogens of public health significance: Bartonella, Brucella, Yersinia, Borrelia, Rickettsia spp., and Anaplasma phagocytophilum. Results: Three animals were positive for Yersinia pestis, and one Sylvilagus audubonii had a novel Borrelia sp. of the relapsing fever group. No Brucella, Rickettsia, or A. phagocytophilum infections were detected. Bartonella prevalence ranged between 0% and 87.5% by animal species, with 74.3% in the predominant Neotoma micropus and 78% in the second most abundant N. albigula. The mean duration of Bartonella bacteremia in mark-recaptured N. micropus and N. albigula was 4.4 months, ranging from <1 to 18 months, and differed among Bartonella genogroups. Phylogenetic analysis of the Bartonella citrate synthase gene (gltA) revealed 9 genogroups and 13 subgroups. Seven genogroups clustered with known or previously reported Bartonella species and strains while two were distant enough to represent new Bartonella species. We report, for the first time, the detection of Bartonella alsatica in North America in Sylvilagus audubonii and expand the known host range of Bartonella washoensis to include Otospermophilus variegatus. Interpretation and Conclusion: This work broadens our knowledge of the hosts and geographic range of bacterial pathogens that could guide future surveillance efforts and improves our understanding of the dynamics of Bartonella infection in wild small mammals.

      2. Potential distributions of Bacillus anthracis and Bacillus cereus biovar anthracis causing anthrax in Africaexternal icon
        Romero-Alvarez D, Peterson AT, Salzer JS, Pittiglio C, Shadomy S, Traxler R, Vieira AR, Bower WA, Walke H, Campbell LP.
        PLoS Negl Trop Dis. 2020 Mar 9;14(3):e0008131.
        BACKGROUND: Bacillus cereus biovar anthracis (Bcbva) is an emergent bacterium closely related to Bacillus anthracis, the etiological agent of anthrax. The latter has a worldwide distribution and usually causes infectious disease in mammals associated with savanna ecosystems. Bcbva was identified in humid tropical forests of Cote d'Ivoire in 2001. Here, we characterize the potential geographic distributions of Bcbva in West Africa and B. anthracis in sub-Saharan Africa using an ecological niche modeling approach. METHODOLOGY/PRINCIPAL FINDINGS: Georeferenced occurrence data for B. anthracis and Bcbva were obtained from public data repositories and the scientific literature. Combinations of temperature, humidity, vegetation greenness, and soils values served as environmental variables in model calibrations. To predict the potential distribution of suitable environments for each pathogen across the study region, parameter values derived from the median of 10 replicates of the best-performing model for each pathogen were used. We found suitable environments predicted for B. anthracis across areas of confirmed and suspected anthrax activity in sub-Saharan Africa, including an east-west corridor from Ethiopia to Sierra Leone in the Sahel region and multiple areas in eastern, central, and southern Africa. The study area for Bcbva was restricted to West and Central Africa to reflect areas that have likely been accessible to Bcbva by dispersal. Model predicted values indicated potential suitable environments within humid forested environments. Background similarity tests in geographic space indicated statistical support to reject the null hypothesis of similarity when comparing environments associated with B. anthracis to those of Bcbva and when comparing humidity values and soils values individually. We failed to reject the null hypothesis of similarity when comparing environments associated with Bcbva to those of B. anthracis, suggesting that additional investigation is needed to provide a more robust characterization of the Bcbva niche. CONCLUSIONS/SIGNIFICANCE: This study represents the first time that the environmental and geographic distribution of Bcbva has been mapped. We document likely differences in ecological niche-and consequently in geographic distribution-between Bcbva and typical B. anthracis, and areas of possible co-occurrence between the two. We provide information crucial to guiding and improving monitoring efforts focused on these pathogens.

    • Environmental Health
      1. All that glitters is not gold: Mercury poisoning in a family mimicking an infectious illnessexternal icon
        Atti SK, Silver EM, Chokshi Y, Casteel S, Kiernan E, Dela Cruz R, Kazzi Z, Geller RJ.
        Curr Probl Pediatr Adolesc Health Care. 2020 Mar 6:100758.
        Three siblings with inhalational elemental mercury toxicity presented with fever, rash, and upper respiratory tract symptoms. The patients were heavily exposed to elemental mercury that was spilled in their home and then vacuumed. Initial whole blood mercury levels were elevated at >200 microg/L, 153 microg/L and 130 microg/L (Mayo Clinic Laboratories lab reference range <9 microg/L) for Cases 1, 2, and 3, respectively. All three required chelation with succimer. Clinically significant elemental mercury toxicity can resemble an infectious illness. Severe morbidity and mortality can be prevented if heavy metal poisoning is considered early, through a detailed history including an environmental exposure history. For elemental mercury spills in the home, safe and effective clean-up steps are needed. Improved public health education is needed to prevent similar household exposures.

      2. Isoprene exposure in the United States based on urinary IPM3: NHANES 2015-2016external icon
        Biren C, Zhang L, Bhandari D, Blount BC, De Jesus VR.
        Environ Sci Technol. 2020 Feb 18;54(4):2370-2378.
        Isoprene is the 2-methyl analog of 1,3-butadiene and is a possible human carcinogen (IARC Group 2B). We assessed isoprene exposure in the general US population by measuring its urinary metabolite, N-acetyl-S-(4-hydroxy-2-methyl-2-buten-1-yl)-l-cysteine (IPM3) in participants (>/=3 year old) from the 2015-2016 National Health and Nutrition Examination Survey. Spot urine samples were analyzed for IPM3 using ultrahigh-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. Exclusive tobacco smokers were distinguished from non-users using a combination of self-reporting and serum cotinine data. IPM3 was detected in 80.2% of samples. The median IPM3 level was higher for exclusive cigarette smokers (39.8 mug/g creatinine) than for non-users (3.05 mug/g creatinine). Sample weighted regression analysis, controlling for creatinine, sex, age, race, body mass index, and diet, showed that IPM3 was positively and significantly associated with serum cotinine. Smoking 1-10 cigarettes per day (CPD, 0.5 pack) was significantly associated with an IPM3 increase of 596% (p < .0001), and smoking >20 CPD (>1 pack) was significantly associated with an IPM3 increase of 1640% (p < .0001), controlling for confounding variables. Drinking beer/ale at median and 90th percentile levels (compared to zero consumption) was associated (p < 0.05) with 0 and 2.9% increase in IPM3 in non-users, respectively. We conclude that tobacco smoke is a major source of isoprene exposure in the US population. This study provides important public health biomonitoring data on isoprene exposure in the general US population.

      3. Associations of blood lead levels with asthma and blood eosinophils in U.S. childrenexternal icon
        Cornwell CR, Egan KB, Zahran HS, Mirabelli MC, Hsu J, Chew GL.
        Pediatr Allergy Immunol. 2020 Mar 11.
        U.S. children are exposed to lead through lead-based paint, lead-contaminated dust in older homes and through contaminated water, air, soil, or consumer and imported products(1,2) . Approximately 24 million housing units have one or more lead-based paint hazards, including 3.6 million homes with children aged </=6 years(1) . Epidemiologic studies have reported positive associations between lead and elevated immunoglobulin E (IgE) in children(3-5) ; IgE is often associated with allergic asthma(6) .

    • Health Economics
      1. Delay discounting of different outcomes: Review and theoryexternal icon
        Odum AL, Becker RJ, Haynes JM, Galizio A, Frye CC, Downey H, Friedel JE, Perez DM.
        J Exp Anal Behav. 2020 Mar 8.
        Steep delay discounting is characterized by a preference for small immediate outcomes relative to larger delayed outcomes and is predictive of drug abuse, risky sexual behaviors, and other maladaptive behaviors. Nancy M. Petry was a pioneer in delay discounting research who demonstrated that people discount delayed monetary gains less steeply than they discount substances with abuse liability. Subsequent research found steep discounting for not only drugs, but other nonmonetary outcomes such as food, sex, and health. In this systematic review, we evaluate the hypotheses proposed to explain differences in discounting as a function of the type of outcome and explore the trait- and state-like nature of delay discounting. We found overwhelming evidence for the state-like quality of delay discounting: Consistent with Petry and others' work, nonmonetary outcomes are discounted more steeply than monetary outcomes. We propose two hypotheses that together may account for this effect: Decreasing Future Preference and Decreasing Future Worth. We also found clear evidence that delay discounting has trait-like qualities: People who steeply discount monetary outcomes steeply discount nonmonetary outcomes as well. The implication is that changing delay discounting for one outcome could change discounting for other outcomes.

      2. Insurance coverage, employment status, and financial well-being of young women diagnosed with breast cancerexternal icon
        Tangka FK, Subramanian S, Jones M, Edwards P, Flanigan T, Kaganova Y, Smith KW, Thomas CC, Hawkins NA, Rodriguez J, Fairley T, Guy GP.
        Cancer Epidemiol Biomarkers Prev. 2020 Mar;29(3):616-624.
        BACKGROUND: The economic cost of breast cancer is a major personal and public health problem in the United States. This study aims to evaluate the insurance, employment, and financial experiences of young female breast cancer survivors and to assess factors associated with financial decline. METHODS: We recruited 830 women under 40 years of age diagnosed with breast cancer between January 2013 and December 2014. The study population was identified through California, Florida, Georgia, and North Carolina population-based cancer registries. The cross-sectional survey was fielded in 2017 and included questions on demographics, insurance, employment, out-of-pocket costs, and financial well-being. We present descriptive statistics and multivariate analysis to assess factors associated with financial decline. RESULTS: Although 92.5% of the respondents were continuously insured over the past 12 months, 9.5% paid a "higher price than expected" for coverage. Common concerns among the 73.4% of respondents who were employed at diagnosis included increased paid (55.1%) or unpaid (47.3%) time off, suffering job performance (23.2%), and staying at (30.2%) or avoiding changing (23.5%) jobs for health insurance purposes. Overall, 47.0% experienced financial decline due to treatment-related costs. Patients with some college education, multiple comorbidities, late stage diagnoses, and self-funded insurance were most vulnerable. CONCLUSIONS: The breast cancer diagnosis created financial hardship for half the respondents and led to myriad challenges in maintaining employment. Employment decisions were heavily influenced by the need to maintain health insurance coverage. IMPACT: This study finds that a breast cancer diagnosis in young women can result in employment disruption and financial decline.

    • Healthcare Associated Infections
      1. Investigation of presumptive HIV transmission associated with hospitalization using nucleotide sequence analysis - New York, 2017external icon
        Anderson BJ, Clement E, Collura R, Gallucci A, Westheimer E, Braunstein S, Southwick K, Adams E, Lutterloh E, Gonzalez C, McDonald R, Jia H, Switzer WM, Patel PR, Joyce MP, Oster AM.
        MMWR Morb Mortal Wkly Rep. 2020 Mar 13;69(10):260-264.
        Since implementation of Standard Precautions* for the prevention of bloodborne pathogen transmission in 1985, health care-associated transmission of human immunodeficiency virus (HIV) in the United States has been rare (1). In October 2017, the New York City Department of Health and Mental Hygiene (NYCDOHMH) and the New York State Department of Health (NYSDOH) were notified by a clinician of a diagnosis of acute HIV infection in a young adult male (patient A) without recognized risk factors (i.e., he was monogamous, had an HIV-negative partner, and had no injection drug use) who had recently been hospitalized for a chronic medical condition. The low risk coupled with the recent hospitalization and medical procedures prompted NYSDOH, NYCDOHMH, and CDC to investigate this case as possible health care-associated transmission of HIV. Among persons with known HIV infection who had hospitalization dates overlapping those of patient A, one person (patient B) had an HIV strain highly similar to patient A's strain by nucleotide sequence analysis. The sequence relatedness, combined with other investigation findings, indicated a likely health care-associated transmission. Nucleotide sequence analysis, which is increasingly used for detecting HIV clusters (i.e., persons with closely related HIV strains) and to inform public health response (2,3), might also be used to identify possible health care-associated transmission of HIV to someone with health care exposure and no known HIV risk factors (4).

      2. RATIONALE & OBJECTIVE: Compared with conventional (rope-ladder cannulation [RLC]) methods, use of buttonhole cannulation (BHC) to access arteriovenous fistulas (AVFs) may be associated with increased risk for bloodstream infection and other vascular access-related infection. We used national surveillance data to evaluate the infection burden and risk among in-center hemodialysis patients with AVFs using BHC. STUDY DESIGN: Descriptive analysis of infections and related events and retrospective observational cohort study using National Healthcare Safety Network (NHSN) surveillance data. SETTING & PARTICIPANTS: US patients receiving hemodialysis treated in outpatient dialysis centers. PREDICTORS: AVF cannulation methods, dialysis facility characteristics, and infection control practices. OUTCOMES: Access-related bloodstream infection; local access-site infection; intravenous (IV) antimicrobial start. ANALYTIC APPROACH: Description of frequency and rate of infections; adjusted relative risk (aRR) for infection with BHC versus RLC estimated using Poisson regression. RESULTS: During 2013 to 2014, there were 2,466 access-related bloodstream infections, 3,169 local access-site infections, and 13,726 IV antimicrobial starts among patients accessed using BHC. Staphylococcus aureus was the most common pathogen, present in half (52%) of the BHC access-related bloodstream infections. Hospitalization was frequent among BHC access-related bloodstream infections (37%). In 2014, 9% (n=271,980) of all AVF patient-months reported to NHSN were associated with BHC. After adjusting for facility characteristics and practices, BHC was associated with significantly higher risk for access-related bloodstream infection (aRR, 2.6; 95% CI, 2.4-2.8) and local access-site infection (aRR, 1.5; 95% CI, 1.4-1.6) than RLC, but was not associated with increased risk for IV antimicrobial start. LIMITATIONS: Data for facility practices were self-reported and not patient specific. CONCLUSIONS: BHC was associated with higher risk for vascular access-related infection than RLC among in-center hemodialysis patients. Decisions regarding the use of BHC in dialysis centers should take into account the higher risk for infection. Studies are needed to evaluate infection control measures that may reduce infections related to BHC.

      3. Transfusion-associated adverse events and implementation of blood safety measures - findings from the 2017 National Blood Collection and Utilization Surveyexternal icon
        Savinkina AA, Haass KA, Sapiano MR, Henry RA, Berger JJ, Basavaraju SV, Jones JM.
        Transfusion. 2020 Mar;60 Suppl 2:S10-s16.
        BACKGROUND: Serious transfusion-associated adverse events are rare in the United States. To enhance blood safety, various measures have been developed. With use of data from the 2017 National Blood Collection and Utilization Survey (NBCUS), we describe the rate of transfusion-associated adverse events and the implementation of specific blood safety measures. STUDY DESIGN AND METHODS: Data from the 2017 NBCUS were used with comparison to already published estimates from 2015. Survey weighting and imputation were used to obtain national estimates of transfusion-associated adverse events, and the number of units treated with pathogen reduction technology (PRT), screened for Babesia, and leukoreduced. RESULTS: The rate of transfusion-associated adverse events requiring any diagnostic or therapeutic interventions was stable (275 reactions per 100,000 transfusions in 2015 and 282 reactions per 100,000 transfusions in 2017). In 2017 among US blood collection centers, 16 of 141 (11.3%) reported screening units for Babesia and 28 of 144 (19.4%) reported PRT implementation; 138 of 2279 (6.1%) hospitals reported transfusing PRT-treated platelets. In 2017, 134 of 2336 (5.7%) hospitals reported performing secondary bacterial testing of platelets (50,922 culture-based and 63,220 rapid immunoassay tests); in 2015, 71 of 1877 (3.8%) hospitals performed secondary testing (87,155 culture-based and 21,779 rapid immunoassay tests). Nearly all whole blood/red blood cell units and platelet units were leukoreduced. CONCLUSIONS: Besides leukoreduction, implementation of most blood safety measures reported in this study remains low. Nationally, hospitals might be shifting from culture-based secondary bacterial testing to rapid immunoassays.

      4. Notes from the Field: Carbapenemase-producing Klebsiella pneumoniae in a ventilator-capable skilled nursing facility - Maricopa County, Arizona, July-November 2018external icon
        Scott SE, Matthews J, Hobbs KC, Maldonado K, Bhattarai R, Sunenshine R, Prasai S.
        MMWR Morb Mortal Wkly Rep. 2020 Mar 13;69(10):274-275.

      5. Mathematical modeling of healthcare associated infections (HAIs) and multidrug resistant organisms (MDROs) improves our understanding of pathogens transmission dynamics and provides a framework for evaluating prevention strategies. One way of improving the communication among modelers is by providing a standardized way of describing and reporting models thereby instilling confidence in the reproducibility and generalizability of such models. We updated the Overview, Design concepts, and Details protocol developed by Grimm et al. for describing agent-based models (ABMs) to better align with elements commonly included in healthcare-related ABMs. The MInD-Healthcare framework includes the following nine key elements: 1. Purpose and scope; 2. Entities, state variables, and scales; 3. Initialization; 4. Process overview and scheduling; 5. Input data; 6. Agent interactions and organism transmission; 7. Stochasticity; 8. Submodels; 9. Model verification, calibration, and validation. Our objective is that this framework will improve the quality of evidence generated utilizing these models.

    • Immunity and Immunization
      1. BACKGROUND: Licensed inactivated influenza vaccines (IIV) are recommended for persons aged >/=65 years, including trivalent high-dose IIV (HD-IIV3) and adjuvanted IIV (aIIV3); both are manufactured in eggs. Quadrivalent recombinant vaccine (RIV4) is produced without eggs. We conducted an exploratory study to compare immunogenicity of HD-IIV3, aIIV3 and RIV4 against cell-grown vaccine and circulating A(H3N2) viruses in 2017-18. METHODS: Eighty-nine adults aged 65-74 years participating in a 2-year, open-label immunogenicity trial ( NCT02872311) were randomized 1:1:1 to receive HD-IIV3, aIIV3, or RIV4 after receipt of standard dose IIV3 in 2016-17. Serum was obtained at baseline and day 28 post vaccination. Microneutralization titers were determined using four cell-propagated A(H3N2) viruses: 2017-18 vaccine strain (clade 3C.2a), circulating viruses from clades 3C.2a1 and 3C.2a2, and 'antigenically advanced' clade 3C.3a (2019-20 vaccine strain). Active surveillance was conducted to identify influenza illnesses. RESULTS: Post vaccination geometric mean titer (GMT) against the vaccine strain was <1:60 in each group and <15% seroconverted. RIV4 generated a greater fold-rise (2.0, 95% CI 1.7-2.5) compared to HD-IIV3 (1.6, 95% CI 1.3-1.8). RIV4 generated higher post vaccination titers against 3C.2a1 and 3C.2a2 viruses, and the mean fold-rise after RIV4 was twice as high (3.3 and 3.5, respectively) relative to HD-IIV3 (1.4 and 1.6) and aIIV3 (1.7 and 1.6). Against the antigenically advanced 3C.3a virus, RIV4 generated a greater mean fold-rise (2.9, 95% CI 2.0-4.3) vs HD-IIV3 (1.3, 95% CI 1.1-1.6) and aIIV3 (1.7, 95% CI 1.3-2.1). Postvaccination titers against 3C.2a2 were >/=1:40 in 5 of 7 participants with PCR-confirmed A(H3N2) infection during the ensuing influenza season. CONCLUSION: High-dose, adjuvanted, and recombinant vaccines generated suboptimal neutralizing antibody responses to the cell-grown vaccine strain, but RIV4 generated a greater cross-protective response against circulating and antigenically advanced viruses. Recombinant technology may contribute to more broadly protective influenza vaccines, and comparative effectiveness studies are needed.

      2. What it will take to achieve a world without measlesexternal icon
        Cochi SL, Schluter WW.
        J Infect Dis. 2020 Mar 5.

      3. Gap in measles vaccination coverage among children aged 9 months to 10 years in Ho Chi Minh City, Viet Nam, 2014external icon
        Cuong HQ, Nguyen HX, Van Hau P, Ha NL, Lan PT, Mounts A, Nguyen TM.
        Western Pac Surveill Response J. 2019 Oct-Dec;10(4):39-45.
        Introduction: When Viet Nam launched the Expanded Programme on Immunization in 1981, it covered six vaccines, including measles. Subsequently, Viet Nam experienced a marked reduction in measles infections. A nationwide measles epidemic occurred in April 2014 and an investigation found that 86% of affected children aged 9 months to 10 years were not fully vaccinated; therefore, understanding the reasons for not vaccinating could improve vaccination coverage. Method: We performed a cross-sectional study to determine vaccination coverage and reasons for non-vaccination among children aged 9 months to 10 years in six districts in Ho Chi Minh City with the highest number of measles cases in 2014. Measles vaccination status of the youngest child in each household was determined and reasons for non-vaccination were investigated. A chi(2) test and multiple logistic regression were used to identify independent predictors of full vaccination. Results: In total, 207 children were enrolled during the study period in 2014. Full measles vaccination coverage was 55% in these households, and 73% of parents were aware of the importance of measles vaccination to protect their children. We found that the father's education level (under high school versus high school and above) and the site where the survey was conducted were significantly associated with vaccination status. Conclusion: The vaccination coverage was lower than the coverage reported by district preventive medicine centres of the seven study wards. Lack of the second vaccination was a key obstacle to eliminating the vaccination gap. A catch-up mass vaccination campaign or health promotion of measles vaccination directed towards parents should be considered to improve vaccination coverage.

      4. Association between rotavirus vaccination and type 1 diabetes in childrenexternal icon
        Glanz JM, Clarke CL, Xu S, Daley MF, Shoup JA, Schroeder EB, Lewin BJ, McClure DL, Kharbanda E, Klein NP, DeStefano F.
        JAMA Pediatr. 2020 Mar 9.
        Importance: Because rotavirus infection is a hypothesized risk factor for type 1 diabetes, live attenuated rotavirus vaccination could increase or decrease the risk of type 1 diabetes in children. Objective: To examine whether there is an association between rotavirus vaccination and incidence of type 1 diabetes in children aged 8 months to 11 years. Design, Setting, and Participants: A retrospective cohort study of 386937 children born between January 1, 2006, and December 31, 2014, was conducted in 7 US health care organizations of the Vaccine Safety Datalink. Eligible children were followed up until a diagnosis of type 1 diabetes, disenrollment, or December 31, 2017. Exposures: Rotavirus vaccination for children aged 2 to 8 months. Three exposure groups were created. The first group included children who received all recommended doses of rotavirus vaccine by 8 months of age (fully exposed to rotavirus vaccination). The second group had received some, but not all, recommended rotavirus vaccines (partially exposed to rotavirus vaccination). The third group did not receive any doses of rotavirus vaccines (unexposed to rotavirus vaccination). Main Outcomes and Measures: Incidence of type 1 diabetes among children aged 8 months to 11 years. Type 1 diabetes was identified by International Classification of Diseases codes: 250.x1, 250.x3, or E10.xx in the outpatient setting. Cox proportional hazards regression models were used to analyze time to type 1 diabetes incidence from 8 months to 11 years. Hazard ratios and 95% CIs were calculated. Models were adjusted for sex, race/ethnicity, birth year, mother's age, birth weight, gestational age, number of well-child visits, and Vaccine Safety Datalink site. Results: In a cohort of 386937 children (51.1% boys and 41.9% non-Hispanic white), 360169 (93.1%) were fully exposed to rotavirus vaccination, 15 765 (4.1%) were partially exposed to rotavirus vaccination, and 11 003 (2.8%) were unexposed to rotavirus vaccination. Children were followed up a median of 5.4 years (interquartile range, 3.8-7.8 years). The total person-time follow-up in the cohort was 2253879 years. There were 464 cases of type 1 diabetes in the cohort, with an incidence rate of 20.6 cases per 100000 person-years. Compared with children unexposed to rotavirus vaccination, the adjusted hazard ratio was 1.03 (95% CI, 0.62-1.72) for children fully exposed to rotavirus vaccination and 1.50 (95% CI, 0.81-2.77) for children partially exposed to rotavirus vaccination. Conclusions and Relevance: The findings of this study suggest that rotavirus vaccination does not appear to be associated with type 1 diabetes in children.

      5. Rift Valley fever virus vaccination induces long-lived, antigen-specific human T cell responsesexternal icon
        Harmon JR, Barbeau DJ, Nichol ST, Spiropoulou CF, McElroy AK.
        NPJ Vaccines. 2020 ;5:17.
        Rift Valley fever virus (RVFV) is a zoonotic arbovirus of clinical significance in both livestock and humans. A formalin-inactivated virus preparation was initially developed for human use and tested in laboratory workers in the 1960s. Vaccination resulted in generation of neutralizing antibody titers in most recipients, but neutralization titers waned over time, necessitating frequent booster doses. In this study, T cell-based immune responses to the formalin-inactivated vaccine were examined in a cohort of seven individuals who received between 1 and 6 doses of the vaccine. RVFV-specific T cell responses were detectable up to 24 years post vaccination. Peripheral blood mononuclear cells from this cohort of individuals were used to map out the viral epitopes targeted by T cells in humans. These data provide tools for assessing human RVFV-specific T cell responses and are thus a valuable resource for future human RVFV vaccine efforts.

      6. Magnitude and diversity of immune response to vaccinia virus is dependent on route of administrationexternal icon
        Hughes LJ, Townsend MB, Gallardo-Romero N, Hutson CL, Patel N, Doty JB, Salzer JS, Damon IK, Carroll DS, Satheshkumar PS, Karem KL.
        Virology. 2020 Feb 13;544:55-63.
        Historic observations suggest that survivors of smallpox maintained lifelong immunity and protection to subsequent infection compared to vaccinated individuals. Although protective immunity by vaccination using a related virus (vaccinia virus (VACV) strains) was the key for smallpox eradication, it does not uniformly provide long term, or lifelong protective immunity (Heiner et al., 1971). To determine differences in humoral immune responses, mice were inoculated with VACV either systemically, using intranasal inoculation (IN), or locally by an intradermal (ID) route. We hypothesized that sub-lethal IN infections may mimic systemic or naturally occurring infection and lead to an immunodominance reaction, in contrast to localized ID immunization. The results demonstrated systemic immunization through an IN route led to enhanced adaptive immunity to VACV-expressed protein targets both in magnitude and in diversity when compared to an ID route using a VACV protein microarray. In addition, cytokine responses, assessed using a Luminex(R) mouse cytokine multiplex kit, following IN infection was greater than that stemming from ID infection. Overall, the results suggest that the route of immunization (or infection) influences antibody responses. The greater magnitude and diversity of response in systemic infection provides indirect evidence for anecdotal observations made during the smallpox era that survivors maintain lifelong protection. These findings also suggest that systemic or disseminated host immune induction may result in a superior response, that may influence the magnitude of, as well as duration of protective responses.

      7. Review of mathematical models of vaccination for preventing congenital cytomegalovirus infectionexternal icon
        Lanzieri TM, Gastanaduy PA, Gambhir M, Plotkin SA.
        J Infect Dis. 2020 Mar 5;221(Supplement_1):S86-s93.
        BACKGROUND: Several cytomegalovirus (CMV) vaccine candidates are under development. To reduce the burden of congenital CMV infection, potential strategies under consideration include vaccination of adult women, adolescent girls, and/or young children (both sexes). METHODS: We reviewed 5 studies that used infectious disease modeling to assess the potential impact of vaccination for preventing congenital CMV infection. All models assumed CMV vaccination would prevent primary infection and 2 models also assumed prevention of reinfections and reactivations. RESULTS: Despite differences in structure, assumptions, and population data, infant vaccination (both sexes) was the optimal strategy in all models, but in 1 model vaccinating seronegative women at 19-21 years of age was also optimal (for duration of vaccine protection >/=8 years). In 3 models, infant vaccination increased average age at primary infection as a result of decreased secondary transmission (herd immunity) combined with waning vaccine-induced immunity. This effect could increase the risk of congenital CMV infections in populations where primary CMV infection occurs early in childhood but could be minimized by administering a second dose of vaccine during adolescence. CONCLUSIONS: Understanding vaccine efficacy and duration of immunity, and how these might vary depending on CMV serostatus and age at vaccination, will be key to defining CMV vaccination strategies.

      8. Surveillance data confirm multiyear predictions of rotavirus dynamics in New York Cityexternal icon
        Olson DR, Lopman BA, Konty KJ, Mathes RW, Papadouka V, Ternier A, Zucker JR, Simonsen L, Grenfell BT, Pitzer VE.
        Sci Adv. 2020 Feb;6(9):eaax0586.
        Prediction skill is a key test of models for epidemic dynamics. However, future validation of models against out-of-sample data is rare, partly because of a lack of timely surveillance data. We address this gap by analyzing the response of rotavirus dynamics to infant vaccination. Syndromic surveillance of emergency department visits for diarrhea in New York City reveals a marked decline in diarrheal incidence among infants and young children, in line with data on rotavirus-coded hospitalizations and laboratory-confirmed cases, and a shift from annual to biennial epidemics increasingly affecting older children and adults. A published mechanistic model qualitatively predicted these patterns more than 2 years in advance. Future efforts to increase vaccination coverage may disrupt these patterns and lead to further declines in the incidence of rotavirus-attributable gastroenteritis.

      9. Consequences of undervaccination - measles outbreak, New York City, 2018-2019external icon
        Zucker JR, Rosen JB, Iwamoto M, Arciuolo RJ, Langdon-Embry M, Vora NM, Rakeman JL, Isaac BM, Jean A, Asfaw M, Hawkins SC, Merrill TG, Kennelly MO, Maldin Morgenthau B, Daskalakis DC, Barbot O.
        N Engl J Med. 2020 Mar 12;382(11):1009-1017.
        BACKGROUND: Measles was declared eliminated in the United States in 2000, but the risk of outbreaks owing to international importations remains. An outbreak of measles in New York City began when one unvaccinated child returned home from Israel with measles; onset of rash occurred on September 30, 2018, 9 days after the child returned home. METHODS: We investigated suspected cases of measles by conducting interviews, reviewing medical and immunization records, identifying exposed persons, and performing diagnostic testing. Measles-mumps-rubella (MMR) vaccine (given as either MMR or measles-mumps-rubella-varicella vaccine and collectively referred to as MMR vaccine) uptake was monitored with the use of the Citywide Immunization Registry. The total direct cost to the New York City Department of Health and Mental Hygiene was calculated. RESULTS: A total of 649 cases of measles were confirmed, with onsets of rash occurring between September 30, 2018, and July 15, 2019. A majority of the patients (93.4%) were part of the Orthodox Jewish community, and 473 of the patients (72.9%) resided in the Williamsburg area of Brooklyn, New York. The median age was 3 years; 81.2% of the patients were 18 years of age or younger, and 85.8% of the patients with a known vaccination history were unvaccinated. Serious complications included pneumonia (in 37 patients [5.7%]) and hospitalization (in 49 patients [7.6%]); among the patients who were hospitalized, 20 (40.8%) were admitted to an intensive care unit. As a result of efforts to promote vaccination, the percentage of children in Williamsburg who received at least one dose of MMR vaccine increased from 79.5% to 91.1% among children 12 to 59 months of age. As of September 9, 2019, a total of 559 staff members at the Department of Health and Mental Hygiene (7% of the agency) had been involved in the measles response. The cost of the Department of Health and Mental Hygiene response was $8.4 million. CONCLUSIONS: Importation of measles and vaccination delays among young children led to an outbreak of measles in New York City. The outbreak response was resource intensive and caused serious illness, particularly among unvaccinated children.

    • Injury and Violence
      1. INTRODUCTION: Exposure to violence victimization may help explain disparities of substance use among gender-nonconforming youth (i.e., those whose gender expression differs from societal expectations). METHODS: In 2015, three large urban school districts (2 in California and 1 in Florida) conducted a Youth Risk Behavior Survey that included the assessment of gender expression among a racially/ethnically diverse population-based sample of 6,082 high school students. Five categories of violence victimization were assessed (felt unsafe at school, threatened or injured with a weapon at school, bullied at school, electronically bullied, and forced sexual intercourse). In 2019, the effect of violence victimization on substance use disparities was examined by calculating sex-stratified prevalence ratios by gender nonconformity, adjusted for sexual identity, race/ethnicity, and grade (adjusted prevalence ratio 1 [APR1]), and comparing these with prevalence ratios adjusted for those variables plus violence victimization (adjusted prevalence ratio 2 [APR2]). RESULTS: Among female students, only being threatened or injured with a weapon was significantly (p<0.05) associated with gender nonconformity and there were no substance use disparities by gender nonconformity. Among male students, every category of violence victimization was more prevalent among gender-nonconforming than among gender-conforming students and most substance use categories demonstrated significant gender nonconformity disparities. After controlling for violence victimization, these disparities decreased but remained statistically significant for the use of cocaine (APR1=2.84 vs APR2=1.99), methamphetamine (APR1=4.47 vs APR2=2.86), heroin (APR1=4.55 vs APR2=2.96), and injection drug use (APR1=7.90 vs APR2=4.72). CONCLUSIONS: School-based substance use prevention programs may benefit from strategies that support gender diversity and reduce violence victimizations experienced by gender-nonconforming students, by providing a safe and supportive school environment.

      2. Deaths from fall-related traumatic brain injury - United States, 2008-2017external icon
        Peterson AB, Kegler SR.
        MMWR Morb Mortal Wkly Rep. 2020 Mar 6;69(9):225-230.
        One in 10 U.S. residents aged >/=18 years reports falling each year (1). Among all age groups, falls can cause serious injury and are the second leading cause of traumatic brain injury (TBI)-related deaths (2). TBI is a head injury caused by a bump, blow, or jolt to the head or body or a penetrating head injury that results in disruption of normal brain function.* CDC estimated national and state-specific rates and trends for TBI-related deaths (TBI deaths) caused by unintentional falls (fall-related TBI deaths) among U.S. residents during 2008-2017, by selected decedent characteristics. The national age-adjusted rate of fall-related TBI deaths increased by 17% from 2008 to 2017. Rate trends at the national level increased significantly for nearly all decedent characteristics, with the most notable increases observed among persons living in noncore (i.e., most rural), nonmetropolitan counties and those aged >/=75 years. Analysis of state-specific rate trends determined that rates of fall-related TBI deaths increased significantly in 29 states over the 10-year study period. A fall can happen to anyone of any age, but falls are preventable. Health care providers and the public need to be aware of evidence-based strategies to prevent falls, given that rates of fall-related TBI deaths are increasing. Health care providers can educate patients on fall and TBI prevention, assess their risk for falls, and when needed, encourage participation in appropriate evidence-based fall prevention programs.(dagger).

      3. Student-reported school safety perceptions, connectedness, and absenteeism following a multiple-fatality school shooting - Broward County, Florida, February 14-21, 2018external icon
        Rasberry CN, Sheremenko G, Lesesne CA, Rose ID, Adkins SH, Barrios LC, Holland KM, Sims V, O'Connor K, Grasso DJ, James SR, Simon TR.
        MMWR Morb Mortal Wkly Rep. 2020 Mar 6;69(9):231-235.
        From July 2009 to June 2018, the rates of multiple-victim, school-associated homicides in the United States fluctuated substantially, with evidence of a significant increase in recent years (1). Data on the effects of such incidents on students' school attendance and perceptions of safety and connectedness are limited (2,3) but important. This study used data from a neighboring within-district school before and after a multiple-fatality shooting at Marjory Stoneman Douglas High School in Parkland, Florida, on February 14, 2018. Self-administered questionnaires were completed by one group of students on February 14 just before the shooting (575) and another group during February 15-21 (502); demographics for these groups appeared similar. Linear and logistic regression analyses controlling for demographic characteristics explored differences between groups for safety-related perceptions or experiences, school connectedness, and absenteeism. Compared with students surveyed before the shooting, students surveyed in the days immediately following the shooting had lower odds of feeling safe at school, higher odds of absenteeism, and higher school connectedness scores. Findings suggest the shooting had an immediate, sizeable effect on safety perceptions and absenteeism among students in a neighboring school. Findings also suggest higher school connectedness following the shooting. Further study of school connectedness, including how to enhance and sustain it, might help schools and communities better respond to traumatic events in the community.

      4. National trends in hospitalizations for self-directed violence related to opioids and/or depression - United States, 2000-2015external icon
        Wang J, Sumner SA, Holland KM, Halpin J, Ivey-Stephenson A, Crosby AE.
        Prev Med. 2020 Mar 7:106051.
        This study examined national trends in self-directed violence in the context of changes in opioid use and depression to better inform prevention measures. Using 2000-2015 National Inpatient Sample (NIS) data, we identified 625,064 hospitalizations for self-directed violence among persons aged >/=10years in the United States. Based on whether co-listing opioid related diagnosis and depression, we categorized hospitalizations for self-directed violence into four comorbid categories as 1) related to opioids alone; 2) related to depression alone; 3) related to both opioids and depression; and 4) related to neither opioids nor depression. Census population estimates served as the denominator for calculating hospitalization rates for self-directed violence. Hospitalization rates for self-directed violence related to opioids doubled from 5.1 per 100,000 persons in 2000 to 11.0 in 2015. The rate of increase was highest for self-directed violence related to both opioids and depression, which increased 9.4% annually during 2000-2011 and then decreased 4.3% annually during 2011-2015. Hospitalizations for self-directed violence related to depression alone remained the predominant category, accounting for approximately 60% of hospitalizations for self-directed violence; the rates among females aged 10-24years were the highest among all subgroups, and rose 7.8% annually since 2011 reaching 93.2 per 100,000 persons in 2015. These findings highlight the importance of assessing the risk for self-directed violence among patients misusing opioids and the importance of treating opioid use disorder and depression, particularly when they co-occur. Prevention and treatment of depression is especially important for young females.

    • Laboratory Sciences
      1. Pragmatic selection of larval mosquito diets for insectary rearing of Anopheles gambiae and Aedes aegyptiexternal icon
        Benedict MQ, Hunt CM, Vella MG, Gonzalez KM, Dotson EM, Collins CM.
        PLoS One. 2020 ;15(3):e0221838.
        Larval mosquitoes are aquatic omnivorous scavengers which scrape food from submerged surfaces and collect suspended food particles with their mouth brushes. The composition of diets that have been used in insectaries varies widely though necessarily provides sufficient nutrition to allow colonies to be maintained. Issues such as cost, availability and experience influence which diet is selected. One component of larval diets, essential fatty acids, appears to be necessary for normal flight though deficiencies may not be evident in laboratory cages and are likely more important when mosquitoes are reared for release into the field in e.g. mark-release-recapture and genetic control activities. In this study, four diets were compared for rearing Anopheles gambiae and Aedes aegypti, all of which provide these essential fatty acids. Two diets were custom formulations specifically designed for mosquitoes (Damiens) and two were commercially available fish foods: Doctors Foster and Smith Koi Staple Diet and TetraMin Plus Flakes. Development rate, survival, dry weight and adult longevity of mosquitoes reared with these four diets were measured. The method of presentation of one diet, Koi pellets, was additionally fed in two forms, pellets or a slurry, to determine any effect of food presentation on survival and development rate. While various criteria might be selected to choose 'the best' food, the readily-available Koi pellets resulted in development rates and adult longevity equal to the other diets, high survival to the adult stage and, additionally, this is available at low cost.

      2. Antivirals targeting the neuraminidaseexternal icon
        Gubareva L, Mohan T.
        Cold Spring Harb Perspect Med. 2020 Mar 9.
        The neuraminidase (NA) of influenza A and B viruses plays a distinct role in viral replication and has a highly conserved catalytic site. Numerous sialic (neuraminic) acid analogs that competitively bind to the NA active site and potently inhibit enzyme activity have been synthesized and tested. Four NA inhibitors are now licensed in various parts of the world (zanamivir, oseltamivir, peramivir, and laninamivir) to treat influenza A and B infections. NA changes, naturally occurring or acquired under selective pressure, have been shown to reduce drug binding, thereby affecting the effectiveness of NA inhibitors. Drug resistance and other drawbacks have prompted the search for the next-generation NA-targeting therapeutics. One of the promising approaches is the identification of monoclonal antibodies (mAbs) targeting the conserved NA epitopes. Anti-NA mAbs demonstrate Fab-based antiviral activity supplemented with Fc-mediated immune effector functions. Antiviral Fc-conjugates offer another cutting-edge strategy that is based on a multimodal mechanism of action. These novel antiviral agents are composed of a small-molecule NA inhibitor and an Fc-region that simultaneously engages the immune system. The significant advancements made in recent years further support the value of NA as an attractive target for the antiviral development.

      3. Modeling the genetic basis of individual differences in susceptibility to Gulf War illnessexternal icon
        Jones BC, Miller DB, Lu L, Zhao W, Ashbrook DG, Xu F, Mulligan MK, Williams RW, Zhuang D, Torres-Rojas C, O'Callaghan JP.
        Brain Sci. 2020 Mar 2;10(3).
        Between 25% and 30% of the nearly one million military personnel who participated in the 1991 Persian Gulf War became ill with chronic symptoms ranging from gastrointestinal to nervous system dysfunction. This disorder is now referred to as Gulf War Illness (GWI) and the underlying pathophysiology has been linked to exposure-based neuroinflammation caused by organophosphorous (OP) compounds coupled with high circulating glucocorticoids. In a mouse model of GWI we developed, corticosterone was shown to act synergistically with an OP (diisopropylflurophosphate) to dramatically increase proinflammatory cytokine gene expression in the brain. Because not all Gulf War participants became sick, the question arises as to whether differential genetic constitution might underlie individual differences in susceptibility. To address this question of genetic liability, we tested the impact of OP and glucocorticoid exposure in a genetic reference population of 30 inbred mouse strains. We also studied both sexes. The results showed wide differences among strains and overall that females were less sensitive to the combined treatment than males. Furthermore, we identified one OP-glucocorticoid locus and nominated a candidate gene-Spon1-that may underlie the marked differences in response.

      4. Genome sequence of a segmented filamentous bacterium strain that confers a rotavirus resistance phenotype in miceexternal icon
        Shi Z, Zhao C, Mattei LM, Bittinger K, Jiang B, Gewirtz AT.
        Microbiol Resour Announc. 2020 Mar 5;9(10).
        Segmented filamentous bacteria (SFB) are well appreciated for eliciting Th17 cell immune responses. Here, we report the genome sequence of a murine isolate of SFB, which confers strong protection against rotavirus infection independent of acquired immunity.

      5. A dual-functioning 5'-PPP-NS1shRNA that activates a RIG-I antiviral pathway and suppresses influenza NS1external icon
        Singh N, Ranjan P, Cao W, Patel J, Gangappa S, Davidson BA, Sullivan JM, Prasad PN, Knight PR, Sambhara S.
        Mol Ther Nucleic Acids. 2020 Mar 6;19:1413-1422.
        Retinoic acid-inducible gene-I (RIG-I) is a cytosolic pathogen sensor that is crucial against a number of viral infections. Many viruses have evolved to inhibit pathogen sensors to suppress host innate immune responses. In the case of influenza, nonstructural protein 1 (NS1) suppresses RIG-I function, leading to viral replication, morbidity, and mortality. We show that silencing NS1 with in-vitro-transcribed 5'-triphosphate containing NS1 short hairpin RNA (shRNA) (5'-PPP-NS1shRNA), designed using the conserved region of a number of influenza viruses, not only prevented NS1 expression but also induced RIG-I activation and type I interferon (IFN) expression, resulting in an antiviral state leading to inhibition of influenza virus replication in vitro. In addition, administration of 5'-PPP-NS1shRNA in prophylactic and therapeutic settings resulted in significant inhibition of viral replication following viral challenge in vivo in mice with corresponding increases of RIG-I, IFN-beta, and IFN-lambda, as well as a decrease in NS1 expression.

    • Maternal and Child Health
      1. Clinical diagnostic testing for human cytomegalovirus infectionsexternal icon
        Razonable RR, Inoue N, Pinninti SG, Boppana SB, Lazzarotto T, Gabrielli L, Simonazzi G, Pellett PE, Schmid DS.
        J Infect Dis. 2020 Mar 5;221(Supplement_1):S74-s85.
        Human cytomegalovirus (HCMV) infections are among the most common complications arising in transplant patients, elevating the risk of various complications including loss of graft and death. HCMV infections are also responsible for more congenital infections worldwide than any other agent. Congenital HCMV (cCMV) infections are the leading nongenetic cause of sensorineural hearing loss and a source of significant neurological disabilities in children. While there is overlap in the clinical and laboratory approaches to diagnosis of HCMV infections in these settings, the management, follow-up, treatment, and diagnostic strategies differ considerably. As yet, no country has implemented a universal screening program for cCMV. Here, we summarize the issues, limitations, and application of diagnostic strategies for transplant recipients and congenital infection, including examples of screening programs for congenital HCMV that have been implemented at several centers in Japan, Italy, and the United States.

    • Medicine
      1. Supplemental findings of the 2017 National Blood Collection and Utilization Surveyexternal icon
        Sapiano MR, Jones JM, Savinkina AA, Haass KA, Berger JJ, Basavaraju SV.
        Transfusion. 2020 Mar;60 Suppl 2:S17-s37.
        INTRODUCTION: This report provides supplemental results from the 2017 National Blood Collection and Utilization Survey on characteristics of the donor population, autologous and directed donations and transfusions, platelets, plasma and granulocyte transfusions, pediatric transfusions, severe donor-related adverse events, cost of blood units, hospitals policies and practices, and inventory, dosing, and supply. METHODS: Weighting and imputation were used to generate national estimates including number of donors, donations, donor deferrals, autologous and directed donations and transfusions, severe donor-related adverse events, platelet and plasma collections and transfusions, number of cross-match procedures, irradiation and leukoreduction, and pediatric transfusions. RESULTS: Between 2015 and 2017, successful donations decreased slightly by 2.1% with a 10.3% decrease in donations by persons aged 16-18 years and a 14.4% increase in donations by donors aged >65 years. The median price paid for blood components by hospitals decreased from $211 to $207 for leukoreduced red blood cell units, from $523 to $517 for leukoreduced apheresis platelet units, and from $54 to $51 for fresh frozen plasma units. Plasma transfusions decreased 13.6%, but group AB plasma units transfused increased 24.7%. CONCLUSION: Between 2015 and 2017, blood donations declined slightly because of decreases in donations from younger donors, but the number of donations from older donors increased. The price hospitals pay for blood has continued to decrease. Plasma transfusions have decreased, but the proportion of plasma transfusions involving group AB plasma have increased.

    • Nutritional Sciences
      1. Factors associated with anaemia in a nationally representative sample of nonpregnant women of reproductive age in Nepalexternal icon
        Ford ND, Bichha RP, Parajuli KR, Paudyal N, Joshi N, Whitehead RD, Chitekwe S, Mei Z, Flores-Ayala R, Adhikari DP, Rijal S, Jefferds ME.
        Matern Child Nutr. 2020 Mar 10:e12953.
        We used cross-sectional data from the 2016 Nepal National Micronutrient Status Survey to evaluate factors associated with anaemia among a nationally representative sample of nonpregnant women 15- 49 years (n = 1, 918). Haemoglobin, biomarkers of iron status and other micronutrients, infection, inflammation, and blood disorders were assessed from venous blood. Soil-transmitted helminth and Helicobacter pylori infections were assessed from stool. Sociodemographic, household, and health characteristics and diet were ascertained by interview. We conducted bivariate analyses between candidate predictors and anaemia (haemoglobin <12.0 g/ dL, altitude- and smoking-adjusted). Candidate predictors that were significant in bivariate models (P < 0.05) were included in the multivariable logistic regression model, accounting for complex sampling design. Anaemia prevalence was 20.2% (95% confidence interval [CI] [17.6, 22.8]). Associated with reduced anaemia odds were living in the Mountain and Hill ecological zones relative to the Terai (adjusted odds ratio [AOR] 0.35, 95% CI [0.21, 0.60] and AOR 0.41, 95% CI [0.29, 0.59], respectively), recent cough (AOR 0.56, 95% CI [0.38, 0.82]), hormonal contraceptive use (AOR 0.58; 95% CI [0.38, 0.88]), ln ferritin (micrograms per litre; AOR 0.43, 95% CI [0.35, 0.54]), and ln retinol binding protein (micrograms per litre; AOR 0.20, 95% CI [0.11, 0.37]). Residing in a house with an earth floor (AOR 1.74, 95% CI [1.18, 2.56]), glucose-6- phosphate dehydrogenase deficiency (AOR 2.44, 95% CI [1.66, 3.60]), and haemoglobinopathies (AOR 6.15, 95% CI [3.09, 12.26]) were associated with increased anaemia odds. Interventions that improve micronutrient status, ensure access to hormonal birth control, and replace dirt floors to reduce infection risk might help reduce anaemia in this population.

      2. Background: Some of the recently piloted innovative approaches for the management of acute malnutrition in children use the "expanded MUAC-only" approach, with Mid Upper Arm Circumference (MUAC) < 125 mm as the sole anthropometric criterion for screening and admission, classification of cases as severe using the 115 mm cut-off, and use Ready-to-Use-Therapeutic-Food (RUTF) for the management of both moderate (MAM) and severe (SAM) cases of acute malnutrition. Our study aimed at exploring the potential consequences of this "expanded MUAC-only" program scenario on the eligibility for treatment and RUTF allocation, as compared with the existing WHO normative guidance. Methods: We analyzed data from 550 population representative cross-sectional cluster surveys conducted since 2007. We retrieved all children classified as SAM and MAM according to currently used case definitions, and calculated the proportions of SAM children who would be excluded from treatment, misclassified as MAM, or whose specific risks (because of having both MUAC and weight-for height deficits) would be ignored. We also analyzed the expected changes in the number and demographics (sex, age) of children meant to receive RUTF according to the new approach. Results: We found that approximately one quarter of SAM children would not be detected and eligible for treatment under the "expanded MUAC-only" scenario, and another 20% would be classified as MAM. A further 17% of the total SAM children would be admitted and followed only according to their MUAC or oedema status, while they also present with a severe weight-for height deficit on admission. Considering MAM targeting, about half of the MAM children would be left undetected. This scenario also shows a 2.5 time increase in the number of children targeted with RUTF, with approximately 70% of MAM and 30% of SAM cases among this new RUTF target. Conclusions: This empirical evidence suggests that adoption of "expanded MUAC-only" programs would likely lead to a priori exclusion from treatment or misclassifying as MAM a large proportion of SAM cases, while redirecting programmatic costs in favor of those less in need. It underscores the need to explore other options for improving the impact of programs addressing the needs of acutely malnourished children.

      3. Background: Mid-upper arm circumference (MUAC) and weight-for-height (WHZ) are commonly used indicators to identify acute malnutrition. However, MUAC and WHZ diagnose different children, and produce prevalence estimates that are meaningfully different. Previous research in Somalia has suggested improved concordance using MUAC-for-age (MUACZ) rather than MUAC. We further evaluate the relationship between MUACZ, MUAC, and WHZ using surveys conducted globally. Methods: We analyzed 882 population representative surveys from 41 countries. Children ages 6-59 months were classified as acutely malnourished using three independent criteria: WHZ < - 2 (WHZ2), MUAC< 125 mm (MUAC125), MUACZ < - 2 (MUACZ2). Population prevalence using each of the three criteria are presented by country and region. Correlations of survey prevalence for each indicator pair were assessed. Multivariable regression models of MUACZ and MUAC125 adjusted for WHZ2, stunting prevalence, age, and sex. To evaluate individual level diagnostic concordance, we compared the proportion of children identified by each of the three criteria. Results: Median prevalence of acute malnutrition overall was highest for MUACZ2 (14.0%) followed by WHZ2 (10.6%), and lowest for MUAC125 (7.3%). The absolute difference in prevalence between MUACZ2 and WHZ2 was smaller than the difference between MUAC125 and WHZ2 for 51.3% of surveys. The correlations of WHZ2 with both MUACZ2 as well as with MUAC125 were weak, positive associations (Pearson's r = 0.5757 and 0.4943, respectively), but MUAC125 and MUACZ2 had a strong, linear relationship (Pearson's r = 0.9265). The adjusted regression model for MUACZ2 had greater fit (R(2) = 0.50) relative to the adjusted model for MUAC125 (R(2) = 0.43). The proportion of children identified by both MUAC125 and WHZ2 was 25.5%, smaller than the proportion identified by both MUACZ2 and WHZ2 (30.6%). Conclusions: MUACZ identified more children as malnourished than MUAC, resulting in a higher prevalence of acute malnutrition in nearly all settings. Prevalence by MUACZ was not consistently more similar to WHZ than that estimated by MUAC, and correlations with WHZ were only slightly improved relative to MUAC. Consequently, programmatic use of MUACZ cannot be justified based on improved concordance with WHZ. Further research on morbidity and mortality of children with low MUACZ only are needed before recommending MUACZ for wider use.

    • Occupational Safety and Health
      1. Effect of continuous cooling on inhibition and attention while wearing firefighter's PPE in a hot environmentexternal icon
        Aljaroudi AM, Kadis DS, Bhattacharya A, Strauch A, Quinn TD, Williams WJ.
        J Occup Environ Hyg. 2020 Mar 9:1-10.
        Firefighting is physically and mentally strenuous, requiring rapid, appropriate decision-making in hot environments. Intact cognitive function is imperative to firefighters' effectiveness and safety. The study purpose was to investigate the effect of hyperthermia and the effect of body cooling on sustained attention and response inhibition while wearing firefighters' personal protective ensembles after exercise in a hot environment. Twelve healthy males were recruited to participate in two randomly assigned exercise sessions (walking on a treadmill for 40 min at 40% [Formula: see text] O2max while wearing firefighter's protective ensemble) in a hot environment: control (no cooling) and intervention (cooling). For intervention sessions, a cooling garment was worn underneath firefighter's protective ensemble and infused with 18 degrees C water supplied by an external water circulator. Participants performed a computerized Go/No-Go (a measure of cognitive function) test three times at baseline and post-exercise for each experimental session. Participants completed baseline testing while wearing cotton athletic clothing. The exercise continued until the core temperature reached approximately 39 degrees C (for all subjects regardless of cooling or non-cooling experimental sessions). Following hyperthermia, participants' physiological responses were significantly increased after exercise. Subjects' reaction time was significantly reduced (improved) after experiencing thermal strain and reaching hyperthermia. The cooling method had a significant impact on suppressing the physiological load, i.e., body cooling delayed the time to reach a Tc of 39 degrees C (p </= 0.05), but not cognitive inhibition and attention (reaction time and accuracy). Unexpectedly, hyperthermia resulted in shorter reaction time following exercise (16.64 +/- 5.62; p < 0.03), likely influenced by increased attention/vigilance. Hyperthermia may trigger an acute increase in alertness, causing decreased reaction time.

      2. Work-related adverse respiratory health outcomes at a machine manufacturing facility with a cluster of bronchiolitis, alveolar ductitis and emphysema (BADE)external icon
        Cummings KJ, Stanton ML, Kreiss K, Boylstein RJ, Park JH, Cox-Ganser JM, Virji MA, Edwards NT, Segal LN, Blaser MJ, Weissman DN, Nett RJ.
        Occup Environ Med. 2020 Mar 4.
        OBJECTIVES: Four machine manufacturing facility workers had a novel occupational lung disease of uncertain aetiology characterised by lymphocytic bronchiolitis, alveolar ductitis and emphysema (BADE). We aimed to evaluate current workers' respiratory health in relation to job category and relative exposure to endotoxin, which is aerosolised from in-use metalworking fluid. METHODS: We offered a questionnaire and spirometry at baseline and 3.5 year follow-up. Endotoxin exposures were quantified for 16 production and non-production job groups. Forced expiratory volume in one second (FEV1) decline >/=10% was considered excessive. We examined SMRs compared with US adults, adjusted prevalence ratios (aPRs) for health outcomes by endotoxin exposure tertiles and predictors of excessive FEV1 decline. RESULTS: Among 388 (89%) baseline participants, SMRs were elevated for wheeze (2.5 (95% CI 2.1 to 3.0)), but not obstruction (0.5 (95% CI 0.3 to 1.1)). Mean endotoxin exposures (range: 0.09-28.4 EU/m(3)) were highest for machine shop jobs. Higher exposure was associated with exertional dyspnea (aPR=2.8 (95% CI 1.4 to 5.7)), but not lung function. Of 250 (64%) follow-up participants, 11 (4%) had excessive FEV1 decline (range: 403-2074 mL); 10 worked in production. Wheeze (aPR=3.6 (95% CI 1.1 to 12.1)) and medium (1.3-7.5 EU/m(3)) endotoxin exposure (aPR=10.5 (95% CI 1.3 to 83.1)) at baseline were associated with excessive decline. One production worker with excessive decline had BADE on subsequent lung biopsy. CONCLUSIONS: Lung function loss and BADE were associated with production work. Relationships with relative endotoxin exposure indicate work-related adverse respiratory health outcomes beyond the sentinel disease cluster, including an incident BADE case. Until causative factors and effective preventive strategies for BADE are determined, exposure minimisation and medical surveillance of affected workforces are recommended.

      3. Selecting a proper respirator requires determining the ratio of an employee's maximum use concentration (MUC) divided by the occupational exposure limit of a chemical. Current industrial hygiene practice often is to obtain a percentile estimate (e.g. 95th) of the measured exposure distribution to apply as the MUC. However, practitioners who are not yet familiar with statistical or mathematical approaches may choose the highest exposure data point as the MUC, a method that is still considered appropriate by the Occupational Safety and Health Administration. Nonetheless, choosing a respirator using the highest exposure data point when only limited data are available may result in not always providing the most adequate respirator. Because some practitioners are not familiar with exposure assessment tools, our primary goal in this study was to demonstrate the best process when selecting respiratory protection by using a combination of exposure data and assessment tools. Three user-friendly tools, IHDataAnalyst, Advanced REACH Tool, and IHSTAT, were selected to demonstrate how to use different types of tool outputs when choosing a respirator. A decision logic was developed to help users navigate the combining of different data inputs. Personal full-shift exposure data collected in four different workplaces were used to describe four different outcomes generated when the maximum exposure data point and the tool's output are compared with the exposure limit of the chemical. Outcomes varied, from determinations of 'high confidence' (or final decision) to 'low confidence' (or indicating more data are needed) in the selection of a respirator recommendation. In conclusion, systematically adopting the combination of exposure data and assessment tools could increase practitioners' confidence in decision-making when choosing respirators from a limited exposure data set. These suggested guidelines will lead practitioners toward good industrial hygiene practices.

      4. Workplace indoor environmental quality and asthma-related outcomes in healthcare workersexternal icon
        Rollins SM, Su FC, Liang X, Humann MJ, Stefaniak AB, LeBouf RF, Stanton ML, Virji MA, Henneberger PK.
        Am J Ind Med. 2020 Mar 10.
        BACKGROUND: Asthma-related health outcomes are known to be associated with indoor moisture and renovations. The objective of this study was to estimate the frequency of these indoor environmental quality (IEQ) factors in healthcare facilities and their association with asthma-related outcomes among workers. METHODS: New York City healthcare workers (n = 2030) were surveyed regarding asthma-related symptoms, and moisture and renovation factors at work and at home during the last 12 months. Questions for workplace moisture addressed water damage (WD), mold growth (MG), and mold odor (MO), while for renovations they addressed painting (P), floor renovations (FR), and wall renovations (WR). Regression models were fit to examine associations between work and home IEQ factors and multiple asthma-related outcomes. RESULTS: Reports of any moisture (n = 728, 36%) and renovations (n = 1412, 70%) at work were common. Workplace risk factors for asthma-related outcomes included the moisture categories of WD by itself, WD with MO (without MG), and WD with MG and MO, and the renovation category with the three factors P, FR, and WR. Reports of home IEQ factors were less frequent and less likely to be associated with health outcomes. Data analyses suggested that MG and/or MO at work and at home had a synergistic effect on the additive scale with a symptom-based algorithm for bronchial hyperresponsiveness. CONCLUSIONS: The current study determined that moisture and renovation factors are common in healthcare facilities, potentially putting workers at risk for asthma-related outcomes. More research is needed to confirm these results, especially prospective studies.

    • Occupational Safety and Health - Mining
      1. LED area lighting to reduce glare for roof bolter operatorsexternal icon
        Sammarco JJ, Mayton AG, Rubinstein EN.
        Min Metall Explor. 2020 .
        Researchers from the National Institute for Occupational Safety and Health (NIOSH) developed a light-emitting diode (LED) area luminaire called the Saturn and conducted a laboratory study using a Fletcher High Dual-boom Mast Feed (HDDR) roof bolting machine. The Saturn luminaire was designed to (1) enhance floor illumination to enable better detection of trip hazards in the interior spaces of a roof bolter and (2) reduce glare that has typically been an issue of concern on roof bolters. This paper reports on the results of achieving the second objective. The existing roof bolter lighting was the baseline and was compared with three versions of the Saturn luminaire relative to light intensity (100%, 75%, and 50%). Discomfort and disability glare data were obtained from 30 participants that comprised three age groups. Discomfort glare perceptions were obtained using the De Boer rating scale, and disability glare was quantified by using Mars Letter Contrast Sensitivity tests. Discomfort glare was reduced at least 3 levels with all Saturn versions. Also, a predictive model was used to estimate discomfort glare, and the results were similar. Disability glare was the least for the Saturn’s 50% intensity, and all Saturn versions had significantly less disability glare than with the baseline lighting. Veiling luminance was calculated and used as another indicator of disability glare. Veiling luminance was 28 to 42 times greater with the baseline lighting as compared with that of the Saturn lighting. Lastly, visibility levels were calculated. The Saturn versions were 4 to 6.5 times better in terms of visibility level.

    • Parasitic Diseases
      1. Impact of indoor residual spraying with pirimiphos-methyl (Actellic 300CS) on entomological indicators of transmission and malaria case burden in Migori County, western Kenyaexternal icon
        Abong'o B, Gimnig JE, Torr SJ, Longman B, Omoke D, Muchoki M, Ter Kuile F, Ochomo E, Munga S, Samuels AM, Njagi K, Maas J, Perry RT, Fornadel C, Donnelly MJ, Oxborough RM.
        Sci Rep. 2020 Mar 11;10(1):4518.
        Indoor residual spraying (IRS) of insecticides is a major vector control strategy for malaria prevention. We evaluated the impact of a single round of IRS with the organophosphate, pirimiphos-methyl (Actellic 300CS), on entomological and parasitological parameters of malaria in Migori County, western Kenya in 2017, in an area where primary vectors are resistant to pyrethroids but susceptible to the IRS compound. Entomological monitoring was conducted by indoor CDC light trap, pyrethrum spray catches (PSC) and human landing collection (HLC) before and after IRS. The residual effect of the insecticide was assessed monthly by exposing susceptible An. gambiae s.s. Kisumu strain to sprayed surfaces in cone assays and measuring mortality at 24 hours. Malaria case burden data were extracted from laboratory records of four health facilities within the sprayed area and two adjacent unsprayed areas. IRS was associated with reductions in An. funestus numbers in the intervention areas compared to non-intervention areas by 88% with light traps (risk ratio [RR] 0.12, 95% CI 0.07-0.21, p < 0.001) and 93% with PSC collections (RR = 0.07, 0.03-0.17, p < 0.001). The corresponding reductions in the numbers of An. arabiensis collected by PSC were 69% in the intervention compared to the non-intervention areas (RR = 0.31, 0.14-0.68, p = 0.006), but there was no significant difference with light traps (RR = 0.45, 0.21-0.96, p = 0.05). Before IRS, An. funestus accounted for over 80% of Anopheles mosquitoes collected by light trap and PSC in all sites. After IRS, An. arabiensis accounted for 86% of Anopheles collected by PSC and 66% by CDC light trap in the sprayed sites while the proportion in non-intervention sites remained unchanged. No sporozoite infections were detected in intervention areas after IRS and biting rates by An. funestus were reduced to near zero. Anopheles funestus and An. arabiensis were fully susceptible to pirimiphos-methyl and resistant to pyrethroids. The residual effect of Actellic 300CS lasted ten months on mud and concrete walls. Malaria case counts among febrile patients within IRS areas was lower post- compared to pre-IRS by 44%, 65% and 47% in Rongo, Uriri and Nyatike health facilities respectively. A single application of IRS with Actellic 300CS in Migori County provided ten months protection and resulted in the near elimination of the primary malaria vector An. funestus and a corresponding reduction of malaria case count among out-patients. The impact was less on An. arabiensis, most likely due to their exophilic nature.

      2. Assessment of subpatent Plasmodium infection in northwestern Ethiopiaexternal icon
        Assefa A, Ahmed AA, Deressa W, Wilson GG, Kebede A, Mohammed H, Sassine M, Haile M, Dilu D, Teka H, Murphy MW, Sergent S, Rogier E, Zhiyong Z, Wakeman BS, Drakeley C, Shi YP, Von Seidlein L, Hwang J.
        Malar J. 2020 Mar 4;19(1):108.
        BACKGROUND: Ethiopia has set a goal for malaria elimination by 2030. Low parasite density infections may go undetected by conventional diagnostic methods (microscopy and rapid diagnostic tests) and their contribution to malaria transmission varies by transmission settings. This study quantified the burden of subpatent infections from samples collected from three regions of northwest Ethiopia. METHODS: Sub-samples of dried blood spots from the Ethiopian Malaria Indicator Survey 2015 (EMIS-2015) were tested and compared using microscopy, rapid diagnostic tests (RDTs), and nested polymerase chain reaction (nPCR) to determine the prevalence of subpatent infection. Paired seroprevalence results previously reported along with gender, age, and elevation of residence were explored as risk factors for Plasmodium infection. RESULTS: Of the 2608 samples collected, the highest positive rate for Plasmodium infection was found with nPCR 3.3% (95% CI 2.7-4.1) compared with RDT 2.8% (95% CI 2.2-3.5) and microscopy 1.2% (95% CI 0.8-1.7). Of the nPCR positive cases, Plasmodium falciparum accounted for 3.1% (95% CI 2.5-3.8), Plasmodium vivax 0.4% (95% CI 0.2-0.7), mixed P. falciparum and P. vivax 0.1% (95% CI 0.0-0.4), and mixed P. falciparum and Plasmodium malariae 0.1% (95% CI 0.0-0.3). nPCR detected an additional 30 samples that had not been detected by conventional methods. The majority of the nPCR positive cases (61% (53/87)) were from the Benishangul-Gumuz Region. Malaria seropositivity had significant association with nPCR positivity [adjusted OR 10.0 (95% CI 3.2-29.4), P < 0.001]. CONCLUSION: Using nPCR the detection rate of malaria parasites increased by nearly threefold over rates based on microscopy in samples collected during a national cross-sectional survey in 2015 in Ethiopia. Such subpatent infections might contribute to malaria transmission. In addition to strengthening routine surveillance systems, malaria programmes may need to consider low-density, subpatent infections in order to accelerate malaria elimination efforts.

      3. Molecular typing of Cyclospora cayetanensis in produce and clinical samples using targeted enrichment of complete mitochondrial genomes and next-generation sequencingexternal icon
        Cinar HN, Gopinath G, Murphy HR, Almeria S, Durigan M, Choi D, Jang A, Kim E, Kim R, Choi S, Lee J, Shin Y, Lee J, Qvarnstrom Y, Benedict TK, Bishop HS, da Silva A.
        Parasit Vectors. 2020 Mar 6;13(1):122.
        BACKGROUND: Outbreaks of cyclosporiasis, a diarrheal illness caused by Cyclospora cayetanensis, have been a public health issue in the USA since the mid 1990's. In 2018, 2299 domestically acquired cases of cyclosporiasis were reported in the USA as a result of multiple large outbreaks linked to different fresh produce commodities. Outbreak investigations are hindered by the absence of standardized molecular epidemiological tools for C. cayetanensis. For other apicomplexan coccidian parasites, multicopy organellar DNA such as mitochondrial genomes have been used for detection and molecular typing. METHODS: We developed a workflow to obtain complete mitochondrial genome sequences from cilantro samples and clinical samples for typing of C. cayetanensis isolates. The 6.3 kb long C. cayetanensis mitochondrial genome was amplified by PCR in four overlapping amplicons from genomic DNA extracted from cilantro, seeded with oocysts, and from stool samples positive for C. cayetanensis by diagnostic methods. DNA sequence libraries of pooled amplicons were prepared and sequenced via next-generation sequencing (NGS). Sequence reads were assembled using a custom bioinformatics pipeline. RESULTS: This approach allowed us to sequence complete mitochondrial genomes from the samples studied. Sequence alterations, such as single nucleotide polymorphism (SNP) profiles and insertion and deletions (InDels), in mitochondrial genomes of 24 stool samples from patients with cyclosporiasis diagnosed in 2014, exhibited discriminatory power. The cluster dendrogram that was created based on distance matrices of the complete mitochondrial genome sequences, indicated distinct strain-level diversity among the 2014 C. cayetanensis outbreak isolates analyzed in this study. CONCLUSIONS: Our results suggest that genomic analyses of mitochondrial genome sequences may help to link outbreak cases to the source.

      4. Barriers to malaria prevention among immigrant travelers in the United States who visit friends and relatives in sub-Saharan Africa: A cross-sectional, multi-setting survey of knowledge, attitudes, and practicesexternal icon
        Volkman HR, Walz EJ, Wanduragala D, Schiffman E, Frosch A, Alpern JD, Walker PF, Angelo KM, Coyle C, Mohamud MA, Mwangi E, Haizel-Cobbina J, Nchanji C, Johnson RS, Ladze B, Dunlop SJ, Stauffer WM.
        PLoS One. 2020 ;15(3):e0229565.
        BACKGROUND: Despite achievements in the reduction of malaria globally, imported malaria cases to the United States by returning international travelers continue to increase. Immigrants to the United States from sub-Saharan Africa (SSA) who then travel back to their homelands to visit friends and relatives (VFRs) experience a disproportionate burden of malaria illness. Various studies have explored barriers to malaria prevention among VFRs and non-VFRs-travelers to the same destinations with other purpose for travel-but few employed robust epidemiologic study designs or performed comparative analyses of these two groups. To better quantify the key barriers that VFRs face to implement effective malaria prevention measures, we conducted a comprehensive community-based, cross-sectional, survey to identify differences in malaria prevention knowledge, attitudes, and practices (KAP) among VFRs and others traveling to Africa and describe the differences between VFRs and other types of international travelers. METHODS AND FINDINGS: Three distinct populations of travelers with past or planned travel to malaria-endemic countries of SSA were surveyed: VFRs diagnosed with malaria as reported through a state health department; members of the general VFR population (community); and VFR and non-VFR travelers presenting to a travel health clinic, both before their pretravel consultation and again, after return from travel. A Community Advisory Board of African immigrants and prior qualitative research informed survey development and dissemination. Across the three groups, 489 travelers completed surveys: 351 VFRs and 138 non-VFRs. VFRs who reported taking antimalarials on their last trip rated their concern about malaria higher than those who did not. Having taken five or more trips to SSA was reported more commonly among VFRs diagnosed with malaria than community VFRs (44.0% versus 20.4%; p = 0.008). Among travel health clinic patients surveyed before and after travel, VFR travelers were less successful than non-VFRs in adhering to their planned use of antimalarials (82.2% versus 98.7%; p = 0.001) and employing mosquito bite avoidance techniques (e.g., using bed nets: 56.8% versus 81.8%; p = 0.009). VFRs who visited the travel health clinic were more likely than VFR respondents from the community to report taking an antimalarial (83.0% versus 61.9%; p = 0.009), or to report bite avoidance behaviors (e.g., staying indoors when mosquitoes were out: 80.9% versus 59.5%; p = 0.009). CONCLUSIONS: We observed heterogeneity in malaria prevention behaviors among VFRs and between VFR and non-VFR traveler populations. Although VFRs attending the travel health clinic appear to demonstrate better adherence to malaria prevention measures than VFR counterparts surveyed in the community, specialized pretravel care is not sufficient to ensure chemoprophylaxis use and bite avoidance behaviors among VFRs. Even when seeking specialized pretravel care, VFRs experience greater barriers to the use of malaria prevention than non-VFRs. Addressing access to health care and upstream barrier reduction strategies that make intended prevention more achievable, affordable, easier, and resonant among VFRs may improve malaria prevention intervention effectiveness.

    • Public Health Leadership and Management
      1. An exploratory review of the literature evaluating nonclinical fellowship programsexternal icon
        Paek M, Radkey C, Honeycutt S, Glynn MK.
        Eval Program Plann. 2020 Feb 27;80:101812.
        Fellowship programs offer career development opportunities, provide experiential training, and can be used to recruit personnel to address specific challenges facing the public health workforce. Given the potential influence fellowships have on the future public health workforce, it is important to understand and articulate the results of such programs and to identify areas of improvement to meet current workforce needs. The purpose of this literature review was to identify common practices used to evaluate nonclinical fellowship programs. After a search of the internet and selected databases, we screened titles and abstracts using predetermined selection criteria. We then conducted a detailed review of selected papers to extract information about program characteristics (program description, sector, and program length) and evaluation characteristics (primary evaluation type, framework for evaluation, data collection methods, and respondent populations) from 33 papers. We found a limited number of published papers on the evaluation of nonclinical fellowship programs, and most focused on outcomes associated with fellows or alumni. The most useful papers for our purposes clearly described the evaluation framework that guided the evaluation.

    • Reproductive Health
      1. Expulsion of intrauterine devices after postpartum placement by timing of placement, delivery type, and IUD type: a systematic review and meta-analysisexternal icon
        Averbach SH, Ermias Y, Jeng G, Curtis KM, Whiteman MK, Berry-Bibee E, Jamieson DJ, Marchbanks PA, Tepper NK, Jatlaoui TC.
        Am J Obstet Gynecol. 2020 Mar 3.
        OBJECTIVES: To provide updated and more detailed pooled IUD expulsion rates and expulsion risk estimates among women with postpartum IUD placement by timing of insertion, delivery type, and IUD type to inform current IUD insertion practices in the United States. DATA SOURCES: We searched PubMed, Cochrane Library, and through June 2019. STUDY ELIGIBILITY CRITERIA: We included all studies, of any study design, that examined postpartum placement of Copper T380A (copper) or Levonorgestrel (LNG)-containing IUDs that reported counts of expulsion. STUDY APPRAISAL AND SYNTHESIS METHODS: We evaluated IUD expulsion among women receiving postpartum IUDs in the 'immediate' (within 10 minutes), 'early inpatient' (greater than 10 minutes to less than 72 hours), 'early outpatient' (72 hours to less than 4 weeks) and interval (4 weeks or greater) time periods after delivery. We assessed study quality using the U.S. Preventive Services Task Force evidence grading system. We calculated pooled absolute rates of partial and complete IUD expulsion separately and estimated adjusted relative risks by the timing of postpartum placement, delivery type and IUD type using log-binomial multivariable regression. RESULTS: We identified 48 level I to II-3 studies of poor to good quality that reported a total of 7,661 IUD placements. Complete IUD expulsion rates varied by timing of placement: 10.2% (range 0.0-26.7) for immediate, 13.2% (3.5-46.7) for early inpatient, 0% for early outpatient, and 1.8% (0.0-4.8) for interval placements. Complete IUD expulsion rates also varied by delivery type: 14.8% (range 4.8-43.1) for vaginal and 3.8% (0.0-21.1) for cesarean deliveries. Among immediate postpartum vaginal placements, the expulsion rate for LNG-IUDs was 27.4% (18.8-45.2) and 12.4% (4.8-43.1) for copper IUDs. Compared with interval placement, immediate and early postpartum placements (inpatient and outpatient combined) were associated with greater risk of complete expulsions (adjusted RR (aRR), 8.33; 95% CI, 4.32-16.08 and aRR, 5.27; 95% CI, 2.56-10.85, respectively). Among immediate postpartum placements, risk of expulsion was greater for placement after vaginal compared with cesarean deliveries (aRR, 4.57; 95% CI, 3.49-5.99). Among immediate placements at the time of vaginal delivery, LNG-IUDs were associated with a greater risk of expulsion compared with copper IUDs (aRR, 1.90; 95% CI, 1.36-2.65). CONCLUSION: While IUD expulsion rates vary by timing of placement, type, and mode of delivery, IUD insertion can take place at any time. Understanding the risk of IUD expulsion at each time period will enable women to make an informed choice about when to initiate an IUD in the postpartum period based on her own goals and preferences.

    • Substance Use and Abuse
      1. Severe lung injury associated with use of e-cigarette, or vaping, products - California, 2019external icon
        Heinzerling A, Armatas C, Karmarkar E, Attfield K, Guo W, Wang Y, Vrdoljak G, Moezzi B, Xu D, Wagner J, Fowles J, Dean C, Cummings KJ, Wilken JA.
        JAMA Intern Med. 2020 Mar 6.
        Importance: Since August 2019, more than 2700 patients have been hospitalized with e-cigarette, or vaping, product use-associated lung injury (EVALI) across the United States. This report describes the outbreak in California, a state with one of the highest case counts and with a legal adult-use (recreational) cannabis market. Objective: To present clinical characteristics and vaping product exposures of patients with EVALI in California. Design, Setting, and Participants: Case series describing epidemiologic and laboratory data from 160 hospitalized patients with EVALI reported to the California Department of Public Health by local health departments, who received reports from treating clinicians, from August 7 through November 8, 2019. Exposures: Standardized patient interviews were conducted to assess vaping products used, frequency of use, and method of product acquisition. Vaping products provided by a subset of patients were tested for active ingredients and other substances. Main Outcomes and Measures: Demographic and clinical characteristics, level of care, and outcomes of hospitalization were obtained from medical record review. Results: Among 160 patients with EVALI, 99 (62%) were male, and the median age was 27 years (range, 14-70 years). Of 156 patients with data available, 71 (46%) were admitted to an intensive care unit, and 46 (29%) required mechanical ventilation. Four in-hospital deaths occurred. Of 86 patients interviewed, 71 (83%) reported vaping tetrahydrocannabinol (THC)-containing products, 36 (43%) cannabidiol (CBD)-containing products, and 39 (47%) nicotine-containing products. Sixty-five of 87 (75%) THC-containing products were reported as obtained from informal sources, such as friends, acquaintances, or unlicensed retailers. Of 87 vaping products tested from 24 patients, 49 (56%) contained THC. Vitamin E or vitamin E acetate was found in 41 (84%) of the THC-containing products and no nicotine products. Conclusions and Relevance: Patients' clinical outcomes and vaping behaviors, including predominant use of THC-containing products from informal sources, are similar to those reported by other states, despite California's legal recreational cannabis market. While most THC products tested contained vitamin E or vitamin E acetate, other underlying cause(s) of injury remain possible. The California Department of Public Health recommends that individuals refrain from using any vaping or e-cigarette products, particularly THC-containing products from informal sources, while this investigation is ongoing.

      2. Screening for alcohol use and brief counseling of adults - 13 states and the District of Columbia, 2017external icon
        McKnight-Eily LR, Okoro CA, Turay K, Acero C, Hungerford D.
        MMWR Morb Mortal Wkly Rep. 2020 Mar 13;69(10):265-270.
        Binge drinking* is a leading preventable public health problem. From 2006 to 2010, binge drinking contributed to approximately 49,000 annual deaths resulting from acute conditions (e.g., injuries and violence) (1). Binge drinking also increases the risk for adverse health conditions, including some chronic diseases (e.g., breast cancer) and fetal alcohol spectrum disorders (2). In 2004, 2013, and again in 2018, for all U.S. adults aged >/=18 years in primary care, the U.S. Preventive Services Task Force (USPSTF) recommended alcohol screening and brief intervention (alcohol SBI) or counseling for persons whose screening indicated drinking in excess of recommended limits or in ways that increase risk for poor health outcomes (3-5). However, previous CDC surveillance data indicate that patients report rarely talking to their provider about alcohol use,(dagger) and alcohol SBI is traditionally delivered through conversation. CDC recently analyzed 2017 data from the Behavioral Risk Factor Surveillance System (BRFSS) survey's five-question module, which asked adults in 13 states( section sign) and the District of Columbia (DC) about the delivery of alcohol SBI during their most recent checkup in the past 2 years. Overall, 81.4% of adults (age-standardized estimate) reported being asked about alcohol use by a health professional in person or on a form during a checkup in the past 2 years, but only 37.8% reported being asked a question about binge-level alcohol consumption, which is included on USPSTF recommended instruments (3). Among module respondents who were asked about alcohol use at a checkup in the past 2 years and reported current binge drinking (past 30 days) at time of survey, only 41.7% were advised about the harms of drinking too much at a checkup in the past 2 years, and only 20.1% were advised to reduce or quit drinking at a checkup in the past 2 years. These findings suggest that missed opportunities remain for health care providers to intervene with patients who report binge drinking. Working to implement alcohol SBI at a systems level, including the provision of the new Healthcare Effectiveness Data Information Set (HEDIS) measure, Unhealthy Alcohol Use Screening and Follow-Up, can improve alcohol SBI's use and benefit in primary care.

      3. Notes from the field: Opioid-involved overdose deaths with fentanyl or fentanyl analogs detected - 28 states and the District of Columbia, July 2016-December 2018external icon
        O'Donnell J, Gladden RM, Goldberger BA, Mattson CL, Kariisa M.
        MMWR Morb Mortal Wkly Rep. 2020 Mar 13;69(10):271-273.

      4. On July 10, 2019, Wisconsin Department of Health Services (WDHS) was notified of five previously healthy adolescents with severe lung injuries who reported use of e-cigarette, or vaping, products before symptom onset. As of December 31, 2019, 105 confirmed or probable cases of e-cigarette, or vaping, product use-associated lung injury (EVALI)* had been reported to WDHS . Three social clusters (A, B, and C), comprising eight EVALI patients (cluster A = two patients, cluster B = three, and cluster C = three) were identified. WDHS investigated these clusters with standard and follow-up interviews; laboratory analysis of e-cigarette, or vaping, products; and analysis of bronchoalveolar lavage (BAL) fluid. All eight patients reported daily use of tetrahydrocannabinol (THC)-containing e-cigarette, or vaping, product cartridges (THC cartridges) in the month preceding symptom onset. All THC cartridges were purchased from local illicit dealers, and all patients reported using THC cartridges labeled as "Dank Vapes," among other illicit brand names. At least two members of each cluster reported frequent sharing of THC cartridges before symptom onset. All eight patients also reported daily use of nicotine-containing e-cigarette, or vaping, products. Vitamin E acetate (VEA) was detected in all five THC cartridges tested from two patients, and in BAL fluid from two other patients. These findings suggest that THC cartridges containing VEA and sold on the illicit market were likely responsible for these small clusters of EVALI. Based on information presented in this and previous reports (1,2) CDC recommends not using THC-containing e-cigarette, or vaping, products, especially those obtained from informal sources such as friends, family, or in-person or online dealers (1). VEA is strongly linked to the EVALI outbreak and should not be added to e-cigarette, or vaping, products (1).

    • Zoonotic and Vectorborne Diseases
      1. Intervention to stop transmission of imported pneumonic plague - Uganda, 2019external icon
        Apangu T, Acayo S, Atiku LA, Apio H, Candini G, Okoth F, Basabose JK, Ojosia L, Ajoga S, Mongiba G, Wetaka MM, Kayiwa J, Balinandi S, Schwartz A, Yockey B, Sexton C, Dietrich EA, Pappert R, Petersen JM, Mead PS, Lutwama JJ, Kugeler KJ.
        MMWR Morb Mortal Wkly Rep. 2020 Mar 6;69(9):241-244.
        Plague, an acute zoonosis caused by Yersinia pestis, is endemic in the West Nile region of northwestern Uganda and neighboring northeastern Democratic Republic of the Congo (DRC) (1-4). The illness manifests in multiple clinical forms, including bubonic and pneumonic plague. Pneumonic plague is rare, rapidly fatal, and transmissible from person to person via respiratory droplets. On March 4, 2019, a patient with suspected pneumonic plague was hospitalized in West Nile, Uganda, 4 days after caring for her sister, who had come to Uganda from DRC and died shortly thereafter, and 2 days after area officials received a message from a clinic in DRC warning of possible plague. The West Nile-based Uganda Virus Research Institute (UVRI) plague program, together with local health officials, commenced a multipronged response to suspected person-to-person transmission of pneumonic plague, including contact tracing, prophylaxis, and education. Plague was laboratory-confirmed, and no additional transmission occurred in Uganda. This event transpired in the context of heightened awareness of cross-border disease spread caused by ongoing Ebola virus disease transmission in DRC, approximately 400 km to the south. Building expertise in areas of plague endemicity can provide the rapid detection and effective response needed to mitigate epidemic spread and minimize mortality. Cross-border agreements can improve ability to respond effectively.

      2. Active monitoring of persons exposed to patients with confirmed COVID-19 - United States, January-February 2020external icon
        Burke RM, Midgley CM, Dratch A, Fenstersheib M, Haupt T, Holshue M, Ghinai I, Jarashow MC, Lo J, McPherson TD, Rudman S, Scott S, Hall AJ, Fry AM, Rolfes MA.
        MMWR Morb Mortal Wkly Rep. 2020 Mar 6;69(9):245-246.
        In December 2019, an outbreak of coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, began in Wuhan, China (1). The disease spread widely in China, and, as of February 26, 2020, COVID-19 cases had been identified in 36 other countries and territories, including the United States. Person-to-person transmission has been widely documented, and a limited number of countries have reported sustained person-to-person spread.* On January 20, state and local health departments in the United States, in collaboration with teams deployed from CDC, began identifying and monitoring all persons considered to have had close contact(dagger) with patients with confirmed COVID-19 (2). The aims of these efforts were to ensure rapid evaluation and care of patients, limit further transmission, and better understand risk factors for transmission.

      3. Vector control in Zika-affected communities: Local views on community engagement and public health ethics during outbreaksexternal icon
        Schoch-Spana M, Watson C, Ravi S, Meyer D, Pechta LE, Rose DA, Lubell KM, Podgornik MN, Sell TK.
        Prev Med Rep. 2020 Jun;18:101059.
        Aerial spraying of products to kill larvae or adult mosquitoes is a public health measure used to control vector-borne diseases. In some outbreaks, the intervention has evoked controversy and community resistance. This study evaluated how local opinion leaders in US localities affected by Zika think about community engagement in public health policies for outbreak response. In December 2017 through March 2018, 4 focus groups were convened in Houston, TX, New Orleans, LA, Miami, FL, and Brooklyn, NY. They discussed a hypothetical scenario that featured vector control by aerial spraying. Participants (N = 20) more readily accepted this vector control method under 4 conditions: They were informed of alternatives, benefits, and risks for human health and the environment. Public health claims were backed by objective evidence and an authority figure genuinely working in the community's interests. They received timely notice about how to mitigate toxin exposure. And, aerial spraying helped to protect vulnerable individuals. The community engagement requirements of the local opinion leaders resonate with core principles of recent public health ethics frameworks: namely, personal autonomy, transparency, reasonableness, and solidarity. Participants foresaw problems with community consent in an era of growing social media use and mistrust in governmental and scientific authority. They also debated whether health authorities should use moral-based arguments, in addition to science-based ones, to communicate aerial spraying's risks and benefits.

      4. Notes from the field: Monkey bite in a public park and possible exposure to herpes B virus - Thailand, 2018external icon
        Wu AC, Rekant SI, Baca ER, Jenkins RM, Perelygina LM, Hilliard JK, Schmid DS, Leman RF.
        MMWR Morb Mortal Wkly Rep. 2020 Mar 6;69(9):247-248.

      5. Pandemic potential of highly pathogenic avian influenza clade A(H5) virusesexternal icon
        Yamaji R, Saad MD, Davis CT, Swayne DE, Wang D, Wong FY, McCauley JW, Peiris JS, Webby RJ, Fouchier RA, Kawaoka Y, Zhang W.
        Rev Med Virol. 2020 Mar 5:e2099.
        The panzootic caused by A/goose/Guangdong/1/96-lineage highly pathogenic avian influenza (HPAI) A(H5) viruses has occurred in multiple waves since 1996. From 2013 onwards, clade viruses of subtypes A(H5N2), A(H5N6), and A(H5N8) emerged to cause panzootic waves of unprecedented magnitude among avian species accompanied by severe losses to the poultry industry around the world. Clade A(H5) viruses have expanded in distinct geographical and evolutionary pathways likely via long distance migratory bird dispersal onto several continents and by poultry trade among neighboring countries. Coupled with regional circulation, the viruses have evolved further by reassorting with local viruses. As of February 2019, there have been 23 cases of humans infected with clade H5N6 viruses, 16 (70%) of which had fatal outcomes. To date, no HPAI A(H5) virus has caused sustainable human-to-human transmission. However, due to the lack of population immunity in humans and ongoing evolution of the virus, there is a continuing risk that clade A(H5) viruses could cause an influenza pandemic if the ability to transmit efficiently among humans was gained. Therefore, multisectoral collaborations among the animal, environmental, and public health sectors are essential to conduct risk assessments and develop countermeasures to prevent disease and to control spread. In this article, we describe an assessment of the likelihood of clade A(H5) viruses gaining human-to-human transmissibility and impact on human health should such human-to-human transmission occur. This structured analysis assessed properties of the virus, attributes of the human population, and ecology and epidemiology of these viruses in animal hosts.

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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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