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CDC Science Clips: Volume 13, Issue 7, February 23, 2021

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.

The report consists of these components:

  1. 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. Characteristics and trends of PCSK9 inhibitor prescription fills in the United Statesexternal icon
        Attipoe-Dorcoo S, Yang P, Sperling L, Loustalot F, Thompson-Paul AM, Gray EB, Park S, Ritchey MD.
        J Clin Lipidol. 2021 Feb 4.
        BACKGROUND: PCSK9 inhibitors were approved by the Food and Drug Administration in 2015 to lower low-density lipoprotein cholesterol (LDL-C) levels. In the years following, additional research findings, changes in national guideline recommendations, and price reductions have occurred. OBJECTIVE: The goal of the study is to describe the characteristics and trends in PCSK9 inhibitor prescription fills and price, from initial FDA approval in Quarter 3 2015 through Quarter 4 2019, at the national and state levels. METHODS: Cross-sectional study of fills obtained using the IQVIA National Prescription Audit®, Extended Insights, New to Brand, and Regional databases. Prescription fills included injections that provided cholesterol-lowering therapy from 14 to 90 days for the two PCSK9 inhibitors: alirocumab (75 mg/mL and 150 mg/mL) or evolocumab (140 mg/mL and 420 mg/3.5 mL). Quarterly prescription fills obtained nationally for Quarter 3 2015 through Quarter 4 2019, by sex, age, and state during 2019. RESULTS: Over the time period examined, 2.75 million PCSK9 inhibitor prescriptions were filled nationally (alirocumab: 38%; evolocumab: 62%), and the average retail price per fill (unadjusted $US) from retail pharmacies decreased by 40% from $1502 to $896 per fill. Year-over-year percent change in new PCSK9 inhibitor users increased throughout the observation period, with 9611 new alirocumab users and 25,381 new evolocumab users in Q4 2019. PCSK9 inhibitor fill rates ranged from 5.6 per 1000 in the Northeast to 3.4 per 1000 in the West in 2019, with the highest rate per 1000 in Louisiana (9.1), and lowest in Wyoming (1.3). CONCLUSIONS: PCSK9 inhibitor prescriptions have increased nationally since 2015, coinciding with additional evidence supporting their use for LDL-C lowering and cardiovascular event reduction. Although the retail price has decreased since introduction, cost and delivery mode likely continue as barriers.

      2. Mortality among minority populations with systemic lupus erythematosus, including Asian and Hispanic/Latino persons - California, 2007-2017external icon
        Gianfrancesco MA, Dall'Era M, Murphy LB, Helmick CG, Li J, Rush S, Trupin L, Yazdany J.
        MMWR Morb Mortal Wkly Rep. 2021 Feb 19;70(7):236-239.
        Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with manifestations that vary widely in severity. Although minority populations are at higher risk for SLE and have more severe outcomes (1), population-based estimates of mortality by race and ethnicity are often lacking, particularly for Asian and Hispanic/Latino persons. Among 812 patients in the California Lupus Surveillance Project (CLSP) during 2007-2009 (2,3), who were matched to the 2007-2017 National Death Index (NDI), 16.6% had died by 2017. This proportion included persons of White (14.4%), Black (25%), Asian (15.3%), and Hispanic/Latino (15.5%) race/ethnicity. Standardized mortality ratios (SMRs) of observed-to-expected deaths among persons with SLE within each racial/ethnic group were 2.3, 2.0, 3.8, and 3.9, respectively. These findings provide the first population-based estimates of mortality among Asian and Hispanic/Latino persons with SLE. Coordination of robust care models between primary care providers and rheumatologists could ensure that persons with SLE receive a timely diagnosis and appropriate treatments that might help address SLE-associated mortality.

      3. The context of sunburn among U.S. adults: Common activities and sun protection behaviorsexternal icon
        Holman DM, Ragan KR, Julian AK, Perna FM.
        Am J Prev Med. 2021 Feb 12.
        INTRODUCTION: Sunburn increases skin cancer risk and is common among U.S. adults. However, little is known about the contexts in which sunburns often occur. The purpose of this study is to examine the contextual factors surrounding sunburns among U.S. adults. METHODS: Cross-sectional data from a 2018 online panel survey were analyzed. A total of 4,088 panel members were recruited by mail using probability-based, random sampling by address. Respondents were asked about their most recent sunburn, and analyses were limited to those who remembered their most recent sunburn (N=3,106). Data were weighted to match the U.S. Current Population Survey proportions; analyses were conducted in 2018 and 2019. RESULTS: Participants' age ranged from 18 to 93 years. About half (50.8%) were women, and most (82.3%) were non-Hispanic White adults. Swimming or spending time in water (32.5%), working outside at home (26.2%), traveling/vacationing (20.7%), and engaging in nonswimming physical activity (14.2%) were the most frequently reported activities. Using sunscreen on the face, neck, and chest (38.8%) and on the body (19.9%) and wearing sunglasses (34.2%) were the most frequently reported sun safety behaviors. Wearing clothes to the ankles (6.6%) and a long-sleeved shirt (4.5%) were least frequently reported. CONCLUSIONS: This study provides new information about the contexts in which adult sunburns often occur, especially about contexts unrelated to intentional tanning, which was relatively infrequent. The results suggest the need to promote multiple forms of sun protection tailored to specific outdoor activities and develop innovative solutions for outdoor physical and aquatic activities, which present unique sun safety challenges.

      4. Michigan Screening and Intervention for Glaucoma and Eye Health through Telemedicine (MI-SIGHT): Baseline methodology for implementing and assessing a community-based programexternal icon
        Newman-Casey PA, Musch DC, Niziol LM, Elam AR, Zhang J, Moroi SE, Johnson L, Kershaw M, Saadine J, Winter S, Woodward MA.
        J Glaucoma. 2021 Feb 15.
        PRECIS: The Michigan Screening and Intervention for Glaucoma and eye Health through Telemedicine Program leverages community engaged research, telemedicine and health coaching to overcome key logistical and psychosocial barriers to improved glaucoma screening in underserved communities. PURPOSE: To describe the methodology of the implementation and evaluation of the Michigan Screening and Intervention for Glaucoma and eye Health through Telemedicine (MI-SIGHT) Program. METHODS: The MI-SIGHT Program utilizes community engagement, telemedicine and health coaching to overcome key logistical and psychosocial barriers to glaucoma identification and care among underserved populations. The MI-SIGHT Program will be evaluated in two community clinics: Hamilton Community Health Network, a federally qualified health center in Flint, MI, and the Hope Clinic, a free clinic in Ypsilanti, MI. A Community Advisory Board including the research team and health care providers, administrators and patients from both clinics will guide program implementation. An ophthalmic technician at the community clinics will conduct screening tests for glaucoma and eye disease. The data will be transmitted via electronic health record to be reviewed by an ophthalmologist who will make recommendations for follow-up care. The ophthalmic technician will conduct a return visit to fit low-or no-cost glasses, help arrange follow-up with an ophthalmologist and provide education. Those diagnosed with glaucoma or suspected glaucoma will be randomized to standard education or personalized glaucoma education and coaching. Costs will be assessed. RESULTS: We hypothesize that the MI-SIGHT program will detect a higher prevalence rate of glaucoma than that found in the general population, improve upon presenting visual acuity, enhance vision-related quality of life and demonstrate that personalized glaucoma education and coaching improve adherence to follow-up care. CONCLUSION: The MI-SIGHT Program may serve as a model for glaucoma screening and care in high-risk communities.

      5. Cancer incidence in older adults in the United States: Characteristics, specificity, and completeness of the dataexternal icon
        Weir HK, Sherman R, Yu M, Gershman S, Hofer BM, Wu M, Green D.
        J Registry Manag. 2020 Fall;47(3):150-160.
        INTRODUCTION: The number of cancer cases in the United States continues to grow as the number of older adults increases. Accurate, reliable and detailed incidence data are needed to respond effectively to the growing human costs of cancer in an aging population. The purpose of this study was to examine the characteristics of incident cases and evaluate the impact of death-certificate-only (DCO) cases on cancer incidence rates in older adults. METHODS: Using data from 47 cancer registries and detailed population estimates from the Surveillance, Epidemiology and End Results (SEER) Program, we examined reporting sources, methods of diagnosis, tumor characteristics, and calculated age-specific incidence rates with and without DCO cases in adults aged 65 through ≥95 years, diagnosed 2011 through 2015, by sex and race/ethnicity. RESULTS: The percentage of cases (all cancers combined) reported from a hospital decreased from 90.6% (ages 65-69 years) to 69.1% (ages ≥95 years) while the percentage of DCO cases increased from 1.1% to 19.6%. Excluding DCO cases, positive diagnostic confirmation decreased as age increased from 96.8% (ages 65-69 years) to 69.2% (ages ≥95 years). Compared to incidence rates that included DCO cases, rates in adults aged ≥95 years that excluded DCO cases were 41.5% lower in Black men with prostate cancer and 29.2% lower in Hispanic women with lung cancer. DISCUSSION: Loss of reported tumor specificity with age is consistent with fewer hospital reports. However, the majority of cancers diagnosed in older patients, including those aged ≥95 years, were positively confirmed and were reported with known site, histology, and stage information. The high percentage of DCO cases among patients aged ≥85 years suggests the need to explore additional sources of follow-back to help possibly identify an earlier incidence report. Interstate data exchange following National Death Index linkages may help registries identify and remove erroneous DCO cases from their databases.

    • Communicable Diseases
      1. PURPOSE: Prescription opioid misuse is associated with behaviors which increase bacterial sexually transmitted diseases (STD) risk among men who have sex with men (MSM). Annual syphilis, gonorrhea, and chlamydia screening is recommended for sexually active MSM at anatomical sites of contact, regardless of condom use. We describe the prevalence of self-reported bacterial STD testing and diagnoses in the past 12 months among sexually active MSM who report prescription opioid misuse. METHODS: We used data from the 2017 and 2018 American Men's Internet Survey to examine the prevalence of self-reported bacterial STD testing and diagnoses in the past 12 months. We calculated unadjusted prevalence ratios, adjusted prevalence ratios (APR), and 95% confidence intervals (CI) to compare bacterial STD testing prevalence across demographic, clinical, and behavioral factors. RESULTS: Of 932 sexually active MSM who reported prescription opioid misuse, 433 (46.5%) self-reported bacterial STD testing in the past 12 months. Of those who reported being tested, 131 (30.2%) self-reported ≥ 1 bacterial STD. Approximately 50% of respondents who reported condomless anal sex (CAS), casual sex, or exchange sex reported bacterial STD testing in past 12 months. Factors associated with bacterial STD testing among MSM who misused prescription opioids included visiting a healthcare provider in the past 12 months (APR=1.70, 95% CI=1.09-2.67), ever disclosing same-sex behavior to a healthcare provider (APR=1.78, 95% CI=1.27-2.50), and CAS in the past 12 months (APR=1.51, 95% CI=1.10-2.04). CONCLUSIONS: Prevalence of self-reported bacterial STD testing in this sample was low and one-third of tested MSM reported ≥ 1 bacterial STD in the past 12 months. Innovative approaches to identify MSM who misuse prescription opioids and expand bacterial STD testing in this population are needed.

      2. A phylogenetic analysis of hepatitis C virus transmission, relapse, and reinfection among people who inject drugs receiving opioid agonist therapyexternal icon
        Akiyama MJ, Lipsey D, Ganova-Raeva L, Punkova LT, Agyemang L, Sue A, Ramachandran S, Khudyakov Y, Litwin AH.
        J Infect Dis. 2020 Jul 6;222(3):488-498.
        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 3 OAT clinics in the Bronx, New York. Next-generation sequencing data from the hypervariable region 1 of HCV were analyzed using Global Hepatitis Outbreak and Surveillance Technology. RESULTS: There were 3 transmission linkages between study participants. Sustained virologic response (SVR) was not achieved in 9 participants: 7 had follow-up specimens with similar sequences to baseline, and 2 died. In 4 additional participants, SVR was achieved but the participants were viremic at later follow-up: 2 were reinfected with different strains, 1 had a late treatment failure, and 1 was transiently viremic 17 months after 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 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 after SVR.

      3. Estimating and characterizing COVID-19 deaths, Puerto Rico, March-July 2020external icon
        Azofeifa A, Valencia D, Rodriguez CJ, Cruz M, Hayes D, Montañez-Báez E, Tejada-Vera B, Villafañe-Delgado JE, Cabrera JJ, Valencia-Prado M.
        Public Health Rep. 2021 Feb 17.
        OBJECTIVES: Using the Council of State and Territorial Epidemiologists (CSTE) classification guidelines, we characterized coronavirus disease 2019 (COVID-19)-associated confirmed and probable deaths in Puerto Rico during March-July 2020. We also estimated the total number of possible deaths due to COVID-19 in Puerto Rico during the same period. METHODS: We described data on COVID-19-associated mortality, in which the lower bound was the sum of confirmed and probable COVID-19 deaths and the upper bound was excess mortality, estimated as the difference between observed deaths and average expected deaths. We obtained data from the Puerto Rico Department of Health COVID-19 Mortality Surveillance System, the Centers for Disease Control and Prevention's National Electronic Disease Surveillance System Base System, and the National Center for Health Statistics. RESULTS: During March-July 2020, 225 COVID-19-associated deaths were identified in Puerto Rico (119 confirmed deaths and 106 probable deaths). The median age of decedents was 73 (interquartile range, 59-83); 60 (26.7%) deaths occurred in the Metropolitana region, and 140 (62.2%) deaths occurred among men. Of the 225 decedents, 180 (83.6%) had been hospitalized and 93 (41.3%) had required mechanical ventilation. Influenza and pneumonia (48.0%), sepsis (28.9%), and respiratory failure (27.1%) were the most common conditions contributing to COVID-19 deaths based on death certificates. Based on excess mortality calculations, as many as 638 COVID-19-associated deaths could have occurred during the study period, up to 413 more COVID-19-associated deaths than originally reported. CONCLUSIONS: Including probable deaths per the CSTE guidelines and monitoring all-cause excess mortality can lead to a better estimation of COVID-19-associated deaths and serve as a model to enhance mortality surveillance in other US jurisdictions.

      4. Laboratory testing is required to distinguish coccidioidomycosis and histoplasmosis from other types of community-acquired pneumonia (CAP). In this nationwide survey of 1258 health care providers, only 3.7% reported frequently testing CAP patients for coccidioidomycosis and 2.8% for histoplasmosis. These diseases are likely underdiagnosed, and increased awareness is needed.

      5. Required and voluntary occupational use of hazard controls for COVID-19 prevention in non-health care workplaces - United States, June 2020external icon
        Billock RM, Groenewold MR, Free H, Haring Sweeney M, Luckhaupt SE.
        MMWR Morb Mortal Wkly Rep. 2021 Feb 19;70(7):250-253.
        Certain hazard controls, including physical barriers, cloth face masks, and other personal protective equipment (PPE), are recommended to reduce coronavirus 2019 (COVID-19) transmission in the workplace (1). Evaluation of occupational hazard control use for COVID-19 prevention can identify inadequately protected workers and opportunities to improve use. CDC's National Institute for Occupational Safety and Health used data from the June 2020 SummerStyles survey to characterize required and voluntary use of COVID-19-related occupational hazard controls among U.S. non-health care workers. A survey-weighted regression model was used to estimate the association between employer provision of hazard controls and voluntary use, and stratum-specific adjusted risk differences (aRDs) among workers reporting household incomes <250% and ≥250% of national poverty thresholds were estimated to assess effect modification by income. Approximately one half (45.6%; 95% confidence interval [CI] = 41.0%-50.3%) of non-health care workers reported use of hazard controls in the workplace, 55.5% (95% CI = 48.8%-62.2%) of whom reported employer requirements to use them. After adjustment for occupational group and proximity to others at work, voluntary use was approximately double, or 22.3 absolute percentage points higher, among workers who were provided hazard controls than among those who were not. This effect was more apparent among lower-income (aRD = 31.0%) than among higher-income workers (aRD = 16.3%). Employers can help protect workers from COVID-19 by requiring and encouraging use of occupational hazard controls and providing hazard controls to employees (1).

      6. Maximizing fit for cloth and medical procedure masks to improve performance and reduce SARS-CoV-2 transmission and exposure, 2021external icon
        Brooks JT, Beezhold DH, Noti JD, Coyle JP, Derk RC, Blachere FM, Lindsley WG.
        MMWR Morb Mortal Wkly Rep. 2021 Feb 19;70(7):254-257.
        Universal masking is one of the prevention strategies recommended by CDC to slow the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1). As of February 1, 2021, 38 states and the District of Columbia had universal masking mandates. Mask wearing has also been mandated by executive order for federal property* as well as on domestic and international transportation conveyances.(†) Masks substantially reduce exhaled respiratory droplets and aerosols from infected wearers and reduce exposure of uninfected wearers to these particles. Cloth masks(§) and medical procedure masks(¶) fit more loosely than do respirators (e.g., N95 facepieces). The effectiveness of cloth and medical procedure masks can be improved by ensuring that they are well fitted to the contours of the face to prevent leakage of air around the masks' edges. During January 2021, CDC conducted experimental simulations using pliable elastomeric source and receiver headforms to assess the extent to which two modifications to medical procedure masks, 1) wearing a cloth mask over a medical procedure mask (double masking) and 2) knotting the ear loops of a medical procedure mask where they attach to the mask's edges and then tucking in and flattening the extra material close to the face (knotted and tucked masks), could improve the fit of these masks and reduce the receiver's exposure to an aerosol of simulated respiratory droplet particles of the size considered most important for transmitting SARS-CoV-2. The receiver's exposure was maximally reduced (>95%) when the source and receiver were fitted with modified medical procedure masks. These laboratory-based experiments highlight the importance of good fit to optimize mask performance. Until vaccine-induced population immunity is achieved, universal masking is a highly effective means to slow the spread of SARS-CoV-2** when combined with other protective measures, such as physical distancing, avoiding crowds and poorly ventilated indoor spaces, and good hand hygiene. Innovative efforts to improve the fit of cloth and medical procedure masks to enhance their performance merit attention.

      7. Differences in rapid increases in county-level COVID-19 incidence by implementation of statewide closures and mask mandates - United States, June 1-September 30, 2020external icon
        Dasgupta S, Kassem AM, Sunshine G, Liu T, Rose C, Kang G, Silver R, Maddox BL, Watson C, Howard-Williams M, Gakh M, McCord R, Weber R, Fletcher K, Musial T, Tynan MA, Hulkower R, Moreland A, Pepin D, Landsman L, Brown A, Gilchrist S, Clodfelter C, Williams M, Cramer R, Limeres A, Popoola A, Dugmeoglu S, Shelburne J, Jeong G, Rao CY.
        Ann Epidemiol. 2021 Feb 14.
        BACKGROUND AND OBJECTIVE: Community mitigation strategies could help reduce COVID-19 incidence. In a national county-level analysis, we examined the probability of being identified as a county with rapidly increasing COVID-19 incidence (rapid riser identification) during the summer of 2020 by implementation of mitigation policies prior to the summer, overall and by urbanicity. METHODS: We analyzed county-level data on rapid riser identification during June 1-September 30, 2020 and statewide closures and statewide mask mandates starting March 19 (obtained from state government websites). Poisson regression models with robust standard error estimation were used to examine differences in the probability of rapid riser identification by implementation of mitigation policies (P-value<.05); associations were adjusted for county population size. RESULTS: Counties in states that closed for 0-59 days were more likely to become a rapid riser county than those that closed for >59 days, particularly in nonmetropolitan areas. The probability of becoming a rapid riser county was 43% lower among counties that had statewide mask mandates at reopening (adjusted prevalence ratio [aPR] = 0.57; 95% confidence intervals [CI] = 0.51-0.63); when stratified by urbanicity, associations were more pronounced in nonmetropolitan areas. CONCLUSIONS: These results underscore the potential value of community mitigation strategies in limiting the COVID-19 spread, especially in nonmetropolitan areas.

      8. Strengthening measurement and performance of HIV prevention programmesexternal icon
        Holmes CB, Kilonzo N, Zhao J, Johnson LF, Kalua T, Hasen N, Morrison M, Marston M, Smith T, Benech I, Baggaley R, Carter A, Khasiani M, DePasse J, Mahy M, Ryan C, Garnett GP.
        Lancet HIV. 2021 Feb 9.
        Indicators for the measurement of programmes for the primary prevention of HIV are less aligned than indicators for HIV treatment, which results in a high burden of data collection, often without a clear vision for its use. As new evidence becomes available, the opportunity arises to critically evaluate the way countries and global bodies monitor HIV prevention programmes by incorporating emerging data on the strength of the evidence linking various factors with HIV acquisition, and by working to streamline indicators across stakeholders to reduce burdens on health-care systems. Programmes are also using new approaches, such as targeting specific sexual networks that might require non-traditional approaches to measurement. Technological advances can support these new directions and provide opportunities to use real-time analytics and new data sources to more effectively understand and adapt HIV prevention programmes to reflect population movement, risks, and an evolving epidemic.

      9. Seroprevalence of hepatitis B virus infection markers among children in Ukraine, 2017external icon
        Khetsuriani N, Zaika O, Chitadze N, Slobodianyk L, Allahverdiyeva V, O'Connor P, Huseynov S.
        Vaccine. 2021 Feb 11.
        BACKGROUND: Before hepatitis B vaccine (HepB) introduction, level of endemicity of hepatitis B virus (HBV) in Ukraine was estimated as intermediate but the prevalence of HBV infection markers has not been measured in population-based serosurveys. Coverage with 3 doses of HepB, introduced in 2002, was 92%-98% during 2004-2007 but declined to 21%-48% during 2010-2016. To obtain data on HBV prevalence among children born after HepB introduction, we tested specimens from a serosurvey conducted in Ukraine in 2017, following circulating vaccine-derived poliovirus outbreak in 2015, among birth cohorts eligible for polio immunization response. METHODS: The serosurvey was conducted in Zakarpattya, Sumy, and Odessa provinces, and Kyiv City, targeting 2006-2015 birth cohorts. One-stage cluster sampling in the provinces and stratified simple random sampling in Kyiv were used for participant selection. All participants were tested for antibodies against HBV core antigen (anti-HBc). Anti-HBc-positive children were tested for HBV surface antigen (HBsAg). We also obtained information on HepB vaccination status for all children. RESULTS: Of 4,596 children tested, 81 (1.8%) were anti-HBc-positive and eight (0.2%) were HBsAg-positive. HBsAg prevalence was 0.7% (95% confidence interval, 0.3%-1.4%) in Zakarpattya, 0.1% (0.0%-0.4%) in Sumy, 0% (0.0%-03%) in Odessa, and 0.1% (0.0%-0.8%) in Kyiv. Across survey sites, the proportion of recipients of ≥ 3 HepB doses was 53%-80% in the 2006-2009 cohort and 28%-59% in the 2010-2015 cohort. CONCLUSION: HBV prevalence among children in surveyed regions of Ukraine in 2017 was low, including in Zakarpattya-the only site above the 0.5% European Regional target for HBsAg seroprevalence. However, HepB vaccination was suboptimal, particularly among children born after 2009, resulting in large numbers of unvaccinated or incompletely vaccinated children at risk of future HBV infection. HepB coverage should be increased to further reduce HBV transmission among children in Ukraine and achieve regional and global hepatitis B control/elimination targets.

      10. Clinical and laboratory findings in patients with potential SARS-CoV-2 reinfection, May-July 2020external icon
        Lee JT, Hesse EM, Paulin HN, Datta D, Katz LS, Talwar A, Chang G, Galang RR, Harcourt JL, Tamin A, Thornburg NJ, Wong KK, Stevens V, Kim K, Tong S, Zhou B, Queen K, Drobeniuc J, Folster JM, Sexton DJ, Ramachandran S, Browne H, Iskander J, Mitruka K.
        Clin Infect Dis. 2021 Feb 18.
        BACKGROUND: We investigated patients with potential SARS-CoV-2 reinfection in the United States during May-July 2020. METHODS: We conducted case finding for patients with potential SARS-CoV-2 reinfection through the Emerging Infections Network. Cases reported were screened for laboratory and clinical findings of potential reinfection followed by requests for medical records and laboratory specimens. Available medical records were abstracted to characterize patient demographics, comorbidities, clinical course, and laboratory test results. Submitted specimens underwent further testing, including RT-PCR, viral culture, whole genome sequencing, subgenomic RNA PCR, and testing for anti-SARS-CoV-2 total antibody. RESULTS: Among 73 potential reinfection patients with available records, 30 patients had recurrent COVID-19 symptoms explained by alternative diagnoses with concurrent SARS-CoV-2 positive RT-PCR, 24 patients remained asymptomatic after recovery but had recurrent or persistent RT-PCR, and 19 patients had recurrent COVID-19 symptoms with concurrent SARS-CoV-2 positive RT-PCR but no alternative diagnoses. These 19 patients had symptom recurrence a median of 57 days after initial symptom onset (interquartile range: 47 - 76). Six of these patients had paired specimens available for further testing, but none had laboratory findings confirming reinfections. Testing of an additional three patients with recurrent symptoms and alternative diagnoses also did not confirm reinfection. CONCLUSIONS: We did not confirm SARS-CoV-2 reinfection within 90 days of the initial infection based on the clinical and laboratory characteristics of cases in this investigation. Our findings support current CDC guidance around quarantine and testing for patients who have recovered from COVID-19.

      11. Quantifying the gender gap in the HIV care cascade in southern Mozambique: We are missing the menexternal icon
        Lopez-Varela E, Augusto O, Fuente-Soro L, Sacoor C, Nhacolo A, Casavant I, Karajeanes E, Vaz P, Naniche D.
        PLoS One. 2021 ;16(2):e0245461.
        BACKGROUND: HIV-infected men have higher rates of delayed diagnosis, reduced antiretroviral treatment (ART) retention and mortality than women. We aimed to assess, by gender, the first two UNAIDS 90 targets in rural southern Mozambique. METHODS: This analysis was embedded in a larger prospective cohort enrolling individuals with new HIV diagnosis between May 2014-June 2015 from clinic and home-based testing (HBT). We assessed gender differences between steps of the HIV-cascade. Adjusted HIV-community prevalence was estimated using multiple imputation (MI). RESULTS: Among 11,773 adults randomized in HBT (7084 female and 4689 male), the response rate before HIV testing was 48.7% among eligible men and 62.0% among women (p<0.001). MI did not significantly modify all-age HIV-prevalence for men but did decrease prevalence estimates in women from 36.4%to 33.0%. Estimated proportion of HIV-infected individuals aware of their status was 75.9% for men and 88.9% for women. In individuals <25 years, we observed up to 22.2% disparity in awareness of serostatus between genders. Among individuals eligible for ART, similar proportions of men and women initiated treatment (81.2% and 85.9%, respectively). Fourfold more men than womenwere in WHO stage III/IV AIDS at first clinical visit. Once on ART, men had a twofold higher 18-month loss to follow-up rate than women. CONCLUSION: The contribution of missing HIV-serostatus data differentially impacted indicators of HIV prevalence and of achievement of UNAIDS targets by age and gender and men were missing long before the second 90. Increased efforts to characterize missing men and their needs will and their needs will allow us to urgently address the barriers to men accessing care and ensure men are not left behind in the UNAIDS 90-90-90 targets achievement.

      12. Urethrocutaneous fistulas after voluntary medical male circumcision for HIV prevention - 15 African countries, 2015-2019external icon
        Lucas T, Hines JZ, Samuelson J, Hargreave T, Davis SM, Fellows I, Prainito A, Watts DH, Kiggundu V, Thomas AG, Ntsuape OC, Dare K, Odoyo-June E, Soo L, Toti-Mokoteli L, Manda R, Kapito M, Msungama W, Odek J, Come J, Canda M, Gaspar N, Mekondjo A, Zemburuka B, Bonnecwe C, Vranken P, Mmbando S, Simbeye D, Rwegerera F, Wamai N, Kyobutungi S, Zulu JE, Chituwo O, Xaba S, Mandisarisa J, Toledo C.
        BMC Urol. 2021 Feb 12;21(1):23.
        BACKGROUND: Voluntary medical male circumcision (VMMC) is an HIV prevention strategy recommended to partially protect men from heterosexually acquired HIV. From 2015 to 2019, the President's Emergency Plan for AIDS Relief (PEPFAR) has supported approximately 14.9 million VMMCs in 15 African countries. Urethrocutaneous fistulas, abnormal openings between the urethra and penile skin through which urine can escape, are rare, severe adverse events (AEs) that can occur with VMMC. This analysis describes fistula cases, identifies possible risks and mechanisms of injury, and offers mitigation actions. METHODS: Demographic and clinical program data were reviewed from all reported fistula cases during 2015 to 2019, descriptive analyses were performed, and an odds ratio was calculated by patient age group. RESULTS: In total, 41 fistula cases were reported. Median patient age for fistula cases was 11 years and 40/41 (98%) occurred in patients aged < 15 years. Fistulas were more often reported among patients < 15 compared to ≥ 15 years old (0.61 vs. 0.01 fistulas per 100,000 VMMCs, odds ratio 50.9 (95% confidence interval [CI] = 8.6-2060.0)). Median time from VMMC surgery to appearance of fistula was 20 days (interquartile range (IQR) 14-27). CONCLUSIONS: Urethral fistulas were significantly more common in patients under age 15 years. Thinner tissue overlying the urethra in immature genitalia may predispose boys to injury. The delay between procedure and symptom onset of 2-3 weeks indicates partial thickness injury or suture violation of the urethral wall as more likely mechanisms of injury than intra-operative urethral transection. This analysis helped to inform PEPFAR's recent decision to change VMMC eligibility policy in 2020, raising the minimum age to 15 years.

      13. During 2018, Black or African American (Black) persons accounted for 43% of all diagnoses of human immunodeficiency virus (HIV) infection in the United States (1). Among Black persons with diagnosed HIV infection in 41 states and the District of Columbia for whom complete laboratory reporting* was available, the percentages of Black persons linked to care within 1 month of diagnosis (77.1%) and with viral suppression within 6 months of diagnosis (62.9%) during 2018 were lower than the Ending the HIV Epidemic initiative objectives of 95% for linkage to care and viral suppression goals (2). Access to HIV-related care and treatment services varies by residence area (3-5). Identifying urban-rural differences in HIV care outcomes is crucial for addressing HIV-related disparities among Black persons with HIV infection. CDC used National HIV Surveillance System(†) (NHSS) data to describe HIV care outcomes among Black persons with diagnosed HIV infection during 2018 by population area of residence(§) (area). During 2018, Black persons in rural areas received a higher percentage of late-stage diagnoses (25.2%) than did those in urban (21.9%) and metropolitan (19.0%) areas. Linkage to care within 1 month of diagnosis was similar across all areas, whereas viral suppression within 6 months of diagnosis was highest in metropolitan areas (63.8%). The Ending the HIV Epidemic initiative supports scalable, coordinated, and innovative efforts to increase HIV diagnosis, treatment, and prevention among populations disproportionately affected by or who are at higher risk for HIV infection (6), especially during syndemics (e.g. with coronavirus disease 2019).

      14. Pediatric respiratory and enteric virus acquisition and immunogenesis in US mothers and children aged 0-2: PREVAIL Cohort Studyexternal icon
        Morrow AL, Staat MA, DeFranco EA, McNeal MM, Cline AR, Conrey SC, Schlaudecker EP, Piasecki AM, Burke RM, Niu L, Hall AJ, Bowen MD, Gerber SI, Langley GE, Thornburg NJ, Campbell AP, Vinjé J, Parashar UD, Payne DC.
        JMIR Res Protoc. 2021 Feb 12;10(2):e22222.
        BACKGROUND: Acute gastroenteritis (AGE) and acute respiratory infections (ARIs) cause significant pediatric morbidity and mortality. Developing childhood vaccines against major enteric and respiratory pathogens should be guided by the natural history of infection and acquired immunity. The United States currently lacks contemporary birth cohort data to guide vaccine development. OBJECTIVE: The PREVAIL (Pediatric Respiratory and Enteric Virus Acquisition and Immunogenesis Longitudinal) Cohort study was undertaken to define the natural history of infection and immune response to major pathogens causing AGE and ARI in US children. METHODS: Mothers in Cincinnati, Ohio, were enrolled in their third trimester of pregnancy, with intensive child follow-up to 2 years. Blood samples were obtained from children at birth (cord), 6 weeks, and 6, 12, 18, and 24 months. Whole stool specimens and midturbinate nasal swabs were collected weekly and tested by multipathogen molecular assays. Saliva, meconium, maternal blood, and milk samples were also collected. AGE (≥3 loose or watery stools or ≥1 vomiting episode within 24 hours) and ARI (cough or fever) cases were documented by weekly cell phone surveys to mothers via automated SMS text messaging and review of medical records. Immunization records were obtained from registries and providers. follow-up ended in October 2020. Pathogen-specific infections are defined by a PCR-positive sample or rise in serum antibody. RESULTS: Of the 245 enrolled mother-child pairs, 51.8% (n=127) were White, 43.3% (n=106) Black, 55.9% (n=137) publicly insured, and 86.5% (n=212) initiated breastfeeding. Blood collection was 100.0% for mothers (n=245) and 85.7% for umbilical cord (n=210). A total of 194/245 (79.2%) mother-child pairs were compliant based on participation in at least 70% (≥71/102 study weeks) of child-weeks and providing 70% or more of weekly samples during that time, or blood samples at 18 or 24 months. Compliant participants (n=194) had 71.0% median nasal swab collection (IQR 30.0%-90.5%), with 98.5% (191/194) providing either an 18- or 24-month blood sample; median response to weekly SMS text message surveys was 95.1% (IQR 76.5%-100%). Compliant mothers reported 2.0 AGE and 4.5 ARI cases per child-year, of which 25.5% (160/627) and 38.06% (486/1277) of cases, respectively, were medically attended; 0.5% of AGE (3/627) and 0.55% of ARI (7/1277) cases were hospitalized. CONCLUSIONS: The PREVAIL Cohort demonstrates intensive follow-up to document the natural history of enteric and respiratory infections and immunity in children 0-2 years of age in the United States and will contribute unique data to guide vaccine recommendations. Testing for pathogens and antibodies is ongoing. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/22222.

      15. Trends in hepatocellular carcinoma incidence and risk among persons with HIV in the US and Canada, 1996-2015external icon
        Sun J, Althoff KN, Jing Y, Horberg MA, Buchacz K, Gill MJ, Justice AC, Rabkin CS, Goedert JJ, Sigel K, Cachay E, Park L, Lim JK, Kim HN, Lo Re V, Moore R, Sterling T, Peters MG, Achenbach CJ, Silverberg M, Thorne JE, Mayor AM, Crane HM, Kitahata MM, Klein M, Kirk GD.
        JAMA Netw Open. 2021 Feb 1;4(2):e2037512.
        IMPORTANCE: People with HIV (PWH) are often coinfected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV), leading to increased risk of developing hepatocellular carcinoma (HCC), but few cohort studies have had sufficient power to describe the trends of HCC incidence and risk among PWH in the combination antiretroviral therapy (cART) era. OBJECTIVE: To determine the temporal trends of HCC incidence rates (IRs) and to compare rates by risk factors among PWH in the cART era. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) study, which was conducted between 1996 and 2015. NA-ACCORD pooled individual-level data from 22 HIV clinical and interval cohorts of PWH in the US and Canada. PWH aged 18 years or older with available CD4 cell counts and HIV RNA data were enrolled. Data analyses were completed in March 2020. EXPOSURES: HBV infection was defined as detection of either HBV surface antigen, HBV e antigen, or HBV DNA in serum or plasma any time during observation. HCV infection was defined by detection of anti-HCV seropositivity, HCV RNA, or detectable genotype in serum or plasma at any time under observation. MAIN OUTCOMES AND MEASURES: HCC diagnoses were identified on the basis of review of medical records or cancer registry linkage. RESULTS: Of 109 283 PWH with 723 441 person-years of follow-up, the median (interquartile range) age at baseline was 43 (36-51) years, 93 017 (85.1%) were male, 44 752 (40.9%) were White, 44 322 (40.6%) were Black, 21 343 (19.5%) had HCV coinfection, 6348 (5.8%) had HBV coinfection, and 2082 (1.9%) had triple infection; 451 individuals received a diagnosis of HCC by 2015. Between the early (1996-2000) and modern (2006-2015) cART eras, the crude HCC IR increased from 0.28 to 0.75 case per 1000 person-years. HCC IRs remained constant among HIV-monoinfected persons or those coinfected with HBV, but from 1996 to 2015, IRs increased among PWH coinfected with HCV (from 0.34 cases/1000 person-years in 1996 to 2.39 cases/1000 person-years in 2015) or those with triple infection (from 0.65 cases/1000 person-years in 1996 to 4.49 cases/1000 person-years in 2015). Recent HIV RNA levels greater than or equal to 500 copies/mL (IR ratio, 1.8; 95% CI, 1.4-2.4) and CD4 cell counts less than or equal to 500 cells/μL (IR ratio, 1.3; 95% CI, 1.0-1.6) were associated with higher HCC risk in the modern cART era. People who injected drugs had higher HCC risk compared with men who had sex with men (IR ratio, 2.0; 95% CI, 1.3-2.9), adjusted for HBV-HCV coinfection. CONCLUSIONS AND RELEVANCE: HCC rates among PWH increased significantly over time from 1996 to 2015. PWH coinfected with viral hepatitis, those with higher HIV RNA levels or lower CD4 cell counts, and those who inject drugs had higher HCC risk.

      16. Sexually transmitted infection testing among transgender women living with HIV in the United States: Medical Monitoring Project, 2015-2019external icon
        Town K, Tie Y, Dasgupta S, Kirkcaldy RD, Crim SM, Weiser J, Bernstein K.
        Clin Infect Dis. 2021 Feb 13.
        National guidelines recommend annual STI testing for sexually active people living with HIV, including transgender women. Using data from the US Medical Monitoring Project during 2015-2019, in the previous 12 months, 63.3% of sexually active HIV-positive transgender women were tested for syphilis, 56.6% for chlamydia, and 54.4% for gonorrhea.


    • Disease Reservoirs and Vectors
      1. Lyme disease is the most common vector-borne disease in the United States. While Lyme disease vectors are widespread, high incidence states are concentrated in the Northeast, North Central and Mid-Atlantic regions. Mapping the distribution of Lyme disease spirochetes in ticks may aid in providing data-driven explanations of epidemiological trends and recommendations for targeting prevention strategies to communities at risk. We compiled data from the literature, publicly available tickborne pathogen surveillance databases, and internal CDC pathogen testing databases to map the county-level distribution of Lyme disease spirochetes reported in host-seeking Ixodes pacificus and Ixodes scapularis across the contiguous United States. We report B. burgdorferi s.s.-infected I. scapularis from 384 counties spanning 26 eastern states located primarily in the North Central, Northeastern, and Mid-Atlantic regions, and in I. pacificus from 20 counties spanning 2 western states, with most records reported from northern and north-coastal California. Borrelia mayonii was reported in I. scapularis in 10 counties in Minnesota and Wisconsin in the North Central United States, where records of B. burgdorferi s.s. were also reported. In comparison to a broad distribution of vector ticks, the resulting map shows a more limited distribution of Lyme disease spirochetes.

      2. The Asian longhorned tick, Haemaphysalis longicornis Neumann (Acari: Ixodidae), was recently introduced into the United States and is now established in at least 15 states. Considering its ability for parthenogenetic propagation and propensity for creating high-density populations, there is concern that this tick may become involved in transmission cycles of endemic tick-borne human pathogens. Human granulocytic anaplasmosis (HGA) caused by Anaplasma phagocytophilum is one of the more common tick-borne diseases in the United States, especially in the northeastern and midwestern states. There is considerable geographical overlap between HGA cases and the currently known distribution of H. longicornis, which creates a potential for this tick to encounter A. phagocytophilum while feeding on naturally infected vertebrate hosts. Therefore, we evaluated the ability of H. longicornis to acquire and transmit the agent of HGA under laboratory conditions and compared it to the vector competence of I. scapularis. Haemaphysalis longicornis nymphs acquired the pathogen with the bloodmeal while feeding on infected domestic goats, but transstadial transmission was inefficient and PCR-positive adult ticks were unable to transmit the pathogen to naïve goats. Results of this study indicate that the Asian longhorned tick is not likely to play a significant role in the epidemiology of HGA in the United States.

    • Environmental Health
      1. Prenatal exposure to mixtures of persistent endocrine disrupting chemicals and early menarche in a population-based cohort of British girlsexternal icon
        Marks KJ, Howards PP, Smarr MM, Flanders WD, Northstone K, Daniel JH, Calafat AM, Sjödin A, Marcus M, Hartman TJ.
        Environ Pollut. 2021 Feb 9;276:116705.
        Exposure to endocrine disrupting chemicals (EDCs) is ubiquitous. EDC exposure, especially during critical periods of development like the prenatal window, may interfere with the body's endocrine system, which can affect growth and developmental outcomes such as puberty. Most studies have examined one EDC at a time in relation to disease; however, humans are exposed to many EDCs. By studying mixtures, the human experience can be more closely replicated. We investigated the association of prenatal exposure to persistent EDCs (poly- and perfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs)) as mixtures with early menarche among female offspring in a nested case-control study within the Avon Longitudinal Study of Parents and Children (ALSPAC) recruited in the United Kingdom in 1991-1992. Concentrations of 52 EDCs were quantified in maternal serum samples collected during pregnancy. Daughter's age at menarche was ascertained through mailed questionnaires sent annually. We used repeated holdout weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) to examine the association between prenatal exposure to multiple EDCs and early menarche (<11.5 (n = 218) vs. ≥11.5 years (n = 230)) for each chemical class separately (PFAS, PCBs, and OCPs) and for all three classes combined. Models adjusted for maternal age at menarche, maternal education, parity, pre-pregnancy body mass index, maternal age, prenatal smoking, and gestational week at sample collection. Mixture models showed null associations between prenatal exposure to EDC mixtures and early menarche. Using WQS regression, the odds ratio for early menarche for a one-decile increase in chemical concentrations for all three classes combined was 0.89 (95% CI: 0.76, 1.05); using BKMR, the odds ratio when all exposures were at the 60th percentile compared to the median was 0.98 (95% CI: 0.91, 1.05). Results suggest the overall effect of prenatal exposure to persistent EDC mixtures is not associated with early menarche.

    • Food Safety
      1. Evaluation of avocados as a possible source of Listeria monocytogenes infections, United States, 2016-2019external icon
        Pomeroy M, Conrad A, Pettengill JB, McClure M, Wellman AA, Marus J, Huffman J, Wise M.
        J Food Prot. 2021 Feb 16.
        Outbreaks of Listeria monocytogenes (L. monocytogenes) infections have historically been associated with contaminated deli meats, but recent outbreaks have been linked to produce. To date, avocados have not been identified as the source of any outbreaks of L. monocytogenes infections in the United States, but avocado samples have yielded strains that were closely related genetically to clinical L. monocytogenes isolates. To determine whether avocados have been a source of listeriosis, we conducted a retrospective review of epidemiological data for clinical isolates that were genetically related to isolates from avocados. Using a national database, we identified clusters containing clinical and at least one avocado isolate. We then selected clusters based upon isolation dates, cluster and composition size, and available food history data. For each cluster, we assessed whether (1) avocado consumption was higher among case-patients in the cluster than among those with sporadic illnesses, and (2) whether the only food isolates within the cluster were from avocados. If both conditions were met, the link was considered "likely," if one condition was met the link was considered "possible," and if neither condition was met evidence was "limited." Five of fifteen clusters met criteria for assessment. Of these, two were classified as having "limited" evidence for a link to avocados, two as "possible," and one as "likely." For the cluster considered "likely", avocado consumption was significantly higher among case-patients in the cluster compared to sporadic illnesses (Odds ratio: 8.5, 95% CI 1.5-86.5). We identified three clusters that were likely or possibly linked to avocados, suggesting avocados could be a source of listeriosis in the United States. Messaging on safe handling might be warranted for groups at higher risk, but further research is first needed to better characterize the ecology of pathogens on avocados and likelihood of internalization of L. monocytogenes.

    • Health Communication and Education
      1. Effectively communicating about HIV and other health disparities: Findings from a literature review and future directionsexternal icon
        Peinado S, Treiman K, Uhrig JD, Taylor JC, Stryker JE.
        Front Commun (Lausanne). 2020 Jun;5.
        Despite significant progress in the prevention and treatment of HIV, disparities in rates of infection remain among key groups in the United States, including blacks and African Americans; Hispanics/Latinos; and men who have sex with men (MSM). The U.S. Department of Health and Human Services' initiative, Ending the HIV Epidemic: A Plan for America, calls for addressing HIV-related disparities and reducing stigma and discrimination associated with HIV. The goal of this literature review was to identify approaches for effectively communicating about health disparities across the HIV care continuum. We reviewed the literature to investigate strategies used to communicate health disparities and to identify potential unintended adverse effects resulting from this messaging. Messages about health disparities often target subgroups at higher risk and can be framed in a variety of ways (e.g., social comparison, progress, impact, etiological). Studies have examined the effects of message framing on the risk perceptions, emotional reactions, and behaviors of individuals exposed to the messaging. The evidence points to several potential unintended adverse effects of using social comparison framing and individual responsibility framing to communicate about health disparities, and visual images and exemplars to target messages to higher-risk subgroups. There is not yet a clear evidence-based approach for communicating about health disparities and avoiding potential unintended effects. However, we offer recommendations for communicating about HIV-related disparities based on our findings. Because we found limited literature that addressed our research questions in the context of HIV, we propose a research agenda to build an evidence base for developing effective messages about HIV-related disparities.

    • Health Disparities
      1. Power and social control of youth during the COVID-19 pandemicexternal icon
        Gabriel MG, Brown A, León M, Outley C.
        Leis Sci. 2020 .
        While people across the globe adapt to the COVID-19 pandemic, young people have been the center of many news stories. Millions of young people are required to stay home due to school closures, and adults are forced to consider alternative structures to support youths’ needs. The COVID-19 pandemic has exposed multiple injustices and forms of oppression experienced by the most vulnerable in our country, which includes young people experiencing poverty, incarceration, foster care, homelessness, and those with marginalized identities. This article will discuss the role of power and social control in the lives of youth during the COVID-19 pandemic and present strategies leisure researchers and practitioners can adopt to overcome the loss of critical support structures and mitigate exponential effects of COVID-19 on our most vulnerable youth.

      2. The implementation cost of a safety-net hospital program addressing social needs in Atlantaexternal icon
        MacLeod KE, Chapel JM, McCurdy M, Minaya-Junca J, Wirth D, Onwuanyi A, Lane RI.
        Health Serv Res. 2021 Feb 12.
        OBJECTIVE: To describe the cost of integrating social needs activities into a health care program that works toward health equity by addressing socioeconomic barriers. DATA SOURCES/STUDY SETTING: Costs for a heart failure health care program based in a safety-net hospital were reported by program staff for the program year May 2018-April 2019. Additional data sources included hospital records, invoices, and staff survey. STUDY DESIGN: We conducted a retrospective, cross-sectional, case study of a program that includes health education, outpatient care, financial counseling and free medication; transportation and home services for those most in need; and connections to other social services. Program costs were summarized overall and for mutually exclusive categories: health care program (fixed and variable) and social needs activities. DATA COLLECTION: Program cost data were collected using a activity-based, micro-costing approach. In addition, we conducted a survey that was completed by key staff to understand time allocation. PRINCIPAL FINDINGS: Program costs were approximately $1.33 million, and the annual per patient cost was $1455. Thirty percent of the program costs was for social needs activities: 18% for 30-day supply of medications and addressing socioeconomic barriers to medication adherence, 18% for mobile health services (outpatient home visits), 53% for navigating services through a financial counselor and community health worker, and 12% for transportation to visits and addressing transportation barriers. Most of the program costs were for personnel: 92% of the health care program fixed, 95% of the health care program variable, and 78% of social needs activities. DISCUSSION: Historically, social and health care services are funded by different systems and have not been integrated. We estimate the cost of implementing social needs activities into a health care program. This work can inform implementation for hospitals attempting to address social determinants of health and social needs in their patient population.

      3. Racial/ethnic and geographic variations in long-term survival among Medicare beneficiaries after acute ischemic strokeexternal icon
        Tong X, Schieb L, George MG, Gillespie C, Merritt RK, Yang Q.
        Prev Chronic Dis. 2021 Feb 18;18:E15.
        INTRODUCTION: Little information is available about racial/ethnic and geographic variations in long-term survival among older patients (≥65) after acute ischemic stroke (AIS). METHODS: We examined data on 1,019,267 Medicare fee-for-service (FFS) beneficiaries aged 66 or older, hospitalized with a primary diagnosis of AIS from 2008 through 2012. Survival was defined as the time from the date of AIS to date of death, or an end of follow-up date of December 31, 2017. We used Cox proportional hazard models to estimate 5-year survival after AIS, adjusted for age, sex, race and Hispanic ethnicity, poverty level, Charlson Comorbidity Index, and state. RESULTS: Among 1,019,267 Medicare FFS beneficiaries hospitalized with AIS from 2008 through 2012, we documented 701,718 deaths (68.8%) during a median of 4 years of follow-up with 4.08 million person-years. The overall adjusted 5-year survival was 44%. Non-Hispanic Black men had the lowest 5-year survival, and 5-year survival varied significantly by state, from the highest at 49.1% (North Dakota) to the lowest at 40.5% (Hawaii). The ranges between the highest and lowest 5-year survival rates across states also varied significantly by racial/ethnic groups, with percentage point differences of 9.6 among non-Hispanic White, 11.3 among non-Hispanic Black, 17.7 among Hispanic, and 28.5 among other racial/ethnic beneficiaries. CONCLUSION: We identified significant racial/ethnic and geographic variations in 5-year survival rates after AIS among 2008-2012 Medicare FFS beneficiaries. Further study is needed to understand the reasons for these variations and develop prevention strategies to improve survival and racial disparities in survival after AIS.

    • Health Economics
      1. OBJECTIVE: To critically review researchers' use of diagnosis codes to identify congenital cytomegalovirus (cCMV) infection or disease in healthcare administrative databases. Understanding the limitations of cCMV ascertainment in those databases can inform cCMV surveillance and health services research. METHODS: We identified published studies that used diagnosis codes for cCMV or CMV in hospital discharge or health insurance claims and encounters records for infants to assess prevalence, use of services, or healthcare costs. We reviewed estimates of prevalence and of charges, costs, or expenditures associated with cCMV diagnosis codes. RESULTS: Five studies assessed hospitalizations with cCMV diagnosis codes recorded in hospital discharge databases, from the United States (n = 3), Australia (n = 1), and the United Kingdom (n = 1). Six other studies analyzed claims or encounters data from the United States (n = 5) or Japan (n = 1) to identify infants with cCMV codes. Prevalence estimates of recognized cCMV ranged from 0.6-3.8 per 10,000 infants. Economic analyses reported a wide range of per-hospitalization or per-infant cost estimates, which lacked standardization or comparability. CONCLUSIONS: The administrative prevalence of cCMV cases reported in published analyses of administrative data from North America, Western Europe, Japan, and Australia (0.6-3.8 per 10,000 infants) is an order of magnitude lower than the estimates of the true birth prevalence of 3-7 per 1,000 newborns based on universal newborn screening pilot studies conducted in the same regions. Nonetheless, in the absence of systematic surveillance for cCMV, administrative data might be useful for assessing trends in testing and clinical diagnosis. To the extent that cCMV cases recorded in administrative databases are not representative of the full spectrum of cCMV infection or disease, per-child cost estimates generated from those data may not be generalizable. On the other hand, claims data may be useful for estimating patterns of healthcare use and expenditures associated with combinations of diagnoses for cCMV and known complications of cCMV.

    • Healthcare Associated Infections
      1. Sustained transmission of Neisseria gonorrhoeae with high-level resistance to azithromycin, Indianapolis, Indiana 2017-2018external icon
        Holderman JL, Thomas JC, Schlanger K, Black JM, Town K, Cyr SB, Pham CD, Kirkcaldy RD.
        Clin Infect Dis. 2021 Feb 13.
        BACKGROUND: Since 2014, Neisseria gonorrhoeae (Ng) azithromycin (AZM) susceptibility has declined in the United States, but high-level azithromycin resistance (HL-AZMR) has been infrequent and sporadic. We describe a cluster of 14 Ng isolates with HL-AZMR identified in Indianapolis over 13 months. METHODS: Ng culture specimens (genital and extragenital) were collected from attendees of the Bell Flower Clinic. Isolates underwent antimicrobial susceptibility testing (AST) by Etest ®. AZM minimum inhibitory concentrations ≥256 µg/ml were classified as HL-AZMR. Local disease intervention specialists interviewed patients whose isolates demonstrated HL-AZMR and conducted partner services. Relatedness of isolates was investigated by genomic analyses. RESULTS: During 2017-2018, 1,016 Ng isolates collected at the Bell Flower Clinic underwent AST. Fourteen isolates (1.4%) from 12 men collected over 13 months demonstrated HL-AZMR; all were cephalosporin-susceptible. Of the 12 men, nine were white and reported male sex partners. Nine of the men were able to be re-tested; all were cured with 250 mg ceftriaxone plus 1g azithromycin. Two men named each other as partners; no other partners in common were reported. Genomic analysis demonstrated close relatedness of the HL-AZMR isolates and a novel combination of a mosaic-mtrR promoter along with 23S rRNA mutations that appear to have emerged from circulating strains. CONCLUSIONS: The close genetic relatedness with limited epidemiological linkages between patients highlights the challenges of gonorrhea partner investigations and suggests undetected local transmission. Local AST, rapid public health action, and epidemiologic investigations combined with genomic analysis provides a multi-pronged approach to understanding an STD outbreak.

      2. Take-home kits to detect respiratory viruses among healthcare personnel: Lessons learned from a cluster randomized clinical trialexternal icon
        Los J, Gaydos CA, Gibert CL, Gorse GJ, Lykken J, Nyquist AC, Price CS, Radonovich LJ, Rattigan S, Reich N, Rodriguez-Barradas M, Simberkoff M, Bessesen M, Brown A, Cummings DA, Perl TM.
        Am J Infect Control. 2021 Feb 10.
        BACKGROUND: Healthcare personnel (HCP) working in outpatient settings routinely interact with patients with acute respiratory illnesses. Absenteeism following symptom development and lack of staff trained to obtain samples limit efforts to identify pathogens among infected HCP. METHODS: The Respiratory Protection Effectiveness Clinical Trial assessed respiratory infection incidence among HCP between 2011 and 2015. Research assistants (RAs) obtained anterior nasal and oropharyngeal swabs from HCP in the workplace following development of respiratory illness symptoms and randomly while asymptomatic. Participants received take-home kits to self-collect swabs when absent from work. Samples mailed to a central laboratory were tested for respiratory viruses by reverse transcription polymerase chain reaction. RESULTS: Among 2,862 participants, 3,467 swabs were obtained from symptomatic participants. Among symptomatic HCP, respiratory virus was detected in 904 of 3,467 (26.1%) samples. Self-collected samples by symptomatic HCP at home had higher rates of viral detection (40.3%) compared to 24% obtained by trained RAs in the workplace (P < 0.001). CONCLUSIONS: In this randomized clinical trial, take-home kits were an easily implemented, effective method to self-collect samples by HCP. Other studies have previously shown relative equivalence of self-collected samples to those obtained by trained healthcare workers. Take-home kit self-collection could diminish workforce exposures and decrease the demand for personnel protective equipment worn to protect workers who collect respiratory samples.

    • Immunity and Immunization
      1. Decline in receipt of vaccines by Medicare beneficiaries during the COVID-19 pandemic - United States, 2020external icon
        Hong K, Zhou F, Tsai Y, Jatlaoui TC, Acosta AM, Dooling KL, Kobayashi M, Lindley MC.
        MMWR Morb Mortal Wkly Rep. 2021 Feb 19;70(7):245-249.
        On March 13, 2020, the United States declared a national emergency concerning the novel coronavirus disease 2019 (COVID-19) outbreak (1). In response, many state and local governments issued shelter-in-place or stay-at-home orders, restricting nonessential activities outside residents' homes (2). CDC initially issued guidance recommending postponing routine adult vaccinations, which was later revised to recommend continuing to administer routine adult vaccines (3). In addition, factors such as disrupted operations of health care facilities and safety concerns regarding exposure to SARS-CoV-2, the virus that causes COVID-19, resulted in delay or avoidance of routine medical care (4), likely further affecting delivery of routine adult vaccinations. Medicare enrollment and claims data of Parts A (hospital insurance), B (medical insurance), and D (prescription drug insurance) were examined to assess the change in receipt of routine adult vaccines during the pandemic. Weekly receipt of four vaccines (13-valent pneumococcal conjugate vaccine [PCV13], 23-valent pneumococcal polysaccharide vaccine [PPSV23], tetanus-diphtheria or tetanus-diphtheria-acellular pertussis vaccine [Td/Tdap], and recombinant zoster vaccine [RZV]) by Medicare beneficiaries aged ≥65 years during January 5-July 18, 2020, was compared with that during January 6-July 20, 2019, for the total study sample and by race and ethnicity. Overall, weekly administration rates of the four examined vaccines declined by up to 89% after the national emergency declaration in mid-March (1) compared with those during the corresponding period in 2019. During the first week following the national emergency declaration, the weekly vaccination rates were 25%-62% lower than those during the corresponding week in 2019. After reaching their nadirs of 70%-89% below 2019 rates in the second to third week of April 2020, weekly vaccination rates gradually began to recover through mid-July, but by the last study week were still lower than were those during the corresponding period in 2019, with the exception of PPSV23. Vaccination declined sharply for all vaccines studied, overall and across all racial and ethnic groups. While the pandemic continues, vaccination providers should emphasize to patients the importance of continuing to receive routine vaccinations and provide reassurance by explaining the procedures in place to ensure patient safety (3).

      2. Recombinant Zoster vaccine (Shingrix) real-world effectiveness in the first two years post-licensureexternal icon
        Izurieta HS, Wu X, Forshee R, Lu Y, Sung HM, Agger PE, Chillarige Y, Link-Gelles R, Lufkin B, Wernecke M, MaCurdy TE, Kelman J, Dooling K.
        Clin Infect Dis. 2021 Feb 13.
        BACKGROUND: Shingrix™ (recombinant zoster vaccine) was licensed to prevent herpes zoster, dispensed as two doses given 2-6 months apart, among adults ages ≥50 years. Clinical trials yielded efficacy of >90% for confirmed herpes zoster,but post-market vaccine performance has not been evaluated. Efficacy of a single dose, delayed second dose, or among persons with autoimmune or general immunosuppressive conditions have also not been studied. We aimed to assess post-market vaccine effectiveness of Shingrix. METHODS: We conducted a cohort study among vaccinated and unvaccinated Medicare Part D community dwelling beneficiaries ages >65 years. Herpes zoster was identified using a medical office visit diagnosis with treatment, and postherpetic neuralgia using a validated algorithm. We used inverse probability of treatment weighting to improve cohort balance, and marginal structural models to estimate hazard ratios. RESULTS: We found a vaccine effectiveness of 70.1% (95% CI, 68.6-71.5) and 56.9% (95% CI, 55.0-58.8) for two and one doses, respectively. The two-dose vaccine effectiveness was not significantly lower for beneficiaries 80+ years, for second doses received at ≥180 days, or for individuals with autoimmune conditions. The vaccine was also effective among individuals with immunosuppressive conditions. Two-dose vaccine effectiveness against postherpetic neuralgia was 76.0% (95% CI, 68.4-81.8). CONCLUSIONS: This large real-world observational study of effectiveness of Shingrix demonstrates the benefit of completing the two-dose regimen. Second doses administered beyond the recommended 6 months did not impair vaccine effectiveness.Our effectiveness estimates were lower than the clinical trials estimates, likely due to differences in outcome specificity.

      3. Immunogenicity of standard, high-dose, MF59-adjuvanted, and recombinant-HA seasonal influenza vaccination in older adultsexternal icon
        Li AP, Cohen CA, Leung NH, Fang VJ, Gangappa S, Sambhara S, Levine MZ, Iuliano AD, Perera R, Ip DK, Peiris JS, Thompson MG, Cowling BJ, Valkenburg SA.
        NPJ Vaccines. 2021 Feb 16;6(1):25.
        The vaccine efficacy of standard-dose seasonal inactivated influenza vaccines (S-IIV) can be improved by the use of vaccines with higher antigen content or adjuvants. We conducted a randomized controlled trial in older adults to compare cellular and antibody responses of S-IIV versus enhanced vaccines (eIIV): MF59-adjuvanted (A-eIIV), high-dose (H-eIIV), and recombinant-hemagglutinin (HA) (R-eIIV). All vaccines induced comparable H3-HA-specific IgG and elevated antibody-dependent cellular cytotoxicity (ADCC) activity at day 30 post vaccination. H3-HA-specific ADCC responses were greatest following H-eIIV. Only A-eIIV increased H3-HA-IgG avidity, HA-stalk IgG and ADCC activity. eIIVs also increased polyfunctional CD4+ and CD8+ T cell responses, while cellular immune responses were skewed toward single-cytokine-producing T cells among S-IIV subjects. Our study provides further immunological evidence for the preferential use of eIIVs in older adults as each vaccine platform had an advantage over the standard-dose vaccine in terms of NK cell activation, HA-stalk antibodies, and T cell responses.


      5. Influenza vaccination coverage among persons seeking outpatient medical care for acute respiratory illness in five states in the United States, 2011-2012 through 2018-2019external icon
        Wu MJ, Chung JR, Kim SS, Jackson ML, Jackson LA, Belongia EA, McLean HQ, Gaglani M, Reis M, Beeram M, Martin ET, Monto AS, Nowalk MP, Zimmerman R, Santibanez TA, Singleton JA, Patel M, Flannery B.
        Vaccine. 2021 Feb 15.
        BACKGROUND: In the United States (U.S.), annual influenza vaccination has been recommended for all persons aged ≥6 months with the Healthy People 2020 coverage target of 70%. However, vaccination coverage has remained around 42-49% during the past eight influenza seasons. We sought to quantify influenza vaccination coverage and factors associated with vaccination in persons seeking outpatient medical care for an acute respiratory illness (ARI). METHODS: We enrolled outpatients aged ≥6 months with ARI from >50 U.S. clinics from 2011 to 2012 through 2018-2019 influenza seasons and tested for influenza with molecular assays. Vaccination status was based on documented receipt of the current season's influenza vaccine. We estimated vaccination coverage among influenza-negative study participants by study site, age, and season, and compared to state-level influenza coverage estimates in the general population based on annual immunization surveys. We used multivariable logistic regression to examine factors independently associated with receipt of influenza vaccines. RESULTS: We enrolled 45,424 study participants with ARI who tested negative for influenza during the study period. Annual vaccination coverage among influenza-negative ARI patients and the general population in the participating states averaged 55% (range: 47-62%), and 52% (range: 46-54%), respectively. Among enrollees, coverage was highest among adults aged ≥65 years (82%; range, 80-85%) and lowest among adolescents aged 13-17 years (38%; range, 35-41%). Factors significantly associated with non-vaccination included non-White race, no college degree, exposure to cigarette smoke, absence of high-risk conditions, and not receiving prior season influenza vaccine. CONCLUSIONS: Influenza vaccination coverage over eight seasons among outpatients with non-influenza respiratory illness was slightly higher than coverage in the general population but 15% lower than national targets. Increased efforts to promote vaccination especially in groups with lower coverage are warranted to attain optimal health benefits of influenza vaccine.

    • Informatics
      1. Trends in use of telehealth among health centers during the COVID-19 pandemic - United States, June 26-November 6, 2020external icon
        Demeke HB, Merali S, Marks S, Pao LZ, Romero L, Sandhu P, Clark H, Clara A, McDow KB, Tindall E, Campbell S, Bolton J, Le X, Skapik JL, Nwaise I, Rose MA, Strona FV, Nelson C, Siza C.
        MMWR Morb Mortal Wkly Rep. 2021 Feb 19;70(7):240-244.
        Telehealth can facilitate access to care, reduce risk for transmission of SARS-CoV-2 (the virus that causes coronavirus disease 2019 [COVID-19]), conserve scarce medical supplies, and reduce strain on health care capacity and facilities while supporting continuity of care. Health Resources and Services Administration (HRSA)-funded health centers* expanded telehealth(†) services during the COVID-19 pandemic (1). The Centers for Medicare & Medicaid Services eliminated geographic restrictions and enhanced reimbursement so that telehealth services-enabled health centers could expand telehealth services and continue providing care during the pandemic (2,3). CDC and HRSA analyzed data from 245 health centers that completed a voluntary weekly HRSA Health Center COVID-19 Survey(§) for 20 consecutive weeks to describe trends in telehealth use. During the weeks ending June 26-November 6, 2020, the overall percentage of weekly health care visits conducted via telehealth (telehealth visits) decreased by 25%, from 35.8% during the week ending June 26 to 26.9% for the week ending November 6, averaging 30.2% over the study period. Weekly telehealth visits declined when COVID-19 cases were decreasing and plateaued as cases were increasing. Health centers in the South and in rural areas consistently reported the lowest average percentage of weekly telehealth visits over the 20 weeks, compared with health centers in other regions and urban areas. As the COVID-19 pandemic continues, maintaining and expanding telehealth services will be critical to ensuring access to care while limiting exposure to SARS-CoV-2.

    • Injury and Violence
      1. Due in part to concern about the potential long-term effects of concussion and repetitive head injuries in football, some programs have implemented tackling interventions. This paper explores youth football coaches' perception of football safety and their experiences implementing these interventions aimed at athlete safety. Using a qualitative approach, coaches were interviewed by means of a semi-structured protocol that covered: (a) demographics; (b) background and experiences; (c) personal relevance risks, safety, and benefits of youth football; (d) experiences with tackling technique; (e) experiences with mouth guard sensors; and (f) opinions on disseminating information on football safety. Most coaches felt that learning tackling at a young age helped prepare them for their playing later in life and believed that youth should begin playing tackle football at a young age. Coaches were mixed regarding their concerns about the risk for concussion and subconcussive head impacts. Still, most were receptive to changes in rules and policies aimed at making football safer. Findings from this study demonstrate that youth football coaches are important stakeholders to consider when implementing changes to youth football. Understanding coach perceptions and experiences may inform future efforts aimed to educate coaches on rules and policies to make the game safer for youth athletes.

    • Laboratory Sciences
      1. Reactive astrocyte nomenclature, definitions, and future directionsexternal icon
        Escartin C, Galea E, Lakatos A, O'Callaghan JP, Petzold GC, Serrano-Pozo A, Steinhäuser C, Volterra A, Carmignoto G, Agarwal A, Allen NJ, Araque A, Barbeito L, Barzilai A, Bergles DE, Bonvento G, Butt AM, Chen WT, Cohen-Salmon M, Cunningham C, Deneen B, De Strooper B, Díaz-Castro B, Farina C, Freeman M, Gallo V, Goldman JE, Goldman SA, Götz M, Gutiérrez A, Haydon PG, Heiland DH, Hol EM, Holt MG, Iino M, Kastanenka KV, Kettenmann H, Khakh BS, Koizumi S, Lee CJ, Liddelow SA, MacVicar BA, Magistretti P, Messing A, Mishra A, Molofsky AV, Murai KK, Norris CM, Okada S, Oliet SH, Oliveira JF, Panatier A, Parpura V, Pekna M, Pekny M, Pellerin L, Perea G, Pérez-Nievas BG, Pfrieger FW, Poskanzer KE, Quintana FJ, Ransohoff RM, Riquelme-Perez M, Robel S, Rose CR, Rothstein JD, Rouach N, Rowitch DH, Semyanov A, Sirko S, Sontheimer H, Swanson RA, Vitorica J, Wanner IB, Wood LB, Wu J, Zheng B, Zimmer ER, Zorec R, Sofroniew MV, Verkhratsky A.
        Nat Neurosci. 2021 Feb 15.
        Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters-preferably in vivo-plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions.

      2. Development of a new barcode-based, multiplex-PCR, next-generation-sequencing assay and data processing and analytical pipeline for multiplicity of infection detection of Plasmodium falciparumexternal icon
        Mitchell RM, Zhou Z, Sheth M, Sergent S, Frace M, Nayak V, Hu B, Gimnig J, Ter Kuile F, Lindblade K, Slutsker L, Hamel MJ, Desai M, Otieno K, Kariuki S, Vigfusson Y, Shi YP.
        Malar J. 2021 Feb 16;20(1):92.
        BACKGROUND: Simultaneous infection with multiple malaria parasite strains is common in high transmission areas. Quantifying the number of strains per host, or the multiplicity of infection (MOI), provides additional parasite indices for assessing transmission levels but it is challenging to measure accurately with current tools. This paper presents new laboratory and analytical methods for estimating the MOI of Plasmodium falciparum. METHODS: Based on 24 single nucleotide polymorphisms (SNPs) previously identified as stable, unlinked targets across 12 of the 14 chromosomes within P. falciparum genome, three multiplex PCRs of short target regions and subsequent next generation sequencing (NGS) of the amplicons were developed. A bioinformatics pipeline including B4Screening pathway removed spurious amplicons to ensure consistent frequency calls at each SNP location, compiled amplicons by SNP site diversity, and performed algorithmic haplotype and strain reconstruction. The pipeline was validated by 108 samples generated from cultured-laboratory strain mixtures in different proportions and concentrations, with and without pre-amplification, and using whole blood and dried blood spots (DBS). The pipeline was applied to 273 smear-positive samples from surveys conducted in western Kenya, then providing results into StrainRecon Thresholding for Infection Multiplicity (STIM), a novel MOI estimator. RESULTS: The 24 barcode SNPs were successfully identified uniformly across the 12 chromosomes of P. falciparum in a sample using the pipeline. Pre-amplification and parasite concentration, while non-linearly associated with SNP read depth, did not influence the SNP frequency calls. Based on consistent SNP frequency calls at targeted locations, the algorithmic strain reconstruction for each laboratory-mixed sample had 98.5% accuracy in dominant strains. STIM detected up to 5 strains in field samples from western Kenya and showed declining MOI over time (q < 0.02), from 4.32 strains per infected person in 1996 to 4.01, 3.56 and 3.35 in 2001, 2007 and 2012, and a reduction in the proportion of samples with 5 strains from 57% in 1996 to 18% in 2012. CONCLUSION: The combined approach of new multiplex PCRs and NGS, the unique bioinformatics pipeline and STIM could identify 24 barcode SNPs of P. falciparum correctly and consistently. The methodology could be applied to field samples to reliably measure temporal changes in MOI.

      3. Susceptibility of widely diverse influenza a viruses to PB2 polymerase inhibitor pimodivirexternal icon
        Patel MC, Chesnokov A, Jones J, Mishin VP, De La Cruz JA, Nguyen HT, Zanders N, Wentworth DE, Davis TC, Gubareva LV.
        Antiviral Res. 2021 Feb 10:105035.
        Pimodivir exerts an antiviral effect on the early stages of influenza A virus replication by inhibiting the cap-binding function of polymerase basic protein 2 (PB2). In this study, we used a combination of sequence analysis and phenotypic methods to evaluate pimodivir susceptibility of influenza A viruses collected from humans and other hosts. Screening PB2 sequences for substitutions previously associated with reduced pimodivir susceptibility revealed a very low frequency among seasonal viruses circulating in the U.S. during 2015-2020 (<0.01%; 3/11,934) and among non-seasonal viruses collected in various countries during the same period (0.2%; 18/8971). Pimodivir potently inhibited virus replication in two assays, a single-cycle HINT and a multi-cycle FRA, with IC(50) values in a nanomolar range. Median IC(50) values determined by HINT were similar for both subtypes of seasonal viruses, A (H1N1)pdm09 and A (H3N2), across three seasons. Human seasonal viruses with PB2 substitutions S324C, S324R, or N510K displayed a 27-317-fold reduced pimodivir susceptibility. In addition, pimodivir was effective at inhibiting replication of a diverse group of animal-origin viruses that have pandemic potential, including avian viruses of A (H5N6) and A (H7N9) subtypes. A rare PB2 substitution H357N was identified in an A (H4N2) subtype poultry virus that displayed >100-fold reduced pimodivir susceptibility. Our findings demonstrate a broad inhibitory activity of pimodivir and expand the existing knowledge of amino acid substitutions that can reduce susceptibility to this investigational antiviral.

      4. Members of the genus Rickettsia range from nonpathogenic endosymbionts to virulent pathogens such as Rickettsia rickettsii, the causative agent of Rocky Mountain spotted fever. Many rickettsiae are considered nonpathogenic because they have been isolated from ticks but not vertebrate hosts. We assessed the ability of three presumed endosymbionts: Rickettsia amblyommatis, Rickettsia bellii, and Rickettsia montanensis, to infect a guinea pig animal model. These species were chosen because of their high prevalence in respective tick vectors or published reports suggestive of human or animal pathogenicity. Following intraperitoneal (IP) inoculation of cell culture suspensions of R. rickettsii, R. amblyommatis, R. bellii, or R. montanensis into guinea pigs, animals were monitored for signs of clinical illness for 13 days. Ear biopsies and blood samples were taken at 2- to 3-day intervals for detection of rickettsial DNA by PCR. Animals were necropsied and internal organ samples were also tested using PCR assays. Among the six guinea pigs inoculated with R. amblyommatis, fever, orchitis, and dermatitis were observed in one, one, and three animals respectively. In R. bellii-exposed animals, we noted fever in one of six animals, orchitis in one, and dermatitis in two. No PCR-positive tissues were present in either the R. amblyommatis- or R. bellii-exposed groups. In the R. montanensis-exposed group, two of six animals became febrile, two had orchitis, and three developed dermatitis in ears or footpads. R. montanensis DNA was detected in ear skin biopsies collected on multiple days from three animals. Also, a liver specimen from one animal and spleen specimens of two animals were PCR positive. The course and severity of disease in the three experimental groups were significantly milder than that of R. rickettsii. This study suggests that the three rickettsiae considered nonpathogenic can cause either subclinical or mild infections in guinea pigs when introduced via IP inoculation.

      5. Detection of 30 fentanyl analogs by commercial immunoassay kitsexternal icon
        Wharton RE, Casbohm J, Hoffmaster R, Brewer BN, Finn MG, Johnson RC.
        J Anal Toxicol. 2021 Feb 13;45(2):111-116.
        Health-care workers, laboratorians and overdose prevention centers rely on commercial immunoassays to detect the presence of fentanyl; however, the cross-reactivity of fentanyl analogs with these kits is largely unknown. To address this, we conducted a pilot study evaluating the detection of 30 fentanyl analogs and metabolites by 19 commercially available kits (9 lateral flow assays, 7 heterogeneous immunoassays and 3 homogenous immunoassays). The analogs selected for analysis were compiled from the Drug Enforcement Administration and National Forensic Laboratory Information System reports from 2015 to 2018. In general, the immunoassays tested were able to detect their intended fentanyl analog and some closely related analogs, but more structurally diverse analogs, including 4-methoxy-butyryl fentanyl and 3-methylfentanyl, were not well detected. Carfentanil was only detected by kits specifically designed for its recognition. In general, analogs with group additions to the piperidine, or bulky rings or long alkyl chain modifications in the N-aryl or alkyl amide regions, were poorly detected compared to other types of modifications. This preliminary information is useful for screening diagnostic, forensic and unknown powder samples for the presence of fentanyl analogs and guiding future testing improvements.

      6. Loss of the virulence plasmid by Shigella sonnei promotes its interactions with CD207 and CD209 receptorsexternal icon
        Wu BC, Olivia NA, Tembo JM, He YX, Zhang YM, Xue Y, Ye CL, Lv Y, Li WJ, Jiang LY, Huo XX, Sun ZY, Chen ZJ, Qin JC, Li AY, Park CG, Klena JD, Ding HH, Chen T.
        J Med Microbiol. 2021 Feb 16.
        Introduction. Shigella sonnei, the cause of bacillary dysentery, belongs to Gram-negative enteropathogenic bacteria. S. sonnei contains a 210 kb virulence plasmid that encodes an O-antigen gene cluster of LPSs. However, this virulence plasmid is frequently lost during replication. It is well-documented that after losing the O-antigen and becoming rough strains, the Gram-negative bacteria may express an LPS core on its surface. Previous studies have suggested that by using the LPS core, Gram-negative bacteria can interact with several C-type lectin receptors that are expressed on antigen-presenting cells (APCs).Hypothesis/Gap Statement. S. sonnei by losing the virulence plasmid may hijack APCs via the interactions of LPS-CD209/CD207.Aim. This study aimed to investigate if the S. sonnei rough strain, by losing the virulence plasmid, interacted with APCs that express C-type lectins of human CD207, human CD209a and mouse CD209b.Methodology. SDS-PAGE silver staining was used to examine the O-antigen expression of S. sonnei WT and its rough strain. Invasion assays and inhibition assays were used to examine the ability of S. sonnei WT and its rough strain to invade APCs and investigate whether CD209 and CD207 are receptors for phagocytosis of rough S. sonnei. Animal assays were used to observe the dissemination of S. sonnei.Results. S. sonnei did not express O-antigens after losing the virulence plasmid. The S. sonnei rough strain invades with APCs, including human dendritic cells (DCs) and mouse macrophages. CD209 and CD207 are receptors for phagocytosis of rough S. sonnei. Expression of the O-antigen reduces the ability of the S. sonnei rough strain to be disseminated to mesenteric lymph nodes and spleens.Conclusion. This work demonstrated that S. sonnei rough strains - by losing the virulence plasmid - invaded APCs through interactions with CD209 and CD207 receptors.

    • Mining
      1. In this study, a parametric study was conducted using FLAC3D numerical models to examine the impact of oblique loading, generated from seam dip, on the strength and the failure propagation pattern of a stone pillar using two simplified geometry types. In type 1, the sidewalls of the pillars were assumed to be perpendicular to the roof and the floor, while in type 2, the sidewalls of pillars were assumed to be vertical. The complex pillar geometry in dipping mines was frequently modeled using these two geometries. To capture a complete picture of the effect of seam dip on pillar stability, the modeled width-to-height (W/H) ratio of the pillars, in situ stress field, and pillars roof/floor interfaces were systematically varied to account for the potential distribution of values for these parameters across the underground stone mines in USA. Results from the numerical modeling indicate that dipping pillars have reduced strength compared with horizontal pillars. Also, an asymmetric failure propagation pattern could be obtained depending on an interaction between the W/H ratio, seam dip, in situ stresses, and pillar geometry.

      2. Ground falls represent a significant hazard at underground mines in the stone, sand, and gravel (SSG) sector in the USA. Researchers from the National Institute for Occupational Safety and Health (NIOSH) are currently conducting detailed investigations into the complex loading conditions at underground stone mines operating in challenging conditions. This paper presents the application of numerical modeling to analyze pillar and roof stability at a dipping underground limestone mine. A validated numerical model was used to explore the potential behavior of the pillars and roof as loading conditions change. The validated model was used to compare changes in mining sequence, overburden depth, and the in situ stress field. This will allow mine operators and engineers to have a better idea of the conditions that could be encountered as mining progresses. Results from the numerical modeling indicate that roof displacement more than doubles as the vertical stress increases from 10 MPa (1450 psi) to 19 MPa (2750 psi) when the maximum and minimum horizontal stresses were 41 MPa (5950 psi) and 22 MPa (3190 psi), respectively. Consequently, as the pillar load increases, the safety factor of the pillars is projected to decrease by about 25%. The impact of the practical application of numerical models can result in a reduction of ground-fall accidents and injuries as well as generally safer working conditions.

    • Nutritional Sciences
      1. Effects of prenatal micronutrients supplementation timing on pregnancy-induced hypertension: Secondary analysis of a double-blind randomized controlled trialexternal icon
        Liu Y, Li N, Mei Z, Li Z, Ye R, Zhang L, Li H, Zhang Y, Liu JM, Serdula MK.
        Matern Child Nutr. 2021 Feb 16:e13157.
        In this secondary analysis of data from a double-blind randomized controlled trial (clinicaltrials.gov identifier: NCT00133744) of micronutrient supplementation (multiple micronutrients [MMN], iron-folic acid [IFA] and folic acid [FA] alone), we examined the potential modifying effect of gestational age at enrolment on the association of antenatal supplementation and pregnancy-induced hypertension (PIH). We included 18,775 nulliparous pregnant women with mild or no anaemia who were enrolled at 20 weeks of gestation or earlier from five counties of northern China. Women were randomly assigned to receive daily FA, IFA or MMN from enrolment until delivery. We used logistic regression to evaluate the association between PIH and timing of micronutrient supplementation. The incidence of PIH was statistically significantly lower among women who began MMN supplementation before 12 gestational weeks compared with women who began MMN supplementation at 12 weeks or later (RR = 0.74, 95% CI: 0.60-0.91). A similar protective effect was observed for both early-onset (<28 weeks, RR 0.45, 0.21-0.96) and late-onset of PIH (≥28 weeks, RR 0.77, 0.63-0.96). No statistically significant association was observed between PIH occurrence and timing of supplementation for FA or IFA. Maternal MMN supplementation and antenatal enrolment during the first trimester of pregnancy appeared to be of importance in preventing both early- and late-onset of PIH.

    • Parasitic Diseases
      1. Reactivation of Chagas disease in a patient with an autoimmune rheumatic disease: Case report and review of the literatureexternal icon
        Czech MM, Nayak AK, Subramanian K, Suarez JF, Ferguson J, Jacobson KB, Montgomery SP, Chang M, Bae GH, Raghavan SS, Wang H, Miranti E, Budvytiene I, Shoor SM, Banaei N, Rieger K, Deresinski S, Holubar M, Blackburn BG.
        Open Forum Infect Dis. 2021 Feb;8(2):ofaa642.
        Reactivation of Chagas disease has been described in immunosuppressed patients, but there is a paucity of literature describing reactivation in patients on immunosuppressive therapies for the treatment of autoimmune rheumatic diseases. We describe a case of Chagas disease reactivation in a woman taking azathioprine and prednisone for limited cutaneous systemic sclerosis (lcSSc). Reactivation manifested as indurated and erythematous cutaneous nodules. Sequencing of a skin biopsy specimen confirmed the diagnosis of Chagas disease. She was treated with benznidazole with clinical improvement in the cutaneous lesions. However, her clinical course was complicated and included disseminated CMV disease and subsequent septic shock due to bacteremia. Our case and review of the literature highlight that screening for Chagas disease should be strongly considered for patients who will undergo immunosuppression for treatment of autoimmune disease if epidemiologically indicated.

      2. Continued low efficacy of artemether-lumefantrine in Angola in 2019external icon
        Dimbu PR, Horth R, Cândido AL, Ferreira CM, Caquece F, Garcia LE, André K, Pembele G, Jandondo D, Bondo BJ, Nieto Andrade B, Labuda S, Ponce de León G, Kelley J, Patel D, Svigel SS, Talundzic E, Lucchi N, Morais JF, Fortes F, Martins JF, Pluciński MM.
        Antimicrob Agents Chemother. 2021 Jan 20;65(2).
        Biennial therapeutic efficacy monitoring is a crucial activity for ensuring the efficacy of currently used artemisinin-based combination therapy in Angola. Children with acute uncomplicated Plasmodium falciparum infection in sentinel sites in the Benguela, Zaire, and Lunda Sul Provinces were treated with artemether-lumefantrine (AL) or artesunate-amodiaquine (ASAQ) and monitored for 28 days to assess clinical and parasitological responses. Molecular correction was performed using seven microsatellite markers. Samples from treatment failures were genotyped for the pfk13, pfcrt, and pfmdr1 genes. Day 3 clearance rates were ≥95% in all arms. Uncorrected day 28 Kaplan-Meier efficacy estimates ranged from 84.2 to 90.1% for the AL arms and 84.7 to 100% for the ASAQ arms. Corrected day 28 estimates were 87.6% (95% confidence interval [CI], 81 to 95%) for the AL arm in Lunda Sul, 92.2% (95% CI, 87 to 98%) for AL in Zaire, 95.6% (95% CI, 91 to 100%) for ASAQ in Zaire, 98.4% (95% CI, 96 to 100%) for AL in Benguela, and 100% for ASAQ in Benguela and Lunda Sul. All 103 analyzed samples had wild-type pfk13 sequences. The 76T pfcrt allele was found in most (92%; 11/12) ASAQ late-failure samples but in only 16% (4/25) of AL failure samples. The N86 pfmdr1 allele was found in 97% (34/35) of treatment failures. The AL efficacy in Lunda Sul was below the 90% World Health Organization threshold, the third time in four rounds that this threshold was crossed for an AL arm in Angola. In contrast, the observed ASAQ efficacy has not been below 95% to date in Angola, including this latest round.

      3. Malaria in migrant agricultural workers in western Ethiopia: entomological assessment of malaria transmission riskexternal icon
        Dugassa S, Murphy M, Chibsa S, Tadesse Y, Yohannes G, Lorenz LM, Solomon H, Yewhalaw D, Irish SR.
        Malar J. 2021 Feb 16;20(1):95.
        BACKGROUND: Ethiopia has made great strides in malaria control over the last two decades. However, this progress has not been uniform and one concern has been reported high rates of malaria transmission in large agricultural development areas in western Ethiopia. Improved vector control is one way this transmission might be addressed, but little is known about malaria vectors in this part of the country. METHODS: To better understand the vector species involved in malaria transmission and their behaviour, human landing collections were conducted in Dangur woreda, Benishangul-Gumuz, between July and December 2017. This period encompasses the months with the highest rain and the peak mosquito population. Mosquitoes were identified to species and tested for the presence of Plasmodium sporozoites. RESULTS: The predominant species of the Anopheles collected was Anopheles arabiensis (1,733; i.e. 61.3 % of the entire Anopheles), which was also the only species identified with sporozoites (Plasmodium falciparum and Plasmodium vivax). Anopheles arabiensis was collected as early in the evening as 18:00 h-19:00 h, and host-seeking continued until 5:00 h-6:00 h. Nearly equal numbers were collected indoors and outdoors. The calculated entomological inoculation rate for An. arabiensis for the study period was 1.41 infectious bites per month. More An. arabiensis were collected inside and outside worker's shelters than in fields where workers were working at night. CONCLUSIONS: Anopheles arabiensis is likely to be the primary vector of malaria in the agricultural development areas studied. High rates of human biting took place inside and outdoor near workers' residential housing. Improved and targeted vector control in this area might considerably reduce malaria transmission.

      4. Natural infections with different Plasmodium species induce antibodies reactive to a chimeric Plasmodium vivax recombinant proteinexternal icon
        McCaffery JN, Singh B, Nace D, Moreno A, Udhayakumar V, Rogier E.
        Malar J. 2021 Feb 12;20(1):86.
        BACKGROUND: As malaria incidence and transmission in a region decreases, it becomes increasingly difficult to identify areas of active transmission. Improved methods for identifying and monitoring foci of active malaria transmission are needed in areas of low parasite prevalence in order to achieve malaria elimination. Serological assays can provide population-level infection history to inform elimination campaigns. METHODS: A bead-based multiplex antibody detection assay was used to evaluate a chimeric Plasmodium vivax MSP1 protein (PvRMC-MSP1), designed to be broadly immunogenic for use in vaccine studies, to act as a pan-malaria serological tool based on its ability to capture IgG in plasma samples obtained from naturally exposed individuals. Samples from 236 US travellers with PCR confirmed infection status from all four major Plasmodium species infecting humans, Plasmodium falciparum (n = 181), Plasmodium vivax (n = 38), Plasmodium malariae (n = 4), and Plasmodium ovale (n = 13) were tested for IgG capture using PvRMC-MSP1 as well as the four recombinant MSP1-19 kD isoforms representative of these Plasmodium species. RESULTS: Regardless of infecting Plasmodium species, a large proportion of plasma samples from infected US travellers provided a high assay signal to the PvRMC-MSP1 chimeric protein, with 115 high responders out of 236 samples assessed (48.7%). When grouped by active infection, 38.7% P. falciparum-, 92.1% of P. vivax-, 75.0% P. malariae-, and 53.4% of P. ovale-infected individuals displayed high assay signals in response to PvRMC-MSP1. It was also determined that plasma from P. vivax-infected individuals produced increased assay signals in response to the PvRMC-MSP1 chimera as compared to the recombinant PvMSP1 for 89.5% (34 out of 38) of individuals. PvRMC-MSP1 also showed improved ability to capture IgG antibodies from P. falciparum-infected individuals when compared to the capture by recombinant PvMSP1, with high assay signals observed for 38.7% of P. falciparum-infected travellers in response to PvRMC-MSP1 IgG capture compared to just 1.1% who were high responders to capture by the recombinant PvMSP1 protein. CONCLUSIONS: These results support further study of designed antigens as an approach for increasing sensitivity or broadening binding capacity to improve existing serological tools for determining population-level exposure to Plasmodium species. Including both broad-reacting and Plasmodium species-specific antigen-coated beads in an assay panel could provide a nuanced view of population-level exposure histories, an extensive IgG profile, and detailed seroestimates. A more sensitive serological tool for detection of P. vivax exposure would aid malaria elimination campaigns in co-endemic areas and regions where P. vivax is the dominant parasite.

    • Physical Activity
      1. Presidential Youth Fitness Program implementation: An antecedent to organizational changeexternal icon
        Barcelona JM, Castelli DM, Duncan Cance J, Pitt Barnes S, Lee S.
        Eval Program Plann. 2021 Feb 10;86:101919.
        INTRODUCTION: Grounded in organizational change theory, the purpose of this study was to investigate the efficacy of the Presidential Youth Fitness Program (PYFP) and its association with healthy cultures within schools. METHODS: Using a qualitative approach, data were collected through interviews, site visits and artifacts across 374 schools. An explanatory collective case study approach was used to identify key events related to implementation. RESULTS: Pivotal antecedents to organizational change included prolonged, continual PD, direct support of PYFP implementation, and recognition. Further, three key themes of leveling of the playing field, strategically overcoming barriers, and recruiting teacher fitness champions were identified. CONCLUSIONS: Creating a healthy school culture was an unexpected, but feasible outcome stemming from the implementation of the PYFP. A collective effort, led by physical education teachers and fitness champions and embraced by the administration, faculty, and community, is necessary for the school culture to unfreeze from its present status.

    • Reproductive Health
      1. BACKGROUND: Little is known about breastfeeding initiation and duration in the context of postpartum marijuana use and safety beliefs. RESEARCH AIMS: (1) To describe characteristics of women who used marijuana postpartum; (2) to evaluate the relationship between postpartum marijuana use and breastfeeding behaviors; and 3) to assess, among women who used marijuana postpartum, how safety perceptions are associated with breastfeeding behaviors. METHODS: Data from the cross-sectional Pregnancy Risk Assessment Monitoring System, a United States national governmental survey, 2017, were analyzed for participants with infants aged ≥ 12 weeks (seven states, unweighted N = 4604). Chi-square tests were used to compare characteristics and counseling for postpartum marijuana use. For participants with postpartum use, adjusted prevalence ratios (aPR) were calculated to evaluate relationships between safety perceptions and breastfeeding initiation and duration. RESULTS: Overall, 5.5% (95% CI [4.6, 6.6]) of participants reported postpartum marijuana use; among these women, 47.2% (CI [37.6, 56.9]) were breastfeeding at the time of the survey. Overall, 25.7% of participants indicated that they had been advised, by their prenatal care provider, against marijuana use while breastfeeding. Breastfeeding initiation or duration did not differ by postpartum marijuana use. Among participants with postpartum use, those who perceived marijuana was safe for breastfeeding women to use were more likely to have breastfed (aPR = 1.22, CI [1.04, 1.43]) and have a breastfeeding duration > 12 weeks (aPR = 1.57, CI [1.08, 2.27]) compared to those who perceived it to be unsafe. CONCLUSIONS: Understanding maternal safety beliefs and provider education about the latest evidence and guidance related to postpartum marijuana use may improve clinical care.

    • Substance Use and Abuse
      1. Tobacco smoking cessation and quitline use among adults aged ≥15 years in 31 countries: Findings from the Global Adult Tobacco Surveyexternal icon
        Ahluwalia IB, Tripp AL, Dean AK, Mbulo L, Arrazola RA, Twentyman E, King BA.
        Am J Prev Med. 2021 ;60(3):S128-S135.
        Introduction: About 80% of the 1.1 billion people who smoke tobacco worldwide reside in low- and middle-income countries. Evidence-based approaches to promote cessation include brief advice from health professionals and referrals through quitlines. This study assesses cessation behaviors and the use of cessation services in the past 12 months among current tobacco smokers in 31 countries who attempted to quit. Methods: Data came from the Global Adult Tobacco Survey, a household-based survey of non-institutionalized adults aged ≥15 years. Surveys were conducted in 31 countries during 2008–2018; sample sizes ranged from 4,250 (Malaysia) to 74,037 (India), and response rates ranged from 64.4% (Ukraine) to 98.5% (Qatar). In 2019, data from the 31 countries were assessed in June 2019, and indicators included self-reported current (daily or less than daily) tobacco smoking, past-year quit attempts, and cessation methods used in the past 12 months. Results: Current tobacco smoking prevalence ranged from 3.7% (Ethiopia) to 38.2% (Greece). Overall, an estimated 176.8 million adults from the 31 countries made a quit attempt in the past 12 months, with country-level prevalence ranging from 16.4% (Greece) to 54.7% (Botswana). Most individuals who made a quit attempt did so without assistance (median=74.4%). Other methods were less prevalent, including quitlines (median=0.2%) and counseling (median=7.2%). Conclusions: In the assessed countries, the majority of those who currently smoked tobacco and made a quit attempt did so without assistance; very few reported using quitlines, partly because of the lack of quitlines in some countries. In resource-limited settings, quitlines can play a greater role in helping people quit smoking as part of a comprehensive approach.

      2. Evaluation of the Asian Smokers' Quitline: A centralized service for a dispersed populationexternal icon
        Chen C, Anderson CM, Babb SD, Frank R, Wong S, Kuiper NM, Zhu SH.
        Am J Prev Med. 2021 March;60(3 Supplement 2):S154-S162.
        Introduction: Asian immigrants to the U.S. smoke at higher rates than U.S.-born Asians. However, few programs exist to help these immigrants quit and little is known about their real-world effectiveness. The Centers for Disease Control and Prevention funded the Asian Smokers' Quitline to serve Chinese, Korean, and Vietnamese immigrants nationwide. This study examines service utilization and outcomes from the first 7 years of the program. Method(s): From August 2012 to July 2019, the Asian Smokers' Quitline enrolled 14,073 Chinese-, Korean-, and Vietnamese-speaking smokers. Service utilization rates and cessation outcomes were compared with those of an earlier trial (conducted 2004-2008) that demonstrated the efficacy of an Asian-language telephone counseling protocol. Data were analyzed in 2019. Result(s): Asian Smokers' Quitline participants came from all 50 states and the District of Columbia. The main referral sources were Asian-language newspapers (37.2%), family and friends (16.4%), healthcare providers (11.9%), and radio (11.9%). Overall, 37.6% were uninsured, 38.8% had chronic health conditions, and 15.4% had mental health conditions. Compared with participants in the earlier trial, Quitline participants received 1 fewer counseling session (3.8 vs 4.9, p<0.001) but were more likely to use pharmacotherapy (73.6% vs 20.9%, p<0.001). More than 90% were satisfied with the services they received. Six-month prolonged abstinence rates were higher in the Quitline than in the trial (complete case analysis: 28.6% vs 20.0%, p<0.001; intention-to-treat analysis: 20.5% vs 16.4%, p=0.005). Conclusion(s): The Asian Smokers' Quitline was utilized by >14,000 Asian-language-speaking smokers across the U.S. in its first 7 years. This quitline could serve as a model for delivering other behavioral services to geographically dispersed linguistic minority populations.

      3. The role of quitlines in tobacco cessation: An introductionexternal icon
        Glover-Kudon RM, Gates EF.
        Am J Prev Med. 2021 ;60(3):S99-S102.


      5. Exposure to nicotine and toxicants among dual users of tobacco cigarettes and e-cigarettes: Population Assessment of Tobacco and Health (PATH) Study, 2013-2014external icon
        Smith DM, Christensen C, van Bemmel D, Borek N, Ambrose B, Erives G, Niaura R, Edwards KC, Stanton CA, Blount BC, Wang L, Feng J, Jarrett JM, Ward CD, Hatsukami D, Hecht SS, Kimmel HL, Travers M, Hyland A, Goniewicz ML.
        Nicotine Tob Res. 2021 Feb 16.
        INTRODUCTION: Concurrent use of tobacco cigarettes and e-cigarettes ("dual use") is common among tobacco users. Little is known about differences in demographics and toxicant exposure among subsets of dual users. AIMS AND METHODS: We analyzed data from adult dual users (current every/some day users of tobacco cigarettes and e-cigarettes, n = 792) included in the PATH Study Wave 1 (2013-2014) and provided urine samples. Samples were analyzed for biomarkers of exposure to nicotine and selected toxicants (tobacco-specific nitrosamine NNK [NNAL], lead, cadmium, naphthalene [2-naphthol], pyrene [1-hydroxypyrene], acrylonitrile [CYMA], acrolein [CEMA], and acrylamide [AAMA]). Subsets of dual users were compared on demographic, behavioral, and biomarker measures to exclusive cigarette smokers (n = 2411) and exclusive e-cigarette users (n = 247). RESULTS: Most dual users were predominant cigarette smokers (70%), followed by daily dual users (13%), non-daily concurrent dual users (10%), and predominant vapers (7%). Dual users who smoked daily showed significantly higher biomarker concentrations compared with those who did not smoke daily. Patterns of e-cigarette use had little effect on toxicant exposure. Dual users with high toxicant exposure were generally older, female, and smoked more cigarettes per day. Dual users who had low levels of biomarkers of exposure were generally younger, male, and smoked non-daily. CONCLUSIONS: In 2013-2014, most dual users smoked cigarettes daily and used e-cigarettes occasionally. Cigarette smoking appears to be the primary driver of toxicant exposure among dual users, with little-to-no effect of e-cigarette use on biomarker levels. Results reinforce the need for dual users to stop smoking tobacco cigarettes to reduce toxicant exposure. IMPLICATIONS: With considerable dual use of tobacco cigarettes and e-cigarettes in the United States, it is important to understand differences in toxicant exposure among subsets of dual users, and how these differences align with user demographics. Findings suggest most dual users smoke daily and use e-cigarettes intermittently. Low exposure to toxicants was most common among younger users, males, and intermittent smokers; high exposure to toxicants was most common among older users, females, and heavier cigarette smokers. Results underscore the heterogeneity occurring within dual users, and the need to quit smoking cigarettes completely in order to reduce toxicant exposure.

      6. BACKGROUND: Prescribing naloxone to patients at increased opioid overdose risk is a key component of opioid overdose prevention efforts, but little is known about naloxone fills among patients receiving buprenorphine for opioid use disorder, one such high risk group. METHODS: This retrospective cross-sectional study used de-identified pharmacy claims representing 90% of all prescriptions filled at retail pharmacies in 50 states and the District of Columbia. We performed a multivariable logistic regression to examine filled naloxone prescriptions among patients receiving buprenorphine treatment and assessed how filled naloxone prescriptions vary by patient, prescriber, and community characteristics. RESULTS: Filled naloxone prescriptions occurred among 4.5% of buprenorphine treatment episodes. Episodes paid through Medicaid (aOR 2.40, 95%CI 2.33-2.47) and Medicare (aOR 1.53, 95%CI 1.46-1.60) had higher odds of filled naloxone prescriptions than commercial insurance episodes. Compared to episodes where the primary prescriber was an adult primary care physician, odds of filling a naloxone prescription were higher among episodes prescribed by addiction specialists (aOR 1.30, 95% CI 1.24-1.37) and physician assistants/nurse practitioners (aOR 1.57, 95% CI 1.53-1.61). CONCLUSIONS: Prescribing naloxone to patients receiving buprenorphine represents a tangible clinical action that can be taken to help prevent opioid overdose deaths. However, despite recommendations to co-prescribe naloxone to patients at increased risk for opioid overdose, rates of filling naloxone prescriptions remain low among patients dispensed buprenorphine. States, insurers, and health systems should consider implementing strategies to facilitate increased co-prescribing of naloxone to at-risk individuals.

      7. BACKGROUND: Naloxone co-prescribing to individuals at increased opioid overdose risk is a key component of opioid overdose prevention efforts. OBJECTIVE: Examine naloxone co-prescribing in the general population and assess how co-prescribing varies by individual and community characteristics. DESIGN: Retrospective cross-sectional study. We conducted a multivariable logistic regression of 2017-2018 de-identified pharmacy claims representing 90% of all prescriptions filled at retail pharmacies in 50 states and the District of Columbia. PATIENTS: Individuals with opioid analgesic treatment episodes > 90 days MAIN MEASURES: Outcome was co-prescribed naloxone. Predictor variables included insurance type, primary prescriber specialty, receipt of concomitant benzodiazepines, high-dose opioid episode, county urbanicity, fatal overdose rates, poverty rates, and primary care health professional shortage areas. KEY RESULTS: Naloxone co-prescribing occurred in 2.3% of long-term opioid therapy episodes. Medicaid (aOR 1.87, 95%CI 1.84 to 1.90) and Medicare (aOR 1.48, 95%CI 1.46 to 1.51) episodes had higher odds of naloxone co-prescribing than commercial insurance episodes, while cash pay (aOR 0.77, 95%CI 0.74 to 0.80) and other insurance episodes (aOR 0.81, 95%CI 0.79 to 0.83) had lower odds. Odds of naloxone co-prescribing were higher among high-dose opioid episodes (aOR 3.19, 95%CI 3.15 to 3.23), when concomitant benzodiazepines were prescribed (aOR 1.12, 95%CI 1.10 to 1.14), and in counties with higher fatal overdose rates. CONCLUSION: Co-prescription of naloxone represents a tangible clinical action that can be taken to help prevent opioid overdose deaths. However, despite recommendations to co-prescribe naloxone to patients at increased risk for opioid overdose, we found that co-prescribing rates remain low overall. States, insurers, and health systems should consider implementing strategies to facilitate increased co-prescribing of naloxone to at-risk individuals.

      8. Differences in quitline registrants' characteristics during national radio versus television antismoking campaignsexternal icon
        Zhang L, Rodes R, Mann N, Thompson J, McAfee T, Murphy R, Frank R, Davis K, Babb S.
        Am J Prev Med. 2021 March;60(3 Supplement 2):S107-S112.
        Introduction: The Centers for Disease Control and Prevention's Tips From Former Smokers campaign encourages smokers to get help with quitting smoking by promoting 1-800-QUIT-NOW. Campaign advertisements featuring an offer of help with obtaining free cessation medication aired nationally on radio for 2 weeks in 2016. Similar advertisements aired nationally on TV for 3 weeks in 2017. The comparison period of 2016 radio campaign and 2017 TV campaign was used to examine the characteristics of quitline registrants by a media referral source (TV or radio). Method(s): Data on the number and demographics of quitline registrants in 2016 and 2017 were obtained from the Centers for Disease Control and Prevention's National Quitline Data Warehouse. The investigators conducted t-tests to assess the demographic differences between registrants who heard about the quitline through the radio advertisements and those who heard about it through the TV advertisements during the comparison period. This analysis was conducted in 2019. Result(s): The registrants who heard about the quitline from radio advertisements were more likely to be male, younger, and have more years of education. However, the registrants who heard about the quitline from TV advertisements were more likely to be Black, non-Hispanic, and have fewer years of education. Conclusion(s): The findings suggest that the demographic profiles of quitline registrants vary significantly based on how registrants hear about the quitline (via radio or TV). These differences in the characteristics of registrants can help inform the tobacco control mass media purchasing strategies and may enable media efforts to target the specific subgroups of smokers in a better way.

    • Zoonotic and Vectorborne Diseases
      1. Rickettsia honei infection in a traveler returning from Indiaexternal icon
        Denison AM, Leitgeb B, Obadiah JM, Schwindt A, Ladd-Wilson SG, Paddock CD, Matkovic E.
        Open Forum Infect Dis. 2021 Feb;8(2):ofaa636.
        We report a case of Rickettsia honei infection in a US tourist returning from India and the Himalayas. This case highlights a need for awareness of various Rickettsia species endemic to India and the importance for physicians to consider rickettsial diseases in returning travelers with eschar or rash-associated febrile illnesses.


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