Issue 26, July 27, 2021

CDC Science Clips: Volume 13, Issue 26, July 27, 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.

  1. Top Articles of the Week
    Selected weekly by a senior CDC scientist from the standard sections listed below.
    The names of CDC authors are indicated in bold text.
    • Chronic Diseases and Conditions
      • Annual Report to the Nation on the Status of Cancer, Part 1: National Cancer Statisticsexternal icon
        Islami F, Ward EM, Sung H, Cronin KA, Tangka FK, Sherman RL, Zhao J, Anderson RN, Henley SJ, Yabroff KR, Jemal A, Benard VB.
        J Natl Cancer Inst. 2021 Jul 8.
        BACKGROUND: The American Cancer Society, Centers for Disease Control and Prevention, National Cancer Institute, and North American Association of Central Cancer Registries collaborate to provide annual updates on cancer incidence and mortality and trends by cancer type, sex, age group, and racial/ethnic group in the United States. In this report, we also examine trends in stage-specific survival for melanoma of the skin (melanoma). METHODS: Incidence data for all cancers from 2001 through 2017 and survival data for melanoma cases diagnosed during 2001-2014 and followed up through 2016 were obtained from the Centers for Disease Control and Prevention- and National Cancer Institute-funded population-based cancer registry programs compiled by the North American Association of Central Cancer Registries. Data on cancer deaths from 2001 through 2018 were obtained from the National Center for Health Statistics' National Vital Statistics System. Trends in age-standardized incidence and death rates and 2-year relative survival were estimated by joinpoint analysis, and trends in incidence and mortality were expressed as average annual percent change (AAPC) during the most recent 5 years (2013-2017 for incidence and 2014-2018 for mortality). RESULTS: Overall cancer incidence rates (per 100,000 population) for all ages during 2013-2017 were 487.4 among males and 422.4 among females. During this period, incidence rates remained stable among males but slightly increased in females (AAPC = 0.2%; 95% confidence interval [CI] = 0.1% to 0.2%). Overall cancer death rates (per 100,000 population) during 2014-2018 were 185.5 among males and 133.5 among females. During this period, overall death rates decreased in both males (AAPC = -2.2%; 95% CI = -2.5% to - 1.9%) and females (AAPC = -1.7%; 95% CI = -2.1% to - 1.4%); death rates decreased for 11 of the 19 most common cancers among males and for 14 of the 20 most common cancers among females, but increased for 5 cancers in each sex. During 2014-2018, the declines in death rates accelerated for lung cancer and melanoma, slowed down for colorectal and female breast cancers, and leveled off for prostate cancer. Among children younger than age 15 years and adolescents and young adults aged 15-39 years, cancer death rates continued to decrease in contrast to the increasing incidence rates. Two-year relative survival for distant-stage skin melanoma was stable for those diagnosed during 2001-2009 but increased by 3.1% (95% CI = 2.8% to 3.5%) per year for those diagnosed during 2009-2014, with comparable trends among males and females. CONCLUSIONS: Cancer death rates in the United States continue to decline overall and for many cancer types, with the decline accelerated for lung cancer and melanoma. For several other major cancers, however, death rates continue to increase or previous declines in rates have slowed or ceased. Moreover, overall incidence rates continue to increase among females, children, and adolescents and young adults. These findings inform efforts related to prevention, early detection, and treatment and for broad and equitable implementation of effective interventions, especially among under-resourced populations.

      • Examining Individual and Synergistic Contributions of PTSD and Genetics to Blood Pressure: A Trans-Ethnic Meta-Analysisexternal icon
        Sumner JA, Maihofer AX, Michopoulos V, Rothbaum AO, Almli LM, Andreassen OA, Ashley-Koch AE, Baker DG, Beckham JC, Bradley B, Breen G, Coleman JR, Dale AM, Dennis MF, Feeny NC, Franz CE, Garrett ME, Gillespie CF, Guffanti G, Hauser MA, Hemmings SM, Jovanovic T, Kimbrel NA, Kremen WS, Lawford BR, Logue MW, Lori A, Lyons MJ, Maples-Keller J, Mavissakalian MR, McGlinchey RE, Mehta D, Mellor R, Milberg W, Miller MW, Morris CP, Panizzon MS, Ressler KJ, Risbrough VB, Rothbaum BO, Roy-Byrne P, Seedat S, Smith AK, Stevens JS, van den Heuvel LL, Voisey J, Young RM, Zoellner LA, Nievergelt CM, Wolf EJ.
        Front Neurosci. 2021 ;15:678503.
        Growing research suggests that posttraumatic stress disorder (PTSD) may be a risk factor for poor cardiovascular health, and yet our understanding of who might be at greatest risk of adverse cardiovascular outcomes after trauma is limited. In this study, we conducted the first examination of the individual and synergistic contributions of PTSD symptoms and blood pressure genetics to continuous blood pressure levels. We harnessed the power of the Psychiatric Genomics Consortium-PTSD Physical Health Working Group and investigated these associations across 11 studies of 72,224 trauma-exposed individuals of European (n = 70,870) and African (n = 1,354) ancestry. Genetic contributions to blood pressure were modeled via polygenic scores (PGS) for systolic blood pressure (SBP) and diastolic blood pressure (DBP) that were derived from a prior trans-ethnic blood pressure genome-wide association study (GWAS). Results of trans-ethnic meta-analyses revealed significant main effects of the PGS on blood pressure levels [SBP: β = 2.83, standard error (SE) = 0.06, p < 1E-20; DBP: β = 1.32, SE = 0.04, p < 1E-20]. Significant main effects of PTSD symptoms were also detected for SBP and DBP in trans-ethnic meta-analyses, though there was significant heterogeneity in these results. When including data from the largest contributing study - United Kingdom Biobank - PTSD symptoms were negatively associated with SBP levels (β = -1.46, SE = 0.44, p = 9.8E-4) and positively associated with DBP levels (β = 0.70, SE = 0.26, p = 8.1E-3). However, when excluding the United Kingdom Biobank cohort in trans-ethnic meta-analyses, there was a nominally significant positive association between PTSD symptoms and SBP levels (β = 2.81, SE = 1.13, p = 0.01); no significant association was observed for DBP (β = 0.43, SE = 0.78, p = 0.58). Blood pressure PGS did not significantly moderate the associations between PTSD symptoms and blood pressure levels in meta-analyses. Additional research is needed to better understand the extent to which PTSD is associated with high blood pressure and how genetic as well as contextual factors may play a role in influencing cardiovascular risk.

    • Communicable Diseases
      • Prevalence of syphilis among men who have sex with men: a global systematic review and meta-analysis from 2000-20external icon
        Tsuboi M, Evans J, Davies EP, Rowley J, Korenromp EL, Clayton T, Taylor MM, Mabey D, Chico RM.
        Lancet Glob Health. 2021 Jul 8.
        BACKGROUND: The WHO Global Health Sector Strategy aims to reduce worldwide syphilis incidence by 90% between 2018 and 2030. If this goal is to be achieved, interventions that target high-burden groups, including men who have sex with men (MSM), will be required. However, there are no global prevalence estimates of syphilis among MSM to serve as a baseline for monitoring or modelling disease burden. We aimed to assess the global prevalence of syphilis among MSM using the available literature. METHODS: In this global systematic review and meta-analysis, we searched MEDLINE, Embase, LILACS, and AIM databases, and Integrated Bio-Behavioral Surveillance (IBBS) reports between April 23, 2019, and Feb 1, 2020, to identify studies done between Jan 1, 2000, and Feb 1, 2020, with syphilis point prevalence data measured by biological assay among MSM (defined as people who were assigned as male at birth and had oral or anal sex with at least one other man in their lifetime). Studies were excluded if participants were exclusively HIV-infected MSM, injection-drug users, only seeking care for sexually transmitted infections (STIs) or genital symptoms, or routine STI clinic attendees. Data were extracted onto standardised forms and cross-checked for accuracy and validity. We used random-effects models to generate pooled prevalence estimates across the eight regions of the Sustainable Development Goals. We calculated risk of study bias based on the Appraisal tool for Cross-Sectional Studies, and stratified results based on low versus high risk of bias. This systematic review and meta-analysis was registered with PROSPERO, CRD42019144594. FINDINGS: We reviewed 4339 records, 228 IBBS reports, and ten articles from other sources. Of these, 1301 duplicate records were excluded, 2467 records were excluded after title and abstract screening, and 534 articles were excluded after full-text analysis. We identified 345 prevalence data points from 275 studies across 77 countries, with a total of 606 232 participants. Global pooled prevalence from 2000-20 was 7·5% (95% CI 7·0-8·0%), ranging from 1·9% (1·0-3·1%) in Australia and New Zealand to 10·6% (8·5-12·9%) in Latin America and the Caribbean. INTERPRETATION: Unacceptably high syphilis prevalence among MSM warrants urgent action. FUNDING: Wellcome Trust.

    • Genetics and Genomics
      • Species and subspecies within the Salmonella genus have been defined for public health purposes by biochemical properties; however, reference laboratories have increasingly adopted sequence-based, and especially whole genome sequence (WGS), methods for surveillance and routine identification. This leads to potential disparities in subspecies definitions, routine typing, and the ability to detect novel subspecies. A large-scale analysis of WGS data from the routine sequencing of clinical isolates was employed to define and characterise Salmonella subspecies population structure, demonstrating that the Salmonella species and subspecies were genetically distinct, including those previously identified through phylogenetic approaches, namely: S. enterica subspecies londinensis (VII), subspecies brasiliensis (VIII), subspecies hibernicus (IX), and subspecies essexiensis (X). The analysis also identified an additional novel subspecies, reptilium (XI). Further, these analyses indicated that S. enterica subspecies IIIa isolates were divergent from the other S. enterica subspecies, which clustered together and, on the basis of ANI analysis, subspecies IIIa was sufficiently distinct to be classified as a separate species, S. arizonae. Multiple phylogenetic and statistical approaches generated congruent results, suggesting that the proposed species and subspecies structure was sufficiently biologically robust for routine application. Biochemical analyses demonstrated that not all subspecies were distinguishable by these means and that biochemical approaches did not capture the genomic diversity of the genus. We recommend the adoption of standardised genomic definitions of species and subspecies and a genome sequence-based approach to routine typing for the identification and definition of novel subspecies.

    • Global Health
      • OBJECTIVE: To describe medical tourism among a subset of US residents; identify possible indicators for medical tourism. METHODS: The US Centers for Disease Control and Prevention collaborated with 11 states and territories to ask 6 questions about medical tourism, using the Behavioral Risk Factor Surveillance System. Data collected from January 1, 2016, through December 31, 2016, included whether respondents traveled internationally for preplanned care, travel reasons and destinations, procedures received, and occurrence and treatment of complications. A descriptive analysis of demographics, socioeconomic status and health access variables was performed, and a regression model with a log-link function and Poisson distribution was used to estimate prevalence ratios (PR) for medical tourism. RESULTS: Of 93,492 respondents, 517 (0.55%) traveled internationally during the previous year for care. Mexico was the most common destination (41% of trips). Dentistry accounted for 55% of treatments. Complications from care received abroad were reported by 5% of medical tourists; 67% sought care upon returning to the United States. The prevalence of medical tourism was 1.32% (95% CI, 1.00-1.64). The prevalence of medical tourism was higher in Hispanics and non-whites (PR, 3.97; 95% CI, 2.48-6.32) and higher among those without current health insurance (PR, 2.70; 95% CI, 1.69-4.34). CONCLUSIONS: This is the largest collection of population-based surveillance data describing medical tourism among US residents from multiple states and territories. Understanding the demographic and socioeconomic factors associated with medical tourism can inform evidence-based recommendations for travelers and clinicians who may advise or care for these individuals before, during, or after travel.

    • Healthcare Associated Infections
      • The role of interspecies recombinations in the evolution of antibiotic resistant pneumococciexternal icon
        D'Aeth JC, van der Linden MP, McGee L, De Lencastre H, Turner P, Song JH, Lo SW, Gladstone RA, Sa-Leao R, Ko KS, Hanage WP, Breiman RF, Beall B, Bentley SD, Croucher NJ.
        Elife. 2021 Jul 14;10.
        Multidrug-resistant Streptococcus pneumoniae emerge through the modification of core genome loci through short inter-species homologous recombinations and acquisition of gene cassettes. Both occurred in the otherwise contrasting histories of the antibiotic-resistant S. pneumoniae lineages PMEN3 and PMEN9. A single PMEN3 clade spread globally, evading vaccine-induced immunity through frequent serotype switching, whereas locally-circulating PMEN9 clades independently gained resistance. Both lineages repeatedly integrated Tn916 and Tn1207.1, conferring tetracycline and macrolide resistance respectively, through homologous recombination importing sequences originating in other species. A species-wide dataset found over 100 instances of such interspecific acquisitions of resistance cassettes and flanking homologous arms. Phylodynamic analysis of the most commonly-sampled Tn1207.1 insertion in PMEN9, originating from a commensal and disrupting a competence gene, suggested its expansion across Germany was driven by a high ratio of macrolide-to-β-lactam consumption. Hence selection from antibiotic consumption was sufficient for these atypically large recombinations to overcome species boundaries across the pneumococcal chromosome.

    • Immunity and Immunization
      • Implementation of quality improvement coaching versus physician communication training for improving human papillomavirus vaccination in primary care: a randomized implementation trialexternal icon
        Grabert BK, Kurtzman R, Heisler-MacKinnon J, Leeman J, Bjork A, Kameny M, Liu A, Todd K, Alton Dailey S, Smith K, Brewer NT, Gilkey MB.
        Transl Behav Med. 2021 Jul 9.
        Many US health departments (HDs) conduct in-person quality improvement (QI) coaching to help primary care clinics improve their HPV vaccine delivery systems and communication. Some HDs additionally conduct remote communication training to help vaccine prescribers recommend HPV vaccination more effectively. Our aim was to compare QI coaching and communication training on key implementation outcomes. In a cluster randomized trial, we offered 855 primary care clinics: 1) QI coaching; 2) communication training; or 3) both interventions combined. In each trial arm, we assessed adoption (proportion of clinics receiving the intervention), contacts per clinic (mean number of contacts needed for one clinic to adopt intervention), reach (median number of participants per clinic), and delivery cost (mean cost per clinic) from the HD perspective. More clinics adopted QI coaching than communication training or the combined intervention (63% vs 16% and 12%, both p < .05). QI coaching required fewer contacts per clinic than communication training or the combined intervention (mean = 4.7 vs 29.0 and 40.4, both p < .05). Communication training and the combined intervention reached more total staff per clinic than QI coaching (median= 5 and 5 vs 2, both p < .05), including more prescribers (2 and 2 vs 0, both p < .05). QI coaching cost $439 per adopting clinic on average, including follow up ($129/clinic), preparation ($73/clinic), and travel ($69/clinic). Communication training cost $1,287 per adopting clinic, with most cost incurred from recruitment ($653/clinic). QI coaching was lower cost and had higher adoption, but communication training achieved higher reach, including to influential vaccine prescribers. Our cluster randomized trial compared two interventions that health departments commonly use to increase HPV vaccination coverage: quality improvement (QI) coaching and physician communication training. We found that QI coaching cost less and was more often adopted by primary care clinics, but communication training reached more staff members per clinic, including vaccine prescribers. Findings provide health departments with data needed to weigh the implementation strengths and challenges of QI coaching and physician communication training for increasing HPV vaccination coverage. eng

    • Nutritional Sciences
      • Use of mid-upper arm circumference to screen for thinness among sub-Saharan African male detaineesexternal icon
        Philpott DC, Belchior-Bellino V, Ververs M.
        Public Health Nutr. 2021 Jul 12:1-24.
        OBJECTIVE: Body mass index (BMI) is a time-intensive measurement to assess nutritional status. Mid-upper arm circumference (MUAC) has been studied as a proxy for BMI in adults, but there is no consensus on its optimal use. DESIGN: We calculated sensitivity, specificity, and area under receiver operating characteristic curve (AUROCC) of MUAC for BMI <18.5, <17, and <16 kg/m2. We designed a system using two MUAC cutoffs, with a healthy (non-thin) "green" group, a "yellow" group requiring BMI measurement, and a "red" group who could proceed directly to treatment for thinness. SETTING: We retrospectively analyzed monitoring data collected by the International Committee of the Red Cross in places of detention. PARTICIPANTS: 11,917 male detainees in eight African countries. RESULTS: MUAC had excellent discriminatory ability with AUROCC: 0.87, 0.90, and 0.92 for BMI<18.5, BMI<17, and BMI<16 kg/m2, respectively. An upper cutoff of MUAC 25.5 cm to exclude healthy detainees would result in 64% fewer detainees requiring BMI screening and had sensitivity 77% (95%CI 69.4,84.7) and specificity 79.6 (95%CI: 72.6,86.5) for BMI<18.5 kg/m2. A lower cutoff of MUAC<21.0 cm had sensitivity 25.4% (95%CI: 11.7,39.1) and specificity 99.0% (97.9,100.0) for BMI<16 kg/m2. An additional 50kg weight requirement improved specificity to 99.6% (95%CI: 99.0,100.0%) with similar sensitivity. CONCLUSIONS: A MUAC cutoff of 25.5 cm, above which detainees are classified as healthy and below receive further screening would result in significant time savings. A cutoff of <21.0 cm and weight <50 kg can identify some detainees with BMI <16 kg/m2 who require immediate treatment.

    • Reproductive Health
      • Sexual and Reproductive Health Discussions During Preventive Visitsexternal icon
        Sieving RE, McRee AL, Mehus C, Gewirtz O'Brien JR, Wang S, Brar P, Catallozzi M, Gorzkowski J, Grilo S, Kaseeska K, Santelli J, Steiner RJ, Klein JD.
        Pediatrics. 2021 Jul 12.
        OBJECTIVES: To quantify adolescent- and parent-perceived importance of provider-adolescent discussions about sexual and reproductive health (SRH), describe prevalence of provider confidentiality practices and provider-adolescent discussions about SRH topics during preventive visits, and identify missed opportunities for such conversations. METHODS: We used data from a national Internet survey of 11- to 17-year-old adolescents and their parents. Data were weighted to represent the noninstitutionalized US adolescent population. Adolescents who had a preventive visit in the past 2 years and their parents reported on perceived importance of provider-adolescent discussions about SRH topics: puberty, safe dating, gender identity, sexual orientation, sexual decision-making, sexually transmitted infections and HIV, methods of birth control, and where to get SRH services. Adolescents and parents reported whether they had ever discussed confidentiality with the adolescent's provider. Adolescents reported experiences at their most recent preventive visit, including whether a provider spoke about specific SRH topics and whether they had time alone with a provider. RESULTS: A majority of adolescents and parents deemed provider-adolescent discussions about puberty, sexually transmitted infections and HIV, and birth control as important. However, fewer than one-third of adolescents reported discussions about SRH topics other than puberty at their most recent preventive visit. These discussions were particularly uncommon among younger adolescents. Within age groups, discussions about several topics varied by sex. CONCLUSIONS: Although most parents and adolescents value provider-adolescent discussions of selected SRH topics, these discussions do not occur routinely during preventive visits. Preventive visits represent a missed opportunity for adolescents to receive screening, education, and guidance related to SRH.

    • Substance Use and Abuse
      • Adverse Birth Outcomes Associated With Prepregnancy and Prenatal Electronic Cigarette Useexternal icon
        Regan AK, Bombard JM, O'Hegarty MM, Smith RA, Tong VT.
        Obstet Gynecol. 2021 Jul 1;138(1):85-94.
        OBJECTIVE: To evaluate the risk of adverse birth outcomes among adults who use electronic cigarettes (e-cigarettes) before and during pregnancy. METHODS: Data from the 2016-2018 PRAMS (Pregnancy Risk Assessment Monitoring System) were used to assess the association between e-cigarette use during the 3 months before and last 3 months of pregnancy among 79,176 individuals with a recent live birth and the following birth outcomes: preterm birth, small for gestational age, and low birth weight (LBW). Adjusted prevalence ratios were generated using average marginal predictions from multivariable logistic regression models. Models were stratified by prenatal combustible cigarette smoking and frequency of e-cigarette use (daily or less than daily use). RESULTS: In the 3 months before pregnancy, 2.7% (95% CI 2.6-2.9%) of respondents used e-cigarettes; 1.1% (95% CI 1.0-1.2%) used e-cigarettes during the last 3 months of pregnancy. Electronic cigarette use before pregnancy was not associated with adverse birth outcomes. Electronic cigarette use during pregnancy was associated with increased prevalence of LBW compared with nonuse (8.1% vs 6.1%; adjusted prevalence ratio 1.33; 95% CI 1.06-1.66). Among respondents who did not also smoke combustible cigarettes during pregnancy (n=72,256), e-cigarette use was associated with higher prevalence of LBW (10.6%; adjusted prevalence ratio 1.88; 95% CI 1.38-2.57) and preterm birth (12.4%; adjusted prevalence ratio 1.69; 95% CI 1.20-2.39). When further stratified by frequency of e-cigarette use, associations were seen only for daily users. CONCLUSION: E-cigarette use during pregnancy, particularly when used daily by individuals who do not also smoke combustible cigarettes, is associated with adverse birth outcomes.

    • Zoonotic and Vectorborne Diseases
      • Knowledge gaps in the epidemiology of severe dengue impede vaccine evaluationexternal icon
        Sharp TM, Anderson KB, Katzelnick LC, Clapham H, Johansson MA, Morrison AC, Harris E, Paz-Bailey G, Waterman SH.
        Lancet Infect Dis. 2021 Jul 12.
        The most severe consequences of dengue virus infection include shock, haemorrhage, and major organ failure; however, the frequency of these manifestations varies, and the relative contribution of pre-existing anti-dengue virus antibodies, virus characteristics, and host factors (including age and comorbidities) are not well understood. Reliable characterisation of the epidemiology of severe dengue first depends on the use of consistent definitions of disease severity. As vaccine trials have shown, severe dengue is a crucial interventional endpoint, yet the infrequency of its occurrence necessitates the inclusion of thousands of study participants to appropriately compare its frequency among participants who have and have not been vaccinated. Hospital admission is frequently used as a proxy for severe dengue; however, lack of specificity and variability in clinical practices limit the reliability of this approach. Although previous infection with a dengue virus is the best characterised risk factor for developing severe dengue, the influence of the timing between dengue virus infections and the sequence of dengue virus infections on disease severity is only beginning to be elucidated. To improve our understanding of the diverse factors that shape the clinical spectrum of disease resulting from dengue virus infection, prospective, community-based and clinic-based immunological, virological, genetic, and clinical studies across a range of ages and geographical regions are needed.

  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. Incidence and mortality of cancers of the biliary tract by sex, age, race/ethnicity, and stage at diagnosis-United States, 2013-2017external icon
        Ellington TD, Momin B, Wilson RJ, Henley SJ, Wu M, Ryerson AB.
        Cancer Epidemiol Biomarkers Prev. 2021 Jul 8.
        BACKGROUND: Few population-based studies have examined incidence and mortality of cancers of the biliary tract, including intrahepatic bile duct, extrahepatic bile duct, ampulla of Vater, and overlapping or other lesion of the biliary tract in one study. METHODS: To further the understanding of recent rates of biliary tract cancers, we used population-based data, to examine incidence and mortality during 2013-2017. We examined how rates varied by sex, age, race/ethnicity, U.S. census region, and stage at diagnosis. RESULTS: Intrahepatic bile duct was the most common biliary tract cancer with an incidence rate of 1.49 per 100,000 persons. Cancer incidence rates per 100,000 persons were 0.96 for extrahepatic bile duct, 0.45 for ampulla of Vater, and 0.24 for overlapping or other lesion of the biliary tract. Cancer death rates per 100,000 persons were 1.66 for intrahepatic bile duct and 0.45 for other biliary tract. Intrahepatic bile duct incidence and death rates were higher among males than females, higher among Hispanic and Asian and Pacific Islander persons compared to non-Hispanic Whites, and higher in the Northeast and in urban counties. CONCLUSION: This report provides national estimates of these rare biliary tract cancers. IMPACT: Key interventions targeted to high-risk populations may help reduce incidence and mortality of cancers of the biliary tract by improving primary prevention through strategies to reduce tobacco and alcohol use, control overweight and obesity, and promote hepatitis B vaccination and use of syringe service programs meant to curb the transmission of infectious diseases such as viral hepatitis.

      2. The Prevalence of Knee Symptoms, Radiographic, and Symptomatic Osteoarthritis at Four Time Points: The Johnston County Osteoarthritis Project, 1999-2018external icon
        Nelson AE, Hu D, Arbeeva L, Alvarez C, Cleveland RJ, Schwartz TA, Murphy LB, Helmick CG, Callahan LF, Renner JB, Jordan JM, Golightly YM.
        ACR Open Rheumatol. 2021 Jul 10.
        OBJECTIVE: To describe point prevalence of knee symptoms, radiographic knee osteoarthritis (rKOA), severe rKOA, and symptomatic rKOA at four time points in the longitudinal, population-based Johnston County Osteoarthritis Project (JoCo OA). METHODS: Data were from 2573 JoCo OA participants with up to 18 years of follow-up (1999-2018) and standardized fixed-flexion knee radiographs read by a single, reliable expert musculoskeletal radiologist. The four outcomes were 1) self-reported knee symptoms, defined by "On most days, do you have pain, aching, or stiffness in your right/left knee?"; 2) rKOA, defined as a Kellgren-Lawrence grade (KLG) of 2 to 4); 3) severe rKOA, defined as a KLG of 3 or 4; and 4) symptomatic rKOA, defined as both symptoms and rKOA in the same joint. Weighted prevalence estimates and 95% confidence intervals (CIs) were generated overall and by age group, sex, race, and body mass index (BMI). RESULTS: Most recently (2017-2018, T4), the overall prevalence (percentage) of knee symptoms, rKOA, severe rKOA, and symptomatic rKOA was 41% (95% CI: 35-47%), 61% (95% CI: 56-67%), 35% (95% CI: 30-40%), and 30% (95% CI: 24-35%), respectively. From time point T1 to T4, prevalence increased for rKOA, severe rKOA, and symptomatic rKOA but not for knee symptoms. The prevalence of both severe rKOA (17-39%) and symptomatic rKOA (23-30%) was consistently higher among women. The prevalence of all outcomes was higher among those with higher BMI and among Black participants at all time points, particularly rKOA (35-69%) and severe rKOA (22-46%). CONCLUSION: These updated estimates demonstrate a large and increasing burden of knee OA, particularly among women and Black individuals.

      3. Sleep duration and quality among U.S. adults with epilepsy: National Health Interview Survey 2013, 2015, and 2017external icon
        Tian N, Wheaton AG, Zack M, Croft JB, Greenlund KJ.
        Epilepsy Behav. 2021 Jul 10;122:108194.
        BACKGROUND: Epilepsy is associated with a high prevalence of sleep disturbance. However, population-based studies on the burden of sleep disturbance in people with epilepsy are limited. This study assessed sleep duration and sleep quality by epilepsy status in the general U.S. adult population aged ≥ 18 years. METHODS: We pooled data of cross-sectional National Health Interview Surveys in 2013, 2015, and 2017 to compare the prevalence of sleep duration and quality among those without epilepsy (N = 93,126) with those with any epilepsy (a history of physician-diagnosed epilepsy) (N = 1774), those with active epilepsy (those with a history of physician-diagnosed epilepsy who were currently taking medication to control it, had one or more seizures in the past year, or both) (N = 1101), and those with inactive epilepsy (those with a history of physician-diagnosed epilepsy who were neither taking medication for epilepsy nor had had a seizure in the past year) (N = 673). We also compared these measures between those with active and those with inactive epilepsy. The prevalences were adjusted for sociodemographics, behaviors, and health covariates, with multivariable logistic regression. We used Z-tests to compare prevalences of sleep duration and quality at the statistical significance level of 0.05. RESULTS: Adults with any epilepsy reported significantly higher adjusted prevalences of short sleep duration (<7 h) (36.0% vs. 31.8%) and long sleep duration (>9 h per day) (6.7% vs. 3.7%) but a lower prevalence of healthy sleep duration (7-9 h per day) (57.4% vs.64.6%) than those without epilepsy. In the past week, adults with any epilepsy reported significantly higher adjusted prevalences than adults without epilepsy of having trouble falling asleep (25.0% vs. 20.3%), staying asleep (34.4% vs. 26.3%), nonrestorative sleep (adults did not wake up feeling well rested) (≥3days) (50.3% vs. 44.3%), and taking medication to help themselves fall asleep or stay asleep (≥1 times) (20.9% vs. 13.5%). However, adults with active epilepsy did not differ from adults with inactive epilepsy with respect to these sleep duration and quality measures. CONCLUSIONS: Adults with epilepsy reported more short or long sleep duration and worse sleep quality than those without epilepsy. Neither seizure occurrence nor antiepileptic drug use accounted for these differences in sleep duration and quality. Careful screening for sleep complaints as well as identifying and intervening on the modifiable risk factors associated with sleep disturbances among people with epilepsy could improve epilepsy outcomes and quality of life.

      4. Changes in mood and health-related quality of life in Look AHEAD 6 years after termination of the lifestyle interventionexternal icon
        Wadden TA, Chao AM, Anderson H, Annis K, Atkinson K, Bolin P, Brantley P, Clark JM, Coday M, Dutton G, Foreyt JP, W. Gregg E, Hazuda HP, Hill JO, Hubbard VS, Jakicic JM, Jeffery RW, Johnson KC, Kahn SE, Knowler WC, Korytkowski M, Lewis CE, Laferrère B, Middelbeek RJ, Munshi MN, Nathan DM, Neiberg RH, Pilla SJ, Peters A, Pi-Sunyer X, Rejeski JW, Redmon B, Stewart T, Vaughan E, Wagenknecht LE, Walkup MP, Wing RR, Wyatt H, Yanovski SZ, Zhang P.
        Obesity (Silver Spring). 2021 Jul 14.
        OBJECTIVE: The Action for Health in Diabetes (Look AHEAD) study previously reported that intensive lifestyle intervention (ILI) reduced incident depressive symptoms and improved health-related quality of life (HRQOL) over nearly 10 years of intervention compared with a control group (the diabetes support and education group [DSE]) in participants with type 2 diabetes and overweight or obesity. The present study compared incident depressive symptoms and changes in HRQOL in these groups for an additional 6 years following termination of the ILI in September 2012. METHODS: A total of 1,945 ILI participants and 1,900 DSE participants completed at least one of four planned postintervention assessments at which weight, mood (via the Patient Health Questionnaire-9), antidepressant medication use, and HRQOL (via the Medical Outcomes Scale, Short Form-36) were measured. RESULTS: ILI participants and DSE participants lost 3.1 (0.3) and 3.8 (0.3) kg [represented as mean (SE); p = 0.10], respectively, during the 6-year postintervention follow-up. No significant differences were observed between groups during this time in incident mild or greater symptoms of depression, antidepressant medication use, or in changes on the physical component summary or mental component summary scores of the Short Form-36. In both groups, mental component summary scores were higher than physical component summary scores. CONCLUSIONS: Prior participation in the ILI, compared with the DSE group, did not appear to improve subsequent mood or HRQOL during 6 years of postintervention follow-up.

    • Communicable Diseases
      1. In contrast to a robust literature on known pathogenic fungi such as Cryptococcus and Aspergillus species that cause pulmonary infections, reports of the uncommon genus Sporopachydermia causing infections are very limited. We present the first case report describing the fungus, Sporopachydermia lactativora as a likely cause of pneumonia in a patient with a history of polysubstance abuse and injection drug use (IDU). The patient recovered following antifungal treatment. The organism was recovered from a blood culture, 3 days post collection. Although CHROMagar was of little value, only yeast-like organisms were observed on cornmeal agar. The organism was not in the matrix-assisted laser desorption/ionization—time of flight (MALDI-TOF) mass spectrometry database. Definitive identification was achieved using the ribosomal DNA (rDNA) sequence analysis by targeting the ITS1 (internal transcribed spacer 1) region. This case report is intended to promote awareness of this fungus as a potential pathogen, by providing new information that has not yet been reported in the literature, and prompts physician awareness to suspect a fungal infection when managing patients with a history of IDU as a potential source of unique environmental organisms not previously encountered, warranting more comprehensive diagnosis and treatment options.

      2. Initial implementation of PrEP in Zambia: health policy development and service delivery scale-upexternal icon
        Claassen CW, Mumba D, Njelesani M, Nyimbili D, Mwango LK, Mwitumwa M, Mubanga E, Mulenga LB, Chisenga T, Nichols BE, Hendrickson C, Chitembo L, Okuku J, O'Bra H.
        BMJ Open. 2021 Jul 9;11(7):e047017.
        INTRODUCTION: Daily pre-exposure prophylaxis (PrEP) for HIV prevention is highly effective, but not yet widely deployed in sub-Saharan Africa. We describe how Zambia developed PrEP health policy and then successfully implemented national PrEP service delivery. POLICY DEVELOPMENT: Zambia introduced PrEP as a key strategy for HIV prevention in 2016, and established a National PrEP Task Force to lead policy advocacy and development. The Task Force was composed of government representatives, regulatory agencies, international donors, implementation partners and civil society organisations. Following an implementation pilot, PrEP was rolled out nationally using risk-based criteria alongside a national HIV prevention campaign. NATIONAL SCALE-UP: In the first year of implementation, ending September 2018, 3626 persons initiated PrEP. By September 2019, the number of people starting PrEP increased by over sixfold to 23 327 persons at 728 sites across all ten Zambian provinces. In the first 2 years, 26 953 clients initiated PrEP in Zambia, of whom 31% were from key and priority populations. Continuation remains low at 25% and 11% at 6 and 12 months, respectively. LESSONS LEARNT: Risk-based criteria for PrEP ensures access to those most in need of HIV prevention. Healthcare worker training in PrEP service delivery and health needs of key and priority populations is crucial. PrEP expansion into primary healthcare clinics and community education is required to reach full potential. Additional work is needed to understand and address low PrEP continuation. Finally, a task force of key stakeholders can rapidly develop and implement health policy, which may serve as a model for countries seeking to implement PrEP.

      3. Effectiveness of HIV Stigma Interventions for Men who have Sex with Men (MSM) With and Without HIV in the United States: A Systematic Review and Meta-Analysesexternal icon
        Gunn JK, Rooks-Peck C, Wichser ME, Denard C, McCree DH, Jeffries WL, DeLuca JB, Ross LW, Herron A, Barham T, Flores SA, Higa DH.
        AIDS Behav. 2021 Jul 14.
        Stigma may contribute to HIV disparities for men who have sex with men (MSM). This systematic review quantified the effects of HIV stigma interventions for MSM on stigma and sex risk. We conducted a systematic search to identify US-based studies published between 2000 and June 2019 focused on HIV and MSM, and either measured stigma pre-post or included a stigma intervention component. Twenty-nine articles, representing 26 unique studies met inclusion criteria. Random effect models showed no intervention effect for reducing stigma and a non-significant increase in HIV testing. Significant decreases in condomless sex with males, condomless sex with females, and substance-influenced sex were found. Few intervention studies measured stigma pre-post. Findings suggest that including a stigma reduction component in interventions can improve HIV testing and reduce sex risk for MSM. Developing interventions to address stigma may be important in decreasing HIV infection among MSM and ending the HIV epidemic.

      4. STI epidemiology and care in rural areas: a narrative reviewexternal icon
        Jenkins WD, Williams L, Pearson WS.
        Sex Transm Dis. 2021 Jul 15.
        BACKGROUND: Though rural areas contain approximately 19% of the US population, little research has explored sexually transmitted infection (STI) risk and how urban-developed interventions may be suitable in more population-thin areas. While STI rates vary across rural areas, these areas share diminishing access to screening and limited rural-specific testing of STI interventions. METHODS: This narrative review utilizes a political ecology model of health, and explores four domains influencing STI risk and screening: epidemiology; health services; political and economic; and social. Articles describing aspects of rural STI epidemiology, screening access and use, and intervention utility within these domains were found by a search of PubMed. RESULTS: Epidemiology contributes to risk via multiple means, such as the presence of increased-risk populations and the at-times disproportionate impact of the opioid /drug use epidemic. Rural health services are diminishing in quantity, often have lesser accessibility, and may be stigmatizing to those needing services. Local political and economic influences include funding decisions, variable enforcement of laws/statutes, and systemic prevention of harm reduction services. Social norms such as stigma and discrimination can prevent individuals from seeking appropriate care, and also lessen individual self-efficacy to reduce personal risk. CONCLUSION: STI in rural areas is significant in scope, and facing diminished prevention opportunities and resources. While many STI interventions have been developed and piloted, few have been tested to scale or operationalized in rural areas. By considering rural STI risk reduction within a holistic model, purposeful exploration of interventions tailored to rural environments may be explored.

      5. Sero-surveillance for SARS-CoV-2 infection among healthcare providers in four hospitals in Thailand one year after the first community outbreakexternal icon
        Kittikraisak W, Piyaraj P, Vachiraphan A, Wongrapee T, Punjasamanvong S, Hunsawong T, Sinthuwattanawibool C, Leepiyasakulchai C, Yoocharoen P, Azziz-Baumgartner E, Mott JA, Chottanapund S.
        PLoS One. 2021 ;16(7):e0254563.
        BACKGROUND: Thailand was the first country outside China to report SARS-CoV-2 infected cases. Since the detection of the first imported case on January 12th, 2020 to the time this report was written, Thailand experienced two waves of community outbreaks (March-April 2020 and December 2020-March 2021). We examined prevalence of SARS-CoV-2 seropositivity among healthcare providers (HCPs) in four hospitals approximately one year after SARS-CoV-2 first detected in Thailand. By March 2021, these hospitals have treated a total of 709 coronavirus disease 2019 (COVID-19) patients. METHODS: Blood specimens, collected from COVID-19 unvaccinated HCPs during January-March 2021, were tested for the presence of SARS-CoV-2 immunoglobulin G (IgG) antibodies to nucleocapsid (IgG-nucleocapsid) and spike (IgG-spike) proteins using Euroimmune® enzyme-linked immunosorbent assays. RESULTS: Of 600 HCPs enrolled, 1 (0.2%) tested positive for the SARS-CoV-2 IgG-spike antibodies, but not the IgG-nucleocapsid. CONCLUSION: The presence of SARS-CoV-2 IgG antibodies was rare in this sample of HCPs, suggesting that this population remains susceptible to SARS-CoV-2 infection.

      6. A New Call to Action to Combat an Old Nemesis: Addressing Rising Congenital Syphilis Rates in the United Statesexternal icon
        Machefsky AM, Loosier PS, Cramer R, Bowen VB, Kersh EN, Tao G, Gift TL, Hogben M, Carry M, Ludovic JA, Thorpe P, Bachmann LH.
        J Womens Health (Larchmt). 2021 Jul;30(7):920-926.
        Congenital syphilis (CS) is on the rise in the United States and is a growing public health concern. CS is an infection with Treponema pallidum in an infant or fetus, acquired via transplacental transmission when a pregnant woman has untreated or inadequately treated syphilis. Pregnant women with untreated syphilis are more likely to experience pregnancies complicated by stillbirth, prematurity, low birth weight, and early infant death, while their children can develop clinical manifestations of CS such as hepatosplenomegaly, bone abnormalities, developmental delays, and hearing loss. One of the ways CS can be prevented is by identifying and treating infected women during pregnancy with a benzathine penicillin G regimen that is both appropriate for the maternal stage of syphilis and initiated at least 30 days prior to delivery. In this article we discuss many of the challenges faced by both public health and healthcare systems with regards to this preventable infection, summarize missed opportunities for CS prevention, and provide practical solutions for future CS prevention strategies.

      7. Annual home-based HIV testing in the Chókwè Health Demographic Surveillance System, Mozambique, 2014 to 2019: serial population-based survey evaluationexternal icon
        MacKellar D, Thompson R, Nelson R, Casavant I, Pals S, Bonzela J, Jaramillo A, Cardoso J, Ujamaa D, Tamele S, Chivurre V, Malimane I, Pathmanathan I, Heitzinger K, Wei S, Couto A, Vergara A.
        J Int AIDS Soc. 2021 Jul;24(7):e25762.
        INTRODUCTION: WHO recommends implementing a mix of community and facility testing strategies to diagnose 95% of persons living with HIV (PLHIV). In Mozambique, a country with an estimated 506,000 undiagnosed PLHIV, use of home-based HIV testing services (HBHTS) to help achieve the 95% target has not been evaluated. METHODS: HBHTS was provided at 20,000 households in the Chókwè Health Demographic Surveillance System (CHDSS), Mozambique, in annual rounds (R) during 2014 to 2019. Trends in prevalence of HIV infection, prior HIV diagnosis among PLHIV (diagnostic coverage), and undiagnosed HIV infection were assessed with three population-based surveys conducted in R1 (04/2014 to 04/2015), R3 (03/2016 to 12/2016), and R5 (04/2018 to 03/2019) of residents aged 15 to 59 years. Counts of patients aged ≥15 years tested for HIV in CHDSS healthcare facilities were obtained from routine reports. RESULTS: During 2014 to 2019, counsellors conducted 92,512 home-based HIV tests and newly diagnosed 3711 residents aged 15 to 59 years. Prevalence of HIV infection was stable (R1, 25.1%; R3 23.6%; R5 22.9%; p-value, 0.19). After the first two rounds (44,825 home-based tests; 31,717 facility-based tests), diagnostic coverage increased from 73.8% (95% CI 70.3 to 77.2) in R1 to 93.0% (95% CI 91.3 to 94.7) in R3, and prevalence of undiagnosed HIV infection decreased from 6.6% (95% CI 5.6 to 7.5) in R1 to 1.7% (95% CI 1.2 to 2.1) in R3. After two more rounds (32,226 home-based tests; 46,003 facility-based tests), diagnostic coverage was 95.4% (95% CI 93.7 to 97.1) and prevalence of undiagnosed HIV infection was 1.1% (95% CI 0.7 to 1.5) in R5. Prevalence of having last tested at home was 12.7% (95% CI 11.3 to 14.0) in R1, 45.2% (95% CI 43.4 to 47.0) in R3, and 41.4% (95% CI 39.5 to 43.2) in R5, and prevalence of having last tested at a healthcare facility was 45.3% (95% CI 43.3 to 47.3) in R1, 40.1% (95% CI 38.4 to 41.8) in R3, and 45.2% (95% CI 43.3 to 47.0) in R5. CONCLUSIONS: HBHTS successfully augmented facility-based testing to achieve HIV diagnostic coverage in a high-burden community of Mozambique. HBHTS should be considered in sub-Saharan Africa communities striving to diagnose 95% of persons living with HIV.

      8. Hepatitis B prevalence association with sexually transmitted infections: a systematic review and meta-analysisexternal icon
        Marseille E, Harris AM, Horvath H, Parriott A, Malekinejad M, Nelson NP, Van Handel M, Kahn JG.
        Sex Health. 2021 Jul;18(3):269-279.
        Background Hepatitis B vaccination is recommended for persons with current or past sexually transmitted infections (STI). Our aim is to systematically assess the association of hepatitis B virus (HBV) sero-markers for current or past infection with syphilis, chlamydia, gonorrhoea, or unspecified STIs. METHODS: We conducted a systematic review and meta-analysis. PubMed, Embase, and Web of Science from 1982 to 2018 were searched using medical subject headings (MeSH) terms for HBV, STIs and epidemiology. We included studies conducted in Organisation for Economic Cooperation and Development countries or Latin America that permit the calculation of prevalence ratios (PRs) for HBV and STIs and extracted PRs and counts by HBV and STI status. RESULTS: Of 3144 identified studies, 43 met inclusion requirements, yielding 72 PRs. We stratified outcomes by HBV sero-markers [surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), combined], STI pathogen (syphilis, gonorrhoea/chlamydia, unspecified), and STI history (current, past) resulting in 18 potential outcome groups, for which results were available for 14. For the four outcome groups related to HBsAg, PR point estimates ranged from 1.65 to 6.76. For the five outcome groups related to anti-HBc, PRs ranged from 1.30 to 1.82; and for the five outcome groups related to combined HBV markers, PRs ranged from 1.15 to 1.89). The median HBsAg prevalence among people with a current or past STI was 4.17; not all studies reported HBsAg. Study settings and populations varied. CONCLUSION: This review found evidence of association between HBV infection and current or past STIs.

      9. Bartonella Seroreactivity Among Persons Experiencing Homelessness During an Outbreak of Bartonella quintana in Denver, Colorado, 2020external icon
        McCormick DW, Rowan SE, Pappert R, Yockey B, Dietrich EA, Petersen JM, Hinckley AF, Marx GE.
        Open Forum Infect Dis. 2021 Jun;8(6):ofab230.
        During a recent outbreak of Bartonella quintana disease in Denver, 15% of 241 persons experiencing homelessness who presented for severe acute respiratory syndrome coronavirus 2 testing were seroreactive for Bartonella. Improved recognition of B quintana disease and prevention of louse infestation are critical for this vulnerable population.

      10. BACKGROUND: Pelvic inflammatory disease (PID) is an infection of the upper female reproductive organs that can lead to infertility and ectopic pregnancies. PID is a reportable condition in North Carolina (NC), but is likely underreported. We aimed to quantify PID diagnoses in NC emergency department (ED) visits. METHODS: The NC Disease Event Tracking and Epidemiology Collection Tool (NC DETECT) tracks all ED visits in NC. We identified PID diagnoses among women of reproductive age (15-44 years) between 2008 and 2017 using ICD-9/10-CM codes, and calculated the yearly proportion with PID diagnoses. We assessed the number of PID visits per patient each year, and the proportion of ED visits with a PID diagnosis by age, proportion of the patient's ZIP code living below the poverty line, insurance coverage, and NC provider region. RESULTS: The percent of women with PID decreased from 6,189 (1.0%) in 2008 to 4,337 (0.58%) in 2016 before increasing slightly to 4,371 (0.61%) in 2017. We identified 54,502 (0.45%) ED visits among 51,847 women (0.76%) with ≥1 PID diagnosis code. Most (95.5%) women with PID had one ED visit during the calendar year. Each year, the proportion with PID was highest among women aged 20-24 years, covered under public insurance, from the most impoverished areas, and whose provider was in the Coastal region of NC. CONCLUSION: The percent with PID among women visiting EDs decreased between 2008 and 2017 in NC. Although this decline was observed across all demographics, disparities associated with PID continued to persist over time.

      11. Prevalence of male circumcision in four culturally non-circumcising counties in western Kenya after 10 years of program implementation from 2008 to 2019external icon
        Odoyo-June E, Davis S, Owuor N, Laube C, Wambua J, Musingila P, Young PW, Aoko A, Agot K, Joseph R, Mwandi Z, Ojiambo V, Lucas T, Toledo C, Wanyonyi A.
        PLoS One. 2021 ;16(7):e0254140.
        INTRODUCTION: Kenya started implementing voluntary medical male circumcision (VMMC) for HIV prevention in 2008 and adopted the use of decision makers program planning tool version 2 (DMPPT2) in 2016, to model the impact of circumcisions performed annually on the population prevalence of male circumcision (MC) in the subsequent years. Results of initial DMPPT2 modeling included implausible MC prevalence estimates, of up to 100%, for age bands whose sustained high uptake of VMMC pointed to unmet needs. Therefore, we conducted a cross-sectional survey among adolescents and men aged 10-29 years to determine the population level MC prevalence, guide target setting for achieving the goal of 80% MC prevalence and for validating DMPPT2 modelled estimates. METHODS: Beginning July to September 2019, a total of 3,569 adolescents and men aged 10-29 years from households in Siaya, Kisumu, Homa Bay and Migori Counties were interviewed and examined to establish the proportion already circumcised medically or non-medically. We measured agreement between self-reported and physically verified circumcision status and computed circumcision prevalence by age band and County. All statistical were test done at 5% level of significance. RESULTS: The observed MC prevalence for 15-29-year-old men was above 75% in all four counties; Homa Bay 75.6% (95% CI [69.0-81.2]), Kisumu 77.9% (95% CI [73.1-82.1]), Siaya 80.3% (95% CI [73.7-85.5]), and Migori 85.3% (95% CI [75.3-91.7]) but were 0.9-12.4% lower than DMPPT2-modelled estimates. For young adolescents 10-14 years, the observed prevalence ranged from 55.3% (95% CI [40.2-69.5]) in Migori to 74.9% (95% CI [68.8-80.2]) in Siaya and were 25.1-32.9% lower than DMMPT 2 estimates. Nearly all respondents (95.5%) consented to physical verification of their circumcision status with an agreement rate of 99.2% between self-reported and physically verified MC status (kappa agreement p-value<0.0001). CONCLUSION: This survey revealed overestimation of MC prevalence from DMPPT2-model compared to the observed population MC prevalence and provided new reference data for setting realistic program targets and re-calibrating inputs into DMPPT2. Periodic population-based MC prevalence surveys, especially for established programs, can help reconcile inconsistencies between VMMC program uptake data and modeled MC prevalence estimates which are based on the number of procedures reported in the program annually.

      12. Persons with isolated antibody to HBV core antigen (IAHBc) may have occult HBV infection (OBI), which is associated with reactivation and potential risk for hepatocellular carcinoma and HBV transmission. We used National Health and Nutrition Examination Survey (NHANES) data to estimate US IAHBc prevalence and published studies of IAHBc-associated OBI prevalence to estimate OBI burden. During 2001-2018, IAHBc prevalence was 0.8% (approximately 2.1 million persons); OBI burden range was 35,500-83,600 persons. These data support the need for more robust estimates of IAHBc-associated OBI prevalence in the general US population.

      13. Real-time CDC consultation during the COVID-19 pandemic—United States, March–July 2020external icon
        Wozniczka D, Demeke HB, Thompson-Paul AM, Ijeoma U, Williams TR, Taylor AW, Tan KR, Chevalier MS, Agyemang E, Dowell D, Oduyebo T, Shiferaw M, Coleman King SM, Minta AA, Shealy K, Oliver SE, McLean C, Glover M, Iskander J.
        Int. J. Environ. Res. Public Health. 2021 ;18(14).
        Context: In response to the COVID-19 pandemic, the Centers for Disease Prevention and Control (CDC) clinicians provided real-time telephone consultation to healthcare providers, public health practitioners, and health department personnel. Objective: To describe the demographic and public health characteristics of inquiries, trends, and correlation of inquiries with national COVID-19 case reports. We summarize the results of real-time CDC clinician consultation service provided during 11 March to 31 July 2020 to understand the impact and utility of this service by CDC for the COVID-19 pandemic emergency response and for future outbreak responses. Design: Clinicians documented inquiries received including information about the call source, population for which guidance was sought, and a detailed description of the inquiry and resolution. Descriptive analyses were conducted, with a focus on characteristics of callers as well as public health and clinical content of inquiries. Setting: Real-time telephone consultations with CDC Clinicians in Atlanta, GA. Partic-ipants: Health care providers and public health professionals who called CDC with COVID-19 related inquiries from throughout the United States. Main Outcome Measures: Characteristics of inquiries including topic of inquiry, inquiry population, resolution, and demographic information. Results: A total of 3154 COVID-19 related telephone inquiries were answered in real-time. More than half (62.0%) of inquiries came from frontline healthcare providers and clinical sites, followed by 14.1% from state and local health departments. The majority of inquiries focused on issues in-volving healthcare workers (27.7%) and interpretation or application of CDC’s COVID-19 guidance (44%). Conclusion: The COVID-19 pandemic resulted in a substantial number of inquiries to CDC, with the large majority originating from the frontline clinical and public health workforce. Analysis of inquiries suggests that the ongoing focus on refining COVID-19 guidance documents is war-ranted, which facilitates bidirectional feedback between the public, medical professionals, and public health authorities. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

    • Community Health Services
      1. Assessing the Effect of School-Based Health Centers on Achievement of National Performance Measuresexternal icon
        Hussaini KS, Offutt-Powell T, James G, Koumans EH.
        J Sch Health. 2021 Jul 12.
        BACKGROUND: We assess the impact of School-Based Health Centers (SBHCs) on National Performance Measures (NPMs) related to health care access and utilization among Medicaid-insured youth in Delaware. METHODS: Our retrospective analysis of Delaware's SBHC program data linked with Medicaid claims during 2014-2016 for 13 to 18-year-olds assessed achievement of NPMs and use of mental health services using propensity scores. We estimated crude and adjusted prevalence ratios (APR) for SBHC-enrolled compared with non-enrolled youth. RESULTS: Students enrolled in SBHCs had more health care visits (M = 8.7; 95% CI: 7.9-9.5) compared with non-SBHC-enrolled youth (M = 4.5; 95% CI: 4.3-4.7). Compared with non-SBHC, those enrolled in SBHCs were more likely to receive: well-child visits (APR = 1.2; 95% CI: 1.1-1.3); annual risk assessment (APR = 11.0; 95% CI: 6.9-17.5); BMI screening (APR = 5.6; 95% CI: 3.3-9.4); nutrition counseling (APR = 4.1; 95% CI: 2.8-6.0); physical activity counseling (APR = 6.3; 95% CI: 4.2-9.4); STIs and chlamydia screening (APR = 1.9; 95% CI: 1.3-2.8); mental health visits (APR = 2.6; 95% CI: 2.2-3.1). CONCLUSIONS: We found that among Medicaid-insured youth, those enrolled in SBHCs vs not enrolled in SBHCs had greater health care utilization as evident from NPMs and mental health services.

    • Disaster Control and Emergency Services
      1. The purpose of this study was to identify factors that motivate public health workers to deploy to the field during an emergency event. We conducted 25 semistructured interviews with employees at the US Centers for Disease Control and Prevention, all of whom had deployed to the field for the 2014-2016 Ebola, 2016-2017 Zika, and 2017 hurricane responses. We used a grounded theory approach in our analysis of the data. Themes that emerged from the interviews related to responder autonomy, competence, and relatedness, which are consistent with self-determination theory. Motivating factors included having clarity about the response role, desire to be challenged, ability to apply existing skills in the field (or apply new skills learned during deployment to their home office), desire to be helpful, and feeling rewarded by working with affected populations, communities, and other response staff. These preliminary findings suggest that introjected and identified motivating factors may form the foundation of willingness among public health workers to assist during an emergency event. Understanding what motivates staff at public health agencies to participate in emergency deployment can inform the development of recruitment strategies, strengthen effectiveness of response activities, and improve overall agency preparedness.

    • Disease Reservoirs and Vectors
      1. Rapid evolution of knockdown resistance haplotypes in response to pyrethroid selection in Aedes aegyptiexternal icon
        Baltzegar J, Vella M, Gunning C, Vasquez G, Astete H, Stell F, Fisher M, Scott TW, Lenhart A, Lloyd AL, Morrison A, Gould F.
        Evol. Appl.. 2021 .
        This study describes the evolution of knockdown resistance (kdr) haplotypes in Aedes aegypti in response to pyrethroid insecticide use over the course of 18 years in Iquitos, Peru. Based on the duration and intensiveness of sampling (~10,000 samples), this is the most thorough study of kdr population genetics in Ae. aegypti to date within a city. We provide evidence for the direct connection between programmatic citywide pyrethroid spraying and the increase in frequency of specific kdr haplotypes by identifying two evolutionary events in the population. The relatively high selection coefficients, even under infrequent insecticide pressure, emphasize how quickly Ae. aegypti populations can evolve. In our examination of the literature on mosquitoes and other insect pests, we could find no cases where a pest evolved so quickly to so few exposures to low or nonresidual insecticide applications. The observed rapid increase in frequency of resistance alleles might have been aided by the incomplete dominance of resistance-conferring alleles over corresponding susceptibility alleles. In addition to dramatic temporal shifts, spatial suppression experiments reveal that genetic heterogeneity existed not only at the citywide scale, but also on a very fine scale within the city. © 2021 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd

      2. Determination of freedom-from-rabies for small Indian mongoose populations in the United States Virgin Islands, 2019-2020external icon
        Browne AS, Cranford HM, Morgan CN, Ellison JA, Berentsen A, Wiese N, Medley A, Rossow J, Jankelunas L, McKinley AS, Lombard CD, Angeli NF, Kelley T, Valiulus J, Bradford B, Burke-France VJ, Harrison CJ, Guendel I, Taylor M, Blanchard GL, Doty JB, Worthington DJ, Horner D, Garcia KR, Roth J, Ellis BR, Bisgard KM, Wallace R, Ellis EM.
        PLoS Negl Trop Dis. 2021 Jul;15(7):e0009536.
        Mongooses, a nonnative species, are a known reservoir of rabies virus in the Caribbean region. A cross-sectional study of mongooses at 41 field sites on the US Virgin Islands of St. Croix, St. John, and St. Thomas captured 312 mongooses (32% capture rate). We determined the absence of rabies virus by antigen testing and rabies virus exposure by antibody testing in mongoose populations on all three islands. USVI is the first Caribbean state to determine freedom-from-rabies for its mongoose populations with a scientifically-led robust cross-sectional study. Ongoing surveillance activities will determine if other domestic and wildlife populations in USVI are rabies-free.

    • Environmental Health
      1. Prenatal urinary concentrations of phenols and risk of preterm birth: exploring windows of vulnerabilityexternal icon
        Zhang Y, Mustieles V, Williams PL, Yland J, Souter I, Braun JM, Calafat AM, Hauser R, Messerlian C.
        Fertil Steril. 2021 Jul 5.
        OBJECTIVE: To explore windows of vulnerability to prenatal urinary phenol concentrations and preterm birth. DESIGN: Prospective cohort. SETTING: A large fertility center in Boston, Massachusetts. PATIENT(S): A total of 386 mothers who sought fertility treatment and gave birth to a singleton between 2005 and 2018. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Singleton live birth with gestational age <37 completed weeks. RESULT(S): Compared with women with non-preterm births, urinary bisphenol A (BPA) concentrations were higher across gestation among women with preterm births, particularly during mid-to-late pregnancy and among those with female infants. Second trimester BPA concentrations were associated with preterm birth (Risk Ratio [RR] 1.24; 95%CI: 0.92, 1.69), which was primarily driven by female (RR 1.40; 95%CI: 1.04, 1.89) and not male (RR 0.85; 95%CI 0.50, 1.46) infants. First trimester paraben concentrations were also associated with preterm birth (RR 1.17; 95%CI: 0.94, 1.46) and similarly the association was only observed for female (RR 1.46; 95% CI: 1.10, 1.94) and not male infants (RR 0.94; 95%CIC: 0.72, 1.23). First trimester urinary bisphenol S concentrations showed a suggested risk of preterm birth (RR 1.25; 95%CI: 0.82, 1.89), although the small case numbers precluded sex-specific examination. CONCLUSION(S): We found preliminary evidence of associations between mid-to-late pregnancy BPA and early pregnancy paraben concentrations with preterm birth among those with female infants only. Preterm birth risk may be compound, sex, and window specific. Given the limited sample size of this cohort, results should be confirmed in larger studies, including fertile populations.

    • Health Economics
      1. Systematic review of the costs for vaccinators to reach vaccination sites: Incremental costs of reaching hard-to-reach populationsexternal icon
        Ozawa S, Yemeke TT, Mitgang E, Wedlock PT, Higgins C, Chen HH, Pallas SW, Abimbola T, Wallace A, Bartsch SM, Lee BY.
        Vaccine. 2021 Jul 5.
        INTRODUCTION: Economic evidence on how much it may cost for vaccinators to reach populations is important to plan vaccination programs. Moreover, knowing the incremental costs to reach populations that have traditionally been undervaccinated, especially those hard-to-reach who are facing supply-side barriers to vaccination, is essential to expanding immunization coverage to these populations. METHODS: We conducted a systematic review to identify estimates of costs associated with getting vaccinators to all vaccination sites. We searched PubMed and the Immunization Delivery Cost Catalogue (IDCC) in 2019 for the following costs to vaccinators: (1) training costs; (2) labor costs, per diems, and incentives; (3) identification of vaccine beneficiary location; and (4) travel costs. We assessed if any of these costs were specific to populations that are hard-to-reach for vaccination, based on a framework for examining supply-side barriers to vaccination. RESULTS: We found 19 studies describing average vaccinator training costs at $0.67/person vaccinated or targeted (SD $0.94) and $0.10/dose delivered (SD $0.07). The average cost for vaccinator labor and incentive costs across 29 studies was $2.15/dose (SD $2.08). We identified 13 studies describing intervention costs for a vaccinator to know the location of a beneficiary, with an average cost of $19.69/person (SD $26.65), and six studies describing vaccinator travel costs, with an average cost of $0.07/dose (SD $0.03). Only eight of these studies described hard-to-reach populations for vaccination; two studies examined incremental costs per dose to reach hard-to-reach populations, which were 1.3-2 times higher than the regular costs. The incremental cost to train vaccinators was $0.02/dose, and incremental labor costs for targeting hard-to-reach populations were $0.16-$1.17/dose. CONCLUSION: Additional comparative costing studies are needed to understand the potential differential costs for vaccinators reaching the vaccination sites that serve hard-to-reach populations. This will help immunization program planners and decision-makers better allocate resources to extend vaccination programs.

    • Immunity and Immunization
      1. Acceptability of a gonococcal vaccine among sexually active men who have sex with menexternal icon
        Abara WE, Kirkcaldy RD, Bernstein KT, Zlotorzynska M, Sanchez T.
        Sex Transm Dis. 2021 Jul 13.
        BACKGROUND: Prospects for a gonococcal vaccine have advanced. Vaccine acceptability is crucial to maximizing population-level protection among key groups, such as men who have sex with men (MSM). We assessed prevalence of gonococcal vaccine acceptability among sexually-active MSM in the United States. METHODS: We used data from the American Men's Internet Study conducted during 8/2019─12/2019. We calculated frequencies of socio-demographic characteristics, vaccine acceptability, and preferred location for vaccine receipt. Using log-binomial regression analyses, we calculated unadjusted prevalence rates (PR) and 95% confidence intervals (CI) to evaluate factors associated with vaccine acceptability. RESULTS: Of 4,951 MSM, 83.5% were willing to accept a vaccine and 16.5% were unwilling. Preferred vaccination locations were primary care provider's clinics (83.5%) and sexually transmitted disease (STD) clinics (64.6%). Vaccine acceptability was greater among young MSM (15─24 years [PR = 1.09, 95% CI = 1.05-1.12], 25─29 years [PR = 1.13, 95% CI = 1.09─1.17], and 30-39 years [PR = 1.10, 95% CI = 1.05─1.14]) compared to MSM ≥ 40 years), MSM living with HIV (PR = 1.05, 95% CI = 1.02─1.09), and MSM who reported (in the past 12 months) condomless anal sex (PR = 1.09, 95% CI = 1.06─1.12), a bacterial STD test (PR = 1.18, 95% CI = 1.15─1.21), HIV pre-exposure prophylaxis use (PR = 1.17, 95% CI = 1.14─1.19), a bacterial STD diagnosis (PR = 1.04, 95% CI = 1.02─1.07), or a healthcare provider visit (PR = 1.11, 95% CI = 1.06─1.16). MSM who reported ≤high school education (PR = 0.93, 95% CI = 0.91-0.97) were less willing to accept a vaccine compared to those with >high school education. CONCLUSION: Most respondents were willing to accept a gonococcal vaccine. These findings can inform the planning and implementation of a future gonococcal vaccination program that focuses on MSM.

      2. Comparison of the Immunogenicity of Cell Culture-Based and Recombinant Quadrivalent Influenza Vaccines to Conventional Egg-Based Quadrivalent Influenza Vaccines among Healthcare Personnel Aged 18-64 Years: A Randomized Open-Label Trialexternal icon
        Dawood FS, Naleway AL, Flannery B, Levine MZ, Murthy K, Sambhara S, Gangappa S, Edwards L, Ball S, Beacham L, Belongia E, Bounds K, Cao W, Gross FL, Groom H, Fry AM, Hunt D, Jeddy Z, Mishina M, Kim SS, Wesley MG, Spencer S, Thompson MG, Gaglani M.
        Clin Infect Dis. 2021 Jul 10.
        BACKGROUND: RIV4 and cell-culture based inactivated influenza vaccine (ccIIV4) have not been compared to egg-based IIV4 in healthcare personnel, a population with frequent influenza vaccination that may blunt vaccine immune responses over time. We conducted a randomized trial among HCP aged 18-64 years to compare humoral immune responses to ccIIV4 and RIV4 to IIV4. METHODS: During the 2018-2019 season, participants were randomized to receive ccIIV4, RIV4, or IIV4 and had sera collected pre-vaccination, 1 and 6 months post-vaccination. Sera were tested by hemagglutination inhibition (HI) for influenza A/H1N1, B/Yamagata, and B/Victoria and microneutralization (MN) for A/H3N2 against cell-grown vaccine reference viruses. Primary outcomes at 1 month were seroconversion rate (SCR), geometric mean titers (GMT), GMT ratio, and mean fold rise (MFR) in the intention-to-treat population. RESULTS: 727 participants were included (283 ccIIV4, 202 RIV4, and 242 IIV4). At 1 month, responses to ccIIV4 were similar to IIV4 by SCR, GMT, GMT ratio, and MFR. RIV4 induced higher SCRs, GMTs, and MFRs than IIV4 against A/H1N1, A/H3N2, and B/Yamagata. The GMT ratio of RIV4 to egg-based vaccines was 1.5 (95%CI 1.2-1.9) for A/H1N1, 3.0 (95%CI 2.4-3.7) for A/H3N2, 1.1 (95%CI 0.9-1.4) for B/Yamagata, and 1.1 (95%CI 0.9-1.3) for B/Victoria. At 6 months, ccIIV4 recipients had similar GMTs to IIV4, whereas RIV4 recipients had higher GMTs against A/H3N2 and B/Yamagata. CONCLUSION: RIV4 resulted in improved antibody responses by HI and MN compared to egg-based vaccines against three of four cell-grown vaccine strains 1 month post-vaccination, suggesting a possible additional benefit from RIV4.

      3. Why aren't we achieving high vaccination rates for rotavirus vaccine in the U.S.?external icon
        Kempe A, O'Leary ST, Cortese MM, Crane LA, Cataldi JR, Brtnikova M, Beaty BL, Hurley LP, Gorman C, Tate JE, St Pierre JL, Lindley MC.
        Acad Pediatr. 2021 Jul 9.
        BACKGROUND: Rotavirus vaccine (RV) coverage levels for U.S. infants are <80%. METHODS: We surveyed nationally representative networks of pediatricians by internet/mail from April-June, 2019. Multivariable regression assessed factors associated with difficulty administering the first RV dose (RV#1) by the maximum age. RESULTS: Response rate was 68% (303/448). 99% of providers reported strongly recommending RV. The most common barriers to RV delivery overall (definite/somewhat of a barrier) were: parental concerns about vaccine safety overall (27%), parents wanting to defer (25%), parents not thinking RV was necessary (12%) and parent concerns about RV safety (6%). The most commonly reported reasons for non-receipt of RV#1 by 4-5 months (often/always) were parental vaccine refusal (9%), hospitals not giving RV at discharge from nursery (7%), infants past the maximum age when discharged from NICU/nursery (6%), and infant not seen before maximum age for well care visit (3%) or seen but no vaccine given (4%). Among respondents 4% strongly agreed and 25% somewhat agreed that they sometimes have difficulty giving RV#1 before the maximum age. Higher percentage of State Child Health Insurance Program/Medicaid-insured children in the practice and reporting that recommendations for timing of RV doses are too complicated were associated with reporting difficulty delivering the RV#1 by the maximum age. CONCLUSIONS: U.S. pediatricians identified multiple, actionable issues that may contribute to suboptimal RV immunization rates including lack of vaccination prior to leaving nurseries after prolonged stays, infants not being seen for well care visits by the maximum age, missed opportunities at visits and parents refusing/deferring.

      4. COVID-19 Vaccination Coverage Among Insured Persons Aged ≥16 Years, by Race/Ethnicity and Other Selected Characteristics - Eight Integrated Health Care Organizations, United States, December 14, 2020-May 15, 2021external icon
        Pingali C, Meghani M, Razzaghi H, Lamias MJ, Weintraub E, Kenigsberg TA, Klein NP, Lewis N, Fireman B, Zerbo O, Bartlett J, Goddard K, Donahue J, Hanson K, Naleway A, Kharbanda EO, Yih WK, Nelson JC, Lewin BJ, Williams JT, Glanz JM, Singleton JA, Patel SA.
        MMWR Morb Mortal Wkly Rep. 2021 Jul 16;70(28):985-990.
        COVID-19 vaccination is critical to ending the COVID-19 pandemic. Members of minority racial and ethnic groups have experienced disproportionate COVID-19-associated morbidity and mortality (1); however, COVID-19 vaccination coverage is lower in these groups (2). CDC used data from CDC's Vaccine Safety Datalink (VSD)* to assess disparities in vaccination coverage among persons aged ≥16 years by race and ethnicity during December 14, 2020-May 15, 2021. Measures of coverage included receipt of ≥1 COVID-19 vaccine dose (i.e., receipt of the first dose of the Pfizer-BioNTech or Moderna COVID-19 vaccines or 1 dose of the Janssen COVID-19 vaccine [Johnson & Johnson]) and full vaccination (receipt of 2 doses of the Pfizer-BioNTech or Moderna COVID-19 vaccines or 1 dose of Janssen COVID-19 vaccine). Among 9.6 million persons aged ≥16 years enrolled in VSD during December 14, 2020-May 15, 2021, ≥1-dose coverage was 48.3%, and 38.3% were fully vaccinated. As of May 15, 2021, coverage with ≥1 dose was lower among non-Hispanic Black (Black) and Hispanic persons (40.7% and 41.1%, respectively) than it was among non-Hispanic White (White) persons (54.6%). Coverage was highest among non-Hispanic Asian (Asian) persons (57.4%). Coverage with ≥1 dose was higher among persons with certain medical conditions that place them at higher risk for severe COVID-19 (high-risk conditions) (63.8%) than it was among persons without such conditions (41.5%) and was higher among persons who had not had COVID-19 (48.8%) than it was among those who had (42.4%). Persons aged 18-24 years had the lowest ≥1-dose coverage (28.7%) among all age groups. Continued monitoring of vaccination coverage and efforts to improve equity in coverage are critical, especially among populations disproportionately affected by COVID-19.

      5. Acceptability of Adolescent COVID-19 Vaccination Among Adolescents and Parents of Adolescents - United States, April 15-23, 2021external icon
        Scherer AM, Gedlinske AM, Parker AM, Gidengil CA, Askelson NM, Petersen CA, Woodworth KR, Lindley MC.
        MMWR Morb Mortal Wkly Rep. 2021 Jul 16;70(28):997-1003.
        On May 10, 2021, the Food and Drug Administration (FDA) expanded its Emergency Use Authorization for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12-15 years; this authorization was followed by interim recommendations from the Advisory Committee on Immunization Practices (ACIP) for the vaccine among this age group (1). Using data from nonprobability-based Internet panel surveys administered by the Healthcare and Public Perceptions of Immunizations (HaPPI) Survey Collaborative, the acceptability of adolescent COVID-19 vaccination and self-reported factors increasing vaccination intent were assessed among independently recruited samples of 985 adolescents aged 13-17 years and 1,022 parents and guardians (parents) of adolescents aged 12-17 years during April 15-April 23, 2021, prior to vaccine authorization for this age group. Approximately one quarter (27.6%) of parents whose adolescents were already vaccine-eligible (i.e., aged 16-17 years) reported their adolescent had received ≥1 COVID-19 vaccine dose, similar to the proportion reported by vaccine-eligible adolescents aged 16-17 years (26.1%). However, vaccine receipt reported by parents of adolescents differed across demographic groups; parents identifying as female or Hispanic, or who had an education lower than a bachelor's degree reported the lowest adolescent COVID-19 vaccination receipt. Among parents of unvaccinated adolescents aged 12-17 years, 55.5% reported they would "definitely" or "probably" have their adolescent receive a COVID-19 vaccination. Among unvaccinated adolescents aged 13-17 years, 51.7% reported they would "definitely" or "probably" receive a COVID-19 vaccination. Obtaining more information about adolescent COVID-19 vaccine safety and efficacy, as well as school COVID-19 vaccination requirements, were the most commonly reported factors that would increase vaccination intentions among both parents and adolescents. Federal, state, and local health officials and primary care professionals were the most trusted sources of COVID-19 vaccine information among both groups. Efforts focusing on clearly communicating to the public the benefits and safety of COVID-19 vaccination for adolescents, particularly by health care professionals, could help increase confidence in adolescent COVID-19 vaccine and vaccination coverage.

      6. Vaccine Hesitancy: Drivers and how the Allergy Community can helpexternal icon
        Turner PJ, Larson H, Dubé È, Fisher A.
        J Allergy Clin Immunol Pract. 2021 Jul 6.
        Vaccine hesitancy - defined by the World Health Organization (WHO) as a "delay in acceptance or refusal of vaccines despite availability of vaccination services" is not a recent phenomenon. Historical records indicate that vaccine hesitancy existed by the 18(th) century in Europe and even resulted in violent riots. The drivers of vaccine hesitancy have evolved over the last 200 years but not, perhaps, as much as one might expect. More problematic are the means by which concerns over vaccine hesitancy are communicated by a new landscape of digital communication, generating what has been described as an "infodemic" where an overabundance of information - both factual and misinformation - contributes to hesitancy. In this review, we discuss the background and current drivers of vaccine hesitancy and the evidence-base for strategies to combat this. We highlight the important role the allergy/immunology community could have in working to mitigate vaccine hesitancy, particularly with respect to the current COVID-19 pandemic.

    • Injury and Violence
      1. Natural prioritization tendencies during texting while walkingexternal icon
        Brennan AC, Breloff SP.
        J Musculoskelet Res. 2021 .
        Dual tasking (DT), or completing more than one task concurrently, has become a common practice. 1 This practice requires the allocation of one's limited attentional resources to different tasks in a proportion that allows for the safe execution and completion of both tasks.1 With nearly 70% of the adult and teen population owning a cell phone,2 it is unsurprising that cell phone-based DTs have become an everyday occurrence in the lives of many. Copyright © 2021 American Medical Association. All rights reserved.

    • Laboratory Sciences
      1. Functional features of the respiratory syncytial virus G proteinexternal icon
        Anderson LJ, Jadhao SJ, Paden CR, Tong S.
        Viruses. 2021 ;13(7).
        Respiratory syncytial virus (RSV) is a major cause of serious lower respiratory tract infections in children <5 years of age worldwide and repeated infections throughout life leading to serious disease in the elderly and persons with compromised immune, cardiac, and pulmonary systems. The disease burden has made it a high priority for vaccine and antiviral drug development but without success except for immune prophylaxis for certain young infants. Two RSV proteins are associated with protection, F and G, and F is most often pursued for vaccine and antiviral drug development. Several features of the G protein suggest it could also be an important to vaccine or antiviral drug target design. We review features of G that effect biology of infection, the host immune response, and disease associated with infection. Though it is not clear how to fit these together into an integrated picture, it is clear that G mediates cell surface binding and facilitates cellular infection, modulates host responses that affect both immunity and disease, and its CX3C aa motif contributes to many of these effects. These features of G and the ability to block the effects with antibody, suggest G has substantial potential in vaccine and antiviral drug design. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

      2. Analysis of Biospecimen Demand and Utilization of Samples from the National Amyotrophic Lateral Sclerosis Biorepositoryexternal icon
        Bledsoe MJ, Rechtman L, Wagner L, Mehta P, Horton DK, Kaye WE.
        Biopreserv Biobank. 2021 Jul 14.
        Amyotrophic lateral sclerosis (ALS) is a rare neurological condition affecting upper and lower motor neurons. The National ALS Biorepository (referred to as the Biorepository) was initiated in 2015, with biospecimen collection beginning in 2017, as a repository for biospecimens for future ALS research. To help ensure the usefulness of the Biorepository, a biospecimen demand analysis is conducted on an annual basis, as well as an analysis of the utilization of the Biorepository. To determine the types of biospecimens to be collected for the Biorepository, an in-depth initial examination occurred followed by ongoing biospecimen demand and utilization analyses. The initial examination included input from an expert panel, discussions with ALS research experts, review of other ALS biorepositories, assessment of biospecimen demand, and analysis of the biospecimen types historically used in ALS research. Of all biospecimen types reported in the literature, the most frequently used were DNA, postmortem spinal cord, blood, and cerebrospinal fluid; while the frequently reported types of biospecimens used in ALS-related grants were induced pluripotent stem cells, brain, blood, and spinal cord. Continuous analysis of potential sample demand and tissues collected, based on an analysis of the literature and funded grants, and actual sample requests can assist the Biorepository in ensuring that the appropriate samples are available for researchers when they are needed.

      3. A Longitudinal Model-Based Biomarker Analysis of Exposure Response in Adults with Pulmonary Tuberculosisexternal icon
        Gewitz AD, Solans BP, Mac Kenzie WR, Heilig C, Whitworth WC, Johnson JL, Nsubuga P, Dorman S, Weiner M, Savic RM.
        Antimicrob Agents Chemother. 2021 Jul 12:Aac0179420.
        The identification of sensitive, specific and reliable biomarkers that can be quantified in the early phases of tuberculosis treatment and predictive of long-term outcome is key for the development of an effective short-course treatment regimen. Time-to-positivity (TTP), a biomarker of treatment outcome against Mycobacterium tuberculosis, measures longitudinal bacterial growth in Mycobacteria Growth Indicator Tube broth culture and may be predictive of standard time-to-stable-culture-conversion (TSCC). In two randomized phase 2b trials investigating dose-ranging rifapentine (Study 29 and 29x), 662 participants had sputum collected over six months where TTP, TSCC and time-to-culture-conversion were quantified. The goals of this post hoc study were to characterize longitudinal TTP profiles and to identify individual patient characteristics associated with delayed time to culture conversion. In order to do so, a nonlinear mixed-effects model describing longitudinal TTP was built. Independent variables associated with increased bacterial clearance (increased TTP), assessed by subject-specific and population-level trajectories, were higher rifapentine exposure, lower baseline grade of sputum acid-fast bacilli smear, absence of productive cough, and lower extent of lung infiltrates on radiographs. Importantly, sensitivity analysis revealed that major learning milestones in phase 2b trials, such as significant exposure-response and covariate relationships, could be detected using truncated TTP data as early as 6 weeks from start of treatment, suggesting alternative phase 2B study designs. The TTP model built depicts a novel phase 2B surrogate endpoint that can inform early assessment of experimental treatment efficacy and treatment failure or relapse in patients treated with shorter and novel TB treatment regimens, improving efficiency of phase 2 clinical trials.

      4. BACKGROUND: Despite the global roll-out of rotavirus vaccines (RotaTeq/Rotarix / ROTAVAC/Rotasiil), mortality and morbidity due to group A rotavirus (RVA) remains high in sub-Saharan Africa, causing 104,000 deaths and 600,000 hospitalizations yearly. In Cameroon, Rotarix™ was introduced in March 2014, but, routine laboratory diagnosis of rotavirus infection is not yet a common practice, and vaccine effectiveness studies to determine the impact of vaccine introduction have not been done. Thus, studies examining RVA prevalence post vaccine introduction are needed. The study aim was to determine RVA prevalence in severe diarrhoea cases in Littoral region, Cameroon and investigate the role of other diarrheagenic pathogens in RVA-positive cases. METHODS: We carried out a study among hospitalized children < 5 years of age, presenting with acute gastroenteritis in selected hospitals of the Littoral region of Cameroon, from May 2015 to April 2016. Diarrheic stool samples and socio-demographic data including immunization and breastfeeding status were collected from these participating children. Samples were screened by ELISA (ProSpecT™ Rotavirus) for detection of RVA antigen and by gel-based RT-PCR for detection of the VP6 gene. Co-infection was assessed by multiplexed molecular detection of diarrheal pathogens using the Luminex xTAG GPP assay. RESULTS: The ELISA assay detected RVA antigen in 54.6% (71/130) of specimens, with 45, positive by VP6 RT-PCR and 54, positive using Luminex xTAG GPP. Luminex GPP was able to detect all 45 VP6 RT-PCR positive samples. Co-infections were found in 63.0% (34/54) of Luminex positive RVA infections, with Shigella (35.3%; 12/34) and ETEC (29.4%; 10/34) detected frequently. Of the 71 ELISA positive RVA cases, 57.8% (41/71) were fully vaccinated, receiving two doses of Rotarix. CONCLUSION: This study provides insight on RVA prevalence in Cameroon, which could be useful for post-vaccine epidemiological studies, highlights higher than expected RVA prevalence in vaccinated children hospitalized for diarrhoea and provides the trend of RVA co-infection with other enteric pathogens. RVA genotyping is needed to determine circulating rotavirus genotypes in Cameroon, including those causing disease in vaccinated children.

      5. Precision of Serologic Testing from Dried Blood Spots Using a Multiplex Bead Assayexternal icon
        Gwyn S, Aragie S, Wittberg DM, Melo JS, Dagnew A, Hailu D, Tadesse Z, Haile M, Zeru T, Nash SD, Arnold BF, Martin DL, Keenan JD.
        Am J Trop Med Hyg. 2021 Jul 12.
        Multiplex bead assays (MBAs) for serologic testing have become more prevalent in public health surveys, but few studies have assessed their test performance. As part of a trachoma study conducted in a rural part of Ethiopia in 2016, dried blood spots (DBS) were collected from a random sample of 393 children aged 0 to 9 years, with at least two separate 6-mm DBS collected on a filter card. Samples eluted from DBS were processed using an MBA on the Luminex platform for antibodies against 13 antigens of nine infectious organisms: Chlamydia trachomatis, Vibrio cholera, enterotoxigenic Escherichia coli, Cryptosporidium parvum, Entamoeba histolytica, Camplyobacter jejuni, Salmonella typhimurium Group B, Salmonella enteritidis Group D, and Giardia lamblia. Two separate DBS from each child were processed. The first DBS was run a single time, with the MBA set to read 100 beads per well. The second DBS was run twice, first at 100 beads per well and then at 50 beads per well. Results were expressed as the median fluorescence intensity minus background (MFI-BG), and classified as seropositive or seronegative according to external standards. Agreement between the three runs was high, with intraclass correlation coefficients of > 0.85 for the two Salmonella antibody responses and > 0.95 for the other 11 antibody responses. Agreement was also high for the dichotomous seropositivity indicators, with Cohen's kappa statistics exceeding 0.87 for each antibody assay. These results suggest that serologic testing on the Luminex platform had strong test performance characteristics for analyzing antibodies using DBS.

      6. Here we report on initial efforts to evaluate enhanced darkfield microscopy (EDFM) and light scattering Vis-NIR hyperspectral imaging (HSI) as a rapid screening tool for the offline analysis of mixed cellulose ester (MCE) filter media used to collect airborne nanoparticulate from work environments. For this study, the materials of interest were nanoscale titanium dioxide (TiO(2) ) and silicon dioxide (SiO(2) ; silica), chosen for their frequent use in consumer products. TiO(2) and SiO(2) nanoscale particles (NPs) were collected on MCE filter media and were imaged and analyzed via EDFM-HSI. When visualized by EDFM, TiO(2) and SiO(2) NPs were readily apparent as bright spherical structures against a dark background. Moreover, TiO(2) and SiO(2) NPs were identified in hyperspectral images. EDFM-HSI images and data were compared to scanning transmission electron microscopy (STEM), a NIST-traceable technique for particle size analysis, and the current gold standard for offline analysis of filter media. As expected, STEM provided more accurate sizing and morphology data when compared to EDFM-HSI, but is not ideal for rapid screening of the presence of NPs of interest since it is a costly, low-throughput technique. In this study, we demonstrate the utility of EDFM-HSI in rapidly visualizing and identifying TiO(2) and SiO(2) NPs on MCE filters. This screening method may prove useful in expediting time-to-knowledge compared to electron microscopy. Future work will expand this evaluation to other industrially relevant NPs, other filter media types, and real-world filter samples from occupational exposure assessments.

      7. Performance and Operational Evaluation of the Access Bio CareStart Rapid Antigen Test in a High-Throughput Drive-Through Community Testing Site in Massachusettsexternal icon
        Pollock NR, Tran K, Jacobs JR, Cranston AE, Smith S, O'Kane CY, Roady TJ, Moran A, Scarry A, Carroll M, Volinsky L, Perez G, Patel P, Gabriel S, Lennon NJ, Madoff LC, Brown C, Smole SC.
        Open Forum Infect Dis. 2021 Jul;8(7):ofab243.
        BACKGROUND: To facilitate deployment of point-of-care testing for severe acute respiratory syndrome coronavirus 2, we evaluated the Access Bio CareStart COVID-19 Antigen test in a high-throughput, drive-through, free community testing site using anterior nasal (AN) swab reverse-transcription polymerase chain reaction (RT-PCR) for clinical testing. METHODS: Consenting symptomatic and asymptomatic children (≤18 years) and adults received dual AN swabs. CareStart testing was performed with temperature/humidity monitoring. All tests had 2 independent reads to assess interoperator agreement. Patients with positive CareStart results were called and instructed to isolate pending RT-PCR results. The paired RT-PCR result was the reference for sensitivity and specificity calculations. RESULTS: Of 1603 participants, 1245 adults and 253 children had paired RT-PCR/CareStart results and complete symptom data. Eighty-three percent of adults and 87% of children were asymptomatic. CareStart sensitivity/specificity were 84.8% (95% confidence interval [CI], 71.1-93.7)/97.2% (95% CI, 92.0-99.4) and 85.7% (95% CI, 42.1-99.6)/89.5% (95% CI, 66.9-98.7) in adults and children, respectively, within 5 days of symptoms. Sensitivity/specificity were 50.0% (95% CI, 41.0-59.0)/99.1% (95% CI, 98.3-99.6) in asymptomatic adults and 51.4% (95% CI, 34.4-68.1)/97.8% (95% CI, 94.5-99.4) in asymptomatic children. Sensitivity in all 234 RT-PCR-positive people was 96.3% with cycle threshold (Ct) ≤25, 79.6% with Ct ≤30, and 61.4% with Ct ≤35. All 21 false-positive CareStart tests had faint but normal bands. Interoperator agreement was 99.5%. Operational challenges included identification of faint test bands and inconsistent swab elution volumes. CONCLUSIONS: CareStart had high sensitivity in people with Ct ≤25 and moderate sensitivity in symptomatic people overall. Specificity was unexpectedly lower in symptomatic versus asymptomatic people. Excellent interoperator agreement was observed, but operational challenges indicate that operator training is warranted.

      8. During the past 15 years, researchers have shown a renewed interest in the study of the Plasmodium parasites that infect orangutans. Most recently, studies examined the phylogenetic relationships and divergence dates of these parasites in orangutans using complete mitochondrial DNA genomes. Questions regarding the dating of these parasites, however, remain. In the present study, we provide a new calibration model for dating the origins of Plasmodium parasites in orangutans using a modified date range for the origin of macaques in Asia. Our Bayesian phylogenetic analyses of complete Plasmodium sp. mitochondrial DNA genomes inferred two clades of plasmodia in orangutans (Pongo 1 and Pongo 2), and that these clades likely represent the previously identified species Plasmodium pitheci and Plasmodium silvaticum. However, we cannot identify which Pongo clade is representative of the morphologically described species. The most recent common ancestor of both Pongo sp. plasmodia, Plasmodium. hylobati, and Plasmodium. inui dates to 3-3.16 million years ago (mya) (95% highest posterior density [HPD]: 2.09-4.08 mya). The Pongo 1 parasite diversified 0.33-0.36 mya (95% HPD: 0.12-0.63), while the Pongo 2 parasite diversified 1.15-1.22 mya (95% HPD: 0.63-1.82 mya). It now seems likely that the monkey Plasmodium (P. inui) is the result of a host switch event from the Pongo 2 parasite to sympatric monkeys, or P. hylobati. Our new estimates for the divergence of orangutan malaria parasites, and subsequent diversification, are all several hundred thousand years later than previous Bayesian estimates.

      9. Cellular Basis for the Enhanced Efficacy of the Fms-Like Tyrosine Kinase 3 Ligand (FL) Adjuvanted VCG-Based Chlamydia abortus Vaccineexternal icon
        Richardson S, Medhavi F, Tanner T, Lundy S, Omosun Y, Igietseme JU, Carroll D, Eko FO.
        Front Immunol. 2021 ;12:698737.
        Efficacious vaccines are needed to control genital chlamydial diseases in humans and the veterinary industry. We previously reported a C. abortus (Cab) vaccine comprising recombinant Vibrio cholerae ghosts (rVCG) expressing the conserved and immunogenic N-terminal region of the Cab polymorphic membrane protein D (rVCG-Pmp18.1) protein that protected mice against intravaginal challenge. In this study, we investigated the immunomodulatory effect of the hematopoietic progenitor activator cytokine, Fms-like tyrosine kinase 3-ligand (FL) when co-administered with the rVCG-Pmp18.1 vaccine as a strategy to enhance the protective efficacy and the potential mechanism of immunomodulation. Groups of female C57BL/6J mice were immunized and boosted twice intranasally (IN) with rVCG-PmpD18.1 with and without FL or purified rPmp18.1 or rVCG-gD2 (antigen control) or PBS (medium) per mouse. The results revealed that co-administration of the vaccine with FL enhanced antigen-specific cellular and humoral immune responses and protected against live Cab genital infection. Comparative analysis of immune cell phenotypes infiltrating mucosal and systemic immune inductive tissue sites following immunization revealed that co-administration of rVCG-Pmp18.1 with FL significantly enhanced the number of macrophages, dendritic and NK cells, γδ and NK T cells in the spleen (systemic) and iliac lymph nodes (ILN) draining the genital tract (mucosal) tissues compared to rVCG-Pmp18.1 alone. Furthermore, FL enhanced monocyte infiltration in the ILN, while CD19+ B cells and CD4+ T cells were enhanced in the spleen. These results indicate that the immunomodulatory effect of FL is associated with its ability to mobilize innate immune cells and subsequent activation of robust antigen-specific immune effectors in mucosal and systemic lymphoid tissues.

    • Maternal and Child Health
      1. Prescription opioid use during pregnancy and risk for preterm birth or term low birthweightexternal icon
        Interrante JD, Scroggs SL, Hogue CJ, Friedman JM, Reefhuis J, Jann MW, Broussard CS.
        J Opioid Manag. 2021 May-Jun;17(3):215-225.
        OBJECTIVE: Examine the relationship between prescription opioid analgesic use during pregnancy and preterm birth or term low birthweight. DESIGN, SETTING, AND PARTICIPANTS: We analyzed data from the National Birth Defects Prevention Study, a US multisite, population-based study, for births from 1997 to 2011. We defined exposure as self-reported prescription opioid use between one month before conception and the end of pregnancy, and we dichotomized opioid use duration by ≤7 days and >7 days. MAIN OUTCOME MEASURES: We examined the association between opioid use and preterm birth (defined as gestational age <37 weeks) and term low birthweight (defined as <2500 g at gestational age ≥37 weeks). RESULTS: Among 10,491 singleton mother/infant pairs, 470 (4.5 percent) reported opioid use. Among women reporting opioid use, 236 (50 percent) used opioids for > 7 days; codeine (170, 36 percent) and hydrocodone (163, 35 percent) were the most commonly reported opioids. Opioid use was associated with slightly increased risk for preterm birth [adjusted odds ratio, 1.4; 95 percent confidence interval, 1.0, 1.9], particularly with hydrocodone [1.6; 1.0, 2.6], meperidine [2.5; 1.2, 5.2], or morphine [3.0; 1.5, 6.1] use for any duration; however, opioid use was not significantly associated with term low birthweight. CONCLUSIONS: Preterm birth occurred more frequently among infants of women reporting prescription opioid use during pregnancy. However, we could not determine if these risks relate to the drug or to indications for use. Patients who use opioids during pregnancy should be counseled by their practitioners about this and other potential risks associated with opioid use in pregnancy.

      2. OBJECTIVE: To assess consistency of state neonatal risk-appropriate care policies with the 2012 AAP policy seven years post-publication. STUDY DESIGN: Systematic, web-based review of all publicly available 2019 state neonatal levels of care policies. Information on infant risk (gestational age, birth weight), technology and equipment capabilities, and availability of specialty staffing used to define neonatal levels of care was extracted for review. RESULT: Half of states (50%) had a neonatal risk-appropriate care policy. Of those states, 88% had language consistent with AAP-defined Level I criteria, 80% with Level II, 56% with Level III, and 55% with Level IV. Comparing policies (2014-2019), consistency increased in state policies among all levels of care with the greatest increase among level IV criteria. CONCLUSION: States improved consistency of policy language by each level of care, though half of states still lack policy to provide minimum standards of care to the most vulnerable infants.

    • Nutritional Sciences
      1. Anemia design effects in cluster surveys of women and young children in refugee settingsexternal icon
        Hulland EN, Leidman E, Wilkinson C, Tondeur M, Bilukha O.
        PLoS One. 2021 ;16(7):e0254031.
        BACKGROUND: Nutrition surveys in many refugee settings routinely estimate anemia prevalence in high-risk population groups. Given the lack of information on anemia design effects (DEFF) observed in surveys in these settings, the goal of this paper is to better understand the magnitude and distribution of DEFFs and intracluster correlation coefficients (ICCs) in order to inform future survey design. METHODS: Two-stage cluster surveys conducted during 2013-2016 were included if they measured hemoglobin in refugee children aged 6-59 months and/or non-pregnant women aged 15-49 years. Prevalence of anemia, anemia DEFFs and ICCs, mean cluster size, number of clusters, and total sample size were calculated per-survey for non-pregnant women and children. Non-parametric tests were used to assess differences and correlations of ICC and DEFF between women and children and inter-regional differences. RESULTS: Eighty-seven unique cluster surveys from nine countries were included in this analysis. More than 90% of all surveys had ICC values for anemia below 0.10. Median ICC for children was 0.032 (IQR: 0.015-0.048), not significantly different from that observed for non-pregnant women for whom the median was 0.024 (IQR: -0.002-0.055). DEFFs were significantly higher for children [1.54 (IQR: 1.21-1.82)] versus women [1.20 (IQR: 0.99-1.46)]. Regional differences in DEFFs and ICCs were observed. CONCLUSIONS: Both ICCs and DEFF were relatively small for both non-pregnant women and preschool children and fall in a narrow range. Differences in ICCs between women and children were non-significant, suggesting similar inter-cluster distributions of anemia; significant differences in DEFF were likely attributable to differing cluster sizes. Given regional differences in both ICCs and DEFFs, location-specific values are preferred. However, in the absence of other context-specific information, we suggest using DEFFs of 1.4-1.8 if mean cluster size is around 20, and DEFFs of 1.2-1.4 if mean cluster size is around 10.

    • Occupational Safety and Health
      1. Evaluating the effectiveness of earplugs in preventing noise-induced hearing loss in an auto parts factory in Chinaexternal icon
        Gong W, Zhao L, Li L, Morata TC, Qiu W, Feng HA, Zhu B.
        Int. J. Environ. Res. Public Health. 2021 ;18(13).
        A survey was administered to 385 noise-exposed workers from an auto parts factory and 1268 non-noise-exposed health department employees in China. Individual 8 h A-weighted equiva-lent sound levels (LAeq,8h), earplug personal attenuation ratings (PARs), and pure-tone audiometric tests were performed. The average LAeq,8h of noise-exposed workers was 87 dB (A) with a mean PAR of 7 dB. The prevalence of high-frequency hearing loss was 65% for noise-exposed workers and 33% for the non-noise-exposed employees. The use of earplugs had no observable effect on the prevalence of high-frequency hearing loss of the study participants (OR 0.964, 95% CI 0.925–1.005, p = 0.085). No significant relationship between the effectiveness offered by earplug use and high-frequency hearing thresholds at 3, 4, and 6 kHz was found (t = −1.54, p = 0.125). The mandatory requirement of earplug use without individualized training on how to wear HPDs correctly had no detectable effect on the prevention of hearing loss at the auto parts factory. The hearing conservation program at the surveyed factory was not effective. Periodic hearing tests, earplug fit testing, expanding the offer of different types of hearing protection, and employee education about the importance of protecting their hearing were recommended to the occupational health and safety program. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

      2. American Frontline Healthcare Personnel's Access to and Use of Personal Protective Equipment Early in the COVID-19 Pandemicexternal icon
        Rich-Edwards JW, Ding M, Rocheleau CM, Boiano JM, Kang JH, Becene I, Nguyen LH, Chan AT, Hart JE, Chavarro JE, Lawson CC.
        J Occup Environ Med. 2021 Jul 7.
        OBJECTIVES: To quantify adequacy of personal protective equipment (PPE) for U.S. healthcare personnel (HCP) at the outset of the COVID-19 pandemic and its association with infection risk. METHODS: March-May 2020 survey of the national Nurses' Health Studies and the Growing Up Today study regarding self-reported PPE access, use and reuse. COVID-19 endpoints included SARS-CoV-2 tests and COVID-19 status predicted from symptoms. RESULTS: Nearly 22% of 22,232 frontline HCP interacting with COVID-19 patients reported sometimes or always lacking PPE. Fifty percent of HCP reported not needing respirators, including 13% of those working in COVID-19 units. Lack of PPE was cross-sectionally associated with two-fold or greater odds of COVID-19 among those who interacted with infected patients. CONCLUSION: These data show the need to improve the U.S. infection prevention culture of safety when confronting a novel pathogen.

      3. Occupational ApplicationsIn recent years, various upper limb exoskeletons have been developed aiming to support industrial workers for a range of tasks and reduce risks of work-related musculoskeletal disorders. Most commercially available upper limb exoskeletons are passive systems that use compliant elements such as springs or elastic components to store and release energy to assist the user's motion. In contrast, many active exoskeletons, which are typically comprised of one or more powered actuators to provide joint assistance, are still in the research and development stages. Nevertheless, the functions and efficacy of various exoskeleton systems need to be further compared and assessed. This study presents a model-based approach to evaluate different designs of passive and active assistance and demonstrates the benefits of both assistance methods in an overhead lifting task. In addition, the modeling and simulation indicate the potential advantages of using the active assistance, based on electromyography.Technical AbstractBackground: In the literature, efficacy of passive upper limb exoskeletons has been demonstrated in reduced activity of involved muscles during overhead occupational tasks. However, there are fewer studies that have investigated the efficacy of active upper limb exoskeletons or compared them with their passive counterparts.Purpose: We aimed to use an approach simulating human-exoskeleton interactions to compare several passive and active assistance methods in an upper limb exoskeleton and to evaluate how different assistance types affect musculoskeletal loadings during overhead lifting.Methods: An upper-extremity musculoskeletal model was integrated with a five degree-of-freedom exoskeleton for virtual human-in-the-loop evaluation of exoskeleton design and control. Different assistance methods were evaluated, including spring-based activation zones and active control based on EMG, to examine their biomechanical effects on musculoskeletal loadings including interaction forces and moments, muscle activations, and joint moments and reaction forces.Results: Our modeling and simulation results suggest the effectiveness of the proposed passive and active assistance methods in reducing biomechanical loadings-the upper-limb exoskeletons could reduce maximum loading on the shoulder joint by up to 46% compared to the no-exoskeleton situation. Active assistance was found to outperform the passive assistance approach. Specifically, EMG-based active assistance could assist over the whole lifting range and had a larger capability to reduce deltoid muscle activation and shoulder joint reaction force.Conclusions: We used a modeling and simulation approach to virtually evaluate various exoskeleton assistance methods without testing multiple physical prototypes and to investigate the effects of these methods on musculoskeletal loadings that cannot be measured directly or noninvasively. Our findings offer new approaches for testing methods and improving exoskeleton designs with "smart" controls. More research is planned to further optimize the exoskeleton control strategies and validate the simulated results in a real-life implementation.

    • Parasitic Diseases
      1. Efficacy of Artemether-Lumefantrine for the Treatment of Plasmodium falciparum Malaria in Bohicon and Kandi, Republic of Benin, 2018-2019external icon
        Kpemasse A, Dagnon F, Saliou R, Yarou Maye AS, Affoukou CD, Zoulkaneri A, Guézo-Mévo B, Moriarty LF, Ndiaye YD, Garba MN, Deme AB, Ndiaye D, Hounto AO.
        Am J Trop Med Hyg. 2021 Jul 12.
        In 2005, artemether-lumefantrine (AL), an artemisinin-based combination therapy, was introduced as the first-line treatment of uncomplicated Plasmodium falciparum malaria in Benin. Per World Health Organization recommendations to monitor the efficacy of antimalarial treatment, we conducted a therapeutic efficacy study with AL for uncomplicated P. falciparum malaria in Bohicon and Kandi, Benin, from 2018 to 2019. Febrile patients aged 6 to 59 months with confirmed P. falciparum monoinfection received supervised doses of AL for 3 days. We monitored patients clinically and parasitologically on days 1, 2, 3, 7, 14, 21, and 28. A molecular analysis to detect mutations in the P. falciparum Kelch propeller gene (Pfk13) gene was carried out on day 0 samples. A total of 205 patients were included in the study. In Bohicon, the uncorrected adequate clinical and parasitological response (ACPR) proportion was 91.3% (95% confidence interval [CI]: 84.6-95.8%), whereas in Kandi this proportion was 96.7% (95% CI: 90.6-99.3%). Genotype-corrected ACPR proportions were 96.3% (95% CI: 90.9-99.0%) and 96.7% (95% CI: 90.6-99.3%) in Bohicon and Kandi, respectively. On day 3, 100% of patients in Bohicon and 98.9% of patients in Kandi had undetectable parasitemia. The C580Y mutation in the Pfk13 gene was not observed. AL remains effective for P. falciparum malaria in these two sites in Benin. Monitoring antimalarial efficacy and prevalence of molecular-resistance markers in Benin should be continued to allow for early detection of antimalarial resistance and to guide treatment policies.

    • Public Health Leadership and Management
      1. Processes for Implementing Community Health Worker Workforce Development Initiativesexternal icon
        Barbero C, Mason T, Rush C, Sugarman M, Bhuiya AR, Fulmer EB, Feldstein J, Cottoms N, Wennerstrom A.
        Front Public Health. 2021 ;9:659017.
        Introduction: The objective of this observational, cross-sectional study was to identify, document, and assess the progress made to date in implementing various processes involved in statewide community health worker (CHW) workforce development initiatives. Methods: From September 2017 to December 2020, we developed and applied a conceptual model of processes involved in implementing statewide CHW initiatives. One or more outputs were identified for each model process and assessed across the 50 states, D.C., and Puerto Rico using peer-reviewed and gray literature available as of September 2020. Results: Twelve statewide CHW workforce development processes were identified, and 21 outputs were assessed. We found an average of eight processes implemented per state, with seven states implementing all 12 processes. As of September 2020, 45 states had a multi-stakeholder CHW coalition and 31 states had a statewide CHW organization. In 20 states CHWs were included in Medicaid Managed Care Organizations or Health Plans. We found routine monitoring of statewide CHW employment in six states. Discussion: Stakeholders have advanced statewide CHW workforce development initiatives using the processes reflected in our conceptual model. Our results could help to inform future CHW initiative design, measurement, monitoring, and evaluation efforts, especially at the state level.

    • Substance Use and Abuse
      1. Changes in Initial Opioid Prescribing Practices After the 2016 Release of the CDC Guideline for Prescribing Opioids for Chronic Painexternal icon
        Goldstick JE, Guy GP, Losby JL, Baldwin G, Myers M, Bohnert AS.
        JAMA Netw Open. 2021 Jul 1;4(7):e2116860.
        IMPORTANCE: The Centers for Disease Control and Prevention (CDC) released the "Guideline For Prescribing Opioids For Chronic Pain" (hereafter, CDC guideline) in 2016, but its association with prescribing practices for patients who are opioid naive is unknown. OBJECTIVE: To estimate changes in initial prescribing rates, duration, and dosage practices to patients who are opioid naive after the release of the CDC guideline. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used 6 sequential cohorts to estimate preguideline trends in prescribing among patients who were opioid naive, project that trend forward, and compare it with postguideline prescribing practices. Participants included commercially insured adults without current cancer or hospice care diagnoses and with no past-year opioid claims in the US from 2011 to 2017. All adjusted models were controlled for patient demographics and state-fixed effects. Data were analyzed from January 2020 to May 2021. EXPOSURES: The release of the CDC guideline. MAIN OUTCOMES AND MEASURES: Indicators of any opioid prescription fills during a 9-month period, the number of days' supply of the initial prescription, and the binary indicator of whether the initial prescription was for 50 or more morphine milligram equivalents (MMEs) per day. RESULTS: There were 12 870 612 eligible unique patients across cohorts (mean [SD] age in 2016, 51.2 [18.7] years; 6 553 458 [50.9%] women); and the mean (SD) age of the cohorts increased annually, from 48.7 (17.9) years in the April 2011 to December 2012 cohort to 51.9 (19.2) years in the April 2016 to December 2017 cohort. The postguideline prescribing prevalence was 532 962 of 5 834 088 individuals (9.1%), which exceeded that projected from the preguideline trend, estimated at 9.0% (95% CI, 9.0%-9.1%). Among patients receiving prescriptions during follow-up, adjusted mean days' supply was 4.7% (95% CI, 4.3%-5.1%) lower in the first year after release of the guideline and 9.8% (95% CI, 9.3%-10.3%) lower in the second year after release, compared with the expected rate from the preguideline trend. The adjusted odds of receiving a high-dose (ie, ≥50 MME/d) initial prescription were lower in the first year (odds ratio, 0.97; 95% CI, 0.96-0.98) and in the second year (odds ratio, 0.94; 95% CI, 0.93-0.96) after the release of the CDC guideline compared with the odds expected from the preguideline trend. CONCLUSIONS AND RELEVANCE: This cohort study found that patients who were opioid naive continued to initiate opioid therapy after the release of opioid prescribing guidelines by the CDC, but trends in prescribing duration reversed and decreased, after increasing in each of 4 preguideline cohorts examined. High-dose prescribing rates were already decreasing, but those trends accelerated after the CDC guideline release. These results suggest that nonmandatory, evidence-based guidelines from trusted sources were associated with prescribing practices. Guideline-concordant care has potential to improve pain management and reduce opioid-related harms.

      2. Associations between biomarkers of exposure and lung cancer risk among exclusive cigarette smokers in the Golestan Cohort Studyexternal icon
        Rostron BL, Wang J, Etemadi A, Thakur S, Chang JT, Bhandari D, Botelho JC, De Jesús VR, Feng J, Gail MH, Inoue-Choi M, Malekzadeh R, Pourshams A, Poustchi H, Roshandel G, Shiels MS, Wang Q, Wang Y, Xia B, Boffetta P, Brennan P, Abnet CC, Calafat AM, Wang L, Blount BC, Freedman ND, Chang CM.
        Int. J. Environ. Res. Public Health. 2021 ;18(14).
        Biomarkers of tobacco exposure are known to be associated with disease risk but previous studies are limited in number and restricted to certain regions. We conducted a nested case–control study examining baseline levels and subsequent lung cancer incidence among current male exclusive cigarette smokers in the Golestan Cohort Study in Iran. We calculated geometric mean biomarker concentrations for 28 matched cases and 52 controls for the correlation of biomarker levels among controls and for adjusted odds’ ratios (ORs) for lung cancer incidence by biomarker concentration, accounting for demographic characteristics, smoking quantity and duration, and opium use. Lung cancer cases had higher average levels of most biomarkers including total nicotine equivalents (TNE-2), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and 3-hydroxyfluorene (3-FLU). Many biomarkers correlated highly with one another including TNE-2 with NNAL and N-Acetyl-S-(2-cyanoethyl)-L-cysteine (2CYEMA), and N-Acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine (t4HBEMA) with N-Acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine (3HMPMA) and N-Acetyl-S-(4-hydroxy-2-methyl-2-buten-1-yl)-L-cysteine (4HMBEMA). Lung cancer risk increased with concentration for several biomarkers, including TNE-2 (OR = 2.22, 95% CI = 1.03, 4.78) and NNN (OR = 2.44, 95% CI = 1.13, 5.27), and estimates were significant after further adjustment for demographic and smoking characteristics for 2CYEMA (OR = 2.17, 95% CI = 1.03, 4.55), N-Acetyl-S-(2-carbamoylethyl)-L-cysteine (2CAEMA) (OR = 2.14, 95% CI = 1.01, 4.55), and N-Acetyl-S-(2-hydroxypropyl)-L-cysteine (2HPMA) (OR = 2.85, 95% CI = 1.04, 7.81). Estimates were not significant with adjustment for opium use. Concentrations of many biomarkers were higher at the baseline for participants who subsequently developed lung cancer than among the matched controls. Odds of lung cancer were higher for several biomarkers including with adjustment for smoking exposure for some but not with adjustment for opium use. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

    • Zoonotic and Vectorborne Diseases
      1. Q Fever: A Troubling Disease and a Challenging Diagnosisexternal icon
        Miller HK, Priestley RA, Kersh GJ.
        Clin. Microbiol. Newsl.. 2021 ;43(13):109-118.
        Q fever is a disease caused by the bacterial pathogen Coxiella burnetii. This hardy organism can easily spread long distances in the wind, and only a few infectious aerosolized particles are necessary to cause serious illness. Presentations of Q fever disease can be wide ranging, allowing it to masquerade as other illnesses, highlighting the importance of laboratory testing for diagnosis and treatment. This review summarizes Q fever's epidemiology and clinical presentations and presents classical laboratory diagnostic assays and novel approaches to detecting this troubling disease. © 2021 Elsevier Inc.

      2. Antimicrobial Treatment and Prophylaxis of Plague: Recommendations for Naturally Acquired Infections and Bioterrorism Responseexternal icon
        Nelson CA, Meaney-Delman D, Fleck-Derderian S, Cooley KM, Yu PA, Mead PS.
        MMWR Recomm Rep. 2021 Jul 16;70(3):1-27.
        This report provides CDC recommendations to U.S. health care providers regarding treatment, pre-exposure prophylaxis, and postexposure prophylaxis of plague. Yersinia pestis, the bacterium that causes plague, leads to naturally occurring disease in the United States and other regions worldwide and is recognized as a potential bioterrorism weapon. A bioweapon attack with Y. pestis could potentially infect thousands, requiring rapid and informed decision making by clinicians and public health agencies. The U.S. government stockpiles a variety of medical countermeasures to mitigate the effects of a bioterrorism attack (e.g., antimicrobials, antitoxins, and vaccines) for which the 21st Century Cures Act mandates the development of evidence-based guidelines on appropriate use. Guidelines for treatment and postexposure prophylaxis of plague were published in 2000 by a nongovernmental work group; since then, new human clinical data, animal study data, and U.S. Food and Drug Administration approvals of additional countermeasures have become available. To develop a comprehensive set of updated guidelines, CDC conducted a series of systematic literature reviews on human treatment of plague and other relevant topics to collect a broad evidence base for the recommendations in this report. Evidence from CDC reviews and additional sources were presented to subject matter experts during a series of forums. CDC considered individual expert input while developing these guidelines, which provide recommended best practices for treatment and prophylaxis of human plague for both naturally occurring disease and following a bioterrorism attack. The guidelines do not include information on diagnostic testing, triage decisions, or logistics involved in dispensing medical countermeasures. Clinicians and public health officials can use these guidelines to prepare their organizations, hospitals, and communities to respond to a plague mass-casualty event and as a guide for treating patients affected by plague.

      3. Implementation of the Ebola Virus Persistence in Ocular Tissues and Fluids (EVICT) study: Lessons learned for vision health systems strengthening in Sierra Leoneexternal icon
        Shantha JG, Crozier I, Kraft CS, Grant DG, Goba A, Hayek BR, Hartley C, Barnes KG, Uyeki TM, Schieffelin J, Garry RF, Bausch DG, Farmer PE, Mattia JG, Vandy MJ, Yeh S.
        PLoS One. 2021 ;16(7):e0252905.
        BACKGROUND: Following the West African Ebola virus disease (EVD) outbreak of 2013-2016 and more recent EVD outbreaks in the Democratic Republic of Congo, thousands of EVD survivors are at-risk for sequelae including uveitis, which can lead to unremitting inflammation and vision loss from cataract. Because of the known risk of Ebola virus persistence in ocular fluid and the need to provide vision-restorative, safe cataract surgery, the Ebola Virus Persistence in Ocular Tissues and Fluids (EVICT) Study was implemented in Sierra Leone. During implementation of this multi-national study, challenges included regulatory approvals, mobilization, community engagement, infection prevention and control, and collaboration between multiple disciplines. In this report, we address the multifacted approach to address these challenges and the impact of implementation science research to address an urgent clinical subspecialty need in an outbreak setting. METHODOLOGY/PRINCIPAL FINDINGS: Given the patient care need to develop a protocol to evaluate ocular fluid for Ebola virus RNA persistence prior to cataract surgery, as well as protocols to provide reassurance to ophthalmologists caring for EVD survivors with cataracts, the EVICT study was designed and implemented through the work of the Ministry of Health, Sierra Leone National Eye Programme, and international partnerships. The EVICT study showed that all 50 patients who underwent ocular fluid sampling at 19 and 34 months, respectively, tested negative for Ebola virus RNA. Thirty-four patients underwent successful cataract surgery with visual acuity improvement. Here we describe the methodology for study implementation, challenges encountered, and key issues that impacted EVD vision care in the immediate aftermath of the EVD outbreak. Key aspects of the EVICT study included defining the pertinent questions and clinical need, partnership alignment with key stakeholders, community engagement with EVD survivor associations, in-country and international regulatory approvals, study site design for infection prevention and control, and thorough plans for EVD survivor follow-up care and monitoring. Challenges encountered included patient mobilization owing to transportation routes and distance of patients in rural districts. Strong in-country partnerships and multiple international organizations overcame these challenges so that lessons learned could be applied for future EVD outbreaks in West and Central Africa including EVD outbreaks that are ongoing in Guinea and Democratic Republic of Congo. CONCLUSIONS/SIGNIFICANCE: The EVICT Study showed that cataract surgery with a protocol-driven approach was safe and vision-restorative for EVD survivors, which provided guidance for EVD ophthalmic surgical care. Ophthalmologic care remains a key aspect of the public health response for EVD outbreaks but requires a meticulous, yet partnered approach with international and local in-country partners. Future efforts may build on this framework for clinical care and to improve our understanding of ophthalmic sequelae, develop treatment paradigms for EVD survivors, and strengthen vision health systems in resource-limited settings.

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

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