Last data update: Sep 16, 2024. (Total: 47680 publications since 2009)
Records 1-30 (of 141 Records) |
Query Trace: Todd J [original query] |
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Early pregnancy plasma per- and polyfluoroalkyl substances (PFAS) and maternal midlife adiposity
Burdeau JA , Stephenson BJK , Chavarro JE , Mahalingaiah S , Preston EV , Hivert MF , Oken E , Calafat AM , Rifas-Shiman SL , Zota AR , James-Todd T . J Clin Endocrinol Metab 2024 CONTEXT: Evidence suggests that exposure to per- and polyfluoroalkyl substances (PFAS) increases the risk of developing cardiometabolic disease risk factors. Limited research has evaluated associations between PFAS, assessed during pregnancy, a sensitive window for maternal endocrine effects, and long-term maternal adiposity. OBJECTIVE: Estimate associations of early pregnancy measures of individual PFAS, and PFAS mixtures, with maternal adiposity in midlife. METHODS: We studied 547 Project Viva participants with measures of early pregnancy (mean gestation 10.0 weeks; mean age 32.5 years) plasma concentrations of 6 PFAS and midlife adiposity outcomes (mean follow-up 17.7 years; mean age 50.7 years), including weight, waist circumference (WC), trunk fat mass (TFM), and total body fat mass (TBFM). We used linear regression and Bayesian Kernel Machine Regression (BKMR). RESULTS: Linear regression estimated higher midlife weight per doubling of perfluorooctane sulfonate (PFOS) (3.8 kg [95% CI: 1.6, 5.9]) and 2-(N-ethyl-perfluorooctane sulfonamido) acetate (2.3 kg [95% CI: 0.9, 3.7]). BKMR analyses of single PFAS plasma concentrations (comparing the 25th percentile concentration to the 75th percentile) showed a positive association between PFOS and midlife adiposity (weight: 7.7 kg [95% CI: 4.0, 11.5]; TFM: 1.2 kg [95% CI: 0.0, 2.3]; TBFM: 3.0 kg [95% CI: 0.8, 5.2]), but inverse associations with perfluorononanoate (weight: -6.0 kg [95% CI: -8.5, -3.5]; WC: -1.8 cm [95% CI: -3.2, -0.3]; TFM: -0.8 kg [95% CI: -1.5, -0.1]; TBFM: -1.4 kg [95% CI: -2.7, -0.3]) and perfluorohexane sulfonate (TFM: -0.8 kg [95% CI: -1.5, -0.1]; TBFM: -1.4 kg [95% CI: -2.6, -0.2]). No associations were observed with the overall PFAS mixture. CONCLUSION: Select PFAS, assessed in pregnancy, may differentially affect maternal midlife adiposity, influencing later-life maternal cardiometabolic health. |
Mixtures of urinary phenol and phthalate metabolite concentrations in relation to serum lipid levels among pregnant women: Results from the EARTH Study
Shen X , Génard-Walton M , Williams PL , James-Todd T , Ford JB , Rexrode KM , Calafat AM , Zhang D , Chavarro JE , Hauser R , Mínguez-Alarcón L , The Earth Study Team . Toxics 2024 12 (8) We examined whether mixtures of urinary concentrations of bisphenol A (BPA), parabens and phthalate metabolites were associated with serum lipid levels among 175 pregnant women who enrolled in the Environment and Reproductive Health (EARTH) Study (2005-2017), including triglycerides, total cholesterol, high-density lipoprotein (HDL), non-HDL, and low-density lipoprotein (LDL). We applied Bayesian Kernel Machine Regression (BKMR) and quantile g-computation while adjusting for confounders. In the BKMR models, we found no associations between chemical mixture and lipid levels, e.g., total cholesterol [mean difference (95% CRI, credible interval) = 0.02 (-0.31, 0.34)] and LDL [mean difference (95% CRI) = 0.10 (-0.22, 0.43)], when comparing concentrations at the 75th to the 25th percentile. When stratified by BMI, we found suggestive positive relationships between urinary propylparaben and total cholesterol and LDL among women with high BMI [mean difference (95% CRI) = 0.25 (-0.26, 0.75) and 0.35 (-0.25, 0.95)], but not with low BMI [mean difference (95% CRI) = 0.00 (-0.06, 0.07) and 0.00 (-0.07, 0.07)]. No association was found by quantile g-computation. This exploratory study suggests mixtures of phenol and phthalate metabolites were not associated with serum lipid levels during pregnancy, while there were some suggestive associations for certain BMI subgroups. Larger longitudinal studies with multiple assessments of both exposure and outcome are needed to corroborate these novel findings. |
First trimester plasma per- and polyfluoroalkyl substances (PFAS) and blood pressure trajectories across the second and third trimesters of pregnanacy
Burdeau JA , Stephenson BJK , Aris IM , Preston EV , Hivert MF , Oken E , Mahalingaiah S , Chavarro JE , Calafat AM , Rifas-Shiman SL , Zota AR , James-Todd T . Environ Int 2024 186 108628 BACKGROUND: Evidence suggests that exposure to per- and polyfluoroalkyl substances (PFAS) increases risk of high blood pressure (BP) during pregnancy. Prior studies did not examine associations with BP trajectory parameters (i.e., overall magnitude and velocity) during pregnancy, which is linked to adverse pregnancy outcomes. OBJECTIVES: To estimate associations of multiple plasma PFAS in early pregnancy with BP trajectory parameters across the second and third trimesters. To assess potential effect modification by maternal age and parity. METHODS: In 1297 individuals, we quantified six PFAS in plasma collected during early pregnancy (median gestational age: 9.4 weeks). We abstracted from medical records systolic BP (SBP) and diastolic BP (DBP) measurements, recorded from 12 weeks gestation until delivery. BP trajectory parameters were estimated via Super Imposition by Translation and Rotation modeling. Subsequently, Bayesian Kernel Machine Regression (BKMR) was employed to estimate individual and joint associations of PFAS concentrations with trajectory parameters - adjusting for maternal age, race/ethnicity, pre-pregnancy body mass index, income, parity, smoking status, and seafood intake. We evaluated effect modification by age at enrollment and parity. RESULTS: We collected a median of 13 BP measurements per participant. In BKMR, higher concentration of perfluorooctane sulfonate (PFOS) was independently associated with higher magnitude of overall SBP and DBP trajectories (i.e., upward shift of trajectories) and faster SBP trajectory velocity, holding all other PFAS at their medians. In stratified BKMR analyses, participants with ≥ 1 live birth had more pronounced positive associations between PFOS and SBP velocity, DBP magnitude, and DBP velocity - compared to nulliparous participants. We did not observe significant associations between concentrations of the overall PFAS mixture and either magnitude or velocity of the BP trajectories. CONCLUSION: Early pregnancy plasma PFOS concentrations were associated with altered BP trajectory in pregnancy, which may impact future cardiovascular health of the mother. |
Clinical course, antifungal susceptibility, and genomic sequencing of trichophyton indotineae
Caplan AS , Todd GC , Zhu Y , Sikora M , Akoh CC , Jakus J , Lipner SR , Babbush K , Acker KP , Morales AE , Rolón RMM , Westblade LF , Fonseca M , Cline A , Gold JAW , Lockhart SR , Smith DJ , Chiller T , Greendyke WG , Manjari SR , Banavali NK , Chaturvedi S . JAMA Dermatol 2024 IMPORTANCE: Trichophyton indotineae is an emerging dermatophyte causing outbreaks of extensive tinea infections often unresponsive to terbinafine. This species has been detected worldwide and in multiple US states, yet detailed US data on infections with T indotineae are sparse and could improve treatment practices and medical understanding of transmission. OBJECTIVE: To correlate clinical features of T indotineae infections with in vitro antifungal susceptibility testing results, squalene epoxidase gene sequence variations, and isolate relatedness using whole-genome sequencing. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study of patients with T indotineae infections in New York City spanned May 2022 to May 2023. Patients with confirmed T indotineae infections were recruited from 6 New York City medical centers. MAIN OUTCOME AND MEASURE: Improvement or resolution at the last follow-up assessment. RESULTS: Among 11 patients with T indotineae (6 male and 5 female patients; median [range] age, 39 [10-65] years), 2 were pregnant; 1 had lymphoma; and the remainder were immunocompetent. Nine patients reported previous travel to Bangladesh. All had widespread lesions with variable scale and inflammation, topical antifungal monotherapy failure, and diagnostic delays (range, 3-42 months). Terbinafine treatment failed in 7 patients at standard doses (250 mg daily) for prolonged duration; these patients also had isolates with amino acid substitutions at positions 393 (L393S) or 397 (F397L) in squalene epoxidase that correlated with elevated terbinafine minimum inhibitory concentrations of 0.5 μg/mL or higher. Patients who were treated with fluconazole and griseofulvin improved in 2 of 4 and 2 of 5 instances, respectively, without correlation between outcomes and antifungal minimum inhibitory concentrations. Furthermore, 5 of 7 patients treated with itraconazole cleared or had improvement at the last follow-up, and 2 of 7 were lost to follow-up or stopped treatment. Based on whole-genome sequencing analysis, US isolates formed a cluster distinct from Indian isolates. CONCLUSION AND RELEVANCE: The results of this case series suggest that disease severity, diagnostic delays, and lack of response to typically used doses and durations of antifungals for tinea were common in this primarily immunocompetent patient cohort with T indotineae, consistent with published data. Itraconazole was generally effective, and the acquisition of infection was likely in Bangladesh. |
Benzophenone-3 and ovarian reserve
Silva EL , Mínguez-Alarcón L , Coull B , Hart JE , James-Todd T , Calafat AM , Ford JB , Hauser R , Mahalingaiah S . Fertil Steril 2024 OBJECTIVE: To evaluate the association between urinary benzophenone-3 concentrations and measures of ovarian reserve (OR) among women in the Environment and Reproductive Health (EARTH) Study seeking fertility treatment at Massachusetts General Hospital in Boston, Massachusetts. DESIGN: Prospective cohort study. METHODS: Women from the EARTH cohort contributed spot urine samples before assessment of OR outcomes. Antral follicle count (AFC) and day-3 follicle stimulating hormone (FSH) levels were evaluated as part of standard infertility workups during unstimulated menstrual cycles. Quasi-Poisson and linear regression models were used to evaluate the association of specific gravity (SG)-adjusted urinary benzophenone-3 concentrations with AFC and FSH, respectively, with adjustment for age and physical activity. In secondary analyses, models were stratified by age. Sensitivity analyses assessed for confounding by season by restricting to women with exposure and outcome measured in the same season and stratifying by summer vs. non-summer months and for confounding by sunscreen use by restricting to women who filled out product questionnaires and adjusting for and stratifying by average sunscreen use score. RESULTS: The study included 142 women (mean age ± SD, 36.1 ± 4.6; range, 22-45 years) enrolled between 2009 and 2017 with both urinary benzophenone-3 and AFC and 57 women with benzophenone-3 and FSH measurements. Most women were white (78%) and highly educated (49% with a graduate degree). Women contributed a mean of 2.7 urine samples (range, 1-10) with 37% contributing 2 or more samples. Benzophenone-3 was detected in 98% of samples. Geometric mean (GM) SG-corrected urinary benzophenone-3 concentration was 85.9 μ g/L (geometric standard deviation 6.2). There were no associations of benzophenone-3 with AFC and day-3 FSH in the full cohort. In stratified models, a 1-unit increase in log GM benzophenone-3 was associated with AFC 0.91 (95% CI, 0.86, 0.97) times lower among women ≤35 years old and was associated with FSH 0.73 (95% CI, 0.12, 1.34) IU/L higher among women >35 years old. Effect estimates from models stratified by season and sunscreen use were null. CONCLUSION: In main models, urinary benzophenone-3 was not associated with OR. However, younger may be vulnerable to potential effects of benzophenone-3 on AFC. Further research is warranted. |
Clinical decision support system for guidelines-based treatment of gonococcal infections, screening for HIV, and prescription of pre-exposure prophylaxis: Design and implementation study
Karki S , Shaw S , Lieberman M , Pérez A , Pincus J , Jakhmola P , Tailor A , Ogunrinde OB , Sill D , Morgan S , Alvarez M , Todd J , Smith D , Mishra N . JMIR Form Res 2024 8 e53000 BACKGROUND: The syndemic nature of gonococcal infections and HIV provides an opportunity to develop a synergistic intervention tool that could address the need for adequate treatment for gonorrhea, screen for HIV infections, and offer pre-exposure prophylaxis (PrEP) for persons who meet the criteria. By leveraging information available on electronic health records, a clinical decision support (CDS) system tool could fulfill this need and improve adherence to Centers for Disease Control and Prevention (CDC) treatment and screening guidelines for gonorrhea, HIV, and PrEP. OBJECTIVE: The goal of this study was to translate portions of CDC treatment guidelines for gonorrhea and relevant portions of HIV screening and prescribing PrEP that stem from a diagnosis of gonorrhea as an electronic health record-based CDS intervention. We also assessed whether this CDS solution worked in real-world clinic. METHODS: We developed 4 tools for this CDS intervention: a form for capturing sexual history information (SmartForm), rule-based alerts (best practice advisory), an enhanced sexually transmitted infection (STI) order set (SmartSet), and a documentation template (SmartText). A mixed methods pre-post design was used to measure the feasibility, use, and usability of the CDS solution. The study period was 12 weeks with a baseline patient sample of 12 weeks immediately prior to the intervention period for comparison. While the entire clinic had access to the CDS solution, we focused on a subset of clinicians who frequently engage in the screening and treatment of STIs within the clinical site under the name "X-Clinic." We measured the use of the CDS solution within the population of patients who had either a confirmed gonococcal infection or an STI-related chief complaint. We conducted 4 midpoint surveys and 3 key informant interviews to quantify perception and impact of the CDS solution and solicit suggestions for potential future enhancements. The findings from qualitative data were determined using a combination of explorative and comparative analysis. Statistical analysis was conducted to compare the differences between patient populations in the baseline and intervention periods. RESULTS: Within the X-Clinic, the CDS alerted clinicians (as a best practice advisory) in one-tenth (348/3451, 10.08%) of clinical encounters. These 348 encounters represented 300 patients; SmartForms were opened for half of these patients (157/300, 52.33%) and was completed for most for them (147/300, 89.81%). STI test orders (SmartSet) were initiated by clinical providers in half of those patients (162/300, 54%). HIV screening was performed during about half of those patient encounters (191/348, 54.89%). CONCLUSIONS: We successfully built and implemented multiple CDC treatment and screening guidelines into a single cohesive CDS solution. The CDS solution was integrated into the clinical workflow and had a high rate of use. |
Racial and ethnic disparities in phthalate exposure and preterm birth: A pooled study of sixteen U.S. Cohorts
Welch BM , Keil AP , Buckley JP , Engel SM , James-Todd T , Zota AR , Alshawabkeh AN , Barrett ES , Bloom MS , Bush NR , Cordero JF , Dabelea D , Eskenazi B , Lanphear BP , Padmanabhan V , Sathyanarayana S , Swan SH , Aalborg J , Baird DD , Binder AM , Bradman A , Braun JM , Calafat AM , Cantonwine DE , Christenbury KE , Factor-Litvak P , Harley KG , Hauser R , Herbstman JB , Hertz-Picciotto I , Holland N , Jukic AMZ , McElrath TF , Meeker JD , Messerlian C , Michels KB , Newman RB , Nguyen RHN , O'Brien KM , Rauh VA , Redmon B , Rich DQ , Rosen EM , Schmidt RJ , Sparks AE , Starling AP , Wang C , Watkins DJ , Weinberg CR , Weinberger B , Wenzel AG , Wilcox AJ , Yolton K , Zhang Y , Ferguson KK . Environ Health Perspect 2023 131 (12) 127015 BACKGROUND: Phthalate exposures are ubiquitous during pregnancy and may contribute to racial and ethnic disparities in preterm birth. OBJECTIVES: We investigated race and ethnicity in the relationship between biomarkers of phthalate exposure and preterm birth by examining: a) how hypothetical reductions in racial and ethnic disparities in phthalate metabolites might reduce the probability of preterm birth; and b) exposure-response models stratified by race and ethnicity. METHODS: We pooled individual-level data on 6,045 pregnancies from 16 U.S. cohorts. We investigated covariate-adjusted differences in nine urinary phthalate metabolite concentrations by race and ethnicity [non-Hispanic White (White, 43%), non-Hispanic Black (Black, 13%), Hispanic/Latina (38%), and Asian/Pacific Islander (3%)]. Using g-computation, we estimated changes in the probability of preterm birth under hypothetical interventions to eliminate disparities in levels of urinary phthalate metabolites by proportionally lowering average concentrations in Black and Hispanic/Latina participants to be approximately equal to the averages in White participants. We also used race and ethnicity-stratified logistic regression to characterize associations between phthalate metabolites and preterm birth. RESULTS: In comparison with concentrations among White participants, adjusted mean phthalate metabolite concentrations were consistently higher among Black and Hispanic/Latina participants by 23%-148% and 4%-94%, respectively. Asian/Pacific Islander participants had metabolite levels that were similar to those of White participants. Hypothetical interventions to reduce disparities in metabolite mixtures were associated with lower probabilities of preterm birth for Black [13% relative reduction; 95% confidence interval (CI): - 34%, 8.6%] and Hispanic/Latina (9% relative reduction; 95% CI: - 19%, 0.8%) participants. Odds ratios for preterm birth in association with phthalate metabolites demonstrated heterogeneity by race and ethnicity for two individual metabolites (mono-n-butyl and monoisobutyl phthalate), with positive associations that were larger in magnitude observed among Black or Hispanic/Latina participants. CONCLUSIONS: Phthalate metabolite concentrations differed substantially by race and ethnicity. Our results show hypothetical interventions to reduce population-level racial and ethnic disparities in biomarkers of phthalate exposure could potentially reduce the probability of preterm birth. https://doi.org/10.1289/EHP12831. |
Using electronic health record data to measure the latent tuberculosis infection care cascade in safety-net primary care clinics
Vonnahme LA , Raykin J , Jones M , Oakley J , Puro J , Langer A , Aiona K , Belknap R , Ayers T , Todd J , Winglee K . AJPM Focus 2023 2 (4) 100148 Introduction: Prevention of tuberculosis disease through diagnosis and treatment of latent tuberculosis infection is critical for achieving tuberculosis elimination in the U.S. Diagnosis and treatment of latent tuberculosis infection in safety-net primary care settings that serve patients at risk for tuberculosis may increase uptake of this prevention effort and accelerate progress toward elimination. Optimizing tuberculosis prevention in these settings requires measuring the latent tuberculosis infection care cascade (testing, diagnosis, and treatment) and identifying gaps to develop solutions to overcome barriers. We used electronic health record data to describe the latent tuberculosis infection care cascade and identify gaps among a network of safety-net primary care clinics. Methods: Electronic health record data for patients seen in the OCHIN Clinical Network, the largest network of safety-net clinics in the U.S., between 2012 and 2019 were extracted. electronic health record data were used to measure the latent tuberculosis infection care cascade: patients who met tuberculosis screening criteria on the basis of current recommendations were tested for tuberculosis infection, diagnosed with latent tuberculosis infection, and prescribed treatment for latent tuberculosis infection. Outcomes were stratified by diagnostic test and treatment regimen. Results: Among 1.9 million patients in the analytic cohort, 43.5% met tuberculosis screening criteria, but only 21.4% were tested for latent tuberculosis infection; less than half (40.4%) were tested using an interferon-gamma release assay. Among those with a valid result, 10.5% were diagnosed with latent tuberculosis infection, 29.1% of those were prescribed latent tuberculosis infection treatment, and only 33.6% were prescribed a recommended rifamycin-based regimen. Conclusions: Electronic health record data can be used to measure the latent tuberculosis infection care cascade. A large proportion of patients in this safety-net clinical network are at high risk for tuberculosis infection. Addressing identified gaps in latent tuberculosis infection testing and treatment may have a direct impact on improving tuberculosis prevention in primary care clinics and accelerate progress toward elimination. © 2023 |
Self-Reported Mask Use among Persons with or without SARS CoV-2 Vaccination -United States, December 2020-August 2021 (preprint)
Calamari LE , Weintraub WS , Santos R , Gibbs M , Bertoni AG , Ward LM , Saydah S , Plumb ID , Runyon MS , Wierzba TF , Sanders JW , Herrington D , Espeland MA , Williamson J , Mongraw-Chaffin M , Bertoni A , Alexander-Miller MA , Castri P , Mathews A , Munawar I , Seals AL , Ostasiewski B , Ballard CAP , Gurcan M , Ivanov A , Zapata GM , Westcott M , Blinson K , Blinson L , Mistysyn M , Davis D , Doomy L , Henderson P , Jessup A , Lane K , Levine B , McCanless J , McDaniel S , Melius K , O'Neill C , Pack A , Rathee R , Rushing S , Sheets J , Soots S , Wall M , Wheeler S , White J , Wilkerson L , Wilson R , Wilson K , Burcombe D , Saylor G , Lunn M , Ordonez K , O'Steen A , Wagner L , McCurdy LH , Gibbs MA , Taylor YJ , Calamari L , Tapp H , Ahmed A , Brennan M , Munn L , Dantuluri KL , Hetherington T , Lu LC , Dunn C , Hogg M , Price A , Leonidas M , Manning M , Rossman W , Gohs FX , Harris A , Priem JS , Tochiki P , Wellinsky N , Silva C , Ludden T , Hernandez J , Spencer K , McAlister L , Weintraub W , Miller K , Washington C , Moses A , Dolman S , Zelaya-Portillo J , Erkus J , Blumenthal J , Romero Barrientos RE , Bennett S , Shah S , Mathur S , Boxley C , Kolm P , Franklin E , Ahmed N , Larsen M , Oberhelman R , Keating J , Kissinger P , Schieffelin J , Yukich J , Beron A , Teigen J , Kotloff K , Chen WH , Friedman-Klabanoff D , Berry AA , Powell H , Roane L , Datar R , Correa A , Navalkele B , Min YI , Castillo A , Ward L , Santos RP , Anugu P , Gao Y , Green J , Sandlin R , Moore D , Drake L , Horton D , Johnson KL , Stover M , Lagarde WH , Daniel L , Maguire PD , Hanlon CL , McFayden L , Rigo I , Hines K , Smith L , Harris M , Lissor B , Cook V , Eversole M , Herrin T , Murphy D , Kinney L , Diehl P , Abromitis N , Pierre TSt , Heckman B , Evans D , March J , Whitlock B , Moore W , Arthur S , Conway J , Gallaher TR , Johanson M , Brown S , Dixon T , Reavis M , Henderson S , Zimmer M , Oliver D , Jackson K , Menon M , Bishop B , Roeth R , King-Thiele R , Hamrick TS , Ihmeidan A , Hinkelman A , Okafor C , Bray Brown RB , Brewster A , Bouyi D , Lamont K , Yoshinaga K , Vinod P , Peela AS , Denbel G , Lo J , Mayet-Khan M , Mittal A , Motwani R , Raafat M , Schultz E , Joseph A , Parkeh A , Patel D , Afridi B , Uschner D , Edelstein SL , Santacatterina M , Strylewicz G , Burke B , Gunaratne M , Turney M , Zhou SQ , Tjaden AH , Fette L , Buahin A , Bott M , Graziani S , Soni A , Mores C , Porzucek A , Laborde R , Acharya P , Guill L , Lamphier D , Schaefer A , Satterwhite WM , McKeague A , Ward J , Naranjo DP , Darko N , Castellon K , Brink R , Shehzad H , Kuprianov D , McGlasson D , Hayes D , Edwards S , Daphnis S , Todd B , Goodwin A , Berkelman R , Hanson K , Zeger S , Hopkins J , Reilly C , Edwards K , Gayle H , Redd S . medRxiv 2022 10 Wearing a facemask can help to decrease the transmission of COVID-19. We investigated self-reported mask use among subjects aged 18 years and older participating in the COVID-19 Community Research Partnership (CRP), a prospective longitudinal COVID-19 surveillance study in the mid-Atlantic and southeastern United States. We included those participants who completed >=5 daily surveys each month from December 1, 2020 through August 31, 2021. Mask use was defined as self-reported use of a face mask or face covering on every interaction with others outside the household within a distance of less than 6 feet. Participants were considered vaccinated if they reported receiving >=1 COVID-19 vaccine dose. Participants (n=17,522) were 91% non-Hispanic White, 68% female, median age 57 years, 26% healthcare workers, with 95% self-reported receiving >=1 COVID-19 vaccine dose through August; mean daily survey response was 85%. Mask use was higher among vaccinated than unvaccinated participants across the study period, regardless of the month of the first dose. Mask use remained relatively stable from December 2020 through April (range 71-80% unvaccinated; 86-93% vaccinated) and declined in both groups beginning in mid-May 2021 to 34% and 42% respectively in June 2021; mask use has increased again since July 2021. Mask use by all was lower during weekends and on Christmas and Easter, regardless of vaccination status. Independent predictors of higher mask use were vaccination, age >=65 years, female sex, racial or ethnic minority group, and healthcare worker occupation, whereas a history of self-reported prior COVID-19 illness was associated with lower use. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Interspecies transmission from pigs to ferrets of antigenically distinct swine H1 influenza A viruses with loss in reactivity to human vaccine virus antisera as measures of relative zoonotic risk (preprint)
Brian Kimble J , Souza CK , Anderson TK , Arendsee ZW , Hufnagel DE , Young KM , Lewis NS , Todd Davis C , Vincent Baker AL . bioRxiv 2022 13 During the last decade, endemic swine H1 influenza A viruses (IAV) from six different genetic clades of the hemagglutinin gene caused zoonotic infections in humans. The majority of zoonotic events with swine IAV were restricted to a single case with no subsequent transmission. However, repeated introduction of human-seasonal H1N1, continual reassortment between endemic swine IAV, and subsequent drift in the swine host resulted in highly diverse swine IAV with human-origin genes that may become a risk to the human population. To prepare for the potential of a future swine-origin IAV pandemic in humans, public health laboratories selected candidate vaccine viruses (CVV) for use as vaccine seed strains. To assess the pandemic risk of contemporary US swine H1N1 or H1N2 strains, we quantified the genetic diversity of swine H1 HA genes, and identified representative strains from each circulating clade. We then characterized the representative swine IAV against human seasonal vaccine and CVV strains using ferret antisera in hemagglutination inhibition assays (HI). HI assays revealed that 1A.3.3.2 (pdm) and 1B.2.1 (delta-2) demonstrated strong cross reactivity to human seasonal vaccines or CVVs. However, swine IAV from three clades that represent more than 50% of the detected swine IAVs in the USA showed significant reduction in cross-reactivity compared to the closest CVV virus: 1A.1.1.3 (alpha-deletion), 1A.3.3.3-clade 3 (gamma), and 1B.2.2.1 (delta-1a). Representative viruses from these three clades were further characterized in a pig-to-ferret transmission model and shown to exhibit variable transmission efficiency. Our data prioritize specific genotypes of swine H1N1 and H1N2 to further investigate in the risk they pose to the human population. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Immunogenicity of adjuvanted versus high-dose inactivated influenza vaccines in older adults: a randomized clinical trial
Schmader KE , Liu CK , Flannery B , Rountree W , Auerbach H , Barnett ED , Schlaudecker EP , Todd CA , Poniewierski M , Staat MA , Harrington T , Li R , Broder KR , Walter EB . Immun Ageing 2023 20 (1) 30 BACKGROUND: Adjuvanted inactivated influenza vaccine (aIIV) and high-dose inactivated influenza vaccine (HD-IIV) are U.S.-licensed for adults aged ≥ 65 years. This study compared serum hemagglutination inhibition (HAI) antibody titers for the A(H3N2) and A(H1N1)pdm09 and B strains after trivalent aIIV3 and trivalent HD-IIV3 in an older adult population. RESULTS: The immunogenicity population included 342 participants who received aIIV3 and 338 participants who received HD-IIV3. The proportion of participants that seroconverted to A(H3N2) vaccine strains after allV3 (112 participants [32.8%]) was inferior to the proportion of participants that seroconverted after HD-IIV3 (130 participants [38.5%]) at day 29 after vaccination (difference, - 5.8%; 95%CI, - 12.9% to 1.4%). There were no significant differences between the vaccine groups in percent seroconversion to A(H1N1)pdm09 or B vaccine strains, in percent seropositivity for any of the strains, or in post-vaccination GMT for the A(H1N1)pdm09 strain. The GMTs for the post-vaccination A(H3N2) and B strains were higher after HD-IIV than after aIIV3. CONCLUSIONS: Overall immune responses were similar after aIIV3 and HD-IIV3. For the primary outcome, the aIIV3 seroconversion rate for H3N2 did not meet noninferiority criteria compared with HD-IIV3, but the HD-IIV3 seroconversion rate was not statistically superior to the aIIV3 seroconversion rate. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03183908. |
Notes from the field: First reported U.S. Cases of tinea caused by Trichophyton indotineae - New York City, December 2021-March 2023
Caplan AS , Chaturvedi S , Zhu Y , Todd GC , Yin L , Lopez A , Travis L , Smith DJ , Chiller T , Lockhart SR , Alroy KA , Greendyke WG , Gold JAW . MMWR Morb Mortal Wkly Rep 2023 72 (19) 536-537 Tinea is a common, highly contagious, superficial infection of the skin, hair, or nails caused by dermatophyte molds.* During the past decade, an epidemic of severe, antifungal-resistant tinea has emerged in South Asia because of the rapid spread of Trichophyton indotineae,† a novel dermatophyte species; the epidemic has likely been driven by misuse and overuse of topical antifungals and corticosteroids§ (1,2). T. indotineae infections are highly transmissible and characterized by widespread, inflamed, pruritic plaques on the body (tinea corporis), the crural fold, pubic region, and adjacent thigh (tinea cruris), or the face (tinea faciei) (1). T. indotineae isolates are frequently resistant to terbinafine, a mainstay of tinea treatment (1,3). T. indotineae infections have been reported throughout Asia and in Europe and Canada but have not previously been described in the United States (3). | | On February 28, 2023, a New York City dermatologist notified public health officials of two patients who had severe tinea that did not improve with oral terbinafine treatment, raising concern for potential T. indotineae infection; these patients shared no epidemiologic links. Skin culture isolates from each patient were previously identified by a clinical laboratory as Trichophyton mentagrophytes and were subsequently forwarded to the Wadsworth Center, New York State Department of Health, for further review and analysis. Sanger sequencing of the internal transcribed spacer region of the ribosomal gene, followed by phylogenetic analysis performed during March 2023, identified the isolates as T. indotineae (Supplementary Figure; https://stacks.cdc.gov/view/cdc/127678). Activity related to this investigation was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.¶ |
Adapterama II: universal amplicon sequencing on Illumina platforms (TaggiMatrix).
Glenn TC , Pierson TW , Bayona-Vásquez NJ , Kieran TJ , Hoffberg SL , Thomas Iv JC , Lefever DE , Finger JW , Gao B , Bian X , Louha S , Kolli RT , Bentley KE , Rushmore J , Wong K , Shaw TI , Rothrock MJ Jr , McKee AM , Guo TL , Mauricio R , Molina M , Cummings BS , Lash LH , Lu K , Gilbert GS , Hubbell SP , Faircloth BC . PeerJ 2019 7 e7786 Next-generation sequencing (NGS) of amplicons is used in a wide variety of contexts. In many cases, NGS amplicon sequencing remains overly expensive and inflexible, with library preparation strategies relying upon the fusion of locus-specific primers to full-length adapter sequences with a single identifying sequence or ligating adapters onto PCR products. In Adapterama I, we presented universal stubs and primers to produce thousands of unique index combinations and a modifiable system for incorporating them into Illumina libraries. Here, we describe multiple ways to use the Adapterama system and other approaches for amplicon sequencing on Illumina instruments. In the variant we use most frequently for large-scale projects, we fuse partial adapter sequences (TruSeq or Nextera) onto the 5' end of locus-specific PCR primers with variable-length tag sequences between the adapter and locus-specific sequences. These fusion primers can be used combinatorially to amplify samples within a 96-well plate (8 forward primers + 12 reverse primers yield 8 × 12 = 96 combinations), and the resulting amplicons can be pooled. The initial PCR products then serve as template for a second round of PCR with dual-indexed iTru or iNext primers (also used combinatorially) to make full-length libraries. The resulting quadruple-indexed amplicons have diversity at most base positions and can be pooled with any standard Illumina library for sequencing. The number of sequencing reads from the amplicon pools can be adjusted, facilitating deep sequencing when required or reducing sequencing costs per sample to an economically trivial amount when deep coverage is not needed. We demonstrate the utility and versatility of our approaches with results from six projects using different implementations of our protocols. Thus, we show that these methods facilitate amplicon library construction for Illumina instruments at reduced cost with increased flexibility. A simple web page to design fusion primers compatible with iTru primers is available at: http://baddna.uga.edu/tools-taggi.html. A fast and easy to use program to demultiplex amplicon pools with internal indexes is available at: https://github.com/lefeverde/Mr_Demuxy. |
Associations of urinary metabolite concentrations of phthalates and phthalate replacements with body composition from mid-childhood to early adolescence
Rokoff LB , Seshasayee SM , Carwile JL , Rifas-Shiman SL , Botelho JC , Gordon CM , Hauser R , James-Todd T , Young JG , Rosen CJ , Calafat AM , Oken E , Fleisch AF . Environ Res 2023 226 115629 BACKGROUND: Phthalates may adversely influence body composition by lowering anabolic hormones and activating peroxisome-proliferator activated receptor gamma. However, data are limited in adolescence when body mass distributions rapidly change and bone accrual peaks. Also, potential health effects of certain phthalate/replacements [e.g., di-2-ethylhexyl terephthalate (DEHTP)] have not been well studied. METHODS: Among 579 children in the Project Viva cohort, we used linear regression to evaluate associations of urinary concentrations of 19 phthalate/replacement metabolites from mid-childhood (median: 7.6 years; 2007-2010) with annualized change in areal bone mineral density (aBMD) and lean, total fat, and truncal fat mass as measured by dual-energy X-ray absorptiometry between mid-childhood and early adolescence (median: 12.8 years). We used quantile g-computation to assess associations of the overall chemical mixture with body composition. We adjusted for sociodemographics and tested for sex-specific associations. RESULTS: Urinary concentrations were highest for mono-2-ethyl-5-carboxypentyl phthalate [median (IQR): 46.7 (69.1) ng/mL]. We detected metabolites of most replacement phthalates in a relatively small number of participants [e.g., 28% for mono-2-ethyl-5-hydrohexyl terephthalate (MEHHTP; metabolite of DEHTP)]. Detectable (vs. non-detectable) MEHHTP was associated with less bone and greater fat accrual in males and greater bone and lean mass accrual in females [e.g., change in aBMD Z-score/year (95% CI): -0.049 (-0.085, -0.013) in males versus 0.042 (0.007, 0.076) in females; p(interaction)<0.01]. Children with higher concentrations of mono-oxo-isononyl phthalate and mono-3-carboxypropyl phthalate (MCPP) had greater bone accrual. Males with higher concentrations of MCPP and mono-carboxynonyl phthalate had greater accrual of lean mass. Other phthalate/replacement biomarkers, and their mixtures, were not associated with longitudinal changes in body composition. CONCLUSIONS: Concentrations of select phthalate/replacement metabolites in mid-childhood were associated with changes in body composition through early adolescence. As use of phthalate replacements such as DEHTP may be increasing, further investigation can help better understand the potential effects of early-life exposures. |
Estimating the impact of HIV PrEP regimens containing long-acting injectable cabotegravir or daily oral tenofovir disoproxil fumarate/emtricitabine among men who have sex with men in the United States: a mathematical modelling study for HPTN 083
Mitchell KM , Boily MC , Hanscom B , Moore M , Todd J , Paz-Bailey G , Wejnert C , Liu A , Donnell DJ , Grinsztejn B , Landovitz RJ , Dimitrov DT . Lancet Reg Health Am 2023 18 100416 BACKGROUND: The HPTN 083 trial demonstrated superiority of HIV pre-exposure prophylaxis (PrEP) containing long-acting injectable cabotegravir (CAB) to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) among men who have sex with men (MSM). We compared the potential population-level impact of TDF/FTC and CAB among MSM in Atlanta, Georgia. METHODS: An MSM HIV transmission model was calibrated to Atlanta-specific data on HIV prevalence and PrEP usage (percentage of uninfected MSM on PrEP), assuming only PrEP-indicated MSM used PrEP. CAB effectiveness (efficacy × adherence) of 91% was estimated using data from HPTN 083 and previous TDF/FTC trials. We estimated HIV infections averted over 5/10 years if TDF/FTC use were maintained, or if all TDF/FTC users switched to CAB in January 2022 (vs. no PrEP or continued TDF/FTC use). CAB scenarios with 10%/20% more users were also considered. Progress towards Ending the HIV Epidemic (EHE) goals (75%/90% fewer HIV infections in 2025/2030 vs. 2017) was estimated. FINDINGS: We predicted TDF/FTC at current usage (∼28%) would avert 36.3% of new HIV infections (95% credible interval 25.6-48.7%) among all Atlanta MSM over 2022-2026 vs. no PrEP. Switching to CAB with similar usage may prevent 44.6% (33.2-56.6%) infections vs. no PrEP and 11.9% (5.2-20.2%) infections vs. continued TDF/FTC. Increasing CAB usage 20% could increase the incremental impact over TDF/FTC to 30.0% over 2022-2026, getting ∼60% towards reaching EHE goals (47%/54% fewer infections in 2025/2030). Reaching the 2030 EHE goal would require 93% CAB usage. INTERPRETATION: If CAB effectiveness were like HPTN 083, CAB could prevent more infections than TDF/FTC at similar usage. Increased CAB usage could contribute substantially towards reaching EHE goals, but the usage required to meet EHE goals is unrealistic. FUNDING: NIH, MRC. |
Cross-neutralization and viral fitness of SARS-CoV-2 Omicron sublineages.
Xia H , Yeung J , Kalveram B , Bills CJ , Chen JY , Kurhade C , Zou J , Widen SG , Mann BR , Kondor R , Todd Davis C , Zhou B , Wentworth DE , Xie X , Shi PY . Emerg Microbes Infect 2023 12 (1) 1-19 The rapid evolution of SARS-CoV-2 Omicron sublineages mandates a better understanding of viral replication and cross-neutralization among these sublineages. Here we used K18-hACE2 mice and primary human airway cultures to examine the viral fitness and antigenic relationship among Omicron sublineages. In both K18-hACE2 mice and human airway cultures, Omicron sublineages exhibited a replication order of BA.5 ≥ BA.2 ≥ BA.2.12.1 > BA.1; no difference in body weight loss was observed among different sublineage-infected mice. The BA.1-, BA.2-, BA.2.12.1-, and BA.5-infected mice developed distinguishable cross-neutralizations against Omicron sublineages, but exhibited little neutralization against the index virus (i.e., USA-WA1/2020) or the Delta variant. Surprisingly, the BA.5-infected mice developed higher neutralization activity against heterologous BA.2 and BA.2.12.1 than that against homologous BA.5; serum neutralizing titers did not always correlate with viral replication levels in infected animals. Our results revealed a distinct antigenic cartography of Omicron sublineages and support the bivalent vaccine approach. |
Predictors of urinary biomarker concentrations of phthalates and some of their replacements in children in the Project Viva cohort
Kalloo G , Janis JA , Seshasayee SM , Rifas SL , Calafat AM , Botelho JC , Hauser R , James-Todd T , Oken E , Fleisch AF . J Expo Sci Environ Epidemiol 2022 33 (2) 255-263 BACKGROUND: Some phthalates are still widely used in food packaging, toys, and personal care products, and links to adverse health have motivated substitution with replacement chemicals. Few studies have examined patterns and predictors of phthalate replacement biomarkers in children. OBJECTIVE: To examine associations of sociodemographic, dietary, and urine collection characteristics with urinary concentrations of biomarkers of select phthalates and their replacements in mid-childhood. METHODS: We studied 830 children ages 6-10 years in 2007-2010 in a Boston-area cohort. We quantified urinary metabolites and summed their concentrations to calculate biomarkers of the concentrations of ten parent phthalates/replacements. We used linear regression to examine mutually adjusted associations of each predictor with each phthalate biomarker. We used logistic regression to examine predictors of 1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH) biomarker detectability. RESULTS: Predictor characteristics explained 25-48% of urinary biomarker variability. Di-2-ethylhexyl terephthalate (DEHTP) biomarker was higher in females (18.7% [95% CI: 0.7, 39.9]), children who consumed more meat and dairy, and samples collected from later years. DINCH biomarker was more detectable in females (odds ratio [OR] 2.1 [95% CI: 1.5, 3.0]) and samples from later years. SIGNIFICANCE: Populations of children with increased urinary concentrations of phthalate and replacement biomarkers can be targeted for future study of sources of exposure, and identifying dietary predictors of biomarkers will directly guide future interventions. IMPACT: Our study uses data from a large cohort that is one of the first to measure DINCH, DEHTP, and metabolites of di-isononyl phthalate and di-isodecyl phthalate. Additionally, we evaluate predictors during mid-childhood when biomarkers might be highest. As the use of replacement phthalates increases, our study is one of the first to examine biomarker patterns and predictors among children. |
Associations between prenatal urinary biomarkers of phthalate exposure and preterm birth: A pooled study of 16 US cohorts
Welch BM , Keil AP , Buckley JP , Calafat AM , Christenbury KE , Engel SM , O'Brien KM , Rosen EM , James-Todd T , Zota AR , Ferguson KK , Alshawabkeh AN , Cordero JF , Meeker JD , Barrett ES , Bush NR , Nguyen RHN , Sathyanarayana S , Swan SH , Cantonwine DE , McElrath TF , Aalborg J , Dabelea D , Starling AP , Hauser R , Messerlian C , Zhang Y , Bradman A , Eskenazi B , Harley KG , Holland N , Bloom MS , Newman RB , Wenzel AG , Braun JM , Lanphear BP , Yolton K , Factor-Litvak P , Herbstman JB , Rauh VA , Drobnis EZ , Sparks AE , Redmon JB , Wang C , Binder AM , Michels KB , Baird DD , Jukic AMZ , Weinberg CR , Wilcox AJ , Rich DQ , Weinberger B , Padmanabhan V , Watkins DJ , Hertz-Picciotto I , Schmidt RJ . JAMA Pediatr 2022 176 (9) 895-905 IMPORTANCE: Phthalate exposure is widespread among pregnant women and may be a risk factor for preterm birth. OBJECTIVE: To investigate the prospective association between urinary biomarkers of phthalates in pregnancy and preterm birth among individuals living in the US. DESIGN, SETTING, AND PARTICIPANTS: Individual-level data were pooled from 16 preconception and pregnancy studies conducted in the US. Pregnant individuals who delivered between 1983 and 2018 and provided 1 or more urine samples during pregnancy were included. EXPOSURES: Urinary phthalate metabolites were quantified as biomarkers of phthalate exposure. Concentrations of 11 phthalate metabolites were standardized for urine dilution and mean repeated measurements across pregnancy were calculated. MAIN OUTCOMES AND MEASURES: Logistic regression models were used to examine the association between each phthalate metabolite with the odds of preterm birth, defined as less than 37 weeks of gestation at delivery (n=539). Models pooled data using fixed effects and adjusted for maternal age, race and ethnicity, education, and prepregnancy body mass index. The association between the overall mixture of phthalate metabolites and preterm birth was also examined with logistic regression. G-computation, which requires certain assumptions to be considered causal, was used to estimate the association with hypothetical interventions to reduce the mixture concentrations on preterm birth. RESULTS: The final analytic sample included 6045 participants (mean [SD] age, 29.1 [6.1] years). Overall, 802 individuals (13.3%) were Black, 2323 (38.4%) were Hispanic/Latina, 2576 (42.6%) were White, and 328 (5.4%) had other race and ethnicity (including American Indian/Alaskan Native, Native Hawaiian, >1 racial identity, or reported as other). Most phthalate metabolites were detected in more than 96% of participants. Higher odds of preterm birth, ranging from 12% to 16%, were observed in association with an interquartile range increase in urinary concentrations of mono-n-butyl phthalate (odds ratio [OR], 1.12 [95% CI, 0.98-1.27]), mono-isobutyl phthalate (OR, 1.16 [95% CI, 1.00-1.34]), mono(2-ethyl-5-carboxypentyl) phthalate (OR, 1.16 [95% CI, 1.00-1.34]), and mono(3-carboxypropyl) phthalate (OR, 1.14 [95% CI, 1.01-1.29]). Among approximately 90 preterm births per 1000 live births in this study population, hypothetical interventions to reduce the mixture of phthalate metabolite levels by 10%, 30%, and 50% were estimated to prevent 1.8 (95% CI, 0.5-3.1), 5.9 (95% CI, 1.7-9.9), and 11.1 (95% CI, 3.6-18.3) preterm births, respectively. CONCLUSIONS AND RELEVANCE: Results from this large US study population suggest that phthalate exposure during pregnancy may be a preventable risk factor for preterm delivery. |
Coaching and communication training for HPV vaccination: A cluster randomized trial
Gilkey MB , Grabert BK , Heisler-MacKinnon J , Bjork A , Boynton MH , Kim K , AltonDailey S , Liu A , Todd KG , Schauer SL , Sill D , Coley S , Brewer NT . Pediatrics 2022 150 (2) BACKGROUND AND OBJECTIVES: US health departments routinely conduct in-person quality improvement (QI) coaching to strengthen primary care clinics' vaccine delivery systems, but this intervention achieves only small, inconsistent improvements in human papillomavirus (HPV) vaccination. Thus, we sought to evaluate the effectiveness of combining QI coaching with remote provider communication training to improve impact. METHODS: With health departments in 3 states, we conducted a pragmatic 4-arm cluster randomized clinical trial with 267 primary care clinics (76% pediatrics). Clinics received in-person QI coaching, remote provider communication training, both interventions combined, or control. Using data from states' immunization information systems, we assessed HPV vaccination among 176189 patients, ages 11 to 17, who were unvaccinated at baseline. Our primary outcome was the proportion of those, ages 11 to 12, who had initiated HPV vaccination at 12-month follow-up. RESULTS: HPV vaccine initiation was 1.5% points higher in the QI coaching arm and 3.8% points higher in the combined intervention arm than in the control arm, among patients ages 11 to 12, at 12-month follow-up (both P < .001). Improvements persisted at 18-month follow-up. The combined intervention also achieved improvements for other age groups (ages 13-17) and vaccination outcomes (series completion). Remote communication training alone did not outperform the control on any outcome. CONCLUSIONS: Combining QI coaching with remote provider communication training yielded more consistent improvements in HPV vaccination uptake than QI coaching alone. Health departments and other organizations that seek to support HPV vaccine delivery may benefit from a higher intensity, multilevel intervention approach. |
Association of urinary phthalate and phthalate replacement metabolite concentrations with serum lipid biomarker levels among pregnant women attending a fertility center
Mnguez-Alarcn L , Williams PL , James-Todd T , Souter I , Ford JB , Rexrode KM , Calafat AM , Hauser R , Chavarro JE . Toxics 2022 10 (6) We examined whether urinary concentrations of phthalate and phthalate replacement metabolites were associated with lipid biomarker levels among pregnant women. This cross-sectional study included 175 women who enrolled in the Environment and Reproductive Health (EARTH) Study (2005-2017). We used linear regression models to assess the relationship between urinary phthalates and lipid biomarkers [triglycerides, total cholesterol, high density lipoprotein (HDL), non-HDL, and low-density lipoprotein (LDL) cholesterol] levels while adjusting for confounders. Pregnant women in the highest quartile of urinary mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) had, overall, 14% [31 (95% CI = 6.56) mg/dL], 21% [33 (95% CI = 9.57) mg/dL] and 25% [30 (95% CI = 8.53) mg/dL] higher serum total, non-HDL and LDL cholesterol, respectively, compared to women in the lowest quartile of MECPP. Similar positive associations were found for urinary concentrations of other metabolites of di(2-ethylhexyl) phthalate, mono(2-ethylhexyl) phthalate, and mono(2-ethyl-5-oxohexyl) phthalate. Pregnant women with urinary mono-n-butyl phthalate (MBP) in the highest quartile had higher triglycerides and non-HDL cholesterol compared to women with MBP in the lowest quartile. Women with detectable concentrations of two phthalate replacement metabolites had lower HDL cholesterol compared to women with non-detectable concentrations. Gestational urinary concentrations of certain phthalate and phthalate replacement metabolites were associated with lipid levels among these women. |
Pathogenesis and Transmission of Human Seasonal and Swine-origin A(H1) Influenza Viruses in the Ferret Model.
Pulit-Penaloza JA , Brock N , Jones J , Belser JA , Jang Y , Sun X , Thor S , Pappas C , Zanders N , Tumpey TM , Todd Davis C , Maines TR . Emerg Microbes Infect 2022 11 (1) 1-20 Influenza A viruses (IAVs) in the swine reservoir constantly evolve, resulting in expanding genetic and antigenic diversity of strains that occasionally cause infections in humans and pose threat of emerging as a strain capable of human-to-human transmission. For these reasons, there is an ongoing need for surveillance and characterization of newly emerging strains to aid pandemic preparedness efforts, particularly for the selection of candidate vaccine viruses and conducting risk assessments. Here, we performed a parallel comparison of the pathogenesis and transmission of genetically and antigenically diverse swine-origin A(H1N1) variant (v) and A(H1N2)v, and human seasonal A(H1N1)pdm09 IAVs using the ferret model. Both groups of viruses were capable of replication in the ferret upper respiratory tract; however, variant viruses were more frequently isolated from the lower respiratory tract as compared to the human-adapted viruses. Regardless of virus origin, observed clinical signs of infection differed greatly between strains, with some viruses causing nasal discharge, sneezing and, in some instances, diarrhea in ferrets. The most striking difference between the viruses was the ability to transmit through the air. Human-adapted viruses were capable of airborne transmission between all ferret pairs. In contrast, only one out of the four tested variant viruses was able to transmit via the air as efficiently as the human-adapted viruses. Overall, this work highlights the need for sustained monitoring of emerging swine IAVs to identify strains of concern such as those that are antigenically different from vaccine strains and that possess adaptations required for efficient respiratory droplet transmission in mammals. |
Pregnancy urinary concentrations of bisphenol A, parabens and other phenols in relation to serum levels of lipid biomarkers: Results from the EARTH study
Mínguez-Alarcón L , Frueh L , Williams PL , James-Todd T , Souter I , Ford JB , Rexrode KM , Calafat AM , Hauser R , Chavarro JE . Sci Total Environ 2022 833 155191 The epidemiologic literature on associations between urinary phenol concentrations and lipid profiles during pregnancy is limited. We examined whether urinary concentrations of phenol and phenol replacement biomarkers were associated with serum lipid levels among pregnant women. This cross-sectional study included 175 women attending the Massachusetts General Hospital Fertility Center who enrolled in the Environment and Reproductive Health (EARTH) Study between 2005 and 2017 and had data available on urinary phenol biomarkers and serum lipids during pregnancy. We used linear regression models to assess the relationship between groups of urinary phenol and phenol replacement biomarkers and serum lipid levels [total cholesterol, high density lipoprotein (HDL), non-HDL, low-density lipoprotein (LDL) cholesterol, and triglycerides], while adjusting for age at sample collection, pre-pregnancy BMI, education, race, infertility diagnosis, cycle type, number of fetuses, trimester and specific gravity. In adjusted models, pregnant women with urinary propylparaben concentrations in the highest tertile had 10% [22 (95% CI = 5, 40) mg/dL], 12% [19 (95% CI = 2, 36) mg/dL] and 16% [19 (95% CI = 3, 35) mg/dL] higher mean total, non-HDL and LDL cholesterol, respectively, compared to women with concentrations in the lowest tertile. Similar elevations were observed for urinary bisphenol A concentrations. Urinary bisphenol S, benzophenone-3, triclosan, methylparaben, ethylparaben, and butylparaben were unrelated to serum lipids. Among pregnant women, urinary concentrations of bisphenol A and propylparaben were associated with higher serum levels of total, non-HDL and LDL cholesterol. |
Urinary phthalate and DINCH metabolite concentrations and gradations of maternal glucose intolerance
James-Todd T , Ponzano M , Bellavia A , Williams PL , Cantonwine DE , Calafat AM , Hauser R , Quinn MR , Seely EW , McElrath TF . Environ Int 2022 161 107099 BACKGROUND: Studies suggest a link between pregnancy phthalate exposures and gestational diabetes mellitus (GDM). Few studies have evaluated associations between phthalate biomarkers (individual or mixtures) with gradations of maternal glucose intolerance. METHODS: In a subset of 606 women participating in LIFECODES pregnancy cohort, a combination of 50-gram 1-h non-fasting glucose load test (GLT) and 100-gram 3-h fasting oral glucose tolerance test was used to determine pregnancy glycemic status (median: 27 weeks gestation): normoglycemia (n = 136), impaired glucose tolerance (IGT) (n = 296), and GDM (n = 174). Nineteen metabolites of phthalates and their replacements were measured during each trimester. We used multivariable logistic regression models to evaluate associations between biomarkers (in quartiles) and maternal glycemic status (GDM v. normoglycemia and IGT v. normoglycemia), adjusting for potential confounders. We also used principal component analysis to evaluate associations jointly accounting for metabolites as chemical mixtures. RESULTS: Higher 1st trimester mono-3-carboxypropyl phthalate (MCPP) was associated with decreased odds of GDM (Q4 v. Q1: 0.30; 95% CI: 0.13, 0.67) and IGT (Q4 v. Q1 OR: 0.37; 95% CI: 0.17, 0.79). Higher 2nd trimester mono-isobutyl phthalate (MiBP) was associated with increased IGT (Q4 v. Q1 OR: 2.07; 95% CI: 1.06, 4.07), and 2nd trimester mono-3-hydroxybutyl phthalate (MHBP) was non-monotonically associated with increased GDM (Q2 v. Q1 OR: 3.21; 95% CI: 1.54, 6.87). Mixture analyses showed similar associations (Q4 v. Q1 for 2nd trimester dibutyl phthalates metabotlites mixtures OR: 2.08; 95% CI: 1.04, 4.22). CONCLUSION: Some phthalate biomarkershad trimester-specific associations with glycemic outcomes, with long and short term health implications. |
Automating case reporting of chlamydia and gonorrhea to public health authorities in Oregon clinics
Todd JV , Collins NV , Oakley J , Menza T , Barber M , Kasarskis I , Weresch A , Morgan S , Jellison J , Mishra N , Pérez A , Karki S . Sex Transm Dis 2021 49 (1) 38-42 BACKGROUND: Optimizing STD reporting to state public health authorities is important to reduce incidence and manage outbreaks of STDs. Electronic lab reporting (ELR) is the standard through which local clinics report STDs to state public health authority. Electronic case reporting (eCR) is an alternative approach which automates transmission of case reports to public health jurisdictions using electronic health record (EHR) data. METHODS: Working with three Community Health Centers (CHCs) in Oregon between February 3, 2020 and May 15, 2020, we piloted an automated electronic case reporting (eCR) approach for gonorrhea (GC) and chlamydia (CT) from these clinics to the Oregon Health Authority. We compared the eCR approach to the existing ELR approach to determine completeness of case reporting for GC/CT. RESULTS: A total of 365 eCRs from 206 unique patients were generated. Among 154 instances where the case detection logic was satisfied for chlamydia, 37% (54 instances) were based on the presence of a diagnosis and 63% (97 instances) were based on laboratory data. Among 232 instances where logic was satisfied for gonorrhea, 44% (102 instances) reflected a diagnosis and 56% (130 instances) reflected laboratory results. Data completeness was uniformly equal or higher for eCRs vs. ELRs. CONCLUSIONS: The eCR approach was successful in identifying chlamydia and gonorrhea cases and provided a more complete set of information to assist public health authorities when compared with ELRs. eCR has the potential to automate and relieve staff burden on an important reporting requirement for clinical providers. |
Monogenic diabetes in youth with presumed type 2 diabetes: Results from the Progress in Diabetes Genetics in Youth (ProDiGY) Collaboration
Todd JN , Kleinberger JW , Zhang H , Srinivasan S , Tollefsen SE , Levitsky LL , Levitt Katz LE , Tryggestad JB , Bacha F , Imperatore G , Lawrence JM , Pihoker C , Divers J , Flannick J , Dabelea D , Florez JC , Pollin TI . Diabetes Care 2021 44 (10) 2312-9 OBJECTIVE: Maturity-onset diabetes of the young (MODY) is frequently misdiagnosed as type 1 or type 2 diabetes. Correct diagnosis may result in a change in clinical treatment and impacts prediction of complications and familial risk. In this study, we aimed to assess the prevalence of MODY in multiethnic youth under age 20 years with a clinical diagnosis of type 2 diabetes. RESEARCH DESIGN AND METHODS: We evaluated whole-exome sequence data of youth with a clinical diagnosis of type 2 diabetes. We considered participants to have MODY if they carried a MODY gene variant classified as likely pathogenic (LP) or pathogenic (P) according to current guidelines. RESULTS: Of 3,333 participants, 93 (2.8%) carried an LP/P variant in HNF4A (16 participants), GCK (23), HNF1A (44), PDX1 (5), INS (4), and CEL (1). Compared with those with no LP/P variants, youth with MODY had a younger age at diagnosis (12.9 ± 2.5 vs. 13.6 ± 2.3 years, P = 0.002) and lower fasting C-peptide levels (3.0 ± 1.7 vs. 4.7 ± 3.5 ng/mL, P < 0.0001). Youth with MODY were less likely to have hypertension (6.9% vs. 19.5%, P = 0.007) and had higher HDL cholesterol (43.8 vs. 39.7 mg/dL, P = 0.006). CONCLUSIONS: By comprehensively sequencing the coding regions of all MODY genes, we identified MODY in 2.8% of youth with clinically diagnosed type 2 diabetes; importantly, in 89% (n = 83) the specific diagnosis would have changed clinical management. No clinical criterion reliably separated the two groups. New tools are needed to find ideal criteria for selection of individuals for genetic testing. |
Implementation of quality improvement coaching versus physician communication training for improving human papillomavirus vaccination in primary care: a randomized implementation trial
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 12 (1) 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 |
A Full Nesterov-Todd Step Infeasible Interior-point Method for Symmetric Optimization in the Wider Neighborhood of the Central Path
Lesaja G , Wang GQ , Oganian A . Stat Optim Inf Comput 2021 9 (2) 250-267 In this paper, an improved Interior-Point Method (IPM) for solving symmetric optimization problems is presented. Symmetric optimization (SO) problems are linear optimization problems over symmetric cones. In particular, the method can be efficiently applied to an important instance of SO, a Controlled Tabular Adjustment (CTA) problem which is a method used for Statistical Disclosure Limitation (SDL) of tabular data. The presented method is a full Nesterov-Todd step infeasible IPM for SO. The algorithm converges to ε-approximate solution from any starting point whether feasible or infeasible. Each iteration consists of the feasibility step and several centering steps, however, the iterates are obtained in the wider neighborhood of the central path in comparison to the similar algorithms of this type which is the main improvement of the method. However, the currently best known iteration bound known for infeasible short-step methods is still achieved. |
Cumulative Risks from Stressor Exposures and Personal Risk Factors in the Workplace: Examples from a Scoping Review.
Fox MA , Niemeier RT , Hudson N , Siegel MR , Dotson GS . Int J Environ Res Public Health 2021 18 (11) Protecting worker and public health involves an understanding of multiple determinants, including exposures to biological, chemical, or physical agents or stressors in combination with other determinants including type of employment, health status, and individual behaviors. This has been illustrated during the COVID-19 pandemic by increased exposure and health risks for essential workers and those with pre-existing conditions, and mask-wearing behavior. Health risk assessment practices for environmental and occupational health typically do not incorporate multiple stressors in combination with personal risk factors. While conceptual developments in cumulative risk assessment to inform a more holistic approach to these real-life conditions have progressed, gaps remain, and practical methods and applications are rare. This scoping review characterizes existing evidence of combined stressor exposures and personal factors and risk to foster methods for occupational cumulative risk assessment. The review found examples from many workplaces, such as manufacturing, offices, and health care; exposures to chemical, physical, and psychosocial stressors combined with modifiable and unmodifiable determinants of health; and outcomes including respiratory function and disease, cancers, cardio-metabolic diseases, and hearing loss, as well as increased fertility, menstrual dysfunction and worsened mental health. To protect workers, workplace exposures and modifiable and unmodifiable characteristics should be considered in risk assessment and management. Data on combination exposures can improve assessments and risk estimates and inform protective exposure limits and management strategies. |
Multifaceted Public Health Response to a COVID-19 Outbreak Among Meat-Processing Workers, Utah, March-June 2020.
Rogers TM , Robinson SJ , Reynolds LE , Ladva CN , Burgos-Garay M , Whiteman A , Budge H , Soto N , Thompson M , Hunt E , Barson T , Boyd AT . J Public Health Manag Pract 2021 28 (1) 60-69 OBJECTIVE: To identify potential strategies to mitigate COVID-19 transmission in a Utah meat-processing facility and surrounding community. DESIGN/SETTING: During March-June 2020, 502 workers at a Utah meat-processing facility (facility A) tested positive for SARS-CoV-2. Using merged data from the state disease surveillance system and facility A, we analyzed the relationship between SARS-CoV-2 positivity and worker demographics, work section, and geospatial data on worker residence. We analyzed worker survey responses to questions regarding COVID-19 knowledge, beliefs, and behaviors at work and home. PARTICIPANTS: (1) Facility A workers (n = 1373) with specimen collection dates and SARS-CoV-2 RT-PCR test results; (2) residential addresses of all persons (workers and nonworkers) with a SARS-CoV-2 diagnostic test (n = 1036), living within the 3 counties included in the health department catchment area; and (3) facility A workers (n = 64) who agreed to participate in the knowledge, attitudes, and practices survey. MAIN OUTCOME MEASURES: New cases over time, COVID-19 attack rates, worker characteristics by SARS-CoV-2 test results, geospatially clustered cases, space-time proximity of cases among workers and nonworkers; frequency of quantitative responses, crude prevalence ratios, and counts and frequency of coded responses to open-ended questions from the COVID-19 knowledge, attitudes, and practices survey. RESULTS: Statistically significant differences in race (P = .01), linguistic group (P < .001), and work section (P < .001) were found between workers with positive and negative SARS-CoV-2 test results. Geographically, only 6% of cases were within statistically significant spatiotemporal case clusters. Workers reported using handwashing (57%) and social distancing (21%) as mitigation strategies outside work but reported apprehension with taking COVID-19-associated sick leave. CONCLUSIONS: Mitigating COVID-19 outbreaks among workers in congregate settings requires a multifaceted public health response that is tailored to the workforce. IMPLICATIONS FOR POLICY AND PRACTICE: Tailored, multifaceted mitigation strategies are crucial for reducing COVID-19-associated health disparities among disproportionately affected populations. |
Adults Hospitalized with COVID-19 -United States, March-June and October-December 2020: Implications for the Potential Effects of COVID-19 Tier-1 Vaccination on Future Hospitalizations and Outcomes.
Sami S , Tenforde MW , Talbot HK , Lindsell CJ , Steingrub JS , Shapiro NI , Ginde AA , Douin DJ , Prekker ME , Erickson HL , Brown SM , Peltan ID , Gong MN , Khan A , Exline MC , Files DC , Gibbs KW , Rice TW , Casey JD , Grijalva CG , Stubblefield WB , Womack KN , Hager DN , Qadir N , Chang SY , Henning DJ , Wilson JG , Self WH , Patel MM . Clin Infect Dis 2021 73 S32-S37 BACKGROUND: Because of the increased risk for severe coronavirus disease 2019 (COVID-19), the Advisory Committee on Immunization Practices (ACIP) initially prioritized COVID-19 vaccination for persons in long-term care facilities (LTCF), persons aged ≥65 years, and persons aged 16-64 years with high-risk medical conditions when there is limited vaccine supply. We compared characteristics and severe outcomes of hospitalized patients with COVID-19 in the United States between early and later in the pandemic categorized by groups at higher risk of severe COVID-19. METHODS: Observational study of sampled patients aged ≥18 years who tested positive for SARS-CoV-2 and admitted to one of 14 academic hospitals in the United States during March-June and October-December 2020. Demographic and clinical information were gathered from electronic health record data. RESULTS: Among 647 patients, 91% met ≥1 of the following risk factors for severe COVID-19 [91% March-June (n=434); 90% October-December (n=213)]; 19% were LTCF residents, 45% were aged ≥65-years, and 84% had ≥1 high-risk condition. The proportion of patients who resided in a LTCF declined significantly (25% vs. 6%) from early to later pandemic periods. Compared with patients at lower risk for severe COVID-19, in-hospital mortality was higher among patients at high risk for severe COVID-19 (20% vs. 7%); these differences were consistently observed between March-June and October-December. CONCLUSIONS: Most adults hospitalized with COVID-19 were those recommended to be prioritized for vaccination based on risk for developing severe COVID-19. These findings highlight the urgency to vaccinate patients at high risk for severe COVID-19 and monitor vaccination impact on hospitalizations and outcomes. |
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