Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-30 (of 289 Records) |
Query Trace: Shaw L[original query] |
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SARS-CoV-2 RNA and nucleocapsid antigen are blood biomarkers associated with severe disease outcomes that improve in response to remdesivir
Singh K , Rubenstein K , Callier V , Shaw-Saliba K , Rupert A , Dewar R , Laverdure S , Highbarger H , Lallemand P , Huang ML , Jerome KR , Sampoleo R , Mills MG , Greninger AL , Juneja K , Porter D , Benson CA , Dempsey W , El Sahly HM , Focht C , Jilg N , Paules CI , Rapaka RR , Uyeki TM , Lane HC , Beigel J , Dodd LE . J Infect Dis 2024 BACKGROUND: Although antivirals remain important for the treatment COVID-19, methods to assess treatment efficacy are lacking. Here, we investigated the impact of remdesivir on viral dynamics and their contribution to understanding antiviral efficacy in the multicenter ACTT-1 clinical trial that randomized patients to remdesivir or placebo. METHODS: Longitudinal specimens collected during hospitalization from a substudy of 642 COVID-19 patients were measured for viral RNA (upper respiratory tract and plasma), viral nucleocapsid antigen (serum), and host immunologic markers. Associations with clinical outcomes and response to therapy were assessed. RESULTS: Higher baseline plasma viral loads were associated with poorer clinical outcomes, and decreases in viral RNA and antigen in blood but not the upper respiratory tract correlated with enhanced benefit from remdesivir. The treatment effect of remdesivir was most pronounced in patients with elevated baseline nucleocapsid antigen levels: the recovery rate ratio was 1.95 (95%CI 1.40-2.71) for levels >245 pg/ml vs 1.04 (95%CI 0.76-1.42) for levels < 245 pg/ml. Remdesivir also accelerated the rate of viral RNA and antigen clearance in blood, and patients whose blood levels decreased were more likely to recover and survive. CONCLUSIONS: Reductions in SARS-CoV-2 RNA and antigen levels in blood correlated with clinical benefit from antiviral therapy. |
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. |
Understanding three approaches to reporting sudden unexpected infant death in the USA
Erck Lambert AB , Parks S , Bergman K , Cottengim C , Woster A , Shaw E , Ma H , Heitmann R , Riehle-Colarusso T , Shapiro-Mendoza C . Inj Prev 2024 INTRODUCTION: In the USA each year, there are approximately 3400 sudden unexpected infant (<1 year of age) deaths (SUID) which occur without an obvious cause before an investigation. SUID includes the causes of death (COD) undetermined/unknown, sleep-related suffocation/asphyxia and sudden infant death syndrome (SIDS); these are often called SUID subtypes. Three common ways SUID subtypes are grouped (SUID subtype groups) include International Classification of Diseases (ICD) Codes, SUID Case Registry Categories or Child Death Review (CDR)-Assigned Causes. These groups are often used to monitor SUID trends and characteristics at the local, state and national levels. We describe and compare the characteristics of these three SUID subtype groups. DISCUSSION: SUID subtype groups are distinct and not directly interchangeable. They vary in purpose, strengths, limitations, uses, history, data years available, population coverage, assigning entity, guidance documentation and information available to assign subtypes. CONCLUSION: Making informed decisions about which SUID subtype group to use is important for reporting statistics, increasing knowledge of SUID epidemiology and informing prevention strategies. |
Community testing practices for autism within the autism and developmental disabilities monitoring network
Robinson Williams A , Amoakohene E , Maenner MJ , Zahorodny W , DiRienzo M , Grzybowski A , Hall-Lande J , Pas ET , Bakian AV , Lopez M , Patrick M , Shenouda J , Shaw KA . Paediatr Perinat Epidemiol 2024 BACKGROUND: No data exist at the population level on what tests are used to aid in the diagnosis of autism spectrum disorder in community practice. OBJECTIVES: To describe autism spectrum disorder testing practices to inform autism spectrum disorder identification efforts. METHODS: Data are from the Autism and Developmental Disabilities Monitoring Network, a multi-site surveillance system reporting prevalence estimates and characteristics of 8-year-old children with autism spectrum disorder. Percentages of children with autism spectrum disorder who received any autism spectrum disorder test or a 'gold standard' test were calculated by site, sex, race, median household income, and intellectual ability status. Risk ratios were calculated to compare group differences. RESULTS: Of 5058 8-year-old children with autism spectrum disorder across 11 sites, 3236 (64.0%) had a record of any autism spectrum disorder test and 2136 (42.2%) had a 'gold standard' ADOS or ADI-R test. Overall, 115 children (2.3%) had both the ADOS and ADI-R in their records. Differences persisted across race, median household income, and intellectual ability status. Asian/Pacific Islander children had the highest percent receiving any ASD test (71.8%; other groups range: 57.4-66.0%) and White children had the highest percent receiving 'gold standard' tests (46.4%; other groups range: 35.6-43.2%). Children in low-income neighbourhoods had a lower percent of any test (62.5%) and 'gold standard' tests (39.4%) compared to medium (70.2% and 47.5%, respectively) and high (69.6% and 46.8%, respectively) income neighbourhoods. Children with intellectual disability had a lower percent of any ASD test (81.7%) and 'gold standard' tests (52.6%) compared to children without intellectual disability (84.0% and 57.6%, respectively). CONCLUSIONS: Autism spectrum disorder testing practices vary widely by site and differ by race and presence of co-occurring intellectual disability, suggesting opportunities to standardise and/or improve autism spectrum disorder identification practices. |
Health conditions, education services, and transition planning for adolescents with autism
Hughes MM , Pas ET , Durkin MS , DaWalt LS , Bilder DA , Bakian AV , Amoakohene E , Shaw KA , Patrick ME , Salinas A , DiRienzo M , Lopez M , Williams S , McArthur D , Hudson A , Ladd-Acosta CM , Schwenk YD , Baroud TM , Robinson Williams A , Washington A , Maenner MJ . Pediatrics 2024 OBJECTIVE: Our objectives with this study were to describe the frequency of selected cooccurring health conditions and individualized education program (IEP) services and post-high school transition planning for adolescents with autism spectrum disorder and identify disparities by sex, intellectual ability, race or ethnicity, and geographic area. METHODS: The study sample included 1787 adolescents born in 2004 who were identified as having autism through a health and education record review through age 16 years in 2020. These adolescents were part of a longitudinal population-based surveillance birth cohort from the Autism and Developmental Disabilities Monitoring Network from 2004 to 2020 in 5 US catchment areas. RESULTS: Attention deficit hyperactivity disorder (47%) and anxiety (39%) were the most common cooccurring health conditions. Anxiety was less commonly identified for those with intellectual disability than those without. It was also less commonly identified among Black adolescents compared with White or Hispanic adolescents. There was wide variation across Autism and Developmental Disabilities Monitoring Network sites in the provision of school-based IEP services. Students with intellectual disability were less likely to receive school-based mental health services and more likely to have a goal for postsecondary independent living skills compared with those without intellectual disability. A total of 37% of students did not participate in standardized testing. CONCLUSIONS: We identified disparities in the identification of cooccurring conditions and school-based IEP services, practices, and transition planning. Working with pediatric health and education providers, families, and adolescents with autism will be important to identify contributing factors and to focus efforts to reduce disparities in the supports and services adolescents with autism have access to and receive. |
Social and demographic factors associated with receipt of a COVID-19 vaccine initial booster dose and with interval between primary series completion and initial booster dose uptake among persons aged ≥ 12 years, United States, August 2021-October 2022
Meng L , Harris L , Shaw L , Lymon H , Reses H , Bell J , Lu PJ , Gibbs-Scharf L , Chorba T . Vaccine 2024 COVID-19 booster dose vaccination has been crucial in ensuring protection against COVID-19 including recently predominant Omicron variants. Because vaccines against newer SARS-CoV- 2 variants are likely to be recommended in future, it will be valuable to understand past booster dose uptake among different demographic groups. Using U.S. vaccination data, this study examined intervals between primary series completion and receipt of first booster dose (monovalent or bivalent) during August 2021 - October 2022 among persons ≥12 years of age who had completed a COVID-19 vaccine primary series by October 2021. Sub-populations who were late booster recipients (received a booster dose ≥12 months after the primary series) or received no booster dose included persons <35 years old, Johnson & Johnson/Janssen vaccine primary dose recipients, persons in certain racial and ethnic groups, and persons living in rural and more socially vulnerable areas, and in the South region of the United States; these groups may benefit the most from public health outreach efforts to achieve timely COVID-19 vaccination completion in future. |
Vaccine-associated varicella and rubella infections in severe combined immunodeficiency with isolated CD4 lymphocytopenia and mutations in IL7R detected by tandem whole exome sequencing and chromosomal microarray.
Bayer DK , Martinez CA , Sorte HS , Forbes LR , Demmler-Harrison GJ , Hanson IC , Pearson NM , Noroski LM , Zaki SR , Bellini WJ , Leduc MS , Yang Y , Eng CM , Patel A , Rodningen OK , Muzny DM , Gibbs RA , Campbell IM , Shaw CA , Baker MW , Zhang V , Lupski JR , Orange JS , Seeborg FO , Stray-Pedersen A . Clin Exp Immunol 2014 178 (3) 459-69 In areas without newborn screening for severe combined immunodeficiency (SCID), disease-defining infections may lead to diagnosis, and in some cases, may not be identified prior to the first year of life. We describe a female infant who presented with disseminated vaccine-acquired varicella (VZV) and vaccine-acquired rubella infections at 13 months of age. Immunological evaluations demonstrated neutropenia, isolated CD4 lymphocytopenia, the presence of CD8(+) T cells, poor lymphocyte proliferation, hypergammaglobulinaemia and poor specific antibody production to VZV infection and routine immunizations. A combination of whole exome sequencing and custom-designed chromosomal microarray with exon coverage of primary immunodeficiency genes detected compound heterozygous mutations (one single nucleotide variant and one intragenic copy number variant involving one exon) within the IL7R gene. Mosaicism for wild-type allele (20-30%) was detected in pretransplant blood and buccal DNA and maternal engraftment (5-10%) demonstrated in pretransplant blood DNA. This may be responsible for the patient's unusual immunological phenotype compared to classical interleukin (IL)-7Rα deficiency. Disseminated VZV was controlled with anti-viral and immune-based therapy, and umbilical cord blood stem cell transplantation was successful. Retrospectively performed T cell receptor excision circle (TREC) analyses completed on neonatal Guthrie cards identified absent TREC. This case emphasizes the danger of live viral vaccination in severe combined immunodeficiency (SCID) patients and the importance of newborn screening to identify patients prior to high-risk exposures. It also illustrates the value of aggressive pathogen identification and treatment, the influence newborn screening can have on morbidity and mortality and the significant impact of newer genomic diagnostic tools in identifying the underlying genetic aetiology for SCID patients. |
Clinical outcomes of US adults hospitalized for COVID-19 and influenza in the Respiratory Virus Hospitalization Surveillance Network, October 2021-September 2022
Kojima N , Taylor CA , Tenforde MW , Ujamaa D , O'Halloran A , Patel K , Chai SJ , Daily Kirley P , Alden NB , Kawasaki B , Meek J , Yousey-Hindes K , Anderson EJ , Openo KP , Reeg L , Tellez Nunez V , Lynfield R , Como-Sabetti K , Ropp SL , Shaw YP , Spina NL , Barney G , Bushey S , Popham K , Moran NE , Shiltz E , Sutton M , Abdullah N , Talbot HK , Schaffner W , Chatelain R , Price A , Garg S , Havers FP , Bozio CH . Open Forum Infect Dis 2024 11 (1) ofad702 Severe outcomes were common among adults hospitalized for COVID-19 or influenza, while the percentage of COVID-19 hospitalizations involving critical care decreased from October 2021 to September 2022. During the Omicron BA.5 period, intensive care unit admission frequency was similar for COVID-19 and influenza, although patients with COVID-19 had a higher frequency of in-hospital death. |
Second nationwide tuberculosis outbreak caused by bone allografts containing live cells - United States, 2023
Wortham JM , Haddad MB , Stewart RJ , Annambhotla P , Basavaraju SV , Nabity SA , Griffin IS , McDonald E , Beshearse EM , Grossman MK , Schildknecht KR , Calvet HM , Keh CE , Percak JM , Coloma M , Shaw T , Davidson PJ , Smith SR , Dickson RP , Kaul DR , Gonzalez AR , Rai S , Rodriguez G , Morris S , Armitige LY , Stapleton J , Lacassagne M , Young LR , Ariail K , Behm H , Jordan HT , Spencer M , Nilsen DM , Denison BM , Burgos M , Leonard JM , Cortes E , Thacker TC , Lehman KA , Langer AJ , Cowan LS , Starks AM , LoBue PA . MMWR Morb Mortal Wkly Rep 2024 72 (5253) 1385-1389 During July 7-11, 2023, CDC received reports of two patients in different states with a tuberculosis (TB) diagnosis following spinal surgical procedures that used bone allografts containing live cells from the same deceased donor. An outbreak associated with a similar product manufactured by the same tissue establishment (i.e., manufacturer) occurred in 2021. Because of concern that these cases represented a second outbreak, CDC and the Food and Drug Administration worked with the tissue establishment to determine that this product was obtained from a donor different from the one implicated in the 2021 outbreak and learned that the bone allograft product was distributed to 13 health care facilities in seven states. Notifications to all seven states occurred on July 12. As of December 20, 2023, five of 36 surgical bone allograft recipients received laboratory-confirmed TB disease diagnoses; two patients died of TB. Whole-genome sequencing demonstrated close genetic relatedness between positive Mycobacterium tuberculosis cultures from surgical recipients and unused product. Although the bone product had tested negative by nucleic acid amplification testing before distribution, M. tuberculosis culture of unused product was not performed until after the outbreak was recognized. The public health response prevented up to 53 additional surgical procedures using allografts from that donor; additional measures to protect patients from tissue-transmitted M. tuberculosis are urgently needed. |
Monitoring and reporting the US COVID-19 vaccination effort
Scharf LG , Adeniyi K , Augustini E , Boyd D , Corvin L , Kalach RE , Fast H , Fath J , Harris L , Henderson D , Hicks-Thomson J , Jones-Jack N , Kellerman A , Khan AN , McGarvey SS , McGehee JE , EMiner C , Moore LB , Murthy BP , Myerburg S , Neuhaus E , Nguyen K , Parker M , Pierce-Richards S , Samchok D , Shaw LK , Spoto S , Srinivasan A , Stearle C , Thomas J , Winarsky M , Zell E . Vaccine 2023 Immunizations are an important tool to reduce the burden of vaccine preventable diseases and improve population health.(1) High-quality immunization data is essential to inform clinical and public health interventions and respond to outbreaks of vaccine-preventable diseases. To track COVID-19 vaccines and vaccinations, CDC established an integrated network that included vaccination provider systems, health information exchange systems, immunization information systems, pharmacy and dialysis systems, vaccine ordering systems, electronic health records, and tools to support mass vaccination clinics. All these systems reported data to CDC's COVID-19 response system (either directly or indirectly) where it was processed, analyzed, and disseminated. This unprecedented vaccine tracking effort provided essential information for public health officials that was used to monitor the COVID-19 response and guide decisions. This paper will describe systems, processes, and policies that enabled monitoring and reporting of COVID-19 vaccination efforts and share challenges and lessons learned for future public health emergency responses. |
Bias analyses to investigate the impact of differential participation: Application to a birth defects case-control study
Petersen JM , Kahrs JC , Adrien N , Wood ME , Olshan AF , Smith LH , Howley MM , Ailes EC , Romitti PA , Herring AH , Parker SE , Shaw GM , Politis MD . Paediatr Perinat Epidemiol 2023 BACKGROUND: Certain associations observed in the National Birth Defects Prevention Study (NBDPS) contrasted with other research or were from areas with mixed findings, including no decrease in odds of spina bifida with periconceptional folic acid supplementation, moderately increased cleft palate odds with ondansetron use and reduced hypospadias odds with maternal smoking. OBJECTIVES: To investigate the plausibility and extent of differential participation to produce effect estimates observed in NBDPS. METHODS: We searched the literature for factors related to these exposures and participation and conducted deterministic quantitative bias analyses. We estimated case-control participation and expected exposure prevalence based on internal and external reports, respectively. For the folic acid-spina bifida and ondansetron-cleft palate analyses, we hypothesized the true odds ratio (OR) based on prior studies and quantified the degree of exposure over- (or under-) representation to produce the crude OR (cOR) in NBDPS. For the smoking-hypospadias analysis, we estimated the extent of selection bias needed to nullify the association as well as the maximum potential harmful OR. RESULTS: Under our assumptions (participation, exposure prevalence, true OR), there was overrepresentation of folic acid use and underrepresentation of ondansetron use and smoking among participants. Folic acid-exposed spina bifida cases would need to have been ≥1.2× more likely to participate than exposed controls to yield the observed null cOR. Ondansetron-exposed cleft palate cases would need to have been 1.6× more likely to participate than exposed controls if the true OR is null. Smoking-exposed hypospadias cases would need to have been ≥1.2 times less likely to participate than exposed controls for the association to falsely appear protective (upper bound of selection bias adjusted smoking-hypospadias OR = 2.02). CONCLUSIONS: Differential participation could partly explain certain associations observed in NBDPS, but questions remain about why. Potential impacts of other systematic errors (e.g. exposure misclassification) could be informed by additional research. |
Author Correction: Multiplexed CRISPR-based microfluidic platform for clinical testing of respiratory viruses and identification of SARS-CoV-2 variants
Welch NL , Zhu M , Hua C , Weller J , Mirhashemi ME , Nguyen TG , Mantena S , Bauer MR , Shaw BM , Ackerman CM , Thakku SG , Tse MW , Kehe J , Uwera MM , Eversley JS , Bielwaski DA , McGrath G , Braidt J , Johnson J , Cerrato F , Moreno GK , Krasilnikova LA , Petros BA , Gionet GL , King E , Huard RC , Jalbert SK , Cleary ML , Fitzgerald NA , Gabriel SB , Gallagher GR , Smole SC , Madoff LC , Brown CM , Keller MW , Wilson MM , Kirby MK , Barnes JR , Park DJ , Siddle KJ , Happi CT , Hung DT , Springer M , MacInnis BL , Lemieux JE , Rosenberg E , Branda JA , Blainey PC , Sabeti PC , Myhrvold C . Nat Med 2023 In the version of the article originally published, some of the oligonucleotide sequences in Supplementary Table 4, on the “21 viruses” and “RVP” tabs, were mislabeled. The Supplementary Tables file has now been corrected. |
Occupational injuries among construction workers by age and related economic loss: findings from Ohio workers' compensation, USA: 2007-2017
Kaur H , Wurzelbacher SJ , Bushnell PT , Bertke S , Meyers AR , Grosch JW , Naber S , Lampl M . Saf Health Work 2023 14 (4) [Epub ahead of print] Background: This study examined age-group differences in the rate, severity, and cost of injuries among construction workers to support evidence-based worker safety and health interventions in the construction industry. Methods: Ohio workers' compensation claims for construction workers were used to estimate claim rates and costs by age group. We analyzed claims data auto-coded into five event/exposure categories: transportation incidents; slips, trips, and falls (STFs); exposure to harmful substances and environments (EHS); contact with objects and equipment (COB); and overexertion and bodily reaction. American Community Survey data were used to determine the proportion of workers by age group. Results: From 2007-2017, among 72,416 accepted injury claims for 166,000 construction full-time equivalent (FTE) per year, nearly half were caused by COB, followed by STFs (20%) and overexertion (20%). Claim rates related to COB and EHS were highest among those 18-24 years old, with claim rates of 313.5 and 25.9 per 10,000 FTE, respectively. STFs increased with age, with the highest claim rates for those 55-64 years old (94.2 claims per 10,000 FTE). Overexertion claim rates increased and then declined with age, with the highest claim rate for those 35-44 years old (87.3 per 10,000 FTE). While younger workers had higher injury rates, older workers had higher proportions of lost-time claims and costs per claim. The total cost per FTE was highest for those 45-54 years old ($1,122 per FTE). Conclusion: The variation in rates of injury types by age suggests age-specific prevention strategies may be useful. |
Characteristics and outcomes among adults aged ≥60 years hospitalized with laboratory-confirmed respiratory syncytial virus - RSV-NET, 12 States, July 2022-June 2023
Havers FP , Whitaker M , Melgar M , Chatwani B , Chai SJ , Alden NB , Meek J , Openo KP , Ryan PA , Kim S , Lynfield R , Shaw YP , Barney G , Tesini BL , Sutton M , Talbot HK , Olsen KP , Patton ME . MMWR Morb Mortal Wkly Rep 2023 72 (40) 1075-1082 Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in older adults. In May 2023, two RSV vaccines were approved for prevention of RSV lower respiratory tract disease in adults aged ≥60 years. In June 2023, CDC recommended RSV vaccination for adults aged ≥60 years, using shared clinical decision-making. Using data from the Respiratory Syncytial Virus-Associated Hospitalization Surveillance Network, a population-based hospitalization surveillance system operating in 12 states, this analysis examined characteristics (including age, underlying medical conditions, and clinical outcomes) of 3,218 adults aged ≥60 years who were hospitalized with laboratory-confirmed RSV infection during July 2022-June 2023. Among a random sample of 1,634 older adult patients with RSV-associated hospitalization, 54.1% were aged ≥75 years, and the most common underlying medical conditions were obesity, chronic obstructive pulmonary disease, congestive heart failure, and diabetes. Severe outcomes occurred in 18.5% (95% CI = 15.9%-21.2%) of hospitalized patients aged ≥60 years. Overall, 17.0% (95% CI = 14.5%-19.7%) of patients with RSV infection were admitted to an intensive care unit, 4.8% (95% CI = 3.5%-6.3%) required mechanical ventilation, and 4.7% (95% CI = 3.6%-6.1%) died; 17.2% (95% CI = 14.9%-19.8%) of all cases occurred in long-term care facility residents. These data highlight the importance of prioritizing those at highest risk for severe RSV disease and suggest that clinicians and patients consider age (particularly age ≥75 years), long-term care facility residence, and underlying medical conditions, including chronic obstructive pulmonary disease and congestive heart failure, in shared clinical decision-making when offering RSV vaccine to adults aged ≥60 years. |
Proteomic and genetic analyses of influenza A viruses identify pan-viral host targets
Haas KM , McGregor MJ , Bouhaddou M , Polacco BJ , Kim EY , Nguyen TT , Newton BW , Urbanowski M , Kim H , Williams MAP , Rezelj VV , Hardy A , Fossati A , Stevenson EJ , Sukerman E , Kim T , Penugonda S , Moreno E , Braberg H , Zhou Y , Metreveli G , Harjai B , Tummino TA , Melnyk JE , Soucheray M , Batra J , Pache L , Martin-Sancho L , Carlson-Stevermer J , Jureka AS , Basler CF , Shokat KM , Shoichet BK , Shriver LP , Johnson JR , Shaw ML , Chanda SK , Roden DM , Carter TC , Kottyan LC , Chisholm RL , Pacheco JA , Smith ME , Schrodi SJ , Albrecht RA , Vignuzzi M , Zuliani-Alvarez L , Swaney DL , Eckhardt M , Wolinsky SM , White KM , Hultquist JF , Kaake RM , García-Sastre A , Krogan NJ . Nat Commun 2023 14 (1) 6030 Influenza A Virus (IAV) is a recurring respiratory virus with limited availability of antiviral therapies. Understanding host proteins essential for IAV infection can identify targets for alternative host-directed therapies (HDTs). Using affinity purification-mass spectrometry and global phosphoproteomic and protein abundance analyses using three IAV strains (pH1N1, H3N2, H5N1) in three human cell types (A549, NHBE, THP-1), we map 332 IAV-human protein-protein interactions and identify 13 IAV-modulated kinases. Whole exome sequencing of patients who experienced severe influenza reveals several genes, including scaffold protein AHNAK, with predicted loss-of-function variants that are also identified in our proteomic analyses. Of our identified host factors, 54 significantly alter IAV infection upon siRNA knockdown, and two factors, AHNAK and coatomer subunit COPB1, are also essential for productive infection by SARS-CoV-2. Finally, 16 compounds targeting our identified host factors suppress IAV replication, with two targeting CDK2 and FLT3 showing pan-antiviral activity across influenza and coronavirus families. This study provides a comprehensive network model of IAV infection in human cells, identifying functional host targets for pan-viral HDT. |
Is gastroschisis associated with county-level socio-environmental quality during pregnancy?
Krajewski AK , Patel A , Gray CL , Messer LC , Keeler CY , Langlois PH , Reefhuis J , Gilboa SM , Werler MM , Shaw GM , Carmichael SL , Nembhard WN , Insaf TZ , Feldkamp ML , Conway KM , Lobdell DT , Desrosiers TA . Birth Defects Res 2023 115 (18) 1758-1769 BACKGROUND: Gastroschisis prevalence more than doubled between 1995 and 2012. While there are individual-level risk factors (e.g., young maternal age, low body mass index), the impact of environmental exposures is not well understood. METHODS: We used the U.S. Environmental Protection Agency's Environmental Quality Index (EQI) as a county-level estimate of cumulative environmental exposures for five domains (air, water, land, sociodemographic, and built) and overall from 2006 to 2010. Adjusted odds ratios (aOR) and 95% confidence interval (CI) were estimated from logistic regression models between EQI tertiles (better environmental quality (reference); mid; poorer) and gastroschisis in the National Birth Defects Prevention Study from births delivered between 2006 and 2011. Our analysis included 594 cases with gastroschisis and 4105 infants without a birth defect (controls). RESULTS: Overall EQI was modestly associated with gastroschisis (aOR [95% CI]: 1.29 [0.98, 1.71]) for maternal residence in counties with poorer environmental quality, compared to the reference (better environmental quality). Within domain-specific indices, only the sociodemographic domain (aOR: 1.51 [0.99, 2.29]) was modestly associated with gastroschisis, when comparing poorer to better environmental quality. CONCLUSIONS: Future work could elucidate pathway(s) by which components of the sociodemographic domain or possibly related psychosocial factors like chronic stress potentially contribute to risk of gastroschisis. |
Neighborhood deprivation and neural tube defects
Pruitt Evans S , Ailes EC , Kramer MR , Shumate CJ , Reefhuis J , Insaf TZ , Yazdy MM , Carmichael SL , Romitti PA , Feldkamp ML , Neo DT , Nembhard WN , Shaw GM , Palmi E , Gilboa SM . Epidemiology 2023 34 (6) 774-785 BACKGROUND: Individual measures of socioeconomic status (SES) have been associated with an increased risk of neural tube defects (NTDs); however, the association between neighborhood SES and NTD risk is unknown. Using data from the National Birth Defects Prevention Study (NBDPS) from 1997 to 2011, we investigated the association between measures of census tract SES and NTD risk. METHODS: The study population included 10,028 controls and 1829 NTD cases. We linked maternal addresses to census tract SES measures and used these measures to calculate the neighborhood deprivation index. We used generalized estimating equations to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) estimating the impact of quartiles of census tract deprivation on NTDs adjusting for maternal race-ethnicity, maternal education, and maternal age at delivery. RESULTS: Quartiles of higher neighborhood deprivation were associated with NTDs when compared with the least deprived quartile (Q2: aOR = 1.2; 95% CI = 1.0, 1.4; Q3: aOR = 1.3, 95% CI = 1.1, 1.5; Q4 (highest): aOR = 1.2; 95% CI = 1.0, 1.4). Results for spina bifida were similar; however, estimates for anencephaly and encephalocele were attenuated. Associations differed by maternal race-ethnicity. CONCLUSIONS: Our findings suggest that residing in a census tract with more socioeconomic deprivation is associated with an increased risk for NTDs, specifically spina bifida. |
Rare variants in CAPN2 increase risk for isolated hypoplastic left heart syndrome
Blue EE , White JJ , Dush MK , Gordon WW , Wyatt BH , White P , Marvin CT , Helle E , Ojala T , Priest JR , Jenkins MM , Almli LM , Reefhuis J , Pangilinan F , Brody LC , McBride KL , Garg V , Shaw GM , Romitti PA , Nembhard WN , Browne ML , Werler MM , Kay DM , Mital S , Chong JX , Nascone-Yoder NM , Bamshad MJ . HGG Adv 2023 4 (4) 100232 Hypoplastic left heart syndrome (HLHS) is a severe congenital heart defect (CHD) characterized by hypoplasia of the left ventricle and aorta along with stenosis or atresia of the aortic and mitral valves. HLHS represents only ∼4%-8% of all CHDs but accounts for ∼25% of deaths. HLHS is an isolated defect (i.e., iHLHS) in 70% of families, the vast majority of which are simplex. Despite intense investigation, the genetic basis of iHLHS remains largely unknown. We performed exome sequencing on 331 families with iHLHS aggregated from four independent cohorts. A Mendelian-model-based analysis demonstrated that iHLHS was not due to single, large-effect alleles in genes previously reported to underlie iHLHS or CHD in >90% of families in this cohort. Gene-based association testing identified increased risk for iHLHS associated with variation in CAPN2 (p = 1.8 × 10(-5)), encoding a protein involved in functional adhesion. Functional validation studies in a vertebrate animal model (Xenopus laevis) confirmed CAPN2 is essential for cardiac ventricle morphogenesis and that in vivo loss of calpain function causes hypoplastic ventricle phenotypes and suggest that human CAPN2(707C>T) and CAPN2(1112C>T) variants, each found in multiple individuals with iHLHS, are hypomorphic alleles. Collectively, our findings show that iHLHS is typically not a Mendelian condition, demonstrate that CAPN2 variants increase risk of iHLHS, and identify a novel pathway involved in HLHS pathogenesis. |
Maternal physical activity, sitting, and risk of non-cardiac birth defects
Evenson KR , Mowla S , Olshan AF , Shaw GM , Ailes EC , Reefhuis J , Joshi N , Desrosiers TA . Pediatr Res 2023 BACKGROUND: The relationship between maternal physical activity (PA)/sitting and birth defects is largely unexplored. We examined whether pre-pregnancy PA/sitting were associated with having a pregnancy affected by a birth defect. METHODS: We used data from two United States population-based case-control studies: 2008-2011 deliveries from the National Birth Defects Prevention Study (NBDPS; 9 states) and 2014-2018 deliveries from the Birth Defects Study To Evaluate Pregnancy exposureS (BD-STEPS; 7 states). Cases with one of 12 non-cardiac birth defects (n = 3798) were identified through population-based registries. Controls (n = 2682) were live-born infants without major birth defects randomly sampled using vital/hospital records. Mothers self-reported pre-pregnancy PA/sitting. Unconditional logistic regression models estimated associations between PA/sitting categories and the 12 birth defects. RESULTS: Mothers engaging in pre-pregnancy PA was associated with a reduced odds of five (spina bifida, cleft palate, anorectal atresia, hypospadias, transverse limb deficiency) and a higher odds of two (anencephaly, gastroschisis) birth defects. Mothers spending less time sitting in pre-pregnancy was associated with a reduced odds of two (anorectal atresia, hypospadias) and a higher odds of one (cleft lip with or without cleft palate) birth defect. CONCLUSIONS: Reasonable next steps include replication of these findings, improved exposure assessment, and elucidation of biologic mechanisms. IMPACT: Using data from two population-based case-control studies, we found that mothers engaging in different types of physical activity in the 3 months before pregnancy had an infant with a reduced odds of five and a higher odds of two birth defects. Mothers spending less time sitting in the 3 months before pregnancy had an infant with a reduced odds of two and a higher odds of one birth defect. Clarification and confirmation from additional studies are needed using more precise exposure measures, distinguishing occupational from leisure-time physical activity, and elucidation of mechanisms supporting these associations. |
Adapterama II: Universal amplicon sequencing on Illumina platforms (TaggiMatrix) (preprint)
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 . bioRxiv 2019 619544 Next-generation sequencing (NGS) of amplicons is used in a wide variety of contexts. Most 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 (eight 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. |
Diabetes mellitus is associated with increased prevalence of latent tuberculosis infection: Results from the National Health and Nutrition Examination Survey (preprint)
Barron MM , Shaw KM , McKeever Bullard K , Ali MK , Magee MJ . bioRxiv 2017 204461 Aims We aimed to determine the association between prediabetes and diabetes with latent TB using National Health and Nutrition Examination Survey data.Methods We performed a cross-sectional analysis of 2011-2012 National Health and Nutrition Examination Survey data. Participants ≥20 years were eligible. Diabetes was defined by glycated hemoglobin (HbA1c) as no diabetes (≤5.6% [38 mmol/mol]), prediabetes (5.7-6.4% [3946mmol/mol]), and diabetes (≥6.5% [48 mmol/mol]) combined with self-reported diabetes. Latent TB infection was defined by the QuantiFERON®-TB Gold In Tube (QFT-GIT) test. Adjusted odds ratios (aOR) of latent TB infection by diabetes status were calculated using logistic regression and accounted for the stratified probability sample.Results Diabetes and QFT-GIT measurements were available for 4,958 (89.2%) included participants. Prevalence of diabetes was 11.4% (95%CI 9.8-13.0%) and 22.1% (95%CI 20.523.8%) had prediabetes. Prevalence of latent TB infection was 5.9% (95%CI 4.9-7.0%). After adjusting for age, sex, smoking status, history of active TB, and foreign born status, the odds of latent TB infection were greater among adults with diabetes (aOR 1.90, 95%CI 1.15-3.14) compared to those without diabetes. The odds of latent TB in adults with prediabetes (aOR 1.15, 95%CI 0.90-1.47) was similar to those without diabetes.Conclusions Diabetes is associated with latent TB infection among adults in the United States, even after adjusting for confounding factors. Given diabetes increases the risk of active TB, patients with co-prevalent diabetes and latent TB may be targeted for latent TB treatment. |
Increased vaccine sensitivity of an emerging SARS-CoV-2 variant (preprint)
Lewnard JA , Hong V , Kim JS , Shaw SF , Lewin B , Takhar H , Lipsitch M , Tartof SY . medRxiv 2023 16 (1) 3854 Host immune responses are a key source of selective pressure driving pathogen evolution. Emergence of many SARS-CoV-2 lineages has been associated with improvements in their ability to evade population immunity resulting from both vaccination and infection. Here we show diverging trends of escape from vaccine-derived and infection-derived immunity for the emerging XBB/XBB.1.5 Omicron lineage. Among 31,739 patients tested in ambulatory settings in Southern California from December, 2022 to February, 2023, adjusted odds of prior receipt of 2, 3, 4, and >=5 COVID-19 vaccine doses were 10% (95% confidence interval: 1-18%), 11% (3-19%), 13% (3-21%), and 25% (15-34%) lower, respectively, among cases infected with XBB/XBB.1.5 than among cases infected with other co-circulating lineages. Similarly, prior vaccination was associated with greater protection against progression to hospitalization among cases with XBB/XBB.1.5 than among non-XBB/XBB.1.5 cases (70% [30-87%] and 48% [7-71%], respectively, for recipients of >=4 doses). In contrast, cases infected with XBB/XBB.1.5 had 17% (11-24%) and 40% (19-65%) higher adjusted odds of having experienced 1 and >=2 prior documented infections, respectively, including with pre-Omicron variants. As immunity acquired from SARS-CoV-2 infection becomes increasingly widespread, fitness costs associated with enhanced vaccine sensitivity in XBB/XBB.1.5 may be offset by increased ability to evade infection-derived host responses. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Effectiveness of 2 and 3 mRNA COVID-19 Vaccines Doses against Omicron and Delta-Related Outpatient Illness among Adults, October 2021 - February 2022 (preprint)
Kim SS , Chung JR , Talbot HK , Grijalva CG , Wernli KJ , Martin ET , Monto AS , Belongia EA , McLean HQ , Gaglani M , Mamawala M , Nowalk MP , Geffel KM , Tartof SY , Florea A , Lee JS , Tenforde MW , Patel MM , Flannery B , Bentz ML , Burgin A , Burroughs M , Davis ML , Howard D , Lacek K , Madden JC , Nobles S , Padilla J , Sheth M , Arroliga A , Beeram M , Dunnigan K , Ettlinger J , Graves A , Hoffman E , Jatla M , McKillop A , Murthy K , Mutnal M , Priest E , Raiyani C , Rao A , Requenez L , Settele N , Smith M , Stone K , Thomas J , Volz M , Walker K , Zayed M , Annan E , Daley P , Kniss K , Merced-Morales A , Ayala E , Amundsen B , Aragones M , Calderon R , Hong V , Jimenez G , Kim J , Ku J , Lewin B , McDaniel A , Reyes A , Shaw S , Takhar H , Torres A , Burganowski R , Kiniry E , Moser KA , Nguyen M , Park S , Wellwood S , Wickersham B , Alvarado-Batres J , Benz S , Berger H , Bissonnette A , Blake J , Boese K , Botten E , Boyer J , Braun M , Breu B , Burbey G , Cravillion C , Delgadillo C , Donnerbauer A , Dziedzic T , Eddy J , Edgren H , Ermeling A , Ewert K , Fehrenbach C , Fernandez R , Frome W , Guzinski S , Heeren L , Herda D , Hertel M , Heuer G , Higdon E , Ivacic L , Jepsen L , Kaiser S , Karl J , Keffer B , King J , Koepel TK , Kohl S , Kohn S , Kohnhorst D , Kronholm E , Le T , Lemieux A , Marcis C , Maronde M , McCready I , McGreevey K , Meece J , Mehta N , Miesbauer D , Moon V , Moran J , Nikolai C , Olson B , Olstadt J , Ott L , Pan N , Pike C , Polacek D , Presson M , Price N , Rayburn C , Reardon C , Rotar M , Rottscheit C , Salzwedel J , Saucedo J , Scheffen K , Schug C , Seyfert K , Shrestha R , Slenczka A , Stefanski E , Strupp M , Tichenor M , Watkins L , Zachow A , Zimmerman B , Bauer S , Beney K , Cheng CK , Faraj N , Getz A , Grissom M , Groesbeck M , Harrison S , Henson K , Jermanus K , Johnson E , Kaniclides A , Kimberly A , Lamerato LE , Lauring A , Lehmann-Wandell R , McSpadden EJ , Nabors L , Truscon R , Balasubramani GK , Bear T , Bobeck J , Bowser E , Clarke K , Clarke LG , Dauer K , Deluca C , Dierks B , Haynes L , Hickey R , Johnson M , Jonsson A , Luosang N , McKown L , Peterson A , Phaturos D , Rectenwald A , Sax TM , Stiegler M , Susick M , Suyama J , Taylor L , Walters S , Weissman A , Williams JV , Blair M , Carter J , Chappell J , Copen E , Denney M , Graes K , Halasa N , Lindsell C , Liu Z , Longmire S , McHenry R , Short L , Tan HN , Vargas D , Wrenn J , Wyatt D , Zhu Y . medRxiv 2022 10 Background: We estimated SARS-CoV-2 Delta and Omicron-specific effectiveness of 2 and 3 mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings. Method(s): Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving 2 or 3 mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 - adjusted odds ratio) x 100%. Result(s): Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA 2-dose recipients and 96% (95% CI: 93% to 98%) for 3-dose recipients. When Omicron predominated, VE was 21% (95% CI: -6% to 41%) among 2-dose recipients and 62% (95% CI: 48% to 72%) among 3-dose recipients. Conclusion(s): In this adult population, 3 mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the U.S. These findings support the recommendation for a 3rd mRNA COVID-19 vaccine dose. 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. |
Are individual-level risk factors for gastroschisis modified by neighborhood-level socioeconomic factors
Neo DT , Martin CL , Carmichael SL , Gucsavas-Calikoglu M , Conway KM , Evans SP , Feldkamp ML , Gilboa SM , Insaf TZ , Musfee FI , Shaw GM , Shumate C , Werler MM , Olshan AF , Desrosiers TA . Birth Defects Res 2023 115 (15) 1438-1449 BACKGROUND: Two strong risk factors for gastroschisis are young maternal age (<20 years) and low/normal pre-pregnancy body mass index (BMI), yet the reasons remain unknown. We explored whether neighborhood-level socioeconomic position (nSEP) during pregnancy modified these associations. METHODS: We analyzed data from 1269 gastroschisis cases and 10,217 controls in the National Birth Defects Prevention Study (1997-2011). To characterize nSEP, we applied the neighborhood deprivation index and used generalized estimating equations to calculate odds ratios and relative excess risk due to interaction. RESULTS: Elevated odds of gastroschisis were consistently associated with young maternal age and low/normal BMI, regardless of nSEP. High-deprivation neighborhoods modified the association with young maternal age. Infants of young mothers in high-deprivation areas had lower odds of gastroschisis (adjusted odds ratio [aOR]: 3.1, 95% confidence interval [CI]: 2.6, 3.8) than young mothers in low-deprivation areas (aOR: 6.6; 95% CI: 4.6, 9.4). Mothers of low/normal BMI had approximately twice the odds of having an infant with gastroschisis compared to mothers with overweight/obese BMI, regardless of nSEP (aOR range: 1.5-2.3). CONCLUSION: Our findings suggest nSEP modified the association between gastroschisis and maternal age, but not BMI. Further research could clarify whether the modification is due to unidentified biologic and/or non-biologic factors. |
Increased vaccine sensitivity of an emerging SARS-CoV-2 variant
Lewnard JA , Hong V , Kim JS , Shaw SF , Lewin B , Takhar H , Lipsitch M , Tartof SY . Nat Commun 2023 14 (1) 3854 Host immune responses are a key source of selective pressure driving pathogen evolution. Emergence of many SARS-CoV-2 lineages has been associated with enhancements in their ability to evade population immunity resulting from both vaccination and infection. Here we show diverging trends of escape from vaccine-derived and infection-derived immunity for the emerging XBB/XBB.1.5 Omicron lineage. Among 31,739 patients tested in ambulatory settings in Southern California from December, 2022 to February, 2023, adjusted odds of prior receipt of 2, 3, 4, and ≥5 COVID-19 vaccine doses were 10% (95% confidence interval: 1-18%), 11% (3-19%), 13% (3-21%), and 25% (15-34%) lower, respectively, among cases infected with XBB/XBB.1.5 than among cases infected with other co-circulating lineages. Similarly, prior vaccination was associated with greater point estimates of protection against progression to hospitalization among cases with XBB/XBB.1.5 than among non-XBB/XBB.1.5 cases (70% [30-87%] and 48% [7-71%], respectively, for recipients of ≥4 doses). In contrast, cases infected with XBB/XBB.1.5 had 17% (11-24%) and 40% (19-65%) higher adjusted odds of having experienced 1 and ≥2 prior documented infections, respectively, including with pre-Omicron variants. As immunity acquired from SARS-CoV-2 infection becomes increasingly widespread, fitness costs associated with enhanced vaccine sensitivity in XBB/XBB.1.5 may be offset by increased ability to evade infection-derived host responses. |
Individualized education programs and transition planning for adolescents with autism
Hughes MM , Kirby AV , Davis J , Bilder DA , Patrick M , Lopez M , DaWalt LS , Pas ET , Bakian AV , Shaw KA , DiRienzo M , Hudson A , Schwenk YD , Baroud TM , Washington A , Maenner MJ . Pediatrics 2023 152 (1) OBJECTIVES: The study objectives were to examine the contents of individualized education programs (IEPs) of adolescents with autism spectrum disorder (ASD), including postsecondary transition goals, services, and changes in special education classification over time. METHODS: This study involved a longitudinal population-based surveillance cohort from the Autism Developmental Disabilities Monitoring Network from 2002 to 2018 in 3 catchment areas in the United States. The sample included 322 adolescents who were born in 2002, identified with ASD, and had an IEP available for review at ages 15-16 years. RESULTS: We found that 297 (92%) adolescents with ASD had an IEP including a transition plan. Those without intellectual disability (ID) were more likely to have postsecondary education and employment goals and have those goals be to pursue higher education or competitive employment compared with those with ID. Forty-one percent of adolescents with ASD had a postsecondary living arrangement goal. Although 28% of adolescents with ASD received school-based mental health services, none of these adolescents were Black; additionally, 15% of those with ID received mental health services compared with 34% without ID. The percentage of adolescents with ASD served under an autism classification increased from 44% at age 8 years to 62% by age 16. CONCLUSIONS: We identified gaps and disparities in school-based postsecondary transition planning. Working with education partners, families, and adolescents will be important to identify what challenges contribute to these findings and what supports are needed to improve the equity and quality of the transition planning process for adolescents with ASD so they are prepared for adulthood. |
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. |
Social vulnerability and prevalence of autism, Metropolitan Atlanta Developmental Disabilities Surveillance Program (MADDSP)
Patrick ME , Hughes MM , Ali A , Shaw KA , Maenner MJ . Ann Epidemiol 2023 83 47-53 e1 PURPOSE: The Metropolitan Atlanta Developmental Disabilities Surveillance Program (MADDSP) tracks autism spectrum disorder (ASD) in selected counties within Georgia as part of the Autism and Developmental Disabilities Monitoring Network. ADDM Network analyses have historically found higher prevalence of ASD in areas of higher socioeconomic status. METHODS: We linked 2018 data from CDC's Social Vulnerability Index (SVI) to two MADDSP counties by census tract, grouped census tracts into tertiles representing low, medium, and high social vulnerability, and calculated ASD prevalence for each tertile, overall and by each of four SVI themes. RESULTS: We found that overall prevalence was higher in areas of low compared to high vulnerability for the socioeconomic status and transportation themes, and in areas of medium compared to high vulnerability for all themes. This pattern was consistent among males but varied for females and by race/ethnicity. CONCLUSION: Linking ASD prevalence to SVI metrics can improve understanding of inequities among children with ASD in racial and ethnic minority groups or those living in low resource settings. These methods can be applied to other ADDM Network surveillance sites and public health surveillance programs. |
The prevalence and characteristics of children with profound autism, 15 sites, United States, 2000-2016
Hughes MM , Shaw KA , DiRienzo M , Durkin MS , Esler A , Hall-Lande J , Wiggins L , Zahorodny W , Singer A , Maenner MJ . Public Health Rep 2023 138 (6) 333549231163551 OBJECTIVES: Autism spectrum disorder (autism) is a heterogeneous condition that poses challenges in describing the needs of individuals with autism and making prognoses about future outcomes. We applied a newly proposed definition of profound autism to surveillance data to estimate the percentage of children with autism who have profound autism and describe their sociodemographic and clinical characteristics. METHODS: We analyzed population-based surveillance data from the Autism and Developmental Disabilities Monitoring Network for 20 135 children aged 8 years with autism during 2000-2016. Children were classified as having profound autism if they were nonverbal, were minimally verbal, or had an intelligence quotient <50. RESULTS: The percentage of 8-year-old children with profound autism among those with autism was 26.7%. Compared with children with non-profound autism, children with profound autism were more likely to be female, from racial and ethnic minority groups, of low socioeconomic status, born preterm or with low birth weight; have self-injurious behaviors; have seizure disorders; and have lower adaptive scores. In 2016, the prevalence of profound autism was 4.6 per 1000 8-year-olds. The prevalence ratio (PR) of profound autism was higher among non-Hispanic Asian/Native Hawaiian/Other Pacific Islander (PR = 1.55; 95 CI, 1.38-1.73), non-Hispanic Black (PR = 1.76; 95% CI, 1.67-1.86), and Hispanic (PR = 1.50; 95% CI, 0.88-1.26) children than among non-Hispanic White children. CONCLUSIONS: As the population of children with autism continues to change, describing and quantifying the population with profound autism is important for planning. Policies and programs could consider the needs of people with profound autism across the life span to ensure their needs are met. |
Firefighting and cancer: A meta-analysis of cohort studies in the context of cancer hazard identification
DeBono NL , Daniels RD , Beane Freeman LE , Graber JM , Hansen J , Teras LR , Driscoll T , Kjaerheim K , Demers PA , Glass DC , Kriebel D , Kirkham TL , Wedekind R , Filho AM , Stayner L , Schubauer-Berigan MK . Saf Health Work 2023 14 (2) 141-152 Objective: We performed a meta-analysis of epidemiological results for the association between occupational exposure as a firefighter and cancer as part of the broader evidence synthesis work of the IARC Monographs program. Methods: A systematic literature search was conducted to identify cohort studies of firefighters followed for cancer incidence and mortality. Studies were evaluated for the influence of key biases on results. Random-effects meta-analysis models were used to estimate the association between ever-employment and duration of employment as a firefighter and risk of 12 selected cancers. The impact of bias was explored in sensitivity analyses. Results: Among the 16 included cancer incidence studies, the estimated meta-rate ratio, 95% confidence interval (CI), and heterogeneity statistic (I2) for ever-employment as a career firefighter compared mostly to general populations were 1.58 (1.14–2.20, 8%) for mesothelioma, 1.16 (1.08–1.26, 0%) for bladder cancer, 1.21 (1.12–1.32, 81%) for prostate cancer, 1.37 (1.03–1.82, 56%) for testicular cancer, 1.19 (1.07–1.32, 37%) for colon cancer, 1.36 (1.15–1.62, 83%) for melanoma, 1.12 (1.01–1.25, 0%) for non-Hodgkin lymphoma, 1.28 (1.02–1.61, 40%) for thyroid cancer, and 1.09 (0.92–1.29, 55%) for kidney cancer. Ever-employment as a firefighter was not positively associated with lung, nervous system, or stomach cancer. Results for mesothelioma and bladder cancer exhibited low heterogeneity and were largely robust across sensitivity analyses. Conclusions: There is epidemiological evidence to support a causal relationship between occupational exposure as a firefighter and certain cancers. Challenges persist in the body of evidence related to the quality of exposure assessment, confounding, and medical surveillance bias. © 2023 Occupational Safety and Health Research Institute |
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