Last data update: Apr 18, 2025. (Total: 49119 publications since 2009)
Records 1-23 (of 23 Records) |
Query Trace: O'Sullivan B[original query] |
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Environmental and Health Care Personnel Sampling and Unobserved Clostridium difficile Transmission in ICU
Keegan LT , Tanner W , Orleans B , Slayton RB , Jernigan JA , McDonald LC , Noble-Wang J , Leecaster M , Haroldsen C , Khader K , Toth DJA , O'Sullivan T , Samore MH , Brazelton W , Rubin M . JAMA Netw Open 2025 8 (4) e252787 ![]() IMPORTANCE: Clostridioides difficile is among the most prevalent health care-associated pathogens worldwide. Controlling it remains a critical challenge, due in part to spore viability on surfaces. OBJECTIVE: To quantify transmission of C difficile within health care facilities and evaluate the roles of environmental surfaces and health care personnel (HCP) hands in C difficile movement. DESIGN, SETTING, AND PARTICIPANTS: In 2018, a 13-week longitudinal, observational study was conducted in 2 intensive care units (ICUs) in Utah with daily culture-based sampling of patient body sites, room environmental surfaces, HCP hands, and shared environmental surfaces. Both toxigenic and nontoxigenic C difficile strains were selected for whole genome sequencing and included in the analysis. Data were analyzed from September 2021 to September 2024. MAIN OUTCOMES AND MEASURES: The primary outcome was the identification of transmission clusters based on genomic relatedness between isolates from patients, environmental surfaces, and HCP hands. Clusters were defined as isolates with 2 or fewer single nucleotide variants between them. RESULTS: Of the 278 unique ICU admissions, 177 patients consented to body site sampling and were sampled. Along with these, environment surfaces and HCP hands were sampled daily for all occupied rooms, leading to 7000 total samples. Sampling patients, their environment, and HCP hands revealed that nearly 8% of all patients had C difficile linked to other admissions and 57% of transmission clusters bridged nonoverlapping patient-stays. Including environmental surfaces and HCP hands, a 3.6-fold higher C difficile movement was identified than with patient sampling alone, highlighting environmental surfaces as reservoirs. CONCLUSIONS AND RELEVANCE: These results challenge the idea that nosocomial transmission is not a primary source of acquisition and underscore the importance of hand hygiene and environmental decontamination. This study reinforces the need to include environmental surfaces and HCP hands in future work characterizing the burden of nosocomial transmission. Understanding the transmission pathways of C difficile within health care facilities, particularly the roles of environmental surfaces and HCP hands, is critical to improving infection control measures. |
Notes from the field: Anthrax on a sheep farm in winter - Texas, December 2023-January 2024
Thompson JM , Spencer K , Maass M , Rollo S , Beesley CA , Marston CK , Hoffmaster AR , Bower WA , Candela MG , Barr JR , Boyer AE , Weiner ZP , Negrón ME , Swaney E , O'Sullivan B . MMWR Morb Mortal Wkly Rep 2024 73 (22) 517-520 |
Improving reporting standards for polygenic scores in risk prediction studies (preprint)
Wand H , Lambert SA , Tamburro C , Iacocca MA , O'Sullivan JW , Sillari C , Kullo IJ , Rowley R , Dron JS , Brockman D , Venner E , McCarthy MI , Antoniou AC , Easton DF , Hegele RA , Khera AV , Chatterjee N , Kooperberg C , Edwards K , Vlessis K , Kinnear K , Danesh JN , Parkinson H , Ramos EM , Roberts MC , Ormond KE , Khoury MJ , Janssens Acjw , Goddard KAB , Kraft P , MacArthur JAL , Inouye M , Wojcik GL . medRxiv 2020 2020.04.23.20077099 Polygenic risk scores (PRS), often aggregating the results from genome-wide association studies, can bridge the gap between the initial discovery efforts and clinical applications for disease risk estimation. However, there is remarkable heterogeneity in the reporting of these risk scores. This lack of adherence to reporting standards hinders the translation of PRS into clinical care. The ClinGen Complex Disease Working Group, in a collaboration with the Polygenic Score (PGS) Catalog, have updated the Genetic Risk Prediction (GRIPS) Reporting Statement to the current state of the field and to enable downstream utility. Drawing upon experts in epidemiology, statistics, disease-specific applications, implementation, and policy, this 22-item reporting framework defines the minimal information needed to interpret and evaluate a PRS, especially with respect to any downstream clinical applications. Items span detailed descriptions of the study population (recruitment method, key demographic and clinical characteristics, inclusion/exclusion criteria, and outcome definition), statistical methods for both PRS development and validation, and considerations for potential limitations of the published risk score and downstream clinical utility. Additionally, emphasis has been placed on data availability and transparency to facilitate reproducibility and benchmarking against other PRS, such as deposition in the publicly available PGS Catalog. By providing these criteria in a structured format that builds upon existing standards and ontologies, the use of this framework in publishing PRS will facilitate translation of PRS into clinical care and progress towards defining best practices.Summary In recent years, polygenic risk scores (PRS) have increasingly been used to capture the genome-wide liability underlying many human traits and diseases, hoping to better inform an individual’s genetic risk. However, a lack of adherence to existing reporting standards has hindered the translation of this important tool into clinical and public health practice; in particular, details necessary for benchmarking and reproducibility are underreported. To address this gap, the ClinGen Complex Disease Working Group and Polygenic Score (PGS) Catalog have updated the Genetic Risk Prediction (GRIPS) Reporting Statement into the 22-item Polygenic Risk Score Reporting Statement (PRS-RS). This framework provides the minimal information expected of authors to promote the validity, transparency, and reproducibility of PRS by encouraging authors to detail the study population, statistical methods, and potential clinical utility of a published score. The widespread adoption of this framework will encourage rigorous methodological consideration and facilitate benchmarking to ensure high quality scores are translated into the clinic.Competing Interest StatementMIM is on the advisory panels Pfizer, Novo Nordisk, and Zoe Global; Honoraria: Merck, Pfizer, Novo Nordisk, and Eli Lilly; Research funding: Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Pfizer, Roche, Sanofi Aventis, Servier & Takeda. As of June 2019, he is an employee of Genentech with stock and stock options in Roche. No other authors have competing interests to declare.Funding StatementClinGen is primarily funded by the National Human Genome Research Institute (NHGRI), through the following three grants: U41HG006834, U41HG009649, U41HG009650. ClinGen also receives support for content curation from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), through the following three grants: U24HD093483, U24HD093486, U24HD093487. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additionally, the views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. Research reported in this publication was supported by the National Human Genome Research Institute of the National Institutes of Health under Award Number U41HG007823 (EBI-NHGRI GWAS Catalog, PGS Catalog). In addition, we acknowledge funding from the European Molecular Biology Laboratory. Individuals were funded from the following sources: MIM was a Wellcome Investigator and an NIHR Senior Investigator with funding from NIDDK (U01-DK105535); Wellcome (090532, 098381, 106130, 203141, 212259). MI, SAL, and JD were supported by core funding from: the UK Medical Research Council (MR/L003120/1), the British Heart Foundation (RG/13/13/30194; RG/18/13/33946) and the National Institute for Health Research (Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust). SAL is supported by a Canadian Institutes of Health Research postdoctoral fellowship (MFE-171279). JD holds a British Heart Foundation Personal Chair and a National Institute for Health Research Senior Investigator Award. This work was also supported by Health Data Research UK, which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation and Wellcome.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:N/AAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesN/A |
Epidemiologic Investigation of Two Welder's Anthrax Cases Caused by Bacillus Cereus Group Bacteria: Occupational Link Established by Environmental Detection.
Dawson P , Salzer JS , Schrodt CA , Feldmann K , Kolton CB , Gee JE , Marston CK , Gulvik CA , Elrod MG , Villarma A , Traxler RM , Negrón ME , Hendricks KA , Moulton-Meissner H , Rose LJ , Byers P , Taylor K , Ware D , Balsamo GA , Sokol T , Barrett B , Payne E , Zaheer S , Jung GO , Long S , Quijano R , LeBouf L , O'Sullivan B , Swaney E , Antonini JM , Perio MA , Weiner Z , Bower WA , Hoffmaster AR . Pathogens 2022 11 (8) ![]() ![]() Abstract Bacillus cereus group bacteria containing the anthrax toxin genes can cause fatal anthrax pneumonia in welders. Two welder's anthrax cases identified in 2020 were investigated to determine the source of each patient's exposure. Environmental sampling was performed at locations where each patient had recent exposure to soil and dust. Samples were tested for the anthrax toxin genes by real-time PCR, and culture was performed on positive samples to identify whether any environmental isolates matched the patient's clinical isolate. A total of 185 environmental samples were collected in investigation A for patient A and 108 samples in investigation B for patient B. All samples from investigation B were real-time PCR-negative, but 14 (8%) samples from investigation A were positive, including 10 from patient A's worksite and 4 from his work-related clothing and gear. An isolate genetically matching the one recovered from patient A was successfully cultured from a worksite soil sample. All welder's anthrax cases should be investigated to determine the source of exposure, which may be linked to their worksite. Welding and metalworking employers should consider conducting a workplace hazard assessment and implementing controls to reduce the risk of occupationally associated illnesses including welder's anthrax. |
Multistate Outbreak of Melioidosis Associated with Imported Aromatherapy Spray.
Gee JE , Bower WA , Kunkel A , Petras J , Gettings J , Bye M , Firestone M , Elrod MG , Liu L , Blaney DD , Zaldivar A , Raybern C , Ahmed FS , Honza H , Stonecipher S , O'Sullivan BJ , Lynfield R , Hunter M , Brennan S , Pavlick J , Gabel J , Drenzek C , Geller R , Lee C , Ritter JM , Zaki SR , Gulvik CA , Wilson WW , Beshearse E , Currie BJ , Webb JR , Weiner ZP , Negrón ME , Hoffmaster AR . N Engl J Med 2022 386 (9) 861-868 ![]() ![]() Melioidosis, caused by the bacterium Burkholderia pseudomallei, is an uncommon infection that is typically associated with exposure to soil and water in tropical and subtropical environments. It is rarely diagnosed in the continental United States. Patients with melioidosis in the United States commonly report travel to regions where melioidosis is endemic. We report a cluster of four non-travel-associated cases of melioidosis in Georgia, Kansas, Minnesota, and Texas. These cases were caused by the same strain of B. pseudomallei that was linked to an aromatherapy spray product imported from a melioidosis-endemic area. |
Notes from the Field: Fatal Anthrax Pneumonia in Welders and Other Metalworkers Caused by Bacillus cereus Group Bacteria Containing Anthrax Toxin Genes - U.S. Gulf Coast States, 1994-2020.
Dawson P , Schrodt CA , Feldmann K , Traxler RM , Gee JE , Kolton CB , Marston CK , Gulvik CA , Antonini JM , Negrón ME , McQuiston JR , Hendricks K , Weiner Z , Balsamo GA , Sokol T , Byers P , Taylor K , Zaheer S , Long S , O'Sullivan B , de Perio MA , Hoffmaster AR , Salzer JS , Bower WA . MMWR Morb Mortal Wkly Rep 2021 70 (41) 1453-1454 ![]() ![]() In 2020, CDC confirmed two cases of pneumonia (one fatal) in welders caused by rare Bacillus cereus group bacteria containing anthrax toxin genes typically associated with Bacillus anthracis. B. cereus group bacteria are gram-positive facultative anaerobes, often toxin-producing, that are ubiquitous in the environment and reside naturally in soil and dust (1). B. cereus can also be found in food, and although infection typically causes illnesses characterized by diarrhea or vomiting, B. cereus can have other clinical manifestations (e.g., pulmonary, ocular, or cutaneous). Among seven persons in the United States reported to be infected with B. cereus group bacteria containing anthrax toxin genes resulting in pneumonia since 1994, five patients died and two had critical illness with prolonged hospitalization and recovery (2–5). All persons with pneumonia were welders or other metalworkers who had worked in Louisiana or Texas (Table). In addition to the seven pneumonia cases, a cutaneous infection with B. cereus group bacteria containing anthrax toxin genes has been reported in a patient with an anthrax eschar in Florida.† |
Improving reporting standards for polygenic scores in risk prediction studies.
Wand H , Lambert SA , Tamburro C , Iacocca MA , O'Sullivan JW , Sillari C , Kullo IJ , Rowley R , Dron JS , Brockman D , Venner E , McCarthy MI , Antoniou AC , Easton DF , Hegele RA , Khera AV , Chatterjee N , Kooperberg C , Edwards K , Vlessis K , Kinnear K , Danesh JN , Parkinson H , Ramos EM , Roberts MC , Ormond KE , Khoury MJ , Janssens Acjw , Goddard KAB , Kraft P , MacArthur JAL , Inouye M , Wojcik GL . Nature 2021 591 (7849) 211-219 Polygenic risk scores (PRSs), which often aggregate results from genome-wide association studies, can bridge the gap between initial discovery efforts and clinical applications for the estimation of disease risk using genetics. However, there is notable heterogeneity in the application and reporting of these risk scores, which hinders the translation of PRSs into clinical care. Here, in a collaboration between the Clinical Genome Resource (ClinGen) Complex Disease Working Group and the Polygenic Score (PGS) Catalog, we present the Polygenic Risk Score Reporting Standards (PRS-RS), in which we update the Genetic Risk Prediction Studies (GRIPS) Statement to reflect the present state of the field. Drawing on the input of experts in epidemiology, statistics, disease-specific applications, implementation and policy, this comprehensive reporting framework defines the minimal information that is needed to interpret and evaluate PRSs, especially with respect to downstream clinical applications. Items span detailed descriptions of study populations, statistical methods for the development and validation of PRSs and considerations for the potential limitations of these scores. In addition, we emphasize the need for data availability and transparency, and we encourage researchers to deposit and share PRSs through the PGS Catalog to facilitate reproducibility and comparative benchmarking. By providing these criteria in a structured format that builds on existing standards and ontologies, the use of this framework in publishing PRSs will facilitate translation into clinical care and progress towards defining best practice. |
Control and prevention of anthrax, Texas, USA, 2019
Sidwa T , Salzer JS , Traxler R , Swaney E , Sims ML , Bradshaw P , O'Sullivan BJ , Parker K , Waldrup KA , Bower WA , Hendricks K . Emerg Infect Dis 2020 26 (12) 2815-2824 The zoonotic disease anthrax is endemic to most continents. It is a disease of herbivores that incidentally infects humans through contact with animals that are ill or have died from anthrax or through contact with Bacillus anthracis-contaminated byproducts. In the United States, human risk is primarily associated with handling carcasses of hoofstock that have died of anthrax; the primary risk for herbivores is ingestion of B. anthracis spores, which can persist in suitable alkaline soils in a corridor from Texas through Montana. The last known naturally occurring human case of cutaneous anthrax associated with livestock exposure in the United States was reported from South Dakota in 2002. Texas experienced an increase of animal cases in 2019 and consequently higher than usual human risk. We describe the animal outbreak that occurred in southwest Texas beginning in June 2019 and an associated human case. Primary prevention in humans is achieved through control of animal anthrax. |
STROBE-metagenomics: a STROBE extension statement to guide the reporting of metagenomics studies.
Bharucha T , Oeser C , Balloux F , Brown JR , Carbo EC , Charlett A , Chiu CY , Claas ECJ , de Goffau MC , de Vries JJC , Eloit M , Hopkins S , Huggett JF , MacCannell D , Morfopoulou S , Nath A , O'Sullivan DM , Reoma LB , Shaw LP , Sidorov I , Simner PJ , Van Tan L , Thomson EC , van Dorp L , Wilson MR , Breuer J , Field N . Lancet Infect Dis 2020 20 (10) e251-e260 ![]() ![]() The term metagenomics refers to the use of sequencing methods to simultaneously identify genomic material from all organisms present in a sample, with the advantage of greater taxonomic resolution than culture or other methods. Applications include pathogen detection and discovery, species characterisation, antimicrobial resistance detection, virulence profiling, and study of the microbiome and microecological factors affecting health. However, metagenomics involves complex and multistep processes and there are important technical and methodological challenges that require careful consideration to support valid inference. We co-ordinated a multidisciplinary, international expert group to establish reporting guidelines that address specimen processing, nucleic acid extraction, sequencing platforms, bioinformatics considerations, quality assurance, limits of detection, power and sample size, confirmatory testing, causality criteria, cost, and ethical issues. The guidance recognises that metagenomics research requires pragmatism and caution in interpretation, and that this field is rapidly evolving. |
Update: Interim guidance for health care providers for managing patients with suspected e-cigarette, or vaping, product use-associated lung injury - United States, November 2019
Jatlaoui TC , Wiltz JL , Kabbani S , Siegel DA , Koppaka R , Montandon M , Adkins SH , Weissman DN , Koumans EH , O'Hegarty M , O'Sullivan MC , Ritchey MD , Chatham-Stephens K , Kiernan EA , Layer M , Reagan-Steiner S , Legha JK , Shealy K , King BA , Jones CM , Baldwin GT , Rose DA , Delaney LJ , Briss P , Evans ME . MMWR Morb Mortal Wkly Rep 2019 68 (46) 1081-1086 CDC, the Food and Drug Administration (FDA), state and local health departments, and public health and clinical stakeholders are investigating a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) (1). CDC has published recommendations for health care providers regarding EVALI (2-4). Recently, researchers from Utah and New York published proposed diagnosis and treatment algorithms for EVALI (5,6). EVALI remains a diagnosis of exclusion because, at present, no specific test or marker exists for its diagnosis, and evaluation should be guided by clinical judgment. Because patients with EVALI can experience symptoms similar to those associated with influenza or other respiratory infections (e.g., fever, cough, headache, myalgias, or fatigue), it might be difficult to differentiate EVALI from influenza or community-acquired pneumonia on initial assessment; EVALI might also co-occur with respiratory infections. This report summarizes recommendations for health care providers managing patients with suspected or known EVALI when respiratory infections such as influenza are more prevalent in the community than they have been in recent months (7). Recommendations include 1) asking patients with respiratory, gastrointestinal, or constitutional symptoms about the use of e-cigarette, or vaping, products; 2) evaluating those suspected to have EVALI with pulse oximetry and obtaining chest imaging, as clinically indicated; 3) considering outpatient management for clinically stable EVALI patients who meet certain criteria; 4) testing patients for influenza, particularly during influenza season, and administering antimicrobials, including antivirals, in accordance with established guidelines; 5) using caution when considering prescribing corticosteroids for outpatients, because this treatment modality has not been well studied among outpatients, and corticosteroids could worsen respiratory infections; 6) recommending evidence-based treatment strategies, including behavioral counseling, to help patients discontinue using e-cigarette, or vaping, products; and 7) emphasizing the importance of annual influenza vaccination for all persons aged >/=6 months, including patients who use e-cigarette, or vaping products. |
Group B streptococcal disease: unmet needs in high-income countries
Schrag SJ . Lancet Infect Dis 2018 19 (1) 8-10 The bacteria group B streptococcus, estimated to cause more than 319 000 infant infections, 90 000 infant deaths, and 57 000 stillbirths annually worldwide,1 emerged as a leading pathogen of newborn babies in the 1960s. Disease in the first week of life (early onset) can be prevented through targeted administration of intrapartum antibiotic prophylaxis. In most low-income countries and many middle-income countries, this strategy is not feasible. By contrast, a majority of high-income countries have implemented intrapartum antibiotic prophylaxis policies.2 Subsequent declines in the burden of early-onset disease have led some stakeholders to consider the prevention mission as accomplished for settings implementing these policies. Currently, there is no prevention strategy for group B streptococcal disease from day 7 to day 89 of life (late onset). In The Lancet Infectious Diseases, Catherine O'Sullivan and colleagues3 remind us that prevention of infant group B streptococcal disease is still an unmet medical need in high-income countries. Adjuncts or alternatives to intrapartum antibiotic prophylaxis such as maternal immunisation will be needed for sustained reductions in the infant disease burden.1 |
Maternal colonization with group B streptococcus and serotype distribution worldwide: Systematic review and meta-analyses
Russell NJ , Seale AC , O'Driscoll M , O'Sullivan C , Bianchi-Jassir F , Gonzalez-Guarin J , Lawn JE , Baker CJ , Bartlett L , Cutland C , Gravett MG , Heath PT , Le Doare K , Madhi SA , Rubens CE , Schrag S , Sobanjo-Ter Meulen A , Vekemans J , Saha SK , Ip M . Clin Infect Dis 2017 65 S100-s111 Background: Maternal rectovaginal colonization with group B Streptococcus (GBS) is the most common pathway for GBS disease in mother, fetus, and newborn. This article, the second in a series estimating the burden of GBS, aims to determine the prevalence and serotype distribution of GBS colonizing pregnant women worldwide. Methods: We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus), organized Chinese language searches, and sought unpublished data from investigator groups. We applied broad inclusion criteria to maximize data inputs, particularly from low- and middle-income contexts, and then applied new meta-analyses to adjust for studies with less-sensitive sampling and laboratory techniques. We undertook meta-analyses to derive pooled estimates of maternal GBS colonization prevalence at national and regional levels. Results: The dataset regarding colonization included 390 articles, 85 countries, and a total of 299924 pregnant women. Our adjusted estimate for maternal GBS colonization worldwide was 18% (95% confidence interval [CI], 17%-19%), with regional variation (11%-35%), and lower prevalence in Southern Asia (12.5% [95% CI, 10%-15%]) and Eastern Asia (11% [95% CI, 10%-12%]). Bacterial serotypes I-V account for 98% of identified colonizing GBS isolates worldwide. Serotype III, associated with invasive disease, accounts for 25% (95% CI, 23%-28%), but is less frequent in some South American and Asian countries. Serotypes VI-IX are more common in Asia. Conclusions: GBS colonizes pregnant women worldwide, but prevalence and serotype distribution vary, even after adjusting for laboratory methods. Lower GBS maternal colonization prevalence, with less serotype III, may help to explain lower GBS disease incidence in regions such as Asia. High prevalence worldwide, and more serotype data, are relevant to prevention efforts. |
Neurodevelopmental impairment in children after group B streptococcal disease worldwide: Systematic review and meta-analyses
Kohli-Lynch M , Russell NJ , Seale AC , Dangor Z , Tann CJ , Baker CJ , Bartlett L , Cutland C , Gravett MG , Heath PT , Ip M , Le Doare K , Madhi SA , Rubens CE , Saha SK , Schrag S , Sobanjo-Ter Meulen A , Vekemans J , O'Sullivan C , Nakwa F , Ben Hamouda H , Soua H , Giorgakoudi K , Ladhani S , Lamagni T , Rattue H , Trotter C , Lawn JE . Clin Infect Dis 2017 65 S190-s199 Background: Survivors of infant group B streptococcal (GBS) disease are at risk of neurodevelopmental impairment (NDI), a burden not previously systematically quantified. This is the 10th of 11 articles estimating the burden of GBS disease. Here we aimed to estimate NDI in survivors of infant GBS disease. Methods: We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data on the risk of NDI after invasive GBS disease in infants <90 days of age. We did meta-analyses to derive pooled estimates of the percentage of infants with NDI following GBS meningitis. Results: We identified 6127 studies, of which 18 met eligibility criteria, all from middle- or high-income contexts. All 18 studies followed up survivors of GBS meningitis; only 5 of these studies also followed up survivors of GBS sepsis and were too few to pool in a meta-analysis. Of meningitis survivors, 32% (95% CI, 25%-38%) had NDI at 18 months of follow-up, including 18% (95% CI, 13%-22%) with moderate to severe NDI. Conclusions: GBS meningitis is an important risk factor for moderate to severe NDI, affecting around 1 in 5 survivors. However, data are limited, and we were unable to estimate NDI after GBS sepsis. Comparability of studies is difficult due to methodological differences including variability in timing of clinical reviews and assessment tools. Follow-up of clinical cases and standardization of methods are essential to fully quantify the total burden of NDI associated with GBS disease, and inform program priorities. |
Risk of early-onset neonatal group B streptococcal disease with maternal colonization worldwide: Systematic review and meta-analyses
Russell NJ , Seale AC , O'Sullivan C , Le Doare K , Heath PT , Lawn JE , Bartlett L , Cutland C , Gravett M , Ip M , Madhi SA , Rubens CE , Saha SK , Schrag S , Sobanjo-Ter Meulen A , Vekemans J , Baker CJ . Clin Infect Dis 2017 65 S152-s159 Background: Early-onset group B streptococcal disease (EOGBS) occurs in neonates (days 0-6) born to pregnant women who are rectovaginally colonized with group B Streptococcus (GBS), but the risk of EOGBS from vertical transmission has not been systematically reviewed. This article, the seventh in a series on the burden of GBS disease, aims to estimate this risk and how it varies with coverage of intrapartum antibiotic prophylaxis (IAP), used to reduce the incidence of EOGBS. Methods: We conducted systematic reviews (Pubmed/Medline, Embase, Latin American and Caribbean Health Sciences Literature (LILACS), World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data from investigator groups on maternal GBS colonization and neonatal outcomes. We included articles with ≥200 GBS colonized pregnant women that reported IAP coverage. We did meta-analyses to determine pooled estimates of risk of EOGBS, and examined the association in risk of EOGBS with IAP coverage. Results: We identified 30 articles including 20328 GBS-colonized pregnant women for inclusion. The risk of EOGBS in settings without an IAP policy was 1.1% (95% confidence interval [CI], .6%-1.5%). As IAP increased, the risk of EOGBS decreased, with a linear association. Based on linear regression, the risk of EOGBS in settings with 80% IAP coverage was predicted to be 0.3% (95% CI, 0-.9). Conclusions: The risk of EOGBS among GBS-colonized pregnant women, from this first systematic review, is consistent with previous estimates from single studies (1%-2%). Increasing IAP coverage was linearly associated with decreased risk of EOGBS disease. |
The TNM classification of malignant tumours-towards common understanding and reasonable expectations
O'Sullivan B , Brierley J , Byrd D , Bosman F , Kehoe S , Kossary C , Pineros M , Van Eycken E , Weir HK , Gospodarowicz M . Lancet Oncol 2017 18 (7) 849-851 Clarity and precision about the anatomical extent of disease in cancer is essential for prognostication, research, and cancer-control activities. Although the addition of predictive markers, molecular and genomic profiling, and imaging data has contributed important advances to the care of cancer patients, it has also complicated the clarity of the purpose and mission of cancer staging. We believe that communication of the core purpose of the Tumour, Node, Metastasis (TNM) classification to different audiences, to address uncertainty about its application and to articulate the future of this system to permit ongoing study of factors that underpin most cancer discoveries, is urgently needed. | The TNM classification provides a synoptic structure for communication about cancer disease extent and has been a cornerstone of cancer care and research for decades. It is an integral part of the cancer language;1,2 however, its purpose, scope, and application warrant clarification to enable maximal benefit for patients and for global cancer control. | The TNM classification has many purposes: in cancer control (specifically surveillance at the population level),3,4 in research activity (clinical trials eligibility and stratification, translational research), and as a framework to guide clinical care and decision making in addition to communicating prognosis.5 The TNM classification therefore attempts to convey a picture of the anatomical extent of disease to multiple user groups in a manner that accommodates their diverse needs. These purposes need to be applied in many jurisdictions, environments, and among different specialties in a consistent manner if the goal of a worldwide language to describe disease extent is to be achieved. As frequently happens with any language, the interpretation of definitions and terms has strayed from the original intention. Moreover, the universal use of the TNM classification has made it a subject of unreasonable expectation. For example, suggestions have been made that TNM needs to serve many additional purposes, such as encompassing all prognostic factors, or becoming a repository to record all attributes encompassed in a synoptic pathology report. Even in this context, the emphasis appears unbalanced with a bias towards the inclusion of tumour biology rather than other important elements such as patient factors (age, performance status, or comorbidity) and treatment variables. |
Online work force analyzes social media to identify consequences of an unplanned school closure - using technology to prepare for the next pandemic
Rainey JJ , Kenney J , Wilburn B , Putman A , Zheteyeva Y , O'Sullivan M . PLoS One 2016 11 (9) e0163207 BACKGROUND: During an influenza pandemic, the United States Centers for Disease Control and Prevention (CDC) may recommend school closures. These closures could have unintended consequences for students and their families. Publicly available social media could be analyzed to identify the consequences of an unplanned school closure. METHODS: As a proxy for an unplanned, pandemic-related school closure, we used the district-wide school closure due to the September 10-18, 2012 teachers' strike in Chicago, Illinois. We captured social media posts about the school closure using the Radian6 social media-monitoring platform. An online workforce from Amazon Mechanical Turk categorized each post into one of two groups. The first group included relevant posts that described the impact of the closure on students and their families. The second group included irrelevant posts that described the political aspects of the strike or topics unrelated to the school closure. All relevant posts were further categorized as expressing a positive, negative, or neutral sentiment. We analyzed patterns of relevant posts and sentiment over time and compared our findings to household surveys conducted after other unplanned school closures. RESULTS: We captured 4,546 social media posts about the district-wide school closure using our search criteria. Of these, 930 (20%) were categorized as relevant by the online workforce. Of the relevant posts, 619 (67%) expressed a negative sentiment, 51 (5%) expressed a positive sentiment, and 260 (28%) were neutral. The number of relevant posts, and especially those with a negative sentiment, peaked on day 1 of the strike. Negative sentiment expressed concerns about childcare, missed school lunches, and the lack of class time for students. This was consistent with findings from previously conducted household surveys. CONCLUSION: Social media are publicly available and can readily provide information on the impact of an unplanned school closure on students and their families. Using social media to assess the impact of an unplanned school closure due to a public health event would be informative. An online workforce can effectively assist with the review process. |
Early breastfeeding problems mediate the negative association between maternal obesity and exclusive breastfeeding at 1 and 2 months postpartum
O'Sullivan EJ , Perrine CG , Rasmussen KM . J Nutr 2015 145 (10) 2369-78 BACKGROUND: Compared with normal-weight women, women with obesity experience poorer breastfeeding outcomes. Successful breastfeeding among women with obesity is important for achieving national breastfeeding goals. OBJECTIVES: The objectives were to determine whether the negative association between obesity and any or exclusive breastfeeding at 1 and 2 mo postpartum is mediated through breastfeeding problems that occur in the first 2 wk postpartum and if this association differs by parity. METHODS: Mothers (1151 normal-weight and 580 obese) in the Infant Feeding Practices Study II provided information on sociodemographic and psychosocial characteristics, body mass index, and breastfeeding outcomes. At 1 mo postpartum, participants reported the breastfeeding problems they experienced in the first 2 wk postpartum from a predefined list of 17 options. We used factor analysis to condense these problems into 4 explanatory variables; continuous factor scores were computed for use in further analyses. We used maximum likelihood logistic regression to assess mediation of the association between obesity and breastfeeding outcomes through early breastfeeding problems. RESULTS: No significant effect of obesity was found on any breastfeeding at 1 or 2 mo. At 1 mo postpartum, for both primiparous and multiparous women, there was a significant direct effect of obesity on exclusive breastfeeding and a significant indirect effect of obesity through early breastfeeding problems related to the explanatory mediating variable "Insufficient Milk" (throughout the remainder of the Abstract, this factor will be denoted by upper case notation). At 2 mo postpartum both the direct effect of obesity and the indirect effect through Insufficient Milk were significant in primiparous women but only the indirect effect remained significant in multiparous women. CONCLUSIONS: Early problems related to Insufficient Milk may partially explain the association between obesity and poor exclusive breastfeeding outcomes. Women who are obese, particularly those reporting breastfeeding problems that grouped in the Insufficient Milk factor in the early postpartum period, may benefit from additional breastfeeding support. |
Health communications and community mobilization during an Ebola response: partnerships with community and faith-based organizations
Santibanez S , Siegel V , O'Sullivan M , Lacson R , Jorstad C . Public Health Rep 2015 130 (2) 128-33 The 2014 Ebola outbreak is the largest Ebola outbreak in history, affecting multiple countries in West Africa.1 Although the risk of a widespread outbreak in the United States is very low, the unfamiliar nature of the disease contributes to uncertainty and mistrust. The Centers for Disease Control and Prevention (CDC) and the Association of State and Territorial Health Officials (ASTHO) are working to educate and prepare communities throughout the United States for the possibility of an Ebola case in their locality. Federal, state, and local authorities; businesses; schools; charitable foundations; and community and faith-based organizations (CFBOs) all have important roles in Ebola preparedness and response. In 2008, CDC and ASTHO developed a 10-step approach for health communications with CFBOs during public health emergencies.2 In this commentary, we describe how a modification of this 10-step approach can be used by state and local health departments to plan for health communications and community mobilization during an Ebola response. |
The role of a state health agency in promoting cancer prevention at the community level: examples from New York State
Dacus HL , O'Sullivan GM , Major A , White DE . Am J Prev Med 2014 46 S81-6 Cancer is a major cause of morbidity and mortality in the U.S. and more work is needed to decrease the number of new cancer cases and the number of cancer cases diagnosed at a late stage. In New York State, about 106,000 people are diagnosed with cancer each year, 37% of which are diagnosed in adults aged 45-64 years and 55% in those aged ≥65 years. State health agencies are in a unique role to support implementation of cancer prevention strategies at the local level that may have a large impact on the burden of cancer by changing the context in which an individual makes health decisions. The New York State Department of Health, with support through the CDC, is implementing an 18-month cancer prevention demonstration project in two counties aimed at increasing access to nutritious foods, promoting exclusive breastfeeding and decreasing barriers to obtainment of cancer screening. The specific activities being used by the two counties are highlighted, and promising results after the first 6 months of the project are described. Lessons learned from these projects will be reported at regular intervals and used to inform development of larger, statewide initiatives aimed at reducing cancer incidence and death in New York State. |
Metabolomics of cerebrospinal fluid from humans treated for rabies
O'Sullivan A , Willoughby RE , Mishchuk D , Alcarraz B , Cabezas-Sanchez C , Condori RE , David D , Encarnacion R , Fatteh N , Fernandez J , Franka R , Hedderwick S , McCaughey C , Ondrush J , Paez-Martinez A , Rupprecht C , Velasco-Villa A , Slupsky CM . J Proteome Res 2013 12 (1) 481-90 ![]() Rabies is a rapidly progressive lyssavirus encephalitis that is statistically 100% fatal. There are no clinically effective antiviral drugs for rabies. An immunologically naive teenager survived rabies in 2004 through improvised supportive care; since then, 5 additional survivors have been associated with use of the so-called Milwaukee Protocol (MP). The MP applies critical care focused on the altered metabolic and physiologic states associated with rabies. The aim of this study was to examine the metabolic profile of cerebrospinal fluid (CSF) from rabies patients during clinical progression of rabies encephalitis in survivors and nonsurvivors and to compare these samples with control CSF samples. Unsupervised clustering algorithms distinguished three stages of rabies disease and identified several metabolites that differentiated rabies survivors from those who subsequently died, in particular, metabolites related to energy metabolism and cell volume control. Moreover, for those patients who survived, the trajectory of their metabolic profile tracked toward the control profile and away from the rabies profile. NMR metabolomics of human rabies CSF provide new insights into the mechanisms of rabies pathogenesis, which may guide future therapy of this disease. |
Impact of smoking during pregnancy on functional coagulation testing
Dizon-Townson D , Miller C , Momirova V , Sibai B , Spong CY , Wendel G , Wenstrom K , Samuels P , Caritis S , Sorokin Y , Miodovnik M , O'Sullivan MJ , Conway D , Wapner RJ , Gabbe SG . Am J Perinatol 2011 29 (3) 225-30 Compounds that are systemically absorbed during the course of cigarette smoking, and their metabolites, affect the coagulation system and cause endothelial dysfunction, dyslipidemia, and platelet activation leading to a prothrombotic state. In addition, smoking increases the activity of fibrinogen, homocysteine, and C-reactive protein. We hypothesize that smoking may affect functional coagulation testing during pregnancy. A secondary analysis of 371 women pregnant with a singleton pregnancy and enrolled in a multicenter, prospective observational study of complications of factor V Leiden mutation subsequently underwent functional coagulation testing for antithrombin III, protein C antigen and activity, and protein S antigen and activity. Smoking was assessed by self-report at time of enrollment (<14 weeks). None of the functional coagulation testing results was altered by maternal smoking during pregnancy. Smoking does not affect the aforementioned functional coagulation testing results during pregnancy. |
Various viral compartments in HIV-1-infected mothers contribute to in utero transmission of HIV-1
Kourtis AP , Amedee AM , Bulterys M , Danner S , Van Dyke R , O'Sullivan MJ , Maupin R , Jamieson DJ . AIDS Res Hum Retroviruses 2011 27 (4) 421-7 ![]() Perinatal HIV transmission occurs in utero or intrapartum. The mechanisms and timing of transmission are not clearly understood. To compare the genetic sequences of the V3 envelope region of infant's plasma HIV to that of the mother's plasma, peripheral blood mononuclear cells (PBMC) and vaginal secretions, and correlate with timing of transmission. All 3 infants had a positive HIV PCR in the first days of life, thus classified as in utero infections. In the first mother-infant pair, two different variants were present in the infant, one correlating with maternal PBMC virus and highly homologous to virus from vaginal secretions and the other identical to sequences in maternal plasma. In the second pair, the infant plasma virus was similar to that of maternal PBMC. In the third pair, the cord blood and infant plasma virus were highly similar to maternal vaginal virus. The presence of more than one HIV variant from the maternal blood and from the vaginal compartment in the cord blood of infants presumably infected in utero could point to more than one episode of transmission or, alternatively, to transmission of PBMC virus. |
Factors associated with declining a rapid human immunodeficiency virus test in labor and delivery
Tan KR , Lampe MA , Danner SP , Kissinger P , Webber MP , Cohen MH , O'Sullivan MJ , Nesheim S , Jamieson DJ . Matern Child Health J 2010 15 (1) 115-21 The Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists recommend routine rapid HIV testing in labor and delivery (L&D) for women with undocumented HIV status using an opt-out approach. Identifying factors associated with declining a rapid HIV test in L&D will be helpful in developing strategies to improve rapid HIV testing uptake. Data from the Mother-Infant Rapid Intervention at Delivery study were analyzed. Women ≥24 weeks gestation, in labor, with undocumented HIV status were offered rapid HIV testing using informed consent. Women who declined rapid HIV testing (decliners) but agreed to be interviewed were compared to women who accepted testing (acceptors). 102 decliners and 478 acceptors met inclusion criteria for analysis. Decliners of rapid HIV testing were more likely to have had prenatal care (PNC), after adjusting for age, Hispanic ethnicity, high-school education and city of enrollment (adjusted OR 2.4, 95% CI 1.06-5.58). Having had PNC was collinear with prior HIV education and previous offer of an HIV test during the current pregnancy, so these factors were not part of the model. During PNC, standard informed consent may involve discussions that negatively affect later uptake of testing in L&D. Therefore an opt-out approach to testing may improve testing rates. Furthermore, decliners may have felt that testing in L&D was redundant because of previous testing during PNC; however, if previous testing occurred, this was undocumented at L&D. Documentation and timely communication of HIV status is critical to provide appropriate HIV prophylaxis. |
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