Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
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CDC's hospital-onset Clostridioides difficile prevention framework in a regional hospital network
Turner NA , Krishnan J , Nelson A , Polage CR , Sinkowitz-Cochran RL , Fike L , Kuhar DT , Kutty PK , Snyder RL , Anderson DJ . JAMA Netw Open 2024 7 (3) e243846 IMPORTANCE: Despite modest reductions in the incidence of hospital-onset Clostridioides difficile infection (HO-CDI), CDI remains a leading cause of health care-associated infection. As no single intervention has proven highly effective on its own, a multifaceted approach to controlling HO-CDI is needed. OBJECTIVE: To assess the effectiveness of the Centers for Disease Control and Prevention's Strategies to Prevent Clostridioides difficile Infection in Acute Care Facilities Framework (hereafter, the Framework) in reducing HO-CDI incidence. DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study was performed within the Duke Infection Control Outreach Network from July 1, 2019, through March 31, 2022. In all, 20 hospitals in the network participated in an implementation study of the Framework recommendations, and 26 hospitals did not participate and served as controls. The Framework has 39 discrete intervention categories organized into 5 focal areas for CDI prevention: (1) isolation and contact precautions, (2) CDI confirmation, (3) environmental cleaning, (4) infrastructure development, and (5) antimicrobial stewardship engagement. EXPOSURES: Monthly teleconferences supporting Framework implementation for the participating hospitals. MAIN OUTCOMES AND MEASURES: Primary outcomes were HO-CDI incidence trends at participating hospitals compared with controls and postintervention HO-CDI incidence at intervention sites compared with rates during the 24 months before the intervention. RESULTS: The study sample included a total of 2184 HO-CDI cases and 7 269 429 patient-days. In the intervention cohort of 20 participating hospitals, there were 1403 HO-CDI cases and 3 513 755 patient-days, with a median (IQR) HO-CDI incidence of 2.8 (2.0-4.3) cases per 10 000 patient-days. The first analysis included an additional 3 755 674 patient-days and 781 HO-CDI cases among the 26 controls, with a median (IQR) HO-CDI incidence of 1.1 (0.7-2.7) case per 10 000 patient-days. The second analysis included an additional 2 538 874 patient-days and 1751 HO-CDI cases, with a median (IQR) HO-CDI incidence of 5.9 (2.7-8.9) cases per 10 000 patient-days, from participating hospitals 24 months before the intervention. In the first analysis, intervention sites had a steeper decline in HO-CDI incidence over time relative to controls (yearly incidence rate ratio [IRR], 0.79 [95% CI, 0.67-0.94]; P = .01), but the decline was not temporally associated with study participation. In the second analysis, HO-CDI incidence was declining in participating hospitals before the intervention, and the rate of decline did not change during the intervention. The degree to which hospitals implemented the Framework was associated with steeper declines in HO-CDI incidence (yearly IRR, 0.95 [95% CI, 0.90-0.99]; P = .03). CONCLUSIONS AND RELEVANCE: In this quality improvement study of a regional hospital network, implementation of the Framework was not temporally associated with declining HO-CDI incidence. Further study of the effectiveness of multimodal prevention measures for controlling HO-CDI is warranted. |
Perceptions of Antimicrobial Stewardship and Antibiotic Use by Healthcare Workers in Latin America
Fabre V , Cosgrove SE , Lessa FC , Patel TS , Patel PK , Quirós RE . Open Forum Infect Dis 2023 10 Background: The burden of antimicrobial resistance (AMR) in Latin America is high. Little is known about healthcare workers’ (HCWs) perceptions of antimicrobial stewardship (AS) and antibiotic use (AU) in the region. Methods: HCWs from 42 hospitals in Panama, Guatemala, Colombia, Ecuador, and Argentina were invited to participate in an electronic, voluntary, anonymous survey regarding perceptions of AS and AU from March-April 2023. All participants were asked 21 questions; prescribers were asked additional questions about antibiotic prescribing. Answers with 5-point Likert scale were categorized into two groups, strongly agree/agree and neutral/disagree/strongly disagree. Results: Of 475 HCWs that completed the survey, 52% were physicians (29% in training), 28% nurses, 13% pharmacists, 3% microbiologists, and 3% “other.” Median years of experience was 12 (interquartile range 6, 20). Although 93% indicated optimizing AU was a priority at their healthcare facility (HCF), only 69% said the importance of AS was communicated at their HCF. Nurses and those in “other” roles were more likely to report lack of familiarity with the term AS than physicians (32% and 27% respectively vs. 21%, P< 0.01).Most (99%) respondents acknowledged that appropriate AU can reduce AMR and that inappropriate AU could harm patients. However, fewer thought antibiotics were overused (30%) or AMR was a problem (52%) in their HCF. Thirty-eight percent of HCWs did not have access to guidelines and 24% did not value recommendations by the AS team (Figure 1). Of prescribers, 99% reported to modify antibiotics based on culture results, 55% do not consult non-physician staff (e.g., pharmacists, nurses) to make antibiotic decisions, 20% do not use local guidelines or do not receive training on how to interpret culture results to make antibiotic decisions (Figure 2). Prescribers felt pressure from colleagues (38%) and patients or their families (63%) to make antibiotic decisions. Conclusion: Although most HCWs perceived improving AU as a priority, they did not perceive AU or AMR to be a problem in their HCF. Opportunities to optimize AU include improved access and adherence to guidelines, access to AMR data, teamwork, and education on AS for HCW. Disclosures: Sara E. Cosgrove, MD, MS, Debiopharm: Advisor/Consultant|Duke Clinical Research Institute: Advisor/Consultant Payal K. Patel, MD MPH, qiagen: Honoraria |
Using regional sero-epidemiology SARS-CoV-2 Anti-S antibodies in the Dominican Republic to inform targeted public health response
Mario Martin B , Cadavid Restrepo A , Mayfield HJ , Then Paulino C , De St Aubin M , Duke W , Jarolim P , Zielinski Gutiérrez E , Skewes Ramm R , Dumas D , Garnier S , Etienne MC , Peña F , Abdalla G , Lopez B , de la Cruz L , Henríquez B , Baldwin M , Sartorius B , Kucharski A , Nilles EJ , Lau CL . Trop Med Infect Dis 2023 8 (11) Incidence of COVID-19 has been associated with sociodemographic factors. We investigated variations in SARS-CoV-2 seroprevalence at sub-national levels in the Dominican Republic and assessed potential factors influencing variation in regional-level seroprevalence. Data were collected in a three-stage cross-sectional national serosurvey from June to October 2021. Seroprevalence of antibodies against the SARS-CoV-2 spike protein (anti-S) was estimated and adjusted for selection probability, age, and sex. Multilevel logistic regression was used to estimate the effect of covariates on seropositivity for anti-S and correlates of 80% protection (PT(80)) against symptomatic infection for the ancestral and Delta strains. A total of 6683 participants from 134 clusters in all 10 regions were enrolled. Anti-S, PT80 for the ancestral and Delta strains odds ratio varied across regions, Enriquillo presented significant higher odds for all outcomes compared with Yuma. Compared to being unvaccinated, receiving ≥2 doses of COVID-19 vaccine was associated with a significantly higher odds of anti-S positivity (OR 85.94, [10.95-674.33]) and PT(80) for the ancestral (OR 4.78, [2.15-10.62]) and Delta strains (OR 3.08, [1.57-9.65]) nationally and also for each region. Our results can help inform regional-level public health response, such as strategies to increase vaccination coverage in areas with low population immunity against currently circulating strains. |
Assessment of school staff knowledge and perceptions of student e-cigarette use and resource needs, and e-cigarettes confiscated at 12 North Carolina high schools-2019
Tanz LJ , Heck C , Herzig CTA , Ranney LM , Herndon S , Martin J , Hast M , McGowan E , Baler G , Shamout M , King BA , Tynan MA , Kansagra SM . NC Med J 2023 84 (6) 49-57 Background E-cigarettes are the most commonly used tobacco product among US youth and are regularly used on school grounds. We assessed school staff’s awareness of students’ e-cigarette use, response by schools, and resources needed to address use, and examined e-cigarettes confiscated by school staff in North Carolina to guide prevention and identify needed resources. methods In May 2019, staff from a random sample of 25 of 451 North Carolina public and charter high schools were invited to complete an online survey and semistructured interview; 12 schools consented to ≥ 1 component (survey, N = 514; interviews, N = 35). Staff knowledge and perceptions of students’ e-cigarette use and school tobacco policies were assessed, including school efforts to address e-cigarette use. E-cigarette products confiscated by nine schools from students during the 2018-2019 school year were collected. limitations Only 12 public high schools participated, and these schools might not be representative of all North Carolina high schools. Quantitative surveys were not collected from all staff at participating schools; however, the response rate was 62% and included different staff positions and both urban and rural schools. Finally, e-cigarette products collected by schools might not be representative of all devices used by students. Results Among surveyed staff, 33% observed students using e-cigarettes on school grounds; 86% believed e-cigarette use somewhat or largely contributes to learning disruptions. Overall, 94% of respondents knew their school’s policy prohibits student e-cigarette use on school grounds, and 57% were not confident their school has resources to help students quit. From 35 interviews, themes included concern that schools’ tobacco-free policies do not deter use and additional resources are needed to address e-cigarette use in schools. Of 336 collected devices, there were different e-cigarette types and most (65%) e-liquid bottles were flavored. conclusion Efforts are warranted to incorporate evidence-based curricula; educate staff, parents, and youth regarding health risks of ecigarette use; and help youth quit e-cigarettes. © 2023 by the North Carolina Institute of Medicine and The Duke Endowment. All rights reserved. |
Emergence and evolution of Plasmodium falciparum histidine-rich protein 2 and 3 deletion mutant parasites in Ethiopia (preprint)
Feleke SM , Reichert EN , Mohammed H , Brhane BG , Mekete K , Mamo H , Petros B , Solomon H , Abate E , Hennelly C , Denton M , Keeler C , Hathaway NJ , Juliano JJ , Bailey JA , Rogier E , Cunningham J , Aydemir O , Parr JB . medRxiv 2021 2021.01.26.21250503 Malaria diagnostic testing in Africa is threatened by Plasmodium falciparum parasites lacking histidine-rich protein 2 (pfhrp2) and 3 (pfhrp3) genes. Among 12,572 subjects enrolled along Ethiopia’s borders with Eritrea, Sudan, and South Sudan and using multiple assays, we estimate HRP2-based rapid diagnostic tests would miss 9.7% (95% CI 8.5-11.1) of falciparum malaria cases due to pfhrp2 deletion. Established and novel genomic tools reveal distinct subtelomeric deletion patterns, well-established pfhrp3 deletions, and recent expansion of pfhrp2 deletion. Current diagnostic strategies need to be urgently reconsidered in Ethiopia, and expanded surveillance is needed throughout the Horn of Africa.Competing Interest StatementJBP reports research support from Gilead Sciences, honoraria from Virology Education for medical education teaching, and non-financial support from Abbott Diagnostics, all outside the scope of the current work. SMF reports research support from AccessBio, outside of the current work.Funding StatementThis work was funded by the Global Fund to Fight AIDS, Tuberculosis, and Malaria through the Ministry of Health-Ethiopia (EPHI5405 to SMF) and the World Health Organization (JAC, JBP). It was also partially supported by MSF Holland, which supported field work in Gambella Region, the Doris Duke Charitable Foundation (JBP), and the US National Institutes of Health (R01AI132547 to JJJ, JAB, OA, and JBP; K24AI134990 to JJJ).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:Ethical approval was obtained from the Ethiopia Public Health Institute (EPHI) Institutional Review Board (IRB; protocol EPHI-IRB-033-2017) and WHO Research Ethics Review Committee (protocol: ERC.0003174 001). Processing of de-identified samples and data at UNC was determined to constitute non-human subjects research by the UNC IRB (study 17-0155). The study was determined to be non-research by the Centers for Disease Control and Prevention Human Subjects office (0900f3eb81bb60b9).All 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.YesGenomic sequencing data will be available through the Sequence Read Archive (BioSample accession numbers pending). De-identified datasets generated during the current study will be available as supplementary files. Code used during data analysis will be made available on GitHub. |
Integrated SARS-CoV-2 serological and virological screening across an acute fever surveillance platform to monitor temporal changes in anti-spike antibody levels and risk of infection during sequential waves of variant transmission - Dominican Republic, March 2021 to August 2022 (preprint)
Nilles EJ , Aubin MDSt , Dumas D , Duke W , Etienne MC , Abdalla G , Jarolim P , Oasan T , Garnier S , Iihoshi N , Lopez B , de la Cruz L , Puello YC , Baldwin M , Roberts KW , Pena F , Durski K , Sanchez IM , Gunter SM , Kneubehl AR , Murray KO , Lino A , Strobel S , Baez AA , Lau CL , Kucharski A , Gutierrez EZ , Skewes-Ramm R , Vasquez M , Paulino CT . medRxiv 2022 26 The global SARS-CoV-2 immune landscape and population protection against emerging variants is largely unknown. We assessed SARS-CoV-2 antibody changes in the Dominican Republic and implications for immunological protection against variants of concern. Between March 2021 and August 2022, 2,300 patients with undifferentiated febrile illnesses were prospectively enrolled. Sera was tested for total anti-spike antibodies and simultaneously collected nasopharyngeal samples for acute SARSCoV-2 infection with RT-PCR. Geometric mean anti-spike titers increased from 6.6 BAU/ml (95% CI 5.1-8.7) to 1,332 BAU/ml (1055-1,682). Multivariable binomial odds ratios for acute SARS-CoV-2 infection were 0.55 (0.40-0.74), 0.38 (0.27-0.55), and 0.27 (0.18-0.40) for the second, third, and fourth versus the first anti-S quartile, with similar findings by viral strain. Integrated serological and virological screening can leverage existing acute fever surveillance platforms to monitor population-level immunological markers and concurrently characterize implications for emergent variant transmission in near real-time. 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. |
SARS-CoV-2 seroprevalence, cumulative infections, and immunity to symptomatic infection - A multistage national household survey and modelling study, Dominican Republic, June-October 2021.
Nilles EJ , Paulino CT , de St Aubin M , Restrepo AC , Mayfield H , Dumas D , Finch E , Garnier S , Etienne MC , Iselin L , Duke W , Jarolim P , Oasan T , Yu J , Wan H , Peña F , Iihoshi N , Abdalla G , Lopez B , Cruz L , Henríquez B , Espinosa-Bode A , Puello YC , Durski K , Baldwin M , Baez AA , Merchant RC , Barouch DH , Skewes-Ramm R , Gutiérrez EZ , Kucharski A , Lau CL . Lancet Reg Health Am 2022 16 100390 BACKGROUND: Population-level SARS-CoV-2 immunological protection is poorly understood but can guide vaccination and non-pharmaceutical intervention priorities. Our objective was to characterise cumulative infections and immunological protection in the Dominican Republic. METHODS: Household members ≥5 years were enrolled in a three-stage national household cluster serosurvey in the Dominican Republic. We measured pan-immunoglobulin antibodies against the SARS-CoV-2 spike (anti-S) and nucleocapsid glycoproteins, and pseudovirus neutralising activity against the ancestral and B.1.617.2 (Delta) strains. Seroprevalence and cumulative prior infections were weighted and adjusted for assay performance and seroreversion. Binary classification machine learning methods and pseudovirus neutralising correlates of protection were used to estimate 50% and 80% protection against symptomatic infection. FINDINGS: Between 30 Jun and 12 Oct 2021 we enrolled 6683 individuals from 3832 households. We estimate that 85.0% (CI 82.1-88.0) of the ≥5 years population had been immunologically exposed and 77.5% (CI 71.3-83) had been previously infected. Protective immunity sufficient to provide at least 50% protection against symptomatic SARS-CoV-2 infection was estimated in 78.1% (CI 74.3-82) and 66.3% (CI 62.8-70) of the population for the ancestral and Delta strains respectively. Younger (5-14 years, OR 0.47 [CI 0.36-0.61]) and older (≥75-years, 0.40 [CI 0.28-0.56]) age, working outdoors (0.53 [0.39-0.73]), smoking (0.66 [0.52-0.84]), urban setting (1.30 [1.14-1.49]), and three vs no vaccine doses (18.41 [10.69-35.04]) were associated with 50% protection against the ancestral strain. INTERPRETATION: Cumulative infections substantially exceeded prior estimates and overall immunological exposure was high. After controlling for confounders, markedly lower immunological protection was observed to the ancestral and Delta strains across certain subgroups, findings that can guide public health interventions and may be generalisable to other settings and viral strains. FUNDING: This study was funded by the US CDC. |
Monitoring temporal changes in SARS-CoV-2 spike antibody levels and variant-specific risk for infection, Dominican Republic, March 2021-August 2022
Nilles EJ , de St Aubin M , Dumas D , Duke W , Etienne MC , Abdalla G , Jarolim P , Oasan T , Garnier S , Iihoshi N , Lopez B , de la Cruz L , Puello YC , Baldwin M , Roberts KW , Peña F , Durski K , Sanchez IM , Gunter SM , Kneubehl AR , Murray KO , Lino A , Strobel S , Baez AA , Lau CL , Kucharski A , Gutiérrez EZ , Skewes-Ramm R , Vasquez M , Paulino CT . Emerg Infect Dis 2023 29 (4) 723-733 To assess changes in SARS-CoV-2 spike binding antibody prevalence in the Dominican Republic and implications for immunologic protection against variants of concern, we prospectively enrolled 2,300 patients with undifferentiated febrile illnesses in a study during March 2021-August 2022. We tested serum samples for spike antibodies and tested nasopharyngeal samples for acute SARS-CoV-2 infection using a reverse transcription PCR nucleic acid amplification test. Geometric mean spike antibody titers increased from 6.6 (95% CI 5.1-8.7) binding antibody units (BAU)/mL during March-June 2021 to 1,332 (95% CI 1,055-1,682) BAU/mL during May-August 2022. Multivariable binomial odds ratios for acute infection were 0.55 (95% CI 0.40-0.74), 0.38 (95% CI 0.27-0.55), and 0.27 (95% CI 0.18-0.40) for the second, third, and fourth versus the first anti-spike quartile; findings were similar by viral strain. Combining serologic and virologic screening might enable monitoring of discrete population immunologic markers and their implications for emergent variant transmission. |
Tracking immune correlates of protection for emerging SARS-CoV-2 variants.
Nilles EJ , Paulino CT , de St Aubin M , Duke W , Jarolim P , Sanchez IM , Murray KO , Lau CL , Gutiérrez EZ , Ramm RS , Vasquez M , Kucharski A . Lancet Infect Dis 2023 23 (2) 153-154 Reliable SARS-CoV-2 correlates of protection (COP) are crucial for predicting individual-level risk of infection, estimating population susceptibility, and assessing future epidemic risks.1 However, COP studies are challenging given that blood samples ideally need to be collected close to the time of exposure, which is hard to predict. Thus, most existing SARS-CoV-2 COP estimates are based on vaccine efficacy trial data,2, 3 which include frequent blood sampling and strict infection monitoring and are therefore well suited for this purpose. Yet these trials were conducted before the circulation of highly immune-evasive variants of concern (VOC), and in populations with little previous exposure to SARS-CoV-2, limiting their current relevance. We previously reported how existing acute fever surveillance platforms could be used to monitor population-level temporal changes in SARS-CoV-2 immune markers, and documented that higher antibody levels were associated with lower risk of SARS-CoV-2 infection.4 Here, we build off that previous work to show that routinely collected fever surveillance data analysed using a prospective test-negative design5 can generate rapid and VOC-specific immune COP for symptomatic infection. |
Using a Birth Defects Surveillance Program to Enhance Existing Surveillance of Stillbirth
Duke W , Alverson CJ , Evans SP , Atkinson M , Ailes EC . J Registry Manag 2022 49 (1) 17-22 OBJECTIVE: Fetal death certificates (FDCs) are the main source of stillbirth surveillance data in the United States, yet previous studies suggest FDCs have incomplete ascertainment. The objectives of this analysis were (1) to evaluate whether the use of an existing birth defects surveillance program (the Metropolitan Atlanta Congenital Defects Program [MACDP]) to conduct surveillance on stillbirths enhances case ascertainment, and (2) to compare stillbirth prevalence estimates in metropolitan Atlanta using data from MACDP and FDCs, independently and combined, from 2009-2015. METHODS: Stillbirths were ascertained by MACDP and FDCs from 2009-2015. Capture-recapture methods were used to estimate the relative contributions of each data source. Prevalence estimates generated from each data source independently and combined were compared. RESULTS: There were 3,031 stillbirths ascertained by FDCs and MACDP in metropolitan Atlanta from 2009-2015. It was assumed that 35% of FDCs unlinked to MACDP were misclassified as stillbirth. Under this assumption, an estimated 2,610 total stillbirths occurred. Accounting for potential misclassification in the FDC, the prevalence rate for stillbirth was 6.9 per 1,000 live births plus stillbirths for stillbirths captured only in FDC, and 6.2 per 1,000 live births plus stillbirths for stillbirths caught only in MACDP. Using both sources combined for casefinding, the prevalence rate was 10.0 per 1,000 live births plus stillbirths for all years combined. CONCLUSIONS: Expanding certain birth defects surveillance programs to conduct surveillance on stillbirths could potentially enhance existing surveillance data on stillbirths when linked to FDCs. |
Exploring the Applicability of Using Natural Language Processing to Support Nationwide Venous Thromboembolism Surveillance: Model Evaluation Study
Wendelboe A , Saber I , Dvorak J , Adamski A , Feland N , Reyes N , Abe K , Ortel T , Raskob G . JMIR Bioinform Biotech 2022 3 (1) BACKGROUND: Venous thromboembolism (VTE) is a preventable, common vascular disease that has been estimated to affect up to 900,000 people per year. It has been associated with risk factors such as recent surgery, cancer, and hospitalization. VTE surveillance for patient management and safety can be improved via natural language processing (NLP). NLP tools have the ability to access electronic medical records, identify patients that meet the VTE case definition, and subsequently enter the relevant information into a database for hospital review. OBJECTIVE: We aimed to evaluate the performance of a VTE identification model of IDEAL-X (Information and Data Extraction Using Adaptive Learning; Emory University)-an NLP tool-in automatically classifying cases of VTE by "reading" unstructured text from diagnostic imaging records collected from 2012 to 2014. METHODS: After accessing imaging records from pilot surveillance systems for VTE from Duke University and the University of Oklahoma Health Sciences Center (OUHSC), we used a VTE identification model of IDEAL-X to classify cases of VTE that had previously been manually classified. Experts reviewed the technicians' comments in each record to determine if a VTE event occurred. The performance measures calculated (with 95% CIs) were accuracy, sensitivity, specificity, and positive and negative predictive values. Chi-square tests of homogeneity were conducted to evaluate differences in performance measures by site, using a significance level of .05. RESULTS: The VTE model of IDEAL-X "read" 1591 records from Duke University and 1487 records from the OUHSC, for a total of 3078 records. The combined performance measures were 93.7% accuracy (95% CI 93.7%-93.8%), 96.3% sensitivity (95% CI 96.2%-96.4%), 92% specificity (95% CI 91.9%-92%), an 89.1% positive predictive value (95% CI 89%-89.2%), and a 97.3% negative predictive value (95% CI 97.3%-97.4%). The sensitivity was higher at Duke University (97.9%, 95% CI 97.8%-98%) than at the OUHSC (93.3%, 95% CI 93.1%-93.4%; P<.001), but the specificity was higher at the OUHSC (95.9%, 95% CI 95.8%-96%) than at Duke University (86.5%, 95% CI 86.4%-86.7%; P<.001). CONCLUSIONS: The VTE model of IDEAL-X accurately classified cases of VTE from the pilot surveillance systems of two separate health systems in Durham, North Carolina, and Oklahoma City, Oklahoma. NLP is a promising tool for the design and implementation of an automated, cost-effective national surveillance system for VTE. Conducting public health surveillance at a national scale is important for measuring disease burden and the impact of prevention measures. We recommend additional studies to identify how integrating IDEAL-X in a medical record system could further automate the surveillance process. |
A modified public health automated case event reporting platform for enhancing electronic laboratory reports with clinical data: Design and implementation study
Mishra N , Duke J , Karki S , Choi M , Riley M , Ilatovskiy AV , Gorges M , Lenert L . J Med Internet Res 2021 23 (8) e26388 BACKGROUND: Public health reporting is the cornerstone of public health practices that inform prevention and control strategies. There is a need to leverage advances made in the past to implement an architecture that facilitates the timely and complete public health reporting of relevant case-related information that has previously not easily been available to the public health community. Electronic laboratory reporting (ELR) is a reliable method for reporting cases to public health authorities but contains very limited data. In an earlier pilot study, we designed the Public Health Automated Case Event Reporting (PACER) platform, which leverages existing ELR infrastructure as the trigger for creating an electronic case report. PACER is a FHIR (Fast Health Interoperability Resources)-based system that queries the electronic health record from where the laboratory test was requested to extract expanded additional information about a case. OBJECTIVE: This study aims to analyze the pilot implementation of a modified PACER system for electronic case reporting and describe how this FHIR-based, open-source, and interoperable system allows health systems to conduct public health reporting while maintaining the appropriate governance of the clinical data. METHODS: ELR to a simulated public health department was used as the trigger for a FHIR-based query. Predetermined queries were translated into Clinical Quality Language logics. Within the PACER environment, these Clinical Quality Language logical statements were managed and evaluated against the providers' FHIR servers. These predetermined logics were filtered, and only data relevant to that episode of the condition were extracted and sent to simulated public health agencies as an electronic case report. Design and testing were conducted at the Georgia Tech Research Institute, and the pilot was deployed at the Medical University of South Carolina. We evaluated this architecture by examining the completeness of additional information in the electronic case report, such as patient demographics, medications, symptoms, and diagnoses. This additional information is crucial for understanding disease epidemiology, but existing electronic case reporting and ELR architectures do not report them. Therefore, we used the completeness of these data fields as the metrics for enriching electronic case reports. RESULTS: During the 8-week study period, we identified 117 positive test results for chlamydia. PACER successfully created an electronic case report for all 117 patients. PACER extracted demographics, medications, symptoms, and diagnoses from 99.1% (116/117), 72.6% (85/117), 70.9% (83/117), and 65% (76/117) of the cases, respectively. CONCLUSIONS: PACER deployed in conjunction with electronic laboratory reports can enhance public health case reporting with additional relevant data. The architecture is modular in design, thereby allowing it to be used for any reportable condition, including evolving outbreaks. PACER allows for the creation of an enhanced and more complete case report that contains relevant case information that helps us to better understand the epidemiology of a disease. |
Myocarditis Occurring After Immunization With mRNA-Based COVID-19 Vaccines.
Shay DK , Shimabukuro TT , DeStefano F . JAMA Cardiol 2021 6 (10) 1115-1117 Two reports in the current issue of JAMA Cardiology describe cases of acute myocarditis that occurred among persons who received the BNT162b2-mRNA (Pfizer-BioNTech) or mRNA-1273 (Moderna) messenger RNA (mRNA)–based COVID-19 vaccines authorized for use in the US.1,2 During the clinical evaluations of these patients, alternative etiologies for myocarditis were not detected. | | The first report describes 4 cases of myocarditis with symptom onset 1 to 5 days after receipt of a second dose of mRNA-based COVID-19 vaccine (2 receiving the BNT162b2-mRNA vaccine and 2 receiving the mRNA-1273 vaccine) who were evaluated in a single tertiary care medical center (Duke University Medical Center) that attempted to define its catchment population.1 Three cases occurred in men aged 23 to 36 years and the fourth in a 70-year-old woman; details about the medical history of the fourth patient were not provided, but she received coronary angiography during her evaluation and no atherosclerosis was found. All presented with severe acute chest pain, had abnormal electrocardiogram results, and had evidence of myocardial injury demonstrated by elevated troponin levels. Cardiac magnetic resonance imaging was performed in these 4 patients on days 3 through 5 after vaccine receipt, and the findings were consistent with acute myocarditis as defined by recent expert consensus guidelines.3 |
Longitudinal investigation of pubertal milestones and hormones as a function of body fat in girls
Ortega MT , McGrath JA , Carlson L , Flores Poccia V , Larson G , Douglas C , Sun BZ , Zhao S , Beery B , Vesper HW , Duke L , Botelho JC , Filie AC , Shaw ND . J Clin Endocrinol Metab 2021 106 (6) 1668-1683 BACKGROUND: Epidemiologic studies demonstrated that overweight/obese girls (OW/OB) undergo thelarche and menarche earlier than normal weight girls (NW). There have been no longitudinal studies to specifically investigate how body weight/fat affects both clinical and biochemical pubertal markers in girls. METHODS: 90 girls (36 OW/OB, 54 NW), aged 8.2-14.7 years, completed 2.8 ± 1.7 study visits over the course of four years. Visits included dual-energy x-ray absorptiometry to calculate total body fat (TBF), Tanner staging, breast ultrasound for morphological staging (BMORPH; A-E), pelvic ultrasound, hormone tests, and assessment of menarchal status. The effect of TBF on pubertal markers was determined using a mixed, multi-state, or Cox proportional hazards model, controlling for baseline BMORPH. RESULTS: NW were older than OW/OB (11.3 vs. 10.2 yrs, p<0.01) at baseline and had more advanced BMORPH (p<0.01). LH, estradiol, and ovarian and uterine volumes increased with time with no effect of TBF. There was a time x TBF interaction for FSH, inhibin B, estrone, total and free testosterone, and androstenedione: levels were initially similar, but after 1 yr, levels increased in girls with higher TBF, plateaued in girls with mid-range TBF, and decreased in girls with lower TBF. Girls with higher TBF progressed through BMORPH stage D more slowly but achieved menarche earlier than girls with lower TBF. CONCLUSIONS: In late puberty, girls with higher TBF demonstrate differences in standard hormonal and clinical markers of puberty. Investigation of the underlying causes and clinical consequences of these differences in girls with higher TBF deserves further study. |
Uptake of online HIV-related continuing medical education training among primary care providers in Southeast United States, 2017-2018
Henny KD , Duke CC , Sutton MY . AIDS Care 2020 33 (12) 1-10 Primary care providers play a vital role for HIV prevention and care in high burden areas of the Southeast United States. Studies reveal that only a third of these providers had previous HIV-related training. We evaluated the effects of targeted online continuing medical education training on HIV-related knowledge, attitudes and practices among providers in the Southeast. During April 2017-February 2018, we administered baseline and six-month follow-up surveys to assess changes attributed to online training among a representative sample of providers from six Southeast locations. Data were analyzed using logistic regression analysis (p < 0.05). Baseline and follow-up surveys were completed by 349 participants (61.2% female, 64.6% white, 69.6% physicians, and 27.5% aged 40 years or less); 18% (n = 63) of whom visited online training websites sent following the baseline survey. Comparing baseline versus follow-up responses, providers who completed online training were half as likely to identify "patients' age" (30% vs. 15%) and "patients' race" (3% vs. 1.4%) as barriers to discussing sex with clients; survey responses by participants who declined training remained unchanged. Based on baseline versus follow-up responses, providers who visited online training websites were more likely to become familiar with preexposure prophylaxis (PrEP) (38% vs. 58%); participants who declined training remained unchanged at 45%. No impact on clinical practices such as PrEP prescriptions was identified. Targeted online training can enhance HIV readiness and should be explored for providers in the Southeast, particularly for enhancing PrEP service delivery. |
Racial and ethnic disparities in fetal deaths - United States, 2015-2017
Pruitt SM , Hoyert DL , Anderson KN , Martin J , Waddell L , Duke C , Honein MA , Reefhuis J . MMWR Morb Mortal Wkly Rep 2020 69 (37) 1277-1282 The spontaneous death or loss of a fetus during pregnancy is termed a fetal death. In the United States, national data on fetal deaths are available for losses at ≥20 weeks' gestation.* Deaths occurring during this period of pregnancy are commonly known as stillbirths. In 2017, approximately 23,000 fetal deaths were reported in the United States (1). Racial/ethnic disparities exist in the fetal mortality rate; however, much of the known disparity in fetal deaths is unexplained (2). CDC analyzed 2015-2017 U.S. fetal death report data and found that non-Hispanic Black (Black) women had more than twice the fetal mortality rate compared with non-Hispanic White (White) women and Hispanic women. Fetal mortality rates also varied by maternal state of residence. Cause of death analyses were conducted for jurisdictions where >50% of reports had a cause of death specified. Still, even in these jurisdictions, approximately 31% of fetal deaths had no cause of death reported on a fetal death report. There were differences by race and Hispanic origin in causes of death, with Black women having three times the rate of fetal deaths because of maternal complications compared with White women. The disparities suggest opportunities for prevention to reduce the U.S. fetal mortality rate. Improved documentation of cause of death on fetal death reports might help identify preventable causes and guide prevention efforts. |
COVID-19 Among American Indian and Alaska Native Persons - 23 States, January 31-July 3, 2020.
Hatcher SM , Agnew-Brune C , Anderson M , Zambrano LD , Rose CE , Jim MA , Baugher A , Liu GS , Patel SV , Evans ME , Pindyck T , Dubray CL , Rainey JJ , Chen J , Sadowski C , Winglee K , Penman-Aguilar A , Dixit A , Claw E , Parshall C , Provost E , Ayala A , Gonzalez G , Ritchey J , Davis J , Warren-Mears V , Joshi S , Weiser T , Echo-Hawk A , Dominguez A , Poel A , Duke C , Ransby I , Apostolou A , McCollum J . MMWR Morb Mortal Wkly Rep 2020 69 (34) 1166-1169 Although non-Hispanic American Indian and Alaska Native (AI/AN) persons account for 0.7% of the U.S. population,* a recent analysis reported that 1.3% of coronavirus disease 2019 (COVID-19) cases reported to CDC with known race and ethnicity were among AI/AN persons (1). To assess the impact of COVID-19 among the AI/AN population, reports of laboratory-confirmed COVID-19 cases during January 22(†)-July 3, 2020 were analyzed. The analysis was limited to 23 states(§) with >70% complete race/ethnicity information and five or more laboratory-confirmed COVID-19 cases among both AI/AN persons (alone or in combination with other races and ethnicities) and non-Hispanic white (white) persons. Among 424,899 COVID-19 cases reported by these states, 340,059 (80%) had complete race/ethnicity information; among these 340,059 cases, 9,072 (2.7%) occurred among AI/AN persons, and 138,960 (40.9%) among white persons. Among 340,059 cases with complete patient race/ethnicity data, the cumulative incidence among AI/AN persons in these 23 states was 594 per 100,000 AI/AN population (95% confidence interval [CI] = 203-1,740), compared with 169 per 100,000 white population (95% CI = 137-209) (rate ratio [RR] = 3.5; 95% CI = 1.2-10.1). AI/AN persons with COVID-19 were younger (median age = 40 years; interquartile range [IQR] = 26-56 years) than were white persons (median age = 51 years; IQR = 32-67 years). More complete case report data and timely, culturally responsive, and evidence-based public health efforts that leverage the strengths of AI/AN communities are needed to decrease COVID-19 transmission and improve patient outcomes. |
Public health reporting and outbreak response: synergies with evolving clinical standards for interoperability
Mishra NK , Duke J , Lenert L , Karki S . J Am Med Inform Assoc 2020 27 (7) 1136-1138 Public health needs up-to-date information for surveillance and response. As healthcare application programming interfaces become widely available, a novel data gathering mechanism could provide public health with critical information in a timely fashion to respond to a fast-moving epidemic. In this article, we extrapolate from our experiences using a Fast Healthcare Interoperability Resource-based architecture for infectious disease surveillance for sexually transmitted diseases to its application to gather case information for an outbreak. One of the challenges with a fast-moving outbreak is to accurately assess its demand on healthcare resources, since information specific to comorbidities is often not available. These comorbidities are often associated with poor prognosis and higher resource utilization. If the comorbidity data and other clinical information were readily available to public health workers, they could better address community disruption and manage healthcare resources. The use of FHIR resources available through application programming and filtered through tools such as described herein will give public health the flexibility needed to investigate rapidly emerging disease while protecting patient privacy. |
Mental health screening practices among primary care providers in high HIV burden areas of the south: Does having patients with HIV matter
Gaines MT , Duke CC , Henny KD . J Behav Health Serv Res 2020 48 (1) 103-111 Mental health (MH) disorders are associated with HIV-related risk and health outcomes. Primary care providers (PCPs) conducting MH screenings can link persons living with HIV (PWH) to appropriate services, particularly in HIV burden areas of Southeastern States (the South). Little data exist on PCPs' MH screening practices. Depression, MH history, and substance use screenings among PCPs were examined in the South. Rao-Scott chi-square (chi(2)[df]) statistics (p </= 0.05) analyzed MH screening between PCPs with and without PWH patients. Compared with PCPs without PWH patients, PCPs with PWH patients routinely screened for substance use more frequently (50.6% vs. 43.2%; chi(2)[1] = 20.3; p < 0.0001). Compared with PCPs without PWH patients, PCPs with PWH patients routinely screened for depression less frequently (36.2% vs. 50.9%; chi(2)[1] = 32.0; p < 0.0001). Providers increasing MH screenings will improve HIV-related outcomes in the South. |
Risk of stillbirth for fetuses with specific birth defects
Heinke D , Nestoridi E , Hernandez-Diaz S , Williams PL , Rich-Edwards JW , Lin AE , Van Bennekom CM , Mitchell AA , Nembhard WN , Fretts RC , Roberts DJ , Duke CW , Carmichael SL , Yazdy MM . Obstet Gynecol 2019 135 (1) 133-140 OBJECTIVE: To estimate the risk of stillbirth (fetal death at 20 weeks of gestation or more) associated with specific birth defects. METHODS: We identified a population-based retrospective cohort of neonates and fetuses with selected major birth defects and without known or strongly suspected chromosomal or single-gene disorders from active birth defects surveillance programs in nine states. Abstracted medical records were reviewed by clinical geneticists to confirm and classify all birth defects and birth defect patterns. We estimated risks of stillbirth specific to birth defects among pregnancies overall and among those with isolated birth defects; potential bias owing to elective termination was quantified. RESULTS: Of 19,170 eligible neonates and fetuses with birth defects, 17,224 were liveborn, 852 stillborn, and 672 electively terminated. Overall, stillbirth risks ranged from 11 per 1,000 fetuses with bladder exstrophy (95% CI 0-57) to 490 per 1,000 fetuses with limb-body-wall complex (95% CI 368-623). Among those with isolated birth defects not affecting major vital organs, elevated risks (per 1,000 fetuses) were observed for cleft lip with cleft palate (10; 95% CI 7-15), transverse limb deficiencies (26; 95% CI 16-39), longitudinal limb deficiencies (11; 95% CI 3-28), and limb defects due to amniotic bands (110; 95% CI 68-171). Quantified bias analysis suggests that failure to account for terminations may lead to up to fourfold underestimation of the observed risks of stillbirth for sacral agenesis (13/1,000; 95% CI 2-47), isolated spina bifida (24/1,000; 95% CI 17-34), and holoprosencephaly (30/1,000; 95% CI 10-68). CONCLUSION: Birth defect-specific stillbirth risk was high compared with the U.S. stillbirth risk (6/1,000 fetuses), even for isolated cases of oral clefts and limb defects; elective termination may appreciably bias some estimates. These data can inform clinical care and counseling after prenatal diagnosis. |
HIV prescriptions on the frontlines: Primary care providers' use of antiretrovirals for prevention in the Southeast United States, 2017
Henny KD , Duke CC , Buchacz K , Brooks JT , Samandari T , Sutton MY . Prev Med 2019 130 105875 HIV disproportionately affects persons in Southeast United States. Primary care providers (PCPs) are vital for HIV prevention. Data are limited about their prescribing of antiretrovirals (ARVs) for prevention, including non-occupational post-exposure prophylaxis (nPEP), pre-exposure prophylaxis (PrEP), and antiretroviral therapy (ART). We examined these practices to assess gaps. During April-August 2017, we conducted an online survey of PCPs in Atlanta, Baltimore, Baton Rouge, Miami, New Orleans, and Washington, DC to assess HIV-related knowledge, attitudes and practices. Adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) were used to estimate correlates of nPEP, PrEP and ART prescribing practices. Adjusting for MSA and specialty, the weighted sample (n=820, 29.6% adjusted response rate) comprised 60.2% white and 59.4% females. PCPs reported ever prescribing nPEP (31.0%), PrEP (18.1%), and ART (27.2%). Prescribing nPEP was associated with nPEP familiarity (aPR=2.63, 95% CI 1.59, 4.35) and prescribing PrEP (aPR=3.57, 95% CI 2.78, 4.55). Prescribing PrEP was associated with PrEP familiarity (aPR=4.35, 95% CI 2.63, 7.14), prescribing nPEP (aPR=5.00, 95% CI 2.00, 12.50), and providing care for persons with HIV (aPR=1.56, 95% CI 1.06, 2.27). Prescribing ART was associated with nPEP familiarity (aPR=1.89, 95% CI 1.27, 2.78) and practicing in outpatient public practice versus hospital-based facilities (aPR=2.14 95% CI 1.51, 3.04), and inversely associated with collaborations involving specialists (aPR=0.60, 95% CI 0.42, 0.86). A minority of PCPs surveyed from the Southeast report ever prescribing ARVs for prevention. Future efforts should include enhancing HIV care coordination and developing strategies to increase use of biomedical tools. |
Early breast development in overweight girls: does estrogen made by adipose tissue play a role
Carlson L , Flores Poccia V , Sun BZ , Mosley B , Kirste I , Rice A , Sridhar R , Kangarloo T , Vesper HW , Duke L , Botelho JC , Filie AC , Adams JM , Shaw ND . Int J Obes (Lond) 2019 43 (10) 1978-1987 BACKGROUND: Girls who are overweight/obese (OB) develop breast tissue but do not undergo menarche (the first menstrual period) significantly earlier than girls of normal weight (NW). It has been proposed that estrogen synthesized by adipose tissue may be contributory, yet OB do not have higher serum estrogen levels than NW matched on breast stage. We hypothesized that estrogen synthesized locally, in mammary fat, may contribute to breast development. This hypothesis would predict that breast development would be more advanced than other estrogen-sensitive tissues as a function of obesity and body fat. METHODS: Eighty premenarchal girls (26 OB, 54 NW), aged 8.2-14.7 years, underwent dual-energy x-ray absorptiometry to calculate percent body fat (%BF), Tanner staging of the breast, breast ultrasound for morphological staging, trans-abdominal pelvic ultrasound, hand x-ray (bone age, BA), a blood test for reproductive hormones, and urine collection to determine the vaginal maturation index (VMI), an index of estrogen exposure in urogenital epithelial cells. RESULTS: When controlling for breast morphological stage determined by ultrasound, %BF was not associated with serum estrogen or gonadotropin (LH and FSH) levels or with indices of systemic estrogen action (uterine volume, endometrial thickness, BA advancement, and VMI). Tanner breast stage did not correlate with breast morphological stage and led to misclassification of chest fatty tissue as breast tissue in some OB. CONCLUSIONS: These studies do not support the hypothesis that estrogen derived from total body fat or local (mammary) fat contributes to breast development in OB girls. |
Design and implementation of a comprehensive surveillance system for venous thromboembolism in a defined region using electronic and manual approaches
Ortel TL , Arnold K , Beckman M , Brown A , Reyes N , Saber I , Schulteis R , Singh BP , Sitlinger A , Thames EH . Appl Clin Inform 2019 10 (3) 552-562 BACKGROUND: Systematic surveillance for venous thromboembolism (VTE) in the United States has been recommended by several organizations. Despite adoption of electronic medical records (EMRs) by most health care providers and facilities, however, systematic surveillance for VTE is not available. OBJECTIVES: This article develops a comprehensive, population-based surveillance strategy for VTE in a defined geographical region. METHODS: The primary surveillance strategy combined computerized searches of the EMR with a manual review of imaging data at the Duke University Health System in Durham County, North Carolina, United States. Different strategies of searching the EMR were explored. Consolidation of results with autopsy reports (nonsearchable in the EMR) and with results from the Durham Veterans' Administration Medical Center was performed to provide a comprehensive report of new VTE from the defined region over a 2-year timeframe. RESULTS: Monthly searches of the primary EMR missed a significant number of patients with new VTE who were identified by a separate manual search of radiology records, apparently related to delays in data entry and coding into the EMR. Comprehensive searches incorporating a location-restricted strategy were incomplete due to the assigned residence reflecting the current address and not the address at the time of event. The most comprehensive strategy omitted the geographic restriction step and identified all patients with VTE followed by manual review of individual records to remove incorrect entries (e.g., outside the surveillance time period or geographic location; no evidence for VTE). Consolidation of results from the EMR searches with results from autopsy reports and the separate facility identified additional patients not diagnosed within the Duke system. CONCLUSION: We identified several challenges with implementing a comprehensive VTE surveillance program that could limit accuracy of the results. Improved electronic strategies are needed to cross-reference patients across multiple health systems and to minimize the need for manual review and confirmation of results. |
HIV-related training and correlates of knowledge, HIV screening and prescribing of nPEP and PrEP among primary care providers in southeast United States, 2017
Henny KD , Duke CC , Geter A , Gaul Z , Frazier C , Peterson J , Buchacz K , Sutton MY . AIDS Behav 2019 23 (11) 2926-2935 The Southeast accounted for most HIV diagnoses (52%) in the United States in 2015. Primary care providers (PCPs) play a vital role in HIV prevention for at-risk persons and treatment of persons living with HIV. We studied HIV-related training, knowledge, and clinical practices among PCPs in the Southeast to address knowledge gaps to inform HIV prevention strategies. Between April and August 2017, we conducted an on-line survey of a representative sample of PCPs in six Southeast jurisdictions with high rates of HIV diagnoses (Atlanta; Baltimore; Baton Rouge; District of Columbia; Miami; New Orleans). We defined HIV-related training as self-reported completion of any certified HIV/STD course or continuing education in past 24 months (prior to survey completion). We assessed associations between training and HIV testing practices, familiarity with nonoccupational post-exposure prophylaxis (nPEP) and pre-exposure prophylaxis (PrEP), and ever prescribing nPEP or PrEP. There were 820 participants after fielding 4595 surveys (29.6% adjusted response rate). In weighted analyses, 36.3% reported HIV-related training. Using adjusted prevalence ratio (aPR) and confidence intervals (CI), we found that PCPs with HIV-related training (compared to those with no training) were more likely to be familiar with nPEP (aPR = 1.32, 95% CI 1.05, 1.67) and PrEP (aPR = 1.67, 95% CI 1.19, 2.38); and to have ever prescribed PrEP to patients (aPR = 1.75, 95% CI 1.10, 2.78). Increased HIV-related trainings among PCPs in high HIV prevalence Southeast jurisdictions may be warranted. Strengthening nPEP and PrEP familiarity among PCPs in Southeast may advance national HIV prevention goals. |
Persistence of endothelial thrombomodulin in a patient with infectious purpura fulminans treated with protein C concentrate
Bendapudi PK , Robbins A , LeBoeuf N , Pozdnyakova O , Bhatt A , Duke F , Sells R , McQuiston J , Humrighouse B , Rouaisnel B , Colling M , Stephenson KE , Saavedra A , Losman JA . Blood Adv 2018 2 (21) 2917-2921 Purpura fulminans (PF) is a rare life-threatening complication of bacterial sepsis that is characterized by a highly thrombotic subtype of disseminated intravascular coagulation (DIC) and mortality of up to 80%.1 Patients with PF develop a severe deficiency in protein C (PC), a serine protease that is a key endogenous anticoagulant.2 PC is activated at the endothelial surface by thrombin in the presence of the cofactor thrombomodulin (TM). Activated PC (APC) is cytoprotective3 and inhibits thrombin generation by cleaving coagulation factors Va and VIIIa.4 Therefore, TM is a crucial regulatory “switch” governing negative feedback of coagulation. The initiating event in PF is hypothesized to be loss of TM from the endothelial surface in response to infection.5 As a result, conversion of PC to APC is impaired, and coagulation proceeds unchecked.3 Although therapy with PC concentrate has been proposed as a strategy to target the underlying pathophysiologic lesion in PF,6 the belief that endothelial TM loss is an early event in PF that renders infused PC ineffective has limited its widespread adoption.2,5 We report herein data on the kinetics of TM loss in a patient with PF that support the use of supplemental PC in upfront treatment of severe cases. |
Role of p53 in the chronic pulmonary immune response to tangled or rod-like multi-walled carbon nanotubes
Duke KS , Thompson EA , Ihrie MD , Taylor-Just AJ , Ash EA , Shipkowski KA , Hall JR , Tokarz DA , Cesta MF , Hubbs AF , Porter DW , Sargent LM , Bonner JC . Nanotoxicology 2018 12 (9) 1-17 The fiber-like shape of multi-walled carbon nanotubes (MWCNTs) is reminiscent of asbestos, suggesting they pose similar health hazards when inhaled, including pulmonary fibrosis and mesothelioma. Mice deficient in the tumor suppressor p53 are susceptible to carcinogenesis. However, the chronic pathologic effect of MWCNTs delivered to the lungs of p53 heterozygous (p53(+/-)) mice has not been investigated. We hypothesized that p53(+/-) mice would be susceptible to lung tumor development after exposure to either tangled (t-) or rod-like (r-) MWCNTs. Wild-type (p53(+/+)) or p53(+/-) mice were exposed to MWCNTs (1 mg/kg) via oropharyngeal aspiration weekly over four consecutive weeks and evaluated for cellular and pathologic outcomes 11-months post-initial exposure. No lung or pleural tumors were observed in p53(+/+) or p53(+/-) mice exposed to either t- or rMWCNTs. In comparison to tMWCNTs, the rMWCNTs induced the formation of larger granulomas, a greater number of lymphoid aggregates and greater epithelial cell hyperplasia in terminal bronchioles in both p53(+/-) and p53(+/+) mice. A constitutively larger area of CD45R(+)/CD3(+) lymphoid tissue was observed in p53(+/-) mice compared to p53(+/+) mice. Importantly, p53(+/-) mice had larger granulomas induced by rMWCNTs as compared to p53(+/+) mice. These findings indicate that a combination of p53 deficiency and physicochemical characteristics including nanotube geometry are factors in susceptibility to MWCNT-induced lymphoid infiltration and granuloma formation. |
Characterization of 108 Genomic DNA Reference Materials for 11 Human Leukocyte Antigen (HLA) Loci: A GeT-RM Collaborative Project.
Bettinotti MP , Ferriola D , Duke JL , Mosbruger TL , Tairis N , Jennings L , Kalman LV , Monos D . J Mol Diagn 2018 20 (5) 703-715 The highly polymorphic human leukocyte antigen (HLA) genes, located in the human major histocompatibility complex, encode the class I and II antigen-presenting molecules which are centrally involved in the immune response. HLA typing is used for several clinical applications such as transplantation, pharmacogenetics, and diagnosis of autoimmune disease. HLA typing is highly complex due to the homology of HLA genes and pseudogenes and the extensive polymorphism in the population. The Centers for Disease Control and Prevention (CDC) established the Genetic Testing Reference Materials Coordination Program (GeT-RM) in partnership with the genetics community to improve the availability of genomic DNA reference materials necessary to assure the quality of genetic laboratory testing. The GeT-RM together with three clinical laboratories and the Coriell Cell Repositories have characterized genomic DNA obtained from a panel of 108 cell lines for all HLA classical polymorphic loci: HLA-A, B, C, DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, DPA1, and DPB1. The goal was to develop a publicly available and renewable source of well-characterized genomic DNA reference materials to support molecular HLA typing assay development, validation, and verification, quality control, and proficiency testing. These genomic DNA samples are publicly available from the National Institutes of General Medical Science (NIGMS) Repository at the Coriell Cell Repositories. |
Impact of the Tips From Former Smokers Campaign on population-level smoking cessation, 2012-2015
Murphy-Hoefer R , Davis KC , Beistle D , King BA , Duke J , Rodes R , Graffunder C . Prev Chronic Dis 2018 15 E71 This study provides estimates of the long-term cumulative impact of the Centers for Disease Control and Prevention's national tobacco education campaign, Tips From Former Smokers (Tips), on population-level smoking cessation. We used recently published estimates of the association between increased Tips campaign media doses and quit attempts to calculate campaign-attributable population sustained (6-month) quits during 2012-2015. Tips led to approximately 522,000 sustained quits during 2012-2015. These findings indicate that the Tips campaign's comprehensive approach to combining evidence-based messages with the promotion of cessation resources was successful in achieving substantial long-term cigarette cessation at the population level over multiple years. |
"ALS reversals": demographics, disease characteristics, treatments, and co-morbidities
Harrison D , Mehta P , van Es MA , Stommel E , Drory VE , Nefussy B , van den Berg LH , Crayle J , Bedlack R . Amyotroph Lateral Scler Frontotemporal Degener 2018 19 1-5 OBJECTIVE: To identify differences in demographics, disease characteristics, treatments, and co-morbidities between patients with "amyotrophic lateral sclerosis (ALS) reversals" and those with typically progressive ALS. METHODS: Cases of possible ALS reversals were found in prior publications, in the Duke ALS clinic, through self-referral or referral from other Neurologists, and on the internet. Of 89 possible reversals identified, 36 cases were included because chart or literature review confirmed their diagnosis and a robust, sustained improvement in at least one objective measure. Controls were participants in the Pooled Resource Open-Access ALS Clinical Trials database and the National ALS Registry. Cases and controls were compared using descriptive statistics. RESULTS: ALS reversals were more likely to be male, have limb onset disease, and initially progress faster. The prevalences of myasthenia gravis (MG) and purely lower motor neuron disease in cases were higher than estimates of these prevalences in the general population. The odds of taking curcumin, luteolin, cannabidiol, azathioprine, copper, glutathione, vitamin D, and fish oil were greater for cases than controls. CONCLUSIONS: When compared to patients with typically progressive ALS, patients with reversals differed in their demographics, disease characteristics, and treatments. While some of these patients may have had a rare antibody-mediated ALS mimicker, such as atypical myasthenia gravis, details of their exams, EMGs and family histories argue that this was unlikely. Instead, our data suggest that ALS reversals warrant evaluation for mechanisms of disease resistance and that treatments associated with multiple ALS reversals deserve further study. |
Outbreak of foodborne botulism in an immigrant community: Overcoming delayed disease recognition, ambiguous epidemiologic links, and cultural barriers to identify the cause
Harvey RR , Cooper R , Bennett S , Richardson M , Duke D , Stoughton C , Smalligan R , Gaul L , Drenzek C , Griffin PM , Geissler A , Rao AK . Clin Infect Dis 2017 66 S82-s84 We describe a botulism outbreak involving 4 Middle Eastern men complicated by delayed diagnosis, ambiguous epidemiologic links among patients, and illness onset dates inconsistent with a point-source exposure. Homemade turshi, a fermented vegetable dish, was the likely cause. Patients ate turshi at 2 locations on different days over 1 month. |
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