Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-30 (of 75 Records) |
Query Trace: Keller M[original query] |
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Consensus guidelines for the monitoring and management of metachromatic leukodystrophy in the United States
Adang LA , Bonkowsky JL , Boelens JJ , Mallack E , Ahrens-Nicklas R , Bernat JA , Bley A , Burton B , Darling A , Eichler F , Eklund E , Emrick L , Escolar M , Fatemi A , Fraser JL , Gaviglio A , Keller S , Patterson MC , Orchard P , Orthmann-Murphy J , Santoro JD , Schöls L , Sevin C , Srivastava IN , Rajan D , Rubin JP , Van Haren K , Wasserstein M , Zerem A , Fumagalli F , Laugwitz L , Vanderver A . Cytotherapy 2024 Metachromatic leukodystrophy (MLD) is a fatal, progressive neurodegenerative disorder caused by biallelic pathogenic mutations in the ARSA (Arylsulfatase A) gene. With the advent of presymptomatic diagnosis and the availability of therapies with a narrow window for intervention, it is critical to define a standardized approach to diagnosis, presymptomatic monitoring, and clinical care. To meet the needs of the MLD community, a panel of MLD experts was established to develop disease-specific guidelines based on healthcare resources in the United States. This group developed a consensus opinion for best-practice recommendations, as follows: (i) Diagnosis should include both genetic and biochemical testing; (ii) Early diagnosis and treatment for MLD is associated with improved clinical outcomes; (iii) The panel supported the development of newborn screening to accelerate the time to diagnosis and treatment; (iv) Clinical management of MLD should include specialists familiar with the disease who are able to follow patients longitudinally; (v) In early onset MLD, including late infantile and early juvenile subtypes, ex vivo gene therapy should be considered for presymptomatic patients where available; (vi) In late-onset MLD, including late juvenile and adult subtypes, hematopoietic cell transplant (HCT) should be considered for patients with no or minimal disease involvement. This document summarizes current guidance on the presymptomatic monitoring of children affected by MLD as well as the clinical management of symptomatic patients. Future data-driven evidence and evolution of these recommendations will be important to stratify clinical treatment options and improve clinical care. |
In-field detection and characterization of B/Victoria lineage deletion variant viruses causing early influenza activity and an outbreak in Louisiana, 2019
Shu B , Wilson MM , Keller MW , Tran H , Sokol T , Lee G , Rambo-Martin BL , Kirby MK , Hassell N , Haydel D , Hand J , Wentworth DE , Barnes JR . Influenza Other Respir Viruses 2024 18 (1) e13246 BACKGROUND: In 2019, the Louisiana Department of Health reported an early influenza B/Victoria (B/VIC) virus outbreak. METHOD: As it was an atypically large outbreak, we deployed to Louisiana to investigate it using genomics and a triplex real-time RT-PCR assay to detect three antigenically distinct B/VIC lineage variant viruses. RESULTS: The investigation indicated that B/VIC V1A.3 subclade, containing a three amino acid deletion in the hemagglutinin and known to be antigenically distinct to the B/Colorado/06/2017 vaccine virus, was the most prevalent circulating virus within the specimens evaluated (86/88 in real-time RT-PCR). CONCLUSION: This work underscores the value of portable platforms for rapid, onsite pathogen characterization. |
Public health data applications using the CDC Tracking Network: Augmenting environmental hazard information with lower-latency NASA data
Amos HM , Skaff NK , Uz SS , Policelli FS , Slayback D , Macorps E , Jo MJ , Patel K , Keller CA , Abue P , Buchard V , Werner AK . Geohealth 2023 7 (12) e2023GH000971 Exposure to environmental hazards is an important determinant of health, and the frequency and severity of exposures is expected to be impacted by climate change. Through a partnership with the U.S. National Aeronautics and Space Administration, the U.S. Centers for Disease Control and Prevention's National Environmental Public Health Tracking Network is integrating timely observations and model data of priority environmental hazards into its publicly accessible Data Explorer (https://ephtracking.cdc.gov/DataExplorer/). Newly integrated data sets over the contiguous U.S. (CONUS) include: daily 5-day forecasts of air quality based on the Goddard Earth Observing System Composition Forecast, daily historical (1980-present) concentrations of speciated PM(2.5) based on the modern era retrospective analysis for research and applications, version 2, and Moderate Resolution Imaging Spectroradiometer (MODIS) daily near real-time maps of flooding (MCDWD). Data integrated into the CDC Tracking Network are broadly intended to improve community health through action by informing both research and early warning activities, including (a) describing temporal and spatial trends in disease and potential environmental exposures, (b) identifying populations most affected, (c) generating hypotheses about associations between health and environmental exposures, and (d) developing, guiding, and assessing environmental public health policies and interventions aimed at reducing or eliminating health outcomes associated with environmental factors. |
Targeted amplification and genetic sequencing of the severe acute respiratory syndrome coronavirus 2 surface glycoprotein
Keller MW , Keong LM , Rambo-Martin BL , Hassell N , Lacek KA , Wilson MM , Kirby MK , Liddell J , Owuor DC , Sheth M , Madden J , Lee JS , Kondor RJ , Wentworth DE , Barnes JR . Microbiol Spectr 2023 e0298223 The COVID-19 pandemic was accompanied by an unprecedented surveillance effort. The resulting data were and will continue to be critical for surveillance and control of SARS-CoV-2. However, some genomic surveillance methods experienced challenges as the virus evolved, resulting in incomplete and poor quality data. Complete and quality coverage, especially of the S-gene, is important for supporting the selection of vaccine candidates. As such, we developed a robust method to target the S-gene for amplification and sequencing. By focusing on the S-gene and imposing strict coverage and quality metrics, we hope to increase the quality of surveillance data for this continually evolving gene. Our technique is currently being deployed globally to partner laboratories, and public health representatives from 79 countries have received hands-on training and support. Expanding access to quality surveillance methods will undoubtedly lead to earlier detection of novel variants and better inform vaccine strain selection. |
Author Correction: Multiplexed CRISPR-based microfluidic platform for clinical testing of respiratory viruses and identification of SARS-CoV-2 variants
Welch NL , Zhu M , Hua C , Weller J , Mirhashemi ME , Nguyen TG , Mantena S , Bauer MR , Shaw BM , Ackerman CM , Thakku SG , Tse MW , Kehe J , Uwera MM , Eversley JS , Bielwaski DA , McGrath G , Braidt J , Johnson J , Cerrato F , Moreno GK , Krasilnikova LA , Petros BA , Gionet GL , King E , Huard RC , Jalbert SK , Cleary ML , Fitzgerald NA , Gabriel SB , Gallagher GR , Smole SC , Madoff LC , Brown CM , Keller MW , Wilson MM , Kirby MK , Barnes JR , Park DJ , Siddle KJ , Happi CT , Hung DT , Springer M , MacInnis BL , Lemieux JE , Rosenberg E , Branda JA , Blainey PC , Sabeti PC , Myhrvold C . Nat Med 2023 In the version of the article originally published, some of the oligonucleotide sequences in Supplementary Table 4, on the “21 viruses” and “RVP” tabs, were mislabeled. The Supplementary Tables file has now been corrected. |
Notes from the field: Severe bartonella quintana infections among persons experiencing unsheltered homelessness - New York City, January 2020-December 2022
Rich SN , Beeson A , Seifu L , Mitchell K , Wroblewski D , Juretschko S , Keller M , Gnanaprakasam R , Agladze M , Kodama R , Kupferman T , Bhatnagar J , Martines RB , Reagan-Steiner S , Slavinski S , Kuehnert MJ , Bergeron-Parent C , Corvese G , Marx GE , Ackelsberg J . MMWR Morb Mortal Wkly Rep 2023 72 (42) 1147-1148 Bartonella quintana infection is a vectorborne disease transmitted by the human body louse (1). In the United States, homelessness is the principal risk factor for B. quintana infection (2), likely attributable to limited access to hygiene facilities (1). This infection is not nationally notifiable in the United States, and its incidence is unknown. Acute B. quintana infection can cause fever, headache, and bone pain; severe manifestations include chronic bacteremia, bacillary angiomatosis, and infective endocarditis (3). Because the bacterium requires special conditions to grow in culture, standard blood cultures are usually negative (4). Diagnosis by serology is most common; however, cross-reactivity with other Bartonella species (e.g., B. henselae) can hamper interpretation. Molecular assays specific for B. quintana have been developed (5), but availability is limited to a few laboratories. Once diagnosed, infection can be cured by several weeks to months of antibiotic therapy. |
Recommendations for setting a criterion and assessing commutability of sample materials used in external quality assessment/proficiency testing schemes
Sandberg S , Fauskanger P , Johansen JV , Keller T , Budd J , Greenberg N , Rej R , Panteghini M , Delatour V , Ceriotti F , Deprez L , Camara JE , MacKenzie F , Lyle AN , van der Hagen E , Burns C , Greg Miller W . Clin Chem 2023 69 (11) 1227-1237 It is important for external quality assessment materials (EQAMs) to be commutable with clinical samples; i.e., they should behave like clinical samples when measured using end-user clinical laboratory in vitro diagnostic medical devices (IVD-MDs). Using commutable EQAMs makes it possible to evaluate metrological traceability and/or equivalence of results between IVD-MDs. The criterion for assessing commutability of an EQAM between 2 IVD-MDs is that its result should be within the prediction interval limits based on the statistical distribution of the clinical sample results from the 2 IVD-MDs being compared. The width of the prediction interval is, among other things, dependent on the analytical performance characteristics of the IVD-MDs. A presupposition for using this criterion is that the differences in nonselectivity between the 2 IVD-MDs being compared are acceptable. An acceptable difference in nonselectivity should be small relative to the analytical performance specifications used in the external quality assessment scheme. The acceptable difference in nonselectivity is used to modify the prediction interval criterion for commutability assessment. The present report provides recommendations on how to establish a criterion for acceptable commutability for EQAMS, establish the difference in nonselectivity that can be accepted between IVD-MDs, and perform a commutability assessment. The report also contains examples for performing a commutability assessment of EQAMs. |
Recommendations for setting a criterion for assessing commutability of secondary calibrator certified reference materials
Miller WG , Keller T , Budd J , Johansen JV , Panteghini M , Greenberg N , Delatour V , Ceriotti F , Deprez L , Rej R , Camara JE , MacKenzie F , Lyle AN , van der Hagen E , Burns C , Fauskanger P , Sandberg S . Clin Chem 2023 69 (9) 966-975 A secondary higher-order calibrator is required to be commutable with clinical samples to be suitable for use in the calibration hierarchy of an end-user clinical laboratory in vitro diagnostic medical device (IVD-MD). Commutability is a property of a reference material that means results for a reference material and for clinical samples have the same numeric relationship, within specified limits, across the measurement procedures for which the reference material is intended to be used. Procedures for assessing commutability have been described in the literature. This report provides recommendations for establishing a quantitative criterion to assess the commutability of a certified reference material (CRM). The criterion is the maximum allowable noncommutability bias (MANCB) that allows a CRM to be used as a calibrator in a calibration hierarchy for an IVD-MD without exceeding the maximum allowable combined standard uncertainty for a clinical sample result (umaxCS). Consequently, the MANCB is derived as a fraction of the umaxCS for the measurand. The suitability of an MANCB for practical use in a commutability assessment is determined by estimating the number of measurements of clinical samples and CRMs required based on the precision performance and nonselectivity for the measurand of the measurement procedures in the assessment. Guidance is also provided for evaluating indeterminate commutability conclusions and how to report results of a commutability assessment. |
Association of E484K and L452R spike protein mutations with SARS-CoV-2 infection in vaccinated persons---Maryland, January – May 2021 (preprint)
Feder KA , Patel A , Vepachedu VR , Dominguez C , Keller EN , Klein L , Kim C , Blood T , Hyun J , Williams TW , Feldman KA , Mostafa HH , Morris CP , Ravel J , Duwell M , Blythe D , Myers R . medRxiv 2021 2021.07.29.21261006 Background The E484K and L452R amino acid substitutions on the spike protein of SARS-CoV-2 are associated with reduced neutralization by antibodies from acquired immunity. This study examines the respective association of these mutations with infection in persons who had previously received a COVID-19 vaccine.Methods Genetic sequences from SARS-CoV-2 specimens collected from Maryland residents and reported to Maryland Department of Health were linked to vaccination history. The prevalence of infections in fully vaccinated persons -- defined as being at least two weeks past receiving the final scheduled dose of a COVID-19 vaccine series -- was compared between infections caused by viruses carrying E484K to those not carrying E484K, and between infections caused by viruses carrying L452R to those not carrying L452R, using logistic regression to adjust for confounding.Results Of 9,048 sequenced SARS-CoV-2 specimens examined, 265 (2.9%) were collected from fully vaccinated persons. In adjusted analysis, the E484K substitution was associated with an increase in the odds of the sequenced specimen being collected from a fully vaccinated person (OR 1.96, 95% CI, 1.36 to 2.83). The L452R mutation was not significantly associated with infections in vaccinated persons (OR 1.07, 95% CI, 0.69 to 1.68).Conclusion Though more than 97% of SARS-CoV-2 infections were in persons who were not fully vaccinated, the E484K mutation was associated with increased odds of SARS-CoV-2 infection in vaccinated persons. Linking vaccination and sequencing data can help identify and estimate the impact SARS-CoV-2 mutations may have on vaccine effectiveness.Summary In viruses sequenced for Maryland’s routine SARS-CoV-2 genomic surveillance, the spike protein amino acid substitution E484K was more prevalent in viruses that infected vaccinated people than in viruses that infected people who were not vaccinated.Competing Interest StatementThe authors have declared no competing interest.Funding StatementNo external funding to report.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:Case investigation, data collection, and analysis were conducted for public health purposes. This project was reviewed by the Division of Scientific Education and Professional Development within the Center for Surveillance, Epidemiology, and Laboratory Services at the Centers for Disease Control and Prevention (CDC). The project was determined to meet the requirements of public health surveillance covered by the U.S. Department of Health and Human Services Policy for the Protection of Human Research Subjects as defined in 45 C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C. Sec.241(d); 5 U.S.C. Sec.552a; 44 U.S.C. Sec.3501 et seq. In., and the decision was made that this project was nonresearch and did not require ethical review by the CDC Human Research Protection Office. Ethical approval was waived and informed consent was not required.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.YesData are the property of the U.S. state of Maryland and are collected for public health surveillance purposes. They are not available to the ublic. |
Mitigating Pandemic Risk with Influenza A Virus Field Surveillance at a Swine-Human Interface (preprint)
Rambo-Martin BL , Keller MW , Wilson MM , Nolting JM , Anderson TK , Vincent AL , Bagal UR , Jang Y , Neuhaus EB , Davis CT , Bowman AS , Wentworth DE , Barnes JR . bioRxiv 2019 585588 Working overnight at a large swine exhibition, we identified an influenza A virus (IAV) outbreak in swine, nanopore-sequenced 13 IAV genomes from samples collected, and in real-time, determined that these viruses posed a novel risk to humans due to genetic mismatches between the viruses and current pre-pandemic candidate vaccine viruses (CVV). We developed and used a portable IAV sequencing and analysis platform called Mia (Mobile Influenza Analysis) to complete and characterize full-length consensus genomes approximately 18 hours after unpacking the mobile lab. Swine are important animal IAV reservoirs that have given rise to pandemic viruses via zoonotic transmission. Genomic analyses of IAV in swine are critical to understanding pandemic risk of viruses in this reservoir, and characterization of viruses circulating in exhibition swine enables rapid comparison to current seasonal influenza vaccines and CVVs. The Mia system rapidly identified three genetically distinct swine IAV lineages from three subtypes: A(H1N1), A(H3N2) and A(H1N2). Additional analysis of the HA protein sequences of the A(H1N2) viruses identified >30 amino acid differences between the HA1 portion of the hemagglutinin of these viruses and the most closely related pre-2009 CVV. All virus sequences were emailed to colleagues at CDC who initiated development of a synthetically derived CVV designed to provide an optimal antigenic match with the viruses detected in the exhibition. In subsequent months, this virus caused 13 infections in humans, and was the dominant variant virus in the US detected in 2018. Had this virus caused a severe outbreak or pandemic, our proactive surveillance efforts and CVV derivation would have provided an approximate 8 week time advantage for vaccine manufacturing. This is the first report of the use of field-derived nanopore sequencing data to initiate a real-time, actionable public health countermeasure. |
Direct RNA Sequencing of the Complete Influenza A Virus Genome (preprint)
Keller MW , Rambo-Martin BL , Wilson MM , Ridenour CA , Shepard SS , Stark TJ , Neuhaus EB , Dugan VG , Wentworth DE , Barnes JR . bioRxiv 2018 300384 For the first time, a complete genome of an RNA virus has been sequenced in its original form. Previously, RNA was sequenced by the chemical degradation of radiolabelled RNA, a difficult method that produced only short sequences. Instead, RNA has usually been sequenced indirectly by copying it into cDNA, which is often amplified to dsDNA by PCR and subsequently analyzed using a variety of DNA sequencing methods. We designed an adapter to short highly conserved termini of the influenza virus genome to target the (-) sense RNA into a protein nanopore on the Oxford Nanopore MinION sequencing platform. Utilizing this method and total RNA extracted from the allantoic fluid of infected chicken eggs, we demonstrate successful sequencing of the complete influenza virus genome with 100% nucleotide coverage, 99% consensus identity, and 99% of reads mapped to influenza. By utilizing the same methodology we can redesign the adapter in order to expand the targets to include viral mRNA and (+) sense cRNA, which are essential to the viral life cycle. This has the potential to identify and quantify splice variants and base modifications, which are not practically measurable with current methods. |
Identification of a Novel SARS-CoV-2 Delta-Omicron Recombinant Virus in the United States (preprint)
Lacek KA , Rambo-Martin BL , Batra D , Zheng XY , Sakaguchi H , Peacock T , Keller M , Wilson MM , Sheth M , Davis ML , Borroughs M , Gerhart J , Hassell N , Shepard SS , Cook PW , Lee J , Wentworth DE , Barnes JR , Kondor R , Paden CR . bioRxiv 2022 21 Recombination between SARS-CoV-2 virus variants can result in different viral properties (e.g., infectiousness or pathogenicity). In this report, we describe viruses with recombinant genomes containing signature mutations from Delta and Omicron variants. These genomes are the first evidence for a Delta-Omicron hybrid Spike protein in the United States. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Number needed to vaccinate with a COVID-19 booster to prevent a COVID-19-associated hospitalization during SARS-CoV-2 Omicron BA.1 variant predominance, December 2021-February 2022, VISION Network: a retrospective cohort study
Adams K , Riddles JJ , Rowley EAK , Grannis SJ , Gaglani M , Fireman B , Hartmann E , Naleway AL , Stenehjem E , Hughes A , Dalton AF , Natarajan K , Dascomb K , Raiyani C , Irving SA , Sloan-Aagard C , Kharbanda AB , DeSilva MB , Dixon BE , Ong TC , Keller J , Dickerson M , Grisel N , Murthy K , Nanez J , Fadel WF , Ball SW , Patel P , Arndorfer J , Mamawala M , Valvi NR , Dunne MM , Griggs EP , Embi PJ , Thompson MG , Link-Gelles R , Tenforde MW . Lancet Reg Health Am 2023 23 100530 BACKGROUND: Understanding the usefulness of additional COVID-19 vaccine doses-particularly given varying disease incidence-is needed to support public health policy. We characterize the benefits of COVID-19 booster doses using number needed to vaccinate (NNV) to prevent one COVID-19-associated hospitalization or emergency department encounter. METHODS: We conducted a retrospective cohort study of immunocompetent adults at five health systems in four U.S. states during SARS-CoV-2 Omicron BA.1 predominance (December 2021-February 2022). Included patients completed a primary mRNA COVID-19 vaccine series and were either eligible to or received a booster dose. NNV were estimated using hazard ratios for each outcome (hospitalization and emergency department encounters), with results stratified by three 25-day periods and site. FINDINGS: 1,285,032 patients contributed 938 hospitalizations and 2076 emergency department encounters. 555,729 (43.2%) patients were aged 18-49 years, 363,299 (28.3%) 50-64 years, and 366,004 (28.5%) ≥65 years. Most patients were female (n = 765,728, 59.6%), White (n = 990,224, 77.1%), and non-Hispanic (n = 1,063,964, 82.8%). 37.2% of patients received a booster and 62.8% received only two doses. Median estimated NNV to prevent one hospitalization was 205 (range 44-615) and NNV was lower across study periods for adults aged ≥65 years (110, 46, and 88, respectively) and those with underlying medical conditions (163, 69, and 131, respectively). Median estimated NNV to prevent one emergency department encounter was 156 (range 75-592). INTERPRETATION: The number of patients needed to receive a booster dose was highly dependent on local disease incidence, outcome severity, and patient risk factors for moderate-to-severe disease. FUNDING: Funding was provided by the Centers for Disease Control and Prevention though contract 75D30120C07986 to Westat, Inc. and contract 75D30120C07765 to Kaiser Foundation Hospitals. |
SARS-CoV-2 spike D614G variant confers enhanced replication and transmissibility (preprint)
Zhou B , Thao TTN , Hoffmann D , Taddeo A , Ebert N , Labroussaa F , Pohlmann A , King J , Portmann J , Halwe NJ , Ulrich L , Trüeb BS , Kelly JN , Fan X , Hoffmann B , Steiner S , Wang L , Thomann L , Lin X , Stalder H , Pozzi B , de Brot S , Jiang N , Cui D , Hossain J , Wilson M , Keller M , Stark TJ , Barnes JR , Dijkman R , Jores J , Benarafa C , Wentworth DE , Thiel V , Beer M . bioRxiv 2020 During the evolution of SARS-CoV-2 in humans a D614G substitution in the spike (S) protein emerged and became the predominant circulating variant (S-614G) of the COVID-19 pandemic (1) . However, whether the increasing prevalence of the S-614G variant represents a fitness advantage that improves replication and/or transmission in humans or is merely due to founder effects remains elusive. Here, we generated isogenic SARS-CoV-2 variants and demonstrate that the S-614G variant has (i) enhanced binding to human ACE2, (ii) increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a novel human ACE2 knock-in mouse model, and (iii) markedly increased replication and transmissibility in hamster and ferret models of SARS-CoV-2 infection. Collectively, our data show that while the S-614G substitution results in subtle increases in binding and replication in vitro , it provides a real competitive advantage in vivo , particularly during the transmission bottle neck, providing an explanation for the global predominance of S-614G variant among the SARS-CoV-2 viruses currently circulating. |
Author Correction: Direct RNA Sequencing of the Coding Complete Influenza A Virus Genome.
Keller MW , Rambo-Martin BL , Wilson MM , Ridenour CA , Shepard SS , Stark TJ , Neuhaus EB , Dugan VG , Wentworth DE , Barnes JR . Sci Rep 2018 8 (1) 15746 A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper. |
Erratum: Vol. 71, No. 6.
Lambrou AS , Shirk P , Steele MK , Paul P , Paden CR , Cadwell B , Reese HE , Aoki Y , Hassell N , Caravas J , Kovacs NA , Gerhart JG , Ng HJ , Zheng XY , Beck A , Chau R , Cintron R , Cook PW , Gulvik CA , Howard D , Jang Y , Knipe K , Lacek KA , Moser KA , Paskey AC , Rambo-Martin BL , Nagilla RR , Rethchless AC , Schmerer MW , Seby S , Shephard SS , Stanton RA , Stark TJ , Uehara A , Unoarumhi Y , Bentz ML , Burhgin A , Burroughs M , Davis ML , Keller MW , Keong LM , Le SS , Lee JS , Madden Jr JC , Nobles S , Owouor DC , Padilla J , Sheth M , Wilson MM , Talarico S , Chen JC , Oberste MS , Batra D , McMullan LK , Halpin AL , Galloway SE , MacCannell DR , Kondor R , Barnes J , MacNeil A , Silk BJ , Dugan VG , Scobie HM , Wentworth DE . MMWR Morb Mortal Wkly Rep 2022 71 (14) 528 The report “Genomic Surveillance for SARS-CoV-2 Variants: Predominance of the Delta (B.1.617.2) and Omicron (B.1.1.529) Variants — United States, June 2021–January 2022” contained several errors. |
SARS-CoV-2 Delta-Omicron Recombinant Viruses, United States.
Lacek KA , Rambo-Martin BL , Batra D , Zheng XY , Hassell N , Sakaguchi H , Peacock T , Groves N , Keller M , Wilson MM , Sheth M , Davis ML , Borroughs M , Gerhart J , Shepard SS , Cook PW , Lee J , Wentworth DE , Barnes JR , Kondor R , Paden CR . Emerg Infect Dis 2022 28 (7) 1442-1445 To detect new and changing SARS-CoV-2 variants, we investigated candidate Delta-Omicron recombinant genomes from Centers for Disease Control and Prevention national genomic surveillance. Laboratory and bioinformatic investigations identified and validated 9 genetically related SARS-CoV-2 viruses with a hybrid Delta-Omicron spike protein. |
Assessing sleep and pain among adults with myalgic encephalomyelitis/chronic fatigue syndrome: psychometric evaluation of the PROMIS sleep and pain short forms
Yang M , Keller S , Lin JS . Qual Life Res 2022 31 (12) 3483-3499 PURPOSE: To evaluate the psychometric properties of the patient-reported outcome measurement information system (PROMIS) short forms for assessing sleep disturbance, sleep-related impairment, pain interference, and pain behavior, among adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). METHODS: Data came from the Multi-Site ME/CFS study conducted between 2012 and 2020 at seven ME/CFS specialty clinics across the USA. Baseline and follow-up data from ME/CFS and healthy control (HC) groups were used to examine ceiling/floor effects, internal consistency reliability, differential item functioning (DIF), known-groups validity, and responsiveness. RESULTS: A total of 945 participants completed the baseline assessment (602 ME/CFS and 338 HC) and 441 ME/CFS also completed the follow-up. The baseline mean T-scores of PROMIS sleep and pain measures ranged from 57.68 to 62.40, about one standard deviation above the national norm (T-score=50). All four measures showed high internal consistency (=0.92 to 0.97) and no substantial floor/ceiling effects. No DIF was detected by age or sex. Known-groups comparisons among ME/CFS groups with low, medium, and high functional impairment showed significant small-sized differences in scores ((2)=0.01 to 0.05) for the two sleep measures and small-to-medium-sized differences ((2)=0.01 to 0.15) for the two pain measures. ME/CFS participants had significantly worse scores than HC ((2)=0.35 to 0.45) for all four measures. Given the non-interventional nature of the study, responsiveness was evaluated as sensitivity to change over time and the pain interference measure showed an acceptable sensitivity. CONCLUSION: The PROMIS sleep and pain measures demonstrated satisfactory psychometric properties supporting their use in ME/CFS research and clinical practice. |
Evolution and applications of recent sensing technology for occupational risk assessment: A rapid review of the literature
Fanti G , Spinazzè A , Borghi F , Rovelli S , Campagnolo D , Keller M , Borghi A , Cattaneo A , Cauda E , Cavallo DM . Sensors (Basel) 2022 22 (13) Over the last decade, technological advancements have been made available and applied in a wide range of applications in several work fields, ranging from personal to industrial enforcements. One of the emerging issues concerns occupational safety and health in the Fourth Industrial Revolution and, in more detail, it deals with how industrial hygienists could improve the risk-assessment process. A possible way to achieve these aims is the adoption of new exposure-monitoring tools. In this study, a systematic review of the up-to-date scientific literature has been performed to identify and discuss the most-used sensors that could be useful for occupational risk assessment, with the intent of highlighting their pros and cons. A total of 40 papers have been included in this manuscript. The results show that sensors able to investigate airborne pollutants (i.e., gaseous pollutants and particulate matter), environmental conditions, physical agents, and workers' postures could be usefully adopted in the risk-assessment process, since they could report significant data without significantly interfering with the job activities of the investigated subjects. To date, there are only few "next-generation" monitors and sensors (NGMSs) that could be effectively used on the workplace to preserve human health. Due to this fact, the development and the validation of new NGMSs will be crucial in the upcoming years, to adopt these technologies in occupational-risk assessment. |
Association of E484K Spike Protein Mutation With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Vaccinated Persons: Maryland, January-May 2021.
Feder KA , Patel A , Vepachedu VR , Dominguez C , Keller EN , Klein L , Kim C , Blood T , Hyun J , Williams TW , Feldman KA , Mostafa HH , Morris CP , Ravel J , Duwell M , Blythe D , Myers R . Clin Infect Dis 2022 74 (11) 2053-2056 Among 9048 people infected with SARS-CoV-2 between January and May 2021 in Maryland, in regression-adjusted analysis, SARS-CoV-2 viruses carrying the spike protein mutation E484K were disproportionately prevalent among persons infected after full vaccination against COVID-19 compared with infected persons who were not fully vaccinated (aOR, 1.96; 95% CI: 1.36-2.83). |
The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysis
Walker TM , Fowler PW , Knaggs J , Hunt M , Peto TE , Walker AS , Crook DW , Walker TM , Miotto P , Cirillo DM , Kser CU , Knaggs J , Iqbal Z , Hunt M , Chindelevitch L , Farhat MR , Comas I , Comas I , Posey J , Omar SV , Peto TE , Walker AS , Crook DW , Suresh A , Uplekar S , Laurent S , Colman RE , Rodwell TC , Nathanson CM , Zignol M , Ismail N , Rodwell TC , Walker AS , Steyn AJC , Lalvani A , Baulard A , Christoffels A , Mendoza-Ticona A , Trovato A , Skrahina A , Lachapelle AS , Brankin A , Piatek A , GibertoniCruz A , Koch A , Cabibbe AM , Spitaleri A , Brandao AP , Chaiprasert A , Suresh A , Barbova A , VanRie A , Ghodousi A , Bainomugisa A , Mandal A , Roohi A , Javid B , Zhu B , Letcher B , Rodrigues C , Nimmo C , Nathanson CM , Duncan C , Coulter C , Utpatel C , Liu C , Grazian C , Kong C , Kser CU , Wilson DJ , Cirillo DM , Matias D , Jorgensen D , Zimenkov D , Chetty D , Moore DA , Clifton DA , Crook DW , vanSoolingen D , Liu D , Kohlerschmidt D , Barreira D , Ngcamu D , SantosLazaro ED , Kelly E , Borroni E , Roycroft E , Andre E , Bttger EC , Robinson E , Menardo F , Mendes FF , Jamieson FB , Coll F , Gao GF , Kasule GW , Rossolini GM , Rodger G , Smith EG , Meintjes G , Thwaites G , Hoffmann H , Albert H , Cox H , Laurenson IF , Comas I , Arandjelovic I , Barilar I , Robledo J , Millard J , Johnston J , Posey J , Andrews JR , Knaggs J , Gardy J , Guthrie J , Taylor J , Werngren J , Metcalfe J , Coronel J , Shea J , Carter J , Pinhata JM , Kus JV , Todt K , Holt K , Nilgiriwala KS , Ghisi KT , Malone KM , Faksri K , Musser KA , Joseph L , Rigouts L , Chindelevitch L , Jarrett L , Grandjean L , Ferrazoli L , Rodrigues M , Farhat M , Schito M , Fitzgibbon MM , Loemb MM , Wijkander M , Ballif M , Rabodoarivelo MS , Mihalic M , Wilcox M , Hunt M , Zignol M , Merker M , Egger M , O'Donnell M , Caws M , Wu MH , Whitfield MG , Inouye M , Mansj M , DangThi MH , Joloba M , Kamal SM , Okozi N , Ismail N , Mistry N , Hoang NN , Rakotosamimanana N , Paton NI , Rancoita PMV , Miotto P , Lapierre P , Hall PJ , Tang P , Claxton P , Wintringer P , Keller PM , Thai PVK , Fowler PW , Supply P , Srilohasin P , Suriyaphol P , Rathod P , Kambli P , Groenheit R , Colman RE , Ong RTH , Warren RM , Wilkinson RJ , Diel R , Oliveira RS , Khot R , Jou R , Tahseen S , Laurent S , Gharbia S , Kouchaki S , Shah S , Plesnik S , Earle SG , Dunstan S , Hoosdally SJ , Mitarai S , Gagneux S , Omar SV , Yao SY , GrandjeanLapierre S , Battaglia S , Niemann S , Pandey S , Uplekar S , Halse TA , Cohen T , Cortes T , Prammananan T , Kohl TA , Thuong NTT , Teo TY , Peto TEA , Rodwell TC , William T , Walker TM , Rogers TR , Surve U , Mathys V , Furi V , Cook V , Vijay S , Escuyer V , Dreyer V , Sintchenko V , Saphonn V , Solano W , Lin WH , vanGemert W , He W , Yang Y , Zhao Y , Qin Y , Xiao YX , Hasan Z , Iqbal Z , Puyen ZM , CryPticConsortium theSeq , Treat Consortium . Lancet Microbe 2022 3 (4) e265-e273 Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (73%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (07%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (914%), moxifloxacin (916%) and ethambutol (933%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation. 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license |
Genomic Surveillance for SARS-CoV-2 Variants: Predominance of the Delta (B.1.617.2) and Omicron (B.1.1.529) Variants - United States, June 2021-January 2022.
Lambrou AS , Shirk P , Steele MK , Paul P , Paden CR , Cadwell B , Reese HE , Aoki Y , Hassell N , Caravas J , Kovacs NA , Gerhart JG , Ng HJ , Zheng XY , Beck A , Chau R , Cintron R , Cook PW , Gulvik CA , Howard D , Jang Y , Knipe K , Lacek KA , Moser KA , Paskey AC , Rambo-Martin BL , Nagilla RR , Rethchless AC , Schmerer MW , Seby S , Shephard SS , Stanton RA , Stark TJ , Uehara A , Unoarumhi Y , Bentz ML , Burhgin A , Burroughs M , Davis ML , Keller MW , Keong LM , Le SS , Lee JS , Madden Jr JC , Nobles S , Owouor DC , Padilla J , Sheth M , Wilson MM , Talarico S , Chen JC , Oberste MS , Batra D , McMullan LK , Halpin AL , Galloway SE , MacCannell DR , Kondor R , Barnes J , MacNeil A , Silk BJ , Dugan VG , Scobie HM , Wentworth DE . MMWR Morb Mortal Wkly Rep 2022 71 (6) 206-211 Genomic surveillance is a critical tool for tracking emerging variants of SARS-CoV-2 (the virus that causes COVID-19), which can exhibit characteristics that potentially affect public health and clinical interventions, including increased transmissibility, illness severity, and capacity for immune escape. During June 2021-January 2022, CDC expanded genomic surveillance data sources to incorporate sequence data from public repositories to produce weighted estimates of variant proportions at the jurisdiction level and refined analytic methods to enhance the timeliness and accuracy of national and regional variant proportion estimates. These changes also allowed for more comprehensive variant proportion estimation at the jurisdictional level (i.e., U.S. state, district, territory, and freely associated state). The data in this report are a summary of findings of recent proportions of circulating variants that are updated weekly on CDC's COVID Data Tracker website to enable timely public health action.(†) The SARS-CoV-2 Delta (B.1.617.2 and AY sublineages) variant rose from 1% to >50% of viral lineages circulating nationally during 8 weeks, from May 1-June 26, 2021. Delta-associated infections remained predominant until being rapidly overtaken by infections associated with the Omicron (B.1.1.529 and BA sublineages) variant in December 2021, when Omicron increased from 1% to >50% of circulating viral lineages during a 2-week period. As of the week ending January 22, 2022, Omicron was estimated to account for 99.2% (95% CI = 99.0%-99.5%) of SARS-CoV-2 infections nationwide, and Delta for 0.7% (95% CI = 0.5%-1.0%). The dynamic landscape of SARS-CoV-2 variants in 2021, including Delta- and Omicron-driven resurgences of SARS-CoV-2 transmission across the United States, underscores the importance of robust genomic surveillance efforts to inform public health planning and practice. |
Multiplexed CRISPR-based microfluidic platform for clinical testing of respiratory viruses and identification of SARS-CoV-2 variants.
Welch NL , Zhu M , Hua C , Weller J , Mirhashemi ME , Nguyen TG , Mantena S , Bauer MR , Shaw BM , Ackerman CM , Thakku SG , Tse MW , Kehe J , Uwera MM , Eversley JS , Bielwaski DA , McGrath G , Braidt J , Johnson J , Cerrato F , Moreno GK , Krasilnikova LA , Petros BA , Gionet GL , King E , Huard RC , Jalbert SK , Cleary ML , Fitzgerald NA , Gabriel SB , Gallagher GR , Smole SC , Madoff LC , Brown CM , Keller MW , Wilson MM , Kirby MK , Barnes JR , Park DJ , Siddle KJ , Happi CT , Hung DT , Springer M , MacInnis BL , Lemieux JE , Rosenberg E , Branda JA , Blainey PC , Sabeti PC , Myhrvold C . Nat Med 2022 28 (5) 1083-1094 The COVID-19 pandemic has demonstrated a clear need for high-throughput, multiplexed, and sensitive assays for detecting SARS-CoV-2 and other respiratory viruses as well as their emerging variants. Here, we present a cost-effective virus and variant detection platform, called microfluidic CARMEN (mCARMEN), that combines CRISPR-based diagnostics and microfluidics with a streamlined workflow for clinical use. We developed the mCARMEN respiratory virus panel (RVP) to test for up to 21 viruses, including SARS-CoV-2, other coronaviruses and both influenza strains, and demonstrated its diagnostic-grade performance on 525 patient specimens in an academic setting and 166 specimens in a clinical setting. We further developed an mCARMEN panel to enable identification of 6 SARS-CoV-2 variant lineages, including Delta and Omicron, and evaluated it on 2,088 patient specimens, with near-perfect concordance to sequencing-based variant classification. Lastly, we implemented a combined Cas13 and Cas12 approach that enables quantitative measurement of SARS-CoV-2 and influenza A viral copies in samples. The mCARMEN platform enables high-throughput surveillance of multiple viruses and variants simultaneously, enabling rapid detection of SARS-CoV-2 variants. |
Impact of Statewide Prevention and Reduction of Clostridioides difficile (SPARC), a Maryland public health-academic collaborative: an evaluation of a quality improvement intervention
Rock C , Perlmutter R , Blythe D , Bork J , Claeys K , Cosgrove SE , Dzintars K , Fabre V , Harris AD , Heil E , Hsu YJ , Keller S , Maragakis LL , Milstone AM , Morgan DJ , Dullabh P , Ubri PS , Rotondo C , Brooks R , Leekha S . BMJ Qual Saf 2021 31 (2) 153-162 To evaluate changes in Clostridioides difficile incidence rates for Maryland hospitals that participated in the Statewide Prevention and Reduction of C. difficile (SPARC) collaborative. Pre-post, difference-in-difference analysis of non-randomised intervention using four quarters of preintervention and six quarters of postintervention National Healthcare Safety Network data for SPARC hospitals (April 2017 to March 2020) and 10 quarters for control hospitals (October 2017 to March 2020). Mixed-effects negative binomial models were used to assess changes over time. Process evaluation using hospital intervention implementation plans, assessments and interviews with staff at eight SPARC hospitals. Maryland, USA. All Maryland acute care hospitals; 12 intervention and 36 control hospitals. Participation in SPARC, a public health-academic collaborative made available to Maryland hospitals, with staggered enrolment between June 2018 and August 2019. Hospitals with higher C. difficile rates were recruited via email and phone. SPARC included assessments, feedback reports and ongoing technical assistance. Primary outcomes were C. difficile incidence rate measured as the quarterly number of C. difficile infections per 10 000 patient-days (outcome measure) and SPARC intervention hospitals' experiences participating in the collaborative (process measures). SPARC invited 13 hospitals to participate in the intervention, with 92% (n=12) participating. The 36 hospitals that did not participate served as control hospitals. SPARC hospitals were associated with 45% greater C. difficile reduction as compared with control hospitals (incidence rate ratio=0.55, 95% CI 0.35 to 0.88, p=0.012). Key SPARC activities, including access to trusted external experts, technical assistance, multidisciplinary collaboration, an accountability structure, peer-to-peer learning opportunities and educational resources, were associated with hospitals reporting positive experiences with SPARC. SPARC intervention hospitals experienced 45% greater reduction in C. difficile rates than control hospitals. A public health-academic collaborative might help reduce C. difficile and other hospital-acquired infections in individual hospitals and at state or regional levels. |
Examining Individual and Synergistic Contributions of PTSD and Genetics to Blood Pressure: A Trans-Ethnic Meta-Analysis.
Sumner JA , Maihofer AX , Michopoulos V , Rothbaum AO , Almli LM , Andreassen OA , Ashley-Koch AE , Baker DG , Beckham JC , Bradley B , Breen G , Coleman JRI , Dale AM , Dennis MF , Feeny NC , Franz CE , Garrett ME , Gillespie CF , Guffanti G , Hauser MA , Hemmings SMJ , Jovanovic T , Kimbrel NA , Kremen WS , Lawford BR , Logue MW , Lori A , Lyons MJ , Maples-Keller J , Mavissakalian MR , McGlinchey RE , Mehta D , Mellor R , Milberg W , Miller MW , Morris CP , Panizzon MS , Ressler KJ , Risbrough VB , Rothbaum BO , Roy-Byrne P , Seedat S , Smith AK , Stevens JS , van den Heuvel LL , Voisey J , Young RM , Zoellner LA , Nievergelt CM , Wolf EJ . Front Neurosci 2021 15 678503 Growing research suggests that posttraumatic stress disorder (PTSD) may be a risk factor for poor cardiovascular health, and yet our understanding of who might be at greatest risk of adverse cardiovascular outcomes after trauma is limited. In this study, we conducted the first examination of the individual and synergistic contributions of PTSD symptoms and blood pressure genetics to continuous blood pressure levels. We harnessed the power of the Psychiatric Genomics Consortium-PTSD Physical Health Working Group and investigated these associations across 11 studies of 72,224 trauma-exposed individuals of European (n = 70,870) and African (n = 1,354) ancestry. Genetic contributions to blood pressure were modeled via polygenic scores (PGS) for systolic blood pressure (SBP) and diastolic blood pressure (DBP) that were derived from a prior trans-ethnic blood pressure genome-wide association study (GWAS). Results of trans-ethnic meta-analyses revealed significant main effects of the PGS on blood pressure levels [SBP: β = 2.83, standard error (SE) = 0.06, p < 1E-20; DBP: β = 1.32, SE = 0.04, p < 1E-20]. Significant main effects of PTSD symptoms were also detected for SBP and DBP in trans-ethnic meta-analyses, though there was significant heterogeneity in these results. When including data from the largest contributing study - United Kingdom Biobank - PTSD symptoms were negatively associated with SBP levels (β = -1.46, SE = 0.44, p = 9.8E-4) and positively associated with DBP levels (β = 0.70, SE = 0.26, p = 8.1E-3). However, when excluding the United Kingdom Biobank cohort in trans-ethnic meta-analyses, there was a nominally significant positive association between PTSD symptoms and SBP levels (β = 2.81, SE = 1.13, p = 0.01); no significant association was observed for DBP (β = 0.43, SE = 0.78, p = 0.58). Blood pressure PGS did not significantly moderate the associations between PTSD symptoms and blood pressure levels in meta-analyses. Additional research is needed to better understand the extent to which PTSD is associated with high blood pressure and how genetic as well as contextual factors may play a role in influencing cardiovascular risk. |
Features and Practicability of the Next-Generation Sensors and Monitors for Exposure Assessment to Airborne Pollutants: A Systematic Review.
Fanti G , Borghi F , Spinazzè A , Rovelli S , Campagnolo D , Keller M , Cattaneo A , Cauda E , Cavallo DM . Sensors (Basel) 2021 21 (13) In the last years, the issue of exposure assessment of airborne pollutants has been on the rise, both in the environmental and occupational fields. Increasingly severe national and international air quality standards, indoor air guidance values, and exposure limit values have been developed to protect the health of the general population and workers; this issue required a significant and continuous improvement in monitoring technologies to allow the execution of proper exposure assessment studies. One of the most interesting aspects in this field is the development of the "next-generation" of airborne pollutants monitors and sensors (NGMS). The principal aim of this review is to analyze and characterize the state of the art and of NGMS and their practical applications in exposure assessment studies. A systematic review of the literature was performed analyzing outcomes from three different databases (Scopus, PubMed, Isi Web of Knowledge); a total of 67 scientific papers were analyzed. The reviewing process was conducting systematically with the aim to extrapolate information about the specifications, technologies, and applicability of NGMSs in both environmental and occupational exposure assessment. The principal results of this review show that the use of NGMSs is becoming increasingly common in the scientific community for both environmental and occupational exposure assessment. The available studies outlined that NGMSs cannot be used as reference instrumentation in air monitoring for regulatory purposes, but at the same time, they can be easily adapted to more specific applications, improving exposure assessment studies in terms of spatiotemporal resolution, wearability, and adaptability to different types of projects and applications. Nevertheless, improvements needed to further enhance NGMSs performances and allow their wider use in the field of exposure assessment are also discussed. |
Association Between Caseload Surge and COVID-19 Survival in 558 U.S. Hospitals, March to August 2020.
Kadri SS , Sun J , Lawandi A , Strich JR , Busch LM , Keller M , Babiker A , Yek C , Malik S , Krack J , Dekker JP , Spaulding AB , Ricotta E , Powers Iii JH , Rhee C , Klompas M , Athale J , Boehmer TK , Gundlapalli AV , Bentley W , Datta SD , Danner RL , Demirkale CY , Warner S . Ann Intern Med 2021 174 (9) 1240-1251 BACKGROUND: Several U.S. hospitals had surges in COVID-19 caseload, but their effect on COVID-19 survival rates remains unclear, especially independent of temporal changes in survival. OBJECTIVE: To determine the association between hospitals' severity-weighted COVID-19 caseload and COVID-19 mortality risk and identify effect modifiers of this relationship. DESIGN: Retrospective cohort study. (ClinicalTrials.gov: NCT04688372). SETTING: 558 U.S. hospitals in the Premier Healthcare Database. PARTICIPANTS: Adult COVID-19-coded inpatients admitted from March to August 2020 with discharge dispositions by October 2020. MEASUREMENTS: Each hospital-month was stratified by percentile rank on a surge index (a severity-weighted measure of COVID-19 caseload relative to pre-COVID-19 bed capacity). The effect of surge index on risk-adjusted odds ratio (aOR) of in-hospital mortality or discharge to hospice was calculated using hierarchical modeling; interaction by surge attributes was assessed. RESULTS: Of 144 116 inpatients with COVID-19 at 558 U.S. hospitals, 78 144 (54.2%) were admitted to hospitals in the top surge index decile. Overall, 25 344 (17.6%) died; crude COVID-19 mortality decreased over time across all surge index strata. However, compared with nonsurging (<50th surge index percentile) hospital-months, aORs in the 50th to 75th, 75th to 90th, 90th to 95th, 95th to 99th, and greater than 99th percentiles were 1.11 (95% CI, 1.01 to 1.23), 1.24 (CI, 1.12 to 1.38), 1.42 (CI, 1.27 to 1.60), 1.59 (CI, 1.41 to 1.80), and 2.00 (CI, 1.69 to 2.38), respectively. The surge index was associated with mortality across ward, intensive care unit, and intubated patients. The surge-mortality relationship was stronger in June to August than in March to May (slope difference, 0.10 [CI, 0.033 to 0.16]) despite greater corticosteroid use and more judicious intubation during later and higher-surging months. Nearly 1 in 4 COVID-19 deaths (5868 [CI, 3584 to 8171]; 23.2%) was potentially attributable to hospitals strained by surging caseload. LIMITATION: Residual confounding. CONCLUSION: Despite improvements in COVID-19 survival between March and August 2020, surges in hospital COVID-19 caseload remained detrimental to survival and potentially eroded benefits gained from emerging treatments. Bolstering preventive measures and supporting surging hospitals will save many lives. PRIMARY FUNDING SOURCE: Intramural Research Program of the National Institutes of Health Clinical Center, the National Institute of Allergy and Infectious Diseases, and the National Cancer Institute. |
Multiplex Real-Time Reverse Transcription PCR for Influenza A Virus, Influenza B Virus, and Severe Acute Respiratory Syndrome Coronavirus 2.
Shu B , Kirby MK , Davis WG , Warnes C , Liddell J , Liu J , Wu KH , Hassell N , Benitez AJ , Wilson MM , Keller MW , Rambo-Martin BL , Camara Y , Winter J , Kondor RJ , Zhou B , Spies S , Rose LE , Winchell JM , Limbago BM , Wentworth DE , Barnes JR . Emerg Infect Dis 2021 27 (7) 1821-1830 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019, and the outbreak rapidly evolved into the current coronavirus disease pandemic. SARS-CoV-2 is a respiratory virus that causes symptoms similar to those caused by influenza A and B viruses. On July 2, 2020, the US Food and Drug Administration granted emergency use authorization for in vitro diagnostic use of the Influenza SARS-CoV-2 Multiplex Assay. This assay detects influenza A virus at 10(2.0), influenza B virus at 10(2.2), and SARS-CoV-2 at 10(0.3) 50% tissue culture or egg infectious dose, or as few as 5 RNA copies/reaction. The simultaneous detection and differentiation of these 3 major pathogens increases overall testing capacity, conserves resources, identifies co-infections, and enables efficient surveillance of influenza viruses and SARS-CoV-2. |
Linked Clusters of SARS-CoV-2 Variant B.1.351 - Maryland, January-February 2021.
Feder KA , Pearlowitz M , Goode A , Duwell M , Williams TW , Chen-Carrington PA , Patel A , Dominguez C , Keller EN , Klein L , Rivera-Colon A , Mostafa HH , Morris CP , Patel N , Schauer AM , Myers R , Blythe D , Feldman KA . MMWR Morb Mortal Wkly Rep 2021 70 (17) 627-631 In late January 2021, a clinical laboratory notified the Maryland Department of Health (MDH) that the SARS-CoV-2 variant of concern B.1.351 had been identified in a specimen collected from a Maryland resident with COVID-19 (1). The SARS-CoV-2 B.1.351 lineage was first identified in South Africa (2) and might be neutralized less effectively by antibodies produced after vaccination or natural infection with other strains (3-6). To limit SARS-CoV-2 chains of transmission associated with this index patient, MDH used contact tracing to identify the source of infection and any linked infections among other persons. The investigation identified two linked clusters of SARS-CoV-2 infection that included 17 patients. Three additional specimens from these clusters were sequenced; all three had the B.1.351 variant and all sequences were closely related to the sequence from the index patient's specimen. Among the 17 patients identified, none reported recent international travel or contact with international travelers. Two patients, including the index patient, had received the first of a 2-dose COVID-19 vaccination series in the 2 weeks before their likely exposure; one additional patient had a confirmed SARS-CoV-2 infection 5 months before exposure. Two patients were hospitalized with COVID-19, and one died. These first identified linked clusters of B.1.351 infections in the United States with no apparent link to international travel highlight the importance of expanding the scope and volume of genetic surveillance programs to identify variants, completing contact investigations for SARS-CoV-2 infections, and using universal prevention strategies, including vaccination, masking, and physical distancing, to control the spread of variants of concern. |
Reaching "hard to reach" workers: Evaluating approaches to disseminate worker safety information via the Mexican consular network
Flynn MA , Eggerth DE , Keller BM , Check P . J Occup Environ Hyg 2021 18 1-17 Mexican immigrants suffer a disproportionately large number of work-related injuries and deaths given their share of the workforce. Barriers of language, culture, and mistrust are often cited as factors that complicate efforts to reach these workers with occupational safety and health (OSH) interventions. By partnering with the Mexican government and its consulate network in the United States, researchers from the National Institute for Occupational Safety and Health were able to assess the impact of four different information dissemination approaches (posters, passively distributed brochures, actively distributed brochures, and video kiosks) in Spanish in a five-phase study. Exit interviews conducted with Mexicans seeking consular services indicated that while nearly all respondents considered OSH to be of importance, significant differences in impact measures, such as noticing the materials and liking of content, were found when comparing the different approaches. Despite these differences, even the least effective approaches were noticed by large numbers of individuals and significantly increased their stated behavioral intentions regarding OSH. Considering all materials together, significantly more participants reported liking the materials (p < 0.001) than did not, learning something new (p < 0.01), trusting the information (p < 0.05), intending to seek out additional OSH information (p < 0.01), and intending to speak to their bosses about OSH (p < 0.05). These findings contribute to building an evidence base for moving research knowledge into practice, which is an essential, but often overlooked, element of occupational safety and health research, particularly among workers from underserved communities. |
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