Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 150 Records) |
Query Trace: Graham S [original query] |
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Personal journeys to and in human genetics and dysmorphology
Schwartz CE , Aylsworth AS , Allanson J , Battaglia A , Carey JC , Curry CJ , Davies KE , Eichler EE , Graham JM Jr , Hall B , Hall JG , Holmes LB , Hoyme HE , Hunter A , Innis J , Johnson J , Keppler-Noreuil KM , Leroy JG , Moore C , Nelson DL , Neri G , Opitz JM , Picketts D , Raymond FL , Shalev SA , Stevenson RE , Stumpel Ctrm , Sutherland G , Viskochil DH , Weaver DD , Zackai EH . Am J Med Genet A 2024 e63514 Genetics has become a critical component of medicine over the past five to six decades. Alongside genetics, a relatively new discipline, dysmorphology, has also begun to play an important role in providing critically important diagnoses to individuals and families. Both have become indispensable to unraveling rare diseases. Almost every medical specialty relies on individuals experienced in these specialties to provide diagnoses for patients who present themselves to other doctors. Additionally, both specialties have become reliant on molecular geneticists to identify genes associated with human disorders. Many of the medical geneticists, dysmorphologists, and molecular geneticists traveled a circuitous route before arriving at the position they occupied. The purpose of collecting the memoirs contained in this article was to convey to the reader that many of the individuals who contributed to the advancement of genetics and dysmorphology since the late 1960s/early 1970s traveled along a journey based on many chances taken, replying to the necessities they faced along the way before finding full enjoyment in the practice of medical and human genetics or dysmorphology. Additionally, and of equal importance, all exhibited an ability to evolve with their field of expertise as human genetics became human genomics with the development of novel technologies. |
State-specific prevalence of adult tobacco product use and cigarette smoking cessation behaviors, United States, 2018-2019
Cornelius ME , Wang TW , Jamal A , Loretan CG , Willis G , Graham-Glover B , Neff L . Prev Chronic Dis 2023 20 E107 INTRODUCTION: Increasing quitting among people who smoke cigarettes is the quickest approach to reducing tobacco-related disease and death. METHODS: We analyzed data from the 2018-2019 Tobacco Use Supplement to the Current Population Survey for 137,471 adult self-respondents from all 50 US states and the District of Columbia to estimate state-specific prevalence of current tobacco product use, interest in quitting smoking, past-year quit attempts, recent successful cessation (past-year quit lasting ≥6 months), receipt of advice to quit smoking from a medical doctor, and use of cessation medications and/or counseling to quit. RESULTS: Prevalence of current any-tobacco use (use every day or some days) ranged from 10.2% in California to 29.0% in West Virginia. The percentage of adults who currently smoked cigarettes and were interested in quitting ranged from 68.2% in Alabama to 87.5% in Connecticut; made a past-year quit attempt ranged from 44.1% in Tennessee to 62.8% in Rhode Island; reported recent successful cessation ranged from 4.6% in West Virginia and Wisconsin to 10.8% in South Dakota; received advice to quit from a medical doctor ranged from 63.3% in Colorado to 86.9% in Rhode Island; and used medications and/or counseling to quit ranged from 25.5% in Nevada to 50.1% in Massachusetts. Several states with the highest cigarette smoking prevalence reported the lowest prevalence of interest in quitting, quit attempts, receipt of advice to quit, and use of counseling and/or medication, and the highest prevalence of e-cigarette, smokeless tobacco, and cigar use. CONCLUSION: Adults who smoke struggle with smoking cessation and could benefit from additional intervention. |
Assessing the relationship between cyanobacterial blooms and respiratory-related hospital visits: Green bay, Wisconsin 2017-2019
Murray JF , Lavery AM , Schaeffer BA , Seegers BN , Pennington AF , Hilborn ED , Boerger S , Runkle JD , Loftin K , Graham J , Stumpf R , Koch A , Backer L . Int J Hyg Environ Health 2023 255 114272 Potential acute and chronic human health effects associated with exposure to cyanobacteria and cyanotoxins, including respiratory symptoms, are an understudied public health concern. We examined the relationship between estimated cyanobacteria biomass and the frequency of respiratory-related hospital visits for residents living near Green Bay, Lake Michigan, Wisconsin during 2017-2019. Remote sensing data from the Cyanobacteria Assessment Network was used to approximate cyanobacteria exposure through creation of a metric for cyanobacteria chlorophyll-a (Chl(BS)). We obtained counts of hospital visits for asthma, wheezing, and allergic rhinitis from the Wisconsin Hospital Association for ZIP codes within a 3-mile radius of Green Bay. We analyzed weekly counts of hospital visits versus cyanobacteria, which was modelled as a continuous measure (Chl(BS)) or categorized according to World Health Organization's (WHO) alert levels using Poisson generalized linear models. Our data included 2743 individual hospital visits and 114 weeks of satellite derived cyanobacteria biomass indicator data. Peak values of Chl(BS) were observed between the months of June and October. Using the WHO alert levels, 60% of weeks were categorized as no risk, 19% as Vigilance Level, 15% as Alert Level 1, and 6% as Alert Level 2. In Poisson regression models adjusted for temperature, dewpoint, season, and year, there was no association between Chl(BS) and hospital visits (rate ratio [RR] [95% Confidence Interval (CI)] = 0.98 [0.77, 1.24]). There was also no consistent association between WHO alert level and hospital visits when adjusting for covariates (Vigilance Level: RR [95% CI] 0.88 [0.74, 1.05], Alert Level 1: 0.82 [0.67, 0.99], Alert Level 2: 0.98 [0.77, 1.24], compared to the reference no risk category). Our methodology and model provide a template for future studies that assess the association between cyanobacterial blooms and respiratory health. |
Macrophage polarization status impacts nanoceria cellular distribution but not its biotransformation or ferritin effects
Graham UM , Dozier AK , Feola DJ , Tseng MT , Yokel RA . Nanomaterials (Basel) 2023 13 (16) The innate immune system is the first line of defense against external threats through the initiation and regulation of inflammation. Macrophage differentiation into functional phenotypes influences the fate of nanomaterials taken up by these immune cells. High-resolution electron microscopy was used to investigate the uptake, distribution, and biotransformation of nanoceria in human and murine M1 and M2 macrophages in unprecedented detail. We found that M1 and M2 macrophages internalize nanoceria differently. M1-type macrophages predominantly sequester nanoceria near the plasma membrane, whereas nanoceria are more uniformly distributed throughout M2 macrophage cytoplasm. In contrast, both macrophage phenotypes show identical nanoceria biotransformation to cerium phosphate nanoneedles and simultaneous nanoceria with ferritin co-precipitation within the cells. Ferritin biomineralization is a direct response to nanoparticle uptake inside both macrophage phenotypes. We also found that the same ferritin biomineralization mechanism occurs after the uptake of Ce-ions into polarized macrophages and into unpolarized human monocytes and murine RAW 264.7 cells. These findings emphasize the need for evaluating ferritin biomineralization in studies that involve the internalization of nano objects, ranging from particles to viruses to biomolecules, to gain greater mechanistic insights into the overall immune responses to nano objects. |
Peri-operative exposure to volatile organic compounds in neonates undergoing cardiac surgery
Gaynor JW , Graham EM , Bhandari D , Fenchel M , Bradman A , Klepczynski B , Collier H , Ittenbach RF , Reese CM , Blount BC . J Thorac Cardiovasc Surg 2023 OBJECTIVE: Volatile organic compounds (VOCs) are used in the sterilization and manufacture of medical equipment. These compounds have high vapor pressures with low water solubility and are emitted as gases from solids or liquids. They can be mutagenic, neurotoxic, genotoxic, and/or carcinogenic. Safe limits of exposure are not known for neonates. This study examined determinants of exposure in newborns undergoing cardiac surgery. METHODS: Twenty metabolites of 16 VOCs (e.g., xylene, cyanide, acrolein, acrylonitrile, N, N-dimethylformamide, 1,3-butadiene, styrene, and benzene) were measured as metabolites in daily urine samples collected from 10 neonates undergoing cardiac operations (n = 150 samples). Metabolites were quantified using reversed-phase ultra-high performance liquid chromatography and electrospray ionization tandem mass spectrometry. Repeated measures ANOVA was performed for each metabolite to examine associations with use of medical devices. RESULTS: At least 3 metabolites were detected in every sample. The median number of metabolites detected in each sample was 14 (range: 3-15). In a model controlling for other factors, the use of extracorporeal membrane oxygenation was associated with significantly (p ≤ 0.05) higher metabolite levels of acrolein, acrylonitrile, ethylene oxide, propylene oxide, styrene, and ethylbenzene. Patients breathing ambient air had higher levels of metabolites of acrolein, xylene, N,N-dimethylformamide, methyl isocyanate, cyanide, 1,3-butadiene (all p≤ 0.05). CONCLUSIONS: Exposure to volatile organic compounds is pervasive in newborns undergoing cardiac surgery. Sources of exposure likely include medical devices and inhalation from the air in the intensive care unit. The contribution of VOC exposure during cardiac surgery in newborns to adverse outcomes warrants further evaluation. |
An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 and multiple endemic, epidemic and bat coronavirus (preprint)
Sheahan TP , Sims AC , Zhou S , Graham RL , Hill CS , Leist SR , Schafer A , Dinnon KH 3rd , Montgomery SA , Agostini ML , Pruijssers AJ , Chappell JD , Brown AJ , Bluemling GR , Natchus MG , Saindane M , Kolykhalov AA , Painter G , Harcourt J , Tamin A , Thornburg NJ , Swanstrom R , Denison MR , Baric RS . bioRxiv 2020 2020.03.19.997890 Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2. Herein, we show that the ribonucleoside analog β-D-N4-hydroxycytidine (NHC, EIDD-1931) has broad spectrum antiviral activity against SARS-CoV 2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c Bat-CoVs, as well as increased potency against a coronavirus bearing resistance mutations to another nucleoside analog inhibitor. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC-prodrug (b-D-N4-hydroxycytidine-5’-isopropyl ester), improved pulmonary function, and reduced virus titer and body weight loss. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral but not host cell RNA, supporting a mechanism of lethal mutagenesis. The potency of NHC/EIDD-2801 against multiple coronaviruses, its therapeutic efficacy, and oral bioavailability in vivo, all highlight its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses. |
Intracellular diversity of WNV within circulating avian peripheral blood mononuclear cells reveals host-dependent patterns of polyinfection (preprint)
Frank DT , Byas AD , Murrieta R , Weger-Lucarelli J , Ruckert C , Gallichotte E , Yoshimoto JA , Allen C , Bosco-Lauth AM , Graham B , Felix TA , Brault A , Ebel GD . bioRxiv 2023 29 Error-prone replication of RNA viruses generates the genetic diversity required for adaptation within rapidly changing environments. Thus, arthropod-borne virus (arbovirus) populations exist in nature as mutant swarms that are maintained between arthropods and vertebrates. Previous studies have demonstrated that West Nile virus (WNV) population dynamics are host dependent: In American crows, which experience extremely high viremia, purifying selection is weak and population diversity is high compared to American robins, which have 100 to 1000-fold lower viremia. WNV passed in robins experiences fitness gains, whereas that passed in crows does not. Therefore, we tested the hypothesis that high crow viremia allows higher genetic diversity within individual avian peripheral-blood mononuclear cells (PBMCs), reasoning that this could have produced the previously observed host-specific differences in genetic diversity and fitness. Specifically, we infected cells and birds with a novel, barcoded version of WNV and sequenced viral RNA from single cells to quantify the number of WNV barcodes that each contained. Our results demonstrate that the richness of WNV populations within crows far exceeds that in robins. Similarly, rare WNV variants were maintained by crows more frequently than by robins. Our results suggest that increased viremia in crows relative to robins leads to maintenance of defective genomes and less prevalent variants, presumably through complementation. Our findings further suggest that weaker purifying selection in highly susceptible crows is attributable to this higher viremia, polyinfections and complementation. These studies further document the role of particular, ecologically relevant hosts in shaping virus population structure. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Intracellular diversity of WNV within circulating avian peripheral blood mononuclear cells reveals host-dependent patterns of polyinfection
Talmi-Frank D , Byas AD , Murrieta R , Weger-Lucarelli J , Rückert C , Gallichotte EN , Yoshimoto JA , Allen C , Bosco-Lauth AM , Graham B , Felix TA , Brault AC , Ebel GD . Pathogens 2023 12 (6) Arthropod-borne virus (arbovirus) populations exist as mutant swarms that are maintained between arthropods and vertebrates. West Nile virus (WNV) population dynamics are host-dependent. In American crows, purifying selection is weak and population diversity is high compared to American robins, which have 100- to 1000-fold lower viremia. WNV passed in robins leads to fitness gains, whereas that passed in crows does not. Therefore, we tested the hypothesis that high crow viremia allows for higher genetic diversity within individual avian peripheral blood mononuclear cells (PBMCs), reasoning that this could have produced the previously observed host-specific differences in genetic diversity and fitness. Specifically, we infected cells and birds with a molecularly barcoded WNV and sequenced viral RNA from single cells to quantify the number of WNV barcodes in each. Our results demonstrate that the richness of WNV populations within crows far exceeds that in robins. Similarly, rare WNV variants were maintained by crows more frequently than by robins. Our results suggest that increased viremia in crows relative to robins leads to the maintenance of defective genomes and less prevalent variants, presumably through complementation. Our findings further suggest that weaker purifying selection in highly susceptible crows is attributable to this higher viremia, polyinfections and complementation. |
Development of an international glossary for clinical guidelines collaboration
Christensen RE , Yi MD , Kang BY , Ibrahim SA , Anvery N , Dirr M , Adams S , Amer YS , Bisdorff A , Bradfield L , Brown S , Earley A , Fatheree LA , Fayoux P , Getchius T , Ginex P , Graham A , Green CR , Gresele P , Hanson H , Haynes N , Hegedüs L , Hussein H , Jakhmola P , Kantorova L , Krishnasamy R , Krist A , Landry G , Lease ED , Ley L , Marsden G , Meek T , Meremikwu M , Moga C , Mokrane S , Mujoomdar A , Newton S , O'Flynn N , Perkins GD , Smith EJ , Prematunge C , Rychert J , Saraco M , Schünemann HJ , Senerth E , Sinclair A , Shwayder J , Stec C , Tanni S , Taske N , Temple-Smolkin RL , Thomas L , Thomas S , Tonnessen B , Turner AS , Van Dam A , van Doormaal M , Wan YL , Ventura CB , McFarlane E , Morgan RL , Ogunremi T , Alam M . J Clin Epidemiol 2023 158 84-91 OBJECTIVE: Clinical practice guidelines are often created through collaboration among organizations. Use of inconsistent terminology may cause poor communication and delays. This study aimed to develop a glossary of terms related to collaboration in guideline development. STUDY DESIGN AND SETTING: A literature review of collaborative guidelines was performed to develop an initial list of terms related to guideline collaboration. The list of terms was presented to the members of the Guideline International Network Guidelines Collaboration Working Group, who provided presumptive definitions for each term and proposed additional terms to be included. The revised list was subsequently reviewed by an international, multidisciplinary panel of expert stakeholders. Recommendations received during this pre-Delphi review were implemented to augment an initial draft glossary. The glossary was then critically evaluated and refined through two rounds of Delphi surveys and a virtual consensus meeting with all panel members as Delphi participants. RESULTS: Forty-nine experts participated in the pre-Delphi survey and 44 participated in the two-round Delphi process. Consensus was reached for 37 terms and definitions. CONCLUSION: Uptake and utilization of this guideline collaboration glossary by key organizations and stakeholder groups may facilitate collaboration among guideline-producing organizations by improving communication, minimizing conflicts, and increasing guideline development efficiency. |
Development of treatment-decision algorithms for children evaluated for pulmonary tuberculosis: an individual participant data meta-analysis.
Gunasekera KS , Marcy O , Muñoz J , Lopez-Varela E , Sekadde MP , Franke MF , Bonnet M , Ahmed S , Amanullah F , Anwar A , Augusto O , Aurilio RB , Banu S , Batool I , Brands A , Cain KP , Carratalá-Castro L , Caws M , Click ES , Cranmer LM , García-Basteiro AL , Hesseling AC , Huynh J , Kabir S , Lecca L , Mandalakas A , Mavhunga F , Myint AA , Myo K , Nampijja D , Nicol MP , Orikiriza P , Palmer M , Sant'Anna CC , Siddiqui SA , Smith JP , Song R , Thuong Thuong NT , Ung V , van der Zalm MM , Verkuijl S , Viney K , Walters EG , Warren JL , Zar HJ , Marais BJ , Graham SM , Debray TPA , Cohen T , Seddon JA . Lancet Child Adolesc Health 2023 7 (5) 336-346 BACKGROUND: Many children with pulmonary tuberculosis remain undiagnosed and untreated with related high morbidity and mortality. Recent advances in childhood tuberculosis algorithm development have incorporated prediction modelling, but studies so far have been small and localised, with limited generalisability. We aimed to evaluate the performance of currently used diagnostic algorithms and to use prediction modelling to develop evidence-based algorithms to assist in tuberculosis treatment decision making for children presenting to primary health-care centres. METHODS: For this meta-analysis, we identified individual participant data from a WHO public call for data on the management of tuberculosis in children and adolescents and referral from childhood tuberculosis experts. We included studies that prospectively recruited consecutive participants younger than 10 years attending health-care centres in countries with a high tuberculosis incidence for clinical evaluation of pulmonary tuberculosis. We collated individual participant data including clinical, bacteriological, and radiological information and a standardised reference classification of pulmonary tuberculosis. Using this dataset, we first retrospectively evaluated the performance of several existing treatment-decision algorithms. We then used the data to develop two multivariable prediction models that included features used in clinical evaluation of pulmonary tuberculosis-one with chest x-ray features and one without-and we investigated each model's generalisability using internal-external cross-validation. The parameter coefficient estimates of the two models were scaled into two scoring systems to classify tuberculosis with a prespecified sensitivity target. The two scoring systems were used to develop two pragmatic, treatment-decision algorithms for use in primary health-care settings. FINDINGS: Of 4718 children from 13 studies from 12 countries, 1811 (38·4%) were classified as having pulmonary tuberculosis: 541 (29·9%) bacteriologically confirmed and 1270 (70·1%) unconfirmed. Existing treatment-decision algorithms had highly variable diagnostic performance. The scoring system derived from the prediction model that included clinical features and features from chest x-ray had a combined sensitivity of 0·86 [95% CI 0·68-0·94] and specificity of 0·37 [0·15-0·66] against a composite reference standard. The scoring system derived from the model that included only clinical features had a combined sensitivity of 0·84 [95% CI 0·66-0·93] and specificity of 0·30 [0·13-0·56] against a composite reference standard. The scoring system from each model was placed after triage steps, including assessment of illness acuity and risk of poor tuberculosis-related outcomes, to develop treatment-decision algorithms. INTERPRETATION: We adopted an evidence-based approach to develop pragmatic algorithms to guide tuberculosis treatment decisions in children, irrespective of the resources locally available. This approach will empower health workers in primary health-care settings with high tuberculosis incidence and limited resources to initiate tuberculosis treatment in children to improve access to care and reduce tuberculosis-related mortality. These algorithms have been included in the operational handbook accompanying the latest WHO guidelines on the management of tuberculosis in children and adolescents. Future prospective evaluation of algorithms, including those developed in this work, is necessary to investigate clinical performance. FUNDING: WHO, US National Institutes of Health. |
Insecticide resistance compromises the control of Aedes aegypti in Bangladesh.
Al-Amin HM , Gyawali N , Graham M , Alam MS , Lenhart A , Hugo LE , Rašić G , Beebe NW , Devine GJ . Pest Manag Sci 2023 79 (8) 2846-2861 BACKGROUND: With no effective drugs or widely available vaccines, dengue control in Bangladesh is dependent on targeting the primary vector Aedes aegypti with insecticides and larval source management. Despite these interventions, the dengue burden is increasing in Bangladesh, and the country experienced its worst outbreak in 2019 with 101,354 hospitalized cases. This may be partially facilitated by the presence of intense insecticide resistance in vector populations. Here, we describe the intensity and mechanisms of resistance to insecticides commonly deployed against Ae. aegypti in Dhaka, Bangladesh. RESULTS: Dhaka Ae. aegypti colonies exhibited high-intensity resistance to pyrethroids. Using CDC bottle assays, we recorded 2 - 24% mortality (recorded at 24 hours) to permethrin and 48 - 94% mortality to deltamethrin, at 10x the diagnostic dose. Bioassays conducted using insecticide-synergist combinations suggested that metabolic mechanisms were contributing to pyrethroid resistance, specifically multi-function oxidases, esterases, and glutathione S-transferases. In addition, kdr alleles were detected, with a high frequency (78-98%) of homozygotes for the V1016G mutation. A large proportion (≤ 74%) of free-flying and resting mosquitoes from Dhaka colonies survived exposure to standard applications of pyrethroid aerosols in an experimental free-flight room. Although that exposure affected Ae. aegypti's immediate host-seeking behavior, the effect was transient in surviving mosquitoes. CONCLUSION: The intense resistance characterized in this study is likely compromising the operational effectiveness of pyrethroids against Ae. aegypti in Dhaka. Switching to alternative chemical classes may offer a medium-term solution, but ultimately a more sustainable and effective approach to controlling dengue vectors is required. This article is protected by copyright. All rights reserved. |
Modeling infection from SARS-CoV-2 wastewater concentrations: promise, limitations, and future directions.
Soller J , Jennings W , Schoen M , Boehm A , Wigginton K , Gonzalez R , Graham KE , McBride G , Kirby A , Mattioli M . J Water Health 2022 20 (8) 1197-1211 Estimating total infection levels, including unreported and asymptomatic infections, is important for understanding community disease transmission. Wastewater can provide a pooled community sample to estimate total infections that is independent of case reporting biases toward individuals with moderate to severe symptoms and by test-seeking behavior and access. We derive three mechanistic models for estimating community infection levels from wastewater measurements based on a description of the processes that generate SARS-CoV-2 RNA signals in wastewater and accounting for the fecal strength of wastewater through endogenous microbial markers, daily flow, and per-capita wastewater generation estimates. The models are illustrated through two case studies of wastewater data collected during 2020-2021 in Virginia Beach, VA, and Santa Clara County, CA. Median simulated infection levels generally were higher than reported cases, but at times, were lower, suggesting a discrepancy between the reported cases and wastewater data, or inaccurate modeling results. Daily simulated infection estimates showed large ranges, in part due to dependence on highly variable clinical viral fecal shedding data. Overall, the wastewater-based mechanistic models are useful for normalization of wastewater measurements and for understanding wastewater-based surveillance data for public health decision-making but are currently limited by lack of robust SARS-CoV-2 fecal shedding data. |
Principles and procedures for assessment of acute toxicity incorporating in silico methods
Zwickl CM , Graham JC , Jolly RA , Bassan A , Ahlberg E , Amberg A , Anger LT , Beilke L , Bellion P , Brigo A , Burleigh-Flayer H , Cronin MTD , Devlin AA , Fish T , Glowienke S , Gromek K , Karmaus AL , Kemper R , Kulkarni S , Lo Piparo E , Madia F , Martin M , Masuda-Herrera M , McAtee BL , Mestres J , Milchak L , Moudgal C , Mumtaz M , Muster W , Neilson L , Patlewicz G , Paulino A , Roncaglioni A , Ruiz P , Szabo DT , Valentin JP , Vardakou I , Woolley D , Myatt GJ . Comput Toxicol 2022 24 Acute toxicity in silico models are being used to support an increasing number of application areas including (1) product research and development, (2) product approval and registration as well as (3) the transport, storage and handling of chemicals. The adoption of such models is being hindered, in part, because of a lack of guidance describing how to perform and document an in silico analysis. To address this issue, a framework for an acute toxicity hazard assessment is proposed. This framework combines results from different sources including in silico methods and in vitro or in vivo experiments. In silico methods that can assist the prediction of in vivo outcomes (i.e., LD50) are analyzed concluding that predictions obtained using in silico approaches are now well-suited for reliably supporting assessment of LD50-based acute toxicity for the purpose of the Globally Harmonized System (GHS) classification. A general overview is provided of the endpoints from in vitro studies commonly evaluated for predicting acute toxicity (e.g., cytotoxicity/cytolethality as well as assays targeting specific mechanisms). The increased understanding of pathways and key triggering mechanisms underlying toxicity and the increased availability of in vitro data allow for a shift away from assessments solely based on endpoints such as LD50, to mechanism-based endpoints that can be accurately assessed in vitro or by using in silico prediction models. This paper also highlights the importance of an expert review of all available information using weight-of-evidence considerations and illustrates, using a series of diverse practical use cases, how in silico approaches support the assessment of acute toxicity. © 2022 Elsevier B.V. |
Performance of Xpert MTB/RIF and mycobacterial culture on multiple specimen types for diagnosis of tuberculosis disease in young children and clinical characterization according to standardized research case definitions
Click ES , Song R , Smith JP , McHembere W , Fajans M , Hariri P , Okeyo E , McCarthy KD , Gethi D , Odeny L , Musau S , Okumu A , Orwa J , Perez-Velez CM , Wright CA , Andres MM , Marais BJ , Schaaf HS , Graham SM , Cruz AT , Cain KP . Pediatr Infect Dis J 2022 41 (8) 671-677 BACKGROUND: Tuberculosis (TB) is a leading cause of illness and death in children globally. Improved bacteriologic and clinical diagnostic approaches in children are urgently needed. METHODS: In a prospective cohort study, a consecutive series of young (<5 years) children presenting with symptoms suggestive of TB and parenchymal abnormality on chest radiograph in inpatient and outpatient settings in Kisumu County, Kenya from October 2013 to August 2015 were evaluated at baseline and over 6 months. Up to 14 specimens per child were tested for the Mycobacterium tuberculosis complex by fluorescence microscopy, Xpert MTB/RIF and mycobacterial culture. Using detailed clinical characterization, cases were retrospectively classified according to standardized research case definitions and the sensitivity and specificity of microbiological tests on different specimen types were determined. RESULTS: Among 300 young children enrolled, 266 had sufficient information to be classified according to the research clinical case definition. Of these, 36% (96/266) had TB disease; 32% (31/96) with bacteriologically confirmed intrathoracic TB. Compared to culture, the sensitivity of a single Xpert test ranged from 60 to 67% and specificity from 97.5 to 100% for different specimen types. CONCLUSIONS: Despite extensive specimen collection and laboratory testing, TB could not be bacteriologically confirmed in almost two-thirds of children with intrathoracic TB classified by research clinical case definitions. Improved diagnostic tests are needed to identify children with TB and to exclude other potential causes of illness. |
Proceedings From a National Heart, Lung, and Blood Institute and the Centers for Disease Control and Prevention Workshop to control hypertension
Commodore-Mensah Y , Loustalot F , Himmelfarb CD , Desvigne-Nickens P , Sachdev V , Bibbins-Domingo K , Clauser SB , Cohen DJ , Egan BM , Fendrick AM , Ferdinand KC , Goodman C , Graham GN , Jaffe MG , Krumholz HM , Levy PD , Mays GP , McNellis R , Muntner P , Ogedegbe G , Milani RV , Polgreen LA , Reisman L , Sanchez EJ , Sperling LS , Wall HK , Whitten L , Wright JT , Wright JS , Fine LJ . Am J Hypertens 2022 35 (3) 232-243 Hypertension treatment and control prevent more cardiovascular events than management of other modifiable risk factors. Although the age-adjusted proportion of US adults with controlled blood pressure (BP) defined as <140/90 mm Hg, improved from 31.8% in 1999-2000 to 48.5% in 2007-2008, it remained stable through 2013-2014 and declined to 43.7% in 2017-2018. To address the rapid decline in hypertension control, the National Heart, Lung, and Blood Institute and the Division for Heart Disease and Stroke Prevention of the Centers for Disease Control and Prevention convened a virtual workshop with multidisciplinary national experts. Also, the group sought to identify opportunities to reverse the adverse trend and further improve hypertension control. The workshop immediately preceded the Surgeon General's Call to Action to Control Hypertension, which recognized a stagnation in progress with hypertension control. The presentations and discussions included potential reasons for the decline and challenges in hypertension control, possible "big ideas," and multisector approaches that could reverse the current trend while addressing knowledge gaps and research priorities. The broad set of "big ideas" was comprised of various activities that may improve hypertension control, including: interventions to engage patients, promotion of self-measured BP monitoring with clinical support, supporting team-based care, implementing telehealth, enhancing community-clinical linkages, advancing precision population health, developing tailored public health messaging, simplifying hypertension treatment, using process and outcomes quality metrics to foster accountability and efficiency, improving access to high-quality health care, addressing social determinants of health, supporting cardiovascular public health and research, and lowering financial barriers to hypertension control. |
A multicenter analytical performance evaluation of a multiplexed immunoarray for the simultaneous measurement of biomarkers of micronutrient deficiency, inflammation and malarial antigenemia
Brindle E , Lillis L , Barney R , Bansil P , Hess SY , Wessells KR , Ouédraogo CT , Arredondo F , Barker MK , Craft NE , Fischer C , Graham JL , Havel PJ , Karakochuk CD , Zhang M , Mussai EX , Mapango C , Randolph JM , Wander K , Pfeiffer CM , Murphy E , Boyle DS . PLoS One 2021 16 (11) e0259509 A lack of comparative data across laboratories is often a barrier to the uptake and adoption of new technologies. Furthermore, data generated by different immunoassay methods may be incomparable due to a lack of harmonization. In this multicenter study, we describe validation experiments conducted in a single lab and cross-lab comparisons of assay results to assess the performance characteristics of the Q-plex™ 7-plex Human Micronutrient Array (7-plex), an immunoassay that simultaneously quantifies seven biomarkers associated with micronutrient (MN) deficiencies, inflammation and malarial antigenemia using plasma or serum; alpha-1-acid glycoprotein, C-reactive protein, ferritin, histidine-rich protein 2, retinol binding protein 4, soluble transferrin receptor, and thyroglobulin. Validations included repeated testing (n = 20 separately prepared experiments on 10 assay plates) in a single lab to assess precision and linearity. Seven independent laboratories tested 76 identical heparin plasma samples collected from a cohort of pregnant women in Niger using the same 7-plex assay to assess differences in results across laboratories. In the analytical validation experiments, intra- and inter-assay coefficients of variation were acceptable at <6% and <15% respectively and assay linearity was 96% to 99% with the exception of ferritin, which had marginal performance in some tests. Cross-laboratory comparisons showed generally good agreement between laboratories in all analyte results for the panel of 76 plasma specimens, with Lin's concordance correlation coefficient values averaging ≥0.8 for all analytes. Excluding plates that would fail routine quality control (QC) standards, the inter-assay variation was acceptable for all analytes except sTfR, which had an average inter-assay coefficient of variation of ≥20%. This initial cross-laboratory study demonstrates that the 7-plex test protocol can be implemented by users with some experience in immunoassay methods, but familiarity with the multiplexed protocol was not essential. |
Use of Cervid Serosurveys to Monitor Eastern Equine Encephalitis Virus Activity in Northern New England, United States, 2009-2017
Mutebi JP , Mathewson AA , Elias SP , Robinson S , Graham AC , Casey P , Lubelczyk CB . J Med Entomol 2021 59 (1) 49-55 Vertebrate surveillance for eastern equine encephalitis virus (EEEV) activity usually focuses on three types of vertebrates: horses, passerine birds, and sentinel chicken flocks. However, there is a variety of wild vertebrates that are exposed to EEEV infections and can be used to track EEEV activity. In 2009, we initiated a pilot study in northern New England, United States, to evaluate the effectiveness of using wild cervids (free-ranging white-tailed deer and moose) as spatial sentinels for EEEV activity. In Maine, New Hampshire, and Vermont during 2009-2017, we collected blood samples from hunter-harvested cervids at tagging stations and obtained harvest location information from hunters. U.S. Centers for Disease Control and Prevention processed the samples for EEEV antibodies using plaque reduction neutralization tests (PRNTs). We detected EEEV antibodies in 6 to 17% of cervid samples in the different states and mapped cervid EEEV seropositivity in northern New England. EEEV antibody-positive cervids were the first detections of EEEV activity in the state of Vermont, in northern Maine, and northern New Hampshire. Our key result was the detection of the antibodies in areas far outside the extent of documented wild bird, mosquito, human case, or veterinary case reports of EEEV activity in Maine, New Hampshire, and Vermont. These findings showed that cervid (deer and moose) serosurveys can be used to characterize the geographic extent of EEEV activity, especially in areas with low EEEV activity or with little or no EEEV surveillance. Cervid EEEV serosurveys can be a useful tool for mapping EEEV activity in areas of North America in addition to northern New England. |
Lake Michigan insights from island studies: the roles of chipmunks and coyotes in maintaining Ixodes scapularis and Borrelia burgdorferi in the absence of white-tailed deer
Sidge JL , Foster ES , Buttke DE , Hojgaard A , Graham CB , Tsao JI . Ticks Tick Borne Dis 2021 12 (5) 101761 Deer management (e.g., reduction) has been proposed as a tool to reduce the acarological risk of Lyme disease. There have been few opportunities to investigate Ixodes scapularis (blacklegged tick) and Borrelia burgdorferi sensu stricto dynamics in the absence of white-tailed deer (Odocoileus virginianus) in midwestern North America. A pair of islands in Lake Michigan presented a unique opportunity to study the role of alternative hosts for the adult stage of the blacklegged tick for maintaining a tick population as a deer herd exists on North Manitou Island but not on South Manitou Island, where coyotes (Canis latrans) and hares (Lepus americanus) are the dominant medium mammals. Additionally, we were able to investigate the maintenance of I. scapularis and B. burgdorferi in small mammal communities on both islands, which were dominated by eastern chipmunks (Tamias striatus). From 2011 to 2015, we surveyed both islands for blacklegged ticks by drag cloth sampling, bird mist netting, and small and medium-sized mammal trapping. We assayed questing ticks, on-host ticks, and mammal biopsies for the Lyme disease pathogen, B. burgdorferi. We detected all three life stages of the blacklegged tick on both islands. Of the medium mammals sampled, no snowshoe hares (Lepus americanus, 0/23) were parasitized by adult blacklegged ticks, but 2/2 coyotes (Canis latrans) sampled on South Manitou Island in 2014 were parasitized by adult blacklegged ticks, suggesting that coyotes played a role in maintaining the tick population in the absence of deer. We also detected I. scapularis ticks on passerine birds from both islands, providing support that birds contribute to maintaining as well as introducing blacklegged ticks and B. burgdorferi to the islands. We observed higher questing adult and nymphal tick densities, and higher B. burgdorferi infection prevalence in small mammals and in adult ticks on the island with deer as compared to the deer-free island. On the islands, we also found that 25% more chipmunks were tick-infested than mice, fed more larvae and nymphs relative to their proportional abundance compared to mice, and thus may play a larger role compared to mice in the maintenance of B. burgdorferi. Our investigation demonstrated that alternative hosts could maintain a local population of blacklegged ticks and an enzootic cycle of the Lyme disease bacterium in the absence of white-tailed deer. Thus, alternative adult blacklegged tick hosts should be considered when investigating deer-targeted management tools for reducing tick-borne disease risk, especially when the alternative host community may be abundant and diverse. |
Use of U.S. Blood Donors for National Serosurveillance of SARS-CoV-2 Antibodies: Basis for an Expanded National Donor Serosurveillance Program.
Stone M , Di Germanio C , Wright DJ , Sulaeman H , Dave H , Fink RV , Notari EP , Green V , Strauss D , Kessler D , Destree M , Saa P , Williamson PC , Simmons G , Stramer SL , Opsomer J , Jones JM , Kleinman S , Busch MP . Clin Infect Dis 2021 74 (5) 871-881 INTRODUCTION: The REDS-IV-P Epidemiology, Surveillance and Preparedness of the Novel SARS-CoV-2 Epidemic (RESPONSE) seroprevalence study conducted monthly cross-sectional testing for SARS-CoV-2 antibodies on blood donors in six U.S. metropolitan regions to estimate the extent of SARS-COV-2 infections over time. STUDY DESIGN/METHODS: During March-August 2020, approximately ≥1,000 serum specimens were collected monthly from each region and tested for SARS-CoV-2 antibodies using a well-validated algorithm. Regional seroprevalence estimates were weighted based on demographic differences with the general population. Seroprevalence was compared with reported COVID-19 case rates over time. RESULTS/FINDINGS: For all regions, seroprevalence was <1.0% in March 2020. New York experienced the biggest increase (peak seroprevalence, 15.8 % in May). All other regions experienced modest increases in seroprevalence(1-2% in May-June to 2-4% in July-August). Seroprevalence was higher in younger, non-Hispanic Black, and Hispanic donors. Temporal increases in donor seroprevalence correlated with reported case rates in each region. In August, 1.3-5.6 estimated cumulative infections (based on seroprevalence data) per COVID-19 case reported to CDC. CONCLUSION: Increases in seroprevalence were found in all regions, with the largest increase in New York. Seroprevalence was higher in non-Hispanic Black and Hispanic blood donors than in non-Hispanic White blood donors. SARS-CoV-2 antibody testing of blood donor samples can be used to estimate the seroprevalence in the general population by region and demographic group. The methods derived from the RESPONSE seroprevalence study served as the basis for expanding SARS-CoV-2 seroprevalence surveillance to all 50 states and Puerto Rico. |
Proposal for Human Respiratory Syncytial Virus Nomenclature below the Species Level.
Salimi V , Viegas M , Trento A , Agoti CN , Anderson LJ , Avadhanula V , Bahl J , Bont L , Brister JR , Cane PA , Galiano M , Graham BS , Hatcher EL , Hellferscee O , Henke DM , Hirve S , Jackson S , Keyaerts E , Kragten-Tabatabaie L , Lindstrom S , Nauwelaers I , Nokes DJ , Openshaw PJ , Peret TC , Piedra PA , Ramaekers K , Rector A , Trovão NS , von Gottberg A , Zambon M , Zhang W , Williams TC , Barr IG , Buchholz UJ . Emerg Infect Dis 2021 27 (6) 1-9 Human respiratory syncytial virus (HRSV) is the leading viral cause of serious pediatric respiratory disease, and lifelong reinfections are common. Its 2 major subgroups, A and B, exhibit some antigenic variability, enabling HRSV to circulate annually. Globally, research has increased the number of HRSV genomic sequences available. To ensure accurate molecular epidemiology analyses, we propose a uniform nomenclature for HRSV-positive samples and isolates, and HRSV sequences, namely: HRSV/subgroup identifier/geographic identifier/unique sequence identifier/year of sampling. We also propose a template for submitting associated metadata. Universal nomenclature would help researchers retrieve and analyze sequence data to better understand the evolution of this virus. |
Reported county-level distribution of Lyme disease spirochetes, Borrelia burgdorferi sensu stricto and Borrelia mayonii (Spirochaetales: Spirochaetaceae), in host-seeking Ixodes scapularis and Ixodes pacificus ticks (Acari: Ixodidae) in the contiguous United States
Fleshman AC , Graham CB , Maes SE , Foster E , Eisen RJ . J Med Entomol 2021 58 (3) 1219-1233 Lyme disease is the most common vector-borne disease in the United States. While Lyme disease vectors are widespread, high incidence states are concentrated in the Northeast, North Central and Mid-Atlantic regions. Mapping the distribution of Lyme disease spirochetes in ticks may aid in providing data-driven explanations of epidemiological trends and recommendations for targeting prevention strategies to communities at risk. We compiled data from the literature, publicly available tickborne pathogen surveillance databases, and internal CDC pathogen testing databases to map the county-level distribution of Lyme disease spirochetes reported in host-seeking Ixodes pacificus and Ixodes scapularis across the contiguous United States. We report B. burgdorferi s.s.-infected I. scapularis from 384 counties spanning 26 eastern states located primarily in the North Central, Northeastern, and Mid-Atlantic regions, and in I. pacificus from 20 counties spanning 2 western states, with most records reported from northern and north-coastal California. Borrelia mayonii was reported in I. scapularis in 10 counties in Minnesota and Wisconsin in the North Central United States, where records of B. burgdorferi s.s. were also reported. In comparison to a broad distribution of vector ticks, the resulting map shows a more limited distribution of Lyme disease spirochetes. |
Borrelia burgdorferi Sensu Stricto DNA in Field-Collected Haemaphysalis longicornis Ticks, Pennsylvania, United States.
Price KJ , Graham CB , Witmier BJ , Chapman HA , Coder BL , Boyer CN , Foster E , Maes SE , Bai Y , Eisen RJ , Kyle AD . Emerg Infect Dis 2021 27 (2) 608-611 We collected questing Haemaphysalis longicornis ticks from southeastern counties of Pennsylvania, USA. Of 263 ticks tested by PCR for pathogens, 1 adult female was positive for Borrelia burgdorferi sensu stricto, yielding a 0.4% infection rate. Continued monitoring of this invasive tick is essential to determine its public health role. |
Impact of community health promoters on awareness of a rural social marketing program, purchase and use of health products, and disease risk, Kenya, 20142016
Kim S , Laughlin M , Morris J , Otieno R , Odhiambo A , Oremo J , Graham J , Hirai M , Wells E , Basler C , Okello A , Matanock A , Eleveld A , Quick R . J Water Sanit Hyg Dev 2020 10 (4) 940-950 The Safe Water and AIDS Project (SWAP), a non-governmental organization in western Kenya, opened kiosks run as businesses by community health promoters (CHPs) to increase access to health products among poor rural families. We conducted a baseline survey in 2014 before kiosks opened, and a post-intervention follow-up in 2016, enrolling 1,517 households with children <18 months old. From baseline to follow-up, we observed increases in reported exposure to the SWAP program (311%, p = 0.01) and reported purchases of any SWAP product (310%, p < 0.01). The percent of households with confirmed water treatment (detectable free chlorine residual (FCR) >0.2 mg/ml) was similar from baseline to follow-up (7% vs. 8%, p = 0.57). The odds of reported diarrhea in children decreased from baseline to follow-up (odds ratios or OR: 0.77, 95% CI: 0.640.93) and households with detectable FCR had lower odds of diarrhea (OR: 0.53, 95% CI: 0.340.83). Focus group discussions with CHPs suggested that high product prices, lack of affordability, and expectations that products should be free contributed to low sales. In conclusion, modest reported increases in SWAP exposure and product sales in the target population were insufficient to impact health, but children in households confirmed to chlorinate their water had decreased diarrhea. |
Prevalence of single and coinfections of human pathogens in Ixodes ticks from five geographical regions in the United States, 2013-2019
Lehane A , Maes SE , Graham CB , Jones E , Delorey M , Eisen RJ . Ticks Tick Borne Dis 2020 12 (2) 101637 As the geographic distributions of medically important ticks and tick-borne pathogens continue to expand in the United States, the burden of tick-borne diseases continues to increase along with a growing risk of coinfections. Coinfection with multiple tick-borne pathogens may amplify severity of disease and complicate diagnosis and treatment. By testing 13,400 Ixodes ticks from 17 US states spanning five geographical regions for etiological agents of Lyme disease (Borrelia burgdorferi sensu stricto [s.s.] and Borrelia mayonii), Borrelia miyamotoi disease (Borrelia miyamotoi), anaplasmosis (Anaplasma phagocytophilum), and babesiosis (Babesia microti) we show that B. burgdorferi s.s. was the most prevalent and widespread pathogen. Borrelia miyamotoi, A. phagocytophilum, and B. microti were widespread but less prevalent than B. burgdorferi s.s. Coinfections with B. burgdorferi s.s. and A. phagocytophilum or B. microti were most common in the Northeast and occurred at rates higher than expected based on rates of single infections in that region. |
Adolescent dating violence prevention programmes: a global systematic review of evaluation studies
McNaughton Reyes HL , Graham LM , Chen MS , Baron D , Gibbs A , Groves AK , Kajula L , Bowler S , Maman S . Lancet Child Adolesc Health 2020 5 (3) 223-232 Adolescent dating violence negatively affects millions of young people worldwide. Through a global systematic review, we synthesised evidence from rigorous studies of prevention programmes for adolescent dating violence. Our aims were to: (1) describe the breadth of research in this area and evidence of programme effects, and (2) identify gaps in the evidence base. We included experimental and controlled quasi-experimental programme evaluations, published before Jan 1, 2020, that assessed effects on victimisation or perpetration, or both, in adolescent dating violence and in which at least half of the study population was 10-19 years old. Study design, programme elements, and outcomes were compared between evaluations implemented in high-income countries (HICs) and low-income and middle-income countries (LMICs). 52 evaluations met inclusion criteria, of which 20 (38%) were implemented in LMICs. Evaluations in HICs were more likely to assess effects on adolescent dating violence victimisation and perpetration, rather than just victimisation, than those in LMICs, and they were also more likely to include boys and girls, as opposed to just a single sex. Overall, 26 (50%) of the 52 evaluations reported a significant preventive effect on at least one outcome for adolescent dating violence, of which nine were implemented in LMICs. Across LMICs and HICs, findings suggest research is needed to shed light on how adolescent dating violence prevention programmes work and to identify whether programme effects generalise across different settings, outcomes, and subgroups. TRANSLATIONS: For the Chinese, French and Spanish translations of the abstract see Supplementary Materials section. |
Severe Acute Respiratory Syndrome Coronavirus 2 Prevalence, Seroprevalence, and Exposure among Evacuees from Wuhan, China, 2020.
Hallowell BD , Carlson CM , Jacobs JR , Pomeroy M , Steinberg J , Tenforde MW , McDonald E , Foster L , Feldstein LR , Rolfes MA , Haynes A , Abedi GR , Odongo GS , Saruwatari K , Rider EC , Douville G , Bhakta N , Maniatis P , Lindstrom S , Thornburg NJ , Lu X , Whitaker BL , Kamili S , Sakthivel SK , Wang L , Malapati L , Murray JR , Lynch B , Cetron M , Brown C , Roohi S , Rotz L , Borntrager D , Ishii K , Moser K , Rasheed M , Freeman B , Lester S , Corbett KS , Abiona OM , Hutchinson GB , Graham BS , Pesik N , Mahon B , Braden C , Behravesh CB , Stewart R , Knight N , Hall AJ , Killerby ME . Emerg Infect Dis 2020 26 (9) 1998-2004 To determine prevalence of, seroprevalence of, and potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among a cohort of evacuees returning to the United States from Wuhan, China, in January 2020, we conducted a cross-sectional study of quarantined evacuees from 1 repatriation flight. Overall, 193 of 195 evacuees completed exposure surveys and submitted upper respiratory or serum specimens or both at arrival in the United States. Nearly all evacuees had taken preventive measures to limit potential exposure while in Wuhan, and none had detectable SARS-CoV-2 in upper respiratory tract specimens, suggesting the absence of asymptomatic respiratory shedding among this group at the time of testing. Evidence of antibodies to SARS-CoV-2 was detected in 1 evacuee, who reported experiencing no symptoms or high-risk exposures in the previous 2 months. These findings demonstrated that this group of evacuees posed a low risk of introducing SARS-CoV-2 to the United States. |
Metabolic response in patients with post-treatment Lyme disease symptoms/syndrome
Fitzgerald BL , Graham B , Delorey MJ , Pegalajar-Jurado A , Islam MN , Wormser GP , Aucott JN , Rebman AW , Soloski MJ , Belisle JT , Molins CR . Clin Infect Dis 2020 73 (7) e2342-e2349 BACKGROUND: Post-treatment Lyme disease symptoms/syndrome (PTLDS) occurs in approximately 10% of Lyme disease patients following antibiotic treatment. Biomarkers or specific clinical symptoms to identify PTLDS patients do not currently exist and the PTLDS classification is based on the report of persistent, subjective symptoms for ≥ 6 months following antibiotic treatment for Lyme disease. METHODS: Untargeted liquid chromatography-mass spectrometry metabolomics was used to determine longitudinal metabolic responses and biosignatures in PTLDS and clinically cured non-PTLDS Lyme patients. Evaluation of biosignatures included: 1) defining altered classes of metabolites; 2) elastic net regularization to define metabolites that most strongly defined PTLDS and non-PTLDS patients at different timepoints; 3) changes in the longitudinal abundance of metabolites; 4) linear discriminant analysis to evaluate robustness in a second patient cohort. RESULTS: This study determined that observable metabolic differences exist between PTLDS and non-PTLDS patients at multiple timepoints. The metabolites with differential abundance included those from glycerophospholipid, bile acid and acylcarnitine metabolism. Distinct longitudinal patterns of metabolite abundance indicated a greater metabolic variability in PTLDS vs non-PTLDS patients. Small numbers of metabolites (6-40) could be used to define PTLDS vs. non-PTLDS patients at defined time points, and the findings were validated in a second cohort of PTLDS and non-PTLDS patients. CONCLUSIONS: These data provide evidence that an objective metabolite-based measurement can distinguish patients with PTLDS and help understand the underlying biochemistry of PTLDS. |
Enrolment characteristics associated with retention among HIV negative Kenyan gay, bisexual and other men who have sex with men enrolled in the Anza Mapema cohort study
Kunzweiler C , Bailey RC , Okall DO , Graham SM , Mehta SD , Otieno-Nyunya B , Djomand G , Otieno FO . J Int AIDS Soc 2020 23 Suppl 6 e25598 INTRODUCTION: Most gay, bisexual and other men who have sex with men (GBMSM) live in rights-constrained environments making retaining them in research to be as hard as recruiting them. To evaluate Anza Mapema, an HIV risk-reduction programme in Kisumu, Kenya, we examined the enrolment sociodemographic, behavioural, psychosocial and clinical factors associated with missing two or more follow-up visits for GBMSM participating in Anza Mapema. METHODS: Between August 2015 and November 2017, GBMSM were enrolled and followed in a prospective cohort study with quarterly visits over 12 months. At enrolment, men were tested for HIV and sexually transmitted infections and completed questionnaires via audio computer-assisted self-interview. Because the Kenya Ministry of Health recommends HIV testing every three to six months for GBMSM, the retention outcome in this cross sectional analysis was defined as missing two consecutive follow-up visits (vs. not missing two or more consecutive visits). Multivariable logistic regression estimated the adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the associations of the enrolment characteristics with the binary outcome of retention. RESULTS AND DISCUSSION: Among 609 enrolled HIV-negative GBMSM, the median age was 23 years (interquartile range, 21 to 28 years), 19.0% had completed ≤8 years of education and 4.1% had resided in the study area <1 year at enrolment. After enrolment, 19.7% missed two consecutive follow-up visits. In the final multivariable model, the odds of missing two consecutive follow-up visits were higher for men who: resided in the study area <1 year at enrolment (aOR, 4.14; 95% CI: 1.77 to 9.68), were not living with a male sexual partner (aOR, 1.59; 95% CI: 1.01 to 2.50), and engaged in transactional sex during the last three months (aOR, 1.70; 95% CI: 1.08 to 2.67). CONCLUSIONS: One in five men missed two consecutive follow-up visits during this HIV prevention study despite intensive retention efforts and compensation for travel and participation. Participants with recent community arrival may require special support to optimize their retention in HIV prevention activities. Live-in partners of participants may be enlisted to support greater engagement in prevention programmes, and men who engage in transactional sex will need enhanced counselling and support to stay in longitudinal studies. |
Exportation of Monkeypox virus from the African continent.
Mauldin MR , McCollum AM , Nakazawa YJ , Mandra A , Whitehouse ER , Davidson W , Zhao H , Gao J , Li Y , Doty J , Yinka-Ogunleye A , Akinpelu A , Aruna O , Naidoo D , Lewandowski K , Afrough B , Graham V , Aarons E , Hewson R , Vipond R , Dunning J , Chand M , Brown C , Cohen-Gihon I , Erez N , Shifman O , Israeli O , Sharon M , Schwartz E , Beth-Din A , Zvi A , Mak TM , Ng YK , Cui L , Lin RTP , Olson VA , Brooks T , Paran N , Ihekweazu C , Reynolds MG . J Infect Dis 2020 225 (8) 1367-1376 BACKGROUND: The largest West African monkeypox outbreak began September 2017, in Nigeria. Four individuals traveling from Nigeria to the UK (2), Israel, and Singapore became the first human monkeypox cases exported from Africa, and a related nosocomial transmission event in the UK became the first confirmed human-to-human monkeypox transmission event outside of Africa. METHODS: Epidemiological and molecular data for exported and Nigerian cases were analyzed jointly to better understand the exportations in the temporal and geographic context of the outbreak. RESULTS: Isolates from all travelers and a Bayelsa case shared a most recent common ancestor and traveled to Bayelsa, Delta, or Rivers states. Genetic variation for this cluster was lower than would be expected from a random sampling of genomes from this outbreak, but data did not support direct links between travelers. CONCLUSIONS: Monophyly of exportation cases and the Bayelsa sample, along with the intermediate levels of genetic variation suggest a small pool of related isolates is the likely source for the exported infections. This may be the result of the level of genetic variation present in monkeypox isolates circulating within the contiguous region of Bayelsa, Delta, and Rivers states, or another more restricted, yet unidentified source pool. |
Evaluation of a health information exchange system for microcephaly case-finding - New York City, 2013-2015
Poirot E , Mills CW , Fair AD , Graham KA , Martinez E , Schreibstein L , Talati A , McVeigh KH . PLoS One 2020 15 (8) e0237392 BACKGROUND: Birth defects surveillance in the United States is conducted principally by review of routine but lagged reporting to statewide congenital malformations registries of diagnoses by hospitals or other health care providers, a process that is not designed to rapidly detect changes in prevalence. Health information exchange (HIE) systems are well suited for rapid surveillance, but information is limited about their effectiveness at detecting birth defects. We evaluated HIE data to detect microcephaly diagnosed at birth during January 1, 2013-December 31, 2015 before known introduction of Zika virus in North America. METHODS: Data from an HIE system were queried for microcephaly diagnostic codes on day of birth or during the first two days after birth at three Bronx hospitals for births to New York City resident mothers. Suspected cases identified by HIE data were compared with microcephaly cases that had been identified through direct inquiry of hospital records and confirmed by chart abstraction in a previous study of the same cohort. RESULTS: Of 16,910 live births, 43 suspected microcephaly cases were identified through an HIE system compared to 67 confirmed cases that had been identified as part of the prior study. A total of 39 confirmed cases were found by both studies (sensitivity = 58.21%, 95% CI: 45.52-70.15%; positive predictive value = 90.70%, 95% CI: 77.86-97.41%; negative predictive value = 99.83%, 95% CI: 99.76-99.89% for HIE data). CONCLUSION: Despite limitations, HIE systems could be used for rapid newborn microcephaly surveillance, especially in the many jurisdictions where more labor-intensive approaches are not feasible. Future work is needed to improve electronic medical record documentation quality to improve sensitivity and reduce misclassification. |
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