Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-30 (of 52 Records) |
Query Trace: Fitzpatrick K[original query] |
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Heterogeneity in measures of illness among patients with myalgic encephalomyelitis/chronic fatigue syndrome is not explained by clinical practice: A study in seven U.S. Specialty clinics
Unger ER , Lin JMS , Chen Y , Cornelius ME , Helton B , Issa AN , Bertolli J , Klimas NG , Balbin EG , Bateman L , Lapp CW , Springs W , Podell RN , Fitzpatrick T , Peterson DL , Gottschalk CG , Natelson BH , Blate M , Kogelnik AM , Phan CC . J Clin Med 2024 13 (5) Background: One of the goals of the Multi-site Clinical Assessment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (MCAM) study was to evaluate whether clinicians experienced in diagnosing and caring for patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) recognized the same clinical entity. Methods: We enrolled participants from seven specialty clinics in the United States. We used baseline data (n = 465) on standardized questions measuring general clinical characteristics, functional impairment, post-exertional malaise, fatigue, sleep, neurocognitive/autonomic symptoms, pain, and other symptoms to evaluate whether patient characteristics differed by clinic. Results: We found few statistically significant and no clinically significant differences between clinics in their patients’ standardized measures of ME/CFS symptoms and function. Strikingly, patients in each clinic sample and overall showed a wide distribution in all scores and measures. Conclusions: Illness heterogeneity may be an inherent feature of ME/CFS. Presenting research data in scatter plots or histograms will help clarify the challenge. Relying on case–control study designs without subgrouping or stratification of ME/CFS illness characteristics may limit the reproducibility of research findings and could obscure underlying mechanisms. © 2024 by the authors. |
Estimates of incidence and predictors of fatiguing illness after SARS-CoV-2 infection
Vu QM , Fitzpatrick AL , Cope JR , Bertolli J , Sotoodehnia N , West TE , Gentile N , Unger ER . Emerg Infect Dis 2024 30 (3) 539-547 This study aimed to estimate the incidence rates of post-COVID-19 fatigue and chronic fatigue and to quantify the additional incident fatigue caused by COVID-19. We analyzed electronic health records data of 4,589 patients with confirmed COVID-19 during February 2020-February 2021 who were followed for a median of 11.4 (interquartile range 7.8-15.5) months and compared them to data from 9,022 propensity score-matched non-COVID-19 controls. Among COVID-19 patients (15% hospitalized for acute COVID-19), the incidence rate of fatigue was 10.2/100 person-years and the rate of chronic fatigue was 1.8/100 person-years. Compared with non-COVID-19 controls, the hazard ratios were 1.68 (95% CI 1.48-1.92) for fatigue and 4.32 (95% CI 2.90-6.43) for chronic fatigue. The observed association between COVID-19 and the significant increase in the incidence of fatigue and chronic fatigue reinforces the need for public health actions to prevent SARS-CoV-2 infections. |
Developing a cognitive assessment toolkit for primary care: qualitative assessment of providers' needs and perceptions of usability in clinical practice
Suchsland MZ , Gaster B , Raetz J , Belza B , McGuire L , Olivari B , Tracy K , Fitzpatrick AL . BMC Health Serv Res 2023 23 (1) 1006 BACKGROUND: Burden of dementia is expected to substantially increase. Early dementia is underdiagnosed in primary care. Given the benefits of active management of dementia, earlier detection in primary care is imperative. The aim of this study was to understand primary care provider (PCP) perceptions of implementing a cognitive assessment toolkit in primary care. METHODS: PCPs in a large health system in the US were recruited to a qualitative study utilizing semi-structured interviews. Interviews captured provider perceptions of options for implementing a cognitive assessment toolkit derived from the Gerontological Society of America (GSA) KAER (Kickstart, Assess, Evaluate, Refer) toolkit, including a workflow and adapted clinical tools. A content analysis approach distinguished themes and exemplary quotes. RESULTS: Ten PCPs were interviewed. They found the toolkit useful, felt the term Kickstart was not specific to dementia care, and stressed that addressing cognitive evaluation would need to be easy to implement in a clinical workflow. Finally, providers knew many resources for referral but were unsure how to help patients navigate options. CONCLUSIONS: Providers stressed simplicity, ease, and efficiency for implementation of a cognitive assessment toolkit. Incorporating these findings into the development of clinical tools and workflows may increase cognitive evaluations conducted by PCPs. |
Transmission of yellow fever vaccine virus through blood transfusion and organ transplantation in the USA in 2021: Report of an investigation
Gould CV , Free RJ , Bhatnagar J , Soto RA , Royer TL , Maley WR , Moss S , Berk MA , Craig-Shapiro R , Kodiyanplakkal RPL , Westblade LF , Muthukumar T , Puius YA , Raina A , Hadi A , Gyure KA , Trief D , Pereira M , Kuehnert MJ , Ballen V , Kessler DA , Dailey K , Omura C , Doan T , Miller S , Wilson MR , Lehman JA , Ritter JM , Lee E , Silva-Flannery L , Reagan-Steiner S , Velez JO , Laven JJ , Fitzpatrick KA , Panella A , Davis EH , Hughes HR , Brault AC , St George K , Dean AB , Ackelsberg J , Basavaraju SV , Chiu CY , Staples JE . Lancet Microbe 2023 4 (9) e711-e721 BACKGROUND: In 2021, four patients who had received solid organ transplants in the USA developed encephalitis beginning 2-6 weeks after transplantation from a common organ donor. We describe an investigation into the cause of encephalitis in these patients. METHODS: From Nov 7, 2021, to Feb 24, 2022, we conducted a public health investigation involving 15 agencies and medical centres in the USA. We tested various specimens (blood, cerebrospinal fluid, intraocular fluid, serum, and tissues) from the organ donor and recipients by serology, RT-PCR, immunohistochemistry, metagenomic next-generation sequencing, and host gene expression, and conducted a traceback of blood transfusions received by the organ donor. FINDINGS: We identified one read from yellow fever virus in cerebrospinal fluid from the recipient of a kidney using metagenomic next-generation sequencing. Recent infection with yellow fever virus was confirmed in all four organ recipients by identification of yellow fever virus RNA consistent with the 17D vaccine strain in brain tissue from one recipient and seroconversion after transplantation in three recipients. Two patients recovered and two patients had no neurological recovery and died. 3 days before organ procurement, the organ donor received a blood transfusion from a donor who had received a yellow fever vaccine 6 days before blood donation. INTERPRETATION: This investigation substantiates the use of metagenomic next-generation sequencing for the broad-based detection of rare or unexpected pathogens. Health-care workers providing vaccinations should inform patients of the need to defer blood donation for at least 2 weeks after receiving a yellow fever vaccine. Despite mitigation strategies and safety interventions, a low risk of transfusion-transmitted infections remains. FUNDING: US Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority, and the CDC Epidemiology and Laboratory Capacity Cooperative Agreement for Infectious Diseases. |
Notes From the Field: First evidence of locally acquired dengue virus infection - Maricopa County, Arizona, November 2022
Kretschmer M , Collins J , Dale AP , Garrett B , Koski L , Zabel K , Staab RN , Turnbow K , Nativio J , Andrews K , Smith WE , Townsend J , Busser N , Will J , Burr K , Jones FK , Santiago GA , Fitzpatrick KA , Ruberto I , Fitzpatrick K , White JR , Adams L , Sunenshine RH . MMWR Morb Mortal Wkly Rep 2023 72 (11) 290-291 On November 7, 2022, dengue virus (DENV), which is not endemic in the continental United States (1), was identified in a Maricopa County, Arizona resident by reverse transcription–polymerase chain reaction (RT-PCR) testing at Arizona State Public Health Laboratory (ASPHL). The patient (patient A) was admitted to a hospital on October 19 for a dengue-like illness, 7 days after traveling to and remaining in Mexicali, Mexico for <4 hours. Patient A was hospitalized for 3 days and subsequently recovered. Maricopa County Environmental Services Department (MCESD) conducted retrospective testing for DENV in samples collected from 21 mosquito pools located within 5 miles (8 km) of patient A’s residence during October 1–November 3. A sample collected from one mosquito pool (pool A) on October 5 was positive for DENV. Whole genome sequencing by CDC’s Dengue Branch later revealed that closely related DENV-3 strains not known to be circulating in the patient’s travel region were identified in both patient A and pool A, suggesting local DENV transmission. |
Increase in Colorado tick fever virus disease cases and effect of COVID-19 pandemic on behaviors and testing practices, Montana, 2020
Soto RA , Baldry E , Vahey GM , Lehman J , Silver M , Panella A , Brault AC , Hughes HR , Fitzpatrick KA , Velez J , Biggerstaff BJ , Wolff B , Randolph J , Ruth LJ , Staples JE , Gould CV . Emerg Infect Dis 2023 29 (3) 561-568 In 2020, Montana, USA, reported a large increase in Colorado tick fever (CTF) cases. To investigate potential causes of the increase, we conducted a case-control study of Montana residents who tested positive or negative for CTF during 2020, assessed healthcare providers' CTF awareness and testing practices, and reviewed CTF testing methods. Case-patients reported more time recreating outdoors on weekends, and all reported finding a tick on themselves before illness. No consistent changes were identified in provider practices. Previously, only CTF serologic testing was used in Montana. In 2020, because of SARS-CoV-2 testing needs, the state laboratory sent specimens for CTF testing to the Centers for Disease Control and Prevention, where more sensitive molecular methods are used. This change in testing probably increased the number of CTF cases detected. Molecular testing is optimal for CTF diagnosis during acute illness. Tick bite prevention measures should continue to be advised for persons doing outdoor activities. |
Japanese encephalitis in a U.S. traveler returning from Vietnam, 2022
Janatpour ZC , Boatwright MA , Yousif SM , Bonilla MF , Fitzpatrick KA , Hills SL , Decker CF . Travel Med Infect Dis 2023 52 102536 Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus which is endemic throughout most of Asia and parts of the Western Pacific [1,2]. Since the availability of a JE vaccine in the United States (U.S.) in 1993, a total of 13 JE cases in U.S. travelers or expatriates have been reported [[3], [4], [5], [6]]. We describe a case of severe JE in an unvaccinated returning traveler. | | A 37-year-old woman presented to Cleveland Clinic in Abu Dhabi, United Arab Emirates with 4 days of headache, fever and confusion. The patient is a U.S. citizen and had been living in Abu Dhabi for the past 2 years. She had returned from a 2-week vacation to Vietnam, where she primarily stayed in urban locales. However, she did participate in a 2-day hike within the Sa Pa region of Northern Vietnam, where she stayed in unscreened lodging and sustained multiple mosquito bites despite using preventive measures. She had not received the JE vaccine prior to travel. Her symptoms began while still in country on day 13 of the 14-day trip. |
Association of asthma with treatments and outcomes in children with critical influenza
Maddux AB , Grunwell JR , Newhams MM , Chen SR , Olson SM , Halasa NB , Weiss SL , Coates BM , Schuster JE , Hall MW , Nofziger RA , Flori HR , Gertz SJ , Kong M , Sanders RCJr , Irby K , Hume JR , Cullimore ML , Shein SL , Thomas NJ , Miller K , Patel M , Fitzpatrick AM , Phipatanakul W , Randolph AG . J Allergy Clin Immunol Pract 2022 11 (3) 836-843 e3 BACKGROUND: Hospitalization for severe influenza infection in childhood may result in post-discharge sequelae. OBJECTIVE(S): To evaluate inpatient management and post-discharge sequelae in children with critical respiratory illness due to influenza with or without pre-existing asthma. METHODS: Prospective, observational multicenter study of children (8-months to 17-years-old) admitted to a pediatric intensive care or high-acuity unit (11/2019-4/2020) for influenza. Results were stratified by pre-existing asthma. Pre-hospital status, hospital treatments and outcomes were collected. Surveys at approximately 90 days post-discharge evaluated post-discharge health resource use, functional status, and respiratory symptoms. RESULTS: 165 children with influenza: 56 (33.9%) with and 109 (66.1%) without pre-existing asthma (41.1% and 39.4% fully vaccinated against influenza, respectively). Fifteen (26.7%) patients with and 34 (31.1%) without pre-existing asthma were intubated. More patients with versus without pre-existing asthma received pharmacologic asthma treatments during hospitalization (76.7% vs 28.4%). Of 136 (82.4%) patients with 90-day survey data (46 [33.8%] with and 90 [66.1%] without pre-existing asthma), a similar proportion had an Emergency Department/urgent care visit (4.3%, 6.6%) or hospital readmission (8.6%, 3.3%) for a respiratory condition. Patients with pre-existing asthma more frequently experienced asthma symptoms (78.2% vs 3.3%) and had respiratory specialist visits (52% vs 20%) post-discharge. Ten of 109 (11.1%) patients without pre-existing asthma reported being newly diagnosed with asthma. CONCLUSIONS: Respiratory health resource use and symptoms are important post-discharge outcomes after influenza critical illness in children with and without pre-existing asthma. Less than half of children were vaccinated for influenza, a tool that could mitigate critical illness and its sequelae. |
Transfusion-Transmitted Cache Valley Virus Infection in a Kidney Transplant Recipient with Meningoencephalitis.
Al-Heeti O , Wu EL , Ison MG , Saluja RK , Ramsey G , Matkovic E , Ha K , Hall S , Banach B , Wilson MR , Miller S , Chiu CY , McCabe M , Bari C , Zimler RA , Babiker H , Freeman D , Popovitch J , Annambhotla P , Lehman JA , Fitzpatrick K , Velez JO , Davis EH , Hughes HR , Panella A , Brault A , Erin Staples J , Gould CV , Tanna S . Clin Infect Dis 2022 76 (3) e1320-e1327 BACKGROUND: Cache Valley virus (CVV) is a mosquito-borne virus that is a rare cause of disease in humans. In the Fall of 2020, a patient developed encephalitis six weeks following kidney transplantation and receipt of multiple blood transfusions. METHODS: After ruling out more common etiologies, metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) was performed. We reviewed the medical histories of the index kidney recipient, organ donor, and recipients of other organs from the same donor and conducted a blood traceback investigation to evaluate blood transfusion as a possible source of infection in the kidney recipient. We tested patient specimens by reverse transcription-polymerase chain reaction (RT-PCR), plaque reduction neutralization test (PRNT), cell culture, and whole genome sequencing. RESULTS: CVV was detected in CSF from the index patient by mNGS, and this result was confirmed by RT-PCR, viral culture, and additional whole genome sequencing. The organ donor and other organ recipients had no evidence of infection with CVV by molecular or serologic testing. Neutralizing antibodies against CVV were detected in serum from a donor of red blood cells received by the index patient immediately prior to transplant. CVV neutralizing antibodies were also detected in serum from a patient who received the co-component plasma from the same blood donation. CONCLUSION: Our investigation demonstrates probable CVV transmission through blood transfusion. Clinicians should consider arboviral infections in unexplained meningoencephalitis after blood transfusion or organ transplantation. The use of mNGS testing might facilitate detection of rare, unexpected infections, particularly in immunocompromised patients. |
An Examination of SARS-CoV-2 Transmission Based on Classroom Distancing in Schools With Other Preventive Measures in Place-Missouri, January-March 2021.
Donovan CV , Worrell MC , Steinberg J , Montgomery BK , Young R , Richardson G , Dawson P , Dinh TH , Botkin N , Fitzpatrick T , Fields A , Rains CM , Fritz S , Malone S , Tong S , Mooney J , Newland JG , Barrios LC , Neatherlin JC , Salzer JS . Public Health Rep 2022 137 (5) 333549221109003 OBJECTIVES: Classroom layout plays a central role in maintaining physical distancing as part of a multicomponent prevention strategy for safe in-person learning during the COVID-19 pandemic. We conducted a school investigation to assess layouts and physical distancing in classroom settings with and without in-school SARS-CoV-2 transmission. METHODS: We assessed, measured, and mapped 90 K-12 (kindergarten through grade 12) classrooms in 3 Missouri public school districts during January-March 2021, prior to widespread prevalence of the Delta variant; distances between students, teachers, and people with COVID-19 and their contacts were analyzed. We used whole-genome sequencing to further evaluate potential transmission events. RESULTS: The investigation evaluated the classrooms of 34 students and staff members who were potentially infectious with COVID-19 in a classroom. Of 42 close contacts (15 tested) who sat within 3 ft of possibly infectious people, 1 (2%) probable transmission event occurred (from a symptomatic student with a longer exposure period [5 days]); of 122 contacts (23 tested) who sat more than 3 ft away from possibly infectious people with shorter exposure periods, no transmission events occurred. CONCLUSIONS: Reduced student physical distancing is one component of mitigation strategies that can allow for increased classroom capacity and support in-person learning. In the pre-Delta variant period, limited physical distancing (<6 ft) among students in K-12 schools was not associated with increased SARS-CoV-2 transmission. |
Qualitative evaluation of enabling factors and barriers to the success and sustainability of national public health institutes in Cambodia, Colombia, Liberia, Mozambique, Nigeria, Rwanda and Zambia
Woldetsadik MA , Bratton S , Fitzpatrick K , Ravat F , Del Castillo L , McIntosh KJ , Jarvis D , Carnevale CR , Cassell CH , Chhea C , Prieto Alvarado F , MaCauley J , Jani I , Ilori E , Nsanzimana S , Mukonka VM , Baggett HC . BMJ Open 2022 12 (4) e056767 OBJECTIVES: The success of National Public Health Institutes (NPHIs) in low-income and middle-income countries (LMICs) is critical to countries' ability to deliver public health services to their populations and effectively respond to public health emergencies. However, empirical data are limited on factors that promote or are barriers to the sustainability of NPHIs. This evaluation explored stakeholders' perceptions about enabling factors and barriers to the success and sustainability of NPHIs in seven countries where the U.S. Centers for Disease Control and Prevention (CDC) has supported NPHI development and strengthening. DESIGN: Qualitative study. SETTING: Cambodia, Colombia, Liberia, Mozambique, Nigeria, Rwanda and Zambia. PARTICIPANTS: NPHI staff, non-NPHI government staff, and non-governmental and international organisation staff. METHODS: We conducted semistructured, in-person interviews at a location chosen by the participants in the seven countries. We analysed data using a directed content analysis approach. RESULTS: We interviewed 43 NPHI staff, 29 non-NPHI government staff and 24 staff from non-governmental and international organisations. Participants identified five enabling factors critical to the success and sustainability of NPHIs: (1) strong leadership, (2) financial autonomy, (3) political commitment and country ownership, (4) strengthening capacity of NPHI staff and (5) forming strategic partnerships. Three themes emerged related to major barriers or threats to the sustainability of NPHIs: (1) reliance on partner funding to maintain key activities, (2) changes in NPHI leadership and (3) staff attrition and turnover. CONCLUSIONS: Our findings contribute to the scant literature on sustainability of NPHIs in LMICs by identifying essential components of sustainability and types of support needed from various stakeholders. Integrating these components into each step of NPHI development and ensuring sufficient support will be critical to strengthening public health systems and safeguarding their continuity. Our findings offer potential approaches for country leadership to direct efforts to strengthen and sustain NPHIs. |
Seroprevalence of Powassan virus infection in an area experiencing a cluster of disease cases: Sussex County, New Jersey, 2019
Vahey GM , Wilson N , McDonald E , Fitzpatrick K , Lehman J , Clark S , Lindell K , Pastula DM , Perez S , Rhodes H , Gould CV , Staples JE , Cervantes K , Martin SW . Open Forum Infect Dis 2022 9 (3) ofac023 In 2019, a geographically focal cluster of 3 Powassan virus neuroinvasive disease cases occurred in New Jersey. We conducted a serosurvey of 273 adult area residents and estimated that immunoglobulin M seroprevalence was 0.31% (95% confidence interval [CI], .04%-1.00%) and 23% (95% CI, 7%-100%) of infections result in neuroinvasive disease. |
Genomic Evaluation of the Genus Coltivirus Indicates Genetic Diversity among Colorado Tick Fever Virus Strains and Demarcation of a New Species.
Hughes HR , Velez JO , Fitzpatrick K , Davis EH , Russell BJ , Lambert AJ , Staples JE , Brault AC . Diseases 2021 9 (4) The type species of the genus Coltivirus, Colorado tick fever virus (CTFV), was discovered in 1943 and is the most common tick-borne viral infection in the Western US. Despite its long history, very little is known about the molecular diversity of viruses classified within the species Colorado tick fever coltivirus. Previous studies have suggested genetic variants and potential serotypes of CTFV, but limited genetic sequence information is available for CTFV strains. To address this knowledge gap, we report herein the full-length genomes of five strains of CTFV, including Salmon River virus and California hare coltivirus (CTFV-Ca). The sequence from the full-length genome of Salmon River virus identified a high genetic identity to the CTFV prototype strain with >90% amino acid identity in all the segments except segment four, suggesting Salmon River virus is a strain of the species Colorado tick fever coltivirus. Additionally, analysis suggests that segment four has been associated with reassortment in at least one strain. The CTFV-Ca full-length genomic sequence was highly variable from the prototype CTFV in all the segments. The genome of CTFV-Ca was most similar to the Eyach virus, including similar segments six and seven. These data suggest that CTFV-Ca is not a strain of CTFV but a unique species. Additional sequence information of CTFV strains will improve the molecular surveillance tools and provide additional taxonomic resolution to this understudied virus. |
Stakeholders' assessment of US Centers for Disease Control and Prevention's contributions to the development of National Public Health Institutes in seven countries
Woldetsadik MA , Fitzpatrick K , Del Castillo L , Miller B , Jarvis D , Carnevale C , Ravat F , Cassell CH , Williams A , Young SK , Clemente J , Baggett HC , Bratton S . J Public Health Policy 2021 42 (4) 589-601 National Public Health Institutes (NPHIs) can strengthen countries' public health capacities to prevent, detect, and respond to public health emergencies. This qualitative evaluation assessed the role of the US Centers for Disease Control and Prevention (CDC) in NPHI development and strengthening of public health functions. We interviewed NPHI staff (N = 43), non-NPHI government staff (N = 29), and non-governmental organization staff (N = 24) in seven countries where CDC has supported NPHI development: Cambodia, Colombia, Liberia, Mozambique, Nigeria, Rwanda, and Zambia. Participants identified four areas of support that were the most important: workforce capacity building, technical assistance for key public health functions, identifying institutional gaps and priorities, and funding to support countries' priorities. Participants underscored the need for capacity building directed toward country-driven priorities during planning and implementation. Continued support for NPHI development from CDC and other partners is vital to building stronger public health systems, improving population health, and strengthening global health security. |
A case report of primary amebic meningoencephalitis in North Florida
Anjum SK , Mangrola K , Fitzpatrick G , Stockdale K , Matthias L , Ali IKM , Cope JR , O'Laughlin K , Collins S , Beal SG , Saccoccio FM . IDCases 2021 25 e01208 Primary amebic meningoencephalitis is a rare, usually fatal disease, caused by Naegleria fowleri. This case highlights the challenging clinicopathologic diagnosis in a 13-year-old boy who swam in freshwater in northern Florida where a previous case had exposure to a body of water on the same property in 2009. © 2021 |
CATMoS: Collaborative Acute Toxicity Modeling Suite.
Mansouri K , Karmaus AL , Fitzpatrick J , Patlewicz G , Pradeep P , Alberga D , Alepee N , Allen TEH , Allen D , Alves VM , Andrade CH , Auernhammer TR , Ballabio D , Bell S , Benfenati E , Bhattacharya S , Bastos JV , Boyd S , Brown JB , Capuzzi SJ , Chushak Y , Ciallella H , Clark AM , Consonni V , Daga PR , Ekins S , Farag S , Fedorov M , Fourches D , Gadaleta D , Gao F , Gearhart JM , Goh G , Goodman JM , Grisoni F , Grulke CM , Hartung T , Hirn M , Karpov P , Korotcov A , Lavado GJ , Lawless M , Li X , Luechtefeld T , Lunghini F , Mangiatordi GF , Marcou G , Marsh D , Martin T , Mauri A , Muratov EN , Myatt GJ , Nguyen DT , Nicolotti O , Note R , Pande P , Parks AK , Peryea T , Polash AH , Rallo R , Roncaglioni A , Rowlands C , Ruiz P , Russo DP , Sayed A , Sayre R , Sheils T , Siegel C , Silva AC , Simeonov A , Sosnin S , Southall N , Strickland J , Tang Y , Teppen B , Tetko IV , Thomas D , Tkachenko V , Todeschini R , Toma C , Tripodi I , Trisciuzzi D , Tropsha A , Varnek A , Vukovic K , Wang Z , Wang L , Waters KM , Wedlake AJ , Wijeyesakere SJ , Wilson D , Xiao Z , Yang H , Zahoranszky-Kohalmi G , Zakharov AV , Zhang FF , Zhang Z , Zhao T , Zhu H , Zorn KM , Casey W , Kleinstreuer NC . Environ Health Perspect 2021 129 (4) 47013 BACKGROUND: Humans are exposed to tens of thousands of chemical substances that need to be assessed for their potential toxicity. Acute systemic toxicity testing serves as the basis for regulatory hazard classification, labeling, and risk management. However, it is cost- and time-prohibitive to evaluate all new and existing chemicals using traditional rodent acute toxicity tests. In silico models built using existing data facilitate rapid acute toxicity predictions without using animals. OBJECTIVES: The U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Acute Toxicity Workgroup organized an international collaboration to develop in silico models for predicting acute oral toxicity based on five different end points: Lethal Dose 50 (LD50 value, U.S. Environmental Protection Agency hazard (four) categories, Globally Harmonized System for Classification and Labeling hazard (five) categories, very toxic chemicals [LD50 (LD50 ≤ 50 mg/kg)], and nontoxic chemicals (LD50 > 2,000 mg/kg). METHODS: An acute oral toxicity data inventory for 11,992 chemicals was compiled, split into training and evaluation sets, and made available to 35 participating international research groups that submitted a total of 139 predictive models. Predictions that fell within the applicability domains of the submitted models were evaluated using external validation sets. These were then combined into consensus models to leverage strengths of individual approaches. RESULTS: The resulting consensus predictions, which leverage the collective strengths of each individual model, form the Collaborative Acute Toxicity Modeling Suite (CATMoS). CATMoS demonstrated high performance in terms of accuracy and robustness when compared with in vivo results. DISCUSSION: CATMoS is being evaluated by regulatory agencies for its utility and applicability as a potential replacement for in vivo rat acute oral toxicity studies. CATMoS predictions for more than 800,000 chemicals have been made available via the National Toxicology Program's Integrated Chemical Environment tools and data sets (ice.ntp.niehs.nih.gov). The models are also implemented in a free, standalone, open-source tool, OPERA, which allows predictions of new and untested chemicals to be made. https://doi.org/10.1289/EHP8495. |
Discordant Clinical Outcomes in a Monozygotic Dichorionic-Diamniotic Twin Pregnancy with Probable Zika Virus Exposure. Case Report.
Mercado M , Daza M , Moore CA , Valencia D , Rico A , Álvarez-Diaz DA , Brault AC , Fitzpatrick K , Mulkey SB . Trop Med Infect Dis 2020 5 (4) Prenatal exposure to Zika virus (ZIKV) is associated with congenital anomalies of the brain and the eye and neurodevelopmental sequelae. The spectrum of disease outcomes may relate to timing of infection as well as genetic and environmental factors. Congenital infections occurring in twin pregnancies can inform the clinical spectrum of these conditions and provide unique information regarding timing of infection and in utero environment with disease pathophysiology. Herein, we report a monozygotic dichorionic-diamniotic twin pregnancy with probable prenatal ZIKV exposure identified through the Colombian ZIKV disease surveillance system. Multidisciplinary clinical evaluations were provided to the twins during their first three years of life through a national program for children with in utero ZIKV exposure. Laboratory evidence of congenital infection as well as microcephaly, brain, eye, and neurodevelopmental compromise related to prenatal ZIKV infection were identified in only one infant of the twin pregnancy. This is the first report of monozygotic twins discordant for Zika-associated birth defects. The evaluation of the pathophysiology of discordance in disease outcome for congenital infections in twin pregnancies may lead to a better understanding of potential complex environmental and genetic interactions between the mother, her offspring, and an infectious exposure. |
Duration of seropositivity following yellow fever vaccination in U.S. military service members
Lindsey NP , Perry L , Fischer M , Woolpert T , Biggerstaff BJ , Brice G , Fitzpatrick K , Kosoy OI , Laven JJ , Myers CA , Hollis EM , Staples JE . Vaccine 2020 38 (52) 8286-8291 BACKGROUND: The United States military regularly deploys thousands of service members throughout areas of South America and Africa that are endemic for yellow fever (YF) virus. To determine if booster doses might be needed for service members who are repetitively or continually deployed to YF endemic areas, we evaluated seropositivity among US military personnel receiving a single dose of YF vaccine based on time post-vaccination. METHODS: Serum antibodies were measured using a plaque reduction neutralization test with 50% cutoff in 682 military personnel at 5-39 years post-vaccination. We determined noninferiority of immune response by comparing the proportion seropositive among those vaccinated 10-14 years previously with those vaccinated 5-9 years previously. Noninferiority was supported if the lower-bound of the 2-tailed 95% CI for p(10-14years) - p(5-9years) was ≥-0.10. Additionally, the geometric mean antibody titer (GMT) at various timepoints following vaccination were compared to the GMT at 5-9 years. RESULTS: The proportion of military service members with detectable neutralizing antibodies 10-14 years after a single dose of YF vaccine (95.8%, 95% CI 91.2-98.1%) was non-inferior to the proportion 5-9 years after vaccination (97.8%, 95% CI 93.7-99.3%). Additionally, GMT among vaccine recipients at 10-14 years post vaccination (99, 95% CI 82-121) was non-inferior to GMT in YF vaccine recipients at 5-9 years post vaccination (115, 95% CI 96-139). The proportion of vaccinees with neutralizing antibodies remained high, and non-inferior, among those vaccinated 15-19 years prior (98.5%, 95%CI 95.5-99.7%). Although the proportion seropositive decreased among vaccinees ≥ 20 years post vaccination, >90% remained seropositive. CONCLUSIONS: Neutralizing antibodies were present in > 95% of vaccine recipients for at least 19 years after vaccination, suggesting that booster doses every 10 years are not essential for most U.S. military personnel. |
Work hours and cognitive function: The Multi-Ethnic Study of Atherosclerosis
Charles LE , Fekedulegn D , Burchfiel CM , Fujishiro K , Al Hazzouri AZ , Fitzpatrick AL , Rapp SR . Saf Health Work 2020 11 (2) 178-186 Background: Cognitive impairment is a public health burden. Our objective was to investigate associations between work hours and cognitive function. Methods: Multi-Ethnic Study of Atherosclerosis (MESA) participants (n = 2,497; 50.7% men; age range 44–84 years) reported hours per week worked in all jobs in Exams 1 (2000–2002), 2 (2002–2004), 3 (2004–2005), and 5 (2010–2011). Cognitive function was assessed (Exam 5) using the Cognitive Abilities Screening Instrument (version 2), a measure of global cognitive functioning; the Digit Symbol Coding, a measure of processing speed; and the Digit Span test, a measure of attention and working memory. We used a prospective approach and linear regression to assess associations for every 10 hours of work. Results: Among all participants, associations of hours worked with cognitive function of any type were not statistically significant. In occupation-stratified analyses (interaction p = 0.051), longer work hours were associated with poorer global cognitive function among Sales/Office and blue-collar workers, after adjustment for age, sex, physical activity, body mass index, race/ethnicity, educational level, annual income, history of heart attack, diabetes, apolipoprotein E-epsilon 4 allele (ApoE4) status, birth-place, number of years in the United States, language spoken at MESA Exam 1, and work hours at Exam 5 (β = –0.55, 95% CI = –0.99, –0.09) and (β = –0.80, –1.51, –0.09), respectively. In occupation-stratified analyses (interaction p = 0.040), we also observed an inverse association with processing speed among blue-collar workers (adjusted β = –0.80, –1.52, –0.07). Sex, race/ethnicity, and ApoE4 did not significantly modify associations between work hours and cognitive function. Conclusion: Weak inverse associations were observed between work hours and cognitive function among Sales/Office and blue-collar workers. |
Assessment of immunoglobulin M enzyme-linked immunosorbent assay ratios to identify West Nile Virus and St. Louis Encephalitis virus infections during concurrent outbreaks of West Nile Virus and St. Louis encephalitis virus diseases, Arizona 2015
Curren EJ , Venkat H , Sunenshine R , Fitzpatrick K , Kosoy O , Krow-Lucal E , Zabel K , Adams L , Kretschmer M , Fischer M , Hills SL . Vector Borne Zoonotic Dis 2020 20 (8) 619-623 West Nile virus (WNV) and St. Louis encephalitis virus (SLEV) are closely related mosquito-borne flaviviruses that cause clinical disease ranging from febrile illness to encephalitis. The standard for serological diagnosis is immunoglobulin M (IgM) testing followed by confirmatory plaque reduction neutralization test (PRNT) to differentiate the infecting virus. However, the PRNT is time-consuming and requires manipulation of live virus. During concurrent WNV and SLEV outbreaks in Arizona in 2015, we assessed use of a diagnostic algorithm to simplify testing. It incorporated WNV and SLEV ratios based on positive-to-negative (P/N) values derived from the IgM antibody-capture enzyme-linked immunosorbent assay. We compared each sample's ratio-based result with the confirmed WNV or SLEV sample result indicated by PRNT or PCR testing. We analyzed data from 70 patients with 77 serum and cerebrospinal fluid samples, including 53 patients with confirmed WNV infection and 17 patients with confirmed SLEV infection. Both WNV and SLEV ratios had specificity >/=95%, indicating a high likelihood that each ratio was correctly identifying the infecting virus. The SLEV ratio sensitivity of 30% was much lower than the WNV ratio sensitivity of 91%, likely because of higher cross-reactivity of SLEV antibodies and generation of lower P/N values. The standard for serological diagnosis of WNV and SLEV infections remains IgM testing followed by PRNT. However, these results suggest the ratios could potentially be used as part of a diagnostic algorithm in outbreaks to substantially reduce the need for PRNTs. |
Comparison of characteristics of patients with West Nile virus or St. Louis encephalitis virus neuroinvasive disease during concurrent outbreaks, Maricopa County, Arizona, 2015
Venkat H , Krow-Lucal E , Kretschmer M , Sylvester T , Levy C , Adams L , Fitzpatrick K , Laven J , Kosoy O , Sunenshine R , Smith K , Townsend J , Chevinsky J , Hennessey M , Jones J , Komatsu K , Fischer M , Hills S . Vector Borne Zoonotic Dis 2020 20 (8) 624-629 West Nile virus (WNV) and St. Louis encephalitis virus (SLEV) are closely related mosquito-borne flaviviruses that can cause neuroinvasive disease. No concurrent WNV and SLEV disease outbreaks have previously been identified. When concurrent outbreaks occurred in 2015 in Maricopa County, Arizona, we collected data to describe the epidemiology, and to compare features of patients with WNV and SLEV neuroinvasive disease. We performed enhanced case finding, and gathered information from medical records and patient interviews. A case was defined as a clinically compatible illness and laboratory evidence of WNV, SLEV, or unspecified flavivirus infection in a person residing in Maricopa County in 2015. We compared demographic and clinical features of WNV and SLEV neuroinvasive cases; for this analysis, a case was defined as physician-documented encephalitis or meningitis and a white blood cell count >5 cells/mm(3) in cerebrospinal fluid. In total, we identified 82 cases, including 39 WNV, 21 SLEV, and 22 unspecified flavivirus cases. The comparative analysis included 21 WNV and 14 SLEV neuroinvasive cases. Among neuroinvasive cases, the median age of patients with SLEV (63 years) was higher than WNV (52 years). Patients had similar symptoms; rash was identified more frequently in WNV (33%) neuroinvasive cases than in SLEV (7%) cases, but this difference was not statistically significant (p = 0.11). In summary, during the first known concurrent WNV and SLEV disease outbreaks, no specific clinical features were identified that could differentiate between WNV and SLEV neuroinvasive cases. Health care providers should consider both infections in patients with aseptic meningitis or encephalitis. |
Prevalence of serum antibodies to Coxiella burnetii in Alaska Native persons from the Pribilof Islands
Kersh GJ , Fitzpatrick K , Pletnikoff K , Brubaker M , Bruce M , Parkinson A . Zoonoses Public Health 2019 67 (1) 89-92 BACKGROUND: Q fever is a febrile illness caused by infection with the bacterium Coxiella burnetii. It is most often transmitted by inhalation of the bacteria after it is shed by infected livestock. Recent studies have found very high C. burnetii infection rates among marine mammals, but it is not known if shedding by marine mammals creates a risk of Q fever among humans. To better understand infection of humans with exposure to marine mammals, the prevalence of antibodies against C. burnetii in serum samples taken from Alaskan Native persons residing on the Pribilof Islands was evaluated. The Pribilof Islands support large populations of northern fur seals infected with C. burnetii that may increase the risk of exposure for island residents. METHODS: Serum testing for IgG antibodies against C. burnetii (phase I and phase II) was performed, and demographic data were analysed utilizing banked serum specimens drawn from island residents from 1980 to 2000. RESULTS: The overall seroprevalence rate was 11.6% (95% CI = 9.3%-14.4%; 72/621). This is higher than the previously reported 3.1% (95% CI = 2.1%-4.3%) seroprevalence for the U.S. POPULATION: CONCLUSIONS: These results suggest that Alaskan Native persons may be at higher risk for exposure to C. burnetii than the general US. population, possibly due to proximity to large populations of infected marine mammals. |
Measles outbreak at a privately operated detention facility: Arizona, 2016
Venkat H , Briggs G , Brady S , Komatsu K , Hill C , Leung J , Patel M , Livar E , Su CP , Kassem A , Sowers SB , Mercader S , Rota PA , Elson D , Timme E , Robinson S , Fitzpatrick K , Franco J , Hickman C , Gastanaduy PA . Clin Infect Dis 2019 68 (12) 2018-2025 BACKGROUND: We describe a measles outbreak and control measures implemented at a privately operated detention facility housing US Immigration and Customs Enforcement detainees in 2016. METHODS: Case-patients reported fever and rash and were either laboratory-confirmed or had an epidemiological link to a laboratory-confirmed case-patient. Immunoglobulin G (IgG) avidity and plaque reduction neutralization tests distinguished between primary acute and reinfection case-patients. Measles-specific IgG was measured to assess detainee immunity levels. We compared attack rates (ARs) among detainees and staff, between IgG-negative and IgG-positive detainees, and by detainee housing units and sexes. RESULTS: We identified 32 measles case-patients (23 detainees, 9 staff); rash onsets were during 6 May-26 June 2016. High IgG avidity and neutralizing-antibody titers >40000 to measles (indicating reinfection) were identified in 18 (95%) and 15 (84%) of 19 tested case-patients, respectively. Among 205 unit A detainees tested for presumptive immunity, 186 (91%) had detectable IgG. Overall, the AR was 1.65%. ARs were significantly higher among detainees in unit A (7.05%) compared with units B-F (0.59%), and among male (2.33%) compared with female detainees (0.38%); however, ARs were not significantly different between detainees and staff or between IgG-negative and IgG-positive detainees. Control measures included the vaccination of 1424 of 1425 detainees and 190 of 510 staff, immunity verification for 445 staff, case-patient isolation, and quarantine of affected units. CONCLUSIONS: Although ARs were low, measles outbreaks can occur in intense-exposure settings, despite a high population immunity, underscoring the importance of high vaccination coverage and containment in limiting measles transmission. |
Exploring current read-across applications and needs among selected U.S. federal agencies
Patlewicz G , Lizarraga L , Rua D , Allen DG , Daniel A , Fitzpatrick SC , Garcia-Reyero N , Gordon J , Hakkinen P , Howard AS , Karmaus A , Matheson J , Mumtaz M , Richarz AN , Ruiz P , Scarano L , Yamada T , Kleinstreuer N . Regul Toxicol Pharmacol 2019 106 197-209 Read-across is a well-established data gap-filling technique applied for regulatory purposes. In US Environmental Protection Agency's New Chemicals Program under TSCA, read-across has been used extensively for decades, however the extent of application and acceptance of read-across among U.S. federal agencies is less clear. In an effort to build read-across capacity, raise awareness of the state of the science, and work towards a harmonization of read-across approaches across U.S. agencies, a new read-across workgroup was established under the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). This is one of several ad hoc groups ICCVAM has convened to implement the ICCVAM Strategic Roadmap. In this article, we outline the charge and scope of the workgroup and summarize the current applications, tools used, and needs of the agencies represented on the workgroup for read-across. Of the agencies surveyed, the Environmental Protection Agency had the greatest experience in using read-across whereas other agencies indicated that they would benefit from gaining a perspective of the landscape of the tools and available guidance. Two practical case studies are also described to illustrate how the read-across approaches applied by two agencies vary on account of decision context. |
Imported toxin-producing cutaneous diphtheria - Minnesota, Washington, and New Mexico, 2015-2018
Griffith J , Bozio CH , Poel AJ , Fitzpatrick K , DeBolt CA , Cassiday P , Kenyon C , Smelser C , Vagnone PS , Culbreath K , Acosta AM . MMWR Morb Mortal Wkly Rep 2019 68 (12) 281-284 From September 2015 to March 2018, CDC confirmed four cases of cutaneous diphtheria caused by toxin-producing Corynebacterium diphtheriae in patients from Minnesota (two), Washington (one), and New Mexico (one). All patients had recently returned to the United States after travel to countries where diphtheria is endemic. C. diphtheriae infection was not clinically suspected in any of the patients; treating institutions detected the organism through matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF) testing of wound-derived coryneform isolates. MALDI-TOF is a rapid screening platform that uses mass spectrometry to identify bacterial pathogens. State public health laboratories confirmed C. diphtheriae through culture and sent isolates to CDC's Pertussis and Diphtheria Laboratory for biotyping, polymerase chain reaction (PCR) testing, and toxin production testing. All isolates were identified as toxin-producing C. diphtheriae. The recommended public health response for cutaneous diphtheria is similar to that for respiratory diphtheria and includes treating the index patient with antibiotics, identifying close contacts and observing them for development of diphtheria, providing chemoprophylaxis to close contacts, testing patients and close contacts for C. diphtheriae carriage in the nose and throat, and providing diphtheria toxoid-containing vaccine to incompletely immunized patients and close contacts. This report summarizes the patient clinical information and response efforts conducted by the Minnesota, Washington, and New Mexico state health departments and CDC and emphasizes that health care providers should consider cutaneous diphtheria as a diagnosis in travelers with wound infections who have returned from countries with endemic diphtheria. |
Human seroprevalence to 11 zoonotic pathogens in the U.S. Arctic, Alaska
Miernyk KM , Bruden D , Parkinson AJ , Hurlburt D , Klejka J , Berner J , Stoddard RA , Handali S , Wilkins PP , Kersh GJ , Fitzpatrick K , Drebot MA , Priest JW , Pappert R , Petersen JM , Teshale E , Hennessy TW , Bruce MG . Vector Borne Zoonotic Dis 2019 19 (8) 563-575 BACKGROUND: Due to their close relationship with the environment, Alaskans are at risk for zoonotic pathogen infection. One way to assess a population's disease burden is to determine the seroprevalence of pathogens of interest. The objective of this study was to determine the seroprevalence of 11 zoonotic pathogens in people living in Alaska. METHODS: In a 2007 avian influenza exposure study, we recruited persons with varying wild bird exposures. Using sera from this study, we tested for antibodies to Cryptosporidium spp., Echinococcus spp., Giardia intestinalis, Toxoplasma gondii, Trichinella spp., Brucella spp., Coxiella burnetii, Francisella tularensis, California serogroup bunyaviruses, and hepatitis E virus (HEV). RESULTS: Eight hundred eighty-seven persons had sera tested, including 454 subsistence bird hunters and family members, 160 sport bird hunters, 77 avian wildlife biologists, and 196 persons with no wild bird exposure. A subset (n = 481) of sera was tested for California serogroup bunyaviruses. We detected antibodies to 10/11 pathogens. Seropositivity to Cryptosporidium spp. (29%), California serotype bunyaviruses (27%), and G. intestinalis (19%) was the most common; 63% (301/481) of sera had antibodies to at least one pathogen. Using a multivariable logistic regression model, Cryptosporidium spp. seropositivity was higher in females (35.7% vs. 25.0%; p = 0.01) and G. intestinalis seropositivity was higher in males (21.8% vs. 15.5%; p = 0.02). Alaska Native persons were more likely than non-Native persons to be seropositive to C. burnetii (11.7% vs. 3.8%; p = 0.005) and less likely to be seropositive to HEV (0.4% vs. 4.1%; p = 0.01). Seropositivity to Cryptosporidium spp., C. burnetii, HEV, and Echinococcus granulosus was associated with increasing age (p </= 0.01 for all) as was seropositivity to >/=1 pathogen (p < 0.0001). CONCLUSION: Seropositivity to zoonotic pathogens is common among Alaskans with the highest to Cryptosporidium spp., California serogroup bunyaviruses, and G. intestinalis. This study provides a baseline for use in assessing seroprevalence changes over time. |
Expanding hospital HIV testing in the Bronx, New York and Washington, D.C.: Results from the HPTN 065 study
Branson BM , Chavez PR , Hanscom B , Greene E , McKinstry L , Buchacz K , Beauchamp G , Gamble T , Zingman BS , Telzak E , Naab T , Fitzpatrick L , El-Sadr WM . Clin Infect Dis 2017 66 (10) 1581-1587 Background: HIV testing is critical for both HIV treatment and prevention. Expanding testing in hospital settings can identify undiagnosed HIV infections. Methods: To evaluate the feasibility of universally offering HIV testing during emergency department (ED) visits and inpatient admissions, 9 hospitals in the Bronx, New York and 7 in Washington DC undertook various efforts to encourage staff to offer HIV testing routinely. Outcomes included the percentage of encounters with an HIV test, the change from year 1 to year 3, and the percentages of tests that were HIV-positive and new diagnoses. Results: From February 1, 2011 to January 31, 2014, HIV tests were conducted during 6.5% of 1,621,016 ED visits and 13.0% of 361,745 inpatient admissions in Bronx hospitals and 13.8% of 729,172 ED visits and 22.0% of 150,655 inpatient admissions in DC, with wide variation by hospital. From year 1 to year 3, testing was stable in the Bronx (6.6% to 6.9% of ED visits, 13.0% to 13.6% of inpatient admissions), but increased in DC (11.9% to 15.8% of ED visits, 19.0% to 23.9% of inpatient admissions). Overall, in the Bronx 0.4% (408) of ED HIV tests were positive, 0.3% (277) were new diagnoses; 1.8% (828) of inpatient tests were positive, 0.5% (244) were new diagnoses. In DC, 0.6% (618) of ED tests were positive, 0.4% (404) were new diagnoses; 4.9% (1349) of inpatient HIV tests were positive, 0.7% (189) were new diagnoses. Conclusion: Hospitals consistently identified previously undiagnosed HIV infections, but universal offer of HIV testing proved elusive. |
A DNA vaccine for Crimean-Congo hemorrhagic fever protects against disease and death in two lethal mouse models.
Garrison AR , Shoemaker CJ , Golden JW , Fitzpatrick CJ , Suschak JJ , Richards MJ , Badger CV , Six CM , Martin JD , Hannaman D , Zivcec M , Bergeron E , Koehler JW , Schmaljohn CS . PLoS Negl Trop Dis 2017 11 (9) e0005908 Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus capable of causing a severe hemorrhagic fever disease in humans. There are currently no licensed vaccines to prevent CCHFV-associated disease. We developed a DNA vaccine expressing the M-segment glycoprotein precursor gene of CCHFV and assessed its immunogenicity and protective efficacy in two lethal mouse models of disease: type I interferon receptor knockout (IFNAR-/-) mice; and a novel transiently immune suppressed (IS) mouse model. Vaccination of mice by muscle electroporation of the M-segment DNA vaccine elicited strong antigen-specific humoral immune responses with neutralizing titers after three vaccinations in both IFNAR-/- and IS mouse models. To compare the protective efficacy of the vaccine in the two models, groups of vaccinated mice (7-10 per group) were intraperitoneally (IP) challenged with a lethal dose of CCHFV strain IbAr 10200. Weight loss was markedly reduced in CCHFV DNA-vaccinated mice as compared to controls. Furthermore, whereas all vector-control vaccinated mice succumbed to disease by day 5, the DNA vaccine protected >60% of the animals from lethal disease. Mice from both models developed comparable levels of antibodies, but the IS mice had a more balanced Th1/Th2 response to vaccination. There were no statistical differences in the protective efficacies of the vaccine in the two models. Our results provide the first comparison of these two mouse models for assessing a vaccine against CCHFV and offer supportive data indicating that a DNA vaccine expressing the glycoprotein genes of CCHFV elicits protective immunity against CCHFV. |
Greater Cognitive Deficits with Sleep-Disordered Breathing among Individuals with Genetic Susceptibility to Alzheimer's Disease: The Multi-Ethnic Study of Atherosclerosis.
Johnson DA , Lane J , Wang R , Reid M , Djonlagic I , Fitzpatrick AL , Rapp SR , Charles LE , O'Hara R , Saxena R , Redline S . Ann Am Thorac Soc 2017 14 (11) 1697-1705 RATIONALE: There are conflicting findings regarding the link between sleep apnea and cognitive dysfunction. OBJECTIVE: Investigate associations between indicators of sleep-disordered breathing (SDB) and cognitive function in the Multi-Ethnic Study of Atherosclerosis and assess effect modification by the apolipoprotein epsilon-4 (APOE-epsilon4) allele. METHODS: A diverse population (N=1,752) underwent Type 2 in-home polysomnography, which included measurement of % sleep time <90% oxyhemoglobin saturation (%Sat<90%) and apnea-hypopnea index (AHI). Epworth Sleepiness Scale score (ESS) and sleep apnea syndrome (SAS; AHI > 5 and ESS> 10) were also analyzed. Cognitive outcomes included the Cognitive Abilities Screening Instrument (CASI); Digit Symbol Coding Test (DSC); and Digit Span Tests (DST) Forward and Backward. RESULTS: Participants were 45.4% male, age 68.1(standard deviation: 9.1) years with a median AHI=9.0 and mean ESS=6.0. Approximately, 9.7% had SAS and 26.8% had at least one copy of the APOepsilon4 allele. In adjusted analyses, a one standard deviation increase in %Sat<90% and ESS score were associated with a poorer attention and memory assessed by the DST Forward score (beta=-0.12 (standard error: 0.06) and beta=-0.13 (0.06), respectively; P<0.05). SAS and higher ESS scores were also associated with poorer attention and processing speed as measured by the DSC, beta=-0.69 (0.35) and beta=-1.42 (0.35), respectively (P<0.05). The presence of APOE-epsilon4 allele modified the associations of %Sat<90% with DST forward and of ESS with DSCT, Pinteraction<0.05. CONCLUSIONS: Overnight hypoxemia and sleepiness were associated with cognition. The average effect estimates were small, similar to effects estimated for several other individual dementia risk factors. Associations were strongest in APOE-epsilon4 risk allele carriers. Our results: 1) suggest that SDB be considered among a group of modifiable dementia risk factors; and 2) highlight the potential vulnerability of APOE-epsilon4 risk allele carriers with SDB. |
Multi-site clinical assessment of myalgic encephalomyelitis/Chronic Fatigue Syndrome (MCAM): Design and implementation of a prospective/retrospective rolling cohort study
Unger ER , Lin JS , Tian H , Natelson BH , Lange G , Vu D , Blate M , Klimas NG , Balbin EG , Bateman L , Allen A , Lapp CW , Springs W , Kogelnik AM , Phan CC , Danver J , Podell RN , Fitzpatrick T , Peterson DL , Gottschalk CG , Rajeevan MS . Am J Epidemiol 2017 185 (8) 617-626 In the Multi-Site Clinical Assessment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (MCAM), we relied on expert clinician diagnoses to enroll patients from 7 specialty clinics in the United States in order to perform a systematic collection of data on measures of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS). Healthy persons and those with other illnesses that share some features with ME/CFS were enrolled in comparison groups. The major objectives were to: 1) use standardized questionnaires to measure illness domains of ME/CFS and to evaluate patient heterogeneity overall and between clinics; 2) describe the course of illness, identify the measures that best correlate with meaningful clinical differences, and assess the performances of questionnaires as patient/person-reported outcome measures; 3) describe prescribed medications, orders for laboratory and other tests, and management tools used by expert clinicians to care for persons with ME/CFS; 4) collect biospecimens for future hypothesis testing and for evaluation of morning cortisol profiles; and 5) identify measures that best distinguish persons with ME/CFS from those in the comparison groups and detect subgroups of persons with ME/CFS who may have different underlying causes. Enrollment began in 2012 and is planned to continue in multiple stages through 2017. We present the MCAM methods in detail, along with an initial description of the 471 patients with ME/CFS who were enrolled in stage 1. |
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