Last data update: Sep 16, 2024. (Total: 47680 publications since 2009)
Records 1-30 (of 72 Records) |
Query Trace: Chou R [original query] |
---|
Molecular mimicry in multisystem inflammatory syndrome in children
Bodansky A , Mettelman RC , Sabatino JJ Jr , Vazquez SE , Chou J , Novak T , Moffitt KL , Miller HS , Kung AF , Rackaityte E , Zamecnik CR , Rajan JV , Kortbawi H , Mandel-Brehm C , Mitchell A , Wang CY , Saxena A , Zorn K , Yu DJL , Pogorelyy MV , Awad W , Kirk AM , Asaki J , Pluvinage JV , Wilson MR , Zambrano LD , Campbell AP , Thomas PG , Randolph AG , Anderson MS , DeRisi JL . Nature 2024 Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection(1,2), yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of samples from patients with MIS-C to identify a distinct set of host proteins targeted by patient autoantibodies including a particular autoreactive epitope within SNX8, a protein involved in regulating an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed antibody responses from patients with MIS-C to the complete SARS-CoV-2 proteome and found enriched reactivity against a distinct domain of the SARS-CoV-2 nucleocapsid protein. The immunogenic regions of the viral nucleocapsid and host SNX8 proteins bear remarkable sequence similarity. Consequently, we found that many children with anti-SNX8 autoantibodies also have cross-reactive T cells engaging both the SNX8 and the SARS-CoV-2 nucleocapsid protein epitopes. Together, these findings suggest that patients with MIS-C develop a characteristic immune response to the SARS-CoV-2 nucleocapsid protein that is associated with cross-reactivity to the self-protein SNX8, demonstrating a mechanistic link between the infection and the inflammatory syndrome, with implications for better understanding a range of post-infectious autoinflammatory diseases. |
Pre-existing immunocompromising conditions and outcomes of acute COVID-19 patients admitted for pediatric intensive care
Rowan CM , LaBere B , Young CC , Zambrano LD , Newhams MM , Kucukak S , McNamara ER , Mack EH , Fitzgerald JC , Irby K , Maddux AB , Schuster JE , Kong M , Dapul H , Schwartz SP , Bembea MM , Loftis LL , Kolmar AR , Babbitt CJ , Nofziger RA , Hall MW , Gertz SJ , Cvijanovich NZ , Zinter MS , Halasa NB , Bradford TT , McLaughlin GE , Singh AR , Hobbs CV , Wellnitz K , Staat MA , Coates BM , Crandall HR , Maamari M , Havlin KM , Schwarz AJ , Carroll CL , Levy ER , Moffitt KL , Campbell AP , Randolph AG , Chou J . Clin Infect Dis 2024 BACKGROUND: We aimed to determine if pre-existing immunocompromising conditions (ICCs) were associated with the presentation or outcome of patients with acute coronavirus disease 2019 (COVID-19) admitted for pediatric intensive care. METHODS: 55 hospitals in 30 U.S. states reported cases through the Overcoming COVID-19 public health surveillance registry. Patients <21 years admitted March 12, 2020-December 30, 2021 to the pediatric intensive care unit (PICU) or high acuity unit for acute COVID-19 were included. RESULTS: Of 1,274 patients, 105 (8.2%) had an ICC including 33 (31.4%) hematologic malignancies, 24 (22.9%) primary immunodeficiencies and disorders of hematopoietic cells, 19 (18.1%) nonmalignant organ failure with solid organ transplantation, 16 (15.2%) solid tumors and 13 (12.4%) autoimmune disorders. Patients with ICCs were older, had more underlying renal conditions, and had lower white blood cell and platelet counts than those without ICCs, but had similar clinical disease severity upon admission. In-hospital mortality from COVID-19 was higher (11.4% vs. 4.6%, p = 0.005) and hospitalization was longer (p = 0.01) in patients with ICCs. New major morbidities upon discharge were not different between those with and without ICC (10.5% vs 13.9%, p = 0.40). In patients with ICC, bacterial co-infection was more common in those with life-threatening COVID-19. CONCLUSIONS: In this national case series of patients <21 years of age with acute COVID-19 admitted for intensive care, existence of a prior ICCs were associated with worse clinical outcomes. Reassuringly, most patients with ICCs hospitalized in the PICU for severe acute COVID-19 survived and were discharged home without new severe morbidities. |
A distinct cross-reactive autoimmune response in multisystem inflammatory syndrome in children (MIS-C) (preprint)
Bodansky A , Sabatino JJ , Vazquez SE , Chou J , Novak T , Moffitt KL , Miller HS , Kung AF , Rackaityte E , Zamecnik CR , Rajan JV , Kortbawi H , Mandel-Brehm C , Mitchell A , Wang CY , Saxena A , Zorn K , Yu DJL , Asaki J , Pluvinage JV , Wilson MR , Loftis LL , Hobbs CV , Tarquinio KM , Kong M , Fitzgerald JC , Espinal PS , Walker TC , Schwartz SP , Crandall H , Irby K , Staat MA , Rowan CM , Schuster JE , Halasa NB , Gertz SJ , Mack EH , Maddux AB , Cvijanovich NZ , Zinter MS , Zambrano LD , Campbell AP , Randolph AG , Anderson MS , DeRisi JL , Kelley H , Murdock M , Colston C , Typpo KV , Sanders RC , Yates M , Smith C , Port E , Mansour R , Shankman S , Baig N , Zorensky F , Chatani B , McLaughlin G , Jones K , Coates BM , Newhams MM , Kucukak S , McNamara ER , Moon HK , Kobayashi T , Melo J , Jackson SR , Rosales MKE , Young C , Chen SR , Da Costa Aguiar R , Gutierrez-Arcelus M , Elkins M , Williams D , Williams L , Cheng L , Zhang Y , Crethers D , Morley D , Steltz S , Zakar K , Armant MA , Ciuculescu F , Flori HR , Dahmer MK , Levy ER , Behl S , Drapeau NM , Kietzman A , Hill S , Cullimore ML , McCulloh RJ , Nofziger RA , Rohlfs CC , Burnett R , Bush J , Reed N , Ampofo KK , Patel MM . medRxiv 2023 30 Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection, yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of MIS-C patient samples (n=199) to identify a distinct set of host proteins that are differentially targeted by patient autoantibodies relative to matched controls. We identified an autoreactive epitope within SNX8, a protein expressed primarily in immune cells which regulates an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed the SARS-CoV-2 proteome-wide MIS-C patient antibody response and found it to be differentially reactive to a distinct domain of the SARS-CoV-2 nucleocapsid (N) protein relative to controls. This viral N region and the mapped SNX8 epitope bear remarkable biochemical similarity. Furthermore, we find that many children with anti-SNX8 autoantibodies also have T-cells cross-reactive to both SNX8 and this distinct domain of the SARS-CoV-2 N protein. Together, these findings suggest that MIS-C patients develop a distinct immune response against the SARS-CoV-2 N protein that is associated with cross reactivity to the self-protein SNX8, demonstrating a link from the infection to the inflammatory syndrome. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license. |
Risk Factors for Multisystem Inflammatory Syndrome in Children: A Case-Control Investigation.
Zambrano LD , Wu MJ , Martin L , Malloch L , Chen S , Newhams MM , Son MB , Sanders C , Patterson K , Halasa N , Fitzgerald J , Leroue M , Hall M , Irby K , Rowan CM , Wellnitz K , Sahni L , Loftis L , Bradford TT , Staat M , Babbitt C , Carroll CL , Pannaraj P , Kong M , Schuster JE , Chou J , Patel MM , Randolph AG , Campbell AP , Hobbs CV . Pediatr Infect Dis J 2023 42 (6) e190-e196 BACKGROUND: In a 2020 pilot case-control study using medical records, we reported that non-Hispanic Black children were more likely to develop multisystem inflammatory syndrome in children (MIS-C) after adjustment for sociodemographic factors and underlying medical conditions. Using structured interviews, we investigated patient, household, and community factors underlying MIS-C likelihood. METHODS: MIS-C case patients hospitalized in 2021 across 14 US pediatric hospitals were matched by age and site to outpatient controls testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 3 months of the admission date. Caregiver interviews queried race/ethnicity, medical history, and household and potential community exposures 1 month before MIS-C hospitalization (case-patients) or after SARS-CoV-2 infection (controls). We calculated adjusted odds ratios (aOR) using mixed-effects multivariable logistic regression. RESULTS: Among 275 case patients and 496 controls, race/ethnicity, social vulnerability and patient or family history of autoimmune/rheumatologic disease were not associated with MIS-C. In previously healthy children, MIS-C was associated with a history of hospitalization for an infection [aOR: 4.8; 95% confidence interval (CI): 2.1-11.0]. Household crowding (aOR: 1.7; 95% CI: 1.2-2.6), large event attendance (aOR: 1.7; 95% CI: 1.3-2.1), school attendance with limited masking (aOR: 2.6; 95% CI: 1.1-6.6), public transit use (aOR: 1.8; 95% CI: 1.4-2.4) and co-resident testing positive for SARS-CoV-2 (aOR: 2.2; 95% CI: 1.3-3.7) were associated with increased MIS-C likelihood, with risk increasing with the number of these factors. CONCLUSIONS: From caregiver interviews, we clarify household and community exposures associated with MIS-C; however, we did not confirm prior associations between sociodemographic factors and MIS-C. |
In-hospital mortality risk stratification in children under 5 years old with pneumonia with or without pulse oximetry: A secondary analysis of the Pneumonia REsearch Partnership To Assess WHO REcommendations (PREPARE) dataset
Hooli S , King C , McCollum ED , Colbourn T , Lufesi N , Mwansambo C , Gregory CJ , Thamthitiwat S , Cutland C , Madhi SA , Nunes MC , Gessner BD , Hazir T , Mathew JL , Addo-Yobo E , Chisaka N , Hassan M , Hibberd PL , Jeena P , Lozano JM , MacLeod WB , Patel A , Thea DM , Nguyen NTV , Zaman SM , Ruvinsky RO , Lucero M , Kartasasmita CB , Turner C , Asghar R , Banajeh S , Iqbal I , Maulen-Radovan I , Mino-Leon G , Saha SK , Santosham M , Singhi S , Awasthi S , Bavdekar A , Chou M , Nymadawa P , Pape JW , Paranhos-Baccala G , Picot VS , Rakoto-Andrianarivelo M , Rouzier V , Russomando G , Sylla M , Vanhems P , Wang J , Basnet S , Strand TA , Neuman MI , Arroyo LM , Echavarria M , Bhatnagar S , Wadhwa N , Lodha R , Aneja S , Gentile A , Chadha M , Hirve S , O'Grady KF , Clara AW , Rees CA , Campbell H , Nair H , Falconer J , Williams LJ , Horne M , Qazi SA , Nisar YB . Int J Infect Dis 2023 129 240-250 OBJECTIVES: We determined pulse oximetry benefit in pediatric pneumonia mortality-risk stratification and chest indrawing pneumonia in-hospital mortality risk factors. METHODS: We report characteristics and in-hospital pneumonia-related mortality of children 2-59-months-old included in the Pneumonia Research Partnership to Assess WHO Recommendations dataset. We developed multivariable logistic regression models of chest indrawing pneumonia to identify mortality risk factors. RESULTS: Among 285,839 children, 164,244 (57·5%) from hospital-based studies were included. Pneumonia case fatality risk (CFR) without pulse oximetry measurement was higher than with measurement (5·8%, 95% CI 5·6-5·9% vs 2·1%, 95% CI 1·9-2·4%). One in five children with chest indrawing pneumonia was hypoxemic (19·7%, 95% CI 19·0-20·4%) and the hypoxemic CFR was 10·3% (95% CI 9·1%-11·5%). Other mortality risk factors were younger age (either 2-5 months (aOR 9·94, 95% CI 6·67-14·84) or 6-11 months (aOR 2·67, 95% CI 1·71-4·16)), moderate malnutrition (aOR 2·41, 95% CI 1·87-3·09), and female sex (aOR 1·82, 95% CI 1·43-2·32). CONCLUSIONS: Children with a pulse oximetry measurement had a lower CFR. Many children hospitalized with chest indrawing pneumonia were hypoxemic and one in ten died. Young age and moderate malnutrition were risk factors for in-hospital chest indrawing pneumonia-related mortality. Pulse oximetry should be integrated in under-five pneumonia hospital care. |
Mpox cases among cisgender women and pregnant persons - United States, May 11-November 7, 2022
Oakley LP , Hufstetler K , O'Shea J , Sharpe JD , McArdle C , Neelam V , Roth NM , Olsen EO , Wolf M , Pao LZ , Gold JAW , Davis KM , Perella D , Epstein S , Lash MK , Samson O , Pavlick J , Feldpausch A , Wallace J , Nambiar A , Ngo V , Halai UA , Richardson CW , Fowler T , Taylor BP , Chou J , Brandon L , Devasia R , Ricketts EK , Stockdale C , Roskosky M , Ostadkar R , Vang Y , Galang RR , Perkins K , Taylor M , Choi MJ , Weidle PJ , Dawson P , Ellington S . MMWR Morb Mortal Wkly Rep 2023 72 (1) 9-14 Monkeypox (mpox) cases in the 2022 outbreak have primarily occurred among adult gay, bisexual, and other men who have sex with men (MSM); however, other populations have also been affected (1). To date, data on mpox in cisgender women and pregnant persons have been limited. Understanding transmission in these populations is critical for mpox prevention. In addition, among pregnant persons, Monkeypox virus can be transmitted to the fetus during pregnancy or to the neonate through close contact during or after birth (2-5). Adverse pregnancy outcomes, including spontaneous abortion and stillbirth, have been reported in previous mpox outbreaks (3). During May 11-November 7, 2022, CDC and U.S. jurisdictional health departments identified mpox in 769 cisgender women aged ≥15 years, representing 2.7% of all reported mpox cases.(†) Among cases with available data, 44% occurred in cisgender women who were non-Hispanic Black or African American (Black), 25% who were non-Hispanic White (White), and 23% who were Hispanic or Latino (Hispanic). Among cisgender women with available data, 73% reported sexual activity or close intimate contact as the likely route of exposure, with mpox lesions most frequently reported on the legs, arms, and genitals. Twenty-three mpox cases were reported in persons who were pregnant or recently pregnant(§); all identified as cisgender women based on the mpox case report form.(¶) Four pregnant persons required hospitalization for mpox. Eleven pregnant persons received tecovirimat, and no adverse reactions were reported. Continued studies on mpox transmission risks in populations less commonly affected during the outbreak, including cisgender women and pregnant persons, are important to assess and understand the impact of mpox on sexual, reproductive, and overall health. |
Assembling a global database of child pneumonia studies to inform WHO pneumonia management algorithm: Methodology and applications
Martin H , Falconer J , Addo-Yobo E , Aneja S , Arroyo LM , Asghar R , Awasthi S , Banajeh S , Bari A , Basnet S , Bavdekar A , Bhandari N , Bhatnagar S , Bhutta ZA , Brooks A , Chadha M , Chisaka N , Chou M , Clara AW , Colbourn T , Cutland C , D'Acremont V , Echavarria M , Gentile A , Gessner B , Gregory CJ , Hazir T , Hibberd PL , Hirve S , Hooli S , Iqbal I , Jeena P , Kartasasmita CB , King C , Libster R , Lodha R , Lozano JM , Lucero M , Lufesi N , MacLeod WB , Madhi SA , Mathew JL , Maulen-Radovan I , McCollum ED , Mino G , Mwansambo C , Neuman MI , Nguyen NTV , Nunes MC , Nymadawa P , O'Grady KF , Pape JW , Paranhos-Baccala G , Patel A , Picot VS , Rakoto-Andrianarivelo M , Rasmussen Z , Rouzier V , Russomando G , Ruvinsky RO , Sadruddin S , Saha SK , Santosham M , Singhi S , Soofi S , Strand TA , Sylla M , Thamthitiwat S , Thea DM , Turner C , Vanhems P , Wadhwa N , Wang J , Zaman SM , Campbell H , Nair H , Qazi SA , Nisar YB . J Glob Health 2022 12 04075 BACKGROUND: The existing World Health Organization (WHO) pneumonia case management guidelines rely on clinical symptoms and signs for identifying, classifying, and treating pneumonia in children up to 5 years old. We aimed to collate an individual patient-level data set from large, high-quality pre-existing studies on pneumonia in children to identify a set of signs and symptoms with greater validity in the diagnosis, prognosis, and possible treatment of childhood pneumonia for the improvement of current pneumonia case management guidelines. METHODS: Using data from a published systematic review and expert knowledge, we identified studies meeting our eligibility criteria and invited investigators to share individual-level patient data. We collected data on demographic information, general medical history, and current illness episode, including history, clinical presentation, chest radiograph findings when available, treatment, and outcome. Data were gathered separately from hospital-based and community-based cases. We performed a narrative synthesis to describe the final data set. RESULTS: Forty-one separate data sets were included in the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) database, 26 of which were hospital-based and 15 were community-based. The PREPARE database includes 285839 children with pneumonia (244323 in the hospital and 41516 in the community), with detailed descriptions of clinical presentation, clinical progression, and outcome. Of 9185 pneumonia-related deaths, 6836 (74%) occurred in children <1 year of age and 1317 (14%) in children aged 1-2 years. Of the 285839 episodes, 280998 occurred in children 0-59 months old, of which 129584 (46%) were 2-11 months of age and 152730 (54%) were males. CONCLUSIONS: This data set could identify an improved specific, sensitive set of criteria for diagnosing clinical pneumonia and help identify sick children in need of referral to a higher level of care or a change of therapy. Field studies could be designed based on insights from PREPARE analyses to validate a potential revised pneumonia algorithm. The PREPARE methodology can also act as a model for disease database assembly. |
NFKB2 haploinsufficiency identified via screening for IFNα2 autoantibodies in children and adolescents hospitalized with SARS-CoV-2-related complications.
Bodansky A , Vazquez SE , Chou J , Novak T , Al-Musa A , Young C , Newhams M , Kucukak S , Zambrano LD , Mitchell A , Wang CY , Moffitt K , Halasa NB , Loftis LL , Schwartz SP , Walker TC , Mack EH , Fitzgerald JC , Gertz SJ , Rowan CM , Irby K , Sanders RC Jr , Kong M , Schuster JE , Staat MA , Zinter MS , Cvijanovich NZ , Tarquinio KM , Coates BM , Flori HR , Dahmer MK , Crandall H , Cullimore ML , Levy ER , Chatani B , Nofziger R , Geha RS , DeRisi J , Campbell AP , Anderson M , Randolph AG . J Allergy Clin Immunol 2023 151 (4) 926-930.e2 BACKGROUND: Autoantibodies against type I IFNs occur in approximately 10% of adults with life-threatening coronavirus disease 2019 (COVID-19). The frequency of anti-IFN autoantibodies in children with severe sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is unknown. OBJECTIVE: We quantified anti-type I IFN autoantibodies in a multicenter cohort of children with severe COVID-19, multisystem inflammatory syndrome in children (MIS-C), and mild SARS-CoV-2 infections. METHODS: Circulating anti-IFN-α2 antibodies were measured by a radioligand binding assay. Whole-exome sequencing, RNA sequencing, and functional studies of peripheral blood mononuclear cells were used to study any patients with levels of anti-IFN-α2 autoantibodies exceeding the assay's positive control. RESULTS: Among 168 patients with severe COVID-19, 199 with MIS-C, and 45 with mild SARS-CoV-2 infections, only 1 had high levels of anti-IFN-α2 antibodies. Anti-IFN-α2 autoantibodies were not detected in patients treated with intravenous immunoglobulin before sample collection. Whole-exome sequencing identified a missense variant in the ankyrin domain of NFKB2, encoding the p100 subunit of nuclear factor kappa-light-chain enhancer of activated B cells, aka NF-κB, essential for noncanonical NF-κB signaling. The patient's peripheral blood mononuclear cells exhibited impaired cleavage of p100 characteristic of NFKB2 haploinsufficiency, an inborn error of immunity with a high prevalence of autoimmunity. CONCLUSIONS: High levels of anti-IFN-α2 autoantibodies in children and adolescents with MIS-C, severe COVID-19, and mild SARS-CoV-2 infections are rare but can occur in patients with inborn errors of immunity. |
CDC Clinical Practice Guideline for Prescribing Opioids for Pain - United States, 2022
Dowell D , Ragan KR , Jones CM , Baldwin GT , Chou R . MMWR Recomm Rep 2022 71 (3) 1-95 This guideline provides recommendations for clinicians providing pain care, including those prescribing opioids, for outpatients aged ≥18 years. It updates the CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016 (MMWR Recomm Rep 2016;65[No. RR-1]:1-49) and includes recommendations for managing acute (duration of <1 month), subacute (duration of 1-3 months), and chronic (duration of >3 months) pain. The recommendations do not apply to pain related to sickle cell disease or cancer or to patients receiving palliative or end-of-life care. The guideline addresses the following four areas: 1) determining whether or not to initiate opioids for pain, 2) selecting opioids and determining opioid dosages, 3) deciding duration of initial opioid prescription and conducting follow-up, and 4) assessing risk and addressing potential harms of opioid use. CDC developed the guideline using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Recommendations are based on systematic reviews of the scientific evidence and reflect considerations of benefits and harms, patient and clinician values and preferences, and resource allocation. CDC obtained input from the Board of Scientific Counselors of the National Center for Injury Prevention and Control (a federally chartered advisory committee), the public, and peer reviewers. CDC recommends that persons with pain receive appropriate pain treatment, with careful consideration of the benefits and risks of all treatment options in the context of the patient's circumstances. Recommendations should not be applied as inflexible standards of care across patient populations. This clinical practice guideline is intended to improve communication between clinicians and patients about the benefits and risks of pain treatments, including opioid therapy; improve the effectiveness and safety of pain treatment; mitigate pain; improve function and quality of life for patients with pain; and reduce risks associated with opioid pain therapy, including opioid use disorder, overdose, and death. |
Prescribing opioids for pain - The New CDC Clinical Practice Guideline
Dowell D , Ragan KR , Jones CM , Baldwin GT , Chou R . N Engl J Med 2022 387 (22) 2011-2013 Pain affects the lives of millions of Americans and potentially reduces their level of function, mental health, and quality of life. Yet limited access to pain treatments and lack of clarity regarding the evidence supporting pain treatments prevent many people with pain from accessing the full range of potentially helpful therapies.1 Furthermore, there are persistent disparities in pain management according to race or ethnic group, gender, socioeconomic status, and population density, among other factors.2 Opioids continue to be commonly used to treat pain, despite evidence that their short-term benefits are small and despite limited evidence of long-term benefits.2,3 |
Investigating Health Disparities Associated With Multisystem Inflammatory Syndrome in Children After SARS-CoV-2 Infection.
Zambrano LD , Ly KN , Link-Gelles R , Newhams MM , Akande M , Wu MJ , Feldstein LR , Tarquinio KM , Sahni LC , Riggs BJ , Singh AR , Fitzgerald JC , Schuster JE , Giuliano JSJr , Englund JA , Hume JR , Hall MW , Osborne CM , Doymaz S , Rowan CM , Babbitt CJ , Clouser KN , Horwitz SM , Chou J , Patel MM , Hobbs C , Randolph AG , Campbell AP . Pediatr Infect Dis J 2022 41 (11) 891-898 BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a postinfectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related complication that has disproportionately affected racial/ethnic minority children. We conducted a pilot study to investigate risk factors for MIS-C aiming to understand MIS-C disparities. METHODS: This case-control study included MIS-C cases and SARS-CoV-2-positive outpatient controls aged less than 18 years frequency-matched 4:1 to cases by age group and site. Patients hospitalized with MIS-C were admitted between March 16 and October 2, 2020, across 17 pediatric hospitals. We evaluated race, ethnicity, social vulnerability index (SVI), insurance status, weight-for-age and underlying medical conditions as risk factors using mixed effects multivariable logistic regression. RESULTS: We compared 241 MIS-C cases to 817 outpatient SARS-CoV-2-positive at-risk controls. Cases and controls had similar sex, age and U.S. census region distribution. MIS-C patients were more frequently previously healthy, non-Hispanic Black, residing in higher SVI areas, and in the 95th percentile or higher for weight-for-age. In the multivariable analysis, the likelihood of MIS-C was higher among non-Hispanic Black children [adjusted odds ratio (aOR): 2.07; 95% CI: 1.23-3.48]. Additionally, SVI in the 2nd and 3rd tertiles (aOR: 1.88; 95% CI: 1.18-2.97 and aOR: 2.03; 95% CI: 1.19-3.47, respectively) were independent factors along with being previously healthy (aOR: 1.64; 95% CI: 1.18-2.28). CONCLUSIONS: In this study, non-Hispanic Black children were more likely to develop MIS-C after adjustment for sociodemographic factors, underlying medical conditions, and weight-for-age. Investigation of the potential contribution of immunologic, environmental, and other factors is warranted. |
Derivation and validation of a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality in 20 countries
Rees CA , Colbourn T , Hooli S , King C , Lufesi N , McCollum ED , Mwansambo C , Cutland C , Madhi SA , Nunes M , Matthew JL , Addo-Yobo E , Chisaka N , Hassan M , Hibberd PL , Jeena PM , Lozano JM , MacLeod WB , Patel A , Thea DM , Nguyen NTV , Kartasasmita CB , Lucero M , Awasthi S , Bavdekar A , Chou M , Nymadawa P , Pape JW , Paranhos-Baccala G , Picot VS , Rakoto-Andrianarivelo M , Rouzier V , Russomando G , Sylla M , Vanhems P , Wang J , Asghar R , Banajeh S , Iqbal I , Maulen-Radovan I , Mino-Leon G , Saha SK , Santosham M , Singhi S , Basnet S , Strand TA , Bhatnagar S , Wadhwa N , Lodha R , Aneja S , Clara AW , Campbell H , Nair H , Falconer J , Qazi SA , Nisar YB , Neuman MI . BMJ Glob Health 2022 7 (4) INTRODUCTION: Existing risk assessment tools to identify children at risk of hospitalised pneumonia-related mortality have shown suboptimal discriminatory value during external validation. Our objective was to derive and validate a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality across various settings. METHODS: We used primary, baseline, patient-level data from 11 studies, including children evaluated for pneumonia in 20 low-income and middle-income countries. Patients with complete data were included in a logistic regression model to assess the association of candidate variables with the outcome hospitalised pneumonia-related mortality. Adjusted log coefficients were calculated for each candidate variable and assigned weighted points to derive the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) risk assessment tool. We used bootstrapped selection with 200 repetitions to internally validate the PREPARE risk assessment tool. RESULTS: A total of 27 388 children were included in the analysis (mean age 14.0 months, pneumonia-related case fatality ratio 3.1%). The PREPARE risk assessment tool included patient age, sex, weight-for-age z-score, body temperature, respiratory rate, unconsciousness or decreased level of consciousness, convulsions, cyanosis and hypoxaemia at baseline. The PREPARE risk assessment tool had good discriminatory value when internally validated (area under the curve 0.83, 95% CI 0.81 to 0.84). CONCLUSIONS: The PREPARE risk assessment tool had good discriminatory ability for identifying children at risk of hospitalised pneumonia-related mortality in a large, geographically diverse dataset. After external validation, this tool may be implemented in various settings to identify children at risk of hospitalised pneumonia-related mortality. |
Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes.
Voss WN , Hou YJ , Johnson NV , Delidakis G , Kim JE , Javanmardi K , Horton AP , Bartzoka F , Paresi CJ , Tanno Y , Chou CW , Abbasi SA , Pickens W , George K , Boutz DR , Towers DM , McDaniel JR , Billick D , Goike J , Rowe L , Batra D , Pohl J , Lee J , Gangappa S , Sambhara S , Gadush M , Wang N , Person MD , Iverson BL , Gollihar JD , Dye J , Herbert A , Finkelstein IJ , Baric RS , McLellan JS , Georgiou G , Lavinder JJ , Ippolito GC . Science 2021 372 (6546) 1108-1112 The molecular composition and binding epitopes of the immunoglobulin G (IgG) antibodies that circulate in blood plasma following SARS-CoV-2 infection are unknown. Proteomic deconvolution of the IgG repertoire to the spike glycoprotein in convalescent subjects revealed that the response is directed predominantly (>80%) against epitopes residing outside the receptor-binding domain (RBD). In one subject, just four IgG lineages accounted for 93.5% of the response, including an N-terminal domain (NTD)-directed antibody that was protective against lethal viral challenge. Genetic, structural, and functional characterization of a multi-donor class of "public" antibodies revealed an NTD epitope that is recurrently mutated among emerging SARS-CoV-2 variants of concern. These data show that "public" NTD-directed and other non-RBD plasma antibodies are prevalent and have implications for SARS-CoV-2 protection and antibody escape. |
Accuracy of HBeAg to identify pregnant women at risk of transmitting hepatitis B virus to their neonates: a systematic review and meta-analysis
Boucheron P , Lu Y , Yoshida K , Zhao T , Funk AL , Lunel-Fabiani F , Guingané A , Tuaillon E , van Holten J , Chou R , Bulterys M , Shimakawa Y . Lancet Infect Dis 2020 21 (1) 85-96 BACKGROUND: Prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV) involves neonatal immunoprophylaxis, with a birth dose of hepatitis B vaccine and immune globulin, and provision of peripartum antiviral prophylaxis in highly viraemic women. However, access to assays to quantify HBV DNA levels remains inadequate in resource-poor settings. This study was commissioned by WHO and aimed to identify the HBV DNA threshold for MTCT, to assess the sensitivity and specificity of hepatitis B e antigen (HBeAg) testing to identify pregnant women with HBV DNA levels above this threshold, and to predict MTCT of HBV infection on the basis of HBeAg testing. METHODS: For this systematic review and meta-analysis, we searched the PubMed, EMBASE, Scopus, CENTRAL, CNKI, and Wanfang databases for studies of pregnant women with chronic HBV infection without concurrent antiviral therapy, published between Jan 1, 2000, and April 3, 2019. Studies were eligible for inclusion if MTCT in mother-child pairs could be stratified by different levels of maternal HBV DNA during pregnancy, if maternal HBeAg status could be stratified by HBV DNA level, and if the MTCT status of infants could be stratified by maternal HBeAg status during pregnancy. Studies that selected pregnant women on the basis of HBeAg serostatus or HBV DNA levels were excluded. Aggregate data were extracted from eligible studies by use of a pre-piloted form; study authors were contacted to clarify any uncertainties about potential duplication or if crucial information was missing. To pool sensitivities and specificities of maternal HBeAg to identify highly viraemic women and to predict MTCT events, we used the DerSimonian-Laird bivariate random effects model. This study is registered with PROSPERO, CRD42019138227. FINDINGS: Of 9007 articles identified, 67 articles (comprising 66 studies) met the inclusion criteria. The risk of MTCT despite infant immunoprophylaxis was negligible (0·04%, 95% CI 0·00-0·25) below a maternal HBV DNA level of 5·30 log(10) IU/mL (200 000 IU/mL) and increased above this threshold. The pooled sensitivity of HBeAg testing to identify HBV DNA levels of 5·30 log(10) IU/mL or greater in pregnant women was 88·2% (83·9-91·5) and pooled specificity was 92·6% (90·0-94·5). The pooled sensitivity of HBeAg testing in predicting MTCT of HBV infection despite infant immunoprophylaxis was 99·5% (95% CI 91·7-100) and pooled specificity was 62·2% (55·2-68·7). INTERPRETATION: Maternal HBV DNA of 5·30 log(10) IU/mL or greater appears to be the optimal threshold for MTCT of HBV infection despite infant immunoprophylaxis. HBeAg is accurate to identify women with HBV DNA levels above this threshold and has high sensitivity to predict cases of immunoprophylaxis failure. In areas where HBV DNA assays are unavailable, HBeAg can be used as an alternative to assess eligibility for antiviral prophylaxis. FUNDING: World Health Organization. |
Efficacy and safety of antiviral prophylaxis during pregnancy to prevent mother-to-child transmission of hepatitis B virus: a systematic review and meta-analysis
Funk AL , Lu Y , Yoshida K , Zhao T , Boucheron P , van Holten J , Chou R , Bulterys M , Shimakawa Y . Lancet Infect Dis 2020 21 (1) 70-84 BACKGROUND: To eliminate mother-to-child transmission (MTCT) of hepatitis B virus (HBV), peripartum antiviral prophylaxis might be required for pregnant women infected with HBV who have a high risk of MTCT despite infant immunoprophylaxis. We aimed to determine the efficacy and safety of peripartum antiviral prophylaxis to inform the 2020 WHO guidelines. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, CENTRAL, CNKI, and Wanfang for randomised controlled trials and non-randomised studies of peripartum antiviral prophylaxis versus placebo or no prophylaxis, with no language restriction, published from database inception until March 28, 2019. We used search terms covering HBV, antiviral therapy, and pregnancy. We included studies that enrolled pregnant women with chronic infection with HBV who received antiviral prophylaxis anytime during pregnancy; that included any of the following antivirals: adefovir, emtricitabine, entecavir, lamivudine, telbivudine, tenofovir alafenamide fumarate, and tenofovir disoproxil fumarate; and that reported the following outcomes: MTCT, indicated by infant HBsAg positivity or HBV DNA positivity, or both, at age 6-12 months, and any infant or maternal adverse events. Two reviewers independently extracted data. Our primary endpoint was MTCT based on infant HBsAg positivity. We assessed pooled odds ratios (ORs) of the efficacy of peripartum antiviral prophylaxis to reduce the risk of MTCT. We assessed safety of prophylaxis by pooling risk differences. The protocol for the systematic review was pre-registered in PROSPERO, CRD42019134614. FINDINGS: Of 7463 articles identified, 595 articles were eligible for full-text review and 129 studies (in 157 articles) were included. The following antivirals were assessed in the meta-analysis: tenofovir disoproxil fumarate 300 mg (19 studies, with 1092 mothers and 1072 infants), lamivudine 100-150 mg (40 studies, with 2080 mothers and 2007 infants), and telbivudine 600 mg (83 studies, with 6036 mothers and 5971 infants). The pooled ORs for randomised controlled trials were similar, at 0·10 (95% CI 0·03-0·35) for tenofovir disoproxil fumarate, 0·16 (0·10-0·26) for lamivudine, and 0·14 (0·09-0·21) for telbivudine. The pooled ORs in non-randomised studies were 0·17 (0·10-0·29) for tenofovir disoproxil fumarate, 0·17 (0·12-0·24) for lamivudine, and 0·09 (0·06-0·12) for telbivudine. We found no increased risk of any infant or maternal safety outcomes after peripartum antiviral prophylaxis. INTERPRETATION: Peripartum antiviral prophylaxis is highly effective at reducing the risk of HBV MTCT. Our findings support the 2020 WHO recommendation of administering antivirals during pregnancy, specifically tenofovir disoproxil fumarate, for the prevention of HBV MTCT. FUNDING: World Health Organization. |
Evaluating coverage of maternal syphilis screening and treatment within antenatal care to guide service improvements for prevention of congenital syphilis in Countdown 2030 Countries
Trivedi S , Taylor M , Kamb ML , Chou D . J Glob Health 2020 10 (1) 010504 Background: Countdown to 2030 (CD2030) tracks progress in the 81 countries that account for more than 90% of under-five child deaths and 95% of maternal deaths in the world. In 2017, CD2030 identified syphilis screening and treatment during antenatal care (ANC) as priority indicators for monitoring. Methods: Country-reported data in the UNAIDS Global AIDS Monitoring System (GAM) system were used to evaluate four key syphilis indicators from CD2030 countries: (1) maternal syphilis screening and (2) treatment coverage during ANC, (3) syphilis seroprevalence among ANC attendees, and (4) national congenital syphilis (CS) case rates. A cascade analysis for CD2030 countries with coverage data for the number of women attending at least 4 antenatal care visits (ANC4), syphilis testing, seroprevalence and treatment was performed to estimate the number of CS cases that were attributable to missed opportunities for syphilis screening and treatment during antenatal care. Results: Of 81 countries, 52 (64%) reported one or more values for CS indicators into the GAM system during 2016-2017; only 53 (65%) had maternal syphilis testing coverage, 41 (51%) had screening positivity, and 40 (49%) had treatment coverage. CS case rates were reported by 13 (16%) countries. During 2016-2017, four countries reported syphilis screening and treatment coverage of >/=95% consistent with World Health Organization (WHO) targets. Sufficient data were available for 40 (49%) of countries to construct a cascade for data years 2016 and 2017. Syphilis screening and treatment service gaps within ANC4 resulted in an estimated total of 103 648 adverse birth outcomes with 41 858 of these occurring as stillbirths among women attending ANC4 (n = 31 914 408). Women not in ANC4 (n = 25 619 784) contributed an additional 67 348 estimated adverse birth outcomes with 27 198 of these occurring as stillbirths for a total of 69 056 preventable stillbirths attributable to syphilis in these 40 countries. Conclusion: These data and findings can serve as an initial baseline evaluation of antenatal syphilis surveillance and service coverage and can be used to guide improvement of delivery and monitoring of syphilis screening and treatment in ANC for these priority countries. |
Development and characterization of a reverse genetics system for influenza D virus.
Yu J , Liu R , Zhou B , Chou TW , Ghedin E , Sheng Z , Gao R , Zhai SL , Wang D , Li F . J Virol 2019 93 (21) Influenza D virus (IDV) of the Orthomyxoviridae family has a wide host range and a broad geographical distribution. Recent IDV outbreaks in swine along with serological and genetic evidence of IDV infection in humans have raised concerns regarding the zoonotic potential of this virus. To better study IDV at the molecular level, a reverse-genetics system (RGS) is urgently needed, but to date, no RGS had been described for IDV. In this study, we rescued the recombinant influenza D/swine/Oklahoma/1314/2011 (D/OK) virus by using a bidirectional seven-plasmid-based system and further characterized rescued viruses in terms of growth kinetics, replication stability, and receptor-binding capacity. Our results collectively demonstrated that RGS-derived viruses resembled the parental viruses for these properties, thereby supporting the utility of this RGS to study IDV infection biology. In addition, we developed an IDV minigenome replication assay and identified the E697K mutation in PB1 and the L462F mutation in PB2 that directly affected the activity of the IDV ribonucleoprotein (RNP) complex, resulting in either attenuated or replication-incompetent viruses. Finally, by using the minigenome replication assay, we demonstrated that a single nucleotide polymorphism at position 5 of the 3' conserved noncoding region in IDV and influenza C virus (ICV) resulted in the inefficient cross-recognition of the heterotypic promoter by the viral RNP complex. In conclusion, we successfully developed a minigenome replication assay and a robust reverse-genetics system that can be used to further study replication, tropism, and pathogenesis of IDV.IMPORTANCE Influenza D virus (IDV) is a new type of influenza virus that uses cattle as the primary reservoir and infects multiple agricultural animals. Increased outbreaks in pigs and serological and genetic evidence of human infection have raised concerns about potential IDV adaptation in humans. Here, we have developed a plasmid-based IDV reverse-genetics system that can generate infectious viruses with replication kinetics similar to those of wild-type viruses following transfection of cultured cells. Further characterization demonstrated that viruses rescued from the described RGS resembled the parental viruses in biological and receptor-binding properties. We also developed and validated an IDV minireplicon reporter system that specifically measures viral RNA polymerase activity. In summary, the reverse-genetics system and minireplicon reporter assay described in this study should be of value in identifying viral determinants of cross-species transmission and pathogenicity of novel influenza D viruses. |
Self-reported oral health status among adults age 40+ years with and without vision impairment: National Health Interview Survey, 2008
Crews JE , Chou CF , Naavaal S , Griffin S , Saaddine JB . Am J Ophthalmol 2019 210 184-191 PURPOSE: To examine self-reported oral health among adults age 40 years and older with and without vision impairment. DESIGN: Cross-sectional with a nationally representative sample. METHODS: We used publicly available data from the Oral Health Module, last administered in 2008 of the National Health Interview Survey. Outcome variables included fair/poor oral health status, mouth condition compared to others the same age, mouth problems (mouth sores, difficulty eating, dry mouth, bad breath and/or jaw pain), teeth problems (toothache; broken/missing fillings or teeth; loose, crooked or stained teeth; and/or bleeding gums) and lack of social participation. Using descriptive statistics and multivariate logistic regression, we examined the association (p<0.05) between vision impairment and oral health outcomes by age-group, sociodemographic, and other explanatory variables. RESULTS: Our study sample included 12,090 adults; 12.8% of adults aged 40-64 years reported vision impairment, and among them, 44.5% reported fair/poor oral health status and 47.2% reported any mouth problems. Among adults aged >/=65 years, 17.3% reported vision impairment, of whom 36.3% reported fair/poor oral health status, and 57.3 reported any mouth problems. There is a strong association between vision impairment and poorer oral health of adults; adults aged 40-64 years with vision impairment reported 90% to 150% greater odds of oral health problems, including fair/poor oral health status, mouth problems, and teeth problems, compared to people without vision impairment. CONCLUSIONS: Oral health disparities exist between adults with and without vision impairment. Targeted interventions are required to improve oral health in this vulnerable population. |
Antimicrobial resistance in Cambodia: a review
Reed TAN , Krang S , Miliya T , Townell N , Letchford J , Bun S , Sar B , Osbjer K , Seng S , Chou M , By Y , Vanchinsuren L , Nov V , Chau D , Phe T , de Lauzanne A , Ly S , Turner P . Int J Infect Dis 2019 85 98-107 OBJECTIVES: Following the launch of the Global Antimicrobial Resistance Surveillance System (GLASS), antimicrobial resistance (AMR) rates in many countries remain poorly described. This review provides an overview of published AMR data from Cambodia in the context of recently initiated national human and food-animal surveillance. METHODS: PubMed and the Cochrane Database of Systematic Reviews were searched for articles published from 2000 to 2018, which reported antimicrobial susceptibility testing (AST) data for GLASS specific organisms isolated from Cambodia. Articles were screened using strict inclusion/exclusion criteria. AST data was extracted, with medians and ranges of resistance rates calculated for specific bug-drug combinations. RESULTS: Twenty-four papers were included for final analysis, with 20 describing isolates from human populations. Escherichia coli was the most commonly described organism, with median resistance rates from human isolates of 92.8% (n=6 articles), 46.4% (n=4), 55.4% (n=8), and 46.4% (n=5) to ampicillin, 3(rd) generation cephalosporins, fluoroquinolones, and gentamicin respectively. CONCLUSIONS: Whilst resistance rates are high for several GLASS organisms, there were insufficient data to draw robust conclusions about the AMR situation in Cambodia. The recently implemented national AMR surveillance systems will begin to address this data gap. |
No shortcuts to safer opioid prescribing
Dowell D , Haegerich T , Chou R . N Engl J Med 2019 380 (24) 2285-2287 Since the Centers for Disease Control and Prevention (CDC) released its Guideline for Prescribing Opioids for Chronic Pain in 2016,1 the medical and health policy communities have largely embraced its recommendations. A majority of state Medicaid agencies reported having implemented the guideline in fee-for-service programs by 2018, and several states passed legislation to increase access to nonopioid pain treatments.2 Although outpatient opioid prescribing had been declining since 2012, accelerated decreases — including in high risk prescribing — followed the guideline’s release.2,3 Indeed, guideline uptake has been rapid. Difficulties faced by clinicians in prescribing opioids safely and effectively, growing awareness of opioid-associated risks, and a public health imperative to address opioid overdose underscored the need for guidance and probably facilitated uptake. Furthermore, the guideline was rated as high quality by the ECRI Guidelines Trust Scorecard. In addition, the CDC (including the authors of this Perspective, who were also authors of the Guideline) engaged clinicians, health systems leaders, payers, and other decision makers in discussions of the Guideline’s intent and provided clinical tools, including a mobile application and training, to facilitate appropriate implementation.4 |
Cancer communication research in the era of genomics and precision medicine: a scoping review
Kaphingst KA , Peterson E , Zhao J , Gaysynsky A , Elrick A , Hong SJ , Krakow M , Pokharel M , Ratcliff CL , Klein WMP , Khoury MJ , Chou WS . Genet Med 2018 21 (8) 1691-1698 Effective use of genetic and genomic data in cancer prevention and treatment depends on adequate communication with patients and the public. Although relevant empirical work has emerged, the scope and outcomes of this communication research have not been characterized. We conducted a comprehensive scoping review of recent published research (2010-2017) on communication of cancer-related genetic and genomic testing (CGT) information. Searches in six databases revealed 9243 unique records; 513 papers were included. Most papers utilized an observational quantitative design; fewer utilized an experimental design. More attention has been paid to outcomes of CGT results disclosure than to decision making regarding CGT uptake or the process of results disclosure. Psychosocial outcomes were most common across studies. This literature has a strong focus on BRCA1/2, with few papers focused on Lynch syndrome or next-generation technologies. Women, Caucasians, older adults, and those of higher socioeconomic status were overrepresented. Research gaps identified include the need for studies on the process of CGT communication; examining behavioral, decision making, and communication outcomes; and inclusion of diverse populations. Addressing these gaps can help improve the use of genomics in cancer control and reduce disparities in access to and use of CGT. |
Prevalence of diabetic retinopathy and associated mortality among diabetic adults with and without chronic kidney disease
Pavkov ME , Harding JL , Chou CF , Saaddine JB . Am J Ophthalmol 2019 198 200-208 Purpose: To estimate prevalence and severity of diabetic retinopathy (DR) among U.S. adults with diabetes and with or without chronic kidney disease (CKD), and assess associated risk of mortality. Design(s): Cross-sectional study with national survey data. Method(s): The cohort included adults >=40 years old with diabetes in the National Health and Nutrition Examination Surveys (NHANES) 2005-2008. Vital status was determined through December 31, 2011. We defined diabetes as hemoglobin A1c >=6.5% or self-report and CKD by urinary albumin/creatinine >=30 mg/g or glomerular filtration rate <60 mL/min/1.73 m2. The main outcomes were DR and mortality. Result(s): Prevalence of DR was 27.8% (95% CI 24.3-31.7), 36.2% (95%CI 30.1-42.7), and 23.4% (95% CI 19.2-28.1), overall, with and without CKD. Prevalence of vision-threatening DR was 4.2% (95% CI 3.2-5.5), 8.2% (95% CI 5.4-12.2), and 2.0% (95% CI 1.2-3.5), respectively. In a multivariable adjusted model, DR was positively but nonsignificantly associated with CKD (OR = 1.1, 95% CI 0.7-1.7), was 40% higher per 1% increase in hemoglobin A1c (OR = 1.4, 95% CI 1.1-1.6), was 30% higher per 5 years additional diabetes duration (OR = 1.3, 95% CI 1.1-1.5), was 30% higher per 10 mm Hg increase in systolic blood pressure (OR = 1.3, 95% CI 1.1-1.5), and was 6-fold higher with insulin treatment (OR = 6.2, 95% CI 2.6-14.8). Compared with diabetic participants with neither DR nor CKD, those with DR and CKD had a 3.6-fold (95% CI 1.5-9.1) increased adjusted risk for all-cause mortality. Conclusion(s): Over one third of persons with diabetes and CKD had DR. The risk of death was higher with than without CKD and DR. Many of the studied risk factors associated with DR are modifiable. |
Outbreak of Tattoo-Associated Nontuberculous Mycobacterial Skin Infections.
Griffin I , Schmitz A , Oliver C , Pritchard S , Zhang G , Rico E , Davenport E , Llau A , Moore E , Fernandez D , Mejia-Echeverry A , Suarez J , Noya-Chaveco P , Elmir S , Jean R , Pettengill JB , Hollinger KA , Chou K , Williams-Hill D , Zaki S , Muehlenbachs A , Keating MK , Bhatnagar J , Rowlinson MC , Chiribau C , Rivera L . Clin Infect Dis 2018 69 (6) 949-955 BACKGROUND: On April 29, 2015, the Florida Department of Health in Miami-Dade County (DOH-Miami-Dade) was notified by a local dermatologist of three patients with suspect nontuberculous mycobacterial (NTM) infection after receiving tattoos at a local tattoo studio. METHODS: DOH-Miami-Dade conducted interviews and offered testing, described below, to tattoo studio clients reporting rashes. Culture of clinical isolates and identification were performed at the Florida Bureau of Public Health Laboratories (BPHL). Characterization of NTM was performed by the Centers for Disease Control and Prevention (CDC) and the United States Food and Drug Administration (FDA), respectively. Whole-genome sequencing (WGS) and single-nucleotide polymorphism (SNP) analyses were used to construct a phylogeny among 21 Mycobacterium isolates at FDA. RESULTS: Thirty-eight of 226 interviewed clients were identified as outbreak-associated cases. Multivariate logistic regression revealed individuals who reported grey tattoo ink in their tattoos were 8.2 times as likely to report a rash [95% CI: 3.07-22.13]. Multiple NTM species were identified in clinical and environmental specimens. Phylogenetic results from environmental samples and skin biopsies indicated that two M. fortuitum isolates (greywash ink and a skin biopsy) and 11 M. abscessus isolates (five from the implicated bottle of greywash tattoo ink, two from tap water, and four from skin biopsies) were indistinguishable. In addition, M. chelonae was isolated from five unopened bottles of greywash ink provided by two other tattoo studios in Miami-Dade County. CONCLUSIONS: WGS and SNP analyses identified the tap water and the bottle of greywash tattoo ink as the sources of the NTM infections. |
Communication of cancer-related genetic and genomic information: A landscape analysis of reviews.
Peterson EB , Chou WS , Gaysynsky A , Krakow M , Elrick A , Khoury MJ , Kaphingst KA . Transl Behav Med 2018 8 (1) 59-70 Cancer-related genetic and genomic testing (CGT) is changing cancer care by personalizing care options, leading to an era of precision medicine. Advances in and increased use of CGT add complexity to clinical communication. This landscape analysis assessed published reviews of communication issues related to CGT and discusses implications for practice and behavioral research. A comprehensive electronic literature search was conducted of peer-reviewed literature reviews on studies related to CGT communication published between January 2010 and January 2017, resulting in a final sample of 24 reviews. Reviews were categorized, with overlaps, into four domains across the genetic testing communication continuum. Reviews on CGT-related knowledge, attitudes, and perceptions (n = 8) found that despite substantial public interest, their knowledge and awareness remains low. Providers also reported insufficient knowledge and overall caution, particularly regarding direct-to-consumer (DTC) genetic testing. Reviews of decision-making about CGT and test uptake (n = 8) identified individual, interpersonal, and systems-level barriers to uptake. Reviews of patient-provider CGT communication (n = 8) revealed limited communication and little empirical research on outcomes of communication or efforts at improving clinical and family communication. There were mixed findings in reviews (n = 15) on the psychological and behavioral impact of CGT, and DTC testing particularly had little effect on behaviors. Taken together, there is very little extant research in CGT in minority and underserved communities. In order for scientific advances in CGT to translate into equitable, patient-centered care, behavioral research, including health literacy and communication, plays critical roles. |
A systematic review and meta-analysis of venous thrombosis risk among users of combined oral contraception
Dragoman MV , Tepper NK , Fu R , Curtis KM , Chou R , Gaffield ME . Int J Gynaecol Obstet 2018 141 (3) 287-294 BACKGROUND: Combined oral contraceptives (COCs) containing various progestogens could be associated with differential risks for venous thromboembolism (VTE). OBJECTIVE: To evaluate the comparative risks of VTE associated with the use of low-dose (less than 50 mug ethinyl estradiol) COCs containing different progestogens. SEARCH STRATEGY: PubMed and the Cochrane Library were searched from database inception through September 15, 2016, by combining search terms for oral contraception and venous thrombosis. SELECTION CRITERIA: Studies reporting VTE risk estimates among healthy users of progestogen-containing low-dose COCs were included. DATA COLLECTION AND ANALYSIS: A random-effects model was used to generate pooled adjusted risk ratios and 95% confidence intervals; subgroup and sensitivity analyses assessed the impact of monophasic-COC use and study-level characteristics. MAIN RESULTS: There were 22 articles included in the analysis. The use of COCs containing cyproterone acetate, desogestrel, drospirenone, or gestodene was associated with a significantly increased risk of VTE compared with the use of levonorgestrel-containing COCs (pooled risk ratios 1.5-2.0). The analysis restricted to monophasic COC formulations with 30 mug of ethinyl estradiol yielded similar findings. After adjustment for study characteristics, the risk estimates were slightly attenuated. CONCLUSIONS: Compared with the use of levonorgestrel-containing COCs, the use of COCs containing other progestogens could be associated with a small increase in risk for VTE. This article is protected by copyright. All rights reserved. |
Multi-segmented trunk motion of healthy non-elderly adults in different decades of life
Breloff SP , Chou LS . Biomed Eng (Singapore) 2017 29 (4) Traditionally, gait analysis models the trunk as one rigid body segment. This approach has limitations; it does not capture all the movements of this area of the body throughout locomotion. Lower-extremity-gait kinematics do not routinely change in healthy non-elderly adults in different decades of life; however, it is unknown if trunk kinematics will be altered during different activities of daily living as a function of age. The purpose of this study was to determine if a previously validated multi-segmented trunk model would detect trunk movement variations in non-elderly healthy adults in different decades of life. Thirty-four non-elderly healthy adults in various decades of life (20-29 years, 30-39 years, 40-49 years, and 50-59 years) completed two tasks of ambulatory daily living (level walking and stair descent). Trunk maximum angle during the gait cycle, timing of the trunk maximum angle during the gait cycle and trunk range of motion were examined using analysis of variance procedures. Findings are that age group did not affect the trunk kinematics of individuals in different decades of life, but that may not represent the experiences of elderly individuals. |
Illicit drug use, illicit drug use disorders, and drug overdose deaths in metropolitan and nonmetropolitan areas - United States
Mack KA , Jones CM , Ballesteros MF . MMWR Surveill Summ 2017 66 (19) 1-12 PROBLEM/CONDITION: Drug overdoses are a leading cause of injury death in the United States, resulting in approximately 52,000 deaths in 2015. Understanding differences in illicit drug use, illicit drug use disorders, and overall drug overdose deaths in metropolitan and nonmetropolitan areas is important for informing public health programs, interventions, and policies. REPORTING PERIOD: Illicit drug use and drug use disorders during 2003-2014, and drug overdose deaths during 1999-2015. DESCRIPTION OF DATA: The National Survey of Drug Use and Health (NSDUH) collects information through face-to-face household interviews about the use of illicit drugs, alcohol, and tobacco among the U.S. noninstitutionalized civilian population aged ≥12 years. Respondents include residents of households and noninstitutional group quarters (e.g., shelters, rooming houses, dormitories, migratory workers' camps, and halfway houses) and civilians living on military bases. NSDUH variables include sex, age, race/ethnicity, residence (metropolitan/nonmetropolitan), annual household income, self-reported drug use, and drug use disorders. National Vital Statistics System Mortality (NVSS-M) data for U.S. residents include information from death certificates filed in the 50 states and the District of Columbia. Cases were selected with an underlying cause of death based on the ICD-10 codes for drug overdoses (X40-X44, X60-X64, X85, and Y10-Y14). NVSS-M variables include decedent characteristics (sex, age, and race/ethnicity) and information on intent (unintentional, suicide, homicide, or undetermined), location of death (medical facility, in a home, or other [including nursing homes, hospices, unknown, and other locations]) and county of residence (metropolitan/nonmetropolitan). Metropolitan/nonmetropolitan status is assigned independently in each data system. NSDUH uses a three-category system: Core Based Statistical Area (CBSA) of ≥1 million persons; CBSA of <1 million persons; and not a CBSA, which for simplicity were labeled large metropolitan, small metropolitan, and nonmetropolitan. Deaths from NVSS-M are categorized by the county of residence of the decedent using CDC's National Center for Health Statistics 2013 Urban-Rural Classification Scheme, collapsed into two categories (metropolitan and nonmetropolitan). RESULTS: Although both metropolitan and nonmetropolitan areas experienced significant increases from 2003-2005 to 2012-2014 in self-reported past-month use of illicit drugs, the prevalence was highest for the large metropolitan areas compared with small metropolitan or nonmetropolitan areas throughout the study period. Notably, past-month use of illicit drugs declined over the study period for the youngest respondents (aged 12-17 years). The prevalence of past-year illicit drug use disorders among persons using illicit drugs in the past year varied by metropolitan/nonmetropolitan status and changed over time. Across both metropolitan and nonmetropolitan areas, the prevalence of past-year illicit drug use disorders declined during 2003-2014. In 2015, approximately six times as many drug overdose deaths occurred in metropolitan areas than occurred in nonmetropolitan areas (metropolitan: 45,059; nonmetropolitan: 7,345). Drug overdose death rates (per 100,000 population) for metropolitan areas were higher than in nonmetropolitan areas in 1999 (6.4 versus 4.0), however, the rates converged in 2004, and by 2015, the nonmetropolitan rate (17.0) was slightly higher than the metropolitan rate (16.2). INTERPRETATION: Drug use and subsequent overdoses continue to be a critical and complicated public health challenge across metropolitan/nonmetropolitan areas. The decline in illicit drug use by youth and the lower prevalence of illicit drug use disorders in rural areas during 2012-2014 are encouraging signs. However, the increasing rate of drug overdose deaths in rural areas, which surpassed rates in urban areas, is cause for concern. PUBLIC HEALTH ACTIONS: Understanding the differences between metropolitan and nonmetropolitan areas in drug use, drug use disorders, and drug overdose deaths can help public health professionals to identify, monitor, and prioritize responses. Consideration of where persons live and where they die from overdose could enhance specific overdose prevention interventions, such as training on naloxone administration or rescue breathing. Educating prescribers on CDC's guideline for prescribing opioids for chronic pain (Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain-United States, 2016. MMWR Recomm Rep 2016;66[No. RR-1]) and facilitating better access to medication-assisted treatment with methadone, buprenorphine, or naltrexone could benefit communities with high opioid use disorder rates. |
The Female Genital Tract Microbiome Is Associated With Vaginal Antiretroviral Drug Concentrations in Human Immunodeficiency Virus-Infected Women on Antiretroviral Therapy.
Donahue Carlson R , Sheth AN , Read TD , Frisch MB , Mehta CC , Martin A , Haaland RE , Patel AS , Pau CP , Kraft CS , Ofotokun I . J Infect Dis 2017 216 (8) 990-999 Background: The female genital tract (FGT) microbiome may affect vaginal pH and other factors that influence drug movement into the vagina. We examined the relationship between the microbiome and antiretroviral concentrations in the FGT. Methods: Over one menstrual cycle, 20 human immunodeficiency virus (HIV)-infected women virologically suppressed on tenofovir (TFV) disoproxil fumarate/emtricitabine and ritonavir-boosted atazanavir (ATV) underwent serial paired cervicovaginal and plasma sampling for antiretroviral concentrations using high-performance liquid chromatography-tandem mass spectrometry. Analysis of 16S ribosomal RNA gene sequencing of cervicovaginal lavage clustered each participant visit into a unique microbiome community type (mCT). Results: Participants were predominantly African American (95%), with a median age of 38 years. Cervicovaginal lavage sequencing (n = 109) resulted in a low-diversity mCT dominated by Lactobacillus (n = 40), and intermediate-diversity (n = 28) and high-diversity (n = 41) mCTs with abundance of anaerobic taxa. In multivariable models, geometric mean FGT:plasma ratios varied significantly by mCT for all 3 drugs. For both ATV and TFV, FGT:plasma was significantly lower in participant visits with high- and low-diversity mCT groups (all P < .02). For emtricitabine, FGT:plasma was significantly lower in participant visits with low- vs intermediate-diversity mCT groups (P = .002). Conclusions: Certain FGT mCTs are associated with decreased FGT antiretroviral concentrations. These findings are relevant for optimizing antiretrovirals used for biomedical HIV prevention in women. |
Multiplex RT-PCR for Simultaneous Surveillance of Influenza A and B Viruses.
Zhou B , Deng YM , Barnes JR , Sessions O , Chou TW , Wilson M , Stark TJ , Volk M , Spirason N , Halpin RA , Kamaraj US , Ding T , Stockwell TB , Salvatore M , Ghedin E , Barr IG , Wentworth DE . J Clin Microbiol 2017 Influenza A and B viruses are the causative agents of annual influenza epidemics that can be severe; influenza A viruses intermittently cause pandemics. Sequence information from influenza genomes is instrumental in determining mechanisms underpinning antigenic evolution and antiviral resistance. However, due to sequence diversity and the dynamics of influenza evolution, rapid and high-throughput sequencing of influenza viruses remains a challenge. We developed a single-reaction FluA/B Multiplex RT-PCR method that amplifies the most critical genomic segments (HA, NA, and M) of seasonal influenza A and B viruses for next-generation sequencing, regardless of viral types, subtypes, or lineages. Herein we demonstrate that the strategy is highly sensitive and robust. The strategy was validated on thousands of seasonal influenza A and B virus positive specimens using multiple next-generation sequencing platforms. |
Early age-related macular degeneration with cardiovascular and renal comorbidities: An analysis of the National Health and Nutrition Examination Survey, 2005-2008
Cheng Q , Saaddine JB , Klein R , Rothenberg R , Chou CF , Il'yasova D . Ophthalmic Epidemiol 2017 24 (6) 1-7 PURPOSE: A cross sectional study was designed to examine the relationship of early age-related macular degeneration (AMD) with comorbidities of cardiovascular and renal conditions in the representative population using National Health and Nutrition Examination Survey (NHANES), 2005-2008. METHODS: Participants (≥40 years) who underwent retinal photography were included. Early AMD was defined by the retinal digital images. The comorbidities were self-reported stroke and heart disease (HD), including angina pectoris (AP), coronary heart disease (CHD), congestive heart failure (CHF), and myocardial infarction (MI). Chronic kidney disease (CKD) was determined based on self-report, estimation of glomerular filtration rate (GFR), or the level of urine albumin. RESULTS: The age-adjusted odds ratio (OR) and 95% CI for having early AMD for persons with the selected conditions were: 2.6 (1.9, 3.6) for any type of HD. When the conditions were considered separately, ORs (95% CIs) were: 2.0 (1.2, 3.4) for AP; 2.5 (1.6, 3.8) for CHD; 2.4 (1.6, 3.6) for MI; 2.3 (1.3, 3.9) for CHF; 3.3 (2.2, 5.0) for stroke; and 2.4 (1.8, 3.2) for CKD. Covariable-adjusted ORs (AOR) were attenuated for all examined conditions, but remained statistically significant. Having any single condition (AOR [95%CI]: 2.7 [1.5, 4.8]) was significantly associated with early AMD, as was having ≥ 2 conditions (AOR [95%CI]: 5.2 [3.0, 9.0]). The strongest association was between early AMD and the combination of HD and stroke (AOR [95% CI]: 6.3 [2.9, 13.8]). CONCLUSION: Cardiovascular and renal comorbidities are associated with early AMD in a representative sample of the US general population. |
- Page last reviewed:Feb 1, 2024
- Page last updated:Sep 16, 2024
- Content source:
- Powered by CDC PHGKB Infrastructure