Last data update: Oct 28, 2024. (Total: 48004 publications since 2009)
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Query Trace: Glidden E[original query] |
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Differences in drug poisonings among those who identify as transgender compared to cisgender: An analysis of the Toxicology Investigators Consortium (ToxIC) Core Registry, United States 2017-2021
Magnusson K , Glidden E , Mustaquim D , Welder LE , Stokes EK , Beauchamp GA , Greenberg MR , Aldy K , Mazzaccaro RJ , Careyva BA , Sabino JN , Fikse DJ , McLain K , Amaducci AM . Clin Ther 2024 PURPOSE: In this manuscript, the abbreviation TG is defined as persons who identify as transgender, GNC is defined as persons who identify as gender nonconforming, and CG is defined as persons who identify as cisgender. TG and GNC (e.g., nonbinary), are those whose gender identity and sex assigned at birth do not align, as opposed to CG. This study describes drug poisonings among TG, GNC, and CG captured in the Toxicology Investigators Consortium (ToxIC) Core Registry during 2017-2021. METHODS: Authors conducted a secondary data analysis of medical toxicology physician consultations involving intentional exposures (i.e., use with the knowledge of the exposed person) within the ToxIC Core Registry from 2017 through 2021. Demographic characteristics, exposure intent, and reported drug classes are reported by gender identity and sex assigned at birth. FINDINGS: From a total of 15,800 medical toxicology consultations, 213 (1.3%) involved both TG (n = 187, 1.2%) and GNC (n = 26, 0.2%), and 15,587 (98.7%) involved CG. Among TG, 128 (68.8%) were transgender men, 58 (31.2%) transgender women. Sixty-two percent of TG/GNC (n = 132) and 34.8% of CG (n = 5,428) were aged ≤18 years. Reported intent for exposure (i.e., self-harm and misuse/harmful use) differed proportionally across both sexes assigned at birth and gender identity among transgender men and cisgender men. IMPLICATIONS: In the ToxIC Core Registry, the consultations varied proportionally by age group across TG/GNC and CG, with more than half of TG/GNC aged ≤18 years. The proportion of consultations also varied by intent across TG/GNC and CG. Further research to delineate differences between TG/GNC and CG could increase knowledge in prevention, assessment, and treatment of drug poisonings in this population. |
Early biological markers of post-acute sequelae of SARS-CoV-2 infection
Lu S , Peluso MJ , Glidden DV , Davidson MC , Lugtu K , Pineda-Ramirez J , Tassetto M , Garcia-Knight M , Zhang A , Goldberg SA , Chen JY , Fortes-Cobby M , Park S , Martinez A , So M , Donovan A , Viswanathan B , Hoh R , Donohue K , McIlwain DR , Gaudiliere B , Anglin K , Yee BC , Chenna A , Winslow JW , Petropoulos CJ , Deeks SG , Briggs-Hagen M , Andino R , Midgley CM , Martin JN , Saydah S , Kelly JD . Nat Commun 2024 15 (1) 7466 To understand the roles of acute-phase viral dynamics and host immune responses in post-acute sequelae of SARS-CoV-2 infection (PASC), we enrolled 136 participants within 5 days of their first positive SARS-CoV-2 real-time PCR test. Participants self-collected up to 21 nasal specimens within the first 28 days post-symptom onset; interviewer-administered questionnaires and blood samples were collected at enrollment, days 9, 14, 21, 28, and month 4 and 8 post-symptom onset. Defining PASC as the presence of any COVID-associated symptom at their 4-month visit, we compared viral markers (quantity and duration of nasal viral RNA load, infectious viral load, and plasma N-antigen level) and host immune markers (IL-6, IL-10, TNF-α, IFN-α, IFN-γ, MCP, IP-10, and Spike IgG) over the acute period. Compared to those who fully recovered, those reporting PASC demonstrated significantly higher maximum levels of SARS-CoV-2 RNA and N-antigen, burden of RNA and infectious viral shedding, and lower Spike-specific IgG levels within 9 days post-illness onset. No significant differences were identified among a panel of host immune markers. Our results suggest early viral dynamics and the associated host immune responses play a role in the pathogenesis of PASC, highlighting the importance of understanding early biological markers in the natural history of PASC. |
Suspected counterfeit m-30 oxycodone pill exposures and acute withdrawals reported from a single hospital - Toxicology Investigators Consortium Core Registry, U.S. Census Bureau Western Region, 2017-2022
Glidden E , Gladden RM , Dion C , Spyres MB , Seth P , Aldy K , Mustaquim D . MMWR Morb Mortal Wkly Rep 2024 73 (29) 642-647 Availability of counterfeit prescription pills (counterfeit pills) containing illegally made fentanyl, including counterfeit M-30 oxycodone (counterfeit M-30) pills, has risen sharply in the United States and has been increasingly linked to overdose deaths. In 2023, approximately 115 million counterfeit pills were seized in U.S. High Intensity Drug Trafficking Areas. However, clinical data on counterfeit pill-related overdoses are limited. Medical toxicology consultations during 2017-2022 from one U.S. Census Bureau Western Region hospital participating in the Toxicology Investigators Consortium Core Registry were analyzed. A total of 352 cases suspected to involve counterfeit M-30 pills, including 143 (40.6%) cases of fentanyl exposure and 209 (59.4%) cases of acute withdrawal were identified; consultations increased from three in 2017, to 209 in 2022. Patients aged 15-34 years accounted for 95 (67.4%) exposure cases. Among all patients with exposures, 81.1% were hospitalized, 69.0% of whom were admitted to an intensive care unit. Additional substances were detected in 131 (91.6%) exposures. Providing outreach to younger persons misusing prescription pills, improving access to and distribution of harm reduction tools including fentanyl test strips and naloxone, and promoting linkage of persons treated for overdose in hospitals to harm reduction and substance use treatment services are strategies to reduce morbidity associated with use of counterfeit M-30. |
Viral determinants of acute COVID-19 symptoms in a nonhospitalized adult population in the pre-Omicron era
Goldberg SA , Lu S , Garcia-Knight M , Davidson MC , Tassetto M , Anglin K , Pineda-Ramirez J , Chen JY , Rugart PR , Mathur S , Forman CA , Donohue KC , Abedi GR , Saydah S , Briggs-Hagen M , Midgley CM , Andino R , Peluso MJ , Glidden DV , Martin JN , Kelly JD . Open Forum Infect Dis 2023 10 (8) ofad396 BACKGROUND: The influence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA level and presence of infectious virus on symptom occurrence is poorly understood, particularly among nonhospitalized individuals. METHODS: The study included 85 nonhospitalized, symptomatic adults, who were enrolled from September 2020 to November 2021. Data from a longitudinal cohort studied over 28 days was used to analyze the association of individual symptoms with SARS-CoV-2 viral RNA load, or the presence or level of infectious (culturable) virus. Presence of infectious virus and viral RNA load were assessed daily, depending on specimen availability, and amount of infectious virus was assessed on the day of maximum RNA load. Participants were surveyed for the start and end dates of 31 symptoms at enrollment and at days 9, 14, 21, and 28; daily symptom presence was determined analytically. We describe symptoms and investigate their possible association with viral determinants through a series of single or pooled (multiple days across acute period) cross-sectional analyses. RESULTS: There was an association between viral RNA load and the same-day presence of many individual symptoms. Additionally, individuals with infectious virus were more than three times as likely to have a concurrent fever than individuals without infectious virus, and more than two times as likely to have concurrent myalgia, chills, headache, or sore throat. CONCLUSIONS: We found evidence to support the association of viral RNA load and infectious virus on some, but not all symptoms. Fever was most strongly associated with the presence of infectious virus; this may support the potential for symptom-based isolation guidance for COVID-19. |
Prevalence and determinants of Kaposi's sarcoma-associated herpesvirus (KSHV) antibody positivity among adults living with HIV in East Africa (preprint)
Gowdara CK , Byakwaga H , Dollard SC , Muzoora CK , Glidden DV , Hunt PW , Bwana BM , Haberer JE , Bangsberg DR , Martin JN . medRxiv 2022 20 Background: Persons living with HIV (PLHIV) who are also infected with Kaposi sarcoma-associated herpesvirus (KSHV) constitute a group among the highest risk for Kaposi sarcoma (KS). As such, understanding KSHV prevalence amongst PLHIV is important for the control of KS. To date, data on KSHV prevalence amongst PLHIV in East Africa - one of the world's hotbeds for KS - is both sparse and variable. Method(s): In a cross-sectional design, we studied consecutive adult PLHIV identified just prior to starting antiretroviral therapy at an ambulatory HIV clinic in Mbarara, Uganda. Results from two enzyme immunoassays (with synthetic K8.1 and ORF 65 antigens as targets) and one immunofluorescence assay (using induced BCBL cells) to detect antibodies to KSHV were combined to classify KSHV antibody positivity. Result(s): We evaluated 727 PLHIV between 2005 to 2013; median age was 34 years (interquartile range (IQR): 28-40), 69% were women, and median CD4 count was 167 cells/microl (IQR: 95-260). Prevalence of KSHV antibody positivity was 42% (95% CI: 38%-46%), with little substantive change after several correction approaches, including Rogan-Gladen. Adjusted prevalence of KSHV antibody positivity was 1.6 times (95% CI: 1.3-1.9) higher in men than women; adjusted absolute prevalence difference was +0.20 (95% CI: +0.11 to +0.30). Lack of formal education (prevalence ratio=1.6 comparing no school to >= 4 years of secondary school; 95% CI: 1.1-2.3) was also associated with KSHV infection. We found no strong evidence for a role for age, alcohol use, or other measurements of sexual behavior, SES, or well-being in the occurrence of KSHV antibody positivity. Conclusion(s): Among adult PLHIV in western Uganda, KSHV prevalence is estimated at 42%, with little change after several approaches to correction for antibody detection inaccuracy. This estimate differs from several others in the region (up to 83%), highlighting need for inter-assay comparison studies using identical local specimens. To the extent HIV does not influence KSHV acquisition, the findings may also represent KSHV prevalence in the general population. The large-magnitude effect of sex and education on KSHV acquisition motivates an accelerated search for mechanisms. The sex effect, in part, may explain the higher incidence of KS among men. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Characterization of nonfatal opioid, cocaine, methamphetamine, and polydrug exposure and clinical presentations reported to the Toxicology Investigators Consortium Core Registry, January 2010-December 2021
Glidden E , Suen K , Mustaquim D , Vivolo-Kantor A , Brent J , Wax P , Aldy K . J Med Toxicol 2023 19 (2) 180-189 INTRODUCTION: To characterize and compare opioid-only, cocaine-only, methamphetamine-only, opioid-and-cocaine exposure, and opioid-and-methamphetamine exposure and to examine clinical presentations, leading to a better understanding of overdose effects involving these drug exposures. METHODS: We examined drug exposures in the Toxicology Investigators Consortium (ToxIC) Core Registry from January 2010 to December 2021, a case registry of patients presenting to participating healthcare sites that receive a medical toxicology consultation. Demographic and clinical presentations of opioid-only, cocaine-only, methamphetamine-only, and opioid-and-cocaine exposure, and opioid-and-methamphetamine exposure consultations were described; differences between single and polydrug exposure subgroups were calculated to determine statistical significance. Clinical presentations associated with exposures were evaluated through calculated adjusted relative risk. RESULTS: A total of 3,883 consultations involved opioids, cocaine, methamphetamine, opioid-and-cocaine exposure, or opioid-and-methamphetamine exposure. Opioid-only (n = 2,268, 58.4%) and methamphetamine-only (n = 712, 18.3%) comprised most consultations. There were significant differences in clinical presentations between exposure subgroups. Opioid-and-cocaine exposure consultations were 8.15 times as likely to present with a sympathomimetic toxidrome than opioid-only. Conversely, opioid-and-cocaine exposure and opioid-and-methamphetamine exposure were 0.32 and 0.42 times as likely to present with a sympathomimetic toxidrome compared to cocaine-only and methamphetamine-only consultations, respectively. Opioid-and-cocaine exposure was 0.67 and opioid-and-methamphetamine exposure was 0.74 times as likely to present with respiratory depression compared to opioid-only consultations. Similarly, opioid-and-cocaine exposure was 0.71 and opioid-and-methamphetamine exposure was 0.78 times as likely to present with CNS depression compared to opioid-only consultations. CONCLUSIONS: Used in combination, opioids and stimulants may mask typical clinical presentations of one another, misattributing incorrect drugs to overdose in both clinical treatment and public health surveillance. |
Morbidity and mortality of unintentional carbon monoxide poisoning: United States 2005 to 2018
Shin M , Bronstein AC , Glidden E , Malone M , Chang A , Law R , Boehmer TK , Strosnider H , Yip F . Ann Emerg Med 2022 81 (3) 309-317 STUDY OBJECTIVE: Centers for Disease Control and Prevention conducts case surveillance through the National Notifiable Diseases Surveillance System (NNDSS). This study aimed to provide surveillance report of unintentional carbon monoxide poisoning across multiple data sources to provide baseline data for the new NNDSS carbon monoxide poisoning surveillance. METHODS: For the period 2005 to 2018, we used 4 data sources to describe unintentional carbon monoxide poisoning: exposures reported by poison centers, emergency department (ED) visits, hospitalizations, and deaths. We conducted descriptive analyses by the cause of exposure (fire, nonfire, or unknown), age, sex, season, and US census region. Additional analyses were conducted using poison center exposure case data focusing on the reported signs and symptoms, management site, and medical outcome. RESULTS: Annually, we observed 39.5 poison center exposure calls (per 1 million, nationally), 56.5 ED visits (per 1 million, across 17 states), 7.3 hospitalizations (per 1 million, in 26 states), and 3.3 deaths (per 1 million, nationally) due to unintentional carbon monoxide poisoning. For 2005 to 2018, there was a decrease in the crude rate for non-fire-related carbon monoxide poisonings from hospital, and death data. Non-fire-related cases comprised 74.0% of ED visits data, 60.1% of hospitalizations, and 40.9% of deaths compared with other unintentional causes. Across all data sources, unintentional carbon monoxide poisonings were most often reported during the winter season, notably in January and December. Children aged 0 to 9 years had the highest reported rates in poison center exposure case data and ED visits (54.1 and 70.5 per 1 million, respectively); adults older than 80 years had the highest rates of hospitalization and deaths (20.2 and 9.9 per 1 million, respectively); and deaths occurred more often among men and in the Midwest region. Poison center exposure call data revealed that 45.9% of persons were treated at a health care facility. Headaches, nausea, and dizziness/vertigo were the most reported symptoms. CONCLUSION: The crude rates in non-fire-related carbon monoxide poisonings from hospitalizations, and mortality significantly decreased over the study period (ie, 2005 to 2018). This surveillance report provides trends and characteristics of unintentional carbon monoxide poisoning and the baseline morbidities and mortality data for the Centers for Disease Control and Prevention national surveillance system of carbon monoxide poisoning. |
Modeling the probability of HIV infection over time in high-risk seronegative participants receiving placebo in five randomized double-blind placebo-controlled HIV pre-exposure prophylaxis trials: A patient-level pooled analysis
Garcia-Cremades M , Hendrix CW , Jayachandran P , Strydom N , Jarlsberg L , Grant R , Celum CL , Martin M , Baeten JM , Marrazzo J , Anderson P , Choopanya K , Vanichseni S , Glidden DV , Savic RM . Pharmaceutics 2022 14 (9) The World Health Organization recommends pre-exposure prophylaxis (PrEP) for individuals at substantial risk of HIV infection. The aim of this analysis is to quantify the individual risk of HIV infection over time, using a large database of high-risk individuals (n = 5583). We used data from placebo recipients in five phase III PrEP trials: iPrEx, conducted in men who have sex with men and transgender women; VOICE, conducted in young women at high sexual risk; Partners PrEP, conducted in HIV serodiscordant heterosexual couples; TDF2, conducted in high-risk heterosexual men and women; and BTS, conducted in persons who inject drugs. The probability of HIV infection over time was estimated using NONMEM7.4. We identified predictors of HIV risk and found a substantial difference in the risk of infection among and within trial populations, with each study including a mix of low, moderate, and high-risk individuals (p < 0.05). Persons who were female at birth were at a higher risk of HIV infection than people who were male at birth. Final models were integrated in a tool that can assess person-specific risk and simulate cumulative HIV risk over time. These models can be used to optimize future PrEP clinical trials by identifying potential participants at highest risk. |
Tobacco product harm perceptions among US middle and high school students, 2016-2020
Glidden E , Hawkins NA , Jamal A , Wang TW . J Adolesc Health 2022 71 (3) 364-369 PURPOSE: The aim of this study is to examine US youths' harm perceptions toward nondaily use of e-cigarettes, cigarettes, cigars, smokeless tobacco, and hookahs. METHODS: The nationally representative, cross-sectional National Youth Tobacco Survey annually assessed the following: "How much do you think people harm themselves when they [use tobacco products] some days but not every day?" Weighted estimates for 2020 were generated overall (grades 6-12) and by select demographics. Multivariable regression examined linear and quadratic changes during 2016-2020 (excluding cigars). RESULTS: In 2020, the prevalence of middle and high school students reporting "no" or "little" harm (vs. "some" or "a lot") was 20.1% for e-cigarettes, 17.4% for hookahs, 14.6% for cigars, 13.5% for smokeless tobacco, and 11.0% for cigarettes. During 2016-2020, perceptions of "no" or "little" harm decreased for e-cigarettes, increased for cigarettes and smokeless tobacco, and exhibited nonlinear changes for hookahs. DISCUSSION: Most youth are aware of tobacco product harms, but opportunities exist to educate youth about the harms of nondaily tobacco product use. |
Characterizing HIV-preventive, plasma tenofovir concentrations. A pooled participant-level data analysis from HIV pre-exposure prophylaxis (PrEP) clinical trials
Garcia-Cremades M , Vuievi K , Hendrix CW , Jayachandran P , Jarlsberg L , Grant R , Celum CL , Martin M , Baeten JM , Marrazzo J , Anderson P , Choopanya K , Vanichseni S , Glidden DV , Savic RM . Clin Infect Dis 2022 75 (11) 1873-1882 BACKGROUND: Daily dosing of tenofovir disoproxil fumarate (TDF), with or without emtricitabine (FTC), has high efficacy in preventing HIV infection when individuals are adherent. The target protective plasma concentration of tenofovir (TFV), however, is not fully understood. The aim of this study is to estimate the protective TFV plasma concentration. METHODS: Participant data from TFV-based daily oral and topical active arms of phase III trials (iPrEx, VOICE and Partners PrEP) were pooled (n=2,950). Individual specific risk scores (low and high risk) of acquiring HIV, based on an earlier placebo analysis, were created. Longitudinal TFV pharmacokinetics (PK), HIV outcome, individual risk scores and the effect of sex at birth data were integrated and analyzed using non-linear mixed effects models (NONMEM). RESULTS: Around 50% of the individuals were estimated to be adherent, which differed from self-reported adherence (90%) and large variation between longitudinal adherence patterns were identified. Following oral administration, the estimated protective TFV trough concentration was substantially higher in high risk females (45.8ng/mL) compared to high risk males (16.1ng/mL) and to low risk individuals (7.5ng/mL). Dosing simulations indicated that high risk women require full adherence to maintain protective levels. CONCLUSIONS: Using the largest PK-HIV outcome database to date, we developed a population adherence-PK-risk-outcome model. Our results indicate that high risk females need higher levels of plasma TFV to achieve HIV protection compared to males. HIV protection exceeds 90% in all populations if daily adherence is achieved. |
Characteristics of e-Cigarette Use Behaviors Among US Youth, 2020
Wang TW , Gentzke AS , Neff LJ , Glidden EV , Jamal A , Park-Lee E , Ren C , Cullen KA , King BA , Hacker KA . JAMA Netw Open 2021 4 (6) e2111336 IMPORTANCE: Comprehensive surveillance of e-cigarette use behaviors among youth is important for informing strategies to address this public health epidemic. OBJECTIVE: To characterize e-cigarette use behaviors among US youth in 2020. DESIGN, SETTING, AND PARTICIPANTS: The 2020 National Youth Tobacco Survey, a nationally representative, cross-sectional, school-based survey of middle school (grades 6-8) and high school (grades 9-12) students, was conducted from January 16, 2020, to March 16, 2020. A total of 14 531 students from 180 schools participated in the 2020 survey, yielding a corresponding student-level participation rate of 87.4% and school-level participation rate of 49.9%. The overall response rate, a product of the school-level and student-level participation rates, was 43.6%. EXPOSURES: Current (past 30-day) e-cigarette use. MAIN OUTCOMES AND MEASURES: Self-reported current e-cigarette use behaviors (frequency of use, usual e-cigarette brand, and access source) by school level and flavored e-cigarette use and flavor types among current e-cigarette users by school level and device type. Prevalence estimates were weighted to account for the complex survey design. RESULTS: Overall, 14 531 students completed the survey, including 7330 female students and 7133 male students with self-reported grade level and sex. In 2020, 19.6% (95% CI, 17.2%-22.2%) of high school students and 4.7% (95% CI, 3.6%-6.0%) of middle school students reported current e-cigarette use. Among them, 38.9% (95% CI, 35.2%-42.6%) of high school users and 20.0% (95% CI, 16.0%-24.8%) of middle school users reported e-cigarette use on 20 to 30 days within the past 30 days. Among current users, JUUL was the most commonly reported usual brand (high school: 25.4%; 95% CI, 18.8%-33.4%; middle school: 35.1%; 95% CI, 27.9%-43.1%). Among current users, the most common source of obtaining e-cigarettes was from a friend (high school: 57.1%; 95% CI, 52.6%-61.4%; middle school: 58.9%; 95% CI, 51.4%-66.1%). Among current users, 84.7% (95% CI, 82.2%-86.9%) of high school students and 73.9% (95% CI, 66.9%-79.8%) of middle school students reported flavored e-cigarette use. Fruit-flavored e-cigarettes were the most commonly reported flavor among current exclusive e-cigarette users of prefilled pods or cartridges (67.3%; 95% CI, 60.9%-73.0%), disposable e-cigarettes (85.8%; 95% CI, 79.8%-90.3%), and tank-based devices (82.7%; 95% CI, 68.9%-91.1%), followed by mint-flavored e-cigarettes. CONCLUSIONS AND RELEVANCE: These results suggest that although current e-cigarette use decreased during 2019 to 2020, overall prevalence, frequent use, and flavored e-cigarette use remained high. Continued actions are warranted to prevent and reduce e-cigarette use among US youth. |
Disposable E-Cigarette Use among U.S. Youth - An Emerging Public Health Challenge
Wang TW , Gentzke AS , Neff LJ , Glidden EV , Jamal A , King BA , Hacker KA , Park-Lee E , Ren C , Cullen KA . N Engl J Med 2021 384 (16) 1573-1576 Previous increases in the use of electronic cigarettes (e-cigarettes) by youth were driven by multiple factors, including advertising, the use of appealing flavors, and the introduction of new devices with prefilled pods or cartridges and high nicotine levels, such as Juul.1 According to data from the National Youth Tobacco Survey (NYTS), 19.6% of high school students (3.02 million) and 4.7% of middle school students (550,000) reported current (within the preceding 30 days) e-cigarette use in 2020 — 1.8 million fewer than in 2019.2 However, e-cigarette use among youth remains prominent and the landscape of devices is evolving, both of which pose a public health challenge. We assessed the changes in device type–specific e-cigarette use during 2019 and 2020. |
Characteristics of hospitalized and nonhospitalized patients in a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury - United States, November 2019
Chatham-Stephens K , Roguski K , Jang Y , Cho P , Jatlaoui TC , Kabbani S , Glidden E , Ussery EN , Trivers KF , Evans ME , King BA , Rose DA , Jones CM , Baldwin G , Delaney LJ , Briss P , Ritchey MD . MMWR Morb Mortal Wkly Rep 2019 68 (46) 1076-1080 CDC, the Food and Drug Administration (FDA), state and local health departments, and public health and clinical stakeholders are investigating a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) (1). As of November 13, 2019, 49 states, the District of Columbia, and two U.S. territories (Puerto Rico and U.S. Virgin Islands) have reported 2,172 EVALI cases to CDC, including 42 (1.9%) EVALI-associated deaths. To inform EVALI surveillance, including during the 2019-20 influenza season, case report information supplied by states for hospitalized and nonhospitalized patients with EVALI were analyzed using data collected as of November 5, 2019. Among 2,016 EVALI patients with available data on hospitalization status, 1,906 (95%) were hospitalized, and 110 (5%) were not hospitalized. Demographic characteristics of hospitalized and nonhospitalized patients were similar; most were male (68% of hospitalized versus 65% of nonhospitalized patients), and most were aged <35 years (78% of hospitalized versus 74% of nonhospitalized patients). These patients also reported similar use of tetrahydrocannabinol (THC)-containing products (83% of hospitalized versus 84% of nonhospitalized patients). Given the similarity between hospitalized and nonhospitalized EVALI patients, the potential for large numbers of respiratory infections during the emerging 2019-20 influenza season, and the potential difficulty in distinguishing EVALI from respiratory infections, CDC will no longer collect national data on nonhospitalized EVALI patients. Further collection of data on nonhospitalized patients will be at the discretion of individual state, local, and territorial health departments. Candidates for outpatient management of EVALI should have normal oxygen saturation (>/=95% while breathing room air), no respiratory distress, no comorbidities that might compromise pulmonary reserve, reliable access to care, strong social support systems, and should be able to ensure follow-up within 24-48 hours of initial evaluation and to seek medical care promptly if respiratory symptoms worsen. Health care providers should emphasize the importance of annual influenza vaccination for all persons aged >/=6 months, including persons who use e-cigarette, or vaping, products (2,3). |
Update: Characteristics of patients in a national outbreak of e-cigarette, or vaping, product use-associated lung injuries - United States, October 2019
Moritz ED , Zapata LB , Lekiachvili A , Glidden E , Annor FB , Werner AK , Ussery EN , Hughes MM , Kimball A , DeSisto CL , Kenemer B , Shamout M , Garcia MC , Reagan-Steiner S , Petersen EE , Koumans EH , Ritchey MD , King BA , Jones CM , Briss PA , Delaney L , Patel A , Polen KD , Sives K , Meaney-Delman D , Chatham-Stephens K . MMWR Morb Mortal Wkly Rep 2019 68 (43) 985-989 CDC, the Food and Drug Administration, state and local health departments, and other public health and clinical stakeholders are investigating a national outbreak of electronic-cigarette (e-cigarette), or vaping, product use-associated lung injury (EVALI) (1). As of October 22, 2019, 49 states, the District of Columbia (DC), and the U.S. Virgin Islands have reported 1,604 cases of EVALI to CDC, including 34 (2.1%) EVALI-associated deaths in 24 states. Based on data collected as of October 15, 2019, this report updates data on patient characteristics and substances used in e-cigarette, or vaping, products (2) and describes characteristics of EVALI-associated deaths. The median age of EVALI patients who survived was 23 years, and the median age of EVALI patients who died was 45 years. Among 867 (54%) EVALI patients with available data on use of specific e-cigarette, or vaping, products in the 3 months preceding symptom onset, 86% reported any use of tetrahydrocannabinol (THC)-containing products, 64% reported any use of nicotine-containing products, and 52% reported use of both. Exclusive use of THC-containing products was reported by 34% of patients and exclusive use of nicotine-containing products by 11%, and for 2% of patients, no use of either THC- or nicotine-containing products was reported. Among 19 EVALI patients who died and for whom substance use data were available, 84% reported any use of THC-containing products, including 63% who reported exclusive use of THC-containing products; 37% reported any use of nicotine-containing products, including 16% who reported exclusive use of nicotine-containing products. To date, no single compound or ingredient used in e-cigarette, or vaping, products has emerged as the cause of EVALI, and there might be more than one cause. Because most patients reported using THC-containing products before symptom onset, CDC recommends that persons should not use e-cigarette, or vaping, products that contain THC. In addition, because the specific compound or ingredient causing lung injury is not yet known, and while the investigation continues, persons should consider refraining from the use of all e-cigarette, or vaping, products. |
Characteristics of tianeptine exposures reported to the National Poison Data System - United States, 2000-2017
El Zahran T , Schier J , Glidden E , Kieszak S , Law R , Bottei E , Aaron C , King A , Chang A . MMWR Morb Mortal Wkly Rep 2018 67 (30) 815-818 Tianeptine (marketed as Coaxil or Stablon) is an atypical tricyclic drug used as an antidepressant in Europe, Asia, and Latin America. In the United States, tianeptine is not approved by the Food and Drug Administration (FDA) for medical use and is an unscheduled pharmaceutical agent* (1). Animal and human studies show that tianeptine is an opioid receptor agonist (2). Several case studies have reported severe adverse effects and even death from recreational abuse of tianeptine (3-5). To characterize tianeptine exposures in the United States, CDC analyzed all exposure calls related to tianeptine reported by poison control centers to the National Poison Data System (NPDS)(dagger) during 2000-2017. Tianeptine exposure calls, including those for intentional abuse or misuse, increased across the United States during 2014-2017, suggesting a possible emerging public health risk. Most tianeptine exposures occurred among persons aged 21-40 years and resulted in moderate outcomes. Neurologic, cardiovascular, and gastrointestinal signs and symptoms were the most commonly reported health effects, with some effects mimicking opioid toxicity. A substantial number of tianeptine exposure calls also reported clinical effects of withdrawal. Among 83 tianeptine exposures with noted coexposures, the most commonly reported coexposures were to phenibut, ethanol, benzodiazepines, and opioids. |
The kynurenine pathway of tryptophan catabolism and AIDS-associated Kaposi sarcoma in Africa
Byakwaga H , Hunt PW , Laker-Oketta M , Glidden DV , Huang Y , Bwana BM , Mocello AR , Bennett J , Walusansa V , Dollard SC , Bangsberg DR , Mbidde EK , Martin JN . J Acquir Immune Defic Syndr 2015 70 (3) 296-303 BACKGROUND: Other than Kaposi sarcoma (KS)-associated herpesvirus and CD4 T-cell lymphopenia, the mechanisms responsible for KS in the context of HIV are poorly understood. One recently explored pathway of HIV pathogenesis involves induction of the enzyme indoleamine 2,3-dioxygenase-1 (IDO), which catabolizes tryptophan into kynurenine and several other immunologically active metabolites that suppress T-cell proliferation. We investigated the role of IDO in the development of KS in HIV disease. METHODS: In a case-control study among untreated HIV-infected Ugandans, cases were adults with KS and controls were without KS. IDO activity was assessed by the ratio of plasma kynurenine to tryptophan levels (KT ratio), measured by liquid chromatography-tandem mass spectrometry. RESULTS: We studied 631 HIV-infected subjects: 222 KS cases and 409 controls. Non-KS controls had a higher median plasma KT ratio (130, interquartile range: 90 to 190 nM/muM) than KS cases (110, interquartile range: 90 to 150 nM/muM) (P = 0.004). After adjustment for age, sex, CD4 count, and plasma HIV RNA level, subjects with the highest (fourth quartile) plasma KT ratios had a 59% reduction (95% confidence interval: 27% to 77%) in the odds of KS compared with those with the lowest (first quartile) levels. KS was also independently associated with lower CD4 count, higher plasma HIV RNA, and men. CONCLUSIONS: Among HIV-infected individuals, greater activity of the kynurenine pathway of tryptophan catabolism, as evidenced by higher levels of plasma KT ratio, was associated with lower occurrence of KS. Some consequences of immune activation in HIV infection might actually suppress certain cancers. |
Tenofovir diphosphate concentrations and prophylactic effect in a macaque model of rectal simian HIV transmission
Anderson PL , Glidden DV , Bushman LR , Heneine W , Garcia-Lerma JG . J Antimicrob Chemother 2014 69 (9) 2470-6 OBJECTIVES: This study evaluated the relationship between intracellular tenofovir diphosphate concentrations in peripheral blood mononuclear cells and prophylactic efficacy in a macaque model for HIV pre-exposure prophylaxis (PrEP). METHODS: Macaques were challenged with simian HIV (SHIV) via rectal inoculation once weekly for up to 14 weeks. A control group (n = 34) received no drug, a second group (n = 6) received oral tenofovir disoproxil fumarate/emtricitabine 3 days before each virus challenge and a third group (n = 6) received the same dosing plus another dose 2 h after virus challenge. PBMCs were collected just before each weekly virus challenge. The relationship between tenofovir diphosphate in PBMCs and prophylactic efficacy was assessed with a Cox proportional hazards model. RESULTS: The percentages of animals infected in the control, one-dose and two-dose groups were 97, 83 and 17, respectively. The mean (SD) steady-state tenofovir diphosphate concentration (fmol/106 cells) was 15.8 (7.6) in the one-dose group and 30.7 (10.1) in the two-dose group. Each 5 fmol tenofovir diphosphate/106 cells was associated with a 40% (95% CI 17%-56%) reduction in risk of SHIV acquisition, P = 0.002. The tenofovir diphosphate concentration associated with a 90% reduction in risk (EC90) was 22.6 fmol/106 cells (95% CI 13.8-60.8). CONCLUSIONS: The prophylactic EC90 for tenofovir diphosphate identified in macaques exposed rectally compares well with the EC90 previously identified in men who have sex with men (MSM; 16 fmol/106 cells, 95% CI 3-28). These results highlight the relevance of this model to inform human PrEP studies of oral tenofovir disoproxil fumarate/emtricitabine for MSM. |
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