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.

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.

Morbidity and Mortality of Unintentional Carbon Monoxide Poisoning: United States 2005 to 2018.

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.

Characteristics of Hospitalized and Nonhospitalized Patients in a Nationwide Outbreak of E-cigarette, or Vaping, Product Use-Associated Lung Injury - United States, November 2019.

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.

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.

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)† 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.

Multiple site acetylation of Rictor stimulates mammalian target of rapamycin complex 2 (mTORC2)-dependent phosphorylation of Akt protein.

The serine/threonine protein kinase Akt is a critical regulator of cell growth and survival in response to growth factors. A key step in Akt activation is phosphorylation at Ser-473 by the mammalian target of rapamycin (mTOR) complex 2 (mTORC2). Although Rictor is required for the stability and activity of mTORC2, little is known about functional regions or post-translational modifications within Rictor that are responsible for regulating mTORC2. Here, we demonstrate that Rictor contains two distinct central regions critical for mTORC2 function. One we refer to as the stability region because it is critical for interaction with Sin1.1 and LST8, and a second adjacent region is required for multisite acetylation. p300-mediated acetylation of Rictor increases mTORC2 activity toward Akt, whereas site-directed mutants within the acetylation region of Rictor exhibit reduced insulin-like growth factor 1 (IGF-1)-stimulated mTORC2 kinase activity. Inhibition of deacetylases, including the NAD+-dependent sirtuins, promotes Rictor acetylation and IGF-1-mediated Akt phosphorylation. These results suggest that multiple-site acetylation of Rictor signals for increased activation of mTORC2, providing a critical link between nutrient-sensitive deacetylases and mTORC2 signaling to Akt.

Effectiveness of Osteopathic Manipulative Treatment in Treating Symptoms of Irritable Bowel Syndrome: A Literature Review.

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that affects a patient for their entire life. Effective treatments for IBS are scarce, leading to an increased interest in alternative treatments such as osteopathic manipulative treatment (OMT). OMT uses hands-on treatment to reduce pain through various methods. By focusing on visceral techniques, OMT can restore autonomic homeostasis and increase lymphatic flow. This literature review aims to investigate the efficacy of visceral OMT in reducing the severity of IBS symptoms. Five primary research studies were evaluated in this analysis. The concluding results show that visceral OMT effectively reduces the symptoms of IBS and improves patients' quality of life. Therefore, OMT should be considered an alternative therapy for treating IBS.

Characterization of Nonfatal Opioid, Cocaine, Methamphetamine, and Polydrug Exposure and Clinical Presentations Reported to the Toxicology Investigators Consortium Core Registry, January 2010-December 2021.

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.

The impact of the method of genetic identity disclosure on the donor conceived adult.

Aim: 106 donor conceived people (DCP) responded to an anonymous survey study that examined the impact of the method of genetic identity disclosure and age at the time of the disclosure on their emotional wellbeing, familial relations, and perceptions of donor conception practices.Methods: Participants were asked to select the way in which they were informed they are DCP and the age group at which this occurred, and then were asked to select strongly agree, agree, neither agree or disagree, disagree, or strongly disagree in response to 26 statements that examined their perceptions of the topics listed above. Responses were grouped based on the age of genetic identity disclosure and the method of genetic identity disclosure, then numerically compared by assigning each type of response a number. Statistical analysis using repeatedmeasures ANOVA was performed to identify differences among these factors.Results: This analysis revealed that most participants 18 ≥ years and most participants who discovered their genetic identity through means other than through their parent(s) had worse emotional wellbeing and familial relations. However, most participants among all categories had a negative perception of donor conception practices.Conclusion: Continued work is needed to understand and support the growing DCP population.

Tobacco Product Harm Perceptions Among US Middle and High School Students, 2016-2020.

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.

Characteristics of e-Cigarette Use Behaviors Among US Youth, 2020.

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.

The cotranslational maturation program for the type II membrane glycoprotein influenza neuraminidase.

The earliest steps in nascent protein maturation greatly affect its overall efficiency. Constraints placed on maturing proteins at these early stages limit available conformations and help to direct the native maturation process. For type II membrane proteins, these cotranslational constraints include N- and C-terminal membrane tethering, chaperone binding, and disulfide bond formation. The cotranslational maturation process for the type II membrane glycoprotein influenza neuraminidase (NA) was investigated to provide a deeper understanding of these initial endoplasmic reticulum events. The type II orientation provides experimental advantages to monitor the first maturation steps. Calnexin was shown to cotranslationally interact with NA prior to calreticulin. These interactions were required for the efficient maturation of NA as it prematurely formed intramolecular disulfides and aggregated when calnexin and calreticulin interactions were abolished. Lectin chaperone binding slowed the NA maturation process, increasing its fidelity. Carbohydrates were required for NA maturation in a regio-specific manner. A subset of NA formed intermolecular disulfides and oligomerized cotranslationally. This fraction increased in the absence of calnexin and calreticulin binding. NA dimerization also occurred for an NA mutant lacking the critical large loop disulfide bond, indicating that dimerization did not require proper NA oxidation. The strict evaluation of proper maturation carried out by the quality control machinery was instilled at the tetramerization step. This study illustrates the type II membrane protein maturation process and shows how important cotranslational events contribute to the proper cellular maturation of glycoproteins.