The Impact of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pandemic on Substance Use in the United States.

The SARS-CoV-2 pandemic has been associated with dramatic increases in substance use, as marked by increased alcohol, nicotine, and cannabis sales. Lethal opioid overdoses also increased dramatically, especially during the initial phases of the epidemic when lockdowns and social isolation combined with increasing fentanyl contamination of the illicit drug supply resulted in more overdoses and fewer opportunities for rescue. Substance use, and especially inhalational drug use, increases the likelihood of both transmission and severe infection. Youth are especially vulnerable to substance use and have increased risk of long-term problems. These outcomes highlight the need for greater access to substance use treatment. Virtual treatment, which emerged as a promising format during the pandemic, may reduce access barriers. This article reviews trends in substance use during the pandemic, explores root causes of increased use and overdose, and examines the potential to increase treatment through virtual care, especially during future periods of disruption.

Dietary sugar intake and risk of Alzheimer's disease in older women.

BACKGROUND: Despite some reports of cardiometabolic disorders associated with the risk of Alzheimer's disease (AD), limited studies have been conducted to examine the association between excessive sugar intake (a risk factor for cardiometabolic disorders) and AD risk. AIM: The purpose of our study was to evaluate if excessive sugar intake has a significant long-term effect on the risk of AD. METHODS: A population sample of 37,689 participants, who enrolled in the United States (US) Women's Health Initiative - Dietary Modification Trial (WHI-DM) in 1993-2005 and its extended observational follow-up study through 1 March 2019, were analyzed. Dietary sugar intake was measured using food frequency questionnaires. AD was classified by reports using a standard questionnaire. A dietary pattern that explained the maxima variations in sugar intake was constructed using reduced rank regression (RRR) technique. Associations of RRR dietary pattern scores and sugar intake (g/day) by quartiles (Q1 through Q4) with AD risk were examined using Cox proportional hazards regression analysis with adjusting for key covariates. RESULTS: During a mean follow-up of 18.7 years, 4586 participants reported having incident AD. The total incidence rate (95% confidence interval [CI]) of AD was 6.5 (6.3-6.7) per 1000 person-years (PYs). The incidence rates (95% CI) of AD by total sugar intake were 6.2 (5.8-6.6), 6.4 (6.0-6.8), 6.6 (6.3-7.0), and 6.9 (6.5-7.3) per 1000 PYs among those in quartiles (Q) 1 to Q4 (toward higher sugar consumption) of total sugar intake, respectively (test for trend of AD incident rates, p < 0.001). Individuals in Q4 of total sugar intake had a 1.19 higher risk of incident AD than those in Q1 (hazard ratio [HR] = 1.19, 95% CI: 1.05-1.34, p = 0.01). An estimated increase of 10 g/day in total sugar intake (about 2.4 teaspoons) was associated with an increased AD risk by 1.3-1.4%. Of six subtypes of sugar intake, lactose was significantly associated with AD risk. CONCLUSIONS: Our study indicates that excessive total sugar intake was significantly associated with AD risk in women. Of six subtypes of sugar intake, lactose had a stronger impact on AD risk.

A Membrane-Modulated Centrifugal Microdevice for Enzyme-Linked Immunosorbent Assay-Based Detection of Illicit and Misused Drugs.

Increased opioid use and misuse have imposed large analytical demands across clinical and forensic sectors. Due to the absence of affordable, accurate, and simple on-site tests (e.g., point of interdiction and bedside), analysis is primarily conducted in centralized laboratories via time-consuming, labor-intensive methods. Many healthcare facilities do not have such analytical capabilities and must send samples to commercial laboratories, increasing turnaround time and care costs, as well as delaying public health warnings regarding the emergence of specific substances. Enzyme-linked immunosorbent assays (ELISAs) are used ubiquitously, despite lengthy workflows that require substantial manual intervention. Faster, reliable analytics are desperately needed to mitigate the mortality and morbidity associated with the current substance use epidemic. We describe one such alternative─a portable centrifugal microfluidic ELISA system that supplants repetitive pipetting with rotationally controlled fluidics. Embedded cellulosic membranes act as microvalves, permitting flow only when centrifugally generated hydraulic pressure exceeds their liquid entry pressure. These features enable stepwise reagent introduction, incubation, and removal simply by tuning rotational frequency. We demonstrate the success of this platform through sensitive, specific colorimetric detection of opiates, a subclass of opioids naturally derived from the opium poppy. Objective image analysis eliminated subjectivity in human color perception and permitted reliable detection of opiates in buffer and artificial urine at the ng/µL range. Opiates were clearly differentiated from other drug classes without interference from common adulterants known to cause false positive results in current colorimetric field tests. Eight samples were simultaneously analyzed in under 1 h, a marked reduction from the traditional multiday timeline. This approach could permit rapid, automatable ELISA-based drug detection outside of traditional laboratories by nontechnical personnel.

The role of catecholamines in modulating responses to stress: Sex-specific patterns, implications, and therapeutic potential for post-traumatic stress disorder and opiate withdrawal.

Emotional arousal is one of several factors that determine the strength of a memory and how efficiently it may be retrieved. The systems at play are multifaceted; on one hand, the dopaminergic mesocorticolimbic system evaluates the rewarding or reinforcing potential of a stimulus, while on the other, the noradrenergic stress response system evaluates the risk of threat, commanding attention, and engaging emotional and physical behavioral responses. Sex-specific patterns in the anatomy and function of the arousal system suggest that sexually divergent therapeutic approaches may be advantageous for neurological disorders involving arousal, learning, and memory. From the lens of the triple network model of psychopathology, we argue that post-traumatic stress disorder and opiate substance use disorder arise from maladaptive learning responses that are perpetuated by hyperarousal of the salience network. We present evidence that catecholamine-modulated learning and stress-responsive circuitry exerts substantial influence over the salience network and its dysfunction in stress-related psychiatric disorders, and between the sexes. We discuss the therapeutic potential of targeting the endogenous cannabinoid system; a ubiquitous neuromodulator that influences learning, memory, and responsivity to stress by influencing catecholamine, excitatory, and inhibitory synaptic transmission. Relevant preclinical data in male and female rodents are integrated with clinical data in men and women in an effort to understand how ideal treatment modalities between the sexes may be different.

Outbreak of Severe Hypoglycemia After Ingestion of a Male Enhancement Supplement - Virginia, August-November 2019.

In August 2019, the Virginia Poison Center (VPC) and the Blue Ridge Poison Center (BRPC) were contacted concerning patients experiencing repeated episodes of marked hypoglycemia following ingestion of a male enhancement supplement tablet marketed as "V8" in convenience stores in central Virginia. Over the following 3 months, the Virginia Department of Agriculture and Consumer Services (VDACS) and the Virginia Department of Health (VDH) conducted an investigation and identified 17 patients meeting the case definition (severe hypoglycemia within 48 hours of consuming an over-the-counter male enhancement supplement in a man with no history of use of insulin or other medication used to control blood glucose). Analysis of the V8 tablets revealed that most contained glyburide, a sulfonylurea oral hypoglycemic used in the treatment of diabetes and associated with prolonged hypoglycemia following overdose (1). To stem this outbreak, V8 was removed from stores when found, and public service announcements were released. The public health implications of V8 use include the potential for substantial morbidity from hypoglycemic episodes and the potential for mortality if health care services are not accessed in a timely manner when hypoglycemia occurs. The presence of V8 in the market poses a serious threat to public health because of its potentially life-threatening adverse effects.

Fine Particulate Air Pollution and Daily Mortality. A Nationwide Analysis in 272 Chinese Cities.

RATIONALE: Evidence concerning the acute health effects of air pollution caused by fine particulate matter (PM2.5) in developing countries is quite limited. OBJECTIVES: To evaluate short-term associations between PM2.5 and daily cause-specific mortality in China. METHODS: A nationwide time-series analysis was performed in 272 representative Chinese cities from 2013 to 2015. Two-stage Bayesian hierarchical models were applied to estimate regional- and national-average associations between PM2.5 concentrations and daily cause-specific mortality. City-specific effects of PM2.5 were estimated using the overdispersed generalized additive models after adjusting for time trends, day of the week, and weather conditions. Exposure-response relationship curves and potential effect modifiers were also evaluated. MEASUREMENTS AND MAIN RESULTS: The average of annual mean PM2.5 concentration in each city was 56 µg/m3 (minimum, 18 µg/m3; maximum, 127 µg/m3). Each 10-µg/m3 increase in 2-day moving average of PM2.5 concentrations was significantly associated with increments in mortality of 0.22% from total nonaccidental causes, 0.27% from cardiovascular diseases, 0.39% from hypertension, 0.30% from coronary heart diseases, 0.23% from stroke, 0.29% from respiratory diseases, and 0.38% from chronic obstructive pulmonary disease. There was a leveling off in the exposure-response curves at high concentrations in most, but not all, regions. The associations were stronger in cities with lower PM2.5 levels or higher temperatures, and in subpopulations with elder age or less education. CONCLUSIONS: This nationwide investigation provided robust evidence of the associations between short-term exposure to PM2.5 and increased mortality from various cardiopulmonary diseases in China. The magnitude of associations was lower than those reported in Europe and North America.

Ergonomics and Beyond: Understanding How Chemical and Heat Exposures and Physical Exertions at Work Affect Functional Ability, Injury, and Long-Term Health.

OBJECTIVE: To honor Tom Waters's work on emerging occupational health issues, we review the literature on physical along with chemical exposures and their impact on functional outcomes. BACKGROUND: Many occupations present the opportunity for exposure to multiple hazardous exposures, including both physical and chemical factors. However, little is known about how these different factors affect functional ability and injury. The goal of this review is to examine the relationships between these exposures, impairment of the neuromuscular and musculoskeletal systems, functional outcomes, and health problems with a focus on acute injury. METHOD: Literature was identified using online databases, including PubMed, Ovid Medline, and Google Scholar. References from included articles were searched for additional relevant articles. RESULTS: This review documented the limited existing literature that discussed cognitive impairment and functional disorders via neurotoxicity for physical exposures (heat and repetitive loading) and chemical exposures (pesticides, volatile organic compounds [VOCs], and heavy metals). CONCLUSION: This review supports that workers are exposed to physical and chemical exposures that are associated with negative health effects, including functional impairment and injury. Innovation in exposure assessment with respect to quantifying the joint exposure to these different exposures is especially needed for developing risk assessment models and, ultimately, preventive measures. APPLICATION: Along with physical exposures, chemical exposures need to be considered, alone and in combination, in assessing functional ability and occupationally related injuries.

Identifying Adolescent Vaping With Screening to Brief Intervention and Brief Screener for Tobacco, Alcohol, and Drugs Screening Tools.

PURPOSE: This study aimed to determine whether the modified Screening to Brief Intervention (S2BI) and Brief Screener for Tobacco, Alcohol, and Drugs (BSTAD) that included e-cigarettes/vaping as examples could identify all nicotine and cannabis use or whether additional questions specifically about vaping are needed. METHODS: Between July 2020 and February 2022, adolescents recruited from primary care or an outpatient adolescent substance use disorder program were randomized to complete S2BI or BSTAD followed by specific questions about vaping. Screen questions were updated to include "vaping" in the parenthetical examples of nicotine and cannabis use. RESULTS: Data from 502 adolescent participants who completed both the S2BI or BSTAD and vaping questions were analyzed. The S2BI and BSTAD identified 92% (23/25) and 100% (16/16) of nicotine vaping and 100% (16/16) and 95.5% (21/22) of cannabis vaping, respectively. DISCUSSION: The S2BI and BSTAD tools accurately identify nicotine and cannabis use without specific questions about vaping.

The Impact of Cannabis Use on Adolescent Neurodevelopment and Clinical Outcomes Amidst Changing State Policies.

Cannabis is the most common illicit substance used by adolescents and the third most common psychoactive substance after alcohol and nicotine. Cannabis use during adolescence interrupts a critical period of brain development and leads to inappropriate activation of the reward pathway. Because the prefrontal cortex, which is responsible for impulse control and other executive functions, is not fully mature until the mid-twenties, the adolescent brain is especially vulnerable to damage from substance use. Although cannabis remains illegal at the federal level, recent changes in state policies have been associated with increased availability of a wide variety of cannabis products. As new products, formulations, and delivery devices that can deliver higher and faster peak doses of tetrahydrocannabinol enter the market, there is an even greater potential for cannabis to have negative clinical impacts on adolescent health. This article reviews the current literature on the impact of cannabis on adolescent health, including the neurobiology of the adolescent brain, potential clinical outcomes in adolescents who use cannabis, and the effects of changing state policies regarding cannabis on the increased availability of unregulated products.

A Systematic Review of Non-Opioid Pain Management in Chiari Malformation (Type 1) Patients: Current Evidence and Novel Therapeutic Opportunities.

Chiari Malformation Type I (CM) includes a range of cranial abnormalities at the junction of the skull with the spine, with common symptoms including pain and headaches. Currently, CM pain is managed medically through anti-inflammatory drugs, muscle relaxants, and opioids, while surgical management includes posterior fossa decompression. Given the adverse effects of opioid use, and an ongoing opioid epidemic, there is a need for safe, non-opioid alternatives for clinical pain management. This systematic review was performed to provide an update on the current literature pertaining to the treatment of CM pain with non-opioid alternatives. A literature search was performed in June 2022 utilizing the PubMed and Google Scholar databases, and articles were identified that included information regarding non-opioid pain management in CM patients. A total of 90 articles were obtained from this search, including 10 relevant, drug-specific studies. Two independent reviewers selected and included all relevant articles based on the chosen search criteria to minimize bias risk. Currently available treatments for neurosurgical pain management include anticonvulsants, corticosteroids, NSAIDs, anti-inflammatory drugs, NMDA receptor antagonists, local anesthetics, nerve blocks, scalp blocks, and neuromuscular blocks. While more information is needed on the use of non-opioid pain management, the present literature provides potential evidence of its efficacy amongst the CM patient population, on account of the success that non-opioid pain management has demonstrated within other neurological pain syndromes. Further research into non-pharmacological pain management would also benefit the CM population and could be generalized to related conditions.

Pediatric Toxicology.

Pediatric poisonings comprise the majority of the toxic exposures reported to U.S. poison centers. Pediatric exposures to specific substances have the potential to cause significant morbidity and mortality, sometimes with even what might be considered small amounts to those not familiar with the risks of exposure. These toxins include such substances as specific prescription medications, over-the-counter medications, essential oils, and common household items. With such a vast array of potential toxic exposures that can affect children, it is imperative that health care practitioners who work with children understand the general management of the poisoned pediatric patient.

Targeting the cannabinoid system to counteract the deleterious effects of stress in Alzheimer's disease.

Alzheimer's disease is a progressive neurodegenerative disorder characterized histologically in postmortem human brains by the presence of dense protein accumulations known as amyloid plaques and tau tangles. Plaques and tangles develop over decades of aberrant protein processing, post-translational modification, and misfolding throughout an individual's lifetime. We present a foundation of evidence from the literature that suggests chronic stress is associated with increased disease severity in Alzheimer's patient populations. Taken together with preclinical evidence that chronic stress signaling can precipitate cellular distress, we argue that chronic psychological stress renders select circuits more vulnerable to amyloid- and tau- related abnormalities. We discuss the ongoing investigation of systemic and cellular processes that maintain the integrity of protein homeostasis in health and in degenerative conditions such as Alzheimer's disease that have revealed multiple potential therapeutic avenues. For example, the endogenous cannabinoid system traverses the central and peripheral neural systems while simultaneously exerting anti-inflammatory influence over the immune response in the brain and throughout the body. Moreover, the cannabinoid system converges on several stress-integrative neuronal circuits and critical regions of the hypothalamic-pituitary-adrenal axis, with the capacity to dampen responses to psychological and cellular stress. Targeting the cannabinoid system by influencing endogenous processes or exogenously stimulating cannabinoid receptors with natural or synthetic cannabis compounds has been identified as a promising route for Alzheimer's Disease intervention. We build on our foundational framework focusing on the significance of chronic psychological and cellular stress on the development of Alzheimer's neuropathology by integrating literature on cannabinoid function and dysfunction within Alzheimer's Disease and conclude with remarks on optimal strategies for treatment potential.

Toxic Alcohol Poisoning.

This article reviews the background, metabolism, clinical effects, and treatment of toxic alcohols, specifically ethylene glycol, methanol, diethylene glycol, propylene glycol, and isopropyl alcohol. This article also reviews the importance of an anion gap metabolic acidosis in relation to toxic alcohols and explores both the utility and the limitations of the osmol gap in patient management.

Pediatric suicides reported to U.S. poison centers.

INTRODUCTION: As the pediatric mental health crisis worsens, the rate of adolescent suicide-related cases is increasing, including adolescent cases of self-poisoning. METHODS: Data from the National Poison Data System was analyzed for trends in rates and frequencies of all pediatric suspected suicides between 2015 and 2020. RESULTS: There were 514,350 pediatric suspected suicides analyzed, with the largest increase in rate of suspected suicides occurring in children ages 10 to 12 years (109.3%, p = 0.002). Rates also increased significantly in children ages 13 to 15 years (30.3%, p < 0.001) and 16 to 19 years (18.1%, p < 0.05). The most commonly utilized substances were ibuprofen and acetaminophen, with the largest increase in rate of exposures seen for acetaminophen. Discussion: This data demonstrates concerning rises in cases of self-poisoning, suggesting that the pediatric mental health crisis is worsening and extending into younger populations. Pediatric populations have easier access to over-the-counter medications, potentially explaining the likelihood of utilization of these medications in pediatric suspected suicides. CONCLUSIONS: Initiation of appropriate mental health screenings and interventions should be considered in these young age groups in order to prevent further rises in self-poisoning cases and associated morbidity and mortality.

Comment on 'effects of acetaminophen on risk taking'.

The article by Keaveney et al. entitled 'Effects of acetaminophen on risk taking' was published in July of 2020 and concluded that using acetaminophen increased risk-taking behaviors, potentially by reducing perceived risk. We believe that there is not enough data to support the generalization of this association and feel that the conclusions were presented without acknowledgement of the limitations of this study. Media articles often further dramatized these findings, presenting the potential correlation between acetaminophen and risk taking as fact. It is unfair to readers to sensationalize the associations seen in controlled experiments in an attempt to generalize the study's findings. As scientists, we need to assure that the discussions and conclusions presented in publications appropriately highlight the limitations of studies. We must also work to assure that the public does not sensationalize preliminary and limited research results.

Toxic Alcohols.

This article reviews the background, metabolism, clinical effects, and treatment of toxic alcohols, specifically ethylene glycol, methanol, diethylene glycol, propylene glycol, and isopropyl alcohol. This article also reviews the importance of an anion gap metabolic acidosis in relation to toxic alcohols and explores both the utility and the limitations of the osmole gap in patient management.

First Aid for Pool Chemical Exposure: A Narrative Review.

Over 4500 visits to emergency departments related to pool chemical exposures occur annually in the United States, and it is likely that many more go unreported. Injury can occur due to sensitivity to standard chemical concentrations in pools (such as with opening one's eyes underwater), accidental exposure to super-concentrated chemicals (such as malfunction of a pool chlorinator), or accidental inhalation of fumes while opening the storage container for chlorination tablets. Therefore, first aid care has the potential to significantly limit morbidity.  A literature review was undertaken to determine the appropriate first aid for pool chemical exposures. This literature search revealed 25 pertinent articles, of which none were systematic reviews or studies directly related to the first aid treatment of pool chemical exposures. However, five articles were included as indirect evidence, and a hand search of references revealed five additional articles for inclusion. Treatment recommendations were extrapolated from the treatment of chemical exposures from other incidents. Symptoms of pool chemical exposure reflect irritation secondary to the caustic chemicals involved. Patients may report irritation of the skin, eyes, nose, or throat; cough; chest tightness; and difficulty breathing. Following any exposure to pool chemicals, the victim should be removed from the source, taken to an area with fresh air, and contaminated materials (e.g. clothing, contact lenses) should be removed. Irrigation of the exposed area should take place immediately with uncontaminated fresh water for at least 15 minutes. It is anticipated that an exposed person will be symptomatically improved by leaving the area of exposure, removing their contaminated clothing items, and irrigating the contaminated body parts. However, if symptoms do not resolve during that time or if symptoms are worsening, the victim should be evaluated by trained medical personnel.

The Locus Coeruleus- Norepinephrine System in Stress and Arousal: Unraveling Historical, Current, and Future Perspectives.

Arousal may be understood on a spectrum, with excessive sleepiness, cognitive dysfunction, and inattention on one side, a wakeful state in the middle, and hypervigilance, panic, and psychosis on the other side. However, historically, the concepts of arousal and stress have been challenging to define as measurable experimental variables. Divergent efforts to study these subjects have given rise to several disciplines, including neurobiology, neuroendocrinology, and cognitive neuroscience. We discuss technological advancements that chronologically led to our current understanding of the arousal system, focusing on the multifaceted nucleus locus coeruleus. We share our contemporary perspective and the hypotheses of others in the context of our current technological capabilities and future developments that will be required to move forward in this area of research.

Feasibility of Portable Fingerstick Cholinesterase Testing in Adolescents in South Texas.

Adolescents are particularly vulnerable to the impacts of pesticide exposures, which can be assessed using surveys, environmental measurements, and biomonitoring. Biomonitoring of blood cholinesterase can be used to determine if an individual has been exposed to pesticides. A limitation of blood cholinesterase testing can be the use of a laboratory as well as time to receive results. In addition to laboratory tests, there are fingerstick cholinesterase (ChE) tests, which can eliminate the need for laboratory testing. Some populations, such as farmworkers, would benefit through fingerstick ChE tests. The objective of this pilot study is to determine the feasibility (eg, can the testing be used to assess ChE levels) of using fingerstick ChE testing in adolescent populations living along the Texas-Mexico border where adolescents who often engage in farm work live. A sub-objective was to explore differences in ChE levels by sex. The Model 400 Test-Mate ChE kit by EQM Research Inc (Cincinnati, OH) was used to assess for ChE inhibition in the participants, specifically acetylcholinesterase (AChE), which is 1 of the 2 ChE enzymes. During the postassessment, males had a mean AChE value of 3.75 U/mL (95% CI 3.51-3.98); whereas females had a mean AChE value of 2.86 U/mL (95% CI 2.64-3.08), which was statistically significant. Overall, the study supports the use of field ChE testing in adolescent populations with a small percentage (6.90%) refusing to complete ChE testing.