Stephanie Carreiro

Here today, gone tomorrow…and back again? A review of herbal marijuana alternatives (K2, Spice), synthetic cathinones (bath salts), kratom, Salvia divinorum, methoxetamine, and piperazines.

Despite their widespread Internet availability and use, many of the new drugs of abuse remain unfamiliar to health care providers. The herbal marijuana alternatives, like K2 or Spice, are a group of herbal blends that contain a mixture of plant matter in addition to chemical grade synthetic cannabinoids. The synthetic cathinones, commonly called “bath salts,” have resulted in nationwide emergency department visits for severe agitation, sympathomimetic toxicity, and death. Kratom, a plant product derived from Mitragyna speciosa Korth, has opioid-like effects, and has been used for the treatment of chronic pain and amelioration of opioid-withdrawal symptoms. Salvia divinorum is a hallucinogen with unique pharmacology that has therapeutic potential but has been banned in many states due to concerns regarding its psychiatric effects. Methoxetamine has recently become available via the Internet and is marked as “legal ketamine.” Moreover, the piperazine derivatives, a class of amphetamine-like compounds that includes BZP and TMFPP, are making a resurgence as “legal Ecstasy.” These psychoactives are available via the Internet, frequently legal, and often perceived as safe by the public. Unfortunately, these drugs often have adverse effects, which range from minimal to life-threatening. Health care providers must be familiar with these important new classes of drugs. This paper discusses the background, pharmacology, clinical effects, detection, and management of synthetic cannabinoid, synthetic cathinone, methoxetamine, and piperazine exposures.

Wearable biosensors to detect physiologic change during opioid use

IntroductionOpioid analgesic use is a major cause of morbidity and mortality in the US, yet effective treatment programs have a limited ability to detect relapse. The utility of current drug detection methods is often restricted due to their retrospective and subjective nature. Wearable biosensors have the potential to improve detection of relapse by providing objective, real time physiologic data on opioid use that can be used by treating clinicians to augment behavioral interventions.MethodsThirty emergency department (ED) patients who were prescribed intravenous opioid medication for acute pain were recruited to wear a wristband biosensor. The biosensor measured electrodermal activity, skin temperature and locomotion data, which was recorded before and after intravenous opioid administration. Hilbert transform analyses combined with paired t-tests were used to compare the biosensor data A) within subjects, before and after administration of opioids; B) between subjects, based on hand dominance, gender, and opioid use history.ResultsWithin subjects, a significant decrease in locomotion and increase in skin temperature were consistently detected by the biosensors after opioid administration. A significant change in electrodermal activity was not consistently detected. Between subjects, biometric changes varied with level of opioid use history (heavy vs. nonheavy users), but did not vary with gender or type of opioid. Specifically, heavy users demonstrated a greater decrease in short amplitude movements (i.e. fidgeting movements) compared to non-heavy users.ConclusionA wearable biosensor showed a consistent physiologic pattern after ED opioid administration and differences between patterns of heavy and non-heavy opioid users were noted. Potential applications of biosensors to drug addiction treatment and pain management should be studied further.

Pretreatment With Intravenous Lipid Emulsion Reduces Mortality From Cocaine Toxicity in a Rat Model

STUDY OBJECTIVE We compare the effects of intravenous lipid emulsion and normal saline solution pretreatment on mortality and hemodynamic changes in a rat model of cocaine toxicity. We hypothesize that intravenous lipid emulsion will decrease mortality and hemodynamic changes caused by cocaine administration compared with saline solution. METHODS Twenty male Sprague-Dawley rats were sedated and randomized to receive intravenous lipid emulsion or normal saline solution, followed by a 10 mg/kg bolus of intravenous cocaine. Continuous monitoring included intra-arterial blood pressure, pulse rate and ECG tracing. Endpoints included a sustained undetectable mean arterial pressure (MAP) or return to baseline MAP for 5 minutes. The log-rank test was used to compare mortality. A mixed-effect repeated-measures ANOVA was used to estimate the effects of group (intravenous lipid emulsion versus saline solution), time, and survival on change in MAP, pulse rate, or pulse pressure. RESULTS In the normal saline solution group, 7 of 10 animals died compared with 2 of 10 in the intravenous lipid emulsion group. The survival rate of 80% (95% confidence interval 55% to 100%) for the intravenous lipid emulsion rats and 30% (95% confidence interval 0.2% to 58%) for the normal saline solution group was statistically significant (P=.045). CONCLUSION Intravenous lipid emulsion pretreatment decreased cocaine-induced cardiovascular collapse and blunted hypotensive effects compared with normal saline solution in this rat model of acute lethal cocaine intoxication. Intravenous lipid emulsion should be investigated further as a potential adjunct in the treatment of severe cocaine toxicity.

Integrating Personalized Technology in Toxicology: Sensors, Smart Glass, and Social Media Applications in Toxicology Research

Rapid proliferation of mobile technologies in social and healthcare spaces create an opportunity for advancement in research and clinical practice. The application of mobile, personalized technology in healthcare, referred to as mHealth, has not yet become routine in toxicology. However, key features of our practice environment, such as frequent need for remote evaluation, unreliable historical data from patients, and sensitive subject matter, make mHealth tools appealing solutions in comparison to traditional methods that collect retrospective or indirect data. This manuscript describes the features, uses, and costs associated with several of common sectors of mHealth research including wearable biosensors, ingestible biosensors, head-mounted devices, and social media applications. The benefits and novel challenges associated with the study and use of these applications are then discussed. Finally, opportunities for further research and integration are explored with a particular focus on toxicology-based applications.

Drugs and Medical Devices: Adverse Events and the Impact on Women’s Health

A large number of medications and medical devices removed from the market by the US Food and Drug Administration over the past 4 decades specifically posed greater health risks to women. This article reviews the historical background of sex and gender in clinical research policy and describes several approved drugs and devices targeted for use in women that have caused major morbidity and mortality. The intended population for the medications and devices, population affected, approval process, and the basic and legal actions taken against the medication/drug company are also discussed. It is recognized that women are still at risk for harm from unsafe medications and devices, and continued improvements in legislation that promotes inclusion of sex and gender into the design and analysis of research will improve safety for both men and women.

Music as an Adjunct to Opioid-Based Analgesia

Epidemic increases in opioid use in the USA and globally highlight the need for effective adjunctive therapies to opioid-based analgesia. Given the shortcomings of behavioral adjuncts to opioid-based pain treatment, an urgent need exists for pain-related behavioral interventions that resonate with broad patient populations, can be delivered confidentially in any environment, and can incorporate new content automatically. Understanding the potential for automated behavioral therapies like music therapy in modulating the experience of pain may unlock methods to transition patients to lower doses of pharmacologic therapy or provide alternatives to opioids during acute exacerbations of pain. This manuscript describes the neurologic mechanism of action, theoretical basis, and potential applications of personalized music as a smartphone-based mHealth intervention for acute and chronic pain management.

mHealth for the Detection and Intervention in Adolescent and Young Adult Substance Use Disorder

Purpose of ReviewThe goal of this review is to highlight recent research in mHealth-based approaches to the detection and treatment of substance use disorders in adolescents and young adults.Recent FindingsThe main methods for mHealth-based detection include mobile phone-based self-report tools, GPS tracking, and wearable sensors. Wearables can be used to detect physiologic changes (e.g., heart rate, electrodermal activity) or biochemical contents of analytes (i.e., alcohol in sweat) with reasonable accuracy, but larger studies are needed. Detection methods have been combined with interventions based on mindfulness, education, incentives/goals, and motivation. Few studies have focused specifically on the young adult population, although those that did indicate high rates of utilization and acceptance.SummaryResearch that explores the pairing of advanced detection methods such as wearables with real-time intervention strategies is crucial to realizing the full potential of mHealth in this population.

Oxycodone Ingestion Patterns in Acute Fracture Pain With Digital Pills

BACKGROUND: Opioid analgesics are commonly prescribed on an as-needed (PRN) basis for acute painful conditions. Uncertainty of how patients actually take PRN opioids, coupled with a desire to completely cover pain, leads to variable and overly generous opioid prescribing practices, resulting in a surplus of opioids. This opioid surplus becomes a source for diversion and nonmedical opioid use. Understanding patterns of actual opioid ingestion after acute painful conditions can help clinicians counsel patients on safe opioid use, and allow timely recognition and intervention when escalating opioid self-dosing occurs, to prevent tolerance and addiction. METHODS: We used a novel oxycodone digital pill system (ingestible biosensor within a standard gelatin capsule combined with 5-mg oxycodone) that when ingested, is activated by the chloride ion gradient in the stomach thereby emitting a radiofrequency signal captured by a wearable reader. The reader relays ingestion data to a cloud-based server that displays ingestion events to the study team. We deployed the oxycodone digital pill among opioid-naive individuals discharged from the emergency department with acute fracture pain. Participants were trained on digital pill operation and discharged with twenty-one 5-mg oxycodone digital pills. They were instructed to take digital pills PRN for pain on discharge. We conducted a brief interview 7 days after study enrollment, at which point participants returned the digital pill system. We identified oxycodone ingestion events in real time by data from the digital pill system and performed pill counts at the return visit to validate digital pill reporting of medication ingestion. RESULTS: In this study, 26 individuals were approached; 16 enrolled with 15 completing the study. Participants ingested a median of 6 (3–9.5) oxycodone digital pills over the course of 7 days, with 82% of the oxycodone dose ingested in the first 3 days. In individuals who required operative repair, 86% (N = 6) continued to ingest opioids at 1 week. There was substantial variability in ingestion patterns between individuals. CONCLUSIONS: The utilization patterns of individuals with acute fracture pain could be captured using a digital pill system and revealed a median opioid ingestion of 45-mg morphine equivalents for acute pain over 7 days. Seven participants ceased using opioids within 4 days after discharge from the emergency department, although operative repair was associated with longer use. This digital pill system was able to measure changes in and patterns of opioid self-dosing, which varied between patients.

A new mining method to detect real time substance use events from wearable biosensor data stream

Detecting real time substance use is a critical step for optimizing behavioral interventions to prevent drug abuse. Traditional methods based on self-reporting or urine screening are inefficient or intrusive for drug use detection, and inappropriate for timely interventions. For example, self-report suffers from distortion or recall bias; while urine screening often detects drug use that occurred only within the previous 72 hours. Methods for real-time substance use detection are severely underdeveloped, partly due to the novelty of wearable biosensor technique and the lack of substantive clinical data for evaluation. We propose a new real-time drug use event detection method using data obtained from wearable biosensors. Specifically, this method is built upon the slide window technique to process the data stream, and a distance-based outlier detection method to identify substance use events. This novel method is designed to examine how to detect and set up the thresholds of parameters in real-time drug use event detection for wearable biosensor data streams. Our numerical analyses empirically identified the thresholds of parameters used to detect the cocaine use and showed that this proposed method could be adapted to detect other substance use events.

SoMe and Self Harm: The Use of Social Media in Depressed and Suicidal Youth

Increased access and use of social media on smartphones and tablets have changed interpersonal communication styles. Because of the ease of social media access and the ability to reach a large number of individuals, social media is an ever more important modality that connects individuals. Importantly, adolescents have adopted social media platforms to discuss issues related to mental health. There is little existing data regarding how adolescents who are depressed or suicidal use social media prior to treatment in the emergency department (ED) for medical care of their psychiatric illness. In this paper, we present formative evidence of social media behaviors in 29 adolescents seeking emergency care for depression or suicidal ideation. Participants were surveyed regarding social media use and motivations to post content regarding depression, death or dying. Among the participants who allowed the research team to view their social media accounts, 40% (n=6) posted content related to depression, death or dying, while 20% (n=3) wrote that they felt depressed and 13.3% (n=2) posted that they wanted to die. Qualitative discussions with participants provided description of reasons for posting content on social media about depression, death and dying, or reasons that individuals refrained from posting online. Despite methodological and technical challenges in research, social media may prove be valuable in detection and intervention of adolescents who are depressed and contemplating suicide.