Peter R. Chai

Levamisole Exposure and Hematologic Indices in Cocaine Users

OBJECTIVES Levamisole is an antihelminthic agent found in nearly 70% of seized U.S. cocaine. Sporadic case literature describes a life-threatening agranulocytosis associated with levamisole exposure secondary to cocaine use. The authors compared the distribution of hematologic indices in a population of cocaine users with and without a confirmed exposure to levamisole. METHODS The records of all patients in the Lifespan hospital system who underwent comprehensive toxicologic testing between September 2009 and December 2009 (n = 799) were reviewed. Of these, 95 patients were eligible for inclusion (cocaine-positive with a simultaneous complete blood count). Patients were grouped into levamisole-positive (n = 47) and -negative (n = 48) groups. The primary outcome measures were total white blood cell count (WBC), absolute neutrophil count (ANC), and absolute lymphocyte count (ALC); secondary outcome measures included percent neutrophils, lymphocytes, eosinophils, monocytes, and basophils, as well as identified co-ingestants. RESULTS Both groups had a similar makeup of age, sex, and race. The total WBC count, ANC, and ALC were not significantly different between the two groups. There was no significant difference in relative proportion of neutrophils, eosinophils, basophils, or monocytes between the groups. There was one neutropenic patient in the levamisole-positive group, while three patients were neutropenic in the negative group. Additionally, a literature review of case reports describing levamisole-induced agranulocytosis (n = 33) was conducted. In 52% of these cases, patients presented with an oropharyngeal chief complaint; in an additional 27%, patients presented with soft tissue infections or purpura. CONCLUSIONS The overall incidence of neutropenia was 4.2% in all cocaine users and 2.1% in the levamisole-positive group. A striking number of the reported patients with levamisole-associated neutropenia have presented to care with oropharyngeal complaints, vasculitis, or fever. A clinical algorithm for identifying levamisole toxicity in the emergency department setting is provided. Further research is necessary to determine the circumstances required for levamisole-associated neutropenia.

Encapsulated Arrays of Self-Assembled Microtissues: An Alternative to Spherical Microcapsules

Micro-encapsulation and immuno-isolation of allogenic and xenogenic tissues and cells is a promising method for the treatment of a variety of metabolic disorders. Many years have been spent optimizing spherical microcapsules, yet micro-encapsulation has not achieved its full clinical potential. As an alternative to spherical microcapsules, this study presents an alginate-encapsulated array of self-assembled three-dimensional (3D) microtissues. Monodispersed HepG2 cells were seeded onto a micro-molded agarose gel. Cells settled to the bottom of the mold recesses and self-assembled 3D microtissues (n = 822) within 24 h. This array of densely packed microtissues was encapsulated in situ using alginate. When separated from the agarose micro-mold, the encapsulated array had HepG2 microtissues in close proximity to its surface. This surface could be further modified by a simple dipping process. Microtissue size, viability, and albumin secretion were all controllable by the number of cells seeded onto the original agarose micro-mold, and microtissue shape and spacing were controllable by the design of the micro-mold. This approach to encapsulation and the use of self-assembled/self-packing 3D microtissues offers new design possibilities that may help to address certain limitations of conventional microcapsules.

The Virtual Toxicology Service: Wearable Head-Mounted Devices for Medical Toxicology

History of Telemedicine Although the Institute of Medicine (IOM) first defined telemedicine in 1996 as the use of electronic information and communications technologies to provide and support health care when distance separates participants, the use of electronic communications technologies in medicine is not new [1]. In 1877, a group of physicians created a telephone exchange including local pharmacies in order to facilitate improved patient communications [2, 3]. In the 1970s, the National Aeronautics and Space Administration (NASA), Lockheed Martin, and the Indian Health Services teamed together to create the Space Technology Applied to Rural Papago Advanced Health Care (STARPACH) program—a telemedicine initiative involving real time video, data and voice-over-microwave interaction to extend healthcare to a rural setting [4]. Over the past two decades, telemedical systems have successfully connected rural and community hospitals to large urban centers with subspecialty expertise. These initiatives have improved care for specific patient subgroups including those in nursing homes, dermatological complaints, and trauma [2, 5]. In particular, the specialties of neurology and dermatology have employed telemedicine to extend their reach in resource poor settings. Telestroke employs a controlled video camera and monitor screen for a remote neurologist to help diagnose and manage emergency department patients with stroke while static photo technology and emerging live video devices have helped a remote dermatologist complete dermatology consults remotely [6–9].

Utilizing an Ingestible Biosensor to Assess Real-Time Medication Adherence

Medication adherence monitoring has relied largely on indirect measures of pill ingestion including patient self-report, pharmacy refills, electronically triggered pill bottles, and pill counts. Our objective is to describe an ingestible biosensor system comprising a radio-frequency identification (RFID)-tagged gelatin capsule. Once the capsule dissolves in the stomach, the RFID tag activates to transmit a unique signal to a relay device which transmits a time-stamped message to a cloud-based server that functions as a direct measure of medication adherence. We describe a constellation of mobile technologies that provide real-time direct measures of medication adherence. Optimizing connectivity, relay design, and interactivity with users are important in obtaining maximal acceptability. Potential concerns including gut retention of metallic components of the ingestible biosensor and drug dissolution within a gelatin capsule should be considered. An ingestible biosensor incorporated into a medication management system has the potential to improve medication compliance with real-time monitoring of ingestion and prompt early behavioral intervention. Integration of ingestible biosensors for multiple disease states may provide toxicologists with salient data early in the care of poisoned patients in the future. Further research on device design and interventions to improve adherence is needed and will shape the evolving world of medication adherence.

Digital Pills to Measure Opioid Ingestion Patterns in Emergency Department Patients With Acute Fracture Pain: A Pilot Study

Background Nonadherence to prescribed regimens for opioid analgesic agents contributes to increasing opioid abuse and overdose death. Opioids are frequently prescribed on an as-needed basis, placing the responsibility to determine opioid dose and frequency with the patient. There is wide variability in physician prescribing patterns because of the lack of data describing how patients actually use as-needed opioid analgesics. Digital pill systems have a radiofrequency emitter that directly measures medication ingestion events, and they provide an opportunity to discover the dose, timing, and duration of opioid therapy. Objective The purpose of this study was to determine the feasibility of a novel digital pill system to measure as-needed opioid ingestion patterns in patients discharged from the emergency department (ED) after an acute bony fracture. Methods We used a digital pill with individuals who presented to a teaching hospital ED with an acute extremity fracture. The digital pill consisted of a digital radiofrequency emitter within a standard gelatin capsule that encapsulated an oxycodone tablet. When ingested, the gastric chloride ion gradient activated the digital pill, transmitting a radiofrequency signal that was received by a hip-worn receiver, which then transmitted the ingestion data to a cloud-based server. After a brief, hands-on training session in the ED, study participants were discharged home and used the digital pill system to ingest oxycodone prescribed as needed for pain for one week. We conducted pill counts to verify digital pill data and open-ended interviews with participants at their follow-up appointment with orthopedics or at one week after enrollment in the study to determine the knowledge, attitudes, beliefs, and practices regarding digital pills. We analyzed open-ended interviews using applied thematic analysis. Results We recruited 10 study participants and recorded 96 ingestion events (87.3%, 96/110 accuracy). Study participants reported being able to operate all aspects of the digital pill system after their training. Two participants stopped using the digital pill, reporting they were in too much pain to focus on the novel technology. The digital pill system detected multiple simultaneous ingestion events by the digital pill system. Participants ingested a mean 8 (SD 5) digital pills during the study period and four participants continued on opioids at the end of the study period. After interacting with the digital pill system in the real world, participants found the system highly acceptable (80%, 8/10) and reported a willingness to continue to use a digital pill to improve medication adherence monitoring (90%, 9/10). Conclusions The digital pill is a feasible method to measure real-time opioid ingestion patterns in individuals with acute pain and to develop real-time interventions if opioid abuse is detected. Deploying digital pills is possible through the ED with a short instructional course. Patients who used the digital pill accepted the technology.

Self-identification of nonpharmaceutical fentanyl exposure following heroin overdose

Abstract Objective: To compare user self-identification of nonpharmaceutical fentanyl exposure with confirmatory urine drug testing in emergency department (ED) patients presenting after heroin overdose. Methods: This was a cross-sectional study of adult ED patients who presented after a heroin overdose requiring naloxone administration. Participants provided verbal consent after which they were asked a series of questions regarding their knowledge, attitudes and beliefs toward heroin and nonpharmaceutical fentanyl. Participants also provided urine samples, which were analyzed using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry to identify the presence of fentanyl, heroin metabolites, other clandestine opioids, common pharmaceuticals and drugs of abuse. Results: Thirty participants were enrolled in the study period. Ten participants (33%) had never required naloxone for an overdose in the past, 20 participants (67%) reported recent abstinence, and 12 participants (40%) reported concomitant cocaine use. Naloxone was detected in all urine drug screens. Heroin or its metabolites were detected in almost all samples (93.3%), as were fentanyl (96.7%) and its metabolite, norfentanyl (93.3%). Acetylfentanyl was identified in nine samples (30%) while U-47700 was present in two samples (6.7%). Sixteen participants self-identified fentanyl in their heroin (sensitivity 55%); participants were inconsistent in their qualitative ability to identify fentanyl in heroin. Conclusions: Heroin users presenting to the ED after heroin overdose requiring naloxone are unable to accurately identify the presence of nonpharmaceutical fentanyl in heroin. Additionally, cutting edge drug testing methodologies identified fentanyl exposures in 96.7% of our patients, as well as unexpected clandestine opioids (like acetylfentanyl and U-47700).

Crowd-Sourced Focus Groups on Twitter: 140 Characters of Research Insight.

Researchers have traditionally relied on in-person focus groups to test and obtain feedback regarding behavioral and technology-based interventions for specific disease processes. An increasing generation of engaged and connected patients turn to Twitter, a popular microblogging service, to discuss health related topics. Regularly scheduled Twitter-based chats (tweetchats) can potentially function as an additional source of input and information from a diverse, global group of engaged participants. We report the first use of a “tweetchat focus group” to explore data collection issues using this methodology. The speed at which tweetchat conversations occur, coupled with the ability to pursue multiple streams of conversation both in real time and in a delayed fashion, make tweetchat data collection particularly challenging. We discuss important considerations and preparation that should be undertaken by the researchers prior to initiating a tweetchat focus group, consider facilitation challenges and issues of confidentiality.

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.

Wearable Devices and Biosensing: Future Frontiers

Since the 1950s, toxicologists have utilized novel technologies to advance our understanding of poisonings while improving our availability to physicians and patients [1]. From rolodexes and telephones to head mounted computers, advanced biosensing, and ingestible sensors, toxicologists have always been pioneers leveraging advanced technologies to solve problems [1, 2]. As smartphones, fitness monitors, and connected devices become ubiquitous, toxicologists are naturally equipped with advanced tools that augment our bedside exam of poisoned patients. A new generation of toxicologists continually pushes the boundaries of technology in an effort to facilitate improved patient care and access to our expertise [1–5]. Head-mounted wearable computers can provide a toxicologist with a firstperson view of a poisoned patient, while a wrist-mounted sensor can stream key biometric data (e.g., heart rate, respiratory rate, skin temperature, and electrodermal activity). Ingestible biosensors can provide historical records of medication ingestion, and linked webcams can stream toxicology lectures to centers seeking expertise on the poisoned patient [2–4, 6]. In an era of integrated care and bundled payments, toxicologists and fellows in training have a unique opportunity to develop novel technology-based methods that respond to a need in our specialty. Creating novel applications using everyday technology requires a contemporary approach—integration of patients, physicians, engineers, and software developers into a multidisciplinary research team.