Ingestible Electronic Sensors for Monitoring Real-time Adherence to HIV Pre-exposure Prophylaxis and Antiretroviral Therapy.

PURPOSE OF REVIEW: This review summarizes the recent advancements and future directions of digital pill systems (DPS) - which utilize ingestible sensors to directly measure medication ingestion events in real-time - in the context of HIV prevention and treatment. RECENT FINDINGS: Two DPS are cleared by the US Food and Drug Administration. The bioequivalence and stability of digitized pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART) have been established, and pilot studies have demonstrated the feasibility and acceptability of using DPS for PrEP and ART adherence measurement. Important bioethical and implementation considerations have been identified for future clinical trials. Continued technological advancement may reduce barriers to use, and integration of DPS into behavioral interventions may facilitate adherence improvement efforts. DPS represent an innovative tool for PrEP and ART adherence measurement. Future work will optimize the technology to reduce operational barriers. DPS have significant potential for expansion across a diverse array of diseases, though key bioethical considerations must be examined prior to large-scale implementation.

"I'd feel like someone was watchin' me watching for a good reason": perceptions of data privacy, access, and sharing in the context of real-time PrEP adherence monitoring among HIV-negative MSM with substance use.

Once-daily oral tenofovir/emtricitabine is highly effective as pre-exposure prophylaxis (PrEP) against HIV but is dependent on adherence, which may be challenging for men who have sex with men (MSM) and use substances. Digital pill systems (DPS) permit the direct, real-time measurement of adherence, though user perceptions of data privacy in this context are unknown. Thirty prospective DPS users - HIV-negative MSM with non-alcohol substance use - completed in-depth qualitative interviews exploring preferences around privacy, access, and sharing of DPS adherence data. Participants discussed some concerns about the impact of DPS use on personal privacy, and emphasized the need for robust data protections in the technology. Participants were interested in having on-demand access to their adherence data, and were most willing to share data with primary care providers and long-term relationship partners. Future investigations exploring bioethical frameworks around DPS use are warranted, and user preferences should inform best practices for protecting DPS data.

Real-World User Experiences with a Digital Pill System to Measure PrEP Adherence: Perspectives from MSM with Substance Use.

Once-daily oral pre-exposure prophylaxis (PrEP) is highly effective for preventing HIV transmission, but adherence can be challenging for men who have sex with men (MSM) who use substances. A novel method for directly measuring ingestion events is a digital pill system (DPS), which comprises an ingestible radiofrequency emitter that signals a wearable Reader device upon PrEP ingestion, relaying ingestion data to a wearable Reader device and then to a smartphone application. Qualitative interviews were conducted with 15 MSM with non-alcohol substance use following an open-label pilot demonstration trial involving use of the DPS to measure PrEP adherence for 90 days. The purpose of this qualitative investigation was to understand overall user experiences and potential barriers and facilitators to using the DPS to measure PrEP adherence among MSM. The DPS was largely perceived as acceptable, novel, and valuable, with most participants reporting that the system was easily integrated into their daily routines. Technological and design factors, especially related to the wearable Reader, impacted participants' interest in using the technology long-term; several suggested improvements were discussed.Trial Registration ClinicalTrials.gov: NCT03842436.

Chronic pain severity, impact, and opioid use among patients with cancer: An analysis of biopsychosocial factors using the CHOIR learning health care system.

BACKGROUND: Despite the biopsychosocial underpinnings of chronic noncancer pain, relatively little is known about the contribution of psychosocial factors to chronic cancer pain. The authors aimed to characterize associations between biopsychosocial factors and pain and opioid use among individuals with chronic pain and cancer. METHODS: The authors conducted a retrospective, cross-sectional study of 700 patients with chronic pain and cancer seeking treatment at an academic tertiary pain clinic. Patients completed demographic questionnaires and validated psychosocial and pain measures. Multivariable, hierarchical linear and logistic regressions assessed the relative contributions of biopsychosocial factors to the primary dependent variables of pain severity, pain interference, and opioid use. RESULTS: Participants were 62% female and 66% White with a mean age of 59 ± 15 years, and 55% held a college degree or higher. Older age, African American or "other" race, sleep disturbance, and pain catastrophizing were significantly associated with higher pain severity (F(5,657) = 22.45; P ≤ .001; R2 = 0.22). Depression, sleep disturbance, pain catastrophizing, lower emotional support, and higher pain severity were significantly associated with pain interference (F(5,653) = 9.47; P ≤ .001; R2 = 0.44). Lastly, a poor cancer prognosis (Exp(B) = 1.62) and sleep disturbance (Exp(B) = 1.02) were associated with taking opioids, whereas identifying as Asian (Exp(B) = 0.48) or Hispanic (Exp(B) = 0.47) was associated with lower odds of using opioids. CONCLUSIONS: Modifiable psychological factors-specifically sleep disturbance, depression, and pain catastrophizing-were uniquely associated with pain and opioid use in patients with chronic pain and diverse cancer diagnoses. Future behavioral pain interventions that concurrently target sleep may improve pain among patients with cancer. LAY SUMMARY: Feeling depressed, worrying about pain, and bad sleep are related to higher pain symptoms in individuals with chronic pain and cancer. Specifically, those who struggle to sleep have worse pain and use more opioids. Also, individuals who have a bad prognosis for their cancer are more likely to be using opioid pain medications. Although race and cancer are related to chronic pain in patients, psychological well-being is also strongly related to this same pain.

Design and Delivery of Real-Time Adherence Data to Men Who Have Sex with Men Using Antiretroviral Pre-exposure Prophylaxis via an Ingestible Electronic Sensor.

Once daily tenofovir/emtricitabine when used for pre-exposure prophylaxis (PrEP) is effective in preventing HIV acquisition but requires consistent medication adherence. The use of ingestible technologies to monitor PrEP adherence can assist in understanding the impact of behavioral interventions. Digital pill systems (DPS) utilize an ingestible radiofrequency emitter integrated onto a gelatin capsule, which permits direct, real-time measurement of medication adherence. DPS monitoring may lead to discovery of nascent episodes of PrEP nonadherence and allow delivery of interventions that prevent the onset of sustained nonadherence. Yet, the acceptance and potential use of DPS in high-risk men who have sex with men (MSM; i.e., those who engage in condomless sex and use substances) is unknown. In this investigation, we conducted individual, semi-structured qualitative interviews with 30 MSM with self-reported non-alcohol substance use to understand their responses to the DPS, willingness and perceived barriers to its use, and their perceptions of its potential utility. We also sought to describe how MSM would potentially interact with a messaging system integrated into the DPS. We identified major themes around improved confidence of PrEP adherence patterns, safety of ingestible radiofrequency sensors, and design optimization of the DPS. They also expressed willingness to interact with messaging contingent on DPS recorded ingestion patterns. These data demonstrate that MSM who use substances find the DPS to be an acceptable method to measure and record PrEP adherence.

Long-Term Stability of the Electronic Sensor Component of a Digital Pill System in Real-World Storage Settings.

Background: Digital pill systems comprise an ingestible sensor integrated into a gelatin capsule that overencapsulates medication allowing real-time measures of medication ingestion. These systems may improve the manner in which medication adherence can be assessed and supported. Objective: In this investigation, we tested the durability of the ingestible sensor as part of a clinical trial to measure the feasibility and acceptability of the system to measure adherence to once daily tenofovir disoproxil fumarate/emtricitabine (NCT03842436). Methods: Digital pills not dispensed during the study were stored in a pharmacy. Seventeen sensors were selected from digital pills stored for at least 12 months and activated in a simulated gastric environment. A radiofrequency spectrum analyzer and the reader device used in the clinical trial to capture ingestion events were used to measure activation of emitters. A passing evaluation was defined as an energized emitter within 30 minutes of immersion, ability to broadcast a signal for 10 minutes, and successful acquisition by the reader. Results: All ingestible sensors passed the stability test. Mean activation time in simulated gastric fluid was 3.33 minutes (SD = 1.47); emitters remained active for a mean of 47.72 minutes (SD = 1.78). These parameters matched guidelines defined in the ID-Cap system requirements for use in patients. Conclusions: Ingestible sensor components of the ID-Cap system were therefore stable after long-term storage.

A review of toxic effects of electronic cigarettes/vaping in adolescents and young adults.

In this review, we examine the known and suspected toxicity of electronic cigarettes (e-cigarettes) in adolescents and young adults, to improve awareness of risks and identification of complications of their use. The use of e-cigarettes, or "vaping," is exploding among the pediatric population. E-cigarettes heat a solution containing a psychoactive compound, most commonly nicotine or tetrahydrocannabinol (THC), along with flavorings and other additives to a vapor, which users inhale. Since their introduction in the early 2000s, e-cigarette use is now prolific among youth, per the Monitoring the Future survey, with over 40% of high school seniors reporting use within the past year. Adolescents are vulnerable to the risks of e-cigarettes, as they are targeted as new consumers with advertisements and flavoring compounds, and are not utilizing them as a means to smoking cessation. The pulmonary risks of vaping are rapidly emerging, with the most immediately alarming being the condition electronic-cigarette/vaping associated lung injury (EVALI). Additionally, there have been more recent studies showing extrapulmonary effects including cardiovascular, immunologic and neuro-developmental effects. Many of these effects are likely dose-dependent. Public health efforts are urgently needed to decrease or eliminate new e-cigarette initiation, and support should be established to assist current e-cigarette users with cessation. We strongly advocate for the elimination of e-cigarette flavorings and advertising directed at adolescents, and call for physicians to be cognizant of this expanding epidemic.

Individual species and cumulative mixture relationships of 24-hour urine metal concentrations with DNA methylation age variables in older men.

BACKGROUND: Globally, toxic metal exposures are a well-recognized risk factor for many adverse health outcomes. DNA methylation-based measures of biological aging are predictive of disease, but have poorly understood relationships with metal exposures. OBJECTIVE: We performed a pilot study examining the relationships of 24-h urine metal concentrations with three novel DNA methylation-based measures of biological aging: DNAmAge, GrimAge, and PhenoAge. METHODS: We utilized a previously established urine panel of five common metals [arsenic (As), cadmium (Cd), lead (Pb), manganese (Mn), and mercury (Hg)] found in a subset of the elderly US Veterans Affairs Normative Aging Study cohort (N = 48). The measures of DNA methylation-based biological age were calculated using CpG sites on the Illumina HumanMethylation450 BeadChip. Bayesian Kernel Machine Regression (BKMR) was used to determine metals most important to the aging outcomes and the relationship of the cumulative metal mixture with the outcomes. Individual relationships of important metals with the biological aging outcomes were modeled using fully-adjusted linear models controlling for chronological age, renal function, and lifestyle/environmental factors. RESULTS: Mn was selected as important to PhenoAge. A 1 ng/mL increase in urine Mn was associated with a 9.93-year increase in PhenoAge (95%CI: 1.24, 18.61, p = 0.03). The cumulative urine metal mixture was associated with increases in PhenoAge. Compared to a model where each metal in the mixture is set to its 50th percentile value, every one-unit increase of the cumulative mixture with each metal at its 70th percentile was associated with a 2.53-year increase in PhenoAge (95%CI: 0.10, 4.96, P<0.05). CONCLUSION: Our results add novel evidence that metals detected in urine are associated with increases in biological aging and suggest that these DNA methylation-based measures may be useful for identifying individuals at-risk for diseases related to toxic metal exposures. Further research is necessary to confirm these findings more broadly.

The Impact of Music on Nociceptive Processing.

OBJECTIVE: Music has been shown to modulate pain, although the impact of music on specific aspects of nociceptive processing is less well understood. Using quantitative sensory testing (QST), we assessed the impact of a novel music app on specific aspects of nociceptive processing. DESIGN: Within-subjects paired comparison of pain processing in control vs music condition. SETTING: Human psychophysical laboratory. SUBJECTS: Sixty healthy adult volunteers. METHODS: Subjects were assessed for baseline anxiety, depression, and catastrophizing using validated questionnaires. QSTs measured included 1) pain threshold and tolerance to deep muscle pressure, 2) pain with mechanical pinprick, 3) temporal summation of pain (TSP) with a repeated pain stimulus, and 4) conditioned pain modulation (CPM) with a second painful stimulus. QSTs were performed in the absence and presence of music delivered through a music app. RESULTS: We found an increase in pressure pain thresholds in both the forearm (P = 0.007) and trapezius (P = 0.002) with music, as well as a decrease in the amount of pinprick pain (P < 0.001) and TSP (P = 0.01) with music. Interestingly, CPM was also significantly diminished (P < 0.001) in the music condition. No significant difference in cold pain, anxiety, or situational catastrophizing was observed with music. Higher baseline pain catastrophizing scores were associated with less music-induced pressure pain reduction. CONCLUSIONS: Several measures of mechanical pain sensitivity were reduced with music. TSP, a measure of central sensitization, also decreased with music, but CPM, a measure of descending modulation of pain, was not further augmented by music.

Accuracy of Resident-Performed Point-of-Care Lung Ultrasound Examinations Versus Chest Radiography in Pneumothorax Follow-up After Tube Thoracostomy in Rwanda.

OBJECTIVES: The aim of this study was to evaluate the accuracy and timeliness of resident-performed point-of-care lung ultrasound (LUS) examinations for the follow-up of pneumothorax (PTX) after tube thoracostomy. METHODS: After brief training, Rwandan surgical residents blinded to chest radiography (CXR) performed and interpreted LUS examinations for PTX in participants undergoing CXR for PTX follow-up. Treating clinicians interpreted CXR for the presence of PTX for therapeutic decisions. Lung ultrasound was later reviewed by ultrasound experts, and CXR was reviewed by a radiologist. We defined expert LUS interpretation as the reference standard. The sensitivity and specificity of resident-performed LUS examinations for diagnosing PTX were calculated. We assessed agreement between trained resident versus expert LUS and clinician versus radiology CXR using the Cohen κ coefficient. We compared the time to results between LUS and CXR. RESULTS: Over an 8-month period, 51 participants were enrolled. Compared to expert LUS interpretation, the sensitivity and specificity (95% confidence intervals) of resident LUS were 100% (85%-100%) and 96% (82%-100%), respectively, whereas the sensitivity and specificity of clinician-interpreted CXR were 48% (27%-69%) and 100% (88%-100%). The agreement between resident and expert LUS was excellent (κ = 0.96), whereas the agreement between clinician and radiologist CXR was only moderate (κ = 0.60). The time to results was significantly longer for CXR than LUS (mean, 1335 versus 396 minutes; P = .0001). CONCLUSIONS: A resident-performed LUS examination was a quicker imaging modality with superior sensitivity compared to clinician-interpreted CXR for PTX follow-up after tube thoracostomy in this Rwandan study. Lung ultrasound can be a valuable imaging tool for PTX follow-up, especially in resource-limited settings.

A Brief Music App to Address Pain in the Emergency Department: Prospective Study.

BACKGROUND: Emergency physicians face the challenge of relieving acute pain daily. While opioids are a potent treatment for pain, the opioid epidemic has ignited a search for nonopioid analgesic alternatives that may decrease the dose or duration of opioid exposure. While behavioral therapies and complementary medicine are effective, they are difficult to deploy in the emergency department. Music is a potential adjunctive therapy that has demonstrated effectiveness in managing pain. OBJECTIVE: Our objective was to understand the feasibility and potential for an effect of a novel music app to address acute pain and anxiety in patients admitted to an emergency department observation unit. METHODS: This prospective cohort study enrolled patients admitted to an emergency department observation unit with pain who had received orders for opioids. We gathered baseline pain and psychosocial characteristics including anxiety, sleep disturbance, and pain catastrophizing using validated questionnaires. Participants received a smartphone-based music intervention and listened to the music in either a supervised (research assistant-delivered music session 3 times during their stay) or unsupervised manner (music used ad lib by participant). The app collected premusic and postmusic pain and anxiety scores, and participants provided qualitative feedback regarding acceptability of operating the music intervention. RESULTS: We enrolled 81 participants and randomly assigned 38 to an unsupervised and 43 to a supervised group. Mean pain in both groups was 6.1 (1.8) out of a possible score of 10. A total of 43 (53%) reported previous use of music apps at home. We observed an overall modest but significant decrease in pain (mean difference -0.81, 95% CI -0.45 to -1.16) and anxiety (mean difference -0.72, 95% CI -0.33 to -1.12) after music sessions. Reduction of pain and anxiety varied substantially among participants. Individuals with higher baseline pain, catastrophizing (about pain), or anxiety reported greater relief. Changes in pain were correlated to changes in anxiety (Pearson ρ=0.3, P=.02) but did not vary between supervised and unsupervised groups. Upon conclusion of the study, 46/62 (74%) reported they liked the music intervention, 57/62 (92%) reported the app was easy to use, and 49/62 (79%) reported they would be willing to use the music intervention at home. CONCLUSIONS: A smartphone-based music intervention decreased pain and anxiety among patients in an emergency department observation unit, with no difference between supervised and unsupervised use. Individuals reporting the greatest reduction in pain after music sessions included those scoring highest on baseline assessment of catastrophic thinking, suggesting there may be specific patient populations that may benefit more from using music as an analgesic adjunct in the emergency department. Qualitative feedback suggested that this intervention was feasible and acceptable by emergency department patients.

Chimeric antigen receptor T-cell toxicity.

PURPOSE OF REVIEW: Chimeric antigen receptor -(CAR) T-cell therapy has become a commonly used immunotherapy originally used in the treatment of B-cell leukemias but which are now applied broadly across tumor classes. Although high rates of remission are associated with CAR T-cell therapy, toxicities associated with these novel treatment regimens can be lethal if not recognized in a timely manner. RECENT FINDINGS: Cytokine release syndrome and neurotoxicity are the two most common toxicities associated with CAR T-cell therapy. Cytokine release syndrome is characterized by a flu-like illness accompanied by significant hemodynamic instability; treatments include administration of tocilizumab and corticosteroids. Neurotoxicity is associated with nonpattern-specific neurological changes and can rapidly progress to a comatose state from cerebral edema and death. Other potential toxicities from CAR T-cell therapy include tumor lysis syndrome, B-cell aplasia, graft versus host disease, and dermatological eruptions. SUMMARY: Clinical awareness of CAR T-cell toxicities is important because prompt treatment leads to improved survival and remission rates.

Relationships of Long-Term Smoking and Moist Snuff Consumption With a DNA Methylation Age Relevant Smoking Index: An Analysis in Buccal Cells.

INTRODUCTION: Currently, there is no widely accepted, non-self-report measure that simultaneously reflects smoking behaviors and is molecularly informative of general disease processes. Recently, researchers developed a smoking index (SI) using nucleated blood cells and a multi-tissue DNA methylation-based predictor of chronological age and disease (DNA methylation age [DNAm-age]). To better understand the utility of this novel SI in readily accessible cell types, we used buccal cell DNA methylation to examine SI relationships with long-term tobacco smoking and moist snuff consumption. METHODS: We used a publicly available dataset composed of buccal cell DNA methylation values from 120 middle-aged men (40 long-term smokers, 40 moist snuff consumers, and 40 nonsmokers). DNAm-age (353-CpGs) and SI (66-CpGs) were calculated using CpG sites measured using the Illumina HumanMethylation450 BeadChip. We estimated associations of tobacco consumption habits with both SI and DNAm-age using linear regression models adjusted for chronological age, race, and methylation technical covariates. RESULTS: In fully adjusted models with nonsmokers as the reference, smoking (ß = 1.08, 95% CI = 0.82 to 1.33, p < .0001) but not snuff consumption (ß = .06, 95% CI = -0.19 to 0.32, p = .63) was significantly associated with SI. SI was an excellent predictor of smoking versus nonsmoking (area under the curve = 0.92, 95% CI = 0.85 to 0.98). Four DNAm-age CpGs were differentially methylated between smokers and nonsmokers including cg14992253 [EIF3I], which has been previously shown to be differentially methylated with exposure to long-term fine-particle air pollution (PM2.5). CONCLUSIONS: The 66-CpG SI appears to be a useful tool for measuring smoking-specific behaviors in buccal cells. Still, further research is needed to broadly confirm our findings and SI relationships with DNAm-age. IMPLICATIONS: Our findings demonstrate that this 66-CpG blood-derived SI can reflect long-term tobacco smoking, but not long-term snuff consumption, in buccal cells. This evidence will be useful as the field works to identify an accurate non-self-report smoking biomarker that can be measured in an easily accessible tissue. Future research efforts should focus on (1) optimizing the relationship of the SI with DNAm-age so that the metric can maximize its utility as a tool for understanding general disease processes, and (2) determining normal values for the SI CpGs so that the measure is not as study sample specific.

An Internet of Things Buttons to Measure and Respond to Restroom Cleanliness in a Hospital Setting: Descriptive Study.

BACKGROUND: Restroom cleanliness is an important factor in hospital quality. Due to its dynamic process, it can be difficult to detect the presence of dirty restrooms that need to be cleaned. Using an Internet of Things (IoT) button can permit users to designate restrooms that need cleaning and in turn, allow prompt response from housekeeping to maintain real-time restroom cleanliness. OBJECTIVE: This study aimed to describe the deployment of an IoT button-based notification system to measure hospital restroom cleanliness reporting system usage and qualitative feedback from housekeeping staff on IoT button use. METHODS: We deployed IoT buttons in 16 hospital restrooms. Over an 8-month period, housekeeping staff received real-time notifications and responded to button presses for restroom cleaning. All button presses were recorded. We reported average button usage by hospital area, time of day, and day of week. We also conducted interviews with housekeeping supervisors and staff to understand their acceptance of and experience with the system. RESULTS: Over 8 months, 1920 requests to clean restrooms in the main hospital lobby and satellite buildings were received. The hospital lobby IoT buttons received over half (N=1055, 55%) of requests for cleaning. Most requests occurred in afternoon hours from 3 PM to midnight. Requests for cleaning remained stable throughout the work week with fewer requests occurring over weekends. IoT button use was sustained throughout the study period. Interviews with housekeeping supervisors and staff demonstrated acceptance of the IoT buttons; actual use was centered around asynchronous communication between supervisors and staff in response to requests to clean restrooms. CONCLUSIONS: An IoT button system is a feasible method to generate on-demand request for restroom cleaning that is easy to deploy and that users will consistently engage with. Data from this system have the potential to enable responsive scheduling for restroom service and anticipate periods of high restroom utilization in a hospital.

Internet of Things Buttons for Real-Time Notifications in Hospital Operations: Proposal for Hospital Implementation.

BACKGROUND: Hospital staff frequently performs the same process hundreds to thousands of times a day. Customizable Internet of Things buttons are small, wirelessly-enabled devices that trigger specific actions with the press of an integrated button and have the potential to automate some of these repetitive tasks. In addition, IoT buttons generate logs of triggered events that can be used for future process improvements. Although Internet of Things buttons have seen some success as consumer products, little has been reported on their application in hospital systems. OBJECTIVE: We discuss potential hospital applications categorized by the intended user group (patient or hospital staff). In addition, we examine key technological considerations, including network connectivity, security, and button management systems. METHODS: In order to meaningfully deploy Internet of Things buttons in a hospital system, we propose an implementation framework grounded in the Plan-Do-Study-Act method. RESULTS: We plan to deploy Internet of Things buttons within our hospital system to deliver real-time notifications in public-facing tasks such as restroom cleanliness and critical supply restocking. We expect results from this pilot in the next year. CONCLUSIONS: Overall, Internet of Things buttons have significant promise; future rigorous evaluations are needed to determine the impact of Internet of Things buttons in real-world health care settings.

Recognition and Management of Pediatric Salt Toxicity.

OBJECTIVES: Immediate recognition of salt toxicity and aggressive resuscitative measures are critical in the treatment of this lethal poisoning. Despite heroic measures, pediatric deaths due to salt toxicity still occur from irreversible neurological damage. The objective of this article is to review the relevant literature and offer a therapeutic algorithm for the management of pediatric patients presenting with salt toxicity. METHODS: A literature search for cases of salt toxicity was conducted. Articles in English that were available electronically through PubMed and Google Scholar were reviewed. RESULTS: Nineteen cases and case series of salt toxicity were located using our search strategy. Salt poisoning has a distinct pathophysiology compared with hypernatremia, most notable for the lack of formation of idiogenic osmoles. CONCLUSIONS: The approach to treatment differs between salt toxicity and hypernatremia, focusing on rapid correction of serum osmolality rather than gradual normalization of serum sodium concentrations. Consultation of nephrology and child protection services are strongly recommended in the comprehensive treatment approach.

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.

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.

PULSE-SMART: Pulse-Based Arrhythmia Discrimination Using a Novel Smartphone Application.

BACKGROUND: Atrial fibrillation (AF) is a common and dangerous rhythm abnormality. Smartphones are increasingly used for mobile health applications by older patients at risk for AF and may be useful for AF screening. OBJECTIVES: To test whether an enhanced smartphone app for AF detection can discriminate between sinus rhythm (SR), AF, premature atrial contractions (PACs), and premature ventricular contractions (PVCs). METHODS: We analyzed two hundred and nineteen 2-minute pulse recordings from 121 participants with AF (n = 98), PACs (n = 15), or PVCs (n = 15) using an iPhone 4S. We obtained pulsatile time series recordings in 91 participants after successful cardioversion to sinus rhythm from preexisting AF. The PULSE-SMART app conducted pulse analysis using 3 methods (Root Mean Square of Successive RR Differences; Shannon Entropy; Poincare plot). We examined the sensitivity, specificity, and predictive accuracy of the app for AF, PAC, and PVC discrimination from sinus rhythm using the 12-lead EKG or 3-lead telemetry as the gold standard. We also administered a brief usability questionnaire to a subgroup (n = 65) of app users. RESULTS: The smartphone-based app demonstrated excellent sensitivity (0.970), specificity (0.935), and accuracy (0.951) for real-time identification of an irregular pulse during AF. The app also showed good accuracy for PAC (0.955) and PVC discrimination (0.960). The vast majority of surveyed app users (83%) reported that it was "useful" and "not complex" to use. CONCLUSION: A smartphone app can accurately discriminate pulse recordings during AF from sinus rhythm, PACs, and PVCs.

Acute Poisonings from Synthetic Cannabinoids - 50 U.S. Toxicology Investigators Consortium Registry Sites, 2010-2015.

Recent reports suggest that acute intoxications by synthetic cannabinoids are increasing in the United States (1,2). Synthetic cannabinoids, which were research compounds in the 1980s, are now produced overseas; the first shipment recognized to contain synthetic cannabinoids was seized at a U.S. border in 2008 (3). Fifteen synthetic cannabinoids are Schedule I controlled substances (3), but enforcement is hampered by the continual introduction of new chemical compounds (1,3). Studies of synthetic cannabinoids indicate higher cannabinoid receptor binding affinities, effects two to 100 times more potent than Δ(9)-tetrahydrocannabinol (the principal psychoactive constituent of cannabis), noncannabinoid receptor binding, and genotoxicity (4,5). Acute synthetic cannabinoid exposure reportedly causes a range of mild to severe neuropsychiatric, cardiovascular, renal, and other effects (4,6,7); chronic use might lead to psychosis (6,8). During 2010-2015, physicians in the Toxicology Investigators Consortium (ToxIC) treated 456 patients for synthetic cannabinoid intoxications; 277 of the 456 patients reported synthetic cannabinoids as the sole toxicologic agent. Among these 277 patients, the most common clinical signs of intoxication were neurologic (agitation, central nervous system depression/coma, and delirium/toxic psychosis). Relative to all cases logged by 50 different sites in the ToxIC Case Registry, there was a statistically significant association between reporting year and the annual proportion of synthetic cannabinoid cases. In 2015, reported cases of synthetic cannabinoid intoxication increased at several ToxIC sites, corroborating reported upward trends in the numbers of such cases (1,2) and underscoring the need for prevention.