Dataset Information

Simple minimally-invasive automatic antidote delivery device (A2D2) towards closed-loop reversal of opioid overdose.

ABSTRACT: With approximately 48,000 attributed deaths in 2017, the opioid overdose is now the leading cause of death amongst Americans under the age of 50. The overdose process can be interrupted by the administration of naloxone, a safe and effective opiate antagonist that can reverse the effects of overdose and minimizing the delay in administering the antidote is critical in preventing permanent damage to patients. A closed-loop implantable drug delivery system is an ideal solution to minimize the response time, however, they often feature complex designs that are expensive to fabricate and require a more invasive surgical implantation. Here we propose a simple, low-cost, minimally-invasive automatic antidote delivery device (A2D2) that can administer a large dose of naloxone upon detection of overdose-induced respiratory failure. The subcutaneously placed device can be activated using an externally applied time varying magnetic field from a wearable device. Using a custom magnetic field generator, we were able to release the drug within 10?s. Our bench-top evaluation showed that A2D2 can release 1.9?mg of powdered drug within 60?s and up to 8.8?mg in 600?s. We also performed in vivo evaluation to demonstrate rapid drug releasing capability in the subcutaneous space of mice. However, we saw a small amount of leakage (1.75% of payload) over the course of 1000?h of simulated implantation. Thus, additional research is needed to verify the long term stability of our device and to demonstrate the closed-loop release mechanism to revive overdosed animals. Nevertheless, our preliminary results show the potential of using a simple, low-cost, subcutaneous device for emergency drug delivery application.

SUBMITTER: Dhowan B

PROVIDER: S-EPMC6629496 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Simple minimally-invasive automatic antidote delivery device (A2D2) towards closed-loop reversal of opioid overdose.

Dhowan Bahar B Lim Jongcheon J MacLean Michael D MD Berman Alycia G AG Kim Min Ku MK Yang Qi Q Linnes Jacqueline J Lee Chi Hwan CH Goergen Craig J CJ Lee Hyowon H

Journal of controlled release : official journal of the Controlled Release Society 20190531

With approximately 48,000 attributed deaths in 2017, the opioid overdose is now the leading cause of death amongst Americans under the age of 50. The overdose process can be interrupted by the administration of naloxone, a safe and effective opiate antagonist that can reverse the effects of overdose and minimizing the delay in administering the antidote is critical in preventing permanent damage to patients. A closed-loop implantable drug delivery system is an ideal solution to minimize the resp ...[more]

PMID: 31158402

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Project description:BACKGROUND:West Virginia is a largely rural state with strong ties of kinship, mutual systems of support and charitable giving. At the same time, wealth inequalities are extreme and the state's drug overdose fatality rate stands above all others in the USA at 51.5/100,000 in 2018, largely opioid-related. In recent years, harm reduction services have been active in the state but in 2018 Charleston's needle and syringe program was forced to close. This paper considers the risk environment in which the state's drug-related loss of life, and those attempting to prevent it, exist. METHODS:This rapid ethnographic study involved semi-structured interviews (n?=?21), observation and video recordings of injection sequences (n?=?5), initially recruiting people who inject heroin/fentanyl (PWIH) at the Charleston needle and syringe program. Snowball sampling led the research team to surrounding towns in southern West Virginia. Telephone interviews (n?=?2) with individuals involved in service provision were also carried out. RESULTS:PWIH in southern West Virginia described an often unsupportive, at times hostile risk environment that may increase the risk of overdose fatalities. Negative experiences, including from some emergency responders, and fears of punitive legal consequences from calling these services may deter PWIH from seeking essential help. Compassion fatigue and burnout may play a part in this, along with resentment regarding high demands placed by the overdose crisis on impoverished state resources. We also found low levels of knowledge about safe injection practices among PWIH. CONCLUSIONS:Hostility faced by PWIH may increase their risk of overdose fatalities, injection-related injury and the risk of HIV and hepatitis C transmission by deterring help-seeking and limiting the range of harm reduction services provided locally. Greater provision of overdose prevention education and naloxone for peer distribution could help PWIH to reverse overdoses while alleviating the burden on emergency services. Although essential for reducing mortality, measures that address drug use alone are not enough to safeguard longer-term public health. The new wave of psychostimulant-related deaths underline the urgency of addressing the deeper causes that feed high-risk patterns of drug use beyond drugs and drug use.

Project description:BackgroundRapid naloxone administration is crucial in reversing an opioid overdose. We investigated whether equipping community members, including people who use opioids (PWUO), with a smartphone application enabling them to signal and respond to suspected overdose would support naloxone administration in advance of Emrgency Medical Services (EMS).MethodsThis observational cohort study of opioid overdose intervention used a dedicated smartphone app, UnityPhilly, activated by volunteers witnessing an overdose to signal other nearby volunteers in Philadelphia (March 2019 - February 2020). Alerted volunteers chose to respond, or declined to respond, or ignored/missed the alert. Witnessing volunteer was connected to 9-1-1 through a semi-automated telephone call. The primary outcome was layperson-initiated overdose reversal before EMS arrival, and a secondary outcome was hospital transfer. This study is registered with ClinicalTrials.gov, NCT03305497.Findings112 volunteers, including 57 PWUO and 55 community members, signaled 291 suspected opioid overdose alerts. 89 (30⸱6%) were false alarms. For 202 true alerts, the rate of layperson initiated naloxone use was 36⸱6% (74/202 cases). Most naloxone-use cases occurred in the street (58⸱11% (43/74)) and some in home settings (22⸱98% (17/74)). The first naloxone dose was provided by a nearby volunteer responding to the alert in 29⸱73% (22/74) of cases and by the signaling volunteer in 70⸱27% (52/74) of cases. Successful reversal was reported in 95⸱9% (71/74) of cases. Layperson intervention preceded EMS by 5 min or more in 59⸱5% of cases. Recovery without hospital transport was reported in 52⸱7% (39/74) of cases.InterpretationOur findings support the benefits of equipping community members, potentially witnessing suspected opioid overdose, with naloxone and an emergency response community smartphone app, alerting EMS and nearby laypersons to provide additional naloxone.FundingFunding provided by NIH through NIDA, grant number: 5R34DA044758.

Project description:Background and aimsTake-home naloxone can prevent death from heroin/opioid overdose, but pre-provision is difficult because naloxone is usually given by injection. Non-injectable alternatives, including naloxone nasal sprays, are currently being developed. To be effective, the intranasal (i.n.) spray dose must be adequate but not excessive, and early absorption must be comparable to intramuscular (i.m.) injection. We report on the pharmacokinetics (PK) of a specially produced concentrated novel nasal spray. The specific aims were to: (1) estimate PK profiles of i.n. naloxone, (2) compare early systemic exposure with i.n. versus i.m. naloxone and (3) estimate i.n. bioavailability.DesignOpen-label, randomized, five-way cross-over PK study.SettingClinical trials facility (Croydon, UK).ParticipantsThirty-eight healthy volunteers (age 20-54 years; 11 female).Intervention and comparatorThree doses of i.n. (1 mg/0.1 ml, 2 mg/0.1 ml, 4 mg/0.2 ml) versus 0.4 mg i.m. (reference) and 0.4 mg intravenous (i.v.) naloxone.MeasurementsRegular blood samples were taken, with high-frequency sampling during the first 15 minutes to capture early systemic exposure. PK parameters were determined from plasma naloxone concentrations. Exploratory analyses involved simulation of repeat administration.FindingsMean peak concentration (Cmax ) values for 1 mg (1.51 ng/ml), 2 mg (2.87 ng/ml) and 4 mg (6.02 ng/ml) i.n. exceeded 0.4 mg i.m. (1.27 ng/ml) naloxone. All three i.n. doses rapidly achieved plasma levels > 50% of peak concentrations (T50%) by 10 minutes, peaking at 15-30 minutes (Tmax ). For comparison, the i.m. reference reached Tmax at 10 minutes. Mean bioavailability was 47-51% for i.n. relative to i.m. naloxone. Simulation of repeat dosing (2 × 2 mg i.n. versus 5 × 0.4 mg i.m. doses) at 3-minute intervals showed that comparable plasma naloxone concentrations would be anticipated.ConclusionsConcentrated 2 mg intranasal naloxone is well-absorbed and provides early exposure comparable to 0.4 mg intramuscular naloxone, following the 0.4 mg intramuscular curve closely in the first 10 minutes post-dosing and maintaining blood levels above twice the intramuscular reference for the next 2 hours.

Project description:BackgroundThe opioid epidemic is a progressively worsening public health crisis that continues to impact healthcare system strategies such as overdose reversal and destigmatization. Even among healthcare professionals, there remains a lack of confidence in naloxone administration and a prevalence of stigma. While training can play a major impact in reducing these shortcomings, the long-term effectiveness has yet to be characterized in training healthcare professionals. This study examined the long-term retention of opioid overdose awareness and reversal training (OOART) by evaluating performance at two-time intervals, immediately post-training and at a 3-month follow-up.MethodsVoluntary training was offered to first-year (M1) medical students at the Drexel University College of Medicine in 2021. At this training, 118 students completed training, 95 completed the post-training survey, and 42 completed the 3-month follow-up.ResultsOpioid reversal knowledge questions assessed significantly increased scores post-training and at the 3-month follow-up. In three of the attitude questions, scores were improved at both follow-up timepoints. In addition, three attitude questions indicating a participant's confidence to respond to an opioid overdose situation increased directly after the training, but regressed at the 3-month follow-up. The remaining questions did not show any statistical difference across the survey intervals.ConclusionsThis study establishes that while OOART provides participants with the knowledge of how to respond to an opioid overdose, the retention of this knowledge at a 3-month interval is reduced. The results were mixed for longitudinal assessment of participant's attitudes toward people with opioid use disorder. Some positive increases in attitudes were retained at the 3-month interval, while others trended back toward pre-training levels. These results support the effectiveness of the training but also provide evidence that OOART must be reinforced often.

Dataset Information

Simple minimally-invasive automatic antidote delivery device (A2D2) towards closed-loop reversal of opioid overdose.

Publications

Simple minimally-invasive automatic antidote delivery device (A2D2) towards closed-loop reversal of opioid overdose.

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