scholarly journals Hypoxia driven opioid targeted automated device for overdose rescue

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohammad S. Imtiaz ◽  
Charles V. Bandoian ◽  
Thomas J. Santoro
Keyword(s):  
Large Scale ◽  
Time Window ◽  
Subcutaneous Administration ◽  
Critical Time ◽  
Rapid Onset ◽  
Opioid Overdose ◽  
Opioid Use ◽  
Self Administration ◽  
Non Invasive ◽  
Sequence Of Events

AbstractOpioid use disorder has been designated a worsening epidemic with over 100,000 deaths due to opioid overdoses recorded in 2021 alone. Unintentional deaths due to opioid overdoses have continued to rise inexorably. While opioid overdose antidotes such as naloxone, and nalmefene are available, these must be administered within a critical time window to be effective. Unfortunately, opioid-overdoses may occur in the absence of antidote, or may be unwitnessed, and the rapid onset of cognitive impairment and unconsciousness, which frequently accompany an overdose may render self-administration of an antidote impossible. Thus, many lives are lost because: (1) an opioid overdose is not anticipated (i.e., monitored/detected), and (2) antidote is either not present, and/or not administered within the critical frame of effectiveness. Currently lacking is a non-invasive means of automatically detecting, reporting, and treating such overdoses. To address this problem, we have designed a wearable, on-demand system that comprises a safe, compact, non-invasive device which can monitor, and effectively deliver an antidote without human intervention, and report the opioid overdose event. A novel feature of our device is a needle-stow chamber that stores needles in a sterile state and inserts needles into tissue only when drug delivery is needed. The system uses a microcontroller which continuously monitors respiratory status as assessed by reflex pulse oximetry. When the oximeter detects the wearer’s percentage of hemoglobin saturated with oxygen to be less than or equal to 90%, which is an indication of impending respiratory failure in otherwise healthy individuals, the microcontroller initiates a sequence of events that simultaneously results in the subcutaneous administration of opioid antidote, nalmefene, and transmission of a GPS-trackable 911 alert. The device is compact (4 × 3 × 3 cm), adhesively attaches to the skin, and can be conveniently worn on the arm. Furthermore, this device permits a centralized remotely accessible system for effective institutional, large-scale intervention. Most importantly, this device has the potential for saving lives that are currently being lost to an alarmingly increasing epidemic.

scholarly journals Low-Intensity Electromagnetic Millimeter Waves for Pain Therapy

2006 ◽  
Vol 3 (2) ◽  
pp. 201-207 ◽  
Author(s):  
Taras I. Usichenko ◽  
Hardy Edinger ◽  
Vasyl V. Gizhko ◽  
Christian Lehmann ◽  
Michael Wendt ◽  
...  
Keyword(s):  
Pain Relief ◽  
Methodological Quality ◽  
Large Scale ◽  
Case Series ◽  
Treatment Method ◽  
Rapid Onset ◽  
Acupuncture Points ◽  
Non Invasive ◽  
Review Criteria

Millimeter wave therapy (MWT), a non-invasive complementary therapeutic technique is claimed to possess analgesic properties. We reviewed the clinical studies describing the pain-relief effect of MWT. Medline-based search according to review criteria and evaluation of methodological quality of the retrieved studies was performed. Of 13 studies, 9 of them were randomized controlled trials (RCTs), only three studies yielded more than 3 points on the Oxford scale of methodological quality of RCTs. MWT was reported to be effective in the treatment of headache, arthritic, neuropathic and acute postoperative pain. The rapid onset of pain relief during MWT lasting hours to days after, remote to the site of exposure (acupuncture points), was the most characteristic feature in MWT application for pain relief. The most commonly used parameters of MWT were the MW frequencies between 30 and 70 GHz and power density up to 10 mW cm−2. The promising results from pilot case series studies and small-size RCTs for analgesic/hypoalgesic effects of MWT should be verified in large-scale RCTs on the effectiveness of this treatment method.

scholarly journals Mechanisms of Pond Expansion in a Rapidly Submerging Marsh

2021 ◽  
Vol 8 ◽  
Author(s):  
Joshua Himmelstein ◽  
Orencio Duran Vinent ◽  
Stijn Temmerman ◽  
Matthew L. Kirwan
Keyword(s):  
Growth Rates ◽  
Large Scale ◽  
Time Window ◽  
Critical Time ◽  
Field Measurements ◽  
Physical Models ◽  
Primary Driver ◽  
Pond Size ◽  
Power Law Equation ◽  
Historical Photographs

The development and expansion of ponds within otherwise vegetated coastal marshes is a primary driver of marsh loss throughout the world. Previous studies propose that large ponds expand through a wind wave-driven positive feedback, where pond edge erosion rates increase with pond size, whereas biochemical processes control the formation and expansion of smaller ponds. However, it remains unclear which mechanisms dominate at a given scale, and thus how, and how fast, ponds increase their size. Here, we use historical photographs and field measurements in a rapidly submerging microtidal marsh to quantify pond development and identify the processes involved. We find that as small ponds emerge on the marsh platform, they quickly coalesce and merge, increasing the number of larger ponds. Pond expansion rates are maximized for intermediate size ponds and decrease for larger ponds, where the contribution of wave-driven erosion is negligible. Vegetation biomass, soil shear strength, and porewater biogeochemical indices of marsh health are higher in marshes adjacent to stable ponds than in those adjacent to unstable ponds, suggesting that pond growth rates are negatively related to the health of the surrounding marsh. We find that the model of Vinent et al. (2021) correctly predicts measured pond growth rates and size distribution, which suggest the different mechanisms driving pond growth are a result of marsh drowning due to sea level rise (SLR) and can be estimated by simplified physical models. Finally, we show that all relevant processes increasing pond size can be summarized by an empirical power-law equation for pond growth which predicts the temporal change of the maximum pond size as a lower bound for the total pond area in the system. This gives a timescale for the growth of ponds by merging and thus the critical time window for interventions to prevent the irreversible pond expansion associated with large scale pond merging.

scholarly journals Pattern of Opioid Overdoses and Interventions at the Emergency Department: Impact of COVID-19

2021 ◽  
Author(s):  
Katherine L Potaka ◽  
Rebecca Freeman ◽  
Danny Soo ◽  
Nam-Anh Nguyen ◽  
Tin Fei Sim ◽  
...  
Keyword(s):  
Emergency Department ◽  
Practice Guidelines ◽  
Large Scale ◽  
Opioid Antagonist ◽  
Opioid Overdose ◽  
Opioid Use ◽  
Post Discharge ◽  
Retrospective Audit ◽  
Drug Overdoses ◽  
The Impact

Abstract BackgroundOpioid-related overdoses cause substantial numbers of preventable deaths. Naloxone is an opioid antagonist available in take-home naloxone (THN) kits as a lifesaving measure for opioid overdose. As the emergency department (ED) is a primary point of contact for patients with high-risk opioid use, evidence-based recommendations from the Society of Hospital Pharmacists of Australia THN practice guidelines include the provision of THN, accompanied by psychosocial interventions. However, implementation of these guidelines in practice is unknown. This study investigated ED opioid-related overdose presentations, concordance of post-overdose interventions with the THN practice guidelines, and the impact, if any, of the SARS-CoV-2 (COVID-19) pandemic on case presentations.MethodsA single-centre retrospective audit was conducted at a major tertiary hospital of patients presenting with overdoses involving opioids and non-opioids between March to August 2019 and March to August 2020. Patient presentations and interventions delivered by the paramedics, ED and upon discharge from the ED were collated from medical records and analysed using descriptive statistics, chi square and independent T-tests.ResultsThe majority (66.2%) of patients presented to hospital with mixed drug overdoses involving opioids and non-opioids. Pharmaceutical opioids were implicated in a greater proportion (72.1%) of overdoses than illicit opioids. Fewer patients presented in March to August 2020 as compared with 2019 (26 vs. 42), and mixed drug overdoses were more frequent in 2020 than 2019 (80.8% vs. 57.1%). Referral to outpatient psychology (22.0%) and drug and alcohol services (20.3%) were amongst the most common post-discharge interventions. Naloxone was provided to 28 patients (41.2%) by the paramedics and/or ED. No patients received THN upon discharge.ConclusionsThis study highlights opportunities to improve ED provision of THN and other interventions post-opioid overdose. Large-scale multi-centre studies are required to ascertain the capacity of EDs to provide THN and the impact of COVID-19 on opioid overdose presentations.

scholarly journals Identifying the critical time window for the association of the early-life gut microbiome and metabolome with childhood neurodevelopment

2022 ◽  
Author(s):  
Zheng Sun ◽  
Kathleen Lee-Sarwar ◽  
Rachel S. Kelly ◽  
Jessica A. Lasky-Su ◽  
Augusto A. Litonjua ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Early Life ◽  
Large Scale ◽  
Time Window ◽  
Human Study ◽  
Critical Time ◽  
Therapeutic Interventions ◽  
First Year ◽  
Two Stages ◽  
First Year Of Life

It has been widely recognized that a critical time window for neurodevelopment occurs in early life, and that the host's gut microbiome plays an important role in neurodevelopment. While murine models have demonstrated that the maternal gut microbiome also influences offspring brain development, for humans it is still unclear if the critical time window for the association between the gut microbiome and neurodevelopment is prenatal, postnatal or both. Here we leverage a large-scale human study and compare the associations between the gut microbiota and metabolites from mothers and their children with the children's neurodevelopment. We show, for the first time, that the maternal gut microbiome is more relevant than the children's gut microbiome to the children's neurodevelopment in the first year of life. Interestingly, the roles of the same taxa with respect to neurodevelopment can be opposite at the two stages of fetal neurodevelopment. These findings shed light on potential therapeutic interventions to prevent neurodevelopmental disorders.

scholarly journals Large-Scale Analysis of Acute Ethanol Exposure in Zebrafish Development: A Critical Time Window and Resilience

PLoS ONE ◽  
2011 ◽  
Vol 6 (5) ◽  
pp. e20037 ◽  
Author(s):  
Shaukat Ali ◽  
Danielle L. Champagne ◽  
Alia Alia ◽  
Michael K. Richardson
Keyword(s):  
Large Scale ◽  
Time Window ◽  
Critical Time ◽  
Ethanol Exposure ◽  
Scale Analysis ◽  
Zebrafish Development ◽  
Large Scale Analysis ◽  
Acute Ethanol

scholarly journals Association between timing of kyphoplasty and opioid prescribing risk after vertebral fracture

2020 ◽  
Vol 49 (2) ◽  
pp. E15 ◽  
Author(s):  
Jay K. Nathan ◽  
Mitchell A. Johnson ◽  
Jennifer F. Waljee ◽  
Nicholas Szerlip ◽  
Paul Park ◽  
...  
Keyword(s):  
Vertebral Fracture ◽  
Large Scale ◽  
Opioid Overdose ◽  
Opioid Use ◽  
Opioid Prescribing ◽  
Large Scale Data ◽  
Before And After ◽  
Cdc Guidelines ◽  
Insurance Claims Data ◽  
Fracture Diagnosis

OBJECTIVEApproximately 550,000 Americans experience vertebral fracture annually, and most receive opioids to treat the resulting pain. Kyphoplasty of the fractured vertebra is a procedural alternative that may mitigate risks of even short-term opioid use. While reports of kyphoplasty’s impact on pain scores are mixed, no large-scale data exist regarding opioid prescribing before and after the procedure. This study was conducted to determine whether timing of kyphoplasty following vertebral fracture is associated with duration or intensity of opioid prescribing.METHODSThis retrospective cohort study used 2001–2014 insurance claims data from a single, large private insurer in the US across multiple care settings. Patients were adults with vertebral fractures who were prescribed opioids and underwent balloon-assisted kyphoplasty within 4 months of fracture. Opioid overdose risk was stratified by prescribed average daily morphine milligram equivalents using CDC guidelines. Filled prescriptions and risk categories were evaluated at baseline and 90 days following kyphoplasty.RESULTSInclusion criteria were met by 7119 patients (median age 77 years, 71.7% female). Among included patients, 3505 (49.2%) were opioid naïve before fracture. Of these patients, 31.1% had new persistent opioid prescribing beyond 90 days after kyphoplasty, and multivariable logistic regression identified kyphoplasty after 8 weeks as a predictor (OR 1.34, 95% CI 1.02–1.76). For patients previously receiving opioids, kyphoplasty > 4 weeks after fracture was associated with persistently elevated prescribing risk (OR 1.84, 95% CI 1.23–2.74).CONCLUSIONSNew persistent opioid prescribing occurred in nearly one-third of patients undergoing kyphoplasty after vertebral fracture, although early treatment was associated with a reduction in this risk. For patients not naïve to opioids before fracture diagnosis, early kyphoplasty was associated with less persistent elevation of opioid overdose risk. Subsequent trials must compare opioid use by vertebral fracture patients treated via operative (kyphoplasty) and nonoperative (ongoing opioid) strategies before concluding that kyphoplasty lacks value, and early referral for kyphoplasty may be appropriate to avoid missing a window of efficacy.

scholarly journals GIANA allows computationally-efficient TCR clustering and multi-disease repertoire classification by isometric transformation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hongyi Zhang ◽  
Xiaowei Zhan ◽  
Bo Li
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Large Scale ◽  
Cell Receptor ◽  
Alignment Algorithm ◽  
Computationally Efficient ◽  
Antigen Specificity ◽  
Non Invasive ◽  
Isometric Transformation ◽  
Specific Receptors

AbstractSimilarity in T-cell receptor (TCR) sequences implies shared antigen specificity between receptors, and could be used to discover novel therapeutic targets. However, existing methods that cluster T-cell receptor sequences by similarity are computationally inefficient, making them impractical to use on the ever-expanding datasets of the immune repertoire. Here, we developed GIANA (Geometric Isometry-based TCR AligNment Algorithm) a computationally efficient tool for this task that provides the same level of clustering specificity as TCRdist at 600 times its speed, and without sacrificing accuracy. GIANA also allows the rapid query of large reference cohorts within minutes. Using GIANA to cluster large-scale TCR datasets provides candidate disease-specific receptors, and provides a new solution to repertoire classification. Querying unseen TCR-seq samples against an existing reference differentiates samples from patients across various cohorts associated with cancer, infectious and autoimmune disease. Our results demonstrate how GIANA could be used as the basis for a TCR-based non-invasive multi-disease diagnostic platform.

scholarly journals Assessing the Relationships Between COVID-19 Stay-at-Home Orders and Opioid Overdoses in the State of Pennsylvania

2021 ◽  
pp. 002204262110063
Author(s):  
Brian King ◽  
Ruchi Patel ◽  
Andrea Rishworth
Keyword(s):  
Age Groups ◽  
The United States ◽  
Opioid Use Disorder ◽  
Opioid Overdose ◽  
Policy Recommendations ◽  
Opioid Use ◽  
Fentanyl Analogs ◽  
Measure Change ◽  
Using Data ◽  
At Home

COVID-19 is compounding opioid use disorder throughout the United States. While recent commentaries provide useful policy recommendations, few studies examine the intersection of COVID-19 policy responses and patterns of opioid overdose. We examine opioid overdoses prior to and following the Pennsylvania stay-at-home order implemented on April 1, 2020. Using data from the Pennsylvania Overdose Information Network, we measure change in monthly incidents of opioid-related overdose pre- versus post-April 1, and the significance of change by gender, age, race, drug class, and naloxone doses administered. Findings demonstrate statistically significant increases in overdose incidents among both men and women, White and Black groups, and several age groups, most notably the 30–39 and 40–49 ranges, following April 1. Significant increases were observed for overdoses involving heroin, fentanyl, fentanyl analogs or other synthetic opioids, pharmaceutical opioids, and carfentanil. The study emphasizes the need for opioid use to be addressed alongside efforts to mitigate and manage COVID-19 infection.

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