1.The development history of enhanced recovery after surgery(ERAS)Enhanced recovery after surgery(ERAS)is a multimodal perioperative care approach that has evolved over the past 2 decades since its inception.In 1997,P...1.The development history of enhanced recovery after surgery(ERAS)Enhanced recovery after surgery(ERAS)is a multimodal perioperative care approach that has evolved over the past 2 decades since its inception.In 1997,Professor Henrik Kehlet,also known as the“father of ERAS”,from the University of Copenhagen in Denmark first proposed the ERAS concept and discovered its clinical feasibility and superiority,achieving remarkable results.ERAS was initially applied in colorectal surgery;subsequently,the concept gradually gained popularity and application worldwide.展开更多
Objective:This research utilizes the FAERS for data mining to identify heart-related side effects caused by opioids,ensuring the safe use of these medications.Methods:Data from 79 quarters(Q12004 to Q32023)involving a...Objective:This research utilizes the FAERS for data mining to identify heart-related side effects caused by opioids,ensuring the safe use of these medications.Methods:Data from 79 quarters(Q12004 to Q32023)involving adverse event(AE)reports for opioids like morphine and oxycodone was reviewed.We applied the MedDRA system to categorize events and used statistical tools,ROR and BCPNN,for signal detection.These findings were cross-checked with drug labels and SIDER 4.1 for accuracy.Identified risks were then categorized by severity using DME and IME classifications.Results:Analysis of adverse events(AEs)for the five examined drugs(35359,14367,144441,10592,and 28848)identified 33,6,12,37,and 34 cardiovascular AEs,and 16,5,7,25,and 21 instances of important medical events(IMEs)respectively.Each drug was linked to cases of cardiac and cardiopulmonary arrest.The cardiovascular AEs varied widely in occurrence and severity,with methadone notably presenting diverse and potent risks,including sudden cardiac death as a distinct medical event(DME).A comparison with SIDER 4.1 showed 11 opioid-related cardiovascular AEs in line with our findings.Standardized MedDRA Queries(SMQs)confirmed these results,indicating stronger signals for methadone and tramadol,while morphine,hydromorphone,and oxycodone exhibited fewer and weaker signals.Conclusion:The study revealed numerous heart-related adverse effects(AEs)not listed on drug labels and identified new AE patterns.Recognizing these differences in AE profiles and risks across different opioids is crucial for safer prescription practices to minimize cardiac complications.展开更多
BACKGROUND Surgical palliative surgery is a common method for treating patients with middle and late stage gastrointestinal tumors.However,these patients generally expe-rience high levels of cancer pain,which can in t...BACKGROUND Surgical palliative surgery is a common method for treating patients with middle and late stage gastrointestinal tumors.However,these patients generally expe-rience high levels of cancer pain,which can in turn stimulate the body’s stress and undermine the effect of external surgery.Although opioid drugs have a signifi-cantly positive effect on controlling cancer pain,they can induce adverse drug reactions and potential damage to the body’s immune function.Hyperthermia therapy produces a thermal effect that shrinks tumor tissues.However,its effect on relieving the pain of middle and late stage gastrointestinal tumors but also the stress of surgical palliative surgery remains unclear.AIM To investigate the effect of hyperthermia combined with opioids on controlling cancer pain in patients with middle and late stage gastrointestinal cancer and evaluate its impact on surgical palliative surgical stress.METHODS This was a retrospective study using the data of 70 patients with middle and late stage gastrointestinal tumors who underwent cancer pain treatment and surgical palliative surgery in the Ninth People’s Hospital of Suzhou,China from January 2021 to June 2024.Patients were grouped according to different cancer pain control regimens before surgical palliative surgery,with n=35 cases in each group,as follows:Patients who solely used opioid drugs to control cancer pain were included in Group S,while patients who received hyperthermia treatment combined with opioid drugs were included in Group L.In both groups,we compared the effectiveness of cancer pain control(pain score,burst pain score,24-hour burst pain frequency,immune function,daily dosage of opioid drugs,and adverse reactions),surgical palliative indicators(surgery time,intraoperative bleeding,stress response),and postoperative recovery time,including first oral feeding time,postoperative hospital stay).RESULTS Analgesic treatment resulted in a significant decrease in the average pain score,burst pain score,and 24-hour burst pain frequency in both Groups L and S;however,these scores were statistically significantly lower in Group L than in Group S group(P<0.001).Analgesic treatment also resulted in significant differences,namely serum CD4+(29.18±5.64 vs 26.05±4.76,P=0.014),CD8+(26.28±3.75 vs 29.23±3.89,P=0.002),CD4+/CD8+(0.97±0.12 vs 0.83±0.17,P<0.001),between Group L and Group S,respectively.The daily dosage of opioid drugs incidence of adverse reactions such as nausea,vomiting,constipation,and difficulty urinating were statistically significantly lower in Group L than those in group S(P<0.05).Furthermore,palliative surgery time and intraoperative blood loss in Group L were slightly lower than those in Group S;however,the difference was not statistically significant(P>0.05).On the first day after surgery,serum cortisol and C-reactive protein levels of patients in group L and group S were 161.43±21.07 vs 179.35±27.86 ug/L(P=0.003)and 10.51±2.05 vs 13.49±2.17 mg/L(P<0.001),respectively.Finally,the first oral feeding time and hospitalization time after surgery in group L were statistically significantly shorter than those in group S(P<0.05).CONCLUSION Our findings showed that hyperthermia combined with opioids is effective in controlling cancer pain in patients with middle and late stage gastrointestinal tumors.Furthermore,this method can reduce the dosage of opioids used and minimize potential adverse drug reactions,reduce the patient’s surgical palliative surgical stress response,and shorten the overall postoperative recovery time required.展开更多
Many older adults suffer from persistent pain but prevalence studies consistently showed high levels of untreated or under-treated pain in old population.Both persistent pain and pain under-treatment adversely affect ...Many older adults suffer from persistent pain but prevalence studies consistently showed high levels of untreated or under-treated pain in old population.Both persistent pain and pain under-treatment adversely affect independence and quality of life in geriatric patients.Pain management is challenging in this age-group because of the declining organ function,the presence of concurrent diseases and polypharmacy.For all the above reasons,persistent pain in the elderly should be considered a geriatric syndrome per se and effective approaches are warranted.Current guidelines and consensus statements recommend opioid therapy for older adults with moderateto-severe persistent pain or functional impairment and diminished quality of life due to pain.However clinicians and patients themselves have some concerns about opioids use.Age-related decline in organs functions and warnings about risk of addiction and drug misuse/abuse also in geriatric patients need particular attention for safe prescribing.On the basis of clinical evidence,these practical recommendations will help to improve the competence on opioid role in persistent pain management and the likelihood of a successful analgesic trial in older patients.展开更多
Women usually suffer from chronic pain due to pregnancy or have an increased level of chronic pain.In view of the definite curative effect of opioids on chronic pain and opioid use disorders,opioids have attracted muc...Women usually suffer from chronic pain due to pregnancy or have an increased level of chronic pain.In view of the definite curative effect of opioids on chronic pain and opioid use disorders,opioids have attracted much attention in the treatment of bone,joint,neuropathic and other chronic pain and opioid use disorders in pregnant women.Considering that the unreasonable use of opioids by pregnant women will lead to risks such as drug accumulation and increased neural sensitivity in the fetus,the correct and reasonable use of opioids is the key to the treatment.In recent years,it has been found that opioids can cross the blood fetal barrier into the fetal circulation,and damage fetal nerve development to varying degrees.However,the studies on the typical diseases such as neonatal neural tube defects and neonatal abstinence syndrome are not comprehensive.Therefore,this article has clarified the unreasonable use of opioids during pregnancy and its effect on fetal nerve development,and put forward relevant measures in order to provide reference for clinicians/pharmacists in obstetrics and gynecology.展开更多
Objective:To study the effects of propofol combined with different types of opioids on inflammatory stress response in painless gastroscopy.Methods: Patients who underwent painless gastroscopy in our hospital between ...Objective:To study the effects of propofol combined with different types of opioids on inflammatory stress response in painless gastroscopy.Methods: Patients who underwent painless gastroscopy in our hospital between August 2014 and January 2018 were retrospectively analyzed, divided into those with nalbuphine hydrochloride, dezocine and sufentanil according to different choice of opioids and included in group A, group B and group C of the study respectively. The contents of inflammatory cytokines and oxidative stress products in serum as well as the expression levels of inflammatory pathway molecules and antioxidant pathway molecules in peripheral blood were measured before and 6 h after gastroscopy.Results: HMGB-1, TNF-α, IFN-γ, CRP, MDA, OH- and O2- contents in serum as well as RhoA, ROCK, Wnt3a,β-catenin, JNK, ERK1/2, Nrf2, ARE, HO-1,γ-GCS and Prx1 expression in peripheral blood of three groups of patients after gastroscopy were higher than those before gastroscopy, and HMGB-1, TNF-α, IFN-γ, CRP, MDA, OH- and O2- contents in serum as well as RhoA, ROCK, Wnt3a,β-catenin, JNK and ERK1/2 expression in peripheral blood of group A after gastroscopy were lower than those of group B and group C whereas Nrf2, ARE, HO-1,γ-GCS and Prx1 expression in peripheral blood were higher than those of group B and group C.Conclusion: Propofol combined with nalbuphine hydrochloride can be more effective than dezocine and sufentanil to reduce the inflammatory stress response in painless gastroscopy.展开更多
Polysubstance (combinations of substances) abuse and overdose deaths now surpass mono-substance abuse and overdose deaths. Several international and governmental organizations such as the WHO (World Health Organizatio...Polysubstance (combinations of substances) abuse and overdose deaths now surpass mono-substance abuse and overdose deaths. Several international and governmental organizations such as the WHO (World Health Organization), CDC (Centers for Disease Control and Prevention), several of the Institutes of the NIH (National Institutes of Health), Regulators, and Enforcement Agencies, among others, track and provide a valuable source of statistical information about drug (prescription and illicit) (mis)use and overdose. The information is disseminated free to stakeholders and the general public for use. Although the numeric presentations of the data are helpful and adequate for professionals, the non-expert and the visual learner often find visual representation more clear and more compelling. With this in mind, the aim of this study was to present polysubstance use and overdose using visual maps of the available data. This article considers the opioids.展开更多
BACKGROUND Several breast cancer studies have reported the use of adjuvant opioids with the paravertebral block(PVB)to improve outcomes.However,there is no level-1 evidence justifying its use.AIM To elucidate if the a...BACKGROUND Several breast cancer studies have reported the use of adjuvant opioids with the paravertebral block(PVB)to improve outcomes.However,there is no level-1 evidence justifying its use.AIM To elucidate if the addition of opioids to PVB improves pain control in breast cancer surgery patients.METHODS We conducted an electronic literature search across PubMed,Embase,Scopus,and Google Scholar databases up to October 20,2020.Only randomized controlled trials(RCTs)comparing the addition of opioids to PVB with placebo for breast cancer surgery patients were included.RESULTS Six RCTs were included.Our meta-analysis indicated significantly reduced 24-h total analgesic consumption with the addition of opioids to PVB as compared to placebo[standardized mean difference(SMD)-1.57,95%confidence interval(CI):-2.93,-0.21,I2=94%].However,on subgroup analysis,the results were nonsignificant for studies using single PVB(SMD:-1.76,95%CI:-3.65,0.13 I2=95.09%)and studies using PVB infusion(SMD:-1.30,95%CI:-4.26,1.65,I2=95.49%).Analysis of single PVB studies indicated no significant difference in the time to first analgesic request between opioid and placebo groups(mean difference-11.28,95%CI:-42.00,19.43,I2=99.39%).Pain scores at 24 h were marginally lower in the opioid group(mean difference-1.10,95%CI:-2.20,0.00,I2=0%).There was no difference in the incidence of postoperative nausea and vomiting between the two groups.CONCLUSION Current evidence suggests a limited role of adjuvant opioids with PVB for breast cancer surgery patients.Further homogenous RCTs with a large sample size are needed to clarify the beneficial role of opioids with PVB.展开更多
This study focused on the influences of opioids on the generation of antibody against sheep erythrocyte in vitro, It was found that morphine. a-CAO, DADLE, MENK were able to inhibit the capacity of murine spleen cell...This study focused on the influences of opioids on the generation of antibody against sheep erythrocyte in vitro, It was found that morphine. a-CAO, DADLE, MENK were able to inhibit the capacity of murine spleen cells to generate antibody and leukotriene C4 and conversely. dynorphin was able to stimulate the capacity of murine spleen cells to generate antibody and leukotriene C4. Morphine, a-CAO, MENK, DADLE, dynorphin decreased intracellular cAMP level, increased [Ca(2+)]i and calmodulin activity. The effects were completely blocked by naloxone, the specific opioid antagonist. Our results showed that opioids regulate the production of antibody in murine spleen cells, and alter intracellular cAMP, [Ca(2+)]i calmodulin activity. and leukotriene C4 production by way of binding to different receptor types.展开更多
Between the illicit use of opioids and attendant overdoses, and accidental overdoses with prescribed drugs, overuse of opioids has become a serious problem. At the same time, finding that fine balance between minimizi...Between the illicit use of opioids and attendant overdoses, and accidental overdoses with prescribed drugs, overuse of opioids has become a serious problem. At the same time, finding that fine balance between minimizing the risk of opioid misuse and abuse while at the same time providing access to treatment for patients who need pain control presents an ongoing challenge. Efforts to discover and develop better agents have led to what we term “new-look” opioids. We summarize here one such approach—known as biased ligands. By targeting a subset of GPCR signal transduction, this approach attempts to increase the separation between therapeutic and adverse effects.展开更多
The abuse of opioids is harmful to the national economy and health.The U.S.government has spent a lot of time,energy and money to deal with this phenomenon.Based on the topic background and team discussion,we deeply e...The abuse of opioids is harmful to the national economy and health.The U.S.government has spent a lot of time,energy and money to deal with this phenomenon.Based on the topic background and team discussion,we deeply excavated the data and information provided in the topic,determined the current use of opioids,and constructed an improved SIR model to determine the source of drug abuse,the mechanism of drug abuse diffusion and the origin of each state through reverse derivation,which provided guidance for the government in the context of opioid abuse.Based on the above results,we simulated and analyzed the improved SIR model and determined the accuracy and stability of the model in the data set.展开更多
AIM To examine the relationship of chronic scheduled opioid use on symptoms, healthcare utilization and employment in gastroparesis(Gp) patients. Methods Patients referred to our tertiary care academic center from May...AIM To examine the relationship of chronic scheduled opioid use on symptoms, healthcare utilization and employment in gastroparesis(Gp) patients. Methods Patients referred to our tertiary care academic center from May 2016 to July 2017, with established diagnosis or symptoms suggestive of Gp filled out the Patient Assessment of Upper GI Symptoms, abdominal pain and demographics questionnaires, and underwent gastric emptying and blood tests. They were asked about taking pain medicines and the types, doses, and duration. We used Mann Whitney U test, Analysis of Variance, Student's t test and χ2 tests where appropriate for data analyses.RESULTS Of 223 patients with delayed gastric emptying, 158(70.9%) patients were not taking opioids(Gp NO), 22(9.9%) were taking opioids only as needed, while 43(19.3%) were on chronic(> 1 mo) scheduled opioids(Gp CO), of which 18 were taking opioids forreasons that included gastroparesis and/or stomach pain. Median morphine equivalent use was 60 mg per day. Gp CO reported higher severities of many gastrointestinal symptoms compared to Gp NO including nausea(mean ± SE of mean of 4.09 ± 0.12 vs 3.41 ± 0.12, P = 0.011), retching(2.86 ± 0.25 vs 1.98 ± 0.14, P = 0.003), vomiting(2.93 ± 0.24 vs 2.07 ± 0.15, P = 0.011), early satiety(4.17 ± 0.19 vs 3.57 ± 0.12, P = 0.004), post-prandial fullness(4.14 ± 0.18 vs 3.63 ± 0.11, P = 0.022), loss of appetite(3.64 ± 0.21 vs 3.04 ± 0.13, P = 0.039), upper abdominal pain(3.86 ± 0.20 vs 2.93 ± 0.13, P = 0.001), upper abdominal discomfort(3.74 ± 0.19 vs 3.09 ± 0.13, P = 0.031), heartburn during day(2.55 ± 0.27 vs 1.89 ± 0.13, P = 0.032), heartburn on lying down(2.76 ± 0.28 vs 1.94 ± 0.14, P = 0.008), chest discomfort during day(2.42 ± 0.20 vs 1.83 ± 0.12, P = 0.018), chest discomfort at night(2.40 ± 0.23 vs 1.61 ± 0.13, P = 0.003), regurgitation/reflux during day(2.77 ± 0.25 vs 2.18 ± 0.13, P = 0.040) and bitter/acid/sour taste in the mouth(2.79 ± 0.27 vs 2.11 ± 0.14, P = 0.028). Gp CO had a longer duration of nausea per day(median of 7 h vs 4 h for Gp NO, P = 0.037), and a higher number of vomiting episodes per day(median of 3 vs 2 for Gp NO, P = 0.002). Their abdominal pain more frequently woke them up at night(78.1% vs 57.3%, P = 0.031). They had a lower employment rate(33.3% vs 54.2%, P = 0.016) and amongst those who were employed less number of working hours per week(median of 23 vs 40, P = 0.005). They reported higher number of hospitalizations in the last 1 year(mean ± SE of mean of 2.90 ± 0.77 vs 1.26 ± 0.23, P = 0.047). CONCLUSION Gp CO had a higher severity of many gastrointestinal symptoms, compared to Gp NO. Hospitalization rates were more than 2-fold higher in Gp CO than Gp NO.Gp CO also had lower employment rate and working hours, when compared to Gp NO.展开更多
Opioid use disorder(OUD)has become a considerable global public health challenge;however,potential medications for the management of OUD that are effective,safe,and nonaddictive are not available.Accumulating preclini...Opioid use disorder(OUD)has become a considerable global public health challenge;however,potential medications for the management of OUD that are effective,safe,and nonaddictive are not available.Accumulating preclinical evidence indicates that antagonists of the dopamine D3 receptor(D3R)have effects on addiction in different animal models.We have previously reported that YQA14,a D3R antagonist,exhibits very high affinity and selectivity for D3Rs over D2Rs,and is able to inhibit cocaine-or methamphetamine-induced reinforcement and reinstatement in self-administration tests.In the present study,our results illustrated that YQA14 dose-dependently reduced infusions under the fixed-ratio 2 procedure and lowered the breakpoint under the progressive-ratio procedure in heroin self-administered rats,also attenuated heroin-induced reinstatement of drug-seeking behavior.On the other hand,YQA14 not only reduced morphine-induced expression of conditioned place preference but also facilitated the extinguishing process in mice.Moreover,we elucidated that YQA14 attenuated opioid-induced reward or reinforcement mainly by inhibiting morphine-induced up-regulation of dopaminergic neuron activity in the ventral tegmental area and decreasing dopamine release in the nucleus accumbens with a fiber photometry recording system.These findings suggest that D3R might play a very important role in opioid addiction,and YQA14 may have pharmacotherapeutic potential in attenuating opioid-induced addictive behaviors dependent on the dopamine system.展开更多
Opioids have been used for treated pain for thousands of years. Meanwhile, opioids induce drug addic- tion, which causes serious medical and social problems. Most opioids research have been concentrated on neurons i...Opioids have been used for treated pain for thousands of years. Meanwhile, opioids induce drug addic- tion, which causes serious medical and social problems. Most opioids research have been concentrated on neurons in the central nerve system （CNS） , however, the action of glia, which accounts for 90% cells in CNS have been long neglected. Unlike the classical opioid-neuron stereoselective interaction opioids were found to non-stereose- lectively bind the accessory protein myeloid differentiation factor 2 （MD-2） of innate immune Toll- like receptor 4 （TLR4） , which induces glial activation and pro-inflammatory factors production, therefore contributing to opioid hyper-analgesia, drug tolerance, dependence and addiction. A series of TLR4 antagonists have been discovered by multiple drug discovery strategies for inhibiting the opioids＇ side effects and treating drug abuse, among which （ ＋ ）-naltrexone and T-5342126 have been transferred to Xalud and BioLineRx respectively, for further pre-clini- cal/clinical drug development.展开更多
Introduction The introduction of 2＇ ,6＇-dimethyl-L＇tyrosine （Dmt） at the N-terminus of Tyr-Tic （1,2,3,4-tetra-hydroisoquinoline-3-carboxylic acid ）-containing δ-opioid antagonists enhances receptor affinity ...Introduction The introduction of 2＇ ,6＇-dimethyl-L＇tyrosine （Dmt） at the N-terminus of Tyr-Tic （1,2,3,4-tetra-hydroisoquinoline-3-carboxylic acid ）-containing δ-opioid antagonists enhances receptor affinity and in vitro bioactivity to several orders of magnitude and its application in the formation of ligands with new properties, such as potent inverse agonism. For example, the δ2 agonist,展开更多
Gastrointestinal endoscopy is a common examination for digestive system.The stimulation of endoscope often causes cough,nausea and vomiting,increased heart rate and blood pressure,arrhythmia,and even cardiovascular an...Gastrointestinal endoscopy is a common examination for digestive system.The stimulation of endoscope often causes cough,nausea and vomiting,increased heart rate and blood pressure,arrhythmia,and even cardiovascular and cerebrovascular accidents,thus makes people fear of this procedure.Sedation or anesthesia can effectively improve the safety,comfort and quality of gastrointestinal endoscopy.A small dose of opioids is a good adjuvant to sedatives.In this narrative review,we summarized the main roles of opioid analgesics in gastrointestinal endoscopy,including reducing visceral pain,throat irritation and the dose of sedatives.Moreover,the frequently used and novel opioids are reviewed.Classic fentanyl,sufentanil and dezocine are preferable by anesthesiologists.Newly approved oliceridine is promising to render ideal analgesic effects for gastrointestinal endoscopy.Clinical studies on oliceridine in endoscopic procedures are urgently needed.展开更多
According to current surveys and overdoses data,there is a drug crisis in the USA.Wastewater-based epidemiology(WBE)is an evolving discipline that analyses wastewater samples to detect drugs and metabolites to estimat...According to current surveys and overdoses data,there is a drug crisis in the USA.Wastewater-based epidemiology(WBE)is an evolving discipline that analyses wastewater samples to detect drugs and metabolites to estimate drug consumption in a certain community.This study demonstrates how drug relative presence could be tracked by testing wastewater,providing real-time results,in different boroughs in New York City throughout 1 year.We developed and fully validated two analytical methods,one for 21 drugs and metabolites,including nicotine,cocaine,amphetamines,opioids and cannabis markers;and another for the normalization factor creatinine.Both methods were performed by liquid chromatography tandem mass spectrometry(LC-MS/MS)using positive electrospray ionization,achieving a limit of quantification of 5–10 ng/L for drugs and metabolites,and 0.01 mg/L for creatinine.These methods were applied to 48 one-time grab wastewater samples collected from six wastewater treatment plants in New York City(Manhattan,The Bronx,Queens and Brooklyn),eight different times throughout 2016,before and after major holidays,including Memorial Day,4th of July,Labour Day and New Year’s.In this study,the drug group normalized concentrations present in the wastewater samples,in decreasing order,were cocaine,nicotine,opioids,cannabis and amphetamines.When looking at individual compounds,the one with the highest normalized concentration was benzoylecgonine(BE),followed by cotinine,morphine and 11-nor-9-carboxy-tetrahydrocannabinol(THCCOOH).To estimate community use,these concentrations were multiplied by the corresponding correction factor,and the most present were THCCOOH,followed by BE,cotinine and morphine.When comparing the treatment plants by drug group(nicotine,cocaine,amphetamines,opioids and cannabis),samples collected from The Bronx had the highest normalized concentrations for nicotine,cocaine and opioids;The Bronx and Manhattan for cannabis;and Manhattan and Queens for amphetamines.In most of the cases,no effect due to holiday was observed.This study provides the first snapshot of drug use in New York City and how that changes between key calendar dates employing wastewater analysis.展开更多
Drugs related to morphine represent not only large range of important therapeutic applications for the relief of moderate to severe pain but also give rise to a relatively large series of novel opioids that mimic the ...Drugs related to morphine represent not only large range of important therapeutic applications for the relief of moderate to severe pain but also give rise to a relatively large series of novel opioids that mimic the action of this naturally occurring analgesic.Most of these are based on fentanyl structures that are much more potent,and dangerous,than fentanyl itself.This publication reviews reports of fatalities attributed to 15 novel opioids with the view to assessing mortality associated with their misuse as well as reviewing published analytical procedures that would be able to detect these and other novel opioids.These drugs include reports of deaths to acetylfentanyl,acrylfentanyl,butr(yl)fentanyl,carfentanil,2-and 4-fluorofentanyls,4-fluorobutyrfentanyl,4-fluoroisobutyrfentanyl,furanylfentanyl,a-and 3-methylfentanyls,4-methoxyfentanyl,ocfentanil,as well as AH-7921,U-47700 and MT-45.Most of these cases reporting a drug-caused death involved other drugs in addition to the opioid.No obvious minimum fatal concentration was discerned for any of the opioids for which details were provided,however,the more potent members required detection limits well under 1 ng/mL and often even well below 0.1 ng/mL requiring use of the most sensitive mass spectral detection procedures,particularly when screening specimens using a non-targeted mode.Four other novel opioids have been reported in admissions to hospitals include 4-chloroisobutryfentanyl,cyclopentylfentanyl and tetrahydrofuranfentanyl,all of which are likely to have the potential to cause death.It is also likely that other analogues will appear with time.展开更多
Over the past few years,there has been an emerging number of new psychoactive drugs.These drugs are frequently mentioned as“legal highs”,“herbal highs”,“bath salts”and“research chemicals”.They are mostly sold ...Over the past few years,there has been an emerging number of new psychoactive drugs.These drugs are frequently mentioned as“legal highs”,“herbal highs”,“bath salts”and“research chemicals”.They are mostly sold and advertised on online forums and on the dark web.The emerging new psychoactive substances are designed to mimic the effects of psychoactive groups,which are often abused drugs.Novel synthetic opioids are a new trend in this context and represent an alarming threat to public health.Given the wide number of fatalities related to these compounds reported within the last few years,it is an important task to accurately identify these compounds in biologic matrices in order to administer an effective treatment and reverse the respiratory depression caused by opioid related substances.Clinicians dealing with fentanyl intoxication cases should consider that it could,in fact,be a fentanyl analogue.For this reason,it is a helpful recommendation to include synthetic opioids in the routine toxicological screening procedures,including analysis in alternative matrices,if available,to investigate poly-drug use and possible tolerance to opioids.To address this public health problem,better international collaboration,effective legislation,effective investigation,control of suspicious“research chemicals”online forums and continuous community alertness are required.This article aims to review diverse reported fatalities associated with new synthetic opioids describing them in terms of pharmacology,metabolism,posology,available forms,as well as their toxic effects,highlighting the sample procedures and analytical techniques available for their detection and quantification in biological matrices.展开更多
BACKGROUND Opioids are commonly used for management of post-operative pain in living kidney donors.Reducing exposure to opioids is desirable to minimize risk of dependence and potential side effects such as nausea,vom...BACKGROUND Opioids are commonly used for management of post-operative pain in living kidney donors.Reducing exposure to opioids is desirable to minimize risk of dependence and potential side effects such as nausea,vomiting,and constipation which may delay discharge.Liposomal bupivacaine,ketorolac,and scheduled acetaminophen have all demonstrated efficacy for management of post-operative pain in this population.AIM To assess the efficacy and safety of an opioid-sparing protocol utilizing a multimodal pain management approach in living kidney donors post-nephrectomy.METHODS Single-center,retrospective chart review study examining 52 living kidney donors(26 pre-protocol implementation,26 post-protocol implementation)from May 24th,2019 to September 27th,2023.Patients in the post-protocol group received intraoperative liposomal bupivacaine,hydromorphone PCA(until able to tolerate oral medications),15 mg of intravenous ketorolac every 6 hours for 3 doses,and scheduled oral acetaminophen,in addition to oxycodone as needed for moderate to severe pain.The primary endpoint was oral morphine equivalent(OME)use within 48 hours post-surgery.Secondary endpoints include average daily pain scale within 48 hours post-surgery,length of stay(LOS)(days),and incidence of new acute kidney injury(AKI)or gastrointestinal(GI)bleed during admission per provider.Differences between the pre-and post-protocol implementation groups were compared utilizing the exact Wilcoxon test for continuous variables and either the Fisher’s Exact orχ^(2) test for categorical variables.RESULTS Patients in the pre-protocol implementation group received more OME(mg)within 48 hours post-surgery when compared to the post-protocol group(median:84.5 vs 69.0).The median of total OME over the course of admission was numerically greater the pre-protocol group(105.0 vs 69.0),and was significantly more per LOS(41.3 vs 25.7,P=0.02).Average daily pain score was not statistically significantly different between the two groups on postoperative day 1(median:5.3 vs 4.4;P=0.43)and post-operative day 2(median:4.7 vs 5.2;P=0.96).No significant differences were found in provider-identified incidences of AKI or GI bleeding during admission.There was no difference in serum creatinine at the time of discharge between the two groups.CONCLUSION A multimodal,opioid-sparing pain management protocol was as effective for pain control and resulted in significantly less opioid daily exposure over LOS.No adverse events were found related to use of ketorolac in patients undergoing donor nephrectomy.Our findings suggest that an opioid-sparing protocol is both safe and effective at minimizing opioid exposure and managing post-operative pain within the first 48 hours post-surgery.展开更多
文摘1.The development history of enhanced recovery after surgery(ERAS)Enhanced recovery after surgery(ERAS)is a multimodal perioperative care approach that has evolved over the past 2 decades since its inception.In 1997,Professor Henrik Kehlet,also known as the“father of ERAS”,from the University of Copenhagen in Denmark first proposed the ERAS concept and discovered its clinical feasibility and superiority,achieving remarkable results.ERAS was initially applied in colorectal surgery;subsequently,the concept gradually gained popularity and application worldwide.
文摘Objective:This research utilizes the FAERS for data mining to identify heart-related side effects caused by opioids,ensuring the safe use of these medications.Methods:Data from 79 quarters(Q12004 to Q32023)involving adverse event(AE)reports for opioids like morphine and oxycodone was reviewed.We applied the MedDRA system to categorize events and used statistical tools,ROR and BCPNN,for signal detection.These findings were cross-checked with drug labels and SIDER 4.1 for accuracy.Identified risks were then categorized by severity using DME and IME classifications.Results:Analysis of adverse events(AEs)for the five examined drugs(35359,14367,144441,10592,and 28848)identified 33,6,12,37,and 34 cardiovascular AEs,and 16,5,7,25,and 21 instances of important medical events(IMEs)respectively.Each drug was linked to cases of cardiac and cardiopulmonary arrest.The cardiovascular AEs varied widely in occurrence and severity,with methadone notably presenting diverse and potent risks,including sudden cardiac death as a distinct medical event(DME).A comparison with SIDER 4.1 showed 11 opioid-related cardiovascular AEs in line with our findings.Standardized MedDRA Queries(SMQs)confirmed these results,indicating stronger signals for methadone and tramadol,while morphine,hydromorphone,and oxycodone exhibited fewer and weaker signals.Conclusion:The study revealed numerous heart-related adverse effects(AEs)not listed on drug labels and identified new AE patterns.Recognizing these differences in AE profiles and risks across different opioids is crucial for safer prescription practices to minimize cardiac complications.
文摘BACKGROUND Surgical palliative surgery is a common method for treating patients with middle and late stage gastrointestinal tumors.However,these patients generally expe-rience high levels of cancer pain,which can in turn stimulate the body’s stress and undermine the effect of external surgery.Although opioid drugs have a signifi-cantly positive effect on controlling cancer pain,they can induce adverse drug reactions and potential damage to the body’s immune function.Hyperthermia therapy produces a thermal effect that shrinks tumor tissues.However,its effect on relieving the pain of middle and late stage gastrointestinal tumors but also the stress of surgical palliative surgery remains unclear.AIM To investigate the effect of hyperthermia combined with opioids on controlling cancer pain in patients with middle and late stage gastrointestinal cancer and evaluate its impact on surgical palliative surgical stress.METHODS This was a retrospective study using the data of 70 patients with middle and late stage gastrointestinal tumors who underwent cancer pain treatment and surgical palliative surgery in the Ninth People’s Hospital of Suzhou,China from January 2021 to June 2024.Patients were grouped according to different cancer pain control regimens before surgical palliative surgery,with n=35 cases in each group,as follows:Patients who solely used opioid drugs to control cancer pain were included in Group S,while patients who received hyperthermia treatment combined with opioid drugs were included in Group L.In both groups,we compared the effectiveness of cancer pain control(pain score,burst pain score,24-hour burst pain frequency,immune function,daily dosage of opioid drugs,and adverse reactions),surgical palliative indicators(surgery time,intraoperative bleeding,stress response),and postoperative recovery time,including first oral feeding time,postoperative hospital stay).RESULTS Analgesic treatment resulted in a significant decrease in the average pain score,burst pain score,and 24-hour burst pain frequency in both Groups L and S;however,these scores were statistically significantly lower in Group L than in Group S group(P<0.001).Analgesic treatment also resulted in significant differences,namely serum CD4+(29.18±5.64 vs 26.05±4.76,P=0.014),CD8+(26.28±3.75 vs 29.23±3.89,P=0.002),CD4+/CD8+(0.97±0.12 vs 0.83±0.17,P<0.001),between Group L and Group S,respectively.The daily dosage of opioid drugs incidence of adverse reactions such as nausea,vomiting,constipation,and difficulty urinating were statistically significantly lower in Group L than those in group S(P<0.05).Furthermore,palliative surgery time and intraoperative blood loss in Group L were slightly lower than those in Group S;however,the difference was not statistically significant(P>0.05).On the first day after surgery,serum cortisol and C-reactive protein levels of patients in group L and group S were 161.43±21.07 vs 179.35±27.86 ug/L(P=0.003)and 10.51±2.05 vs 13.49±2.17 mg/L(P<0.001),respectively.Finally,the first oral feeding time and hospitalization time after surgery in group L were statistically significantly shorter than those in group S(P<0.05).CONCLUSION Our findings showed that hyperthermia combined with opioids is effective in controlling cancer pain in patients with middle and late stage gastrointestinal tumors.Furthermore,this method can reduce the dosage of opioids used and minimize potential adverse drug reactions,reduce the patient’s surgical palliative surgical stress response,and shorten the overall postoperative recovery time required.
文摘Many older adults suffer from persistent pain but prevalence studies consistently showed high levels of untreated or under-treated pain in old population.Both persistent pain and pain under-treatment adversely affect independence and quality of life in geriatric patients.Pain management is challenging in this age-group because of the declining organ function,the presence of concurrent diseases and polypharmacy.For all the above reasons,persistent pain in the elderly should be considered a geriatric syndrome per se and effective approaches are warranted.Current guidelines and consensus statements recommend opioid therapy for older adults with moderateto-severe persistent pain or functional impairment and diminished quality of life due to pain.However clinicians and patients themselves have some concerns about opioids use.Age-related decline in organs functions and warnings about risk of addiction and drug misuse/abuse also in geriatric patients need particular attention for safe prescribing.On the basis of clinical evidence,these practical recommendations will help to improve the competence on opioid role in persistent pain management and the likelihood of a successful analgesic trial in older patients.
基金Key Research Base of Philosophy and Social Sciences in Shaanxi Province,Shaanxi Health Culture Research Center Projects(Grand JKWH2019-Q19).
文摘Women usually suffer from chronic pain due to pregnancy or have an increased level of chronic pain.In view of the definite curative effect of opioids on chronic pain and opioid use disorders,opioids have attracted much attention in the treatment of bone,joint,neuropathic and other chronic pain and opioid use disorders in pregnant women.Considering that the unreasonable use of opioids by pregnant women will lead to risks such as drug accumulation and increased neural sensitivity in the fetus,the correct and reasonable use of opioids is the key to the treatment.In recent years,it has been found that opioids can cross the blood fetal barrier into the fetal circulation,and damage fetal nerve development to varying degrees.However,the studies on the typical diseases such as neonatal neural tube defects and neonatal abstinence syndrome are not comprehensive.Therefore,this article has clarified the unreasonable use of opioids during pregnancy and its effect on fetal nerve development,and put forward relevant measures in order to provide reference for clinicians/pharmacists in obstetrics and gynecology.
基金Natural Science Foundation of the Xinjiang Uygur Autonomous Region No:2016D01C017.
文摘Objective:To study the effects of propofol combined with different types of opioids on inflammatory stress response in painless gastroscopy.Methods: Patients who underwent painless gastroscopy in our hospital between August 2014 and January 2018 were retrospectively analyzed, divided into those with nalbuphine hydrochloride, dezocine and sufentanil according to different choice of opioids and included in group A, group B and group C of the study respectively. The contents of inflammatory cytokines and oxidative stress products in serum as well as the expression levels of inflammatory pathway molecules and antioxidant pathway molecules in peripheral blood were measured before and 6 h after gastroscopy.Results: HMGB-1, TNF-α, IFN-γ, CRP, MDA, OH- and O2- contents in serum as well as RhoA, ROCK, Wnt3a,β-catenin, JNK, ERK1/2, Nrf2, ARE, HO-1,γ-GCS and Prx1 expression in peripheral blood of three groups of patients after gastroscopy were higher than those before gastroscopy, and HMGB-1, TNF-α, IFN-γ, CRP, MDA, OH- and O2- contents in serum as well as RhoA, ROCK, Wnt3a,β-catenin, JNK and ERK1/2 expression in peripheral blood of group A after gastroscopy were lower than those of group B and group C whereas Nrf2, ARE, HO-1,γ-GCS and Prx1 expression in peripheral blood were higher than those of group B and group C.Conclusion: Propofol combined with nalbuphine hydrochloride can be more effective than dezocine and sufentanil to reduce the inflammatory stress response in painless gastroscopy.
文摘Polysubstance (combinations of substances) abuse and overdose deaths now surpass mono-substance abuse and overdose deaths. Several international and governmental organizations such as the WHO (World Health Organization), CDC (Centers for Disease Control and Prevention), several of the Institutes of the NIH (National Institutes of Health), Regulators, and Enforcement Agencies, among others, track and provide a valuable source of statistical information about drug (prescription and illicit) (mis)use and overdose. The information is disseminated free to stakeholders and the general public for use. Although the numeric presentations of the data are helpful and adequate for professionals, the non-expert and the visual learner often find visual representation more clear and more compelling. With this in mind, the aim of this study was to present polysubstance use and overdose using visual maps of the available data. This article considers the opioids.
文摘BACKGROUND Several breast cancer studies have reported the use of adjuvant opioids with the paravertebral block(PVB)to improve outcomes.However,there is no level-1 evidence justifying its use.AIM To elucidate if the addition of opioids to PVB improves pain control in breast cancer surgery patients.METHODS We conducted an electronic literature search across PubMed,Embase,Scopus,and Google Scholar databases up to October 20,2020.Only randomized controlled trials(RCTs)comparing the addition of opioids to PVB with placebo for breast cancer surgery patients were included.RESULTS Six RCTs were included.Our meta-analysis indicated significantly reduced 24-h total analgesic consumption with the addition of opioids to PVB as compared to placebo[standardized mean difference(SMD)-1.57,95%confidence interval(CI):-2.93,-0.21,I2=94%].However,on subgroup analysis,the results were nonsignificant for studies using single PVB(SMD:-1.76,95%CI:-3.65,0.13 I2=95.09%)and studies using PVB infusion(SMD:-1.30,95%CI:-4.26,1.65,I2=95.49%).Analysis of single PVB studies indicated no significant difference in the time to first analgesic request between opioid and placebo groups(mean difference-11.28,95%CI:-42.00,19.43,I2=99.39%).Pain scores at 24 h were marginally lower in the opioid group(mean difference-1.10,95%CI:-2.20,0.00,I2=0%).There was no difference in the incidence of postoperative nausea and vomiting between the two groups.CONCLUSION Current evidence suggests a limited role of adjuvant opioids with PVB for breast cancer surgery patients.Further homogenous RCTs with a large sample size are needed to clarify the beneficial role of opioids with PVB.
文摘This study focused on the influences of opioids on the generation of antibody against sheep erythrocyte in vitro, It was found that morphine. a-CAO, DADLE, MENK were able to inhibit the capacity of murine spleen cells to generate antibody and leukotriene C4 and conversely. dynorphin was able to stimulate the capacity of murine spleen cells to generate antibody and leukotriene C4. Morphine, a-CAO, MENK, DADLE, dynorphin decreased intracellular cAMP level, increased [Ca(2+)]i and calmodulin activity. The effects were completely blocked by naloxone, the specific opioid antagonist. Our results showed that opioids regulate the production of antibody in murine spleen cells, and alter intracellular cAMP, [Ca(2+)]i calmodulin activity. and leukotriene C4 production by way of binding to different receptor types.
文摘Between the illicit use of opioids and attendant overdoses, and accidental overdoses with prescribed drugs, overuse of opioids has become a serious problem. At the same time, finding that fine balance between minimizing the risk of opioid misuse and abuse while at the same time providing access to treatment for patients who need pain control presents an ongoing challenge. Efforts to discover and develop better agents have led to what we term “new-look” opioids. We summarize here one such approach—known as biased ligands. By targeting a subset of GPCR signal transduction, this approach attempts to increase the separation between therapeutic and adverse effects.
文摘The abuse of opioids is harmful to the national economy and health.The U.S.government has spent a lot of time,energy and money to deal with this phenomenon.Based on the topic background and team discussion,we deeply excavated the data and information provided in the topic,determined the current use of opioids,and constructed an improved SIR model to determine the source of drug abuse,the mechanism of drug abuse diffusion and the origin of each state through reverse derivation,which provided guidance for the government in the context of opioid abuse.Based on the above results,we simulated and analyzed the improved SIR model and determined the accuracy and stability of the model in the data set.
文摘AIM To examine the relationship of chronic scheduled opioid use on symptoms, healthcare utilization and employment in gastroparesis(Gp) patients. Methods Patients referred to our tertiary care academic center from May 2016 to July 2017, with established diagnosis or symptoms suggestive of Gp filled out the Patient Assessment of Upper GI Symptoms, abdominal pain and demographics questionnaires, and underwent gastric emptying and blood tests. They were asked about taking pain medicines and the types, doses, and duration. We used Mann Whitney U test, Analysis of Variance, Student's t test and χ2 tests where appropriate for data analyses.RESULTS Of 223 patients with delayed gastric emptying, 158(70.9%) patients were not taking opioids(Gp NO), 22(9.9%) were taking opioids only as needed, while 43(19.3%) were on chronic(> 1 mo) scheduled opioids(Gp CO), of which 18 were taking opioids forreasons that included gastroparesis and/or stomach pain. Median morphine equivalent use was 60 mg per day. Gp CO reported higher severities of many gastrointestinal symptoms compared to Gp NO including nausea(mean ± SE of mean of 4.09 ± 0.12 vs 3.41 ± 0.12, P = 0.011), retching(2.86 ± 0.25 vs 1.98 ± 0.14, P = 0.003), vomiting(2.93 ± 0.24 vs 2.07 ± 0.15, P = 0.011), early satiety(4.17 ± 0.19 vs 3.57 ± 0.12, P = 0.004), post-prandial fullness(4.14 ± 0.18 vs 3.63 ± 0.11, P = 0.022), loss of appetite(3.64 ± 0.21 vs 3.04 ± 0.13, P = 0.039), upper abdominal pain(3.86 ± 0.20 vs 2.93 ± 0.13, P = 0.001), upper abdominal discomfort(3.74 ± 0.19 vs 3.09 ± 0.13, P = 0.031), heartburn during day(2.55 ± 0.27 vs 1.89 ± 0.13, P = 0.032), heartburn on lying down(2.76 ± 0.28 vs 1.94 ± 0.14, P = 0.008), chest discomfort during day(2.42 ± 0.20 vs 1.83 ± 0.12, P = 0.018), chest discomfort at night(2.40 ± 0.23 vs 1.61 ± 0.13, P = 0.003), regurgitation/reflux during day(2.77 ± 0.25 vs 2.18 ± 0.13, P = 0.040) and bitter/acid/sour taste in the mouth(2.79 ± 0.27 vs 2.11 ± 0.14, P = 0.028). Gp CO had a longer duration of nausea per day(median of 7 h vs 4 h for Gp NO, P = 0.037), and a higher number of vomiting episodes per day(median of 3 vs 2 for Gp NO, P = 0.002). Their abdominal pain more frequently woke them up at night(78.1% vs 57.3%, P = 0.031). They had a lower employment rate(33.3% vs 54.2%, P = 0.016) and amongst those who were employed less number of working hours per week(median of 23 vs 40, P = 0.005). They reported higher number of hospitalizations in the last 1 year(mean ± SE of mean of 2.90 ± 0.77 vs 1.26 ± 0.23, P = 0.047). CONCLUSION Gp CO had a higher severity of many gastrointestinal symptoms, compared to Gp NO. Hospitalization rates were more than 2-fold higher in Gp CO than Gp NO.Gp CO also had lower employment rate and working hours, when compared to Gp NO.
文摘Opioid use disorder(OUD)has become a considerable global public health challenge;however,potential medications for the management of OUD that are effective,safe,and nonaddictive are not available.Accumulating preclinical evidence indicates that antagonists of the dopamine D3 receptor(D3R)have effects on addiction in different animal models.We have previously reported that YQA14,a D3R antagonist,exhibits very high affinity and selectivity for D3Rs over D2Rs,and is able to inhibit cocaine-or methamphetamine-induced reinforcement and reinstatement in self-administration tests.In the present study,our results illustrated that YQA14 dose-dependently reduced infusions under the fixed-ratio 2 procedure and lowered the breakpoint under the progressive-ratio procedure in heroin self-administered rats,also attenuated heroin-induced reinstatement of drug-seeking behavior.On the other hand,YQA14 not only reduced morphine-induced expression of conditioned place preference but also facilitated the extinguishing process in mice.Moreover,we elucidated that YQA14 attenuated opioid-induced reward or reinforcement mainly by inhibiting morphine-induced up-regulation of dopaminergic neuron activity in the ventral tegmental area and decreasing dopamine release in the nucleus accumbens with a fiber photometry recording system.These findings suggest that D3R might play a very important role in opioid addiction,and YQA14 may have pharmacotherapeutic potential in attenuating opioid-induced addictive behaviors dependent on the dopamine system.
文摘Opioids have been used for treated pain for thousands of years. Meanwhile, opioids induce drug addic- tion, which causes serious medical and social problems. Most opioids research have been concentrated on neurons in the central nerve system （CNS） , however, the action of glia, which accounts for 90% cells in CNS have been long neglected. Unlike the classical opioid-neuron stereoselective interaction opioids were found to non-stereose- lectively bind the accessory protein myeloid differentiation factor 2 （MD-2） of innate immune Toll- like receptor 4 （TLR4） , which induces glial activation and pro-inflammatory factors production, therefore contributing to opioid hyper-analgesia, drug tolerance, dependence and addiction. A series of TLR4 antagonists have been discovered by multiple drug discovery strategies for inhibiting the opioids＇ side effects and treating drug abuse, among which （ ＋ ）-naltrexone and T-5342126 have been transferred to Xalud and BioLineRx respectively, for further pre-clini- cal/clinical drug development.
文摘Introduction The introduction of 2＇ ,6＇-dimethyl-L＇tyrosine （Dmt） at the N-terminus of Tyr-Tic （1,2,3,4-tetra-hydroisoquinoline-3-carboxylic acid ）-containing δ-opioid antagonists enhances receptor affinity and in vitro bioactivity to several orders of magnitude and its application in the formation of ligands with new properties, such as potent inverse agonism. For example, the δ2 agonist,
基金Supported by Wu Jieping Foundation,No.320.6750.2024-05-55.
文摘Gastrointestinal endoscopy is a common examination for digestive system.The stimulation of endoscope often causes cough,nausea and vomiting,increased heart rate and blood pressure,arrhythmia,and even cardiovascular and cerebrovascular accidents,thus makes people fear of this procedure.Sedation or anesthesia can effectively improve the safety,comfort and quality of gastrointestinal endoscopy.A small dose of opioids is a good adjuvant to sedatives.In this narrative review,we summarized the main roles of opioid analgesics in gastrointestinal endoscopy,including reducing visceral pain,throat irritation and the dose of sedatives.Moreover,the frequently used and novel opioids are reviewed.Classic fentanyl,sufentanil and dezocine are preferable by anesthesiologists.Newly approved oliceridine is promising to render ideal analgesic effects for gastrointestinal endoscopy.Clinical studies on oliceridine in endoscopic procedures are urgently needed.
基金Support for this project was provided by a PSC-CUNY Award(cycle 47)jointly funded by The Professional Staff Congress and The City University of New Yorkby FY2016 Department of Defense(DoD)Research and Education Program for Historically Black Colleges and Universities and Minority-Serving Institutions(HBCU/MI)Equipment/Instrumentation grant W911NF-15-R-0025.
文摘According to current surveys and overdoses data,there is a drug crisis in the USA.Wastewater-based epidemiology(WBE)is an evolving discipline that analyses wastewater samples to detect drugs and metabolites to estimate drug consumption in a certain community.This study demonstrates how drug relative presence could be tracked by testing wastewater,providing real-time results,in different boroughs in New York City throughout 1 year.We developed and fully validated two analytical methods,one for 21 drugs and metabolites,including nicotine,cocaine,amphetamines,opioids and cannabis markers;and another for the normalization factor creatinine.Both methods were performed by liquid chromatography tandem mass spectrometry(LC-MS/MS)using positive electrospray ionization,achieving a limit of quantification of 5–10 ng/L for drugs and metabolites,and 0.01 mg/L for creatinine.These methods were applied to 48 one-time grab wastewater samples collected from six wastewater treatment plants in New York City(Manhattan,The Bronx,Queens and Brooklyn),eight different times throughout 2016,before and after major holidays,including Memorial Day,4th of July,Labour Day and New Year’s.In this study,the drug group normalized concentrations present in the wastewater samples,in decreasing order,were cocaine,nicotine,opioids,cannabis and amphetamines.When looking at individual compounds,the one with the highest normalized concentration was benzoylecgonine(BE),followed by cotinine,morphine and 11-nor-9-carboxy-tetrahydrocannabinol(THCCOOH).To estimate community use,these concentrations were multiplied by the corresponding correction factor,and the most present were THCCOOH,followed by BE,cotinine and morphine.When comparing the treatment plants by drug group(nicotine,cocaine,amphetamines,opioids and cannabis),samples collected from The Bronx had the highest normalized concentrations for nicotine,cocaine and opioids;The Bronx and Manhattan for cannabis;and Manhattan and Queens for amphetamines.In most of the cases,no effect due to holiday was observed.This study provides the first snapshot of drug use in New York City and how that changes between key calendar dates employing wastewater analysis.
文摘Drugs related to morphine represent not only large range of important therapeutic applications for the relief of moderate to severe pain but also give rise to a relatively large series of novel opioids that mimic the action of this naturally occurring analgesic.Most of these are based on fentanyl structures that are much more potent,and dangerous,than fentanyl itself.This publication reviews reports of fatalities attributed to 15 novel opioids with the view to assessing mortality associated with their misuse as well as reviewing published analytical procedures that would be able to detect these and other novel opioids.These drugs include reports of deaths to acetylfentanyl,acrylfentanyl,butr(yl)fentanyl,carfentanil,2-and 4-fluorofentanyls,4-fluorobutyrfentanyl,4-fluoroisobutyrfentanyl,furanylfentanyl,a-and 3-methylfentanyls,4-methoxyfentanyl,ocfentanil,as well as AH-7921,U-47700 and MT-45.Most of these cases reporting a drug-caused death involved other drugs in addition to the opioid.No obvious minimum fatal concentration was discerned for any of the opioids for which details were provided,however,the more potent members required detection limits well under 1 ng/mL and often even well below 0.1 ng/mL requiring use of the most sensitive mass spectral detection procedures,particularly when screening specimens using a non-targeted mode.Four other novel opioids have been reported in admissions to hospitals include 4-chloroisobutryfentanyl,cyclopentylfentanyl and tetrahydrofuranfentanyl,all of which are likely to have the potential to cause death.It is also likely that other analogues will appear with time.
基金funded by FEDER funds through the POCI-COMPETE 2020-Operational Programme Competitiveness and Internationalization in Axis IStrengthening Research,Technological Development and Innovation[grant number:Project POCI-01-0145-FEDER-007491]National Funds by FCT-Fundac¸ão para a Ciência e a Tecnologia[grant number:Project UID/Multi/00709/2013]S.Soares and J.Gonc¸alves acknowledge Program Santander-Totta Universidades in the form of a fellowship grant number[Bolsa BID/UBISantander Universidades/2018].Â.Luís acknowledges the contract in the scientific area of Microbiology(Scientific Employment)financed by FCT.
文摘Over the past few years,there has been an emerging number of new psychoactive drugs.These drugs are frequently mentioned as“legal highs”,“herbal highs”,“bath salts”and“research chemicals”.They are mostly sold and advertised on online forums and on the dark web.The emerging new psychoactive substances are designed to mimic the effects of psychoactive groups,which are often abused drugs.Novel synthetic opioids are a new trend in this context and represent an alarming threat to public health.Given the wide number of fatalities related to these compounds reported within the last few years,it is an important task to accurately identify these compounds in biologic matrices in order to administer an effective treatment and reverse the respiratory depression caused by opioid related substances.Clinicians dealing with fentanyl intoxication cases should consider that it could,in fact,be a fentanyl analogue.For this reason,it is a helpful recommendation to include synthetic opioids in the routine toxicological screening procedures,including analysis in alternative matrices,if available,to investigate poly-drug use and possible tolerance to opioids.To address this public health problem,better international collaboration,effective legislation,effective investigation,control of suspicious“research chemicals”online forums and continuous community alertness are required.This article aims to review diverse reported fatalities associated with new synthetic opioids describing them in terms of pharmacology,metabolism,posology,available forms,as well as their toxic effects,highlighting the sample procedures and analytical techniques available for their detection and quantification in biological matrices.
文摘BACKGROUND Opioids are commonly used for management of post-operative pain in living kidney donors.Reducing exposure to opioids is desirable to minimize risk of dependence and potential side effects such as nausea,vomiting,and constipation which may delay discharge.Liposomal bupivacaine,ketorolac,and scheduled acetaminophen have all demonstrated efficacy for management of post-operative pain in this population.AIM To assess the efficacy and safety of an opioid-sparing protocol utilizing a multimodal pain management approach in living kidney donors post-nephrectomy.METHODS Single-center,retrospective chart review study examining 52 living kidney donors(26 pre-protocol implementation,26 post-protocol implementation)from May 24th,2019 to September 27th,2023.Patients in the post-protocol group received intraoperative liposomal bupivacaine,hydromorphone PCA(until able to tolerate oral medications),15 mg of intravenous ketorolac every 6 hours for 3 doses,and scheduled oral acetaminophen,in addition to oxycodone as needed for moderate to severe pain.The primary endpoint was oral morphine equivalent(OME)use within 48 hours post-surgery.Secondary endpoints include average daily pain scale within 48 hours post-surgery,length of stay(LOS)(days),and incidence of new acute kidney injury(AKI)or gastrointestinal(GI)bleed during admission per provider.Differences between the pre-and post-protocol implementation groups were compared utilizing the exact Wilcoxon test for continuous variables and either the Fisher’s Exact orχ^(2) test for categorical variables.RESULTS Patients in the pre-protocol implementation group received more OME(mg)within 48 hours post-surgery when compared to the post-protocol group(median:84.5 vs 69.0).The median of total OME over the course of admission was numerically greater the pre-protocol group(105.0 vs 69.0),and was significantly more per LOS(41.3 vs 25.7,P=0.02).Average daily pain score was not statistically significantly different between the two groups on postoperative day 1(median:5.3 vs 4.4;P=0.43)and post-operative day 2(median:4.7 vs 5.2;P=0.96).No significant differences were found in provider-identified incidences of AKI or GI bleeding during admission.There was no difference in serum creatinine at the time of discharge between the two groups.CONCLUSION A multimodal,opioid-sparing pain management protocol was as effective for pain control and resulted in significantly less opioid daily exposure over LOS.No adverse events were found related to use of ketorolac in patients undergoing donor nephrectomy.Our findings suggest that an opioid-sparing protocol is both safe and effective at minimizing opioid exposure and managing post-operative pain within the first 48 hours post-surgery.
