AIM:To investigate whether stress-induced visceral hypersensitivity could be alleviated by electroacupuncture(EA) and whether EA effect was mediated by endogenous opiates.METHODS:Six to nine week-old male SpragueDawle...AIM:To investigate whether stress-induced visceral hypersensitivity could be alleviated by electroacupuncture(EA) and whether EA effect was mediated by endogenous opiates.METHODS:Six to nine week-old male SpragueDawley rats were used in this study.Visceral hypersensitivity was induced by a 9-d heterotypic intermittent stress(HIS) protocol composed of 3 randomly stressors,which included cold restraint stress at 4?℃ for 45 min,water avoidance stress for 60 min,and forced swimming stress for 20 min,in adult male rats.The extent of visceral hypersensitivity was quantified by electromyography or by abdominal withdrawal reflex(AWR) scores of colorectal distension at different distention pressures(20 mmHg,40 mmHg,60 mmHg and 80 mmHg).AWR scores either 0,1,2,3 or 4 were obtained by a blinded observer.EA or sham EA was performed at classical acupoint ST-36(Zu-San-Li) or BL-43(Gao-Huang) in both hindlimbs of rats for 30 min.Naloxone(NLX) or NLX methiodide(m-NLX) was administered intraperitoneally to HIS rats in some experiments.RESULTS:HIS rats displayed an increased sensitivity to colorectal distention,which started from 6 h(the first measurement),maintained for 24 h,and AWR scores returned to basal levels at 48 h and 7 d after HIS compared to pre-HIS baseline at different distention pressures.The AWR scores before HIS were 0.6 ± 0.2,1.3 ± 0.2,1.9 ± 0.2 and 2.3 ± 0.2 for 20 mmHg,40 mmHg,60 mmHg and 80 mmHg distention pressures,respectively.Six hours after termination of the last stressor,the AWR scores were 2.0 ± 0.1,2.5 ± 0.1,2.8 ± 0.2 and 3.5 ± 0.2 for 20 mmHg,40 mmHg,60 mmHg and 80 mmHg distention pressures,respectively.EA given at classical acupoint ST-36 in both hindlimbs for 30 min significantly attenuated the hypersensitive responses to colorectal distention in HIS rats compared with sham EA treatment [AWRs at 20 mmHg:2.0 ± 0.2 vs 0.7 ± 0.1,P = 4.23 711 E-4;AWRs at 40 mmHg:2.6 ± 0.2 vs 1.5 ± 0.2,P = 0.00 163;AWRs at 60 mmHg:3.1 ± 0.2 vs 1.9 ± 0.1,P = 0.003;AWRs at 80 mmHg:3.6 ± 0.1 vs 2.4 ± 0.2,P = 0.0023;electromyographic(EMG) at 20 mmHg:24 ± 4.7 vs 13.8 ± 3.5;EMG at 40 mmHg:60.2 ± 6.6 vs 30 ± 4.9,P = 0.00 523;EMG at 60 mmHg:83 ± 10 vs 39.8 ± 5.9,P = 0.00 029;EMG at 80 mmHg:94.3 ± 10.8 vs 49.6 ± 5.9,P = 0.00 021].In addition,EA at the acupuncture point BL-43 with same parameters did not alleviate visceral hypersensitivity in HIS rats.EA in healthy rats also did not have any effect on AWR scores to colorectal distention at distention pressuresof 20 and 40 mmHg.The EA-mediated analgesic effect was blocked by pretreatment with NLX in HIS rats [AWR scores pretreated with NLX vs normal saline(NS) were 2.0 vs 0.70 ± 0.20,2.80 ± 0.12 vs 1.50 ± 0.27,3 vs 2.00 ± 0.15 and 3.60 ± 0.18 vs 2.60 ± 0.18 for 20 mmHg,40 mmHg,60 mmHg and 80 mmHg;P = 0.0087,0.0104,0.0117 and 0.0188 for 20,40,60 and 80 mmHg,respectively].Furthermore,EA-mediated analgesic effect was completely reversed by administration of m-NLX,a peripherally restricted opioid antagonist(EMG pretreated with m-NLX vs NS were 30.84 ± 4.39 vs 13.33 ± 3.88,74.16 ± 9.04 vs 36.28 ± 8.01,96.45 ± 11.80 vs 50.19 ± 8.28,and 111.59 ± 13.79 vs 56.42 ± 8.43 for 20 mmHg,40 mmHg,60 mmHg and 80 mmHg;P = 0.05 026,0.00 034,0.00 005,0.000 007 for 20 mmHg,40 mmHg,60 mmHg and 80 mmHg,respectively).CONCLUSION:EA given at classical acupoint ST-36 alleviates stress-induced visceral pain,which is most likely mediated by opioid pathways in the periphery.展开更多
Since the pioneering work by Panksepp et al,the neurobiological bases of attachment behavior have been closely linked with opioid neurotransmission.Candidate gene studies of adult individuals have shown that variation...Since the pioneering work by Panksepp et al,the neurobiological bases of attachment behavior have been closely linked with opioid neurotransmission.Candidate gene studies of adult individuals have shown that variation in the muopioid receptor gene(OPRM1)influences attachment behavior.Early maternal care and the A/A genotype of the A118G polymorphism interact in modulating levels of fearful attachment.Compared to their counterparts carrying the A/A genotype,individuals expressing the minor 118G allele show lower levels of avoidant attachment and experience more pleasure in social situations.Brain imaging research has strengthened the biological plausibility of candidate gene studies.The avoidance dimension of attachment correlates negatively with muopioid receptor availability in the thalamus and anterior cingulate cortex,as well as the frontal cortex,amygdala,and insula.Overall,findings from human studies combined with those from animal models suggest that research on the genetic bases of attachment should include the endogenous opioid system among the investigated variables.展开更多
The United States is in the throes of a severe opioid overdose epidemic,primarily fueled by the pervasive use of fentanyl and the emerging threat of xylazine,a veterinary sedative often mixed with fentanyl.The high po...The United States is in the throes of a severe opioid overdose epidemic,primarily fueled by the pervasive use of fentanyl and the emerging threat of xylazine,a veterinary sedative often mixed with fentanyl.The high potency and long duration of fentanyl is compounded by the added risks from xylazine,heightening the lethal danger faced by opioid users.Measures such as enhanced surveillance,public awareness campaigns,and the distribution of fentanylxylazine test kits,and naloxone have been undertaken to mitigate this crisis.Fentanyl-related overdose deaths persist despite these efforts,partly due to inconsistent policies across states and resistance towards adopting harm reduction strategies.A multifaceted approach is imperative in effectively combating the opioid overdose epidemic.This approach should include expansion of treatment access,broadening the availability of medications for opioid use disorder,implementation of harm reduction strategies,and enaction of legislative reforms and diminishing stigma associated with opioid use disorder.展开更多
BACKGROUND The use of opioids for pain is linked to an increased risk of developing opioid use disorder,and has resulted in the emergence of the opioid crisis over the last few years.AIM The systematic review question...BACKGROUND The use of opioids for pain is linked to an increased risk of developing opioid use disorder,and has resulted in the emergence of the opioid crisis over the last few years.AIM The systematic review question is“How does the use of opioid medications in pain management,compared with non-opioid medications,affect pain intensity over the short,intermediate,and long-term in adults with acute traumatic pain?”.METHODS The protocol was prospectively registered on the International Prospective Re-gister of Systematic Reviews:CRD42021279639.Medline and Google Scholar were electronically searched for controlled peer-reviewed studies published in full,with the PICO framework:P:Adult patients with traumatic injuries,I:Opioid medications,C:Non-opioid medi-cations,O:A minimum clinically important difference(MCID)in pain.RESULTS After full-text screening,we included 14 studies in the qualitative synthesis.Of these 14 studies,12 were rando-mized clinical trials(RCTs)and 2 were pseudo-RCTs with a total of 2347 patients enrolled.There was heteroge-neity in both medication utilized and outcome in these studies;only two studies were homogeneous regarding the type of study conducted,the opioid used,its comparator,and the outcome explored.The MCID was evaluated in 8 studies,while in 6 studies,any measured pain reduction was considered as an outcome.In 11 cases,the setting of care was the Emergency Department;in 2 cases,care occurred out-of-hospital;and in one case,the setting was not well-specified.The included studies were found to have a low-moderate risk of bias.CONCLUSION Non-opioids can be considered an alternative to opioids for short-term pain management of acute musculoskeletal injury.Intravenous ketamine may cause more adverse events than other routes of administration.展开更多
Opioid use disorder(OUD)is a major public health problem affecting millions of people worldwide.Although OUD is a chronic and relapsing disorder,a variety of pharmacological and non-pharmacological interventions are a...Opioid use disorder(OUD)is a major public health problem affecting millions of people worldwide.Although OUD is a chronic and relapsing disorder,a variety of pharmacological and non-pharmacological interventions are available.Medication-assisted treatment of OUD generally relies on competition for opioid receptors against the addictive substance.The mechanisms of this competition are to block or inactivate the opioid receptor or activate the receptor with a substance that is intermittent or long acting.Methadone and buprenorphine are two United States Food and Drug Administration-approved medications that have long-term positive effects on the health of opioid-dependent individuals.Although clinical studies of drugs generally demonstrate efficacy in thousands of people and toxicity is excluded,it cannot be predicted whether the given drug will cause side effects in one of the patients at the treatment dose.Individual differences can be explained by many biological and environmental factors.Variations in genes encoding drug metabolism or cellular drug targets significantly explain the variability in drug response between individuals.Therefore,for the effects of candidate genes to be accepted and included in individual treatment protocols,it is important to repeat studies on individuals of different ethnic backgrounds and prove a similar effect.展开更多
The opioid epidemic in the United States continues to take the lives of many individuals, with overdoses continuing to rise every year. Naloxone is an opioid antagonist that is efficacious in temporarily reversing opi...The opioid epidemic in the United States continues to take the lives of many individuals, with overdoses continuing to rise every year. Naloxone is an opioid antagonist that is efficacious in temporarily reversing opioid overdoses. Pharmacists play an important role in the accessibility and education of naloxone in both the community and health system settings. Recent efforts, such as co-dispensing naloxone with opioid prescriptions, naloxone training programs, and approval of naloxone to be over-the-counter, have been implemented in hopes to better control the opioid epidemic. Despite the efforts to make naloxone more accessible, there are still some barriers to overcome such as lack of training, cost, stigma, and patient refusal. This review aims to explore the contributions pharmacists have made thus far and define the barriers that still have to be resolved.展开更多
Background and Purpose: Opioids, used for centuries to alleviate pain, have become a double-edged sword. While effective, they come with a host of adverse effects, including memory and cognition impairment. This revie...Background and Purpose: Opioids, used for centuries to alleviate pain, have become a double-edged sword. While effective, they come with a host of adverse effects, including memory and cognition impairment. This review delves into the impact of opioid drugs on cognitive functions, explores underlying mechanisms, and investigates their prevalence in both medical care and illicit drug use. The ultimate goal is to find ways to mitigate their potential harm and address the ongoing opioid crisis. Methods: We sourced data from PubMed and Google Scholar, employing search combinations like “opioids,” “memory,” “cognition,” “amnesia,” “cognitive function,” “executive function,” and “inhibition.” Our focus was on English-language articles spanning from the inception of these databases up to the present. Results: The literature consistently reveals that opioid use, particularly at high doses, adversely affects memory and other cognitive functions. Longer deliberation times, impaired decision-making, impulsivity, and behavioral disorders are common consequences. Chronic high-dose opioid use is associated with conditions such as amnesiac syndrome (OAS), post-operative cognitive dysfunction (POCD), neonatal abstinence syndrome (NAS), depression, anxiety, sedation, and addiction. Alarming trends show increased opioid use over recent decades, amplifying the risk of these outcomes. Conclusion: Opioids cast a shadow over memory and cognitive function. These effects range from amnesiac effects, lessened cognitive function, depression, and more. Contributing factors include over-prescription, misuse, misinformation, and prohibition policies. Focusing on correct informational campaigns, removing punitive policies, and focusing on harm reduction strategies have been shown to lessen the abuse and use of opioids and thus helping to mitigate the adverse effects of these drugs. Further research into the impacts of opioids on cognitive abilities is also needed as they are well demonstrated in the literature, but the mechanism is not often completely understood.展开更多
A research study collected intensive longitudinal data from cancer patients on a daily basis as well as non-intensive longitudinal survey data on a monthly basis. Although the daily data need separate analysis, those ...A research study collected intensive longitudinal data from cancer patients on a daily basis as well as non-intensive longitudinal survey data on a monthly basis. Although the daily data need separate analysis, those data can also be utilized to generate predictors of monthly outcomes. Alternatives for generating daily data predictors of monthly outcomes are addressed in this work. Analyses are reported of depression measured by the Patient Health Questionnaire 8 as the monthly survey outcome. Daily measures include numbers of opioid medications taken, numbers of pain flares, least pain levels, and worst pain levels. Predictors are averages of recent non-missing values for each daily measure recorded on or prior to survey dates for depression values. Weights for recent non-missing values are based on days between measurement of a recent value and a survey date. Five alternative averages are considered: averages with unit weights, averages with reciprocal weights, weighted averages with reciprocal weights, averages with exponential weights, and weighted averages with exponential weights. Adaptive regression methods based on likelihood cross-validation (LCV) scores are used to generate fractional polynomial models for possible nonlinear dependence of depression on each average. For all four daily measures, the best LCV score over averages of all types is generated using the average of recent non-missing values with reciprocal weights. Generated models are nonlinear and monotonic. Results indicate that an appropriate choice would be to assume three recent non-missing values and use the average with reciprocal weights of the first three recent non-missing values.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
Objective:To investigate the action mechanisms of electroacupuncture(EA)on postoperative immunosuppression.Methods:Male C57 BL/6 mice(5–7 weeks old)were randomly divided into:the sham injury group,the surgical trauma...Objective:To investigate the action mechanisms of electroacupuncture(EA)on postoperative immunosuppression.Methods:Male C57 BL/6 mice(5–7 weeks old)were randomly divided into:the sham injury group,the surgical trauma stressed group,the EA group[surgery+2/100 Hz EA at Neiguan(PC 6)],and the EA+Nal(surgery+EA+intraperitoneal injection of naloxone).Abdominal surgical trauma stress mice model was established.EA was performed on bilateral PC 6 acupoints by an EA apparatus(2/100 Hz)for 20 min once a day for 3 days.The m RNA expressions of MOR,DOR,and KOR in thymus and L3-5 dorsal root ganglions(DRG)were determined by quantitative real-time polymerase chain reaction(q RT-PCR)and the protein expressions of MOR,DOR,and KOR in thymus were measured by Western blot.Flow cytometry assay was used to detect the levels of T lymphocyte subtypes in the peripheral blood.Results:Surgical trauma induced decreased the m RNA expression level of MOR in both thymus(P<0.01)and L3-L5 DRGs(P<0.05).Moreover,EA treatment not only significantly attenuated the MOR protein and m RNA expression in the thymus(both P<0.05),but also markedly increased expression of DOR and KOR opioid receptor in thymus(P<0.01).However,the m RNA expressions of opioid receptors were not regulated by EA in the DRG(all P>0.05).Furthermore,T lymphocyte population of CD3^+ and CD4^+ was decreased in the peripheral blood after surgical trauma(both P<0.01).EA treatment can significantly elevate the population of CD3^+(P<0.01),CD4^+(P<0.05)and CD8^+T cells(P<0.01).Intraperitoneal injection of the non-selective opioid receptor antagonist naloxone blocked the up-regulation of T lymphocytes by EA.Conclusion:EA may improve postoperative immunosuppression through the peripheral opioid system.展开更多
L-3,4-Dihydroxyphenylalanine(L-DOPA)-induced dyskinesia(LID)is a major clinical complication in the treatment of Parkinson’s disease(PD).This debilitating side effect likely reflects aberrant compensatory responses f...L-3,4-Dihydroxyphenylalanine(L-DOPA)-induced dyskinesia(LID)is a major clinical complication in the treatment of Parkinson’s disease(PD).This debilitating side effect likely reflects aberrant compensatory responses for a combination of dopaminergic neuron denervation and repeated L-DOPA administration.Abnormal endogenous opioid signal transduction pathways in basal ganglia have been well documented in LID.Opioid receptors have been targeted to alleviate the dyskinesia.However,the exact role of this altered opioid activity is remains under active investigation.In the present review,we discuss the current understanding of opioid signal transduction in the basal ganglia and how the malfunction of opioid signaling contributes to the pathophysiology of LID.Further study of the opioid system in LID may lead to new therapeutic targets and improved treatment of PD patients.展开更多
Little is known about the roles of dynorphin and Kappa opioid receptor(KOR) in mollusks. In this study, we aim to determine the distribution of dynorphin A and KOR-1 in the digestive system of the scallop Chlamys farr...Little is known about the roles of dynorphin and Kappa opioid receptor(KOR) in mollusks. In this study, we aim to determine the distribution of dynorphin A and KOR-1 in the digestive system of the scallop Chlamys farreri. Using immunohistochemical staining, we confirmed the expression of dynorphin A and KOR-1 in the digestive system of C. farreri. Dynorphin A immunopositive cells were identified in intestine and hepatopancreas. In intestine, small and spherical dynorphin A immunopositive cells(4–9 μm in diameter) were scattered among the long columnar epithelial cells(ECs). In hepatopancreas, cells containing masses(5–14 μm in diameter) of dynorphin A immunopositive products were observed in epithelium of acinis. These immunopositive cells may be synthetic and/or secretory cells of dynorphin A. Dynorphin A immunoreactive products were commonly observed in epithelium and connective tissue(CT) of labial palps, mouth labia and stomach, which presented in forms of grains, fibers or flakes. KOR-1 immunoreactive material was observed in ECs and CTs of labial palps, mouth labia and stomach, intestine and hepatopancreas. The distribution of both dynorphin A and KOR-1 in the digestive organs suggests an involvement of dynorphin via KOR-1 in the functional regulation of the digestive system of C. farreri.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
BACKGROUND The literature suggests that there is a high degree of co-occurrence between chronic pain and posttraumatic stress disorder(PTSD). An association has been found between PTSD and substance abuse. PTSD is a s...BACKGROUND The literature suggests that there is a high degree of co-occurrence between chronic pain and posttraumatic stress disorder(PTSD). An association has been found between PTSD and substance abuse. PTSD is a severe disorder that should be taken into account when opioids are prescribed. It has been found that the prevalence of opioid use disorder(OUD) in chronic pain patients is higher among those with PTSD than those without this disorder.AIM To perform a systematic review on the association between PTSD, chronic noncancer pain(CNCP), and opioid intake(i.e., prescription, misuse, and abuse).METHODS We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Patient, Intervention,Comparator, and Outcomes(PICOS) criteria were formulated a priori in the protocol of the systematic review. A search was conducted of the PROSPERO database. In March 2019, searches were also conducted of 5 other databases:Pub Med, MEDLINE, Psyc INFO, Web of Science, and PILOTS. The Scottish Intercollegiate Guidelines Network checklist for cohort studies was used to assess the selected studies for their methodological quality and risk of bias. Each study was evaluated according to its internal validity, participant sampling,confounding variables, and the statistical analysis.RESULTS A total of 151 potentially eligible studies were identified of which 17 were retained for analysis. Only 10 met the selection criteria. All the studies were published between 2008 and 2018 and were conducted in the United States. The eligible studies included a total of 1622785 unique participants. Of these, 196516 had comorbid CNCP and PTSD and were consuming opiates. The participants had a cross-study mean age of 35.2 years. The majority of participants were men(81.6%). The most common chronic pain condition was musculoskeletal pain:back pain(47.14% across studies;range: 16%-60.6%), arthritis and joint pain(31.1%;range: 18%-67.5%), and neck pain(28.7%;range: 3.6%-63%). In total,42.4% of the participants across studies had a diagnosis of PTSD(range: 4.7%-95%). In relation to opioid intake, we identified 2 different outcomes: opioid prescription and OUD. All the studies reported evidence of a greater prevalence of PTSD in CNCP patients who were receiving prescribed opioids and that PTSD was associated with OUD in CNCP patients.CONCLUSION Opioid analgesic prescription as the treatment of choice for CNCP patients should include screening for baseline PTSD to ensure that these drugs are safely consumed.展开更多
<strong>Background:</strong> Ketamine is increasingly being used as an alternative to opioids in the management of acute pain in the emergency department. In turn, there is increasing research attention to...<strong>Background:</strong> Ketamine is increasingly being used as an alternative to opioids in the management of acute pain in the emergency department. In turn, there is increasing research attention to prove the efficacy of ketamine as an analgesic in children presenting in the emergency department. <strong>Objective:</strong> The first objective of this systematic review was to investigate the effectiveness of ketamine compared to opioid analgesics for pain management in children aged two months to 18 years who have acute pain in the emergency department. The second objective was to compare the adverse events and side effects associated with ketamine with those associated with opioids used for pain management. <strong>Methods:</strong> A systematic review, using the JBI systematic review was completed. A computerised search from five databases;CINAHL, EMBASE, EMCARE and PubMed, and Cochrane. The included studies were appraised by JBI critical appraisal tool for randomised controlled trials and the study results analysed. <strong>Findings: </strong>Four randomised control trial studies were included in this systematic review. All the included studies compared ketamine with opioids (morphine and fentanyl) for the management of severe pain in children. The studies were of high methodological quality based on JBI critical appraisal outcome. Meta-analysis was not possible because of the heterogeneity of the studies, especially in terms of different outcome measures, and the approaches (pain assessment tool) used to measure the pain outcomes. The review identified that ketamine demonstrated a non-inferior analgesia effect compared to opioid medication (morphine or fentanyl) as determined by various pain scores used in different studies. However, ketamine use was associated with increased frequency of occurrence of temporary adverse effects that do not require clinical attention.<strong> Conclusion: </strong>Based on the findings from the review, ketamine is a suitable alternative for opioid analgesics for the management of acute and severe pain in children in ED. The minor transient side effects associated with ketamine should not limit the use of ketamine. Future studies should investigate the appropriate dosage and route of administration of ketamine to be used while managing pain among children with acute and severe pain in the emergency department.展开更多
Objectives: Opioid medications consistently rank among the drugs most frequently associated with adverse events. We reviewed cases of naloxone administration to assess our opioid prescribing and administration practi...Objectives: Opioid medications consistently rank among the drugs most frequently associated with adverse events. We reviewed cases of naloxone administration to assess our opioid prescribing and administration practices before and after implementation of a computerized provider order entry (CPOE) system. Our primary measure was the rate of opioid reversal with naloxone in the two time periods. Methods: We systematically reviewed all cases of naloxone administration at our institution from March 2016 through May 2016 (before period) compared with cases from October 2017 through December 2017 (after period). Results: In the before period, 0.58% of patients who received an opioid required reversal with naloxone compared with 0.16% in the after period (p 〈 0.001). Subject demographics such as age, sex, BMI, and serum creatinine were not significantly different between the two groups. Similarly large proportions of patients in the before and after groups had at least 2 risk factors for over-sedation (79.5% and 75%, respectively, p = 0.17). More than 84% and 61% of patients in the before and after groups, respectively, did not have documentation of an opioid on the admission medication history, suggesting they were opioid-naYve (p= 0.10). Per our institution's policy on range orders, nurses should begin with the lowest prescribed opioid dose; this policy was followed in 58.3% in the before period and 69.2% in the after period (p = 0.36). Conclusions: Doses of naloxone that were required for opioid reversal were significantly reduced after implementation of a CPOE system. Our opioid-reversal rate was comparable to similar studies; however, secondary endpoints indicate that opioid prescribing and administration habits may not account for patient-specific risk factors for over-sedation.展开更多
Background Individual differences have been detected in individuals with opioid use disorders(OUD)in rehabilitation following protracted abstinence.Recent studies suggested that prediction models were effective for in...Background Individual differences have been detected in individuals with opioid use disorders(OUD)in rehabilitation following protracted abstinence.Recent studies suggested that prediction models were effective for individual-level prognosis based on neuroimage data in substance use disorders(SUD).Aims This prospective cohort study aimed to assess neuroimaging biomarkers for individual response to protracted abstinence in opioid users using connectome-based predictive modelling(CPM).Methods One hundred and eight inpatients with OUD underwent structural and functional magnetic resonance imaging(fMRI)scans at baseline.The Heroin Craving Questionnaire(HCQ)was used to assess craving levels at baseline and at the 8-month follow-up of abstinence.CPM with leave-one-out cross-validation was used to identify baseline networks that could predict follow-up HCQ scores and changes in HCQ(HCQtolow V-up-HCQpa baseline).Then,the follow-up aseline predictive ability of identified networks was tested in a separate,heterogeneous sample of methamphetamine individuals who underwent MRI scanning before abstinence for SUD.Results CPM could predict craving changes induced by long-term abstinence,as shown by a significant correlation between predicted and actual HCQ fllow-up(r=0.417,p<0.001)and changes in HCQ(negative:r=0.334,p=0.002;positive:r=0.233,p=0.038).Identified craving-related prediction networks included the somato-motor network(SMN),salience network(SALN),default mode network(DMN),medial frontal network,visual network and auditory network.In addition,decreased connectivity of frontal-parietal network(FPN)-SMN,FPN-DMN and FPN-SALN and increased connectivity of subcortical network(SCN)-DMN,SCN-SALNandSCN-SMN were positively correlated with craving levels.Conclusions These findings highlight the potential applications of CPM to predict the craving level of individuals after protracted abstinence,as well as the generalisation ability;the identified brain networks might be the focus of innovative therapies in the future.展开更多
Nigeria has a very high number of sickle cell disease (SCD) population with addition of 150,000 babies born annually with the disease. Early infant diagnosis and good care make many of these babies survive to adulthoo...Nigeria has a very high number of sickle cell disease (SCD) population with addition of 150,000 babies born annually with the disease. Early infant diagnosis and good care make many of these babies survive to adulthood. Severe pain requiring moderately strong or very strong analgesics is a common presentation of patients with Sickle Cell Anaemia. Paediatricians find ready usefulness of Opioids which are very useful for the painful episodes among these patients. Therefore, the chances of abuse and addiction to these medications become very high and constitute additional burden on the deficient manpower in the health sector. Opioid Use Disorder among Sickle Cell Disease patients has subtle presentation, so a high index of suspicion is required to make both the diagnosis and referral to treatment centres. In this review, the epidemiology, pain pathophysiology, behavioural and pharmacologic therapy have been re-examined.展开更多
基金Supported by An NIH grant,No. AT005158,to Xu GYNational Natural Science Foundation of China,No. 81070884a grant from Jiangsu Province,China,No. SR21500111
文摘AIM:To investigate whether stress-induced visceral hypersensitivity could be alleviated by electroacupuncture(EA) and whether EA effect was mediated by endogenous opiates.METHODS:Six to nine week-old male SpragueDawley rats were used in this study.Visceral hypersensitivity was induced by a 9-d heterotypic intermittent stress(HIS) protocol composed of 3 randomly stressors,which included cold restraint stress at 4?℃ for 45 min,water avoidance stress for 60 min,and forced swimming stress for 20 min,in adult male rats.The extent of visceral hypersensitivity was quantified by electromyography or by abdominal withdrawal reflex(AWR) scores of colorectal distension at different distention pressures(20 mmHg,40 mmHg,60 mmHg and 80 mmHg).AWR scores either 0,1,2,3 or 4 were obtained by a blinded observer.EA or sham EA was performed at classical acupoint ST-36(Zu-San-Li) or BL-43(Gao-Huang) in both hindlimbs of rats for 30 min.Naloxone(NLX) or NLX methiodide(m-NLX) was administered intraperitoneally to HIS rats in some experiments.RESULTS:HIS rats displayed an increased sensitivity to colorectal distention,which started from 6 h(the first measurement),maintained for 24 h,and AWR scores returned to basal levels at 48 h and 7 d after HIS compared to pre-HIS baseline at different distention pressures.The AWR scores before HIS were 0.6 ± 0.2,1.3 ± 0.2,1.9 ± 0.2 and 2.3 ± 0.2 for 20 mmHg,40 mmHg,60 mmHg and 80 mmHg distention pressures,respectively.Six hours after termination of the last stressor,the AWR scores were 2.0 ± 0.1,2.5 ± 0.1,2.8 ± 0.2 and 3.5 ± 0.2 for 20 mmHg,40 mmHg,60 mmHg and 80 mmHg distention pressures,respectively.EA given at classical acupoint ST-36 in both hindlimbs for 30 min significantly attenuated the hypersensitive responses to colorectal distention in HIS rats compared with sham EA treatment [AWRs at 20 mmHg:2.0 ± 0.2 vs 0.7 ± 0.1,P = 4.23 711 E-4;AWRs at 40 mmHg:2.6 ± 0.2 vs 1.5 ± 0.2,P = 0.00 163;AWRs at 60 mmHg:3.1 ± 0.2 vs 1.9 ± 0.1,P = 0.003;AWRs at 80 mmHg:3.6 ± 0.1 vs 2.4 ± 0.2,P = 0.0023;electromyographic(EMG) at 20 mmHg:24 ± 4.7 vs 13.8 ± 3.5;EMG at 40 mmHg:60.2 ± 6.6 vs 30 ± 4.9,P = 0.00 523;EMG at 60 mmHg:83 ± 10 vs 39.8 ± 5.9,P = 0.00 029;EMG at 80 mmHg:94.3 ± 10.8 vs 49.6 ± 5.9,P = 0.00 021].In addition,EA at the acupuncture point BL-43 with same parameters did not alleviate visceral hypersensitivity in HIS rats.EA in healthy rats also did not have any effect on AWR scores to colorectal distention at distention pressuresof 20 and 40 mmHg.The EA-mediated analgesic effect was blocked by pretreatment with NLX in HIS rats [AWR scores pretreated with NLX vs normal saline(NS) were 2.0 vs 0.70 ± 0.20,2.80 ± 0.12 vs 1.50 ± 0.27,3 vs 2.00 ± 0.15 and 3.60 ± 0.18 vs 2.60 ± 0.18 for 20 mmHg,40 mmHg,60 mmHg and 80 mmHg;P = 0.0087,0.0104,0.0117 and 0.0188 for 20,40,60 and 80 mmHg,respectively].Furthermore,EA-mediated analgesic effect was completely reversed by administration of m-NLX,a peripherally restricted opioid antagonist(EMG pretreated with m-NLX vs NS were 30.84 ± 4.39 vs 13.33 ± 3.88,74.16 ± 9.04 vs 36.28 ± 8.01,96.45 ± 11.80 vs 50.19 ± 8.28,and 111.59 ± 13.79 vs 56.42 ± 8.43 for 20 mmHg,40 mmHg,60 mmHg and 80 mmHg;P = 0.05 026,0.00 034,0.00 005,0.000 007 for 20 mmHg,40 mmHg,60 mmHg and 80 mmHg,respectively).CONCLUSION:EA given at classical acupoint ST-36 alleviates stress-induced visceral pain,which is most likely mediated by opioid pathways in the periphery.
文摘Since the pioneering work by Panksepp et al,the neurobiological bases of attachment behavior have been closely linked with opioid neurotransmission.Candidate gene studies of adult individuals have shown that variation in the muopioid receptor gene(OPRM1)influences attachment behavior.Early maternal care and the A/A genotype of the A118G polymorphism interact in modulating levels of fearful attachment.Compared to their counterparts carrying the A/A genotype,individuals expressing the minor 118G allele show lower levels of avoidant attachment and experience more pleasure in social situations.Brain imaging research has strengthened the biological plausibility of candidate gene studies.The avoidance dimension of attachment correlates negatively with muopioid receptor availability in the thalamus and anterior cingulate cortex,as well as the frontal cortex,amygdala,and insula.Overall,findings from human studies combined with those from animal models suggest that research on the genetic bases of attachment should include the endogenous opioid system among the investigated variables.
文摘The United States is in the throes of a severe opioid overdose epidemic,primarily fueled by the pervasive use of fentanyl and the emerging threat of xylazine,a veterinary sedative often mixed with fentanyl.The high potency and long duration of fentanyl is compounded by the added risks from xylazine,heightening the lethal danger faced by opioid users.Measures such as enhanced surveillance,public awareness campaigns,and the distribution of fentanylxylazine test kits,and naloxone have been undertaken to mitigate this crisis.Fentanyl-related overdose deaths persist despite these efforts,partly due to inconsistent policies across states and resistance towards adopting harm reduction strategies.A multifaceted approach is imperative in effectively combating the opioid overdose epidemic.This approach should include expansion of treatment access,broadening the availability of medications for opioid use disorder,implementation of harm reduction strategies,and enaction of legislative reforms and diminishing stigma associated with opioid use disorder.
文摘BACKGROUND The use of opioids for pain is linked to an increased risk of developing opioid use disorder,and has resulted in the emergence of the opioid crisis over the last few years.AIM The systematic review question is“How does the use of opioid medications in pain management,compared with non-opioid medications,affect pain intensity over the short,intermediate,and long-term in adults with acute traumatic pain?”.METHODS The protocol was prospectively registered on the International Prospective Re-gister of Systematic Reviews:CRD42021279639.Medline and Google Scholar were electronically searched for controlled peer-reviewed studies published in full,with the PICO framework:P:Adult patients with traumatic injuries,I:Opioid medications,C:Non-opioid medi-cations,O:A minimum clinically important difference(MCID)in pain.RESULTS After full-text screening,we included 14 studies in the qualitative synthesis.Of these 14 studies,12 were rando-mized clinical trials(RCTs)and 2 were pseudo-RCTs with a total of 2347 patients enrolled.There was heteroge-neity in both medication utilized and outcome in these studies;only two studies were homogeneous regarding the type of study conducted,the opioid used,its comparator,and the outcome explored.The MCID was evaluated in 8 studies,while in 6 studies,any measured pain reduction was considered as an outcome.In 11 cases,the setting of care was the Emergency Department;in 2 cases,care occurred out-of-hospital;and in one case,the setting was not well-specified.The included studies were found to have a low-moderate risk of bias.CONCLUSION Non-opioids can be considered an alternative to opioids for short-term pain management of acute musculoskeletal injury.Intravenous ketamine may cause more adverse events than other routes of administration.
文摘Opioid use disorder(OUD)is a major public health problem affecting millions of people worldwide.Although OUD is a chronic and relapsing disorder,a variety of pharmacological and non-pharmacological interventions are available.Medication-assisted treatment of OUD generally relies on competition for opioid receptors against the addictive substance.The mechanisms of this competition are to block or inactivate the opioid receptor or activate the receptor with a substance that is intermittent or long acting.Methadone and buprenorphine are two United States Food and Drug Administration-approved medications that have long-term positive effects on the health of opioid-dependent individuals.Although clinical studies of drugs generally demonstrate efficacy in thousands of people and toxicity is excluded,it cannot be predicted whether the given drug will cause side effects in one of the patients at the treatment dose.Individual differences can be explained by many biological and environmental factors.Variations in genes encoding drug metabolism or cellular drug targets significantly explain the variability in drug response between individuals.Therefore,for the effects of candidate genes to be accepted and included in individual treatment protocols,it is important to repeat studies on individuals of different ethnic backgrounds and prove a similar effect.
文摘The opioid epidemic in the United States continues to take the lives of many individuals, with overdoses continuing to rise every year. Naloxone is an opioid antagonist that is efficacious in temporarily reversing opioid overdoses. Pharmacists play an important role in the accessibility and education of naloxone in both the community and health system settings. Recent efforts, such as co-dispensing naloxone with opioid prescriptions, naloxone training programs, and approval of naloxone to be over-the-counter, have been implemented in hopes to better control the opioid epidemic. Despite the efforts to make naloxone more accessible, there are still some barriers to overcome such as lack of training, cost, stigma, and patient refusal. This review aims to explore the contributions pharmacists have made thus far and define the barriers that still have to be resolved.
文摘Background and Purpose: Opioids, used for centuries to alleviate pain, have become a double-edged sword. While effective, they come with a host of adverse effects, including memory and cognition impairment. This review delves into the impact of opioid drugs on cognitive functions, explores underlying mechanisms, and investigates their prevalence in both medical care and illicit drug use. The ultimate goal is to find ways to mitigate their potential harm and address the ongoing opioid crisis. Methods: We sourced data from PubMed and Google Scholar, employing search combinations like “opioids,” “memory,” “cognition,” “amnesia,” “cognitive function,” “executive function,” and “inhibition.” Our focus was on English-language articles spanning from the inception of these databases up to the present. Results: The literature consistently reveals that opioid use, particularly at high doses, adversely affects memory and other cognitive functions. Longer deliberation times, impaired decision-making, impulsivity, and behavioral disorders are common consequences. Chronic high-dose opioid use is associated with conditions such as amnesiac syndrome (OAS), post-operative cognitive dysfunction (POCD), neonatal abstinence syndrome (NAS), depression, anxiety, sedation, and addiction. Alarming trends show increased opioid use over recent decades, amplifying the risk of these outcomes. Conclusion: Opioids cast a shadow over memory and cognitive function. These effects range from amnesiac effects, lessened cognitive function, depression, and more. Contributing factors include over-prescription, misuse, misinformation, and prohibition policies. Focusing on correct informational campaigns, removing punitive policies, and focusing on harm reduction strategies have been shown to lessen the abuse and use of opioids and thus helping to mitigate the adverse effects of these drugs. Further research into the impacts of opioids on cognitive abilities is also needed as they are well demonstrated in the literature, but the mechanism is not often completely understood.
文摘A research study collected intensive longitudinal data from cancer patients on a daily basis as well as non-intensive longitudinal survey data on a monthly basis. Although the daily data need separate analysis, those data can also be utilized to generate predictors of monthly outcomes. Alternatives for generating daily data predictors of monthly outcomes are addressed in this work. Analyses are reported of depression measured by the Patient Health Questionnaire 8 as the monthly survey outcome. Daily measures include numbers of opioid medications taken, numbers of pain flares, least pain levels, and worst pain levels. Predictors are averages of recent non-missing values for each daily measure recorded on or prior to survey dates for depression values. Weights for recent non-missing values are based on days between measurement of a recent value and a survey date. Five alternative averages are considered: averages with unit weights, averages with reciprocal weights, weighted averages with reciprocal weights, averages with exponential weights, and weighted averages with exponential weights. Adaptive regression methods based on likelihood cross-validation (LCV) scores are used to generate fractional polynomial models for possible nonlinear dependence of depression on each average. For all four daily measures, the best LCV score over averages of all types is generated using the average of recent non-missing values with reciprocal weights. Generated models are nonlinear and monotonic. Results indicate that an appropriate choice would be to assume three recent non-missing values and use the average with reciprocal weights of the first three recent non-missing values.
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.
基金Supported by the National Natural Science Foundation of China(No.81573796,81673756,and 81503395)Medical Guidance Project of the Shanghai Science and Technology Commission(No.16401932400)+1 种基金research grant from Shanghai Hospital Development Center(No.16CR1031B)The Interdisciplinary Project of"Clinical Immunology of Traditional Chinese Medicine"in Shanghai(No.30304113598)。
文摘Objective:To investigate the action mechanisms of electroacupuncture(EA)on postoperative immunosuppression.Methods:Male C57 BL/6 mice(5–7 weeks old)were randomly divided into:the sham injury group,the surgical trauma stressed group,the EA group[surgery+2/100 Hz EA at Neiguan(PC 6)],and the EA+Nal(surgery+EA+intraperitoneal injection of naloxone).Abdominal surgical trauma stress mice model was established.EA was performed on bilateral PC 6 acupoints by an EA apparatus(2/100 Hz)for 20 min once a day for 3 days.The m RNA expressions of MOR,DOR,and KOR in thymus and L3-5 dorsal root ganglions(DRG)were determined by quantitative real-time polymerase chain reaction(q RT-PCR)and the protein expressions of MOR,DOR,and KOR in thymus were measured by Western blot.Flow cytometry assay was used to detect the levels of T lymphocyte subtypes in the peripheral blood.Results:Surgical trauma induced decreased the m RNA expression level of MOR in both thymus(P<0.01)and L3-L5 DRGs(P<0.05).Moreover,EA treatment not only significantly attenuated the MOR protein and m RNA expression in the thymus(both P<0.05),but also markedly increased expression of DOR and KOR opioid receptor in thymus(P<0.01).However,the m RNA expressions of opioid receptors were not regulated by EA in the DRG(all P>0.05).Furthermore,T lymphocyte population of CD3^+ and CD4^+ was decreased in the peripheral blood after surgical trauma(both P<0.01).EA treatment can significantly elevate the population of CD3^+(P<0.01),CD4^+(P<0.05)and CD8^+T cells(P<0.01).Intraperitoneal injection of the non-selective opioid receptor antagonist naloxone blocked the up-regulation of T lymphocytes by EA.Conclusion:EA may improve postoperative immunosuppression through the peripheral opioid system.
基金This review was supported by the intramural research programs of National Institute on Aging(HC,AG000928).
文摘L-3,4-Dihydroxyphenylalanine(L-DOPA)-induced dyskinesia(LID)is a major clinical complication in the treatment of Parkinson’s disease(PD).This debilitating side effect likely reflects aberrant compensatory responses for a combination of dopaminergic neuron denervation and repeated L-DOPA administration.Abnormal endogenous opioid signal transduction pathways in basal ganglia have been well documented in LID.Opioid receptors have been targeted to alleviate the dyskinesia.However,the exact role of this altered opioid activity is remains under active investigation.In the present review,we discuss the current understanding of opioid signal transduction in the basal ganglia and how the malfunction of opioid signaling contributes to the pathophysiology of LID.Further study of the opioid system in LID may lead to new therapeutic targets and improved treatment of PD patients.
基金Supported by the Natural Science Foundation of Shandong Province,China(No.ZR2012CM004)the National Natural Science Foundation of China(No.41506190)
文摘Little is known about the roles of dynorphin and Kappa opioid receptor(KOR) in mollusks. In this study, we aim to determine the distribution of dynorphin A and KOR-1 in the digestive system of the scallop Chlamys farreri. Using immunohistochemical staining, we confirmed the expression of dynorphin A and KOR-1 in the digestive system of C. farreri. Dynorphin A immunopositive cells were identified in intestine and hepatopancreas. In intestine, small and spherical dynorphin A immunopositive cells(4–9 μm in diameter) were scattered among the long columnar epithelial cells(ECs). In hepatopancreas, cells containing masses(5–14 μm in diameter) of dynorphin A immunopositive products were observed in epithelium of acinis. These immunopositive cells may be synthetic and/or secretory cells of dynorphin A. Dynorphin A immunoreactive products were commonly observed in epithelium and connective tissue(CT) of labial palps, mouth labia and stomach, which presented in forms of grains, fibers or flakes. KOR-1 immunoreactive material was observed in ECs and CTs of labial palps, mouth labia and stomach, intestine and hepatopancreas. The distribution of both dynorphin A and KOR-1 in the digestive organs suggests an involvement of dynorphin via KOR-1 in the functional regulation of the digestive system of C. farreri.
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BACKGROUND The literature suggests that there is a high degree of co-occurrence between chronic pain and posttraumatic stress disorder(PTSD). An association has been found between PTSD and substance abuse. PTSD is a severe disorder that should be taken into account when opioids are prescribed. It has been found that the prevalence of opioid use disorder(OUD) in chronic pain patients is higher among those with PTSD than those without this disorder.AIM To perform a systematic review on the association between PTSD, chronic noncancer pain(CNCP), and opioid intake(i.e., prescription, misuse, and abuse).METHODS We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Patient, Intervention,Comparator, and Outcomes(PICOS) criteria were formulated a priori in the protocol of the systematic review. A search was conducted of the PROSPERO database. In March 2019, searches were also conducted of 5 other databases:Pub Med, MEDLINE, Psyc INFO, Web of Science, and PILOTS. The Scottish Intercollegiate Guidelines Network checklist for cohort studies was used to assess the selected studies for their methodological quality and risk of bias. Each study was evaluated according to its internal validity, participant sampling,confounding variables, and the statistical analysis.RESULTS A total of 151 potentially eligible studies were identified of which 17 were retained for analysis. Only 10 met the selection criteria. All the studies were published between 2008 and 2018 and were conducted in the United States. The eligible studies included a total of 1622785 unique participants. Of these, 196516 had comorbid CNCP and PTSD and were consuming opiates. The participants had a cross-study mean age of 35.2 years. The majority of participants were men(81.6%). The most common chronic pain condition was musculoskeletal pain:back pain(47.14% across studies;range: 16%-60.6%), arthritis and joint pain(31.1%;range: 18%-67.5%), and neck pain(28.7%;range: 3.6%-63%). In total,42.4% of the participants across studies had a diagnosis of PTSD(range: 4.7%-95%). In relation to opioid intake, we identified 2 different outcomes: opioid prescription and OUD. All the studies reported evidence of a greater prevalence of PTSD in CNCP patients who were receiving prescribed opioids and that PTSD was associated with OUD in CNCP patients.CONCLUSION Opioid analgesic prescription as the treatment of choice for CNCP patients should include screening for baseline PTSD to ensure that these drugs are safely consumed.
文摘<strong>Background:</strong> Ketamine is increasingly being used as an alternative to opioids in the management of acute pain in the emergency department. In turn, there is increasing research attention to prove the efficacy of ketamine as an analgesic in children presenting in the emergency department. <strong>Objective:</strong> The first objective of this systematic review was to investigate the effectiveness of ketamine compared to opioid analgesics for pain management in children aged two months to 18 years who have acute pain in the emergency department. The second objective was to compare the adverse events and side effects associated with ketamine with those associated with opioids used for pain management. <strong>Methods:</strong> A systematic review, using the JBI systematic review was completed. A computerised search from five databases;CINAHL, EMBASE, EMCARE and PubMed, and Cochrane. The included studies were appraised by JBI critical appraisal tool for randomised controlled trials and the study results analysed. <strong>Findings: </strong>Four randomised control trial studies were included in this systematic review. All the included studies compared ketamine with opioids (morphine and fentanyl) for the management of severe pain in children. The studies were of high methodological quality based on JBI critical appraisal outcome. Meta-analysis was not possible because of the heterogeneity of the studies, especially in terms of different outcome measures, and the approaches (pain assessment tool) used to measure the pain outcomes. The review identified that ketamine demonstrated a non-inferior analgesia effect compared to opioid medication (morphine or fentanyl) as determined by various pain scores used in different studies. However, ketamine use was associated with increased frequency of occurrence of temporary adverse effects that do not require clinical attention.<strong> Conclusion: </strong>Based on the findings from the review, ketamine is a suitable alternative for opioid analgesics for the management of acute and severe pain in children in ED. The minor transient side effects associated with ketamine should not limit the use of ketamine. Future studies should investigate the appropriate dosage and route of administration of ketamine to be used while managing pain among children with acute and severe pain in the emergency department.
文摘Objectives: Opioid medications consistently rank among the drugs most frequently associated with adverse events. We reviewed cases of naloxone administration to assess our opioid prescribing and administration practices before and after implementation of a computerized provider order entry (CPOE) system. Our primary measure was the rate of opioid reversal with naloxone in the two time periods. Methods: We systematically reviewed all cases of naloxone administration at our institution from March 2016 through May 2016 (before period) compared with cases from October 2017 through December 2017 (after period). Results: In the before period, 0.58% of patients who received an opioid required reversal with naloxone compared with 0.16% in the after period (p 〈 0.001). Subject demographics such as age, sex, BMI, and serum creatinine were not significantly different between the two groups. Similarly large proportions of patients in the before and after groups had at least 2 risk factors for over-sedation (79.5% and 75%, respectively, p = 0.17). More than 84% and 61% of patients in the before and after groups, respectively, did not have documentation of an opioid on the admission medication history, suggesting they were opioid-naYve (p= 0.10). Per our institution's policy on range orders, nurses should begin with the lowest prescribed opioid dose; this policy was followed in 58.3% in the before period and 69.2% in the after period (p = 0.36). Conclusions: Doses of naloxone that were required for opioid reversal were significantly reduced after implementation of a CPOE system. Our opioid-reversal rate was comparable to similar studies; however, secondary endpoints indicate that opioid prescribing and administration habits may not account for patient-specific risk factors for over-sedation.
文摘Background Individual differences have been detected in individuals with opioid use disorders(OUD)in rehabilitation following protracted abstinence.Recent studies suggested that prediction models were effective for individual-level prognosis based on neuroimage data in substance use disorders(SUD).Aims This prospective cohort study aimed to assess neuroimaging biomarkers for individual response to protracted abstinence in opioid users using connectome-based predictive modelling(CPM).Methods One hundred and eight inpatients with OUD underwent structural and functional magnetic resonance imaging(fMRI)scans at baseline.The Heroin Craving Questionnaire(HCQ)was used to assess craving levels at baseline and at the 8-month follow-up of abstinence.CPM with leave-one-out cross-validation was used to identify baseline networks that could predict follow-up HCQ scores and changes in HCQ(HCQtolow V-up-HCQpa baseline).Then,the follow-up aseline predictive ability of identified networks was tested in a separate,heterogeneous sample of methamphetamine individuals who underwent MRI scanning before abstinence for SUD.Results CPM could predict craving changes induced by long-term abstinence,as shown by a significant correlation between predicted and actual HCQ fllow-up(r=0.417,p<0.001)and changes in HCQ(negative:r=0.334,p=0.002;positive:r=0.233,p=0.038).Identified craving-related prediction networks included the somato-motor network(SMN),salience network(SALN),default mode network(DMN),medial frontal network,visual network and auditory network.In addition,decreased connectivity of frontal-parietal network(FPN)-SMN,FPN-DMN and FPN-SALN and increased connectivity of subcortical network(SCN)-DMN,SCN-SALNandSCN-SMN were positively correlated with craving levels.Conclusions These findings highlight the potential applications of CPM to predict the craving level of individuals after protracted abstinence,as well as the generalisation ability;the identified brain networks might be the focus of innovative therapies in the future.
文摘Nigeria has a very high number of sickle cell disease (SCD) population with addition of 150,000 babies born annually with the disease. Early infant diagnosis and good care make many of these babies survive to adulthood. Severe pain requiring moderately strong or very strong analgesics is a common presentation of patients with Sickle Cell Anaemia. Paediatricians find ready usefulness of Opioids which are very useful for the painful episodes among these patients. Therefore, the chances of abuse and addiction to these medications become very high and constitute additional burden on the deficient manpower in the health sector. Opioid Use Disorder among Sickle Cell Disease patients has subtle presentation, so a high index of suspicion is required to make both the diagnosis and referral to treatment centres. In this review, the epidemiology, pain pathophysiology, behavioural and pharmacologic therapy have been re-examined.