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The Cochrane Database of Systematic... Jul 2017Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for... (Review)
Review
BACKGROUND
Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past, pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as importantWe designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol as priority areas) in order to review the evidence for children's pain utilising pharmacological interventions in children and adolescents.As the leading cause of morbidity in children and adolescents in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (lasting three months or longer) can arise in the paediatric population in a variety of pathophysiological classifications: nociceptive, neuropathic, idiopathic, visceral, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, and other unknown reasons.Opioids are used worldwide for the treatment of pain. They bind to opioid receptors in the central nervous system (mu, kappa, delta, and sigma) and can be agonists, antagonists, mixed agonist-antagonists, or partial agonists. Opioids are generally available in healthcare settings across most high-income countries, but access may be restricted in low- and middle-income countries. For example, opioids currently available in the UK include: buprenorphine, codeine, fentanyl, hydromorphone, methadone, morphine, oxycodone, and tramadol. Opioids are used in varying doses (generally based on body weight for paediatric patients) by means of parenteral, transmucosal, transdermal, or oral administration (immediate release or modified release). To achieve adequate pain relief in children using opioids, with an acceptable grade of adverse effects, the recommended method is a lower dose gradually titrated to effect in the child.
OBJECTIVES
To assess the analgesic efficacy and adverse events of opioids used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years, in any setting.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Library, MEDLINE via Ovid, and Embase via Ovid from inception to 6 September 2016. We also searched the reference lists of retrieved studies and reviews, and searched online clinical trial registries.
SELECTION CRITERIA
Randomised controlled trials, with or without blinding, of any dose and any route, treating chronic non-cancer pain in children and adolescents, comparing opioids with placebo or an active comparator.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio and number needed to treat, using standard methods. We assessed GRADE (Grading of Recommendations Assessment, Development and Evaluation) and planned to create a 'Summary of findings' table.
MAIN RESULTS
No studies were eligible for inclusion in this review. We rated the quality of the evidence as very low. We downgraded the quality of evidence by three levels due to the lack of data reported for any outcome.
AUTHORS' CONCLUSIONS
There was no evidence from randomised controlled trials to support or refute the use of opioids to treat chronic non-cancer pain in children and adolescents. We are unable to comment about efficacy or harm from the use of opioids to treat chronic non-cancer pain in children and adolescents.We know from adult randomised controlled trials that some opioids, such as morphine and codeine, can be effective in certain chronic pain conditions.This means that no conclusions could be made about efficacy or harm in the use of opioids to treat chronic non-cancer pain in children and adolescents.
Topics: Adolescent; Analgesics, Opioid; Child; Child, Preschool; Chronic Pain; Humans; Infant; Infant, Newborn
PubMed: 28745394
DOI: 10.1002/14651858.CD012538.pub2 -
Patient-Reported Opioid Analgesic Use After Discharge from Surgical Procedures: A Systematic Review.Pain Medicine (Malden, Mass.) Jan 2022This systematic review synthesizes evidence on patient-reported outpatient opioid analgesic use after surgery.
OBJECTIVE
This systematic review synthesizes evidence on patient-reported outpatient opioid analgesic use after surgery.
METHODS
We searched PubMed (February 2019) and Web of Science and Embase (June 2019) for U.S. studies describing patient-reported outpatient opioid analgesic use. Two reviewers extracted data on opioid analgesic use, standardized the data on use , and performed independent quality appraisals based on the Cochrane Risk of Bias Tool and an adapted Newcastle-Ottawa scale.
RESULTS
Ninety-six studies met the eligibility criteria; 56 had sufficient information to standardize use in oxycodone 5-mg tablets. Patient-reported opioid analgesic use varied widely by procedure type; knee and hip arthroplasty had the highest postoperative opioid use, and use after many procedures was reported as <5 tablets. In studies that examined excess tablets, 25-98% of the total tablets prescribed were reported to be excess, with most studies reporting that 50-70% of tablets went unused. Factors commonly associated with higher opioid analgesic use included preoperative opioid analgesic use, higher inpatient opioid analgesic use, higher postoperative pain scores, and chronic medical conditions, among others. Estimates also varied across studies because of heterogeneity in study design, including length of follow-up and inclusion/exclusion criteria.
CONCLUSION
Self-reported postsurgery outpatient opioid analgesic use varies widely both across procedures and within a given procedure type. Contributors to within-procedure variation included patient characteristics, prior opioid use, intraoperative and perioperative factors, and differences in the timing of opioid use data collection. We provide recommendations to help minimize variation caused by study design factors and maximize interpretability of forthcoming studies for use in clinical guidelines and decision-making.
Topics: Analgesics, Opioid; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Humans; Pain, Postoperative; Patient Discharge; Patient Reported Outcome Measures
PubMed: 34347101
DOI: 10.1093/pm/pnab244 -
Traffic Injury Prevention Nov 2017The objective of this study was to look for dose- and concentration-effect relationships in experimental studies on single-dose administration of morphine on... (Review)
Review
Acute impairing effects of morphine related to driving: A systematic review of experimental studies to define blood morphine concentrations related to impairment in opioid-naïve subjects.
OBJECTIVE
The objective of this study was to look for dose- and concentration-effect relationships in experimental studies on single-dose administration of morphine on traffic-relevant behavioral tests by a systematic literature review and possibly to see whether a dose/concentration could be defined below which few or no tests would be affected.
METHODS
Searches for corresponding literature were conducted using MEDLINE, EMBASE, and PsycINFO, throughout March of 2016. The search strategy consisted of words colligated to cognitive and psychomotor functions of relevance to driving, in relation to morphine administration. The tests were arranged in main groups, and tests showing impairment were categorized by doses as well as calculated plasma concentrations.
RESULTS
Fifteen studies were included in the review. Impairment after the administration of a single intravenously dose of morphine was found in some of the tests on reaction time, attention, and visual functions. No impairment was observed in tests on psychomotor skills and en-/decoding. Tests on reaction time appeared to be less sensitive to the morphine administration, whereas tests on visual functions and attention appeared to be the most sensitive to the morphine administration. Single-dose administration of morphine with dosages up to 5 mg appeared to cause very few effects on traffic-relevant performance tasks. At higher dosages, impairment was found on various tasks but with no clear dose-effect relationship. Plasma morphine concentrations less than 50 nmol/L are most probably accompanied by few effects on traffic-relevant performance tasks.
CONCLUSIONS
A plasma morphine concentration of 50 nmol/L (approximately 14.3 ng/mL) could represent an upper level, under which there is little accompanying road traffic risk. A single dose of 5 mg morphine IV and analgetic equivalence doses of fentanyl, hydromorphone, oxycodone, and oxymorphone are presented with the suggestion that few traffic-relevant effects will appear after such doses.
Topics: Attention; Driving Under the Influence; Humans; Morphine; Psychomotor Performance; Reaction Time; Visual Acuity
PubMed: 28481682
DOI: 10.1080/15389588.2017.1326595 -
Schmerz (Berlin, Germany) Feb 2015We updated a systematic review on the comparative efficacy, tolerability and safety of opioids and of their routes of application in chronic noncancer pain (CNCP). (Comparative Study)
Comparative Study Meta-Analysis Review
[Opioids in chronic noncancer pain-are opioids different? A systematic review and meta-analysis of efficacy, tolerability and safety in randomized head-to-head comparisons of opioids of at least four week's duration].
BACKGROUND
We updated a systematic review on the comparative efficacy, tolerability and safety of opioids and of their routes of application in chronic noncancer pain (CNCP).
METHODS
We screened MEDLINE, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) up until October 2013, as well as the reference sections of original studies and systematic reviews of randomized controlled trials (RCTs) of opioids in CNCP. We included randomized head-to-head comparisons of opioids (opioid of the sponsor of the study versus standard opioid) of at least 4 week's duration. Using a random effects model, absolute risk differences (RD) were calculated for categorical data and standardized mean differences (SMD) for continuous variables. The quality of evidence was rated by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.
RESULTS
We included 13 RCTs with 6748 participants. Median study duration was 15 weeks (range 4-56 weeks). Hydromorphone, morphine, oxymorphone and tapentadol were compared to oxycodone; fentanyl to morphine and buprenorphine to tramadol. In pooled analysis, there were no significant differences between the two groups of opioids in terms of mean pain reduction (low-quality evidence), the patient global impression to be much or very much improved outcome (low-quality evidence), physical function (very low-quality evidence), serious adverse events (moderate-quality evidence) or mortality (moderate-quality evidence). There was no significant difference between transdermal and oral application of opioids in terms of mean pain reduction, physical function, serious adverse events, mortality (all low-quality evidence) or dropout due to adverse events (very low-quality).
CONCLUSION
Pooled head-to-head comparisons of opioids (opioid of the sponsor of the study versus standard opioid) provide no rational for preferring one opioid and/or administration route over another in the therapy of patients with CNCP. The English full-text version of this article is freely available at SpringerLink (under "Supplemental").
Topics: Administration, Cutaneous; Administration, Oral; Analgesics, Opioid; Chronic Pain; Data Accuracy; Evidence-Based Medicine; Humans; Long-Term Care; Randomized Controlled Trials as Topic
PubMed: 25376545
DOI: 10.1007/s00482-014-1432-4 -
Drug and Alcohol Dependence Feb 2017To systematically review the quantitative and qualitative evidence base pertaining to the prevalence, practice of, and treatment response to the diversion of prescribed... (Review)
Review
BACKGROUND
To systematically review the quantitative and qualitative evidence base pertaining to the prevalence, practice of, and treatment response to the diversion of prescribed opiates in the prison setting.
METHODS
Medline, Embase, CINAHL, PsycINFO, Google Scholar, ASSIA and Science Direct databases were searched for papers from 1995 to the present relevant to the abuse of prescribed opiate medication. Identified journals and their reference lists were hand searched for other relevant articles. Of the abstracts identified as relevant, full text papers were retrieved and critiqued against the inclusion criteria for the review.
RESULTS
Three hundred and fifty-five abstracts were identified, leading to 42 full-text articles being retrieved. Of those, 10 papers were included in the review. Significant differences in abuse behaviours between different countries were reported. However, a key theme emerged from the data regarding a culture of nasal administration of prescribed sublingual buprenorphine within some prisons due to both reduced prevalence of injection within prison and reduced supplies of illicit drugs within prison. The buprenorphine/naloxone preparation appears to be less amenable to abuse. The review highlighted a paucity of empirical research pertaining to both prevalence of the phenomenon and treatment responses.
CLINICAL AND RESEARCH IMPLICATIONS
Healthcare providers within prisons need to prescribe opioids in the least abuseable preparation since the risk of abuse is significant, despite widespread processes of supervised dispensing. Prescription medication abuse is not limited to opioids and the predominant drug of abuse in an individual prison can rapidly change according to availability.
Topics: Administration, Sublingual; Analgesics, Opioid; Buprenorphine; Drug Prescriptions; Humans; Illicit Drugs; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Prescription Drug Misuse; Prevalence; Prisons; Treatment Outcome
PubMed: 28086177
DOI: 10.1016/j.drugalcdep.2016.11.032 -
European Journal of Pain (London,... Jan 2020This updated systematic review evaluated the efficacy, tolerability and safety of opioids compared to placebo in chronic non-cancer neuropathic pain. (Meta-Analysis)
Meta-Analysis
Opioids for chronic non-cancer neuropathic pain. An updated systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks duration.
BACKGROUND AND OBJECTIVE
This updated systematic review evaluated the efficacy, tolerability and safety of opioids compared to placebo in chronic non-cancer neuropathic pain.
DATABASES AND DATA TREATMENT
Clinicaltrials.gov, CENTRAL, PubMed and PsycINFO were searched from October 2013 to June 2019. Randomized controlled trials comparing opioids with placebo and at least 4 weeks double-blinded duration were analysed. Primary outcomes were pain relief of 50% or greater, disability, tolerability and safety. Effects were summarized by a random effects model using risk differences (RD) or standardized mean differences (SMD). We added four new studies with 662 participants for a total of 16 included studies with 2,199 participants. Study duration ranged between 4 and 12 weeks. Studies with a parallel and cross-over design: Based on low to moderate quality evidence, opioids (buprenorphine, hydromorphone, morphine, oxycodone, tramadol) provided a clinically relevant pain relief of 50% or greater and reduction of disability compared to placebo. There was no clinically relevant harm with regards to the drop out rate due to adverse and serious adverse events by opioids compared to placebo. Enriched enrolment randomized withdrawal design: Based on low to moderate quality evidence, tapentadol provided a clinically relevant pain relief of 50% or greater and reduction of disability compared to placebo in diabetic polyneuropathy. There was no clinically relevant harm with regards to the drop out rate due to adverse and serious adverse events by tapentadol compared to placebo.
CONCLUSIONS
Some opioids provided a short-term substantial pain relief in highly selected patients in some neuropathic pain syndromes.
SIGNIFICANCE
Some opioids (buprenorphine, morphine, oxycodone, tramadol, tapentadol) provide substantial pain relief compared to placebo in postherpetic neuralgia and peripheral neuropathies of different aetiologies for 4-12 weeks. There is insufficient evidence to support or refute the suggestion that these drugs are effective in other neuropathic pain conditions. The safety of opioids with regards to abuse and deaths in the studies analysed cannot be extrapolated to routine clinical care.
Topics: Analgesics, Opioid; Chronic Pain; Humans; Morphine; Neuralgia; Oxycodone; Tapentadol
PubMed: 31705717
DOI: 10.1002/ejp.1494 -
Pain Practice : the Official Journal of... Nov 2014A large percentage of patients with chronic pain on around-the-clock (ATC) opioids may experience increased pain occurring at the end of a scheduled dose, also known as... (Review)
Review
A large percentage of patients with chronic pain on around-the-clock (ATC) opioids may experience increased pain occurring at the end of a scheduled dose, also known as end-of-dose pain. Despite the significant prevalence and impact of end-of-dose pain in patients using extended-release (ER) opioids, there are no detailed analyses examining how the frequency of end-of-dose pain is linked to the formulations of long-acting opioids. Consequently, we performed a systematic review to evaluate how many published studies on patients with chronic cancer or noncancer pain identified end-of-dose pain. As only a few studies mentioned end-of-dose pain explicitly, we used breakthrough pain (BTP) as a surrogate parameter. We determined if any opioid formulation had a greater association with the frequency of BTP, the use of rescue medication for BTP, and the frequency of end-of-dose pain. Of the 39 studies entered in the final analysis, 14 studies across different formulations showed that ER opioids were effective in the prevention of BTP. The opioids most frequently studied were hydromorphone (26%), followed by morphine (23%), and transdermal buprenorphine (23%). Only 5% of the studies used immediate-release preparations. Overall, most studies showed that patients using ER preparations experienced fewer episodes of BTP compared with patients on placebo or an active comparator. This could reflect the favorable duration of action of these opioids compared with short-acting formulations. Future studies should examine the incidence of end-of-dose pain and use of rescue medicine in a longitudinal manner in patients with chronic pain taking short- vs. long-acting ATC opioids.
Topics: Analgesics, Opioid; Breakthrough Pain; Chronic Pain; Humans; Pain Measurement; Time; Treatment Outcome
PubMed: 24373184
DOI: 10.1111/papr.12156 -
The Cochrane Database of Systematic... Sep 2017Needle syringe programmes and opioid substitution therapy for preventing hepatitis C transmission in people who inject drugsNeedle syringe programmes (NSP) and opioid... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Needle syringe programmes and opioid substitution therapy for preventing hepatitis C transmission in people who inject drugsNeedle syringe programmes (NSP) and opioid substitution therapy (OST) are the primary interventions to reduce hepatitis C (HCV) transmission in people who inject drugs. There is good evidence for the effectiveness of NSP and OST in reducing injecting risk behaviour and increasing evidence for the effectiveness of OST and NSP in reducing HIV acquisition risk, but the evidence on the effectiveness of NSP and OST for preventing HCV acquisition is weak.
OBJECTIVES
To assess the effects of needle syringe programmes and opioid substitution therapy, alone or in combination, for preventing acquisition of HCV in people who inject drugs.
SEARCH METHODS
We searched the Cochrane Drug and Alcohol Register, CENTRAL, the Cochrane Database of Systematic Reviews (CDSR), the Database of Abstracts of Reviews of Effects (DARE), the Health Technology Assessment Database (HTA), the NHS Economic Evaluation Database (NHSEED), MEDLINE, Embase, PsycINFO, Global Health, CINAHL, and the Web of Science up to 16 November 2015. We updated this search in March 2017, but we have not incorporated these results into the review yet. Where observational studies did not report any outcome measure, we asked authors to provide unpublished data. We searched publications of key international agencies and conference abstracts. We reviewed reference lists of all included articles and topic-related systematic reviews for eligible papers.
SELECTION CRITERIA
We included prospective and retrospective cohort studies, cross-sectional surveys, case-control studies and randomised controlled trials that measured exposure to NSP and/or OST against no intervention or a reduced exposure and reported HCV incidence as an outcome in people who inject drugs. We defined interventions as current OST (within previous 6 months), lifetime use of OST and high NSP coverage (regular attendance at an NSP or all injections covered by a new needle/syringe) or low NSP coverage (irregular attendance at an NSP or less than 100% of injections covered by a new needle/syringe) compared with no intervention or reduced exposure.
DATA COLLECTION AND ANALYSIS
We followed the standard Cochrane methodological procedures incorporating new methods for classifying risk of bias for observational studies. We described study methods against the following 'Risk of bias' domains: confounding, selection bias, measurement of interventions, departures from intervention, missing data, measurement of outcomes, selection of reported results; and we assigned a judgment (low, moderate, serious, critical, unclear) for each criterion.
MAIN RESULTS
We identified 28 studies (21 published, 7 unpublished): 13 from North America, 5 from the UK, 4 from continental Europe, 5 from Australia and 1 from China, comprising 1817 incident HCV infections and 8806.95 person-years of follow-up. HCV incidence ranged from 0.09 cases to 42 cases per 100 person-years across the studies. We judged only two studies to be at moderate overall risk of bias, while 17 were at serious risk and 7 were at critical risk; for two unpublished datasets there was insufficient information to assess bias. As none of the intervention effects were generated from RCT evidence, we typically categorised quality as low. We found evidence that current OST reduces the risk of HCV acquisition by 50% (risk ratio (RR) 0.50, 95% confidence interval (CI) 0.40 to 0.63, I = 0%, 12 studies across all regions, N = 6361), but the quality of the evidence was low. The intervention effect remained significant in sensitivity analyses that excluded unpublished datasets and papers judged to be at critical risk of bias. We found evidence of differential impact by proportion of female participants in the sample, but not geographical region of study, the main drug used, or history of homelessness or imprisonment among study samples.Overall, we found very low-quality evidence that high NSP coverage did not reduce risk of HCV acquisition (RR 0.79, 95% CI 0.39 to 1.61) with high heterogeneity (I = 77%) based on five studies from North America and Europe involving 3530 participants. After stratification by region, high NSP coverage in Europe was associated with a 76% reduction in HCV acquisition risk (RR 0.24, 95% CI 0.09 to 0.62) with less heterogeneity (I =0%). We found low-quality evidence of the impact of combined high coverage of NSP and OST, from three studies involving 3241 participants, resulting in a 74% reduction in the risk of HCV acquisition (RR 0.26 95% CI 0.07 to 0.89).
AUTHORS' CONCLUSIONS
OST is associated with a reduction in the risk of HCV acquisition, which is strengthened in studies that assess the combination of OST and NSP. There was greater heterogeneity between studies and weaker evidence for the impact of NSP on HCV acquisition. High NSP coverage was associated with a reduction in the risk of HCV acquisition in studies in Europe.
Topics: Female; Hepatitis C; Humans; Male; Needle-Exchange Programs; Opiate Substitution Treatment; Program Evaluation; Substance Abuse, Intravenous
PubMed: 28922449
DOI: 10.1002/14651858.CD012021.pub2 -
Journal of the American Pharmacists... 2021To evaluate opioid prescribing, dispensing, and use in relation to hydrocodone-containing product (HCP) rescheduling.
OBJECTIVE
To evaluate opioid prescribing, dispensing, and use in relation to hydrocodone-containing product (HCP) rescheduling.
METHODS
Seven biomedical databases and grey literature sources were searched with keywords and database-specific controlled vocabulary relevant to HCP rescheduling for items published between January 2014 and July 2019. We included English-language quasi-experimental studies that assessed changes in HCP and other opioid prescribing, dispensing, utilization, and opioid-related health outcomes before and after HCP rescheduling. A data extraction sheet was created for this review. Two authors evaluated risk of bias for each included study. Two of 4 authors each independently extracted patient demographics and opioid-related outcomes from the included studies. Conflicts were resolved by a third author.
RESULTS
All studies identified (n = 44) were quasi-experimental in design with 10 using an interrupted time series approach. A total of 24 studies reported a decrease in HCP prescribing by 3.1%-66.0%. Six studies reported a decrease in HCP days' supply or doses by 14.0%-80.8%. There was increased prescribing of oxycodone-containing products by 4.5%-13.9% in 5 studies, tramadol by 2.7%-53.0% in 9 studies, codeine-containing products by 0.8%-1352.9% in 8 studies). Five studies reported a decrease in morphine equivalents by at least 10%, whereas 2 studies reported an increase in morphine equivalents. Differences in populations, sample sizes, and approaches did not allow for a meta-analysis. Details regarding approach and findings were limited in published conference abstracts (n = 16).
CONCLUSIONS
Hydrocodone rescheduling was associated with reductions in prescribing and use of HCPs but was also associated with increased prescribing and use of other opioids, both schedule II and nonschedule II.
Topics: Analgesics, Opioid; Controlled Substances; Drug Prescriptions; Drug and Narcotic Control; Humans; Hydrocodone; Practice Patterns, Physicians'
PubMed: 33127312
DOI: 10.1016/j.japh.2020.09.013 -
Journal of Opioid Management 2021To determine the incidence of addiction and dependence in persons with chronic noncancer pain (CNCP) who are treated with oxycodone.
OBJECTIVE
To determine the incidence of addiction and dependence in persons with chronic noncancer pain (CNCP) who are treated with oxycodone.
DESIGN
Systematic review following PRISMA guidelines.
METHODS
PubMed, MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Library were searched from inception to January 2020. Of 1,320 retrieved citations screened by two independent raters at title and abstract and full-text screening, six articles fulfilled the eligibility criteria for the systematic review. Data extraction and risk of bias assessment followed article screening. The Cochrane Collaboration tool and the Newcastle-Ottawa Scale (NOS) were used to assess the risk of bias in individual studies.
RESULTS
Two of the six articles reported addiction and the remaining four reported dependence. The incidence rates of addiction were 2.91 percent and 1.72 percent, and the incidence rates of dependence were 0.00 percent, 0.44 percent, 0.45 percent, and 5.77 percent. In all articles, addiction and dependence were treated as secondary outcomes. Three randomized controlled trials (RCTs) had follow-up lengths of less than 31 days, which is insufficient to assess the incidence of addiction or dependence.
CONCLUSIONS
The results of this systematic review show that oxycodone use leads to addiction and dependence in a small proportion of individuals with CNCP. However, one must exercise caution when drawing conclusions from the six included articles. Future studies in the area should examine addiction and dependence as primary outcomes using adequate follow-up periods.
Topics: Analgesics, Opioid; Chronic Pain; Humans; Iatrogenic Disease; Oxycodone; Prescriptions
PubMed: 33735430
DOI: 10.5055/jom.2021.0616