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Current Drug Metabolism 2020Despite recent therapeutic advances, osteoarthritis continues to be a challenging health problem, especially in the elderly population. Opioids, which are potent... (Meta-Analysis)
Meta-Analysis
Model-based Meta-analysis to Compare Primary Efficacy-endpoint, Efficacy-time Course, Safety, and Tolerability of Opioids Used in the Management of Osteoarthritic Pain in Humans.
BACKGROUND
Despite recent therapeutic advances, osteoarthritis continues to be a challenging health problem, especially in the elderly population. Opioids, which are potent analgesics, have shown an extraordinary ability to reduce intense pain in many osteoarthritic clinical trials; however, there is an increased need for a study to integrate the reported outcomes and utilize them to achieve a better understanding. Herein, efficacy and safety aspects of opioids used to manage osteoarthritic pain were assessed and compared using a model-based meta-analysis (MBMA).
METHODS
To perform the analysis, a comprehensive database consisting of pain relief compounds with information on summary-level of efficacy over time, adverse events and dropout rates was compiled from multiple sources. MBMA was conducted using a nonlinear mixed-effects modeling approach.
RESULTS
The results of primary efficacy endpoint analysis indicated that the doses of oxycodone, oxymorphone, and tramadol required to produce 50% of the maximum effect were 47, 84, and 247 mg per day, respectively. Efficacytime course analysis showed that opioids had rapid time to efficacy onset, suggesting potentially powerful painrelieving effects. It was also found that gastrointestinal adverse events were the most opioid-associated and dosedependent adverse effects. In addition, the analysis revealed that opioids were well-tolerated at low to moderate doses.
CONCLUSION
This MBMA provides clinically meaningful insights into the efficacy and safety profiles of oxycodone, oxymorphone, and tramadol. Resultantly, the presented framework analysis can have an impact in the clinic on drug development where it can guide: the optimization of doses of opioids required to manage osteoarthritic pain; the making of precise key decisions for the positioning of new drugs, and; the design of more efficient trials.
Topics: Analgesics, Opioid; Humans; Models, Biological; Osteoarthritis; Oxycodone; Oxymorphone; Pain; Randomized Controlled Trials as Topic; Tramadol; Treatment Outcome
PubMed: 32407270
DOI: 10.2174/1389200221666200514130441 -
PloS One 2020To evaluate the efficacy, safety and cost-effectiveness of Oxycodone Hydrochloride Controlled-release Tablets (CR oxycodone) and Morphine Sulfate Sustained-release... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
To evaluate the efficacy, safety and cost-effectiveness of Oxycodone Hydrochloride Controlled-release Tablets (CR oxycodone) and Morphine Sulfate Sustained-release Tablets (SR morphine) for moderate to severe cancer pain titration.
METHODS
Randomized controlled trials meeting the inclusion criteria were searched through Medline, Cochrane Library, Pubmed, EMbase, CNKI,VIP and WanFang database from the data of their establishment to June 2019. The efficacy and safety data were extracted from the included literature. The pain control rate was calculated to eatimate efficacy. Meta-analysis was conducted by Revman5.1.4. A decision tree model was built to simulate cancer pain titration process. The initial dose of CR oxycodone and SR morphine group were 20mg and 30mg respectively. Oral immediate-release morphine was administered to treat break-out pain. The incremental cost-effectiveness ratio was performed with TreeAge Pro 2019.
RESULTS
19 studies (1680 patients)were included in this study. Meta-analysis showed that the pain control rate of CR oxycodone and SR morphine were 86% and 82.98% respectively. The costs of CR oxycodone and SR morphine were $23.27 and $13.31. The incremental cost-effectiveness ratio per unit was approximate $329.76. At the willingness-to-pay threshold of $8836, CR oxycodone was cost-effective, while the corresponding probability of being cost-effective at the willingness-to-pay threshold of $300 was 31.6%. One-way sensitivity analysis confirmed robustness of results.
CONCLUSIONS
CR oxycodone could be a cost-effective option compared with SR morphine for moderate to severe cancer pain titration in China, according to the threshold defined by the WHO.
Topics: Cancer Pain; Cost-Benefit Analysis; Decision Trees; Delayed-Action Preparations; Economics, Pharmaceutical; Humans; Morphine; Oxycodone; Publication Bias; Risk; Treatment Outcome
PubMed: 32302346
DOI: 10.1371/journal.pone.0231763 -
Australian Health Review : a... Apr 2020Objective This review systematically identified studies that estimated the prevalence of prescription opioid use in Australia, assessed the prevalence estimates for bias...
Objective This review systematically identified studies that estimated the prevalence of prescription opioid use in Australia, assessed the prevalence estimates for bias and identified areas for future research. Methods Literature published after 2000 containing a potentially representative estimate of prescription opioid use in adults, in the community setting, in Australia was included in this review. Studies that solely assessed opioid replacement, illicit opioid usage or acute hospital in-patient use were excluded. Databases searched included PubMed, EMBASE, Web of Science and the grey literature. Results The search identified 2253 peer-reviewed publications, with 34 requiring full-text review. Of these, 20 were included in the final qualitative analysis, in addition to four publications from the grey literature. Most studies included analysed prescription claims data for medicines dispensed via Australia's national medicines subsidy scheme (the Pharmaceutical Benefits Scheme). Although data sources were good quality, all prevalence estimates were at least at moderate risk of bias, predominantly due to incompleteness of data or potential confounding. Included publications demonstrated a significant rise in opioid use up to 2017 (including a 15-fold increase in prescriptions dispensed over the 20 years to 2015), predominantly driven by a sharp rise in oxycodone use. Although opioid prescription numbers continue to escalate, usage, as measured by oral morphine equivalent per capita, may have plateaued since 2014. Codeine remains the most prevalently obtained opioid, followed by oxycodone and tramadol. There was a substantial delay (median 30 months; interquartile range 20-37 months) to publication of opioid usage data from time of availability. Conclusions Australia has experienced a marked increase in opioid prescribing since the 1990s. Current published literature is restricted to incomplete, delayed and historical data, limiting the ability of clinicians and policy makers to intervene appropriately. What is known about the topic? Opioid prescriptions in Australia have continued to increase since the 1990s and may be mirroring the epidemic being seen in the US. What does this paper add? This paper systematically identifies all publications that have examined the prevalence of prescription opioid use in Australia since 2000, and only identified prevalence estimates that were at moderate or high risk of bias, and found significant delays to publication of these estimates. What are the implications for practitioners? Because published literature on the prevalence of prescription opioid consumption is restricted to incomplete, delayed and historical data, the ability of clinicians and policy makers to appropriately intervene to curb prescription opioid use is limited. A national policy of real-time monitoring and reporting of opioid prescribing may support improvements in practice.
Topics: Adult; Age Distribution; Aged; Analgesics, Opioid; Australia; Drug Prescriptions; Drug Utilization; Female; Humans; Male; Middle Aged; Practice Patterns, Physicians'; Sex Distribution; Young Adult
PubMed: 32241339
DOI: 10.1071/AH18245 -
Journal of Internal Medicine May 2020Guidelines now discourage opioid analgesics for chronic noncancer pain because the benefits frequently do not outweigh the harms. We aimed to determine the proportion of... (Meta-Analysis)
Meta-Analysis
Guidelines now discourage opioid analgesics for chronic noncancer pain because the benefits frequently do not outweigh the harms. We aimed to determine the proportion of patients with chronic noncancer pain who are prescribed an opioid, the types prescribed and factors associated with prescribing. Database searches were conducted from inception to 29 October 2018 without language restrictions. We included observational studies of adults with chronic noncancer pain measuring opioid prescribing. Opioids were categorized as weak (e.g. codeine) or strong (e.g. oxycodone). Study quality was assessed using a risk of bias tool designed for observational studies measuring prevalence. Individual study results were pooled using a random-effects model. Meta-regression investigated study-level factors associated with prescribing (e.g. sampling year, geographic region as per World Health Organization). The overall evidence quality was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. Of the 42 studies (5,059,098 participants) identified, the majority (n = 28) were from the United States of America. Eleven studies were at low risk of bias. The pooled estimate of the proportion of patients with chronic noncancer pain prescribed opioids was 30.7% (95% CI 28.7% to 32.7%, n = 42 studies, moderate-quality evidence). Strong opioids were more frequently prescribed than weak (18.4% (95% CI 16.0-21.0%, n = 15 studies, low-quality evidence), versus 8.5% (95% CI 7.2-9.9%, n = 15 studies, low-quality evidence)). Meta-regression determined that opioid prescribing was associated with year of sampling (more prescribing in recent years) (P = 0.014) and not geographic region (P = 0.056). Opioid prescribing for patients with chronic noncancer pain is common and has increased over time.
Topics: Analgesics; Analgesics, Opioid; Chronic Pain; Drug Therapy; Humans; Observational Studies as Topic; Pain Management
PubMed: 32100394
DOI: 10.1111/joim.13026 -
The Clinical Journal of Pain May 2020Tapentadol (TAP) immediate release (IR) is a newer opioid option for acute pain. The aim of this systematic review was to examine the efficacy and safety of TAP IR... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Tapentadol (TAP) immediate release (IR) is a newer opioid option for acute pain. The aim of this systematic review was to examine the efficacy and safety of TAP IR compared with other opioids for acute pain.
METHODS
A systematic literature search as conducted using the Cochrane Library, Embase, International Pharmaceutical Abstracts, MEDLINE, PubMed, and Web of Science. The search included all randomized controlled trials and observational studies examining TAP IR versus other orally administered IR opioids for acute pain. The protocol for this study was registered on PROSPERO (CRD42018110267).
RESULTS
Thirteen studies and 1 abstract were included in the systematic review (n=12,814 patients). Of these, 5 studies and 1 abstract were included in the qualitative review (n=9108 patients). Eight randomized controlled trials (n=3706 patients) comparing 50 to 100 mg TAP IR versus 5 to 15 mg oxycodone IR were included in the meta-analysis. The lowest dose of TAP IR (ie, 50 mg) was associated with less pain control compared with oxycodone IR (standardized mean difference=0.25, 95% confidence interval: 0.06-0.44, P<0.01). However, there were no significant differences at higher doses (ie, 75, 100 mg, or when a titration strategy was used). In the qualitative analysis, pain control with TAP IR was also similar to morphine IR and tramadol IR. TAP IR was less likely to have gastrointestinal adverse effects such as nausea and constipation compared with other opioids.
DISCUSSION
TAP IR is as effective as other opioids at higher doses for acute pain and is associated with fewer gastrointestinal adverse effects. On the basis of these findings, TAP IR can be considered as a first-line opioid for acute pain.
Topics: Acute Pain; Analgesics, Opioid; Humans; Observational Studies as Topic; Oxycodone; Randomized Controlled Trials as Topic; Tapentadol
PubMed: 31990693
DOI: 10.1097/AJP.0000000000000809 -
BioMed Research International 2019Oxycodone is a widely used opioid analgesic, which is involved in cancer pain and non-cancer pain. This study is intended to understand the publication characteristics...
BACKGROUND
Oxycodone is a widely used opioid analgesic, which is involved in cancer pain and non-cancer pain. This study is intended to understand the publication characteristics of oxycodone research field and assess the quality of pertinent articles from 1998 to 2017.
METHODS
Oxycodone-related publications from 1998 to 2017 were retrieved from the Web of Science (WOS) and PubMed database. These papers were coded across several categories, such as total number, journals, countries, institutions, authors and citations reports. And the analysis of co-occurrence keywords was handled by VOSviewer software.
RESULTS
According to search strategies, a total of 2659 articles on oxycodone were published in world from 1998 to 2017 in WOS. Among the top 10 most productive organizations, six of them were American institutes, two of them were pharmaceutical enterprises and the other three were Finnish, Australian and Canadian institutes, which is similar with the distribution by country/region. Drewes AM from Denmark published most articles and PAIN MEDICINE is the most productive journal in oxycodone area. Meanwhile, clinical studies occupy a dominant position during the past 20 years. The 10 most cited papers were listed. Among these articles, 8 of them are reviews and 2 of those are meta-analysis. And the last decade (2008-2017) displayed that the newest keywords focus on "double-blind", "randomized controlled trial" and "neuropathic pain".
CONCLUSIONS
The findings provided a comprehensive overview of oxycodone research. In view of the adverse effects of oxycodone, high-quality oxycodone studies both in basic studies and clinical trials need to be completed.
Topics: Analgesics, Opioid; Bibliometrics; Cancer Pain; Humans; Neuralgia; Oxycodone; Publications
PubMed: 31781650
DOI: 10.1155/2019/9096201 -
Pain Physician Nov 2019Opioid medications are frequently used effectively for analgesia in acute settings, however, they are associated with dependence and addiction, and were implicated in...
BACKGROUND
Opioid medications are frequently used effectively for analgesia in acute settings, however, they are associated with dependence and addiction, and were implicated in 47,600 American fatalities in 2017. Evidence suggests that despite guidelines and professional body recommendations, acute prescribing remains highly variable. Educational interventions targeting prescribers have potential to optimize prescribing in-line with evidence-based best practice.
OBJECTIVES
To identify the objective impacts of education interventions on opioid prescribing in the acute care setting.
STUDY DESIGN
A systematic literature review.
SETTING
The electronic databases MEDLINE, Embase, and Cochrane for works published until December 31, 2018. Bibliographies of relevant studies and the gray literature were also searched.
METHODS
Databases were searched for interventional studies (clinical trials and pre- and poststudies). Studies describing an educational intervention delivered to clinicians and reporting at least one objective measure of opioid use in the acute care setting were included. Studies reporting only subjective outcomes and those focused on chronic pain or set in primary care were excluded. Two reviewers (RB, TB) extracted data and assessed the quality of included studies using the Downs and Black Tool.
RESULTS
Nine studies met inclusion criteria; all used pre- and postdesigns. Three studies described stand-alone education, and the others described multifaceted interventions. All 9 interventions significantly reduced at least one of the following: high-risk agent use including meperidine use by up to 71%; total or daily dosage of opioids at discharge, including median morphine milligram equivalence (MME) from 90 mg to 45 mg per patient; and quantity of medications such as oxycodone supplied to patients, halved in one study from 6,170 expected to 2,932 supplied tablets. No increase in pain complaints or prescription refill requests were reported in those studies assessing these outcomes. The longest study examined prescribing 15 months after education delivery, reporting sustained practice changes.
LIMITATIONS
Overall study quality was fair to poor. Significant heterogeneity in settings, patient groups, methodologies, and outcomes prevented pooled quantitative analysis. No studies examined all available opioid agents or formulations.
CONCLUSIONS
These findings support prescriber education as an effective strategy to reduce opioid use and optimize prescribing in acute settings. Further research, particularly high quality randomized studies, describing the impact of education on all available opioid formulations and total MME is required. Reviewing the existing literature has offered useful models that can be implemented to improve care with opioid prescribing in acute settings.
KEY WORDS
Opioids, education, physician education, prescriber education, opioid education, opioid prescribing, systematic review, prescriptions, prevention.
Topics: Analgesics, Opioid; Drug Prescriptions; Humans; Opioid-Related Disorders; Oxycodone; Pain; Practice Patterns, Physicians'; Primary Health Care
PubMed: 31775401
DOI: No ID Found -
Scientific Reports Nov 2019Chemotherapy induced painful peripheral neuropathy (CIPN) is a common dose-limiting side effect of several chemotherapeutic agents. Despite large amounts of human and... (Meta-Analysis)
Meta-Analysis
Chemotherapy induced painful peripheral neuropathy (CIPN) is a common dose-limiting side effect of several chemotherapeutic agents. Despite large amounts of human and animal studies, there is no sufficiently effective pharmacological treatment for CIPN. Although reducing pain is often a focus of CIPN treatment, remarkably few analgesics have been tested for this indication in clinical trials. We conducted a systematic review and meta-analyses regarding the effects of analgesics on stimulus evoked pain-like behaviour during CIPN in animal models. This will form a scientific basis for the development of prospective human clinical trials. A comprehensive search identified forty-six studies. Risk of bias (RoB) analyses revealed that the design and conduct of the included experiments were poorly reported, and therefore RoB was unclear in most studies. Meta-analyses showed that administration of analgesics significantly increases pain threshold for mechanical (SMD: 1.68 [1.41; 1.82]) and cold (SMD: 1. 41 [0.99; 1.83]) evoked pain. Subgroup analyses revealed that dexmedetomidine, celecoxib, fentanyl, morphine, oxycodone and tramadol increased the pain threshold for mechanically evoked pain, and lidocaine and morphine for cold evoked pain. Altogether, this meta-analysis shows that there is ground to investigate the use of morphine in clinical trials. Lidocaine, dexmedetomidine, celecoxib, fentanyl, oxycodone and tramadol might be good alternatives, but more animal-based research is necessary.
Topics: Analgesics; Animals; Disease Models, Animal; Pain; Peripheral Nervous System Diseases
PubMed: 31772391
DOI: 10.1038/s41598-019-54152-8 -
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 -
Sleep Medicine Reviews Jun 2019Current guidelines recommend opioid therapy to chronic non-malignant pain (CNP) patients when the benefits for pain and function outweigh risks. This systematic review... (Meta-Analysis)
Meta-Analysis
Current guidelines recommend opioid therapy to chronic non-malignant pain (CNP) patients when the benefits for pain and function outweigh risks. This systematic review examined the effects of opioid therapy on sleep - a valued functional outcome- in CNP. Electronic and hand searches of relevant studies up through July 2017 identified 18 eligible studies providing data from 3,746 CNP patients for analysis. Twelve of these studies were randomised controlled trials of up to 12-month in duration. Morphine sulfate, oxycodone and transdermal fentanyl were the most tested therapies (n = 4 each). Only two studies used objective sleep measures in addition to self-report ratings, questionnaires or sleep diaries. Whilst calmer sleep with less body/leg movements and fewer awakenings could be achieved following opioid therapy, these might occur with increased sleep-disordered breathing and a much-shortened rapid eye movement (REM) sleep latency. Both the narrative synthesis and exploratory meta-analysis suggest that opioid therapy in CNP is associated with improved self-reported sleep quality. However, the effect is inconsistent, small (Standardised Mean Difference = 0.36), and may be accompanied by excessive daytime sleepiness. As a Cochrane-recommended assessment revealed "unclear" or "high" overall risk of bias for all studies, future opioid trials of stronger methodology and better reporting are needed to confirm and elucidate the effect.
Topics: Analgesics, Opioid; Chronic Pain; Humans; Sleep; Sleep Apnea, Obstructive; Sleep Wake Disorders
PubMed: 31085434
DOI: 10.1016/j.smrv.2019.03.005