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Arquivos de Neuro-psiquiatria 2020Central neuropathic pain (CNP) is often refractory to available therapeutic strategies and there are few evidence-based treatment options. Many patients with neuropathic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Central neuropathic pain (CNP) is often refractory to available therapeutic strategies and there are few evidence-based treatment options. Many patients with neuropathic pain are not diagnosed or treated properly. Thus, consensus-based recommendations, adapted to the available drugs in the country, are necessary to guide clinical decisions.
OBJECTIVE
To develop recommendations for the treatment of CNP in Brazil.
METHODS
Systematic review, meta-analysis, and specialists opinions considering efficacy, adverse events profile, cost, and drug availability in public health.
RESULTS
Forty-four studies on CNP treatment were found, 20 were included in the qualitative analysis, and 15 in the quantitative analysis. Medications were classified as first-, second-, and third-line treatment based on systematic review, meta-analysis, and expert opinion. As first-line treatment, gabapentin, duloxetine, and tricyclic antidepressants were included. As second-line, venlafaxine, pregabalin for CND secondary to spinal cord injury, lamotrigine for CNP after stroke, and, in association with first-line drugs, weak opioids, in particular tramadol. For refractory patients, strong opioids (methadone and oxycodone), cannabidiol/delta-9-tetrahydrocannabinol, were classified as third-line of treatment, in combination with first or second-line drugs and, for central nervous system (CNS) in multiple sclerosis, dronabinol.
CONCLUSIONS
Studies that address the treatment of CNS are scarce and heterogeneous, and a significant part of the recommendations is based on experts opinions. The CNP approach must be individualized, taking into account the availability of medication, the profile of adverse effects, including addiction risk, and patients' comorbidities.
Topics: Analgesics, Opioid; Brazil; Consensus; Humans; Neuralgia; Neurology
PubMed: 33331468
DOI: 10.1590/0004-282X20200166 -
Pain and Therapy Jun 2021Peripheral neuropathic pain (PNP) arises either acutely or in the chronic phase of a lesion or disease of the peripheral nervous system and is associated with a notable... (Review)
Review
INTRODUCTION
Peripheral neuropathic pain (PNP) arises either acutely or in the chronic phase of a lesion or disease of the peripheral nervous system and is associated with a notable disease burden. The management of PNP is often challenging. The aim of this systematic review was to evaluate current evidence, derived from randomized controlled trials (RCTs) that have assessed pharmacological interventions for the treatment of PNP due to polyneuropathy (PN).
METHODS
A systematic search of the PubMed database led to the identification of 538 papers, of which 457 were excluded due to not meeting the eligibility criteria, and two articles were identified through screening of the reference lists of the 81 eligible studies. Ultimately, 83 papers were included in this systematic review.
RESULTS
The best available evidence for the management of painful diabetic polyneuropathy (DPN) is for amitriptyline, duloxetine, gabapentin, pregabalin and venlafaxine as monotherapies and oxycodone as add-on therapy (level II of evidence). Tramadol appears to be effective when used as a monotherapy and add-on therapy in patients with PN of various etiologies (level II of evidence). Weaker evidence (level III) is available on the effectiveness of several other agents discussed in this review for the management of PNP due to PN.
DISCUSSION
Response to treatment may be affected by the underlying pathophysiological mechanisms that are involved in the pathogenesis of the PN and, therefore, it is very important to thoroughly investigate patients presenting with PNP to determine the causes of this neuropathy. Future RCTs should be conducted to shed more light on the use of pharmacological approaches in patients with other forms of PNP and to design specific treatment algorithms.
PubMed: 33145709
DOI: 10.1007/s40122-020-00210-3 -
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 -
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 -
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