Research Gaps on Methadone Harms and Comparative Harms: Findings From a Review of the Evidence for an American Pain Society and College on Problems of Drug Dependence Clinical Practice Guideline

Methadone-associated overdose deaths have dramatically increased. In order to inform an evidence-based clinical practice guideline to improve safety of methadone prescribing, the American Pain Society commissioned a systematic review on various aspects related to methadone safety. We searched Ovid MEDLINE, Cochrane Library, and PsycINFO databases through July 2012 to identify studies that addressed 1 or more of 17 Key Questions related to methadone safety; an update search was performed in 2014 for new studies related to methadone-related overdose and risks related to cardiac arrhythmias. A total of 168 studies met inclusion criteria for the review. The purpose of this article is to highlight critical research gaps in the literature related to methadone safety. These include lack of evidence on risk factors associated with methadone-overdose deaths and adverse events, limited evidence to evaluate the comparative mortality of methadone versus other opioids, insufficient evidence to fully understand the harms associated with methadone use during pregnancy, and insufficient evidence to determine effects of risk mitigation strategies such as electrocardiogram monitoring, strategies for managing patients with prolonged QTc intervals on screening, urine drug testing, alternative dosing regimens for initiation and titration of therapy, and timing of follow-up. Therefore, most guideline recommendations are based on weak evidence. More research is needed to guide safe methadone prescribing practices and decrease the adverse events associated with methadone.PerspectiveThis article summarizes critical research gaps in the literature related to methadone safety, based on a systematic review commissioned by the American Pain Society. Critical research gaps were identified in a number of areas, highlighting the need for additional research to guide safer prescribing and risk mitigation strategies.     

Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain

Use of chronic opioid therapy for chronic noncancer pain has increased substantially. The American Pain Society and the American Academy of Pain Medicine commissioned a systematic review of the evidence on chronic opioid therapy for chronic noncancer pain and convened a multidisciplinary expert panel to review the evidence and formulate recommendations. Although evidence is limited, the expert panel concluded that chronic opioid therapy can be an effective therapy for carefully selected and monitored patients with chronic noncancer pain. However, opioids are also associated with potentially serious harms, including opioid-related adverse effects and outcomes related to the abuse potential of opioids. The recommendations presented in this document provide guidance on patient selection and risk stratification; informed consent and opioid management plans; initiation and titration of chronic opioid therapy; use of methadone; monitoring of patients on chronic opioid therapy; dose escalations, high-dose opioid therapy, opioid rotation, and indications for discontinuation of therapy; prevention and management of opioid-related adverse effects; driving and work safety; identifying a medical home and when to obtain consultation; management of breakthrough pain; chronic opioid therapy in pregnancy; and opioid-related polices.PerspectiveSafe and effective chronic opioid therapy for chronic noncancer pain requires clinical skills and knowledge in both the principles of opioid prescribing and on the assessment and management of risks associated with opioid abuse, addiction, and diversion. Although evidence is limited in many areas related to use of opioids for chronic noncancer pain, this guideline provides recommendations developed by a multidisciplinary expert panel after a systematic review of the evidence.     

Methadone Overdose and Cardiac Arrhythmia Potential: Findings From a Review of the Evidence for an American Pain Society and College on Problems of Drug Dependence Clinical Practice Guideline

The number of deaths associated with methadone use increased dramatically in parallel with marked increases in its use, particularly for treatment of chronic pain. To develop a clinical guideline on methadone prescribing to reduce potential harms, the American Pain Society commissioned a review of various aspects related to methadone safety. This article summarizes evidence related to unintentional overdose due to methadone and harms related to cardiac arrhythmia potential. We searched Ovid MEDLINE, the Cochrane Library, and PsycINFO databases through January 2014 for studies assessing harms associated with methadone use; we judged 70 studies to be relevant and to meet inclusion criteria. The majority of studies on overdose and cardiac arrhythmia risk are observational and provide weak evidence on which to base clinical guidelines. In patients prescribed methadone for treatment of opioid dependence, data suggest that mortality benefits related to reduction in illicit drug use outweigh harms. Despite epidemiologic data showing marked increases in the numbers of methadone-related deaths that have been primarily attributed to increased use of methadone for chronic pain, evidence on methadone and mortality risk in this population has been somewhat contradictory. There is some evidence that recent initiation of methadone, psychiatric admissions, and concomitant use of benzodiazepines are associated with a higher risk for overdose. Evidence on cardiac risks is primarily limited to case reports of torsades de pointes, primarily in patients on high doses of methadone, and to studies showing an association between methadone use and prolongation of QTc intervals. Research is needed to understand the effectiveness of dosing methods, electrocardiogram monitoring, and other risk mitigation strategies in patients prescribed methadone.PerspectiveThis systematic review synthesizes the evidence related to methadone use and risk for overdose and cardiac arrhythmia. Findings regarding the association between methadone use and QTc interval prolongation and risk factors for methadone-associated overdose suggest potential targets for risk mitigation strategies, though research is needed to determine the effectiveness of such strategies at reducing adverse outcomes.     

Research Gaps on Use of Opioids for Chronic Noncancer Pain: Findings From a Review of the Evidence for an American Pain Society and American Academy of Pain Medicine Clinical Practice Guideline

Chronic noncancer pain is common and use of opioids is increasing. Previously published guidelines on use of opioids for chronic noncancer pain have been based primarily on expert consensus due to lack of strong evidence. We conducted searches on Ovid MEDLINE and the Cochrane databases through July 2008 to identify studies that addressed one or more of 37 Key Questions that a multidisciplinary expert panel identified as important to be answered to generate evidence-based recommendations on the use of opioids for chronic noncancer pain. A total of 14 systematic reviews, 38 randomized trials not included in a previously published systematic review, and 13 other studies met inclusion criteria. Almost all of the randomized trials of opioids for chronic noncancer pain were short-term efficacy studies. Critical research gaps on use of opioids for chronic noncancer pain include: lack of effectiveness studies on long-term benefits and harms of opioids (including drug abuse, addiction, and diversion); insufficient evidence to draw strong conclusions about optimal approaches to risk stratification, monitoring, or initiation and titration of opioid therapy; and lack of evidence on the utility of informed consent and opioid management plans, the utility of opioid rotation, the benefits and harms specific to methadone or higher doses of opioids, and treatment of patients with chronic noncancer pain at higher risk for drug abuse or misuse.PerspectiveCurrently, clinical decisions regarding the use of opioids for chronic noncancer pain need to be made based on weak evidence. Research funding priorities need to be set to address these critical research needs if the care of patients with chronic noncancer pain is to improve.     

Expert panel’s guideline on cervicogenic headache: The Chinese Association for the Study of Pain recommendation

Cervicogenic headache (CEH) has been recognized as a unique category of headache that can be difficult to diagnose and treat. In China, CEH patients are managed by many different specialties, and the treatment plans remain controversial. Therefore, there is a great need for comprehensive evidence-based Chinese experts’ recommendations for the management of CEH. The Chinese Association for the Study of Pain asked an expert panel to develop recommendations for a series of questions that are essential for daily clinical management of patients with CEH. A group of multidisciplinary Chinese Association for the Study of Pain experts identified the clinically relevant topics in CEH. A systematic review of the literature was performed, and evidence supporting the benefits and harms for the management of CEH was summarized. Twenty-four recommendations were finally developed through expert consensus voting for evidence quality and recommendation strength. We hope this guideline provides direction for clinicians and patients making treatment decisions for the management of CEH.     

American Society for Pain Management Nursing Guidelines on Monitoring for Opioid-Induced Advancing Sedation and Respiratory Depression: Revisions

ObjectivesThis report presents up-to-date evidence and expert consensus-based revisions to the ASPMN 2011 guidelines that inform interprofessional clinical decision-making for hospitalized adults receiving opioid analgesics.DesignSystematic review of the literature.MethodsA 14-member expert panel was charged with reviewing and grading the strength of scientific evidence published in peer reviewed journals and revising the ASPMN 2011 existing guidelines. Panel members formulated recommendations based on the strength of evidence and reached consensus through discussion, reappraisal of evidence, and voting by majority when necessary. The American Society of Anesthesiologists evidence categories for grading and classifying the strength of the evidence were used. Recommendations were subjected to a critical review by ASPMN members as well as external reviews.ResultsThe 2011 guidelines were found to still be relevant to clinical practice, but new evidence substantiated refinement and more specific recommendations for electronic monitoring. The revised guidelines present risk factors divided into three categories: patient-specific, treatment-related, and environment of care. Specific recommendations for the use of electronic monitoring are delineated.ConclusionsAll hospitalized patients that are administered opioids for acute pain are at risk of opioid induced advancing sedation and respiratory depression, but some patients are at high risk and require extra vigilance to prevent adverse events. All patients must be assessed for level of risk. Adaptations to the plan of care and monitoring strategies should be driven by iterative re-assessments according to level of risk.Nursing Practice ImplicationsOpioid medications continue to be a major component in the management of acute pain. Clinicians have the primary responsibility for safe and effective pain management. Evidence based monitoring strategies can improve patient safety with opioids.     

Safe and Appropriate Use of Methadone in Hospice and Palliative Care: Expert Consensus White Paper

Methadone has several unique characteristics that make it an attractive option for pain relief in serious illness, but the safety of methadone has been called into question after reports of a disproportionate increase in opioid-induced deaths in recent years. The American Pain Society, College on Problems of Drug Dependence, and the Heart Rhythm Society collaborated to issue guidelines on best practices to maximize methadone safety and efficacy, but guidelines for the end-of-life scenario have not yet been developed. A panel of 15 interprofessional hospice and palliative care experts from the U.S. and Canada convened in February 2015 to evaluate the American Pain Society methadone recommendations for applicability in the hospice and palliative care setting. The goal was to develop guidelines for safe and effective management of methadone therapy in hospice and palliative care. This article represents the consensus opinion of the hospice and palliative care experts for methadone use at end of life, including guidance on appropriate candidates for methadone, detail in dosing, titration, and monitoring of patients' response to methadone therapy.     

American Society for Pain Management Nursing Position Statement: Pain Management in Patients with Substance Use Disorders

The American Society for Pain Management Nursing (ASPMN) has updated its position statement on managing pain in patients with substance use disorders. This position statement is endorsed by the International Nurses Society on Addictions (IntNSA) and includes clinical practice recommendations based on current evidence. It is the position of ASPMN and IntNSA that every patient with pain, including those with substance use disorders, has the right to be treated with dignity, respect, and high-quality pain assessment and management. Failure to identify and treat the concurrent conditions of pain and substance use disorders will compromise the ability to treat either condition effectively. Barriers to caring for these patients include stigmatization, misconceptions, and limited access to providers skilled in these two categories of disorders. Topics addressed in this position statement include the scope of substance use and related disorders, conceptual models of addiction, ethical considerations, addiction risk stratification, and clinical recommendations.     

Non-Surgical Interventions for Lumbar Spinal Stenosis Leading To Neurogenic Claudication: A Clinical Practice Guideline

Lumbar spinal stenosis (LSS) causing neurogenic claudication (NC) is increasingly common with an aging population and can be associated with significant symptoms and functional limitations. We developed this guideline to present the evidence and provide clinical recommendations on nonsurgical management of patients with LSS causing NC. Using the GRADE approach, a multidisciplinary guidelines panel based recommendations on evidence from a systematic review of randomized controlled trials and systematic reviews published through June 2019, or expert consensus. The literature monitored up to October 2020. Clinical outcomes evaluated included pain, disability, quality of life, and walking capacity. The target audience for this guideline includes all clinicians, and the target patient population includes adults with LSS (congenital and/or acquired, lateral recess or central canal, with or without low back pain, with or without spondylolisthesis) causing NC. The guidelines panel developed 6 recommendations based on randomized controlled trials and 5 others based on professional consensus, summarized in 3 overarching recommendations: (Grade: statements are all conditional/weak recommendations) Recommendation 1. For patients with LSS causing NC, clinicians and patients may initially select multimodal care nonpharmacological therapies with education, advice and lifestyle changes, behavioral change techniques in conjunction with home exercise, manual therapy, and/or rehabilitation (moderate-quality evidence), traditional acupuncture on a trial basis (very low-quality evidence), and postoperative rehabilitation (supervised program of exercises and/or educational materials encouraging activity) with cognitive-behavioral therapy 12 weeks postsurgery (low-quality evidence). Recommendation 2. In patients LSS causing NC, clinicians and patients may consider a trial of serotonin–norepinephrine reuptake inhibitors or tricyclic antidepressants. (very low-quality evidence). Recommendation 3. For patients LSS causing NC, we recommend against the use of the following pharmacological therapies: nonsteroidal anti-inflammatory drugs, methylcobalamin, calcitonin, paracetamol, opioids, muscle relaxants, pregabalin (consensus-based), gabapentin (very low-quality), and epidural steroidal injections (high-quality evidence).PerspectiveThis guideline, on the basis of a systematic review of the evidence on the nonsurgical management of lumbar spine stenosis, provides recommendations developed by a multidisciplinary expert panel. Safe and effective non-surgical management of lumbar spine stenosis should be on the basis of a plan of care tailored to the individual and the type of treatment involved, and multimodal care is recommended in most situations.     

Systematic review of agents for the management of gastrointestinal mucositis in cancer patients

Purpose

The aim of this study was to review the available literature and define clinical practice guidelines for the use of agents for the prevention and treatment of gastrointestinal mucositis.

Methods

A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, and no guideline possible.

Results

A total of 251 clinical studies across 29 interventions were examined. Panel members were able to make one new evidence-based negative recommendation; two new evidence-based suggestions, and one evidence-based change from previous guidelines. Firstly, the panel recommends against the use of misoprostol suppositories for the prevention of acute radiation-induced proctitis. Secondly, the panel suggests probiotic treatment containing Lactobacillus spp., may be beneficial for prevention of chemotherapy and radiotherapy-induced diarrhea in patients with malignancies of the pelvic region. Thirdly, the panel suggests the use of hyperbaric oxygen as an effective means in treating radiation-induced proctitis. Finally, new evidence has emerged which is in conflict with our previous guideline surrounding the use of systemic glutamine, meaning that the panel is unable to form a guideline. No guideline was possible for any other agent, due to inadequate and/or conflicting evidence.

Conclusions

This updated review of the literature has allowed new recommendations and suggestions for clinical practice to be reached. This highlights the importance of regular updates.     

Pain Management and Risks Associated With Substance Use: Practice Recommendations

Assessing and managing pain while evaluating risks associated with substance use and substance use disorders continues to be a challenge faced by health care clinicians. The American Society for Pain Management Nursing and the International Nurses Society on Addictions uphold the principle that all persons with co-occurring pain and substance use or substance use disorders have the right to be treated with dignity and respect, and receive evidence-based, high quality assessment, and management for both conditions. The American Society for Pain Management Nursing and International Nurses Society on Addictions have updated their 2012 position statement on this topic supporting an integrated, holistic, multidimensional approach, which includes nonopioid and nonpharmacological modalities. Opioid use disorder is used as an exemplar for substance use disorders and clinical recommendations are included with expanded attention to risk assessment and mitigation with interventions targeted to minimize the risk for relapse or escalation of substance use. Opioids should not be excluded for anyone when indicated for pain management. A team-based approach is critical, promotes the active involvement of the person with pain and their support systems, and includes pain and addiction specialists whenever possible. Health care systems should establish policies and procedures that facilitate and support the principles and recommendations put forth in this article.     

Psychosocial health care needs assessment of adult cancer patients: a consensus-based guideline

Purpose

Although recommended as an essential part of cancer care, there is limited evidence regarding the optimum approach to psychosocial health care needs assessment in this setting. To address this gap, the Cancer Journey Action Group of the Canadian Partnership Against Cancer (CPAC) and the Canadian Association of Psychosocial Oncology (CAPO) partnered to develop consensus-based recommendations regarding the routine assessment of psychosocial and supportive care needs. The purpose of this paper is to summarize the evidence that informed the guideline and disseminate the recommendations developed by the expert panel.

Methods

Clinical practice recommendations were developed by a panel comprised of psychosocial and interdisciplinary experts. Recommendations were informed by a review of oncology clinical practice guidelines, systematic reviews, and primary research, through to May 2008. Following expert consensus on the recommendations, the clinical practice guideline was externally reviewed by a purposively selected sample of national and international interdisciplinary experts.

Results

A total of nine clinical practice guidelines, three systematic reviews, and 14 primary studies were included in the review. Overall, this body of literature suggested that routine collection of psychosocial health care data has an influence on communication with oncologists and other study specific outcomes, but the evidence was limited by heterogeneity and methodological limitations. Based on the interpretation of this body of evidence by clinical experts, research methodologists, and external reviewers, 12 substantive recommendations were developed regarding the process and parameters of psychosocial needs assessment in adult cancer patients.

Conclusion

Given the limitations in the current body of evidence, there remains a need for rigorous empirical research regarding the optimal approach to psychosocial needs assessment, including the specific characteristics that influence effectiveness on patient outcomes. This guideline fills an important gap in psychosocial care, regarding the routine assessment of psychosocial health care needs.     

European Headache Federation guideline on the use of monoclonal antibodies targeting the calcitonin gene related peptide pathway for migraine prevention – 2022 update

BackgroundA previous European Headache Federation (EHF) guideline addressed the use of monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway to prevent migraine. Since then, randomized controlled trials (RCTs) and real-world evidence have expanded the evidence and knowledge for those treatments. Therefore, the EHF panel decided to provide an updated guideline on the use of those treatments.MethodsThe guideline was developed following the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. The working group identified relevant questions, performed a systematic review and an analysis of the literature, assessed the quality of the available evidence, and wrote recommendations. Where the GRADE approach was not applicable, expert opinion was provided.ResultsWe found moderate to high quality of evidence to recommend eptinezumab, erenumab, fremanezumab, and galcanezumab in individuals with episodic and chronic migraine. For several important clinical questions, we found not enough evidence to provide evidence-based recommendations and guidance relied on experts’ opinion. Nevertheless, we provided updated suggestions regarding the long-term management of those treatments and their place with respect to the other migraine preventatives.ConclusionMonoclonal antibodies targeting the CGRP pathway are recommended for migraine prevention as they are effective and safe also in the long-term.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-022-01431-x.     

Management of Chronic Multisymptom Illness: Synopsis of the 2021 US Department of Veterans Affairs and US Department of Defense Clinical Practice Guideline

In 2019, senior leaders within the US Department of Veterans Affairs and the US Department of Defense commissioned the update of a clinical practice guideline for managing chronic multisymptom illness. Clinical experts were assembled across both agencies to systematically review evidence and to develop treatment recommendations based on that evidence. This effort resulted in the development of 29 evidence-based recommendations for providing care for individuals with chronic multisymptom illness.     

An Evidence-based Guideline for Prehospital Analgesia in Trauma

Abstract

Background. The management of acute traumatic pain is a crucial component of prehospital care and yet the assessment and administration of analgesia is highly variable, frequently suboptimal, and often determined by consensus-based regional protocols. Objective. To develop an evidence-based guideline (EBG) for the clinical management of acute traumatic pain in adults and children by advanced life support (ALS) providers in the prehospital setting. Methods. We recruited a multi-stakeholder panel with expertise in acute pain management, guideline development, health informatics, and emergency medical services (EMS) outcomes research. Representatives of the National Highway Traffic Safety Administration (sponsoring agency) and a major children's research center (investigative team) also contributed to the process. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to guide the process of question formulation, evidence retrieval, appraisal/synthesis, and formulation of recommendations. The process also adhered to the National Prehospital Evidence-Based Guideline (EBG) model process approved by the Federal Interagency Council for EMS and the National EMS Advisory Council. Results. Four strong and three weak recommendations emerged from the process; two of the strong recommendations were linked to high- and moderate-quality evidence, respectively. The panel recommended that all patients be considered candidates for analgesia, regardless of transport interval, and that opioid medications should be considered for patients in moderate to severe pain. The panel also recommended that all patients should be reassessed at frequent intervals using a standardized pain scale and that patients should be re-dosed if pain persists. The panel suggested the use of specific age-appropriate pain scales. Conclusion. GRADE methodology was used to develop an evidence-based guideline for prehospital analgesia in trauma. The panel issued four strong recommendations regarding patient assessment and narcotic medication dosing. Future research should define optimal approaches for implementation of the guideline as well as the impact of the protocol on safety and effectiveness metrics.     

NICE guidelines: the management, treatment and care of COPD

Over a year ago the National Institute for Clinical Excellence (NICE) commissioned national guidelines for managing chronic obstructive pulmonary disease (COPD) in both primary and secondary care. The resulting guidelines published earlier this year are the result of a systematic review of the evidence in the published literature and where this has not been available expert opinion has informed recommendations. The document makes over 200 recommendations for practice with seven key areas where it was felt that implementation of the recommendations would have the largest impact on the management of COPD. The result is a comprehensive document concentrating on the health aspects of COPD and the following article looks at the guidelines and concentrates on the seven priority areas.     

Spinal Manipulative Therapy and Other Conservative Treatments for Low Back Pain: A Guideline From the Canadian Chiropractic Guideline Initiative

Objective

The objective of this study was to develop a clinical practice guideline on the management of acute and chronic low back pain (LBP) in adults. The aim was to develop a guideline to provide best practice recommendations on the initial assessment and monitoring of people with low back pain and address the use of spinal manipulation therapy (SMT) compared with other commonly used conservative treatments.