Comprehensive, Evidence-Based, Consensus Guidelines for Prescription of Opioids for Chronic Non-Cancer Pain from the American Society of Interventional Pain Physicians (ASIPP).

BACKGROUND: Opioid prescribing in the United States is decreasing, however, the opioid epidemic is continuing at an uncontrollable rate. Available data show a significant number of opioid deaths, primarily associated with illicit fentanyl use. It is interesting to also note that the data show no clear correlation between opioid prescribing (either number of prescriptions or morphine milligram equivalent [MME] per capita), opioid hospitalizations, and deaths. Furthermore, the data suggest that the 2016 guidelines from the Centers for Disease Control and Prevention (CDC) have resulted in notable problems including increased hospitalizations and mental health disorders due to the lack of appropriate opioid prescribing as well as inaptly rapid tapering or weaning processes. Consequently, when examined in light of other policies and complications caused by COVID-19, a fourth wave of the opioid epidemic has been emerging. OBJECTIVES: In light of this, we herein seek to provide guidance for the prescription of opioids for the management of chronic non-cancer pain. These clinical practice guidelines are based upon a systematic review of both clinical and epidemiological evidence and have been developed by a panel of multidisciplinary experts assessing the quality of the evidence and the strength of recommendations and offer a clear explanation of logical relationships between various care options and health outcomes. METHODS: The methods utilized included the development of objectives and key questions for the various facets of opioid prescribing practice. Also utilized were employment of trustworthy standards, and appropriate disclosures of conflicts of interest(s). The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed. The recommendations were developed after the appropriate review of text and questions by a panel of multidisciplinary subject matter experts, who tabulated comments, incorporated changes, and developed focal responses to questions posed. The multidisciplinary panel finalized 20 guideline recommendations for prescription of opioids for chronic non-cancer pain. Summary of the results showed over 90% agreement for the final 20 recommendations with strong consensus. The consensus guidelines included 4 sections specific to opioid therapy with 1) ten recommendations particular to initial steps of opioid therapy; 2) five recommendations for assessment of effectiveness of opioid therapy; 3) three recommendations regarding monitoring adherence and side effects; and 4) two general, final phase recommendations. LIMITATIONS: There is a continued paucity of literature of long-term opioid therapy addressing chronic non-cancer pain. Further, significant biases exist in the preparation of guidelines, which has led to highly variable rules and regulations across various states. CONCLUSION: These guidelines were developed based upon a comprehensive review of the literature, consensus among expert panelists, and in alignment with patient preferences, and shared decision-making so as to improve the long-term pain relief and function in patients with chronic non-cancer pain. Consequently, it was concluded - and herein recommended - that chronic opioid therapy should be provided in low doses with appropriate adherence monitoring and understanding of adverse events only to those patients with a proven medical necessity, and who exhibit stable improvement in both pain relief and activities of daily function, either independently or in conjunction with other modalities of treatments.

Comprehensive, evidence-based, consensus guidelines for prescription of opioids for chronic non-cancer pain from the American Society of Interventional Pain Physicians (ASIPP)

Opioid prescribing in the United States is decreasing, however, the opioid epidemic is continuing at an uncontrollable rate. Available data show a significant number of opioid deaths, primarily associated with illicit fentanyl use. It is interesting to also note that the data show no clear correlation between opioid prescribing (either number of prescriptions or morphine milligram equivalent [MME] per capita), opioid hospitalizations, and deaths. Furthermore, the data suggest that the 2016 guidelines from the Centers for Disease Control and Prevention (CDC) have resulted in notable problems including increased hospitalizations and mental health disorders due to the lack of appropriate opioid prescribing as well as inaptly rapid tapering or weaning processes. Consequently, when examined in light of other policies and complications caused by COVID-19, a fourth wave of the opioid epidemic has been emerging. In light of this, we herein seek to provide guidance for the prescription of opioids for the management of chronic non-cancer pain. These clinical practice guidelines are based upon a systematic review of both clinical and epidemiological evidence and have been developed by a panel of multidisciplinary experts assessing the quality of the evidence and the strength of recommendations and offer a clear explanation of logical relationships between various care options and health outcomes. The methods utilized included the development of objectives and key questions for the various facets of opioid prescribing practice. Also utilized were employment of trustworthy standards, and appropriate disclosures of conflicts of interest(s). The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed. The recommendations were developed after the appropriate review of text and questions by a panel of multidisciplinary subject matter experts, who tabulated comments, incorporated changes, and developed focal responses to questions posed

A Systematic Review and Meta-analysis of the Effectiveness of Radiofrequency Neurotomy in Managing Chronic Neck Pain.

BACKGROUND: Extensive research into potential sources of neck pain and referred pain into the upper extremities and head has shown that the cervical facet joints can be a potential pain source confirmed by precision, diagnostic blocks. STUDY DESIGN: Systematic review and meta-analysis utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, quality assessment of the included studies, conventional and single-arm meta-analysis, and best evidence synthesis. OBJECTIVE: The objective of this systematic review and meta-analysis is to evaluate the effectiveness of radiofrequency neurotomy as a therapeutic cervical facet joint intervention in managing chronic neck pain. METHODS: Available literature was included. Methodologic quality assessment of studies was performed from 1996 to September 2021. The level of evidence of effectiveness was determined. RESULTS: Based on the qualitative and quantitative analysis with single-arm meta-analysis and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system of appraisal, with inclusion of one randomized controlled trial (RCT) of 12 patients in the treatment group and eight positive observational studies with inclusion of 589 patients showing positive outcomes with moderate to high clinical applicability, the evidence is level II in managing neck pain with cervical radiofrequency neurotomy. The evidence for managing cervicogenic headache was level III to IV with qualitative analysis and single-arm meta-analysis and GRADE system of appraisal, with the inclusion of 15 patients in the treatment group in a positive RCT and 134 patients in observational studies. An overwhelming majority of the studies produced multiple lesions. LIMITATIONS: There was a paucity of literature and heterogeneity among the available studies. CONCLUSION: This systematic review and meta-analysis shows level II evidence with radiofrequency neurotomy on a long-term basis in managing chronic neck pain with level III to IV evidence in managing cervicogenic headaches.

A Systematic Review and Meta-analysis of the Effectiveness of Radiofrequency Neurotomy in Managing Chronic Neck Pain.

Background: Extensive research into potential sources of neck pain and referred pain into the upper extremities and head has shown that the cervical facet joints can be a potential pain source confirmed by precision, diagnostic blocks. Study Design: Systematic review and meta-analysis utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, quality assessment of the included studies, conventional and single-arm meta-analysis, and best evidence synthesis. Objective: The objective of this systematic review and meta-analysis is to evaluate the effectiveness of radiofrequency neurotomy as a therapeutic cervical facet joint intervention in managing chronic neck pain. Methods: Available literature was included. Methodologic quality assessment of studies was performed from 1996 to September 2021. The level of evidence of effectiveness was determined. Results: Based on the qualitative and quantitative analysis with single-arm meta-analysis and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system of appraisal, with inclusion of one randomized controlled trial (RCT) of 12 patients in the treatment group and eight positive observational studies with inclusion of 589 patients showing positive outcomes with moderate to high clinical applicability, the evidence is level II in managing neck pain with cervical radiofrequency neurotomy. The evidence for managing cervicogenic headache was level III to IV with qualitative analysis and single-arm meta-analysis and GRADE system of appraisal, with the inclusion of 15 patients in the treatment group in a positive RCT and 134 patients in observational studies. An overwhelming majority of the studies produced multiple lesions. Limitations: There was a paucity of literature and heterogeneity among the available studies. Conclusion: This systematic review and meta-analysis shows level II evidence with radiofrequency neurotomy on a long-term basis in managing chronic neck pain with level III to IV evidence in managing cervicogenic headaches. Supplementary Information: The online version contains supplementary material available at 10.1007/s40122-022-00455-0.

COVID-19 Pandemic Reduced Utilization Of Interventional Techniques 18.7% In Managing Chronic Pain In The Medicare Population In 2020: Analysis Of Utilization Data From 2000 To 2020.

BACKGROUND: Multiple publications have shown the significant impact of the COVID-19 pandemic on US healthcare and increasing costs over the recent years in managing low back and neck pain as well as other musculoskeletal disorders. The COVID-19 pandemic has affected many modalities of treatments, including those related to chronic pain management, including both interventional techniques and opioids. While there have not been assessments of utilization of interventional techniques specific to the ongoing COVID-19 pandemic, previous analysis published with data from 2000 to 2018 demonstrated a decline in utilization of interventional techniques from 2009 to 2018 of 6.7%, with an annual decline of 0.8% per 100,000 fee-for-service (FFS) in the Medicare population. During that same time, the Medicare population has grown by 3% annually. OBJECTIVES: The objectives of this analysis include an evaluation of the impact of the COVID-19 pandemic, as well as an updated assessment of the utilization of interventional techniques in managing chronic pain in the Medicare population from 2010 to 2019, 2010 to 2020, and 2019 to 2020 in the FFS Medicare population of the United States. STUDY DESIGN: Utilization patterns and variables of interventional techniques with the impact of the COVID-19 pandemic in managing chronic pain were assessed from 2000 to 2020 in the FFS Medicare population of the United States. METHODS: The data for the analysis was obtained from the master database from the Centers for Medicare & Medicaid Services (CMS) physician/supplier procedure summary from 2000 to 2020. RESULTS: The results of the present investigation revealed an 18.7% decrease in utilization of all interventional techniques per 100,000 Medicare beneficiaries from 2019 to 2020, with a 19% decrease for epidural and adhesiolysis procedures, a 17.5% decrease for facet joint interventions and sacroiliac joint blocks, and a 25.4% decrease for disc procedures and other types of nerve blocks. The results differed from 2000 to 2010 with an annualized increase of 10.2% per 100,000 Medicare population compared to an annualized decrease of 0.4% from 2010 to 2019, and a 2.5% decrease from 2010 to 2020 for all interventional techniques. For epidural and adhesiolysis procedures decreases were more significant and annualized at 3.1% from 2010 to 2019, increasing the decline to 4.8% from 2010 to 2020. For facet joint interventions and sacroiliac joint blocks, the reversal of growth patterns was observed but maintained at an annualized rate increase of 2.1% from 2010 to 2019, which changed to a decrease of 0.01% from 2010 to 2020. Disc procedures and other types of nerve blocks showed similar patterns as epidurals with an 0.8% annualized reduction from 2010 to 2019, which was further reduced to 3.6% from 2010 to 2020 due to COVID-19. LIMITATIONS: Data for the COVID-19 pandemic impact were available only for 2019 and 2020 and only the FFS Medicare population was utilized; utilization patterns in Medicare Advantage Plans, which constitutes almost 40% of the Medicare enrollment in 2020 were not available. Moreover, this analysis shares the limitations present in all retrospective reviews of claims based datasets. CONCLUSION: The decline driven by the COVID-19 pandemic was 18.7% from 2019 to 2020. Overall decline in utilization in interventional techniques from 2010 to 2020 was 22.0% per 100,000 Medicare population, with an annual diminution of 2.5%, despite an increase in the population rate of 3.3% annualized (38.9% overall) and Medicare enrollees of 33.4% and 2.9% annually.

Fourth Wave of Opioid (Illicit Drug) Overdose Deaths and Diminishing Access to Prescription Opioids and Interventional Techniques: Cause and Effect.

BACKGROUND: In the midst of the COVID-19 pandemic, data has shown that age-adjusted overdose death rates involving synthetic opioids, psychostimulants, cocaine, and heroin have been increasing, including prescription opioid deaths, which were declining, but, recently, reversing the trends. Contrary to widely held perceptions, the problem of misuse, abuse, and diversion of prescription opioids has been the least of all the factors in recent years. Consequently, it is important to properly distinguish between the role of illicit and prescription opioids in the current opioid crisis. Multiple efforts have been based on consensus on administrative policies for certain harm reduction strategies for individuals actively using illicit drugs and reducing opioid prescriptions leading to curbing of medically needed opioids, which have been ineffective. While there is no denial that prescription opioids can be misused, abused, and diverted, the policies have oversimplified the issue by curbing prescription opioids and the pendulum has swung too far in the direction of severely limiting prescription opioids, without acknowledgement that opioids have legitimate uses for persons suffering from chronic pain. Similar to the opioid crisis, interventional pain management procedures have been affected by various policies being applied to reduce overuse, abuse, and finally utilization. Medical policies have been becoming more restrictive with reduction of access to certain procedures, with the pendulum swinging too far in the direction of limiting interventional techniques. Recent utilization assessments have shown a consistent decline for most interventional techniques, with a 18.7% decrease from 2019 to 2020. The causes for these dynamic changes are multifactorial likely including the misapplication of the 2016 Centers for Disease Control and Prevention (CDC) guidelines for prescribing opioids for chronic pain, the relative ease of access to illicit synthetic opioids and more recently issues related to the COVID-19 pandemic. In addition, recent publications have shown association of dose tapering with overdose or mental health crisis among patients prescribed long-term opioids. These findings are leading to the hypothesis that federal guidelines may inadvertently be contributing to an increase in overall opioid deaths and diminished access to interventional techniques. Together, these have resulted in a fourth wave of the opioid epidemic. METHODS: A narrative review. RESULTS: The fourth wave results from a confluence of multiple factors, including misapplication of CDC guidelines, the increased availability of illicit drugs, the COVID-19 pandemic, and policies reducing access to interventional procedures. The CDC guidelines and subsequent regulatory atmosphere have led to aggressive tapering up to and including, at times, the overall reduction or stoppage of opioid prescriptions. Forced tapering has been linked to an increase of 69% for overdoses and 130% for mental health crisis. The data thus suggests that the diminution in access to opioid prescriptions may be occurring simultaneously with an increase in illicit narcotic use.Combined with CDC guidelines, the curbing of opioid prescriptions to medically needed individuals, among non-opioid treatments, interventional techniques have been affected with declining utilization rates and medical policies reducing access to such modalities. CONCLUSION: The opioid overdose waves over the past three decades have resulted from different etiologies. Wave one was associated with prescription opioid overdose deaths and wave two with the rise in heroin and overdose deaths from 1999 to 2013. Wave three was associated with a rise in synthetic opioid overdose deaths. Sadly, wave four continues to escalate with increasing number of deaths as a confluence of factors including the CDC guidelines, the COVID pandemic, increased availability of illicit synthetic opioids and the reduction of access to interventional techniques, which leads patients to seek remedies on their own.

Evaluation of the Effectiveness of Autologous Bone Marrow Mesenchymal Stem Cells in the Treatment of Chronic Low Back Pain Due to Severe Lumbar Spinal Degeneration: A 12-Month, Open-Label, Prospective Controlled Trial.

BACKGROUND: Regenerative medicine interventions are applied to assist in the repair, and to potentially replace or restore damaged tissue through the use of autologous/allogenic biologics and it continues to expand. The anti-inflammatory, immunomodulatory, and regenerative properties of bone marrow mesenchymal stem cells (BM-MSCs), and investigation into their therapeutic efficacy and safety in patients with severe chronic low back pain, have not been demonstrated in controlled studies. Multiple pain generators have been hypothesized to be responsible in severe spinal degeneration and it is difficult to identify a single pain generator; consequently, resulting in inadequate therapeutic results. OBJECTIVES: The study was undertaken to evaluate the effectiveness of autologous bone marrow MSCs in the treatment of chronic low back pain due to severe lumbar spinal degeneration with involvement of multiple structures. STUDY DESIGN: Prospective, open-label, nonrandomized, parallel-controlled, 2-arm exploratory study. SETTING: A private, specialized, interventional pain management and regenerative medicine clinic. METHODS: The treatment group patients received a one-time bone marrow concentrate injection into spinal structures (i.e., discs, facets, spinal nerves, and sacroiliac joints), along with conventional treatment, whereas, the control group received conventional treatment with nonsteroid anti-inflammatory drugs, over-the-counter drugs, structured exercise programs, physical therapy, spinal injections and opioids, etc., as indicated. OUTCOMES ASSESSMENT: Outcomes were assessed utilizing multiple instruments, including the Oswestry Disability Index (ODI), Numeric Rating Scale (NRS-11), EuroQOL 5-Dimensional Questionnaire (EQ-5D-3L), Global Mental Health (GMH), and Global Physical Health (GPH). Multiple outcomes were assessed with primary outcomes being minimal clinically important differences (MCID) in ODI scores between the groups and/or a 2-point reduction in pain scores. In the study group, total nucleated cells, colony forming units-fibroblast, CD34-positive  cell numbers and platelets were also recorded, along with post-procedure magnetic resonance imaging changes. Outcomes were assessed at 1, 3, 6, and 12 months. RESULTS: Significant improvement was achieved in functional status measured by ODI, pain relief measured by NRS-11, and other parameters measured by EQ-5D-3L, GMH, and GPH, in the study group relative to the control group at all time periods. The results showed significant improvements at 12-month follow-up with 67% of the patients in the study group achieving MCID utilizing ODI when compared to 8% in the control group. Greater than 2-point pain reduction was seen in 74% of the patients at 3 months, 66% of the patients at 6 months, and 56% of the patients at 12 months. Both MCID and pain relief of 2 points were significantly different compared to the control group. Opioid use decreased in the investigational group, whereas, there was a slight increase in the control group. Age, gender, opioid use, and body mass index did not affect the outcomes in the stem cell group. LIMITATIONS: Single center, nonrandomized study. CONCLUSIONS: The first available controlled study utilizing BM-MSCs in severe degenerative spinal disease with interventions into multiple structures simultaneously, including disc, facet joints, nerve roots, and sacroiliac joint based on symptomatology, showed promising results.

Low-Dose Naltrexone Use for Patients with Chronic Regional Pain Syndrome: A Systematic Literature Review.

BACKGROUND: Complex regional pain syndrome is a rare, neuropathic disorder that affects fewer than 200,000 individuals in the United States annually. Current treatments often focus on pain management and fall short of relieving symptoms of pain and dystonia in patients. OBJECTIVE: The goal of this systematic qualitative review is to evaluate the evidence for the use of low-dose naltrexone in the treatment of chronic pain syndromes. STUDY DESIGN: This is a systematic review. METHODS: PubMed, Embase, and Web of Science were searched for articles containing the keywords "low-dose naltrexone" AND ("pain" OR "chronic pain" OR "fibromyalgia" OR "complex regional pain syndrome" OR "neuropathic pain" OR "nociceptive pain") between 1950 and July 17, 2020. A total of 30 publications were systematically reviewed. Exclusion criteria were articles that were unavailable in English, focused on acute pain only, and evaluated only animal models. Case studies were included for the purposes of our qualitative review. RESULTS: Out of 29 articles, we reviewed 11 prospective studies, 10 case studies, 3 systematic reviews, 2 retrospective studies, 2 simulation models, and one combination study. Articles focused on chronic pain syndromes as well as painful rheumatologic disorders and neurological disorders. We found that low-dose naltrexone treatment was positively associated with symptom relief in patients experiencing chronic pain, dystonia, and sleep disturbances. LIMITATIONS: Due to the limited number of available articles focusing on the treatment of complex regional pain syndrome with low-dose naltrexone, the majority of studies analyzed focused on other chronic pain syndromes. CONCLUSIONS: There is a need for additional prospective and interventional studies addressing the use of low-dose naltrexone in the treatment of complex regional pain syndrome symptoms.

COVID-19 and the Opioid Epidemic: Two Public Health Emergencies That Intersect With Chronic Pain.

The COVID-19 pandemic has affected the entire world and catapulted the United States into one of the deepest recessions in history. While this pandemic rages, the opioid crisis worsens. During this period, the pandemic has resulted in the decimation of most conventional medical services, including those of chronic pain management, with the exception of virtual care and telehealth. Many chronic pain patients have been impacted in numerous ways, with increases in cardiovascular disease, mental health problems, cognitive dysfunction, and early death. The epidemic has also resulted in severe economic and physiological consequences for providers. Drug deaths in America, which fell for the first time in 25 years in 2018, rose to record numbers in 2019 and are continuing to climb, worsened by the coronavirus pandemic. The opioid epidemic was already resurfacing with a 5% increase in overall deaths from 2018; however, the preliminary data show that prescription opioid deaths continued to decline, while at the same time deaths due to fentanyl, methamphetamine, and cocaine climbed, with some reductions in heroin deaths. The health tracker data also showed that along with an almost 88% decline in elective surgeries, pain-related prescriptions declined 15.1%. Despite increases in telehealth, outpatient services declined and only began returning towards normal at an extremely slow pace, accompanied by reduced productivity and increased practice costs. This review, therefore, emphasizes the devastating consequences of concurrent epidemics on chronic pain management and the need to develop best practice efforts to preserve access to treatment for chronic pain.

Methodology for Evidence Synthesis and Development of Comprehensive Evidence-Based Guidelines for Interventional Techniques in Chronic Spinal Pain.

BACKGROUND: The re-engineered definition of clinical guidelines in 2011 from the IOM (Institute of Medicine) states, "clinical practice guidelines are statements that include recommendations intended to optimize patient care that is informed by a systematic review of evidence and an assessment of the benefit and harms of alternative care options." The revised definition distinguishes between the term "clinical practice guideline" and other forms of clinical guidance derived from widely disparate development processes, such as consensus statements, expert advice, and appropriate use criteria. OBJECTIVE: To assess the literature and develop methodology for evidence synthesis and development of comprehensive evidence-based guidelines for interventional techniques in chronic spinal pain. METHODS: A systematic review of the literature including methodology of guideline development encompassing GRADE approach for guidance on evidence synthesis with recommendations. RESULTS: Some of the many factors described in 2011 continue as of 2020 and impede the development of clinical practice guidelines. These impediments include biases due to a variety of conflicts and confluence of interest, inappropriate and poor methodological quality, poor writing and ambiguous presentation, projecting a view that these are not applicable to individual patients or too restrictive with the elimination of clinician autonomy, and overzealous and inappropriate recommendations, either positive, negative, or non-committal. Thus, ideally, a knowledgeable, multidisciplinary panel of experts with true lack of bias and confluence of interest must develop guidelines based on a systematic review of the existing evidence. This manuscript describes evidence synthesis from observational studies, various types of randomized controlled trials (RCTs), and, finally, methodological and reporting quality of systematic reviews. The manuscript also describes various methods utilized in the assessment of the quality of observational studies, diagnostic accuracy studies, RCTs, and systematic reviews. LIMITATIONS: Paucity of publications with appropriate evidence synthesis methodology in reference to interventional techniques. CONCLUSION: This review described comprehensive evidence synthesis derived from systematic reviews, including methodologic quality and bias measurement. The manuscript described various methods utilized in the assessment of the quality of the systematic reviews, RCTs, diagnostic accuracy studies, and observational studies.

Epidural Interventions in the Management of Chronic Spinal Pain: American Society of Interventional Pain Physicians (ASIPP) Comprehensive Evidence-Based Guidelines.

BACKGROUND: Chronic spinal pain is the most prevalent chronic disease with employment of multiple modes of interventional techniques including epidural interventions. Multiple randomized controlled trials (RCTs), observational studies, systematic reviews, and guidelines have been published. The recent review of the utilization patterns and expenditures show that there has been a decline in utilization of epidural injections with decrease in inflation adjusted costs from 2009 to 2018. The American Society of Interventional Pain Physicians (ASIPP) published guidelines for interventional techniques in 2013, and guidelines for facet joint interventions in 2020. Consequently, these guidelines have been prepared to update previously existing guidelines. OBJECTIVE: To provide evidence-based guidance in performing therapeutic epidural procedures, including caudal, interlaminar in lumbar, cervical, and thoracic spinal regions, transforaminal in lumbar spine, and percutaneous adhesiolysis in the lumbar spine. METHODS: The methodology utilized included the development of objective and key questions with utilization of trustworthy standards. The literature pertaining to all aspects of epidural interventions was viewed with best evidence synthesis of available literature and  recommendations were provided. RESULTS: In preparation of the guidelines, extensive literature review was performed. In addition to review of multiple manuscripts in reference to utilization, expenditures, anatomical and pathophysiological considerations, pharmacological and harmful effects of drugs and procedures, for evidence synthesis we have included 47 systematic reviews and 43 RCTs covering all epidural interventions to meet the objectives.The evidence recommendations are as follows: Disc herniation: Based on relevant, high-quality fluoroscopically guided epidural injections, with or without steroids, and results of previous systematic reviews, the evidence is Level I for caudal epidural injections, lumbar interlaminar epidural injections, lumbar transforaminal epidural injections, and cervical interlaminar epidural injections with strong recommendation for long-term effectiveness.The evidence for percutaneous adhesiolysis in managing disc herniation based on one high-quality, placebo-controlled RCT is Level II with moderate to strong recommendation for long-term improvement in patients nonresponsive to conservative management and fluoroscopically guided epidural injections. For thoracic disc herniation, based on one relevant, high-quality RCT of thoracic epidural with fluoroscopic guidance, with or without steroids, the evidence is Level II with moderate to strong recommendation for long-term effectiveness.Spinal stenosis: The evidence based on one high-quality RCT in each category the evidence is Level III to II for fluoroscopically guided caudal epidural injections with moderate to strong recommendation and Level II for fluoroscopically guided lumbar and cervical interlaminar epidural injections with moderate to strong recommendation for long-term effectiveness.The evidence for lumbar transforaminal epidural injections is Level IV to III with moderate recommendation with fluoroscopically guided lumbar transforaminal epidural injections for long-term improvement. The evidence for percutaneous adhesiolysis in lumbar stenosis based on relevant, moderate to high quality RCTs, observational studies, and systematic reviews is Level II with moderate to strong recommendation for long-term improvement after failure of conservative management and fluoroscopically guided epidural injections. Axial discogenic pain: The evidence for axial discogenic pain without facet joint pain or sacroiliac joint pain in the lumbar and cervical spine with fluoroscopically guided caudal, lumbar and cervical interlaminar epidural injections, based on one relevant high quality RCT in each category is Level II with moderate to strong recommendation for long-term improvement, with or without steroids. Post-surgery syndrome: The evidence for lumbar and cervical post-surgery syndrome based on one relevant, high-quality RCT with fluoroscopic guidance for caudal and cervical interlaminar epidural injections, with or without steroids, is Level II with moderate to strong recommendation for long-term improvement. For percutaneous adhesiolysis, based on multiple moderate to high-quality RCTs and systematic reviews, the evidence is Level I with strong recommendation for long-term improvement after failure of conservative management and fluoroscopically guided epidural injections. LIMITATIONS: The limitations of these guidelines include a continued paucity of high-quality studies for some techniques and various conditions including spinal stenosis, post-surgery syndrome, and discogenic pain. CONCLUSIONS: These epidural intervention guidelines including percutaneous adhesiolysis were prepared with a comprehensive review of the literature with methodologic quality assessment and determination of level of evidence with strength of recommendations.

Triaging Interventional Pain Procedures During COVID-19 or Related Elective Surgery Restrictions: Evidence-Informed Guidance from the American Society of Interventional Pain Physicians (ASIPP).

BACKGROUND: The COVID-19 pandemic has worsened the pain and suffering of chronic pain patients due to stoppage of "elective" interventional pain management and office visits across the United States. The reopening of America and restarting of interventional techniques and elective surgical procedures has started. Unfortunately, with resurgence in some states, restrictions are once again being imposed. In addition, even during the Phase II and III of reopening, chronic pain patients and interventional pain physicians have faced difficulties because of the priority selection of elective surgical procedures.Chronic pain patients require high intensity care, specifically during a pandemic such as COVID-19. Consequently, it has become necessary to provide guidance for triaging interventional pain procedures, or related elective surgery restrictions during a pandemic. OBJECTIVES: The aim of these guidelines is to provide education and guidance for physicians, healthcare administrators, the public and patients during the COVID-19 pandemic. Our goal is to restore the opportunity to receive appropriate care for our patients who may benefit from interventional techniques. METHODS: The American Society of Interventional Pain Physicians (ASIPP) has created the COVID-19 Task Force in order to provide guidance for triaging interventional pain procedures or related elective surgery restrictions to provide appropriate access to interventional pain management (IPM) procedures in par with other elective surgical procedures. In developing the guidance, trustworthy standards and appropriate disclosures of conflicts of interest were applied with a section of a panel of experts from various regions, specialties, types of practices (private practice, community hospital and academic institutes) and groups. The literature pertaining to all aspects of COVID-19, specifically related to epidemiology, risk factors, complications, morbidity and mortality, and literature related to risk mitigation and stratification was reviewed. The evidence -- informed with the incorporation of the best available research and practice knowledge was utilized, instead of a simplified evidence-based approach. Consequently, these guidelines are considered evidence-informed with the incorporation of the best available research and practice knowledge. RESULTS: The Task Force defined the medical urgency of a case and developed an IPM acuity scale for elective IPM procedures with 3 tiers. These included urgent, emergency, and elective procedures. Examples of urgent and emergency procedures included new onset or exacerbation of complex regional pain syndrome (CRPS), acute trauma or acute exacerbation of degenerative or neurological disease resulting in impaired mobility and inability to perform activities of daily living. Examples include painful rib fractures affecting oxygenation and post-dural puncture headaches limiting the ability to sit upright, stand and walk. In addition, emergency procedures include procedures to treat any severe or debilitating disease that prevents the patient from carrying out activities of daily living. Elective procedures were considered as any condition that is stable and can be safely managed with alternatives. LIMITATIONS: COVID-19 continues to be an ongoing pandemic. When these recommendations were developed, different stages of reopening based on geographical regulations were in process. The pandemic continues to be dynamic creating every changing evidence-based guidance. Consequently, we provided evidence-informed guidance. CONCLUSION: The COVID-19 pandemic has created unprecedented challenges in IPM creating needless suffering for pain patients. Many IPM procedures cannot be indefinitely postponed without adverse consequences. Chronic pain exacerbations are associated with marked functional declines and risks with alternative treatment modalities. They must be treated with the concern that they deserve. Clinicians must assess patients, local healthcare resources, and weigh the risks and benefits of a procedure against the risks of suffering from disabling pain and exposure to the COVID-19 virus.

Lack of Superiority of Epidural Injections with Lidocaine with Steroids Compared to Without Steroids in Spinal Pain: A Systematic Review and Meta-Analysis.

BACKGROUND: Multiple randomized controlled trials (RCTs) and systematic reviews have been conducted to summarize the evidence for administration of local anesthetic (lidocaine) alone or with steroids, with discordant opinions, more in favor of equal effect with local anesthetic alone or with steroids. OBJECTIVE: To evaluate the comparative effectiveness of lidocaine alone and lidocaine with steroids in managing spinal pain to assess superiority or equivalency. STUDY DESIGN: A systematic review of RCTs assessing the effectiveness of lidocaine alone compared with addition of steroids to lidocaine in managing spinal pain secondary to multiple causes (disc herniation, radiculitis, discogenic pain, spinal stenosis, and post-surgery syndrome). METHODS: This systematic review was performed utilizing Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) for literature search, Cochrane review criteria, and Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB) to assess the methodologic quality assessment and qualitative analysis utilizing best evidence synthesis principles, and quantitative analysis utilizing conventional and single-arm meta-analysis. PubMed, Cochrane Library, US National Guideline Clearinghouse, Google Scholar, and prior systematic reviews and reference lists were utilized in the literature search from 1966 through December 2019. The evidence was summarized utilizing principles of best evidence synthesis on a scale of 1 to 5. OUTCOME MEASURES: A hard endpoint for the primary outcome was defined as the proportion of patients with 50% pain relief and improvement in function. Secondary outcome measures, or soft endpoints, were pain relief and/or improvement in function. Effectiveness was determined as short-term if it was less than 6 months. Improvement that lasted longer than 6 months, was defined as long-term. RESULTS: Based on search criteria, 15 manuscripts were identified and considered for inclusion for qualitative analysis, quantitative analysis with conventional meta-analysis, and single-arm meta-analysis. The results showed Level II, moderate evidence, for short-term and long-term improvement in pain and function with the application of epidural injections with local anesthetic with or without steroid in managing spinal pain of multiple origins. LIMITATIONS: Despite 15 RCTs, evidence may still be considered as less than optimal and further studies are recommended. CONCLUSION: Overall, the present meta-analysis shows moderate (Level II) evidence for epidural injections with lidocaine with or without steroids in managing spinal pain secondary to disc herniation, spinal stenosis, discogenic pain, and post-surgery syndrome based on relevant, high-quality RCTs. Results were similar for lidocaine, with or without steroids.

Safety and Effectiveness of Intravascular Mesenchymal Stem Cells to Treat Organ Failure and Possible Application in COVID-19 Complications.

BACKGROUND: Although only a small percentage of patients with COVID-19 deteriorate to a critical condition, because of the associated high mortality rate and the sheer number of cases, it imposes a tremendous burden on the society and unprecedented strains the health care resources. Albeit lung is the primary organ involved resulting in acute respiratory distress syndrome (ARDS), many patients additionally present with secondary multiorgan failure. Unfortunately, there is no definitive or curative treatment for this condition, and the management has been predominantly confined to supportive care, which necessitates an urgent need for novel therapies. Mesenchymal stem cell (MSC) therapy has a vast array of preclinical data and early, preliminary clinical data that suggests its potential to regenerate and restore the function of damaged tissues and organs. To date, there has been no review of all the clinical trials that have assessed the safety and efficacy of MSC therapy in organ failure commonly seen in seriously complicated COVID-19 patients. OBJECTIVES: To evaluate the effectiveness of MSC therapy in managing multiorgan failure, utilizing currently available literature. STUDY DESIGN: A review of human randomized controlled trials (RCTs) and observational studies assessing the role of MSC therapy in managing multiorgan failure. METHODS: PubMed, Cochrane Library, US National Guideline Clearinghouse, Google Scholar, and prior systematic reviews and reference lists were utilized in the literature search from 1990 through May 2020. Studies that included embryonic stem cells, induced pluripotent stem cells, differentiated MSCs into specific lineage cells, and hematopoietic stem cells were excluded. Trials with intraorgan infiltration of MSC were also excluded. OUTCOME MEASURES: The primary outcome evaluated the improvement in clinical assessment scores and indices of organ function. The secondary outcome assessed the safety of MSC therapy in the clinical trials. RESULTS: Based on search criteria, 12 studies were found for lung, 52 for heart, 23 for liver, 16 for stroke, and 9 for kidney. Among the 6 studies that specifically assessed the effectiveness of MSC therapy in ARDS, 4 showed positive outcomes. Forty-one of the 52 trials that examined ischemic and nonischemic heart failure reported beneficial effects. Twenty of 23 trials for liver failure from different etiologies revealed favorable outcomes. Nine out of the 15 studies evaluating stroke had satisfactory effects. However, only 3 out of the 9 studies for kidney failure showed positive results. Nonexpanded bone marrow mononuclear cells were used in most of the negative studies. The incidence of disease worsening or major complications was extremely rare from MSC therapy. LIMITATIONS: Among the studies evaluated, although there were many RCTs, there were also numerous case series. Additionally, most recruited a small number of patients. CONCLUSIONS: MSC therapy seems to be promising to treat multiorgan failure from COVID-19. More studies are urgently needed to assess both safety and efficacy.

Comprehensive Evidence-Based Guidelines for Facet Joint Interventions in the Management of Chronic Spinal Pain: American Society of Interventional Pain Physicians (ASIPP) Guidelines Facet Joint Interventions 2020 Guidelines.

BACKGROUND: Chronic axial spinal pain is one of the major causes of significant disability and health care costs, with facet joints as one of the proven causes of pain. OBJECTIVE: To provide evidence-based guidance in performing diagnostic and therapeutic facet joint interventions. METHODS: The methodology utilized included the development of objectives and key questions with utilization of trustworthy standards. The literature pertaining to all aspects of facet joint interventions, was reviewed, with a best evidence synthesis of available literature and utilizing grading for recommendations.Summary of Evidence and Recommendations:Non-interventional diagnosis: • The level of evidence is II in selecting patients for facet joint nerve blocks at least 3 months after onset and failure of conservative management, with strong strength of recommendation for physical examination and clinical assessment. • The level of evidence is IV for accurate diagnosis of facet joint pain with physical examination based on symptoms and signs, with weak strength of recommendation. Imaging: • The level of evidence is I with strong strength of recommendation, for mandatory fluoroscopic or computed tomography (CT) guidance for all facet joint interventions. • The level of evidence is III with weak strength of recommendation for single photon emission computed tomography (SPECT) . • The level of evidence is V with weak strength of recommendation for scintography, magnetic resonance imaging (MRI), and computed tomography (CT) .Interventional Diagnosis:Lumbar Spine: • The level of evidence is I to II with moderate to strong strength of recommendation for lumbar diagnostic facet joint nerve blocks. • Ten relevant diagnostic accuracy studies with 4 of 10 studies utilizing controlled comparative local anesthetics with concordant pain relief criterion standard of ≥80% were included. • The prevalence rates ranged from 27% to 40% with false-positive rates of 27% to 47%, with ≥80% pain relief.Cervical Spine: • The level of evidence is II with moderate strength of recommendation. • Ten relevant diagnostic accuracy studies, 9 of the 10 studies with either controlled comparative local anesthetic blocks or placebo controls with concordant pain relief with a criterion standard of ≥80% were included. • The prevalence and false-positive rates ranged from 29% to 60% and of 27% to 63%, with high variability. Thoracic Spine: • The level of evidence is II with moderate strength of recommendation. • Three relevant diagnostic accuracy studies, with controlled comparative local anesthetic blocks, with concordant pain relief, with a criterion standard of ≥80% were included. • The prevalence varied from 34% to 48%, whereas false-positive rates varied from 42% to 58%.Therapeutic Facet Joint Interventions: Lumbar Spine: • The level of evidence is II with moderate strength of recommendation for lumbar radiofrequency ablation with inclusion of 11 relevant randomized controlled trials (RCTs) with 2 negative studies and 4 studies with long-term improvement. • The level of evidence is II with moderate strength of recommendation for therapeutic lumbar facet joint nerve blocks with inclusion of 3 relevant randomized controlled trials, with long-term improvement. • The level of evidence is IV with weak strength of recommendation for lumbar facet joint intraarticular injections with inclusion of 9 relevant randomized controlled trials, with majority of them showing lack of effectiveness without the use of local anesthetic. Cervical Spine: • The level of evidence is II with moderate strength of recommendation for cervical radiofrequency ablation with inclusion of one randomized controlled trial with positive results and 2 observational studies with long-term improvement. • The level of evidence is II with moderate strength of recommendation for therapeutic cervical facet joint nerve blocks with inclusion of one relevant randomized controlled trial and 3 observational studies, with long-term improvement. • The level of evidence is V with weak strength of recommendation for cervical intraarticular facet joint injections with inclusion of 3 relevant randomized controlled trials, with 2 observational studies, the majority showing lack of effectiveness, whereas one study with 6-month follow-up, showed lack of long-term improvement. Thoracic Spine: • The level of evidence is III with weak to moderate strength of recommendation with emerging evidence for thoracic radiofrequency ablation with inclusion of one relevant randomized controlled trial and 3 observational studies. • The level of evidence is II with moderate strength of recommendation for thoracic therapeutic facet joint nerve blocks with inclusion of 2 randomized controlled trials and one observational study with long-term improvement. • The level of evidence is III with weak to moderate strength of recommendation for thoracic intraarticular facet joint injections with inclusion of one randomized controlled trial with 6 month follow-up, with emerging evidence. Antithrombotic Therapy: • Facet joint interventions are considered as moderate to low risk procedures; consequently, antithrombotic therapy may be continued based on overall general status. Sedation: • The level of evidence is II with moderate strength of recommendation to avoid opioid analgesics during the diagnosis with interventional techniques. • The level of evidence is II with moderate strength of recommendation that moderate sedation may be utilized for patient comfort and to control anxiety for therapeutic facet joint interventions. LIMITATIONS: The limitations of these guidelines include a paucity of high-quality studies in the majority of aspects of diagnosis and therapy. CONCLUSIONS: These facet joint intervention guidelines were prepared with a comprehensive review of the literature with methodologic quality assessment with determination of level of evidence and strength of recommendations. KEY WORDS: Chronic spinal pain, interventional techniques, diagnostic blocks, therapeutic interventions, facet joint nerve blocks, intraarticular injections, radiofrequency neurolysis.

Comprehensive evidence-based guidelines for facet joint interventions in the management of Chronic Spinal Pain: American Society of Interventional Pain Physicians (ASIPP) guidelines

Chronic axial spinal pain is one of the major causes of significant disability and health care costs, with facet joints as one of the proven causes of pain. To provide evidence-based guidance in performing diagnostic and therapeutic facet joint interventions. The methodology utilized included the development of objectives and key questions with utilization of trustworthy standards. The literature pertaining to all aspects of facet joint interventions, was reviewed, with a best evidence synthesis of available literature and utilizing grading for recommendations.

Expanded Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) as a Therapeutic Strategy in Managing Critically Ill COVID-19 Patients: The Case for Compassionate Use.

COVID-19 has affected the United States leading to a national emergency with health care and economic impact, propelling the country into a recession with disrupted lifestyles not seen in recent history. COVID-19 is a serious illness leading to multiple deaths in various countries including the United States. Several million Americans satisfy the Center for Disease Control and Prevention (CDC) criteria for being high risk. Unfortunately, the available supply of medical beds and equipment for mechanical ventilation are much less than is projected to be needed. The World Health Organization (WHO) and multiple agencies led by the CDC in the United States have attempted to organize intensive outbreak investigation programs utilizing appropriate preventive measures, evaluation, and treatment. The clinical spectrum of COVID-19 varies from asymptomatic forms to conditions encompassing multiorgan and systemic manifestations in terms of septic shock, and multiple organ dysfunction (MOD) syndromes. The presently approved treatments are supportive but not curative for the disease. There are multiple treatments being studied. These include vaccines, medications Remdesivir and hydroxychloroquine and potentially combination therapy. Finally, expanded umbilical cord mesenchymal stem cells or (UC-MSCs) may have a role and are being studied. The cure of COVID-19 is essentially dependent on the patients' own immune system. When the immune system is over activated in an attempt to kill the virus, this can lead to the production of a large number of inflammatory factors, resulting in severe cytokine storm. The cytokine storm may induce organ damage followed by the edema, dysfunction of air exchange, acute respiratory distress syndrome (ARDS), acute cardiac injury, and secondary infection, which may lead to death. Thus, at this point, the avoidance of the cytokine storm may be the key for the treatment of HCOV-19 infected patients.In China, where there was limited availability of effective modalities to manage COVID-19 several patients were treated with expanded UC-MSCs. Additionally, the Italian College of Anesthesia, Analgesia, Resuscitation and Intensive Care have reported guidelines to treat coronavirus patients with stem cells in the hope of decreasing the number of patients going to the ICU, and, also relatively quickly getting them out of ICU. In this manuscript, we describe the urgent need for various solutions, pathogenesis of coronavirus and the clinical evidence for treatment of COVID-19 with stem cells. The limited but emerging evidence regarding UC MSC in managing COVID-19 suggests that it might be considered for compassionate use in critically ill patients to reduce morbidity and mortality in the United States. The administration and Coronavirus Task Force might wish to approach the potential of expanded UC-MSCs as an evolutionary therapeutic strategy in managing COVID-19 illness with a 3-pronged approach: If proven safe and effective on a specific and limited basis…1. Minimize regulatory burden by all agencies so that critically ill COVID-19 patients will have access regardless of their financial circumstance.2. Institute appropriate safeguards to avoid negative consequences from unscrupulous actors.3. With proper informed consent from patients or proxy when necessary, and subject to accumulation of data in that cohort, allow the procedure to be initiated in critically ill patients who are not responding to conventional therapies.KEY WORDS: Coronavirus, COVID-19, cytokine storm, multiorgan failure, expanded umbilical cord mesenchymal stem cells.

Bone Marrow Concentrate (BMC) Therapy in Musculoskeletal Disorders: Evidence-Based Policy Position Statement of American Society of Interventional Pain Physicians (ASIPP).

BACKGROUND: The use of bone marrow concentrate (BMC) for treatment of musculoskeletal disorders has become increasingly popular over the last several years, as technology has improved along with the need for better solutions for these pathologies. The use of cellular tissue raises a number of issues regarding the US Food and Drug Administration's (FDA) regulation in classifying these treatments as a drug versus just autologous tissue transplantation. In the case of BMC in musculoskeletal and spine care, this determination will likely hinge on whether BMC is homologous to the musculoskeletal system and spine. OBJECTIVES: The aim of this review is to describe the current regulatory guidelines set in place by the FDA, specifically the terminology around "minimal manipulation" and "homologous use" within Regulation 21 CFR Part 1271, and specifically how this applies to the use of BMC in interventional musculoskeletal medicine. METHODS: The methodology utilized here is similar to the methodology utilized in preparation of multiple guidelines employing the experience of a panel of experts from various medical specialties and subspecialties from differing regions of the world. The collaborators who developed these position statements have submitted their appropriate disclosures of conflicts of interest. Trustworthy standards were employed in the creation of these position statements. The literature pertaining to BMC, its effectiveness, adverse consequences, FDA regulations, criteria for meeting the standards of minimal manipulation, and homologous use were comprehensively reviewed using a best evidence synthesis of the available and relevant literature. RESULTS/Summary of Evidence: In conjunction with evidence-based medicine principles, the following position statements were developed: Statement 1: Based on a review of the literature in discussing the preparation of BMC using accepted methodologies, there is strong evidence of minimal manipulation in its preparation, and moderate evidence for homologous utility for various musculoskeletal and spinal conditions qualifies for the same surgical exemption. Statement 2: Assessment of clinical effectiveness based on extensive literature shows emerging evidence for multiple musculoskeletal and spinal conditions. • The evidence is highest for knee osteoarthritis with level II evidence based on relevant systematic reviews, randomized controlled trials and nonrandomized studies. There is level III evidence for knee cartilage conditions. • Based on the relevant systematic reviews, randomized trials, and nonrandomized studies, the evidence for disc injections is level III. • Based on the available literature without appropriate systematic reviews or randomized controlled trials, the evidence for all other conditions is level IV or limited for BMC injections. Statement 3: Based on an extensive review of the literature, there is strong evidence for the safety of BMC when performed by trained physicians with the appropriate precautions under image guidance utilizing a sterile technique. Statement 4: Musculoskeletal disorders and spinal disorders with related disability for economic and human toll, despite advancements with a wide array of treatment modalities. Statement 5: The 21st Century Cures Act was enacted in December 2016 with provisions to accelerate the development and translation of promising new therapies into clinical evaluation and use. Statement 6: Development of cell-based therapies is rapidly proliferating in a number of disease areas, including musculoskeletal disorders and spine. With mixed results, these therapies are greatly outpacing the evidence. The reckless publicity with unsubstantiated claims of beneficial outcomes having putative potential, and has led the FDA Federal Trade Commission (FTC) to issue multiple warnings. Thus the US FDA is considering the appropriateness of using various therapies, including BMC, for homologous use. Statement 7: Since the 1980's and the description of mesenchymal stem cells by Caplan et al, (now called medicinal signaling cells), the use of BMC in musculoskeletal and spinal disorders has been increasing in the management of pain and promoting tissue healing. Statement 8: The Public Health Service Act (PHSA) of the FDA requires minimal manipulation under same surgical procedure exemption. Homologous use of BMC in musculoskeletal and spinal disorders is provided by preclinical and clinical evidence. Statement 9: If the FDA does not accept BMC as homologous, then it will require an Investigational New Drug (IND) classification with FDA (351) cellular drug approval for use. Statement 10: This literature review and these position statements establish compliance with the FDA's intent and corroborates its present description of BMC as homologous with same surgical exemption, and exempt from IND, for use of BMC for treatment of musculoskeletal tissues, such as cartilage, bones, ligaments, muscles, tendons, and spinal discs. CONCLUSIONS: Based on the review of all available and pertinent literature, multiple position statements have been developed showing that BMC in musculoskeletal disorders meets the criteria of minimal manipulation and homologous use. KEY WORDS: Cell-based therapies, bone marrow concentrate, mesenchymal stem cells, medicinal signaling cells, Food and Drug Administration, human cells, tissues, and cellular tissue-based products, Public Health Service Act (PHSA), minimal manipulation, homologous use, same surgical procedure exemption.