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Short-term prediction of opioid prescribing patterns for orthopaedic surgical procedures: a machine learning framework

Mortaz, Ebrahim; Dag, Ali; Hutzler, Lorraine; Gharibo, Christopher; Anzisi, Lisa; Bosco, Joseph
Overprescribing of opioids after surgical procedures can increase the risk of addiction in patients, and under prescribing can lead to poor quality of care. In this study, we propose a machine learning-based predictive framework to identify the varying effects of factors that are related to the opioid prescription amount after orthopaedic surgery. To predict the prescription classes, we train multiple classifiers combined with random and SMOTE over-sampling and weight-balancing techniques to cope with the imbalance state of the dataset. Our results show that the gradient boosting machines (XGB) with SMOTE achieve the highest classification accuracy. Our proposed analytical framework can be employed to assist and therefore, enable the surgeons to determine the timely changing effects of these variables.
SCOPUS:85099588238
ISSN: 2573-234x
CID: 4770092

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

Manchikanti, Laxmaiah; Knezevic, Nebojsa Nick; Navani, Annu; Christo, Paul J; Limerick, Gerard; Calodney, Aaron K; Grider, Jay; Harned, Michael E; Cintron, Lynn; Gharibo, Christopher G; Shah, Shalini; Nampiaparampil, Devi E; Candido, Kenneth D; Soin, Amol; Kaye, Alan D; Kosanovic, Radomir; Magee, Trevor R; Beall, Douglas P; Atluri, Sairam; Gupta, Myank; Helm Ii, Standiford; Wargo, Bradley W; Diwan, Sudhir; Aydin, Steve M; Boswell, Mark V; Haney, Bill W; Albers, Sheri L; Latchaw, Richard; Abd-Elsayed, Alaa; Conn, Ann; Hansen, Hans; Simopoulos, Thomas T; Swicegood, John R; Bryce, David A; Singh, Vijay; Abdi, Salahadin; Bakshi, Sanjay; Buenaventura, Ricardo M; Cabaret, Joseph A; Jameson, Jessica; Jha, Sunny; Kaye, Adam M; Pasupuleti, Ramarao; Rajput, Kartic; Sanapati, Mahendra R; Sehgal, Nalini; Trescot, Andrea M; Racz, Gabor B; Gupta, Sanjeeva; Sharma, Manohar Lal; Grami, Vahid; Parr, Allan T; Knezevic, Emilija; Datta, Sukdeb; Patel, Kunj G; Tracy, Deborah H; Cordner, Harold J; Snook, Lee T; Benyamin, Ramsin M; Hirsch, Joshua A
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/CONCLUSIONS: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.
PMID: 33492918
ISSN: 2150-1149
CID: 4766982

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

Gharibo, Christopher; Sharma, Amit; Soin, Amol; Shah, Shalini; Diwan, Sudhir; Buenaventura, Ricardo; Nampiaparampil, Devi E; Aydin, Steve; Bakshi, Sanjay; Abdi, Salahadin; Jha, Sachin Sunny; Cordner, Harold; Kaye, Alan D; Abd-Elsayed, Alaa; Candido, Kenneth D; Knezevic, Nebojsa Nick; Atluri, Sairam; Wargo, Bradley W; Sanapati, Mahendra R; Datta, Sukdeb; Hirsch, Joshua A; Manchikanti, Laxmaiah; Rajput, Kartic
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 emergent, urgent, and elective procedures. Examples of emergent and urgent 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, urgent 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.
PMID: 32942785
ISSN: 2150-1149
CID: 4609582

Evidence-Based Risk Mitigation and Stratification During COVID-19 for Return to Interventional Pain Practice: American Society of Interventional Pain Physicians (ASIPP) Guidelines

Shah, Shalini; Diwan, Sudhir; Soin, Amol; Rajput, Kartic; Mahajan, Amit; Manchikanti, Laxmaiah; Kaye, Alan D; Hirsch, Joshua A; Gharibo, Christopher
BACKGROUND:Chronic pain patients require continuity of care even during the COVID-19 pandemic, which has drastically changed healthcare and other societal practices. The American Society of Interventional Pain Physicians (ASIPP) has created the COVID-ASIPP Risk Mitigation & Stratification (COVID-ARMS) Return to Practice Task Force in order to provide guidance for safe and strategic reopening. OBJECTIVES:The aims are to provide education and guidance for interventional pain specialists and their patients during the COVID-19 pandemic that minimizes COVID-related morbidity while allowing a return to interventional pain care. METHODS:The methodology utilized included the development of objectives and key questions with utilization of trustworthy standards, appropriate disclosures of conflicts of interest, as well as a panel of experts from various regions, specialities, 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 were reviewed. The principles of best evidence synthesis of available literature and grading for recommendations as described by the Agency for Healthcare Research and Quality (AHRQ) typically utilized in ASIPP guideline preparation was not utilized in these guidelines due to limitations because of their lack of available literature on COVID-19, risk mitigation and stratification. These guidelines are considered evidence -- informed with incorporation of best available research and practice knowledge. Consequently, these guidelines are considered evidence-informed with incorporation of best available research and practice knowledge. RESULTS:Numerous risk factors have emerged that predispose patients to contracting COVID-19 and/or having a more severe course of the infection. COVID-19 may have mild symptoms, even be asymptomatic, or may be severe and life threatening. Older age and certain comorbidities, such as underlying pulmonary or cardiovascular disease, have been associated with worse outcomes. In pain care, COVID-19 patients are a heterogeneous group with some individuals relatively healthy and having only a short course of manageable symptoms while others become critically ill. It is necessary to assess patients on a case-by-case basis and craft individualized care recommendations. A COVID-ARMS risk stratification tool was created to quickly and objectively assess patients. Interventional pain specialists and their patients may derive important benefits from evidence-informed risk stratification, protective strategies to prevent infection, and the gradual resumption of treatments and procedures to manage pain. LIMITATIONS:COVID-19 was an ongoing pandemic at the time during which these recommendations were developed. The pandemic has created a fluid situation in terms of evidence-informed guidance. As more and better evidence is gathered, these recommendations may be modified. CONCLUSIONS:Chronic pain patients require continuity of care but during the time of the COVID-19 pandemic, steps must be taken to stratify risks and protect patients from possible infection to safeguard them from COVID-19-related illness and transmitting the disease to others. Pain specialists should optimize telemedicine encounters with their pain patients, be cognizant of risks of COVID-19 morbidity, and take steps to evaluate risk-benefit on a case-by-case basis. Pain specialists may return to practice with lower-risk patients and appropriate safeguards.
PMID: 32942784
ISSN: 2150-1149
CID: 4609572

The Technological Impact of COVID-19 on the Future of Education and Health Care Delivery

Shah, Shalini; Diwan, Sudhir; Kohan, Lynn; Rosenblum, David; Gharibo, Christopher; Soin, Amol; Sulindro, Adrian; Nguyen, Quinn; Provenzano, David A
BACKGROUND:The unexpected COVID-19 crisis has disrupted medical education and patient care in unprecedented ways. Despite the challenges, the health-care system and patients have been both creative and resilient in finding robust "temporary" solutions to these challenges. It is not clear if some of these COVID-era transitional steps will be preserved in the future of medical education and telemedicine. OBJECTIVES:The goal of this commentary is to address the sometimes substantial changes in medical education, continuing medical education (CME) activities, residency and fellowship programs, specialty society meetings, and telemedicine, and to consider the value of some of these profound shifts to "business as usual" in the health-care sector. METHODS:This is a commentary is based on the limited available literature, online information, and the front-line experiences of the authors. RESULTS:COVID-19 has clearly changed residency and fellowship programs by limiting the amount of hands-on time physicians could spend with patients. Accreditation Council for Graduate Medicine Education has endorsed certain policy changes to promote greater flexibility in programs but still rigorously upholds specific standards. Technological interventions such as telemedicine visits with patients, virtual meetings with colleagues, and online interviews have been introduced, and many trainees are "techno-omnivores" who are comfortable using a variety of technology platforms and techniques. Webinars and e-learning are gaining traction now, and their use, practicality, and cost-effectiveness may make them important in the post-COVID era. CME activities have migrated increasingly to virtual events and online programs, a trend that may also continue due to its practicality and cost-effectiveness. While many medical meetings of specialty societies have been postponed or cancelled altogether, technology allows for virtual meetings that may offer versatility and time-saving opportunities for busy clinicians. It may be that future medical meetings embrace a hybrid approach of blending digital with face-to-face experience. Telemedicine was already in place prior to the COVID-19 crisis but barriers are rapidly coming down to its widespread use and patients seem to embrace this, even as health-care systems navigate the complicated issues of cybersecurity and patient privacy. Regulatory guidance may be needed to develop safe, secure, and patient-friendly telehealth applications. Telemedicine has affected the prescribing of controlled substances in which online counseling, informed consent, and follow-up must be done in a virtual setting. For example, pill counts can be done in a video call and patients can still get questions answered about their pain therapy, although it is likely that after the crisis, prescribing controlled substances may revert to face-to-face visits. LIMITATIONS:The health-care system finds itself in a very fluid situation at the time this was written and changes are still occurring and being assessed. CONCLUSIONS:Many of the technological changes imposed so abruptly on the health-care system by the COVID-19 pandemic may be positive and it may be beneficial that some of these transitions be preserved or modified as we move forward. Clinicians must be objective in assessing these changes and retaining those changes that clearly improve health-care education and patient care as we enter the COVID era.
PMID: 32942794
ISSN: 2150-1149
CID: 4608212

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

Manchikanti, Laxmaiah; Kaye, Alan D; Soin, Amol; Albers, Sheri L; Beall, Douglas; Latchaw, Richard; Sanapati, Mahendra R; Shah, Shalini; Atluri, Sairam; Abd-Elsayed, Alaa; Abdi, Salahadin; Aydin, Steve; Bakshi, Sanjay; Boswell, Mark V; Buenaventura, Ricardo; Cabaret, Joseph; Calodney, Aaron K; Candido, Kenneth D; Christo, Paul J; Cintron, Lynn; Diwan, Sudhir; Gharibo, Christopher; Grider, Jay; Gupta, Mayank; Haney, Bill; Harned, Michael E; Helm Ii, Standiford; Jameson, Jessica; Jha, Sunny; Kaye, Adam M; Knezevic, Nebojsa Nick; Kosanovic, Radomir; Manchikanti, Maanasa V; Navani, Annu; Racz, Gabor; Pampati, Vidyasagar; Pasupuleti, Ramarao; Philip, Cyril; Rajput, Kartic; Sehgal, Nalini; Sudarshan, Gururau; Vanaparthy, Rachana; Wargo, Bradley W; Hirsch, Joshua A
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/CONCLUSIONS: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/UNASSIGNED:Chronic spinal pain, interventional techniques, diagnostic blocks, therapeutic interventions, facet joint nerve blocks, intraarticular injections, radiofrequency neurolysis.
PMID: 32503359
ISSN: 2150-1149
CID: 4477552

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

Manchikanti, Laxmaiah; Centeno, Christopher J; Atluri, Sairam; Albers, Sheri L; Shapiro, Shane; Malanga, Gerard A; Abd-Elsayed, Alaa; Jerome, Mairin; Hirsch, Joshua A; Kaye, Alan D; Aydin, Steve M; Beall, Douglas; Buford, Don; Borg-Stein, Joanne; Buenaventura, Ricardo M; Cabaret, Joseph A; Calodney, Aaron K; Candido, Kenneth D; Cartier, Cameron; Latchaw, Richard; Diwan, Sudhir; Dodson, Ehren; Fausel, Zachary; Fredericson, Michael; Gharibo, Christopher G; Gupta, Mayank; Kaye, Adam M; Knezevic, Nebojsa Nick; Kosanovic, Radomir; Lucas, Matthew; Manchikanti, Maanasa V; Mason, R Amadeus; Mautner, Kenneth; Murala, Samuel; Navani, Annu; Pampati, Vidyasagar; Pastoriza, Sarah; Pasupuleti, Ramarao; Philip, Cyril; Sanapati, Mahendra R; Sand, Theodore; Shah, Rinoo V; Soin, Amol; Stemper, Ian; Wargo, Bradley W; Hernigou, Philippe
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/OBJECTIVE: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/UNASSIGNED: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.
PMID: 32214287
ISSN: 2150-1149
CID: 4358072

The pharmacological management of dental pain

Pergolizzi, Joseph V; Magnusson, Peter; LeQuang, Jo Ann; Gharibo, Christopher; Varrassi, Giustino
Introduction: Dental pain is primarily treated by dentists and emergency medicine clinicians and may occur because of insult to the tooth or oral surgery. The dental impaction pain model (DIPM) has been widely used in clinical studies of analgesic agents and is generalizable to many other forms of pain.Areas Covered: The authors discuss the DIPM, which has allowed for important head-to-head studies of analgesic agents, such as acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and combinations. Postsurgical dental pain follows a predictable trajectory over the course of one to 3 days. Dental pain may have odontic origin or may be referred pain from other areas of the body.Expert opinion: Pain following oral surgery has sometimes been treated with longer-than-necessary courses of opioid therapy. Postsurgical dental pain may be moderate to severe but typically resolves in a day or two after the extraction. Opioid monotherapy, rarely used in dentistry but combination therapy (opioid plus acetaminophen or an NSAID), was sometimes used as well as nonopioid analgesic monotherapy. The dental impaction pain model has been valuable in the study of analgesics but does not address all painful conditions, for example, pain with a neuropathic component.
PMID: 32027199
ISSN: 1744-7666
CID: 4301482

Eastern Pain Association Annual Meeting 2019 Abstract Session Award Winners [Meeting Abstract]

Gharibo, Christopher; Nicholas, D; Ohara, K; Cao, L; Saint-Preux, Fabienne; Mendoza, J; Portugal, Salvador; Gupta, A; Sze-Tu, R; Ibim, SE; Levy, HJ; El-Amin, SF III
(1) Spinal Cord Microglial Phenotypic Changes Following Sciatic Nerve Crush in CD137LKO Mice / David Nicholas, Kinuyo Ohara, Ling Cao -- (2) Notalgia Paresthetica Successfully Treated with Cervical Epidural Injection and Occipital Nerve Block: A Case Report / Fabienne Saint-Preux, Justin Mendoza, Salvador Portugal
ISI:000527919600001
ISSN: 1178-7090
CID: 4630782

Long-term treatment with capsaicin 8% patches: A subgroup analysis in patients with postherpetic neuralgia from an open-label study [Meeting Abstract]

Gharibo, C; Eerdekens, M; Engelen, S; Marcondes, L
Purpose Painful neuropathy or peripheral neuropathic pain (PNP) is a common neurological condition estimated to affect ~7-8% of the general population in Europe. Managing patients with PNP is challenging; it often becomes chronic and can have a significant impact on quality of life. According to the revised International Association for the Study of Pain (IASP) recommendations for ICD11, PNP is considered to be a distinct chronic pain condition (Scholz et al., 2019)1. Postherpetic neuralgia (PHN) following shingles infection, has specifically been named as one of the PNP conditions. High concentration 8% capsaicin patch (HCCP) is commonly recommended as a second line therapy for PHN. HCCP is indicated for the treatment of peripheral neuropathic pain (PNP) in the EU and for the treatment of neuropathic pain associated with postherpetic neuralgia (PHN) and for neuropathic pain associated with diabetic peripheral neuropathy (DPN) of the feet in the US. Capsaicin is a highly selective, potent and highaffinity exogenous agonist for the transient receptor potential cation channel subfamily V member 1 (TRPV1) receptors which, through a combination of activities, defunctionalizes nociceptor fibers and reduces cutaneous hypersensitivity. As a result, capsaicin is an attractive peripherally acting treatment to control localized pain, hyperalgesia, or allodynia (Anand and Bley, 2011)2. The HCCP delivers the drug effectively and directly to the skin while limiting the risk of systemic effects and drug interactions. Whilst controlled trials have demonstrated the safety and effectiveness of capsaicin patches, the STRIDE study was designed to investigate the long-term safety of repeated patch administration in patients with non-diabetic neuropathic pain (Galvez et al., 2017)3. The present analysis considers the effect on treatment outcomes among a subgroup of patients with PHN included in the STRIDE study. Methods The STRIDE study was an open-label, multicenter, 52-week observational trial conducted in Europe. A diagnosis of PHNwas based on pain persisting since shingles vesicle crusting, for a minimum of 3 months. Prior treatment with capsaicin patches and a history of diabetes were among the exclusion criteria. Patients received up to 6 capsaicin 640 g/cm2 (8% weight for weight) HCCP treatments at 9-to 12-week intervals. At each application visit, a maximum of 4 patches equivalent to an area of up to 1120 cm2 were applied for 60 minutes. HCCP retreatment was at the investigator's discretion and according to patient feedback. Long-term tolerability and safety were the primary objectives of the study. In addition, areas of spontaneous pain and allodynia were monitored, and various scales were used to assess pain, quality of life and overall treatment outcome at each retreatment assessment timepoint. Descriptive statistics (including means and standard deviations) are presented; missing observations were not imputed. Results Of the 107 PHN patients included in the study, 66 completed the trial. The reason for withdrawal was lack of efficacy (14.95%), adverse events in (4.67%) and other reasons (18.69%). HCCP was applied once in 22 patients, twice in 26, three times in 24 and >=4 times in 35. All but 1 patient used preapplication topical anesthesia during the study, and 79.4% used concomitant medications for neuropathic pain. 73% of patients experienced possible or probable drugrelated adverse events, mostly associated with transient application site reactions (57.9%). The maximum severity was mild or moderate in 57% of cases, and only 1 drug-related event required treatment discontinuation. The average daily pain score was reduced from a baseline value of 6.6 (SD, 1.46) to 5.0 (1.99) after 6 months and 4.6 (2.18) after 12 months. The overall change in mean daily pain intensity by the end of study was approximately -1.7. The proportion of responders (>=30% decrease from baseline on a Numerical Pain Rating Scale) progressively increased during the study, to 22.7% after 3 months, and 33.3% and 39.7% after 6 and 12 months, respectively. Over 50% of patients showed at least minimal improvement according to the assessment of their condition by the end of study. The area of allodynia/ hyperplasia and the extent of spontaneous pain (reported in most patients at baseline, mainly on the torso) decreased during the study by just over 20%. Conclusions HCCP repeat application over 12 months in patients with PHN was well tolerated, with mostly transient local adverse events directly linked to the site of application. Progressive and sustained reduction in pain intensity was achieved, as well as reductions in the area of allodynia and spontaneous pain. Overall, the findings from this study demonstrate that repeated HCCP application is a well-tolerated and effective long-term treatment option in patients with PHN
EMBASE:634270856
ISSN: 1941-9260
CID: 4805622