Surgical procedures are key drivers of pain development and opioid utilization globally. Various organizations have generated guidance on postoperative pain management, enhanced recovery strategies, multimodal analgesic and anesthetic techniques, and postoperative opioid prescribing. Still, comprehensive integration of these recommendations into standard practice at the institutional level remains elusive, and persistent postoperative pain and opioid use pose significant societal burdens. The multitude of guidance publications, many different healthcare providers involved in executing them, evolution of surgical technique, and complexities of perioperative care transitions all represent challenges to process improvement. This review seeks to summarize and integrate key recommendations into a “roadmap” for institutional adoption of perioperative analgesic and opioid optimization strategies. We present a brief review of applicable statistics and definitions as impetus for prioritizing both analgesia and opioid exposure in surgical quality improvement. We then review recommended modalities at each phase of perioperative care. We showcase the value of interprofessional collaboration in implementing and sustaining perioperative performance measures related to pain management and analgesic exposure, including those from the patient perspective. Surgery centers across the globe should adopt an integrated, collaborative approach to the twin goals of optimal pain management and opioid stewardship across the care continuum. Surgery is an indispensable part of healthcare, and over 300 million surgical procedures are performed around the world annually . DespitePerioperative pain management and opioid stewardship are therefore comparable in necessity and interrelated in execution. To this end, many organizations have offered guidance on components of their application. This has included general postoperative pain management ,16,17, pApproximately one out of every ten opioid-exposed postoperative patients will experience at least one opioid-related adverse event (ORAE), conferring significant morbidity and economic burden ,41. ManyDespite an apparent overreliance on opioids by prescribers, less than half of postoperative patients endorse adequate pain relief, with 75–88% reporting a pain severity of moderate, severe, or extreme ,15. ShorAn additional risk of poorly managed acute postoperative pain is the development of persistent postoperative pain, frequently defined as new and enduring pain of the operative or related area without other evident causes lasting more than 2 months after surgery. While prevalence of such “chronic” postsurgical pain (CPSP) varies by surgery type and generally decreases with time, it may occur in 10–60% of patients after common procedures ,51,52,53®) Society . Pa. Pa18]. Patients using opioids prior to surgery should also receive a customized evaluation of their current analgesic regimen for optimization opportunities, which may include maximizing pre-admission multimodal therapies and/or tapering of opioid therapies. Conversely, certain pain medications may need to be interrupted for surgery , in which case clinicians should provide clear rationale and education on safe resumption after surgery. Patients on long-term opioid therapies prior to surgery experience increased rates of postoperative complications in addition to higher rates of persistent postsurgical pain and prolonged opioid use, so preoperative opioid minimization has emerged as a potentially modifiable risk factor. To this end, current consensus statements and expert opinion suggest titrating preoperative opioid therapies to the lowest effective dose, depending on the patient’s underlying condition ,105,106.High-quality data does not exist at this time to support strong recommendations regarding preoperative opioid reduction strategies, so a patient-specific, collaborative approach informed by appropriate expertise is vital. General guidance exists for opioid tapering in patients on chronic opioid therapy, but application to the preoperative setting is not discussed ,110. OpiPatients with chronic pain and/or substance use disorders pose significant challenges to perioperative pain management and opioid stewardship. These complex surgical populations are expected to continue growing, necessitating increased clinical knowledge and creativity from perioperative providers . It is i®), methadone, a multitude of buprenorphine products, and the pure opioid antagonist naltrexone (®). Perioperative management of chronic long-acting opioid receptor therapies, including those used as medication-assisted treatment (MAT) for substance use disorders, should be planned during the pre-admission phase of care. These high-risk medications include long-acting pure mu-opioid receptor agonists  poses no risk of opioid reversal when the dosage form is taken appropriately. The naloxone is only made bioavailable when the dosage form is altered in an attempt to inject it, and was developed as an abuse deterrent .,55.15,55To provide effective multimodal and opioid-sparing analgesia, clinicians should standardly provide around-the-clock nonopioid medications after surgery ,18,33. ASelective COX-2 inhibitors or other NSAIDs should be incorporated into most postoperative pain regimens with consideration of the type of surgery, renal function, and cardiovascular risk factors see . Since iOther nonopioid agents including cannabinoids, muscle relaxants, and tricyclic antidepressants cannot be recommended for routine postoperative use based on available data but may have roles in select surgical populations  ,402,403.In addition to nonopioid analgesia, many patients undergoing major painful procedures may benefit from short-term postoperative opioid therapy. When complete reliance on the intravenous route is considered necessary due to severe gastrointestinal dysfunction or surgical need for strict bowel rest, patient-controlled analgesia (PCA) is recommended over intermittent bolus by healthcare providers by some guidelines ,403. ThiEmpiric opioid selection should align with generally preferred agents, patient-specific pharmacologic needs, and the oral route of administration. Oxycodone, hydrocodone, and hydromorphone should be used preferentially due to their decreased propensities for active metabolites, accumulation in end organ dysfunction, drug-drug interactions, and histamine release  410,411,413,414.Individual patient response to preferred opioids still varies substantially. Genetic polymorphisms affecting opioid metabolism are not uncommon, so rotation to an agent utilizing an alternative metabolic pathway should be considered in patients with unexplained lack of response and/or significant intolerance   414,418418,419. While allergic reactions to opioids are frequently reported, true IgE-mediated hypersensitivity is rare. Only 15% of patients referred for drug provocation testing due to concern with anaphylactic opioid reactions were diagnosed with opioid allergy in one analysis, and opioids are believed to be implicated in less than 2% of all cases of intraoperative anaphylaxis ,432. AngClinicians should adjust the empiric postoperative pain management plan in cases for efficacy and tolerability, taking into account the duration and intensity of expected pain for the specific surgical procedure . The useDespite employing opioid minimization and evidence-based opioid selection when treating postoperative pain, the interprofessional team should actively anticipate and mitigate opioid-related adverse events ORAEs, . Nausea/Patients prescribed opioids should also receive scheduled stimulant bowel regimens to avoid opioid-induced constipation and progression to ileus, a risk that is heightened in the postoperative period . StandarPostoperative pain management in patients with preexisting opioid tolerance and/or substance use disorders is more complicated and high-risk than that of opioid-naïve counterparts, and specialist consultation is strongly advised ,18,36. NEmpiric as-needed opioid regimens should be dosed with consideration to baseline opioid use and closely monitored, recognizing that higher doses and/or longer tapers may be warranted. Patients on preoperative opioids have increased risk for suffering if undertreated and increased rates of ORAEs if overexposed. Still, opioids should be utilized only after first-line administration of nonopioids and used at the lowest effective dose, avoiding persistent dose escalations in the postoperative period . To this(a)oxycodone 10 mg PO q4hr PRN moderate-to-severe pain, may repeat 5 mg dose within 1 h if pain unrelieved; oxycodone 5 mg SL q4hr PRN moderate-to-severe breakthrough pain × 24 h(b)oxycodone 10 mg PO q4hr scheduled while awake; oxycodone 5 mg PO q4hr PRN moderate-to-severe pain; oxycodone 5 mg SL q4hr PRN moderate-to-severe breakthrough pain × 24 h(c)oxycodone 10 mg q3hr PRN moderate-to-severe pain; oxycodone 5 mg SL q4hr PRN moderate-to-severe breakthrough pain × 24 h.After major painful procedures, opioid-tolerant patients often warrant opioid exposure equivalent to a 50–100% increase from their baseline MED to achieve adequate analgesia and functional outcomes in the immediate postoperative period. Some literature suggests postoperative opioid requirements up to four times that of opioid-naïve patients may be necessary after the same procedure, and little published guidance exists on how best to accomplish this ,117,128.All initial opioid options are in addition to maximal scheduled nonopioid and nonpharmacologic orders, and accompanied by close monitoring for any appropriate adjustments. Orders for opioids as-needed for breakthrough pain should generally still be limited to the immediate postoperative period . Ongoing need for breakthrough pain opioid doses should prompt evaluation for nonsurgical causes of pain, further optimization nonopioid therapies, and an increase to the primary as-needed opioid order on a patient-specific basis.Patients with chronic pain and/or opioid use disorders may benefit from a patient-controlled analgesia (PCA) modality when pain is very difficult to control or when the oral route cannot be used ,128,468.Continuation of chronic long-acting pain medication regimens is recommended, in consultation with the patient’s outpatient prescriber see . ChronicDespite available evidence and guidance, healthcare providers may carry prejudices that result in under-treatment of postoperative pain in the opioid-tolerant and/or opioid use disorder populations. Such misconceptions often include that maintenance therapy with buprenorphine or methadone alone provides sufficient postoperative analgesia, that additional opioids for analgesia may cause addiction relapse or undue respiratory depression risk, or that the use of patient-controlled analgesia (PCA) may exacerbate these risks. In actuality, receptor up-regulation and the pharmacology of these agents confer the need for additional short-acting opioids at opioid-tolerant doses in order to provide equipotent analgesia to that provided to opioid-naïve patients. Available evidence does not support that this strategy exacerbates substance use disorders or increases risk for respiratory depression when appropriate dosing and monitoring are employed. Conversely, under-treated pain is likely a more significant risk factor for opioid misuse, ORAEs, and relapse ,128,470.Discharge opioid prescribing following surgery has significantly contributed to the ongoing U.S. opioid epidemic . CollaboUntil recently, evidence-based guidelines on postoperative opioid prescribing were not readily available. Variable and often excessive opioid quantities have been prescribed after surgery, especially in the U.S. ,473. In These guidelines should be used as a foundation to inform procedure-specific institutional practices for opioid prescribing at the point of hospital discharge after surgery. However, opioid prescribing must be individualized within this framework. The patient’s pain control and opioid use in the 12–24 h preceding discharge should be evaluated before prescribing discharge analgesics . PatientDespite successful institutional efforts to decrease inpatient opioid prescribing, this has not necessarily translated into reduced opioid quantities prescribed at hospital discharge . DischarPain management exit plans (PMEP) are an excellent resource for all postoperative patients, especially those with high opioid requirements . Exit plDischarge counseling, with an emphasis on nonopioid analgesics as first line therapy, is essential for safe and successful postoperative pain control ,101,478.Careful attention to the quantity of opioids prescribed at discharge to patients planning to resume medical marijuana or other illicit substances, such as heroin, is vital. In 2018, 67,367 drug overdoses were reported in the U.S., with 69.5% involving opioids . IncidenWhile acute pain management prescribing is the responsibility of the surgical team, collaboration with chronic pain prescribers and/or addiction medicine specialists is crucial for successful postoperative pain control and mitigation of adverse events in these high-risk populations. This communication can help prevent relapse in those with a history of substance use disorder and promote a smooth transition to maintenance medication regimens; hence, the outpatient provider should be engaged before surgery and as soon as feasible after discharge ,119. ForDevelopment of persistent opioid use is a risk when prescribing opioids for the treatment of acute pain. This risk is amplified by increased doses, additional days supplied, and duration of use. The likelihood of long-term opioid use significantly increases after five days of opioid therapy . For thiFollow-up assessments should evaluate ongoing postoperative pain, opioid and nonopioid use, and the status of unused opioids. The pain evaluation should assess pain trajectory, which includes pain intensity as well as time to resolution of pain. Patients identified as having an abnormal pain trajectory  have been found to have a higher risk of developing persistent postoperative pain and should be monitored closely . Closer Patients identified as having difficulty with postoperative pain control should receive education about proactive pain management. By taking scheduled doses of nonopioid medications, patients are able to “stay ahead” of their pain and prevent severe pain breakthroughs. For those struggling to wean off of opioids, providers should further optimize nonopioid medications, reiterate nonpharmacologic modalities, and encourage opioid tapers whenever possible. Pain management exit plans can be employed as they are at hospital discharge or updated in the outpatient setting, and should be strongly considered in this patient population . The neeFor patients with unused opioids, medication disposal education should be reiterated. Providing patients with local medication take-back locations or safe disposal devices can facilitate appropriate narcotic disposal and limit redistribution within the community ,493,494.Pain assessment and management metrics have been critical focus areas for healthcare institutions in recent decades, sometimes with deleterious effects. In 2001, as part of a national effort to address the widespread underassessment and undertreatment of pain, The Joint Commission  introduced pain management standards for healthcare organizations . While wThe Joint Commission and other organizations have since recognized a need to modify standards to mitigate unintended consequences in the wake of the ensuing opioid epidemic ,509,512.In addition to reimbursement-driving quality metrics and legal pressures, healthcare institutions are motivated by increased transparency of their patients’ pain management-related outcomes. Tools such as the CMS Hospital Compare websites and Leapfrog Hospital Safety Grade are available online to consumers ,516,517.Some institutions have implemented opioid stewardship programs (OSPs) to achieve these goals. Core pillars of OSPs include interprofessional collaboration on protocols and services related to multimodal pain management, education on opioid prescribing and stewardship to staff and providers, education to patients, caregivers and community members on safe opioid use and disposal, opioid-related risk reduction, and data analysis and reporting of related quality metrics ,521,522.Although current quality standards and market incentives better align with shared goals by patients, providers, and institutions, the cost of nonopioid medications can pose a barrier for institutions to implement multimodal analgesia throughout perioperative care. Intravenous acetaminophen (pending the widespread availability of this formulation from generic manufacturers in early 2021), intravenous NSAID formulations, and liposomal bupivacaine represent newer nonopioid interventions that drive analgesics to rank among the most expensive therapeutic drug categories . The subIt has long been recognized that successful perioperative care involves interdisciplinary collaboration among surgeons, anesthetists, medicine physicians, nurses, and physical therapy providers. Perhaps historically underrecognized has been the value of the clinical pharmacist in improving perioperative patient outcomes and efficiencies . DespiteThe surgeon perspective of best-practices evidence-based perioperative performance is a team approach within standardized enhanced recovery pathways. Each member of the perioperative interdisciplinary team provides valuable knowledge that contributes to opioid stewardship efforts. Where resources are available, perioperative pain management and opioid stewardship is ideally pharmacist-led, from preoperative evaluation through the inpatient stay and postdischarge follow-up . DescribNonopioid pain management options are optimized throughout the care continuum for all patients on the surgical service. Through preadmission screening, an enhanced recovery nurse navigator may identify patients with a history of chronic opioid use. This allows the pharmacist to contact the patient and develop a focused perioperative pain management plan. Anesthetists are other important enhanced recovery collaborators. Their expertise in perioperative pain management and postoperative nausea and vomiting (PONV) prevention assist with minimizing the need for opioids. Enhanced recovery patients without complications typically receive transversus abdominis plane (TAP) blocks in the preoperative suite from the anesthetist. Postoperative patients are never “nothing by mouth” after surgery when awake and alert, therefore, enhanced recovery postoperative orders should not routinely include intravenous opioids. The pharmacist leads the multimodal pain management strategy at daily inpatient interdisciplinary rounds that include surgeon, resident surgeon, physician assistant, case manager, social worker, enterostomal nursing, and patient care unit nursing staff. Knowledgeable patient care nurses, well-informed in pain management goals and providing consistent care plan messages to patients, are an integral component of standardized perioperative pain control.Surgeon opioid and nonopioid discharge prescriptions are written in consultation with the enhanced recovery team pharmacist and are based on inpatient pain control and opioid needs in the 12–24 h leading up to discharge. Pain management exit plans are developed by the pharmacist and provided to those with high opioid requirements. Patients receiving an exit plan are seen by pharmacy and educated about the importance of multimodal analgesia and opioid tapers. One study showed that a pharmacist-led enhanced recovery pain management plan resulted in less than 50% of patients requiring opioid prescriptions at the time of discharge for patients having robotic colorectal surgery. The average number of 5 mg oxycodone tablets prescribed in those who received prescriptions was 6 to 8 while the average number used was 2.5 to 3 tablets. Only 0.5% to 0.75% of patients required opioid prescription refills .Perioperative pain management and opioid stewardship continues after patient discharge in the surgeon clinic. One study showed that enhanced recovery pharmacist participation in an early post-discharge clinic where all postoperative patients are seen within 4–7 days of discharge maximized assessment of pain management and reinforcement of nonopioids as the primary pain management option. Additionally, overall readmission rates were significantly decreased, especially with postoperative pain as a readmission diagnosis . In addiPain management in enhanced recovery is therefore a dynamic, collaborative, interprofessional effort that requires reassessment and evidence-based changes. A prospectively maintained database allows real-time collection and evaluation of enhanced recovery data that includes opioid and nonopioid information . ImplemePatient-centered outcomes and the surgical patient experience should remain the focus of collaborative care and process improvement. Clinical practice guidelines endorse an individualized approach to all aspects of postoperative pain management based on patient needs and preferences, and echo the need to engage patients in shared decision-making throughout this process . AvailabTo illustrate the importance of postoperative pain management and opioid stewardship to the patient perspective, the following account was authored by a colorectal surgical patient of two of the authors and published with his permission (edited only for brevity):“For patients, fully understanding how surgery will affect them physically and emotionally and what type of pain management practices will be employed both before and after is a critical first step if they are to take charge of their own health care. Surgery is a scary proposition for the patient. If you add in the anticipated discomfort and pain it only escalates the unknown, elevating fear and anxiety. Speaking from experience, this quickly takes center stage in a patient’s mind. With my three surgeries, I found it essential to take ownership and control and learn as much as I could about these surgeries and my recovery. Fully understanding possible surgical risks and complications, as well as the overall goal and expected positive outcomes, was vital if I was going to gain mental control of a challenging health situation.Most patients do not realize the power exists within themselves to take better control of their surgical outcomes. Deciding on my frame of mind and focusing on the positives, rather than the negatives, immediately put me in a better position to reach my recovery goals. As I saw it, I had two choices: (1) I could worry about the possible complications associated with surgery. If I took that route, I was sure to be miserable, anxious, and not fully connected with my end goal; or (2) I could prepare by becoming knowledgeable about my surgery, perceiving it as another life challenge that would enable me to continue living and to improve my quality of life. For me, surgical challenges are a lot like flying a kite. If you run your kite before the wind, you cannot take off and fly. You have to turn into the wind and face it head-on. The challenge you push against is the very force that lifts you. Therefore, it was clear to me I had to face the headwinds.”“My three surgeries would involve perioperative pain control, with transverse abdominis plane (TAP) or epidural pain blocks and a combination of oral pain medications including acetaminophen, ibuprofen, gabapentin, and oxycodone. Today, I’m a veteran when it comes to pain medication, but the real inspiration that empowered me and gave me reassurance that I could make a significant contribution to my recovery was the Enhanced Recovery Program (ERP) offered by my health provider. Along with that, I was able to use a phone application when I returned home. This application allowed me to have morning check-ins with my health-care team, if needed. My health provider also offered an informative class several weeks before my surgery that gave me valuable and concise information to help me understand my upcoming procedure and how to prepare for it and my hospital stay. The class also gave me important information about my postoperative care and recovery at home.The ERP gave me the reassurance and tools needed to control my health care, creating a solid foundation for a good outcome. After attending this class, I realized that I had the power to actively engage as a patient who can contribute, participate, and determine outcomes. I was no longer a bystander but a player in this game. This significantly reduced my anxiety, replacing it with positive energy. I honestly believe this shortened my recovery time for all three surgeries.In the ERP class, a nurse navigator and a pharmacist addressed the most concerning aspect of my surgery: How to control pain? I realized I am afraid of pain. I honestly believe all of us are. However, getting preoperative education on pain management led to the insight that I needed to take control of my pain rather than let it control me. Understanding opioid risks and benefits gave me the confidence and courage to set a goal to get them out of my life after surgery as soon as reasonably possible. Most of us are keenly aware of the opioid crisis still raging both worldwide and in the United States. I was initially concerned that this might eventually be me.Well, it could have been me. All of us can be throttled by addictions when we least expect it. However, the underlying key to my success was the preoperative and postoperative education I received. What I did learn, and benefit from was the powerful combination of ibuprofen and acetaminophen and how they work together very well to relieve surgical pain. After stopping opioids, I was continued on a regimen of these over-the-counter pain relievers and quickly discovered my pain was being managed without the use of narcotics. This alternate step was presented and outlined in my ERP class. This was an enabler for me, and I was able to be more mentally alert, have less constipation issues and feel comfortable enough to go home. The ERP umbrella provided an open and honest conversation through clear and straightforward directions about what must be done before and after surgery. ERP and the medical staff gave me realistic and attainable goals for my recovery. I was a partner in my own health-care decisions, and I took ownership for my successful recovery. The well-trained medical staff promptly addressed my concerns. The addition of the phone application, which I found to be an excellent communication tool, provided me much needed emotional reassurance and support before, during, and after surgery.”“As a frequent-flyer patient with lots of surgeries, treatments, and narcotics use, I can report that I landed safely back in my everyday life. Additionally, this was mainly because of the expert care as well as the comprehensive education I received from the medical staff, doctors, pharmacists, and nurses. In all cases, my ERP experience gave me the solid foundation I needed to empower myself and focus on the win, not the illness. I discovered journaling every day with accompanying photos, audio, and video. I now have five solid years of life experience, good and bad, that I can look back on.All of us will eventually face fragility and mortality. However, for this patient, my medical experiences and the numerous medical staff who helped me during trying times have given me the gift of life. I am grateful that I was forced to confront an often inevitable part of being alive and to now fully understand that we as patients can take ownership of and apply direction to our recoveries.”While myriad multimodal strategies exist, ongoing comparative assessments of analgesic combinations and anesthetic approaches within enhanced recovery practice are warranted to further understand and optimize perioperative patient care. Novel analgesic agents and modalities continue to be developed, and their place in therapy should be thoughtfully studied ,535,536.Effective perioperative pain management requires a multifaceted team-based approach that begins prior to admission and continues after discharge. Healthcare providers must collaborate throughout institutional practice and process improvement with the shared goals of providing optimal patient care while minimizing opioid exposure. Standardized perioperative pathways should maximize nonpharmacologic therapies and multimodal analgesics, provide decision-support for the judicious use of opioids, and include mitigation strategies for ORAEs and postsurgical opioid dependence. Collaborative practice models should ensure appropriate patient-specific application of available strategies to high-risk and/or opioid-tolerant surgical populations. Pain and addiction medicine specialist consultation, transitional pain services, and opioid stewardship programs should be appropriately resourced across healthcare systems and surgery centers. Incorporating evidence-based pain management and opioid stewardship strategies into a standardized perioperative program will support safe, high-quality, and consistent surgical patient care.


There were no differences for all other variables between groups. Regarding pre- to post-comparisons, both groups showed improvements in all dependent variables (p < 0.001). Conclusion: The treatment with PNE/MCE was more effective in improving pain disability and unipodal static and dynamic balance than treatment with CST. Even so, both treatments were shown to be valid and safe in improving all dependent variables analyzed in women with CLBP.Background: Several interventions have been used to relieve chronic low back pain (CLBP). This study aimed to compare the effects of pain neuroscience education (PNE) followed by motor control exercises (MCEs) with core stability training (CST) on pain, disability, and balance in women with CLBP. Methods: Thirty-seven women with CLBP were randomly divided into two groups of PNE/MCE  or CST . Eight weeks of PNE/MCE or CST were prescribed for each group, independently. Pain intensity , disability (Roland Morris Disability Questionnaire), unipodal static balance, and dynamic balance (time up and go test) were measured at the beginning and 8 weeks after the intervention. Two-way mixed ANOVA was used to analyze the results with alpha of 5%. Results: After 8 weeks, there was a significant difference in VAS scale between groups ( Chronic low back pain (CLBP) is considered a frequent condition in women that has increased significantly worldwide, but few studies have been conducted to explain it ,2. Low bMoreover, several methodologies such as strength, endurance, and core training programs available for treating CLBP seem to be weak because they ignore pain recognition, behavioral aspects, and knowledge of pain physiology .Meanwhile, spinal stabilization exercises for CLBP have received some research attention and are regarded to be effective, through improved core stability of the central axis of the role of these muscles in this area during limb use and movement . In factIn addition, more knowledge of spinal motor dysfunction in patients with CLBP has emerged ,17. PatiA methodology that included pain neuroscience education (PNE) followed by motor control exercises (MCEs) has recently been used ,23. ThisIn this sense, a study showed that a PNE program combined with motor control education with cognitive goals presented decreases in pain and disability and an increase in spinal function compared to physiotherapy intervention in patients with CBP. Moreover, a recent systematic review and meta-analysis showed that exercise training programs obtained identical clinical effects when compared with physiotherapy interventions .Given the scarce knowledge on how effective the previous interventions are, the scarce information on what kind of exercises are best to improve LBP ,28,29,30Sixty-five participants aged between 50 and 60 years with CLBP were enrolled in this study. CLBP was diagnosed by a specialist physician by the cross straight leg raise test. The participants were purposefully selected, and only those registered for physiotherapy treatment through brochures displayed in physiotherapy clinics were enrolled by physiotherapists. The sample size was calculated using G*Power as in a previous study  with theThus, the following inclusion criteria were applied: (1) native Persian-speaking women between 50 and 60 years old and (2) primary complaints of low back pain  diagnosed by an experienced physiotherapist and completion of the consent form. The exclusion criteria were (1) any history of surgery on the spine, (2) pathological records (disease) of the spine, (3) orthopedic and neurological injuries, (4) unwillingness to continue to participate in the exercises, (5) failed any exercise session , and (6) absence in the post-test stage (n = 2) . AdditioThe present research design was a two-group study with exercise intervention in the experimental groups (PNE/MCE and CST groups) without a control group with pre- to post-test. A random method to allocate participants in the groups was used with blinding in the experimental group. The following evaluation was applied to all participants:Visual Analog Scale (VAS): A visual analog scale was used to measure the severity of pain in the subjects. The scale is a 10 cm horizontal strip starting from 0 (no pain) to 10 (the most severe pain possible). This scale is one of the most reliable quantitative scales widely used in research .Disability: The Persian version of the Roland–Morris Disability Questionnaire (RMDQ) was used to assess disability by LBP . The RMDUnipodal static balance (USB): The test of standing on the dominant foot on a square piece of wood (40 cm × 40 cm) was used to measure the static balance of the subjects. The procedure is performed in a manner that the subject stands barefoot in such a way that the superior foot is on the ground and the non-superior foot is above the ground, and the hands are placed on the waist on the crown of the pelvis. The length of time a person can maintain this position (in seconds) is counted as their score. Time recording stops when the support foot moves, the free foot touches the ground, or the hand is detached from the waist .Dynamic balance: The “Timed Up and Go (TUG) test” was used as a rapid way to determine balance problems affecting motor skills in the daily lives . The TUGCore stability training: After familiarization with all core stability exercises, all participants performed the CST for eight weeks  supervised by a physiotherapist. The CST in each session was composed of a warm-up  to 45 min , and cool down for 5 min. Progress in exercises was based on the principles of overload and gradual increase in the volume of exercises; progress was in the duration or repetition of each exercise . Table 1Pain neuroscience education/motor control exercises: Three PNE sessions took 30–60 min and were conducted by a physical therapist. The purpose of PNE was to control patients’ negative perceptions of recurring pain ,37. ThesThe MCEs were similar to Malfliet et al. . This php-value < 0.05 was used to determine statistical significance, while Partial Eta Squared (ηp2) values were calculated as effect size (ES), which were considered as 0.2 = small effect, 0.5 = moderate effect, and 0.8 = large effect based on the study of Cohen [The Shapiro–Wilk test and Levene’s tests were conducted to confirm the normality and homogeneity of the dependent variables, respectively. After both were confirmed, a 2 × 2 ANOVA (treatment group × time) with Bonferroni correction post hoc was conducted with a mixed model analyses design. For each dependent variable, mean ± standard deviation (SD) was used. The percentage of change was calculated and compared with the baseline. A of Cohen . All datp > 0.05). The demographic and clinical variables of the participants are presented in There was no significant difference between the two groups in the pre-test stage in terms of demographic and clinical variables (There was a difference in the mean score of pain (−0.78)  and disability (0.79)  (RMDQ) (better performance in the PNE/MCE group) in the post-tests. Additionally, the mean difference in the PNE/MCE group and the core stability group was 0.79  in the USB and −0.62  in the dynamic balance variable (better performance in the PNE/MCE group) .The aim of this study was to compare two interventions, PNE/MCE and CST, on pain, disability, and balance in women with CLBP. The results showed a significant effect of both interventions after eight weeks. Additionally, the comparison of the two exercise programs showed a greater effect of motor control with cognitive purpose compared to the core stability exercises on the variables of pain and disability . A possible justification could be associated with the individualized, PNE treatment employed using cognitive-based education followed by an exercise program as previously suggested .Moreover, the findings of many previous studies are consistent with the present results in terms of core stability and motor control exercises with a cognitive goal ,24,42,43The results of some studies have shown that the size of type II muscle fibers is reduced in people with LBP ,47. StabIn people with CLBP, the trunk protection response is inadequate due to a delay in predictive activation and a reduction in relative muscle thickness . The disWhen compared with static balance, dynamic balance requires the body to balance during the transition from dynamic to static status, which is difficult  for peopWith regard to the effect of PNE/MCE with a cognitive goal, a growing body of evidence shows that brain abnormality changes in the structure and function of the brain and excessive brain sensitization have major importance in patients with CLBP ,24. CentThe addition of PNE to MCE seems to help patients by reducing pain and disability by activating proprioception, coordination, and sensory–motor control of the spine ,43,59. MThis study presents limitations, namely: (a) only eight weeks were evaluated, which suggests more longitudinal studies are needed to access long-term effects of the interventions; (b) central sensitization was not accessed because there is no translated Persian version; (c) brain imaging techniques were not used, which could be relevant for future studies to understand brain communication during CLBP recovery and during the application of the different training methodologies; (d) it was not possible to apply the ideal division for all groups, which would include five different groups: (1) MCE; (2) PNE/MCE; (3) CST; (4) PNE/CST, and (5) the control group. For those reasons, we recommend such an approach for future studies.According to the percentage of changes, PNE/MCE was shown to provide more improvements than CST in relieving pain and to some extent in the RMDQ disability than in the CST group. This is probably due to the focus of neuroscience with motor control exercises on the correction of incorrect postures during daily activities. In addition, PNE/MCE were shown to possibly be effective in improving static and dynamic balance, although further studies would be needed to substantiate this. Even so, both PNE/MCE and CST protocols improved all variables analyzed . Therefore, both training programs seem to be recommended for women with CLBP.


The minimal clinically important difference of the global score was determined to be 10.9. Conclusions: The ENDOPAIN-4D questionnaire is easy to use, valid, and effective in assessing patient reported pain symptoms in women treated for endometriosis. This new instrument can be used as the primary outcome for future clinical trials and as a tool for routine patient follow-up.Objectives: To study the measurement properties, the responsiveness and the minimal clinically important difference of the ENDOPAIN-4D: a new questionnaire for assessing pain in endometriosis. Methods: A prospective, observational, multicentre study was conducted including all women ≥18 years consulting for symptomatic proven endometriosis between 1 January 2017 and 30 June 2018 and volunteering to participate. Each patient had to answer a new self-administered patient-reported outcome (PRO) questionnaires (the ENDOPAIN-4D) at inclusion (T0) and 12 months after medical or surgical treatment (T1). Criteria defined by COSMIN were used to validate the questionnaire’s measurement properties. The minimal clinically important difference was estimated by the anchor-based method. Results: The study included 199 women. The ENDOPAIN-4D score had a four dimensional structure with good internal consistency (measured by Cronbach α): (I) pain-related disability (α = 0.79), (II) painful bowel symptoms (α = 0.80), (III) dyspareunia (α = 0.83), and (IV) painful urinary tract symptoms (α = 0.77). They produced four subscores that can be summed to obtain a single score (α = 0.61). The ENDOPAIN-4D total score ranged from 0 to 94.00 (mean ± SD: 46.7 ± 22). The total score was significantly correlated with the PROs used in endometriosis. Sensitivity to change was good with large effect sizes (ES) (mean of the differences: 36.3  Endometriosis is a chronic inflammatory disease that occurs in about 10% of women of childbearing age , and womConsideration of patients’ feelings about their symptoms and the impact of various diseases or symptoms on their quality of life has developed substantially in recent years with the increasing use of patient-reported outcomes (PROs), assessed by questionnaires or other tools . PROs foTo date, there is no score able to assess overall pain in endometriosis by considering all of its heterogeneous symptoms. For this reason, we have designed a self-administered questionnaire: the ENDOPAIN-4D questionnaire. Initially based on women’s verbal descriptions  to measuThe translation was performed according to previously published guidelines . Three nThe aim of this study is to assess the measurement properties of the ENDOPAIN-4D according to criteria defined by the COSMIN taxonomy, we also examined the responsiveness and determine its minimal clinically important difference.The ENDOPAIN-4D comprises 21 items divided into four subparts: spontaneous pelvic pain and dysmenorrhoea (questions 1 to 10), dyspareunia (questions 11 to 13), intestinal pain symptoms (questions 14 to 16), and other symptoms (questions 17 to 21). Each question is first scored dichotomously as yes/no. If this answer is ‘yes’, the woman scores it according to the extent of the symptom from ‘0’: no pain to ‘10’: worst pain imaginable. If the answer is ‘no’, a score of ‘0’ is automatically assigned on the numerical rating scale. Ten questions relate to different types of pain , and 11 cover discomfort or patients’ feeling about their pain symptoms  scan or magnetic resonance imaging (MRI) by practitioners experienced in endometriosis and working in a reference centre.Physicians and patients jointly decided on the option of medical or surgical management, with physicians deciding the type of hormonal treatment and its timing (prescribed before or after surgery). Medical treatment uses both analgesics and combined or progestogen-only hormonal contraceptive pills or a Gonadotropin-Releasing Hormone (GnRH) agonist. Surgical treatment consists, whenever possible, of complete excision of endometriosis lesions. The type of surgery depends on the lesion characteristics and locations .The study included all women aged 18 years or older consulting for symptomatic proven endometriosis in one of the three centres between 1 January 2017 and 30 June 2018 and volunteering to participate. For women with surgical management, proof came from histological results, and for those treated medically, by typical images of endometriosis implants  on radiological assessment. On US, lesions appeared as solid nodules of variable sizes, hypo- or iso-echoic, regardless of the regularity of their contours. They could also be in the form of hypoechoic thickening of the intestinal wall, vagina, or bladder . On MRI,Each included patient had to answer at least one of the ENDOPAIN-4D questions to be included in the analysis. The exclusion criteria were: no health insurance, inability to read French, presence of another major pelvic pathology, chronic pain other than endometriosis, and history of major pelvic surgery (including resection of deep endometriosis).At the first visit before treatment (T0), each women who agreed to participate in the study completed a self-administered questionnaire containing, alongside the ENDOPAIN-4D, epidemiologic data  and different validated PROs widely used in the field of endometriosis and pelvic pathology: the French version of the International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms (ICIQ-Fluts), the International Prostate Symptom Score (IPSS) , the KnoAll women were asked to complete the same questionnaire 12 months (T1) after medical or surgical treatment. Simultaneously, they also rated their overall improvement of pain symptoms, with the Clinical Global Impression (CGI) scale-global improvement item .The CGI-In order to be used in clinical or research practice, any questionnaire need a complex and specific validation respecting the recommendations issued by the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN).We therefore used the COSMIN criteria  for the Construct validity—which determines ‘how well a test measures what it is supposed to measure?’ by comparing the questionnaire to other questionnaires that measure similar qualities—was evaluated by testing the presupposed relations of the ENDOPAIN-4D total score and its four subscores with PROs used and validated in endometriosis as well as with prespecified characteristics and extent of disease. We therefore hypothesised a gradation of pain based on endometriosis severity according to its revised American Society for Reproductive Medicine (rASRM) stage , and on Pearson correlation coefficients and analysis of variance (ANOVA) were used to test the relations between the ENDOPAIN-4D scores and the continuous and categorical variables, respectively.For variables correlated with the ENDOPAIN-4D scores, we estimated the effect size according to Cohen’s method and its confidence interval. An effect size of 0.2 was considered a small effect, 0.5 a moderate effect, and 0.8 or higher a large effect.For continuous variables, the median score was used as the cut-off to define groups.Sensitivity or responsiveness to change was calculated by comparing results of the 4 subscores and the ENDOPAIN-4D total score between T1 and T0 with the paired data Student’s t-test. Effect sizes were then obtained by Cohen’s method.The minimal clinically important difference (MCID) is the smallest difference perceived by patients as beneficial or harmful in the score of an instrument’s measure . BecauseAll statistical analyses were done with the R Studio version 4.0.3 software (2020-10-10) Copyright © 2021 The R Foundation for Statistical Computing Platform. 51 Franklin Street, Fifth Floor, Boston, MA 02110-1301, USA.Our study was purely observational and involved no intervention. As such, no written informed consent was required by the relevant statute, the Huriet-Serusclat Act dated 20 December 1998. Nevertheless, all patients received information about the study and were free to participate or not. The confidentiality of patients’ data has been respected. The IVth southeast Ethics Committee  in France approved this study.The study included 199 women who completed the T0 questionnaire . Among tThe descriptive analyses of the ENDOPAIN-4D questionnaire at T0 are presented in A floor effect was observed for ‘right shoulder pain’, which was thus excluded from further analysis. The question on infertility was excluded from further analysis because it did not relate to a painful symptom.The scree plot showed that the ENDOPAIN-4D questionnaire was multidimensional (data not shown). Principal component analysis with orthogonal varimax rotation found a four-dimensional structure  with gooAs the first dimension, which included three of the 19 questionnaire items, accounted for 17% of the total variance, we chose to sum it to obtain a single score (α = 0.63) The ENDOPAIN-4D total scores ranged from 0 to 94.00 (mean ± SD: 46.7 ± 22) for a maximum theoretical value of 110, where 0 corresponds to no pain and 110 to the worst pain possible.p = 0.035, ES = 1.35). The score was not, on the other hand, significantly associated with the severity of endometriosis assessed by the rASRM stage, the presence of anterior or posterior DIE, the number of locations, or the obliteration of the pouch of Douglas.The ENDOPAIN-4D total score was significantly associated with the size of the endometriomas . No other significant association was found between the four subscores and the pre-established hypotheses.Dyspareunia and functional urinary symptom subscores were significantly associated with the severity of endometriosis assessed by the rASRM stage .The 132 patients who completed the ENDOPAIN-4D questionnaire at T0 and T1 comprise the population used to analyse responsiveness to change and to calculate the MCID. All four subscales differed significantly between T0 and T1 . SimilarAll results are statistically significant.p = 1.8 × 10−7, ES 0.76) (p < 0.05). Of the 132 respondents at T1, 105 (79.5%) reported improvement on the CGI-I after treatment, and among these 105 patients, 24 had a difference of only one degree on CGI-I after treatment. This method showed that MCID for the ENDOPAIN-4D total score was 10.9.The ENDOPAIN-4D total score also decreased significantly after treatment  . ChangesThis prospective study provides evidence of the validity of the ENDOPAIN-4D questionnaire according to the COSMIN criteria for assessing pain in patients with endometriosis. The ENDOPAIN-4D was four-dimensional and thus made it possible to explore separately specific important domains related to endometriotic pain, including pain-related disability, sexual dysfunction, and bowel and lower urinary tract symptoms. Furthermore, adding together the four subscores produced a single score that captures the overall pain of endometriosis patients, regardless of the specific pain symptoms they have. The significant correlation between the ENDOPAIN-4D total score and the PROs generally used in endometriosis demonstrates the questionnaire’s construct validity. Finally, the changes in the ENDOPAIN-4D total score with surgical and medical treatment show its responsiveness to treatment.The strength of this study lies in its methodological design, which meets all the criteria for questionnaire validation set forth by COSMIN. In addition, it is a prospective multicentric study including women with different subtypes of endometriotic involvement  that was specifically designed to evaluate the psychometric and clinimetric properties of the ENDOPAIN-4D questionnaire.Several limitations must nonetheless be emphasised:First, the response rate for each item was acceptable except for items related to sexual intercourse. This disparity may be explained by the study’s inclusion of women without partners or by the intrusiveness of such questions, or both.Second, it is a selected population. The recruitment of women at reference centres for endometriosis resulted in a high proportion of patients with severe endometriosis (37.4% with stage IV). Nevertheless, there are no clear design rules for sampling a target population to validate a health measurement instrument. For example, Terwee et al. recommended simply an adequate description of the target population to be able to judge the completeness and applicability of the questionnaire in other population .Moreover, only weak associations were found between the extent of the disease, its locations, and the ENDOPAIN-4D total score. These data should not affect the validation of this questionnaire because many studies have failed to establish a link between some symptoms of endometriosis and lesion sites. The fact that the patients included in the study had severe forms of endometriosis and also severe symptoms, which lead a decision to treat, may result in referral bias , which iAlthough each of the subscores as well as the ENDOPAIN-4D total score are significantly correlated with the EHP-5, the EQ-5D 3L and EQ5D-VAS taking into account the psychological impact of endometriosis on patients; it is important to emphasize that no subscore of our questionnaire is entirely dedicated to the assessment of the negative impact of endometriosis on women’s psychological health and general wellbeing. To date, many studies have reported the impact of endometriosis on anxiety and depression ,29 and rRecent studies have reported the importance of superficial dyspareunia as an endometriosis-related symptom, defined as complaint of pain or discomfort on vaginal entry or at the vaginal introitus ,32. In aFinally, despite a correct response rate 12 months after treatment (T1) (66.3%) might raise the question of the risk of selection bias in the women who responded and could therefore call the results into question. We are reassured by the absence of significant differences between women who responded at follow-up and those who did not. Finally, the number of women included in the responsiveness study was sufficient to estimate the responsiveness and the MCID with precision.To the best of our knowledge, our questionnaire is the only one to assess all the pain symptoms in endometriosis and to have been fully validated according to the COSMIN criteria. Only a few questionnaires assessing pain symptoms in endometriosis have been published, and most of them have been used to predict endometriotic involvement based on symptoms ,32,33,34Two other scores have been developed to assess pain symptoms of endometriosis. The daily electronic Endometriosis Pain and Bleeding Diary, developed by Deal et al., is a self-administered questionnaire with 17 items that assess intermittent and continuous pain in endometriosis with good internal consistency. Although it appears able to characterize the types of pain that endometriosis patients identified as important, its use appears limited by the absence of studies of its dimensionality, construct validity, and responsiveness ,37.In 2018, Wyrwich et al. developed the Endometriosis Daily Pain Impact Diary Items to assess dysmenorrhoeal and non-menstrual pelvic pain . This quPreviously published trials on pain treatment in endometriosis have lacked a single outcome capable of assessing all the various heterogenous pain symptoms of endometriosis patients ,40. The Because endometriosis is a common disease responsible for pain in 80% of cases and impairs quality of life, often severely, it is crucial to develop easy-to-use validated tools for clinical practice and therapeutic evaluation. The ENDOPAIN-4D PRO can be used as a primary outcome for future clinical studies but also as a tool for routine patient follow-up. An international multicentric evaluation outside the French setting is needed.


BackgroundOsteoarthritis (OA) can result in significant pain, requiring pain management with opioids. Medical cannabis (MC) has the potential to be an alternative to opioids for chronic pain conditions. This study investigates whether MC used in the management of OA-related chronic pain can reduce opioid utilization.MethodsForty patients with chronic OA pain were certified for MC. Average morphine milligram equivalents (MME) per day of opioid prescriptions filled within the six months prior to MC certification was compared to that of the six months after. Visual analog scale (VAS) for pain and Global Health scores were measured at baseline, three, and six months post MC certification.ResultsAverage MME/day decreased from 18.2 to 9.8 . The percentage of patients who dropped to 0 MME/day was 37.5%. VAS scores decreased significantly at three and six months, and Global Physical Health score increased significantly by three months.ConclusionsMC reduces opioid prescription for patients with chronic OA pain and improves pain and quality of life. The United States (US) currently faces an opioid crisis with opioid-related deaths nearly quadrupling between 1999 and 2015 and 37.8% of adults using opioids in 2015 .Medical cannabis (MC) is a new therapeutic option for chronic pain. As of 2020, it has been approved for the treatment of pain in over 30 states across the US . MC has Population studies show that MC legalization has been associated with reduced mortality due to opioid overdose, reduced opioid-related hospitalizations, and decreased opioid prescription . HoweverPatient outcome measures for this study were obtained by querying the Rothman Orthopaedic Cannabis Data Repository (ROCDR). The establishment of the data repository was approved by the Institutional Review Board of Thomas Jefferson University, Philadelphia, Pennsylvania (protocol #19D.159). Patients with non-spinal chronic OA diagnoses who were certified for MC at the Medical Cannabis Department of the Rothman Orthopaedic Institute between February 2018 and July 2019 were prospectively enrolled and included. Inclusion criteria for study analysis included patients actively consuming opioids for chronic pain, and OA was the primary contributor to their pain. Exclusion criteria included patients having undergone surgery within six months before or after MC certification, and not consuming opioids at the time of MC certification. Patient demographic information was collected. Outcome measures were collected at baseline and at three and six months post-MC using the Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire and included visual analog scale (VAS) pain score, Global Mental Health (GMH) quality of life (QoL) score, and Global Physical Health (GPH) QoL score. Due to variability in the site of joint pain, global pain outcome measures were used instead of OA joint-specific measures. Data on the route of MC administration and adverse effects were retrospectively collected during the three and six-month follow-up visits and analyzed.All physicians who were involved with MC certification had previously undergone a four-hour Continuing Medical Education (CME) course and applied to the Pennsylvania Department of Health in order to become approved practitioners as mandated by the state of Pennsylvania . MC was Data regarding filled prescriptions of controlled substances were gathered using Pennsylvania’s Prescription Drug Monitoring Program (PDMP) system. PDMP is a state-run program that collects information on all filled prescriptions for controlled substances and can be accessed online by licensed providers. Study data were logged into a password-protected Microsoft Excel  database.Data on opioid prescriptions that were filled within six months before and after MC certification for all enrolled patients were collected. Opioid prescriptions filled were calculated based on the average morphine milligram equivalents (MME) filled per day over the six-month period before and after MC certification. Total MME per patient was calculated by multiplying PDMP-provided raw daily MME by the number of days the patient had an active opioid prescription. Daily opioid consumption was normalized by dividing each patient’s total MME prescribed in a six-month period by the total number of days within six months. The six-month period was chosen to normalize opioid prescription variability for their chronic pain over a longer time period of time. Primary study outcome measures consisted of the change in opioid prescriptions filled pre- and post-MC certification and use. Secondary study outcome measures included pain and QoL scores.Statistics were calculated within Microsoft Excel using a paired, two-tailed T-test for paired data and a two-tailed T-test with unequal variance for non-paired data. An alpha threshold of alpha = 0.05 was applied for all unique significance tests.A total of 632 patients were certified for MC for a musculoskeletal pain diagnosis between February 2018 and July 2019. Of those patients, 117 patients had a diagnosis related to OA, with 48 having filled an opioid prescription within the six months prior to MC certification  between six months pre-MC to six months post-MC use  post MC certification. Compared to baseline (prior to the initiation of MC therapy), VAS pain score decreased significantly from 6.6 to 5.0 (p<0.01) and 5.4 (p<0.05) at three and six months, respectively Figure . GMH scoVarious routes of MC administration were used including vaporized oil, vaporized flower, and oral, topical, and sublingual tincture. We collected data on the route of MC administration for 33 82.5%) patients. Of these, 21 (63.6%) used only a single route, 11 (33.3%) used two routes, one (3%) used three routes. The most commonly used route of administration was sublingual tincture  followed by topical , vaporized oil , oral , and vaporized flower  (Table .5% patieData on adverse effects were collected for 21 (52.5%) patients. Of the respondents, 12 patients (57.1%) did not feel intoxicated or high, and nine patients 42.9%) felt intoxicated or high. Of the patients who felt intoxicated or high, three (1.4%) said that it did not interfere with their daily activities, three (1.4%) said that it made their day even better, and three (1.4%) said that they did not like it or that it interfered with their daily activities  . Based oOur findings support the literature in that MC reduces the use of opioids for the treatment of chronic pain ,18-24. TOne study looking at a cohort of patients undergoing primary joint arthroplasty showed that tetrahydrocannabinol (THC) and other cannabidiol (CBD) product use was not associated with differences in length of opioid use, total MME used, average postoperative pain score, percentage of patients requiring a refill of narcotics, or length of stay in the perioperative period . This stOpioids are still routinely used for OA conditions despite issues of tolerability, dependency, and abuse ,4. MC isPhysicians are often hesitant to prescribe MC due to uncertainty of its efficacy and limited experience with its use. In a study conducted in Germany, only 1.9% of patients with nociceptive, neuropathic, or neuroplastic pain were prescribed MC despite its beneficial outcomes . There iThis study has several limitations. It was an uncontrolled observational study. Our population was fairly small and limits generalizability, so larger follow-up is warranted. Tracking filled opioid prescriptions does not necessarily indicate the actual use of opioids and only serves as a proxy for opioid consumption. Furthermore, prescriptions are often shared, and we could not account for the acquisition and use of illicit opioids. The dosage and route of MC use were not tracked and are difficult to ascertain, as it is typically up to the patient once access is granted. Our study only follows patients for six months post MC certification and may miss attrition of MC effectiveness. Data on MC toxicity and side effects are difficult to generalize given the variability in patient MC consumption.Patients with chronic pain due to OA who were certified for MC filled significantly less opioid prescriptions post MC certification compared to pre-MC certification. Over one-third of patients stopped filling opioid prescriptions altogether. Pain and QoL measures were improved following MC certification. Sublingual tincture was the most commonly used route of MC administration.


Lung cancer (LC) is the malignant tumor with the highest incidence in the world, and treatment methods include surgery, radiotherapy, chemotherapy, and immunotherapy. Cancer pain is a common symptom in patients with LC, and the clinical treatment is to relieve it with analgesics. Acupuncture can relieve cancer pain. This study aims to systematically study the efficacy and safety of acupuncture combined with analgesics on cancer pain in patients with LC.From the beginning to April 2021, search Medline, Embase, Cochrane Central Controlled Trials Register , China National Knowledge Infrastructure (CNKI), Wanfang Database, China Biomedical Literature Database (CBM), and Chinese Science Journal Database (VIP database). Search the international clinical trial registration platform and the Chinese clinical trial registration platform to find ongoing or unpublished trials. The main outcome indicator is the total effective rate of analgesia, and the secondary outcome indicator is pain intensity score and adverse reactions. The RevMan 5.4 software will be used for statistical analysis.This study will provide the latest evidence for acupuncture combined with analgesics to relieve LC pain.The conclusion of this study is to evaluate the effectiveness and safety of acupuncture combined with analgesics in alleviating LC pain.INPLASY202150051 Smoking is almost one of the important factors in the development of LC. The current main treatments for LC include surgery, chemotherapy, radiotherapy, and targeted therapy, etc. Patients with LC reported a series of physical and psychological social symptoms, including coughing, dyspnea, pain, and anxiety. Pain is one of the most serious symptoms of LC patients and seriously affect the patient's quality of life. The cause of LC pain is related to the location of the tumor, the spread and metastasis of the tumor, and the treatment plan.,8 Regarding LC pain, the current main treatment is the use of analgesics, but studies have shown that opioids can cause hypogonadism, inhibit the hypothalamic-pituitary-adrenal axis, and have an impact on bone health. Patients with significant pain are more likely to use alternative therapies such as massage, acupuncture, herbal medicine, and hyperthermia.Primary bronchial lung cancer, also known as lung cancer (LC), ranks second in absolute incidence globally and in developing countries, and is the most common cause of cancer death in the world. A large number of studies have shown that acupuncture can be effective for patients with pain symptoms in cancer patients. The main mechanism of action is to activate the pain modulation system in the body, regulate the human nerve-endocrine-immune system, activate the production, and release of endogenous opioids, and at the same time promote the reduction of substance P and the increase of β-EP content, to achieve the purpose of alleviating cancer pain. In addition, related studies have shown that acupuncture can reduce postoperative opioid consumption and improve postoperative analgesia.As a traditional treatment method, acupuncture has been used clinically, and it may be a better choice for the treatment of LC pain.In recent years, some research data have shown that acupuncture can relieve cancer pain. Although some existing studies have shown that acupuncture combined with analgesics can improve LC pain, there is a lack of relevant comprehensive evaluation. Therefore, we decided to conduct this study to further evaluate the efficacy and safety of acupuncture combined with analgesics in patients with LC pain and provide clinical evidence.2The aim of this study was to evaluate the efficacy and safety of acupuncture combined with analgesics on LC pain, and provide the latest evidence of evidence-based medicine for the clinical treatment of LC pain.33.1https://inplasy.com/inplasy-2021-5-0051/). This protocol will be reported in accordance with the Preferred Reporting Project (PRISMA-P) Statement Guidelines for Systematic Reviews and Meta-Analysis Agreements.The review scheme of this study has been registered on the INPLASY website  of acupuncture combined with analgesics in the treatment of LC pain, whether blinded or unblinded.3.2.2All the patients included in the study were diagnosed LC pain, regardless of age, sex, race, and course of disease.3.2.3The treatment plan is acupuncture combined with analgesics. Acupuncture treatment includes all types, such as electric acupuncture, fire acupuncture, warm acupuncture, body acupuncture, and so on.3.2.4Conventional analgesic treatment.3.2.5The main outcome measure was the total effective rate of analgesia . The secondary outcome indicators were pain intensity score and adverse reactions.3.31.RCTs comparing 2 different types of needle knife;2.Non-randomized controlled trials;3.Duplicated data;4.Invalid outcome indexes.3.4The English databases include PubMed, Embase, Web of Science, Cochrane Library, and Chinese databases include China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP Database (VIP), China Biomedical Literature (CBM). From the establishment of the database to April, 2021, the key words include “acupuncture,” “body acupuncture,” “electro-acupuncture,” “warm acupuncture,” “auricular acupuncture,” “fire needling,” “analgesics,” “lung cancer,” “pain.” In addition, we will also retrieve ongoing or unpublished trials from the International Clinical Trial Registration Platform and Chinese Clinical Trial Registry Platform. PubMed's search strategy is shown in Table 3.53.5.1The literature search results were independently completed by 2 examiners according to the inclusion criteria. Import all the documents searched in the database into EndNote X9 to exclude duplicate documents. Exclude obviously unqualified articles by reading the title and abstract, then read the full text of the remaining articles, and discuss the final included documents in groups. When there is a difference in the results of the literature screening, it will be discussed and resolved with the third examiner. The selection process will be shown in the PRISMA flow chart Fig. .3.5.2The 2 researchers used predesigned tables to collect data, collect the following information: study data , subject details , research methods , intervention measures in the treatment group and the control group, acupuncture therapy, result measurement . Any differences in the data collection process will be resolved through discussion by a third researcher. If the above data in the article is incomplete, we will contact the author to supplement it.3.6 It includes the following 7 domains: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other sources of bias. Each domain includes a judgment of low, high, and unclear risk of bias according to information provided by authors. Disagreements between reviewers will be resolved through discussion with a third reviewer.Two reviewers will use Cochrane collaborative tools to evaluate the quality of the literature.3.73.7.1For continuous data, will be used mean difference (MD) as the effect indicator with 95% confidence interval, and dichotomous data will be calculated as risk ratio (RR) or odds ratio (OR) as the effect index with 95% confidence interval. If the studies are with no statistical homogeneity, the fixed-effect model can be used for analysis; if the studies are with significant statistical heterogeneity, random-effects model analysis will be used. The Review Manager (RevMan) V.5.3 software will be used for statistical analysis.3.7.2χ2 test was used to estimates the degree of heterogeneity. When I2 < 40%, it indicates that no significant statistical heterogeneity. When 40% < I2 < 75%, it indicates that there is statistics heterogeneity, and the source of heterogeneity needs to be further analyzed. When I2 > 75%, it indicates that there is statistics heterogeneity between the studies.3.7.3Subgroup analysis will be performed if there have heterogeneity between the study results, following items will be considered: type of acupuncture, cancer stage, sex, and age.3.7.4We will eliminate the “high-risk” low-quality articles for sensitivity analysis to judge the robustness of the results.3.7.5Two researchers used the Recommendation, Evaluation, Development, and Evaluation system to independently evaluate the quality of evidence for each result, which system divides the level of evidence into 4 levels: high, medium, low, and very low.3.7.6When >10 trials were included in this study, the funnel chart was used to judge the report bias. I3.8The study does not involve the personal information of participants, so no ethical approval is required, and the research will be published in a peer-reviewed journal or related journal meeting.4 this disease has almost become the most widespread and the highest mortality disease in the world. Tumor invasion makes LC pain the most common symptom of patients, which seriously affects the quality of life of patients.,6 At present, common clinical treatments for LC include surgery, chemotherapy, radiotherapy, and targeted therapy, but opioid analgesics are still used for LC pain. Opioids have a good analgesic effect, but their adverse reactions and dependence have always been a problem that has not been effectively solved, and cancer patients are easily tolerated by analgesics. Acupuncture as a traditional Chinese medical technique is widely used in modern clinical practice. A large number of research reports have shown that acupuncture can effectively relieve pain. Its main mechanism is to stimulate the central nervous system to regulate inflammation and significantly reduce the expression of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6.LC is a global health burden. Due to the limited conditions for lung cancer screening,So far, although some RCTs have shown that acupuncture therapy combined with analgesics is effective for LC pain, there is no systematic review. Therefore, this study conducted a systematic review and meta-analysis of acupuncture combined with analgesics in the treatment of LC pain, aiming to provide the latest evidence for the treatment of LC pain and guide clinical decision-making.Conceptualization: Renqing kuang, Guojiang xiong.Data curation: Yun Zhao, Wei Lv, Jiawang Jiang.Formal analysis: Guojiang Xiong, Wei Lv.Methodology: Guojiang xiong, Yun Zhao.Software: Wei Lv, Yun Zhao.Supervision: Guojiang xiong, Wei Lv.Writing – original draft: Renqing Kuang, Jiawang Jiang, Min Yu.Writing – review & editing: Renqing Kuang, Jiawang Jiang.


A significant decrease in clinic visits (p < 0.001) and healthcare utilization (p < 0.05) was also observed. Opioid and non-opioid prescriptions did not change significantly (p = 0.43). 83% of providers agreed that MDC improved patient care. While previous studies have shown the effect of multi-disciplinary care, we show notable improvements with a team established around a once-a-month MDC.Approximately 100 million adults in the United States have chronic pain, though only a subset utilizes the vast majority of healthcare resources. Multidisciplinary care has been shown to improve outcomes in a variety of clinical conditions. There is concern that multidisciplinary care of chronic pain patients may overwhelm existing resources and increase healthcare utilization due to the volume of patients and the complexity of care. We report our findings on the use of multidisciplinary conferences (MDC) to facilitate care for the most complex patients seen at our tertiary center. Thirty-two of nearly 2,000 patients seen per year were discussed at the MDC, making up the top 2% of complex patients in our practice. We evaluated patients' numeric rating score (NRS) of pain, medication use, hospitalizations, emergency department visits, and visits to pain specialists prior to their enrollment in MDC and 1 year later. Matched samples were compared using Wilcoxon's signed rank test. Patients' NRS scores significantly decreased from 7.64 to 5.54 after inclusion in MDC ( Chronic pain (CP) costs between $USD 560–635 billion in health care expenditures, loss of productivity, and disability . CP is aMultidisciplinary care teams have been shown to be effective in specialist care settings such as oncology, inflammatory bowel disease, pediatrics, and cardiology –11. CP pAt our tertiary center, CP patients were referred to a newly formed MDC by their treating physician and were discussed by the care team to create an individualized and holistic treatment plan. We examined outcomes 1 year after patients were added for discussion at MDC, including patients' pain relief and healthcare utilization . Additionally, we surveyed team members' views of the conferences. Findings from this study could encourage the use of a single monthly MDC to facilitate care of complex chronic pain patients as a starting point for multi-disciplinary care.A multidisciplinary team of physicians, nurse practitioners, physician assistants, registered nurses, and medical assistants in anesthesia, pain neurology, psychology, and neurosurgery  was established at Albany Medical Center. Patients were referred to the MDC by their treating provider after failure of multiple therapies and/or if their diagnosis was complex and complicated by comorbidities. As these conferences were initiated to improve quality of patient care, our Institutional Review Board approved data collection and publication with an appropriate HIPAA waiver.Thirty-two chronic pain patients were discussed in MDC between May 2019 to December 2020 and included in this study. Only patients with at least 1 year follow-up since time of inclusion in MDC were considered. Demographic data were collected including age, sex, primary and comorbid pain diagnoses, past medical and surgical history, and insurance.The number of clinical visits  to pain providers, hospitalizations, ED visits, and pain medications were collected from patients' medical records for the year preceding enrollment in the conference and 1 year after enrollment. We also calculated total health care utilization (HCU) using our own equation  which we developed based on similar studies –19. InclQuestionnaires were sent to providers participating in the MDCs to evaluate the impact MDC had on patient care. Providers were asked whether they agreed, held a neutral option, or disagreed with the conference's success in simplifying and improving care, providing more comprehensive treatment plans, and improving pain relief, communication between colleagues, fellow teaching, and job satisfaction. The survey was sent three times to improve response rate.t tests. Healthcare utilization and outcome measures before and after enrollment were assessed using Wilcoxon signed-rank tests. Results were reported as mean ± standard error of the mean (SEM) unless stated otherwise. A p < 0.05 was considered statistically significant. Data were analyzed using GraphPad Prism Software Version 7 . Additional figures were generated with MATLAB Release 2018b .Baseline statistics were compared using independent sample n = 1), continuous CSF leak (n = 1), avascular necrosis (n = 1), scleroderma (n = 1), treatment resistant lumbar radiculopathy (n = 1), and complex regional pain syndrome . Five patients (15.63%) had an additional comorbid pain diagnosis of post-laminectomy syndrome. Twenty patients (62.5%) had previously undergone spine surgeries and 16 patients (50%) were treated with neuromodulation. Payer mix included commercial insurance (71.9%), government insurance (25%), and worker's compensation insurance (3.13%).A total of 32 chronic pain patients were included in this study. A summary of the demographic data is shown in p < 0.001), such that the mean NRS was 7.64 ± 0.30 before enrollment and 5.54 ± 0.50 after enrollment. Mean difference was 2.11 ± 0.5. Twenty-one patients (65.6%) experienced a decrease in NRS pain scores after enrollment, while seven patients (21.88%) experienced no change. Four patients did not have NRS scores documented.Wilcoxon Signed-Ranks test indicated post-enrollment NRS scores were significantly lower than pre-enrollment NRS scores , despite three patients with increased clinic visits after enrollment due to intrathecal pump medication adjustments. Total healthcare utilization decreased significantly as well, from 8.0 ± 1.26 to 4.81 ± 0.74 before and after enrollment respectively . Twenty-two patients (68.75%) had lower total health care utilization after enrollment while seven patients (21.88%) had higher utilization after enrollment, and three patients (9.38%) had no change.To calculate health care utilization scores, we added the number of hospitalizations, the number of outpatient visits (office or clinic visits) and number of ED visits in the year leading up to MDC enrollment and 1-year post-MDC. The number of clinic visits to pain providers and total health-care utilization significantly decreased following inclusion in MDC . Clinic W = 26.5, p = 0.96). The average amount of ED visits was 0.41 ± 0.20 pre-enrollment and 0.50 ± 0.17 1-year post-enrollment . Nineteen patients (59.38%) had no ED visits for pain etiologies before or after enrollment. Of the 13 that utilized the ED, eight patients (25%) had more ED visits post-enrollment, four patients (12.5%) had fewer ED visits post-enrollment, and one had the same number of ED visits. Among patients with increased ED visits, eight visits were pain related visits and five visits were due to a pain-related therapy or intervention they were receiving.There were no significant changes in the number of hospitalizations or ED visits related to pain . The meaW = 12, p = 0.90). MME remained the same for 25 patients (78.13%), decreased for four (12.5%) by an average of 32.81 ± 21.30 MME, and increased for three (9.38%) by an average of 24.17 ± 11.02 MME. On average, patients took 2.03 ± 0.25 non-opioid pain medications 1-year before enrollment and 2.06 ± 0.28 medications after enrollment (p = 0.43). Eleven patients (34.38%) used less non-opioid pain medication 1-year after enrollment, while nine patients (28.13%) used more. Medications taken by each patient along with dosage and MME are listed in There was no significant change in medication usage following inclusion in MDC. The mean MME of opioid medications was 30.42 ± 12.72 prior to enrollment and 28.59 ± 11.05 1-year after enrollment   therapy involved neuromodulation. Ten (31.25%) patients had neuromodulation therapy throughout the study period. Three (12.5%) patients had neuromodulation added to their therapy regimen. Five patients were referred for multidisciplinary care as a result of failure of neuromodulation. One patient had an explant and one patient added IDD to existing SCS.Six of 13 team members responded (46% responder rate). The responders included four physicians (66.67%), one registered nurse (16.67%), and one advanced practice provider (16.67%). Five responders (83.33%) agreed that the conferences improved patient care as a whole and provided patients with more comprehensive treatment plans. Four responders (66.67%) agreed than the conferences provided patients with more pain relief, streamlined patient care, improved communication between colleagues, and improved teaching .We assessed healthcare utilization, pain outcomes, and medication use for the most complex chronic pain patients before and after inclusion in a newly formed MDC. Only 2% of our total patients were felt to warrant inclusion based on expertise of pain providers on our team. We observed a clear shift in healthcare utilization following inclusion in a multidisciplinary discussion. Patients achieved more pain relief with fewer clinic visits during the year after MDC inclusion. Medication use, hospitalizations and ED visits remained stable. Five of 6 providers felt that MDC improved holistic care for patients.At the time of inclusion in MDC, our patients had a mean NRS score between 7 and 8, categorized as severe pain, despite having a mean of 8 pain clinic visits, 0.41 emergency visits and 0.31 hospitalizations a year. Minimal clinically important differences (MCID) have been established to accurately determine clinically significant and insignificant improvements in subjective pain rating scales , 22. TheClinic visits decreased 60% after inclusion in the MDC and ED and hospital visits remained the same. ED and hospitalization rates were lower than typical in this group of patients . We suspOur patients' management did include opioids, which is not surprising as a tertiary center. Stringent regulations often prevent patients from receiving opioids, regardless of proof of need and careful observation by professionals . AdditioFinally, we show that MDC increased physician perception of patient care, and improved communication, fellow teaching, and job satisfaction. MDCs allows physicians of all backgrounds and specialties to learn from one another, exposing them to different perspectives and integrating expert advice from various specialties . FurtherWe acknowledge our study has limitations. First, it is retrospective. Next, we created our own healthcare utilization score equation based on several studies utilizing a similar method –19. NextWe aimed to evaluate the efficacy of MDC in pain relief and decreased healthcare utilization in the top 2% of complex patients in our practice. While previous studies have shown the effect of multi-disciplinary care, we show notable improvements with a team established around a once-a-month MDC. Our study suggests that the implementation of MDC will not only provide better patient care but will improve provider satisfaction when working with complex pain patients.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Albany Medical College Institutional Review Board. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.JP created and coordinated the study, provided patient care, directed chart review and analysis, and assisted in writing the manuscript. ZC, GD, OK, RT, and MN also assisted in writing the manuscript. GD and OK composed figures and tables. CA and JP provided patient care and patient data. ZC, GD, OK, and RB performed chart review and statistical analysis. All authors contributed to manuscript editing and approved the final submission.JP is a consultant for Boston Scientific, Nevro, Medtronic, Saluda and Abbott and receives grant support from Medtronic, Boston Scientific, Abbott, Nevro, NIH R01CA166379 and NIH U44NS115111. She is the medical advisor for Aim Medical Robotics and Karuna and has stock equity. CA is a consultant for Teva, Lilly, Allergan, Amgen, Novartis, and Flowonix. He provides research support to Teva and Allergan. He has stock in Pfizer. He is part of the Speaker's Bureau for Theranica, Tercera, Teva, Lilly, Allergan, Amgen, Novartis, and Flowonix. GD receives fellowship support from Medtronic, Boston Scientific, and Abbott. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflictof interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.