Objective: This systematic review and meta-analysis compared the patient-reported outcomes of intra-articular facet joint injections of normal saline and selected active substances to identify a more effective agent for treating subacute and chronic low back pain (LBP). Methods: The PubMed, Embase, Scopus, Web of Science, and CENTRAL databases were searched for randomized controlled trials and observational studies published in English. A research quality assessment was performed using ROB2 and ROBINS-I. A meta-analysis was conducted using a random-effects model, and the mean differences (MD) with 95% confidence intervals (CI) in efficacy outcomes, including pain, numbness, disability, and quality of life, were assessed. Results: Of the 2467 potential studies, 3 were included (247 patients). The active substances and normal saline had similar therapeutic effects on pain within 1 h, after 1–1.5 months, and after 3–6 months, with MD and 95% CI of 2.43 and −11.61 to 16.50, −0.63 and −7.97 to 6.72, and 1.90 and −16.03 to 19.83, respectively, as well as on the quality of life after 1 and 6 months. Conclusions: The short- and long-term clinical effects of intra-articular facet joint injections of normal saline are comparable to those of other active substances in patients with LBP. Low back pain (LBP) is characterized by discomfort, stiffness, or muscular tension between the lower rib edge and buttock creases with or without sciatica . Chronic or occasional lower back pain (LBP) is a common musculoskeletal disorder. This is true for people of all ages and countries regardless of whether they are economically developed . In 2019Non-surgical treatment for chronic LBP has been promoted as the first-line treatment, whereas surgical options are considered only when non-surgical treatment is not available or fails. However, more recent studies have shown that spinal fusion is not superior to non-surgical treatment based on the long-term outcomes of pain and disability in patients with chronic LBP . For nonIntra-articular FJI was developed when some authors attempted to identify the pain pattern of facet syndrome by using hypertonic saline and lidocaine as placebos. The injected substance options varied from a commonly used mixture of steroids and local anesthetic agents, steroids alone, and local anesthetic agents alone to more novel substances, including ozone, autologous platelet-rich plasma, and hyaluronic acid .Some recent meta-analyses examined how intra-articular normal saline injections help knee osteoarthritis and found that they reduce pain in the short and long term ,7. A netThis study was conducted according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 Statement. This systematic review was registered in the PROSPERO International Prospective Register of Ongoing Systematic Reviews (registration number CRD42020216426).PubMed , Embase For this systematic review, we worked with an information specialist to design an appropriate search strategy to identify original peer-reviewed RCTs and observational studies evaluating and comparing PROs including pain, numbness, disability, quality of life, and complications associated with FJIs of active substances and normal saline as a placebo in patients diagnosed with chronic LBP. Eligible studies were screened by three independent reviewers . Discrepancies between the reviewers were resolved by consensus .Data extraction was performed by three independent reviewers  for the published summary data. Discrepancies between the reviewers were resolved by consensus .The following data were extracted: (1) study characteristics , (2) patient characteristics , (3) intervention , (4) comparators , and (5) outcomes , as well as any other relevant information. Data were extracted from all relevant text, tables, and figures. We contacted the authors of studies with incomplete data. If the trial authors did not respond within 14 days, analyses were conducted using available data.The authors worked independently to assess the risk of bias for the included trials using the Cochrane Risk of Bias Tool 2.0 for RCT studies . We asse2 and χ2 statistics. We determined the levels of heterogeneity using the I2 statistic, as defined in Chapter 9 of the Cochrane Handbook for Systematic Reviews of Interventions, as follows: 0–40% may not be important, 30–60% may represent moderate heterogeneity, 50–90% may represent substantial heterogeneity, and 75–100% may represent considerable heterogeneity. For missing standard deviation data, we imputed the standard deviation as suggested in Chapter 6 of the Cochrane Handbook for Systematic Reviews of Interventions using what is referred to as the Furukawa methods [The primary outcome was the visual analog scale (VAS) score for pain, and the mean difference (MD) between the VAS scores before and after treatment with an associated 95% confidence interval (CI) was determined. Disability outcomes, including the Oswestry Disability Index (ODI) and Pain Disability Questionnaire (PDQ), were also retrieved, including numbness, quality of life outcomes, and adverse events. The results of the studies were included in the meta-analysis and presented as a forest plot, which also showed the statistical power, confidence intervals, and heterogeneity. We assessed clinical and methodological heterogeneity by examining the participant characteristics, intervention regimens, types of interventions, follow-up durations, outcomes, and study design. Statistical heterogeneity was assessed using the I methods . SensitiThe patients and public were not involved in the design, conduct, reporting, or dissemination of our research.A database search identified 2467 records. After removing duplicates, 1305 titles that passed the initial screening, and 112 theme-related abstracts were reviewed to select full-text articles for the eligibility assessment . A totalThe three included studies were published between 1989 and 1998  11,12,1,112,13. Three RCTs did not use the same active substances in their respective treatment arms. One study used a mixture of corticosteroids and a local anesthetic as the intervention . One stuThe risk of bias assessment of the three trials in this study showed adequate randomization in one trial, deviations from the intended interventions in two trials, missing outcome data in two trials, adequate measurement of the outcome in three trials, and selection of the reported result in one trial ,12,13. AThe primary outcome, assessed using the visual analog scale (VAS), was examined in all the included studies, comprising three randomized controlled trials involving 247 patients. Only the study by Lilius reported a disability outcome using a combined score proposed by the authors for the entire study group; a disability outcome was not reported for each intervention group . CaretteA study by Lilius, et al. demonstrated a significant reduction in subjective pain for all participants at all follow-up points ; however, there was no significant difference in the VAS score reduction for intra-articular injection with a mixture of local anesthetics and steroids compared with intra-articular normal saline injection for facet joints L3/4 to L5/S1 for both short- and long-term responses, ranging from 1 h to 3 months after injection .Carette’s study demonstrated no difference in pain reduction after corticosteroid and normal saline injections based on responses to the McGill pain questionnaire  after onp = 0.01) in a specific patient group with five or more of the seven clinical characteristics proposed by the author: (1) age >65 years, (2) no pain exacerbation due to cough, (3) no pain exacerbation by forward flexion, (4) no pain exacerbation when rising from flexion, (5) no pain exacerbation by hyperextension, (6) no pain exacerbation by extension rotation, and (7) pain relief in the recumbent position. For patients who did not satisfy the five criteria, the FJI of normal saline showed better pain improvement, although not significantly [Revel, et al. concluded that the FJI of a local anesthetic significantly improved the VAS score for pain relative to the FJI of normal saline (ficantly .All three studies that reported pain outcomes assessed by the VAS scale were included in the meta-analysis ,12,13. TThe studies by Lilius and Carette reported no difference in pain after FJIs of active substances and normal saline as a placebo within 1–1.5 months of follow-up ,12,13. TTwo studies reported pain scores after long-term follow-up ranging from 3 to 6 months. The study reported significantly greater pain reduction by normal saline than by active substances in the long term , while CSensitivity analysis was performed with an alternative method of standard deviation imputation using the standard deviation from a study included in this meta-analysis instead of the previous meta-analysis. The pooled effect of pain reduction within 1 h, after 1–1.5 months of follow-up, and after long-term follow-up was similar to that obtained using the main imputation method.Our meta-analysis suggests that treatment with intra-articular FJI of normal saline as a placebo showed similar effectiveness as intra-articular FJI of active substances based on patient-reported pain outcomes measured by VAS scales at all studied time points ranging from 0.5 h to 6 months.It is difficult to draw conclusions from these trials because of the heterogeneity in the age range of the populations, types of active substances, locations of back pain, follow-up times, and outcome measurements. The findings suggested no difference in pain reduction after FJIs with normal saline or active substances in patients with CLBP; however, more robustness is required to provide a high level of evidence.A study by Lilius, et al. showed significant pain reduction for both FJIs of normal saline and steroids with local anesthetics and no significant differences between intra-articular saline and intra-articular steroids with local anesthetic injections on a subjective pain scale at all follow-up points ranging from 1 h to 3 months. One-fourth of the participants experienced pain reduction for up to three months after the FJI, and the overall disability score significantly improved, regardless of the injected substance. The therapeutic effect of sarin was unexpected, and only suggestions from a psychosocial point of view and self-regression were provided without clear evidence or explanations .Carette’s study demonstrated similar LBP reduction effects of corticosteroid FJI after 1 and 6 months of follow-up, evaluated using the VAS and McGill Pain Questionnaire . The autRevel, et al. explored the characteristics of patients with chronic LBP that were significant predictors of favorable pain reduction after intra-articular FJI with a local anesthetic, and five characteristics of back pain were found. Normal saline was considered a true placebo, and its therapeutic effect was attributable to inadequate diagnostic criteria, which resulted in the false-positive selection of patients with chronic LBP who would potentially benefit from FJI .A high-quality systematic review and meta-analysis was conducted to identify the injection therapy for subacute and chronic LBP, and only one study that compared the FJIs of active substances with placebo was identified and included in a meta-analysis of pain outcomes, with comparisons of short-term and long-term therapeutic effects showing no significant difference . More reTwo meta-analyses that focused on the efficacy of intra-articular normal saline injections for knee osteoarthritis demonstrated therapeutic effects on pain ,7 and fuNo early trials validated any significant benefit of the active substance over normal saline as the placebo ,12,13, wPain reduction by normal saline has been demonstrated in meta-analyses of osteoarthritis involving the knee ,7 and hiBased on these data, it is reasonable to believe that intra-articular FJI of any solution can reduce LBP in patients with spinal stenosis ,27,28,29This meta-analysis has several limitations. First, the heterogeneous characteristics of the patients, including the type of injected substance and timing of outcome assessment, made it difficult to draw conclusions from the data. Second, some trials did not report the standard deviations required for meta-analysis. Thus, standard deviations were imputed, which may not reflect the actual variation in the outcomes of the study. Third, only a few studies focused on injected substances for intra-articular FJI; therefore, only a few studies were included in the meta-analysis, and some PROs had insufficient outcomes to conduct a meta-analysis. Fourth, no new trials have compared the effects of active substances and normal saline administered via FJIs for more than 20 years. This evidence may not be completely relevant to the current practices of intra-articular JFI. However, this study provides the up-to-date evidence to shed light on the therapeutic effects of intra-articular normal saline FJI.This systematic review and meta-analysis suggests that the short- and long-term clinical outcomes after intra-articular FJIs with normal saline and other active substances in patients with LBP are comparable. Normal saline may not be considered a placebo. Because desensitization, the eradication of calcification and fibrosis, or spurs make it difficult for substances to reach the facet joint, these are possible reasons why normal saline has an effect that is comparable to that of other substances. This may change the paradigm of using saline as a placebo. Additionally, the efficacy of other substances for regeneration may increase if the calcification and fibrosis have been removed before, which needs further research.


Approximately 20% of adults in the United States experience chronic pain. Integrative Medical Group Visit (IMGV) offers an innovative approach to chronic pain management through training in mindfulness, nutrition, and other mind-body techniques combined with peer support. To date, there are no studies on IMGV implementation, despite its promise as a feasible non-pharmacological intervention for chronic pain management. In this study, we assessed the feasibility of implementing IMGV and assessing its effectiveness for chronic pain.t-tests were used to assess changes between scores at baseline and post intervention. Qualitative data were coded by three experienced qualitative researchers using thematic content analysis.Implementation Mapping was used to develop and evaluate implementation strategies for IMGV. Strategies included disseminating educational materials, conducting ongoing training, and conducting educational meetings. IMGV was delivered by three healthcare providers: an allopathic physician, registered yoga teacher, and naturopathic physician. The effectiveness of IMGV on patient health outcomes was assessed through qualitative interviews and a Patient-Reported Outcomes Scale (PROMIS-29). Provider perspectives of acceptability, appropriateness, and feasibility were assessed through periodic reflections (group interviews reflecting on the process of implementation) and field notes. Paired Of the initial 16 patients enrolled in research, 12 completed at least two sessions of the IMGV. Other than fatigue, there was no statistically significant difference between the pre- and post-scores. Patients reported high satisfaction with IMGV, noting the development of new skills for self-care and the supportive community of peers. Themes from patient interviews and periodic reflections included the feasibility of virtual delivery, patient perspectives on acceptability, provider perspectives of feasibility and acceptability, ease of recruitment, complexity of referral and scheduling process, balancing medical check-in with group engagement, and nursing staff availability.IMGV was feasible, acceptable, and effective from the perspectives of patients and providers. Although statistically significant differences were not observed for most PROMIS measures, qualitative results suggested that participants experienced increased social support and increased pain coping skills. Providers found implementation strategies effective, except for engaging nurses, due to staff being overwhelmed from the pandemic. Lessons learned from this pilot study can inform future research on implementation of IMGV. Despite evidence of effectiveness and lower use of high-cost care among participants, IMGV has been minimally implemented.•This is the first study to investigate implementation of IMGV. Due to the COVID-19 pandemic, IMGV was adapted to be delivered virtually via zoom. Here, we describe this adaptation, as well as implementation and effectiveness outcomes.•These findings contribute to a gap in the literature on implementation of evidence-based integrative pain management interventions.Over 50 million adults in the United States, or approximately 20%, experience chronic pain . To manaDespite growing evidence on the effectiveness and importance of integrative pain management, limited accessibility, affordability, and pre-existing patient and provider assumptions complicate their implementation into clinical settings , 7. Barrp = .005), depression (p < .001), sleep quality (p = .04), and perceived stress (p = .04) (n = 65). Qualitative findings included patients gaining a supportive network to share coping strategies for their chronic condition and feeling “not alone.” In a randomized controlled trial (RCT), a nine weekly session IMGV with booster (n = 76) was compared with a usual care control group (n = 79), and demonstrated significant between group differences ; however, recruitment and retention were noted challenges in conducting the trial  model is an innovative approach to integrative pain management, reimbursed by healthcare insurers, that offers training in mindfulness and other complementary approaches to chronic pain in a group setting with a healthcare provider. IMGV combines elements of existing group medical visit models, principles and practices of mindfulness-based stress reduction, and integrative approaches to chronic pain . IMGV wahe trial .These data provide evidence in support of the effectiveness of IMGV among participants who receive the intervention. Further study of the barriers and facilitators to IMGV implementation is needed to broaden IMGV reach and improve outcomes in populations at greatest risk for chronic pain. In this pilot study, we assessed the feasibility of implementing an IMGV and measuring its effects on chronic pain in an outpatient setting with a high burden of patients with chronic pain. By simultaneously studying effectiveness and implementation in a hybrid design, we can speed efforts to close the research-to-practice gap for pressing public health crises .This pilot study took place in the UNC Health Center for Rehabilitation Care (CRC). The CRC is the primary outpatient clinical site for the UNC Department of Physical Medicine and Rehabilitation and the UNC Program on Integrative Medicine. In a recent survey of patients seen at the CRC, patients most frequently identified chronic pain as their primary complaint . PreviouIMGV, as developed by Gardiner et al. 2017, consists of nine weekly 2.5 h sessions, with a tenth follow-up session 3 months later . During In this pilot study, IMGV was delivered by a medical doctor trained in family medicine, a registered yoga teacher, and a naturopathic physician. Patients completed an initial one-on-one visit with the physician co-facilitator, who determined that they were eligible and invited them to participate in the IMGV. The physician also asked for their verbal consent to share contact information with the research team to confirm their initial interest in participating in the research study. Patients who were eligible to participate in the IMGV could participate in the group sessions without taking part in the research component. Due to the COVID-19 pandemic, all recruitment was conducted virtually and IMGV was delivered via telehealth using the HIPAA-compliant version of Zoom teleconferencing software. Zoom was chosen due to the ease of using breakout-rooms for one-on-one visits with the physician. For telehealth delivery, IMGV was shortened to 2 h (from 2.5 h). For this pilot, the 3-month follow up (tenth session) was removed.1.The IMGV participant and facilitator manuals were reviewed and edited by the study team to ensure that language in the curriculum related to physically attending a live session was removed or adapted to fit the virtual setting.2.Hard copies of IMGV participant manuals were mailed to participants and they had access to an online version as well as a website with supplemental materials.3.Participants received individual email meetings and a zoom link containing the meeting information prior to the first IMGV session.4.Participants were called the day before and an hour prior to the first session to address technical challenges and to ensure access to the IMGV manual.5.The healthy meal at the end of each session was replaced with a cooking demonstration of the recipes included in the participant manual.The following adaptations were made prior to recruiting the first cohort:The selection and tailoring of implementation strategies for IMGV was guided by implementation mapping . During Outcome measures were chosen based on both the RE-AIM framework and Proctor’s Outcome Measures , 24. To  Reach was assessed as the percentage and demographics of those referred to IMGV who enrolled versus declined. Demographic information included age, race, ethnicity, gender identity, and insurance status. Engagement was measured by attendance at IMGV sessions.To assess effectiveness of the intervention, patient perspectives were assessed through open-ended questions, and health outcomes through a Patient-Reported Outcomes measure, the PROMIS-29, which was administered by a research assistant (RA) over zoom or telephone before and after participation in the telehealth IMGV program. Participants were given a $20 gift card as an incentive for completing each interview. The PROMIS-29, a comprehensive measure of pain and related quality of life measures, was administered before and after completing the 9-week program. The PROMIS-29 has been shown to have high reliability and validity in the general population .Provider perspectives of acceptability, appropriateness, and feasibility were assessed through periodic reflections (group interviews reflecting on the process of implementation) and field notes . The RA t-tests were used to assess statistically significant changes between scores at baseline and post intervention to control for within-individual variability. In addition to paired t-tests, Wilcoxon Signed-Ranks Tests were also selected to assess changes in pain ratings and PROMIS measures measured at two time points  and frequency data (n and percent) is reported for categorical variables and demographic data. Paired e points . All anae points .Qualitative data, including patient interview transcripts and periodic reflection transcripts, were coded by three experienced qualitative researchers  using thematic content analysis . DedooseA total of 25 patients with chronic pain were referred to participate in the IMGV program see . SixteenOf the four participants who dropped out of the IMGV, two (50%) were Black or African American, one (25%) was Asian or Pacific Islander, and one (25%) was White. Regarding insurance, three (75%) participants were enrolled in Medicaid, two (50%) in private insurance, one (25%) in Medicare, and one (25%) held Military (Veteran’s Administration) coverage. The average age of participants who dropped out was 55, ranging from 37 to 76 years old. One patient was lost to follow up after the initial Zoom orientation and never attended an IMGV session, one participant withdrew after week two because they were moving homes and had difficulty hearing about other patients’ pain, one patient attended two of the first four sessions and then withdrew due to unrelated health issues, and one patient withdrew after week five due to a change in their insurance coverage (and related inability to afford the new co-pay).   Of these patients, 83.3% were female, 75% were white, 16.6% were Black or African American, and 8.3% were Asian or Pacific Islander. No patients identified as Spanish, Hispanic, or Latino/a (0%). The mean age was 52.6, ranging from 31 to 70 years. A total of 41.6% were enrolled in private insurance, 25% in Medicaid, 16.6% in Medicare, 16.6% were uninsured, and 8.3% were covered by the health system’s financial aid program .Over the course of two nine-week cohorts, each session was attended by an average of five patients per session see . Nine paAttendance at each session ranged from two to nine attendees, with higher overall attendance in cohort 1 (6.44) than cohort 2 (4.00). Cohort 1 ran continuously from late August through early November of 2020. Cohort 2 ran from November of 2020 through February of 2021, with breaks for Thanksgiving and winter holidays.   t-tests found a statistically significant difference in one measure: an increase of 3.98 points  on the fatigue subscale of the PROMIS-29 , t(11) = 2.53, p = 0.03. Physical function scores increased as did depression, fatigue, and satisfaction with social roles. Anxiety, sleep disturbance and pain interference decreased. However, other than fatigue, there was no statistically significant difference between the pre- and post-scores. This finding was supported by the non-parametric Wilcoxon Signed-Rank test results  experienced a decrease in their pain score when the post-IMGV rating was compared with the pre-IMGV rating. The largest difference was a decrease of 3 (a pre-IMGV pain rating of 10 and post-IMGV rating of 7). This individual also experienced an increase in physical functioning, anxiety and pain interference while reporting an increase in depression, fatigue, sleep disturbance and satisfaction with participation in social roles. The three other people who experienced decreases in pain rating all exhibited a decrease of one point on the pain scale. Three people experienced no change in their pain rating, all three people rated their pain as a 7 at both pre and post measurements. Five people reported a higher pain rating after IMGV, with the largest increase being a 2-point increase (from 6 to 8). This individual had no change in physical functioning, pain interference, fatigue or sleep disturbance, increased anxiety, depression, and a decrease in satisfaction with participation.For PROMIS measures: a score of 50 is the standard population level mean, and an increase/decrease of 10 represents 1 standard deviation. In this sample, the mean physical functioning score is almost 1 standard deviation lower than the population mean, indicating physical functioning is low in this group. The summary scores as extreme as 1 standard deviation from the normal are the pain interference and anxiety scores, indicating this sample has higher pain interference and higher anxiety than the population level mean. All scores reference the last 7 days except the physical functioning score which has no temporal anchor.Qualitative themes from patient interviews included that the IMGV provides connection with others who can understand chronic pain, participants gain new tools to cope with chronic pain, and participants value the positive group environment. Patients expressed that the information and skills gleaned from the group were helpful, even if they didn’t eliminate pain. One patient said, “the meditation and the yoga itself was a little bit of a physical release. It doesn’t exactly make the pain go away but it makes it easier to deal with.” She went on to describe the components of the program that were helpful.“One was just the camaraderie. I had people to talk with and get to know who’s had similar problems. I got a lot of good information on nutritional eating. I’ve gotten a lot of help with learning to do meditations and that has been very helpful to me. The yoga that we know has been very helpful to me.”-pt.1015Some patients noted that specific tools helped their functional abilities.“…Other ways to help ease my pain. The nutrition information, foods that were good. The proteins, what’s good for inflammation, the chair yoga. I've been doing more. At first it hurt, but I've tried each day and it is getting better and easier to turn. The acupressure really helps my neck.”-pt. 1011For many patients, being able to have improved quality of life without adding new medications felt important, particularly in light of the challenges associated with many pain medications.“I got some new tools and ways that I can- things that I can do to help me feel better without having to do any medications.”-pt. 1004Patients particularly appreciated the social support from others who could understand their experiences.“I think that part of it was good because there was communication between other chronic pain patients, and I think that that’s really good for chronic pain people…it’s nice to connect with people who have the same thing”-pt. 1010Virtual delivery of the IMGV proved to be incredibly helpful for some patients, who noted that they were able to participate on days when they were in so much pain that they wouldn’t have otherwise been able to leave the house.“The big plus for me being virtual was that I'm currently not really able to drive. I don't have–If it is one of those situations where I would have to rely on Uber or Lyft or my husband to get me to a weekly session, that probably would have not been possible. One of the benefits was I could sit on my bed and log into the computer and participate”-pt.1012Participants would regularly attend the IMGV and note that they were having a particularly hard day. Some patients did not have their cameras on for the full session when they felt this way. Others noted that on days when they were experiencing a lot of pain, it was difficult to focus on the session content.“Just trying to sit and the chronic pain does interrupt your thought processes. At certain points, my brain would be focused on the pain instead of focused on the class. There was a little bit of that during the second hour each week.”-pt. 1010This presents a challenge for any behavioral intervention for people in pain—it is difficult to focus or be active during pain flare-ups. Others noted that it would have been more comfortable if sessions had been held in-person.“It was difficult doing it through the computer…I prefer actual in a group versus online. It was a little uncomfortable, you don't see everybody, and you don't really see what’s going on in the space. I guess, I'm used to seeing something different like what I saw in [a group program for substance use disorder]. It was just a little uncomfortable, but not uncomfortable enough to make me not want to participate.”-pt. 1009Overall, patient participants found the IMGV highly acceptable, and advocated that the University health system continue the program. One patient said,“My general takeaway is that it was a wonderful program…I would like to be able to see UNC continue groups like this, even if it’s not part of a study, because it was a very good experience, and the support system was just very beneficial. I know I was sad when it was over. I was asking, are you going to start a second group? I want to be part of a second group!”-pt.1012At the same time, she went on to note that the curriculum material was not equally applicable across all chronic pain conditions. She said,“I think some of the material was helpful, but sometimes it was hard for me to participate because the program seems to be aimed at people who have chronic pain from inflammation, like chronic arthritis or something and for degenerative disc disease or something. The type of chronic pain that I have really doesn't fit in that category. So some of the sessions and some of the material presented really didn't fit my particular needs.”Other patients noted that the IMGV was well-structured and wouldn’t have wanted to change it.“I thought the program was well structured with just enough accountability without being pushy or overly aggressive on doing the homework. It was perfect, I thought the way it was structured was perfect.”-pt. 1004Providers noted the ease of recruiting patients into the program, the complexity of setting up a new referral and scheduling process, the challenge of balancing the medical check-in portion of the IMGV with group engagement, and that nursing staff had conflicting clinical roles that prevented participation in the program [5 months into the COVID-19 pandemic].Despite launching recruitment efforts during the first year of the COVID-19 pandemic, recruitment into the IMGV proceeded smoothly. The IMGV physician was familiar with the patient population at the clinic and recognized a need for interventions for patients with chronic pain. As implementation efforts got underway, she perceived that the main need was to inform other clinicians that the program was happening.“I’m not incredibly worried about recruitment, but I do think it’ll be important, at least within our department, to tell everybody this is happening so that there’s at least the option of recruiting those patients. Starting a wait list, I think, would actually be helpful for assisting in the program.”-IMGV PhysicianA flyer was developed and approved by the department leadership and emailed to department staff and faculty. Other than developing the flyer and emailing it out to the clinic staff, there were relatively few other staff engagement activities planned, as the clinic was understaffed and staff were short on time, and many others were working from home at the time.“Yeah, so we did complete—the flyers were approved and completed. I think that making sure that those flyers are up and that [clinic] staff have access to them…I sent in that email to the [department] listserv talking about the group, but that’s really the only effort that I’ve made to involve staff.”-IMGV Yoga TeacherAnother recruitment effort included giving a departmental grand rounds on the program, though due to scheduling issues this was done late in the process. Additionally, referring physicians were invited to participate in a group session to have direct experience and improve their initial communication with their patients for recruitment. One referring MD did do this and enjoyed the interactive role during that session, especially seeing known patients being engaged.Faculty physicians began referring patients with chronic pain to the IMGV physician, who then scheduled individual visits with patients to discuss integrative medicine approached to chronic pain and assess interest in group-based care. During this phase, few barriers were encountered when recruiting patients in the IMGV. Patients were interested in the model and were looking for new approaches to manage their chronic pain conditions. The IMGV physician was excited to begin the groups and that patients expressed interest in participating.One of the challenges the implementation team faced was developing a simple referral process for the IMGV in the electronic health record. The team members noted that referrals for patients with pain could sometimes be confusing, noting that referrals did not always specify which physician the patient was being referred to see. In addition to IMGV, the physician offered integrative medicine consults at the clinic. This began during the same time period and there was confusion among staff about who should be referred to integrative medicine and what to tell patients to expect. The implementation team realized that they needed the collaboration of the scheduling team and the embedded electronic health record specialist to develop a referral process to easily direct patients to the IMGV.“there’s some step there of getting people on to my schedule. I don’t think I have access rights in [the electronic health record] to do that. We’ll need someone to do that.”- IMGV PhysicianIn addition to developing a process to easily direct referrals to the IMGV physician, a new template needed to be built so that multiple patients could be scheduled to see the same physician at the same time.“There was building a new scheduling template so that [IMGV Physician] could see 10 patients at a time, and a lot of back and forth with the scheduling staff about how to communicate with them.” -IMGV Yoga TeacherWhile developing this electronic infrastructure required some initial set-up and explanation of the group visit model to the clinic staff, once the referral process and scheduling templates were in place, there were few hiccups.To deliver the groups online, the implementation team needed to re-design the medical check-in portion of IMGV. When sessions had been held in-person in previous studies, patients were handed a check-in sheet which they filled out and handed to the doctor. The doctor was then able to review patient’s check-in sheets with them quickly and pull them aside one-on-one, or patients could share their check-in with the group. For virtual delivery, patients were given a brief survey to fill out weekly for the medical check-in. This facilitated the physician being able to address any pressing medical questions with the participants. However, it also became apparent that participants felt comfortable completing their check-ins with the group, and only wanted to meet with the physician one-on-one to discuss particularly private or complex topics. Many patients wanted to share updates related to their chronic pain with other members of the group weekly. The physician said,  “Yeah, something for us to figure out, how to do this efficiently…the other thing we had asked was about, do we need to pull people out? The answer was no. The check-ins can happen in a Zoom group the way they can happen in-person in a group…with the group there’s a lot of sharing that happens”—IMGV PhysicianThe IMGV physician also noted that because the group was co-facilitated by a yoga instructor, she was able to complete notes while the group was going on. One-on-one check-ins with patients happened before and after the two hours of group time , but overall, the physician felt that this was a manageable workload.One of the planned implementation strategies identified through the implementation mapping process was to train nursing staff to administer the check-in process for patients as they arrived for the IMGV. However, as the pandemic continued and it became clear that the only way to deliver a group intervention would be through telehealth, this strategy became less tenable. Shortly before the IMGV program was scheduled to begin, the nurse manager passed away unexpectedly, and the small team was left grief-stricken and shorthanded. Rather than ask the nursing team to take on the task of learning how to administer a new clinical intervention, the implementation team chose to take on the enrollment and check-in process themselves.“I think we’re assuming that staff is pretty much overworked with the shortage and nursing and scheduling folks. We’re proceeding on the assumption that, basically, [yoga instructor] and I are gonna do all of that…I don’t think we’ll be asking for much from staff.”-IMGV PhysicianWhile the implementation team had initially intended to manage the check-in process temporarily and involve the nursing staff more integrally once a new nurse was hired, it became clear over time that there were continuing demands on the small nursing team. Ultimately, while one nurse shadowed several IMGV sessions, nursing staff did not take on any role in the IMGV, and the facilitators managed the check-in process independently.In this pilot study, IMGV was successfully implemented into an outpatient rehabilitation center. Ten of the eleven implementation strategies developed using the five tasks of implementation mapping were feasible and successfully executed. Patients and providers found the IMGV program highly acceptable and feasible. Quantitative measures of IMGV showed that physical functioning and satisfaction with participation in social roles increased, while anxiety, pain interference, and sleep disturbance decreased. However, fatigue significantly increased, and though not significant, depression increased as well. Qualitative findings indicated that patients found that IMGV gave them new tools to cope with their pain and social support from others who understood their unique circumstances. Interpretation of the PROMIS-29 changes may be linked to the onset of the COVID-19 pandemic and the disruption in activities due to the stay-at-home order in North Carolina.The use of a hybrid implementation-effectiveness study design helped to create a holistic if complex picture of the process of implementation. To assess both implementation and effectiveness outcomes, this small pilot study involved several data capture methods, including patient interviews, periodic reflections, field notes, patient reported outcome measures, and recruitment, retention, and attendance data. While this was feasible, future larger trials with larger volumes of qualitative data may benefit from the use of rapid qualitative data analysis methods .The IMGV program was initially designed for primary care settings, and this implementation context was distinct in that it was an outpatient rehabilitation clinic. Patients in this setting may present with more complex pain than average primary care patients, as indicated by the low physical functioning scores in this sample. The patients in this study represented a heterogeneous population; some people had experienced chronic pain for decades, some for less than 1 year, with a wide range of diagnoses.There was substantial interest in IMGV from providers and patients, and a clear perceived need for non-pharmacologic, integrative resources for chronic pain management in this setting. However, only 12 of the 16 patients who initially enrolled in research on IMGV went on to complete the intervention. Previous studies of IMGV have similarly found that more patients initially express interest in the program than actually enroll and attend . From the administrative lens, a budget impact analysis and/or cost effectiveness analysis would provide key information to decision-makers, as staff time and financing was of principal concern for sustaining the program.To date, there have been no studies on implementation of IMGV specifically, despite its promise as a feasible non-pharmacological intervention for chronic pain management. Use of a hybrid implementation-effectiveness design allowed us to look at issues impacting implementation and effectiveness simultaneously. Using periodic reflections allowed for data capture while minimizing burden on busy clinicians and implementation staff. Incorporating multiple learners , allowed for a complex pilot study and data collection with a small budget. Finally, methods prioritized patient perspectives and preferences.There is substantial interest and need among patients with chronic pain and the healthcare providers who treat them to make integrative pain management programs affordable and accessible. Prior studies have established that IMGV is a promising model to improve physical functioning, decrease anxiety, and improve social satisfaction among patients with chronic pain in a format that is reimbursed by insurance companies. In this study, Implementation Mapping allowed for the development of theory-based implementation strategies evaluated using implementation outcomes. In this small, single-site pilot study, IMGV was successfully implemented into an outpatient rehabilitation center, with a population of patients with chronic pain with low physical functioning.However, in this small sample, fatigue was the only sub-score of the PROMIS-29 to change significantly, and fatigue was significantly worse post-intervention. It is unclear from this pilot study if the intervention was not effective, the adaptations from the original intervention were too substantial, the measures being used were not responsive enough in the short time frame, or were not measuring the correct constructs. With a very small sample size, no control condition, and no randomization, limited conclusions can be drawn from this pilot study.Lessons learned in this pilot study provide valuable insight for future, fully powered trials. Methods used in this pilot study could be replicated in future research with larger sample sizes, control conditions, and randomization to determine effective implementation strategies for IMGV. Future research should include multiple clinical sites with diverse patient populations, development of sustainment strategies, a cost evaluation component, measurement of fidelity to core components of IMGV, and use rapid qualitative analysis methods to act upon qualitative findings. While disruptive events like the COVID-19 pandemic cannot be predicted, future research should plan for some flexibility in implementation efforts, as well as thorough documentation of adaptations, given the unpredictability of world events.


Overcrowding in the emergency department (ED) is a growing phenomenon worldwide, which is associated with increased length of hospital stay, high healthcare costs and worse patient outcomes. With the rapidly aging population in the Netherlands and frequent ED shutdowns due to staff shortages, this problem will probably not decrease in the near future. Chest pain is responsible for about 10% of all ED visits. It is important to rapidly diagnose or exclude life-threatening causes of chest pain. When an acute coronary syndrome (ACS) is suspected, the diagnostic work-up is a combination of a 12-lead electrocardiogram (ECG), clinical evaluation and cardiac troponin measurement(s) [Netherlands Heart Journal, Manten et al. evaluate the performance of two clinical decision rules for telephone triage of chest pain patients contacting out-of-hours primary care facilities, the Marburg Heart Score (MHS) and the INTERCHEST score [Multiple clinical decision rules to improve pre-hospital triage of chest pain patients have been developed and evaluated, both in the primary care setting and in the ambulance care setting. When patients contact the general practitioner or the emergency number, triage is initially performed by telephone consultation using standardised Netherlands Triage Standard (NTS) protocols. However, in chest pain patients the NTS leads to a high number of unnecessary referrals to the ED, while the level of urgency is underestimated in 27% of the patients with an ACS or other life-threatening conditions . In thisST score . Both clST score . With reST score . The maiST score . ImportaST score . Ruling In conclusion, these studies demonstrate that implementation of pre-hospital clinical decision rules has the potential to improve efficiency in the triage of chest pain patients, while reducing ED overcrowding. Moreover, ruling out an ACS in the pre-hospital setting with the HEART score in low-risk patients leads to a reduction in healthcare costs without increasing the number of patients with an ACS after 30 days, as compared to transporting all patients to the ED.Novel developments include high-sensitivity POC troponin assays, the use of artificial intelligence to assist and expand pre-hospital ECG interpretation, and the introduction of regional pre-hospital triage networks with cardiologist videoconsultation options. These promising initiatives have the potential to further improve the diagnostic accuracy of the algorithms used and the logistics of care for chest pain patients.


Prospective single-center observational study.To investigate the effects and limitations of self-motor-control exercise in patients with chronic low back pain.Although exercise therapy and physical therapy have been shown to be effective in treating chronic low back pain, these therapies are often discontinued due to patients’ non-compliance, and their effectiveness cannot be fully demonstrated.Fifteen patients with low back pain, no apparent organic disease, who had been symptomatic for at least three months, and could continue motor-control exercise at home for at least six months were included in the study. Low back pain , locomotor 25, stand-up test, two-step test, trunk and total body muscle mass by the impedance method, and spinal sagittal alignment were examined before the intervention to establish a baseline, and at two and six months after the intervention.Significant improvement was observed in the back pain VAS (p<0.01), stand-up test (p = 0.03), two-step test (p = 0.01), and locomotor 25 (p = 0.04) before and after the intervention. In contrast, there were no significant changes in muscle mass and sagittal alignment. The effect of long-term exercise was more pronounced in patients without spinal deformity.Self-exercise for patients with chronic low back pain was effective in improving pain and function, although it did not directly affect muscle mass or alignment. Moreover, strength training of the lumbar back muscles alone was not found to be effective in patients with spinal deformities. Chronic low back pain is defined as low back pain that persists longer than three months . PatientExercise therapy is also known to be helpful treating chronic low back pain. It is associated with the prevention and improvement of low back pain, and there is a known correlation between an active daily lifestyle and prevention of chronic low back pain. Therefore, a lifestyle that incorporates a moderate degree of exercise is recommended. In a randomized controlled trial of patients with chronic low back pain, exercise therapy was found to be effective in improving the range of motion in individuals with low back pain, as well as improving the functional disability, pain, motor function, health status, muscle strength, and endurance . ExercisMotor-control exercise involves training to improve the muscle function of the deep extensor muscles of the trunk, such as the transversus abdominis, internal abdominal oblique, and multifidus muscles, with the aim of improving spinal stability. Compared to a control group, improvements in pain and physical function have been observed through motor-control exercise training . TraininThe purpose of this study was therefore to determine the effectiveness and limitations of performing motor-control exercises at home in patients with chronic low back pain.This is a single-center prospective observational study.The institutional review board of the representative facility reviewed and approved this study . Informed consent documents obtained from all participants in this study are availbale for publication (as outlined in PLOS consent form). Further, the study participant provided written informed consent (as outlined in the PLOS consent form) to publish the case details, including images shown in Fifteen patients with low back pain, no apparent organic disease, had been symptomatic for at least three months, and could continue motor-control exercise at home for at least six months were included in the study (average age 60.4 years). In addition, based on the Scoliosis Research Society–Schwab adult spinal deformity (ASD) classification , four paPatients with a history of surgery, cases in which the back pain was caused by malignancies, fractures, or infections, and cases in which back pain was of visceral origin, such as of the renal–urinary system or due to gynecological disease, were excluded. Baseline testing, prior to intervention, confirmed that the stand-up and locomotor 25 tests yielded significantly worse motor function results for the ASD group when compared to the non-ASD group. In contrast, there were no significant differences in muscles mass or the degree of back pain between the two groups .The intervention exercises were the following: “cat-dog” as a trunk flexion exercise, “bridge” as an extension exercise, and “draw-in” for deep muscle strengthening . In cat-The patients were instructed on content and intensity of the exercises during the rehabilitation sessions at the clinic. The patients were instructed to exercise at least twice weekly for 20 minutes a day for six months.The low back pain , locomotor 25 , stand-ut-tests. Non-continuous variables were evaluated using the Fisher’s exact test. To compare multiple groups, one-way analysis of variance and the Bonferroni post-hoc testing were employed. A p-value of <0.05 denoted statistical significance. All statistical analyses were conducted with SPSS version 25.0 .Continuous variables were evaluated using the Student’s and paired The present study was conducted in accordance with the Helsinki Declaration, and the patients provided informed consent prior to participation. The study protocol was approved by the institutional review boards of all participating hospitals.The low back pain (VAS) improved as a function of time between pre-intervention and six months post-intervention [ . The nonThere was no significant change in the muscle volume in the ASD and non-ASD groups .There was no significant change in the spinal sagittal alignment in the ASD and non-ASD groups .In this study, self-exercise was shown to improve motor function and pain in patients with chronic low back pain, although spinal alignment and muscle mass did not improve. There are several hypotheses that could explain how exercise facilitates these improvements. First, exercise therapy may have helped relieve nociceptive or neuropathic pain by gradually stretching immobilized tissues and restoring structural and functional mechanisms including alignment, blood flow, and oxygen uptake. Second, the strengthening of paraspinal muscles may contribute to pain relief by stabilizing the areas of nociceptive pain caused by mechanical instability. Third, exercise tends to increase endogenous opioid secretion, contributing to the activation of the descending pain suppression system . ContinuPatients without spinal deformity showed improvement with prolonged exercise, but no effect was observed in patients with spinal deformity. There is a significant correlation between abnormal spinal sagittal alignment and health-related quality of life scores . ProgresThe significance of exercise therapy for adult spinal deformity remains unclear. There is sufficient evidence that the progression of deformity is associated with degeneration of the intervertebral discs as well as weakness of the back muscles. Therefore, exercise therapy may be effective in preventing the progression of spinal deformity. However, in this study, trunk muscle training alone did not improve pain or motor function in cases of spinal deformity.A previous report has shown the effectiveness of stretching and strength training interventions in improving the flexibility of the lower extremities, such as the hip joint, as well as the trunk, in the treating the spinal deformity ; howeverNevertheless, the long-term effects of exercise therapy on low back pain have not been clearly demonstrated. While some reports indicate that the effects of pain relief and improvement in functional disability are maintained 12 months after the end of treatment , others In the present study, exercise improved motor function and pain over a longer period of time, especially in patients without spinal deformity. Exercise has been shown to be effective in preventing new or recurrent low back pain , and we There are several limitations to this study. First, the sample size was small. Second, the intervention period was limited to six months. Third, oral medications were not investigated. Nevertheless, the effects of self-motor-control exercise from multiple perspectives, including pain, motor function, muscle mass, and sagittal alignment have not been previously prospectively investigated. Self-motor-control exercise at home is extremely useful for alleviating pain and restoring motor functions in patients with chronic low back pain, in the absence of spinal deformity. In future, it would be desirable to examine in more detail how varying the intensity of self-motor control exercises and the duration of intervention affect chronic low back pain.S1 Data(XLSX)Click here for additional data file.


In total, 74% of patients with MS relapse reported a poorer QoL due to pain. A lower psychological well-being was correlated with greater pain (MSIS29psy score). An increased number of prior relapses was a predictor of more pain at relapse onset. Conclusions: Pain was common at the time of MS relapse and improved, but was still significant, six weeks after treatment with corticosteroids. Further studies are required to better understand relapse-related pain.Background: We assessed the prevalence and risks associated with pain during and after a multiple sclerosis (MS) relapse, and the impact of pain on quality of life (QoL), in MS patients. Methods: 117 patients suffering an acute MS relapse were evaluated with clinician- and patient-reported outcomes, including the expanded disability status scale (EDSS), Multiple Sclerosis Impact Scale (MSIS-29), and MS Walking scale-12 (MSWS-12). Relapse-related pain was assessed via the short-form 36 (SF-36) questionnaire upon first visit (relapse onset) and at 6 weeks after treatment with intravenous methylprednisolone (follow-up visit). Results: Pain was present in 80% of patients at relapse onset. Patients with pain were more impaired physically (higher mean scores on MSIS-29 Chronic pain is a common symptom in multiple sclerosis (MS). In one study that included patients with relapsing and progressive MS, 98% of patients reported bodily pain . For somSeveral studies have explored the risk factors for pain in patients with MS. In a systematic review of 21 studies, factors including female gender, non-relapsing-remitting MS type, a longer duration of MS, poor physical and emotional well-being, fatigue, and social factors  were associated with chronic pain . In the Few studies have looked at pain following MS relapses. Indeed, many studies on MS-related pain actively exclude patients during relapse. In a large systematic review and meta-analysis, Foley et al. analysed 28 papers studying pain in people with relapsing-remitting or secondary progressive MS . Only onThe aim of our study was to use the SF-36 patient-reported outcome measure to assess the prevalence and risks associated with pain both during an MS relapse and after treatment with corticosteroids, and the impact of pain on the QoL of MS patients.p < 0.001) and at 6-week follow-up   at the time of relapse with a mean age and SD of 38.3 (8.8) years. The mean SF-36 bodily pain scores between patients with and without pain significantly differed at relapse onset  .At relapse onset, 80% of the patients reported pain. More than half of the patients had moderate to very severe pain. Six weeks after relapse, the number of patients with moderate, severe, and very severe pain decreased, and the number of patients with no pain, very mild, and mild pain increased .p value < 0.0001).For all patients, the EDSS, MSIS-29 , and MSWS-12 scores were higher and the mean values on all the SF-36 scales were lower (more pain) at relapse onset than six weeks later . At relaphys and MSWS-12 and lower mean scores on the role physical, physical, pain, and vitality scales .We found a significant association between more bodily pain and a greater physical and psychological impact at the time of the MS relapse and six weeks later , as demop < 0.001). The correlations were stronger at the six-week follow-up than relapse onset. A moderately positive correlation was found between pain and all the SF-36 variables (p < 0.001).Bodily pain was also significantly correlated with the other SF-36 variables. At relapse onset, a positive moderate correlation between pain and all the SF-36 variables was noted, except for emotional role functioning and general health perceptions, where the correlations were weak , the worse the pain in people with MS. In most studies, EDSS does not correlate with the intensity of pain [Taken together, our results suggest that the worse the physical impairment at relapse, as evaluated by MSIS-29 of pain ,16,17. F of pain . In anot of pain . HoweverPSY or the mental domains of SF-36 . The scores in all of these domains significantly decreased in patients with more severe pain, both at relapse and six weeks later  at 1 g daily for 3 days given in an out-patient setting versus in an in-home setting, conducted at the National Hospital for Neurology and Neurosurgery, London, UK ,30.In the original trial, only patients with relapsing-remitting MS who did not have disease progression between relapses were included. They had acute MS relapses with a worsening of their neurological symptoms which lasted more than 24 h and less than 4 weeks. There were 149 eligible patients and 138 patients participated in the end. In the present study, we analysed the data from 117 adult MS patients; for 21 patients, we did not have information on their pain or the other analysed parameters. Therefore, we excluded them.Patients were excluded if they had mild relapses defined by the treating physician as not having a significant effect on their function, or if they had relapses severe enough to require inpatient hospitalisation. Data on pain at the follow-up visit were not available for five patients. All the patients received corticosteroid treatment.All the patients signed informed consent and the study was approved by the Ethics Committee of University College London Hospital, UK.Data regarding pain were collected via the SF-36 bodily pain scale for the 4 weeks leading up to the first visit (relapse onset) and for the 4 weeks leading up to the post-corticosteroid visit at 6 weeks (follow-up visit) . Patients who scored less than 80 points on the SF-36 were considered to have an impaired quality of life due to pain, relative to the normative data established for the healthy population in England . All thephys; 20 items) and psychological  impairments. The Twelve-Item MS Walking scale (MSWS-12) was used to evaluate patient-reported walking disability. The SF-36 scale assessed eight different patient domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, mental health, and two global scores . Higher scores on EDSS, MSIS-29, and MSWS-12 indicated greater patient disability.The patients were also evaluated with the EDSS to assess their disability across eight functional systems: pyramidal, cerebellar, brainstem, sensory system, bowel/bladder function, visual function, and mental function. The patients were also assessed with the Multiple Sclerosis Impact Scale (MSIS-29), a patient-reported outcome scale that consists of two subscales, which evaluate physical , and 95% confidence intervals (CI) were calculated. The means between the groups and means for the total sample at baseline and at six-week follow-up were compared with a t-test, corrected for multiple comparisons. phys, MSIS-29psych, MSWS-12, and the SF-36 categories  at relapse onset and six weeks later.The Pearson’s correlation coefficient was calculated between bodily pain and age, duration of MS, EDSS, MSIS-29 Pain was common in our cohort of MS patients; it worsened following relapse and was still significant six weeks after treatment with corticosteroids, where it was albeit less severe than at relapse onset. Patients with a greater number of prior relapses and greater disability experienced greater pain at relapse onset. Pain was associated with a poorer physical and psychological well-being and quality of life.Our data indicate a bi-directional relationship between relapse-related pain and physical and psychological well-being, a finding that argues for an interdisciplinary approach to treating MS patients during a relapse.


The SANE score at 36 months indicated that 54 patients (83.08%) were completely satisfied with the treatment. Conclusion: ADMSC treatment exerted favorable effects on the clinical outcomes of patients with GOA, providing pain relief and improving shoulder function. Our data support its use as a conservative treatment option for osteoarthritis.Background: Glenohumeral osteoarthritis (GOA) is associated with disabling shoulder pain that affects everyday life. Its management comprises various treatment approaches, both conservative and surgical. Regenerative medicine has gained a major role in the conservative treatment of osteoarthritis. Intra-articular injection of adipose-derived mesenchymal stem cells (ADMSCs) is a widely used regenerative medicine approach. The aim of this retrospective study was to report the safety and clinical outcomes of intra-articular injection of ADMSCs in patients with GOA over 36-months. Methods: This retrospective observational study involved patients with chronic shoulder pain resistant to standard conservative treatment and a diagnosis of concentric GOA, who received an intra-articular injection of autologous micro-fragmented adipose tissue (μFAT). The values of the Constant–Murley score (CMS), the visual analog scale (VAS), and the simple shoulder test (SST), collected at baseline and at 12, 24, and 36 months, were analyzed to assess treatment efficacy. The single assessment numeric evaluation (SANE) was used to rate patient satisfaction. The Friedman test was used to compare observations of CMS, VAS, and SST values repeated on the same subjects. The significance threshold was set at 0.05. Results: The participants were 65 patients with a mean age of 54.19 years and a nearly equal gender distribution. Most had mild concentric GOA classified as Samilson–Prieto grade 1. The mean follow-up duration was 44.25 months. The postoperative clinical scores showed significant improvement. At 36 months, the CMS was 84.60, the VAS score was 3.34, and the SST score was 10.15 (all  Osteoarthritis (OA) is a highly complex multifactorial condition, where cartilage, subchondral bone, and the synovial membrane play a critical role in disease development . AlteratGlenohumeral osteoarthritis (GOA) can loosely be categorized into primary and secondary categories. Primary GOA accounts for the overwhelming majority of cases (approximately 90%) and typically affects individuals aged 60 years or older. It commonly involves degeneration of the articular cartilage, abnormally dense subchondral bone, development of osteophytes, and erosion of the posterior glenoid, with consequent posterior displacement of the humeral head . NotablySecondary GOA is more common in younger patients ,10. OtheBefore undertaking surgical management of GOA, a non-operative treatment approach aiming to mitigate pain, enhance function, and where possible minimize disease progression should be considered ,11. GeneIn the past decade, the use of orthobiologics in shoulder surgery has rapidly expanded. Commonly employed biologics in such patients include progenitor cells, growth factors, PRP, and biological matrices. The potential benefits of incorporating biological augmentation in traditional shoulder surgery protocols include minimal invasiveness, enhanced healing capacity, and expedited recovery. However, their wider use is currently hampered by cost and by limited evidence of their long-term effectiveness. Moreover, the literature regarding the use and efficacy of biologics in shoulder surgery is quite variable in terms of indications, type of product, processing methods, and mode of administration. Notably, some studies have reported encouraging results for isolated biologic treatment or biologic-enhanced surgery, whereas others have demonstrated no consistent advantages.Products based on PRP and mesenchymal stem cells (MSCs) have undergone a rapid surge in popularity after they were reported to improve knee function and pain . HoweverThe role of MSCs as “guardians of inflammation”  has gradAdipose-derived mesenchymal stem cells (ADMSCs) possess significant multipotency, particularly in the chondrogenic lineage . AdiposeGiven the increasing use of ADMSCs in the conservative treatment of OA, the aim of this study was to examinate functional outcomes, pain, and satisfaction in a cohort of patients with GOA treated with intra-articular injection of autologous micro-fragmented adipose tissue over a 36-month follow-up period. This is simple retrospective design with one group  that wasThe study was approved by the Ethics Committee of Verona and Rovigo, Italy (protocol no. 61386-19 September 2018). We searched the institutional database for the records of the patients who received an intra-articular injection of autologous μFAT in the shoulder joint from October 2018 to June 2020 at IRCSS Sacro Cuore-Don Calabria Hospital  and had a follow-up pereiod of at least 36 months.Inclusion criteria were as follows: patients with a history of at least 6 months of chronic shoulder pain resistant to conservative treatment, e.g., physical therapy, activity modification, non-steroidal anti-inflammatory drugs, corticosteroids, PRP, or hyaluronic acid injection, and a clinical and radiological diagnosis of concentric GOA.Exclusion criteria were acute or chronic rotator cuff tears, acute tendonitis or bursitis, adhesive capsulitis, impingement syndrome, chronic subacromial pain, eccentric GOA, and severe concentric or eccentric GOA with a recommendation of shoulder replacement. All procedures were performed by a single surgeon (S.N.).® system  as recommended by the manufacturer [Participants were positioned in supine position on a table in a dedicated room. Employing aseptic and sterile conditions, a small incision was executed in the abdominal region, below the umbilicus under local anesthesia. This incision facilitated the insertion of a 17 G blunt cannula that was connected to a Luer lock syringe with a volume capacity of 60 cc. Subsequently, patients underwent percutaneous administration of a solution composed of 500 mL of saline, 50 mL of lidocaine at a concentration of 2%, and 1 mL of epinephrine at a dilution of 1:1000 into the subcutaneous adipose tissue of the abdominal region. Following a 10 min interval, approximately 60 mL of adipose tissue was hand extracted using a 13 G blunt cannula connected to the syringe. The acquired lipoaspirate was then subjected to processing through the Lipogemsfacturer . This syBefore the surgical procedure, we collected the following patient data: gender, age, body mass index (BMI), American Society of Anesthesiologists (ASA) class, affected side, and whether arthroscopy had been performed before the procedure.We examined the X-rays taken for GOA diagnosis and graded the stage of arthrosis according to Samilson–Prieto grade ,36: 0  was used for the preoperative and postoperative assessment of shoulder pain (up to 15 points), activities of daily living (up to 20 points), range of movement up to 40 points), and strength (up to 25 points). The maximum score (100 points) is given for an absence of symptoms and good health, the lowest score is 0 ,38,39,40 points, The simple shoulder test (SST), a rapid and effective 12-item questionnaire requiring affirmative or negative responses, was also employed to assess shoulder pain and function before and after the procedure ,42,43. Sp-value < 0.05 was considered significant.All analyses were conducted using Excel (Microsoft (version 16.75.2), Redmond, WA, USA) with the XLSTAT resource pack . The Shapiro–Wilk test was performed to assess whether the data showed a nonparametric distribution. The calculated mean values were also reported for all continuous data. Percentage frequencies were used for qualitative variables. The baseline and postoperative clinical scores were compared using the nonparametric Friedman test, which is used for repeated measures analysis, to determine differences in the Constant-Murley score (CMS), the visual analog scale (VAS), and the simple shoulder test (SST) at baseline and at 12, 24, and 36 month follow-ups. A 2 , range 18.79–36.58. There were 47 patients (72.31%) with ASA 1 , 17 (26.15%) with ASA 2 (mild systemic disease), and a single patient (1.54%) with ASA 3 (severe systemic disease).The participants were 65 patients, 33 men (50.77%) and 32 women (49.23%), with a mean age of 54.19 years . Their age ranged from 34 to 73 years. The right shoulder was affected in 35 patients (53.85%) and the left in 30 (46.15%). The mean BMI was 25.00 kg/mAs regards to the radiological stage using Samilson–Prieto grading, 53 patients (81.54%) were rated as grade 1 , 7 patients (10.77%) as class 2 (moderate osteoarthritis changes), and 5 patients (7.69%) as class 3 (severe osteoarthritis changes). Four patients (6.15%) had undergone preoperative arthroscopy.The mean follow-up duration was 44.25 months , range 36 to 58.All these data are reported in All the clinical scales reflected significant improvement in all measures . The basCompared with the baseline score of 5.57 , the postoperative VAS scores fell to 2.99 at 12 months , 3.15 at 24 months , and 3.34 at 36 months .The preoperative SST value of 8.19  rose to 10.06 at 12 months , 10.91 at 24 months , and 10.15 at 36 months .p < 0.0001).The Friedman test demonstrated statistically significant differences in CMS, VA, and SST during the entire follow-up (The SANE results at 36 months were ≤60% (unsatisfactory outcome) for 5 patients (7.69%), ≥80% (complete satisfaction) for 54 patients (83.08%), and between 60% and 80% (adequate treatment) for 6 patients (9.23%).We designed this study to assess the effect of autologous μFAT on chronic shoulder pain and GOA. Several systematic reviews have demonstrated the safety and efficacy of stem cell therapy in patients with a variety of orthopedic conditions .In particular, MSCs have the potential to facilitate cartilage tissue repair, reduce inflammation, and alleviate OA pain, providing significant improvement as assessed by several widely accepted clinical rating systems ,47. The Clearly, the improvement experienced by our patients cannot match the imporovements achieved with other procedures, especially joint replacement. For arthroplasty, Kim et al. reported a change in the mean CMS from 35.4 to 57.8 points at 24 months , whereasHowever, the results of such studies cannot be compared with ours, principally because patient characteristics determine the indication for conservative or surgical treatment. Indeed, most of the patients enrolled in our study had mild concentric GOA according to the Samilson–Prieto classification and were consequently more likely to benefit from ADMSC treatment and experience greater improvement. In contrast, patients receiving a joint replacement are typically older and have a more severe condition. The disparity between the two types of patients thus depends on the different indication for treatment. In younger patients and in those with more advanced OA, ADMSC treatment may be critical to alleviate pain and bridge the interval to joint replacement. Finally, the effectiveness of ADMSC treatment is reflected in the satisfaction of our patients, since at 36 months 54 of our 65 participants were completely satisfied with the outcome of their procedure. This finding provides novel evidence for the effectiveness of ADMSC treatment in patients with chronic shoulder pain and GOA and is in line with the earlier reports ,51.Our study has two main strengths: a large sample size compared with similar studies and a follow-up of at least three years. Notably, the therapeutic effects of the treatment began to decline at two years, particularly pain reduction.Among the limitations of the study are the lack of a control group, such as a cohort receiving hyaluronic acid or corticosteroid injection, and the absence of pre- and postoperative MRI to prove cartilage repair. Furthermore, the outcomes were not subjected to stratified analysis based on age, BMI, or the OA. A stratification based on the degree of OA was not performed, consequently, clinical outcomes could not be assessed in patients with severe grades of Samilson–Prieto classification. Lastly, the postoperative phase omitted the surveillance of patient activities aimed at mitigating issues such as excessive joint utilization. Another drawback is the fact that only four patients underwent preoperative arthroscopy, since the scan would have provided useful information both for differential diagnosis and for the assessment of therapeutic effects. In addition, the extensive saline irrigation performed during arthroscopy may ameliorate local inflammation .All these limitations should be taken into account when interpreting the findings of our research, and future studies should address these aspects to enhance the understanding of ADMSC treatment in shoulder conditions.This retrospective observational study of the safety and efficacy of autologous μFAT in patients with chronic shoulder pain and GOA documented significant improvements in clinical outcomes as measured by the CMS, the VAS, and the SST. The changes compared with baseline were statistically significant at 12, 24, and 36 months. The SANE demonstrated that most patients were completely satisfied.These findings support the safety and efficacy of autologous μFAT as a treatment for chronic shoulder pain and GOA. Notably, in younger patients and in those with more advanced OA, conservative treatment with ADMSCs may be a valuable tool to alleviate pain and bridge the interval to joint replacement.Further studies are warranted to validate these results and explore longer-term outcomes.


P = .005). Mortality rates were found to be 28.4%, 7.5%, and 2.6% in patients with CCI ≥ 2, CCI 1, and CCI 0, respectively. The mortality rate of the CCI ≥ 2 group was significantly higher than those of the other 2 groups (P < .001). The multivariate Cox proportional hazard regression model showed that CCI was an independent predictor for 1-year all-cause mortality . CCI may contribute to treatment and follow-up management, as it indicates a poor prognosis in elderly patients who have undergone percutaneous coronary intervention.Elderly patients with acute syndrome are frailer due to the burden of comorbidity. Comorbidities that increase with age result in an increased risk of mortality in patients with acute coronary syndrome (ACS). Many scales have been developed to assess the burden of comorbidity, including the Charlson Comorbidity Index (CCI). The aim of our study is to show the effect of the CCI on 1-year mortality and poor clinical outcomes in elderly patients who underwent percutaneous coronary intervention due to ACS. This single-center retrospective study included 704 patients aged 75 years and older. The study population consisted of patients who were admitted to the hospital with ACS between April 2017 and September 2021 and underwent successful percutaneous intervention. The patients were divided into 3 groups according to their CCI scores as CCI 0 (n:156), 1 (n:266), and ≥2 (n:282). Stroke development was significantly higher in patients with CCI scores ≥ 2 compared to the other 2 groups ( Comorbidities that increase with age result in an increased risk of mortality in patients with ACS. Clinical decision-making and treatment are difficult in elderly patients with ACS because of the increased risk of mortality and additional cardiovascular events due to the burden of comorbidity.The incidence of ischemic heart disease is increasing along with the aging of the world population, and it is the leading cause of death globally. Aging causes patients to be physically weaker and frailer. Therefore, old age is an independent predictor of poor prognosis in patients with acute coronary syndrome (ACS).–6 The aim of our study is to show the effect of the CCI on 1-year mortality and poor clinical outcomes in elderly patients who underwent percutaneous coronary intervention after ACS.Comorbid conditions that pose a risk for the development of cardiovascular disease should be considered as a whole. Elderly patients usually have more than 1 comorbid condition. Thus, many scales have been developed to assess the burden of comorbidity, including the Charlson Comorbidity Index (CCI). Previous myocardial infarction, congestive heart failure, peripheral arterial disease, cerebrovascular accident or transient ischemic attack, dementia, chronic obstructive pulmonary disease, connective tissue disorder, peptic ulcer disease, liver disease, diabetes, hemiplegia, chronic kidney disease, malignant neoplasm, leukemia and lymphoma, metastatic solid tumor, and AIDS are comorbid conditions included in the CCI. Each condition is scored between 1 and 6 based on its prognostic value. The CCI has previously been used to predict prognosis in diseases such as ACS, heart failure, cerebrovascular disease, and cancer.This single-center retrospective study included 704 patients aged 75 years and older. The study population consisted of patients who applied to the Bandirma Training and Research Hospital with ACS between April 2017 and September 2021 and underwent successful percutaneous intervention. Clinical and laboratory results, demographic data, and current comorbidity status were obtained from the hospital archive and electronic registry system. This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Bandirma Onyedi Eylül School of Medicine, approval number 2022/7-1 and dated 19.08.2022. Since the study was conducted in a center with 24-hour coronary angiography facilities, early percutaneous coronary intervention was performed in all of the patients. Patients who had regular cardiology outpatient visits and received dual antiplatelet therapy until the end of the follow-up period were included in the study. Patients using oral anticoagulants were excluded from the study, as they may affect clinical outcomes. Other exclusion criteria were patients who did not undergo percutaneous coronary intervention, patients who were recommended coronary bypass surgery after coronary angiography, and patients with in-hospital mortality. Since the patient population consisted of patients over 75 years of age, it was expected that most of them would have at least 1 comorbidity. The patients were divided into 3 groups according to their CCI scores as CCI 0, 1, and ≥2.CCI is a widely used death assessment model. The necessary information for CCI was obtained from the hospital registry system. Age was not evaluated in the CCI score as the study population consisted of elderly patients. All-cause mortality, which was the study endpoint, was obtained from the national electronic health record system. In addition, hospital admissions due to major and minor bleeding, cerebrovascular accident, and recurrent myocardial infarction were obtained from hospital records. Major and minor hemorrhages were determined according to the International Society on Thrombosis and Hemostasis criteria.P value).In summarizing the data obtained from the study, descriptive statistics were tabulated as mean ± standard deviation or median, quartile 1, and quartile 3 depending on the distribution for continuous  variables. Categorical variables were summarized as numbers and percentages. The normality of numeric variables was checked with the Kolmogorov–Smirnov, test. Comparisons of the CCI groups were made using a 1-way analysis of variance when the numerical variables showed a normal distribution and a Kruskal–Wallis H test when they did not. Multiple comparisons were evaluated with the Tukey test when parametric tests were used and with the Dwass–Steel–Critchlow–Fligner test when non-parametric tests were used. Pearson chi-squared test was used for comparisons when there were 5 or more expected cells in the differences between the categorical variables according to the groups, and the Fisher–Freeman–Halton test was used for the tables when there were fewer than 5 expected cells. The association between CCI and 1-year all-cause mortality was analyzed using multivariate Cox proportional hazards regression models, and the results were expressed as hazard ratio and 95% confidence interval. The selection of variables for the multivariate analysis was based on previous reports and clinical importance. Kaplan–Meier survival analysis and a log-rank test were performed to compare 1-year all-cause mortality between the CCI groups. Statistical analyses were performed with the SPSS Version 22 for Windows , and the level of significance was considered to be .05  and 328 female patients (46.6%). There were 156 (22.2%) patients in the CCI 0 group, 266 (37.8%) in the CCI 1 group, and 282 (40.0%) in the CCI ≥ 2 group. Demographics, clinical characteristics are summarized in Table P < .001). There was a significant age difference between the CCI ≥ 2 and CCI 1 groups (P = .04). The groups were similar in terms of gender and Body Mass Index (P = .64 and P = .57). There were significant differences between the groups in terms of hypertension (P < .001), hyperlipidemia (P = .03), and previous coronary bypass surgery (P = .005). Patients with CCI ≥ 2 had significantly higher hypertension than patients in the CCI 1 and CCI 0 groups. The rate of hyperlipidemia was significantly higher in patients in the CCI ≥ 2 and CCI 1 groups than in patients in the CCI 0 group (P = .03). The rates of previous coronary bypass surgery were significantly higher in patients in the CCI ≥ 2 group than in patients in the other 2 groups (P = .005). There was no significant difference between the groups in terms of ACS presentations (P = .66). There was a significant difference between the groups in terms of median systolic blood pressure value, median heart rate and ejection fraction .Significant differences were found between the groups in terms of age and comorbidities. The patients in the CCI ≥ 2 group were older than the patients in the CCI 1 and CCI 0 groups (P = .03). The groups were similar in terms of other variables (P > .05).Laboratory parameters are summarized in Table Major bleeding was observed in 88 (12.5%) and minor bleeding in 74 (10.5%) patients in the study group. The median time to bleeding was 135 days. Target vessel revascularization was performed in 48 patients (6.8%), and stroke was observed in 64 patients (9.1%). The mortality rate of the patients in the study group was 14.8%. The clinical features and other prognostic implications of bleeding after ACS are detailed in Table P > .05). Acute ischemic stroke development was significantly higher in patients in the CCI ≥ 2 group compared to the other 2 groups (P = .005). Mortality rates were found to be 28.4%, 7.5%, and 2.6% in patients with CCI ≥ 2, CCI 1, and CCI 0, respectively. The mortality rate of the CCI ≥ 2 group was significantly higher than those of the other 2 groups (P < .001).As shown in Table P < .001). The Kaplan–Meier survival analysis revealed differences in the all-cause mortality rates between the CCI groups at the 1-year follow-up shown in Figure The results of Cox regression analysis are presented in Table Our studied revealed the relationship between CCI, which is an indicator of comorbidity burden, and cerebrovascular accidents and all-cause mortality in a 1-year follow-up of elderly patients who underwent percutaneous coronary intervention due to ACS. While studies have shown the prognostic value of the CCI after ACS, our study stands out due to the mean age of the patients and the number of participants.,9Elderly patients are more fragile due to the increasing burden of comorbidity with age, and scoring systems, which are indicators of the comorbidity burden based on this frailty, can be used to predict patients’ prognosis. CCI, developed in 1987, is still used as an indicator of the comorbidity burden. Similarly, in our study, patients with 2 or more comorbidities had worse survival rates at the 1-year follow-up. As the number of comorbidities increases, patients become more vulnerable and fragile. It has been shown that CCI, which is an indicator of comorbidity burden, has prognostic importance not only for cardiovascular diseases but also for cerebrovascular diseases, trauma, and infection.–13The CCI includes non-cardiovascular comorbidities, such as chronic liver diseases, malignant neoplasm, and lymphoma. Previous studies have shown that the prognosis of patients with cardio vascular diseases worsens as the comorbidity burden increases.,15 The GRACE  score is used to predict in-hospital and 6-month mortality in patients with ACS. However, comorbidities are ignored in the GRACE score. In our study, although there was no significant difference between the CCI groups in terms of GRACE scores, a significant difference was observed in mortality rates. This shows that apart from the GRACE score, the burden of comorbidity and comorbidity scores are also important in terms of mortality. A previous study showed that the CCI was not superior to the GRACE score at the 2-year follow-up and made no additional contribution. However, the fact that the participants in that study were younger than those in our study and that patients who did not receive invasive treatment were excluded in this study due to their poor overall prognosis, probably due to the high comorbidity burden, may have caused this difference. Comorbidity indices are more important for these patients, as the comorbidity burden increases with age, which makes elderly patients more vulnerable and fragile. Another study showed that the CCI added to the GRACE risk prediction index can be useful in predicting patient prognoses.Previous studies have demonstrated that the CCI is important both in the short term  and in the long term . In our study, target vessel revascularization was higher in the patient group with a high comorbidity burden at the 1-year follow-up, although the difference was not statistically significant. The reason for the lack of a significant difference may be that the patients in our study felt less angina because they were older, or they did not feel exertional angina due to their reduced daily activities.In our study, as the comorbidity burden of patients who underwent percutaneous coronary intervention due to ACS increased, more cases of acute ischemic stroke were observed during the follow-up period. In previous studies, as in our study, it has been shown that more acute ischemic stroke is observed in patients as the comorbidity burden increases.Further, no significant differences were found in major and minor bleeding. The fact that patients with more comorbidities are less mobile causes them to be exposed to less trauma. Moreover, they may have applied to the hospital less because of minor bleeding due to their immobility.Our study has some limitations. First, some comorbidities  occur in low frequencies in the general population as well as in the study population, which consisted of elderly patients. Another limitation is the underreporting of secondary diagnoses, as the data were obtained from the hospital registry system since this was a retrospective study.For elderly patients, frailty is a major concern, and the biggest cause of frailty in elderly patients is the comorbidity burden, which increases with age. Previous studies have shown that the patient prognosis will be worse as the comorbidity burden increases. Although there was no difference GRACE scores between the different CCI groups in our study, patients with high CCI scores had significantly higher rates of mortality and acute ischemic stroke at the 1-year follow-up. CCI was an independent predictor for 1-year all-cause mortality. CCI may contribute to treatment and follow-up management, as it indicates a poor prognosis in elderly patients who have undergone percutaneous coronary intervention.All individuals who contributed to this publication have been included as authors. The authors did not receive support from any organization for the submitted work.Conceptualization: Ahmet Balun.Data curation: Ahmet Balun, Alkame Akgümüş.Formal analysis: Ahmet Balun, Alkame Akgümüş.Investigation: Ahmet Balun, Alkame Akgümüş.Methodology: Ahmet Balun.Resources: Ahmet Balun, Alkame AkgümüşSoftware: Ahmet Balun.Supervision: Ahmet Balun, Alkame Akgümüş.Validation: Ahmet Balun.Visualization: Alkame Akgümüş.Writing – original draft: Ahmet Balun, Alkame AkgümüşWriting – review & editing: Ahmet Balun, Alkame Akgümüş