Sickle cell disease (SCD) affects the red blood cells, which become sickle-shaped, leading to their adhesion to vascular walls, impeding blood flow and causing the unpredictable, abrupt onset of intense pain episodes in the form of vaso-occlusive crises (VOC) as well as affecting multiple organ systems. The primary aim of this review is to assess the effectiveness of opioid analgesic intervention for pain management in sickle cell disease during an acute painful crisis. A literature search was done electronically on PubMed Central (PMC), PubMed, and Google Scholar databases. The reports included in the study were from 2010 to 2021, and the bibliographies of retrieved studies are included in the references. This systematic review was undertaken as per the Preferred Reporting Items for Systematic Review and Meta-Analysis. This study included reports discussing opioid analgesics in SCD patients during VOC in different settings. After extensive research, there were no clear current opioid treatment patterns described, and our conclusion suggested conducting more evidence-based research to improve the quality of VOC management and outcome. Sickle cell disease (SCD) is the most common inherited blood disorder that prevails in a specific population worldwide, primarily African Americans. In the United States, it is estimated to affect over 100,000 people, and about one out of every 365 African-American births is estimated to be living with sickle cell disease . The mosThe majority of acute moderate-to-severe painful vaso-occlusive attacks are managed in the hospital using different pain management strategies, including non-opioids as well as opioid medications. Adequate pain management is by far the most important goal for these patients . Potent Furthermore, as most treatments of VOC are initiated during the ED encounter as being considered the first point of care utilization, little is known regarding the pattern of opioid usage during VOC events and its effect in the long run, especially in the era of the opioid epidemic and narcotic addiction.Moreover, healthcare providers are not adequately informed on how variable and intense these painful VOC can be and what should be initially done for managing them as they often view SCD patients as "opioid medication/drug seekers" due to the stigma associated with the need to control their pain with potent opioids and concerns regarding addiction . OverallThe primary objective of this systematic review will be to evaluate the pattern of opioid use in patients with SCD during a VOC and address if using narcotic analgesics to control and improve pain adequately will result in opioid-seeking behavior. Given the paucity of data, it also highlights the need for a deeper understanding of the clinical complexity of the disease and the role of using opioid analgesics with the need for further research and clinical correlation to set high-quality evidence for acute severe VOC management.MethodsIn this systematic review, the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 standards and principles were followed .Search StrategyThree databases, namely, PubMed, Google Scholar, and PubMed Central (PMC), were extensively explored electronically, using the appropriate traditional keywords and medical subject headings (MeSH) keywords to accurately include all the potentially relevant articles that have sickle cell anemia and the role of opioid use in a vaso-occlusive crisis. The keywords used include SCD, sickle cell anemia, opioid medication, vaso-occlusive crisis, and VOC. The Boolean scheme was also used to precisely traditional and MeSH keyword searches and was employed in PubMed. All articles were retrieved, and only articles and subject headings relevant to this article were used.Inclusion and Exclusion CriteriaThis article only included randomized control trials, systematic reviews, and other published articles from 2010 to 2021. Among all the studies included, the articles selected were related to patients with SCD, vaso-occlusive crisis, and opioid medication use in different settings, including ED, and during hospitalization. Our eligibility criteria were based on population, intervention, comparison, outcomes, and study criteria (PICOs). Only studies published in the English language were included in this study. The review excluded studies that focused on chronic opioid use, pregnant women with SCD, and the use of other pain medications.Data ExtractionTwo researchers selected and extracted data autonomously, including all articles relevant to our inclusion and exclusion criteria, intervention used, and outcome combined. Quality Assessment and Analysis of the StudiesFor traditional papers, the Scale for the Assessment of Narrative Review Articles (SANRA) was implemented. The score of each criterion was reported as having a score of more than nine. Similarly, the PRISMA checklist was used for quality appraisal of the systematic reviews. We evaluated the methodological quality of the research papers through this method, with a score of 23 and above set as the benchmark for inclusion.ResultsA total of 109 articles were identified from different search tools using the specific search strategies identified in the keywords. Out of 109 articles, 34 were from PubMed, 25 were from PMC, and 50 were obtained from Google Scholar; 56 articles remained following the removal of 40 duplicate reports, and 13 were removed for other reasons. The remaining 56 articles were filtered according to the relevance extracted from the abstract for the title and content, after which 16 articles were excluded from this study. After applying inclusion/exclusion criteria with a full-text screen, 15 articles were excluded, and 17 articles were excluded during data extraction. The final eight reports were found relevant based on the eligibility criteria. A comprehensive PRISMA flow chart is shown in Figure Table VOC is a leading cause of morbidity and a common reason for ED visits, which leads to subsequent hospitalization among patients with SCD. Opioid analgesics remain the treatment of choice for alleviating the acute and severe pain associated with VOC. The following sections discuss the pathophysiology of VOC, different opioids used in the management of acute pain crises in the ED and during hospitalization, and lastly, the potential adverse effects that might develop from opioid use.Pathophysiologic events in acute VOC in SCD patientsThe most frequent presentation of SCD is an acute pain crisis, which requires a clinic visit or hospitalization. Multifactorial processes can trigger VOC in the form of patient-related or environmental factors or both, including infection, fever, dehydration, acidosis, exposure to temperature extremes, humidity, and pain itself, which can precipitate painful crises . These pOpioids are a widely used and acceptable form of analgesic for treating acute and severe pain. In 2014, the National Heart, Lung, and Blood Institute (NHLBI) released guidelines in an effort to improve outcomes for SCD patients during painful VOEs. They set recommendations for assessing APC patients through level two triage, administering IV opioids within 60 minutes of arrival to the ED, as well as implementing an individualized dosing protocol for additional analgesics if needed .In a study comparing the NHLBI-recommended opioid dosing strategies for acute SCD pain in the ED, using a patient-specific protocol by employing patient-controlled analgesia (PCA) showed a significant reduction in pain scores, led to lower hospital admission rates and resulted in an acceptable side effect compared to weight-based protocol patients . MoreoveMorphine and hydromorphone have been used as the first-line intravenous opioid analgesics of choice for APC but are considered a less ideal form of analgesic as they raise multiple concerns. Fentanyl has also been described as an alternative to or in combination with morphine. It acts more rapidly in the CNS, is more potent with a shorter half-life than morphine, and can be administered through different routes . In one study comparing opioid doses given to SCD patients during acute pain episodes in the acute care unit (ACU) were significantly lower than in the ED as this was explained by quicker administration of pain medication, use of higher mg/kg doses of morphine or hydromorphone for management of acute pain episodes of SCD than those used during ED management, which led to improvements in patients' quality of life and care, decrease the need for hospital admissions, and lower overall medical costs . In another study, given careful attention to the severity of patient-reported pain, including assessing adequate pain relief following administration of the initial dose of morphine in the ED, should be used to help predict those who might need hospital admission for further pain management of VOE afterward with the initiation of PCA and prevent premature discharge. Furthermore, assessing the number of morphine doses prescribed in conjunction with overall reported pain scores can be used as an indirect measure of the physician's pain assessment for further management .Therefore, using individualized opioid dosing with earlier administration of early analgesia with a maximum opioid dose would result in a shorter hospital stay . Kim et Potential adverse effect following the use of narcotic analgesics in the treatment of VOCThe pharmacology and multi-organ adverse effects of opioids remain good areas of investigation due to a scarcity of clinical studies and considering the overall safety and efficacy of different opioids in the management of acute pain crises. Thus, understanding potential side effects and the need for adequate patient evaluation and ongoing monitoring is warranted. Gupta et al. suggested that as morphine has a multi-organ effect, this might result in exacerbating organ-specific pathological events as well as causing pathology by itself .The documented acute adverse effects of morphine, described in a literature review done by Ballas et al., include overdose, respiratory depression, excessive sedation, altered mental status, nausea, vomiting, pruritus, and bowel habit changes in the form of constipation. These adverse effects are due to morphine's side effects on both neural and non-neural targets, as well as being described as the most histaminergic opioid and are excreted primarily in the urine . In addiMoreover, there were no consistent data exists to address the type, method, and amount of opioid administration in hospitalized sickle cell patients during VOC with the need to implement multi-modal evidence-based strategies as well as educate health care personnel in the management of VOC and the resulting SCD pain . For theOpioid analgesics seem to be widely used in patients with SCD, mortality data in those patients is actually related to the complications of the disease itself rather than opioid use. The problem relies on the misuse of opioids . Al ZahrLimitationsThe limitations to be considered in this systematic review are the relatively small number of articles selected and included in this review. In addition, no clinical trials and evidence-based data might be one of the limiting factors. Moreover, the included articles were different in study design and some were narrative reviews. Finally, this study didn't review reports that describe other therapies, including non-opioid analgesics used during the crisis episode.No studies addressed the immediate and long-term adverse effects of using opioid medications during acute, severe, painful sickle cell disease attacks. Given the paucity of data, there is a lack of evidence-based studies that suggest the development of frequent or severe adverse effects, including opioid addiction, during VOCs. Furthermore, no high-quality studies describe the optimal pain control regimen in adult SCD patients, and there is no recommendation for a specific agent to be used. Overall, the need for information about opioid dosage, route, and selection should be individualized based on the patient's pain score and the degree of pain relief following opioid administration to develop dosing guidelines to improve outcomes of VOC. In order to alleviate the current stigma of opioid use in the era of the opioid epidemic in concern to the use of non-standardized dosages of opioids to relieve VOC, continuous evidence-based research is needed.


Objective: This study aimed to demonstrate the safety and the efficacy of the self-gripping mesh (ProgripTM) for inguinal hernia repair in morbid patients of the higher American Society of Anesthesiologists (ASA) classification (ASA III and IV). The incidence of chronic pain, postoperative complications, and hernia recurrence was evaluated.Methods: Data were collected retrospectively from the files of the patient and were analyzed for 198 hernias in 147 patients. All the patients included in this study had undergone inguinal hernia repair by Lichtenstein approach with the self-gripping mesh (ProgripTM) in the same clinical center. Preoperative, perioperative, and postoperative data were collected and a long-term follow-up of 31.8 ± 19.5 m (5–60 m) was performed. Complications, pain scored on a 0–10 numeric rating scale (NRS), and hernia recurrence were assessed.Results: During the past 5 years, 198 hernias in 147 patients were repaired with the Lichtenstein procedure with the self-gripping mesh (ProgripTM). The majority of the patients were high level of the ASA classification (ASA III and IV) (95.9%), with ASA III (10.2%) and IV (85.7%). The mean operation time was 71.2 ± 23.8 min. The mean length of postoperative stay was 2.5 ± 2.1 days. There were no intraoperative complications. About 14 cases (7.1%) suffered from postoperative surgical wound complications, which were limited to the skin and subcutaneous tissue and were cured with the conservative methods successfully; there was no mesh infection, the acute postoperative pain was low or mild [visual analog scale (VAS) score ≤ 4] and the chronic postoperative pain was reported in three patients (1.5%) and tolerable, hernia recurrence  occurred in one patient half a year after during the follow-up period.Conclusion: This study demonstrated the advantages of the self-gripping mesh in hernia repair of the high-risk patients with inguinal hernia (ASA III and IV) by Lichtenstein procedure under local anesthesia. Inguinal hernia repair is the most common procedure in general surgery, with more than 20 million patients being repaired globally each year , 2. The TM) has been developed to avoid the use of additional fixation  grips indicated for inguinal hernia repair. Recent studies have demonstrated a reduction in operating time and costs of a hernia repair for the Lichtenstein technique with Parietex ProGripTM self-gripping mesh compared to a classically fixed mesh for relatively inexperienced surgeons  classification (ASA III and IV) has not yet been studied. In addition, this study aimed to evaluate the long-term results of the use of ProGripTM mesh in this group of patients (ASA III and IV).In this study, we routinely used the Lichtenstein technique for inguinal hernia repair with the self-gripping mesh, if the patients are not suitable for laparoscopic repairs as judged by surgeons. Although the short-term results of a large comparative randomized study have demonstrated the safety and the efficacy of the use of ProGripapproach , the lonTM) were used in all the procedures. Approval of the patient was obtained from each patient before operation, and ethical approval was not required for this retrospective type of study. Preoperative, perioperative, and postoperative data were collected. Perioperative data collected included patient demography , type and location of the hernia, and medical risk factors . Postoperative data collected at discharge were assessment of postoperative medical and surgical complications, acute and chronic pain, and hernia recurrence. The pain was assessed by using a visual analog scale (VAS) score (0–10), score 0 is no pain and score 10 is worse pain. If the patient reported hernia recurrence symptoms, the patient was recalled for a visit, and a physical examination was performed to confirm recurrence. Hernia recurrence was defined as a clinical manifest bulge or protrusion exacerbated by a Valsalva maneuver in the operated groin region, a CT scan or sonography was ordered, if necessary.A total of 198 inguinal hernias were operated on with the Lichtenstein procedure between January 2015 and June 2020 in 147 patients . Each prTM Self-Gripping Polyester Mesh, Covidien, Trevoux, France) was used in each patient, the ProgripTM mesh is a lightweight, self-gripping mesh composed of monofilament polyester and PLA grips indicated for inguinal hernia repair. A meta-analysis has demonstrated the reduction in operating time of hernia repair for the Lichtenstein technique with Parietex ProGripTM self-gripping mesh compared to a classically fixed mesh . In all the patients, a skin incision 4–6 cm parallel to the inguinal ligament was performed. The three inguinal nerves  were intraoperatively identified and preserved, the iliohypogastric nerve may be resected if it preventing mesh placement. The fibers of the cremaster muscle were divided, but not resected. The small direct hernia sac was not ligated, but returned to its normal course. The large indirect hernia sac was transected in middle, and the distal sac was left  Chastan , the pos Chastan , with sp Chastan , make su Chastan , the wou2 at the surgery. Among the 147 patients, 92.5% of them were male (n = 136), 7.5% were female (n = 11), and 37 patients with only left-side hernias (25.2%), 59 cases with only right-side hernias (40.2%), and 51 cases were bilateral hernias (34.7), and with 45 hernias were direct-type hernias, 120 hernias were indirect type, and 32 hernias were combined hernias. Therefore, 198 hernias were repaired with the Lichtenstein procedure.Patient demography and perioperative data are presented in n = 126) and 10.2% of them were the ASA classification of III patients (n = 15), the total number of ASA III and IV were 141 (95.9%).Of note, this group of patients were all morbidity patients, 85.7% of them were the ASA classification of IV patients (The most frequent risk factors were hypertension (53.7%) followed by cardiac disease (30.6%), smoking (23.1%), obesity (18.4%), pulmonary disease (9.5%), and cirrhosis (4.8%), 29.3% of the patients were taking antiplatelet at the time of surgery, and 4.1% were taking an anticoagulant, also 2.7% were taking heparin. Emergent operations due to incarcerated hernias were operated in six patients.There were 88 hernias located on the left side and 110 hernias located on the right side. Of the 198 hernias, 45 of them were medial (direct) hernias, 120 were indirect hernias, and 32 were combined hernias. The mean operation time was 71.2 ± 23.8 min. The mean length of postoperative stay was 2.5 ± 2.1 days .There were no intraoperative complications. About 14 cases (7.1%) suffered from postoperative surgical wound complications; as illustrated in All patients reported no or low to mild acute pain (VAS score ≤ 4), there was no patient experienced severe acute pain during the early period of postoperative time. Chronic postoperative pain over 3 months after surgery was reported in three patients (1.5%), but the pain level was mild and tolerable and the pain level decreased over time. At the mean follow-up of 31.8 ± 19.5 m (5–60 m), one patient had a hernia recurrence, and this recurrence occurred as a femoral hernia recurrence half a year after the initial operation, a redo operation was successfully performed by open preperitoneal repair. The follow-up rate was 91.2% (134/147). Eight patients died during the follow-up period; however, the death was not related to hernia repair.Inguinal hernia repair is one of the most commonly performed operations worldwide and the repair methods can be performed under a variety of approaches, namely, open, laparoscopic, or robotic . In 2018Laparoendoscopic inguinal hernia repair is superior to open in terms of lower postoperative pain incidence , 9; howeInguinal hernia is feasible to be repaired under local, regional, or general anesthesia ; usuallyTM) was developed, and this mesh was associated with shorter operative time compared with the conventional suture mesh and provided comparable perioperative and long-term outcomes  or Lichtenstein in selected cases and we agree with others that nonviable intestine cannot be regarded as an absolute contraindication for prosthetic repair , 35. TheThis study has several limitations; first, this is a retrospective study, second, there was no comparative group of the conventional suture mesh; however, this study aimed to evaluate the efficacy of self-gripping mesh and the safety of this repair in morbidity patients, rather than to compare two different techniques.TM in exclusive the patients with high comorbidities  under local anesthesia (92.5%), there was no perioperative death, and with a low incidence of postoperative complication rate and low recurrence rate  (0.5%). This study demonstrated the several advantages of the self-gripping mesh Lichtenstein procedure in high-risk inguinal hernia patients (ASA III and IV), namely, short operative time, safe and simple manipulation, less overall and surgical postoperative complications, and low recurrence rate.To the best of our knowledge, this report is the first study evaluating the use of ProgripThe original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements.WZ, YZ, ZJ, and JL: conception and design of the study. WZ, YZ, XS, and JL: acquisition of data. WZ, YZ, TC, ZJ, and JL: data analysis. WZ, YZ, XS, TC, ZJ, and JL: drafting of the manuscript and/or critical revision and approval of a final version of the manuscript. All the named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article.This work was supported by the Medical Science and Technology Development Foundation, Nanjing Municipality Health Bureau (ZKX18052).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


An intractable plantar keratoma (IPK) is a conical thickening of the epidermis’ stratum corneum and a common cause of foot pain which can have a significant, detrimental impact on the mobility, quality of life and independence of individuals. Conservative treatments are currently offered to patients with IPK, but they are unsatisfactory since they do not offer a sufficient or permanent reduction of symptoms. The purpose of this study was the evaluation of the feasibility, safety and effectiveness of innovative treatments for intractable plantar keratoma (IPK).A randomized single blind trial with 40 patients divided with block randomization in four parallel groups was conducted to compare treatment combinations: conservative sharp debridement only or sharp debridement with needle insertion, physiological water injection or lidocaine injection. All patients obtained the same treatment four times at a four-week interval. At each visit, visual analog scale (VAS), Foot Function Index (FFI) and IPK size were evaluated. VAS and FFI were also completed at a six and twelve-month follow-up.p > 0.05). However, the analysis revealed a statistically significant effect of time on VAS (p < 0.001), FFI score (p < 0.001) and IPK’s size (width and depth (p < 0.001); length (p = 0.001)), but no group x time interaction was found (p > 0.05).Our findings in regards to feasibility demonstrated recruitment challenges because of the anticipated pain that would be provoked by needle insertion may not be worth the potential pain relief compared to debridement alone from the patient’s perspective. This was also the principal cause of drop out. Our preliminary results show no main effect of group for any of the clinical outcomes: pain felt on VAS, FFI score, IPK’s size .ClinicalTrials.gov, The online version contains supplementary material available at 10.1186/s13047-021-00467-7. Callosities are a common cause of foot pain which can have a significant, detrimental impact on the mobility, quality of life and independence of individuals –5. A comEvidence is scarce especially for IPKs management in the literature even if it is a widespread painful problem. A previous study at our institution compared the effect on pain relief and functional capacity of a subcutaneous injection of physiological saline water (PSW) compared to a subcutaneous injection of hyaluronic acid (HA) under a debrided IPK . ConsideThis single blind feasibility study focused on safety and outcomes of an injection therapy for IPKs and was conducted in a private podiatric medicine clinic (Clinique Podiatres Plus) located in Quebec City and at the University of Québec at Trois-Rivières podiatry teaching clinic, in the province of Quebec, Canada. The study protocol was approved by the institutional ethical committee (UQTR CER-15-214-07.17). Initial protocol was amended in order to improve enrollment rate with use of publicity in local newspaper and add an additional recruitment clinical site (Clinique Podiatres Plus). Initial recruitment was realized by the professionals and the students in both settings as well as through a local newspaper advertisement. A total of 63 patients were approached to join the study. Forty patients met inclusion criteria which were verified by the principal investigator (MPM). Selection questionnaire is available in Additional file Treatment allocation was made by block randomization for four parallel groups following a computer-generated list of random numbers . Patients were assigned to a number in order of subscription. Patients were blinded to their treatment regimen during the whole study. Only independent research assistants had access to this list to prepare the treatment material in a covered container to avoid any bias during evaluation. The container was open once the podiatrist (MPM) had completed the physical evaluation and had confirmed a clinical IPK diagnosis . All syraccuracy ± 0.1 mm). The depth was estimated with a cotton tip applicator technique measured with the same ruler [Once the clinical diagnosis was confirmed, IPK debridement was completed using a scalpel and number 15 blade, a podiatry drill and a spherical podiatry burr. In case of multiple IPKs, the patient chose the most painful lesion to be considered for the trial. IPK’s length and width was measured with a millimeter scale ruler used in wound care  and Excel . Finally, we did an intention-to-treat analysis since missing data by dropped-out patients were replaced by the last value available. Feasibility data are reported with descriptive statistics in a narrative synthesis. Finally, this feasibility study is reported using CONSORT extension for pilot and feasibility trials checklist [All non-parametric values (baseline characteristics) have been subjected to a chi-squared test. Pain intensity (VAS) and FFI-R scores were independently subjected to a repeated-measures analysis of variance (ANOVA x r) having four levels of group , scalpel debridement combined with needle insertion (group 2), scalpel debridement combined with subcutaneous injection of PSW (group 3) or scalpel debridement combined with subcutaneous injection of LS (group 4)) and five levels of time of measurements , third intervention (T3), fourth intervention (T4), and 6-month (T6) and 12-month (T12) follow-ups). Statistical significance was set, for all analyses, at hecklist . The stun = 36) attended all four prescribed interventions and completed the 6-month follow-up. However, only 67.5% (n = 27) completed the 12-month follow-up. Several attempts had been made by the podiatrist to reach patients by phone, but efforts remained unfruitful to collect follow-up data in some cases. Throughout the protocol, the major reason for dropout was anticipated pain that would be provoked by the injection. At the 6-month follow-up phone call, 12.5% of group 2, 30% of group 3 and 14.3% of groups 4 patients said that the effectiveness of the treatments was not worth the pain felt during the interventions. The pain was felt during the needle insertion or the injection. Furthermore, some patients still had discomfort few days after the intervention. No patient in the group 1 reported pain secondary to the intervention (debridement only). Except for pain, no patient reported any other side effects for the duration of the feasibility study related to the intervention.As showed in Fig. Only pain at the injection site for a few hours have been stated by a limited number of patients. No other adverse effect has happened.p > 0.05). They were equivalent for age, time since apparition of IPK, time before first consultation, time spent standing up per day and daily cigarette smoking. Women represented 57.5% (23/40) of all patients. IPKs selected for study intervention were located under a metatarsal head, the styloid process of the fifth metatarsal and the heel respectively for 87.5% (34/40), 7.5% (3/40) and 5% (2/40). Thirty-five percent (14/40) of patients wore plantar orthoses on a daily basis and 37.5% (15/40) had at least one foot deformity. It was observed by the podiatrist during the first evaluation (baseline) that 11 of the 14 smokers (78.5%) and 4 of the 22 non-smokers (18%) presented macerated skin around the selected. Based on patient self-reporting data, none received another intervention than what was provided during the trial.Patient baseline characteristics are presented in the Table p = 0.26), FFI-R score , IPK’s width  = 0.55, p = 0.65), IPK’s length  and IPK’s depth . However, analysis revealed an effect of time on VAS , FFI-R score , IPK’s width , IPK’s length  and IPK’s depth . Trends for outcomes measures VAS and FFI-R are presented in Fig. p = 0.83), FFI-R score  = 0.93, p = 0.35), IPK’s width  = 1.40, p = 0.20), IPK’s length  = 1.27, p = 0.26) and IPK’s depth  = 1.41, p = 0.19).Clinical outcomes data are detailed in Table The objectives of this study were to determine feasibility, safety and gather preliminary outcomes in relation with four IPK treatment combinations, including scalpel debridement alone, scalpel debridement combined with needle insertion, scalpel debridement combined with subcutaneous injection of PSW or scalpel debridement combined with subcutaneous injection of LS. This study was conducted to explore new treatments for IPK. Regarding feasibility, the main comment from groups 2, 3 and 4 patients was that pain felt during the intervention was important and that it was not worth treatment’s overall efficacy. This was stated by more that 55% of the patients respectively at 6 and 12-month follow-ups. To avoid this situation, an anesthetic block of the tibialis nerve could have been performed before the needle insertion and injection, but callus treatment does not represent a current indication for this procedure . FurtherThe treatment combinations have been determined by a literature review, previous work and hypotheses , 39. ManThe VAS and the IPK measurements taken at each follow-up interventions furthermore show a downward trend in patients who received an injection (either group 3 or 4) compared with the other groups. The FFI-R score demonstrated a higher tendency to produce low scores with the PSW and LS injection interventions. Also, patients who had scalpel debridement only reported higher mean of VAS, FFI-R score and IPK measurements. Those results are not statistically significant, but this can possibly be explained by the small number of patients in each group. It is also important to note the shorter interval of time between treatments planned during the experimental protocol in comparison with what the patients where used to before this study. In fact, during the study all patients had a scalpel debridement every 28 to 30 days, compared with reported previous debridement frequency at an average interval of 108.5 days all groups combined. The statistically significant time effect could be explained by the fact that all treatments were highly effective after the first intervention and as a result of higher treatment frequency. The shorter period of time between treatments leads to a decrease in hyperkeratosis’ accumulation. Since the accumulation is less, this could explain the lower scores obtained on VAS and FFI-R. These results cannot be directly compared with other studies on the subject as this project is the first one comparing all treatment combinations with scalpel debridement alone for IPKs. However, pain alleviation after callus debridement including IPK, is reported for short and medium terms and are consistent with our results , 23, 50.The strength of this study is its innovative quality as it explores potential IPKs treatments that could be long-lasting and its contribution to raise new hypotheses for people who suffer from this prevalent foot health problem . RegardiIn conclusion, the treatment by needle insertion, PSW injection or LS injection of painful IPKs is feasible and safe. Findings has demonstrated a trend towards diminished pain intensity on VAS and FFI-R compared to scalpel debridement alone. On the other hand, despite this observed trend, there was no statistically significant difference in the final scores (VAS and FFI-R) between all groups. Further research with strongest design including more patients need to be done before considering the use of an injection therapy for painful IPKs.Additional file 1:Patient selection questionnaire (french version). (DOCX 20 kb)Additional file 2:Patient #30 photos: Example of an IPK receiving an injection. (DOCX 182 kb)Additional file 3:Patient Interview (french version). (DOCX 21 kb)Additional file 4:Foot-Function-Index-Revised (French version). (DOCX 24 kb)Additional file 5:Questions about the pain perceived during the experimental interventions at 6 and 12-month follow-ups (French version). (DOCX 21 kb)


The structural properties unique to MNTX restrict it from traversing the blood-brain barrier (BBB); however, the BBB may become more permeable in patients with brain metastases. We investigated whether the presence of brain metastases in cancer patients compromises the central effects of opioids among patients receiving MNTX for OIC.Peripherally acting μ-opioid receptor antagonists such as methylnaltrexone  within 4 or 24 h of the first dose, and treatment-emergent adverse events (TEAEs), including those potentially related to opioid withdrawal symptoms.n = 27; placebo n = 20) had brain metastases and 309  did not have brain metastases. No significant differences in current pain, worst pain, or change in pain scores from baseline were observed between patients treated with MNTX or placebo. Among patients with brain metastases, a significantly greater proportion of patients who received MNTX versus placebo achieved an RFL within 4 h after the first dose . TEAEs were similar between treatment groups and were generally gastrointestinal in nature and not related to opioid withdrawal.Among 356 cancer patients in the pooled population, 47 (MNTX Focal disruptions of the BBB caused by brain metastases did not appear to alter central nervous system penetrance of MNTX. When conservative pharmacologic measures are inadequate to treat cancer-related pain, opioid treatment should be considered. Opioids activate the endogenous pain-modulating system through agonism of several opioid receptor types such as μ-, κ-, and δ-opioid receptors in the central nervous system . μ-OpioiThe blood-brain barrier (BBB) comprises endothelial cells interconnected by tight junctions that line capillaries within the brain and allows the selective, highly regulated diffusion of specific molecules into the brain via facilitated or active transport . RestricIn patients with brain metastases, changes in vasculature within brain tumors can lead to loss of tight junctions and increased fenestrations in endothelial cells, compromising the biochemical and structural integrity of the BBB , 18. Hyp®, Salix Pharmaceuticals, a division of Bausch Health US, LLC, Bridgewater, NJ, USA) is a PAMORA that is similar in structure to naltrexone, but is methylated to form a quaternary amine which, due to its polarity, is much less likely to diffuse across the BBB  [n = 63) or placebo (n = 71) every other day for 2 weeks. The dose could be adjusted up to 0.30 mg/kg beginning on day 9. In study 4000 [NCT00672477]  , patientOIC was defined as < 3 bowel movements during the previous week and no clinically significant laxation during the 24 h (studies 302 and 4000) or 48 h (study 301) preceding the first dose of study drug. If the patient was receiving a laxative , the regimen had to be stable for ≥ 3 days prior to the first dose of study drug. For all studies, rescue laxatives and enemas were permitted but not within 4 h before or after study drug administration. Rescue doses of opioids were permitted as necessary.For eligibility in the pooled analysis, men and women were required to be ≥ 18 years of age, with a life expectancy of ≥ 1 month (studies 302 and 4000) or 1 to 6 months (study 301); receiving opioids routinely for discomfort or pain management for ≥ 3 days (study 301) or ≥ 2 weeks (studies 302 and 4000), excluding as needed or rescue doses and taking a stable regimen for ≥ 3 days before the first dose of study medication. A stable regimen was defined as no reduction of ≥ 50% in opioid dose within 3 days prior to study drug administration.Candidates were excluded from the study if they had a prior history of MNTX treatment , any disease process suggestive of mechanical bowel obstruction, evidence of fecal impaction, history of fecal ostomy, or any potential nonopioid cause of bowel dysfunction that, in the opinion of the investigator, may have been primarily responsible for the constipation.Baseline characteristics, including the baseline morphine equivalent dose, were collected. For the purposes of this analysis, baseline demographics and safety data were reported for cancer patients with brain metastases who received MNTX or placebo and for cancer patients without brain metastases who received MNTX or placebo. Efficacy outcomes (pain intensity and rescue-free laxation [RFL] response within 4 and 24 h after the first dose) were analyzed to compare patients with brain metastases who received MNTX versus placebo. Changes in pain score from baseline to 4 h after the first dose (both current pain and worst pain since baseline) were measured using a patient-reported rating scale of 0 (no pain) to 10 (worst possible pain).Safety assessments included treatment-emergent adverse events (TEAEs) reported on treatment day 1 and treatment day 2. TEAEs potentially related to opioid withdrawal symptoms were collected by identifying MedDRA-defined TEAEs that are described on the modified Subjective Opioid Withdrawal Scale (SOWs). The SOWs has been used in previous MNTX studies as a patient-rated measurement of the severity of opioid withdrawal symptoms , 27. Thep values were based on t tests to compare the MNTX and placebo groups. Analyses of RFL response and change from baseline for pain scores were performed on the intent-to-treat analysis set, defined as all patients who received at least 1 dose of study drug. Patients who reported an RFL within the first 4 or 24 h were considered responders. p values for an RFL response within 4 and 24 h were based on chi-squared tests. Nominal levels of significance were set at 0.05, with no adjustment made for multiplicity. Safety data were assessed among the safety population, which included all randomized patients.Baseline characteristics were assessed using descriptive statistics. For the analysis of pain scores, n = 27 MNTX; n = 20 placebo) had brain metastases and 309  did not have brain metastases , representing changes from baseline of − 0.4 and − 0.2 .Among patients with brain metastases, a significantly greater proportion of those who received MNTX than placebo achieved an RFL response within 4 h after the first dose . The authors speculated that the mechanism may have direct effects on gut function or possibly an indirect effect on immunosuppression [There is evolving research on the influence of μ-receptor antagonism on all-cause mortality and cancer progression –41. PrecThere were several limitations to our study that should be considered. First, this was a retrospective, post hoc analysis examining a small subset of patients from 3 larger studies. As a result, we were limited to a small population of patients, and the analysis was not powered for effective statistical comparisons. This analysis only assessed the effects of MNTX on OIC for an acute period of time (up to 24 h); longer observation periods may be useful to see the longer-term effects of brain metastases on central analgesia among patients taking MNTX. Moreover, the designs of the original studies varied slightly, including different dosages of MNTX and slight differences in the definitions of OIC and in inclusion/exclusion criteria. It is unknown if these differences may have impacted the results. However, it should be noted that the efficacy and safety results of this post hoc analysis were similar to those observed in the overall studies. Patients with brain metastases were identified post hoc based on a retrospective review of patient narratives. Since the double-blind period of the pooled studies were of short duration, it is likely that the majority of patients in this subanalysis had metastases at baseline. None of the patients in this series had a primary brain tumor, and the exact location of the brain metastases was not recorded.In conclusion, this analysis demonstrated that in patients with brain metastases—a condition likely to increase permeability of the BBB—MNTX did not lead to any significant changes in pain or opioid withdrawal symptoms yet reduced the occurrence of OIC. This suggests that MNTX is safe and effective in these patients. Hence, focal disruptions in the BBB caused by brain metastases may not sufficiently alter the penetrance of MNTX across the BBB to the extent that might cause clinical concern.


Chronic pain affects approximately 30% of the general population, severely degrades quality of life  and professional life (inability or reduction in the ability to work and loss of employment), and leads to billions in additional health care costs. Moreover, available painkillers are old, with limited efficacy and can cause significant adverse effects. Thus, there is a need for innovation in the management of chronic pain. Better characterization of patients could help to identify the predictors of successful treatments, and thus, guide physicians in the initial choice of treatment and in the follow-up of their patients. Nevertheless, current assessments of patients with chronic pain provide only fragmentary data on painful daily experiences. Real-life monitoring of subjective and objective markers of chronic pain using mobile health  programs can address this issue.We hypothesized that regular patient self-monitoring using an mHealth app would lead physicians to obtain deeper understanding and new insight into patients with chronic pain and that, for patients, regular self-monitoring using an mHealth app would play a positive therapeutic role and improve adherence to treatment. We aimed to evaluate the feasibility and acceptability of a new mHealth app called eDOL.We conducted an observational study to assess the feasibility and acceptability of the eDOL tool. Patients completed several questionnaires using the tool over a period of 2 weeks and repeated assessments weekly over a period of 3 months. Physicians saw their patients at a follow-up visit that took place at least 3 months after the inclusion visit. A composite criterion of the acceptability and feasibility of the eDOL tool was calculated after the completion of study using satisfaction surveys from both patients and physicians.Data from 105 patients (of 133 who were included) were analyzed. The rate of adherence was 61.9% (65/105) after 3 months. The median acceptability score was 7 (out of 10) for both patients and physicians. There was a high rate of completion of the baseline questionnaires and assessments (mean 89.3%), and a low rate of completion of the follow-up questionnaires and assessments (63.8% (67/105) and 61.9% (65/105) respectively). We were also able to characterize subgroups of patients and determine a profile of those who adhered to eDOL. We obtained 4 clusters that differ from each other in their biopsychosocial characteristics. Cluster 4 corresponds to patients with more disabling chronic pain (daily impact and comorbidities) and vice versa for cluster 1.This work demonstrates that eDOL is highly feasible and acceptable for both patients with chronic pain and their physicians. It also shows that such a tool can integrate many parameters to ensure the detailed characterization of patients for future research works and pain management.ClinicalTrial.gov NCT03931694; http://clinicaltrials.gov/ct2/show/NCT03931694 Chronic pain affects approximately 30% of the general population -6 and waVarious reasons are given for this, including the relevance of animal research . In partWe hypothesized that regular self-monitoring by patients using a digital app would generate in-depth knowledge and new insights for physicians, and would allow patients to be active in their own care and benefit from web-based counseling. Regular self-monitoring would not only contribute to better patient characterization and help in choosing the most appropriate treatment but may also improve adherence to treatment. Moreover, recent studies ,20,24-31Comité de Protection des Personnes Ile de France V (2018-A01790-5546) and is registered (NCT03931694). The study was conducted in accordance with French laws and regulations on research on human beings and data protection and with the Declaration of Helsinki [The study was approved by the Helsinki .Data were collected and managed using the eDOL app, developed by Bepatient and hosted by Avenir Télématique. In accordance with the provisions relating to the confidentiality of information concerning, in particular, the people who took part in the research and the results obtained , individAnswers to questionnaires and medical data were transmitted in spreadsheet format . All anonymized data were accessible to the biostatisticians , the coordinator (ND), and the project manager (NK). Only the investigators could access their patients' personal data to identify them. A dashboard linking patients’ identities and study IDs was available only on the investigators' professional interface on the eDOL web platform. The final database, used for statistical analyses, included only study IDs to preserve anonymity.To evaluate the feasibility and acceptability of the eDOL app for the characterization, real-life monitoring of patients with chronic pain from 12 pain clinics in France took place between February 8, 2019 and January 8, 2020. The study was offered to all physicians in the investigating centers.Participation in the study was offered to patients with chronic pain who did not have cancer, who were owners and regular users of a smartphone, and who were followed up in a pain clinic. All adult (≥18 years old) patients able to read and understand French and provide consent to participate in the study were included (with a yes-or-no choice on the eDOL app). Participants were free to withdraw their consent at any time by informing the sponsor. Each patient had access to the information document (paper or electronic) detailing the purpose, content, and conduct of the study. If they agreed to participate, they were asked to download the eDOL app and complete the questionnaires using the eDOL app. The URL to access this app was sent by email from physicians to their patients. After downloading the app and creating their profile, patients could accept the general terms and conditions of use and confirm that they agree to the use of their medical data in this study.Each patient had 1 initial study visit, during which, the physician introduced the study to the patient, checked their eligibility, explained the eDOL tool, and gave the patient a brief training document on how to use the eDOL smartphone app. Participants completed several questionnaires and assessments using the eDOL app over a period of 2 weeks  and then repeatedly over a period of 3 months and up to 6 months for patients who wished to continue using the app . Physicians saw their patient at a follow-up visit that took place at least 3 months after the inclusion visit, with the possibility of continuing the follow-up for up to 6 months. The study was considered complete for patients who completed their questionnaires and assessments for at least 3 months and made a follow-up visit 3 to 6 months after the inclusion visit.All data were collected using the eDOL digital health tool, which includes a smartphone app for patients that allows self-questionnaires and assessments to be completed for semiological monitoring , and a web interface for physicians, to allow them to graphically visualize the summary of data provided by their patients for clinical and therapeutic monitoring.Patients completed questionnaires and weekly assessments . The queFor physicians, the eDOL internet platform included a simple and ergonomic dashboard which allowed the physician to find all of their patients included in the study, with the following tabs: (1) Management, in which all of the medical records completed by the physician could be found ; (2) Health Measures, which showed a graphic display of the real-life follow-up of all the weekly assessments; and (3) Questionnaires, which showed all the questionnaires completed by the patients . The eDOL platform enabled physicians to complete medical elements during consultation visits with various medical form . The physicians could also activate new questionnaires to be filled in by their patients, either to complete the characterization  or to evaluate other criteria . DiagnoThe primary study endpoint reflected the acceptability of the eDOL app and the feasibility of its use and was assessed with a satisfaction survey .Patients were described according to epidemiological characteristics, clinical characteristics, and treatment characteristics. The key indicators for acceptability (patient and physician) were questionnaire completion and completion of follow-up medical forms. We determined the association between adherence and all baseline variables. A patient was defined as adherent if 100% of baseline questionnaires and 75% of assessments after 3 months follow-up were completed.Continuous variables and scale variables  were presented as mean and standard deviation , or median and quartiles (for asymmetric distributions). The normality assumption was assessed with graphical criterion and the Shapiro-Wilk test. Categorical variables were expressed in number and percentage.We performed clustering analysis. Patients were clustered according the symptoms and comorbidity information y. This clustering analysis included data imputation, principal component analysis of baseline data, and ascending hierarchical classification gathering 90% of total inertia. From these components, the hierarchical classification  in EucliP value was statistically significant (P<.05), posthoc tests (independent t test or Mann-Whitney) were applied to compare subgroups with each other. The results were expressed using effect sizes  with 95% confidence intervals. Pearson  or Spearman correlation coefficients (otherwise) were calculated depending on the nature of the distribution.Comparisons  were performed using the chi-square test or Fisher exact test when assumptions to apply chi-square were not met , for categorical variables, and using analysis of variance . When the omnibus We used Stata  and R (version 4.0.3) software. All statistical tests were 2-sided with type I error set at 5%.Of 133 patients from 12 French pain clinics, 28 patients  did not install the eDOL app; data from 105 patients were analyzed. The first patient was enrolled on February 6, 2019, and the last patient was enrolled on October 31, 2019.At baseline, participating patients were mostly middle-aged women, in a couple, nonsmoking, and professionals. Among these patients, 35.3% (30/85) were in work stoppage due to their chronic pain. A more detailed characterization of the patients, with the help of several validated questionnaires, mainly showed that a significant number were considered precarious , with kinesiophobia , alexithymia , degraded life satisfaction , catastrophism  and a possible cognitive disorder . More than 65%  of patients had impaired sleep, and 37.2% (35/94) and 27.7% (26/94) had proven anxiety or depressive disorders respectively.Regarding the characterization of pain disorders and their treatments, most patients  had moderate to severe pain intensity, of which 20.5% (17/83) had a high chronic pain interference score . Most pThere was no difference in any of these characteristics between baseline and the 3-month follow-up .Among 105 patients, 65 (61.9%) adhered to the use of the eDOL tool and 50 patients continued using the eDOL tool up to 6-month follow-up .In detail, the overall rate of patient who completed the baseline questionnaires was 89.3% (range 79.0%-95.2%). The quarterly questionnaires, Brief Pain Inventory and Medical Outcomes Study Sleep Scale, were repeatedly filled at 3-month follow-up by 63.8% (67/105) of patients. For the half-yearly questionnaires , 58.7% (range 53.8%-63.1%) of patients completed the questionnaires. The filling rate of the weekly assessments for the real-life monitoring of the different parameters  was 88.6% (93/105) of patients at the end of the first week and 61.9% (65/105) at 3-month follow-up . Due to Among the 12 pain clinics participating in the study, 10 (83.3%) included patients, and 2 withdrew from participation before the start of the study. The median inclusion number per center was 8  patients. The inclusion objective  was achieved in less than a year as requested from the investigating centers.The satisfaction questionnaire was filled in by 65.7% (69/105) of patients at the end of the study. The median acceptability score was 7.0 , with only 9.5% (10/105) of the patients providing a rating less than 5.0 out of 10. Moreover, 88.6% (93/105) of the patients who responded wanted to participate in the further development of the eDOL app. The items with the lowest scores corresponded to the patients’ perception of the physicians’ use of eDOL in their follow-up , patients’ perception of the potential positive impact of eDOL on their pain management , and quality of life .A total of 21 physicians participated in the study and included at least one patient, and 15 (71.4%) answered the satisfaction questionnaire. The physicians were mostly women , approximately 50.1 years old (range 33-61), and were from various specialties . The median acceptability score was 7.2 , with only 6.7% (1/15) of physicians rating less than 5.0 out of 10. The items with the lowest scores corresponded to the compatibility of eDOL with the electronic medical file systems  and the possibility of eventually replacing the electronic medical files with the eDOL tool  .P<.001) associated with a greater impact of pain and conversely for cluster 1. Clusters 2 and 3 were intermediate groups.We obtained 4 clusters that did not differ with respect to sociodemographic and chronic pain characteristics (except for pain interference with daily life) and their treatments . InteresP=.01). It is noteworthy that 2 other items  were related to adherence (P=.04), but with a small effect size (Cramer V=.03 and Cramer V=.20 respectively).In Cluster 4, 80.0% (24/30) of patients adhered to the use of the tool, compared with 51.0% (19/37), 64.3% (9/14), and 43.5% (10/23) in clusters 1, 2, and 3, respectively . MoreoveP=.03), seemed to be those who adhered most to eDOL .With reference to the profile of patients in cluster 4, the most severe patients, with a significant impact of pain on their daily life , we did not explore the impact of eDOL on pain disorders and related comorbidities.Our results showed a rate of adherence, after 3-month follow-up, of approximately 60%  of patients using eDOL. Three similar recent studies ,27,31, wThe good acceptability score, from both patients and physicians, reflects the interest expressed for eDOL and its contribution to the follow-up. Thus, eDOL could meet the urgent need to develop self-management and chronic pain management strategies through eHealth programs , and their therapeutic interest, as described by several studies ,20,24-30In our exploratory analyses, our study population was similar to the profile of patients suffering from chronic pain in France , GermanyWith our smartphone app, we were able to collect data on precariousness, kinesiophobia, catastrophism, alexithymia, feelings of injustice, personality, life satisfaction, beliefs about pain, anxiety-depression, sleep, quality of life, cognitive disorders, optimism and belief in a just world. We made this choice because all of these factors are related to chronic pain ,77,82-90P=.01). According to our experience with chronic pain treatment management, this characteristic could be explained both by the fact that patients suffering from nociplastic pain  are younger than the general chronic pain population  and very involved in the management of their pain. Interestingly, the presence of cognitive disorders and alexithymia, independent of clusters, was related to adherence (P=.04). We hypothesize that patients with these disorders are aware of this and compensate by using eDOL as a digital companion, resulting in better adherence.Finally, the multifactorial analysis of all our data enabled us to group our study population into 4 clusters. Interestingly, subpopulations of our patients could be distinguished only on the basis of biopsychosocial questionnaires and impact of pain on daily life whereas sociodemographic aspects, symptomatology, seniority and treatment of pain did not differ between our clusters. Cluster 4 represented patients with more disabling chronic pain, more severe comorbidities, and more pronounced psychological disorders, while cluster 1 represented patients with chronic pain that has little impact on their daily life, as well as a lower presence of comorbidity. Cluster 4 had a higher proportion of adherent patients. Our findings were similar results to those in a recent study , which sIn addition, our results support the importance of questionnaires assessing the biopsychosocial aspect of chronic pain in addition to the biomedical aspect in the medical follow-up and characterization of patients with chronic pain. Moreover, in a classical medical follow-up, patients typically only see their pain specialist every 3 to 6 months. During these interviews, patients often have difficulties recalling their various symptoms and the impact of their pain over the past few months, which corresponds to a recall or memory bias . NeverthThere was a selection bias mainly because requiring the use of a smartphones excludes patients who do not have or do not know how to use this tool. This could exclude the older or more precarious patients. Nevertheless, in view of our results, the age of the participants and the rate of precariousness were similar to those found in the general French population, with and without chronic pain ,99. We aMoreover, our satisfaction survey was not a standardized but was a custom-made tool. We built this tool based on existing tools, such as the Patient Satisfaction Questionnaire  and the Finally, only physicians were involved in this feasibility study; other members of the care team, such as nurses, physiotherapists, and psychologists, did not participate in the study. The absence of the point of view of the rest of care teams is a limitation to the interpretation of the acceptability of the eDOL tool. In future studies of the eDOL tool, we plan to include all the members of the care team as well as the addition of a chatbot and a new therapeutic education tool.The study demonstrated the feasibility and acceptability of eDOL for both patients with chronic pain and their physicians. These points justify continuing the deployment of the tool while providing information to improve its use and adherence to provide patients with chronic pain and their physicians with a better longitudinal characterization of pain and its impacts for an optimized and more personalized therapeutic management.


The control group  underwent a placebo taping application. At post-treatment time there was a statistically significant reduction both in disability (Roland-Morris Disability Questionnaire) and pain  in the experimental group  and the control group . However, at six months, these changes only remained significant in the experimental group . As a conclusion, the application of targeted kinesio taping produced a significant reduction in pain and disability, at 4 weeks and at 6 moths follow-up, although there were no differences between groups at any measurement time point.The aim of the present clinical trial is to evaluate the efficacy of kinesio taping on patients with chronic low back pain, when the exploration identifies skin/fascia mobilization as a factor that could modify the treatment effect. This study is a randomized controlled trial with intention-to-treat analysis. Sixty-two participants with chronic low back pain were therefore recruited from a tertiary referral hospital. Targeted kinesio taping, according to skin/fascia mobility exploration, was applied in the experimental group  Non-specific low back pain is, nowadays, one of the main health problems in developed populations, not only for its high prevalence (ranging from 22% to 65%)  but alsoDetermining the effectiveness of different approaches used for treating chronic low bak pain (CLBP) is a priority for healthcare systems ,5. PhysiThe duration of the KT intervention, ranging from 24 hours to 4 weeks, indicates a different characteristic between the studies. Some of them have not found additional benefit of KT when combining with other physical therapies [Evidence from randomized clinical trials (RCTs) focused on assessing the efficacy of KT in CLBP has a wide range of results. herapies –11, howeherapies . Others herapies ,14. Contherapies –18.about chronic low back pain, concluded that although KT was not superior to placebo taping in terms of alleviating pain intensity, it did significantly improve disability [A recent meta-analysis sability . Standarsability –10,14–17sability ,17,20, asability , or a ‘tsability . None ofsability ,22.Indeed, many clinicians recognize that they base their therapeutic decisions on the patterns of signs and symptoms seen in each patient without requiring a prerequisite diagnosis of an anatomical injury . This haThe fascia is a continue structure throughout the human body which allows numerous sliding directions. It has been suggested that mechanical forces applied at the macroscale produce changes in biochemistry and gene expression within individual living cells. This phenomenon called mechanotransduction is the basis to explain how physical manipulation may influence tissue physiology –28. Given that fascia tissue displacement is diminished in LBP patients [ manual skin/fascia mobilization in different directions would be able to modify a patient’s signs or symptoms, considering this exploratory maneuver a TEM. In the present study we developed a novel kinesiotaping application considering the previous skin/fascia mobilization, an issue which has not yet been arisen. Therefore, this study aimed to evaluate the short and medium-term efficacy of treatment with KT in patients with CLBP in terms of disability, pain, and quality-of-life when their initial exploration indicated that skin/fascia mobilization was a possible TEM.On the other hand, lumbar fascia has been suggested to be involved in CLBP . The fasThis was a randomized, double-blinded, parallel clinical trial with two treatment arms in which 1:1 allocation was used. The participants were recruited from December 2015 to November 2016 at the outpatient service of a Physical Medicine and Rehabilitation Service and they all signed their informed consent to participation. An investigator from the Physical Medicine and Rehabilitation Service was responsible for enrolling the participants, and a statistician outside this research team generated a random number list using random number allocation software . The ranRoland-Morris Disability Questionnaire (RMDQ); 4) improvement of pain with skin/fascia mobilization during the initial exploration and therefore considered a TEM. The exclusion criteria were: 1) previous experience with KT treatments; 2) neuropathic pain component ; 3) pain of a specific origin ; 4) prior lumbar spinal surgery; 5) mental disability, severe mental illness, abuse or dependence on substances, illiteracy; 6) allergy or dermal lesions that could prevent the application of tapes.The following inclusion criteria were applied: 1) age between 18 and 65 years; 2) non-specific CLBP present for at least 6 months; 3) a disability score equal to or greater than 4 on the Each participant received a physical examination at the beginning of the study by a physician. The clinical examination included: 1) pain detection with active lumbar mobility; 2) palpation in the prone position while applying Maigne segmental exploratory maneuvers ; 3) actiBefore being randomized into the KT or placebo-taping group, the basic rules of postural control and tonic lumbar stabilization were explained to all the patients. In addition, they were all also given a photocopy of a basic set of quadruped exercises and were instructed to perform them daily.Targeted therapy was applied in each session in the KT group, according to the following guidelines: 1) if the pain, during active lumbar mobility, decreased when longitudinally mobilizing the skin/fascia over the paravertebral musculature fibers, the “muscle technique” was applied  The tap, but somIn the placebo group, two strips of the same tape were applied in a neutral body sitting position and at non-painful segmental levels, without applying tension at any point along the tape .The same doctor carried out all the interventions. Participants in both groups were advised to maintain the tape for seven days , if possThe primary outcome of the study was changes in the level of disability. This variable was assessed by means of the Validated Spanish version of the Roland-Morris Disability Questionnaire (RMDQ)  with scoNumeric Pain Rating Scale (NPRS), in which 0 represents ‘no pain’ and 10 ‘the maximum pain imaginable’; EuroQol five-dimensions questionnaire five-level version (EuroQol 5D-5L) is a self-administered questionnaire which includes a EQ Visual Analog Scale (EQ-VAS) scored from 0, ‘the worst health you can imagine’ to 100, ‘the best health you can imagine’ and the EQ-5D-5L Index Value (EQ-INDEX) which, in the Spanish population, ranges from −0.654, ‘the worst possible quality of life’ and 1, ‘complete well-being’ [The secondary outcomes of the study were pain and quality-of-life. Pain perception was measured by means of the l-being’ .The desired sample size was calculated  taking disability as the main variable, with a minimum clinically relevant difference of 3 points in the RMDQ score . Conside©), considering a probability of p < .05 as a statistically significant result.The statistical analysis was performed based on an intention-to-treat approach. Normality of the variables was confirmed using the Shapiro-Wilk test. Two-way mixed ANCOVA tests were used to compare the effects of the intervention on the outcome metrics  between the groups, using time  as the within-group factor, and the intervention type (KT or placebo taping) as the between-group factor. The analysis was adjusted for pre-intervention (baseline) data. To determine the independent relationship between ´pre-treatment´ disability and pain scores and the ´6-month minus pre-treatment´ disability or pain scores, the Pearson correlation coefficient was also calculated. Chi-squared tests were used to determine if there were any differences between the groups in terms of adherence to the prescribed quadruped exercises. The statistical analyses were performed using SPSS Statistics software, version 17.0 . Figs  The intra-group post-treatment analysis showed a statistically significant difference in terms of the level of disability and pain reduction in both groups and the quality-of-life  in the placebo group. The intra-group analysis at the 6-month follow up showed a statistically significant difference in terms of level of disability and pain reduction only in the KT group. The inter-group analysis showed no differences in any of the comparisons . The incidence of adverse effects over all the sample was low, and these included itching (4.92%), dermatitis (6.55%), or excessive adhesion of the acrylic adhesive (1.64%). The Chi-square test did not show any significant differences between either group in the incidence of these effects. The Pearson correlation results indicated that a higher level of initial disability did not significantly correspond to a greater reduction in disability at the 6-month follow-up. However, higher initial levels of pain intensity did correspond to a greater reduction in pain at the 6-month follow up.The Chi-square test showed no significant differences between the groups in terms of the proportion of patients who said they had done the prescribed exercises and those who admitted not having completed them  , it is nRegarding quality-of-life assessment, there was no significant intra-group change at 6 months. Indeed, a study evaluating the sensitivity to change of the outcome measures in patients undergoing spinal surgery concluded that, compared with the pain and disability scales, the SF-36 and EuroQol-5D quality-of-life scales are not sensitive enough to detect clinical changes . Thus, tAt the 6-month follow-up, the results of this trial did not show any significant differences in, any variable, between both treatment groups. These results concur with those from the only one previous RCT that has collected data from the 6-month follow-up point in patients with non-specific CLBP, after a conventional application of KT .significant intragroup reduction in medium-term (at 6 months) in disability and pain scores, however this difference was not significant when compared with the placebo-taping group. The mechanism by which the KT application would cause a long-lasting reduction in disability and pain is not clear. One of the differences between the present study and other studies not reporting medium-term effects of KT, apart from considering skin/fascia mobilization as a TEM, is the duration of the taping application. Our intervention protocol lasted four weeks, while other treatment protocols registered the effect of 7-day KT [reduction in pain and disability observed in the KT group may be due to a neuromuscular input to the central nervous system originating from mechanoreceptors embedded in the fascia. The KT applied according to the exploration of the skin/fascia mobility could lead to a stimulation of these mechanoreceptors which could elicit a neural feedback providing the participants a modified movement pattern which could lead, temporarily, in a better performance of daily activities. The neuroreflex mechanism could also be related to the biological theory of tensegrity/mechanotransduction, according to which physical forces are able to regulate cellular biochemical responses [Only the KT group showed a 7-day KT ,18, 2- w7-day KT  or a max7-day KT . Accordiesponses .On the other hand, the clinical improvement seen in the placebo group may be the result of these patients’ natural clinical progression, the regression to the mean phenomenon, co-interventions, researcher and patient biases, or be because of the real placebo effect ,38.Prospective cohort studies show that lumbar pain persists in 65% of patients at the one-year follow-up , some ofThe correlation between the pre-treatment values and the ‘6-month minus pre-treatment’ difference led us to conclude that, although it is possible that the regression to the mean phenomenon could have influenced the pain results, it is unlikely to explain why a clinical improvement in the level of disability was seen. Moreover, the RCT study design is recognized as the best method for mitigating the regression to the mean phenomenon  and thisFar from being inert, real placebos—the use of patient psychosocial contexts —have genGiven that, with few exceptions, therapeutic interventions cannot be decontextualized from their psychosocial contexts, several authors have warned that RCT designs with placebo controls may underestimate treatment effects . Patientthere were no differences in these outcomes between groups. Maybe, future studies with larger sample size could confirm differences between groups at medium-term. Moreover, a recent systematic review including sixteen RCT investigating KT effects in patients with CLBP, concluded that there is strong evidence that KT improves pain and disability in this population [Our results showed a reduction in pain and disability at 6 months follow up only in the KT group, although pulation . AccordiOn the other hand, no measurement of treatment credibility was performed so we cannot ensure the success of participants blinding. Finally, although this was a trial about chronic pain, the possible concomitant pharmacological analgesic treatment of patients was not considered. Nevertheless, the evaluation of medication is recognized as a complex aspect of patient outcomes and assessment of this domain is only recommended when it is the specific object of study [One limitation of this trial was that it did not include a third untreated group to objectify the extent to which the improvement seen in the placebo group was the result of natural patient evolution, the regression to the mean phenomenon, or to the true placebo effect . Furtherof study .Reduction in both variables continued to 6 moths only in the KT group, although there were no differences between groups at any measurement time point.The application of KT in CLBP patients after first having identified skin/fascia mobilization as TEM during exploration, produced a significant reduction in pain and disability, at the post-treatment time point. S1 Checklist(DOC)Click here for additional data file.S1 Protocol(DOCX)Click here for additional data file.S2 Protocol(DOCX)Click here for additional data file.


To explore the technical points, approach selection and short-term clinical efficacy of PELD through the intervertebral foramina or interlaminar approach in the treatment of highly shifted LDH.From September 2018 to June 2020, 19 patients with highly shifted LDH were treated with PELD in The First Hospital of Yulin. It included, 10 males and 9 females; aged 34 to 69 years, with an average of 48 years. Thirteen cases were shifted to the caudal side, and six cases were shifted to the head side. The responsible segments included L3/41 cases, L4/511 cases, and L5/S17 cases. All patients had symptoms of low back and leg pain. The Sowerby dysfunction index (ODI) was 63.5%±10.7% before surgery. The visual analogue scale of pain (VAS) was low back pain (5.2±2.1) and leg pain (7.1±2.4). 14 cases used transforaminal approach, and 5 cases used translaminar approach.All cases completed the operation successfully, the operation time was 60~110min, with an average of 70 minutes. The follow-up time ranged from 6 to 42 months, with an average of 20.8 months. At the last follow-up, ODI was 10.8%±6.8%, VAS back pain score (2.1±1.1) and leg pain score (1.8±0.9). Compared with preoperative, ODI and VAS scores were significantly decreased (P<0.05). The results of Mac Nab method were 14 excellent, four good, and one fair. During the follow-up period, one patient’s leg pain symptoms recurred seven days after operation. No further hernia was found under intervertebral foramen. The symptoms disappeared after two weeks of symptomatic treatment such as swelling and analgesia, and he was discharged. No perioperative complications such as infection and nerve root injury occurred.When PELD is used to treat high-displacement LDH, the choice of transforaminal approach or interlaminar approach needs to be personalized according to the LDH segment and the direction of displacement. The clinical incidence of disc herniation is high.7Some researchers have gradually applied MELD to LDH with high displacement to ensure surgical efficacy and further reduce surgical trauma.Since September 2012, our department has applied PELD through the intervertebral foramen or interlaminar approach to highly displaced LDH and achieved good results. This study intends to explore the feasibility and safety of PELD in the treatment of highly shifted LDH, analyze the short-term efficacy after surgery; discuss the selection strategy of the surgical approach, and analyze the technical points, advantages and disadvantages of each approach.From September 2018 to June 2019, 19 patients with highly shifted LDH were treated with PELD in The First Hospital of Yulin after IRB approval , including 10 males and 9 females; aged 34 to 69 years, with an average of 48 years.A. Patients diagnosed with high-displacement LDH according to the definition of Choid, with low back or hip pain, combined with sciatica in one or both lower limbs; B. Conservative treatment for more than 3 months with poor results or repeated symptoms Onset; C. Preoperative Sowerby dysfunction index (ODI)> 30%; D. Preoperative visual analogue scale (VAS) for low back pain and leg pain> three points; E. CT, MRI, lumbar spine hyperextension flexion X The radiograph showed the imaging findings without lumbar instability.A. disc herniation, protrusion, or mild prolapse; B. disc herniation with more than one responsibility segment; C. imaging suggestion of lumbar spine instability.The segments of the responsible eight cases on the tail side), L5/S17 cases . Preoperative X-ray films showed no obvious lumbar spine instability; CT all showed compression and displacement of the nerve roots of the responsible segment, and compression and deformation of the Dural sac; MRI showed grades II to III of the responsible segment intervertebral disc.It is theoretically applicable to all types of nucleus pulposus prolapse and displacement in all segments, but the advantage is more obvious in L5/S1. The patient was in a prone position with the abdomen hanging. Continuous epidural anesthesia was used. X-ray vertical fluoroscopy locates the L5/S1 interlaminar space, and determines the puncture point according to the displacement of the nucleus pulposus toward the head or tail. Routine disinfection and towel laying. Cut the skin about seven mm at about one cm beside the spinous process, insert the dilation guide, and then insert the working tube. C-arm X-ray machine perspective confirms that the working pipe is in the correct position. Connect the endoscopic, endoscopic bipolar radiofrequency and intraoperative physiological saline lavage interface. Under the microscope, the nucleus pulposus forceps remove the soft tissue at the interlaminar space and expose the ligamentum flavum at the interlaminar space. Under the microscope, blue forceps bite the yellow ligament, revealing the dura mater and nerve root. Bipolar radiofrequency blunt separation of the dura mater and the posterior longitudinal ligament, the tip of the working pipe is rotated between the dura mater and the nerve root or on the shoulder, and the nucleus pulposus is removed under the microscope Dearmel area of nerve root. After bipolar radiofrequency hemostasis, properly withdraw from the working pipeline, check for the presence of nucleus pulposus tissue, and re-bipolar radiofrequency hemostasis. Withdraw from the working pipeline, sew one needle through the incision, and cover it with a sterile small dressing.The radial deformation of the endoscopic image is severe, while the tangential deformation is negligible. Its deformation model can be described as:d,yd)TTT is the deformation parameter; dr is the deformation radius. The corner points in ijL are located on the same straight line in the real physical world, but due to the radial deformation of the image, they are in the image the above are not collinear. In order to evaluate the degree of their collinearity, a straight line ax+by+c=0 is fitted to ijL solve. Among them, ijL. If ijL is strictly collinear, the greater the deformation of f = 0 ijLmin  the greater the fmin . The actual calculation does not need to solve for T. Note that f is a quadratic about T function:Take the residual of Eq. (9) as the straightness of set ijL. Since T has scale invariance , the limit is:Is the number of corner points in 3(M)λ, and its corresponding unit eigenvector is denoted as 3(M)u, denoted by:The minimum value of Eq. (4) under the restriction of Eq. (5) is the smallest eigenvalue of the three non-negative eigenvalues of the semi-positive definite symmetric matrix M, denoted as ijL using equations (6) and (7), where:Is the set of points corrected for For all elements in L, construct the following objective function:In this paper, the Levenberg-Marquardt algorithm is used for nonlinear optimization. In order to effectively optimize the iteration, the Jacobian matrix of S(k) needs to be given.After bed rest for two hours after operation, wear a soft waist to get out of bed, avoid bending and weight-bearing, and avoid squat toilet for one month and instruct patients to perform functional exercises of the lower back muscles and straight leg raising exercises on the bed. At 1, 3, 6, and 12 months postoperatively, the clinic was reexamined to evaluate the VAS back pain and leg pain scores and the ODI score. The efficacy was evaluated according to MacNab clinical evaluation criteria.Statistical analysis was performed using SPSS13.0 statistical software . The measurement data were expressed as mean ± standard deviation. The comparison of VAS back pain score, VAS leg pain score, and ODI at pre-operation, one month after operation, and last follow-up was performed by analysis of variance of repeated measurement data.The operation time of this group was 60~110min, with an average of 70min. All patients with L3/4 and L4/5 prolapse and displacement and two patients with L5/S1 prolapse and downward displacement adopted transforaminal approach, two patients with L5/S1 prolapse and 3 patients with L5/S1 prolapse Patients with prolapse and displacement and high iliac crest use laminar space approach. One patient’s leg pain symptom reappeared seven days after surgery. In the remaining 18 cases, the nerve root and the Dural sac were fully decompressed during the operation, and no perioperative complications such as infection and nerve root injury occurred.The patient underwent endoscopic L5/S1 nucleus pulpectomy through the interlaminar approach, and the postoperative MacNab method was effective A. The preoperative MRI sagittal T2WI showed that the nucleus pulposus prolapse of L5/S1 disc moved upward and exceeded L5. /S1 intervertebral space height, nucleus pulposus signal decreased; B. preoperative MRI cross-sectional T2WI showed prolapsed nucleus pulposus tissue compression of the right nerve root and Dural sac; C. preoperative CT showed LDH, no obvious calcification; D. Intraoperative picture, the working channel points to the caudal side; E. Intraoperative perspective prompts that the working channel tip is inclined to the head side, the working channel is located above the intervertebral space, and the range of intraoperative decompression has reached the upper vertebral body pedicle Margin; F. large amount of prolapsed nucleus pulposus tissue removed during operation; G, H. Postoperative MRI review showed that nerve root and Dural sac obtained good decompression; I. J. six months postoperative review showed fiber The annulus was well repaired and there was no recurrence of disc herniation.Nineteen patients were followed up for 6 to 42 months, with an average of 20.8 months. Postoperative VAS back pain score, VAS leg pain score, and ODI were all lower than before operation, and the difference was statistically significant. There was no statistically significant difference between the last follow-up and 1 month after surgery . The resTo improve the clinical effect of endoscopic resection of the nucleus pulposus, physicians need to choose a reasonable approach. In this research, the excellent and good effects of clinical treatment, VAS, and ODI scores were analyzed. VAS is mainly used to score the state of pain, with 0 indicating no pain and 10 representing the most intense unbearable pain.The follow-up results of the patients confirmed that PELD can achieve satisfactory clinical efficacy in the treatment of highly shifted LDH, with less surgical trauma and fewer complications. However, the study has small number of cases. As the number of cases increases, more types of surgical complications may occur. This operation requires a high degree of endoscopic operation technique, and it needs to be carefully selected before obtaining a wealth of clinical experience.BC conceived the study, literature review, data analysis, drafting the manuscript.ZD takes the responsibility and is accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.


Musculoskeletal pain (MSP) is recognized worldwide as a major cause of increased years lived with disability. In addition to known generic prognostic factors, illness perceptions (IPs) may have predictive value for poor recovery in MSP. We were interested in the added predictive value of baseline IPs, over and above the known generic prognostic factors, on clinical recovery from MSP. Also, it is hypothesized there may be overlap between IPs and domains covered by the Four-Dimensional Symptom Questionnaire (4DSQ), measuring distress, depression, anxiety and somatization. The aim of this study is twofold; 1) to assess the added predictive value of IPs for poor recovery and 2) to assess differences in predictive value for poor recovery between the Brief Illness Perception Questionnaire - Dutch Language Version (Brief IPQ-DLV) and the 4DSQ.An eligible sample of 251 patients with musculoskeletal pain attending outpatient physical therapy were included in a multi-center longitudinal cohort study. Pain intensity, physical functioning and Global Perceived Effect were the primary outcomes. Hierarchical logistic regression models were used to assess the added value of baseline IPs for predicting poor recovery. To investigate the performance of the models, the levels of calibration (Hosmer-Lemeshov test) and discrimination (Area under the Curve (AUC)) were assessed.Baseline ‘Treatment Control’ added little predictive value for poor recovery in pain intensity  and global perceived effect . Baseline ‘Timeline’ added little predictive value for poor recovery in physical functioning . There was a non-significant difference between AUCs in predictive value for poor recovery between the Brief IPQ-DLV and the 4DSQ.Based on the findings of this explorative study, assessing baseline IPs, over and above the known generic prognostic factors, does not result in a substantial improvement in the prediction of poor recovery.Also, no recommendations can be given for preferring either the 4DSQ or the Brief IPQ-DLV to assess psychological factors. Musculoskeletal pain (MSP) is a major cause of increased years lived with disability . There aThe CSM model provides a framework for identifying unhelpful cognitions and emotions people may have about their MSP condition . It is bTo investigate the added predictive value of IPs, we used the term ‘predictor’ defined as: “A patient characteristic that identifies subgroups of treated patients having different outcomes” . In our Previous research has found that IPs are predictive for and associated with psychological factors, such as depression and anxiety, in patients with fibromyalgia , chronicThe following are our three research goals; First, to what extent do baseline illness perceptions in MSP patients have added predictive value for poor recovery in PI, PF and patient GPE after 3 months? Second, what is the correlation between the 4DSQ and the BIPQ-DLV? Third, what is the difference in added predictive value for poor recovery between the 4DSQ and the BIPQ-DLV?Twenty-eight primary care physiotherapy centres participated in this five-month-long exploratory study, approved by the Medical Ethical Committee of the University of Applied Sciences Utrecht (HU) (Ref. no. 430012019). Physiotherapists at these centres collected the data as part of their HU Master of Physiotherapy study. All participating patients were treated according to the Good Clinical Practice guidelines .A consecutive sample of patients attending outpatient physiotherapy was invited at first contact by participating physiotherapists to take part. As part of an assignment in their master’s program, these physiotherapists included in the study 10–30 consecutive patients over a period of 2 months .At baseline (T0), we collected data on demographic characteristics and the independent variables listed below:Pain intensity (PI)Average pain in the last 24 h : 0 = no pain; 10 = worst pain imaginable) .Physical functioning (PF)Difficulty in performing daily activities : 0 = no difficulty; 10 = unable to perform the activity). The PSFS is reportedly feasible and reliable , 21.Pain durationPatients rated how long their pain had existed prior to consultation: 1: pain < 7 weeks; 2: pain 7–13 weeks; 3: > 13 weeks.Number of pain sitesBased on patients’ reports, the number of different pain sites were categorized as: 1: 1–2 sites; 2: > 2 sites.Psychological measuresThe Four-Dimensional Symptom Questionnaire (4DSQ) was used to assess patients’ level of risk  for developing Distress (16 items), Somatization (16 items), Anxiety (12 items), and Depression (6 items). The 4DSQ is suitable for clinical applications. The items are answered on a 5-point frequency scale. To calculate sum scores, responses are coded on a 3-point scale: “no” (0 points), “sometimes” (1 point), “regularly”, “often”, and “very often or constantly” (2 points). Then, sum scores are calculated for each dimension, and cut-off points applied to categorize each patient as at low, medium or high risk .Illness perceptionsThe cross-cultural adapted and validated Brief Illness Perceptions Questionnaire- Dutch language Version (IPQ-DLV) was used , 23: thiFor Global Perceived Effect (GPE), we used a 7-point scale ranging from ‘completely recovered’ to ‘very much worsened’. The GPE is a reliable measurement  with a cPI at follow-up; score of ≥3 on an 11-point NRS (0–10)PF at follow-up; score of ≥3 on an 11-point NRS (0–10)GPE; score of ≥3 on a 7-point ordinal scaleWe defined poor recovery in three different ways ;PI at fPain intensity and physical function were also assessed at T1 together with the Global Perceived Effect.In addition to age and gender, baseline scores were assessed for PI, PSFS, pain duration, number of pain sites, the 4DSQ, and the Brief IPQ-DLV, as percentages or means (standard deviation (SD)).p <  0.10) were added to the model. The final model was obtained by using the backward stepwise method. The goodness-of-fit of the model was described by the Nagelkerke R2 and the Receiver Operating Characteristics (ROC) curve with Area Under the Curve (AUC). Goodness-of-fit of the AUC was judged thus: 0.90–1.0 Excellent; 0.80–0.89 Good; 0.70–0.79 Fair; 0.60–0.69 Poor; 0.50–0.59 Fail. For calibration, we checked the goodness-of-fit using the Hosmer & Lemeshow test (p <  0.05). The SPSS package 25™ was used to analyze the data.Hierarchical logistic regression models were constructed to examine the added predictive value of baseline ‘poor recovery’ (at 3 months). In the first block, age, gender and baseline scores for generic prognostic factors  were entered as fixed (independent) variables. In the second block, baseline IPs with univariate significant ORs . In our first model, we entered age, gender and the baseline scores for generic prognostic factors  and added the baseline score of the 4DSQ. In our second model, we replaced the 4DSQ with the Brief-IPQ-DLV. To test the discrimination of the each model, a ROC-curve with Area Under the Curve (AUC) was applied. To compare the two AUCs, we used the empirical (non-parametric) method with NCSS 2020 software.For our research question ‘max) participants was included in this study (see Table p > 0.05). Numbers of missing items are reported in Table A total of 251  for PI, 109 out of 200 (54.5%) for PF, and 59 out of 199(30%) for GPE.For distribution of the generic prognostic factors according with baseline IPs for good or poor recovery, see Table Table For the hierarchical model, the following IP dimensions were statistically significant and were therefore selected for entering in Block 2: for the clinical outcome PI, Timeline, Treatment Control, Identity, Concern, Coherence and Emotional Response; for PF, Consequences, Timeline, Identity, Concern and Emotional Response; for GPE, Consequences, Timeline, Treatment Control, Identity, Concern and Emotional Response.Table p = 0.57; PSFS: p = 0.68; GPE: p = .08)).After being added to Block 2, most IP dimensions did not increase predictive values for poor outcomes on PI, PF or GPE. Two IP dimensions did add predictive value: lower scores on Treatment Control for PI and GPE; and a higher score on Timeline for PF. The discrimination of each model after adding IPs increased slightly (the AUC increased by 2–3%). The goodness-of-fit was adequate  were for the IP dimensions Consequences and Emotional Response. There were no significant differences in the added predictive values for poor recovery between the Brief IPQ-DLV and the 4DSQ.Most IPs did not add predictive value for poor recovery. The amount of explained variance in Block 1 increased when adding Block 2 Table  but the The IP Timeline (patients’ beliefs about how long their condition will last) is an additional prognostic factor of poor recovery in PF Table . This isFor interpretation of our findings on the additional predictive value of baseline IPs, the chosen generic prognostic factors must be taken into account. Using other prognostic factors may lead to different outcomes and interpretation of the predictive value of baseline IPs.The weak associations of the Brief IPQ-DLV with the 4DSQ indicate that they address different constructs. Additionally, both performed equally weakly as predictors for poor recovery in all three clinical outcomes. This indicates that the Brief IPQ-DLV (9-items) could not be replaced by the 4DSQ (50-items), and that neither makes a clinical contribution of added predictive value for poor recovery.First, despite the large number of participating primary care physiotherapy centers, selection bias may have occurred. Gender differences are reported for increased female risk of chronic pain and more severe pain . This mip-values (Table p-value threshold to 0.10.A strength of this study is that it is the first multicenter study done in primary care physiotherapy centers, with 28 primary care physiotherapy centers, geographically spread throughout the Netherlands. Hence, our findings are generalizable to patients in private practice in the Netherlands. Secondly, according to Hayden et al.’s criteria , our deses Table . To over, assessing baseline IPs, over and above the known generic prognostic factors, does not result in a substantial improvement in the prediction of poor recovery. In addition, the baseline outcome score of the Brief IPQ-DLV does not indicate the use of the questionnaire as a baseline predictor of poor recovery.Overall, the additional contribution of the two IP dimensions, Treatment Control and Timeline, to predictions of poor recovery after three months of usual physiotherapy care were small, the increase in the AUC being only 2–3%. Based on these resultsHowever, this does not rule out a value for IPs in MSP, as their possible role as mediators has yet to be researched. Other research designs, such as Single-Case Experimental Designs, have been shown to be of value when looking for relevant factors for recovery from low back pain , 37.In this study, treatment followed KGNF guidelines or, when not relevant, the physical therapist’s usual practice. Therefore, specific interventions aimed at patients’ beliefs cannot be assumed to have taken place. This could influence existing poor recovery outcomes of 39% for PI, 55% for PF and 30% for GPE. Tailoring interventions that match specific risk factors and patients’ needs has recently brought forward as a preventative strategy for the transition of acute to chronic low back pain , so matcBased on the findings of this explorative study, assessing baseline IPs, over and above the known generic prognostic factors, does not result in a substantial improvement in the prediction of poor recovery. Also, no recommendations can be given for preference between the 4DSQ and the Brief IPQ-DLV to assess psychological factors.The role of IPs as possible mediators has still to be researched. We recommend future research with suitable designs that can look at changeability and possible effectiveness of high IPs on PI, PF and GPE in patients with musculoskeletal pain.