Despite its widespread use for assessing pain and disability in patients suffering from neck pain, the Northwick Park Neck Pain Questionnaire (NPQ) has yet to be translated and validated in Urdu. The purpose of the present study was to translate and cross-culturally adapt the NPQ into Urdu language (NPQ-U), and to investigate the NPQ-U’s psychometric properties in patients with non-specific neck pain (NSNP).The NPQ was translated and cross-culturally adapted into Urdu in accordance with the previously described guidelines. The study included 150 NSNP patients and 50 healthy participants. The NPQ-U, Urdu version of neck disability index (NDI-U), neck pain and disability scale (NPDS), and numerical pain rating scale (NPRS) were completed by all participants on first visit. After three weeks of physical therapy, the patients completed all of the questionnaires listed above, along with the global rating of change scale. Test-retest reliability was determined on 46 randomly selected patients who completed the NPQ-U again two days after the first response. The NPQ-U was evaluated for internal consistency, content validity, construct (convergent and discriminative) validity, factor analysis, and responsiveness.The NPQ-U demonstrated excellent test-retest reliability (intra-class correlation coefficient = 0.96) and high internal consistency . There were no floor or ceiling effects for the NPQ-U total score, indicating good content validity. A single factor was extracted, which explained 54.56% of the total variance. For convergent validity, the NPQ-U showed a strong correlation with NDI-U , NPDS , and NPRS . The results revealed a significant difference between patients and healthy controls in the NPQ-U total scores (P < 0.001) demonstrating significant discriminative validity. A significant difference in the NPQ-U change scores between the stable and the improved groups (P < 0.001) confirmed its responsiveness. Furthermore, the NPQ-U change score showed a moderate correlation with NPDS change score  and NPRS change score , but a strong correlation with NDI-U change score .The NPQ-U is a reliable, valid, and responsive tool for assessing neck pain and disability in Urdu-speaking patients with NSNP. Neck pain has emerged as one of the major global health problems because of its high prevalence, incidence and associated disability , 2. ArouIn clinical practice, patient-reported outcome measures are commonly used. These outcome measures, according to a recent systematic review, stimulate active patient participation, improve quality of care, boost consultation focus (by prioritizing patient needs), allows for standardized assessment of patient outcomes, and strengthen the patient–clinician relationship . Many reThe Neck Disability Index (NDI)  and the The purpose of this study was to translate and culturally adapt the NPQ into Urdu (NPQ-U) using recognized methodologies, as well as to examine the translated version’s psychometric properties in Urdu-speaking patients with non-specific neck pain (NSNP).After receiving consent from the developer of the original NPQ, the translation and cultural adaption processes were initiated. These procedures were carried out in accordance with the COSMIN  criteria and the previously mentioned standards , 23. TheThe NPQ was independently translated from English into Urdu by two native Urdu-speaking translators who were also fluent in English. One of the translators was an English professor, and the other was a senior lecturer in physiotherapy. Both translators were given the instruction to translate conceptually rather than literally. Both of them provided written reports.By combining the findings of the two translated versions and resolving differences, the translators and two researchers created a consensus version.Two professional translators blinded to the original version translated the agreed-upon Urdu version back into English. Both translators were unfamiliar with the questionnaire concept, and neither had any medical background.An expert committee comprised of researchers, translators, an assistant professor of Physiotherapy, and a methodologist reviewed all translations, the consensus version, and the original questionnaire. A pre-final NPQ-U was obtained after reaching agreement on idiomatic, semantic, experiential, and conceptual equivalence.Forty patients with NSNP were recruited to test the face validity of the NPQ-U’s pre-final version . The patThe NPQ assesses neck pain and the resulting patient disability . It consThe NPDS, which consists of 20 items, is one of the most widely used neck pain-related disability scales . Each itThe NDI-U consists of ten items, each with six possible responses . Each itThe NPRS is an 11-point scale that ranges from 0 (no pain) to 10 (worst pain imaginable) and is used to assess the patient’s pain intensity. Patients were asked to rate their neck pain by selecting a number on the scale that best represented their pain level over the previous 24 h. The NPRS has been demonstrated to be a reliable and valid tool for assessing pain intensity .The GROC scale, having good reproducibility and sensitivity to change, is widely used to assess subject’s progress and deterioration over time usually to determine the outcome of an intervention. The outcomes were determined by asking the patients to mark a number from − 7 (“a very much worse”) to + 7 (“a very much better”) that represented their current health condition after recalling their condition at the start of the treatment .Psychometric testing of the NPQ-U was performed according to COSMIN guidelines .Both male and female patients with age 18–65 years having NSNP and able to read Urdu were recruited from two hospitals and one Rehabilitation Centre of Islamabad and Rawalpindi, Pakistan through convenience sampling technique. To calculate sample size for general psychometric testing, ten subjects per item of instrument are required . DespiteA self-structured questionnaire was used to collect demographic and disease-related information. Both patients and healthy controls were asked to fill the NPQ-U, NPDS, NDI-U, and NPRS on day first. Then out of 150 patients, 46 randomly selected patients were asked to fill the NPQ-U again following 48 h of the first response. Patients received physical therapy treatment for 3 weeks and after 3 weeks, patients were asked to fill the NPQ-U, NPDS, NDI-U, NPRS, and GROC scale. All participants provided written informed consent. This study was approved by the ethics review committee of Margalla Institute of Health Sciences, Rawalpindi.One basic issue with the NPQ is that some patients frequently missed Sect. 9, which is relevant to driving. The current study included questionnaires with this missing item, and the patient’s total score was calculated using the formula: Total scores of 8 items / 32 × 100% , 16, 18.Data analysis was performed using the Statistical Product and Service Solution (SPSS) version 20. The significance level was set at 0.05.2,1) was used to determine test-retest reliability [The reliability of the NPQ-U was assessed by analyzing test-retest reliability and internal consistency as well as measurement errors . To carriability , 30, 32.iability . Cronbaciability , 34. Croiability . The smaiability , 36 and Content validity examines the completeness of item responses, the distribution of the scores, and the magnitudes of ceiling and floor effects . Floor aExploratory factor analysis (EFA) was performed to determine the dimensionality of the items of the questionnaire. To check the appropriateness of the factor analysis Kaiser–Meyer–Olkin’s measure of sample adequacy (KMO) and Bartlett’s test of sphericity were used. Principal component analysis was used as the extraction method with varimax rotation. Using Kaiser’s rule  and the scree plot, the number of factors retained were determined .2/df), standardized root mean square residual (SRMR), root mean square error of approximation (RMSEA) with 90% confidence interval, comparative fit index (CFI), and Tucker-Lewis index (TLI) were used to assess the goodness of fit. The following criteria were used to determine acceptable model fit: X2/df ˂ 5, RMSEA ≤ 0.08, SRMR ≤ 0.08, CFI ≥ 0.90, and TLI ≥ 0.90 [Confirmatory factor analysis (CFA) was performed with AMOS software using maximum likelihood estimation to confirm the underlying factor structure from the EFA. Modification indices for the correlation of error terms were determined to improve model fit. The relative chi-square . Correlation coefficients’ values ranging from 0.00 to 0.09, 0.10–0.39, 0.40–0.69, 0.70–0.89, and 0.90-1.00 indicate a negligible, weak, moderate, strong, or very strong relationship, respectively .Construct validity was also assessed using an independent t-test to determine the difference in total NPQ-U score between patients and healthy participants .GROC scale was used to dichotomize the patients in to stable (GROC < 3 to > -3) and improved groups (GROC score ≥ 3) at the end of the treatment . ResponsThere were no significant issues while translating. During the face validity determination, 13 patients did not respond to question 9 (driving). These patients stated that they were unable to answer this question because it was unrelated to their lives. It was decided not to change this section because no modification could solve the problem.The patients’ overall impression of the NPQ-U was that the instructions and questionnaire items were simple to understand and that they could complete it quickly. They also stated that all of the items are relevant to their condition. As a result, the translated version was finalized without any changes to the original version, allowing the NPQ-U to resume the original version’s concepts and meanings.The study included 150 NSNP patients and 50 healthy participants with female predominance in each group. Table 2,1 = 0.80–0.93) and total scores  had good to excellent test-retest reliability. The Cronbach’s alpha of the NPQ-U was 0.89, indicating that the scale has a high level of internal consistency. The mean and reliability results of the individual items and the total NPQ-U scores are summarized in Table All of the NPQ-U items , and the Bartlett’s test of sphericity was significant p < 0.001). As a result, the data was suitable for factor analysis. A 1-factor solution with eigenvalues greater than one was discovered by principal component analysis, accounting for 54.56% of the total variance. A scree plot revealed one factor structure as well , NPDS , and NPRS . The results revealed a significant difference between patients and healthy controls in the NPQ-U total scores (P < 0.001), demonstrating significant construct (discriminative) validity.The difference in NPQ-U change scores between the two groups was statistically significant  outnumbered males (24%). This is consistent with previous research findings that recruited more females (65.5–82.8%) , 16, 18,The NPQ-U demonstrated excellent test-retest reliability in the current study, which is consistent with previous research findings –21, 43. According to the current study’s findings, a minimum change of 10.75 points on the NPQ-U  is required to be labeled as a “real change”. In other words, a difference of 10.75 points between total NPQ-U scores before and after treatment was accepted as the threshold value to determine whether there was a clinically significant change without a measurement error. This result is comparable to that of the Brazilian Portuguese version .In the current study, 70 patients (46.7%) did not complete Sect. 9 about driving. Indeed, missing driving data has been reported in Spanish (62.3%) , TurkishIt is worth mentioning that the NPQ’s factorial structure was not observed in the original English version developed by Leak et al.  or in soDue to the lack of a gold standard for health-related questionnaires, the NPQ-U’s criterion validity was not examined . The conThe NPQ-U, as demonstrated by the findings of this study, is an outcome measure capable of detecting changes in condition over time which is comparable with the findings of previous studies , 43, 46.The current study only included patients with NSNP, and it is unclear whether the results can be applied to patients with other types of neck pain. Furthermore, data were primarily gathered from patients who visited out-patient departments. As a result, the sample might not be a true representation of the general population suffering from neck pain, and the results cannot be generalized to inpatients.The strength of this study is that the translation and testing of the different psychometric properties of the NPQ-U, including face validity, reliability, content validity, construct (convergent and discriminative) validity, factor analysis, and responsiveness were carried out using standard guidelines. Another strength of the study is that an adequate sample size was used to conduct all of the analyses. In addition, the CFA was used to determine the structure of the NPQ-U. Moreover, though the NDI-U is available to measure disability related to neck pain in Urdu-speaking patients, the NPQ-U appears to have some advantages because it addresses some common daily activities that are likely to be affected by neck pain, such as watching television, carrying objects, and so on, as well as questions about pins and needles or numbness in the arms at night and the duration of symptoms, which the NDI does not. Other than that, the NPQ-U has better psychometric properties to the NDI-U, as its convergent validity and responsiveness were tested against other neck pain and disability scales, such as the NPDS, which the NDI-U lacks. Finally, to the best of the authors’ knowledge, this is the first study that translated and cross-culturally adapted the NPQ into Urdu, as well as tested the psychometric properties of the NPQ-U.The NPQ-U can be used in clinical and research settings to evaluate patients and monitor the effectiveness of physiotherapy, manipulative therapy, and any other treatment for neck pain to assess disability because of its good psychometric properties and ease of use. Furthermore, it can contribute to more valid cross-cultural comparisons of neck disorders between English and Urdu speaking populations by serving as the primary outcome measure.According to the findings of this study, the NPQ-U is a reliable, valid, and responsive questionnaire. The NPQ-U’ items are simple and easy to complete. As a result, it can be used to assess neck pain and disability in Urdu-speaking NSNP patients.


In November 2022, the Centers for Disease Control and Prevention updated a 2016 practice guideline for opioid prescription.The 2022 Centers for Disease Control and Prevention guideline reiterates that clinicians should prescribe opioids at the lowest effective dose for the expected duration of pain warranting opioid use. The guideline also endorses patient-centered approaches to the initiation or taper of opioids. Clinicians should discuss benefits and risks of opioids and consider patient preference. The 2022 guideline further suggests that clinicians “evaluate benefits and risks with patients within 1-4 weeks of starting opioid therapy for subacute or chronic pain or of dosage escalation.” This recommendation is particularly relevant to the chronic management of patients who begin opioids for hidradenitis suppurativa, erosive lichen planus, or chronic ulcerating conditions, or even in the emergency department, where opioids are frequently prescribed for cellulitis and abscess.Postsurgical pain management comprises the majority of opioid prescriptions among dermatologists.An added 2022 recommendation outlines the use of prescription drug monitoring or high-sensitivity screening questions to mitigate opioid prescriptions to patients at higher risk for substance use. This recommendation is accompanied with the caveat that prescription drug monitoring data should be used with “all patients rather than differentially on the basis of assumptions about what [clinicians] will learn about specific patients.” The 2022 guideline also uses five new guiding principles, which emphasize an individualized, flexible, and multidisciplinary approach to opioid prescription. The fifth guiding principle encourages culturally informed communication to promote access to affordable, diversified pain management regimens and recognizes the role of bias in pain management. The 2022 guideline update is an important step toward thoughtful, safe, and patient-centered opioid stewardship. Dermatologists should continue to build on this national policy update and consider more specific opioid appropriateness recommendations for chronic, nonsurgical dermatologic conditions.None disclosed.


Chronic pain is not a singular disorder and presents in various forms and phenotypes. Here we show data from a cohort of patients seeking treatment in a transdisciplinary pain clinic. Patients completed a multidimensional patient-reported battery as part of routine initial evaluation at baseline and at each of the four subsequent visits over 1-year follow-up . The goal of this work was to use unsupervised modeling approach to identify whether patients with chronic pain undergoing transdisciplinary intensive rehabilitation treatment: (1) can be derived based upon self-reported outcome measures at baseline (or before treatment initiation), (2) are clinically validated based on their clinical diagnosis and medication use, and (3) differ in treatment trajectories over 1 year of transdisciplinary treatment. We applied unsupervised clustering on baseline outcomes using nine patient-reported symptoms and examined treatment trajectories. The three-cluster solution was internally validated. Psychiatric diagnosis, chronic back pain-related disability and symptoms severity determined cluster assignment and treatment prognosis. Conversely, clinical pain severity had lesser effect. Furthermore, clusters showed stability over time despite symptoms improvement. The accurate and meaningful subgrouping of the underlying chronic pain phenotypes would greatly enhance treatment and provide personalized and effective pain management. Beyond the diversity of its representation, the comorbidities associated with chronic pain lead to further heterogeneity2, treatment failures or marginal treatment results3. The accurate and meaningful subgrouping of the underlying pain phenotypes among patients with chronic pain would greatly enhance treatment strategies and effectiveness4. Data-driven approaches that characterize patients with similar diagnosis based on patient-reported outcomes show great promise in understanding clinical conditions6. Clustering approaches have been informative in the detection of subsamples among chronic pain patients9 and, potentially, in predicting patients’ prognosis4. A recent study in a large sample of real-world patients seeking treatment at a tertiary academic pain clinic found three robust clusters in their sample defined by graded symptoms severity with negative-affect-related symptoms being a key determinant in cluster separation4. Symptom severity at follow-up was predicted by baseline cluster assignment in this study suggesting cluster stability and, potentially, trait-based than state-based cluster characterization4. Although informative, translating these classification systems into effective treatments approaches has been challenging, as longitudinal data from specific and controlled treatment approaches are lacking.Chronic pain affects up to 60 million people worldwide and the annual cost of chronic pain in the United Sates is as high as $635 billion a year, more than the yearly costs for cancer, heart disease, and diabetes, combined. Chronic pain is not a singular disorder4 and provides unique evidence for patients’ prognosis following transdisciplinary pain management. As transdisciplinary pain care is becoming a “go to” pain management approach10, we believe our findings will: (1) increase knowledge of the chronic pain illness experience and effects of treatment on patient’s physical and mental functioning, and (2) provide initial evidence for personalized treatment assignment and optimization.The current study examined the trajectories of treatment effects of the transdisciplinary treatment approach for patients with chronic pain through the completion and collection of study subject questionnaires (patient-reported outcomes) and applying unsupervised modeling. The subjects were assessed at different time points . Here we wanted to investigate whether robust subgroups of subjects (1) can be derived based upon self-reported outcome measures at baseline, i.e., before initiation of treatment, (2) are clinically validated, and (3) differ in treatment trajectories over a year of follow-up treatment. We also examined whether the services used in the transdisciplinary pain care differed between the subgroups and explored cluster dynamics over the course of treatment. Our large longitudinal dataset with multiple assessments points builds on the existing models of the underlying chronic pain phenotypesMclust) produced a three-group solution based on subjects’ baseline responses (Time 0), sorting 1064 patients into Cluster1 (MCL1), 1709 patients into Cluster2 (MCL2) and 523 patients into Cluster 3 (MCL3). Questionnaire completion was the same in each of the three cluster groups , thus longitudinal analysis was conducted in completers to minimize inference.Study design is summarized in Fig. 2 = 69.129, p < 0.001). Whereas proportion of male/females was similar in MCL1 (36%/64%) and MCL2 (30%/70%), it differed in MCL3 (50%/50%).Mclust subgroups demographic characteristics are shown in Table Examination of baseline outcome measures showed that Mclust subgroups differed on several patient reported outcomes. This is graphically demonstrated by the radial plot in Fig. 2 = 3.847, p > 0.1) with ~ 80% of individuals taking opioids in each of the subgroups. Nevertheless, we found significant between subgroup difference in the amount of prescribed opioids   = 3.439, p = 0.032). Post-hoc comparison showed that MCL3 were prescribed more opioid medication that MCL1 (p < 0.05). We found that severe back pain (ICD-10: M54) was the most prevalent diagnosis in all the three subgroups with the overall prevalence of ~ 92% , followed by the biomechanical lesions (ICD-10: M99) with the overall prevalence of ~ 84% . We found that other joint disorder, not elsewhere classified (ICD-10: M25) was most prevalent in MCL1, least in MCL3 and MCL2 falling in the middle , with overall prevalence of ~ 45%. Likewise, soft tissue disorders/myalgia (ICD-10: M79), was most prevalent in MCL1, least in MCL3 and MCL2 falling in the middle , with the overall prevalence ~ 18%. Notably, fibromyalgia, (ICD-10: M79.7) was the most prevalent diagnosis under this category (45%). Pain not elsewhere classified (ICD-10: G89), was most prevalent in MCL2, least in MCL3 and MCL1 falling in the middle , with overall prevalence ~ 18%. Recurrent depressive disorder (ICD-10: F33) was most prevalent in MCL3, least in MCL1 and MCL2 falling in the middle , with the overall prevalence ~ 33%. Examination of most commonly prescribed medications in our study did not show significant differences between the three subgroups . In other words, all three subgroups used comparable proportion of services provided throughout their treatment  = 3.72, p = 0.023) and the group difference approached significance in the number of visits/encounters  = 2.823, p = 0.060)  on Patient’s Global Impression of Change (PGIC) with sex and age as covariates. PGIC at each time point showed overall increase indicating improvement over the course of treatment in all three groups, which was significant F4,8,4,4) = 4.128, p = 0.002) .Transition of patients across clusters over the five longitudinal time points are shown in Fig. 11. Nevertheless, differences in resource utilization and treatment prognosis between the subgroups were noted that we discuss below.The goal of this work was to address the knowledge gap in the field whether a personalized medicine approach, such as transdisciplinary pain care, can successfully adapt to the needs of a heterogeneous chronic pain population. To address this gap, the unsupervised, data-driven modeling was used to identify whether subgroups of patients with chronic pain undergoing transdisciplinary treatment: (1) can be derived based upon self-reported outcome measures at baseline (or before treatment initiation), (2) are clinically validated based on their clinical diagnosis and medication use, and differ in (3) resource utilization and (4) treatment trajectories over 1-year of transdisciplinary treatment. Several important findings were observed. First, we identified three robust clusters based on baseline patient reported outcomes. Second, our data-driven subgroups showed a pattern of significant differences across clinical diagnosis and presentation. Third, we found that all three subgroups improved over time suggesting that treatment could be considered effective across the numerous presentations of chronic pain patients; this is consistent with the goals of transdisciplinary approach to chronic pain care14. A Spanish study in adult population (n = 1957) identified two clusters separable by the severity of pain and mental health problems8. Likewise, a Swedish study in older adults with chronic pain (n = 2415), revealed four clusters9, similar to another Swedish study of patients with chronic pain (n = 4665) based on data collected from the Swedish quality registry7. A German study of patients with low back pain (n = 1238) in primary care identified four clusters13, while a Canadian study in veterans with chronic pain (n = 2754) found three clusters14. An older U.S. study of patients with chronic pain (n = 453) in treatment at a pain center used data from Symptom Checklist 90(SCL-90) and a comprehensive pain evaluation questionnaire and found three clusters12. A cluster analysis of a larger number of members of a U.S. health maintenance organization with two or more chronic conditions identified ten clusters, one of which was dominated by patients with chronic pain, a majority of whom also had mental health conditions, and about half had obesity15. A recent large scale.  U.S. study used only pain-agnostic symptoms and identified a three clusters solution based on graded symptom severity4; negative-affect-related symptoms were the key determinants in cluster assignment in this large study4. This work also examined longitudinal timecourse from a subset of patients (n = 1283) who completed a follow-up survey between 3 and 12 months after the initial assessment and found that the severity of symptoms at follow-up could be reliably predicted by baseline subgrouping4. These prior studies confirm that cluster analysis can consistently identify unique and potentially stable subgroups of people with chronic pain irrespective of chronic pain population. Our findings are consistent with these studies in symptom distribution and unique cluster identification among chronic pain sufferers thus providing the premise of our treatment trajectories through transdisciplinary pain care being conceptually generalizable to other population clusters.Several studies used cluster-based approach in chronic pain patients and are consistent with our results, in that generally, the majority of these studies identified 2–4 clusters based on pain and mental health symptom severity4. However, despite similar clinical pain presentation in all three subgroups, several striking differences were observed. We found that group 1, or MCL1, was characterized by lower ratings on all but substance use measures at baseline. Subjective ratings and clinical presentation of this group is consistent with the least impaired chronic pain population, in terms of pain and pain-related disability. We observed similar findings in our recent brain imaging study whereby individuals with low psychological and pain measures clustered out based on the pattern of brain connectivity at rest16. We found that the brain connectivity at rest in this low symptom group was consistent with resilient brain function, suggesting that even though these individuals have chronic pain and/or trauma, they have the capacity to deal with their symptoms in a more resilient way and thus report lower symptoms16. Nevertheless, our least impaired chronic pain population (MCL1) did not show the lowest scores on substance use measure; it is possible that these individuals are likely to self-medicate and thus report lower ratings. We found that group 2, or MCL2, was characterized by the highest disability due to back pain. Compared to the least impaired group, this group showed less improvement at 6 months but similar improvement at 12 months follow-up. Otherwise, this group was clinically and psychologically very similar to the least impaired chronic pain group, or MCL1. This group was also slightly younger and, similarly to MCL1, had a greater proportion of women consistent with the sexual dimorphism in chronic pain prevalence in the general population17. We found that group 3, MCL3 reported more mental health symptoms , had the greatest proportion of major depressive disorder diagnosis, were prescribed higher dose of daily opioids, stayed in the program longer and showed less improvement at the end of the follow-up, or at 12 months post program initiation. This group is consistent with the most impaired, or high-impact, chronic pain group with more severe pain, multiple mental health concerns and showed similar prevalence to that in the U.S. adult population (~ 16% in our study)19. Higher dose of daily opioids found in this group are consistent with our recent work that showed association of daily opioids with mental health status rather than pain severity20. Likewise, poorer improvement overtime and higher disability in this high-impact pain group is consistent with the literature21. Particularly for those also affected by psychiatric disorders, chronic pain is an important driver of health care utilization in primary and other health care services22. Those whose chronic pain is aggravated by co-occurring mental health conditions show poorer treatment outcomes, increased pain severity and disability23. Thus, our results provide clinical validation for the identified subgroups within a large sample of chronic pain patients. It is also interesting, that unlike the other two clusters, this high impairment, high-risk subgroup had greater proportion of men.Our unsupervised, data-driven approach identified three stable clusters of patients with chronic pain based on nine patient-reported pain and psychiatric symptoms. We found that all three groups reported moderate-severe chronic pain at baseline. Likewise, the proportion of patients on opioid medication was not significantly different between the three subgroups (see below for further discussion). These results suggest that pain symptoms reported by the patients at baseline were unlikely to drive the cluster separation in our study. This is consistent and extends recent findings on the role of pain intensity measure in determining reliable cluster solutions11. We believe that it is largely due to the fact that current treatment program is dictated by patient choice, which is guided by patient’s expectations and is adapted accordingly24. In other words, treatment plan is modified according to patient’s choices, which are based on the most positive expectation of clinical benefit thereby potentially incurring greatest benefit24. It is plausible that a less adaptive treatment plan would show greater divergence of outcomes across the subgroups. Nevertheless, the high-impact chronic pain group  reached ceiling effect around 6 months. This points to the possibility that high-impact chronic pain patients may need more guidance and/or more aggressive approaches in their treatment. Perhaps targeting mental health prior to targeting pain issues would mitigate these ceiling effects. It is generally accepted that non-volitional, or not controlling their interventions, has poorer outcomes compared to volitional treatment choices25. Likewise, individual vs. group approach should be considered when high-risk patients are involved26. Interestingly, despite symptoms improvement over time, clusters were relatively stable, in that the majority of patients remained with their own cluster. This was mostly pronounced in MCL2, or the younger group with the highest back-pain related disability, suggesting that patients within this group have unique features that may not change with treatment despite symptoms improvement.Importantly, we found that overall, all three groups improved comparably overtime. We found that patient’s global impression of change (PGIC) increased as treatment progressed, indicating improvement. Likewise, subjective pain rating (PEG) decreased as treatment progressed, indicating gradual decrease in perceived pain impact over time. From this perspective, treatment was effective. This finding was not surprising, considering the transdisciplinary nature of the program whose goals are to maximize patient’s benefit10. However, there are potentially warning signals that some subject populations may tend to have a waning benefit after a year of treatment, thus potentially encouraging a re-visitation of treatment needs and goals at the 6-month timepoint in this population.A key aspect of the current work is translatability to clinical practice. Specifically, this work presents insight as to the types of patients that approach transdisciplinary treatment and provides insight into how this presentation may affect the course and trajectory of treatment. Importantly, it should be noted that there were striking similarities between treatment paths in the transdisciplinary clinic across a variety of patient types. This bolsters the trend that a transdisciplinary approach is becoming a “go-to” method for chronic non-cancer painMclust approach as this was similar to the approaches taken in prior work and thus added more directly to this body of literature. Similarly, the determination of the ultimate number of clusters was limited to the range of prior samples, thus enhancing replication and contrast to prior work . However, the findings in this sample appear to replicate similar work done in other samples. Secondly, there are numerous cluster-based or unsupervised modeling approaches that could be taken, which potentially, may affect the resulting solution. We selected the In summary, we used unsupervised, data-driven modeling approach to examine whether patients with chronic pain undergoing transdisciplinary pain care at the same clinic could be separated based on patient reported outcomes that are known to affect the expression of chronic pain. We found that, even in an adaptive transdisciplinary treatment program, subgroups with higher pain and psychiatric symptoms exist, may need more care, and may have greater treatment resistance detectable in long term care.https://savashealth.com/) and completed a set of standardized assessment tools (see below) at baseline/screening visit month 0 (t0), month 1 (t1), month 3 (t3), month 6 (t6) and month 12 (t12). The overview of the program is outlined in Supplemental Material Study was approved by the Western Institutional Review Board. Data collection was performed in accordance with relevant guidelines and regulations. All patients included in this study provided informed consent, received transdisciplinary pain treatment at Desert Clinic Pain Institute and Summit Institute  and were ≥ 18 years of age and met at least one of the following inclusion criteria and none of the exclusion criteria (mandatory to be included in the program): (1) Current high dose Opioid use (Dose at or above 120 mg MED per day); (2) Help with tapering/discontinuing of medication needed; (3) Presents with psychiatric illness or symptoms complicating treatment of chronic pain; (4) Chronic pain refractory to usual interventions; (5) Member's work or lifestyle has been significantly impaired due to chronic pain; (6) Member not satisfied with current pain care outcomes; 7) Complex pain conditions. Patients were excluded if: (1) Is not covered by Inland Empire Health Plan  Pain Intensity and Interference (PEG)29; (3) Oswestry Low Back Pain Disability Questionnaire (ODQ), which is considered the ‘gold standard’ of low back functional outcome tools30; (4) Pain Disability Index (PDI)31 to measure overall pain-related disability; (5) Pain Catastrophizing Scale (PCS) to measure individual’s catastrophic thinking about their pain32; (6) Patient Health Questionnaire-9 (PHQ-9) to evaluate depressive symptoms33; (7) General Anxiety Disorder (GAD-7) to measured anxiety symptoms34; (8) DAST-10 Questionnaire (DAST) to assess drug use, not including alcohol or tobacco use, in the past 12 months35; (9) The Alcohol Use Disorders Identification Test (AUDIT) to assess alcohol consumption, drinking behaviors, and alcohol- related problems36; and (10) Patient’s Global Impression of Change (PGIC), a 7 point Likert scale rating the subjects change in activity limitations, symptoms, emotions and overall quality of life since beginning of the treatment; this measure was used to evaluate longitudinal outcomes of treatment. Note, for the baseline rating, patients were asked to rate relative to all past treatments tried. For the following time-points, the rating referred to the beginning of the current treatment. The following anchors were used: 1 = No change (of condition has got worse); 2 = Almost the same, hardly any change at all; 3 = A little better, but no noticeable change; 4 = Somewhat better, but the change has not made any real difference; 5 = Moderately better, and a slight but noticeable change; 6 = Better, and a definite improvement that has made a real and worthwhile difference; 7 = A great deal better, and a considerable improvement that has made all the difference.Subjects completed the following self-reported battery of questionnaires: (1) The Numeric Pain Rating Scale  corresponding to current pain experienced14. The quality of a given cluster was assessed based on the Bayesian Information Criterion (BIC) score for the entire sample , as well as well as the Jaccard index of overlap between subsamples of the data that were modified through bootstrapping, jittering, and replacement by noise . From this selection similar fits were achieved with 3, 4, and 6 cluster solutions (depending on metric). The three-group solution was selected due to maximal parsimony, and, if successful, optimal clinical efficiency.All statistical analyses were performed using the statistical program R version 4.0.2, RStudio. The missing values in the self-report measures were imputed using multivariate imputation by chained equations (MICE) consisting of 5 multiple imputations with 3 iterations, in R using the MICE package version 3.12.0. For the self-report measures, imputation was used for patients that had < 20% of a questionnaire missing. Patients were excluded if they had > 20% of the questionnaire missing. Ultimate cluster size was determined using two approaches. Clusters were selected from a range of groups from 1 to 6 based on prior literatureMclust in R (version 6.0.0)37 in order to identify whether clinically relevant subgroups of subjects (1) can be derived based upon self-reported outcome measures at baseline, (2) are clinically validated and (3) differ in treatment trajectories over the 1 year of follow-up treatment. Mclust is a contributed R package for model-based clustering, classification, and density estimation based on finite normal mixture modelling. It provides functions for parameter estimation via the mixture estimation (EM) algorithm for normal mixture models with a variety of covariance structures, and functions for simulation from these models. Also included are functions that combine model-based hierarchical clustering, EM for mixture estimation and the BIC in comprehensive strategies for clustering, density estimation and discriminant analysis. For trajectories analysis, PGIC and PEG scores were examined at each time point, i.e., baseline (t0), 1 month (t1), 3 months (t3), months (t6) and 12 months (t12). To assess cluster dynamic, i.e. to examine patient movement across clusters between the baseline and subsequent time points we applied the cluster modeling developed at baseline at each following point (mclust::predict.Mclust). This confirmatory analysis was applied only to patients that had complete data at each time point (n = 353). The transitions were depicted across time using a Sankey diagram (R: networkD3 version 0.4).An unsupervised subgroup classification was performed using subgrouping within t-tests and chi-square tests were used to compare Mclust subgroups on clinical and demographic variables . Results were corrected using Holm method. For the treatment trajectory’s analysis, we used repeated measures ANOVA with Mclust as a fixed factor and assessment time  as the repeated measure to examine effects of time. Groups were compared at each time point using ANCOVAs. Sex and age were used as covariates in all of the analyses.Statistical analysis of clinical and psychological variables was conducted in R and JASP (JASP Team (2020). JASP (Version 0.14.1) (Computer software). ANCOVAs, Supplementary Information.


P > .05), while the extension grip strength was found to be significantly lower in patients with neovascularity (P = .045). In addition, patients with peritendinous fluid or bursitis, were found to be significantly lower in both flexion (P = .033) and extension (P = .023) grip strength, while PRTEE function (P = .021) subgroup and total (P = .038) scores were significantly higher. Hypoechoic region, cortical irregularities and enthesopathy were not evaluated to be associated with disease severity, pain and muscle strength. Neovascularity was found to be associated only with extension grip strength. Peritendinous fluid or bursitis was found to be associated with both flexion and extension grip strength and disease activity, but not associated with pain.To evaluate the relationship of ultrasonographic evaluation parameters with pain, muscle strength and disease severity in lateral epicondylitis (LE). 64 people were included in present retrospective, cross-sectional study. Activity and rest pain was questioned with Visual Analog Scale (VAS). Also, Patient Rated Tennis Elbow Evaluation (PRTEE) and the maximum grip strength were evaluated. Hypoechoic region, neovascularity, cortical irregularity, enthesopathy and peritendinous fluid or bursitis were evaluated by ultrasonography. 48 of the patients were female and 16 were male. Mean age was 48.53 ± 6.12, body mass index was 27.70 ± 4.75. 55 (85.9%) hypoechoic region, 31 (48.4%) neovascularity, 21 (32.8%) cortical irregularity, 19  enthesopathy, and 18 (28.1%) peritendinous fluid or bursitis were detected by ultrasonography. When the ultrasonographic findings and clinical findings of the patients were compared, no significant difference was found between the hypoechoic region, cortical irregularity, enthesopathy and clinical findings ( LE is caused by pathological alterations in the tendons of the extensor carpi radialis brevis, extensor carpi ulnaris, extensor digitorum, and extensor digiti minimi muscles, which comprise the same extensor origin. Currently, there is still not a definitive method for diagnosing LE. However, the Cozen, Mill, and Maudsley tests are frequently used provocation tests that are regarded as positive if they duplicate lateral elbow discomfort in clinical practice and research. As a result of the lack of a gold standard diagnostic technique, variable diagnostic tools are needed. Musculoskeletal ultrasound (MUS) is a reliable, accessible, noninvasive, and cost-effective option for diagnosis.,6 Additionally, MUS offers the chance for a dynamic examination, giving it an advantage over MRI and CT. When it comes to diagnosing epicondylitis, sonography is sensitive but not specific as MRI. Gray-scale ultrasonography (USG) can be used to identify LE with intermediate sensitivity and high specificity. MUS can reveal bone abnormalities, calcifications, enthesopathy, localized hypoechoic regions, peritendinous fluid, linear intrasubstance tears, and thickening of the tendon in tendinosis of the common extensor tendon.Lateral epicondylitis (LE) is the most common cause of discomfort in the lateral region of the elbow, characterized by pain in that area.Previous studies have provided evidence for the diagnostic utility of MUS in LE. However, there is a lack of understanding regarding the relationship between ultrasonographic evaluations and the severity of the condition. The objective of our study was to examine the correlation between pain, muscle strength, and disease severity in LE using ultrasonographic evaluation measures.Our study was carried out in a single-center at Fatih Sultan Mehmet Training and Research Hospital, Department of Orthopedics and Traumatology between January 2021 and February 2023. Prior to the study, participants provided consent. Ethical approval was obtained from the Agri İbrahim Cecen University Ethics Committee, adhered to the principles of the Declaration of Helsinki.In this study, we enrolled 64 patients who were over the age of 18 and sought treatment at our clinic for elbow pain, diagnosed with LE after physical examination, no other pathology detected on direct radiographs. Additionally, these patients had been experiencing their symptoms for more than 6 months despite previous conservative treatments. We collected demographic information and medical history from all participants. For painless grip strength evaluation, patients were instructed to squeeze the dynamometer until they felt discomfort.In the physical examination, palpation of the LE and Mills, Maudsley and Cozen tests were performed. The patients were also asked to rate their level of activity and rest pain using the Visual Analogue Scale (between 0 and 10 points). Jamar hydraulic hand dynamometer, considered as the gold standard by the American Association of Hand Therapists, was utilized to assess the rough grip strength.The evaluation of maximum grip strength was conducted to assess the strength reached by patients beyond their pain threshold. The first test was performed with patients seated in a chair with their arms supported, shoulder in adduction and neutral position, elbow flexed at 90°, forearm in a neutral position, and wrist in a position of 0° to 30° extension and 0° to 15° ulnar deviation. The second test was performed with patients in a standing position, shoulder adducted and elbow extended. A 30-second rest period was given between each measurement.In this study, the ultrasonographic examination was performed with the Esaote Mylab 60 device using a linear probe with a frequency of 6 to 18 MHz. During the examination, the patients were positioned with their shoulders adducted, elbows flexed at 90 degrees, and wrists pronated. The USG probe was placed longitudinally on the radial surface of the elbow to measure the thickness of the common extensor tendon.Patient Rated Tennis Elbow Evaluation (PRTEE) formerly known as the Patient-Rated Forearm Questionnaire was developed by Overand et al This evaluation form is designed specifically for patients with LE. It consists of 2 sections that assess pain and function. The function subheading includes specific activities and general activities. Each subsection takes a value between 0 and 100. For the total score, the pain total score and the average of the specific and general activity scores are added. As a result, a value between 0 and 100 is obtained.t test or Mann–Whitney U test was performed for quantitative variables. The value P < .05 was accepted to indicate statistical significance.Statistical analysis of all the study data was performed using IBM SPSS Statistics for Windows, Version 25.0. Descriptive data were expressed in mean ± standard deviation or number and frequency. The distribution of variables was checked with the Kolmogorov–Smirnov test. To compare between 2 groups, an independent sample 64 individuals who met the inclusion criteria were included in this retrospective study. 48 of the patients were female and 16 were male. Mean age was 48.53 ± 6.12, body mass index was 27.70 ± 4.75, and duration of complaint was 20.37 ± 22.19 months. While the dominant hand was the right hand in 62 (96.8%) patients and the left side in 2 (3.1%) patients, 41 patients (64.1%) reported complaints on the right elbow, and 23 patients (35.9%) on the left elbow. While 29 (45.3%) of the patients included in the study were actively working, 35 (54.7%) were not working.P = .609).While the mean Visual Analog Scale (VAS) values of the patients were 3.28 ± 2.30 at rest, it was 7.43 ± 1.62 during activity. In the PRTEE evaluation, the pain sub-values were 29.54 ± 5.37, the function sub-evaluation was 30.61 ± 7.21, and the total values were 60.16 ± 11.22. When the painless values of the patients’ handgrip strength were examined, the mean values were 14.37 ± 7.19 in the elbow flexion position and 12.54 ± 7.15 in the extension position. While the tendon thickness measurements of the patients were 4.61 ± 0.60 on the sick side, it was 4.55 ± 0.60 on the healthy side, and there was no statistically significant difference between the 2 sides (P > .05), while the extension grip strength was found to be significantly lower in patients with neovascularity (P = .045). In addition, in patients with peritendinous fluid or bursitis, was found to be significantly lower in both flexion (P = .033) and extension (P = .023) grip strength, while the PRTEE function subgroup (P = .021) and total scores (P = .038) were significantly higher. The results are shown in Table MUS findings of the patients with LE were examined. 55 (85.9%) hypoechoic region, 31 (48.4%) neovascularity, 21 (32.8%) cortical irregularity, 19 (29.7%) enthesopathy, and 18 (28.1%) peritendinous fluid or bursitis were detected. MUS findings and clinical findings of the patients were compared and no significant difference was found between the hypoechoic region, cortical irregularity, enthesopathy and clinical findings .In a study, comparing the ultrasonographic changes on 60 patients with LE and 264 participants with no symptoms demonstrated the tendon thickness and color Doppler activity on LE patients. They concluded that the tendon thickness cannot be used as a stand-alone diagnostic tool, however color Doppler activity is a marker of the ongoing tendinopathy and supports the diagnosis of LE. Lee et al found that hypoechoic regions (35.3%), peritendinous fluid (3.9%), and cortical irregularities (17.6%) had low sensitivity for LE. Although focal hypoechogenicity was moderately sensitive and highly specific for LE, it was not found to be associated with pain, muscle strength, and disease severity. Our study results align with these findings, as we also found no relationship between hypoechoic regions and disease severity, pain, or muscle strength. Bone changes in the lateral epicondyle were moderately susceptible to chronic lateral epicondylalgia. Although cortical irregularities have been suggested as features of the chronic stage of musculoskeletal disease, they are less frequently detected in lateral epicondylalgia elbows compared to focal hypoechogenicity.Struijs et al discovered sonographic abnormalities in 75% of the patients, including hypoechoic and hyperechoic regions, swelling, calcification, bursitis, enthesopathy, and tendinosis. The positive predictive value of sonography ranged from 0.78 and 0.82, and the negative predictive value ranged from 0.23 and 0.71. When the predictive value was examined among the subgroups, it was not found to be associated with treatment success and pain. Cortical irregularities and hypoechoic regions, which have limited diagnostic value, were not associated with pain, functionality, or wrist flexion and extension muscle strength in our study. Bone spur could not be associated with outcomes such as pain, disability, PRTEE, and disease duration. However, pain and functionality assessments in cases of peritendinous fluid or bursitis were related to wrist flexion and extension muscle strength. Additionally, color Doppler detected peritendinous hyperemia or neovascularity in the intratendinous region. The absence of neovascularity and grayscale changes on MUS examination should prompt consideration of other causes of lateral elbow pain. Conversely, although healthy elbows usually do not have neovascularity, there are studies with inconsistent results in the diagnostic ability to confirm the presence of lateral epicondylalgia in painful elbow.,21Furthermore, the relationship between calcifications, which is considered to be the main feature of degenerative tendon changes, and lateral epicondylalgia was found inconsistent. This may indicate that pathological changes in elbows with LE are more traumatic than degenerative. In our study, neovascularity, despite its diagnostic value for LE, was not associated with pain, functionality, or wrist flexion muscle strength. Similarly, du Toit et al found that common extensor tendon neovascularity and clinical severity measures did not correlate with neovascularity scores. Krogh et al also did not find a relationship between Doppler activity and outcomes such as pain, disability, PRTEE, or disease duration. In contrast, in our study, it was found to be associated with neovascularity and wrist extension muscle strength.Similarly, Yuill et al identified neovascularity, calcifications, and cortical irregularities as highly specific but weakly sensitive indicators of chronic LE. There is little clarity about the role of these findings in the diagnosis of LE.Our study has several limitations. The diagnosis of LE was made clinically and the differences in body structure were not taken into account in the ultrasonographic evaluation. The results of our study are limited due to the small number of patients participating in the study. We recommend planning future studies with a larger sample size.One of the strengths of our study is that patients’ muscle strength was evaluated with the Jamar hand dynamometer, which is considered the gold standard. Disease activity was assessed with a large-scale questionnaire that included both pain and function and reflects disease exposure in detail. The use of both gray and color Doppler is one of the strengths of our study.Hypoechoic regions, cortical irregularities and enthesopathy were not evaluated to be associated with disease severity, pain and muscle strength. Neovascularity was found to be associated only with muscle strength of wrist extension. Peritendinous fluid or bursitis was found to be associated with both muscle strength of wrist flexion and extension and disease activity, but not associated with pain. Demonstrating the relationship of ultrasonographic parameters used in the evaluation of LE with pain, disease severity and muscle strength may provide an idea for the use of ultrasonographic evaluation in the effectiveness of LE diagnosis and treatments.We thank for the Radiology Department of the Fatih Sultan Mehmet Education and Research Hospital for their ultrasonographic evaluation on patients.Data curation: Emre Bal.Formal analysis: Onur Cetin.Investigation: Emre Bal.Methodology: Onur Cetin.Project administration: Emre Bal.Resources: Emre Bal.Visualization: Emre Bal.Writing – original draft: Emre Bal.Writing – review & editing: Onur Cetin.


To compare the effectiveness and safety of central venous catheter thoracic drainage (CVCTD) with traditional closed thoracic drainage (TCTD) after minimally invasive surgery for esophageal cancer.We conducted a retrospective investigation of 103 patients who underwent minimally invasive esophageal cancer surgery at our institution between January 2017 and December 2019. Among them, 44 patients underwent CVCTD, while 59 received TCTD. We compared the following outcomes between the two cohorts: drainage volume, duration of drainage, postoperative complications , length of hospital stay, and postoperative pain assessment.No significant differences were observed between the experimental and control groups regarding postoperative thoracic drainage, the timing of postoperative tube removal, or postoperative complications. However, significant disparities were noted in the duration of postoperative hospitalization, drainage tube healing time, and pain threshold among the esophageal cancer patients in both cohorts (p < 0.05).CVCTD is a secure and potent alternative to TCTD following minimally invasive surgery for esophageal carcinoma. It potentially contributes to reducing the incidence of postoperative complications while curtailing the duration of hospitalization. Additional research is warranted to substantiate these findings. Esophageal carcinoma, a dire and frequently fatal condition, calls for prompt and effective remedial measures –4. MinimThe medical fraternity specializing in minimally invasive surgery is witnessing a paradigm shift in the quest for safer alternatives to conventional closed thoracic drainage (TCTD) or even the elimination of drainage tubes. Consequently, CVCTD has been posited as a potential replacement for TCTD, and antecedent studies have corroborated the safety and viability of routine thoracic drainage via central venous catheters (CVCs) –10. NotwIn light of these considerations, this retrospective study is intended to juxtapose the outcomes of CVCTD and TCTD in patients subjected to MIS for esophageal carcinoma. To authenticate this supposition, we have contrived a single-center, randomized controlled trial to probe the influence of these two distinct drainage methodologies on the prevalence of complications, duration of hospital stays, and postoperative pain assessment succeeding an esophagectomy for esophageal carcinoma.This retrospective study included patients who underwent minimally invasive surgery for esophageal cancer at our institution between January 2017 and December 2019. The hospital’s Ethics Committee backed our inquiry (Ethics number: 2021-12).  the exisWe endeavored to employ a hybrid methodology of Randomized Retrospective Study, retrospectively reviewing past data or records pertaining to thoracic drainage via central venous catheters or traditional chest tubes following esophageal cancer surgery, and attempting random grouping. Although genuine random assignment was unachievable, we sought to simulate a randomized effect to mitigate potential bias and enhance the reliability of the research outcomes.Patient demographic data, surgical details, postoperative progression, and complications were collated from electronic medical records. Variables documented encompassed age, gender, body mass index (BMI), tumor location , pathological type, tumor staging , historyThis investigation incorporates two variants of thoracic drainage techniques: following the completion of minimally invasive surgery for esophageal cancer, patients are randomly assigned to receive either a central venous catheter thoracic drainage or a conventional closed thoracic drainage. The preference of the attending surgeon dictates the choice of drainage technique. The central venous catheter thoracic drainage is performed by introducing a central venous catheter into the pleural cavity via a small incision under ultrasound guidance. The outer extremity of the Central Venous Catheter  is attached to a drainage bag, and to prevent blockage in the lumen, the CVC is regularly cleansed with 20 milliliters of normal saline every eight hours. The conventional closed thoracic drainage  is executed by placing a chest tube into the pleural cavity through a small incision. The tube’s outer terminal was linked to a water-sealed drainage container, subject to daily replacement. , whether a catheter was reinserted post-extubation, duration of hospitalization, and pain scores. Safety was assessed via thoracic CT scans. Upon the appearance of light-yellow thoracic drainage fluid for three consecutive days, a drainage volume of fewer than 150 milliliters, and absence of gas discharge in the thoracic cavity, the central venous catheter or the conventional closed thoracic drainage tube can be removed.The Numeric Rating Scale is the most widely utilized evaluation tool globally for quantifying postoperative pain. The numeric grading method uses a scale of 0–10 to represent varying degrees of pain. Postoperative pain is evaluated using the Numeric Rating Scale (0–10): 0 signifies no pain; 1–3 denotes mild pain; 4–6 indicates moderate pain; 7–10 signifies severe pain. For mild to severe pain, oral administration of Lofenidine, Paracetamol, Hydrocodone, and Pethidine Hydrochloride is recommended.Data analysis was performed using SPSS software . Continuous variables were presented as mean ± standard deviation (SD), and categorical variables were presented as frequencies and percentages. Differences in continuous variables between the two groups were analyzed using independent-samples t-tests. Differences in categorical variables were analyzed using chi-squared tests or Fisher’s exact tests. P values < 0.05 were considered statistically significant.Blood loss-related data within the baseline statistics of the two cohorts disclosed a statistically significant divergence between the CVCTD and TCTD groups. However, no discernable disparity was observed in other data parameters Table .The findings of our investigation elucidate a notable divergence amongst cohorts concerning the duration of postoperative hospitalization and the continuum of healing subsequent to catheter extraction (P < 0.05). In contrast, no prominent disparities were discerned in other facets Table .Our research findings indicate that no significant variation exists between the two cohorts concerning postoperative complications Table .We compared postoperative Numeric Rating Scale (NRS) pain assessments between the two cohorts. Evidently from Table The postoperative employment of closed thoracic drainage tubes in esophageal cancer surgeries has been substantiated to aid in the expulsion of extraneous fluid and gas, invigorate lung lobe recruitment, and mitigate the probability of subsequent pulmonary infections. Despite this, conventional wisdom advocates for the application of broader diameter drainage tubes to augment the proficiency of drainage , 13. OurOur study builds upon previous research demonstrating the safe and effective use of CVCs in ICU patients, suggesting their potential as an alternative to traditional thoracic drainage methods . We founWhile CVCs offer numerous benefits, they are not without potential shortcomings. Various types of these catheters may have small side openings that are susceptible to blockages from fibrous bands in the pleura, compromising their effectiveness , 20. OpeTraditional teaching methods recommend large-diameter chest tubes, but smaller-diameter catheters have recently gained popularity , 28. A cAs a retrospective study, we employed a hybrid approach of a randomized retrospective investigation, reviewing past data or records and randomly grouping the study subjects. While it was not feasible to genuinely randomize the assignment, we could simulate an impression of randomization to minimize potential bias and augment the reliability of our findings. However, this approach cannot supplant the advantages of randomized trials in terms of causal inference and evidence level; the results may contain inherent biases.We carried out a renewed analysis of data related to blood loss, revealing a statistically significant disparity between the CVCTD and TCTD cohorts. This discovery implies that surgeons may exhibit a propensity for the utilization of conventional thoracic drainage, particularly during procedures that incur substantial blood loss. Undeniably, inherent limitations are inextricable from a retrospective study. As such, we have endeavored to implement a hybrid approach of randomized retrospective investigation. However, genuinely random allocation remains elusive, which is an inherent shortfall that will be compensated for by prospective randomized controlled trials in future research. Furthermore, the lack of long-term follow-up impedes the evaluation of the sustained benefits of this novel technique for patients. Hence, future studies necessitate larger sample sizes and extended follow-up periods to further substantiate the efficacy and safety of central venous catheter (CVC) technology. Additionally, few clinical studies compare the effectiveness of CVC and traditional chest tubes in esophageal surgeries, which restricts our understanding of their performance in varied circumstances. Therefore, rigorous and extensive clinical trials are required to explore their comparative effectiveness.In conclusion, our study highlights the merits of using CVCs for thoracic drainage in esophageal cancer surgeries, including their ability to alleviate pain, promote patient mobility, and offer comparable efficacy to traditional chest tubes. Despite potential drawbacks and complications, such as catheter blockages and operative complications, the use of CVCs provides advantages over conventional drainage methods. Selecting the optimal chest tube size should consider the specific clinical scenario, with smaller caliber catheters proving effective in our study. However, further research with larger-scale studies and longer follow-up periods is needed to validate the findings and establish the safety and effectiveness of CVC technology.


Controlling postoperative pain is essential for the greatest recovery following major abdominal surgery. Thoracic epidural analgesia (TEA) has traditionally been considered the preferred method of providing pain relief after major abdominal surgeries. Thoracic epidural analgesia has a wide range of complications, including residual motor blockade, hypotension, urine retention with the need for urinary catheterisation, tethering to infusion pumps, and occasional failure rates. In recent years, rectus sheath catheter (RSC) analgesia has been gaining popularity.The purpose of this review is to compare the effectiveness of TEA and RSC in reducing pain following major abdominal surgeries. Four randomised controlled trials (RCTs) reporting outcomes of the visual analogue scale (VAS) pain score were included according to the set criteria. A total of 351 patients undergoing major abdominal surgery were included in this meta-analysis. There were 176 patients in the TEA group and 175 patients in the RSC group. In the random effect model analysis, there was no significant difference in VAS pain score in 24 hours at rest (standardised mean difference (SMD) -0.46; 95% CI -1.21 to 0.29; z=1.20, P=0.23) and movement  between TEA and RSC. Similarly, there was no significant difference in pain score after 48 hours at rest  or movement .In conclusion, our findings show that there was no significant difference in pain score between TEA and RSC following major abdominal surgery, and we suggest that both approaches can be used effectively according to the choice and expertise available. Pain relief is a basic human right, as per the World Health Organization and the International Association for the Study of Pain . For decThere is a wide range of documented complications that can be due to suboptimal pain management, such as increased morbidity, impaired physical function, reduced quality of life, and slowed recovery . Pain haExcessive use of systemic opioid analgesia is associated with a high rate of side effects postoperatively, such as unwanted sedation, compromised respiratory function, pseudo-obstruction or ileus, postoperative nausea and/or vomiting, constipation, urine retention, and, in some cases, itching. Through the use of multimodal analgesics, we can reduce the risk of these effects on our patients . CurrentRectus sheath catheters (RSC) act on structures superficial to the peritoneum and provide pain relief for anterior abdominal wall structures; they are therefore used in procedures requiring a midline incision .Considering this, the aim of this study is to compare the effectiveness of TEA and RSCs in terms of pain relief following major abdominal surgeries.This article was previously presented as a talking poster at the 2023 Association of Surgeons of Great Britain and Ireland (ASGBI) International Surgical Congress on May 18, 2023.MethodsStudy DesignThis is a systematic review and meta-analysis of comparative studies. This research project, including the scientific writing and submission, is in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Cochrane Handbook for Systematic Reviews of Interventions , 14.Data Sources and Search PlanThe following electronic databases were searched for randomised controlled trials for this meta-analysis: PubMed, Cochrane Library, Medical Literature Analysis and Retrieval System Online (MEDLINE), and Excerpta Medica database (EMBASE). We utilised Medical Subject Headings (MeSH) search terms to gather purposeful information on randomised controlled trials. The search was broad and conclusive, including multiple aspects, e.g., gender, language, study place of origin, and sample size. We used Boolean operators  to further widen our results. Articles that were found were studied in depth and assessed against the inclusion criteria. References were also explored as a tool in the selection of suitable trials.Inclusion CriteriaPapers were required to meet several inclusion criteria to be included in the meta-analysis. Firstly, the study must include a comparison between RCS and TEA following laparotomy surgery. Secondly, the study had to report outcomes of the visual analogue scale (VAS) pain score during rest and mobility states at 24 and 48 hours. Lastly, the papers had to be a randomised controlled trial. No restrictions were made for language, study location, or date of publication.Data ExtractionUsing a pre-established meta-analysis data form, two independent reviewers collaborated to extract pertinent data and reach an agreement. The extracted information on the forms was matched, which resulted in a high and satisfactory inter-reviewer agreement. Data were recorded, including the first author's name, year and country of publication, title of the published study, testing sample size (with gender differentiation if applicable), and the number of patients in each group based on who had TEA or rectus sheath analgesia after midline laparotomy regarding postoperative VAS pain score in 24 and 48 hours. Subsequently, the two reviewers looked at the results, and if any discrepancies were present, the resolution would be through mutual agreement.Evidence SynthesisWe used the RevMan 5.3 software package  for statistical analysis . For thePrimary EndpointPostoperative pain scores at rest and on movement were analysed after 24 hours as the primary endpoint in this study.Secondary EndpointPostoperative pain scores at rest and on movement were analysed after 48 hours of the laparotomy as the secondary endpoint.ResultsOur primary search retrieved 22 articles. Seven studies were duplicates, five were found to be irrelevant, three were non-comparative, and three were other reviews. By exclusion, only the four remaining studies were eligible to be included in this review Figure .Characteristics of Studies and PatientsFour RCTs on 351 patients were included in this meta-analysis -27. Two Methodological Quality of Included StudiesThe methodological quality of the included trials was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) tool . A summaThe Mantel-Haenszel random effects model was used to compute robustness and susceptibility to any outlier among these trials. The randomization technique was conducted via computerised systems in all trials. Blinding and concealment via sealed envelopes were reported in two trials , 27. WhiPrimary OutcomesIn the random effect model analysis, there was no significant difference in VAS pain score after 24 hours at rest   (Figure DiscussionThis systematic review of four RCTs on 351 patients undergoing open major abdominal surgery has shown that there is no significant difference in VAS pain score between TEA and RSC after 24 hours and 48 hours at both rest and during movement. There is no significant statistical difference between the two groups' pain scores in the random effect model analysis. However, significant heterogeneity was noted, meaning that the included studies are inconsistent due to a reason other than chance.The present meta-analysis's findings align with those of the previously published meta-analyses on this subject . Due to This study has several limitations. First, it consists of only four RCTs on 351 patients, which is considered a small number of patients. Moreover, other parameters, such as the need for additional analgesia and the effect on the functional status of the patient's shoulder, must be considered in order to properly assess the effectiveness of any analgesic technique. Furthermore, the safety of these treatment modalities and associated complications should be considered when comparing modes of analgesia. However, this was not possible in this review due to the limited volume of published data. Lastly, there was significant heterogeneity noted amongst the included studies, which can be a potential source of bias.Our study concludes that there is no significant difference between TEA and RSC use for pain relief following major abdominal surgeries. This was evident by nearly similar VAS pain scores at 24 hours and 48 hours during both rest and mobility states. We surmise that, according to the literature, both approaches can be effectively utilised as long as the expertise is available.Due to the limitations of this study, the safety of both methods was not explored. A multicentre RCT with a large study population comparing all elements of a successful mode of analgesia is suggested to determine which mode of analgesia is safer and more effective for postoperative pain relief in major abdominal surgery patients.


Background: The cognitive distraction caused by Virtual Reality (VR) seems to cause a decrease both in pain and its perception as in the time spent thinking about possible pain, among anxiety about hysteroscopy procedure. The main objective of this investigation was to evaluate the efficacy of virtual reality for pain relief during outpatient hysteroscopy. Method: A total of 83 patients underwent outpatient diagnostic hysteroscopy in a single-centre, open-label, randomized control trial. Overall, 180 women with medical indication for an outpatient diagnostic hysteroscopy were randomized. Ten were excluded due to the impossibility of entering the endometrial cavity caused by a cervical canal that was not permeable, and 15 did not tolerate the pain at the beginning and during the procedure, excluding themselves from the final model. Finally, 154 were analysed per protocol to use VR  or standard treatment  assessing the differences between both groups by reduction in pain using Visual Analogue Scale score (VAS: 0–10 cm) and clinical data  at the end of hysteroscopy, at 15 and 30 min after hysteroscopy. Results: Women with VR outpatient diagnostic hysteroscopy experienced less pain at final  −1.521, 95% CI −2.601 to −0.440; p = 0.006), at 15 min , and at 30 min  after the ending of the hysteroscopy, compared with no VR. Conclusions: The use of VR during outpatient diagnostic hysteroscopy proved effective in the reduction of pain in this randomized control trial. It shows wide potential role in ambulatory gynaecologic procedures to avoid repeating tests, perform surgeries without anaesthesia, and the use of medication and its side effects. The appearance of hsysteroscopes with smaller calibres allows for a minimally invasive approach and can be performed on an ambulatory basis  as a safMultiple treatments have been used to try to alleviate the pain, objectifying that the use of analgesia  along with an adequate prior cervix preparation does not provide a consistent adequate quality evidence on the safety nor the effectiveness of any treatment in this group of patients, with the current recommendation being not to use analgesics or the prior cervix preparation in a routinely approach ahead of the procedure, as they can cause side effects such as bleeding, blood clots in the legs or pelvis, infections, and uterine perforation, without reducing pain during the hysteroscopy ,6,7. OutVirtual reality (VR), a relatively new intervention, has been studied as a distraction technique for nonpharmacological pain relief . Put sim2, paracervical nerve blocks, TENS  presents at least the same results as the best ones regarding the reduction in pain perception [Findings in a randomised controlled trial in paediatric cancer patients undergoing peripheral intravenous cannulation procedure indicate that VR is safe and effective to alleviate pain and anxiety in this population . Most ofrception ,21 with rception . It is trception .Therefore, the aim of this study was to assess whether patients with a medical indication for outpatient diagnostic hysteroscopy benefit from the use of VR to decrease the pain perception compared to current clinical practice standard treatment of non-use analgesia.ClinicalTrials.gov (accessed on 24 January 2019) (NCT03827824) prior to enrolment. Between March 2019 and October 2019, consecutive women with an indication for outpatient diagnostic hysteroscopy according to the criteria of the Sociedad Española de Ginecología y Obstetricia  were invited to participate in the trial. Only data on pain perception among patients with VR and standard treatment are presented in the manuscript, with a deviation of the study protocol in which data on anxiety and pain perception are presented.This is a single-centre, open label, randomized controlled trial. The protocol was approved by the Clinical Research Ethics Committee, Puerta de Hierro University Hospital, Madrid  and conducted in El Escorial University Hospital, Madrid, Spain. It was registered with All patients agreed to participate in the study and signed a written informed consent. Women were randomly allocated after baseline data collection in a parallel-group (1:1 ratio) to either a VR (study group) or standard treatment (control group). Participants were randomized on an Excel-generated randomization schedule, without block randomisation. The research coordinators regularly performed data quality control, management, and protocol compliance verification. Due to the nature of the intervention, blinding of participants, care providers, and outcome assessors was not possible.Inclusion criteria were: (i) those established by SEGO  to perfoThe study methods have been reported in accordance with the CONSORT statement .The patients were selected by different physicians from the gynaecology’s office, where they were requested an appointment for an outpatient diagnostic hysteroscopy following the criteria of the SEGO and priority established by Madrid Region, oncological priority, preferential, and non-priority. The administrative staff of the Hospital Admission Service provided them with a day and a serial number for their appointment. On the day, the signed consents were collected and any possible doubts were answered by the gynaecologist who would perform the procedure. At that time and based on their appointment order generated by admission, the patients were included in the different groups—the study group or the control group—according to the appointment order and the corresponding number obtained using the stipulated randomisation computer program.All the hysteroscopies were performed by the same gynaecologists, in the same room, and with the same equipment .All procedures were performed with a rigid 5 mm diagnostic hysteroscope, Bettocchi model. All surgical instruments that were used when necessary were semi-rigid, 5 Charr., with a length of 34 cm. The vaginoscopy approach was used to access the endometrial cavity ,28. DistPatients included in the intervention group were placed with the VR glasses, Samsung’s Oculus GO model. This model is equipped with spatial sound drivers built into the viewfinder, so no external headphones are required or used.The chosen distraction was a free demo called “A Night Sky, where the patient is invited to relax on the edge of a peaceful vale, beside a crackling campfire, and beneath the open night sky—connecting constellations to form patterns among the stars using a device “go controller” in the dominant hand as a “laser pointer”. As the different shapes are revealed, wonderful creatures are brought to life”.A similar procedure was carried out with the standard treatment patients in the control group.The primary outcome was the pain score during the hysteroscopy, repeated 15 min and 30 min after the end of the procedure measured on a Visual Analogue Scale (VAS: 0–10 cm) . Secondat-test for quantitative variables. Between group differences were reported with 95% confidence intervals (95% CI) and p-value . Assuming a power of 80% to detect difference in pain scores between groups with two-tailed at 95% CI, the standardized mean difference (SMD) was used for measuring the pain-effect. Cohen’s d, the difference in scores measured on a standard deviation scale, was used to determine the effect size, with values above 0.7 considered to be large [® software .Continuous data were summarised as mean and standard deviation, and categorical data as counts and percentages. Demographic data were compared using the chi-square test for qualitative variables and be large . We usedFrom March to October 2019, 352 women with an indication for outpatient diagnostic hysteroscopy according to the criteria of SEGO were selected from the El Escorial University Hospital gynaecologist’s office. A total of 312 women were interested to participate. Out of this number, 52 had a contraceptive treatment and 80 did not meet the eligibility criteria. A total of 180 women were finally randomised into 2 groups: 88 in the study group and 92 in the control group. Ten were excluded due to the impossibility of entering the endometrial cavity caused by a cervical canal that was not permeable, which included five in the study group and five in the control group. Fifteen women in the control group and one in the study group did not tolerate the pain at the beginning and during the procedure and were cited for surgical hysteroscopy under anaesthesia, excluding themselves from the final model. Finally, 154 women were analysed PP: 82 in study group and 72 in control group .Baseline characteristics were similar in both groups regarding age, reproductive stage, parity, smoking habit, previous surgery on the cervix, biopsy sampling, performing polypectomy, or myomectomy during the hysteroscopy .Only 10 women in the study have had previous surgeries on the cervix, 23 were nulliparous, and 61 were experiencing menopause .The suspension rate due to pain during hysteroscopy was 6.9% in the control group versus 6.1% in the study group.The procedure time was 6.67 min (±0.52 min) in the study group and 7.95 min (±1.01 min) in the control group. The time for VR goggles placement and resolution of the patients’ doubts was 10.94 min (±0.95 min) in the study group and 10.34 min (±1.42 min) in the control group.p = 0.006), at 15 min (p = 0.004) and 30 min after surgery (p = 0.044) compared to the standard treatment  on VAS. There was also a significant effect of time . However, time x group interaction was not significant .There was a significant effect of group , SatO2 (p = 0.797), and blood pressure (p = 0.558). During procedure; heart rate (p = 0.237), SatO2 (p = 0.732), and blood pressure (p = 0.584) and at the end of hysteroscopy; heart rate (p = 0.802), SatO2 (p = 0.633), and blood pressure (p = 0.293)  .Four cases of vagal reaction have been described in our study (2.6%), specifically dizziness during the hysteroscopy, of which there were three in the control group (3.6%) (two women underwent biopsy) and one in the study group (1.4%) (a biopsy was performed). No woman in the study required any treatment except for posture changes.2, but with a greater in the virtual reality group compared to the control group. Among the registered side effects, four minor reflex syncope stand out, of which there were three in the control group versus one in the virtual reality group.In this randomised controlled trial, we have been able to observe that the virtual reality pain management intervention had a large effect in reducing the pain in outpatient diagnostic hysteroscopy at the end of the procedure, at 15 and 30 min after surgery, and similar values were shown in both groups regarding blood measurements and SatOCompared to standard treatment, the virtual reality pain management intervention had a large effect in reducing pain in outpatient diagnostic hysteroscopy. This effect was robust, even after controlling for baseline pain expectations and a range of patient covariates. Staff and the majority of patients found the procedure to be both feasible and acceptable and patients reported a range of experiences, suggestive of the mechanisms by which VR technology may influence pain via immersion, relaxation, distraction, and imagery. The study additionally demonstrated the willingness of patients to participate. Insights generated from the themes suggested offering a multimodal pain relief strategy to improve the experience at outpatient hysteroscopy. Quantitative analysis suggested patient profiling based on history, taking into consideration patient preferences by offering a variety of distraction techniques with a range of videos to choose from if they were to choose virtual reality as a distraction technique.The analysis offered key insights into patient expectations concerning the degree of pain relief that is possible with virtual reality technology and implementation strategies to facilitate around the transfer of research finding in a clinical setting. To avoid bias, the same diversion, A Night Sky, which is a free version included in the Oculus Go catalogue, was used on all patients. The authors believe that by using a VR option that could be chosen according to the patient’s taste, with greater immersion possibilities, the results presented in this trial would be even more significant. Subsequent works should look at the type of VR technology and anxiety perception, the context where it is deployed and for what kind of procedure. The optimal VR program may vary according to patient characteristics, the invasiveness of the intervention, and its duration. VR technology should be tested in more painful gynaecological interventions such as endometrial ablation, cervical biopsy, and transvaginal egg collection. Moreover, the prospective benefit of VR does not need to be restricted to gynaecological practice but should be evaluated in a whole host of ambulatory procedures involving conscious patients .Side effects have been described during hysteroscopy performed by a gynaecologist , which aDuring hysteroscopy, a moderate to severe pain level has been reported, which is defined as a score of 4 or higher on a VAS scale of 10 cm . The rolThe greatest strength of our study resides in being a randomised controlled study, where the selection of the subjects was made from the doctor’s office by different gynaecologists not associated with the office of hysteroscopy by the SEGO criteria and the inclusion in the different study groups was made by a program using an agenda created by an Administrative Assistant from outside the Gynaecology Department, avoiding selection bias. The good results due to the application of VR are very promising and since the hardware used is financially accessible, it is possible to scale the solution for many hospitals (including public ones). This study presents VR as a potential role in outpatient gynaecological procedures in need of further evaluation. The use of VR also represents not only savings for the health system by avoiding repeat tests, surgeries without anaesthesia, the use of drugs, but also and above all, for the women by not needing to repeat tests, reducing the risks of anaesthesia and surgeries, the use of drugs and their side effects, stress, as well as loss of work or leisure hours. VR technology should be tested in more painful gynaecological interventions such as endometrial ablation cervical biopsy and transvaginal egg collection.This study presents several limitations; first, this research did not present anxiety during hysteroscopy, a result that will be addressed in future studies to complete the evidence presented in this research; and second, other avenues would be interesting, including the use of VR in patient education to familiarise patients with the procedure and use as a triage before offering it as a pain relief intervention.The use of virtual reality diversions is a well-tolerated option that decreases pain perception after outpatient diagnostic hysteroscopy in women compared to standard treatment, without side effects and with less suspension rate due to pain, reducing the need for other surgical tests with anaesthesia that would increase the risk rate for these women by proposing to use a pain killer after a hysteroscopy.


Disability caused by hip osteoarthritis has increased due to population aging, obesity, and lifestyle behaviors. Joint failure after conservative therapies results in total hip replacement, which is considered to be one of the most successful interventions. However, some patients experience long-term postoperative pain. Presently, there are no reliable clinical biomarkers for the prognosis of postoperative pain prior to surgery. Molecular biomarkers can be considered as intrinsic indicators of pathological processes and as links between clinical status and disease pathology, while recent innovative and sensitive approaches such as RT-PCR have extended the prognostic value of clinical traits. In light of this, we examined the importance of cathepsin S and proinflammatory cytokine gene expression in peripheral blood in addition to the clinical traits of patients with end-stage hip osteoarthritis (HOA) to predict postoperative pain development prior to surgery. This study included 31 patients with radiographic Kellgren and Lawrence grade III–IV HOA who underwent total hip arthroplasty (THA) and 26 healthy volunteers. Before surgery, a visual analog scale (VAS), DN4, PainDETECT, and the Western Ontario and McMaster Universities osteoarthritis index scores were used for pain and function assessment. Three and six months post-surgery, VAS pain scores of 30 mm and higher were reported. The intracellular protein levels of cathepsin S were measured using ELISA. The expression of the cathepsin S, tumor necrosis factor α, interleukin-1β, and cyclooxygenase-2 genes in peripheral blood mononuclear cells (PBMCs) was assessed using quantitative real-time RT-PCR. Pain persisted in 12 (38.7%) patients after THA. Patients who developed postoperative pain demonstrated significantly higher cathepsin S gene expression in the PBMCs and higher rates of neuropathic pain based on the DN4 testing compared to the other HOA subjects that were examined. No significant differences in proinflammatory cytokine gene expression were noted in either patient cohort prior to THA. The development of postoperative pain in patients with hip osteoarthritis might be associated with disturbances in pain perception, while increased expression of cathepsin S in the peripheral blood prior to surgery may serve as its prognostic biomarker and could be used in clinical settings to improve medical service for patients with end-stage hip OA. Osteoarthritis of the hip joint (HOA) is a major source of pain, disability, and socioeconomic expenditures worldwide . Total h2+ release and induces inflammation . A receiver operating characteristic (ROC) curve analysis included calculating the area under the curve (AUC) and the 95% confidence interval (CI). The diagnostic efficacy of the gene expression values was assessed using the sensitivity and specificity at the cut-off point. To compare percentages, a two-tailed Z-test for percentages was applied. Statistica for Windows and Statistical Package for the Social Sciences (SPSS) version 19 software  were used for all the statistical analyses. n = 31) was 61.3 ± 14.3 years (range: 46–79 years), whereas the average duration of the disease was 8.0 years (range: 2–50 years). These patients demonstrated K and L HOA grades of III to IV  and increased body mass index (BMI) values . The total WOMAC scores fluctuated from 670 to 2450 (average: 1385), whereas the average total pain, total physical function, and total stiffness scores were 241.2 (range: 120–380), 873 (range: 440–1300), and 91.5 (range: 60–130), respectively.The average age of the examined patients with end-stage HOA (All patients had suffered from permanent hip pain during the previous six months. The pain scoring according to the VAS demonstrated severe pain rates of 72.5 (range: 60–90) during movement and mild pain of 29 (range: 0–70) at rest in these patients with HOA. According to the Brief Pain Inventory (BPI) questionnaire, the average pain severity at that moment was 4.5 (range: 0–8) in the examined cohort. However, in the past 24 h, the worst average pain was self-assessed as a severe score of 7.0 (range: 0–9), while the lowest level of pain was reported as a mild score of 3.0 (range: 0–7). In addition, hip pain moderately interfered with walking and working abilities . A neuropathic pain evaluation using the DN4 questionnaire revealed an average score of 1.16 (range: 0–2). The average score according to the PainDETECT questionnaire was 3.9 (range: 0–22), indicating one patient with neuropathic pain (score > 18). According to the Hospital Anxiety and Depression Scale (HADS), abnormal anxiety (score >11) was not observed, while 3 (10%) patients out of 31 exhibited borderline levels (scores of 8–10). In addition, 3 (10%) of 31 patients were depressed because they showed total scores of 11–13, whereas 14 (45%) of 31 patients had borderline values (scores of 8–10), according to the HADS depression scale.n = 19). A comparative analysis of the baseline clinical parameters in both subgroups demonstrated significant differences in the values of several indices (p = 0.056) and higher WOMAC (p = 0.06) and HADS anxiety (p = 0.07) scores. Twelve patients with end-stage HOA developed POP 3 (mean VAS: 37.2 ± 9.0 mm) and 6 (mean VAS: 39.1 ± 8.3 mm) months post-surgery, while the others did not develop POP ( indices . For exa2), and no comorbidities. The average age of the healthy control subjects was 62.8 ± 7.3 years (range: 42–74 years). The control group consisted of 11 females and 15 males. They had normal erythrocyte sedimentation rates (2–30 mm/h), healthy BMI values (18.5–24.99 kg/mp = 0.02) compared to painless patients, whereas there were no intergroup differences in the expression of the IL1β, TNFα, and COX2 genes at baseline (n = 12) and painless subjects (n = 19) compared to healthy individuals, are presented in Before surgery, the expression of the cathepsin S, IL1β, TNFα, and COX2 genes was significantly higher in all examined patients with end-stage HOA compared to the healthy controls. However, the patients who developed POP showed significantly higher expression of the cathepsin S gene (baseline . The rawp = 0.01) cathepsin S amounts compared to the pain-free subjects  positive correlations with the PainDETECT score . IL1β gene expression was significantly positively correlated with the WOMAC pain score (r = 0.560). The expression of the cathepsin S gene was significantly (p < 0.05) positively correlated with the expression of the IL1β (r = 0.638) and COX2 (r = 0.433) genes. A Spearman rank correlation analysis of cathepsin S gene and protein expression also revealed a significant positive correlation (r = 0.637). In addition, we observed a tendency (p = 0.07) towards a positive correlation between IL-1β and COX2 gene expression (r = 0.323). Another non-significant negative correlation (p = 0.07) was noted between IL-1β gene expression and the HADS depression score (r = −0.325). We also performed a Spearman rank correlation test on the gene expression values of cathepsin S and IL-1β and found significant (p = 0.02).To assess the prognostic value of cathepsin S gene expression, we performed an ROC curve analysis , which cThe identification of predictors of pain, as a part of an international initiative promoted by multiple organizations including the WHO , might hIn contrast, the gene expression of the proinflammatory cytokines TNFα, IL-1β, and COX2 demonstrated no significant differences between the examined patient cohorts. This observation demonstrates the differences in the prognostic validity of POP molecular biomarkers in patients with HOA and end-stage KOA subjects. The latter revealed significantly higher expression of IL1β and TNFα genes in individuals who developed POP compared to pain-free patients before surgery . Our datHowever, we did not observe any association between the level of preoperative pain and the development of pain after surgery, in contrast to previous studies on HOA that observed a link between the long-term use of opioids for pain relief before surgery and POP development . On the In addition, we observed significantly higher levels of neuropathic pain, according to the DN4 questionnaire, and a trend towards increased anxiety, according to HADS testing, before surgery in patients with HOA who developed POP, supporting previous findings on positive correlations between anxiety, pain, and joint dysfunction . In addiOur study has several limitations. We present only very limited data on the healthy subjects that were used as study controls. The fact that we performed an ELISA assay using cell lysates rather than secreted cathepsin S protein can be considered to be another limitation of our study. However, an intracellular cathepsin S protein assessment was only required for the confirmation of our cathepsin S gene expression evaluation, which we found to be a prognostic biomarker of postoperative pain in end-stage patients with HOA prior to surgery. Finally, we used a visual analog scale (VAS) rather than a numerical rating scale (NRS), which some authors consider more reliable ,51, althIn summary, our preliminary study demonstrated that high baseline gene expression of cathepsin S measured in the peripheral blood of patients with end-stage hip OA prior to arthroplasty may serve as an important biomarker for the development of postoperative pain. The importance of clinical assessments of the WOMAC score, BMI, and the psychological traits that were previously noted in association with postoperative pain after THA was also confirmed. Further studies involving large cohorts of patients are required to verify our findings on the importance of preoperative molecular and clinical assessments for the prognosis of postoperative pain development. These data will contribute to a significant improvement in the management of patients with end-stage hip OA who are recommended to undertake total hip arthroplasty.