These effects were not modified by treatment arm and were no longer significant at 6 months. Following induction therapy, the rs13361160 SNP near the CCT5 and FAM173B genes was associated with higher global health (p = 0.027) and physical functioning (p = 0.013). This exploratory study supports associations between subjective parameters in MM with SNPs previously identified in genome-wide association studies of pain. Conversely, SNPs in candidate genes involved in opioid and transporter pathways showed no effect. Further studies are warranted in well-defined cancer populations, and potentially assisted by whole genome sequencing with germline analysis in routine diagnostics in haematological cancers.The Myeloma X trial provided a platform to explore genetics in relation to systematic assessment of patient-reported outcomes at key points during salvage treatment in multiple myeloma (MM) patients. Blood DNA was obtained in 191 subjects for single nucleotide polymorphism (SNP) genotyping. By univariable analysis, the non-coding rs2562456 SNP, upstream of LINC00664, was associated with several relevant pain and health-related quality-of-life (HRQoL) scores at 100 days after allocation to consolidation with autologous stem cell transplantation or weekly cyclophosphamide. Presence of the minor (C) allele was associated with lower pain interference ( Multiple myeloma (MM) forms ~10% of haematological cancers and is largely incurable. However, therapeutic advances in the last two decades have led to major extension of survival. With improving survival, MM is being experienced by an increasing proportion of patients as a chronic illness, and therefore supportive and symptomatic care is a cornerstone of disease management, particularly in relation to pain control. There is a significant symptom burden at all stages of disease, including pain, fatigue and other elements which impact directly on health-related quality of life (HRQoL) .Pain in myeloma arises not only from infiltration of the bone marrow by malignant plasma cells, bone osteolysis and fracture, but also from side effects of treatments, particularly chemotherapy-induced peripheral neuropathy, and may continue to be significant in patients with stable disease who are off active treatment . In animExamples of genetic factors contributing to pain experience include the three main opioid receptors  whose genes contain inherited variants that occur relatively frequently in human populations –14. SuchGenome-wide association studies (GWAS) carried out to date have not included cancer-related pain, but GWAS of post-surgical and chronic widespread pain have generated some potentially relevant candidate gene regions , 23. PreThe UK National Cancer Research Institute Myeloma X trial was a phase III randomised controlled trial which recruited relapsed myeloma patients from 2008 to 2012. Its aims were to determine the role of a second or ‘salvage’ autologous stem cell transplant (sASCT) as a novel consolidation therapy in patients at first relapse following prior high-dose chemotherapy and ASCT. Myeloma X provided definitive evidence of the efficacy of a sASCT in terms of significantly improved time to progression, progression-free survival and overall survival, compared to conventional non-transplant consolidation (NTC) , 25. A sMyeloma X provided the only comprehensive picture of HRQoL before and after sASCT in patients with relapsed MM and highlighted the need to improve symptom management in the peri-transplant period . The triCollection of pain and HRQoL data was intrinsic to the Myeloma X trial and consent for the use of translational research samples in additional genetic studies was incorporated to cover this and other studies associated with the trial . The Myeloma X trial is registered with ClinicalTrials.gov, number NCT00747877 and European Clinical Trials Database, number 2006–005890–24.n = 89; 88 consenting to QoL studies) or NTC ). Baseline demographic and disease characteristics were well balanced between the treatment groups, except for a higher proportion of patients with International Staging System III in the transplant group.Details of the Myeloma X trial population are summarised in previous publications –26. BetwA secondary aim of Myeloma X was to determine the impact of the treatment strategies on pain and HRQoL . These wBlood DNA was available for 191 subjects for genotyping. Table SNPs were selected in candidate genes relating to pain pathways  and genes relating to drug absorption and metabolism , based on previous reports of association with pain and QoL in the literature, including two SNPs identified in GWAS of pain in non-cancer populations . The selected SNPs and corresponding assays used are listed in Table Genotyping was carried out for each consenting patient registered in Myeloma X and with blood DNA available using the Applied Biosystems Taqman platform (Thermo Fisher Scientific). The assay for rs9479757 gave poor allelic discrimination and these data were not included, but call rates for all other SNPs were >98%. Nineteen (~10%) of samples were duplicated on the assay plates for all SNPs, and there was 1 discrepancy in genotype calls amongst the duplicates (<0.1%).We hypothesised that inherited genetic variants of relevant pain receptor pathways previously reported to be associated with pain and quality of life outcomes are associated with BPI pain scores and HRQoL in patients with relapsed MM. To test this hypothesis, pain   and HRQop value threshold to help identify effects of interest would be 0.05/8 = 0.006. All p values are two-sided and are shown unadjusted.Exploratory univariable linear regression with SNP genotype as explanatory variable was carried out for eight SNPs and eight pain and quality of life variables at four time points; study registration, end PAD, 100 days post-randomisation and 6 months post randomisation. SNP genotypes were coded as 0, 1, 2 for common homozygous, heterozygous and rare homozygous genotypes respectively. Multivariable regression was carried out to control for treatment arm, with NTC as the reference group. Statistical analyses were carried out in Stata Version 12 and all statistical tests were two-sided. The eight SNPs represent independent tests, but many of the outcome variables are correlated with one another. A guideline Bonferroni-adjusted p = 0.014) and HRQoL pain score (p = 0.003), and higher HRQoL global health status (p = 0.011) and physical functioning scores (p = 0.007). The graphs in Fig. A summary of the age and gender distributions of consenting patients with SNP genotype and BPI Pain/HRQoL scores available is shown in Table We reported previously that global health status scores were better in the NTC group at 100 days post-randomisation . We, thep values across more than one pain or HRQoL score. Following induction therapy, the minor C allele of the rs13361160 SNP near the CCT5 and FAM173B genes was associated with higher global health (p = 0.027) and physical functioning scores (p = 0.013) at this time point  included the association of rs1799971 in OPRM1 with BPI Least Pain score and rs2562456 upstream of LINC00664 with HRQoL fatigue score, after induction therapy, and rs2035282 in ABCB1 with BPI Average Pain, and rs8065080 in TRPV1 with Pain Interference score, at registration (Supplementary Table We also identified some less significant SNP effects with individual pain and HRQoL scores at other time points (highlighted in Supplementary Table h p = 0.07 and phyThe Myeloma X trial provided us a unique opportunity to study pain and HRQoL in a well-defined relatively homogenous cancer population all receiving a set of acute standardised anti-cancer interventions. A key difference between our study and previous ones in cancer and many other long-term conditions is that we have focused on a relatively earlier stage of disease and in the context of a well-defined clinical scenario, namely myeloma in first relapse undergoing consolidation treatment with sASCT or weekly cyclophosphamide.Our exploratory study has provided evidence to support a role for some candidate SNPs identified in previous GWAS for pain, but, interestingly, we found only very minimal support for SNPs in candidate pain pathways such as opioid receptors. Because we also studied a range of HRQoL endpoints, we were able to identify gene associations beyond the pain outcomes that are normally reported.Our previous results from the Myeloma X trial showed that at 100 days after randomisation global health scores were better in the NTC arm compared to the sASCT arm . InteresCCT5 and FAM173B genes has previously been shown to be important in GWAS study of patients who had chronic widespread pain. We have now also identified this as being potentially relevant in MM patients, although it was associated not with pain scores, but rather with higher global health and physical functioning scores.A SNP in rs13361160 SNP near the The results for both SNPs need to be interpreted with caution due to the large number of comparisons carried out in this exploratory study, and further research specifically in myeloma cohorts is required, in order to validate the present findings. The potential mechanisms of action are not clear, as non-coding SNPs may act by altering the expression of genes that are distant from the SNP in the genome. Thus, if the findings are validated, the next steps will be to identify the target genes through functional genomics, and to tease out the precise genetic models and biological mechanisms.In contrast to the above results for two SNPs identified through GWAS, many of the positive gene associations with pain that have previously been reported in cancer patients were negative in this study. This may result from a lack of statistical power in the present study, as others have been larger. Alternatively, it may reflect the much more defined population and very specific treatments in the present study, compared to previous studies which have been in more heterogeneous settings. The Myeloma X trial did not standardise the opioid regimens for pain management which could explain why we failed to identify associations between pain outcomes and specific opioid receptor pathways. However, it should be noted that previously published studies exploring genetic influences on pain have mostly used heterogeneous samples of non-cancer populations, and in cancer, mixed primary sites and patients at different stages of disease and on differing anti-cancer or analgesic treatments . Not surThis study is subject to several limitations including an open-label design where lack of blinding may have relevance in relation to subjectively reported endpoints, using paper-based questionnaires subject to adherence, especially when patients are experiencing periods of increased illness and attrition rates as a possible source of bias. The sample size for this study was not specified a priori, and therefore results should be interpreted with caution. We have previously reported that randomisation to sASCT led to a significantly worse short-term HRQoL and pain outcomes compared to standard treatment; in addition, those patients who reported more acute treatment-related side effects experienced different HRQoL outcomes . It is pIn conclusion, although exploratory, with uncertain generalisability and reproducibility at present, our study paves the way for further research of HRQoL, pain and other symptomatology both in MM and potentially other cancers associated with pain. The ultimate benefit of this and subsequent research will be to identify patients who are more at risk of developing pain and other symptoms, or who are more likely to have variant responses to conventional medical analgesic interventions, in order to improve the patient experience as well as enhance survival. Further exploration is warranted to increase our understanding and provide therapeutic benefits in personalised care, both in myeloma-specific and in broader cancer settings. This may be assisted by whole genome sequencing with germline analysis in routine diagnostics in haematological and other cancers.Supplementary table 1. Complete regression results organised by time point and by SNP with the results mentioned in the text highlighted.


To evaluate the efficacy for symptomatic knee and hip osteoarthritis (OA) patients of a mindfulness-based stress reduction (MBSR) program versus usual care.Randomized, physician-blind, clinical trial in a monocentric prospective pilot study. Adult participants with symptomatic knee or hip OA were randomized into either intervention or control groups. The intervention group completed the MBSR program for a two-and-a-half-hour weekly session for 8 weeks. Usual care management was similar in both groups. All patients were evaluated at baseline, 3 months and 6 months. The primary objective was to evaluate the change in WOMAC pain score between baseline and 3 months in the MBSR group compared to usual care group. Secondary objectives were to evaluate changes in pain VAS, WOMAC scores, quality of life (SF-36), HAD scores between baseline and 3/6 months.p = 0.03) has been reached.Forty patients were enrolled in the study. No differences in the WOMAC pain score between the two groups were observed in the different time points. A similar pattern was found for the other assessment outcomes. However, a significant pain VAS reduction in favor of the MBSR group between baseline and 6 months .The online version contains supplementary material available at 10.1186/s41927-022-00277-9. Osteoarthritis (OA) is the most common and endemic rheumatism in the world, resulting in pain and deformation which can lead to loss of function. OA is the first cause of disability in the elderly, characterized by a major socio-economic cost , 2. The Actually, OA patients are known to suffering of chronic nociceptive and neuropathic pain, induced by an association of peripheral and central mechanisms. The pain experience is modulated by many factors, including the individual patient’s psychological, socio economics context and genetic factors. Several studies of neuroimaging using functional MRI –7 have dAlthough current OA medications using are active on peripheral nociceptive and neuropathic pain, these central modifications could still be a target. Mindfulness is a technique of attention training, which involves bringing attention back to the present moment and examining the sensations that arise in the mind. The "Mindfulness-Based Stress Reduction" (MBSR) cognitive therapy is a meditative exercise program aimed at reducing stress and eliminating anxiety states developed by Jon Kabat-Zinn , 16. TheA prospective pilot controlled randomized monocentric study was performed, and patients aged 30 to 75 years with knee OA or hip OA were recruited into the Rheumatology Department at the Montpellier University Hospital, France. The measurements were conducted between September, 2018 and September 2019. Patients, diagnosed as having knee or hip OA according to the American College of Rheumatology clinical criteria , were elThe MINDFULNESS-OA study was approved by the French ethics committee for Health Research  and by the national competent authority (ANSM). The study was registered in ClinicalTrials.gov . All the participant gave their written informed consent according to the Declaration of Helsinki prior to inclusion.Eligible participants were randomized to 2 groups by a central randomization system at a 1:1 ratio, using a random block sequence, and a stratification on the OA site (hip or knee).The MBSR program consisted of two-and-a-half-hour weekly sessions for 8 weeks, without the 7-h retreat, with a total of 20 h. It was delivered by an instructor (physician and psychotherapist) who trained at the Association pour le Développement de la Mindfulness , attended silent retreats and have more than 3 years of teaching experience mindfulness-based interventions. MBSR program included training in mindfulness through (1) a body scan, the gradual moving of attention through the body from head to feet while lying on a mat on the floor, bringing awareness particularly to bodily sensations; (2) sitting meditation, in which attention is brought to breathing sensations and the flow of bodily sensations, sounds, thoughts, and emotions; and (3) mindful stretching exercises, to cultivate awareness during simple stretching movement. The program included 45-min daily homework exercises that consisted of guided (MP3 sent by email) or unguided awareness exercises directed at increasing moment-by-moment non-judgmental awareness of bodily sensations, thoughts and feelings, together with exercises designed to integrate the application of awareness skills into daily life. The key themes of MBSR included the empowerment of participants and a focus on awareness and acceptance of experience of the present moment . The MBSUsual care management was similar in both groups and included advice on the importance of weight loss, physical activity and self-management education in a booklet given to the patient. Management of pain and depressive symptoms was carried out according to standard practice.All patients were clinically evaluated at baseline and for each visit, by a blinded physician. Two following visits were scheduled at 3 months and 6 months. Measurements of weight, height, blood pressure, were collected for each subject as well as the examination of knees and hips.Pain was assessed by VAS, functional impact was collected as well as analgesics consumption and eventual adverse events. The VAS used in this study was a 10-cm line ranging from 0 (no pain) to 10 (pain as bad as it could be) that assessed peak pain intensity over the last 24 h. Several questionnaires were also performed at each visit: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), 36-Item Short-Form Health Survey (SF-36) , Five FaThe primary outcome was to evaluate the change in WOMAC pain score between baseline and 3 months in the MBSR group compared to usual care group. Secondary objectives were to evaluate changes in pain VAS, WOMAC scores , quality of life (SF-36), HAD scores between baseline and 3 months, and between baseline and 6 months. We also performed the FFMQ questionnaire to find a predictive factor of patient response to the MBSR program.Bilateral knees postero-anterior (PA) radiographs in standing and pelvis position were performed at baseline for each patient to evaluate the Kellgren-Lawrence (K/L) score unless it had been carried out within 6 months.The current methods for setting pilot trial sample sizes are based on a set of rules, which is called flat rules of thumb. Browne recommended a general rule to use at least 30 subjects or greater to estimate a parameter . NoteworVariables were described using mean and standard deviation (SD) for gaussian quantitative variables, median and quartiles for non-gaussian quantitative variables, and counts and percent for categorical variables. Variables were described in each group and compared using usual tests, after assessment of application conditions: t-test or Wilcoxon-Mann–Whitney test for quantitative variables, and Chi-square of Fisher’s exact test for qualitative variables.Forty patients were enrolled and randomly allocated in either MBSR group or the usual care group Fig. . At the p = 0.33) at 6 months  Table . The chahs Table .Table 2ONo significant difference between the two groups either in 3-month or in 6-month visit were observed concerning the WOMAC subscales  or the OMERACT-OARSI response Table .p = 0.37) (Table p = 0.03)  Table .No differences between the two groups were reported neither after 3 months nor 6 months regarding anxiety/depression (HAD) or quality of life (SF-36). However, it was interesting to note that SF-36 mental score was exclusively improved in the MBSR group (48.1 ± 9.6 at baseline and 50.0 ± 8.6 at 6 months) while a decrease trend in the usual care group was found (42.4 ± 12.0 at baseline and 41.3 ± 14.3 after 6 months)  at 3 months or 6 months. Several reasons can explain the lack of differences between the two groups. First, we enrolled a low number of patients due to the exploratory design of the study that could lead to a poor statistical power. The WOMAC score is also more difficult and complicated for patients to understand than the VAS scale , 33 and p = 0.02) and the WOMAC function  12 months post-surgery, but no between group differences were observed at 3-months for any outcome which is similar to the results of ours at the same time point. This might imply the importance of observation of long-term effect of MBSR program. It’s also interesting to point out in their study that participants could only be included if patient’s SF-12 survey mental component summary score was less than 40 points, other than patients in general, which might overrate the efficacy of intervention.The reduction of pain and improved function in knee or hip OA after mindfulness workshops have already been reported. Ahn et al. demonstrated a pain reduction (WOMAC pain) in 15 patients with symptomatic knee OA after receiving ten home-based sessions of transcranial direct current stimulation paired with mindfulness over 2 weeks . The stuWith regard to MBSR assiduousness, we distinguished session assiduousness and home training assiduousness (Additional files Finally, it is worth mentioning that although a significant difference could be observed in a pilot trial, it does not necessarily lead to a definitive conclusion. Conversely, no significant difference between groups does not mean that it would not have significance in the main trial. Therefore, the favorable results of this study are a possibility towards MBSR program for OA patients, but conclusive results will require future studies with larger sample sizes to verify its validity.The strengths of our study include the RCT design, the use of standardized scales, and the good assiduousness of participants without many losses of follow-up. The non-invasive and safely MBSR program may become an alternative pain treatment strategy in OA care management. Nevertheless, limitations of the study may be acknowledged. Firstly, due to the nature of the intervention group, participants were not blinded, which might affect some outcome measurements, and could be the reason of four participants loss of follow-up in the control group compared to none in the MBSR group at the final visit. It may be due to their disappointment of not receiving active treatment. Secondly, this preliminary study included a small number of patients which could be responsible for the lack of power analysis; also, the follow-up time was relatively short, further research evaluating over 12-month efficacy would be required for this matter. Thirdly, the lack of active comparator, as rehabilitation or cognitive behavioral program prevented us from making comparison among them to draw a more definitive conclusion. Finally, due to the pilot design, the alpha risk was not controlled for secondary outcomes, which needs particular precociousness in their interpretation.Our pilot RCT found encouraging results with a delayed but long-term efficacy in pain VAS following a MBSR program in symptomatic knee or hip OA patients. Patients may experiment wider benefits in their daily life with a stress reduction, a quality of life improvement, and less depressive symptoms, compared to usual care. However, future studies with larger sample size are mandatory to confirm these preliminary results.Additional file 1. Painkillers consumption during the 6-month study among all participants.Additional file 2. Analysis of assiduousness to the MBSR workshops.


Gallstones in western countries are primarily composed of cholesterol. However, mixed or pigment stones, which contain a higher proportion of bilirubin, are more frequently seen in developing nations and Asia than in western countries. Abdominal and shoulder tip pains (STPs) are common complaints following the standard laparoscopic cholecystectomy procedure. To date, all pain management modalities have proven variable outcomes. This prospective randomized study included 82 patients who underwent elective laparoscopic cholecystectomy. The control group received 20 mL of normal saline, whereas the study group received a 20-mL instillation of 0.5% bupivacaine at the gallbladder bed after surgical resection. The Visual Analog Scale (VAS) was used to analyze abdominal pain and STP. The mean age ranged from 20 to 80 years. Abdominal VAS at 6, 12, 18, 24, 30, 36, and 48 hours were statistically insignificant. The majority were discharged on postoperative day 1 . Follow-up VAS after 1 week for STP VAS and abdominal pain VAS in both groups were statistically insignificant. Even with small numbers of a well-conducted randomized trial, we demonstrated that bupivacaine irrigation at the gallbladder bedpost laparoscopic cholecystectomy does not affect pain relief. Laparoscopic cholecystectomy (LC) is the gold standard in addressing benign gallbladder diseaseVisceral pain is caused by intra-abdominal cavity content stretching and peritoneal inflammation. Furthermore, phrenic nerve irritation is caused by residual carbon dioxide. Postoperative abdominal pain develops within the first 24 hours, and STP usually manifests only on the second day.Abdominal pain and dyspepsia were the most common presenting symptoms occurring, either alone or together, in patients with gallbladder stones. Many other studies revealed these two symptoms as the most commonly reported symptoms among patients with cholelithiasis.This prospective randomized study was conducted in the Department of General Surgery, Sagar Hospitals, Bangalore, Karnataka, India over 18 months, which included 82 patients who were admitted and subsequently underwent elective standard four-port LC. The patients had their gallstones imaged by ultrasound before surgery ward admission and were divided randomly by a computer-generated table into two groups . STP was experienced by 13 patients at 12 hours, wherein 9 had a VAS of 2 , 3 had a VAS of 4 , and 1 had a VAS of 6 from the control group, without a significant difference in both groups . At 18 hours, 8 patients had STP, wherein 5 had a VAS of 2  and 3 had a VAS of 4 , without significant difference in both groups . At 24 hours, 4 patients had STP, wherein 2 had a VAS of 2 from the study group, without a statistically significant difference in both groups . The majority were discharged on postoperative day 1 .The collected data was entered in Microsoft Excel and analyzed using the Statistical Package for the Social Sciences version 17. A total of 82 patients were analyzed and formulated. The demographic data were analyzed as frequencies, central tendency measures, and dispersion. The mean age (years) of groups A and B ranged from 20 to 80 years. With the highest age in the fifties (26%) followed by forties (20.7%). STP was experienced by 15 patients at 6 hours, wherein 10 patients had a VAS of 2 , 2 had a VAS of 4 from the control group, and 2 had a VAS of 6 from the study group, without a significant difference in both groups  , and abdominal pain (VAS score). STP VAS at 30, 36, and 48 hours were statistically insignificant. Abdominal pain VAS at 6, 12, 18, 24, 30, 36, and 48 hours was statistically insignificant  . The Fiificant .Nowadays, LC is one of the common procedures in the general surgery and gastroenterology departments. The learning curve for laparoscopy is long; however, surgical trainees are remarkably exposed to this procedure, thereby making them more comfortable with performing LC than other procedures.Radiologic studies demonstrate the presence of pneumoperitoneum for as long as 24 hours after LC, The amount of free gas remaining in the abdominal cavity is usually small and has not been regarded as a cause of postoperative morbidity. Components of post-LC pain include visceral pain (78.33%), parietal pain (70%), and STP (23.33%). Intraperitoneal irrigation of the diaphragmatic surface and gallbladder fossa using normal saline, bupivacaine, or lignocaine may effectively control visceral abdominal pain after LC.In conclusion, the present study had a small sample size; thus, drawing a definitive conclusion was difficult. However, this randomized trial was well-conducted and demonstrated that bupivacaine irrigation at the gallbladder bedpost LC does not affect pain relief. The background that most patients who underwent LC have minimal pain should also be considered; hence, several patients are required to conclude with a suitable outcome to demonstrate a tangible and significant difference between both groups.LCLaparoscopic CholecystectomyOCOpen CholecystectomyLALocal AnesthesiaSTPShoulder Tip PainVASVisual Analog Scale


Chronic pain and depression are closely related conditions, which commonly exist as comorbid disorders. Understanding the prevalence of depression in patients presenting with chronic pain is vital for effective pain management.Our study aimed to establish the prevalence of a history of depression in patients presenting with chronic pain to a chronic pain management clinic at a tertiary academic hospital and to describe the characteristics of patients with both conditions.Groote Schuur Hospital, Chronic Pain Management Clinic, Cape Town, South Africa.A retrospective review of 665 medical charts of consecutive patients accessing the clinic over a 7-year period was conducted. Baseline, patient-centred data were collected.p < 0.01). Overall, 51% of the patients assessed were unemployed with low levels of education. The majority of our study patients had received a tricyclic antidepressant at some time prior to presentation.Of the 665 charts, 623 were analysed. The median age of patients was 53 years. The prevalence of depression in patients presenting with chronic pain was 32%, three times higher than the national life-time prevalence in South Africa. The majority (77%) of patients with chronic pain and depression were female (The high prevalence of a history of depression in patients presenting with chronic pain in our study, emphasises the importance of looking for and understanding the interrelation of the physiological, psychiatric, psychological and socio-economic factors that are common to both depression and chronic pain. Pain relief alone is insufficient to ensure optimal rehabilitation of these patients and integrating the management of their depression should improve patient outcomes and overall well-being. Both are debilitating conditions that exist as comorbid disorders in as many as 80% of patients attending specialist pain units.3 Pain and depression share biological pathways and neurotransmitters with recent studies suggesting overlaps between pain- and depression-induced neuroplastic and neurobiological changes.4 Therefore, the successful management of a patient’s chronic pain, requires the clinician to assess for and treat any underlying clinical depression.5Chronic pain is an extremely complex and poorly understood medical condition that may result in a patient repeatedly seeking medical care. This condition can have profound effects on a patient’s physical and mental well-being and on their ability to function daily.2 In a study published in 2016 evaluating people with chronic pain attending a specialist pain clinic in the United Kingdom, 60.8%  met the criteria for probable depression whilst 33.8% met the threshold for severe depression on the 9-item Patient Health Questionnaire. Multivariate analysis showed a positive association between severe depression and an increase in total healthcare costs as compared with patients without depression.2 In a recent systematic review and meta-analysis, Kleykamp et al. found that a quarter of all patients with fibromyalgia had major depressive disorder (MDD) and more than 50% of all fibromyalgia patients experienced a MDD during their lifetime.6 This was confirmed by Løge-Hagen et al., who in their systematic review describing the prevalence of psychiatric and chronic pain comorbidities in fibromyalgia, found the weighted prevalence of MDD in patients with fibromyalgia to range from 52% to 63%.7The prevalence of depression in patients with chronic pain is described from 4.7% to 22% in population-based studies and estimated to be between 6% and 46% in studies from the primary care sector.8 Major depressive disorder, agoraphobia and alcohol abuse were the most prevalent 12-month Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) and Composite International Diagnostic Interview (CIDI) disorders in the sample population. The prevalence of major depression was 9.7% for lifetime and 4.9% for the 12 months prior to the interview. In a recently published study conducted in a large nationally representative sample, the prevalence of chronic pain in South Africa was described at 18.3% (95% CI: 17.0–19.7).9 There are, however, a paucity of studies describing the co-prevalence of chronic pain and depression in the sub-Saharan African context. Cross-national data from 17 countries in Europe, the Americas, the Middle East, Africa, Asia and the South Pacific based on large population surveys of community-dwelling adults, revealed that mental disorders are more common amongst persons with back and neck pain than amongst persons without. Pooled odds ratios were 2.3 (95% CI: 2.1–2.5) for mood disorders and 2.2 (95% CI: 2.1–2.4) for anxiety disorders in people with, versus without chronic back and neck pain. Mental health disorders were associated with chronic back and neck pain and this pattern was consistently evident across both developed and developing countries.10In the first nationally representative psychiatric epidemiological survey, the South Africa Stress and Health (SASH) study indicated that there is an elevated risk of mental health disorders in South Africa (SA) compared with several other high- and middle-income countries.12 South Africa is a country with significant socio-economic inequalities; which translates to health system inequalities and negatively impacts health.13 Therefore, in a country where the majority of people live in low-resource settings with high stressors and poor access to adequate healthcare services; they may be at an increased risk of both depression and chronic pain.Literature suggests that socio-demographic risk factors for the development of chronic pain include being female, of older age, lower socio-economic status, geographical and cultural background, employment status, occupational factors and having a history of abuse or interpersonal violence. These factors may overlap with the risk of development of depression.14 There is a two-tier healthcare system in South Africa with a large subsidised public sector and a small private sector, funded through individual contributions to medical aid schemes or health insurance. The public sector is state-funded and caters to the majority – approximately 71% – of the population and has a five-layered structure, which was developed to provide cost effective healthcare to all citizens, namely primary healthcare (clinic-based); secondary level district and regional hospitals; tertiary (academic) hospitals; central (academic) hospitals and Specialised hospitals. Tertiary, central and specialised hospitals rely on a referral process. Generally, the referral population originates from specialist units at GSH including general surgery, orthopaedics, rheumatology and neurology services and patients who have sought previous care at primary and secondary healthcare facilities. Most referrals are from Cape Town, Western Cape, South Africa.The setting for our study was the Groote Schuur Hospital (GSH) Chronic Pain Management Clinic (CPMC), a specialist, interdisciplinary clinic that provides outpatient consultation and treatment for patients with chronic pain, described as pain experienced on most days for a period of three months or longer.15Understanding the prevalence of depression in the Pain Clinic population in South Africa and its relationship to patient characteristics is beneficial to clinicians managing these patients, to the patients themselves and to stakeholders. Acknowledgement of the risk of depression in patients presenting with chronic pain is imperative to effectively managing these patients. It is important for clinicians to understand that pain relief alone may be insufficient to ensure optimal rehabilitation and that the management of underlying depression should be integrated into the treatment plan. This information is essential for stakeholders as staff and resource allocation to pain management services need to be sufficient to provide psychiatric and psychological input. Chronic pain in association with depression should therefore be considered a serious condition and a risk marker requiring intensive management to minimise the detrimental impact on life and health.The aims of our study were to (1) establish the prevalence of a history of depression in patients presenting with chronic pain to the CPMC at GSH over a 7-year period and (2) describe the co-prevalence of chronic pain and depression by patient characteristics, namely age, sex, income status and the use of recreational drugs, tobacco or alcohol.A retrospective review of 665 medical charts of consecutive patients who accessed the CPMC at GSH, over a specified period, was conducted.The sampling frame included all patients attending an initial assessment between June 2010 and June 2017. In June 2010, a clerking form that required documentation of a patient’s history of depression to be captured on admission to the CPMC was implemented. Medical folders were excluded if the admission data captured by the clerking doctor were missing or incomplete.16 The documented pain interference scale characterised the degree of pain-related functional impairment using scales from 0 (‘does not interfere’) to 10 (‘completely interferes’).We collected baseline, patient-centred data that was manually recorded in the admission notes as part of the routine self-reported history obtained on the initial assessment of the patient at the clinic. A standardised data collection form was used for data extraction and the following data were collected: age; sex; employment and income status; use of recreational drugs, tobacco and alcohol; details of the referring team, patient-reported and clinician-reported  history of depression (or other psychiatric conditions), the current or previous use of antidepressant medication and the admission pain score. The latter included an assessment of pain intensity or severity, which is modelled on the Brief Pain Inventory (BPI) and determined pain on admission using a numeric scale ranging from 0 (‘no pain’) to 10 (‘pain as bad as you can imagine’).To protect patient anonymity all data extraction was performed by the principal investigator who is a registered healthcare professional, trained in good clinical practice. The ethical principles of patient confidentiality were protected throughout by anonymising data at the source. Data were collated into Microsoft Excel 2013 for analysis. Data were subject to quality control procedures by an external auditor who performed a 10% quality control check of the folders assessed, the data collection forms and the data entry procedure.p < 0.05.Statistical analysis was performed using statistical software Statistica . A non-parametric approach to analysis was adopted based on the categorical nature of most of the data. In addition, patient ages were not normally distributed and were analysed using a non-parametric approach. Numerical data are presented as medians (interquartile range), categorical data as frequencies (with percentages). Differences in numerical data were compared using the Mann–Whitney U test. Differences in distribution of categorical data were tested using Spearman’s rank order correlations. Significance was accepted throughout as Our study was approved by the Human Research Ethics Committee of the Faculty of Health Sciences at the University of Cape Town (HREC REF: 505/2018) and the Departmental Research Committee of the Department of Anaesthesia and Perioperative Medicine at Groote Schuur Hospital. The principles of the Declaration of Helsinki were adhered to throughout.A total of 665 consecutive patient folders were reviewed for the period June 2010–June 2017, of which 42 were excluded because of incomplete data. Thus, 623 patient folders were included in the analysis.n = 529), 328 (62%) had not completed 12 years of schooling. In addition, 139 (22%) were receiving either state funded or privately funded disability grants (The median (interquartile range [IQR]) age of the patients was 53 (44–63) years with 428 (69%) being female. At the time of initial assessment at the CPMC, the majority of patients were unemployed  and of those whose level of education was determined  of the referrals, with referrals from the Department of Orthopaedics  predominant . RecreatA BPI was completed by all patients on admission to the CPMC. The median (IQR) scores on the BPI for pain severity scores (PSS) were 8 (6.5–9.0) and 8 (6.0–9.0) for the pain interference with function score (PIS).In the 623 folders reviewed, 197 (32%) of the patients provided a history of being diagnosed with depression. Of these, 160 were diagnosed only with depression, 29 had comorbid anxiety with depression and a further three had depression, anxiety and one other psychiatric condition. In total, 229 (37%) of all patients reported a history of being diagnosed with one or more psychiatric disorder, with depression accounting for 86% of the 229 . The dia17 Several patients were receiving therapeutic doses of more than one medication from the same class or from different classes (multiclass polypharmacy) of psychotropic drugs. Polypharmacy is a common clinical practice for many psychiatric and pain conditions.18Patients were receiving a range of central nervous system (CNS) acting agents , which mA comparison between two groups: patients with chronic pain and a history of depression (PD) and patients with chronic pain only (P), with no history of depression was performed to explore the interactions between certain baseline characteristics.p < 0.01), with more women giving a comorbid history of depression with chronic pain than men. There was no difference between the two groups with respect to age, employment status and the level of education received.As shown in 20 The prevalence of depression in patients with chronic pain varies widely in population-based studies, however, our results are in keeping with a 2016 publication evaluating people with chronic pain attending a specialist pain clinic in the United Kingdom, where 33.8% of attendees met the threshold for severe depression.2We found a high prevalence of comorbid pre-existing depression in patients presenting with chronic pain to our specialised CPMC (32%). This is more than three times higher than the described life-time prevalence in South Africa of 9.7%.21 The organisation also emphasises the significance of the relationship between mental and physical health.22 In their World Health Survey, they reported that the:A World Health Organization (WHO) report predicted that MDD will become the leading cause of disability in the world by 2030.C]omorbidity of depression with a chronic illness incrementally worsens health outcomes in comparison to depression alone, any chronic disease alone, or any combination of chronic diseases in the absence of depression.20[23 Apart from the common pathophysiological mechanisms, however, these two entities have been thought to have several other social, demographic and clinical links, which we aimed to explore.Accumulating evidence suggests than neuroinflammation plays a critical role in the pathogenesis of both depression and chronic pain.p < 0.01). In the Global Burden of Disease Study 2017, the annual prevalence of major depression was found to be higher in women at 4.1% compared with 2.7% in men, representing a 1.5-fold greater incidence in women.25 Women have a higher risk of depression than men, particularly during puberty, prior to menstruation, during pregnancy and the postpartum period and at perimenopause. In South Africa it is quoted that one in three women during or after childbirth, experience a mental health disorder, primarily depression.26 This figure is threefold higher than the WHO described worldwide prevalence.27 The mechanisms that appear to contribute to women’s vulnerability to depression may overlap with those for chronic pain. In the peripartum periods, besides the physiological hormonal changes present, multiple life changes contribute to vulnerability.28 The low levels of oestrogen during the transition to menopause, either biologically or abruptly after a hysterectomy, combined with acute sleep disruptions and inherited traits account for the increased prevalence of depression in this group of patients. In South Africa, women may also be vulnerable to domestic abuse, both physical and emotional and may be victims of sexual or racial discrimination on a social level, affecting their self-esteem and contributing to their vulnerability to depression. A further social factor contributing to women’s susceptibility is poverty, with studies showing that women are more likely than men to live in poverty. All these female hormonal fluctuations that have been implicated in depression29 have also been implicated in the development of chronic pain. However, other biological and genetic factors, plus personal life events or triggers are also associated with a risk of both depression and chronic pain. Women in South Africa play an important role in the nation’s economy and an essential domestic role at home with their families, so this finding merits more attention to ensure women’s overall physical health and mental well-being.Of significance, we found that 77% of patients with chronic pain plus a history of depression were female compared with 23% of male patients with chronic pain and a history of depression  supports the notion that ‘higher educational level or the factors that are reflected by higher education, may protect against anxiety and depression’, with the protective effect accumulating throughout life.Our study has numerous limitations associated with retrospective chart reviews and our study relied on accurate information being captured on admission to the CPMC via a qualitative interview process. The patients reflected on their condition but are inherently subject to recall and response biases. The major limitation of our study was reliance on the patient self-reporting a history of depression and this information was not being routinely classified by a specialist using the DSM-V. This method lacks the depth and diagnostic accuracy of a clinical assessment by a trained healthcare professional and the validity of not using the gold standard clinical interview as opposed to a retrospective chart review means that our study may both miss possible undiagnosed cases and erroneously identify or classify cases as patients with depression. In addition, the calculated prevalence in this group of chronic pain patients may be subject to inclusion bias because of preferential referral of patients with greater pain and disability who get referred to a specialist clinic at a tertiary academic hospital. Given these inconsistencies, we recommend further studies in this field be performed in a prospective manner, with the utilisation of a psychiatrist or a clinical psychologist, to accurately classify patients according to their mental health status. Research is also required to determine which treatment approaches would be most successful in managing chronic pain and depression in these patients; whether psychological treatment with or without pharmacological interventions is effective and which combinations and dosages would be the best to improve the physical and mental health outcome of the patient in a cost-effective manner that would be sustainable in the South African setting.The prevalence of a history of depression in patients presenting with chronic pain to our pain clinic was found to be 32%, which is three times higher than the national lifetime prevalence in South Africa. In the last decade, the significant role of depression in chronic pain syndromes has been emphasised; acknowledging that chronic pain and depression share neurobiology and neuroanatomy. Our study provides essential insight into the importance of psychiatric and psychological management as an integral part of an effective pain management strategy and the need for an interdisciplinary team approach in chronic pain management. Our findings emphasise the importance of the interrelation of the physiological, psychiatric, psychological and socio-economic factors that link depression and chronic pain. Pain relief alone is insufficient to ensure optimal rehabilitation and integrating the management of depression using pharmacological and non-pharmacological treatment modalities with an interdisciplinary approach should be utilised to improve patient outcomes and overall well-being.


The study aimed to compare the intra-individual 2 procedures of tonsillectomy (Coblation and diode laser) concerning the operative time, the amount of blood loss, postoperative pain, and other complications. A comparative study was conducted at many Private Hospitals, Baghdad, Iraq from February 2019- February 2020. Coblation and diode laser tonsillectomy were performed on the same patient (one for each side) which was blinded to the patients or their caregivers and the surgeon who did the tonsillectomy. A double blinded randomization process of 1 to 1 of these two procedures according to the side involved was performed. Data concerning the age, gender, indications for tonsillectomy, operative time, the amount of the blood loss, post-tonsillectomy pain by VAS scores, and other complications were recorded for each patient. Out of 62 participants, there were 34 (54.8%) females. The majority were from the age group ≤18 years . The operative time and amount of the intraoperative blood loss were significantly lower in the Coblation than a diode laser tonsillectomy. However, the postoperative pain scores in the diode laser were a statistically significant difference less than the Coblation group at the periods 3 hours, 8 hours, 24 hours, and 7 days . Coblation was better than diode laser because of shorter operative time and less intraoperative blood loss. However, the diode laser technique had lesser postoperative pain at the postoperative periods 3 hours, 8 hours, 24 hours, and 7 days than Coblation.  One of the most common operations in the field of otolaryngology is a tonsillectomy, which is most commonly indicated in cases of recurrent tonsillitis or obstructive upper airway due to tonsillar enlargement ,2. ConveThe drawback of the conventional dissection tonsillectomy is an open postoperative wound that heals by secondary intention with its sequel of postoperative pain and bleeding. Therefore, otolaryngologists use many other procedures for removal of the tonsils such as laser, electrocautery, Coblation, radio-frequency, monopolar or bipolar diathermy, and harmonic scalpel .The term Coblation is derived from controlled ablation. It was first discovered by Hira V. Thapliyal and Philip E. Eggers . It depeThere are various types of lasers have been used in tonsillectomy procedure like CO2, KTP, NDYAG, and diode . The advThis double-blinded randomized controlled trial was conducted at many Private Hospitals, Baghdad city, Iraq. The study covered the period of one year (February 2019 to January 2020). Patients with an age range of 5-40 years, both sexes, and with an indication of tonsillectomy due to recurrent tonsillitis or obstructive tonsillar hypertrophy of grade 4 tonsils according to the Brodsky tonsillar grading scale were enrolled in the study . RecurreSample sizeThe calculation of the sample size was depended on similar previous tonsillectomy study . To reacSurgical methodAll cases had general anesthesia in a supine position with a draping of the whole body exposing only the mouth, then a Boyle –Davis mouth gag was inserted with Draffin suspensors applied. The tonsil was held by tonsil holding forceps and pulled medially, by using either Coblation or diode laser handle, the anterior pillar was incised till reaching the tonsil capsule, then the tonsil dissected till reaching the inferior pole starting from the superior one. In the Coblation tonsillectomy group, we used a Coblator® II system  and the Evac T&A Plasma Wand (ENTec) was used at an intensity setting of 7 for dissection of the tonsils at the subcapsular plane. Bleeding points were secured using an intensity setting of 4 on coagulation mode. In the diode laser tonsillectomy group, a diode laser  was used. The machine was set to 5 W continuous beams for subcapsular dissection. Besides, bleeding points were secured by diode laser. The laser beam was delivered via a 0.6 mm Endostat fiber. Routine precautions for the safety of theatre personnel were followed during the use of the laser. The amount of blood loss was estimated by using standard pieces of gauze which were soaked in normal saline then squeezed then weighed by an electric scale before and after it is used to dry blood oozing from the incision or dissection. All procedures were performed by well expertise surgeons in the field of the diode laser and Coblation tonsillectomy. The time taken to remove each tonsil was measured by minutes and any complications that occurred during surgery were recorded. After surgery, the patients were kept in the ward, monitored for vital signs and signs of bleeding regularly (six-hourly for 24 hours) then they were discharged home. The two sides were compared for pain in the throat and healing signs at 3 hours, 8 hours, 24 hours, 7 days, and 2 weeks post-operatively. Intravenous and oral paracetamol per body weight was the analgesic used according to the standard pain control regime in all cases given 3 times per day for the first day. Thereafter, the analgesic is used according to the need of the patients. Additionally, prophylactic amoxicillin for the first 10 post-tonsillectomy periods was given for all patients. All patients were seen at 7, and 14 postoperative days in the outpatient clinic. Pain assessment depends on a 0-10 visual analog scale (VAS) score of pain, the mean ± SD was measured for each subject. The VAS was valid and used in the past for the assessment of postoperative pain in children and adults after tonsillectomy ,18. t Test of the two identical continuous variables to find the means of them plus SD. According to Cohen's equation, the clinical effect size = (mean 1- mean 2)/SD. If the result is 0.2 means small, 0.5 moderate, and 0.8 large effect.The data were entered and analyzed using IBM SPSS version 25 for windows. The categorical variables were presented in a simple table of the frequencies and percentages. Chi-squared test was used to compare the categorical variables between the Coblation and diode laser tonsillectomy. Independent sample T-Test was used to compare the means of the variables. P-value at <0.05 considered a statistically significant difference. For the calculation of the clinical effect size, we used Paired Sample Sixty-two patients fulfilled the inclusion criteria and enrolled in the study. The age range of the patients was 8-31 years with a median age was 9 years with an inter quarter range (IQR) 3. The most involved age group was ≤ 18 years . Females  out the number of the males , with a male/female ratio of 1/1.21 . Recurrent infection comprises 64.5% (n = 40) of the tonsillectomy indications Despite tonsillectomy is one of the most common surgical procedures performed by an otolaryngologist through various techniques, postoperative bleeding and pain remain complications of this operation. The otolaryngologists try to practice and compare different procedures of tonsillectomy to achieve the best way regarding the shorter operative time with less blood loss, avoidance of intra and postoperative complications including mainly post-tonsillectomy hemorrhage and pain. We aimed to compare the diode laser and Coblation tonsillectomy both in children and adults. The strength of the study was the use of both procedures in the same patient (Coblation on one side and diode laser on the other side) to lessen the bias. Similar studies used 2 methods of tonsillectomy in the same patient ,19. The Although Coblation and laser tonsillectomies are relatively new techniques, if one compares them with the cold steel dissection method, they have gained popularity in the otolaryngology practice owing to the advancement in the technology of their machines. In Iraq, few randomized controlled trials studied the comparison between the cold steel dissection method with CO2 laser , Coblati Powell et al. in 1997 studied the effect of radiofrequency on the tissue of the tongue in animal models, both in vitro and in vivo. They concluded that radiofrequency can reduce the volume of the tongue in a perfect and controlled way . Since t In a study from China by Zhou et al., they coA recent systematic review study by Ahmed and Arya  reviewedA recent study by Kumar et al.  reportedPost-tonsillectomy bleeding (primary or secondary) is a major complication of tonsillectomy with variable incidences 0.95%-7.8%) among previous investigations %-7.8% am,27. The The parameters in defining the improvement of tonsillectomy operation are shorter operative time, less intraoperative blood loss, low incidence of primary or secondary post-tonsillectomy bleeding, less postoperative pain, and early recovery and return to usual activities. Despite, many researchers studied these parameters among various tonsillectomy methods -14,19, tThere were a moderately clinically significant effect  of all statistically significant differences parameters between the Coblation tonsillectomy and diode laser tonsillectomy a part from the post-tonsillectomy pain at 7 days had a small clinically significant effect . Therefore, we suggest further study on a large sample size to get a large clinical effect size. Although the current study tried to avoid result bias by comparing the two sides of the same patient still it did not bypass the intrapersonal differences in size, fibrosis, and blood supply between the two tonsils of the same patient. This actually cannot be overcome and may have some effect on the results but the arbitrary selection of the sides may minimize this effect. The difference among surgeons efficacy in performing the tonsillectomy by diode laser and Coblation can make some bias in the cases. Even this is minimal as they were high standard consultants in the field, it is considered another limitation of the study. The Wong–Baker FACES® pain scale is a valid test for the assessment of the post-tonsillectomy pain in children and was used in previous studies . HoweverEven though the time in preparing the 2 devices didn't take into consideration when calculating the operative time in the current study, it had a drawback on the patients as it prolongs the total operative time with its risk of anesthesia. Therefore, we don't advise using 2 techniques of tonsillectomy in the same patient in daily clinical practice as here we used them for research purposes.The study revealed that the Coblation tonsillectomy was better than the diode laser concerning the operative time and amount of intraoperative blood loss. However, the diode laser had significant low postoperative pain VAS scores in the first 7 days postoperatively. The current study found that there was a moderate clinical effect size for all parameters except the pain score at the 7 post-operative day . Owing to the above three mentioned limitations of the current study, the results cannot be generalized.


This prospective longitudinal study of 80 patients analysed the effect ofpreoperative pain catastrophizing, anxiety, depression and sense of coherence onthe Disabilities of the Arm, Shoulder and Hand, Patient-Rated Wrist Evaluation,quality of life, grip strength and range of motion during the first year aftersalvage surgery for wrist osteoarthritis. Generalized estimating equations wereused to analyse the effect of the psychological factors on the outcomevariables. Pain catastrophizing or a tendency for anxiety preoperatively had astrong negative impact on postoperative Disabilities of the Arm, Shoulder andHand and Patient-Rated Wrist Evaluation. Anxiety also predicted a lowerpostoperative quality of life, whereas pain catastrophizing had a negativeimpact on grip strength. Sense of coherence did not influence the outcome.Level of evidence: II Patient-reported function and pain relief after salvage surgery for wristosteoarthritis varies, and patients with similar diagnoses and degree ofosteoarthritis who receive the same type of surgery and rehabilitation may ratetheir outcome differently. In recent years, there has been increasing interest inthe impact of psychological factors on the post-surgical outcome. Anxiety,depression and pain catastrophizing have been reported to predict poor outcome,persisting pain and delayed recovery after surgery in a wide variety of chronic andtraumatic medical conditions in the upper extremity .Sense oThe influence of psychological status on the outcome after salvage procedures forwrist osteoarthritis has not been investigated. The primary aim of this study was toanalyse whether pain catastrophizing, anxiety, depression and SOC has any impact onthe result in terms of patient-reported outcome measures (PROMs), grip strength andrange of motion (ROM) after salvage procedures for wrist osteoarthritis during thefirst year after surgery. We hypothesized that depression, anxiety and paincatastrophizing would have a negative effect on the Disability of the Arm, Shoulderand Hand (DASH) score, Patient-Rated Wrist Evaluation (PRWE), quality of life, gripstrength and ROM, whereas a high SOC would have a positive impact. The secondary aimwas to investigate whether the psychological scores change during the first yearafter surgery. The null hypothesis was that the pre- and postoperative psychologicalscores would be equal.n = 49) or a prospective randomization between two methodsof midcarpal fusion (n = 31). The inclusion criteria werechronic (≥6 months) symptomatic wrist osteoarthritis caused by scapholunateadvanced collapse (SLAC) or scaphoid nonunion advanced collapse (SNAC),osteoarthritis after distal radial fracture or secondary to Kienböck’s disease.Only patients that had tried nonsurgical management, such as bracing,corticosteroid injections, oral analgesics and/or physiotherapy, were included.The exclusion criteria were age <18 years and inability to cooperate with thefollow-up protocol . All operations were carried out bysurgeons with level three expertise  , EuroQol-5D-3L (EQ5D-3L))    is a 13-The Hospital Anxiety and Depression Scale (HADS)  compriseThe sense of coherence (SOC-13)  reflectsp = 0.05). SD was estimated to 15. Eighty patients wereincluded to account for some loss to follow-up.To detect a difference of 10 points in DASH score, which is considered theminimal clinically important difference (MCID) , betweenp-value, where β reflects the expectedpopulation mean change of the outcome variables between the preoperativeassessment and the assessments 6 and 12 months after operation. Significance wasset at p ≤ 0.05.Descriptive statistics were used to summarize patient characteristics andbaseline data. DASH, PRWE, EQ5D, SOC, PCS and HADS scores were reported asmedian (IQR) and continuous variables as mean (SD). To analyse the repeatedmeasurements, we used two separate generalized estimating equations (GEE) with arobust estimator covariance matrix, autoregressive (AR1) working correlationmatrix and a linear model for all variables. In the first model DASH, PRWE,EQ5D, grip strength and ROM were dependent variables with time, sex, age, typeof surgery and preoperative PCS ≥ 30, HADS ≥ 8 and SOC ≥ 73 included as possiblepredictors. In the second model PCS, HADS and SOC were dependent variables withtime, age, sex and type of surgery as covariates. The changes in outcomevariables over time and the effects of the predictors are presented as betacoefficient (β) with One patient was lost to follow-up 3 months after operation owing to the developmentof severe psychiatric problems, leaving 79 patients for analysis. Twelve-month datawere missing in two patients from the denervation group, who dropped out after6 months since they required additional wrist surgery for persisting symptoms. Owingto the COVID-19 pandemic, four patients declined clinical assessment and thereforeobjective physical variables are missing for those patients at one timepoint.Twelve-month physical data are also missing in one patient who moved during thestudy period. Completeness of the DASH scores was 97%, PRWE 97%, EQ5D 97%, SOC 95%,HADS 96% and PCS 97%, respectively.The types of wrist osteoarthritis and demographic data are described in The mean and median values of the outcome variables preoperatively and 6 and12 months postoperatively are presented in p = 0.007), PRWE  and grip strength , but no effect on EQ5D or ROM.Sixteen patients had a PCS score ≥30 at baseline. PCS ≥ 30 had a negative predictiveeffect on both DASH , PRWE  and EQ5D at follow-up. A baseline HADS anxietyscore ≥8 did not influence grip strength or ROM.HADS depression was omitted from the analyses since only five patients had a score of≥8 at baseline. Nineteen patients had a HADS anxiety score of ≥8. A preoperativeHADS anxiety score ≥8 had a negative predictive effect on DASH  and a positive predictive effect on ROM comparedwith partial wrist fusion .A high SOC did not have a significant impact on any of the outcomes. Partial wristdenervation had a small but significant negative predictive effect on PRWE ; β = 0.41(p < 0.001); β = –0.003 (p = 0.015);β = −0.39 (p < 0.001); and β = –0.44(p = 0.004)) for every 1-year increase in age). Female genderpredicted a worse DASH score  and a lower gripstrength .Higher age had a negative predicted effect on DASH, PRWE, EQ5D, grip strength and ROMat follow-up (β = 0.45 (There was a significant improvement of PCS 6 months after surgery and PCS improvedeven more by 12 months . The HADIn patients with painful wrist osteoarthritis, we found that pain catastrophizing ora tendency for anxiety had a negative impact on the patient-reported outcomes aftersalvage procedures. Sense of coherence did not influence outcome.Others have reported negative effects of pain catastrophizing and anxiety on PROMsafter surgery for various chronic conditions and injuries to the hand and wrist. SimilarIn our sample, pain catastrophizing had a negative impact on grip strength but not onROM, whereas anxiety did not influence grip strength or ROM. Pain catastrophizinghas been shown to have a negative effect on ROM after surgery for distal radialfractures . AlthougWe report that anxiety, but not pain catastrophizing, has a strong negative impact onquality of life. The negative association between anxiety and quality of life hasbeen confirmed by a recent systematic review  whereas There is a need for studies on psychological factors with a positive effect onoutcomes . SatisfaWe found that anxiety and SOC were stable over time, whereas pain catastrophizingdiminished during the year after surgery. In accordance with this, reduction of PCShas been reported after total knee arthroplasty  and afteThe major limitation of this study is the lack of control group, with a resultantrisk for bias and confounding. Demographic data are included in the analysis toreduce the risk of confounding, but the risk of bias cannot be accounted for. Thestudy population consisted of patients that had either a partial wrist denervationor a midcarpal fusion, which is also a potential weakness. To control for anydifferences in outcomes attributable to the surgical treatments, the type of surgerywas included as a covariate in the GEE analyses. Depression has been reported toinfluence postoperative outcome in hand and wrist surgery . OwingtThe foremost strengths of this study are the prospective longitudinal design with theloss of few patients and the pre- and postoperative assessments by validated andwidely used upper-extremity and wrist-specific PROMs and well-establishedpsychological scores.In summary, we found a negative predictive effect of pain catastrophizing and anxietyon patient-reported outcomes after salvage surgery for wrist osteoarthritis. Anxietyalso predicted a lower postoperative quality of life, whereas pain catastrophizinghad a negative impact on grip strength. Anxiety and depressive status seem to bestable over time, whereas pain catastrophizing may be improved by the surgicaltreatment itself. Psychological problems are common and hand surgeons need to beaware of the negative impact of preoperative psychological problems on the outcomesof surgery. The outcomes may be improved by identifying patients with theseconditions, and by giving them preoperative counselling or treatment.


Chronic postoperative pain (CPOP) is prevalent, with particularly high rates in breast surgery, thoracotomy, and amputation. As the world emerges from the coronavirus disease 2019 (COVID-19) lockdowns, it is expected that there will be an increase in surgical procedures, elevating the importance of preventing CPOP in the coming years. Risk factors are emerging to better stratify patients at high risk for CPOP. Perioperative analgesia plays an important role in managing acute postoperative pain and in some cases may limit its transition to CPOP. Acute postoperative pain is adaptive, normal, expected, and has a well-defined trajectory, while CPOP is maladaptive and, as a form of chronic pain, is challenging to treat. Good analgesia, early ambulation, and rehabilitation efforts may be helpful in preventing CPOP following certain surgeries. Enhanced Recovery After Surgery (ERAS) protocols present guidance to help promote recovery and prevent CPOP. Acute postoperative pain is the expected consequence of certain surgical procedures and because pain diminishes as the tissue heals, it has a predictable trajectory. Chronic postoperative pain (CPOP) has been defined as pain persisting after surgery and for which other causes, such as pre-existing pain, can be excluded . In a suWhile certain surgery-related and patient-specific risk factors for CPOP have emerged, it appears crucial that acute postoperative pain control is essential to mitigate the risk for CPOP . To bettEpidemiology and risk factorsIt is difficult to state one figure for the incidence of CPOP, as the rate of this condition varies among patients and procedures. For example, the incidence of CPOP is particularly high following limb amputation and thoracotomy . MoreoveAlthough multiple definitions appear in the literature , CPOP wiAn increase in surgical procedures is anticipated as the coronavirus disease 2019 (COVID-19) pandemic ends . An incrCPOP often has a neuropathic component, making it particularly challenging to treat . In a stPreoperative pain sensitivity may also predict CPOP, and preoperative quantitative sensory testing may turn out to be a useful predictor of CPOP risk . PatientMurine studies identified certain receptors, mediators, and neurotransmitters involved in peripheral and central sensitization following surgical incision, confirming that some were unique and specific to incisional pain . The sizAnalgesics for acute postoperative painThe International Association for the Study of Pain (IASP) declared 2017 to be the global year against pain after surgery to raise awareness about this pain state and encourage policies to advance better treatment and clinician education . In partThe role of ketamine in managing surgical pain is expanding, and it is a field of current investigation . In a stGabapentinoids, such as pregabalin and gabapentin, are gamma-aminobutyric acid (GABA) analogs active at the NMDA receptors. Gabapentinoids bind at the voltage-gated Ca2+ channel subunits, which are proteins that interact with the NMDA receptors and increase their synaptic activity, leading to neuropathic pain. While the exact mechanism of action is not yet elucidated, it appears that gabapentinoids can inhibit the anterograde trafficking of these subunits from the dorsal root ganglion to the dorsal horn neurons and, in this way, reduce neuropathic pain . GabapenThere has yet to be a consensus about the use of perioperative ketamine and postoperative gabapentinoids for the control of surgical pain . There iChronic inflammation can initiate neuroplastic changes that result in aberrant pain signaling known as sensitization, which may result in CPOP .Regional anesthesiaRegional anesthesia may offer benefits beyond better acute pain control. In a retrospective study of patients undergoing primary hip or knee arthroplasty n = 382,236), 74.8% of patients had only general anesthesia, while 11% had neuraxial anesthesia, and 14.2% had a combination. Patients who had neuraxial anesthesia or the combination of neuraxial plus general anesthesia had significantly better outcomes in 30-day mortality along with shorter hospital lengths of stay, lower in-hospital complication rates, and reduced costs 2,236, 74. A meta-There are essentially three potential injection sites for regional anesthesia: the perineural and sub-perineural region, the sub-epineural area, and the intrafascicular. The perineural region is outside the nerve itself, the sub-epineural region is below the epineurium, and the intrafascicular injection injects the anesthetic directly into the fascicles containing nerve fibers within the perineurium . The useIt is not clear if neurological insult sustained during regional anesthesia is caused by nerve puncture and/or intraneural injection . The optHemidiaphragmatic paresis may occur in up to 100% of patients undergoing ultrasound-guided interscalene brachial plexus block . In a stFascial plane blocks allow needle insertion and injection into two separate fascial layers, which permits the local anesthetic to spread to the nerves in that plane . Known tIn a systematic review and meta-analysis comparing pectoral nerve type 2 (PECS2) analgesic block to systemic analgesia alone and with a thoracic paravertebral block in breast cancer surgery , the primary endpoint was postoperative opioid consumption in the first 24 hours after surgery and secondary outcomes included pain scores at zero, three, six, nine, and 24 hours following surgery, time to first request for a pain reliever, and postoperative nausea and vomiting. Compared to systemic analgesia alone, the PECS2 block significantly reduced postoperative opioid consumption and decreased acute pain intensity at all time points in the first 24 hours. PECS2 and thoracic paravertebral block had similar opioid consumption after surgery and similar pain scores. Thus, PECS2 offered more effective analgesia to breast cancer patients than systemic analgesia alone and comparably effective analgesia with respect to a thoracic paravertebral block .In a retrospective cohort study of 79 patients who underwent erector spinae plane block for treatment of multiple rib fractures, pain scores were reduced from a mean of 7.7 to 4.7 in the first three hours p < 0.01), no changes were observed in the mean arterial blood pressure versus baseline, and incentive spirometry volumes improved from 784 to 1,375 ml (p < 0.01) over the first 24 hours with the block . Thus, p, no chanAn important consideration with any regional anesthesia is the duration of effect. Continuous catheterization can help sustain durable results but is limited to the ability to maintain the catheter in place. While the catheter is in place, continuous catheterization allows for flexibility in analgesia, prolonging the duration and increasing the intensity of pain relief as needed; it may also mitigate rebound pain. The main drawback to continuous catheterization is that insertions take time and precision, it may be complex to maintain throughout surgery, and it likely requires referral to acute pain care for follow-up . Other rModifiable risk factorsA prospective multicenter cohort study evaluated 2,929 patients undergoing inguinal hernia repair, hysterectomy , or thoracotomy, with the primary endpoint being the presence of CPOP at four months following surgery; CPOP was also measured at 12 and 24 months . In a meEarly mobilizationEarly mobilization is important to recovery and is only possible when good analgesia has been delivered. Knowing the value of early mobilizations, clinicians are better equipped to help improve perioperative patient status by enhancing the patient’s physical function, addressing their mental status, and relieving pre-existing pain. Note that long ago, patients and their families received little to no information about the perioperative process. Large scars, prolonged hospital stays, and pain medications given on an as-needed basis were not just the norm, but they were expected and accepted. Apart from simple breathing exercises, patients were more or less expected to stay in bed and passively await recovery. In the past decades, the paradigm has radically shifted. Today, patients and their families are expected to be active participants in care, to be informed about the operation, to share decision-making, and to understand the recovery process and its milestones. With these changes, faster recovery times, earlier discharges, and more ambulatory procedures have become the norm. Minimally invasive surgeries, regional analgesia, and multimodal pain control are increasingly common. Despite this major shift in caring for surgical patients, a study of 45 patients in a veterans’ hospital  with a mean hospital stay of 5.1 days found that patients spent, on average, 83% of their time in bed. The time they spent standing or walking ranged from 0.2% to 21% of the time for a mean of 43 minutes per day .Exercise before surgery has been found to be effective in reducing hospital length of stay and complication rates following cardiac surgery and this benefit appears most pronounced in vulnerable patients . ApproprThe Enhanced Recovery After Surgery (ERAS) protocol defines a multimodal course of evidence-based practices for perioperative patient care with the goal of improved outcomes. ERAS is a multidisciplinary approach and ERAS guidance has been published for specific surgeries . While eClinical pathwaysClinical pathways are process tools designed to help improve postoperative recovery and promote high-quality care. They have been created for specific surgical procedures and can be further tailored to the individual patient. When implemented, clinical pathways have been associated with significantly shorter hospital lengths of stay and fewer in-hospital complications . While bPrior to surgery, clinicians should provide preoperative patients with instructions about recovery, particularly in terms of ambulation, movement, and exercise. Take-home materials or videos can be very helpful, such as the “Prep Well” program from the United Kingdom with instructions on self-guided prehabilitation . These pThe benefits of prehabilitation and early mobilization can vary by type of surgery. Colorectal surgeries have been extensively evaluated and prehabilitation may be more effective than postoperative rehabilitation in restoring the patient’s baseline level of function . Those wTelehealth exercise programs using smartphone apps or other online technologies have allowed patients at home to benefit from supervised and monitored exercise programs . CliniciWhile early mobilization and postoperative exercise programs may be encouraged, there are numerous barriers that can prevent their use or minimize their effectiveness . Pain caPostoperative pain can itself be an impediment to postoperative rehabilitation; therefore, it is important to provide adequate pain treatment along with educational support to encourage rehabilitation. Patients should be informed about “good pain” and “bad pain” in the course of their rehabilitation and be encouraged to work through tolerable amounts of appropriate pain but to stop the program and alert the clinical team when pain signals something is wrong. Pain on movement needs to be adequately controlled to allow for appropriate exercise, but the pain should not be dulled to the point that the patient is unable to detect “bad pain” from overuse or improper movements. It is important to counsel patients that complete elimination of all postoperative pain may not be helpful (if it is even possible) because rehabilitation and early mobilization are crucial to recovery and they may require awareness of some level of pain. Also, patients should be made aware that "pain trajectory" is a natural process, and with therapy, we may help to speed up the process .Pain following surgery is normal, expected, and typically follows a predictable trajectory, but a subset of patients will develop CPOP. CPOP may be addressed by adequate perioperative analgesia, control of acute postoperative pain, and early ambulation, mobilization, and rehabilitation. The new paradigm for surgical patients regards patients and their families as active participants in care. Patient education, shared decision-making models, and early rehabilitation can help reduce hospital stays and speed recovery. It is important that acute postoperative pain be interrupted so it does not transition to CPOP, a condition that is more challenging to manage and may be associated with dysfunction and disability.


Several bone-seeking radionuclides have been developed for palliation of metastatic bone pain since 1956, however, so far radium-223 dichloride is the first and only Food and Drug Administration (FDA) approved targeted alpha therapy for metastatic castration-resistant prostate cancer (mCRPC) based on ALSYMPCA phase 3 study. While radium-223 does improve pain and overall survival outcomes, the improvement can come at the expense of side effects such as bone marrow toxicity. The development of new and better treatment with long-standing pain relief is clearly an unmet medical need.The study is a non-randomized phase II study. The study population consists of 25 patients with CRPC who had progressed on any lines of prior therapies and whose serum testosterone level is less than 50 ng/dl and have metastatic lesions to at least two bone sites, with at least one site that has clinically meaningful pain at baseline . Eligible patients will be given two cycles of Sn-117 m-DTPA every 8 weeks or 56 days. Treatment will be administered by slow IV injection over 5–10 min. Retreatment after two cycles is allowed if patients meet the following retreatment criteria. The primary objective is to evaluate the efficacy of Sn-117 m-DTPA on sustained pain response in patients with CRPC metastatic to at least two bone sites and at least one with clinically meaningful pain at baseline . Sustained pain response is defined as: 1) achieving pain index ≤ 3 within a 12-week period and 2) maintaining pain index ≤ 3 over a 16-week period. The secondary objectives are: safety and tolerability, measurement of Sn-117 m-DTPA activity by gamma-camera dosimetry scans, therapeutic efficacy, time to the first symptomatic skeletal event, duration of pain response, changes in PSA and ALP levels, patient-reported outcomes and progression free survival and overall survival.Sn-117 m-DTPA is a unique bone-targeting theranostic radiopharmaceutical agent that selectively binds most heavily to bone metastases sites. This study will be the first prospective phase II trial to assess the pain efficacy and anti-tumor activity of Sn-117 m-DTPA in mCRPC with at least one clinically meaningful pain at baseline.Trial registration.ClincialTrials.gov Identifier: NCT04616547. More than 80% of advanced prostate cancer patients develop bone metastases , and oftSeveral bone-seeking radionuclides have been developed for palliation of metastatic bone pain since 1956 –6. AmongSn-117 m-diethylenetriaminepentaacetic acid  is a radiopharmaceutical agent being developed for treatment of malignant bone metastases for any solid tumors including prostate, breast, and lung, starting in the 1980s by Srivastava and colleagues at Brookhaven National Laboratory . Sn-117 . studied the biokinetics and imaging characteristics of Sn-117 m-DTPA radioactivity in 17 patients with metastatic bone pain [A pilot study of 15 patients with painful skeletal metastases from myriad solid tumors evaluated treatment with Sn-117 m-DTPA at 71–143 mcCi/kg . Resultsone pain . Three done pain .In a phase 1/2 study, 47 patients with painful bone metastases from a variety of malignancies (including 30 patients with prostate cancer) were treated with five different levels of Sn-117 m-DTPA radioactivity . The dosCollectively, there is mounting evidence that Sn-117 m-DTPA has promising palliative efficacy with minimal toxicity. Thus, a focused evaluation of this agent in patients with bony metastases is urgently required. The primary objective is to evaluate the efficacy of Sn-117 m-DTPA on sustained pain response in patients with CRPC metastatic to at least two bone sites and at least one with clinically meaningful pain at baseline . Sustained pain response is defined as: 1) achieving pain index ≤ 3 within a 12-week period and 2) maintaining pain index ≤ 3 over a 16-week period.Secondary objectives include: 1) assessment of the safety and tolerability by Sn-117 m-DTPA per Common Terminology Criteria for Adverse Events (CTCAE) v.50; 2) measurement of Sn-117 m-DTPA activity by gamma-camera dosimetry scans  at 1 h, 4 h evaluation of the therapeutic efficacy of Sn-117 m-DTPA at 24 weeks as measured by Prostate Cancer Working Group 3 (PCWG3) criteria; 4) evaluation of time to the first symptomatic skeletal event defined as i) the first use of external-beam radiation therapy to relieve skeletal symptoms; ii) new symptomatic pathologic vertebral or nonvertebral bone fractures; iii) spinal cord compression; or iv) tumor-related orthopedic surgical intervention; 5) to evaluate the overall pain response rate at 24 weeks; 6) to evaluate the duration of pain response as defined from the time of improvement in pain response (pain index ≤ 3) until the pain recurs; 7) to measure changes and time to progression in serum prostate-specific antigen (PSA) and serum alkaline phosphatase (ALP) levels; 8) to assess patient-reported outcomes (PROs) and adverse events (AEs) (PRO-CTCAE) captured by digital instruments; 9) to evaluate progression-free survival (PFS) and overall survival (OS).The present study is a non-randomized phase II study. This study aims to compare the efficacy and safety of Sn-117 m-DTPA as a pain palliative agent in patients with symptomatic CRPC metastatic to at least two bone sites detected by 99Tc bone scintigraphy with at least one site with clinically meaningful pain at baseline . The efficacy and safety of Sn-117 m-DTPA will be evaluated, and the effect of therapy on pain palliation will be investigated. Ethics approval is obtained at central IRB. The trial is registered at clinicaltrial.gov (NCT04616547). The study schema is shown in Fig. The study population consists of 25 patients with CRPC who had progressed on any lines of prior therapies and whose serum testosterone level is less than 50 ng/dl and have metastatic lesions to at least two bone sites, with at least one site that chronicles clinically meaningful pain at baseline .Patients must have histologically or cytologically confirmed adenocarcinoma of the prostate that is castration-resistant, defined as: i) a castrate serum testosterone level ≤ 50 ng/dL or 1.7 nmol/L; ii) bilateral orchiectomy or maintenance on androgen ablation therapy with luteinizing hormone-releasing hormone (LHRH) or antiandrogen such as bicalutamide; androgen deprivation therapy needs to be maintained throughout the study unless a patient has had orchiectomy by surgery; iii) serum PSA progression defined as two consecutive increases in PSA over a previous reference value, each measurement at least 1 week apart.Progression after androgen receptor blockers  or androgen synthesis blockers (abiraterone acetate) or chemotherapy (docetaxel or cabazitaxel). There are no maximum number of prior therapies.Progressive castration-resistant prostate cancer with two or more skeletal metastases identified by Tc-99 m bone scintigraphy.Patients must have self-reported moderate to severe pain at trial entry .Patients must either currently employ regular  analgesic medication use for cancer-related bone pain or have undergone treatment with external beam radiation therapy for bone pain within 12 weeks before starting study treatment.Patients must not have visceral metastases (such as liver and lung) as assessed by abdominal/pelvic CT or chest X-ray within 12 weeks before starting study treatment.Patients must not have malignant lymphadenopathy exceeding 3 cm in short-axis diameter.Patients must not have imminent or established spinal cord compression based on clinical findings and/or MRI.Patients who have had chemotherapy, immunotherapy, or external radiotherapy within 4 weeks prior to entering the study are excluded.Patients must not have received systemic radiotherapy with radium-223, strontium-89, samarium-153, rhenium-186, or rhenium-188 for the treatment of bony metastases within 24 weeks before starting study treatment.Patients must not have unmanageable urinary incontinence.Patients must not have had known non-pathological bone fractures within 2 months before starting study treatment.Eligible patients will be given two cycles of Sn-117 m-DTPA every 8 weeks or 56 days Table . TreatmePatients will be instructed to maintain a high fluid intake (drink at least two to three quarts of fluid every 24 h) for 2 weeks after each Sn-117 m-DTPA treatment to minimize a concentrated radioactive excretion. In general, drinking alcoholic beverages should be kept to a minimum or avoided completely. Patients will be on hygiene instruction/precautions on post-therapy treatment.Patients will be followed every 2 weeks during treatment period (16 weeks), then every 4 weeks until week 28, and then every 3 months or as clinically indicated for 12 months after the first Sn-117 m-DTPA dose or until death, whichever occurs first. After a 1-year follow-up period, dates of death will be collected for all patients until the final patient completes his 1-year follow-up. Patients removed from study for unacceptable adverse event will be followed until resolution or stabilization of the adverse event. The following investigations should be performed at every follow-up visit: 1) pain medication; 2) patient-reported pain intensity scale and analgesic use; 3) patient-reported CTCAE; 4) urine collection for urinalysis; 5) PSA; 6) CBD with diff and serum chemistry. (Table The study coordinator and investigators will monitor adherence by reviewing questionnaires via electronic or paper. Patient-derived information obtained will include: 1); a pain intensity scale Fig. ; analgesBoth narcotic and non-narcotic analgesic use and pain intensity scales will be captured using pain score and analgesic log electronically or a paper format.The Sn-117 m-DTPA palliative pain effect will be measured by using a pain index as described in the Table This pain index is derived from a combination of the following 11-piont pain intensity scale and analgesic consumption categorized according to the World Health Organization analgesic ladder.Pain at baseline and analgesic use  will be measured via serial (daily) assessments in a 7-day run-in period. Patients will be considered evaluable if they complete assessments on ≥ 4 days within the 7-day run-in period. During treatment, pain and analgesic use will be measured every 2 weeks through week 28, followed by routine clinic follow-up until 1 year or when patients experience new pain. Complete pain assessments via the full BPI-SF will be collected at baseline, after cycle1, after cycle2, and at week 28. Pain assessments will be halted at the patient’s request or if the patient discontinues study treatment for reasons other than disease progression.This is a single-arm, open-label phase 2 study to evaluate the efficacy of Sn-117 m-DTPA on sustained pain response in patients with CRPC metastatic to at least two bone sites. Sustained pain-response is defined as: 1) achieving pain index ≤ 3 within a 12-week period and 2) maintaining that pain index ≤ 3 over a 16-week time period . The maximum duration of follow-up required to declare a patient a responder is 28 weeks, representing a patient who initially achieves pain index ≤ 3 toward the end of the 12-week period and is followed for an additional 16 weeks to confirm maintenance of pain index ≤ 3.Eligible patients will be assigned to receive Sn-117 m-DTPA at 20 mCi/70 kg (0.28 mCi/kg) every 8 weeks for two cycles. The study utilizes a mini-max Simon two-stage design to assess anti-tumor activity and pain benefit of Sn-117 m-DTPA.0 = 0.1 and the alternative hypothesis is p1 = 0.3. The literature on sustained pain-relieving benefit with radiopharmaceutical drugs in prostate cancer with bone metastases is limited. Nilsson et al. studied the dose–response relationship and pain-relieving effect of radium-223 [The sustained pain response rate under null hypothesis is pdium-223 . Pain reThe efficacy of the primary endpoint will also be summarized by the point estimation of the overall response rate with the corresponding 95% confidence intervals. Patients who received any amount of study drug will be included in the denominator for the calculation of ORR.Post-hoc analysis on PSA and ALP levels may be conducted to explore possible trends in PSA and ALP levels. Time to the first symptomatic skeletal event will be analyzed using the Kaplan–Meier method. Estimation and confidence intervals for the median time to first symptomatic skeletal event will be provided. Patients who did not have a symptomatic skeletal event will be censored at the last study visit. Progression free survival will be analyzed in a similar manner as the time to first skeletal event. Patients who did not have observed clinical progression will be censored at the last assessment.Secondary endpoints will be summarized depending on data type. Categorical endpoints will be summarized by frequency and percent. Continuous variables will be summarized by mean and standard deviation at each assessment time point. Time-to-event endpoints will be summarized by Kaplan–Meier Methods. Safety and toxicity will be assessed through the frequency and percent of AEs, serious adverse events (SAEs), and adverse events of special interests. Toxicity will be assessed by clinical staff using  captured by digital instruments during treatment and 8 weeks after the last injection to monitor for acute toxicity and every 2–4 weeks for 6 months post-therapy for monitoring of long-term toxicity. CTCAE grades for the corresponding time period will be presented in conjunction with PRO-CTCAE scores. PSA and ALP response rates will be calculated for each of the above defined categories with the corresponding confidence intervals. Grade 3 or higher renal and genitourinary AEs will be reported as expedited AEs, including but not limited to: 1) renal failure  suspected radiation nephropathy of any type, such as radiation-induced thrombotic microangiopathy, manifesting as proteinuria, hypertension, edema, anemia and decreased serum haptoglobin; 3) general symptoms and signs of acute radiation toxicity, such as increased frequency/urgency of urination, nocturia, dysuria, bladder spasm, bladder obstruction, genitourinary ulceration of necrosis; 4) grade 3 or higher bone marrow toxicities will also be reported as expedited AEs.Medidata Rave is a clinical data management system being used for data collection for this study. Access to the trial in Rave is controlled through the CTEP-IAM system and role assignments. All data will be monitored by the Clinical Trials Monitoring Service (CTMS). Data will be submitted to CTMS at least once every two weeks via Medidata Rave. Onsite audits will be conducted by the CTMS. The PI, investigators and statistician will have access to all the data for analysis.Sn-117 m-DTPA is a unique bone-targeting theranostic radiopharmaceutical agent, that selectively binds most heavily to bone metastases sites. Unlike Radium-223, an alpha-emitter, Sn-117 m-DTPA releases mono-energetic conversion electrons of ~ 140 keV discrete energy for therapy with an average range of ~ 300 µm in tissue penetrance. Therefore, Sn-117 m-DTPA effectively treats only the targeted tissue and reduces the external radiation hazard. Like Radium-223, it yields gamma emission (159 keV) similar to Tc-99 m (140 keV) allowing for existing standard gamma camera imaging and techniques. Biodistribution of Sn-117 m-DTPA in animal models indicates high uptake in cortical bone, and approximately tenfold more radioactivity than in bone marrow. Thus, it appears to have less bone marrow toxicity compared to Radium-223. Sn-117 m-DTPA has a slightly longer half-life (14.5 days) and thus it can be given every 8 weeks.The previous phase 1/2 dose-ranging study evaluated the effects of Sn-117 m-DTPA administration on pain relief using daily 5-point numeric pain rating scales in all solid tumors after one injection , 21. AboThis study will be the first prospective phase II trial to assess the pain efficacy and anti-tumor activity of Sn-117 m-DTPA in metastatic castration resistant prostate cancer with at least one clinically meaningful pain at baseline.