Myofascial pain syndrome (MPS) is one of the most common causes of chronic skeletal muscle pain, which is closely related to skeletal muscle myofascial trigger point (MTRP). Since there is no first-line treatment for MPS, we investigated Loxoprofen Sodium Cataplasm combined with physiotherapy as a non-invasive therapy in patients at different levels to a protocol with superior efficacy that is safe and easy to promote. Moreover, this treatment could represent an alternative therapeutic strategy for low-income patients to a safer, more convenient, and more economical treatment scheme.A randomized clinical study was aimed at evaluating the safety and efficacy of Loxoprofen Sodium Cataplasm combined with physiotherapy in patients diagnosed with MPS in the pain clinic. We screened 100 patients with MPS, and using a computer-generated random allocation sequence, we stratified patients in a ratio of 2:1:1:1 (A: B: C: D) to one of the four treatment groups. Group A received Loxoprofen Sodium Cataplasm combined with extracorporeal shock wave therapy (ESWT) and transcutaneous electrical nerve stimulation (TENS). Group B received Loxoprofen Sodium Cataplasm alone. Group C received physiotherapy alone. Group D received Flurbiprofen Cataplasm combined with physiotherapy. After 2 weeks of treatment, the overall efficiency and secondary assessment indicators, including visual analog scale (VAS) scores, chronic soft tissue injury (CSTI) scores, Oswestry Disability Index (ODI) scores, or Northwick Park Neck Pain Questionnaire (NPQ) scores, were evaluated before and after treatment to analyze the difference in efficacy of each group.P = 0.0078) were observed in subjects of groups A and C.All groups were well tolerated with no reported adverse events. Significant treatment differences in the change from baseline in overall efficiency (primary efficacy endpoint) . Myofascial pain syndrome (MPS) is one of the most common causes of chronic musculoskeletal pain. The main symptoms are asymmetric pain at the trigger point, local or systemic, and even some patients have symptoms of autonomic dysfunction, including flushing, lacrimation, dermatographia, diaphoresis, goose rash, and dizziness , 2. TherMyofascial pain syndrome has a huge patient population, with a prevalence of up to 55–90% in pain clinics, and is prone to recurrence after treatment , 17, 18,Currently, topical analgesics such as Loxoprofen Sodium Cataplasm, Flurbiprofen Cataplasm, and Compound Methyl Salicylate Cataplasm are often used in the treatment of MPS in pain clinics. Physical therapy such as ESWT/TENS is also used. There is also a combination of the two treatment options, but there is no clear and more effective treatment.Therefore, this study used the visual analog scale (VAS) scores, Oswestry Disability Index (ODI) scores, and NPQ scores as evaluation indicators to explore the efficacy and safety of different regimens in the treatment of MPS and to provide a safer, more effective, more convenient, and less expensive treatment plan for the treatment of MPS.www.chictr.org.cn/ with the following number: ChiCTR2100054756.From 1 August 2021, to 31 December 2021, outpatients in the Pain Department of the Third Xiangya Hospital of Central South University aged 18–75 years were screened and diagnosed with MPS according to diagnostic criteria . After eGroup A received Loxoprofen Sodium Cataplasm combined with physiotherapy, and 40 patients were planned to be included. Physiotherapy used extracorporeal shock wave therapy (ESWT) and TENS. Group B received Loxoprofen Sodium Cataplasm alone, and 20 patients were planned to be included. Group C received physiotherapy alone, and 20 patients were planned to be included. Group D received Flurbiprofen Cataplasm combined with physiotherapy, and 20 patients were planned to be included.2, and 15 mm treating head diameter to the trigger point and its vicinities. The parameters of TENS were 100 Hz, pulse duration (width) of 250 μs, and treatment for 15 min. Patients in groups A, C, and D were treated with the same model, operated by the same physician, in the Pain Department of the Third Xiangya Hospital of Central South University. In addition, health education was provided to each enrolled patient, including moderate exercise, attention to the intensity of work, and correction of poor posture.In groups A, B, and D, the method of external drug use is 1 cataplasm once per day, stick to the painful area; each application exists 12 h to 24 h; and the course of treatment is 2 weeks. In groups A, C, and D, physiotherapy consisted of ESWT and TENS, once a week, with a total of two times, i.e., on the day of enrollment and 1 week after enrollment, and no topical drug was used on the day of treatment. The frequency of physiotherapy was once a week, the same as described by Kiraly et al. .The paraMain evaluation indicators are total effective rate: the VAS-weighted value was used to determine the curative effect, i.e., VAS-weighted value = (VAS scores before treatment-VAS scores after treatment)/VAS scores before treatment × 100%; recover: VAS weighted 75–100%; evident: VAS weighted 50–75%; effective: VAS weighted 25–50%; effectless: VAS weighted <25%.Secondary evaluation indicators are (1) VAS scores, (2) chronic soft tissue injury (CSTI) scores, and (3) ODI scores or NPQ scores. The VAS scores range from 0 to 10, and are based on self-reporting with the VAS; lower scores indicate less pain. The CSTI score covers the degree of pain, the size of palpation of the taut band and/or nodule, and the functional status; lower scores indicate less pain, smaller taut band or nodule, and better functional status. The ODI assesses the change in the functional status of adults with low back pain. The ODI contains ten pain-related questions scored from zero (no pain) to five (most severe pain). Scores are expressed as a percentage of total points; lower scores indicate better functional status . The Nor2 tests , and non-parametric tests (Mann–Whitney U test) were used to compare differences in clinical symptom improvement rates and patient compliance between groups. Analyses were performed using IBM SPSS Statistics 24 (version 24.0.0.0) at a significance level of P < 0.05.Differences in overall efficiency were compared using χWe included a total of 94 patients, including 34 in group A, 21 in group B, 19 in group C, and 20 in group D; the flowchart of patient grouping is shown in P > 0.999, P = 0.7657), which was not statistically significant. There were significant differences between group A vs. group C, and group B vs. group C , with statistical significance. It is suggested that the combination of Loxoprofen Sodium Cataplasm and physiotherapy or Loxoprofen Sodium Cataplasm alone is better than physiotherapy alone.As shown in P > 0.05).As shown in As shown in P > 0.05). All groups have an obvious curative effect. As shown in P = 0.0145, P = 0.0005); there were significant differences in CSTI scores in group B vs. group C before and after treatment (P = 0.0280).The results show that, as shown in As shown in There are various treatment options for MPS, but there is still no optimal one . To summWe found that after 2 weeks of treatment, the different non-invasive treatment regimens were effective in terms of overall efficiency and evaluation of secondary indicators. There was no difference in the overall efficiency between group A, group B, and group D. Group C, the physiotherapy group, has a lower overall efficiency, which suggested that physiotherapy was not suitable for the clinical treatment of MPS alone. In addition, we found that there was no significant difference in the overall efficiency between group A and group B, indicating that after the external application of Loxoprofen Sodium Cataplasm, even combined ESWT and TENS would not significantly improve the overall efficiency of the treatment. This may suggest that the pain of MPS can be effectively relieved after the Loxoprofen Sodium Cataplasm is applied alone. Whether the Flurbiprofen Cataplasm alone can achieve the same effect remains to be further studied.When analyzing secondary indicators for intragroup comparison, we found consistent and significant improvements in VAS scores, CSTI scores, ODI scores, and NPQ scores after loxoprofen, with or without physical therapy. With physiotherapy alone, only one secondary indicator, VAS scores, was improved, which did not relieve soft tissue injury and limitations in daily life. In addition, the Flurbiprofen Cataplasm combined with the physiotherapy group showed effectiveness in pain, CSTI, and neck and shoulder pain, but the improvement of ODI scores was not significant, suggesting that this regimen is not suitable for patients with back pain. In addition, when comparing between groups, we found that Loxoprofen Sodium Cataplasm combined with physiotherapy significantly improved CSTI and VAS scores compared with physical therapy alone, and Loxoprofen Sodium Cataplasm alone was associated with significant improvements in CSTI scores, which shows that Loxoprofen Sodium Cataplasm has a significant therapeutic effect on MPS, and a single application can significantly improve the quality of daily life of patients, which is helpful for patients' work and life.To further analyze the efficacy of Loxoprofen Sodium Cataplasm alone and Loxoprofen Sodium Cataplasm combined with physiotherapy on MPS patients with different pain sites, we conducted intragroup comparisons of secondary evaluation indicators for patients with different pain sites in the two regimens. We found that compared with before treatment, Loxoprofen Sodium Cataplasm improved the secondary evaluation indicators in patients with back pain with or without combined physiotherapy. The possible reason is that the efficacy of ESWT and TENS physical therapy is dose-dependent , 25, andThis study has several limitations. First of all, although outpatients have been guided by doctors on daily-related precautions and exercise methods after patients leave the outpatient clinic, their exercise and rehabilitation cannot be objectively evaluated. We did not perform a systematic neurological examination of the patients, such as EMG or MRC scales. Especially in patients with MPS in the neck and shoulders, when the pain occurs, the activities of the neck and shoulders are limited. After ESWT and TENS treatment, the immediate improvement effect is obvious . The incLoxoprofen Sodium Cataplasm combined with physiotherapy can help relieve pain in patients with MPS, improve CSTI, and facilitate the recovery of patients' daily life functions. The treatment regimen in the control group has certain advantages.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by the Clinical Trial Ethics Committee of the Third Xiangya Hospital of Central South University (No. 21136). The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.ZW conceived and designed the experiments. XZ and XL wrote the paper. ZW and XL interpreted and analyzed the data. ZW, XZ, and XL performed the experiments and acquired the data. XL performed the statistical analysis. ZW and DH had full access to all the data in the study and had final responsibility for the decision to submit it for publication. All authors stated were involved in the critical revision of the manuscript and approved the final version of the article, including the authorship list.This study was supported by Hunan Jiudian Pharmaceutical Co., Ltd. which made the Loxoprofen Sodium Cataplasm available to the investigators. Funders of the study had no role in study design, data analysis, data interpretation, or writing of the report.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. 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This cross-sectional study aims to find the prevalence of chronic pain and its correlation with the quality of life and vitamin D levels among hemodialysis patients in Palestine. We used the brief pain inventory, the medical outcomes study 36-item short-form health survey, and Serum 25-hydroxyvitamin D to assess chronic pain, quality of life, and vitamin D levels, respectively. The study included 200 patients, 38.1%  of whom had chronic pain, and 77.7%  had deficient Vitamin D levels. Quality of life scores were generally low, with the lowest in role emotional and physical functioning. Sex, comorbidities, and vitamin D level significantly correlate with pain severity. Employment, number of comorbidities, pain severity, and albumin level are significantly associated with the Physical component of quality of life. On the other hand, employment and pain severity are significantly related to the mental component of quality of life. In conclusion, low vitamin D levels, chronic pain, and low quality of life scores are common among hemodialysis patients. In addition, vitamin D is negatively correlated with pain severity. Therefore, healthcare workers should assess and manage hemodialysis patients' chronic pain to improve their quality of life and reduce suffering. End-stage kidney disease (ESKD), the last stage of CKD, is an estimated glomerular filtration rate of less than 15 mL per minute per 1.73 m2 body surface area or those requiring dialysis2. The current management of ESKD is renal replacement therapy, either by dialysis or transplantation3. Saving the lives of ESKD patients is very important, and dialysis has succeeded in doing so, but maintaining a high quality of life (QoL) is also essential. Patient's quality of life may be impacted by hemodialysis due to its chronic nature, frequency, and the fact that most suffer from additional conditions that make them reliant on others. Quality of life, a general term for well-being, covers many aspects of individual life, including wealth, employment, environment, physical and mental health, and religious beliefs. The concept of health-related quality of life (HRQoL) has been used to correlate a people's health status to their QoL. It has been investigated among hemodialysis patients, and some determinants have been proposed, with the majority of scores indicating that it is decreased in these patients4. Demographic characteristics , and clinical and laboratory characteristics  have been found to correlate with HRQoL in hemodialysis patients5.Chronic kidney disease (CKD) is a common disabling disease with a prevalence of approximately 700 million people worldwide6. In contrast, the prevalence of chronic pain in the general adult population with or without kidney problems in the US was 20%7. Chronic pain could limit the daily activities of hemodialysis patients and affect their QoL8. Some social, clinical, and laboratory factors have been suggested as chronic pain determinants, including age, educational level, employment, body mass index and comorbidities, hemoglobin, and vitamin D9.Pain is a common complaint among hemodialysis patients. Recent studies show that about 33%-82% of hemodialysis patients report chronic pain10, is an emerging worldwide problem in the general population11. In particular, ESKD patients are at high risk of vitamin D deficiency, with some studies finding the prevalence was 80%12. Furthermore, the role of vitamin D in chronic pain has been reported in some literature13. Again, its relation with QoL has been studied with controversial results; some noted that QoL's physical and mental components are affected, but others found that only the mental component is affected15.Vitamin D is a lipid-soluble vitamin that can be taken from the diet or synthesized in the skin and converted into its active form by a two-step process in the liver 25-hydroxylation and kidney 1-hydroxylation. Vitamin D deficiency, defined as the level of 25-hydroxyvitamin D (< 20 ng/mL)16. Given the Palestinians' difficult living conditions and the unique circumstances of ESKD patients, we anticipated their QoL would be severely impacted. Some studies have investigated the QoL and its relation to chronic pain17. However, the role of vitamin D deficiency in chronic pain and QoL is still under-assessed.In the Occupied Palestinian Territories, hemodialysis patients have increased in the last few years. The prevalence of vitamin D deficiency among hemodialysis patients was found to be approximately 87%In the last decades, the mortality among ESKD patients has decreased at the expense of their QoL. However, efforts are still being made to know the possible determinants of QoL for these patients and how to improve it. Therefore, this study aimed to assess the Vitamin D level of Palestinian hemodialysis patients and correlate it with their chronic pain and quality of life.This cross-sectional study was conducted between October 2021 to February 2022 at the hemodialysis unit of An-Najah National University Hospital, Palestine. It is the region's largest dialysis center, receiving referred patients from the entire North West Bank of Palestine, with over 300 patients currently undergoing chronic hemodialysis. We included patients who were over the age of 18 and had been on hemodialysis for more than six months. Those who were critically ill, had cognitive dysfunction, or refused to complete the questionnaire or provide informed consent were excluded.The sample size was calculated as n = [DEFF*Np (1 − p)]/ . All procedures performed in this study have been carried out following the Declaration of Helsinki and relevant national guidelines and regulations. Patients were invited to participate in the study voluntarily after explaining the goal, objectives, and risk of involvement. No identifying information was collected, and patients were referred to as codes. Access to collected data was restricted to the study team and was used solely for research purposes. Informed consent was obtained from all patients.10.Demographic, clinical, and laboratory data were collected from the patient's medical records. This included age, sex, body mass index, living arrangement, residency, marital status, educational level, employment status, income, smoking habits, dialysis duration, comorbidities , pain severity and its duration. The laboratory parameters were vitamin D level, parathyroid hormone, alkaline phosphatase, phosphorus, calcium, albumin, ferritin, and hemoglobin. In addition, serum 25-hydroxyvitamin D was measured at the beginning of the data collection period using the Elecsys vitamin D total test. Patients were classified as vitamin D deficient if their 25-hydroxyvitamin D level was less than 20 ng/ml and nondeficient if it was equal to or greater than 20 ng/ml18. Additionally, we computed Cronbach's alpha to determine the internal consistency of our tool, which was 0.91, suggesting excellent reliability.We used the brief pain inventory (BPI) scale to measure pain intensity and asked about the duration of pain. We considered pain for more than three months as chronic pain. The BPI, a widely used, valid, and reliable tool, is divided into two sections: one for pain intensity and one for pain interference with everyday activities. The pain severity scale was employed to determine the severity of the pain. It consists of four questions: worst, least, average, and current pain, each rated from 0 (no pain) to 10 (worst pain), with the mean of these four questions indicating the pain severity. Pain interference of daily activity scored as the mean of seven items . The pain was classified as mild (1–4 points), moderate (5–6 points), or severe (7–10 points). The Arabic version of the BPI was found to be reliable and valid for usage among Arabic-speaking patients19. In our study, Cronbach's alpha for PCS was 0.91 and for the MCS was 0.89, indicating excellent reliability. Before the beginning of the study, we conducted a pilot study of 15 patients to pretest the questionnaire and standardize the data collection method.The medical outcome study 36-item short-form health survey (SF-36) was used to assess the HRQoL. The SF-36 questionnaire assesses eight dimensions of HRQoL, yielding two summary measures: physical and mental health. The Physical Component Summary (PCS) includes four dimensions: physical functioning (10 questions), physical role (4 questions), bodily pain (2 questions), and general health (5 questions). The Mental Component Summary (MCS) includes four dimensions: vitality (3 questions), social functioning (4 questions), role emotional (5 questions), and mental health (2 questions)). The final question, self-reported health transition, is answered by the patients but not counted in the scoring process. The score of each dimension ranges from 0 to 100, with a higher score indicating better health. PCS and MCS scores are expressed by either the sum or the average of dimensions. The SF-36 has proven its reliability and validityWe conducted data entry, cleaning, and statistical analysis using IBM SPSS Statistics for Windows, version 21 . Descriptive analysis was used to describe the characteristics of patients using frequencies and percentages for categorical variables, mean ± standard deviation (SD) or medians, and interquartile ranges for continuous data. We used Cronbach’s alpha to check for the reliability of the used scales. The normality of the data was checked using the Kolmogorov–Smirnov test. We used the Mann–Whitney U and Kruskal-Walis tests to examine whether demographic and clinical variables are associated with MCS, PCS, and pain severity scale. Also, we used the Spearman correlation coefficient to test the correlation between patients’ Laboratory characteristics and their scores on the used scales. A multiple linear regression analysis model was used to determine the factors independently associated with QoL. All variables that demonstrated a significant relationship with pain and QoL in bivariate analysis were included in the model. A P-value of less than 0.05 was accepted as significant.The study enrolled 200 hemodialysis patients, of whom 65% were males, and 54% were under the age of 60 years. A large proportion of the patients (79.9%) had only completed high school or below, 83% were unemployed, and 39.7% were smokers. A large number of patients (72.2%) have more than two years of dialysis. The number of comorbidities varies among patients, with 33% having more than four comorbidities. The results showed that 38.1%  31.3–45.4%) of hemodialysis patients had chronic pain, and 77.7% (95% CI 71.0–83.4%) had Vitamin D deficiency , while the lowest was found in both role emotional (41.9 ± 45.9) and physical functioning (42.1 ± 32.3).We conducted a bivariate analysis to find the possible factors related to pain severity and QoL main domains. Age and the number of comorbidities were related to pain severity, with a p-value equal to 0.037 and 0.003 for each, respectively. Sex, educational level, employment, number of comorbidities, duration of dialysis, and pain severity are significantly related to the PCS component of QoL. On the other hand, educational level, employment, number of comorbidities, duration of dialysis, and pain severity are significantly related to the MCS component of QoL Table .Table 2PFurthermore, we conducted a bivariate analysis to identify potential laboratory factors correlated with pain severity and QoL. The results showed that alkaline phosphatase, phosphorous, albumin, and vitamin D are significantly correlated with the PCS component of QoL. On the other hand, only alkaline phosphatase is significantly correlated with the MCS component Table .Table 3CMultiple linear regression was run to find factors independently associated with pain severity and the QoL Table . After a22, indicating that the QoL in hemodialysis patients is lower than in the general population4. Additionally, the QoL was progressively impaired across the five CKD stages5. These findings could be attributed to the chronic nature of hemodialysis and possibly the patients' reliance on others, which affects them psychologically and their physical disease. This highlights the importance of developing methods for regular assessment and improvement of QoL.The present study showed low QoL scores, averaging 41.4 ± 21.1 for the PCS domain and 54 ± 24.4 for the MCS domain. This is consistent with previous studies17. Others found no significant association24. Being employed allows hemodialysis patients to improve their social life and be more physically active, which may improve their QoL.Many studies have been conducted to find the factors that may affect QoL in hemodialysis patients. In the multivariate analysis, we found that employment, number of comorbidities, albumin level, and pain severity are all significantly related to QoL. Employment had a statistically significant positive effect on both PCS and MCS scores, similar to Samoudi AF et al.17. However, no association was found in studies conducted in Ethiopia and China20. Comorbidities exacerbate complications, resulting in increased patient complaints and decreased QoL.Furthermore, PCS was associated with increased comorbidities in this study, similar to a previous study in Palestine23. Protein-energy wasting may impair physical functioning in hemodialysis patients, so albumin levels may help assess those patients. On the other hand, we found that advanced age and income did not affect QoL, in contrast to other studies24. In many countries, ESKD patients are responsible for paying all or a portion of their dialysis treatment costs on their own, whereas hemodialysis patients in Palestine are provided with all health services for free; thus, income may appear to have a less impact on hemodialysis patients' QoL.Albumin levels correlated positively with PCS in this study. The same association was found in another research20. However, a systemic review and a previous study in Palestine reported a higher prevalence of chronic pain, 60.5% and 66.3%, respectively25. This difference could be due to different sample sizes or differences in pain perception among different cultures. Nevertheless, this indicates that pain is a prevalent complaint among hemodialysis patients and should be assessed routinely during their follow-up care.In our study, more than one-third of hemodialysis patients have chronic pain, similar to the prevalence in a Chinese study17. However, others found no association between pain severity and QoL20. Chronic pain patients often have physical limitations that make it more difficult for them to engage in daily activities and social interactions than healthy people, lowering their QoL. Furthermore, they occasionally deal with comorbid conditions such as anxiety, depression, and sleep problems, which reduce their QoL. This highlights the need for greater attention to pain and an early management protocol to reduce its possible negative effect on QoL.Among the pain group, the median pain severity was 4.75, classified as moderate severity according to the BPI scale. Furthermore, we found that the severity of pain was negatively correlated with PCS and MCS scores in multiple regression analysis, which is consistent with the findings of other studies26. Pain sensitivity is suggested to be higher in females, and their response to pain management could be lower27. Also, higher rates of depression and stress among females could be a contributing factor28. An increasing number of comorbidities is usually accompanied by increasing disease complications and patient suffering, which can be reflected as somatic pain. Our study shows a positive correlation between the number of comorbidities and pain severity; these results align with other literature29.Awareness of factors affecting chronic pain and its severity may facilitate pain management. Females have a higher pain severity than males in this study which is consistent with other studies16.Vitamin D is a fat-soluble vitamin obtained primarily through sunlight-induced skin synthesis, with the remainder obtained through diet. The kidney is essential for vitamin D metabolism. Patients with ESKD are at increased risk for vitamin D deficiency because they frequently lack access to sunlight and adequate nutrition, and their impaired kidneys inefficiently reabsorb 25-hydroxyvitamin D. The prevalence of Vitamin D deficiency in our group is 77.7%, which is similar to the literature30. Another study suggests a potential interaction between vitamin D and its receptors with pain signaling genes and pathways; Vitamin D receptors have been identified in the brain, spinal cord, and dorsal sensory ganglia31. Our findings revealed a negative correlation between pain severity and vitamin D level, consistent with the results of a previous study13, whereas another study found a marginal correlation32.Vitamin D is essential for musculoskeletal function because it aids in bone formation, maintenance, remodeling, and muscle protein synthesis. A lack of vitamin D increases bone resorption, resulting in osteomalacia, characterized by bone pain and muscle weakness, gait instability, recurrent falls, and fractures33. Additionally, vitamin D deficiency has been linked to CKD progression and increases morbidity and mortality in CKD and hemodialysis patients, potentially affecting QoL35. The role of vitamin D in QoL has been investigated here, but no significant correlation was found. In contrast, one study demonstrated the significance of vitamin D levels on PCS and MCS scores14, while another found the significance on MCS only15. The difference in measurement tools could explain this controversy, emphasizing the need for more research to clarify the possible relationship between vitamin D and QoL.On the other hand, some researchers suggest that vitamin D may play a role in neuropsychiatric function. For instance, people with low levels of 25-hydroxyvitamin D commonly have depression and score poorly on the mini-mental state test36. However, the evidence is still weak and needs more randomized control trials to put general recommendations about vitamin D supplementation. This study paves the way for additional investigation into whether vitamin D supplementation alleviates pain in these patients so that it might be routinely utilized in pain management.Some interventional studies demonstrated the possible beneficial effect of vitamin D supplementation among vitamin D deficient people in contrast to vitamin D sufficient people who showed no improvement in painThis study has possible limitations. First, the cross-sectional study design limits the ability to suggest causality between related variables. Second, the results should be cautiously generalized because the study was conducted at a single clinical center. Thirdly, we did not gather information on certain psychosocial factors that may influence pain perception and QoL. Lastly, the quantitative nature of the data prevented a complete explanation of the reasons for the low quality of life from the patient's point of view, which would have been better revealed through in-depth interviews or focus group discussions.In conclusion, our study demonstrated that low vitamin D levels and chronic pain are common among hemodialysis patients. Vitamin D level is negatively correlated with pain severity. Lower QoL scores were found in hemodialysis patients and found to be significantly related to unemployment, comorbidities, severe pain, and low level of albumin. Healthcare workers should devote more time to assessing and managing chronic pain in hemodialysis patients to improve their QoL and reduce their suffering. Further studies should be conducted to investigate more determinants of chronic pain and QoL, ways to assess and manage chronic pain and study the effect of some supplementations like Vitamin D on chronic pain and QoL.


Diabetic peripheral neuropathic pain (DPNP) is a prevalent chronic complication in patients with diabetes. Using a questionnaire is helpful for DPNP screening in outpatients. In this retrospective cohort, we aimed to examine whether DPNP diagnosed based on scoring questionnaires could predict long-term mortality in outpatients with type 2 diabetes.We enrolled 2318 patients who had joined the diabetes pay-for-performance program and completed the annual assessments, including both the identification pain questionnaire (ID pain) and Douleur Neuropathique en 4 questionnaire (DN4), between January 2013 and October 2013. Information on registered deaths was collected up to August 2019.r = 0.935, P < 0.001). During the median follow-up of 6.2 years (interquartile range: 5.9−6.4 years), 312 patients deceased. Patients with an ID pain score of ≥ 2 had a higher mortality risk than those with a score of < 2 , and patients with a DN4 score of ≥ 4 had a higher mortality risk than those with a score of < 4 . Patients consistently diagnosed with DPNP by the ID pain and DN4 had a significantly higher mortality risk , but not those discrepantly diagnosed with DPNP (P = 0.107), as compared with those without DPNP.There was high consistency in the scores between the ID pain and DN4 (Both the ID pain and DN4 for DPNP screening were predictive of long-term mortality in patients with type 2 diabetes. However, a discrepancy in the diagnosis of DPNP weakened the power of mortality prediction. Diabetic peripheral neuropathy (DPN) is the presence of peripheral nerve dysfunction in patients with diabetes after the exclusion of other causes , 2. DPN DPN is a heterogeneous group of disorders with diverse clinical manifestations . More thIt was reported that DPN diagnosed based on low signal amplitude and slow conduction velocity in a nerve conduction study is associated with total mortality in patients with type 2 diabetes . DPN diaThis retrospective cohort study was conducted at Taichung Veterans General Hospital. The inclusion criteria were [1] adult patients who had joined the diabetes pay-for-performance program and [2] patients who had completed both the ID pain and DN4 for DPNP screening between January 2013 and October 2013. The exclusion criteria were [1] end-stage renal disease; [2] an open wound or amputation of the lower extremities; [3] diabetes other than type 2; [4] malignancy, psychiatric disorders, current use of any pain medication involving the central nervous system, other severe systemic diseases, or pregnancy; and [5] other conditions unsuitable for the study.The diabetes pay-for-performance program is an important health policy for clinical diabetic care . PatientThe six items of ID pain were reported by patients themselves: each item was scored 0 when a participant answered “no”. Items 1−5 received a score of 1 when a participant answered “yes”, and Item 6 received a score of -1 when a participant answered “yes” . The totFurthermore, laboratory data, including plasma glucose, glycated hemoglobin (HbA1c), serum levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and creatinine, and urinary levels of albumin and creatinine, were collected during the annual comprehensive survey. Information on the use of antidiabetic drugs, antihypertensive drugs, antiplatelet drugs, and statins was also collected.-0.411 × 0.993age (year) in men with serum creatinine ≤ 0.9 mg/dL; 141 × (serum creatinine [mg/dL]/0.9)-1.209 × 0.993age (year) in men with serum creatinine > 0.9 mg/dL; 144 × (serum creatinine [mg/dL]/0.7)-0.329 × 0.993age (year) in women with serum creatinine ≤ 0.7 mg/dL; or 144 × (serum creatinine [mg/dL]/0.9)-1.209 × 0.993age (year) in women with serum creatinine > 0.7 mg/dL . HbA1c levels were determined by cation-exchange high performance liquid chromatography . Serum concentrations of total cholesterol, HDL cholesterol, and triglycerides were determined using enzymatic methods . Creatinine levels were determined using the Jaffé method . Urinary albumin was determined using the polyethylene glycol enhanced immunoturbidimetric method . The estimated glomerular filtration rate (eGFR) was calculated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation as follows: 141 × (serum creatinine [mg/dL]/0.9).7 mg/dL , 27. CKDmg/dL (2 . The urimg/dL (2 . HyperteWe present the mean ± standard deviation (SD) for continuous variables and numbers with percentages (%) for categorical data. The clinical variables were tested for statistically significant differences using Student’s t test for continuous variables between two groups, and the χ2 test for categorical variables. The relationship between the scores of the questionnaires was determined by Pearson’s correlation.r] = 0.870, P < 0.001) and DN4 score  were observed between the first and second measurements. The 95% confidence intervals (CIs) were 0.078 ± 0.158 for the bias of the ID pain and 0.020 ± 0.221 for the DN4 between repeated measurements based on Bland-Altman plots (The reproducibility of the ID pain and DN4 was examined in a group of 51 subjects by repeated assessments on different days. The median period between repeated measurements was 161 days (interquartile range [IQR] between 112 and 252 days). Highly positive correlations of ID pain score  curve was used to determine the prediction for mortality in patients with DPNP according to different criteria. Multivariate Cox proportional hazards regression analyses were used to determine the primary endpoint according to the diagnosis of DPNP. The CV mortality was defined based on the International Classification of Diseases 10th Revision, and the codes included those for heart diseases , stroke (I60−I69), and peripheral artery disease (I70.2−I75). A two-tailed P value of < 0.05 was considered statistically significant. Statistical analysis was performed using SPSS 22.0 .Of a total of 2318 patients, 505 (21.8%) and 179 (7.7%) were diagnosed with DPNP based on ID pain scores ≥ 2 and DN4 score ≥ 4, respectively. The baseline characteristics of the patients grouped by DPNP are shown in During a median follow-up of 6.2 years (IQR: 5.9−6.4 years), 312 patients died Figure 1The Kaplan-Meier analysis showed that the survival rates were significantly different between patients with and without DPNP . According to the criteria of peripheral neuropathic pain based on these two scoring questionnaires, 1805 (77.9%) patients were consistently grouped as no DPNP, and 171 (7.4%) patients were consistently grouped as DPNP. However, 8 (0.3%) patients were grouped as no DPNP based on the ID pain score but were discrepantly grouped as DPNP based on the DN4 score; 334 (14.4%) patients were grouped as DPNP based on the ID pain score but were discrepantly as no DPNP based on the DN4 score. The consistent group of diagnosed DPNP showed a sensitivity of 17.0%, a specificity of 92.6%, a positive predictive value (PPV) of 25.1%, and a negative predictive value (NPV) of 88.4% to predict mortality; the discrepant group of DPNP diagnoses showed a sensitivity of 21.9%, a specificity of 84.9%, a PPV of 17.3%, and a NPV of 88.4% to predict mortality during follow-up , the National Health Research Institute (grant number NHRI-EX111-10927HT), and the Ministry of Science and Technology, Taiwan (grant number MOST 110-2314-B-075A-004 -MY3). The funders had no role in the decision to publish the results.We thank the Diabetes Care Center of Taichung Veterans General Hospital for their support. Statistical analysis was performed by the Biostatistics Task Force of Taichung Veterans General Hospital, Taichung, Taiwan.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Patients who call for emergency medical services (EMS) due to abdominal pain suffer from a broad spectrum of diseases, some of which are time sensitive. As a result of the introduction of the concept of ‘optimal level of care‘, some patients with abdominal pain are triaged to other levels of care than in an emergency department (ED). We hypothesised that it could be challenging in a patient safety perspective.This study aims to describe consecutive patients who call for EMS due to abdominal pain and are triaged to self-care by EMS clinicians.This was an observational study performed in an EMS organisation in Western Sweden during 2020. The triage tool Rapid Emergency Triage and Treatment System (RETTS), which included Emergency Signs and Symptom (ESS) codes, was used to find medical records where patients with abdominal pain have been triaged to self-care and 194 patients was included in the study.n = 1), acute appendicitis with peritonitis (n = 2) and acute pancreatitis (n = 3). All these patients required extensive evaluation and different treatments, including acute surgery, antibiotics and fluid therapy.Of total 48,311 ambulance missions, A total of 1747 patients were labelled with ESS code six , including 223 (12.8%) who were given the code for self-care and 194 who were further assessed by the research group. Of these patients, 32 (16.3%) had a return visit within 96 hours due to the same symptoms and 11 (5.6%) were hospitalised. In six of these patients, the EMS triage was evaluated retrospectively and assessed as inappropriate. These patients had a final diagnosis of ruptured abdominal aneurysm  were triaged to self-care. Of the 194 patients who were further assessed, 16.3% required a return visit to the ED within 96 hours and 5.6% were hospitalised. Six patients had obvious time-sensitive conditions. Our study highlights the difficulties in the early assessment of abdominal pain and the requirement for an accurate decision support tool. An increasing demand for emergency medical services (EMS) has been observed both nationally and internationally . At the However, some symptoms can be connected to higher patient safety risks. For example, neurological symptoms, such as dizziness, are difficult to distinguish from stroke , 8. SepsWhen it comes to the concept of ‘the optimal level of care’, abdominal pain is another symptom with potential patient safety risks and hundreds of differential diagnoses, including some time-sensitive diagnoses . Furtherinvestigate requirement of hospitalisation and incidence of incorrect triage by mapping return visits within 4 days with the same symptoms amongst patients with abdominal pain who are triaged to self-care; andinvestigate which examinations are performed on site by EMS.To the best of our knowledge, no previous study has examined the safety of prehospital patients with abdominal pain triaged to self-care by EMS. We hypothesised that it is challenging to safely assess patients in the prehospital setting and to triage them to self care. Therefor the aims of our study were to:EMS and hospital medical records were examined in this retrospective observational study. The model for processes in chart review studies suggested by Kaji et al.  was usedThe study was conducted in an EMS organisation in Western Sweden consisting of six ambulance stations serviced by 27 ambulance units. It has approximately 55,000 EMS missions annually. An ambulance is staffed by at least one registered nurse (RN) with or without 1 year of specialist education in prehospital care. The other crew member can also be an RN or an emergency medical technician (EMT) with an assistant nurse education and a one-year EMT education .According to the local guidelines followed by the EMS organisation in this study, the ambulance team should triage a patient to the optimal level of care. First, all patients are assessed on site at home and then triaged to the optimal level of care . The RN, who is responsible for the triage, refers to the clinical guidelines, a triage tool, a triage handbook and telephone contact with ED physicians.The EMS organisation is using the Rapid Emergency Triage and Treatment System (RETTS)  as a triThe organisation also uses a symptom-based web decision support system (triage handbook). By clicking on a symptom, the EMS team can access suggestions of examination, diagnoses and advice for further processing. Except as described in guidelines, specific training of assessment in connection with abdominal pain has not been carried out in the included organisation.First survey with the assessment of airway, breathing, circulation and disability (ABCD)Second survey with anamnesis according to Signs and symptoms, Allergies, Medications, Pertinent past history, Last oral intake, Events leading to the injury or illness, Onset, Provokes or Palliates, Quality, Radiates, Severity and Time Measurement of vital signs, including respiration rate, oxygen saturation, pulse rate, blood pressure, degree of consciousness and body temperatureFocused assessment in connection to abdominal pain, including inspection, palpation and auscultation of abdomen and blood test of serum glucoseRETTS colour blue, green or yellowContact with a physicianUse of triage handbook with descriptions of self-care adviceWritten information to the patientThe included EMS organisation has the following mandatory examinations and actions in connection to triage to self-care amongst patients with abdominal pain:Data were abstracted from prehospital and hospital medical records. In all, there were 48311primary ambulance missions during the time of the survey. Among them did 1747 patients have ESS code six  of which 223 patients had the assignment code A05 ‘triaged to self-care’. A total of 194 patients had no exclusion criteria and were therefor included in the study , focused assessment, triage colour, contact with physician, use of triage handbook, written information to the patient and time on scene. These data were searched for in the EMS organisation’s prehospital medical record system (Ambulink). After conducting individual reviews in Ambulink, the respective prehospital medical records were followed up in the hospital’s medical record system (Melior), from which data on return visit to ED within 96 hours, hospitalisation, care time and ICD code were sampled.Two of the authors (EO and PH) performed the data collection. They manually screened the medical records together. Both free text and fixed data were used. The relevant data were then transferred to a database where the data was de-anonymised and personal data linked to serial numbers were transferred to a separate codebook stored apart from the dataset. No inter-rater reliability test was performed, as the data collection was executed by two persons together.P-value of ≤0.05 was considered significant in the regression. All analyses were performed using SPSS 21.0 .The outcome data were summarised using descriptive statistics. A univariate logistical regression analysis was used for predictors of return visits within 96 hours on binary (sex) and continuous variables . Significant variables in the univariate regression were considered eligible for inclusion in the multivariate model. A The study was accepted by the research ethics board of Stockholm, Sweden (Dnr 2021–03440) and conducted in agreement with the ethical references of the Swedish Research Council .Amongst patients with abdominal pain who were triaged to self-care, 109 (55.6%) were females. The mean age of the patients was 56.3 years. On average, EMS teams spent a total of 28.0 minutes on the scene with each patient. The patients had normal vital signs (mean) and only three patients were assigned a RETTS colour of orange or red , whilst 11 (5.6%) were hospitalised. Fourteen patients (7.1%) were transported to a hospital by ambulance and 18 (9.2%) by other transport modes Table . Of 6 paIn the univariate logistic regression, there was only one significant variable that predicted outcome; thus, a multivariate logistic regression was not performed. A lower prehospital oxygen saturation level was a predictor for return visits, with an odds ratio of 0.68 0.53–0.88)  were assessed to be incorrectly triaged to self-care by the EMS team, thereby endangering patient safety. This statement is made despite the fact that the EMS team’s compliance with guidelines can be considered relatively high.The prehospital compliance to guidelines has been shown  to vary The EMS team in this study had low compliance when it came to conducting focused examinations, such as abdominal auscultation, inspection and palpation. These are important examinations in the management of patients with abdominal pain. However, even properly performed examinations cannot rule out serious conditions. For example, one study showed that half of patients with peritonitis had normal bowel sounds and that palpation had low sensitivity and specificity for peritonitis . In moreThe population in the current study is relatively young compared to patients with abdominal pain who are typically admitted to EDs . This isFurthermore, EMS teams have limited opportunities to safely assess and examine patients with abdominal pain. For example, point-of-care blood tests are unusual, and it is impossible to have a patient undergo an X-ray examination on the spot. The common examination methods available are inspection, palpation and auscultation. It is also possible to measure ECG and vital parameters. Anamnesis is also a very important aspect of the examination done in the prehospital setting. At the same time, patients with abdominal pain are also difficult to assess at the ED, despite opportunities for more advanced examinations. Patient history and physical examinations have a sensitivity of 0.25 and a specificity of 0.92 compared to patient history, physical examination, laboratory analysis, acute abdominal series radiographs and non-enhanced helical computed tomography, with a sensitivity of 0.92 and a specificity of 0.90 . Thus, oMeanwhile, we found that oxygen saturation is a critical clinical predictor associated with the risk of a return visit within 96 hours after the initial assessment, with a lower oxygen saturation indicating an increased risk of a return visit. The risk increased even above 90%. Previous studies have indicated that low oxygen saturation in the early phase is associated with an increased risk of adverse events amongst patients with acute myocardial infarction  and an iFurthermore, our findings indicate the need for an accurate decision support tool so that not all patients have to be transported to an ED for evaluation. In developing such a tool, the definition of time-sensitive conditions must be carefully considered. Diseases, such as appendicitis and cholecystitis, should most likely be included in such a definition, regardless of any complication.The main limitation of the present study is the low number of included patients. A study with a larger population could provide a better picture of the prehospital assessment and triage of patients with abdominal pain. Nevertheless, even though generalisability is limited by the small number of patients, the total number from 1 year of ambulance assignments is relatively large enough to highlight potential medical risks amongst patients triaged to self-care. Transferability to other ambulance organisations with similar guidelines should be approached with some caution.Another limitation is the retrospective study design, which does not allow subsequent analyses of patients’ conditions or diagnoses when they are asked to remain at home. It has been suggested that there is a lack of a clear definition of what constitutes time-sensitive conditions . The curAmongst the 1747 patients assessed by EMS due to abdominal pain, 223 (12.8%) were triaged to self-care of which 194 (87%) did not have any exclusion criteria. Among them 16.3% required return visits to EDs within 96 hours and 5.6% were hospitalised. Six patients had obvious time-sensitive conditions. Our study highlights the difficulties involved in the early assessment of patients with abdominal pain and the requirement for an accurate decision support tool.


For the conditions, neuropathic pain/peripheral neuropathy had the highest rate of perceived benefit (66.6%), followed by Parkinson’s disease (60.9%), multiple sclerosis (60.0%), migraine (43.8%), chronic pain syndrome (42.1%), and spondylosis (40.0%). For the indications, medicinal cannabis had the greatest perceived effect on sleep (80.0%), followed by pain (51.5%), and muscle spasm (50%). Oral oil preparations of balanced delta-9-tetrahydrocannabinol/cannabidiol  were mainly prescribed. Somnolence was the most frequently reported side effect (21%). This study supports medicinal cannabis’ potential to safely treat non-cancer chronic conditions and indications.Research describing patients using medicinal cannabis and its effectiveness is lacking. We aimed to describe adults with non-cancer diagnoses who are prescribed medicinal cannabis via a retrospective medical record review and assess its effectiveness and safety. From 157 Australian records, most were female . Most patients had neurological (58.0%) or musculoskeletal (24.8%) conditions. Medicinal cannabis was perceived beneficial by 53.5% of patients. Mixed-effects modelling and post hoc multiple comparisons analysis showed significant changes overtime for pain, bowel problems, fatigue, difficulty sleeping, mood, quality of life (all  Cannabis (Cannabaceae) has been used medicinally since 400 AD for its analgesic, appetite enhancement, and myorelaxant properties ,2,3. EmeIn Australia, impressive public support instigated legislative changes in 2016 allowing medical doctors to prescribe cannabis-based medicines for chronically ill patients subject to the approval from the Therapeutic Goods Administration  which isRapidly increasing public interest in medicinal cannabis necessitates research into the conditions/symptoms it can potentially treat, and its safety profile and this has prompted the Australian government to fund clinical trials to ascertain its place in mainstream medicine . Whilst This retrospective study will aim to answer the questions: (1) What are the characteristics of people with non-cancer diagnoses using medicinal cannabis? and (2) Does medicinal cannabis provide effective relief for patient conditions and symptoms? Secondary objectives include determining dosage, side effects, and reasons for cessation of treatment.A retrospective medical record review was conducted at Wolper Jewish Hospital in Sydney, Australia, which is a stand-alone, not-for-profit clinic specializing in rehabilitation and palliative care. A consent form was provided which talks about the risk of psychosis and schizophrenia. Medical records of patients prescribed medicinal cannabis between 1 February 2018 and 30 November 2021 were reviewed using the inclusion criteria: (1) 18 years or older; and (2) non-cancer diagnosis. This study was approved by the St Vincent’s Hospital Sydney Human Research Ethics Committee .Patient demographic data , medical data (condition(s), primary and secondary indication(s)), administration route, cannabinoid ratio, dose, number of cannabis-based medicine(s), and previous cannabis use were recorded. Side effects, treatment continuation, and reasons for cessation were quantitatively described.The effectiveness of medicinal cannabis treatment was examined by the following: (1) The patient’s own perceived benefit reported as ‘beneficial’, ‘not beneficial’ or ‘unclear’; this data was used as a proxy to determine overall and condition-specific perceived benefit. (2) The Palliative Care Outcomes Collaboration (PCOC) Symptom Assessment Scale (SAS) scores. This validated tool reliably measures patient-reported symptom distress amongst those with advanced disease and includes pain, fatigue, breathing problems, bowel problems, appetite, nausea, difficulty sleeping, and mood. Each symptom is rated out of 10 . Scores 0–3 depict mild distress, 4–7 moderate distress, and 8–10 severe distress . Patientt-test compared the highest doses of cannabidiol (CBD) and delta-9-tetrahydrocannabinol (Δ-9-THC). Statistical significance was set at p < 0.05. Statistical tests were performed using GraphPad Prism .De-identified patient data were entered into an Excel spreadsheet and analyzed descriptively. To account for missing data, patient scores for each SAS symptom were grouped into baseline and three-month blocks, averaged, and analyzed by fitting a mixed-effects model . Post hoTwo-hundred-and-seven patients met the study inclusion criteria. Fifty patients were excluded due to missing files/poor data, resulting in 157 patients analyzed.Patients were predominantly female (63.7%), aged 63.0 years, and from the Greater Sydney region (86.6%). Most patients were born in Australia (66.9%) and partnered (57.3%), with 17.8% stating previous cannabis use .Patients reported an array of conditions  and indip < 0.0001) than Δ-9-THC (16.9 ± 17.23 mg/day) , an oral oil CBM (99.4%) with balanced Δ-9-THC and CBD (84.7%). The mean highest CBD dose (34.8 ± 48.04 mg/day) was significantly higher ( mg/day) .n = 75) compared to those aged ≥65   perceived medicinal cannabis as being ‘beneficial’ regardless of their condition/indication a. Patien n = 82) b.The conditions and indications with ≥10 patients were analyzed further. For the conditions, neuropathic pain/peripheral neuropathy had the highest rate of perceived benefit (66.6%), followed by Parkinson’s disease (60.9%), multiple sclerosis (60.0%), migraine (43.8%), chronic pain syndrome (CPS) (42.1%), and spondylosis (40.0%) c. For thIn patients with spondylosis, improved trends were observed for ‘fatigue’, ‘difficulty sleeping’, ‘mood’, and ‘QoL’ scores to 6 months; and ‘pain’ and ‘bowel problems’ to 9 months a. Mixed-In patients with Parkinson’s disease, improved trends were observed for scores to 3 months (‘QoL’ to 6 months), with general stabilization over time b. Mixed-In patients with chronic pain syndrome, improved trends were observed for the scores to 3 months which generally continued to 9 months c. Mixed-In patients with neuropathic pain/peripheral neuropathy, improved trends were observed for ‘fatigue’ and ‘difficulty sleeping’ scores to 3 months; ‘pain’ and ‘QoL’ to 6 months; ‘bowel problems’ to 9 months, and mood to 12 months d. Mixed-In patients with migraine, improved trends were observed for ‘mood’ to 3 months; ‘fatigue’, ‘bowel problems’, ‘difficulty sleeping’, and ‘QoL’ scores to 6 months, and ‘pain’ to 18 months e. Mixed-There are downward trends for ‘pain’  and ‘bowel problems’  scores to 12 months, and ‘fatigue’, ‘difficulty sleeping’, and ‘mood’  to 15 months, with improvement in ‘QoL’ to 6 months in patients with multiple sclerosis f. A WilcIn patients with pain, improved trends were observed for all symptom scores to 3 months (‘QoL’ to 6 months) with general stabilization over time a. Mixed-In patients with muscle spasm, initial improved trends were observed for all symptom scores to 3 months; ‘pain’, ‘fatigue’, and ‘bowel problems’ to 12 months; and ‘difficulty sleeping’, ‘QoL’, and ‘mood’ to 15 months b. Mixed-In patients with sleep issues, improved trends were observed for ‘fatigue’, ‘bowel problems’, and ‘mood’ scores to 3 months; ‘difficulty sleeping’ to 6 months; and ‘pain’ and ‘QoL’ scores  to 9 months c. Wilcoxn = 157) were somnolence (21.0%), dry mouth (7.6%), disorientation/confusion (3.8%), intoxication (3.8%), constipation (2.5%), and dizziness (2.5%)  a. Unstean = 157). Thirty-nine reasons were reported for treatment cessation, with the main being inefficacy (51.3%), followed by side effects (25.6%), and relief from other medications/treatment (12.8%)  b. One paThis retrospective medical record review describes the population characteristics of patients using medicinal cannabis at a clinic in Sydney, Australia and provides data on the effectiveness and safety of medicinal cannabis treatment on patient conditions and indications. In our study, the mean age of patients was higher than in international studies (40–50 years) ,17,18,19It difficult to ascertain the actual numbers of patients that had used cannabis before attending the clinic as patients are under no obligation to state previous cannabis use. However, the results here are similar to another Australian study which showed that 14.1% had not used cannabis before using it for medical reasons .In this study, most patients were prescribed oral oil cannabis-based medicines of balanced Δ-9-THC:CBD ratios reflecting their availability for prescription in Australia . This coLiterature shows that therapeutic doses of Δ-9-THC (5–20 mg) tend to be smaller than CBD (50–1500 mg)  and our Most patients in our study sought treatment for neurological and musculoskeletal conditions, with pain as the main indication. This agrees with data indicating that most approvals in Australia are for chronic pain, and pain ranks as the number one indication in several studies ,14,16,21The presence of symptoms such as pain, fatigue, sleep difficulties, and poor mood in this study indicates high symptom burden across these chronic diseases ,28. For When comparing age groups, 56% of patients under <65 years found medicinal cannabis to be beneficial compared to 51.2% of patients aged ≥65. A study of patients with cancer indicated that younger age was associated with the therapeutic success of medicinal cannabis, which could indicate more tolerance to higher doses, and this may be reflected in the present study .p < 0.001), as well as significant improvements in QoL (p < 0.05) [In terms of patient-perceived benefit, the results suggest that medicinal cannabis is more effective at treating neuropathic pain conditions compared to nociceptive pain conditions such as spondylosis , findings congruent with available evidence on different pain conditions ,30,31,32 < 0.05) . These r < 0.05) ,16. With < 0.05) .Medicinal cannabis was beneficial to around 60% of patients with Parkinson’s disease. A systematic review of the effects of cannabis on Parkinson’s disease, including RCTs and non-RCTs, reported improvements in sleep and pain, which agree with our findings . p < 0.0001) [p < 0.001) [For migraine, our study revealed that under half of the patients believed treatment to be beneficial, with significant SAS scores for ‘fatigue’ and a downward trend for ‘difficulty sleeping’. One retrospective chart review analyzing migraine showed that 85.1% of patients reported a decrease in mean migraine headache frequency from 10.4 to 4.6 at follow-up ( 0.0001) . Similar< 0.001) . Another< 0.001) . ®  effectiveness on multiple sclerosis pain and spasticity, with improvements in sleep and QoL [Symptoms such as fatigue, pain, sleep, and mood disorders are also prevalent in multiple sclerosis . In this and QoL . Another and QoL , which aPoor sleep is an important symptom in chronic disease as it coincides with poor symptom control and impacts QoL . Many stMedicinal cannabis was generally safe as shown by the follow-up SAS scores to 12 months for many of the conditions/indication. Moreover, dosing was tailored to each patient  by the prescribing medical doctor, thus minimizing dose-related toxicities . A scopiThe strength of this study is that patient data up to 30 months can be assessed which is longer than prospective and clinical trials ,15. AlthOne limitation relates to the location of the study (undertaken at one clinic) which can introduce locality bias, and retrospective design of the study which limits the ability to evaluate the causality of medicinal cannabis use and improvements in symptom scores. Confounding factors may have influenced patient SAS scores. For example, a patient with spondylosis may have a higher score for their pain distress due to another developing issue. Whilst the PCOC SAS can accurately and reliably measure symptom distress in a palliative population, it lacks specific measures for many condition-specific indications e.g., mobility for Parkinson’s disease , number This study indicates that medicinal cannabis, in a balanced formulation, may address a variety of non-cancer conditions and indications concurrently and can be safely prescribed by a medical doctor. The results can be used to guide future clinical trials which could investigate the conditions and indications identified here as sensitive to treatment. It is recommended that ‘pain’ and ‘difficulty sleeping’ (which may improve fatigue) be investigated further as treating these two symptoms may have reciprocating effects on each other, on mood, and QoL. Future studies should address how cannabinoids interact in the body and with one another in differing ratios and formulations, and include relevant patient-reported outcome measures and longer-term safety studies. It is recommended that patients are assessed individually to determine whether medicinal cannabis is an appropriate treatment option, considering the associated safety risks to potential therapeutic benefit. Understanding how medicinal cannabis can be used in mainstream medicine is crucial as it has the potential to positively impact millions of lives around the world.


Post-craniotomy pain is a common occurrence which is associated with poor outcomes. Pre-emptive scalp infiltration with dexamethasone and ropivacaine has been proven effective in previous studies but with limited clinical significance. Dexamethasone palmitate emulsion (D-PAL) is a pro-drug incorporating dexamethasone into lipid microspheres with greater anti-inflammatory activity and fewer side effects than free dexamethasone. However, its effects in post-craniotomy pain management remain unknown. This study hypothesizes that pre-emptive scalp infiltration with ropivacaine plus D-PAL emulsion can achieve superior analgesic effects to ropivacaine alone in adult patients undergoing craniotomy.This is a single center, randomized controlled trial enrolling 130 patients scheduled for supratentorial craniotomy, which is expected to last longer than 4 h. We compare the efficacy and safety for postoperative pain relief of ropivacaine plus D-PAL group and ropivacaine alone group following pre-emptive scalp infiltration. Primary outcome will be pain Numerical Rating Scale at 24 h postoperatively. Secondary outcomes will include further analgesia evaluations and drug-related complications within a follow-up period of 3 months.This is the first randomized controlled trial aiming to assess the possible benefits or disadvantages of D-PAL emulsion for incisional pain in craniotomy. It may provide an alternative to optimize pain outcome for neurosurgical patients.ClinicalTrials.gov (NCT04488315). Registered on 19 July 2020.The online version contains supplementary material available at 10.1186/s13063-022-06936-z. Over two-thirds of patients have been reported to suffer moderate to excruciating incisional pain during the first 48 h after neurosurgical craniotomy , 2. InadHowever, there are no guidelines for post-craniotomy pain management yet. Traditionally, systemic opioids are the mainstay of treatment. However, therapeutic doses of opioids are associated with a moderate-to-high risk of postoperative nausea and vomiting (PONV). And the postoperative neurological assessments would be delayed or interfered due to sedation and miosis caused by opioids. Also, opioid-induced respiratory depression could lead to hypoxia and hypercarbia, which subsequently increase cerebral blood flow and intracranial pressure . So opioAt present, the benefits of regional anesthesia have been positively valued, which indicate more effective and stable effects than intravenous analgesia within 24 h postoperatively . Wound iIt has been reported that post-craniotomy pain originates from the damage of muscles and soft tissues at surgical site. It is caused by the release of inflammatory mediators after incisional injury, which activate the peripheral nociceptors and lead to abnormal action potential transmitted along afferent Aδ and C-fibers , 16. TheDexamethasone palmitate emulsion (D-PAL emulsion) is a pro-drug incorporating dexamethasone palmitate (D-PAL) into lipid microspheres. It is gradually hydrolyzed to dexamethasone by carboxylesterase in the reticuloendothelial system and some inflammatory cells but not in human serum, therefore indicating an uptake of 8 times higher and an anti-inflammatory activity of 5-6 times greater than its corresponding amount of free dexamethasone. Furthermore, the location of D-PAL at inflammatory lesions could reduce the risks of systemic side effects , 24. TheThis trial is a prospective, single-center, randomized, open-label, and blinded-endpoint study. Participants will be assigned to either ropivacaine plus D-PAL group or the ropivacaine alone group in an allocation ratio of 1:1 for this superiority trial. The trial will be conducted at Beijing Tiantan Hospital, Capital Medical University, China, from October 2022. We have used the SPIRIT reporting guidelines  and compThe primary objective of this trial is to determine whether preemptive incisional infiltration with ropivacaine plus D-PAL is superior to ropivacaine alone in relieving postoperative pain for adults undergoing neurosurgical craniotomy. The effects of both interventions on postoperative pain management and patients’ safety and quality of recovery will also be compared.The study plan is in accordance with “Declaration of Helsinki” and approved by the Ethics Committee of Beijing Tiantan Hospital (KY-2018-034-02-8). The strategy has been registered at ClinicalTrials.Gov . This trial does not involve biological specimens, and protocol modifications will be not expected. All patients scheduled for elective supratentorial craniotomy for resection of a tumor, clipping of an unruptured aneurysm, or removal of an epileptic focus will be recruited and screened for participation by one researcher. This independent research will also be responsible for obtaining the informed consent by visiting the eligible patients 1 day before surgery and providing them with a verbal explanation of the written consent. Each participant will have sufficient time to ask any questions or concerns regarding this study and then decide whether to participate in this study. Eligible patients will sign informed consent and participants will have the right to withdraw their consent or discontinue participation without restrictions at any time point throughout the study. The confidentiality of participant data will be protected and patients will have the right to obtain relevant information and decide whether their data is to be shared with the regulatory authorities on reasonable request.Scheduled for elective supratentorial craniotomy with an anticipated duration of > 4 hAmerican Society of Anesthesiologists (ASA) physical status of I-–IIAge 18-64 yearsAnticipated tracheal extubation, full recovery, and cooperation within 2 h postoperativelyPreoperative Glasgow Coma Scale < 15History of craniotomyUnable to comprehend the pain Numerical Rating Scale (NRS)Extreme body mass index (BMI) of < 15 or > 35Peri-incisional infectionAllergy to dexamethasone, ropivacaine, or other analgesicsHistory of alcohol or drugs abuse (more than 2 weeks)History of psychiatric disorders, uncontrolled epilepsy, or chronic headacheHistory of severe cardiopulmonary, renal, or liver dysfunctionHistory of radiation therapy and chemotherapy or with a high probability of such treatment postoperativelyPregnant or breastfeedingRefusal to give written informed consentOperation duration ≤ 4 hNot awake or extubated within 2 h after surgeryUnexpected radiation therapy or chemotherapy postoperativelyRevision for hematoma or brain swelling except wound problems within 72 h after surgeryGCS < 15 within 72 h after surgeryPoor cognitive function within 72 h after surgeryHaving a fever (≥ 39°C) within 72 h after surgeryLost in follow-upVoluntary withdrawalRandomization sequence will be generated by a designated staff not involved in outcome data collection and analysis, who will use the block randomization method via SPSS version 22.0 , with an electronic table of random numbers to allocate eligible participants to either of the two groups (in a 1:1 ratio). The allocation sequences will be prepared and be kept inside sealed, opaque, and consecutively numbered envelopes. The envelope will be opened by the neurosurgeons in charge, who will then prepare the study solution based on the respective allocation scheme and be therefore made aware of group assignations. Participants will be enrolled by a dedicated research nurse not involved in the data collection and analysis, and the neurosurgeons in charge are responsible for assigning participants to interventions. This is an open-label design with only patients and independent researchers in charge of follow-up and data analysis blinded to allocation. The D-PAL is a lipid emulsion in the infiltration solution, which can be easily distinguished from the clear ropivacaine alone study solution. Therefore, unblinding will not occur.Prior to the commencement of the study, all investigators will receive standardized training on trial content, treatment strategies, evaluation, and quality control. All interventions will be carried out in accordance with clinical practice guidelines. During preoperative visit, eligible patients should be acquainted with pain NRS ranging from 0 (no pain) to 10 (worst possible pain) . They wiThe neurosurgeons in charge will be responsible for the preparation of the respective drugs in a sterile fashion: 2 mL D-PAL emulsion  and 15 mL of 1% ropivacaine  diluted to a total volume of 30 mL in normal saline for ropivacaine plus D-PAL group, and 15 mL of 1% ropivacaine diluted to a total volume of 30 mL in normal saline for ropivacaine alone group.2), bispectral index (BIS), and temperature. All patients will be preoxygenated with FiO2 > 0.8 before anesthesia induction with intravenous midazolam 0.05 mg/kg, sufentanil 0.3-0.5 μg/kg, propofol 1.5-2 mg/kg, and cisatracurium 0.2 mg/kg. After endotracheal intubation, anesthesia will be maintained with sevoflurane (0.4 MAC) and propofol (2-4 mg/kg∙h) to keep BIS values 40-60. The ventilation protocol consists of volume-controlled mechanical ventilation  with an air-oxygen mixture (60:40), TV of 6-8 mL/kg, inspiratory to expiratory ratio of 1:2, fresh gas of 1-2L/min and a respiratory rate adjusted to normocapnia (PaCO2 between 35 and 45 mmHg). Intraoperative analgesia will be provided with continuous remifentanil infusion (0.1-0.3 μg/kg∙min) until the removal of Mayfield head holder at the end of surgery. Remifentanil infusion dose will be adjusted to attenuate potent stress responses and to keep mean arterial pressure (MAP) and HR within ± 20% of baseline values. Tramadol 100 mg will be administered intravenously before skin closure to prevent postoperative shivering and remifentanil-induced hyperalgesia, and ondansetron 4 mg will be given simultaneously to prevent tramadol-induced nausea and vomiting. No additional analgesics and antiemetics will be administered intraoperatively. Intraoperative hypertension and/or tachycardia will be treated with esmolol 0.5 mg/kg or nicardipine (10 μg/kg). Bradycardia (< 50/min) will be treated with atropine bolus 0.01 mg/kg. Muscle relaxants will be used as needed intraoperatively and the residual neuromuscular block will be antagonized with neostigmine 0.04 mg/kg and atropine 0.02 mg/kg after spontaneous ventilation recovery postoperatively. Patients will be shifted to the Post Anesthesia Care Unit (PACU) for monitoring after successful extubation, with stable hemodynamic, respiratory, and neurologic conditions.All patients will follow a standard anesthesia technique. In the operating room, standard monitoring will be continuously established, which includes electrocardiography, pressure (BP), heart rate (HR), pulse oxygen saturation  test . The cogFollow-up will last 3 months postoperatively, during which an independent researcher blinded to the patient’s group allocation will conduct the following evaluations at different time points: pain NRS, sufentanil consumption in the PCA device, time to first PCA demand button press, cumulative consumption of OC/APAP, PONV scores, wound healing scores, World Health Organization QoL abbreviated version (WHOQOL-BREF), Patient and Observer Scar Assessment Scale (POSAS) scores, etc . AdverseThe demographic characteristics include age, gender, BMI, ASA status, neurological pathology, and comorbidity. Surgery and anesthesia characteristics include surgical site, length of incision, volume of local infiltration solution, duration of surgery and anesthesia, intraoperative analgesics (sufentanil and remifentanil) consumption, perioperative hemodynamic parameters, cumulative intravenous dexamethasone prescribed by a neurosurgeon, etc.Primary outcome will be the pain NRS scores at 24 h after craniotomy.Pain NRS scores at 2, 4, 12, 48, and 72 h after craniotomy;Prolonged post-craniotomy pain NRS at 1 and 3 months;Number of patients needing no sufentanil at 24, 48, and 72 h after craniotomy;Total consumption of sufentanil with PCA device at 24, 48, and 72 h postoperatively;Total number of times that patients press the PCA button, including valid and invalid presses at 24, 48, and 72 h postoperatively;Time to first PCA button press after surgery;Time to first rescue analgesia with OC/APAP after surgery;Duration of hospitalization postoperatively.PONV scores at 24, 48, and 72 h after surgery. PONV is rated by patients as 0, absent; 1, nausea not requiring treatment; 2, nausea requiring treatment; and 3, vomiting.WHOQOL-BREF scores at 1 and 3 months after craniotomy. The WHOQOL-BREF is a questionnaire of 26 items, including social relationships (3 items), physical health (7 items), psychological health (6 items), environment (8 items), overall QoL (1 item), and general health (1 item). Each domain’s mean score can range between 4 and 20 with a higher score indicating a better QoL.Local soft-tissue atrophy at 72 h, 1 and 3 months after craniotomy. It is presented as superficial atrophy of skin and adipose tissue, central discoloration of the skin, yellow subcutaneous deposits, small sebaceous glands, cessation of hair growth, or mauve colored periphery at the injection site.Wound healing score at 72 h, 1 and 3 months postoperatively. Wound Healing Score is rated by an independent researcher as excellent, good, and suboptimal.Patient and Observer Scar Assessment Scale (POSAS) at 72 h, 1 and 3 months after craniotomy . POSAS cOther complications such as respiratory depression, allergic reaction, local or systemic toxicity, wound infection, hematoma, and injection site infection throughout the treatment and follow-up period.α = 0.05, β = 0.1, and power = 90%. Considering a dropout rate of 20%, a total of 130 patients will be required in this trial (n = 65 per group).Earlier studies have reported that incision-site infiltration with ropivacaine plus dexamethasone could reduce about 30-50% of postoperative pain severity compared with ropivacaine alone , 19, 22.In this study, adverse events (AEs), defined as negative or unintended clinical manifestations throughout the treatment and follow-up period, will be monitored and recorded in detail on a case report form (CRF). All AEs related to the surgery, anesthesia, steroid, or analgesics, together with the soft-tissue atrophy and local infection, which might be induced by scalp infiltration with the mixture of ropivacaine and D-PAL emulsion, should be monitored during the 3 months’ follow-up. The soft-tissue atrophy, clinically manifested as superficial atrophy of skin and adipose tissue, central discoloration of the skin, yellow subcutaneous deposits, small sebaceous glands, cessation of hair growth, or mauve-colored periphery at the site of injection , will beData collection and management will be performed via the hospitalized medical record system or CRF by an independent researcher. All data will be kept strictly confidential for research purposes only. Only the primary investigator can obtain final test data. Follow-up will be conducted on days 1, 2, and 3 and at months 1 and 3 by an independent and experienced researcher, either in person or by contact via telephone (after discharge). Participants who discontinue or deviate from intervention protocols will not be replaced. They will be allowed to withdraw their consent without any restriction at any time. Their data will be retained, including all the primary and secondary outcomes until termination, except for the cases that are unable to complete the assessment of the primary outcome at 24 h postoperatively.All personal information and data about the participants will be recorded into the CRFs, which are coded by an identification number and stored in a secure cabinet throughout the trial to guarantee confidentiality. All data will be entered into the Excel form for analysis by two independent researchers with double-checking. The electronic data will be stored on a double password-protected computer. Only the primary investigator and the statistician will have access to the files.This trial will be monitored by an independent Data Monitoring Committee (DMC) composed of specialists in ethics, statistics, and methodology through regular interviews. The DMC will audit the assessment and collection of all data after 30%, 60%, and 100% of patient inclusions. DMC will have access to interim results. Any AE will be reported to both the DMC and the IRB for judgement. Although there are no anticipated problems that may be detrimental to the participants, serious life-threatening AEs leading to prolonged hospital stay or death will be reported and the study will be terminated immediately.Multiple imputations will be used to handle missing data during the whole study.The trial results will be made public through publication in a scientific journal.t tests if they are normally distributed or by Mann-Whitney U test if they are abnormally distributed. Similarly, secondary outcomes including pain NRS scores at 2, 4, 12, 48, and 72 h after craniotomy, sufentanil consumption with PCA device, PONV scores, WHOQOL-BREF, wound healing score, and POSAS scores at different time points and the duration of hospitalization will be compared by independent two-tailed t tests as normally distributed data or by Mann-Whitney U test as skewed data. In addition, the time to first button press or to first requirement of OC/PAPA will be compared by log-rank test and reported as hazard ratios (HRs) with 95% CI in Kaplan-Meier curves. Safety analyses will be compared with the incidence of AEs recorded in the safety data set using Chi-square test or Fisher’s exact test. The same statistical methods will be used for demographic characteristics and baseline information. We will judge a P value of less than 0.05 as significant for all tests.All statistical analyses will be performed by a statistician who is blinded to the entire study. All analyses will include the patients completing 3 months of follow-up and will follow the intention-to-treat principle. Data analysis will be performed using SPSS 26.0 . Kolmogorov-Smirnov test will be used to check for normal distribution. Normally distributed continuous variables will be described as mean ± SD and abnormally distributed variables as median . Categorical variables will be reported as the number or proportion of patients. The primary outcome will be the pain NRS scores at 24 h postoperatively. These continuous data will be compared by independent two-tailed P < 0.01 using the alpha-sparing technique (O’Brien-Fleming) for benefit or harm.Two interim analyses will be conducted for assessment of efficacy and safety after completion of the first 40 and 80 patients. The efficacy of the primary outcome and the incidence of AEs will be compared between two groups, and the study discontinuation threshold will be set at In this prospective, randomized controlled trial, we seek to determine whether pre-emptive scalp infiltration with the addition of D-PAL emulsion to ropivacaine would offer superior analgesic efficacy for post-craniotomy pain compared to ropivacaine alone. To the best of our knowledge, this is the first study to evaluate the effects of D-PAL emulsion in scalp infiltration for craniotomy. D-PAL emulsion, dexamethasone palmitate incorporated into lipid microspheres, has a stronger anti-inflammatory activity, as well as a longer duration of action and fewer side effects than free dexamethasone. The clinical utility of D-PAL emulsion has been reported to treat inflammatory diseases or pain diseases by intravenous administration or local infiltration , 29, 37.Ropivacaine is the most widely used long-acting LAs for incisional infiltration . In thisMixtures of local anesthetics and steroids have been used in common practice. However, the safety of this mixture has not been considered carefully. Combination of non-particulate steroids with local anesthetics could form crystals in solution, which may be caused by alkalinization of steroids. The deposits of insoluble crystals could partly account for the depressed and atrophic skin at the site of injection . HoweverCraniotomy site may be a determinant for the incidence and intensity of post-craniotomy pain, which is partly explained by the anatomical location of peri-cranial muscles being damaged. Studies suggest that patients undergoing infratentorial procedures may have more pain than those submitted to a supratentorial approach . FurtherThere are some limitations in our study. Firstly, this is a single-center study. However, ours is a large institution in Asia that specializes in neurosurgery and offers clinical, scientific, and teaching base of neurosurgery, which represents a great advantage in generalizability of our outcomes in this field. Secondly, neurosurgical patients have high levels of anxiety and depression, which are also possible risk factors for post-craniotomy pain . HoweverIn conclusion, post-craniotomy pain is a common occurrence associated with poor outcomes. At present, there is no generally accepted opinion regarding the most suitable analgesic method. If our results reveal a significant decrease in postoperative analgesics with the addition of D-PAL emulsion in pre-incision infiltration, this trial will provide an effective alternative to optimize pain outcome for patients undergoing craniotomy.Not recruiting. Protocol (V3.2/2018-07-05). The recruitment will be expected to begin on October 1, 2022, and to be completed on May 1, 2023.Additional file 1. SPIRIT checklist.


Coccygodynia (coccydynia) is a painful condition of the perineum in the region of the tailbone or coccyx, aggravated by sitting on hard surfaces. It is frequently associated with injuries to the coccyx following direct trauma. Nevertheless, idiopathic coccygodynia without antecedent trauma history is not uncommon. Most of these patients respond to anti-inflammatory medications and physical therapy. Those who are unresponsive may require additional intervention for pain relief. Blockade of ganglion impar, the terminal end of the pelvic sympathetic chain, can dramatically alleviate the pain in patients suffering from coccygodynia. In the current case series, four patients in the age range of 21 to 69 years suffering from chronic idiopathic coccygodynia  were treated with ganglion impar block. All four patients received a course of medical management, and two of the patients additionally received local infiltration of the coccyx before ganglion impar block administration. The block was performed with fluoroscopy guidance by either the trans-sacrococcygeal joint approach or the intra-coccygeal joint approach. The pre-intervention average numeric rating pain score (NRS) was 7.5. After a single ganglion impar block intervention, all four patients experienced complete pain relief (NRS=0). No patients required a repeat injection, and all were pain-free for the entire one-year follow-up period. Coccygodynia (coccydynia) is a painful condition of the perineum first described by Simpson in the 19th century . CoccygoThere are multiple etiologies described in the literature. One of the consistent findings is a subluxated or hypermobile coccyx. Injuries of the coccyx are often caused by backward falls onto hard ground. Trauma during childbirth is another common antecedent factor. Idiopathic causes are also reported without a prior history of trauma. Rarely, malignant pathologies of the perineum cause coccygodynia .The management of coccygodynia always begins with conservative therapies such as anti-inflammatory medications, physical therapy, mobilization of the coccyx, and stretching exercises . PatientThe ganglion impar block is the most promising of the minimally invasive injection techniques . GanglioNeurolytic ganglion impar block is usually reserved for coccygodynia of malignant etiology . RadiofrFour patients  between the ages of 21 and 69 presented to our pain clinic with pain around the tailbone  (piroxicam 20 mg once daily for ten days), sitz bath treatment, use of a doughnut cushion while sitting on hard surfaces, and perineal stretching exercises for at least two weeks. None of the patients significantly responded to conservative therapy and later received local coccygeal infiltration, ganglion impar block, or both. Physical visits or phone calls were used to follow up on the patients one year after the intervention. All the patients underwent routine investigations before intervention. Informed consent was obtained for the procedure from all patients before any intervention. The interventions were daycare procedures, and the patients went home the same day after one hour of observation. The first and second cases initially received local infiltration of the coccyx and later underwent ganglion impar block. The third and fourth cases exclusively received ganglion impar block. Local infiltration anesthesia provided good short-term pain relief in the first and second cases, but the pain recurred. However, a single shot of ganglion impar block produced long-term pain relief (NRS= 0) until one year of follow-up . There was a linear contrast spread anterior to the coccyx and posterior to the rectum. It looked like an inverted comma and was described in the literature as a "comma sign" , transcutaneous electrical nerve stimulation (TENS), sacrococcygeal joint mobilization, and levator ani relaxation exercises should be the first line of management . PatientGanglion impar block, on the other hand, can provide excellent, long-lasting pain relief, as demonstrated in the current case series and validated by previous studies -14. The Sometimes, in elderly patients, there is ossification of the sacrococcygeal disc, leading to difficulty in needle passage. In this situation, the needle can be passed through intra-coccygeal joints, as employed in the fourth case of the current series. The intra-coccygeal approach has been described previously as a proxy for the trans-sacrococcygeal technique . LiteratThe paracoccygeal approach is another method that avoids the needle passing through the sacrococcygeal or intra-coccygeal joint . It is aRecurrence of pain after a single-shot ganglion impar block in coccygodynia is not uncommon. It can be managed by either a repeat block or radiofrequency ablation treatment. The latter can be easily applied to get long-term pain relief . ChemicaIn most patients, idiopathic coccygodynia is usually self-remitting and responds to physical therapy, ergonomic modifications, and medications. Some of them may develop chronic pain and respond poorly to conservative management. In these patients, a combination of minimally invasive injections and physical therapy can significantly reduce pain and improve quality of life. Ganglion impar block is one of the minimally invasive injection modalities that can be employed for managing coccygodynia. The procedure can be easily performed under fluoroscopy guidance, and a single-shot ganglion impar block can provide excellent long-term pain relief. The trans-sacrococcygeal technique of ganglion impar block is usually the technique of choice, where the needle must pass through the sacrococcygeal disc. Intra-coccygeal and paracoccygeal techniques are a few other fluoroscopic methods described in the literature. These alternative methods can come into play in challenging scenarios, especially in elderly patients with an ossified sacrococcygeal joint.