Chronic pain is a significant risk factor for suicidal ideation (SI) and suicidal behavior (SB), including a 20%-40% prevalence rate of SI, a prevalence between 5% and 14% of suicide attempts, and a doubled risk of death by suicide in patients with chronic pain compared to controls. In most studies, associations between chronic pain and suicidality are robust, even after adjusting for the effect of sociodemographics and psychiatric comorbidity, and particularly for depressive conditions. A number of specific conditions that can modulate suicidality risk in patients with chronic pain have been investigated, but there is a need for their more specific characterization. Numerous recent studies have shown that demoralization and meaning in life (MiL) constructs affect suicidality as risk and protective factors, respectively. These constructs have been mainly investigated in patients with somatic illness and in community-dwelling individuals who may present with SI or SB independently of a psychiatric diagnosis of depression. However, a paucity of studies investigated them in suicidal patients affected by chronic pain.The primary objective of this project is to investigate the relationship between demoralization and MiL on SI risk in patients with chronic pain. The secondary objectives are (1) to test whether demoralization can occur independently of depression in patients with chronic pain and SI, (2) to examine whether the expected association between demoralization and SI may be explained by a sole dimension of demoralization: hopelessness, (3) to examine whether the presence of MiL, but not the search for MiL, is associated with less SI, and (4) to explore whether previously described MiL profiles  emerge in our cohort.This project is a single-center, observational, case-control study—the Demoralization and Meaning in Life (DEMiL) study—conducted by the Division of Clinical Pharmacology and Toxicology, the Multidisciplinary Pain Centre, and the Service of Liaison Psychiatry and Crisis Intervention at the Geneva University Hospitals. Self- and hetero-administered questionnaires were conducted among patients and controls, matched by age and gender. The Ethics Committee of the Canton of Geneva approved the scientific utilization of collected data . Data have been analyzed with SPSS, version 23.0, software (IBM Corp).From March 1, 2018, to November 30, 2019, 70 patients and 70 controls were enrolled. Statistical analyses are still in progress and are expected to be finalized in November 2020. To date, we did not observe any unfavorable event for which a causal relationship with the collection of health-related personal data could be ruled out. Results of this study are expected to form the basis for possible prevention and psychotherapeutic interventions oriented toward demoralization and MiL constructs for suicidal patients with chronic pain.The interest in exploring demoralization and MiL in chronic pain patients with SI arises from the common clinical observation that experiencing chronic pain often requires a revision of one’s life goals and expectations. Hence, the impact of chronic pain is not limited to patients’ biopsychosocial functioning, but it affects the existential domain as well. The major clinical implications in suicidal patients with chronic pain consist in trying to (1) delineate a more precise and individualized suicide risk profile, (2) improve detection and prevention strategies by investigating SI also in individuals who do not present with a clinically diagnosed depression, and (3) enhance the panel of interventions by broadening supportive or psychotherapeutic actions, taking into consideration the existential condition of a person who suffers and strives to deal with his or her suffering.DERR1-10.2196/24882 Chronic pain conditions are associated with an elevated risk of suicidal ideation (SI) and suicidal behavior (SB). Literature reviews indicate a 20%-40% prevalence rate of SI, a lifetime prevalence between 5% and 14% of suicide attempts, and a 2-fold higher risk of death by suicide in patients with chronic pain as compared to controls . Most stIn an analogous study conducted in our institution, the same constructs -20, togeThe constitutive components of the demoralization construct, according Kissane and Clarke’s model, are loss of MiL, hopelessness or disheartenment, helplessness, sense of failure, and dysphoria ,32  the relationship between demoralization and depression and (2) the role of one of the components of the demoralization definition  in influencing SI and SB. By focusing on their phenomenological differentiation, most studies have suggested that demoralization is an independent condition distinguishable from depression ,31,40. Ipresence of and search for MiL [narrative model, inspired by logotherapy described by Frankl [A consensus in recent psychological research in defining MiL can be centered on two dimensions: coherence, or a sense of comprehensibility and one’s life making sense, and purpose, or a sense of core goals, aims, and direction in life. A third facet, significance, which focuses on values, worth, and importance of one’s life, is gaining increasing attention   , which wThe primary objective of this project is to investigate the relationship between demoralization and MiL on SI risk in patients with chronic pain. The secondary objectives are (1) to verify if demoralization can occur independently of depression in patients with chronic pain and SI, (2) to examine if the expected association between demoralization and SI may be explained by a sole dimension of demoralization: hopelessness, (3) to examine whether the presence of MiL, but not the search for MiL, is associated with a lower SI, and (4) to explore if previously described MiL profiles ,63 . All participant-related documents were stored in a secure and locked location. Electronic data were protected using strong password encryption. Data generation, transmission, storage, and analysis of health-related personal data followed the current Swiss legal requirements for data protection and were performed according to Human Research Ordinance Article 5.This project is an observational study—the Demoralization and Meaning in Life (DEMiL) study—conducted by the Division of Clinical Pharmacology and Toxicology and the Service of Liaison Psychiatry and Crisis Intervention at the Multidisciplinary Pain Centre (MPC) of the Geneva University Hospitals  of the Canton of Geneva . During their routine MPC visit, about 15 days after receiving the questionnaires, all participants received a written communication informing them about the research project and were able to pose questions or raise concerns with the project sponsor. Each participant was given at least 24 hours to review the written communication before being asked to sign the informed consent document, which took place during a subsequent study visit. A qualified team member reviewed the questionnaires for presence of SI and communicated relevant information about this study to the participants. Appropriate measures were taken for cases where severe SI was identified, including, if necessary, accompanying the patient to the psychiatric emergency ward. About 1-7 days after the routine MPC visit, patients who had agreed to be included in the study had a second study visit where they signed the informed consent form. All patients underwent completion of the MLQ .The desire and possibility of being included in the study did not influence in any way the patients’ overall evaluation or treatment. All patients received the appropriate treatment for their clinical situation as recommended by the MPC, which included pharmacological modifications, individual or group psychiatric treatment, and/or physical treatment.They also underwent a clinical interview and a structured diagnostic interview to screen for psychiatric diagnoses, including major depressive disorder, according to the DSM-IV  and the French version 5.0.0 of the Mini-International Neuropsychiatric Interview (MINI) . PatientParticipants were enlisted by ongoing recruitment through a project anchored in daily clinical practice at the MPC. To control for potential confounding individual differences, we screened for quality of life, assessed using the 36-Item Short Form Survey ; illnessInclusion criteria consisted of patients affected by chronic pain referred to the MPC and presenting with SI and control subjects not presenting with SI; groups were matched for age and gender. As the MPC is a third-line ambulatory referral center, most of the patients referred to the center by their treating physicians suffer from chronic neuropathic or nociceptive pain. Over the course of a typical year, about 40%-50% of incoming patients suffer from neuropathic pain; about 40% have osteoarticular pain, mostly lower back pain, fibromyalgia, and joint pain; while the remaining 10%-20% suffer from chronic visceral pain or from single-fraction radiotherapy cancer-related pain. Participants had to provide informed written consent and be 18 years of age or older. Exclusion criteria included patients with an insufficient comprehension of the French language and those affected by dementia, psychotic disorder, or borderline personality disorder. In cases of withdrawal of informed consent or noncompliance, participants were excluded from the study. If participants withdrew due to personal reasons, they were asked to inform the project leader about their withdrawal. Additional participants were recruited to replace those who had withdrawn.Regarding primary endpoints, we expected to observe a higher score on the Demoralization Scale (DS)  and a loRegarding secondary endpoints, we expected that patients with SI (presence and severity) would have (1) a higher DS score but not necessarily a higher BDI-II score, (2) a higher score for search for MiL and a lower score for presence of MiL, and (3) an MiL profile of combined presence and search, with higher scores for search for MiL and lower scores for presence of MiL.The following tools were used to assess secondary endpoints:The BDI-II was utilized to assess depression severity . The preThe MLQ  was usedThe sense of hopelessness was determined with thehelplessnesssubscale of the DS , which cA serious event (SE) is defined as any unfavorable event for which a causal relationship with the collection of health-related personal data cannot be ruled out and which (1) requires hospitalization or prolongation of hospitalization, (2) results in persistent or significant disability or incapacity, or (3) is life-threatening or results in death. When an SE occurs, the research project is put on hold and the EC is informed.This would be followed by an assessment by the project leader with regard to the project-specific measure relationship according to the following definitions:Unrelated: the occurrence of the event has no temporal relationship to the project-specific measures applied and can be explained by the underlying disease or other factors.Related: there is a plausible temporal relationship between the occurrence of the event and the project-specific, applied measures and cannot be explained by the underlying disease or other factors.SEs are documented in each participant’s case report form and source document and reported to the EC within 7 days. A report would be submitted to evaluate the relationship between our study and the event, explaining how the event affected the project and, if applicable, outline further protective measures to prevent reoccurrence.Assuming a 5% margin of error; a confidence level of 95%; a target population size of 400, as around 400 new patients are evaluated annually at the MPC; and a response distribution of 50%, then the minimum sample size required for this study is approximately 200: 100 presenting SI and 100 nonpresenting SI participants matched by age and gender. Questionnaire data were manually entered into an SPSS, version 23.0, database (IBM Corp) [P values of less than .05 and effect size. Missing value analysis was performed for all questionnaire scores to check for significant patterns. Where no patterns could be identified, the random missing values were replaced by the mean.Descriptive statistical analyses were conducted to compute means and SDs for numerical variables and frequencies (%) for categorical variables. The chi-square test or Fisher exact test was used for categorical variables and checked for matching between groups regarding age, gender, and years of education. To test our main hypothesis, repeated-measures analyses of variance were conducted to test for significant interaction between DS and MLQ variables and group factors (SI vs non-SI). The post hoc Tukey multiple-comparison test was used to find significant differences between means. In addition, hierarchical multiple regressions were used to test for predictive effects of MLQ and DS scores. Multivariate linear and logistic regression models were employed to explore the associations between MLQ score, DS score, and suicidal risk. Covariates were introduced into our model using a stepwise backward procedure to attain a parsimonious model to test effect modifications related to sociodemographic  and pain characteristics. All results are reported with a significance threshold of 2-sided From March 1, 2018, to November 30, 2019, 70 patients and 70 control participants were enrolled. Statistical analyses are still in progress and are expected to be finalized in December 2020. We did not observe any unfavorable event for which a causal relationship with the collection of health-related personal data could be ruled out. The results of this study will be used to develop new proposals for prevention and psychotherapeutic interventions oriented toward demoralization and MiL in patients with chronic pain, which will be based on the model of already-existing psychotherapeutic interventions for patients with other somatic conditions.narrative model [The interest in exploring demoralization and MiL in chronic pain patients with SI arises from the common clinical observation that experiencing chronic pain often requires a revision of one’s life goals and expectations. Different coping mechanisms have been proposed for chronic pain ,97. Howeve model ,59,66-70


Background: Percutaneous ablation of renal carcinoma is frequently a favourable treatment alternative, especially in elderly patients suffering from co-morbidities. Also, it is less resource-demanding than conventional surgery of renal carcinoma, and one may, therefore, assume that the incidence of this procedure may increase. Analgesia is necessary during this intervention. The aim of this study was to explore the possibility of analgosedation and its relation to patient comfort and safety during percutaneous ablation of renal carcinoma.Methods: Forty-six patients, sedated with dexmedetomidine and remifentanil, supplemented with infiltration anaesthesia (lidocaine 1%), underwent percutaneous (radiofrequency or microwave) ablation of renal carcinoma in this prospective study.Results: The patients expected pain intensity around the numerical rating score (NRS) 4.5 (interquartile range [IQR] 3.5–5.5), which was slightly lower than pain experienced during the procedure NRS 5 . Eight percent of the patients needed supplementary morphine during the ablation procedure. Sedation score did not differ during ablation, at arrival to or discharge from the recovery ward. Median periprocedural treatment time was 12 minutes (IQR 12–16). Treatment time did not correlate with experienced pain . The median length of stay in the recovery room was 120 minutes (IQR 84–154). There were seven serious adverse events.Conclusions: This proof-of-concept study has shown that analgosedation during percutaneous ablation of renal carcinoma can be performed with a generally tolerable degree of patient satisfaction. However, pain occurs and should be managed adequately. Patient safety must be a major concern for the anaesthetic care. The number of discovered cases of renal cancer is increasing, the most rapid increase being in small tumours . This seAdvantages of radiofrequency ablation include the rare occurrence of deterioration of renal function with an overall 5-year survival rate of 58–85%, according to meta-analyses . RadiofrIn a retrospective study, 19 patients with renal cell carcinoma were treated with radiofrequency ablation, while 21 patients were treated with partial nephrectomy. Length of hospital stay, mean procedural time, and blood loss were lower in patients treated with radiofrequency ablation. Elevated serum creatinine concentrations were noted in patients undergoing partial nephrectomy, but not in those undergoing radiofrequency ablation. Regarding the occurrence of metastasis, there were no differences ,6.Since radiofrequency ablations are performed in the radiological department, the anaesthetic procedure is more time-consuming and space-occupying than in a regular operating room, designed for pre- and postanesthetic management. Also, the distance between the radiological department and the surgical unit may cause problems when assistance is needed in an anaesthetic emergency. Furthermore, there is an advantage to the radiologist if the patient is cooperative and able to follow instructions. Thus, we decided to evaluate whether sedation in combination with local anaesthetic could be a favourable approach. Initially, we used midazolam in combination with remifentanil for this purpose. However, we had some complications in the form of mental confusion, too heavy sedation, agitation, etc.Therefore, we decided to change this concept and instead use dexmedetomidine and remifentanil during percutaneous ablation of renal cell carcinoma. This drug combination has proven efficacy in several surgical procedures, including awake craniotomy . InitialThe primary aim of our study was to evaluate overall patient comfort, focussing on the possibility to substitute anaesthesia with analgosedation during percutaneous ablation of renal carcinoma.Evaluate anaesthetic consumption as well as analgesic requirements during the first 24 hours after the procedure.Evaluate patient safety during the per- and postprocedural phases of percutaneous ablation of renal cell carcinoma in analgosedated patients.Describe patient characteristics and periprocedural circumstances for reference and guidance in similar interventions, either therapeutic or diagnostic.The secondary aims were to:Fifty-one patients planned for percutaneous ablation of renal carcinoma were screened for participation in this study. All patients gave their oral and written consent to participate in this study, which was approved (2013/409) by the Regional Ethical Review Board at Uppsala University, Sweden. According to Eudralex, we do not see this study as a clinical trial, which would need approval by the Swedish Medical Products Agency. This study was registered at Clinicaltrials.gov on December 13, 2013.In two patients, general anaesthesia was considered a better option, and one patient refused to participate in this study. Two patients were excluded because of other treatment options.n = 7), and only 2 were ASA 3.Demographic data of the 46  remaining patients were as follows: age (mean ± SD) was 66 ± 12 years; mean weight 79 ± 16 kg; mean height 170 ± 9 cm. The majority of patients  had limited co-morbidities and were considered to be classified as ASA 2, according to the American Society of Anaesthesiologists (ASA) physical status classification system; some were classified as ASA 1 , where ‘0’ is no pain and ‘10’ is the worst imaginable pain . The pat−1 h−1 and remifentanil administered by a target-controlled infusion, where the initial plasma level was set to be 0.5 ng mL−1. When necessary, infusion rate of remifentanil was changed at the investigators’ discretion, in order to achieve a comfortable sedation for the patient. Dexmedetomidine infusion was kept stable throughout the procedure. Local anaesthetic (8–10 ml of lidocaine 1%) was infiltrated in the kidney at the radiologist’s discretion during the treatment. An anaesthetic nurse and/or anaesthetist was present during the entire procedure.Nineteen patients asking for premedication received paracetamol 1 g orally, approximately 1 h before start of the ablation procedure. No other analgesic was given before the radiofrequency ablation. Conventional anaesthetic variables  were monitored. After administration of 0.5 mg of atropine, all patients received a continuous infusion of dexmedetomidine, starting at 0.4 μg kgSerious adverse events (SAEs) were defined as complications that were either fatal, life-threatening, requiring hospitalization, resulting in persistent significant disability, or requiring intervention to prevent permanent damage. n = 37) or two different microwave (MW) ablation systems . The choice of electrodes or probes was based on the manufacturers’ recommendations. Hydrodissection was used in 27 patients.The procedure was performed under CT-guidance . In 42 sessions one tumour was ablated, and in 4 sessions two tumours were ablated. When an optimal needle path was identified, the skin and needle track were infiltrated with 8–10 ml local anaesthesia. Prior to ablation, core biopsies with a 1.2 mm cutting needle were taken . Tumours were ablated using either a radiofrequency (RF) ablation system  and/or median, first (Q1) and third (Q3) quartiles, respectively. Paired Wilcoxon signed rank test was used for evaluating possible differences in expected versus periprocedural pain perception. A 40-patient sample size was calculated to achieve 85% power for the paired Wilcoxon signed rank test of expected versus experienced pain to detect a 2 NRS mean difference at the 5% significance level. In 16 patients the renal carcinoma was exophytic, in 13 patients the tumour was endophytic, and in 17 cases it was both exophytic and endophytic. Three patients had bilateral renal tumours, and in two cases a suprarenal gland was involved. In one patient the procedure was interrupted because of severe pain.p = 0.49). Four patients (8%) needed supplementary morphine during the roentgenological interventional procedure.The patients expected pain around NRS 4–5 , which was slightly lower than how they assessed their pain during the procedure , although the difference was not statistically significant by Mann–Whitney   min. Treatment time did not correlate with experienced pain ( 0.9553) .Treatment options were either RF or MW. The majority, 37 patients, received RF, while 9 patients received MW. There was no difference between the two treatment groups in experienced pain level, average RF = 4.94 (SD 3.04) versus MW = 5.36 (SD 2.58) .Maximal pain during the recovery phase was lower than both expected and experienced pain during the periprocedural phase . Sedation score  during tFour patients (8%) experienced postoperative nausea and vomiting, which needed treatment with metoclopramide, ondansetron, betamethasone, or a mixture thereof, during the post-interventional phase. Thirty-five patients (73%) experienced pain (NRS > 0) during the recovery phase. Morphine, usually at low dose  was administered to 25 of these patients. Ketobemidone at 2 mg was given to 2 of these 35 patients. Paracetamol was given to 18 patients, who had not received paracetamol as premedication. Eleven patients were given clonidine intravenously. Fifteen patients needed mixtures of these analgesic drugs during the recovery phase.Three patients needed supplementary morphine in the ward, and 15 of the 46 patients were given further paracetamol in the ward. One patient received ibuprofen for pain relief in the ward.Mean length of stay in the recovery ward was 143 ± 168 min . One patient (see below) stayed overnight.Mean satisfaction score was 3.7 ± 0.7 . Patient satisfaction at discharge from the recovery ward was in the same range. Mean satisfaction score was 4.4 ± 0.6 .n = 2), pain in shoulder (n = 1), and pruritus (n = 1).There were six procedural complications (SAEs) in the form of pneumothoraxes  and five reported post-procedural adverse events, one of which was a perioperative cardiac arrest, which was successfully resuscitated. This SAE was, at least partly, explained by the fact that a high dose of remifentanil was administered shortly before the termination of the intervention. After this incident, our handling routines of extensive pain were somewhat modified, and use of local anaesthetic was further encouraged. The other AEs that required treatments were severe nausea  during percutaneous ablation of hepatocellular carcinoma has been retrospectively investigated . The choAlthough some patients scored high pain levels during the renal intervention, the overall patient comfort in this prospective investigation seems satisfactory, since there were no significant differences in expected versus experienced periprocedural pain. Also, the need for supplementary morphine during the procedure was 8%, suggesting that the vast majority of patients found the administered amounts of dexmedetomidine and remifentanil sufficient. Postoperative pain was experienced in nearly three out of four patients, which is not surprising due to the fact that short-acting drugs were used. However, the total amount of opioids given at the recovery unit was not high.Dexmedetomidine is a potent alfa-2 agonist, having anxiolytic, analgesic, and sedative properties. It is an efficient adjunct to regional anaesthesia and reduces the need for opioids. Furthermore, dexmedetomidine may decrease the inflammatory response to renal ischaemia, which may be an advantage in this context . The othOur use of dexmedetomidine and remifentanil in the roentgenological department is an example of the known demand for sedation during regional anaesthetic procedures outside the operating room . In the Pneumothoraxes may occur during percutaneous ablation of renal carcinoma. Spontaneously breathing patients may be less prone to develop intrapleural inflation of gas, if the visceral pleura is perforated, compared to general anaesthesia, where intermittent positive pressure ventilation is applied, and, especially, when nitrous oxide is used. According to our experience, the incidence of pneumothoraxes in this study is in the same range as in fully anaesthetized patients.This study has several limitations. The most obvious one is the fact that this was not a randomised controlled trial. In a retrospective study performed between 2010 and 2015, including 51 patients, Kim et al. (Sedation with dexmedetomidine and remifentanil during percutaneous ablation of renal carcinoma appears to be efficacious, although several patients reported high pain scores.Somewhat surprisingly, the patients assessed the procedure as overall acceptable. Postoperative pain is a frequent problem, especially during the first two hours after the radiological intervention, and prophylactic analgesic regimen should be applied. However, care must be taken to avoid overdosage of opioids in this population. Analgosedation during ablation of renal carcinoma should be performed only by dedicated and well-trained anaesthetic staff.A large, preferably multi-center, prospective, randomized controlled trial, comparing analgosedation versus general anaesthesia during percutaneous ablation of renal carcinoma focussing on long-term therapeutic effects, safety, patient comfort, optimal dosage, and health economy would be advantageous. A non-opioid premedication is also recommended in order to limit the need for extra analgesics pre- and postoperatively.


Effective analgesia during delivery can not only decrease pain, but also have a significant function in ensuring the safety of baby and mother. Sufentanil is generally used opioid with ropivacaine in epidural anesthesia in labor pain management; however it can cause some adverse reaction. Dexmedetomidine is an a2-adrenoceptor agonist with high selectivity. It possesses opioid-sparing and analgesic effects and it is suitable for the long-term and short-term intraoperative sedation. The purpose of this present study is to compare the analgesic effect of ropivacaine with dexmedetomidine against ropivacaine with sufentanyl in epidural labor.n = 40 per group): the RD1 group , and the RD2 group , the RS1 group , as well as RS2 group . Clinical outcomes are pain score, a modified Bromage scale, the Ramsay Sedation Scale, and adverse reactions during analgesia. All the needed analyses are implemented through utilizing SPSS for Windows Version 20.0.This is a single center, placebo-controlled randomized trial which will be performed from May 2020 to May 2021. It was authorized via the Institutional Review Committee in the first medical center of Chinese PLA General Hospital (S2018-211-0). One hundred sixty full-term protozoa are included in this work. They are randomly divided into four groups . The labor pain is a strong respiratory stimulus that leads to a significant increase in oxygen consumption and minute ventilation in the process of contractions. Stress and pain during the labor stimulates sympathetic nervous system. The increase of catecholamine is related to the reduction of the uterine blood flow, and the increase of blood pressure and cardiac output. Non-treatment approaches have no adverse effects on maternal and newborn health but have poor analgesic effects. Therefore, it is used in mild to moderate pain conditions. Appropriate analgesics are necessary for parturient women during labor.,5Labor is considered to be one of the most painful and unforgettable things in a life of woman.–8 Other drugs associated with the axonal block or use alone include nitrous oxide, non-opioids, and opioids, distraction therapy as well as the patient-controlled analgesia.,10 Ropivacaine is local anesthetic agent which is widely used in the surgical procedure for pain control, including general surgery, joint arthroplasties, and cardiac surgery. The combined use of ropivacaine with opioid, such as sufentanil, in epidural anesthesia has a significant effect on postoperative pain management, but opioid have adverse reactions such as vomiting, headache, urinary retention, and respiratory depression.,13 Dexmedetomidine is an a2-adrenoceptor agonist with high selectivity. It possesses opioid-sparing and analgesic effects and it is suitable for the long-term and short-term intraoperative sedation. Published research studies have shown that the ropivacaine combined with dexmedetomidine can effectively relieve postoperative pain. The purpose of this present study is to compare the analgesic effect of ropivacaine with dexmedetomidine against ropivacaine with sufentanyl in epidural labor.The gold standard for the laboring patients is nerve axis block, containing epidural block, spinal cord, or the spinal-epidural combination techniques.22.1This is a single center, placebo-controlled randomized trial will be performed from May 2020 to May 2021, which is performed in accordance with the SPIRIT Checklist for randomized studies. It was authorized via the Institutional Review Committee in the first medical center of Chinese PLA General Hospital (S2018-211-0) and then was registered in research registry (researchregistry5877). The obstetrician will explain the details of trial, afterward, patiently answer all the questions from primigravidae. The primigravidae is then presented with the written information of our trial. Each patient received a written informed consent. Since all patients participated voluntarily, they could withdraw at any time during the trial.2.2n = 40 per group): the RD1 group , and the RD2 group , the RS1 group , as well as RS2 group . Physicians, statisticians, data collectors, and evaluators are all blinded to the allocation.One hundred sixty full-term primigravidae are included in this work. In the random envelope, all participating parturients will be assigned a random number via utilizing the random number table, and the result of allocation is hidden. They are randomly divided into four groups  is used to measure the parameters of hemodynamics (heart rate and the diastolic and systolic blood pressure) at various stages of delivery. Hemodynamic parameters are measured by the anesthesiologists of institutes.2.6Pain score was measured by nursing staff  of institutes by administrating visual analog scale (VAS) score at various stages of delivery. Ten: the maximum possible pain and 0: absent pain.The improved Bromage score is utilized to grade the motor block caused by intraspinal anesthesia in the parturient women. Zero point represents no movement obstacle; 1, cannot lift the straight leg, cannot move the feet and knees; 2, cannot lift the straight leg and move the knee, and can move the feet; and 3, the movement limb is completely blocked. And Ramsay Sedation Scale is utilized to evaluate the sedation levels of patients. The score of 1, indicates anxiety, uneasiness, and irritability; 2, oriented, cooperative, and calm; 3, only responsive to the commands; 4, brisk response to stimulus; 5, sluggish response to stimulus; and 6, no response to stimulus.Adverse reactions during analgesia are observed in these four groups, including bradycardia, respiratory depression, hypotension, nausea and vomiting, and pruritus. At the same time, urinary retention is monitored at 8 hours and 20 hours after delivery.2.7t-test or the Mann-Whitney U test is utilized for the comparison between groups. Chi-square detection is utilized to compare the categorical variables among the groups. The analysis of repeated measurement of the variance is applied to analyze the repeated data. A P < 0.05 is regarded the significant in statistics.All the needed analyses are implemented through utilizing SPSS for Windows Version 20.0. All the data are represented with proper characteristics as median, mean, percentage as well as standard deviation. Independent samples 3Table 4,16 Labor analgesia , that is, the use of pharmacological, psychological, physical, and other related therapies to relieve the pain of maternal childbirth. Common approaches in this area include the non-pharmacological and pharmacological methods. Drug-induced analgesia is more popular in the clinical practice, including intravenous anesthesia, epidural anesthesia, as well as inhalation anesthesia. Effective analgesia during delivery can not only relieve pain, but also have a significant function in ensuring the safety of baby and mother. Sufentanil and dexmedetomidine are commonly used in epidural analgesia. However, the optimal drug and regime remain controversial. We conduct this work to compare the ropivacaine with dexmedetomidine against ropivacaine with sufentanil for the epidural analgesia in labor. The limitation of the study is that the sample size of our study is small; a multicenter randomized controlled trial is still required.The labor pain will bring great mental and physical pain to the parturient women, and meanwhile, a series of stress reactions in the process of delivery will also have a negative impact. In recent years, with the continuous development of modern medicine, labor analgesia has been extensively utilized in obstetrics.5This current work can provide a primary evidence regarding the clinical outcomes of dexmedetomidine versus sufentanil for labor epidural analgesia.Yi Liu planned the study design. Maowei Gong reviewed the study protocol and collected data. Gang Chen finished the manuscript. All of the authors approved the article.Data curation: Maowei Gong.Formal analysis: Maowei Gong.Writing – original draft: Gang Chen.


Women with endometriosis are commonly treated by their sole provider. In this single-provider model of care, women frequently report long diagnostic delays, unresolved pelvic pain, multiple laparoscopic surgeries, sequential consultations with numerous providers, and an overall dissatisfaction with care. The emergence of multidisciplinary endometriosis centers aims to reduce diagnostic delays, improve pain management, and promote patient satisfaction; however, baseline data at the time of presentation to a multidisciplinary center are lacking.A real-world, retrospective, single-site, cross-sectional study of women with surgically confirmed and/or clinically diagnosed endometriosis generated baseline data for a planned longitudinal assessment of multidisciplinary care of endometriosis. The primary objective was to determine the proportion of patients experiencing mild, moderate, or severe pain for dysmenorrhea, non-menstrual pelvic pain (NMPP), and dyspareunia at entry into a multidisciplinary endometriosis clinic. Also explored were relationships between pain scores and clinical endpoints obtained from electronic medical records.n = 638) reported experiencing pelvic pain for ≥ 5 years. Pain intensity was highest for patients reporting dysmenorrhea, followed by NMPP, and dyspareunia. Significant correlations were observed between total pelvic pain and patient age  and number of previous healthcare providers ; number of previous providers and duration of pain ; and duration of pain and years since diagnosis . Mean pain scores differed significantly by age group for dysmenorrhea (p < 0.001), NMPP (p = 0.005), and total pelvic pain (p < 0.001), but not for dyspareunia (p = 0.06), with the highest mean pain scores reported among those < 30 years of age.More than half (59%) of the study participants (These real-world data indicate that in the single-provider model of care, unresolved pelvic pain is common among women with endometriosis. Alternative care models, including a multidisciplinary approach, need to be evaluated for improvements in clinical outcomes. These data also highlight the importance of addressing NMPP, which may be particularly troublesome for patients. Endometriosis is a chronic, inflammatory, and estrogen-dependent condition characterized by the implantation of endometrial-like tissue outside the uterus and is associated with pelvic pain and subfertility . An estiPatients with chronic pelvic pain display an array of symptoms, potentially related to several common gynecologic and non-gynecologic conditions, making timely diagnosis of endometriosis challenging and resulting in diagnostic delays of up to 12 years , 8. DelaAnother potential reason for the observed diagnostic delay may be that women with endometriosis conventionally seek and receive treatment from a single healthcare provider, often their usual gynecologist or primary care physician , 11. ThiConversely, a multidisciplinary model of care, leveraging the expertise of practitioners in multiple domains who are familiar with the treatment of endometriosis, has been proposed as an alternative treatment paradigm with the potential to improve outcomes for women with endometriosis , 13. WitThis study was a retrospective, single-site, cross-sectional, descriptive study of patients seeking care at the University of California San Diego Center for Endometriosis Research and Treatment (CERT) clinic between 2011 and 2018. All patients had previously received care from one or more single providers for endometriosis prior to enrolling in CERT for multidisciplinary care management. Women aged 16–55 years with surgically confirmed endometriosis and/or clinically diagnosed endometriosis were included. A clinical diagnosis of endometriosis was made based on the presence of symptoms suggestive of endometriosis in the absence of other explanations for the pain including adenomyosis, fibroids, ovarian cysts, and musculoskeletal abnormalities . ClinicaData from the initial CERT consultation were abstracted from electronic medical records  for all patients meeting inclusion/exclusion criteria and stored in a Microsoft Access  database. Because the objective of this study was to gain insight into the patients’ experiences within the single-provider model of care, before entry into our multidisciplinary program, data abstraction was limited to the initial visit in CERT. Patient characteristics included age at entry into the CERT clinic, race, body mass index (BMI), family history of endometriosis, current smoking status, and history of alcohol consumption. Medical history variables included type of pain , pelvic or abdominal tenderness, length of time since onset of pain and diagnosis, duration of pain, and prior endometriosis-related surgeries at non-specialist centers, as well as current and prior use of medications for endometriosis-related pain. Duration of pain was defined as the length of time between onset of pain and entry into the CERT clinic. Prior use of medications was defined as those medications used for the management of symptoms since onset of symptoms and prior to the time of presentation. We also captured the number of previous healthcare providers consulted since the onset of symptoms for the management of pelvic pain before entry into the CERT clinic. Results from transvaginal ultrasound imaging for clinically significant comorbid conditions were abstracted and included ovarian cysts greater than 2 cm in size, fibroids greater than 3 cm in size, adenomyosis, and other potential causes of pelvic pain, such as hydrosalpinx. Endometriomas greater than 2 m in size were also noted. Operative reports were obtained for patient’s prior surgeries.Pain severity was assessed using patient responses on the modified Biberoglu and Behrman pain scale questionnaire, which patients completed on their entry into the CERT clinic. The Biberoglu and Behrman scale was modified to capture only the three patient-reported pain symptoms  . Consistp < 0.05.Demographic and medical history variables were summarized using descriptive statistics. The mean and standard deviation (SD) were calculated for the continuous pain severity scores for dysmenorrhea, NMPP, dyspareunia, and total pelvic pain. Pearson’s correlation coefficients were computed to identify potential associations between total pelvic pain score and demographic and medical history variables. Chi-square tests, Pearson correlation, and analysis of variance were used to assess differences between groups in stratified analyses for categorical and continuous variables, respectively. Analysis of variance was also used to examine relationships between clinical variables and opioid use and frequent surgery. Analyses were conducted using IBM SPSS Statistics for Windows, Version 24  and results were considered statistically significant when n = 392) or clinical (n = 246) diagnosis of endometriosis. Patients mean age at entry into the CERT clinic was 33 years with 75% being younger than 40 years , with 48% reporting all three symptoms Table . As expeOf the 386 women who had been surgically treated and provided the number of endometriosis surgeries they had undergone since their initial diagnostic surgery, 226 (59%) reported one surgery and the remaining 160 (41%) reported repeat surgeries with 93% reporting three or fewer surgeries. While most patients had not undergone repeat surgeries to treat endometriosis, those treated surgically underwent an average of 1.7 ± 1.4 endometriosis surgeries (range 1–18) from diagnosis to entry into the CERT clinic. Interestingly, left oophorectomy was more common (5%) than right oophorectomy (2%) in this patient population. Of those treated surgically, the mean number of endometriosis surgeries per year since diagnostic surgery was 0.5 ± 0.4, (range 0.030–52.1). The patient reporting 52.1 surgeries per patient-year visited CERT 1 week following her surgery, and thus represents an outlier, highlighting a limitation of this type of analysis.Patients received healthcare for endometriosis from an average of four previous healthcare providers range 0–26) prior to entry to the CERT clinic, regardless of when they were diagnosed with endometriosis. The most common previous healthcare providers reported by patients entering CERT were obstetrician/gynecologists (512 [80%]) or primary care physicians (276 [43%]). Emergency room physicians and gastroenterologists were seen by 93 (15%) and 63 (10%) patients, respectively. Approximately one-third of the study population reported current analgesic use   of the patients with dysmenorrhea reported severe pain, and most patients with NMPP reported moderate (42%) or severe (30%) pain, regardless of current treatment at the time of the initial CERT visit Fig. . However% of the r = –0.22, p < 0.001, n = 506) and increased number of previous healthcare providers . Significant correlations were also observed between the number of previous providers and time since onset of pain  as well as time since onset of pain and years since surgical diagnosis , confirming the assumption that patients with longer duration of pain saw more previous healthcare providers. Significant correlations with higher number of previous providers was due mainly to correlations with NMPP  rather than dyspareunia  or dysmenorrhea .The mean (SD) total pelvic pain score on a 0–9 scale for the overall population was 5.22 ± 2.16. Patients reported higher pain scores for dysmenorrhea than they did for NMPP or dyspareunia Table . When evp < 0.001), NMPP (p = 0.005), and total pelvic pain (p < 0.001) (Table p = 0.03) and total pelvic pain (p = 0.04) were observed for patients who have previously seen ≥ 6 providers compared with those who have seen 0–1 provider. Significant differences by duration of pain were observed only for dysmenorrhea (p = 0.01), with the highest mean pain scores observed among those experiencing pain for 5–10 years. There were no significant differences in mean pain scores by years since diagnosis. Pain scores for dysmenorrhea, NMPP, and total pelvic pain differed significantly by opioid (p < 0.01) and NSAID (p < 0.01) use, while significant differences in pain scores for dyspareunia were observed only for opioid use (p < 0.01). When stratified by ultrasound-identified comorbidities of fibroids, adenomyosis, ovarian cysts, and endometriomas, significant differences in pain scores were observed only for endometrioma among patients with NMPP (p = 0.002).To further investigate these correlations, we stratified the pain scores for dysmenorrhea, dyspareunia, NMPP, and total pelvic pain by patient age, number of previous providers, duration of pain, and years since diagnosis. We also stratified pain scores by analgesic use and ultrasound-identified comorbidities. Lower mean pain scores were reported by patients in older age categories for all pain types and total pelvic pain, with statistically significant differences between age categories observed for dysmenorrhea (1) Table . Patientp < 0.001), dysmenorrhea (p < 0.001), dyspareunia (p = 0.006), NMPP (p < 0.001), number of previous healthcare providers (p < 0.001), and number of previous surgeries before attending the CERT clinic (p < 0.02)  Table . Pain scp = 0.004), had higher BMI (p = 0.001), and had been previously treated by a higher number of healthcare providers compared with those treated non-surgically. Mean pain scores for NMPP (p < 0.001), dyspareunia (p = 0.032), and total pelvic pain (p = 0.015) were higher among patients treated surgically, compared with those not treated surgically. No significant differences in mean pain score were observed for dysmenorrhea by surgical treatment status.Patients treated surgically were older , a coordinated multidisciplinary endometriosis center can also manage these other types of pain by providing integrative services including physiotherapy, acupuncture, and nutrition. Furthermore, patients benefit from staff members readily available to coordinate care between physician team members, which expedites timely referrals and ensures communication of clinical findings and patient management between the leading physician and other team members. Although endometriosis care at a large, experienced center is preferred, some specialist endometriosis care may require the establishment of satellite endometriosis clinics where additional interdisciplinary or multidisciplinary care services can be offered to ensure optimal whole-patient care for patients who reside further away from a large center.Use of a multidisciplinary treatment paradigm has been evaluated for deep dyspareunia and chronic pelvic pain. Using an 11-point scale, Yong et al. evaluated the severity of deep dyspareunia among 278 women (84.9% with or suspected to have endometriosis) treated at a multidisciplinary center . They foWomen with endometriosis who are treated under the single-provider model of care face substantial hurdles in receiving effective treatment, including long diagnostic delays, unresolved pain, multiple physician consultations in search of diagnosis, lack of timely referrals to specialists, and lack of multimodal and/or holistic therapies. Multidisciplinary care is hypothesized to improve patient care and outcomes by removing some of these obstacles. Our analysis provides baseline data from a real-world clinical population of women with endometriosis previously treated by one or more single healthcare providers, which may be used in future studies to assess the efficacy of the multidisciplinary care approach in improving treatment outcomes for patients with endometriosis.Limitations of our study include the cross-sectional, retrospective, and descriptive nature of the analysis. Because our data were captured at a single point in time, we could not evaluate changes in pain severity with disease progression or adjustments to pain medications. Patients were asked to report their medical histories and pain symptoms, which could result in misclassification due to inaccurate recall. The real-world data used for this analysis consistently lacked information on the use of magnetic resonance imaging to diagnose adenomyosis, thus, some of the reports of dysmenorrhea may have been due to adenomyosis. As data collection was limited to clinically relevant variables necessary for patient management, there may be other important variables affecting pain severity that we did not measure. Finally, our data were drawn from a population of women who were either self- or physician-referred to a single specialized center for endometriosis treatment and who may have had more severe symptoms than the overall population of women with endometriosis. Our findings may therefore not be generalizable to all other clinical settings.Strengths of this study include the detailed assessment of pain and other clinical characteristics in a large, real-world clinical population. Importantly, detailed and consistently applied pain severity scores based on the modified Biberoglu and Behrman scale were available. Medical histories and pain assessment questionnaires were also collected with the same physician at entry into the CERT clinic, reducing the potential for misclassification due to interrater variability.Our current understanding of the burden of endometriosis and related symptoms is limited by the self-selected nature of the study populations in the published literature. Because the burden of disease may differ between women who do or do not choose to participate in research studies, such real-world data could improve our understanding of current practice patterns in the management of endometriosis and related pain. This study provides real-world baseline medical history and pain severity data for women entering our multidisciplinary endometriosis treatment program. The data suggest that the traditional, single-provider model of care may be insufficient for a substantial proportion of women who have endometriosis and that NMPP may be a particular problem for these patients, leading them to seek multiple opinions in search of satisfactory care. Given the consistent and increasing data illustrating the limitations of single-provider models of endometriosis care, alternative healthcare delivery models need to be sought. Multidisciplinary care has potential benefits. However, additional studies to prospectively examine clinically relevant treatment outcomes, such as rate of opioid use and persistent improvements in pain and quality of life, are needed to evaluate the efficacy of the multidisciplinary endometriosis care model.


Palliative care is seeing cancer patients earlier in the disease trajectory with a multitude of chronic issues. Chronic non-malignant pain (CNMP) in cancer patients is under-studied. In this prospective study, we examined the prevalence and management of CNMP in cancer patients seen at our supportive care clinic for consultation. We systematically characterized each pain type with the Brief Pain Inventory (BPI) and documented current treatments. The attending physician made the pain diagnoses according to the International Association for the Study of Pain (IASP) task force classification. Among 200 patients , the median number of pain diagnosis was 2 (IQR 1–2); 67  had a diagnosis of CNMP; 133 (67%) had cancer-related pain; and 52 (26%) had treatment-related pain. In total, 12/31 (39%) patients with only CNMP and 21/36 (58%) patients with CNMP and other pain diagnoses were on opioids. There was a total of 94 CNMP diagnoses among 67 patients, including 37 (39%) osteoarthritis and 20 (21%) lower back pain; 30 (32%) were treated with opioids. In summary, CNMP was common in the timely palliative care setting and many patients were on opioids. Our findings highlight the need to develop clinical guidelines for CNMP in cancer patients to standardize its management. Pain is one of the most common and distressing symptoms in cancer patients, occurring in 50% to 90% of patients with advanced malignancies ,2. PoorlIn patients with cancer, pain can be classified as cancer-related pain, cancer treatment-related pain, or chronic non-malignant pain. There is a paucity of literature on the prevalence and impact of chronic non-malignant pain in the cancer literature. Chronic non-malignant pain has been studied mostly in patients with non-malignant diagnoses while pain research in cancer patients has focused mostly on cancer-related pain and cancer treatment-related pain. Indeed, the Center for Disease Control Clinical Practice Guideline on chronic pain specifically excluded cancer and palliative care patients ,8,9,10. A systematic and comprehensive examination of the prevalence of chronic non-malignant pain would inform clinical practice in the timely palliative care setting because the management of chronic non-malignant pain can be different from cancer pain. This is a particularly relevant issue in the era of an opioid epidemic, in which multiple pain management guidelines recommend minimizing the prescription of opioids for chronic non-malignant pain . In this prospective study, we examined the prevalence and management of chronic non-malignant pain in cancer patients referred to the supportive care clinic at our comprehensive cancer center.n = 117), the patient did not show up (n = 92), competing studies (n = 61), the patient was ineligible (n = 45), and other reasons (n = 77). Among the remaining 214 patients, 200 (96%) of the 208 fully eligible patients were enrolled.Recruitment occurred between 16 August 2018 and 14 March 2019. During this period, there were 606 scheduled palliative care consultations. In total, 392 patients were not approached because research staff were not available  and respiratory , and 138 (69%) had metastatic cancer. Pain was the symptom with the highest intensity on the Edmonton Symptom Assessment System (ESAS) . The median number of pain diagnosis was 2 (IQR 1–2) per patient.Among the 200 patients, 67  had a diagnosis of chronic non-malignant pain; 133 (67%) reported cancer pain, 52 (26%) had treatment-related pain, and 20 (10%) had pain that was not classifiable at the time of assessment. Among the 67 patients with chronic non-malignant pain, 31 (46%) had chronic non-malignant pain only, 20 (30%) had concurrent cancer-related pain, 12 (18%) had concurrent treatment-related pain, and 4 (6%) had both cancer-related pain and cancer treatment-related pain A.p < 0.001), less likely to be married (69% vs. 73% p = 0.048), more likely to have >1 pain diagnoses , and had a lower morphine equivalent daily dose (MEDD) . They were also less likely to have metastatic cancer  and had a higher Charlson Comorbidity Index (CCI) , albeit non-statistically significant. Patients with non-malignant pain also had a longer 1-year survival . In the multivariate logistic regression analysis, only the number of pain diagnoses was associated with the presence of chronic non-malignant pain (1 vs. 2: odds ratio 10.7 (95% 2.1–54.6), p = 0.71; 1 vs. 3 or more: odds ratio 75.1 , p < 0.001).In the univariate analysis , patientn = 37, 39%), low back pain , rheumatoid arthritis , and fibromyalgia . There was a total of 361 pain diagnoses, with 182 (50%), 60 (17%), 94 (26%), and 25 (7%) classified as cancer-related pain, treatment-related pain, chronic non-malignant pain, and unclassified pain, respectively . Physicip = 0.08), with corresponding mean BPI pain interfere score of 3.5, 2.5, and 2.5, respectively (p = 0.004). Among the 67 patients with chronic non-malignant pain, 41 (62%) ranked their chronic non-malignant pain as the most important pain diagnosis (p < 0.0001).The mean Brief Pain Inventory (BPI) intensity score was 4.0 for cancer-related pain, 3.5 for cancer treatment-related pain, and 3.4 for chronic non-malignant pain  patients who reported chronic non-malignant pain were on opioids, in contrast to 97/133 (73%) patients with cancer-related pain and 31/52 (60%) patients with cancer treatment-related pain B. An exaWhen analyzed by pain diagnoses, chronic non-malignant pain was most commonly treated with acetaminophen (36%), opioids (32%), and non-steroidal anti-inflammatory drugs (NSAIDs) (29%) . For canWe found that one in three cancer patients seen at the supportive care clinic for timely palliative care consultation had a diagnosis of chronic non-malignant pain. Chronic non-malignant pain often co-existed with other cancer-related pain and cancer treatment-related pain, and half of patients reporting chronic non-malignant pain were using opioids. Our findings highlight the need to develop clinical guidelines specifically for chronic non-malignant pain in cancer patients to standardize its management.To our knowledge, this prospective study is the first to focus on examining the prevalence of chronic non-malignant pain in palliative cancer care populations. One-third of cancer patients presented with chronic non-malignant pain at consultation. A handful of studies have reported the prevalence of chronic non-malignant pain in cancer patients, which varied between 2% and 76% ,14. ThisIn contrast to chronic pain in patients without cancer, chronic non-malignant pain in the palliative cancer care setting necessitates special considerations. From a diagnostic standpoint, the identification of cancer-related or treatment-related pain may sometimes be complicated by chronic non-malignant pain syndromes. For instance, spinal cord compression may be masked in a cancer patient with a history of chronic lower back pain. Furthermore, cancer treatments, such as immunotherapy, may exacerbate rheumatoid arthritis and chemotherapy could worsen existing diabetic peripheral neuropathy. Despite these potential challenges, we found that palliative care clinicians were able to make a diagnosis for 93% (336/361) of pain syndromes at the time of consultation and with a high level of supporting evidence.From a pain management standpoint, chronic non-malignant pain in the cancer patient can pose a challenge clinically. First, cancer patients often have concurrent pain diagnoses and may be prescribed other analgesics for those pain syndromes. For instance, 33 of 67 (49%) cancer patients with chronic non-malignant pain were on opioids, and 17 of 60 (28%) cancer treatment-related pain diagnoses were treated with gabapentinoids. Second, cancer patients have multiple comorbidities, which may either limit pain treatment options  and/or increase the number of existing medications . The mean CCI was 7.2 in this study. Third, chronic pain may significantly limit patients’ function, compounding the impact of cancer on the patient’s quality of life. Fourth, patients with advanced cancer often have a limited prognosis, which may impact their management. Fifth, some patients may be seeing primary care or pain clinics for the management of their chronic non-malignant pain while seeking advice from oncology and/or palliative care for their cancer pain, resulting in a “congress” approach to symptom management . Sixth, This topic is of particular relevance because palliative care is seeing a greater number of cancer patients earlier in the disease trajectory ,20. ManyIn the absence of high-quality evidence, how should clinicians manage chronic non-malignant pain in cancer patients? It is important to educate clinicians, patients, and caregivers on the difference between cancer pain and non-malignant pain in terms of natural history and management strategies. Proper treatment strategies of chronic non-malignant pain include rehabilitation therapy, cognitive-behavioral therapy, movement-based interventions, and non-opioid analgesics, such as acetaminophen and non-steroidal anti-inflammatory drugs ,24. In cThis study has several limitations. First, we only enrolled patients from a single comprehensive cancer center. Our findings may not be generalizable to other settings. Patients referred to palliative care generally have a higher symptom burden and more complex pain issues. However, our proportion of patients with chronic non-malignant pain was consistent with the estimate of 10% to 50% in the general population . Second,This was a prospective cross-sectional survey. We recruited patients from the supportivecare outpatient clinic at MD Anderson Cancer Center. Patients were eligible if they were seen for initial consultation, age ≥ 18, had a diagnosis of cancer with or without evidence of active disease, reported having pain within the last 3 months, and did not have delirium . The Institutional Review Board (2016-0901) at MD Anderson Cancer Center approved this study and all participants provided written informed consent.We collected patient demographics at enrollment, including Cut down-Annoyed-Guilt-Eye opener-Adapted to Include Drugs (CAGE-AID) questionnaire, the Screener and Opioid Assessment for Patients with Pain-14 (SOAPP14), ESAS, and CCI. The CAGE-AID is a validated questionnaire that examines the pattern of alcohol and drug use. An affirmative answer in at least 2 out of 4 questions has a 70% sensitivity and 85% specificity for substance use disorder . SOAPP14Our research physician asked patients how many types of pain they had experienced based on duration, location, and previous diagnoses, which were subsequently verified by the outpatient palliative care physician. For each type of pain, we administered the Brief Pain Inventory and documented the current treatment regimen, including opioids. The BPI is a validated questionnaire consisting of 12 numeric rating scales that range from 0 to 10 each (10 = worst) . The paiWe asked the attending palliative care physicians to ascertain the clinical diagnosis for each pain type based on the Caraceni and Portenoy classification system, which included 10 major categories and 91 subcategories . The majThe palliative care physician also recorded the supporting evidence for each pain diagnosis based on 4 previously published criteria : (1) PaiWe calculated that 200 evaluable patients would allow us to estimate the proportion of patients who had chronic non-malignant pain with a standard error of 2.5%, assuming that the proportion of chronic non-malignant pain was 15%.p < 0.10 were entered into a multivariable logistic regression model to identify factors associated with chronic non-malignant pain. Baseline demographics were summarized using descriptive statistics. Because patients often had more than one pain diagnosis, we analyzed the data by patient  and also by pain diagnosis . We estimated the proportion of patients who had chronic non-malignant pain with 95% confidence intervals. To compare among patients with and without non-malignant pain, we used the Wilcoxon rank-sum test or Kruskal–Wallis test for continuous variables, the Chi-squared test or Fisher’s exact test for categorical variables, and the log rank test for survival data. Overall survival was calculated from time of study enrollment to last date of follow-up. To compare among the pain diagnoses, we used generalized linear mixed models for both categorical and continuous variables to account for the partially overlapping data structure because many patients had more than 1 pain diagnosis. Variables with p-value of <0.05 was considered to be statistically significant. The Statistical Analysis System version 9.4  was used for statistical analysis. A We found that chronic non-malignant pain was common in cancer patients, often co-presented with cancer-related pain, and one in three patients were already using opioids for their chronic non-malignant pain when presenting to palliative care. Given the frequent use of opioids and the growing concern about non-medical opioid use in multiple countries ,38, care


Placebo can have a significant therapeutic effect in patients with hand osteoarthritis (OA). This aim of the study is to identify factors associated with a clinically meaningful placebo response in patients with hand OA.This post-hoc analysis of two double-blind, placebo-controlled, randomized trials (RCTs) investigating the efficacy of GCSB-5 or diacerein as treatments for hand OA analyzed the efficacy of a placebo. Clinical and laboratory factors associated with a clinically meaningful response, defined as an improvement in the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) pain score > 10 at 4 weeks relative to baseline, were identified.p = 0.001) and a worse AUSCAN stiffness  at baseline than non-responders. Improvements in pain correlated with the baseline pain level . Structural joint changes such as tender, swollen, enlarged, or deformed joint counts did not differ between placebo responders and non-responders. In a multivariable analysis, only baseline AUSCAN pain was associated with a clinically meaningful placebo response .The mean improvement in the AUSCAN pain score was − 6.0 ± 20.3, with marked variation between 143 hand OA patients (range: − 76.4 to 33.2). A clinically meaningful improvement was observed in 54 (37.8%) patients. Placebo responders had worse AUSCAN pain scores (55.7 ± 19.7 vs. 43.6 ± 21.6, High levels of pain at baseline are predictive of a clinically meaningful placebo response in patients with hand OA. Further studies are needed to optimize and utilize the benefit of placebo responses in patients with hand OA.The online version contains supplementary material available at 10.1186/s12891-021-04089-9. Osteoarthritis (OA) of the hands is common in middle-aged and elderly populations, especially women . The marA previous randomized clinical placebo-controlled trial (RCT) involving patients with hand OA reported that 30.2% of patients in the placebo group demonstrated a positive Outcome Measures in Rheumatology-OA Research Society International (OMERACT-OARSI) response at Week 4 , suggestClinicalTrials.gov (study no: NCT01910116 and NCT00685542). The post-hoc analysis included 102 patients with hand OA that were in the placebo group of the first RCT and 41 patients that were in the placebo group of the second RCT; patients with available clinical and laboratory parameters at baseline and at Week 4 were included in the analysis group (n = 143) , the AUSCAN stiffness score (0–100), the AUSCAN function score (0–100), a patient global assessment (0–100), a physician global assessment (0–100), and the OMERACT-OARSI response criteria. A clinically significant improvement in pain was defined as an improvement in the AUCAN pain score of 10 (0–100) or more . PatientP < 0.05 was considered to indicate statistical significance. All analyses were performed by using IBM SPSS Statistics 22 software. All statistical analyses were performed by the authors.An independent t-test and the Chi-squared test or Fisher’s exact test (as appropriate) were used to compare placebo responders and non-responders in terms of demographics and clinical variables. Normality of variables was examined using Kolmogorov-Smirnov test. Correlations between pain and clinical parameters were assessed using Pearson’s correlation. Multivariable logistic regression analysis was performed to identify factors associated with a clinically meaningful response. The mean age of the 102 patients with hand OA in RCT 1 and 41 patients in RCT 2 were 59.4 ± 8.0 years and 61.7 ± 18.9 years, respectively. Women were dominant in both RCTs. The mean disease duration of patients in RCT 1 and those in RCT 2 were 31.5 ± 47.7 months and 60.4 ± 61.1 months, respectively. Baseline characteristics of patients including AUSCAN pain, stiffness and function score were comparable between both groups , the AUSCAN function score , the patient global assessment , and the physician global assessment . However, the AUSCAN pain score was not associated with the tender joint count , the swollen joint count , the enlarged joint count , or the deformed joint count  at baseline. Similar correlations between baseline AUSCAN pain and other clinical characteristics were observed in RCT 2, except for TJC, which correlated with baseline AUSCAN-pain  (Supplementary Table SThe mean AUSCAN pain score at baseline was 47.8 ± 19.8 in RCT 1 and 48.9 ± 25.9 in RCT 2 (Table p = 0.944). The change in pain varied markedly between patients, ranging from − 76.4 to 33.2 in RCT 1 and − 59 to 46.0 in RCT 2 from baseline , a worse AUSCAN stiffness  than patients without clinical improvement. The tender joint count (TJC), the swollen joint count (SJC), the enlarged joint count, and the deformed joint count did not differ between patients with or without clinically meaningful improvement. More patients showing clinically meaningful improvement used tramadol-AAP at baseline than those not showing clinical improvement . There was no difference between groups with respect to other medications, including NSAIDs and glucosamine  of the 143 patients showed a clinically meaningful improvement  Table . These pr = − 0.427, p < 0.001). In addition, change in stiffness and function from baseline correlated with baseline stiffness  and baseline function , respectively  and baseline AUSCAN function  were associated with a better placebo response. In a multivariable analysis, only baseline AUSCAN pain was associated with clinically meaningful placebo response .A logistic regression analysis was performed to identify factors associated with a clinically meaningful placebo response. In a univariable analysis, baseline AUSCAN pain , the retention rate for tramadol/AAP is higher than that for placebo , 33. TheIt might be unethical to prescribe a placebo in routine clinical practice. However, the inherent placebo effect of any pharmacological and non-pharmacological treatment could be optimized in routine clinical practice. This is of particular importance since the placebo response might account for about 75% of response to drugs that are commonly used in OA treatment . To optiThis study has several limitations. First, the lack of a control group that did not receive any treatment (even placebo) makes estimating the placebo effect difficult. Second, we did not consider depressive mood disorders and/or emotional or physical stress, which might influence pain processing and so placebo responses. Third, RCT 2 (41 patients in the placebo arm) is too small to enable comparison of clinical parameters between clinical responders and non-responders. However, both RCT 1 and RCT 2 showed remarkably similar placebo responses (Supplementary Table SThe placebo effect can be significant in patients with hand OA who have high pain levels at baseline. Further studies are needed to understand the pathophysiology and underlying mechanisms, and to optimize the placebo effect as an OA treatment in clinical practice.Additional file 1: Table S1. Correlation between AUSCAN pain with baseline characteristics. Table S2. Placebo response at 4 weeks in RCT 1 and RCT 2.


There is no consensus in existing literature on the pulse power, application time, frequency and the dose of energy of laser therapy for the patients. Therefore, we conducted this research for the assessment of safety and efficiency of ultrasound and high-intensity laser therapy (HILT) in the lumbar disc herniation (LDH) patients.Our present research was approved by the institutional review board in the West China-Guangan Hospital. All the participants would acquire the written informed consent. From December 2020 to December 2021, we will conduct a prospective evaluation via a senior surgeon for 1 hundred LDH patients who plan to undergo the conservative treatment at our hospital. In this research, the inclusion criteria contained: the patients with lumbar disc herniation diagnosed by lumbar MRI; the patients with no history of trauma or congenital abnormalities; and the patients with sufficient psychological ability to understand and then answer the questions raised in assessment scale. The participants were randomly divided into the control group or HILT group after performing the examination of baseline. The main outcome was the pain score of visual analog scale. The other results contained the adverse effects, back range of motion as well as functional scores.We assumed that the HILT is as effective as the ultrasound therapy in treating pain for LDH.This study protocol was registered in Research Registry (researchregistry5975). The treatment of LDH is of great significance in managing pain, developing the disability and chronic pain and preventing the recurrence, and then accelerating the process of returning to work. The first-line management for the LDH is non-surgical treatment, which may include the pharmacologic and physical therapies, and/or the injection of epidural steroid.–9About 5% to 15% of the low back pain patients suffer from the lumbar disc herniation (LDH).–15 Another benefit of HILT, in particular the neodymium-doped yttrium aluminum garnet laser, is its higher power and penetration depth to the deep tissues. The application of HILT obviously decreases the degrees of pain in the chronic and acute diseases, for instance, carpal tunnel syndrome, chronic osteoarthritis, and rheumatoid arthritis, shoulder pain, the injuries of knee, fibromyalgia, as well as the pain after operation.,17–20The high-intensity laser therapy (HILT), which involves laser radiation with high-intensity, is a kind of novel, powerful and painless mode and has significant effects on relieving pain. The HILT possesses its own photomechanical, photothermal, and the photo-chemical properties, and it has many therapeutic effects, containing anti-edema, analgesic and the biological stimulation.There is no consensus in existing literature on the pulse power, application time, frequency and the dose of energy of laser therapy for the patients. At present, there are a few investigations on the effects of HILT treatment on the lateral epicondylitis, frozen shoulder, and cervical radiculopathy, knee arthritis, LDH as well as post-mastectomy. Nevertheless, in the chronic lumbar radiculopathy patients, the literature on the treatment of HILT is limited. Therefore, we conducted this research for the assessment of safety and efficiency of ultrasound and HILT in the LDH patients. We assumed that the HILT is as effective as the ultrasound therapy in treating pain for LDH.22.1Our present research was approved by the institutional review board in the West China-Guangan Hospital (GA20201703). All the participants would acquire the written informed consent. From December 2020 to December 2021, we will conduct a prospective evaluation via a senior surgeon for one hundred LDH patients who plan to undergo the conservative treatment at our hospital. Our present investigation was registered with the Research Registry (researchregistry5975) before registration started. All the surgeons, patients, statisticians, as well as research assistants who participated in this study were not aware of the group assignment.2.2In this research, the inclusion criteria contained: the patients with lumbar disc herniation diagnosed by lumbar MRI; the patients with no history of trauma or congenital abnormalities; and the patients with sufficient psychological ability to understand and then answer the questions raised in assessment scale. Patients with the history of severe osteoporosis or lumbar injections in past 4 weeks, and the patients with inflammatory pain, acute trauma, lumbar surgery, lumbar instability and neurological disorders, patients with severe diseases and severe or uncontrolled cardiovascular, as well as the patients undergoing physical treatment in the past 3 months will be excluded.2.3The participants were randomly divided into the control group or HILT group after performing the examination of baseline. The computer random number generator was applied for the random grouping. It priori produced one hundred random integers, and the random number already exist before this research starts. The randomly assigned, sequentially numbered and separated index cards were prepared. These above index cards were folded, and then kept in the opaque sealed envelopes. A researcher who did not know the baseline examination opened these envelopes and determined the interventions in accordance with the assignments of group Fig. .2.42 dose, the lumbar area exceeding 25 cm2 was stimulated with a biological stimulation mode for 4 minutes, and then performing the continuous pattern for 6 minutes with the dosage of 120 j/cm2 and 7 W power. The control group utilized the mobile ultrasound equipment during the treatment. The ultrasound was utilized for ten minutes at a power of 1.5 watt/cm in lumbar paravertebral region. Conductivity gel could be applied to enhance the efficiency of absorption and accomplish the thermal effects of deep muscle.The intervention group received the HILT (BTL 6000) after twenty minutes of hot compress for 2 weeks, and 5 days a week, in all, the intervention group received 10 times high intensity laser treatment. The device was set at 10 W power, 25 Hz frequency and 12 j/cm2.5The main outcome was the pain score of visual analog scale (VAS). VAS has been proved as an effective and reliable method for the pain measurement. On a 10-centimeter line, the score of 0 represented no pain, and 10 represented maximum pain. On this 10-centimeter line, the patients needed to show the severity of their low back pain. Afterwards, using a ruler to measure the distance from 0 to the marked point.The other results contained the adverse effects, back range of motion (ROM), as well as functional scores . Roland Disability Questionnaire is a kind of sensitive, effective and reliable questionnaire, which could be used for the measurement of the functional level of patients in conducing daily tasks. The score ranges are between 0 and 24, and the patient is asked to put a marker next to each proper statement in the 24 statements list. Oswestry disability index consists of ten questions that evaluate weight lifting, personal care, pain, standing and sitting, walking, and sleeping, social life, the pain variation level and trave, with each question scoring from 0 point to 5 point. The highest score is 50. Multiply the total score by 2 to obtain the percentage result. For ease of use, a ROM goniometer was applied for the measurement of the spine ROM: the extension and flexion of the spine was measured by sagittal plane meter, and lateral flexion was measured via lateral plane meter. The measurements of ROM were implemented twice via 2 independent observers prior to treatment initiation and during a 4-week follow-up examination.2.6The power and sample size were calculated through using the statistical software of nQuery Advisor (version 6.0). The VAS difference between the 2 repeated measurements can reach 80% with 0.05 level of alpha, 1.5 standard deviation, and when the correlation between observed values of the same participant was 0.7 and the sample size of the intervention group and the control group is 50 and 50 respectively.2.7t-test, and for the categorical variables comparison, it can be implemented with the pearson Chi Square test. The obtained results were assessed in the 95% confidence interval with P < .05 significance level.The software of SPSS v22.0 could be utilized to conduct the statistical analyses . KolmogoroveSmirnov test was applied to test the consistency between the normal distribution and the data. The continuous variables were compared with the independent 2 samples 3LDH is 1 of the most familiar causes of the low back pain. According to a survey, about 70% to 85% of people have the low back pain, with an annual incidence of 15% to 45% and an annual medical cost of 26.3 million dollars for the LDH, which creates a serious financial burden on the society. Thus, the focus of research on the disease is to find a cost-effective treatment approach. Laser therapy is a kind of painless, non-invasive and it can be easily managed in a wide variety of conditions in the primary care setting. We conducted this research for the assessment of safety and efficiency of ultrasound and HILT in the LDH patients. We assumed that the HILT is as effective as the ultrasound therapy in treating pain for LDH.Conceptualization: Youyi Huang.Data curation: Youyi Huang, Daxin Gao.Formal analysis: Youyi Huang, Daxin Gao.Funding acquisition: Daxin Gao.Investigation: Daxin Gao.Methodology: Youyi Huang.Resources: Daxin Gao.Software: Daxin Gao.Supervision: Daxin Gao.Validation: Youyi Huang.Visualization: Youyi Huang.Writing – original draft: Youyi Huang.Writing – review and editing: Daxin Gao.


Conclusion: Given the feasibility of rapid online deployment, low cost, and low risk of adverse events, this eHealth intervention for HRQOL may be useful for patients with chronic pain during the COVID-19 pandemic.Purpose: This study was conducted to determine the feasibility of providing an eHealth intervention for health-related quality of life (HRQOL) to facilitate patient self-management. Methods: A randomized controlled trial was conducted from 2019–2020 within the Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation. Eligible patients included those with chronic low back pain and a SPADE  cluster score ≥ 55 based on the relevant scales from the Patient-Reported Outcomes Measurement Information System instrument with 29 items (PROMIS-29). Patients were randomized to the eHealth treatment group, which received a tailored HRQOL report and interpretation guide, or to a wait-list control group. The primary outcome was change in the SPADE cluster score, including its five component scales, over 3 months. Secondary outcomes were changes in low back pain intensity and back-related disability. Treatment effects were measured using the standardized mean difference (SMD) in change scores between groups. The eHealth intervention was also assessed by a survey of the experimental treatment group 1 month following randomization. Results: A total of 102 patients were randomized, including 52 in the eHealth treatment group and 50 in the wait-list control group, and 100 (98%) completed the trial. A majority of patients agreed that the HRQOL report was easy to understand (86%), provided new information (79%), and took actions to read or learn more about self-management approaches to improve their HRQOL (77%). Although the eHealth intervention met the criteria for a small treatment effect in improving the overall SPADE cluster score (SMD = 0.24;  Many discretionary health care services were curtailed throughout the United States in March 2020 because of the national emergency attributable to the declaration by the World Health Organization of the pandemic of coronavirus disease COVID-19) caused by the novel virus known as SARS-CoV-2 [9 caused A variety of remotely supported pain management approaches under the umbrella of telehealth have been considered for deployment during the COVID-19 pandemic, including eHealth, mHealth, virtual reality, augmented reality, remote treatment, and digital therapeutics . The WorThe Patient-Reported Outcomes Measurement Information System (PROMIS) was developed with support from the National Institutes of Health for research on physical function, anxiety, depression, low energy/fatigue, sleep disturbance, participation in social roles and activities, and pain interference with activities . ElementHealth-related quality of life may be an attractive paradigm for guiding and improving chronic pain management because it is patient centered and may be more readily understood by patients than other more technical information, such as the results of laboratory tests or imaging studies. However, HRQOL measures have not been widely adopted in health care settings or by patients for self-management. The primary aim of this study was to determine the feasibility of providing a simple eHealth intervention pertaining to HRQOL to facilitate patient self-management.The Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation (PRECISION Pain Research Registry) was established in 2016 and subsequent operations were guided by principles recommended by the Agency for Healthcare Research and Quality . A histoTo be considered for inclusion in the trial, patients must have been 21 to 79 years of age at the time of registry enrollment and have had sufficient English language proficiency to complete the registry case report forms independently or with assistance from registry staff. Additionally, patients must have met the diagnostic criteria for chronic low back pain established by the National Institutes of Health Task Force  at the tPatients were randomized to either the experimental or control treatment group using a random number generator. The experimental treatment group received the eHealth intervention consisting of a HRQOL report that was tailored to patients based on their scores for the SPADE cluster and each of its five component scales. The report included a graphic summary of scores for each measure and interpretation guide. A sample report is provided in the Patients in the experimental treatment group were surveyed 1 month following randomization to measure the value and utility of the eHealth intervention and patient behavior in response to it. The primary areas of interest included the value of the HRQOL report on a numerical rating scale (NRS) from 0  to 100 ; perceptions of the report (ease of understanding and acquisition of new information about HRQOL); and actions taken in response to the report (reading and learning about or implementing self-management approaches to improve HRQOL).Outcomes were assessed 3 months following randomization. The primary outcome measure was the SPADE cluster score, including its five component scales. Secondary outcomes included low back pain intensity and back-related disability. Low back pain intensity was measured with an NRS for the average pain intensity over the past 7 days, ranging from 0 (no pain) to 10 (worst pain). Back-related disability was measured with the Roland-Morris Disability Questionnaire (RMDQ) , rangingA total of 102 patients were included during the limited 2-month enrollment period. Detection of a small-to-medium effect size for the experimental treatment vs. control treatment, as manifested by a standardized mean difference (SMD) = 0.35 for change on the SPADE cluster score over the course of the trial, would have required 258 patients (129 patients in each treatment arm) to achieve 80% statistical power in intention-to-treat analysis . Thus, tThe baseline characteristics of patients in the experimental and control treatment groups were measured using standard descriptive statistics and compared using contingency table methods for dichotomous variables and the Student’s t-test for continuous variables. Mean change scores for the primary and secondary outcome measures from baseline to the 3-month follow-up were used to compare the experimental and control treatment groups. Change scores were reversed so that a positive score represented an improvement in each measure . Because the trial was not powered to detect treatment effects at or below the threshold for a small-to-medium effect size (SMD = 0.35), statistical significance was of secondary interest compared with the magnitude of the effect size of the eHealth intervention for each primary and secondary outcome measure . As withA total of 100 (98%) of the 102 randomized patients completed the trial . There wThe mean value rating of the eHealth intervention was 62.9 (SD = 29.0) ; howeverp = 0.06) and back-related disability . No adverse events were reported during the trial. Missing data were not imputed because 3-month follow-up was virtually complete.There were no significant differences between the experimental and control treatment groups in any primary or secondary outcome . The chaThe eHealth intervention yielded several small or small-to-medium treatment effects over 3 months of follow-up in patients with chronic low back pain. Small treatment effects were observed for the SPADE cluster score for overall HRQOL and for anxiety. Small-to-medium treatment effects were also observed for the SPADE component scale of depression and for the secondary outcome of back-related disability. Interestingly, low back pain intensity did not trend in the direction of improvement with the eHealth intervention. These findings suggest that the eHealth intervention more specifically targeted HRQOL outcomes, and the related aspect of back-related functioning, rather than low back pain intensity. The importance of improving HRQOL in patients with pain has been emphasized in the Federal Pain Research Strategy . MoreoveAlthough the observed treatment effects for changes in overall HRQOL  and back-related disability were considered to be of small or small-to-medium effect size, it is important to note that they were observed within only 3 months of randomization using a simple intervention that was tailored to individual patients and administered online at minimal cost and without reported adverse events. Most research on pharmacological therapy for chronic low back pain has focused on such outcomes as pain intensity, back-related disability, and adverse events. A systematic review and meta-analysis of nonsteroidal anti-inflammatory drugs, the recommended first-line pharmacological interventions for chronic low back pain ,20 foundOur PRECISION Pain Research Registry has shown decreased utilization of various recommended non-pharmacological treatments for chronic low back pain within the first three months of the COVID-19 pandemic in the United States . SpecifiAs eHealth interventions for chronic pain are likely to remain after the COVID-19 pandemic ends , more reOur intervention was aimed at patients primarily to help them initiate self-management of chronic low back pain, particularly involving HRQOL. A majority of patients in our trial who received the eHealth intervention indicated that the report was easy to understand and provided new information about their HRQOL. Within only 1 month, a majority of patients also began reading and learning more about self-management approaches to improve their HRQOL. However, a shortcoming of the intervention was that standardized and validated information about improving HRQOL was not provided directly to patients. Thus, we could not determine if patients accessed self-management strategies that were appropriate for their HRQOL deficits and likely to result in improved outcomes at 3 months.Our feasibility trial had several strengths. First, it involved a pragmatic approach using registry patients who received their usual care for chronic low back pain from community-based providers. Second, based on recommendations from the National Institutes of Health Task Force , diagnosIn summary, the present study demonstrated the feasibility of rapidly deploying an eHealth intervention for HRQOL in patients with chronic low back pain. A majority of patients who received the eHealth intervention indicated that the report was easy to understand, provided new information, and prompted them to read or learn more about self-management approaches to improve their HRQOL. The intervention yielded small or small-to-medium treatment effects over 3 months in several aspects of HRQOL. Given its relative ease, rapidity, and low cost of deployment, its low risk of adverse events, and its treatment effect sizes generally comparable to nonsteroidal anti-inflammatory drugs, it appears that this eHealth intervention for HRQOL may be useful for patients with chronic pain during the COVID-19 pandemic.