This study aimed to compare outcomes of mini-invasive surgical treatment ofendometriosis, especially conventional laparoscopy with robotic-assistedlaparoscopy, and to evaluate the quality of life.One hundred three consecutive patients with endometriosis who had surgeryfrom 2014 to 2017 owing to an indication of pain were enrolled in thisretrospective study. The majority  of patients underwentconventional laparoscopy and 18 (17%) had robotic-assisted laparoscopy. Thequality of life was postoperatively assessed with a questionnaire.The rates of parametrectomy  and rectovaginal resection (28%vs. 4%) were significantly higher in robotic-assisted laparoscopy than inlaparoscopy. Additionally, the rate of bowel operations (50% vs. 17%),especially the shaving technique, was higher in robotic-assisted laparoscopysurgery than in laparoscopy (39% vs. 8%). There was no difference in therate of postoperative complications between laparoscopy and robotic-assistedlaparoscopy. Most (91%) of the patients who answered the questionnaire feltthat surgical treatment had relieved their pain. In the laparoscopic androbotic-assisted groups, 88% of respondents felt that their quality of lifehad improved after surgery.This study suggests that robotic-assisted laparoscopy is a feasible method toresect deep infiltrating endometriosis, especially in the rectosigmoidarea. Indications for surgical management arefailure of medical management, the purpose of diagnosis, treatment of an adnexalmass or treatment of infertility.4Endometriosis is an inflammatory, estrogen-dependent, chronic disorder infertile-aged women. Endometriosis is defined as the presence of endometrial glandsand stroma outside the uterine cavity. Although endometriosis is considered as abenign disease, it can cause severe chronic pain and infertility, and decrease thequality of life.5 However, a disadvantage of surgery is that when removing DIE lesions,complications often occur affecting gastrointestinal, urinary or sexual functions.Complications after surgery of DIE include rectal fistula (0.3%–2%), bowel stenosis(2%) and bladder atony (4%–6%).68 Therefore, the decision ofsurgery with its risks, benefits and extension should be carefully considered anddiscussed with patients who have endometriosis.The mini-invasive approach of laparoscopic or robotic-assisted laparoscopy is highlyrecommended for endometriosis.10 A few studies compared laparoscopic or robotic-assistedapproaches in the surgical management of endometriosis.1115 Robotic-assisted laparoscopicsurgery is associated with a longer operation time than laparoscopicsurgery,16 but results are controversial.14 The results of previousstudies regarding benefits of robotic-assisted laparoscopy over conventionallaparoscopy are somewhat heterogeneous. However, patients with features of a complexpelvic situation, such as severe endometriosis, an increased body mass index orprior surgeries, might benefit from robotic-assisted surgery.17Currently, even extensive radical operations of the bowels or urinary tract can beperformed mini-invasively.In our institution, robotic-assisted surgeries were initiated in 2016. This studyaimed to evaluate the results of mini-invasive surgery for DIE in a single tertiaryinstitution. Specifically, we aimed to 1) compare outcomes after conventional orrobotic-assisted laparoscopic surgery in our institution and 2) evaluate the qualityof life after surgery by a specific questionnaire.This retrospective study investigated consecutive patients who had been operated onfor endometriosis-related pain between January 2014 and December 2017 in KuopioUniversity Hospital. The Research Ethical Committee of Northern Savo approved thestudy protocol (1012/13.02.00/2018) and written informed consent was obtained fromall patients.18 Briefly, the stage of endometriosis is divided into the four stages of I, II (mild), III (moderate) and IV (severe). Data collected from medicalfiles included prognostic, diagnostic and operative information, such as age, bodymass index, operation date, preoperative symptoms, cancer antigen 125 (CA125) andhuman epididymis protein 4 (HE4) biomarkers, magnetic resonance imaging (MRI)findings, previous operations due to endometriosis, Clavien–Dindo classification,19 operation technique, operative areas, hormonal treatments and postoperativecontact with a clinic because of pain from endometriosis. The upper normal limit forCA125 levels is 35 kU/L and that for HE4 levels is 70 pmol/L in premenopausal womenin our hospital laboratory.Endometriosis was diagnosed by laparoscopy or histologically in all patients. Thestage of endometriosis was classified in accordance with revised American Societyfor Reproductive Medicine classification.All of the patients were also sent a questionnaire inquiring about their well-beingin January 2019. This questionnaire included questions about pain postoperatively,if the operation caused any short- or long-term harm, alternative treatments theyhad tried and their benefits, whether and how endometriosis was still affectingtheir daily lives and if the patients felt that the operation was beneficial andcaused some change in their quality of life. The numeric rating scale (NRS) from 0to 10 was used, where 0 indicates no pain and 10 the worst possible pain.IBM SPSS Statistics for Windows, version 27  was used instatistical analysis. Values are presented as mean ± standard deviation, unlessotherwise stated. The Kruskal–Wallis test followed by the Mann–Whitney test forcontinuous variables in multiple comparisons were used when appropriate. We used thechi-square test to analyze frequency tables. A p value of < 0.05 was consideredsignificant.The characteristics of the patients are shown in Preoperative hormonal treatments are shown in As shown in In the majority  of patients with CA125 level measurement,preoperative serum CA125 levels were above the normal limit. In contrast, serumHE4 levels were within the normal limit (n = 37).Most patients underwent conventional laparoscopy or robotic-assisted laparoscopy. InthreDetails of the operated areas are shown in There were no significant differences in the rates of postoperative complicationsbetween conventional laparoscopy and robotic-assisted laparoscopy . The mosAlmost half  of the patients returned the well-being questionnaire,which was sent to them after the operation. The median time between theiroperation and their answers to the questionnaire was 38 months (range: 14–61months). Detailed results of the questionnaire are shown in Most (91%) of the respondents felt that surgical treatment had relieved theirpain and 90% of the respondents thought that the operation had been beneficial.In the laparoscopic and robotic-assisted groups, 88% of the respondents feltthat their quality of life had improved after surgery.Two-thirds (62%) of the respondents who had laparoscopy and one-third ofrespondents who had robotic-assisted laparoscopy reported that they were stillexperiencing pain due to endometriosis less or more often than monthly. Patientswere asked in the questionnaire to score their pain by the NRS at the currentmoment. The mean NRS value was 1.9 ± 1.2 at 1 year after surgery, 1.0 ± 0.8 at 2years, 3.1 ± 1.0 at 3 years, 1.7 ± 1 at 4 years and 3.6 ± 0.8 at 5 years . There wApproximately half of the respondents described short-term adverse effects afterthe operation . DysuriaWe found that robotic-assisted laparoscopy was a feasible method for resection ofDIE, especially in the rectosigmoid area. Furthermore, pain and quality of life ofthe patients were evaluated by asking them to fill in a questionnaire. Most of theresponders reported that surgery relieved their endometriosis-related pain and theirquality of life had improved.13 Pelvic pain, dyspareunia and dyschezia were the most common symptoms in ourpatients. Hormonal treatments were widely used preoperatively in most cases.According to the European Society of Urogenital Radiology, MRI is recommended as asecond-line imaging technique preoperatively.20 Transvaginal ultrasound and MRI achieve a similar accuracy in the diagnosisof DIE.21 Currently, MRI imaging is a routine procedure before surgery to evaluate thelocation and extent of DIE being used in addition to transvaginal ultrasound in ourhospital.We report a single tertiary center experience of mini-invasive surgical treatment ofpainful endometriosis. Our patients represent a typical cohort of those who haveendometriosis-related pain.CA125 levels are often elevated in patients with endometriosis. As expected, in ourcohort, 72% of the patients had elevated CA125 levels. However, the benign nature ofthese findings was confirmed because HE4 levels were normal in all of our patientsand no ovarian carcinomas were diagnosed.22 They found that less complications were associated with shaving than withsegmental resection. In a large study by Mabrouk et al., the overall rate ofshort-term postoperative complications was significantly higher in patients whounderwent segmental resection compared with those who underwent discoid excision or shaving.8 Furthermore, segmental resection does not appear to achieve more long-lastingimprovement of symptoms compared with discoid resection or shaving.23 Especially at the level of the low rectum, shaving is the recommended methodto avoid injury of vascular and sympathetic and parasympathetic nervebundles.25 However, discoid excision or segmental resection is still anoption to treat DIE at or above the sigmoid colon.23 In our study, we preferred shaving in accordance with recommendations. In therobotic-assisted laparoscopic group, shaving was used in 78% of patients who hadundergone a bowel operation and no segmental resection was performed. The managementof bowel endometriosis depends on the number of lesions, and their depth ofinvasion, size and circumferential involvement.26 Therefore, selection of thesurgical technique needs to be tailored to each individual patient.Kondo et al. reported complication rates in patients who underwent a rectal operationthat involved segmental resection, discoid excision or shaving.11 This trial was not able to detect any differences in perioperative outcomesor the operative time between the robotic-assisted procedure and laparoscopy.Nonetheless, patients who required bowel resection were excluded from this trial.Results from other smaller mainly retrospective studies were heterogeneous. Some ofthese studies reported longer operation times with robotic-assisted procedures thanwith laparoscopy, while other studies found benefits from robotic-assistedsurgery.16 Ercoli et al. showed that robotic-assisted laparoscopicnerve-sparing rectal nodulectomy appeared to be a feasible and safe approach intreating isolated retrocervical–rectal DIE.27 Recently, intravenous indocyanine green and near-infrared radiation imagingwere reported to have an additional benefit in rectosigmoid endometriosis inassessing the blood supply of the bowel after resection.28 These techniques might also be helpful in separating endometrial nodules fromhealthy tissue. However, intraoperative near-infrared radiation imaging can be usedduring conventional or robotic-assisted laparoscopy.29To date, there are only limited data comparing management of rectosigmoid DIE betweenrobotic-assisted laparoscopy and conventional laparoscopy. The LAROSE trial, whichwas a randomized, multicenter trial, compared the treatment of endometriosis betweenrobotic-assisted laparoscopy and conventional laparoscopy.30 In our cohort, all of the laparotomies were performed when robotic-assistedsurgeries were not available in our institution. In the current study, noconversions to laparotomy were performed, which suggested the feasibility of usingrobotics. However, a multidisciplinary robotic team is necessary to operate onpatients with rectosigmoid or urinary tract DIE.In our study, there was no difference in the rate of complications between patientswho had robotic-assisted laparoscopy or conventional laparoscopy. However, twopatients who had robotic-assisted laparoscopy had Clavien–Dindo grade IIIpostoperative complications. This complication rate was acceptable because thesepatients had complicated DIE in the pelvis. Our results are also in line with arecent pilot study that compared robotic-assisted and conventional laparoscopy intreating colorectal endometriosis.32 However, after 2 to 5 years, 36% of surgically treated patientsmight need to undergo a new operation33 These results are in line with the present findings. In the present study,most of the patients with endometriosis-related pain reported less pain and animprovement in their quality of life after surgery. According to the NRS scores,during the first 2 years after surgery, the patients’ pain symptoms were lessintense, but subsequently, a trend towards higher NRS scores was observed. Notably,in this study, the first 2 years of follow-up included patients who had undergoneeither robotic-assisted or laparoscopic surgery, but the later evaluation includedonly those who had been treated with conventional laparoscopic operations.Approximately 50% to 80% of patients with endometriosis consider a surgical treatmentto be beneficial for endometriosis-related pain during the first 2 years after theoperation.There are some limitations to this study. First, our study was retrospective and thenumber of patients was limited. There might have been some bias because the morecomplex cases were routinely operated on using robotic-assisted techniques after2016. These patients had a shorter follow-up time than patients who were operated onbefore this time. Second, our questionnaire of well-being has not been validated.Third, we had no information on the quality of life before the patients had surgery.Furthermore, pain was the only symptom that we evaluated.In conclusion, the present study suggests that robotic-assisted laparoscopy is afeasible method to resect DIE. Mini-invasive surgical treatment also improves thequality of life in the majority of patients suffering from endometriosis-relatedpain. Further prospective investigations of mini-invasive treatment of patients withbowel endometriosis are warranted.


The overall severity of pain reduced from 6.51 ± 0.86 to 1.83 ± 1.25 in the intervention group (p < 0.05). It increased from 6.41 ± 1.12 to 6.65 ± 1.37 in the control group (p = 0.02). The repeated measures ANOVA showed that there is a significant difference in the change of pain scores between intervention and control groups . Garlic extract can reduce pelvic and back pain, dysmenorrhea, and dyspareunia which are important symptoms of endometriosis.Endometriosis is a common chronic inflammatory disease. Garlic contains components that have antiproliferative, anti-inflammatory, and antioxidative effects. The current study aimed to evaluate the effectiveness of garlic on endometriosis symptoms. This was a randomized placebo-controlled triple-blind clinical trial. A convenience sample of 60 women was randomly allocated into two groups. The intervention group received usual care supplemented with 400 mg garlic tablets, and the placebo group received identical placebo tablets. A four-part Visual Analogue Scale (VAS) was used to measure the severity of pains. The pains were measured on four occasions . Data were analyzed using the  Endometriosis is a chronic inflammatory disease. It is characterized by the presence of endometrial-like tissue outside the uterine cavity . It is aThe etiology of endometriosis has not been fully understood. There are some theories about its etiology including the theory of retrograde menstruation, the theory of coelomic metaplasia, and the theory of the embryonic rest . SmokingEndometriosis has four stages: stage 1 , stage 2 (mild), stage 3 (moderate), and stage 4 (severe). The minimal stage is characterized by small lesions and superficial endometrial implants on the ovaries. Small lesions and shallow implants on the ovaries and the presence of a pelvic lining are the characteristics of the mild stage. The characteristic of the moderate stage is the appearance of deep and more implants on the ovary and pelvic lining. In the severe stage, deep implants cover the pelvic lining and ovaries . OvarianChronic pains in the form of dysmenorrhea, dyspareunia, and nonmenstrual pelvic and back pain are the main symptoms of endometriosis. More than 80% of women with endometriosis have reported pain symptoms. Some studies considered it as a disabling condition that may affect the quality of life, social relationships, mental health, and sexuality of women . The posThe main treatment of endometriosis is the resection of lesions. Surgical treatment or laparoscopic removal of lesions can reduce the symptoms and increase the quality of life of patients significantly. However, patients will need long-term medication even after surgery . In mostThe present study was a randomized placebo-controlled triple-blind clinical trial that investigated the effect of garlic tablets on the pain related to endometriosis in women. Data were gathered from July 2015 to March 2016.The study population was all women with confirmed endometriosis (confirmed by surgery or laparoscopy) who attended to the Valiasr Fertility Research Center, Tehran University of Medical Sciences, Tehran, Iran. A convenience sample was recruited from women who had inclusion criteria. The inclusion criteria were age between 20 and 45 years, being currently married, not being diagnosed with severe physical or mental illness , being able to write and read Persian, receiving routine treatment for endometriosis, and not being diagnosed with other pelvic inflammatory diseases. The exclusion criteria were missing two or more consequent doses of garlic tablets, being diagnosed with other diseases, and using multivitamin supplements. The minimum sample size was determined after a pilot study on 10 women from the original population. They were asked to rate their pain in a 0–10 cm Visual Analogue Scale (VAS). The mean and standard deviation of pain was 7.2 ± 2.5. Based on an effect size of 1.5, a power of 80%, and a two-sided type-I error rate of 5%, the minimum sample size was calculated to be 60 patients per trial arm with a 25% probability of sample loss. Study subjects, the persons who carried out the intervention, and the statistician did not know who received which intervention.Samples were randomly allocated into two groups in a 1 : 1 ratio using permuted blocks of four. Within each group of four, two samples were allocated to the intervention, and two were allocated to the placebo. The order in which women were allocated in each block was random. There are six possible permutations of allocation if there are blocks of four and two groups, AABB, ABAB, ABBA, BABA, BAAB, and BBAA. Samples with letter A were placed in the garlic tablets group, and samples with letter B were placed in the placebo group. Blocks sequences were determined by the dice rolling by the statistic consultant. Allocating the samples at random within a block in a 1 : 1 ratio ensured that the two groups had similar numbers of participants. The H.R. and Z.B. were not present in the patient enrollment, and the S.S. was not involved in data analysis. A CONSORT diagram representing the allocation of patients within the 3-month follow-up is presented in The data-gathering tools were a sociodemographic questionnaire and a four-part visual analog scale. A researcher-designed questionnaire was used to collect data on sociodemographic variables . Weight was measured to the nearest kilogram without shoes and light clothing. Height was measured without shoes to the nearest centimeter using standardized measuring equipment. The stage of endometriosis is determined based on the surgery report. The pain was assessed using a four-part Visual Analogue Scale (VAS). The VAS has been repeatedly used in the literature as a way to measure patient-perceived pain . PatientPatient enrollment was conducted at the Valiasr Fertility Research Center, Tehran University of Medical Sciences. The diagnosis was confirmed by surgery or laparoscopy. All patients with a confirmed diagnosis of endometriosis (within a month) were approached by the S.S. The aim of the study was explained to the study participants. The intervention was described to them. The VAS and pain assessment method were explained to the samples. In the end, written informed consent was obtained from them.μg of allicin). The placebo group received usual care and placebo tablets which were identical to the garlic tablets.All patients received their routine and standard treatment for endometriosis which was recommended by their physicians. The intervention group received usual care supplemented by a garlic tablet per day. Each tablet contains 400 mg of dried garlic powder . The mean ± SD of BMI was 22.21 ± 4.32 and 21.85 ± 3.43 in intervention and placebo groups, respectively . The mean ± SD of age at diagnosis in intervention and placebo groups was 25.76 ± 5.00 and 26.15 ± 4.34 years, respectively . The distribution of women based on history of infertility, irregular menstruation, familial history of endometriosis, alcohol consumption, and smoking is presented in One hundred and twenty women completed the twelve-week intervention. The mean ± SD of age in intervention and placebo groups was 29.41 ± 8.54 and 29.71 ± 5.67 years, respectively (p < 0.05). In contrast, the pain in the garlic tablet group was significantly reduced (p < 0.05). Because there were significant differences between the two groups in terms of education level and endometriosis stage, the ANCOVA test was conducted to evaluate their effects on the results. A one-way ANCOVA was conducted to determine if there is a statistically significant difference between the two groups on pain reduction controlling for the endometriosis stage. There was a significant effect of garlic tablets on the reduction of pain after controlling for the endometriosis stage, F  = 2.01, p = 0.161. Another one-way ANCOVA was conducted to determine if there is a statistically significant difference between the two groups on pain reduction controlling for the education level. There was a significant effect of garlic tablets on the reduction of pain after controlling for the education level, F  = 1.49, p = 0.226.Changes in the pelvic and low back pain, dysmenorrhea and dyspareunia, and the overall score of pain are presented in Allium sativum tablets in the reduction of pain related to endometriosis. The results showed that the twelve-week use of garlic tablets could significantly reduce back and pelvic pain, dyspareunia, and dysmenorrhea. Pelvic and low back pain, dyspareunia, and dysmenorrhea were severe before the treatment period. The pain was significantly reduced during the intervention period. The reduction of pain may be an indicator of damage decrease or decline of factors that affect the pain-producing mechanisms. Based on the partial eta squared, the effect of the garlic pill on the reduction of pain related to endometriosis was high. The highest effect was on dyspareunia.The current study aimed to evaluate the effectiveness of the daily use of 400 mg of Pelvic pain is one of the symptoms of endometriosis, and its severity is a marker of the endometriosis stage. It is associated with problems such as depression and other psychiatric disorders . DyspareThere is limited evidence on the effect of garlic pills on pain induced by endometriosis. The present study was one of the first clinical trials that investigated the effects of garlic extract on endometriosis symptoms. Previous research has been conducted on animal tissues and animal models. The results of laboratory models showed that garlic extract could reduce endometriosis pain . The resThere are four ways in which garlic can relieve pain in endometriosis: decrease of oxidative stress, reduction of prostaglandin production, a decrease of endometriosis cell proliferation, and an increase of estrogen elimination , 32–34.The severity of endometriosis has a significant effect on pain and other symptoms, and its treatment can reduce the symptoms , 36. It Garlic is a rich source of N-acetylcysteine . It is tThe third mechanism that can reduce endometriosis pain is its effect on estrogen elimination. The liver eliminates estrogen through phase I and II detoxifications. It is a process by which the liver dissolves the estrogen in the bile and the estrogen leaves the body through the stool. As endometrial cells respond to estrogen by growing and becoming more sensitive, an increase in detoxification can reduce the estrogen and the symptoms of endometriosis. The results of studies have shown that garlic extract can help to increase estrogen detoxification . AllicinThe clinical studies about the use of garlic in the treatment and reduction of pain in endometriosis are limited. The results of a review showed that while herbal extracts (including garlic) had antiproliferative, anti-inflammatory, antiangiogenic, and antioxidant effects on endometrial cells and endometriotic lesions, the existing evidence supporting their use in endometriosis therapy is quite limited . Most stOne of the most important limitations of the present study was that there were no similar studies for comparisons. One of the most important limitations of the present study was that one of the exclusion criteria was not taking more than two consecutive doses of the drug by patients. For this criterion, we could only rely on patient reports that may not be entirely accurate. Another limitation was short time of follow-up. We could not follow-up subjects after three months. We recommend to follow-up patients for longer periods and assess for how much time the effect of garlic will remain after not taking it.The results of this study showed that garlic extract could reduce the symptoms of endometriosis. It can reduce pelvic and back pain, dysmenorrhea, and dyspareunia which are essential symptoms of endometriosis. These pains are the results of inflammation which is the underlying cause of endometriosis. Garlic can reduce the pain and other symptoms by a decrease of oxidative stress, reduction of prostaglandin production, a decrease of endometriosis cell proliferation, and an increase of estrogen elimination. The results of the study showed that pelvic pain gradually increased in the absence of treatment of endometriosis, as in the control group. But in the intervention group, with the consumption of garlic extract, pelvic pain decreased, indicating a decrease in inflammation.Endometriosis is a chronic disease that can negatively affect the quality of life of patients. While patients need long-term medical treatments to relieve their symptoms, some of them need to undergo surgical procedures. Garlic extract contains a significant amount of allicin and other anti-inflammatory components. Further studies are recommended on the effectiveness and determination of the best dose of garlic extract. Also, garlic is a cheap substance that can be recommended for women with endometriosis.


The objective of this study was to investigate in a real-life context the effectiveness of long-term opioid therapy for reducing pain intensity and interference and improving health-related quality of life (QOL) in patients with chronic noncancer pain.Participants were 893 patients  enrolled in the Quebec Pain Registry (2008–2011) who completed questionnaires before their first visit at one of three multidisciplinary pain management clinics and 6 and 12 months thereafter. Based on their opioid use profile (OUP), patients were categorized as nonusers, non-lasting users, or lasting users. Data were analyzed using generalized estimating equations.P values < 0.001). Lasting users of opioids reported higher levels of pain intensity and interference and poorer pQOL than nonusers and/or non-lasting users over the 12-month follow-up . However, all effect sizes were small, thus questioning the clinical significance of these group differences. Among lasting users, more than 20% of patients experienced a meaningful amelioration in pain intensity and interference as well as mental QOL (mQOL), whereas only 8% exhibited improved pQOL.More than 60% of patients newly initiated on opioid therapy stopped their medication mainly because of adverse effects and/or lack of pain relief. OUP significantly predicted pain intensity and interference and physical QOL (pQOL; A significant subgroup of patients may benefit from long-term opioid therapy in terms of pain severity and mQOL but the majority do not. The challenge facing clinicians is how to identify who the responders will be. Two studies found that patients with CNCP using long-term opioid therapy reported more pain and greater disability than those not using opioids.21,22 Two other studies, conducted among long-term opioid users only, found that patients reported relatively high pain intensity and interference,23,24 with an important proportion of patients having a deteriorated quality of life.23There is a lack of evidence in the literature supporting the effectiveness of long-term opioid therapy among CNCP patients. A literature review published in 2009 by the American Pain Society in collaboration with the American Academy of Pain Medicine found that very few studies have investigated the long-term benefits of opioids (≥6 months) in CNCP,25 These authors therefore concluded that opioid therapy may not be beneficial in the majority of patients with chronic neuropathic pain.25 A subsequent subanalysis of this study, conducted by Bostick et al. involving 537 patients with chronic neuropathic pain, found that physical functioning and disability did not improve in patients who were prescribed opioids compared with those who were not.26 In contrast, Watson et al. surveyed 84 patients using opioids on a regular basis and found that the majority reported at least 50% or greater pain relief and a moderate improvement in disability.27 However, this study involved highly selected patients and the authors acknowledge that their results may not be generalizable to all CNCP patients in whom opioids are being initiated. Brooks et al. conducted a qualitative study focusing on the lived experience of nine patients using opioids to manage their CNCP came to the conclusion that positive effects of opioids outweighed the negative for most participants.28 However, further observational studies involving large samples of patients suffering from a variety of CNCP syndromes are needed in this field as the results can complement those of randomized clinical trials for evidence-based guidance of treatment decisions.Recently, Moulin et al. conducted a long-term national study in patients suffering from neuropathic pain and found that those who were on high dose of opioids at baseline and at follow-up exhibited poorer outcomes at 12-month follow-up.The objective of the present longitudinal study was to investigate in a real-life context the effectiveness of long-term opioid therapy for reducing pain severity (intensity and interference) and improving health-related quality of life  in patients with CNCP over a 1-year period.29 Patients were enrolled in the QPR between October 2008 and November 2014 if they were (1) scheduled for a first visit at the pain clinic for multidisciplinary treatment considerations, (2) aged 18 years or more, (3) fluent in spoken and written French and/or English, and (4) physically and cognitively able to complete questionnaires. Biopsychosocial data were collected prior to the initial visit at the pain clinic (baseline) and 6 months later. Up to March 2012, additional follow-up data were gathered at 12 and 24 months but only in those patients who had not been discharged from the pain clinic in the meantime, mainly because they do not have a family physician. Patients suffering from CNCP (≥3 months) were therefore selected for the present study among those enrolled in the QPR between October 2008 and April 2011. Only patients who provided written consent for their QPR data to be used for research purposes (more than 90% of patients29) and who were not currently taking opioids at the time of their first visit at the pain clinic were included in the study. Given small sample size at 24-month follow-up due to patients’ discharge in the meantime, only data collected up to 12 months were taken into account in the present study.Participants were recruited from the Quebec Pain Registry (QPR), which is a vast database of patients referred to university-affiliated multidisciplinary pain treatment clinics in the province of Quebec, Canada.The Research Ethics Boards of the Centre hospitalier de l’Université de Montréal, McGill University Health Center, and Centre hospitalier de l’Université de Sherbrooke approved the QPR project. Data at baseline and follow-up  were collected with a self-report questionnaire (patient self-administered questionnaire) and medical/clinical data  were gathered by the QPR nurses using a structured interview protocol (nurse-administered questionnaire).All of the questionnaires were structured so that patients who reported multiple pain sites were asked to focus on the most painful one to complete the questionnaires.30 is a widely used scale to measure pain intensity.31 It consists of an 11-point scale  on which the participants are asked to select the number corresponding to the intensity of their pain. The NRS has good reliability, validity, and sensitivity.30,31 Participants were asked to rate on the NRS their average and worst pain intensity over the past 7 days at each time point (baseline and follow-ups).The Numeric Rating Scale (NRS)32 consists of ten items  assessing the extent to which pain impacts on various aspects of daily living. Participants are asked to rate on a scale from 0 (does not interfere) to 10 (completely interferes) the extent to which pain has interfered in the past 7 days with general activity, mood, mobility, normal work, relationships with others, sleep, enjoyment of life, self-care, recreational activities, and social activities.32 A global interference score can be derived by adding the ratings on all items, with higher scores indicating greater pain interference. The psychometric qualities of the BPI are well documented32,33 and it has been shown to have good validity and sensitivity to change in chronic pain patients attending a multidisciplinary pain treatment clinic.35 The BPI has been translated into French using a forward–backward translation method.36The Brief Pain Inventory (BPI-10)37 is a valid and reliable 12-item scale that assesses health-related quality of life (QOL). For each item, patients are asked to choose the answer that best describes their condition. The SF-12v2 generates norm-based scores for eight different domains as well as two composite scores representing physical and mental health–related QOL. Higher scores indicate better QOL.The Short-Form-12 Health Survey Version 2 (SF-12v2)Patients were asked information on their pain history  and type(s) of medication currently used and used in the past 6 months to treat their pain.38 is a well-validated screening tool that assesses the presence of neuropathic pain through self-report and physical examination. Each of the ten items is answered yes (score 1) or no (score 0). The total score is calculated as the sum of the ten items and the cutoff value for the presence of neuropathic pain is a total score of four out of ten.The Douleur Neuropathique 4 (DN4)39A summary of the data collected with the patient and nurse questionnaires was given to the pain physician at the patient’s initial visit. Once the visit was over, the physician was provided with a standardized form on which she or he was invited to record the patient’s diagnostic code(s) using the QPR pain diagnostic grid.The opioid use profile (OUP) variable was created by classifying patients into one of three categories based on current and past medication reported at each time point . All patients included in the study were opioid naïve at baseline. Patients who reported not taking any opioids during the course of the study  were categorized as nonusers. Patients who started using opioids within the first 6 months but stopped taking them thereafter (at 6 or 12 month) were categorized as non-lasting users. Patients who were put on opioids within the first 6 months and continued taking them at each follow-up period (6 and 12 months) were categorized as lasting users.A type of pain variable was also created and was composed of the three following categories: patients who were diagnosed with neuropathic pain by the physician of the pain clinic and had a DN4 score ≥ 4 were classified into the neuropathic pain category. Patients with a neuropathic pain diagnosis and DN4 score < 4 as well as those with a nonneuropathic pain diagnosis and DN4 score ≥ 4 were categorized as having mixed evidence of neuropathic pain. Last, patients with a pain diagnosis other than a neuropathic origin and a DN4 score < 4 were categorized as having nonneuropathic pain.t tests and Pearson’s chi-square tests were employed to compare the baseline characteristics of patients who did and did not complete all questionnaires at each time point . Mean and standard deviations along with frequency tables were used to describe participants’ characteristics. All patients included in this study were not using opioids at baseline.Independent Student’s Generalized estimating equations (GEEs) adjusting for sex, age, pain duration, and frequency were used to examine whether OUP and type of pain were associated over the 1-year follow-up period (time effect) with reported average and worst pain intensities, pain interference global scores, physical health–related quality of life (pQOL), and mental health–related quality of life (mQOL). In our five GEE models, the time effect encompassed measures collected at baseline, 6 months, and 12 months, thereby allowing group comparisons over time and at each time point in the event of a significant interaction. Pairwise comparisons were then used to assess the statistical significance of the group differences.d40 for continuous variables, the phi (φ) statistic for binary categorical variables, and Cramér’s v for discrete variables with more than two categories41) were also examined given that significant testing in studies involving large sample sizes like the present one can be misleading because even small differences can reach statistical significance, whereas clinically, they can be viewed as trivial and not meaningful.42–44 Only differences reaching a Cohen’s d value equal to or greater than  ±0.5 or a φ or a Cramér’s v value equal to or greater than  ±0.3 were considered meaningful and clinically important.42–44Effect sizes of group differences , suggesting that these differences were not clinically meaningful.A total of 2650 patients were enrolled in the QPR during the selected study period and consented for their information to be used for research purposes. As shown in n = 554). Patients suffered from CNCP from 3 months to 60 years, the median being 3 years. More than 75% of the participants were classified as having neuropathic pain or mixed evidence of neuropathic pain. At baseline, pain intensity on the average in the past 7 days was 6.75 (SD = 1.9) on the 0–10 NRS.Among the users of opioids, close to two thirds (63.1%) stopped taking them during the follow-up period, mainly because of side effects (36.2%) and/or lack of efficacy (20.5%).2 (df = 2) = 20.41, P < 0.001, worst pain intensity, χ2 (df = 2) = 54.13, P < 0.001, pain interference, χ2 (df = 2) = 20.89, P < 0.001, and pQOL, χ2 (df = 2) = 28.29, P < 0.001, over time . This was true irrespective of the type of pain the patients were suffering from . As shown in P < 0.001, Cohen’s d = 0.27, and worst pain, P < 0.001, Cohen’s d = 0.46), greater pain interference , as well as poorer pQOL  over time than the nonusers. Compared to nonusers, non-lasting users reported higher pain intensity , greater pain interference , and poorer pQOL . Comparison between non-lasting users and lasting users revealed that the latter group reported higher pain intensity  during the follow-up period. All of the above Cohen’s d values were less than ±0.5, thereby questioning the clinical significance of the observed differences.Results of the GEE, which are summarized in Examination of the types of response among the lasting users of opioids revealed that at 12-month follow-up, close to one in four lasting users experienced a significant improvement (≥20%) in their pain intensity and interference. The same was true for their mQOL. In contrast, pQOL improved from baseline to 12 months among only 8% of the lasting users see .Table 3.42 In this article, none of the group differences reached a medium to large size effect . Although Cohen’s criteria are guides rather than absolutes, the clinical significance of the mean group differences can be viewed as questionable. In other words, although a significant subgroup among those who took opioids over a 1-year period did experience improvement in pain severity (intensity and interference) and mQOL, the majority did not and continued to report high pain severity scores as well as poor health-related quality of life .To our knowledge, this multicenter study is the first to have examined the effectiveness of long-term opioid therapy for reducing pain severity and improving health-related QOL in a large heterogeneous sample of patients with CNCP newly initiated on this type of treatment and followed in a real-life context. Our study revealed statistically significant differences in the patients’ outcomes according to their OUP. However, in studies involving large sample sizes like the present one, examination of effect sizes may prove to be more informative than statistical significance testing.25 Studies carried out in primary care settings showed much lower prevalence rates of opioid use ranging from 7.1% to 19.9%.21,46–48 The high rate of opioid use among our sample may be explained by the fact that these patients were recruited in tertiary care centers and have typically tried many other alternative therapies without significant success.49 However, as important, if not more important, to emphasize is the high percentage of patients (63.1%) who interrupted the use of opioids during the follow-up period, because this can be viewed as an important treatment failure rate. These results are consistent with those of the literature reviews of Noble et al.,50 Furlan et al.,20 and Abdel Shaheed et al.,51 who reported high rates of opioid discontinuation across studies mainly due to adverse events and/or insufficient pain relief.Results of our study showed that nearly half of patients referred to specialized pain clinics and who were not discharged before the end of the 1-year follow-up period were on opioids at one time or another during the course of their treatment, a finding that is consistent with Moulin et al.’s results.21,22 In one of these studies, persistent opioid use was defined based on dispensed opioid volume and number of prescriptions during 365 days,22 whereas in the other, patients were considered long-term opioid therapy users if they reported using this type of medication on a regular basis.21The lasting opioid users continued to report high mean pain intensity scores (average and worst pain) during the follow-up period. This result is consistent with those of two studies that found that long-term opioid therapy did not contribute to lower pain intensity on average among patients with CNCP.52 Since then, several other studies have assessed functional outcomes among patients with CNCP using long-term opioid therapy and found that opioids did not improve physical functioning and disability.23–26Our study also showed the same pattern of results with regard to the effects of long-term opioid use on pain interference in various aspects of daily living. In his systematic review, Ballantyne reported that function has been investigated in a limited number of trials, and these studies vary considerably in both their design and principal findings.4 Another possible reason for the lack of long-term opioid effectiveness may be related to the fact that this type of medication can also induce hyperalgesia, a phenomenon called “opioid-induced hyperalgesia” (OIH) and defined as a state of nociceptive sensitization caused by exposure to opioids and characterized by a paradoxical response whereby a patient receiving opioids for the treatment of pain may actually become more sensitive to certain painful stimuli.53–55 However, the precise mechanism of OIH is not yet understood, and this phenomenon has been mainly studied in the context of a short-time exposure rather than a long-time exposure to opioids.54 That patients with CNCP on long-term opioid therapy may develop OIH cannot be excluded, and this issue certainly merits further investigation.Relatively little scientific evidence exists on the reasons why long-term opioid treatment may fail to improve patients’ pain severity. It is commonly believed that sustained administration of this type of medication can be accompanied by a tolerance phenomenon leading to a progressive loss of the drug effects with a decrease in the apparent analgesic efficacy.21 and Campbell et al.’s23 observations suggesting that long-term use of opioids would not be really helpful for improving health-related quality of life. This is problematic in view of the fact that the amelioration of patients’ quality of life commonly constitutes the primary goal of CNCP management, a goal that is often set as important as reducing the pain itself.56–58 In an earlier study, Choinière et al found that health-related quality of life was remarkably low in patients with CNCP on waitlists of multidisciplinary pain treatment.59 Similar results were obtained in the present study, where the patients’ norm-based scores on the physical scale of the SF-12v2 were much lower than those in the general population, and this was true whether or not they were on opioid treatment. These findings further highlight the deteriorated quality of life of this group of patients.In our sample, lasting users of opioids continued to report poor QOL on the average. These results are consistent with Eriksen et al.’s25 This is not negligible, because these results suggest that long-term use of opioids may be effective for a subgroup of patients with CNCP. Further research is clearly needed to identify the characteristics of patients who are most likely (and least likely) to benefit from long-term opioid treatment. Some earlier reports60–63 suggest that factors such as sex, depression, anxiety, and treatment expectations may play a role, but additional studies involving large sample sizes are needed to address this important issue.Results from this study showed that though the majority of lasting users remained stable over time, about one in five patients experienced a significant improvement in their pain condition and mental health–related quality of life. This is similar to the findings of Moulin el al.’s study where close to one fifth of patients with neuropathic pain treated with opioids in tertiary care pain centers showed clinically significant improvement in their pain and function 12 months later.64 Furthermore, it is important to mention that access to tertiary care clinics in the province of Quebec requires a physician referral; access to these clinics is free but limited due to relatively long waiting lists, as is the case in other Canadian provinces.65 As a result, it is unclear how the data obtained in the present study compare to what would be obtained in other health care systems . In addition, patients were classified into different OUP categories based on their self-reported current medication use at the time of the first visit at the pain clinic and at follow-up interviews at 6 and 12 months; it is possible that patients interrupted their opioid treatment for a while within each 6-month period separating the follow-up interviews, and this was not taken into account in the OUP classification. Finally, because our study was not a randomized controlled trial, it is unknown whether or not persistent opioid users’ conditions would have worsened over time if they had not taken this type of medication.Like any other studies, the present one has limitations that merit comments. First, our sample did not include 476 patients who were discharged from the pain clinic within the 12-month follow-up and therefore did completed all follow-up questionnaires. Thus, we may have missed some patients who continued to use opioids and were doing well or patients who did not respond to opioids and were discharged from the clinic because no other treatments could be offered. Second, in our sample, the follow-up period was limited to 12 months, though it may take more than a year to really be able to assess the effectiveness of long-term opioid therapy. Third, this study is limited to patients with CNCP attending tertiary care pain clinics. Most of them had chronic pain for years and had tried several approaches to treating their condition. In addition, this study does not capture patients who are doing well on opioids in the community and who are not referred to pain clinics. This may impact the generalizability of the findings. However, one can suspect that opioids are more commonly prescribed at the tertiary care level because many family physicians may not feel comfortable using this type of medication due to the risk of substance abuse.Close to one quarter of patients who were lasting users of opioids experienced a significant improvement in terms of pain intensity, pain interference, and mental health–related quality of life. The majority of opioid-naïve patients who were followed at the pain clinic for a 1-year period did not benefit from opioid therapy, and a great proportion of them discontinued opioids due to lack of effect or presence of side effects. Results are in line with the literature suggesting that though most patients do not benefit from long-term opioid therapy, there is a significant subgroup of patients who do benefit from this therapy. The challenge facing clinicians is how to identify who the responders will be.


Background and Objectives: Osteogenesis imperfecta is a rare pathology involving the bones and the connective tissues, generating alterations that lead to frequent fractures during childhood. When fractures occur at birth, they are associated with an impairment of walking and the quality of life. Although surgical techniques have significantly improved in recent years, functional outcomes and the quality of life for pediatric patients that benefited from surgical management with telescopic rods have been less evaluated. This study aimed to measure functional results and determine the factors that influence the quality of life for the pediatric population diagnosed with Osteogenesis imperfecta and surgically treated using the telescopic rod approach after suffering a fracture or severe deformity. Materials and Methods: We conducted a cohort study that consisted of 15 patients diagnosed with Osteogenesis imperfecta (average age of 11.6 years). All individuals possessed at least one intramedullary telescopic rod as a result of the surgical treatment. Results: We observed that the pain, both acute and chronic, impairs the quality of life and interferes with daily living activities, for instance, self-care tasks. Conclusions: Osteogenesis imperfecta is associated with a severely damaged level of walking. All of the aspects of the pediatric patient’s daily life activity seem to be affected. Furthermore, these patients, especially those residing in rural areas, have a poor quality of life. Osteogenesis imperfecta (OI) represents a genetically transmitted group of disorders characterized by increased bone fragility and connective tissue dysfunction. The leading cause is the mutation of one of two genes COL1A1 and COL1A2, which are responsible for encoding type I procollagen  and Odds Ratio [OR = 6.25 (>1)], we can conclude that the type of Osteogenesis imperfecta is associated with the current capability of children to walk and their pattern of walking. No changes were perceived in the postoperative modified Bleck score compared to the preoperative results. As an example, a 5 year old pediatric patient diagnosed with Osteogenesis imperfecta Sillence type IV’s leg X-ray aspects from before and after the surgery is represented in For pain intensity assessment, we calculated the prevalence for each pain level, as seen in Chronic pain was related to the whole body in addition to the surgical site. All patients present chronic pain fluctuating from mild to severe. After surgery, according to gender, 26.67% of answers recorded in the “mild pain” category were represented by females. For male patients, the most common response was “severe pain” (20%). The age group between 14–17 years has shown the highest percentage of “severe pain” compared to the other age groups. We calculated the average score of the FIM questionnaire in order to specify our study group ability, as seen in From a maximum of 100%, the patients were described as 65% able after surgery (range 46–100%). A significant disability was observed in the following categories when combined with a lower FIM score: males, the patients living in rural areas and the group with the first fracture diagnosed at childbirth, or as we presumed the patients that identify as Osteogenesis imperfecta type III, accordingly to Sillence. However, no statistical significance was found.−non-walker older than two years of age−therapy walker with the help of crutches or canes, and−therapy walker without the help of crutches or canes. The most impaired categories, revealed by the modified Bleck score, are:All patients present chronic pain fluctuating from mild to severe. The age group between 14–17 years has shown a significant percentage of “severe pain” compared to the other age groups. A lower FIM score was a more significant disability in the following categories: males and the patients living in rural areas.A critical aspect not often described in the evaluation of the quality of life, is chronic pain. The presence of intense chronic pain interferes with daily living activities, for instance, the self-care tasks of these patients. The quality of life can be improved overall after surgery but still remains a controversial topic.Chronic and severe pain is a major complaint of the children diagnosed with Osteogenesis imperfecta decreasing their quality of life. In addition, pain intensity is strongly correlated with these children’s ability to perform the activities of daily living (ADL) and have a healthy cognitive function. Widmann, R.F. et al.  performeR. Engelbert et al.  noted thAll the patients we evaluated have impaired ambulation. However, due to the difficulty in differentiating between type I and III of Osteogenesis imperfecta, a small number of patients, and for other statistical reasons, we included the patients with the first fracture diagnosed in childbirth in class III and the rest in type I, as identified by Sillence. Consistent with the Bleck score, patients with type III, as identified by Sillence, showed a lower chance of independent walking than type I.A total of 20% of patients belong to the first category of the Bleck classification, not walking. In addition, we observed that patients who achieved decent ambulation levels (Bleck score 7–9) were predominantly females. Also, assessing pain intensity, most recorded answers for “mild pain” were from female patients. The FIM score revealed a severe dysfunction in both physical and mental health. These results have been mostly seen in rural living patients suffering from difficulties in problem-solving and social interaction. There was no correlation found between the severity of motor and cognitive function impairment.Some limitations can be observed, such as the small number of patients included in the study. Studies of larger population groups for a more extended follow-up period should be done to assess the quality of life and disability for patients diagnosed with osteogenesis imperfecta and treated with a telescopic rod. Further studies can compare and evaluate if early treatment with bisphosphonates can reduce chronic pain and the need for surgery.Additional evaluation of the quality of life elements is fundamental in improving treatment procedures and social assistance care, supporting the category of children affected by osteogenesis imperfecta and their families.Evaluating functional outcomes for patients with Osteogenesis imperfecta and telescopic rods, we noticed a significant ambulation impairment.Treatment with bisphosphonates and surgery with telescopic rods are currently the gold standard for realigning bone deformities and multiple fractures. The results show an improvement regarding the quality of life, but the postoperative ambulation still remains to be improved. Generalized chronic pain still represents a significant problem involved in the treatment of pediatric patients diagnosed with Osteogenesis imperfecta.The evaluation will be discussed in the following works. However, this study highlights the specific areas of quality of life affected in these pediatric patients in order to implement further appropriate measures that are intended to improve them.


Well-controlled postoperative pain is essential for early recovery after uniportal video-assisted thoracoscopic surgery (UVATS). Conventional analgesia like opioids and thoracic epidural anaesthesia have been associated with hypotension and urinary retention. Intercostal catheters are a regional analgesic alternative that can be inserted during UVATS to avoid these adverse effects.This feasibility study aims to evaluate the postoperative pain scores and analgesic requirements with incorporation of an intercostal catheter into a multimodal analgesic strategy for UVATS.In this observational study, 26 consecutive patients who underwent UVATS were administered a multilevel intercostal block and oral paracetamol. All of these patients received 0.2% ropivacaine continuously at 4 ml/h via an intercostal catheter at the level of the incision. Rescue analgesia including etoricoxib, gabapentin and opioids were prescribed using a pain ladder approach. Postoperative pain scores and analgesic usage were assessed. The secondary outcomes were postoperative complications, days to ambulation and length of stay.No technical difficulties were encountered during placement of the intercostal catheter. There was only one case of peri-catheter leakage. Mean pain score was 0.31 (range 0–2) on post-operative day 1 and was 0.00 by post-operative day 5. 16 patients (61.6%) required only oral rescue analgesia. The number of patients who required rescue non-opioids only increased from 1 in the first 7 months to 8 in the next 7 months. There were no cases of hypotension or urinary retention. Median time to ambulation was 1 day (range 1–2). Mean post-operative length of stay was 4.17 ± 2.50 days.Incorporation of an intercostal catheter into a multimodal analgesia strategy for UVATS is feasible and may provide adequate pain control with decreased opioid usage. Pain management in thoracic surgery is essential to promote early recovery and avoid complications like urinary retention, atelectasis and pneumonia. For pain control after thoracotomy, thoracic epidural analgesia (TEA) and paravertebral blocks (PVB) have been regarded as the gold standards . In receStudies have demonstrated that both TEA and PVB provide adequate analgesic effect after major thoracic surgery, but the former may be associated with adverse effects such as urinary retention and hypotension –5. FailuThere has been a shift away from systemic opioids to regional options for pain management after thoracic surgery , 15. ThiThis case series was conducted at the National University Hospital, Singapore. 26 consecutive patients who underwent UVATS and received the ICC over a period of 14 months were included. The exclusion criteria were open thoracotomy, UVATS converted to open thoracotomy, reoperation and age below 21 years old.UVATS was performed in all patients. A single 3–4 cm incision was made at an appropriate intercostal space along the anterior axillary line. The exact level of the incision was tailored and individualized to each patient, depended on various factors like the extent of resection, patient’s body habitus and width of intercostal space. Generally an incision at the 4th or 5th intercostal space was made for abnormalities in the upper lobe, which the 5th or 6th intercostal space was used for the lower lobe. As our standard practice, a total muscle-sparing technique was employed, where the latissimus dorsi, serratus anterior and intercostal muscles were preserved. Subperiosteal entry into the pleural space was obtained without any spreading, resection or fracture of ribs. We retracted the incision with a small plastic wound protector . A lubricating gel was applied on the wound protector to facilitate removal of any resected specimens. At the end of surgery, a chest tube was inserted via the same incision and attached to a drainage system. An indwelling urinary catheter, if inserted to monitor intraoperative fluid status, was removed at the end of the surgery.All patients received a standardised analgesic regimen consisting of a single-shot intercostal block and paracetamol 1 g 6 hourly, starting on the day of surgery. Before wound closure, a bolus of 1 mg/kg of 0.5% bupivacaine was injected into the intercostal space at the level of the incision, two levels above and below, as well as along the incision. This multilevel block was performed to fully cover overlapping innervation from the intercostal nerves, and to ensure adequate analgesia in the immediate postoperative period before the ICC takes into full effect. Rescue analgesics such as etoricoxib 90 mg once daily, gabapentin 300 mg in the evening, tramadol 50 mg 3 times a day, morphine 5 mg once and oxycodone 5 mg once, were prescribed by the thoracic surgery team when required. Intravenous patient-controlled analgesia (PCA) with a demand dose of morphine 1 mg was selectively prescribed and ceased by the acute pain team depending on their daily assessment of the patient.The administration of the ICC  was standardised across all patients. The ICC was inserted at the level of the same intercostal space as the incision. The provided blunt tunneler was inserted via the incision along the inferior rib border and used to dissect the extrapleural space under direct thoracoscopic vision, while keeping the pleura intact. The ON-Q multihole catheter was then introduced over the tunneler, followed by the removal of the tunneler. Ropivacaine was then administered via the catheter to visualise an intercostal bulge between the ribs. Subsequently, the catheter was connected to a 400 ml elastomeric pump filled with 0.2% ropivacaine solution as per the manufacturer’s recommendation, at a fixed flow rate of 4 ml/h. The pump was either kept for 4 days until it was depleted, or removed earlier if the patient was fit for discharge earlier. The ICC tubing was secured to the skin by a 3 M™ Tegaderm™ Transparent Film Dressing and the pump was placed in a small portable pouch that patients can carry around. All patients were regularly reviewed by our specialised thoracic nurse for symptoms of ropivacaine toxicity and the ICC tubing would be clamped in the event of an emergency. Our thoracic nurse also checked for the patency of the ICC and troubleshooted as appropriate, such as unkinking the tubing and reapplying another Tegaderm™ to secure it to the skin.We performed a retrospective review of electronic medical records to obtain baseline patient characteristics, incidence of postoperative complications, duration of chest tube drainage, time to ambulation and length of stay. All patients were admitted to the cardiothoracic high dependency unit (HDU) after surgery, and were transferred to the general ward from the second postoperative day (POD) onwards when deemed suitable by the thoracic surgery team. Starting from POD 1, all patients were also assessed by a physiotherapist daily on their ability to ambulate. A pain score using a visual analogue scale (VAS) with numeric ratings of 0–10 was used by trained nurses to assess the level of pain, and this was recorded electronically. On POD 1, pain scores were recorded every 4 h in the HDU and the mean was calculated. For subsequent POD, the mean of all pain scores reported on that day was obtained. The type and amount of rescue analgesics required was also recorded electronically in a standardised fashion.All collected data was analysed with Statistical Package for the Social Sciences Version 22 . For categorical variables, the frequency and percentage are reported while the mean ± standard deviation or mean and range were calculated for continuous variables.Table Table Secondary outcomes are presented in Table With the introduction of muscle-sparing and nerve-sparing incisions in thoracic surgery, pain due to rib or intercostal nerve trauma have been shown to be minimized –19. HoweTill date, there has been no consensus on the gold standard for regional analgesia after video-assisted thoracoscopic surgery (VATS), much less UVATS . ProspecIn our experience, the placement of an ICC provides adequate pain control after UVATS. In our earlier case series on muscle-sparing UVATS , we obtaThe ICC has multiple benefits in UVATS aside from pain control. Firstly, the catheter can be placed easily under direct vision, with confirmation of its placement by visualisation of an intercostal bulge after bolus administration of the analgesic. This is in contrast to TEA catheters which are inserted blindly and hence prone to mispositioning. The dosage of TEA also has to be titrated regularly which can be labour intensive. This is avoided with the ICC as the fixed pump volume and flow-limiting valve ensure an independent and constant flow rate. In addition, the ICC can be utilised when TEA is contraindicated, such as previous spine surgery or morbid obesity. Moreover, the ICC can deliver a continuous infusion beyond POD 1, thereby avoiding the short analgesic duration associated with single shot PVB. The ICC also enables early mobilisation since it is not associated with loss of motor function, as is the case with TEA. De Cosmo et al.  used an As with all equipment, technical failure is a concern but evidence on continuous anaesthetic infusion techniques like the ICC have shown the rate to be very low at 1% . Our teaOur preliminary observational study was understandably not without its limitations. It was retrospective and based on a small sample size. We also acknowledge that the lack of a control group meant that our results should be interpreted with care. However, the use of a standardised ICC placement method, as well as a standardised analgesic regimen may have strengthened the validity of our findings. Pain score assessment was performed by uniformly trained nurses and analgesic usage was documented in a standardised manner in the electronic medical records, which may have helped to minimize biases in our study. Our findings have suggested that the ICC is simple and safe to utilize, and pain relief post-UVATS is also adequate. In the future, it is warranted to conduct larger-scale prospective randomized studies to further support the role of the ICC as regional analgesia in UVATS.Our initial experience with the ICC demonstrated that it is feasible for incorporation into a multimodal analgesic strategy for UVATS. Its usage appears to be associated with minimal post-operative pain and reduced usage of opioids. It can therefore be considered as an adjunct to achieve early recovery after UVATS.


The incidence of total knee arthroplasty (TKA) is increasing, especially among younger working-age patients. However, dissatisfaction rates in this population are higher than among older patients. The aim of this study was to assess the rates of dissatisfaction and persistent pain after TKA and to evaluate those factors that predict these outcomes.In total, 186 patients undergoing unilateral TKA aged 65 years or less were enrolled into this prospective observational study with 2-year follow-up. To assess the outcome, the visual analogue scales regarding satisfaction and persistent pain at rest and during exercise were used. In addition, the association between patients´ demographics, radiographic severity of knee osteoarthritis (OA), patient-reported outcome measures (PROMs) and dissatisfaction and persistent pain were tested by univariate logistic regression analysis. Mild OA was defined as Kellgren-Lawrence (KL) grade 2 and severe OA as KL grade 3–4. Furthermore, multiple logistic regression analysis was also conducted to test statistically significant relations.n = 23) of patients were dissatisfied with the outcome of TKA, 27 % (n = 50) reported persistent pain during exercise and 10 % (n = 18) at rest. Patients with mild knee OA were significantly more dissatisfied (28.6 %) than patients with more severe OA (8.7 %) (p = 0.003). Younger patients had an increased risk for both dissatisfaction and persistent pain. Apart from KOOS Quality of Life, poor preoperative KOOS subscores were also predictive for these outcomes.After 2 years, 12 %  on 28 July 2017.The study was retrospectively registered with ClinicalTrials.gov (registration number  Recent studies clearly indicate that the incidence of total knee arthroplasty (TKA) will increase in the near future –3. IndeeFor the original 2-year prospective cohort study assessing the results of unilateral and bilateral TKAs and UKAs, 255 patients scheduled for knee arthroplasty were enrolled between 1st March 2012 and 30th October 2014 at our high-volume academic tertiary referral centre .The inclusion criteria of the original study cohort were as follows: (1) Age 65 or less and (2) scheduled for knee arthroplasty for primary OA . The excFor the purposes of this study, bilateral TKAs and unicompartmental knee arthroplasties were excluded, leaving 205 unilateral TKA patients to be included. Two patients 1 %) died during follow-up. Three patients did not return questionnaires, despite repeated requests, and were therefore considered unwilling to continue in the study. Thus, two hundred patients were available for the 2-year follow up visits, which were carried out via questionnaires by mail. However, 14 patients (7 %) returned only partially completed questionnaires and had left the visual analogue scales regarding satisfaction and persistent pain. These patients were also excluded, and the analysis of the final results was based on 186 (91 %) TKAs  or Nexgen . In 8 (4 %) of the TKAs, the patella was resurfaced due to perioperative maltracking. Primary implant was cruciate retaining (CR) model in all patients but posterior stabilised (PS) implants were used if PCL insufficiency was detected peroperatively. Of the 186 TKAs, 177 (95 %) were CR and the remaining 9 were PS.The visual analogue scale (VAS) was measured with a scale from 0 to 100. It is widely used for evaluating pain intensity and in this study was used to evaluate pain both at rest and during exercise. Satisfaction regarding the studied knee was also measured with VAS as was done by Scott et al. and it is shown to be a reliable method for measuring satisfaction , 12. AllPatients were asked to fill out a background questionnaire that included information on working status and physical activities. Medical comorbidities were asked as “Do you have any other conditions that limit your physical activity more than your diagnosed knee osteoarthritis? Yes/No”. Patients were also asked to fill three additional PROMs both pre- and postoperatively: the Oxford Knee Score (OKS) , the KneThe severity of knee OA was assessed from preoperative standing fixed flexion view (FFV) radiographs using the Kellgren-Lawrence (KL) classification . Mild kn1 to Q3), range (min to max), or as mean (CI 95 %). The KOOS scores were divided into five subscale scores , function in sport and knee related quality of life (QoL)) and were analysed separately. RAND-36 questionnaire scores were divided into two subscale scores  and Mental Component Score (MCS)) and were analysed separately. Univariate logistic regression was used to evaluate the association between the preoperative factors and dissatisfaction and persistent pain. Fisher’s exact test was used to compare the dissatisfaction rates, the achieved MCID rates and the prevalence of comorbidities between the KL 2 and KL 3–4 subgroups. Multiple logistic regression analysis was also used to compare the dissatisfaction rates between these two KL subgroups adjusted with age, gender and BMI, which are known or potential risk factors for more severe knee OA, and were thus considered as confounding factors [p-value less than 0.05 was considered statistically significant. Data were analysed using the SPSS (version 26) statistical package .Demographic data were presented as the median with quartiles  on 28/07/2017. All methods were performed according to the relevant guidelines and regulations and the reporting guideline Strobe was used , 23.Patients´ demographics are shown in Table n = 23) of the patients were dissatisfied with their operated knee. Those patients with mild radiographic knee OA were significantly more dissatisfied than patients with more severe knee OA . There was also no difference in prevalence of comorbidities limiting physical activity between mild and severe OA subgroups . Patients with more severe knee OA also showed a trend to more often achieve clinically significant improvement (exceeding MCID) in VAS satisfaction between the preoperative and the 2-year measurements. This finding, however, lacked statistical significance (Table p = 0.029).At the time of the 2-year follow-up, 12.4 % n = 2 of the pn = 50) of patients reported persistent knee pain during exercise and 10 % (n = 18) at rest, respectively. Younger age was significantly associated with persistent pain both during exercise  and at rest . Other demographic factors had no effect  and similar tendencies were also found regarding dissatisfaction and persistent pain during exercise. Both poor mental and physical state, measured with RAND-36 MCS and PCS, were associated with persistent pain at rest, the latter also exceeding the threshold for statistical difference. In addition, lower RAND-36 PCS showed a similar tendency with dissatisfaction and persistent pain during exercise. As we found age to be associated with dissatisfaction and persistent pain, we conducted also age adjusted multiple logistic regression analysis to further assess the relations between preoperative PROMs and dissatisfaction and persistent pain. All the reported findings persisted, apart from the relations between RAND-36 and persistent pain at rest, as the statistical significance was lost .Using univariate logistic regression analysis, we also assessed whether preoperative PROMs predicted dissatisfaction and persistent pain at 2 years postoperatively Table . We founThe number of TKAs is rapidly increasing, especially among younger patients . This maWe found that dissatisfaction was significantly more common among patients with milder radiographic OA – 29 % in patients with KL 2 OA and only around 9 % among patients with more severe OA. This finding is supported by Scott et al., who reported that over 50 % of patients with KL 2 OA are dissatisfied after TKA . Also NiWe also found that younger age increases the risk for dissatisfaction. This finding is in line with the findings of Lange et al., who included a matched control group of older patients aged 65–75 years in their study and found patients aged 55 years or less to be more dissatisfied with their TKA (satisfaction 86 % vs. 91 %) . This fiSimilarly to the findings of Scott et al., we also found a trend for worse preoperative OKS being associated with dissatisfaction . HoweverIn this study, multiple standardised PROMs  were collected and analysed, but all in all the associations found with dissatisfaction and persistent pain seem somewhat scattered. Some previous studies have tried to identify threshold values for preoperative OKS that indicate postoperative satisfaction but found no association between these two variables , 38. In Our study was a prospective observational study that used multiple standardised PROMs. We acknowledge a few limitations in our study. First, our study lacked a control group comprising patients over the age of 65. This would have enabled us to compare the results between these two age groups. Second, an additional weakness in our study was the limited sample size, which suffered from 14 (7 %) patients missing critical data. Thus, for some comparisons, our study might have been inadequately powered to find significant differences. We also did not discuss patient expectations which might have been a confounding factor. Additionally, we analysed mainly self-reported data and outcome at 2 years and therefore were not able to evaluate immediate postoperative complications, infections, tromboembolisms or other adverse events that might have affected the results. Also, comorbidities were self-reported and limited to conditions limiting patient’s physical activity more than their knee OA. Thus, mental health issues, chronic pain and other conditions predisposing to persistent pain and dissatisfaction might not have been considered. Our study also had some obvious strengths. The study population consisted of non-selected real-world patients, and therefore, along with the study setup, was equivalent to everyday clinical practice. Additional strengths of the study were the 2-year follow-up period and the high response rate – only 4 % of patients were lost to follow-up during the study.We found that a vast majority of patients aged less than 65 years clearly benefit from TKA surgery in terms of pain relief, improved function and overall satisfaction. Dissatisfaction in this age group seems to be strongly related to mild radiographic OA. Thus, TKA should primarily be performed for patients with end-stage OA. Although severe preoperative knee pain is shown to be related to both dissatisfaction and persistent pain, based on the findings of the present study, the value of PROMs in predicting these outcomes remains uncertain. Further research with a lot larger patient cohorts on PROMs’ value in predicting satisfaction is certainly needed to provide support for the surgical decision making.


However, the underlying mechanisms in the early stage remain unclear. The study was aimed to explore the alterations of large-scale neural networks in de novo PD patients with depression (dPD), 34 de novo PD patients without depression (ndPD), and 43 healthy controls (HCs) to extract functional networks. Intranetwork and internetwork connectivity was calculated for comparison between groups, correlation analysis, and predicting the occurrence of depression in PD.We performed independent component analysis (ICA) on the data of resting-state functional magnetic resonance imaging from 21 We observed an ordered decrease of connectivity among groups within the ventral attention network (VAN) (dPD < ndPD < HCs), mainly located in the left middle temporal cortex. Besides, dPD patients exhibited hypoconnectivity between the auditory network (AUD) and default mode network (DMN) or VAN compared to ndPD patients or healthy controls. Correlation analysis revealed that depression severity was negatively correlated with connectivity value within VAN and positively correlated with the connectivity value of AUD-VAN in dPD patients, respectively. Further analysis showed that the area under the curve (AUC) for dPD prediction was 0.863 when combining the intranetwork connectivity in VAN and internetwork connectivity in AUD-DMN and AUD-VAN.Our results demonstrated that early dPD may be associated with abnormality of attention bias and especially auditory attention processing. Altered neural network connectivity is expected to be a potential neuroimaging biomarker to predict depression in PD. Parkinson’s disease (PD) affects 2–3% of the population over 65 years of age, which is the second most common neurodegenerative disorder next to Alzheimer’s disease . As one Resting-state functional magnetic resonance imaging (rsfMRI) is a non-invasive technique, which can be used to detect how aberrant brain activity or functional connectivity between core areas leads to clinical depressive symptoms in PD. Previous studies using the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) methods showed that dPD was related to abnormal neural activity in several specific brain regions, including the supplementary motor area (SMA) and the prefrontal-limbic network . Seed-baIndependent component analysis is a data-driven whole-brain blind source separation method that can separate a multivariate signal into independent networks, thus avoiding the inherent deviation in selecting specific seeds . Our preIn this study, we applied the ICA approach to rsfMRI data to investigate intrinsic connectivity within and between several classical functional networks, focusing on the drug-naïve PD patients with depression. We hypothesize that disrupted network function may contribute to depression in PD patients.de novo PD patients and forty-three HCs were finally included in this study. All the participants provided written informed consent, completed all the clinical assessments and MRI scans during the baseline visit. The study was approved by the Medical Ethics Committee of the Affiliated Brain Hospital of Nanjing Medical University.Parkinson’s disease patients recruited from the Affiliated Brain Hospital of Nanjing Medical University were diagnosed by an experienced neurologist according to the United Kingdom Parkinson’s Disease Society Brain Bank diagnostic criteria . The excDepression in PD was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria by an experienced psychiatrist. The severity of depression was quantified with the 17-item Hamilton Depression Rating Scale (HAMD-17). dPD patients were required to have a HAMD-17 score higher than 14 . A totalMagnetic resonance imaging was performed using a 3T MRI scanner . All participants lay supine with their head fixed by foam pads with a standard birdcage head coil to minimize head movement. The participants were instructed to remain as still as possible and to close their eyes while remaining awake without thinking of anything. Axial anatomical images were acquired using a T1 fluid-attenuated inversion recovery sequence with the following parameters: repetition time (TR) = 2,530 ms; echo time (TE) = 3.34 ms; field of view (FOV) = 256 mm × 256 mm; matrix = 256 × 192; slice thickness/gap = 1.33/0.5 mm; flip angle (FA) = 7 degrees; bandwidth = 180 HZ/PX; 128 slices covered the whole brain, for image registration and functional localization. Functional images were subsequently collected in the same slice orientation with a gradient-recalled echo-planar imaging pulse sequence. A total of 240 volumes were obtained .1 and DPARSF.2 The first 10 volumes of each functional section were discarded for magnetization equilibrium. The remaining 230 volumes were then corrected for slice timing using the middle slice as a reference, realigned for head motion correction, segmented into white matter, gray matter, and cerebrospinal fluid (CSF) using tissue probability maps derived from the T1 images, normalized into the standard Montreal Neurological Institute space using diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL), resampled to a 3 mm × 3 mm × 3 mm voxel size, and smoothed with a 6 mm full-width at half-maximum (FWHM) Gaussian kernel (P = 0.12).Preprocessing of the fMRI data was carried out using SPM12n kernel . To furtn kernel , resulti3 The procedures included three steps: (1) data reduction, (2) group ICA, and (3) back-reconstruction. In this study, 32 ICs were estimated through the minimum description length (MDL) criteria  implemented in the Group ICA of the fMRI Toolbox (GIFT v4.0b).criteria . The dimcriteria . Finallycriteria . Each bacriteria . Nine cot-tests were performed on the spatial z-maps across all participants for each component in SPM12 to determine regions that are positively significantly integrated into each network  , followed by post-hoc two-sample t-tests to compare the internetwork connectivity between groups .In order to evaluate the internetwork connectivity, the subject-specific time courses of the selected ICs were postprocessed by detrending, despiking, filtering with a high cutoff frequency of 0.15 HZ, and regressing out the head motion parameters . Pair-wit-test or Mann-Whitney U test was applied to compare two groups. One-way ANOVA or Kruskal–Wallis test was performed to compare HCs, ndPD, and dPD groups. Chi-squared test was used to compare categorical variables such as gender. Pearson correlation analyses were conducted to assess the relationships between the altered intra- or internetwork connectivity and HAMD-17 scores. Simple and multiple binary logistic regression was used to determine the risk factors associated with depression in PD patients. The predictive value of individual or combined brain network indices for depression in PD was assessed by the receiver operating characteristic (ROC) curve, and the area under the curve (AUC) was calculated simultaneously. The threshold for statistical significance was set at P < 0.05.Statistical analyses were calculated using SPSS Statistic 24.0 . Two-sample A total of 34 ndPD patients, 21 dPD patients, and 43 healthy controls were eventually included in the further analysis. There were no significant differences in age, gender, education, MMSE scores, and mean FD among the three groups. No significant differences in disease duration, H&Y stage, and UPDRS-III scores were observed between dPD and ndPD groups. In contrast, the HAMD-17 scores of dPD patients were significantly higher than that of ndPD patients or healthy controls .P < 0.05, FDR-corrected) . Besides, ndPD group also showed significantly decreased connectivity in this brain region compared to HCs group   . Post-horrected) . No signP < 0.05, FDR-corrected) . Compared to HCs group, dPD group had increased connectivity between LFPN and VAN and decreased connectivity between AUD and DMN/VAN/VIS, between DAN and DMN, and between VAN and VIS . Compared to HCs group, ndPD group had increased connectivity between LFPN and VAN and decreased connectivity between DMN and DAN and between VAN and VIS   . Post-horrected) .P = 0.016, r = −0.518)   . In addi= 0.438) .Based on the results of the initial comparisons between ndPD and dPD groups in terms of the brain network indices, we included intranetwork connectivity in VAN, internetwork connectivity between AUD and DMN, and between AUD and VAN in the simple binary logistic regression analysis. The results showed that these network indices were significant predictors associated with depression in PD. Multiple binary logistic regression with step-wise selection showed that intranetwork connectivity in VAN and internetwork connectivity between AUD and DMN were independently associated with depression in PD .P = 0.002), 0.688 for internetwork connectivity between AUD and DMN , and 0.755 for internetwork connectivity between AUD and VAN , respectively. The accuracy improved (AUC = 0.863) when combining the three brain network indices   for dPD prediction was 0.751 for intranetwork connectivity in VAN  .The present study investigated altered connectivity within and between large-scale brain networks in drug-naïve PD patients with depression, thereby excluding the confounding effects of anti-parkinsonism therapy and chronic duration. We observed an ordered decrease of intranetwork connectivity among groups in VAN (dPD < ndPD < HCs), mainly located in the left middle temporal cortex, and the connectivity value was negatively correlated with depression severity in dPD patients. Besides, the internetwork connectivity between AUD and DMN/VAN differed significantly between dPD patients and ndPD patients or healthy controls. Further analysis revealed a positive correlation between the connectivity value of AUD-VAN and depression severity in dPD patients. Importantly, we found the combination of intra- and internetwork connectivity could predict the occurrence of depression in PD with a relatively high diagnostic accuracy.Ventral attention network is related to stimulus-driven attention orientation and is activated in detecting unexpected stimuli and triggering shifts of attention . SpecifiDopamine modulated auditory processing in different stages of auditory system from peripheral to central hearing-related regions . When doAdditionally, we also found that both subgroups of PD patients had increased connectivity between LFPN and VAN and decreased connectivity between DAN and DMN and between VAN and VIS compared to HCs. Enhanced connectivity between FPN and VAN was demonstrated to help to capture environmental information in time, so as to realize the flexible cognitive control . The strThe ROC analysis showed that altered intranetwork connectivity in VAN and internetwork connectivity between AUD and DMN/VAN could be effective biomarkers to differentiate dPD patients from ndPD patients. Despite the higher accuracy of our results to predict dPD patients than the previous studies , single Nevertheless, our study has several limitations. First, the relatively small sample size limited the generalizability of our results, for the patients in our study were newly diagnosed and were followed up for at least 1 year to ensure the diagnosis. A larger sample size would be implemented in the future to validate the results. Second, cognition was proposed to be associated with depression, but MMSE was not effective enough to identify the possible cognitive impairment. Thus, more comprehensive neuropsychological tests should be conducted to exclude the confounding effects of cognition. Third, as mentioned above, only using neural network connectivity as a biomarker is restricted, so multimodality imaging, genetic or plasma markers are expected to be involved in our patient cohort.de novo PD patients with depression, suggesting that the neural network mechanism of dPD may be associated with abnormality of attention bias, especially auditory attention processing. These findings could provide new insights into the potential diagnostic markers and therapeutic targets of depression in PD.In summary, we observed decreased intranetwork connectivity in VAN and internetwork connectivity between AUD and DMN/VAN in The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by the Medical Research Ethics Committee of the Affiliated Brain Hospital of Nanjing Medical University. The patients/participants provided their written informed consent to participate in this study.WL designed and organized the research. JX, YC, YL, LL, and JR collected the imaging and assessment scale data. JX, YC, and HW were responsible for formal analysis. JX drafted the manuscript. WL and YS made important revisions to the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.