Multiple linear regression models were used to adjust effect by baseline differences between groups. Sixty patients were included in the trial. A period effect was noted, with residual effect of WBC; therefore, only results from the first sequence were analysed. ∆VAS pain, ∆FIQ and ∆ICAF scores were significantly larger in the WBC group after the first period , and were confirmed after adjustment. In conclusion, WBC with a Cryosense TCT cabin may be a useful adjuvant therapy for FM; further studies on long-term effect and compared to other physical therapies are warranted.Evidence of symptomatic treatment for fibromyalgia (FM) is very low. Whole body cryotherapy (WBC) modulates different neurotransmitters, which might have a role in pain alleviation and could exert an effect on FM. Our aim was to evaluate the efficacy of WBC for the control of pain and impact of disease in FM. For this we run an open, randomized, crossover trial of Cryosense TCT™ cabin vs rest. Patients with FM according to ACR criteria were recruited consecutively from general practices. Trial endpoints were change (∆) in pain after 2 and 4 weeks, measured by a visual analogue scale (VAS), ∆ burden of disease, evaluated by the Fibromyalgia Impact Questionnaire (FIQ), and severity of FM, measured by the Combined Index of Severity of Fibromyalgia (ICAF). Within group differences, sequence and period effects were tested with Student’s Trial registration NCT03425903.The online version of this article (10.1007/s00296-018-4176-0) contains supplementary material, which is available to authorized users. Fibromyalgia (FM) is a syndrome characterised by chronic generalized musculoskeletal pain, hyperalgesia, and allodynia. Musculoskeletal pain is usually accompanied by fatigue, sleep problems, anxiety and depression, paresthesiae, joint stiffness, headache, subjective sensation of swelling, concentration difficulties, and memory impairment, among other unexplained symptoms , 2. FM hThe natural course of FM is chronic, and fluctuating, becoming disabling in some individuals, with a devastating effect on people’s lives, affecting their ability to work and engage in everyday activities, as well as their relationships with family and friends. The limitation in the performance of activities of daily living, together with its high prevalence—it affects 2% or more of the population , 9—, makAlthough there are several drugs and other non-pharmacological measures available for the management of fibromyalgia, at present there is no a definitive cure. Some drugs act on pathogenic mechanisms of pain processing while most non-pharmacological measures, as well as other drugs, provide mainly a symptomatic relieve . ExpertsCryotherapy refers to the application of cold as a therapeutic agent for pain relief, a remedy widely used in sports related trauma, based on its capacity to decrease the inflammatory reaction, including oedema . Cold paChryotherapy induces many physiological reactions in the organism with an increase in white blood cells, antiinflammatory cytokines, ACTH, beta-endorphins, cortisol and catecholamines. Another possible mechanisms of action of cryotherapy have been postulated and include immunostimulation due to noradrenalin response to cold, reduction of pain through the alteration of nerve conduction, an increase in the level of plasma total antioxidant status and improving immune function .Muscle activity and inflammation produce oxidants in the intercellular space with the consequences of membranes damage as well as more inflammation in a vicious cycle. Through a reduction of inflammation, cold has been suggested to reduce oxidants production .The reduction of pain in FM produces a chain reaction, triggering improvement in mood, leading in turn to better pain adjustment and facilitation of physical and mental activities, all of which justify testing therapies that may reduce pain without harming the patient. Exercise produces the largest effect on pain in FM , but posThe scientific evidence about efficacy of cryotherapy in fibromyalgia patients is limited to an observational study that showed promising results . The purThis was a randomised, open, crossover trial of 3 weeks duration (7 weeks in both periods included) to test the efficacy of WBC as adjuvant therapy for the control of pain and impact of disease in patients with FM. The study protocol and materials were approved by the Clinical Research Ethics Committee of the Hospital Puerta de Hierro of Madrid .Eligible patients were recruited consecutively from participating general practices. Selection criteria included: age between 25 and 80 years old; diagnosis of FM according to ACR criteria [http://www.randomization.com website [After inclusion, subjects were randomly assigned to a sequence starting by WBC or control using a randomization scheme generated through the  website .Patients on WBC group were treated on alternate days during 3 weeks. At each session, patients were introduced in Cryosense TCT™ cabins during 3 min, where temperatures reached − 196 °C—the evaporation point of liquid nitrogen—. After ten sessions, patients underwent a 1-week washout period to eliminate any possible residual effect of the previous application of WBC. Subsequently, the groups were inverted; those initially treated with WBC became controls and vice versa , and in impact of disease, assessed by the Fibromyalgia Impact Questionnaire (FIQ) . As secoOn the other hand, ICAF is a tool for assessing the severity of FM based on its most prevalent clinical manifestations, resulting in a total score of the severity where higher scores represent greater importance of the condition and its consequences in the patient’s life. The ICAF questionnaire also provides information on emotional, physical, and of coping (active and passive) aspects of the patient. The emotional factor emphasizes the role of emotional aspects such as anxiety and depression; the physical factor assesses pain, fatigue, sleep quality and functional ability; active coping includes positive coping strategies, and passive coping identifies a group of particularly severe patients. The ICAF contains 59 items and its score ranges from 0 to 84, with higher values indicating greater severity .All patients were assessed after 22 and 50 days from period start—visits 3 and 6, corresponding to the evaluation of the first and second periods, respectively— .A sample size of 60 participants was deemed sufficient to detect a significant treatment group difference on pain VAS, accounting for a dropout rate of 20% .t or Mann–Whitney U tests, depending on the distribution of continuous variables, and Chi square for qualitative variables. Normality was tested with the Kolmogorov–Smirnov test.The sample was described by summary statistics . Differences between groups at baseline  were tested with Student’s Within-group differences in outcome measures by time were assessed using repeated measures ANOVA.t or Mann–Whitney U tests, depending on the distribution of the respective variables, with an intention to treat approach.Sequence and period effects were evaluated. The comparison of response in terms of ∆VAS pain and ∆FIQ, and of the secondary outcomes, between treatment groups was carried out using Student’s Finally, and to take account possible differences in baseline between both study groups, multiple linear regression was used. Models were constructed using the outcome measures as dependent variables, and treatment group, controlling for variables with significant baseline differences (complete model), as independent variables. Backward stepwise regression was used for modelling variables selection with successive elimination of those without confounding effect. Comparison of models was performed by information measures, Akaike information criteria (AIC), and Bayesian information criteria (BIC). The final models were the most parsimonious and with the lowest values on information criteria.Eligibility criteria were fulfilled by 72 patients of whom 12 were excluded for not fulfilling all criteria or declining participation, leaving 60 patients, whose randomisation resulted in two groups of 34 and 26 patients, assigned to WBC and control, respectively , SF36 dimensions  and standardized total score of the physical component, with consistently higher values for the WBC group, which could indicate a worse baseline clinical situation for this group, whereas no differences were found in pain score. In addition, there were no differences between groups in the total number of medications consumed by the patients at baseline , as well as in the number of drugs for treating other comorbidities.p = 0.013), which reflects a residual effect of therapy  and total FIQ . That is, individuals did not return to baseline situation after the first treatment. Therefore, the second period after cross-over could not be included in the analysis.The difference or change of score between baseline and the evaluation visit was used as the outcome variable; that is, the differences between visit 1 and visit 3, for the first period, and between 4 and 6 for the second one. There was no sequence effect. However, a period effect was observed with significant differences between the responses of the first and second period in the main outcome measures: VAS pain  in the intervention group, but not in the control group Table  Fig. 2)2).p < 0.0001). Similarly, the change in ICAF score, both total  and by domains , was significantly greater in the treated group than in the non-treated. Finally, no significant changes were observed in SF-36 dimensions between groups, except in the physical function and in the emotional role, which presented larger changes in the WBC group than in the control group , FIQ score (β = 29.7), and ICAF (β = 12.8), independently of baseline values. Finally, the models explained 45.5% of the variance of ∆VAS pain, 54.3% of the variance of ∆FIQ score, and 47.6% of the variance of ∆ICAF  all those variables with significant basal differences were introduced Table . HoweverFive patients referred adverse events during cryotherapy, including: heartbeat feeling in whole body (1), palpitations (1), sleep difficulties (2), bowel sounds and bloating (1), muscle stiffness (1), tremor (1), headache (1). All of them were mild and appeared during the first sessions, waning afterwards. In one patient, muscle stiffness and tremor obliged the discontinuation of therapy after two sessions. Adverse events were recorded prior and after each session, therefore, there is no information on adverse events in the control phase.In this study, we have shown a significant effect of WBC on pain, impact of disease, and severity in a group of patients with FM and severe symptomatology and with mild undesired effects.A study had already reported an improvement in quality of life with WBC in 50 patients with FM . The WBCThe mechanisms of action of cryotherapy are not well understood. Since there is no proven inflammatory component in fibromyalgia, it has been postulated that cryotherapy through a reduction of oxidants levels may reduce muscular damage and accelerate recovery after normal physical activity. As a consequence pain and fatigue may substantially improve reducing symptomatology and improving physical function in these patients. Cryotherapy also relieves stress by the activation of neuroendocrine and metabolic functions and it is known that in patients with fibromyalgia stress is an important component , 28–30.The crossover design allows all subjects receiving the treatment under study acting as their own control. This design is usually efficient, allowing smaller samples sizes due to reduced variability. However, we were affected by significant differences between the responses of the first and second period in the two outcome measures . That is, individuals did not return to baseline situation after the first treatment. The washout period was not long enough to ensure the disappearance of the effect of the treatment administered in the first period. We could not anticipate such a good outcome of WBC. In fact, based on the previous study by Bettoni et al. , we expeIn summary, and taking into account the limitations of the study design, WBC during 3 weeks appears to produce a beneficial effect compared to no cold treatment in terms of pain and impact of disease in FM. The effect may last longer than a week after therapy, but will need to be demonstrated in future studies.Below is the link to the electronic supplementary material.Supplementary material 1 (DOCX 17 KB)


Clinical studies have shown that total intravenous anesthesia (TIVA) with propofol is associated with better postoperative pain control compared with inhalational anesthesia, while other studies have not shown any benefit. The analgesic effect of TIVA with propofol in colorectal surgery has not been studied. The aim of this study is to evaluate the postoperative analgesic effects of TIVA with propofol versus inhalational sevoflurane in colorectal surgery.This is a retrospective case–control study. Records of patients undergoing colorectal surgery from 2014 to 2016 (36 months) were retrieved. Ninety-five patients who received TIVA with propofol were matched against 95 patients who received inhalational sevoflurane. Acute postoperative numerical rating scale (NRS) pain scores, postoperative morphine consumption, patient satisfaction, and side effects were compared and analyzed for differences between TIVA with propofol and sevoflurane.P < .001), and daily morphine consumption on postoperative days 1 (P = .031), 2 (P = .002), and 3 (P = .031) compared with those receiving sevoflurane.There were no significant differences in NRS pain scores, incidence of side effects, and patient satisfaction between the 2 groups. Patients receiving TIVA with propofol had significantly reduced total morphine consumption (TIVA with propofol was not associated with improved postoperative analgesia, better patient satisfaction, or reduced side effects. It may reduce postoperative opioid consumption after colorectal surgery. Propofol also has analgesic properties. In animal studies, propofol has been shown to reduce pro-inflammatory cytokine levels and inhibit activation of N-methyl-D-aspartate (NMDA) receptors.,7 Clinical studies have shown that propofol provided improved acute postoperative analgesia compared with inhalational anesthesia.–11 A meta-analysis of 14 clinical trials also found that propofol was associated with lower pain scores 24 hours after surgery. Furthermore, TIVA with propofol may reduce incidence of chronic postsurgical pain.,13 However, other clinical studies have found no beneficial analgesic effect after surgery with propofol.,15 As pain intensity and mechanism of pain is probably different with different types of surgery, the usefulness of propofol as an analgesic may vary in the context of different surgical procedures. This is in agreement with the concept of procedure-specific analgesia.Propofol is one of the most commonly used intravenous anesthetic drugs both for induction and maintenance of general anesthesia. Advantages of total intravenous anesthesia (TIVA) with propofol also include reduced nausea and vomiting, reduced atmospheric pollution, and a better wake up profile. Reduced opioid use is associated with earlier return of bowel function and shorter length of hospital stay.,19 Opioid-sparing analgesics that may be useful for colorectal surgery include paracetamol, selective and nonselective nonsteroidal anti-inflammatory analgesic drugs (NSAIDs and COX-2 inhibitors), alpha-2-delta ligands, intravenous lignocaine, and alpha 2-agonists.–25 The analgesic properties of propofol may make it a useful opioid-sparing analgesic adjunct for colorectal surgery in the context of a multimodal analgesic regime. The analgesic effect of intraoperative maintenance with propofol versus inhalational agents specifically for colorectal surgery has not been evaluated before. The main aims of this study were to determine whether TIVA with propofol would improve postoperative analgesia and reduce opioid consumption after colorectal surgery. A retrospective case-controlled study was performed to compare the analgesic effects of TIVA with propofol versus inhalational sevoflurane. We hypothesized that TIVA with propofol would be associated with less postoperative pain and reduced postoperative opioid consumption.Multimodal opioid-sparing analgesia is recommended for colorectal surgery and is a vital component of enhanced recovery after surgery (ERAS) programs.2The study was approved by the Institutional Review Board of Queen Mary Hospital and the University of Hong Kong. It was registered at ClinicalTrials.gov (NCT03058354). There was no requirement to obtain written informed consent from patients, as this study was retrospective in nature. The data were delinked from patient identifiers and anonymized before analysis so that none of the researchers were aware of patient identification. Records of patients after colorectal surgery and under the care of the acute pain service (APS) between January 1, 2014, and December 29, 2016, in Queen Mary hospital were reviewed and analyzed. Data collected included demographic data ; types of colorectal surgery performed ; types of general anesthesia techniques ; with or without intraoperative use of ketamine; pain intensity as verbal numerical rating scale  at rest and during coughing from postoperative days 1 to 3; daily, accumulative and total postoperative morphine consumption and duration of morphine patient-controlled analgesia (PCA) use; incidence of adverse events , and patient satisfaction with pain relief. Exclusion criteria included the following: missing essential data, difficulty in assessment of postoperative pain , early termination of PCA morphine due to deterioration of patients’ condition, patients requiring a second operation, and patients participating in other research projects.Patients did not receive premedication. Patients receiving inhalational sevoflurane anesthesia (SEVO group) were induced with 1 to 2 mg/kg of intravenous propofol, and then given a bolus of 1 μg/kg of remifentanil and 0.5 mg/kg of atracurium or 0.6 mg/kg of rocuronium before endotracheal intubation. General anesthesia was then maintained with sevoflurane, air, and oxygen, with sevoflurane level titrated to between 0.7 and 1 MAC. Patients receiving intravenous maintenance with propofol (TIVA group) were induced and maintained with a target-controlled infusion of propofol using the Marsh effect site model. Patients in the TIVA group also received 1 μg/kg bolus of remifentanil and 0.5 mg/kg of atracurium or 0.6 mg/kg of rocuronium before intubation. Patients from both groups received intraoperative remifentanil infusion titrated according to hemodynamic response up to a maximum of 0.2 μg/kg/min. Zero-point 1 mg/kg of intravenous morphine was given before surgical incision. An additional 0.1 mg/kg of morphine was given in divided doses at the discretion of the anesthetist for surgical procedures lasting more than 2 hours. Intravenous ketamine at a dose of 0.5 to 1 mg/kg was given at the discretion of the anesthetist. Up to 2 mL/kg of 0.5% levobupivicaine was infiltrated into the surgical wound by the surgeon during wound closure. Reversal of neuromuscular blockade was achieved with 0.02 mg/kg of atropine and 0.05 mg/kg of neostigmine.Vital signs, including blood pressure, oxygen saturation (SpO2), heart rate, and body temperature, were monitored in the postanesthesia care unit (PACU). Two milligrams of intravenous morphine were given to patients if their verbal NRS was 4 or above. This was repeated every 5 minutes until their NRS was 3 or below. All patients were given intravenous PCA with morphine. The PCA morphine setting was 1 mg bolus, 5-minute lockout interval, maximum hourly dose limit of 0.1 to 0.15 mg/kg/hour, and without background morphine infusion. Rescue pain medication was prescribed in the form of subcutaneous or intramuscular morphine injection at a dose of 0.05 mg/kg every 4 hours as needed. Intravenous ondansetron 4 mg every 4 hours was prescribed for nausea and vomiting on an as needed basis.Fluid diet was started on postoperative day 0 in the absence of obvious surgical complications. Regular oral analgesics consisting of tramadol 50 mg 3 times a day, paracetamol 1 g 3 times daily, and celecoxib 200 mg twice daily were started. The patients were assessed by an anesthetist from the APS team at least once a day. In addition, the APS team was informed if pain control was poor. PCA morphine settings could then be adjusted after assessment to give a larger bolus dose and higher hourly limit. NRS pain scores at rest and with coughing, daily PCA morphine consumption, and side effects were recorded every day until APS discharge. PCA morphine was stopped when NRS score was less than 3 during coughing; daily PCA morphine use was less than 0.1 mg/kg, or upon patient request. Oral analgesics and rescue analgesics were continued after cessation of PCA morphine. At the time of PCA morphine cessation, patient satisfaction regarding pain service was evaluated. Patients were asked to rate their satisfaction as “good,” “fair,” or “unsatisfactory.” Reasons for “unsatisfactory” grading were sought. The mean visual analogue scale (VAS) pain score of the treatment group was 1.8, while the mean VAS pain score of the control group was 2.7 with P = .002 and an estimated pooled standard deviation of 2.2. At a power of 0.80 and an alpha value of 0.05, 94 patients would be required in each group. As this study was retrospective in nature, all patients who underwent colorectal surgery between January 2014 and December 2016 were screened for eligibility. A total of 95 patients in each group who satisfied our matching criteria were included in this study from our database.Calculation for the sample size was based on the effect from a previous study on analgesic efficacy for colorectal surgery using the primary outcome of pain at rest at 24 hours. This 1:1 patient matching is a more comprehensive method than using the propensity score.,29 Patient demographics are presented as means (SD) for parametric data, and percentage where appropriate. Differences in pain scores were tested for using unpaired t test with Welch correction, while Mann–Whitney test was used to look for differences in PCA morphine consumption after it was determined that the data did not follow a normal distribution. Differences in postoperative side effects and overall satisfaction were tested for using Fisher exact test. Statistical Package for the Social Sciences  statistical software and GraphPad Prism version 7.00 for Windows, GraphPad Software, La Jolla California USA were used for data analysis.Each patient who received TIVA was matched 1:1 to patients who had received sevoflurane according to age, gender, ASA physical status, types of surgery performed , and with or without intraoperative use of ketamine.3P < .001). In the SEVO group, there were no chronic pain patients and none of the patients were taking opioids preoperatively. There was 1 chronic pain patient who was on preoperative opioids in the TIVA group. There was no significant difference in the number of patients with chronic pain or those taking preoperative opioids between the 2 groups (both P = 1.000) . Total PCA morphine consumption over the 3 days was also significantly less in TIVA group compared with SEVO group .Nonaccumulative daily PCA morphine consumption is summarized in Table No differences were observed between the number of patients suffering from nausea, vomiting, dizziness, pruritus, and confusion between the 2 groups Table . It shou4In this study, we found no differences in postoperative pain scores, incidence of side effects, or patient satisfaction with pain control between patients anesthetized with TIVA propofol and those having inhalational sevoflurane. However, TIVA with propofol was associated with significantly reduced postoperative morphine consumption from postoperative days 1 to 3.,15 However, a meta-analysis of 14 randomized controlled trials showed that TIVA with propofol was associated with reduced postoperative NRS pain scores 24 hours after surgery compared with inhalational anesthesia, although difference was marginal. Another meta-analysis also showed reduced postoperative pain scores at rest 30 minutes, 1 hour, and 12 hours after surgery, although the difference was not significant when a conservative P value of less than .1 was used. Using a similar anesthetic/analgesic protocol to the one used in this current study, patients receiving TIVA with propofol had significantly lower NRS pain scores with coughing on postoperative days 1 to 2 after liver surgery. The difference observed between the 2 studies may be due to the nature of the surgical wounds. Liver surgery is associated with large upper abdominal wounds, which usually result in more postoperative pain than lower abdominal wounds, especially with coughing. Therefore, use of TIVA with propofol in that setting probably produced a relatively bigger difference in NRS pain scores. This suggests that the effectiveness of TIVA with propofol in reducing postoperative pain is procedure specific and dependent on the type of surgery being performed. Another reason why no differences in pain scores were found may be due to the effect of intraoperative remifentanil. Intraoperative remifentanil consumption was significantly higher in the TIVA group than in SEVO group in this current study  was one of the factors associated with early discharge within 48 hours. In this study, reduced postoperative morphine consumption was observed from postoperative days 1 to 3. A multimodal analgesic regime consisting of local wound infiltration and multiple oral analgesics was used in this study, which is in line with the concept of multimodal analgesia in ERAS. As TIVA with propofol was associated with reduced opioid consumption, it may potentially enhance recovery and reduce bowel dysfunction in patients undergoing colorectal surgery within a multimodal analgesic regime. However, information regarding recovery, hospital discharge, and return of bowel function were not available for analysis.Analgesic adjuvants that can reduce perioperative opioid consumption are important in colorectal surgery, especially in the context of ERAS programs. Reduced opioid consumption reduces bowel dysfunction and is associated with earlier recovery.,37 In our study, there was a trend toward reduced nausea in the TIVA group compared with SEVO group , but this was not statistically significant. However, this study was not powered to detect significant differences in side effects, which have a low incidence.No differences between groups were noted for the incidence of side effects: nausea, vomiting, dizziness, confusion, and pruritus. In addition, there was no significant difference in patient satisfaction with pain control. TIVA with propofol has been shown to reduce nausea and vomiting compared with inhalational anesthesia.A limitation of this study was that the data were retrospectively collected. Thus, not all variables could be controlled. Depth of anesthesia was not controlled nor monitored using depth of anesthesia monitoring. In addition, as mentioned earlier, intraoperative remifentanil consumption was significantly higher in the TIVA group, which could have affected the pain scores. Another limitation in this study was that some patients received open surgery, while others had minimally invasive surgery. These patients were matched equally between the TIVA and SEVO group. When analyzing the subgroup receiving open surgery, there was still no significant difference in pain scores, which was consistent with the results of the total combined data. In our analgesic regime, we employed a multimodal approach using a combination of local anesthetic wound infiltration, intravenous PCA morphine, and multimodal oral analgesics. However, regional techniques such as thoracic epidural analgesia were not performed, as thoracic epidural analgesia was not routinely used in our center for colorectal surgery. The opioid-sparing effect of TIVA with propofol demonstrated in this study may not be present when thoracic epidurals are used. Finally, we did not have information about the total dose of oral analgesics taken postoperatively. Although patients from both groups were prescribed regular paracetamol, celecoxib, and tramadol, we cannot be certain that all patients took the same amount of oral analgesic drugs. Therefore, we cannot rule out the possibility of significant differences in oral analgesic consumption between the 2 groups that may have affected the results of the study.In conclusion, TIVA with propofol was not associated with improvements in postoperative pain scores, side effects, and patient satisfaction compared with inhalational sevoflurane in patients undergoing colorectal surgery. It was associated with significantly reduced postoperative PCA morphine consumption. Larger sample sized randomized controlled studies are needed to confirm the opioid-sparing effects of TIVA with propofol.The authors wish to thank Ms J. Man for input in statistical analysis, and The Department of Anaesthesiology, University of Hong Kong for supporting this project.Conceptualization: Stanley Sau Ching Wong.Data curation: Siu Wai Choi, Yvonne Lee.Formal analysis: Siu Wai Choi.Investigation: Yvonne Lee.Methodology: Stanley Sau Ching Wong, Siu Wai Choi.Supervision: Stanley Sau Ching Wong, Chi Wai Cheung.Writing – original draft: Stanley Sau Ching Wong, Siu Wai Choi.Writing – review & editing: Stanley Sau Ching Wong, Michael Garnet Irwin, Chi Wai Cheung.


The best surgical technique for managing ovarian endometriomas is still widely debated, though the current standard is stripping cystectomy. The use of plasma energy as a treatment option is a relatively new concept and little data is currently available on this method. The aim of this study was to determine the feasibility of the use of plasma energy in our daily clinical practice by looking at various postoperative outcomes.Twenty-one women previously diagnosed with uni- or bilateral ovarian endometriomas by transvaginal ultrasound, associated with pelvic pain and/or infertility, were included in this retrospective cohort study performed in a tertiary endometriosis referral centre. All women underwent endometriotic cyst ablation using plasma energy. At follow up postoperative pain, number of days until return to work following surgery, postoperative pregnancy rate and recurrence rate were determined.This study demonstrates a significant decrease in the proportion of patients reporting pain postoperatively when comparing the number of patients with dysmenorrhoea, dyspareunia, and chronic pelvic pain pre- and postoperatively. In addition, the median number of days until women returned to work postoperatively was 9 days (interquartile range (IQR) 8-11 days). The postoperative pregnancy rate was 46.2% (6 of 13 women wishing to conceive) and the recurrence rate was 9.5%.In conclusion, plasma energy is a promising alternative to stripping cystectomy, as comparable results for postoperative pregnancy and recurrence rates can be observed. However, further research is necessary to draw firm conclusions when comparing these two techniques. Endometriomas are ovarian cysts formed by endometriotic deposits within the ovary, and occur in 17% to 44% of women with endometriosis . The priThe biggest challenge in operative management of endometriomas is to ensure complete cyst removal and reducing the risk of recurrence whilst maintaining ovarian reserve, as many of the affected women are of childbearing age.Stripping cystectomy is considered the standard recommended treatment since a Cochrane review published by Hart et al. . HoweverA new technique currently being trialled is ablation using plasma energy. Limited data is available on this technique and a randomized controlled trial comparing stripping cystectomy and ablation using plasma energy is yet to be published. The data that is available from a series of non-comparative case-control studies report encouraging results and suggest that ovarian endometrioma ablation using plasma energy is a promising alternative to stripping cystectomy . The aimInstitutional review board approval was not required for this retrospective study.We performed a retrospective cohort study of all the women who underwent unilateral or bilateral ovarian endometrioma ablation using plasma energy  between February 2015 and February 2016 at the VU University Medical Centre (VUmc), Amsterdam, the Netherlands. The VUmc is a tertiary endometriosis referral centre. During the study period 65 patients underwent laparoscopic surgery for treatment of endometriotic cysts at the VUmc. All 65 patients were informed about the use of plasma energy and 21 patients elected for ablation using plasma energy.Preoperatively patients underwent transvaginal ultrasound examination to confirm the presence and record the dimensions of the endometriomas.The surgical procedures were performed by three gynaecologists , all of whom are specialists in endometriosis and reproductive medicine and are trained and certified in the use of plasma energy (in pigs and humans). All three gynaecologists are also experienced in the use of CO2 lasers for endometriosis surgery. Ovarian endometrioma ablation was performed as previously described by Roman et al. ; 2013. DPain scores were recorded preoperatively at the outpatient clinic, post-operatively prior to discharge and at follow up 6-8 weeks later in the outpatient clinic by the attending gynaecologist using the Visual Analogue Scale (VAS) in all cases. The Endometriosis Fertility Index (EFI) was calculated for all patients. If their chances of spontaneous conception in the next 12 months were lower than 30%, which corresponds to an EFI score of ≤ 6, they were referred for medically assisted reproduction (MAR) postoperatively.The most recent postoperative pelvic ultrasound examination results were collected and used to determine the endometrioma recurrence rate.The electronic medical records were individually reviewed and information was sourced from pre- and postoperative outpatient clinic records, as well as intraoperative records and inpatient notes. The primary outcomes of this study were incidence and severity of pain postoperatively. Secondary outcomes measured were recurrence of ovarian endometriomas, pregnancy following surgery, and return to work. Recurrence was defined as the presence of a homogenous hypo-echogenic cyst on the ablated ovary on the most recent postoperative transvaginal ultrasound examination. Pregnancy was diagnosed by serum Beta human chorionic gonadotropin and confirmed by the presence of a gestational sac seen on transvaginal ultrasound examination performed at 8 weeks gestation. Return to work was considered the number of days following surgery until women returned to work.The data collected included demographic data, incidence and severity of pain pre- and postoperatively, use of hormone therapy, subfertility and MAR pre- and postoperatively, intraoperative findings and perioperative characteristics, complications and postoperative outcomes . Women were considered subfertile if attempts to conceive were unsuccessful for longer than 12 months.Follow up was variable and was dependent on timing and frequency of outpatient clinic attendance postoperatively. The most recent postoperative outpatient clinic visit before we concluded data collection in December 2017 was considered the end of follow up.Statistical analysis was performed using the Statistical Package for the Social Sciences version 22.0 . Categorical data were reported as absolute numbers and percentages. Normally distributed continuous variables were reported as a mean with standard deviation, and non-normally distributed continuous variables were reported as a median with a minimum-maximum range or with interquartile ranges. Continuous outcomes were analysed using an independent T-test or Mann-Whitney U-test as appropriate. We analysed the effects of blood loss, duration of surgery, and size of ovarian endometrioma on return to work with Spearman’s rank-order correlations. The cut-off value for return to work was based on the median number of days.The differences in proportion of patients (pre- and postperatively) with dysmenorrhea, dyspareunia, and for chronic pelvic pain were tested using the McNemar test for paired dichotomous data. A P-value of < 0.05 was considered to be statistically significant.From February 2015 to February 2016, 21 women underwent ablation of ovarian endometriomas using plasma energy. All the included women had at least one ovarian endometrioma with a diameter of 25 mm or more associated with pain and/or subfertility. Four patients did not report any pain prior to surgery, however all four were subfertile. The diameters of these patients’ cysts were 25 mm, 30 mm, 30 mm and 40 mm.Patient demographic data and baseline clinical characteristics are shown in The follow up time of our study was relatively varied, with a median follow up time of 10 months, and ranging from 3 to 31 months.Postoperative outcomes are summarized in There was a statistically significant decrease in the proportion of patients reporting dysmenorrhoea, dyspareunia, and chronic pelvic pain postoperatively, as well as a considerable reduction in the pain scores when comparing women pre-and postoperatively. This is illustrated in This retrospective cohort study revealed similar intra- and postoperative outcomes to those previously reported. In addition we observed a significant decrease in post-operative pain scores and a quick postoperative recovery, suggesting that ablation using plasma energy might be a promising new surgical technique for the treatment of ovarian endometriomas. Extensive research has been done regarding the most suitable surgical technique for the management of ovarian endometriomas and many different approaches have been trialled, the most common of which being (laparoscopic) stripping cystectomy; ablation, including electrical/thermal and CO2 laser ablation; fenestration/aspiration; and combined techniques . The useOne of our principal objectives was to look at the efficacy of this new technique for pain reduction postoperatively. We observed a considerable reduction in the VAS scores postoperatively as well as a statistically significant decrease in the proportion of patients with dysmenorrhoea, dyspareunia and chronic pelvic pain postoperatively. A statistically significant decrease in dysmenorrhoea VAS scores was also found by Roman et al. , though According to Roman et al.  the duraRecent data published in a number of case series has demonstrated that the rates of recurrence and postoperative pregnancy in women following ovarian endometrioma ablation using a plasma energy device are comparable to the rates previously reported in women in whom other surgical approaches were employed .The pregnancy rate in our retrospective study was 46.2%, as 6 of the 13 women wishing to conceive fell pregnant and delivered within the follow-up period. Though our postoperative pregnancy rates are lower than those seen in women from the CIRENDO  database in France (ranging from 56.8%-68.7%) , our resThe principal limitations of our study are comprised of the inherent methodological limitations that tend to accompany a retrospective pilot study lacking a control group such as this one. In addition, the variable follow-up time, owing to varying clinical factors and resulting differences in necessary management, is a disadvantage and makes comparison to other studies difficult. We can therefore not say with certainty whether the use of plasma energy alone may account for the results presented in this study or whether the results were the consequence of, or influenced by, the (pre-) operative workup.Conversely, a major strength of our study is related to our investigating in more detail the efficacy of this technique in terms of improvement in pain following surgery, in addition to pregnancy and recurrence rates. It is necessary to consider these factors as well in order to determine how well a plasma energy device can be implemented in our daily practice and whether our patient population can benefit. Whilst it would be ideal to observe this in a larger trial in the future, our findings for pain scores postoperatively presented in this study are promising.Our results suggest that the use of plasma energy for the management of ovarian endometriomas is a feasible and an attractive alternative to stripping cystectomy.Nevertheless, no definitive conclusions can be drawn until randomized trials are performed comparing plasma energy ablation to other management approaches in the treatment of endometriomas, including stripping cystectomy.


Introduction: Early recovery of mobilization after a fracture of the hip is associated with improved long-term ability to walk, lower complication rates, and mortality. In this context, early mobilization and full weight bearing are favorable. The aim of this study was (1) to analyze the influence of time between operation and first mobilization on in-hospital outcome and (2) the influence of early mobilization, full weight bearing, and ASA on pain, mobility of the hip, and ability to walk during the in-hospital phase of recovery.Methods: This is a retrospective in-hospital study of 219 patients aged 70 years or older who were treated with surgery after a hip fracture. Data were collected by a review of medical records. The outcomes were mortality, complications, length of stay, and the Merle d’Aubigné score which evaluates pain, mobility of the hip, and ability to walk. Factors were sought in bivariate and multivariate analyses.Results: A shorter time between operation and first mobilization was significantly associated with lower in-hospital mortality and complications. Early mobilization (within 24 h after the operation) and full weight bearing had no influence on pain, mobility of the hip, and ability to walk as well as length of stay in our cohort. Fracture type and treatment influenced mobility of the hip, while age as well as physical health status affected the ability to walk.Discussion: Patients with femoral neck fractures, respectively after total hip arthroplasty, had less pain and showed better mobility of the hip and ability to walk during hospitalization than patients with trochanteric fractures; these results were irrespective of early vs. late mobilization and full vs. partial weight bearing. Foremost, a shorter time between operation and first mobilization is associated with lower complication and mortality rates. The increase in life expectancy in the past few decades has led to a substantial increase in fragility fractures. Especially, hip fractures are common and serious injuries of elderly people that lead to loss of mobility and independency and result in significant socioeconomic consequences ,2. ElderEarly recovery of mobilization has not only a significant impact on short-term results, such as lower complication rates and shorter length of stay, but also results in better long-term outcomes such as higher autonomy and reduced mortality –11. KrisA multidisciplinary postoperative approach and early ambulation have been identified to increase functional outcome at discharge and enhanced performance in activities of daily living after hip fracture ,7,18–21.The purpose of this study was (1) to analyze the influence of time between operation and first mobilization on in-hospital mortality as well as complications and (2) the association between early and late mobilization, full or partial weight bearing as well as American Society of Anesthesiologist Physical Status classification  (ASA) onThis retrospective observational study was approved by the local ethics committee (KEK-ZH-Nr. 2011-0382), and written informed consent was obtained from all patients.®, Stryker Corporation, Kalamazoo, MI), total or partial hip prosthesis at our institution; (c) complete Merle d’Aubigné score [Patients meeting the following criteria were included: (a) age over 70 years; (b) diagnosis of a femoral neck or trochanteric fracture treated with intramedullary nail , and the femoral head lag as well as femoral shaft locking screws were placed using the targeting device. After removing the targeting device, the final position of the implant was verified using the image intensifier.Total and partial hip prostheses were done in supine position on an orthopedic table with a mobile leg positioner. Arthrotomy was done by a minimal anterolateral access following osteotomy of the femoral neck and extraction of the femoral head. Following standard surgical procedures in hip prosthesis, the acetabulum was exposed followed by reaming and placing of the acetabular implant in the correct angle under image intensifier. After positioning the femur in hyperextension, adduction, and external rotation, the medullary canal of the proximal femur was opened and the stem was placed in both total and partial hip replacements. Using the image intensifier, positioning was controlled intraoperative.An orthopedic medical doctor reviewed the medical records, anesthesiological and surgical reports, and reports from physiotherapists as well as nurses. The following parameters were collected: (a) gender; (b) age; (c) diagnosis; (d) type of treatment; (e) Merle d’Aubigné score with its three modalities; (f) ASA score; (g) full or partial weight bearing; (h) time interval between surgery and first mobilization; (i) complications; (j) mortality and (k) length of stay.For the first research question, the outcomes were (a) in-hospital mortality, (b) length of stay, and (c) occurrence of the following complications during hospitalization: deep vein thrombosis, pulmonary embolism, urinary tract infection, decubitus, gastroduodenal ulcers, pseudomembranous colitis, urosepsis, electrolyte dysregulation requiring treatment, delirium, renal insufficiency, pneumonia including aspiration pneumonia, heart and respiratory insufficiency, myocardial infarction, ileus, wound infection, transient ischemic attack or stroke, and death.For the second research question , the outcome was assessed at the end of hospitalization with the Merle d’Aubigné score which evaluated pain, mobility of the hip, and ability to walk on a scale of 0–6 for each item, where 0 indicated the worst and 6 the best outcome of the patient. The total minimum score was 0 and the maximum was 18 .The seven subgroups were the following: 0: Pain is intense and permanent; 1: Pain is severe, even at night; 2: Pain is severe when walking and prevents activity; 3: Pain is tolerable with limited activity; 4: Mild pain when walking and the pain disappears with rest; 5: Pain is mild and inconsistent, normal activity is possible; 6: No pain.The seven subgroups were the following: 0: Ankylosis with bad position of the hip; 1: No movement possible; 2: Flexion <40°; 3: Flexion 40–60°; 4: Flexion 60–80°, patient can reach his foot; 5: Flexion 80–90° and abduction 15–30°; 6: Flexion >90° and abduction >30°.The seven subgroups were the following: 0: The patient is not able to walk; 1: The patient is bedridden or uses canes or crutches and personal help to go to the bathroom; 2: The patient can walk only with crutches or walking frame; 3: The patient can walk with canes; 3: The patient can walk with one cane for less than an hour, without a can only with much difficulties; 4: The patient can walk for a long period (>1 h) with a cane, short time without cane but with a limp; 5: The patient can walk without a walking aid but with a slight limp; 6: Normal walking abilities.Independent variables were age, gender, fracture type as well as fracture treatment. Confounders were the ASA score, full or partial weight bearing, and time interval between surgery and first mobilization.An anesthesiologist preoperatively classified the patients undergoing surgery by the American Society of Anesthesiologist Physical Status classification (ASA) and documented it in the anesthesiologic report. The physical status were: Class I: a normally healthy patient; Class II: a patient with mild systemic disease; Class III: a patient with severe systemic disease that is not incapacitating; Class IV: a patient with an incapacitating systemic disease that is a constant threat to life; Class V: a moribund patient who is not expected to survive for 24 h with or without operation. No patient was classified ASA V. For statistical analysis, the patients were dichotomized into ASA I/II and ASA III/IV.The postoperative level of weight bearing was determined by the surgeon. Because not all patients were able to follow postsurgical weight bearing according to the surgeons’ prescription, there were discrepancies between surgical reports and reports from physiotherapists. The actual weight bearing performed by the patient was used as the postoperative level of weight bearing. Patients were mobilized either with full or partial weight bearing.For the first research question, patients were classified into three categories by the time between the operation and first mobilization: (a) within 24 h, (b) between 24 and 48 h, (c) after 48 h.For the second research question, early mobilization was defined as first mobilization of the patient within 24 h after surgery and late mobilization after 24 h.t-test or Mann–Whitney U-test. Differences in frequencies of categorical data were assessed by chi-squared test or Fisher’s exact test, depending on the number of expected cases per group. For the first research question, only variables, which were significant or nearly significant (p < 0.1) in bivariate analysis, were entered into a regression analysis with the main primary outcome complications. Due to a low number of deaths, no regression analysis was done for mortality. For the second research question, all independent and confounding variables were entered into a linear regression analysis with the main primary outcome parameters as well as the Merle d’Aubigné score, and length of stay.Standard descriptive statistical analyses were performed using SPSS software package . Continuous data were presented as mean values with standard deviation (SD), were examined for normal distribution by exact Kolmogorov–Smirnov test, and compared with either p-value of 0.05 was chosen as the significance cut-off level.A p = 0.001 and p < 0.001).The overall in-hospital mortality rate was 7.3% . In bivap = 0.033, p < 0.001, and p = 0.023). In multivariate analysis, a higher ASA score and longer time between operation and first immobilization (less than 24 h vs. longer than 48 h) were significant predictors for a higher complication rate . The level of pain in patients treated with intramedullary nail was significantly higher compared to patients with total and partial hip replacements (p < 0.001 and p = 0.004). No predictors for pain were found in multivariate analysis . Patients treated with a total hip replacement were significantly better mobilized than patients after intramedullary nailing or partial hip replacement (p < 0.001 and p = 0.008). In multivariate analysis, fracture type and fracture treatment were significant: femoral neck as well as total hip replacement were associated with higher mobility of the hip . Patients treated with total hip replacement had a better ability to walk than patients with an intramedullary nail or partial hip replacement (p < 0.001 and p = 0.002). In multivariate analysis, younger age as well as lower ASA score were found as predictors for ability to walk . In multivariate analysis, femoral neck fracture was a significant predictor for a higher Merle d’Aubigné score  femoral neck fracture or b) with a total hip replacement were associated with a higher (better) Merle d’Aubigné score . In multivariate analysis, gender was the only significant predictor for length of stay  to analyze the influence of time between operation and first mobilization on in-hospital mortality as well as complications and (2) the influence of early mobilization, full weight bearing, and healthy physical status on in-hospital pain, mobility of the hip, and ability to walk in geriatric patients with hip fractures. First, a shorter time between operation and first mobilization was significantly associated with lower in-hospital mortality and complications. Second, early mobilization and full weight bearing had no influence on pain, mobility of the hip, and ability to walk as well as length of stay in our cohort. Fracture type and treatment mainly influenced mobility of the hip, and age as well as physical health status impacted the ability to walk.There are several limitations of the study. First, it is a retrospective, observational study; second, scores were obtained by a review of medical records and reports; third, only in-hospital follow-up was analyzed; and last, the limited number of patients.The in-hospital mortality rate in our study is 7.3%. This is consistent with international studies which showed in-hospital mortality rates between 3 and 10% ,16,28–31We found less complication in patients mobilized in the first 24 h after operation than in patients mobilized later than 24 or 48 h. This is comparable with previous studies –9. At thThe level of pain was higher in trochanteric fractures and patients treated with an intramedullary nail. This is consistent with international studies ,35,36. IWe found no negative predictors for pain; however we only analyzed several factors. Besides fracture type and fracture treatment, a short time to fracture treatment, the mental health status or depression have been identified as a predictor for pain in different studies ,7. The fNinety percent of our patients reached a mobility score of four or higher at the end of the hospital stay. In other words, only 10% were not able to reach their feet. Fracture type and treatment were predictors for hip mobility, but early mobilization and full weight bearing had no influence on hip mobility.Different assessment tools have been used to evaluate the functional outcome after surgery of the hip. In this study we used the Merle d’Aubigné score, which contains the mobility of the hip score. Since nearly all patients, independent of our confounders, had the same mobility of the hip score, this mobility of the hip score seems inadequate to be used for this purpose. The cumulative ambulation score (CAS) seems to be more useful in the clinical context. It evaluates specific motion sequences like getting in and out of bed or sit to stand from a chair over the first three postoperative days.In this study group, only 3% of the patients were able to walk without crutches for a short distance. Forty one percent of the patients were able to walk with crutches. This seems to be low compared with other studies reporting 53–80% of patients reaching pre-injury functional level ,30,31. EFull weight bearing seems to be favored and associated with a better functional outcome ,24. In aThis study emphasizes the importance of early mobilization after a surgical hip procedure to reduce complications and death. It showed also reproducible risk factors for a negative in-hospital outcome, such as higher age and higher ASA score. Early mobilization and weight bearing did yet not have any short-term effect on pain, mobility of the hip, and ability to walk in our cohort. Fracture type and fracture treatment mainly influenced the in-hospital functional outcome.


Participants were grouped into 1 of 3 categories: high risk of OSA ; intermediate risk of OSA ; and low risk of OSA . Candidate risk factors for delirium and pain were also extracted from this record. RESULTS/ANTICIPATED RESULTS: Logistic regression will be used to test whether OSA independently predicts postoperative delirium and linear regression to assess OSAs relationship to acute pain severity. We hypothesize that patients in the HR-OSA category will experience a higher incidence of postoperative delirium and greater postoperative pain severity. We also predict a step-wise increase in risk of these adverse outcomes when analyzing patients stratified by OSA risk (HR-OSA vs. IR-OSA vs. LR-OSA). For our secondary analyses, we anticipate these outcomes are modified by compliance with CPAP treatment. We believe patients with OSA who do not use prescribed CPAP will experience a higher incidence of postoperative delirium as well as increased pain severity. DISCUSSION/SIGNIFICANCE OF IMPACT: OSA is a common and frequently undiagnosed perioperative problem associated with altered pain processing and a high incidence of postoperative delirium. While likely providing stronger evidence of OSA’s reported impact on postoperative delirium and pain, our findings might also help discern points of intervention for treatment and prevention. Since OSA’s presumed impact poses challenges to clinicians and patients, prospective, randomized trials testing preventative or mitigating interventions are necessary. We hope to use these results to design such trials and clinical plans, with the goal of reducing postoperative delirium and acute postsurgical pain severity for the large number of patients at risk due to OSA.OBJECTIVES/SPECIFIC AIMS: To study the role of OSA as an independent predictor of perioperative outcomes. METHODS/STUDY POPULATION: For this single-institution cohort study, we included data from patients who were enrolled into 1 of 3 prospective parent studies. All participants underwent in-patient surgeries, excluding neurosurgeries, which required general anesthesia and a postoperative stay of at least 1 day. Patients included in this study were assessed daily for postoperative delirium and pain severity as part of the parent studies. In the current study, determination of delirium diagnosis was based on the 3-minute Diagnostic Confusion Assessment Method (3D-CAM), and the Visual Analogue Pain Scale (VAS) was used for pain severity. Data on OSA diagnosis (determined by sleep study); OSA risk (determined by the STOP-Bang tool; snoring, tiredness, observed apnea, high blood pressure, body mass index>35 kg/m


Past decades have seen a surge of studies investigating the role of spouses in chronic illness. The present study explored an interpersonal model of health-related quality of life in chronic pain settings. Spouse personality was tested as a moderator of pain intensity-to-health associations in patients with chronic pain.  This is a cross-sectional study. Participants were 185 noncancer chronic pain patients and their spouses. Patients were mostly females (58.4%). Mean age was approximately 56 years for patients and spouses. Patients completed a measure of pain intensity, health-related quality of life, and personality. Spouses also reported on their personality characteristics. Spouse personality was used as the moderator in the relationship between patients' pain intensity and health status. Patient personality was used as a covariate in the moderation analyses.  Spouse neuroticism moderated the relationship between pain intensity and physical health status, while spouse introversion moderated the pain-to-mental health association.  Results support the idea that the relationship between a chronic stressor, namely, chronic pain, and health-related quality of life may be complex and contextually determined by spousal characteristics. Clinical implications are discussed in the context of couples. Chronic pain is a common and disabling disease –3. SimilPersonality can be defined as relatively stable ways in which people think, feel, and behave . The fivConsistent with the literature on neuroticism, when spouse interaction styles are characterized by negative emotionality , patients tend to report increased mental distress. By contrast, the relationship between these negative responses and pain intensity and physical disability levels is weaker and inconsistent, and the role of arguably positive spouse behaviors, such as solicitous and validating responses, is still inconclusive –17. One There is, indeed, some support for this contextual  role of spouse personality in the context of couples. For instance, a study showed that spouse neuroticism influenced the associations between everyday problems and affect and physical symptoms in older couples . In anotThe present study aims at testing whether the negative influence of patient pain (stressor) on patient health-related quality of life (outcome) is moderated by psychological factors in the spouse . Research has consistently shown that health-related quality of life decreases with pain , 22. BasThis observational study was conducted at the Pain Clinic of the Valld'Hebron Hospital in Barcelona, which is a tertiary care pain clinic. This clinic was selected because it was the home institution of the corresponding author, C. S. R., when the study was conducted. Also, past research by our team has revealed that patient characteristics at this clinic are comparable to those of other tertiary pain clinics , so the Eligibility criteria included (i) having a diagnosis of chronic noncancer pain (>3 months of duration), (ii) having an appointment at the Pain Clinic of the Valld'Hebron Hospital between January 2014 and December 2015, and (iii) being married at the time of assessment. Consecutive sampling was used for recruitment, which started in January 2014 and finished in December 2015. One month prior to the patients' appointment at the Pain Clinic, the lead researcher, C. S. R., explored the eligibility criterion of having a diagnosis of chronic pain in the electronic medical records and ICD-9 code 338.2. Patients meeting this criterion were called to explore the eligibility criterion of marital status. If they were married and willing to participate in the study, two letters were sent to the patient's home, one for the patient and the other for the spouse. For both, each letter included a description of the goals, procedures, and possible risks of participating in the study, together with the contact information of the lead researcher, C. S. R., the informed consent form, and the questionnaires.Couples were asked to complete the forms separately and were given an envelope that had to be sealed and returned to the physician the day of the patient's first visit to the Pain Clinic. All participants provided their written consent to participate in the study and did not receive any economic compensation for their participation.The Ethics Committee of the Vall d'Hebron Hospital in Barcelona approved the current study.The NEO five-factor Inventory (NEO-FFI)  evaluatetotally disagree; 4 = completely agree). Each of the five personality dimensions is composed of 12 items, so scores for each dimension range from 0 to 48. The internal reliability of the personality dimensions in our study (0.64 < α < 0.84) was comparable to previous findings (0.66 < α < 0.81) [In the NEO-FFI participants rate their degree of agreement on a 5-point Likert scale (0 =  < 0.81) , 24.no pain to 10 = worst possible pain.Current pain intensity was assessed with a Numerical Rating Scale, which has become a standard in the measurement of pain  and is wα < 0.95), which is calculated for the 8 subscales, was consistent with previous findings (0.78 < α < 0.94) [Physical and mental components of quality of life were assessed with the Short Form-36 Health Survey , which h < 0.94) .Patient age, sex, pain duration, educational level, and personality were used as covariates due to their relationship with patient health status , 31. PatThe moderating effect of spouse personality on the relationship between pain and health-related quality of life in the patient was tested using multiple linear regressions. In the regressions, patient sex, age, and personality were included as covariates in the first block. Patient pain intensity was entered next. The third and the forth blocks included spouse personality and the interaction term , respectively. Multiple regression diagnostics included an analysis of multicollinearity  and a test of unusual and influential data .All analyses were computed using SPSS version 22 .SD = 13.59) and were mostly females (58.4%). The mean age for spouses was 56.66 years (SD = 13.85) and 41.6% were females. Approximately 94% of participants were born in Spain. Academic degree was similar for both samples, with approximately half of the participants having achieved more than 12 years of education (47.3% of patients and 50.3% of spouses). Patients had been suffering pain for an average of 6.55 years (SD = 8.57). Pain was mostly located in the back (58.8%) and neck (11.1%).From January 2014 to December 2015, 515 phone calls were made. In total, 203 patients met the eligibility criteria, so a letter was sent to these patients and their spouses. Eighteen patients did not return the protocol (either them or the spouse lost interest in the study). The final sample comprised 185 chronic pain patients and their spouses (91.1% response rate). All couples were heterosexual. Patients had an average age of 56.55 years (SD = 1.56) with a range of 3 to 10. The sample would be characterized as experiencing moderate to severe pain [SD and −1 SD) to those of previous investigations assessing similar pain populations [SD and 1 SD below the mean of the general population in Spain [SD) with previously reported scores in the general population in Spain [Means and standard deviations of study variables are presented in ere pain . Scores ulations –36. Compin Spain . Pain pain Spain , 38.Before performing the moderation analyses, all predictors were centered. Patient openness and agreeableness were not used as covariates due to their weak associations with patient health-related quality of life and to reduce multicollinearity problems.β = 0.19, p=0.009, 95% CI = 0.08, 0.54) means that patient pain intensity is less intensely associated with physical functioning at higher levels of spouse neuroticism. On the contrary, the negative coefficient in the interaction between extraversion and pain intensity in the prediction of mental health  reveals that patient pain intensity is less intensely associated with mental health at low levels of spouse extraversion. No moderation effect was found for spouse openness to experience, agreeableness, and conscientiousness.Spouse neuroticism moderated the association between patients' pain intensity and patient Physical Functioning , while sβ = −0.47, t = −4.22, p < 0.001; 95% CI = −14.08, −5.03) or moderate , as opposed to high .Post hoc analyses were then performed to explore if the simple slopes were significant and in the expected direction. Simple slopes are often calculated at one standard deviation from the sample mean, but its use has been argued to be arbitrary and sample specific, which might limit the generalizability of the findings  . Thus, wβ = −0.15, t = −1.5, p=0.115; 95% CI = −2.38, 0.26). On the contrary, pain intensity was significantly related to mental health when the spouse extraversion was either high  or moderate .The post hoc probing with extraversion as a moderator  showed sMultiple regression diagnostics revealed no problems of model fit to the data. Specifically, the variance inflation factor, which reveals to what extent the variance is inflated due to multicollinearity, was lower than 2 for all predictors. To test the existence of influential cases, we assessed how the regression coefficients changed by excluding an observation by means of the standardized DFBETA, with a particular interest in the interaction coefficient. All values were smaller than 1, suggesting that none of the observations substantially influenced the model .The present investigation aimed at exploring the moderating role of spouse personality in the relationship between pain intensity and health-related quality of life in patients with chronic pain. Based on previous research showing pain intensity and certain personality dispositions  associated with poor health outcomes , 9, we eResearch has repeatedly shown that experiencing pain impacts negatively on the physical and mental health status of individuals –45. In oThe Transactional Model Of Health and more recent discussions on interpersonal models of health in chronic pain , 18 propIn our study, pain-to-health associations in the patient also varied as a function of spouse extraversion. Specifically, patients whose spouses presented low levels of extraversion  showed poor mental health irrespective of the intensity of their pain. Research in chronic pain has indicated that optimism, social interactions, and physical activities are key factors associated with the mental well-being of pain patients , 51–53. Regarding the other personality dimensions, our study revealed that spouse openness to experience, agreeableness, and conscientiousness did not moderate the pain-health relationship in the pain patient. Research has previously shown that the contribution of openness and agreeableness to well-being is small when compared with that of neuroticism, extraversion, and conscientiousness , 55, 56.In our study, spouse neuroticism moderated pain-to-physical health associations, while the moderation of extraversion occurred for mental health. Extraversion is frequently associated with better physical and mental health in the general population . HoweverThe study of spouse personality, the inclusion of important covariates of patient health , and the analysis of moderation are some of the strengths of the present investigation. Previous research had explored the association between spouse behaviors  and several outcomes in the patient, including pain intensity reports and physical and mental health status , 61, 62.The present study is not without limitations. Although some mechanisms explaining the moderation effects were proposed, they should be considered as hypotheses and need further investigation. Also, the effect sizes of the moderator were low. Although this is frequent in moderation studies, the power of the associations should not be overestimated. Additionally, some factors that might be important for the mental well-being of couples, such as length and quality of marriage, were not assessed in this investigation. In fact, while being married was a key eligibility factor in the study, the quality of the relationship, even without marriage, might be an interesting factor to be considered in the present study, as well as in future, similar investigations. Finally, there are methodological limitations in this study too. For example, the design used prevents us from drawing any causal relationship from our findings and do not allow us to determine the direction of the associations. Also, the exclusion of unmarried couples inevitably affects the generalizability of findings.While acknowledging the aforementioned shortcomings, our study might be important for applied settings: first, because patient and spouse characteristics in this study  were comparable to those of previous investigations, thus supporting the generalizability of the results; also, because the results revealed that the relationship between a chronic stressor  and health status may be complex. Specifically, our results suggest that this relationship may be influenced by contextual variables , as suggested in previous research , 64. The


DETECT (PainDETECT-Dlv) in a large population of patients with chronic pain.Neuropathic pain is defined as pain caused by a lesion or disease of the somatosensory nervous system and is a major therapeutic challenge. Several screening tools have been developed to help physicians detect patients with neuropathic pain. These have typically been validated in populations pre-stratified for neuropathic pain, leading to a so called “Catch-22 situation:” “a problematic situation for which the only solution is denied by a circumstance inherent in the problem or by a rule”. The validity of screening tools needs to be proven in patients with pain who were not pre-stratified on basis of the target outcome: neuropathic pain or non-neuropathic pain. This study aims to assess the validity of the Dutch PainDETECT-Dlv validity. Included where patients with low back pain radiating into the leg(s), patients with neck-shoulder-arm pain and patients with pain due to a suspected peripheral nerve damage. Patients’ pain was classified as having a neuropathic pain component (yes/no) by two experienced physicians (“gold standard”). Physician opinion based on the Grading System was a secondary comparison.A cross-sectional multicentre design was used to assess Painn = 228). Compared to the physician’s classification, PainDETECT-Dlv had a sensitivity of 80% and specificity of 55%, versus the Grading System it achieved 74 and 46%.In total, 291 patients were included. Primary analysis was done on patients where both physicians agreed upon the pain classification  research. Catch-22 situations in the validation of screening tools can be prevented by not pre-stratifying the patients on basis of the target outcome before inclusion in a validation study for screening instruments.Despite its internal consistency and test-retest reliability the PainNTR 3030.The protocol was registered prospectively in the Dutch National Trial Register: The online version of this article (10.1186/s12883-018-1094-4) contains supplementary material, which is available to authorized users. The International Association for the Study of Pain defines neuropathic pain as “pain caused by a lesion or disease of the somatosensory nervous system” and states that “neuropathic pain is not a medical diagnosis but a clinical description which requires a demonstrable lesion or a disease that satisfies established neurological diagnostic criteria” . In the An easy to use and validated screening tool for clinical triage and epidemiological purposes could aid uniform classification and quantification of NePC and hence lead to better therapy, particularly when used by non-specialists –8, 11–15DETECT is such a patient friendly screening tool for the screening for neuropathic pain. It was originally developed and validated in Germany [DETECT this instrument has been used in many clinical and epidemiological studies [DETECT outcome, NePC was present [The Pain Germany  based on Germany . Subsequ Germany , Turkey  Germany , Japan [ Germany , India ( Germany  and Kore Germany . Since t studies . In a Da present  in aboutDETECT as a screening tool was performed in pre-stratified groups of patients based on the target outcome (pain of predominantly neuropathic origin or of predominantly nociceptive origin and limitation to pain scores). The inclusion of only patients with a known pain classification on forehand might lead to a prerequisite for the determination of validity of the PainDETECT. For this situation, the term “Catch-22” is used in the English language for“ a problematic situation for which the only solution is denied by a circumstance inherent in the problem or by a rule” [In the above-mentioned validation studies , 16–20,  a rule” . It was DETECT as a screening tool for use in daily outpatient practices for detecting a NePC. The current validation study is being conducted in a general patient population having common chronic pain syndromes, not pre-stratified on the target outcome: low back with leg pain (LBLP), neck-shoulder-arm pain (NSA pain) or a suspected peripheral nerve damage pain (suspected PND pain).The objective of this study is to further validate the PainDETECT. This study, to detect a NePC in patients suffering from chronic pain, was approved by the medical and ethical review board Committee on Research Involving Human Subjects region Arnhem-Nijmegen, Nijmegen, the Netherlands, Dossier number: 2008/348; NL 25343.091.08 and conducted in accordance with the declaration of Helsinki and the declaration of the World Medical Association. As required, written informed consent was obtained from patients prior to study participation. The protocol is registered in the Dutch National Trial Register: NTR 3030. The PainDETECT was translated and cross-culturally adapted into the Dutch language (PainDETECT-Dlv)  in a separate study [The study was conducted in a cross-sectional, observational, research design with two weeks and three months follow up to study the clinimetric quality  of the Painte study  before tte study  .: Patients diagnosed with an active malignant disorder, compression fractures, patients with diffuse pains , severe mental illness, chronic alcoholism or substance abuse, inability to fill in the questionnaire adequately or incapable of understanding the Dutch language.The patients were recruited from October 2009 until July 2013. Multicenter recruitment took place in the Netherlands in three academic centers specialized in pain medicine, three non-academic centers specialized in pain medicine and one non-academic department of neurology. The question to participate in the study was asked by the patients’ own physician. At that moment they only had a provisional diagnosis: LBLP, NSA pain or pain due to a suspected PND . These three groups of patients include a majority of the patients referred towards an academic or peripheral pain clinic from the general practitioner. Patients had to be diagnosed for the initial cause of the pain as classified according to the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10)-2015-WHO Version 2015 . ImportaDETECT-Dlv. The assessment of the Grading System was implemented in the standardized assessment protocol and thus included in the diagnostic work-up of the patients [Patients were examined for the presence of NePC by two physicians which was considered to be the “gold standard” in this study. The physicians  worked independently from each other and were blinded to the classification made by the other physician. The physicians were not selected on basis of age, years of experience as a physician or other criteria. A full medical history was taken followed by a thorough clinical examination. A bedside examination  to assess patients’ pain  was basepatients . The outpatients –34. All patients . TraininDETECT-Dlv  [DETECT. For the original German version [The Painerlands)  was desiDETECT-Dlv directly after the clinical assessment by the participating physicians but without any interference by the physicians. The researcher (HT) was available for help via telephone or in person when it was not clear how to fill in the questionnaires. Besides screening for NePC via the PainDETECT-Dlv [DETECT-Dlv) were sent to the patient by mail.The patient completed five questionnaires .DETECT were assessed in the original validation study as respectively 85 and 80% [DETECT-Dlv was, on forehand, expected to be 80% with a prevalence of 37%. The lower 95% confidence limit was required to be > 0.55. According to the calculations following the formulas by Flahault et al. [Power calculation for this study was based on a expected NePC prevalence of 37% in an unselected cohort of patients with chronic low back pain . Sensiti and 80% . The sent et al.  132 patit et al. .Qualitative variables were presented as frequencies and percentages. The quantitative variables were presented as mean and standard deviation (SD) or as median and inter quartile range (IQR). Based on the classifications of the two physicians, all patients were categorized as absent-NePC, NePC or ‘undetermined’ .One-way ANOVA  or Kruskal-Wallis test were used to study differences between the three groups .DETECT-Dlv between the fixed time points (baseline versus two weeks & baseline versus three months). The ICC and responsiveness of the PainDETECT-Dlv were assessed between each point of measurement.Intraclass correlation (ICC) was used to assess reproducibility (‘test-retest reliability’) of the PainDETECT-Dlv to discriminate patients classified as with or without a NePC. The classification was based on the physicians’ assessment outcome or based on the Grading System outcome, respectively. The theoretical maximum of the AUC is 100%, indicating a perfect discrimination and 50% is equal to tossing a coin. The optimal cut-off point of the PainDETECT-Dlv – sum score was calculated under the condition of equal-costs of misclassification, using the Youden-index. Sensitivity, specificity, positive and negative predictive values and the likelihood ratio in the population in this study was calculated at this cut-off point. Also, the ‘number needed to diagnose (NND)’ was assessed [A receiver operating characteristic (ROC) curve was calculated and the area under the curve (AUC) with 95% confidence interval is presented to indicate the discriminatory power of the Painassessed  by use oassessed .DETECT-Dlv  outcome was evaluated by using Cohen’s kappa (K), prevalence index (Pi) and percentage of pair wise agreement (PA) [Κ ≥ 0.40 and a PA ≥ 70% is considered indicative of interobserver reliability which is acceptable for use in clinical practice [The agreement between the pain classification by the physicians, the NeuPSIG Grading Systems and the Painent (PA) . A Κ ≥ 0practice .p-value below 0.05 was considered statistically significant.Data analysis and statistics were performed by use of Statistical Package for the Social Sciences . Two-tailed n = 37) was due to not fulfilling the in- and exclusion criteria (n = 13); not returning the baseline questionnaires by the patient (n = 16); missing pain classification by one physician (n = 5) or both physicians (n = 3). In eight patients the assessment of the grading system (secondary comparison) was missing by one or both physicians. Finally, 291 patients participated in the study between October 2009 and July 2013. According to the international classification of diseases  [In this study 330 patients, not pre-stratified on the target outcome, with chronic LBLP, NSA pain or suspected PND pain were assessed for eligibility. Two patients did not give their informed consent. Exclusion (on 2015)  these pan = 86; ErasmusMC, Rotterdam n = 62; Radboudumc, Nijmegen n = 59; Bernhoven Ziekenhuis, Oss n = 56; Rijnstate Ziekenhuis, Arnhem n = 15; St. Anna ziekenhuis, Geldrop n = 12 and UMC Utrecht, Utrecht n = 1. 132 patients had LBLP with radiation in one or two legs (45.4%), 51 NSA pain with radiation into one or both arms (17.5%) and 108 (37.1%) had suspected PND pain. The group of patients with suspected PND consisted of 86 patients with pain who were treated because of breast cancer . The remaining 22 patients had pain because of various reasons: peripheral nerve damage (n = 12), polyneuropathy (n = 3), central post stroke pain (n = 2), Complex Regional Pain Syndrom (n = 2) and spinal radicular pain (n = 3). After assessment by physicians A and physicians B, 170 patients were classified as having present-NePC, 58 as absent-NePC. In 63 patients the two physicians made a non-concordant pain classification, so the outcome based on the physicians assessment was classified as ‘undetermined’. Based on the NeuPSIG Grading System in 139 patients NePC was classified as present, in 93 patients NePC was absent and in 51 patients the two physicians made a non-concordant pain classification in which the outcome was classified as ‘undetermined’  were as follows: Reinier de Graaf Gasthuis, Delft Social-demographic and clinical details of the 291 patients were analyzed and divided from each other based on the pain classification , from seven different hospitals, assessed all included patients. All patients were assessed two times by two different physicians. Of all participating physicians, 21 physicians assessed ≤2 patients during the execution of the study, 23 physicians saw ≤9 patients, 10 physicians saw ≥10 patients and 8 physicians saw ≥20 patients.DETECT-Dlv  for patients classified as absent-NePC was 10.7 (SD ± 5.7); for patients classified as present-NePC it was 15.7 (SD ± 6.3) and for patients with an undetermined outcome it was 11.8 (SD ± 5). As calculated based on a one-way ANOVA with Tukey’s studentized range post-hoc test, there was a statistical significant difference between absent-NePC and present-NePC (P < 0.001) and between present-NePC and undetermined (P < 0.001). No significant difference was seen between absent-NePC and undetermined (P = 0.57). Patients pain course pattern and if the pain was radiating to other regions of the body were not significantly different between the three groups. Pain descriptors  were all statistically significant discriminators for the presence of NePC (P ≤ 0.005) except for pressure evoked pain (P = 0.07). See Table DETECT-Dlv outcomes divided according to the pain classification by the physicians  (See Table The mean score of the Painn = 228): 58 patients were classified as absent-NePC (25.4%) and 170 were classified as present-NePC (74.6%) 80%, specificity 55.2%, positive predictive value 84% and the positive likelihood ratio was 1.78. Based on the neuropathic pain Grading System, the sensitivity was 74.1%, specificity 46.2%, positive predictive value 67.3%, and positive likelihood ratio of 1.38.The gold standard for presence of the NePC in this study was the concordant opinion of both physicians. On basis of this gold standard, patients with an identical pain classification were included in the initial analysis n = 28: 58 paDETECT-Dlv: AUC, cut-off value, sensitivity, specificity positive and negative predictive values, positive likelihood ratios and the number needed to diagnose (NND).We also constructed ROC-curves for the classification by solely physicians A or B and according to the neuropathic pain Grading System by physicians A or B and all the combinations. Except for classification of patients’ pain based on the description of physicians A and the outcome of the Grading System by physicians B all cut-off scores were calculated at 11-points out of 38: The sensitivity ranges from 57.6–86.1% and specificity from 43.9–59.2%. The classification of patients’ pain based on the classification of physicians A resulted in a cut-off score of 9-points: Sensitivity 86.1% and specificity 45.8%. The classification of patients’ pain based on the Grading System according to physicians B resulted in a cut-off score of 14-points: Sensitivity of 57.6% and specificity of 59.2%. In Table DETECT-Dlv. All the possible outcome combinations were computed based on the outcome: Is a NePC present, or not? In 283 patients all the five outcome variables were available and are displayed in a Venn-diagram [Patients were screened on a NePC (positive outcome) by two physicians, two times the Grading System, and the patient completed the Pain-diagram   NePC, Cohen’s kappa (K) and percentage of pair wise agreement (PA) were assessed (see Table K for the classification of patients’ pain (absent-NePC or NePC) by the physicians was 0.49, with a PA of 78.4% . The K for the classification of patients’ pain based on the Grading System was 0.63 and PA was 82% . The outcome of K and PA regarding the PainDETECT-Dlv compared to the classification of physicians A was respectively 0.34 and 74.6% . Compared to physicians B it was 0.27 and 67.7% . Comparing the outcome of the PainDETECT-Dlv to the outcome of the Grading System, was 0.18 and 61.5% for physicians A, and 0.17 and 58.3% for physicians B.To determine the interobserver reliability between the physicians, the Grading System and the outcome of the Pain-Dlv over time was assessed over a period of two weeks. The mean sum score of the PainDETECT-Dlv at baseline for the total group was 13.8 ± 6.3. The mean sum score after two weeks was 14.1 ± 6.1. Test-retest reliability via ICC was 0.83 . Taking into consideration the fact that patients’ pain should not have changed (outcome based on the PGIC), because otherwise the ICC would not reflect the consistency of the PainDETECT-Dlv, and a time gap of 7–21 days was allowed (to rule out the early or delayed return of questionnaires) between the first and second PainDETECT-Dlv, the ICC was 0.87 . After three months, with no change in the degree of patients’ pain and a time gap of 60–120 days between the first and third PainDETECT-Dlv, ICC was 0.86 .Stability and responsiveness of the PainDETECTDETECT-Dlv, a screening instrument for the presence of a NePC, on a large population of patients, with chronic pain due to low back with leg pain, neck-shoulder-arm pain or pain due to a suspected peripheral nerve damage as normally present in a physician’s daily practice. Because the patients were included without pre-stratification on the target outcome, previous Catch-22 situations in the assessment of the validity of screening instruments were avoided. Under these conditions, the PainDETECT-Dlv failed to be predictive for the existence of a NePC due to a moderate sensitivity and low specificity, irrespective of comparison with the expert opinion via the classification by two physicians (gold standard) as well as with the outcome of the NeuPSIG Grading System. Moreover, the predictive values were also not indicating that the PainDETECT-Dlv is a valid screening tool for the assessment of a NePC. The likelihood ratios were also not suggestive for the usefulness of this instrument.This study demonstrates the clinimetric quality of the PainDETECT-Dlv of ≥11 points corresponding to a sensitivity of 80% and a specificity of 55%. In the original development and validation study of the PainDETECT by Freynhagen et al. [no ‘unclear’ outcome) and only patients with a VAS of > 40 mm (0 - 100 mm) were included. In the Spanish validation study by De Andrés et al. [DETECT [DETECT [DETECT [We found an optimal cut-off score for the Painn et al.  a sensits et al.  only pat [DETECT  was vali [DETECT  in patie [DETECT  patients [DETECT  was valiIn a cohort of patients with a spinal cord injury for more than one year, pain lasting more than six months and a pain intensity of than more three on a NRS (0–10) a sensitivity was found of 68% and specificity of 83% .The present study included patients with chronic pain without limits to the minimal pain intensity or other limitations. At the moment of inclusion in the study our patients had only a provisional diagnosis  established in primary or secondary care without further refinement or confirmation. Then, after referral to a (non-) academic pain clinic, they were assessed as to their complaints for the first time at study inclusion. Thus this was a ‘real-life’ clinical out-patient population. Avoiding patient selection due to pre-stratification to the outcome target makes our study unique and clinically more relevant as compared to other studies on the same topic and is crucial for the validation of a screening instrument.n = 158) a cut-off score of 17 was found with a sensitivity of 79% and specificity of 53% (Gold standard: the classification by one experienced physician). This study, like ours, did not pre-stratify patients according to the pain classification either, and patients were not excluded because of a low pain level. The outcome of Gauffin’s sensitivity analyses in this fibromyalgia study was comparable to our study. Tampin et al. [DETECT of respectively 64 and 62% (cut-off score 18.5) in a population of patients with neck/upper limb pain (n = 122). In our study, the outcome for patients with neck-shoulder-arm pain was 83 and 44% respectively (cut-off score of ≥9).In a study by Gauffin et al.  in patien et al.  found, bDETECT-Dlv resulted to be 74 and 46% respectively . Using the classification of patients’ pain based solely on the Grading System by one physician results in a lower validity than based on the physicians assessment. This might suggest that the classification of patients’ pain based on the Grading System is less accurate than the classification based on the physicians’ assessment in respect to the outcome of the PainDETECT-Dlv. However, the grading system was assessed by the same physician who also performed the physician’s assessment so it is also possible that the physician had difficulties to classify patients pain based on the Grading System or vice versa. When using the physicians’ assessments as well as the Grading Systems of both physicians (n = 161), sensitivity was 78%, specificity was 53% and the cut-off score was 11: The same poor result as for the gold standard. In the papers by Vaegter et al. [DETECT was also compared with the NeuPSIG Grading System. In both papers, like in ours, the outcome of the Grading System was not comparable to the outcome of the PainDETECT. As stated by Finnerup et al. [DETECT (and other screening tools for the assessment of neuropathic pain) is only to alert the physician to further assess the patient who may have a NePC.In this study the physicians assessed patients for the presence of a NePC according to the Grading System . Probablr et al.  and Tampr et al.  the Painp et al.  the Pain“a consistent clinical entity, but it is multidimensional in terms of its clinical expression, with different sensory profiles, potentially reflecting specific pathophysiological mechanisms” [The initial classification of patients’ pain in our study was based on an interview and  examination by trained (pain-) physicians. There is a lack of consensus with respect to the classification of a NePC in patients with pain of different origins . Moreovehanisms” . As stathanisms”  physicalhanisms” . Howeverhanisms” .DETECT-Dlv (compared to the gold standard and the NeuPSIG Grading System) as used in our study seems not valid for the assessment of patients with neuropathic pain based on a suspected PND in which the majority of patients was suffering of pain after treatment for breast cancer.In this study we used a mandatory standardized assessment  in additThere are several strengths in this study. Firstly, we included a large population of patients with diagnoses who are regularly seen in daily clinical practice. Secondly, there was no pre-stratification on the target outcome, clear inclusion criteria and almost no exclusion criteria. Thirdly, we used the NeuPSIG Grading System , 52 as aDETECT-Dlv has a good internal consistency and test-retest reliability but is not an effective screening tool for the assessment of a neuropathic pain component in a population of patients with chronic pain, irrespective of the chosen comparison because of its moderate sensitivity and low specificity. However, the agreement by both the physicians and the agreement with the grading systems (performed by the physicians) were also not impressive. Moreover, the differences in the cut-off scores for the different comparisons reflects the fact that agreement in a not pre-stratified to the target outcome patient population is not easy to accomplish. Using the PainDETECT-Dlv  may result in unreliably separating NePC presence from non-presence in patients with chronic pain in clinical outpatient practices and in research settings. Catch-22 situations in the validation of screening tools can be prevented by not pre-stratifying the patients on basis of the target outcome before inclusion in a validation study for screening instruments. For now, classifying patients pain still needs the clinical assessment based on history and physical examination including bed-side sensory testing by the physician and cannot be replaced by the use of the PainDETECT.The PainAdditional file 1:Table S1. The AUC and the sensitivity / specificity at the optimal cut-off point of the PainDETECT under the condition of equal costs of misclassification to classify a NePC by the diagnosis and the grading system of the physicians for the total group and according the pain locations. (PDF 423 kb)