Osteoarthritis (OA) is one of the most common causes of musculoskeletal system’s ailments. In the prevention of the disease and in its comprehensive treatment, proper health-related behavior becomes an extremely important factor for maintaining an optimal health condition. The aim of the study is to assess the relationship between the reported pain and the disability level, and the health-related behaviors undertaken by OA patients as well as their acceptance of the disease.The study group consisted of 198 patients with diagnosed OA, according to ACR criteria (1988). The method used in the study employed a Pain VAS (0-10), Health Assessment Questionnaire Disability Index (HAQ DI 0-3), Acceptance of Illness Scale (AIS 8-40) and Health and Behavior Inventory (IZZ 24-120).rs = 0.319, p < 0.001) and at rest  correlated positively with physical disability (HAQ DI). Studies indicated a positive linear correlation between the age and physical disability . Acceptance of the disease (AIS) depends mostly on age , on pain in motion  and at rest  and on the disability levels . Analysis of the health-related behaviors (IZZ) indicates that the average severity of declared behavior is statistically significant with physical disability (HAQ DI) (p = 0.029).The average age among respondents with OA has been 59.16 years of age (±15.87), duration of disease 5.5 years (±4.32). Pain experienced both during movement (The acceptance of illness is significantly reduced with age and progressive levels of disability as well as with the severity of pain. The progressive levels of disability and the younger age of the respondents motivate them to engage in health beneficial behavior. The disease affects ligaments, joint capsules, synovium, bursae, tendons, muscles, and it is often accompanied by the secondary damage to the nerves and veins .The researchers hypothesized that patients who engage in pro-health behaviors are able to better cope with pain and progressive physical disability. The health beneficial behaviors should improve the acceptance of the disease, which usually decreases with age and duration of osteoarthritis. An important task for health professionals is to motivate the patient to engage in behaviors that are health beneficial. The authors have attempted to identify the factors affecting the acceptance of disease and positive lifestyle, so that educational activities and support for OA patients could be planned deliberately and accurately.This cross-sectional correlational study included 198 patients diagnosed with osteoarthritis of the knee, osteoarthritis of the hip and degenerative disease of the spine, within the program of inpatient and outpatient care. The study was conducted at the Department of Rheumatology and Internal Diseases, Medical University of Bialystok, Poland, during patients’ hospitalization, and at Rheumatology Outpatient Clinic in Augustow, during inspection visits to rheumatologists, from April to November 2011. The patients were informed about the study and instructed how to fill in the questionnaires independently and confidentially.The inclusion criteria were: age ≥40 years, diagnosis of OA according to ACR criteria (1988) and informed consent to participate in the study. The criterion for exclusion from the study was the existence of other, overlapping diseases of bones and joints, including inflammatory joint diseases. Patients who met the criteria were qualified for the study according to the order of their admission to the Department of Rheumatology or visit in Rheumatology Outpatient Clinic.Good Clinical Practice guidelines and it is in accordance with the 1975 Helsinki Declaration revised in 2000  and with the ethical standards of the Institutional Committee on Human Experimentation .The study follows the The method used was a diagnostic survey using measurement tools employed in the promotion of health and health psychology that are accessible to health professionals, such as: the Acceptance of Illness Scale (AIS 8-40) by The Acceptance of Illness Scale (AIS) has been used for studying patients. It contains eight statements that describe the negative consequences of ill health, taking into account the limitations imposed by the disease, lack of self-sufficiency, the sense of dependence on others and low self-esteem. The scale is used to measure the degree of disease acceptance . To evalThe Health Behavior Inventory (IZZ) is designed for studying healthy and ill adults. It comprises 24 statements that describe the intensity of health-related behaviors. The scale allows for the evaluation of the intensity of health-related behaviors in four areas (1-5): proper eating habits  preventive behavior , positive mental attitude (avoiding strong emotions and stress) and healthy practices . IZZ is helpful in planning measures of prevention, behavior modification determining the direction and monitoring of changes in health practices . For theThe severity of pain (Pain VAS 0-10) has been interpreted in three ranges: 0–3.5—a slight degree of pain (low); 3.6–6.5—an average pain (medium); 6.6–10—a strong degree of felt pain (strong) .The HAQ-DI evaluates the ability to perform daily activities during the last week. The questionnaire consists of 20 basic questions divided into eight sections, in which the patient has a choice of four possible answers: without difficulty, with certain difficulty, with difficulty, unable to perform, regarding the activities of everyday life functioning . The questionnaire also includes additional questions regarding the assistive devices used to facilitate the functioning and the activities that require help of other people. The total score ranges from 0–3: 0–1—little degree dysfunctions in any field of daily life; >1–2—serious limitations or need for help in daily activities; >2–3—total inability to do daily activities without help .rp) and Spearman (rs) correlation coefficient is reported together with p-values, with r of 0.10, 0.20 and 0.50 representing small, medium and large effects, respectively. The effects of sex, age and disease duration were tested across all measures. Students’ t-test was used to assess gender differences and One-Way ANOVA for differences across age groups and disease duration. The level of significance α = 0.05.All data were analyzed using PQStat v.1.4.2 software. We tested the null hypothesis of no correlation between health behavior, acceptance of disease and patient pain problem and disability. Pearson (n = 110) of patients diagnosed with OA was women (55.6%). The mean age was 59.16 (±15.87). The average time of disease duration was 5.5 (±4.32) years. More than half of respondents (56%) had OA longer than 10 years. As shown in n = 100, 50.5%) declared primary education/vocational training and lived in the city . The vast majority  of subjects were retired and married .Generally, as presented in n = 117, 59%) were taking analgesics during the periods of the disease’s worsening. The level of physical activity was not satisfactory. More than half of respondents  declared that they did not practice any sport. A large percentage of respondents  did not use any form of rehabilitation.The majority of respondents  declared a strong degree of experienced pain, 29.8% of patients (n = 59) declared pain while resting.The mean of pain during movement in the studied group of OA patients, as presented in p < 0.001). Patients who declared average level of pain during movement—Pain VAS 6.10 (±1.91), more frequently admitted regular taking analgesics. As shown in p < 0.001). With the increase of pain at rest the frequency of intake of analgesics has been intensified.The statistical analysis showed a statistically significant relationship between the perception of pain during movement and taking analgesics. Patients who did not take analgesics rated their pain lower significantly more often—Pain VAS 3.94 (±1.81)  suggest that the level of pain experienced both during movement and at rest was slightly reduced through performing physical exercises at home, although it was not statistically significant data in .In order to analyze the degree of patients’ physical disability, the HAQ DI questionnaire was used. In the study group, as it is indicated in p = 0.012) , while in men 0.92 (±0.64). The statistical analysis showed that there is a statistically significant relationship between the level of inability in performing daily activities and sex ( data in .p = 0.028). The study has shown that more than half of the patients (62.4%) aged ≥77 years, declared major restrictions or the need for help in daily living activities (HAQ DI>1-2). The study indicated a positive linear correlation, showed in rs = 0.200, p = 0.005).The average level of disability in the age group ≥77 years was 1.22 (±0.72)  (p = 0.012).The evaluation of skills in everyday life, as presented in p < 0.001), as presented in rs = 0.319, p < 0.001) between the Pain VAS and HAQ DI. The average value for the level of disability among patients who declared a strong level of pain at rest was 1.47 (±0.63). It has been observed that along with mobility improvement, the level of pain decreased   (< 0.001) .The average value level of the acceptance of disease in the study group, as presented in rs =  − 0.325, p < 0.001).With age the level of acceptance of the disease significantly worsened. The results of statistical analysis showed that there was a statistically significant correlation between the level of acceptance of the disease and the age (p < 0.001).In the statistical analysis of the variable of disease duration and the level of acceptance of the disease, it was observed, as shown in p = 0.023)  and those who take analgesics systematically pointed to the average level of the disease acceptance—AIS 24.35 (±9.10)  between the level of the disease acceptance and the degree of pain during movement. Along with the seriousness of pain the capacity to accept the disease decreased. A relation between the level of acceptance of disease and the degree of pain at rest  has been also demonstrated.As shown in rp =  − 0.353, p < 0.001). This proves that the higher the acceptance of OA, the lower the level of physical disability.The results also indicate a negative linear correlation between the acceptance of illness and the level of disability (HAQ DI) (p < 0.001)  was 28.75 (±8.53), and among patients reporting a total inability in performing activities of daily living (HAQ>2-3)—21.06 (±6.02)  .p < 0.001). The detailed analysis showed that 61.8% of women and 42% of men reported a high occurrence of health-related behaviors.As shown in p = 0.033) . The analysis showed a statistically significant relationship between the declared health behavior and the age of the patients (= 0.033) .p < 0.001) , while those who did not practice any sport pointed to medium/average occurrence of pro-health behaviors—IZZ 82.67 (±15.91) ( data in .p = 0.029). The study showed no statistical significant linear correlation between health-related behaviors and the studied variables.In seeking the significant relationship between health behaviors (IZZ), and the level of disability (HAQ DI), presented in Separate calculation of the four categories of health behaviors (1-5), indicates that the average value for healthy eating habits was to 3.70 (±0.55), preventive behaviors—4.13 (±0.60), positive mental attitude—3.87 (±0.60), and health practices—3.76 (±0.60). The study has shown that the patients received the highest score in the category of preventive behaviors, regarding treatment compliance and obtaining information about health and disease, and the lowest in the category of proper eating habits (type of food they eat).In the analysis of the relationship between the level of acceptance of the disease (AIS) and undertaking health-related behaviors (IZZ), there was no statistically significant dependence between two analyzed variables.Osteoarthritis is the most common rheumatic disease that leads to progressive disability, and it influences all spheres of the patient’s life: the physical, psychological, social and occupational .The progressive nature of osteoarthritis undoubtedly affects the level of disease acceptance and development of individual pro-health behaviors. It should be remembered that health beneficial activities promote better health, well-being and might affect further development of the disease and disability . An esseGenerally, in our study, it was observed that the acceptance of osteoarthritis was affected mainly by such factors as age, pain, disability, and disease duration. Taking pro-health behaviors depended greatly on the level of disability, age and sex. One of the manifestations of pro-health behaviors was performing physical exercises from two to three times a week. Considering the analysis of the main health problems, the study has shown a positive correlation between the perception of pain and the level of physical disability. The intensification of both variables impacted the intake of analgesics. The evaluation of the level of disability depended also on age and sex.The dominant problem, from the patient’s point of view, is pain experienced during performing physical activities and, to a lesser extent, during resting. The pain of the disease contributes to the feeling of anxiety, irritability, exhaustion, which in turn causes disturbances in the everyday life functioning .Study result indicate a negative linear correlation between the level of disease acceptance, the, pain felt during movement and at rest and the level of disability. Severe pain and progressive difficulty in daily functioning significantly influence the level of acceptance of the disease.In terms of disability in OA patients In the reviewed literature, there is a significant correlation between the level of pain and disability in OA patients. Pain created various limitations to varying degrees, not only in the performance of professional duties, but also in daily activities and in the pursuing of personal interests . Reis etTaking the age factor into account it can be noticed that the younger group had a higher degree of disease acceptance than the group of elderly people. It has been also observed that along with the disease duration the acceptance of health situation deteriorated and the patients presented worse adaptation and a greater sense of psychological discomfort. The study of In our study, patients who experienced pain of a fairly large severity and who have difficulty in performing daily life activities more often take analgesics and non-steroidal non-inflammatory drugs. According to the recommendations for the therapeutic approach to OA on the basis of the American College of Rheumatology (ACR), European League Against Rheumatism (EULAR) and Osteoarthritis Research Society International (OARSI) recommendations, in case of treatment ineffectiveness, the recommended pharmacotherapy of pain is based on non-steroidal anti-inflammatory drugs such as paracetamol, at the lowest effective dose and for as short period of time as possible. The optimal therapeutic management of OA requires the combined use of non-pharmacological and pharmacological treatment. It should be noted that the literature review reveals that patients with osteoarthritis tend to overuse the aforementioned drugs . The patIn the prophylaxis and during treatment of the osteoarthritis it is also important to implement behaviors that are beneficial for health. Literature review shows that little physical activity and lack of motivation for regular exercising is a substantial problem in patients with OA., It is important to know what are the recommended types of physical exercises for the individual patient, how to effectively perform them, and how to combat the pain. It is advised that patients understand the benefits of physiotherapy, because many of them do not follow the physical treatment recommendations out of fear of exacerbating the pain . In our There has been observed a statistically significant relationship between the declared health behavior and the age of patients. Patients aged 61–76 years compared with older and younger patients, pointed to the higher occurrence of pro-health behaviors. However according to the study of Detailed analysis of the categories of health behavior showed that the study group obtained the lowest average score in healthy eating habits, and the higher score in prevention. Nevertheless, according to Juczyński, women during menopause declared the overall behavior somewhat lower, especially for health practices, and the highest score, as in our study, was in prophylactics. Scores for pro-health behavior of adult men were lower than in women . StandarIt is worth noting that the social situation of the elderly, i.e., the possibility of obtaining emotional support from the immediate environment, significantly affects the level of acceptance of the disease and disability. The task of the therapeutic team is not only administering effective treatment, but also providing support and advice on how to handle problems of everyday life, as well as stress and limitations caused by the disease .The study of patients with osteoarthritis has its limitations due to the applied research tool questionnaire that is based on the patients’ assessment of their own health; thus, independent verification of data is impossible. The correlational design prevents causal interference. Another limitation of the study stems from the fact that it was been conducted in a particular part of Poland (Podlasie voivodeship); therefore, the results do not refer to the entire population of Polish patients diagnosed with OA. 1.Although women declare slightly higher difficulties in everyday activities than men, they exhibit more positive health conducive behavior. 2.With age and progressive levels of disability as well as with the severity of pain, the acceptance of disease is significantly reduced. 3.The progressive levels of disability and the younger age of the patients motivate them to engage in health beneficial behaviors. The subjects present positive pro-health behavior and undertake regular physical exercises. 4.A high intensity of pain and a progressive disability impact patients’ decisions to follow treatment recommendations regarding analgesics.The study has shown the need for taking measures aimed at stimulating patients’ motivation to improve their physical ability and health education. In particular, elderly people should be more engaged in daily physical activity. The challenge for health professionals is to fight off pain caused by arthritis, primarily through the use of non-pharmacological methods of pain management, as well as with a greater access to the various forms of rehabilitation. In planning the health education, the attention should be paid also to the pro-health dietary advice.Further work is planned to develop and implement an education program to promote healthy, active lifestyles and rehabilitation for patients with osteoarthritis, especially for patients with long disease duration and the elderly, with the level of disability HAQ DI >1 and Pain VAS >5 cm. It will be also important to motivate men to participate in organized educational activities as well as in rehabilitation. Three and six months after the program ending, we plan to evaluate the effectiveness of pro-health behaviors undertaken independently by the patients and their impact on the evaluation of pain, disability and the disease acceptance while using standardized measurement tools.10.7717/peerj.3276/supp-1Data S1Click here for additional data file.


Previous studies have revealed that hepatitis B core antibody (anti-HBc) levels vary throughout the different phases of treatment-naïve chronic hepatitis B (CHB) patients and can be used as a predictor of treatment response in both interferon-α and nucleoside analogue therapies. However, few data have been published regarding the relationship between quantitative anti-HBc (qAnti-HBc) levels and liver fibrosis in patients with CHB.p < 0.05). Multiple logistic regression analysis showed that the parameters for predicting significant fibrosis (S ≥ 2) included age, PLT and qAnti-HBc. In HBeAg (+) subjects, the AUROC of qAnti-HBc for predicting significant fibrosis was 0.734 (95% CI 0.689 to 0.778) and the optimal cut-off was 4.58 log10IU/mL, with a sensitivity of 63.08% and a specificity of 74.83%. In HBeAg (−) subjects, the AUROC was 0.707 (95% CI 0.612 to 0.801) and the optimal cut-off value was 4.37 log10IU/mL, with a sensitivity of 75.53% and a specificity of 56.10%.A total of 489 HBeAg-positive (HBeAg (+)) and 135 HBeAg-negative (HBeAg (−)) patients were recruited. In both HBeAg (+) and HBeAg (−) groups, the S0−1/S0 subjects had significantly lower qAnti-HBc levels than the S2−4 subjects  serological markers, HBV DNA, hepatitis B surface antigen (HBsAg) titers and HBV genotype were determined using commercial assays, and serum qAnti-HBc levels were measured using double-sandwich immunoassay. Liver biopsies and serum samples were obtained on the same day.The present study showed an association between high serum qAnti-HBc levels and significant fibrosis (S ≥ 2) in treatment-naïve CHB patients. Furthermore, we described a serum qAnti-HBc cut-off for predicting significant fibrosis in CHB patients infected with HBV genotype B or C. Worldwide, chronic hepatitis B virus (HBV) infection is a significant public health problem. The spectrum of disease and natural history of chronic HBV infection are highly variable, ranging from an inactive carrier status to progressive chronic hepatitis, which may lead to cirrhosis, liver failure and hepatocellular carcinoma (HCC) , 2. EachLiver biopsy is generally considered the reference standard for identifying liver fibrosis, as it allow for direct measurements. However, this procedure is invasive and associated with the risk of serious complications , 7. TherRecently, an inverse correlation has been described between levels of the hepatitis B surface antigen (HBsAg) and the liver fibrosis stage in HBeAg-positive patients , 16. As p < 0.001). Mean platelet (PLT) levels were significantly higher in HBeAg (+) patients. No significant differences were found for gender, ALT level, AST level, or HBV genotype between the two cohorts . The HBeAg (+) individuals exhibited significantly higher serum levels of both HBV DNA and HBsAg compared with HBeAg (−) patients. However, the HBeAg (+) group presented a significantly lower average qAnti-HBc level than the HBeAg (−) group. The distributions of the liver necroinflammation grades and fibrosis stages of the two cohorts are shown in Figure p < 0.001). The proportion of patients with insignificant necroinflammation (< G2) among the two patient groups was also significantly different .A total of 489 HBeAg-positive (HBeAg (+)) and 135 HBeAg-negative (HBeAg (−)) patients were included in the study. The baseline characteristics of the patients are presented in Table 10IU/mL), S2 (4.54 ± 0.73 log10IU/mL), S3 (4.70 ± 0.68 log10IU/mL) and S4 (4.63 ± 0.74 log10IU/mL). The mean qAnti-HBc level of the S0–1 subjects was significantly lower than that of the S2, S3 and S4 subjects (p < 0.05) , S2 (4.55 ± 0.53 log10IU/mL), S3 (4.76 ± 0.51 log10IU/mL), and S4 (4.83 ± 0.50 log10IU/ mL). The mean qAnti-HBc levels in the S1 subjects were also significantly lower than those in the S2, S3, and S4 subjects (p < 0.05)  CHB patients, the mean levels of qAnti-HBc for different stages of fibrosis were as follows: S0–1 (3.84 ± 1.14 log) Figure . Among t) Figure .When the presence or absence of significant fibrosis S ≥ 2) was considered as a binary dependent variable in patients, univariable analyses indicated that age, PLT, ALT, AST, TB, HBV DNA, HBsAg and qAnti-HBc levels were associated with significant fibrosis in HBeAg (+) patients, whereas multiple logistic regression analysis identified that age, PLT and qAnti-HBc levels were associated with significant fibrosis (Table  was consIn HBeAg (−) patients, univariable analyses indicated that only age, PLT, AST, HBV DNA and qAnti-HBc levels were associated with significant fibrosis. Subsequent multiple logistic regression analysis identified that PLT and qAnti-HBc levels were associated with significant fibrosis, which is similar to the results found for HBeAg (+) patients Table .In both the HBeAg (+) and HBeAg (−) groups, patients with significant fibrosis exhibited significantly lower PLT levels compared to patients with insignificant fibrosis. However, mean serum qAnti-HBc levels were significantly higher in patients with significant fibrosis. Patients with significant fibrosis were older than patients with insignificant fibrosis Figure .10IU/mL, with a sensitivity of 63.08% and a specificity of 74.83%. The AUROC of serum qAnti-HBc levels was similar to that of age  and PLT , but it was lower than the AUROC values for APRI  and FIB-4   patients, the AUROC was 0.734 (95% CI 0.689 to 0.778), and the optimal cut-off was 4.58 log5) Table .10IU/mL, with a sensitivity of 75.53% and a specificity of 56.10%. (Table In HBeAg (−) patients, the AUROC of serum qAnti-HBc levels for the prediction of significant fibrosis  was also similar to that of PLT , and it was lower than that of APRI  and FIB-4 . For predicting significant fibrosis, the optimal cut-off value of qAnti-HBc was 4.37 log%. Table .Liver fibrosis, which is the result of the normal wound healing process of necroinflammation frequently caused by chronic HBV infection, is essential to the pathogenic processes that lead to cirrhosis. In terms of establishing cirrhosis, the annual incidence of HBV-related HCC in CHB patients ranges from 2% to 5%. The 2012 European Association for the Study of the Liver (EASL) clinical practice guideline recommended that patients should be considered for treatment when they have at least moderate fibrosis (S ≥ 2) [Anti-HBc, as classical serological marker of HBV infection, is an indicator of both past and persistent HBV infection. The present study provided the first detailed investigation of the relationship between serum qAnti-HBc levels and liver fibrosis stages across a large cohort of treatment-naïve patients with CHB. All patients’ serum samples were taken on the day of their biopsies and therefore represent an accurate snapshot of the state of disease situation at that specific time. We observed a correlation between qAnti-HBc levels and liver fibrosis. The qAnti-HBc levels were positively correlated with stage of fibrosis in treatment-naïve CHB patients. Both HBeAg (+) and HBeAg (−) patients with moderate to severe fibrosis (S2–S4) showed significantly higher levels of qAnti-HBc compared with patients with no or mild fibrosis (S0-S1/S1). No significant differences were found in the qAnti-HBc titers among the S2-S4 subjects, excepted between S2 and S4 subjects in HBeAg (−) group.Most previous studies have investigated the predictors for liver fibrosis that can avoid liver biopsy in CHB patients, especially for patients with moderate to severe fibrosis, who required immediate antiviral therapy. In the present study, we examined routine parameters for predicting moderate to severe liver fibrosis. Our study showed that PLT and qAnti-HBc were independently associated with significant fibrosis in different chronic HBV groups, that is, HBeAg (+) and HBeAg (−) patients. And age was also independently associated with significant fibrosis in HBeAg (+) group. Age and PLT had been shown in previous studies to be associated with significant fibrosis in CHB –24. Age The present study demonstrated that serum qAnti-HBc levels can play an important role in identifying treatment-naïve CHB patients with significant fibrosis and may help reduce the need for liver biopsies. To our knowledge, our study was the first to formally use liver biopsy as an outcome measure to assess the role of qAnti-HBc titers in distinguishing significant fibrosis. The mechanistic explanation for why higher serum qAnti-HBc levels are associated with increasingly severe liver fibrosis in treatment-naïve CHB patients is unclear. qAnti-HBc levels in immune clearance and HBeAg negative hepatitis phases were significantly higher than those in the immune tolerance and low or no-replicative phases , 19. Mor10IU/mL) and HBeAg (−) (> 4.37 log10IU/mL) patients with significant fibrosis (S ≥ 2). The use of this prediction score of qAnti-HBc may potentially reduce the need for liver biopsies and help guide clinical decision making in the management of HBV genotype B or C associated CHB patients.In conclusion, our data suggest that treatment-naïve CHB patients with moderate to severe fibrosis (S ≥ 2) had a significant higher level of qAnti-HBc compared with patients with no or mild fibrosis (S < 2). And our analyses established an optimal cutoff value of qAnti-HBc for distinguishing HBeAg (+)  hepatitis A, C, or E or human immunodeficiency virus co-infection; (2) decompensated liver cirrhosis or HCC; (3) treatment with antiviral therapy or any liver functional protection therapy to alleviate the hepatic inflammation; (4) immunosuppressive treatment; and (5) causes of liver disease other than HBV.The study protocol was in compliance with the 1975 Declaration of Helsinki and was approved by the Medical Ethics Committee of The Fifth Hospital of Shijiazhuang. Written informed consent was obtained from all patients.The serum samples used for measurements were obtained on the day of the biopsy. The complete blood cell counts and biochemical tests were performed using automated techniques. The upper limit of normal alanine transaminase (ALT) was 40 U/L. Hepatitis B e antigen (HBeAg) and antibodies to HBeAg (anti-HBe) were measured using commercially available immunoassays . The serum HBV DNA levels were determined by real time fluorescence quantitative polymerase chain reaction (FQ-PCR) on an ABI 7500, with a lower detection limit of 500 IU/ml.Serum HBsAg levels were quantified using an Elecsys HBsAg II quant assay , with a diagnostic range from 0.05 to 130 IU/mL. Serial 1:10 dilutions were performed if the HBsAg levels were >130 IU/mL, according to the manufacturer's instructions. The serum qAnti-HBc level was measured using a newly developed double-sandwich immunoassay  that was calibrated using the WHO standard  .HBV genotypes were determined by analysis of the sequences obtained after amplification of the preS/S gene .Percutaneous liver biopsies were performed using a 16-gauge needle with a biopsy length of at least 1.5 cm and including six or more portal tracts. The samples were formalin-fixed, paraffin-embedded, and prepared by hematoxylin-eosin staining for morphological evaluation, Masson's trichrome staining, and reticulin staining for fibrosis assessment. Liver biopsy specimens were scored for fibrosis according to the Scheuer classification: no fibrosis (S0); portal fibrosis (S1); septum formation (S2); architectural distortion (S3); cirrhosis, probable or definite (S4) . “Insign2 or Fisher's exact test. Continuous variables are presented as the mean ± SD or the medians. Student's t test or the Mann-Whitney U-test was used for statistical comparisons where appropriate. Multinomial (binary) logistic regression was applied to evaluate factors predicting significant fibrosis based on histology. Receiver operating characteristic (ROC) curves and areas under the ROC curves (AUROC) were calculated to evaluate the diagnostic accuracy of qAnti-HBc for liver fibrosis activity. P values of < 0.05 were considered statistically significant. Statistical analyses were performed using SPSS ver. 19.0 software .Categorical variables are expressed as counts and percentages and were analyzed using the χ


There are few studies with an assessment of the levels of cytokines or neuropeptides as correlates of pain and pain relief in patients with painful joint diseases. Our objective was to assess whether improvements from baseline to 2-months in serum cytokine, chemokine and substance P levels were associated with clinically meaningful pain relief at 2-months post-injection in patients with painful total knee arthroplasty (TKA).Using data from randomized trial of 60 TKAs, we assessed the association of change in cytokine/chemokine/Substance P levels with primary study outcome, clinically important improvement in Western Ontario McMaster Osteoarthritis Index (WOMAC) pain subscale at 2-months post-injection using Student’s t-tests and Spearman’s correlation coefficient (non-parametric). Patients were categorized as pain responders (20-point reduction or more on 0-100 WOMAC pain) vs. pain non-responders. Sensitivity analysis used 0–10 daytime pain numeric rating scale (NRS) instead of WOMAC pain subscale.n = 23) on WOMAC pain scale at 2-months, pain responders (n = 12) had significantly greater increase in serum levels of IL-7, IL-10, IL-12, eotaxin, interferon gamma and TNF-α from baseline to 2-months post-injection . Change in several cytokine/chemokine and substance P levels from pre-injection to 2-month follow-up correlated significantly with change in WOMAC pain with correlation coefficients ranging −0.37 to −0.51: IL-2, IL-7, IL-8, IL-9, IL-16, IL-12p, GCSF, IFN gamma, IP-10, MCP, MIP1b, TNF-α and VEGF (n = 35). Sensitivity analysis showed that substance P decreased significantly more from baseline to 2-months in the pain responders  than in the pain non-responders  and that this change in serum substance P correlated significantly with change in daytime NRS pain, correlation coefficient was 0.53 . Findings should be interpreted with caution, since cytokine analyses were performed for a sub-group of the entire trial population.In a pilot study, compared to non-responders (Serum cytokine, chemokine and Substance P levels correlated with pain response in patients with painful TKA after an intra-articular injection in a randomized trial. Total knee arthroplasty (TKA) is one of the most successful procedures performed in patients with end-stage osteoarthritis (OA) and other arthritides with refractory pain . While mThe role that cytokines and neurotransmitters play in joint pain is of great interest and has been the focus of recent research . In an aWe examined the data from a randomized trial of patients with persistently painful TKA  to test We used the data from patients enrolled in a previously published 6-month, 2-arm, parallel group, blinded placebo-controlled randomized trial (NCT00403273), details provided elsewhere . BrieflyPrimary outcome assessment was at 2-months. A protocol modification to collect blood specimens to understand the mechanism of pain relief in patients with persistently painful TKA was made around the mid-point of patient recruitment upon receipt of federal funds, which provided resources to perform these assays, which were not available previously . The Inshttp://www.bio-rad.com/en-jp/sku/m500kcaf0y-bio-plex-pro-human-cytokine-27-plex-assay). 100 μl of Bio-Plex assay buffer was added to each well of a Multiscreen MABVN 1.2 μm microfiltration plate followed by the addition of 50 μl of the multiplex bead preparation. Following washing of the beads with the addition of 100 μl of wash buffer, 50 μl of the samples or the standards was added to each well and incubated with shaking for 30 min at room temperature. Standard curves were generated with a mixture of 27 cytokine standards and eight serial dilutions ranging from 0 to 32,000 picogram/ml. The plate was then washed three times followed by incubation of each well in 25 μl of pre-mixed detection antibodies for 30 min with shaking. The plate was further washed and 50 μl of streptavidin solution were added to each well and incubated for 10 min at room temperature with shaking. The beads were given a final washing and re-suspended in 125 μl of Bio-Plex assay buffer. Cytokine levels in the sera were quantitated by analyzing 100 μl of each well on a Bio-Plex using Bio-Plex Manager software version 4.0.Specimens were drawn both at baseline pre-injection and 2-month post-injection. We performed the serum cytokine assay using the BioRad human 27-plex cytokine panel , which was performed as per manufacturer’s instructions in a standard fashion. Samples, standards and controls were placed in a 96 well plate pre-coated with a polyclonal antibody. Primary antibody (for SP) solution and SP conjugated to horseradish peroxidase, were added to the wells and the plate was incubated overnight at 4° Celsius. After washing, substrate solution was added to the wells, incubated for 30 min, at room temp, in the dark and stop solution was added. The optical density of wells was determined using a micro plate reader set to 450 nm, with a reference wavelength of 570 nm.Serum neuropeptide assay included enzyme linked immunoassays for Substance P (SP), ; or 2-point reduction or more in index TKA daytime numeric rating scale (NRS) pain severity on 0–10 scale (higher = more pain) at 2-month post-injection , as previously published . PatientPatients in the randomized trial had a mean age of 67 years, 84% were male and 96% were Caucasian. The mean duration of TKA pain was 4.5 years  and 75% were primary TKAs.n = 23) on WOMAC pain scale at 2-months, pain responders (n = 12) had significantly greater increase in serum levels of IL-7, IL-10, IL-12 (p70), eotaxin, IFN- γ and TNF-α from baseline to 2-months post-injection  than in the pain non-responders  2-months post-injection.Compared to non-responders n = 3 on WOMAn = 35; Table p = 0.021; n = 19).Change in several cytokine and chemokine levels from pre-injection to 2-month follow-up correlated significantly with change in WOMAC pain with correlation coefficients ranging −0.37 to −0.51: IL-2, IL-7, IL-8, IL-9, IL-16, IL-12 (p70), GCSF, IFN- γ, IP-10, MCP, MIP1b, TNF-α and VEGF (p = 0.32) in the main analysis, but significant in sensitivity analysis (p = 0.023). This is a hypothesis-generating study and therefore, these findings need to be replicated in future studies.In this ancillary pilot study, we assessed whether changes in serum levels of cytokines, chemokines and Substance P from baseline to 2-month post-injection were associated with clinically meaningful pain relief at 2-month post-injection. We performed a mechanistic study and used data from our randomized study of intra-articular injection for painful TKA . In manyThe traditional view of cytokines/chemokines being either anti- or pro-inflammatory  has beenp < 0.025) in 10 patients with stable, painless, well-functioning, cemented total knee or hip arthroplasties (TKA/THA) than patients with aseptically loosened, painful, arthroplasties [Other recent uncontrolled studies have documented a potential role of cytokines, chemokines and Substance P in the failure of total joint replacement. In a recent study, both IL-1 beta and IL-2 levels were significantly lower p < 0.0 in 10 paplasties . Compareplasties .In patients undergoing revision surgery for painful primary hip arthroplasty, nerve fibers with positive immunostaining to Substance P were found in bone-prosthesis interface membranes . Joint fOur study findings must be interpreted considering study limitations. The sample size for this ancillary study was small. A protocol modification was made to the main study on receipt of federal funding that allowed us to collect specimens and perform analyses, and therefore these analyses were performed on a subset of the main trial, since almost 40% of the study cohort had already been enrolled in the study. Therefore, we likely missed several important findings due to type II error. Subsequent studies should enroll a larger number of patients to explore this important aspect of treatment for patients with painful arthroplasty. We examined the patients in the pain responder vs. non-responder categories, as specified a priori in our analytic plan. Since our hypothesis was to assess the cytokine, chemokine and neuropeptide mediators of joint pain relief in painful arthroplasty, we limited our analyses by whether patient was or was not a responder by clinically meaningful pain relief at 2-months post-injection. We adopted this approach rather than comparing Botulinum toxin group vs. placebo group, since we only had samples on half of the study participants in the RCT and both groups of patients with samples consisted of a mix of pain responders and non-responders, leading to an inadequate sample size for this comparison. We believe that the associations we noted are unlikely to be drug-specific, since responders included patients from both intervention and control arms. This analysis addressed our main objective to better understand the mechanism of pain improvement in patients who have had a failed TKA, and are undergoing a medical treatment to improve pain. Study strengths include the randomized, blinded study design, use of paired samples and focus on a condition that has significant public health impact. The presence of significant associations, even under the stringent categorization (responders/non-responders), with the current sample size, supports our underlying theoretical framework that cytokine, chemokine and substance P level changes after an intra-articular injection might be associated with pain relief.In conclusion, our exploratory study shows that patients who experience pain relief after an intra-articular injection have a different pattern of change in serum cytokine/chemokine levels than patients without pain relief. Our study identifies several cytokines that might play a role in relief of joint pain with local therapies. Our study has generated interesting hypotheses of mechanisms of pain relief in patients with painful TKA. Future studies need to confirm our findings in patients with painful arthroplasty, with similar intra-articular interventions, but also other dissimilar interventions, since pain pathways/mechanisms may be similar.


Median arcuate ligament syndrome is a rare disorder that is clinically characterized by the triad of postprandial abdominal pain, weight loss, and often an abdominal bruit due to compression of the celiac artery by the median arcuate ligament. Given the nonspecific symptoms, this is a rare and difficult diagnosis to obtain. We present a patient with nonspecific abdominal pain in whom etiology was ultimately determined to be median arcuate ligament syndrome. We present the case of a patient with nonspecific abdominal pain in whom etiology was ultimately determined to be median arcuate ligament syndrome.Median arcuate ligament syndrome is a rare disorder that is clinically characterized by the triad of postprandial abdominal pain, weight loss, and often an abdominal bruit due to compression of the celiac artery by the median arcuate ligament. Median arcuate ligament is a fibrous arch that usually passes just superior to the celiac artery near the first lumbar vertebra. In 10% to 24% of the general population, the ligament crosses anterior to the celiac artery, and a few of these patients may have hemodynamically significant stenosis causing abdominal pain.A 38-year-old woman with no known past medical history presented to the emergency room with diffuse, cramping, nonradiating abdominal pain episodes lasting for 30 to 60 minutes. The patient also had associated symptoms of nausea and bilious vomiting, which temporarily relieved the pain. These episodes had no known precipitating factor and were not associated with food or exercise. She had 2 similar episodes in the past and was admitted to hospital 4 months ago. Imaging and labs at that time were normal. She denied any significant alcohol, tobacco, or drug use. She also denied any significant family medical history. Her physical examination revealed mild epigastric tenderness to palpation but no other abnormalities.Complete blood counts, liver function tests, serum lipase, and urinalysis were all within normal limits. Esophagogastroduodenoscopy showed mild antral gastritis. However, pantoprazole failed to relieve severe pain episodes. A mesenteric ultrasound was ordered, which demonstrated increased celiac axis flow velocities with a peak systolic velocity of 320 cm/s . These f1Median arcuate ligament syndrome (MALS) is a very rare and difficult diagnosis to make due to its nonspecific symptoms and presentation. MALS is also referred to as celiac artery compression syndrome or Dunbar syndrome. MALS was first described by Harolja in 1963 in a patient who presented with abdominal pain that was attributed to mesenteric ischemia caused by compression of the celiac artery by a low-lying median arcuate ligament.3 One of the proposed theory is compression of the celiac artery by a median arcuate ligament that causes mesenteric ischemia, which leads to classical symptoms of MALS.2 However, It is not well known how celiac artery compression alone can cause mesenteric ischemia since generally there is extensive collateral blood supply to the mesenterium from other blood vessels.4 Another proposed mechanism for MALS is due to celiac plexus nerve dysfunction.3Even though the etiology of MALS is not well understood, there are 2 main theories, mainly mesenteric ischemia and nerve dysfunction.1 Patients are generally young woman between 30 and 50 years of age who have had multiple workups for abdominal pain. Abdominal pain is usually located in the epigastric area and worse after food. Even though there are no unique physical exam findings to MALS, an epigastric bruit may be observed in up to 35% of the symptomatic patients.3 In our patient, her abdominal pain was diffuse and she was tender to palpation on the epigastric area. Abdominal bruit was absent.Although in CT analysis compression of celiac artery is observed in up to 25% of patients, yet clinically symptomatically MALS is very rare.5 Sagittal view CTA or MRA will be able to detect focal narrowing of the proximal celiac axis.5 In our patient, CTA demonstrated focal narrowing of the celiac axis at the origin with a poststenotic dilation along with some degree of superior compression of the celiac axis suggestive of MALS.Since symptoms of MALS are nonspecific and overlap with other causes of abdominal pain, it is a diagnosis of exclusion. There are different imaging modalities that are used to diagnose MALS, such as mesenteric ultrasound, computed tomography angiography (CTA), magnetic resonance angiogram (MRA), and conventional angiography. Although conventional angiography is considered that gold standard for the diagnosis of MALS, angiography has largely been replaced by CTA and MRA.6 Combination of maximum expiratory peak velocity of >350 cm/s and deflection angle greater than 50° seems to be most reliable indicator for MALS on ultrasound.7Mesenteric ultrasound is another modality that is used to diagnose MALS. Performed during deep expiration, duplex ultrasound shows increased blood flow velocity across the compressed area of the celiac artery supports the presence of constriction.8 Typically, pain relief is immediate after the surgery. However, outcomes following surgical decompression are varied.9 There are multiple case reports with abdominal pain that did not resolve immediately after surgery.10 Since postsurgical pain can mimic presurgical symptoms, it may take up to 1 month for complete resolution of symptoms.8 Therefore, patients should be closely observed after surgery.Surgical decompression of the median arcuate ligament is the treatment of choice for symptomatic MALS patients. There are different modalities of surgery. Open surgery with decompression of the celiac artery and celiac plexus by division of the median arcuate ligament fibers is the most common treatment. However, laparoscopic and robotic-assisted laparoscopic approaches have also been utilized successfully and are recently getting popular.This case illustrates that MALS is an often missed diagnosis due to its nonspecific symptoms. Although MALS is a diagnosis of exclusion, when evaluating patients, especially young females, who present with abdominal pain of unclear etiology, MALS should be considered. MALS should be evaluated with a mesenteric ultrasound to assess celiac artery velocities. Patients with elevated velocities on mesenteric ultrasound should undergo confirmatory test with CTA or angiography. Patients who are diagnosed with MALS should be referred to surgery for decompression of the median arcuate ligament.


Lavandula angustifolia Mill. (lavender) oil or linalyl acetate on pain relief and lower urinary tract symptoms (LUTS) following the removal of indwelling urinary catheters from patients after CRC surgery. This randomised control study recruited 66 subjects with indwelling urinary catheters after undergoing CRC surgery who later underwent catheter removal. Patients inhaled 1% lavender, 1% linalyl acetate, or vehicle (control group) for 20 minutes. Systolic and diastolic blood pressure (BP), heart rate, LUTS, and visual analog scales of pain magnitude and quality of life (QoL) regarding urinary symptoms were measured before and after inhalation. Systolic BP, diastolic BP, heart rate, LUTS, and QoL satisfaction with urinary symptoms were similar in the three groups. Significant differences in pain magnitude and urinary residual sense of indwelling catheters were observed among the three groups, with inhalation of linalyl acetate being significantly more effective than inhalation of lavender or vehicle. Inhalation of linalyl acetate is an effective nursing intervention to relieve pain and urinary residual sense of indwelling urinary catheters following their removal from patients who underwent CRC surgery.Pain and urinary symptoms following colorectal cancer (CRC) surgery are frequent and carry a poor recovery. This study tested the effects of inhalation of The incidence of colorectal cancer (CRC) in Korea has increased markedly due to a transition to Western dietary patterns . At presEfficient and immediate pain control following CRC surgery can facilitate earlier hospital discharge by reducing the length of hospital stay, thereby minimizing complications in the respiratory system, such as atelectasis and pneumonia, as well as gastrointestinal complications, including intestinal obstruction and abdominal inflation. Typical types of pain relief management after CRC surgery include patient-controlled anesthesia (PCA), narcotic (opioid) analgesics, nonsteroidal anti-inflammatory drugs, and epidural anesthesia . Despite Lavandula angustifolia Mill. (lavender) oil have shown that lavender essential oil has a diuretic effect [Aromatherapy, defined as inhalation of herb oil essences, is a type of complementary and alternative therapy. Analyses of hexane extracts ofc effect . Althougc effect . Inhaledc effect . Furtherc effect . Studiesc effect . Moreovec effect .Although lavender oil and its core constituent linalyl acetate relieve pain and anxiety reduce blood pressure and heart rate and have diuretic activity, no study to date has assessed the effect of aromatherapy with lavender and linalyl acetate on the degree of pain relief and urination satisfaction after the removal of indwelling urinary catheters. This study therefore analyzed the effects of lavender and linalyl acetate on the relief of pain in the surgery area and the level of urination satisfaction. These results may indicate an effective nursing intervention for patients following the removal of indwelling urinary catheters.This randomised pre- and posttest controlled trial assessed the effects of inhalation of 1% (v/v) lavender and 1% (v/v) linalyl acetate in almond oil on pain relief and lower urinary tract symptoms in patients who have undergone removal of indwelling urinary catheters after CRC surgery. Using a G-power program, it was calculated that the minimum number of subjects necessary for intergroup comparisons to achieve a significance level of 0.05, an effect size of 0.40, and test power of 0.80 was >21 subjects per group. Twenty-two (22) subjects were assigned to each group and randomised using table of random numbers to inhalation of 1% lavender oil, 1% linalyl acetate, or almond oil .The study protocol was approved by the institutional bioethics committee of Korea University Anam Hospital (ED15045). All subjects were informed about the objectives and procedures of this study, and all provided written informed consent. All patients had been diagnosed with and underwent robotic or laparoscopic surgery for CRC at Korea University Medical Center and were given postoperative fentanyl as a painkiller and ketorolac tromethamine as an anti-inflammatory agent, with all attaining a specific stable drug dosage at the time of testing. None of the included patients had any complications, inflammatory diseases, loss of consciousness, communication disorders, or disorientation after surgery. None had olfactory impairments or allergy to any of the essential oils; and none had been treated with drugs, hormones, or aromatherapy for a psychiatric disorder.Prior to testing, the selected subjects were informed about the study objectives and asked to fill out a questionnaire regarding general characteristics, VAS pain, and urination. After a 10-minute rest, blood pressure and heart rate were measured in the supine position; all measurements were taken by a single trained researcher to minimize the effects of emotional stimuli on cardiovascular responses. All subjects were not informed about the types, concentrations, and efficacy of aroma oils.Following the removal of the indwelling urinary catheter implanted after CRC surgery, curtains were drawn to exclude the effects of experimental cues. After completing the above survey, the subjects were allowed to rest for 10 minutes and placed in the supine position. In taking three deep breaths through a 4 × 2 cm sized gauze suspended in above the philtrum of the subject, 1 ml 1% lavender oil, 1% LA, or almond oil was dropped onto the gauze, and the subject were allowed to inhale the aroma for about 20 minutes. To ensure the objectivity of this study, the researcher was not involved in formulating the inhaled oils, and testing was performed in a double blind fashion.After each test, subjects were asked to complete a posttest survey, using the same method as that employed for the pretest survey. Subjects were allowed to rest for about 10 minutes, and blood pressure and heart rate were measured in the supine position, as above.The main components of the lavender oil , as determined by gas chromatography, were  linalyl Pain was measured by a visual analog scale (VAS) score . This toBlood pressure (BP) and heart rate (HR) are parameters revealing autonomic nervous system reactions in a state of pain and were used to measure physiological reactions. BP was measured after a rest of 10 minutes or longer using an electronic manometer , placed on the brachial artery with the subject comfortably seated in a supine position before and after essential oil inhalation. HR was measured in the radial artery for 1 minute before and after essential oil inhalation.Micturition function was assessed using a self-administered questionnaire that measures lower urinary tract symptoms (LUTS) based on seven items . Each response was scored on a 5-point scale, assessing the frequency of events during the past five urination episodes, with scores of 0–5 points indicating never, 1 in 5 times, 1 in 3 times, 1 in 2 times, 2 in 3 times, and always, respectively. Scores of each of the seven items were summed to yield the total symptom score. Current urinary satisfaction as a QoL measure was scored on a 6-point scale, ranging from very happy (0 point) to terrible (6 points).Data were analyzed using SPSS 20.0 software. To preliminarily determine homogeneity across the three patient groups, categorical variables were assessed using Chi-squared or Fisher's exact tests. Continuous variables were analyzed using Kolmogorov-Smirnov tests to determine regularity, with normally distributed variables analyzed by ANOVA  and nonnormally distributed variables analyzed by Kruskal-Wallis tests. Differences in dependent variables across the three groups before and after testing were analyzed by Kruskal-Wallis tests, whereas within group differences in dependent variables from before to after testing were analyzed by Wilcoxon's rank sum tests.The mean age of the 66 subjects who participated in this study was 60.9 years. Of these subjects, 42 (63.6%) were male and 29 (43.9%) were smokers, with a mean smoking period of 11.5 years and a mean 7.2 cigarettes per day. Of these 66 subjects, 36 (54.5%) exercised every day, 33 (50%) consumed alcohol, 23 (34.8%) took antihypertensive drugs, 11 (16.7%) took hypoglycemic agents, 66 (100%) consumed at least one cup of coffee per day, 23 (34.6%) underwent robotic surgery, and 21 (31.8%) had metastatic disease. None of these factors differed significantly among the three groups .Prior to essential oil inhalation, the mean VAS pain score after removing indwelling urinary catheters was 4.25, mean systolic BP was 126.69 mmHg, mean diastolic BP was 73.87 mmHg, mean HR was 74.54 beats/min, mean total LUTS score was 5.44 points, and mean QoL score was 2.65 points. None of these scores differed significantly among the three groups of subjects .P = 0.035, P = 0.002) and linalyl acetate (P < 0.001) groups being significantly more reduced than in the control group  but was reduced significantly in both the lavender  and linalyl acetate subgroups .Pain magnitude in the three groups was not significantly affected by administration of an antihypertensive drug after the intervention . Pain man = 7, P = 0.001) and lavender  groups who underwent robotic surgery showed significantly greater reductions in pain score compared with control patients who underwent robotic surgery (n = 7) but decreased in control patients who underwent laparoscopic surgery (n = 15). Pain magnitude in both the lavender and linalyl acetate groups decreased after both robotic  and laparoscopic surgery .Patients in the linalyl acetate .P = 0.234; P = 0.004) and linalyl acetate  groups than in the control (0.63 ± 1.67) group but that the postintervention scores were similar in the three groups (P = 0.540). Change in satisfaction with urination from before to after inhalation was similar in the three groups (P = 0.488).Inhalation altered symptom scores slightly, but not significantly, in each of the three groups. Comparisons among the three groups showed that inhalation increased mean LUTS score by 0.63 ± 6.39 in the control group but decreased mean LUTS score by 2.83 ± 4.69 in the lavender group and 0.48 ± 7.15 in the linalyl acetate group, with no significant difference among these three groups -(−) linalool and lavender essential oils by healthy individuals reduced HR . Both toThe results described in this study indicate that inhalation of essential oils containing linalyl acetate can relieve pain and urinary residual sense following the removal of indwelling urinary catheters from patients who have undergone CRC surgery. Future research should determine the concentration dependence of these effects, especially with regard to satisfaction with urination. Inhalation of linalyl acetate by these patients may be an effective nursing intervention to enhance comfort and control pain and micturition disorders.


The Quebec Pain Registry (QPR) is a large research database of patients suffering from various chronic pain (CP) syndromes who were referred to one of five tertiary care centres in the province of Quebec (Canada). Patients were monitored using common demographics, identical clinical descriptors, and uniform validated outcomes. This paper describes the development, implementation, and research potential of the QPR. Between 2008 and 2013, 6902 patients were enrolled in the QPR, and data were collected prior to their first visit at the pain clinic and six months later. More than 90% of them  consented that their QPR data be used for research purposes. The results suggest that, compared to patients with serious chronic medical disorders, CP patients referred to tertiary care clinics are more severely impaired in multiple domains including emotional and physical functioning. The QPR is also a powerful and comprehensive tool for conducting research in a “real-world” context with 27 observational studies and satellite research projects which have been completed or are underway. It contains data on the clinical evolution of thousands of patients and provides the opportunity of answering important research questions on various aspects of CP (or specific pain syndromes) and its management. In the field of pain research, like in other medical fields, randomized controlled trials (RCTs) are the gold standard for establishing the efficacy of interventions. However, RCTs have several limitations –8. TypicA patient registry is defined as “an organized system that uses observational study methods to collect uniform data  to evaluate specified outcomes for a population defined by a particular disease, condition or exposure, and that serves a predetermined scientific, clinical or policy purpose(s)” . PatientIn 2008, the Health Ministry of the province of Quebec (Canada) designated four Pain Centres of Expertise within the Montreal, McGill, Sherbrooke, and Laval University Health Networks which altogether cover the entire province. The Ministry wished to monitor the clinical outcomes of patients treated in these newly designated centres  and obtain relevant administrative statistics. In parallel, one of the strategic plans of the Quebec Pain Research Network for 2007–2011 was to develop a province-wide clinical pain research infrastructure to facilitate the conduct of large observational and clinical studies. To meet the objectives of both of these organizations, there was a need to develop a uniform multisite registry that documents the clinical condition and evolution of patients treated in tertiary care pain clinics. This gave the impetus to implement in the Quebec Pain Registry (QPR) project designed to serve both clinical/administrative and research purposes. To our knowledge, only two other registries of patients with various types of chronic pain disorders treated in multidisciplinary clinics have been developed so far, one in the UK (Pain Audit Collection System)  (PACS) aThe present paper describes how the QPR was developed and implemented detailing its strength and shortcomings with the aim of facilitating the creation of other pain patient registries. The QPR structure and content are also presented along with the characteristics of the enrolled patients. The policy and procedures for accessing QPR data sets for research purposes are described as well as the type of access requests made.The aims of the QPR project were to (1) put in place a prospective web-based registry of ambulatory patients suffering from various types of pain syndromes who were referred for multidisciplinary treatment in large university-affiliated pain clinics in the province of Quebec, (2) assess and monitor their condition over time using common demographics, identical clinical descriptors, and uniform outcomes measured with standardized/validated measurement tools in each participating site, (3) document pain treatments patients received and/or used over time, (4) provide clinicians with a summary of the individual condition of their patients along with useful administrative statistics for their pain treatment facility, and (5) provide reliable “real-world” data to researchers wishing to answer important research questions or test hypotheses regarding various aspects of chronic pain (or specific pain syndromes) and its management, to assess study feasibility, and to facilitate and speed up patient recruitment in research projects or clinical trials.Using the guidelines proposed by Solomon et al. 1991) [91 [19] a minimal needs-based data set. The item choice had to be balanced between the clinicians' and researchers' interests for large amount of data, the burden placed on the patients, and the time/costs associated with the data collection process.The choice of items to be included in the QPR was made with the objective of creating a uniformDemographic and Clinical Variables. All medical directors of large Canadian university-affiliated pain treatment clinics were contacted to share the questionnaires they used to record patients' demographics and clinical data  at the first visit in their facility and at follow-up time(s). These questionnaires were carefully reviewed by one researcher (M.C.), one pain clinician (D.D.), and a research nurse coordinator (H.L.) who selected the items to be included in the QPR based on recurrence of their appearance across questionnaires along with what they considered as the most optimal question formulation and categories of responses to measure these variables. Canadian and Quebec governmental health surveys  were alAll the above information except for patient sociodemographics was incorporated into a single questionnaire named the Initial Nurse-administered Questionnaire. A second questionnaire was also developed using the approach described above in order to collect follow-up data after the patients' first visit at the pain clinic (6-Month Nurse-administered Questionnaire).With regard to patient pain diagnoses to be established by the pain physicians at the participating sites, it was felt that the International Classification of Diseases (ICD-9 or 10 systems) , 24 did Patient Outcomes. Different sources of information such as the recommendations made by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) Group [T) Group , 28 guidT) Group  were alsT) Group ), the itT) Group . The que Centre Hospitalier de l'Université de Montréal (CHUM), McGill University Health Centre (MUHC), and Centre Hospitalier de l'Université de Sherbrooke (CHUS). Once patients provided informed consent, the QPR questionnaires were administered to them prior to their first visit at the pain clinic and six months later. All the data collected in this pilot study were analysed using descriptive statistics. The results of these analyses along with the comments/suggestions from the stakeholders (unpublished data) were summarized by the two principal investigators (PIs) of the QPR project  along with D.D. and H.L. and were used to develop the final versions of the QPR questionnaires and clinical summary forms, adjust the procedures to maximize patients' responsiveness and retention at follow-up, and ensure optimal collaboration of the pain clinicians in the project.Paper Case Report Forms (CRFs) were then prepared and used in a pilot prospective study to test the feasibility of implementing/running the QPR. Additional pieces of information were collected during the pilot study such as the time taken to complete each questionnaires/interview, patients' perceived degree of difficulty for filling out the questionnaires, and clinical usefulness of the collected material. Physicians were also asked to check the items they would like to be included in a clinical summary form. After having obtained institutional ethic approval of the research protocol, the pilot study was conducted in 2007-2008 with 90 consecutive patients recruited in three multidisciplinary pain treatment facilities which were candidates for becoming the designated tertiary care clinics of the Quebec Pain Centres of Expertise. These clinics were, respectively, located at theQPR Measures and Tools. http://www.quebecpainregistry.com). Several items contained in the original version of the registry were withdrawn at the end of June 2012 (see https://doi.org/10.1155/2017/8123812) of the online version of the present article.2012 see  to reducDevelopment of the Web-Based QPR Database. Dacima Software Inc.  developed, tested, hosted, and maintained the central web-based quality-controlled QPR database which was FDA 21 CFR 11-compliant. They also developed the electronic CRFs and database-generated clinical summary forms which were beta tested by the Registry Nurse Coordinator (H.L.) and her assistant (L.G.). In April 2012, the QPR central database was transferred to Typhon Solutions Inc.  who also developed and updated the electronic CRFs and clinical summary forms. System access controls were in place for registered users from the participating sites. Access to the central anonymized database was limited to authorized staff . Each patient was given a unique code number in the database which was not linked to her/his medical record. All the names, addresses, and phone numbers of the participants along with their unique code number were kept in each participating site in a separate and password secured Excel file which was accessible only to the RN and RA. This was aimed at preventing the transmission of specific patient identifiers in the central data repository.Ethics Approval. The protocol, questionnaires, and procedures for implementing the QPR in the multidisciplinary pain clinics of the CHUM, MUHC, and CHUS were approved in 2008 by the REB of the CHUM which acted as the central ethic committee in charge of obtaining approval from the local ones. Given that the designation of the tertiary care pain clinics affiliated to the Pain Center of Expertise of Laval University   and the Hôtel-Dieu de Lévis (HDL)) was considerably delayed for administrative reasons, ethic approval was obtained only in 2012 for implementation of the QPR in these two sites.Implementation of the QPR. The QPR was implemented at the multidisciplinary pain treatment clinics of the CHUM, CHUS, and MUHC in November 2008, January 2009, and March 2009, respectively. At the HDL, the QPR project started in July 2012, and in August 2012 at the CHUQ. Due to a restructuring of the Pain Center of Expertise of the Sherbrooke University Health Network, enrolment of new patients in the QPR had to be stopped at the pain clinic of the CHUS in August 2012 but 6-month follow-up measures were collected up to February 2013. In each clinic, patient pain management was personalized and involved various types of pharmacological , interventional , physical , and/or psychological  modalities as well as teaching of self-management techniques . Patients could be seen by professionals from various disciplines at the pain clinic including anesthesiology, family medicine, neurology, nursing, pharmacy, physiatry, psychology, psychiatry, and physiotherapy. Choice of the treatment modalities was based on the patients' needs and varied from one to the other.Patient Enrolment. Consecutive ambulatory patients scheduled for a first visit at the pain clinic for multidisciplinary pain treatment considerations were enrolled in the QPR if they were (1) aged ≥ 18 years and (2) able to understand and read French or English. Patients who were unable to complete questionnaires due to severe physical or cognitive inability were excluded. Patients who were eligible for enrolment in the preexisting registry of fibromyalgia patients [patients  at the MData Collection Procedures. Once the patients' first appointment was fixed, the receptionist of the pain clinic faxed their contact information to the Registry Assistant (RA) who contacted them to explain the QPR procedures and confirm their eligibility. She informed them that they would receive by mail the Initial Patient Questionnaire along with the QPR consent form and a preaddressed/stamped envelope. At the time the QPR was implemented in 2008, e-technologies such as IPad, IPhone, and other android devices were not widely spread in the province and a substantial number of patients did not have access to Internet yet. For those who did, they were sent by e-mail an electronic copy of the Patient Questionnaire that they completed on screen. Patients were told that completion of the questionnaire would require 20–30 minutes of their time and that the Registry Nurse will contact them by phone prior to their first visit at the pain clinic. Upon reception of the questionnaire, the RA carefully reviewed it to make sure that all questions had been answered and if not, the patient was contacted by phone. If the questionnaire was not returned within the week preceding the scheduled appointment at the pain clinic, the RA phoned the patient and asked to bring it on the day of her/his appointment at the pain clinic. Data collected with the Initial Patient Questionnaire were entered by the RA into the web-based QPR portal.The RA contacted the Registry Nurse (RN) who conducted a structured telephone or face-to-face interview with the patients in the days/hours preceding their first appointment at the pain clinic using the Initial Nurse Questionnaire. Depending on the patient's clinical condition, the interview lasted between 30 and 90 minutes, and the information was entered by the RN or RA into the online QPR database. A summary of the patient's clinical condition  was then generated from the database and transmitted to the treating physician of the pain clinic. Follow-up data were collected using the 6-Month Patient and Nurse Questionnaires using a similar methodology as the one described above. Additional follow-up data were gathered at 12 and 24 months after the initial visit but only in those patients who had not been discharged from the pain clinic in the meantime. These data were collected with questionnaires containing the same measures as those administered at the 6-month follow-up. Due to financial considerations, follow-up data were not collected at 12 and 24 months in newly enrolled patients after March 2012. Due to budget cuts in the QPR project for the year 2014-2015, collection of 6-month follow-up data had to be interrupted in newly registered patients after June 2014, and enrolment of new patients ended in November 2014.In order to have a more complete picture of patient pain management than the one provided in medical records, all data about pharmacotherapy (prescribed and over-the-counter medication) and nonpharmacological treatments used inside and outside of the pain clinic  were collected by the Registry Nurses who did not have clinical duties in the QPR participating sites. The purpose of having nurses rather than RA for conducting the interviews with the patients was twofold: (1) to ensure accuracy of the patient clinical summary transmitted to the treating physician at the pain clinic and (2) to optimize the quality of the medical/clinical data contained in the QPR database.Quality Safeguards. Standard operating procedures (SOPs) were prepared to standardize patient enrolment and data collection, entry, and quality. Training of the QPR staff was under the responsibility of the Registry Nurse Coordinator and her assistant and consisted of a 2-day meeting during which the SOPs were carefully reviewed, explained, and illustrated with examples and mock patient interviews. Phone and e-mail follow-ups were made to maintain staff competency, inform them about modifications in the SOPs, and answer questions. Onsite audits were also carried out in the participating clinics to review screening/follow-up logs and ensure procedural consistency across sites. Finally, all the QPR staff attended a face-to-face meeting with the PIs and the Coordinator at least once a year to monitor QPR progress, review the SOPs, and reiterate the high importance of data completeness.Quality monitoring of the QPR database was under the responsibility of the Registry Nurse Coordinator and her assistant. Each participating site was requested to provide a monthly report of the number of patients enrolled in the registry, reasons for exclusion, number of questionnaires not completed and reasons why, losses to follow-up, and so on. With regard to data quality monitoring, a series of quality controls were programmed in the QPR database to allow instant automated data validation checks . To facilitate medication data entry and ensure consistency , a medication dictionary was built in the database. Manual data cleaning was also carried out on a regular basis to identify discrepancies and missing data on variables targeted as important  and to generate “queries” to be sent to the participating sites for resolution. Statistical programs to identify errors or inconsistencies on specific measures were also part of quality control activities. Errors identified when data were analysed for administrative or research purposes were also corrected in the database.Access Policy. Once the QPR was implemented, a comprehensive policy to access/use data from QPR patients contained in the registry and a business cost-recovery model were developed by the two PIs of the present project  in collaboration with members of the Executive Committee of the Quebec Pain Research Network  and legal/administrative advisers. The data access policy received ethical approval from the central REB for the QPR project at the CHUM and is available in the supplementary files of the online version of the present article and on the QPR website (http://www.quebecpainregistry.com).Datasets of patients who gave informed consent can be accessed for conducting observational studies. Assessment of feasibility of research projects or clinical trials is also possible . The QPR can also be used to conduct “satellite” research projects, that is, studies in which data contained in the QPR  are linked to other sets of data . However, the research protocol and the accompanying patient consent form of the satellite projects have to receive prior approval by the clinical team of the participating site(s), the central REB of the CHUM, and the local REBs. Once the project is approved by these authorities, the Medical Director of the participating clinic(s) sends a letter to inform the eligible QPR patients about the research project and invites them if they are interested in participating to contact the person in charge of the study or her/his representative. Finally, the QPR data can be accessed to facilitate and speed up patients' recruitment in research projects or clinical trials; the procedure is the same as the one used for satellite research projects.Business Model. The registry is an academic, not-for-profit project. The business model relies on fees to cover (1) administrative costs for running the data access requests based on their complexity level  and (2) financial contribution to maintain the QPR data repository and ensure its long-term sustainability. Access fees vary according to the type of requesters, the lowest costs being for academic researchers who are members of the Quebec Pain Research Network (QPRN), followed by academic researchers who are not part of the QPRN, and industry researchers whose companies were or were not funding partners of the QPRN. Fees for accessing QPR data also vary as a function of the number of variables requested, complexity of the extraction process and statistical analysis (if applicable), and whether they have to be linked or not to external data sets .http://www.quebecpainregistry.com) but the data included in the present article cover the period during which new patients were enrolled in the QPR up to December 31, 2013, and followed up at 6 months until to June 30, 2014. Patients who did not give consent for their QPR data to be used for research purposes were excluded from the analyses. Data describing the clinical evolution of the subgroup of patients with follow-up data not only at 6 but also at 12 and 24 months have been presented at the Annual Scientific Meeting of the Canadian Pain Society in 2014 [The total number of patients enrolled in the QPR between November 1, 2008, and December 21, 2014, is 9363 ( in 2014  and are t-tests. Chi-squared tests were carried out on differences between sex and participating pain clinics (study site). However, such significant testing in studies involving large sample sizes like the present one can be misleading because even small differences can reach statistical significance while they can be viewed as trivial and not meaningful clinically [d [d value ≥ ±0.5) were considered meaningful [φ) [V [φ or Cramér's V value ≥ ±0.3) were judged as being clinically important [The number and percentages of the Patient and Nurse Questionnaires which were completed prior to the initial visit at the pain clinic and at 6-month follow-up were computed. In order to assess if missing questionnaires qualified as “missing at random” , 36, difinically , 37, 38.cally [d . Only dically [d    and Craml [φ) [V  statistimportant , 38.t-tests were used to compare mean scores obtained on the physical and mental summary scales of the SF-12v2 [Descriptive statistics including measures of central tendency (mean or median) and dispersion (standard deviation or range) along with frequency tables were used to document the characteristics of the patients enrolled in the QPR. Due to space limitation, only a subset of the variables in  SF-12v2 , 43 in Q SF-12v2 .Descriptive statistics were computed on the kind and number of requests made for accessing QPR data and the type of users.N = 2052 (32.4%); MUHC: N = 2292 (36.2%); CHUS: N = 745 (11.8%); CHUQ: N = 810 (12.8%); HDL: N = 438 (6.9%). The percentages of patients who completed the Initial Patient and Nurse Questionnaires were 98.5% and 99.2%, respectively. At 6-month follow-up, 89.1% of the patients (5647/6337) completed at least one of the two questionnaires (P ≤ 0.05). However, all the effect sizes were small  suggesting that the differences are not clinically meaningful [Of the 8,233 patients who were referred to the participating pain clinics between November 2008 and December 2013 (inclusively), 7021 (85.3%) qualified for enrolment in the QPR and only 1.7% refused to do so . Ninety-onnaires . ResultsPatients enrolled in the QPR during the study period were aged between 18 and 88 years , 59.1% were female, and the vast majority (92.0%) were of Caucasian origin . Nearly The median amount of time elapsed between patients' referral and first visit at the pain clinic was 3.5 months; 35.0% of the patients waited more than 6 months for their appointment, some of them (5.2%) having waited between 2 and 4 years . Close tAn accident or a trauma was at the origin of the pain in more than half of the cases (52.5%); 31.4% of the patients reported that their pain occurred during or following an illness or and 14.2% after a surgery while one patient out of five (22.5%) was unable to associate the onset of her/his their pain to any precise event.  P ≤ 0.001 and Cohen's d values between 0.6 and 3.3). With regard to depression symptomatology, scores obtained on the Beck Depression Inventory-I [The majority of the patients (85.0%) reported that their pain was present continuously in the 7 days preceding their first visit at the pain clinic. Mean pain intensity scores for the “average” pain and “worse” pain during this time period were 6.71 (SD = 2.0) and 8.16 (SD = 1.80), respectively. Patients' ratings on the interference scales of the Brief Pain Inventory-10 –46 reveaentory-I , 48 reveWhen questioned about the expected percentage of pain relief at six months after initiating treatment at the pain clinic, more than half of the patients (53.4%) anticipated pain relief ranging between 50 to 80% while one patient out of four (25.0%) expected pain relief superior to 80%. A large percentage of patients also anticipated that their functioning level (63.4% of patients) and quality of life (65.3% of patients) would be greatly or considerably improved over the next six months.As shown in the present paper, developing and implementing a multisite patient registry is a complex task. Although maintaining a registry such as the QPR is very costly, we have shown that it is feasible to collect uniform and reliable data in a large number of tertiary care patients suffering from a variety of pain syndromes and across different clinics. The collected information can help clinicians in making their diagnosis and management plan and can provide participating pain clinics with useful statistics on their practices. In addition to documenting the characteristics and management of patients referred to multidisciplinary pain clinics, our results showed that the QPR made possible the conduct of observational studies and satellite research projects using “real-world” data on various aspects of chronic pain.In terms of the feasibility of implementing the QPR, our results showed that only 1.7% of the potentially eligible patients refused to complete any questionnaires and 8.2% did not consent that their data be used for research purposes. Close to 100% of patients completed both the Initial Patient Questionnaire and Nurse Questionnaire. At 6-month follow-up, the percentage decreased but the overall retention rate remained high; that is, nearly 90% completed at least one of the two questionnaires. Some statistically significant differences were found in terms of patients' age, sex, and study site between those who did and did not answer the questionnaires at each time point and between time points. However, all effect sizes were not clinically meaningful suggesting that missing questionnaires did not introduce bias in the QPR data .https://choir.stanford.edu) [Compared to the majority of existing pain patient registries –16, the ord.edu)  had seveord.edu)  which arord.edu) , 60. Theord.edu) , 62 alloord.edu) . As a reord.edu) . Howeverord.edu)  and effeord.edu) . Furtherord.edu) , 65. Thiord.edu) . A last ord.edu) . Other rord.edu) , 67 or hord.edu) .With regard to the characteristics of the participants enrolled in the QPR prior to their first visit at the pain clinic, our results highlight the fact that patients attending tertiary care pain clinics are significantly impaired in multiple domains. The majority of patients experienced continuous pain that reached intensity levels severe enough to interfere substantially with various aspects of their daily living including emotional well-being. Consistent with earlier results obtained in a smaller sample , we obseInterestingly, the median time elapsed between patients' referral and first visit at the pain clinic was found to be 3.5 months. Eleven years ago, Veillette et al. (2005) examined the waitlists of pain services across the province of Quebec and found that two-thirds of the patients were waiting for 9 months or more . In a suIn terms of expectations toward treatment, our results revealed that close to 70% of the patients anticipated great or considerable improvement in their functioning and quality of life while one patient out of five was expecting 80–100% pain relief following treatment at the pain clinic. Whether such high expectations can be detrimental to patients' outcomes was recently investigated using the initial visit and 6-month follow-up QPR data. The results of this study suggest that individuals who expected positive changes were more inclined to perceive improvements in their overall condition, leading to superior clinical outcomes .Although our above study findings are informative and are based on a large sample size of patients followed prospectively in several sites and in a real-world context, they have limitations that should be acknowledged. First, they characterized only a small proportion of the chronic pain population, that is, those who are referred to tertiary care clinics, such that the results cannot be generalized to other populations of patients treated in primary or secondary care settings. Second, it is important to point out that access to tertiary care clinics in the province of Quebec requires a physician referral; access to these clinics is free but limited due to relatively long waiting lists as is the case in other Canadian provinces . As a reThe present paper finally illustrates how “real-world” patient registries such as the QPR can be valuable and powerful research tools , 2, 6. SThe QPR is a vast registry of patients referred to multidisciplinary pain treatment clinics that was designed for clinical/administrative and research purposes. This registry provides numerous opportunities to study various aspects of chronic pain (or specific pain syndromes) and its management using longitudinal “real-world” data on a large set of variables collected in tertiary care patients. The most important challenge posed by the QPR remains to be its maintenance costs which have compromised its long-term sustainability and its expansion in other pain clinics.The first file shows the list of pain diagnoses and their corresponding codes contained in the Quebec Pain Registry (QPR). The pain physicians at the participating sites used this diagnostic grid to record the type(s) of pain the patients suffered from. The second file shows the list of medical interventions and their corresponding codes in the QPR. This grid was used to record the type(s) of medical interventions the patients received.The third file displays the policy to access and use data from the QPR.


Recent advances in the treatment of postoperative pain (POP) have increased the quality of life in surgical patients. The aim of this study was to examine the quality of POP management in patients after CS in comparison with patients after comparable surgical procedures.  This was a prospective observational analysis in patients after CS in comparison with the patients of the same age, who underwent comparable abdominal gynaecological surgeries (GS group) at the university hospital. A standardised questionnaire including pain intensity on the Verbal Rating Scale (VRS-11), incidence of analgesia-related side effects, and incidence of pain interference with the items of quality of life and patients' satisfaction with the treatment of POP was used. N=63): mean 6.1 versus 3.6 . The patients after CS reported less nausea (8 versus 41%) and vomiting  and demonstrated better satisfaction with POP treatment than the patients after GS: 1.4 (0.7) versus 1.7 (0.7) (mean (SD); VRS-5; P=0.02).  Sixty-four patients after CS reported more pain on movement than the patients after GS ( The disparity between the high level of pain and excellent satisfaction with POP treatment raises the ethical and biomedical considerations of restrictive pharmacological therapy of post-CS pain. New methods of analgesia and the organisational approach to analgesia, including the procedure-specific, multimodal analgesic protocols, may decrease the levels of postoperative pain (POP) and increase the quality of life of surgical patients –3. DespiWe recently measured the clinical effectiveness of the quality management system (QMS) based on procedure-specific, multimodal analgesic protocols, modified to meet the individual patient's requirements in our hospital . The impHowever, only patients from the departments of general surgery, gynaecology, orthopaedics, and traumatology were included in the previous study ; the facPerforming the annual audits, which are the part of our organisational measures to maintain a high quality of POP treatments and to improve it further, we have achieved a similar decrease in POP and analgesic-related side effects as well as increased quality of life in patients from all surgical departments, except for caesarean section (CS) patients, after QMS implementation (unpublished data).To address this, we aimed to prospectively compare the results of audits in patients after CS with the data of women who underwent abdominal surgical procedures in the department of gynaecology at our hospital.The local institutional review board  approved the protocol of this prospective observational investigation in January 2015 . The investigation was performed using the data from the biannual audits within the frame of the QMS for POP [The audits were performed during one month in spring each year, when 30 audit questionnaires per ward were distributed. All patients who were scheduled to elective CS were included. For the control group, patients aged 19–45 years who underwent gynaecological surgery (GS group) with an anticipated intensity of POP ≥3 from 10 on NRS-11 “a priori”-defined procedure-specific POP intensity depending on the size and location of surgical lesion  were incThe audit questionnaire was based on the questionnaire from our previous investigation  and inclAll items concerning pain intensity were measured using the Verbal Rating Scale (VRS-11) from 0 = no pain to 10 = maximal pain imaginable. Satisfaction with the POP treatment was measured using the VRS-5 from 1 = excellent to 5 = bad, which, to facilitate the rating, resembles the scale of grades in German schools.The standard anaesthetic technique for elective CS procedures in our institution is spinal anaesthesia with 7.5 mg hyperbaric bupivacaine and 5 mcg sufentanil, which provides sufficient analgesia maximally 4 hours after the surgery. The treatment of POP after CS includes oral acetaminophen 4 × 1 g daily supplemented by diclofenac 3 × 50 mg daily, if necessary. In case of insufficient analgesia, subcutaneous injections of 7.5 mg piritramide  were allowed up to 6 times daily .The standard anaesthetic technique for GS was mainly general anaesthesia. For POP treatment following gynaecological surgery, basic analgesia was provided by the nonopioid analgesics acetaminophen, ibuprofen, and metamizole. In cases of expected moderate-to-severe pain, opioids were added, including oral tramadol or parenteral piritramide, applied via patient-controlled analgesia pumps. Continuous epidural analgesia with ropivacaine was used for POP treatment, where appropriate, according to abovementioned guidelines on POP treatment , 7.In order to compare the severity of pain after various surgical procedures, each type of surgery received the value of “a priori”-defined POP intensity, using the previously described procedure-specific POP intensity scale .t-test, and skewed data were compared using the Mann–Whitney test. Binomially distributed data were analysed using the chi-square test and presented as frequency distribution with absolute numbers and relative distribution in percent.The intensity of pain taken on VRS-11, side effects of analgesia, quality-of-life items, and patients' satisfaction with their POP treatment were compared between the CS and GS groups. Using the IBM SPSS Statistics 24.0 software, these data were presented as mean and standard deviation (SD) of mean values. Continuous data were analysed using Student's The data of 64 consecutive patients after CS and 63 women of the same age who underwent other surgical procedures were available for analysis. The ASA physiological status was comparable among the patients of both groups . During P < 0.0001 (P < 0.0001) than the patients scheduled to other surgical procedures  was higher in the GS group, the patients after CS reported more pain on movement: 6.2 (2.0) versus 3.6 (1.9) (mean (SD)); < 0.0001 ). Other Using the validated questionnaire for monitoring the quality of POP treatment at a university hospital, we have observed that, despite the higher levels of clinically relevant pain (pain on movement after the surgery), the patients after caesarean section (CS) were more satisfied with the treatment of POP than the patients after comparable gynaecological surgeries.Our findings support the data from the previous cohort investigations, where high pain intensity scores were reported in patients after CS in comparison with patients after hysterectomy , 5. The The high levels of pain after CS in comparison with other surgical procedures were not astonishing since the pharmacological treatment of post-CS pain is restricted in the obstetrical wards worldwide (including our institution) due to peculiarities of the patients' category . The maiThe gap between the severity of pain among the patients after CS and high levels of their satisfaction with POP treatment may be explained by both psychological and biological factors. Antenatal fears, especially concerning the health of the neonate, may worsen the severity of peripartal pain and then resolve after successful delivery . On the The extensive use of spinal anaesthesia for elective CS and restrictive use of opioids for treatment of post-CS pain in our institution are probably responsible for extremely low incidence of PONV in women after CS.The limitations of our investigation are as follows: (i) small sample from the single-centre setting; (ii) questionnaire methodology ; and (iii) inhomogeneity of the control group (including both laparoscopic and laparotomic procedures), which can be improved in future studies. Moreover, such an outcome parameter as patients' satisfaction with postoperative pain treatment is subjective in its nature and is prone to bias in clinical trials, where participants are exposed to the factors, influencing their emotional sphere.The disparity between the high levels of pain and excellent satisfaction with POP treatment with low incidence of analgesic-related side effects raises the ethical and medical questions of restrictive pharmacological therapy of post-CS pain.However, regarding the recent findings about high risk of persistent pain development in patients with severe post-CS pain  and cons