The prevalence of endometriosis is considerable but its diagnosis is a dilemma. The aim of this study was to explore the perception and experiences of endometriosis patients and physicians about occurrence and diagnosis of endometriosis.A qualitative research using content analysis was used to obtain data from purposely selected endometriosis patients (12 participants) and gynecologists (6 participants) from January to September 2013 in Tehran. Data were coded and analyzed using a thematic approach.Seven themes emerged: 1) pain localization, 2) Severity of pain and struggle for pain relief, 3) Feeling inability to play the role of femininity, 4) Reducing physical health, 5) Disruption of social life, 6) Looking for a reliable diagnostic indicator, 7) Uncertainty of physical examination. The results highlighted that patients with the disease can experience different feelings that interfere with their wellbeing and their lives, and sometimes could be disabling.Patients and physicians are looking for a certain, noninvasive and inexpensive diagnostic method. This study helps to promote clinical diagnostic view and knowledge development about description of endometriosis diagnosis to decrease diagnostic delay and mismanagement. Endometriosis is a disease with considerable prevalence in communities. It has been estimated to affect 10% to 15% of women of reproductive age and 35% to 50% of women with pelvic pain, infertility, or both -4. A higThere are significant challenges in the disease diagnosis. Currently there is no reliable laboratory test or imaging technique that can detect the disease . Thus, dMost studies on endometriosis usually focus on issues related to either (i) clinical manifestations or, (ii) imaging techniques, or (iii) laboratory and surgical techniques, while it seems that to have a better understanding of the disease both experts’ and patients’ perspectives also are needed. There are few papers that report on patients’ experiences or clinicians’ perspectives about the disease diagnosis and they mostly come from western culture -16 or haThis was a qualitative study to explore the perception and experiences of patients and physicians about occurrence and diagnosis of endometriosis. To collect data semi structured face-to-face in-depth interviews were conducted from January to September 2013 in a teaching hospital affiliated to Tehran University of Medical Sciences.The participants included both physicians and patients. The sampling continued until data saturation was reached. In all 18 individuals were interviewed (6 gynecologists and 12 patients). The only criterion for inclusion was a confirmed diagnosis of endometriosis for patients and having experience in endometriosis for physicians. The characteristics of participants showed maximum variances of samples. Sampling with maximum variation increases rigor of findings of qualitative studies . PatientData were collected using semi-structured interviews with patients and physicians. Most patients were asked the following questions: How did you realize your illness? Would you please describe your symptoms? Where did you go and what did you tell the doctor? What did they ask and what did they do for you? How did you feel? In the same way, most physicians were asked the following questions: Have you ever managed an endometriosis from the beginning to the end? How these patients express their problems? What do you do for diagnosis? To deepen the interviews such questions were asked: Is it possible to explain more? What do you mean? Why? How? Interviews were conducted in the hospital and lasted from 20 to 60 minutes. All interviews were carried out by H.R. and were recorded by using voice recorder and transcribed verbatim.Content analysis of transcribed data was done immediately after each interview. Data were coded and analyzed using a thematic approach . The patTo maintain data efficacy and credibility, manuscript was reviewed and modified with each unit analysis along with the extracted implications using supplementary participant views and suggestions. In addition, one qualitative researcher supervised and evaluated the entire study process.Interview transcripts and codes were presented to participants and they were asked if they agree with the meaning of the codes. In addition interviews were peer checked by academic colleagues who were not involved in the study to ensure the external validity.The ethics committee of Terbiat Modares University approved the study . Participants signed an informed written consent. They were assured of their safety, anonymity and confidentiality. Refusal to take part in the study or withdrawal at any point posed no harm to participants. In order to ensure anonymity, participants’ number has been used in reporting the study.Data analysis from interviews produced 245 codes, 26 categories, and 7 themes. The identified themes included: 1) Pain localization, 2) Severity of pain and struggle for pain relief, 3) Feeling inability to play the role of femininity, 4) Reducing physical health, 5) Disruption of social life, 6) Looking for a reliable diagnostic indicator and 7) Uncertainty of physical examination. Categories and themes are shown in Table This theme shows that many patients with endometriosis suffer from various pains caused many problems for them. Discomfort and pain in different parts of the body and the sense of vulnerability, has been expressed by the majority of patients and physicians who have experienced various forms of it. This theme consists of 6 categories included: 1) abdominal pain, 2) headache, 3) low back pain, 4) anal pain, 5) mastalgia and 6) lower limb pain.I always had pain but in the menstrual period it was much more, Pain was so intense that I could not touch my belly”.Pain is one of the main points repeatedly expressed by participants. These pains experienced with variety of intensity associated with menstrual period. Abdominal pain is almost existed, aggravated by menstrual period. Most physicians stressed that these patients refer due to painful menstrual periods and suffer from dysmenorrhea. One of the participants patient number 12 (pa12) said: “I had very severe headaches starting from behind my head and coming up to top of my head and it was very severe in the first and second day of menstruation but my doctor said: “it is normal” (pa8). The other patient (pa2) said: “10 days left to menstrual period I have been suffering from very severe headache causing blurred vision and nausea and I could not even get up because I would fell down and this pain continued for 24 hours but my doctor said: “It is premenstrual migraine and is normal””.Severe headache is another complaint which may feel stronger in early menstrual period but the important thing we have found is imagine the headache as a normal feature of menstrual period from physicians or lack of enough attention to it: There is no description for that pain. For example sometimes my belly and my lower back were pulling down. It seemed that something heavy heat my back drastically (pa11). This pain May be present in the whole of the cycle but may be felt with greater intensity during menstruation.Low back pain aggravated by menstruation was experienced with majority of patients: It's like a pressure on the anus and is a special pain. It was so unbearable that I wanted to scream (pa4).Another complaint and fear of its vulnerability expressed was anal pain usually experienced as a pressure pain. It feels more when defecating and often increases during menstruation: “I had a severe radiating pain in my nipples and I couldn’t even touch them” (pa8).Some patients complained of mastalgia which is particularly reported pre-menstrual and sometimes this pain feels so severe that the patient cannot tolerate even her bra for example one of them said: Finally, lower limb pain is another complaint which concerns in this theme hurting the patients. This pain is sometimes experienced following dragging pain from abdomen or low back pain and in many cases the patient is suffering throughout the menstrual period. Some of patients described that they feel numbness or coldness in their feet. These findings showed that patients express discomfort from different and diffused pain.Two categories created this theme: 1) the severity and type of pain and 2) pain response to different actions.I had terrible pain ...... It was unbearable (pa9). Another patient said: I was in such a severe pain that I couldn’t do anything, neither sitting nor standing , really nothing. It would get worse even if somebody would walk close to me. It was very very severe ……(pa5). Some patients described it as explosive pain. This issue is also seen in the experience reported by physicians: Some come with the chronic pelvic pain and pressure feel constantly (physician number 5 (phys5)).Severity and type of pain imply the types such as intermittent and aggravated pain, chronic pain or severe and unbearable pain that was mentioned by nearly all cases. Patients described the pain and its severity in different types of descriptions for example: I felt that if I put something heavy on my belly it would reduce my pain. This would pacify me at least for a few minutes (pa9), and patient number 5 said: “My pain didn’t respond to even 2 or 3 Gelophens and only IV analgesic infusion could stop my pain”.Patients have been seeking to find a solution to reduce pain, such as analgesics or steroids or nonpharmacological methods such as taking help of warmth and rest. Some participants mentioned that the pain was too severe to respond to conventional analgesics so intravenous analgesics and fluid therapy was needed to relieve pain. One of the patients said: These findings showed that patients tend to do anything for pain relief.This study is conducted in a country that being a wife and being a mother makes women feel perfect and valuable. In other words, by performing the role of an spouse and ultimately being a mother, women will feel maturation and do realize themselves as a real woman. Disruptive factors which have interactions with these two important matters can cause problem in the role of femininity. Two categories created this theme: 1) dyspareunia and 2) infertility.I suffered from painful sex; I wouldn’t be able to have sex. I cried. I felt a severe pain under my stomach. It was so severe that I couldn’t breathe at all. I just felt pain. I cried during intercourse but I had to bear the pain to make my partner happy (pa12). Dyspareunia is so severe in some patients’ experiences that they feel they have an explosion in suprapubic region. Patients’ experiences show that the pain will go away after intercourse and only in rare occasions it will be continued for 24 hours.The majority of patients complained lower abdominal pain, severe itching during intercourse and inability to perform coitus. Many women endure the pain to be able to play their feminine role: In the first two years after marriage I did not want to get pregnant but when I wanted to get pregnant, I faced with infertility (pa3). All the physicians mentioned that patients may refer to us due to infertility. The majority of patients refer to gynecologists due to an important problem which is infertility. Complaint of infertility and its ineffective treatments, increased incidence of miscarriage in case of pregnancy, are common problems. Since these two categories are important factors of interaction with the women’s roles of femininity so they created this theme.Infertility is another factor which may interfere with sense of self as a woman. Many women realize that they cannot become pregnant following the disease: The main focus of this theme was to all categories which could interfere with physical health including: 1) menstrual disturbances, 2) Digestive Disorders, 3) Urinary Disorders, 4) Complaint of irritating cyst and 5) pelvic infection problems. Following these problems which involves various systems and divert patients from the road of health, finally, the patient feels that her health is reduced.My bleeding was clotty and I had spotting from one week before menstruation (pa2).Irregularity and changing the pattern of menstrual cycles and spotting, result in feeling sick or feeling of disorder. Some patients complained of bimonthly menstruation or premenstrual or postmenstrual spotting which is mentioned by physicians too: In the first day of menstrual period, I was very sensitive to the smell of food just like a pregnant woman and even one spoon of food made me vomit. I did not eat food or even drink water for a day, I hated water. I would be nauseated after drinking water and I preferred not to drink at all, although I felt too thirsty” (pa9).Digestive Disorders such as constipation or diarrhea, nausea, vomiting or bloody stools are some other kinds of problems, diminish health situation. Sometimes the patient is so critically ill that intolerance to food and water will appear. Digestive Disorders would be worse during the menstruation. One of participants expressed: “Dysuria and hematuria are other disorders that can threaten the health of patients and majority of physicians had experienced it about endometriosis patients.I felt a severe pain in my whole abdomen that could not even breathe and my doctor diagnosed cysts by ultrasound.…(pa4).Ovarian cysts are another aspect of interfering health condition causing pain or other symptoms and are almost resistant to treatment: Each time I visited the doctor after marriage, he said that it was resistant pelvic infection; I was fine for 2 or 3 months with pills but would recur again (pa6).The last category of this theme is complaint of severe pelvic or gynecologic infections expressed by patients or physicians. Some patients complained of acute or chronic cervicitis and some others had severe infections resistant to treatment: Endometriosis can interfere with patient's lives and daily programs or communications. Two categories developed this theme: 1) impairment in daily activities and 2) Emotional and communicational disturbance.Pain was so intense that made me lie down in bed; I could not do anything even going to the bathroom was troublesome; I could not get up; I worked less; I cared less about my life; Every day I went to my mother’s house because she took care of me; she put hot towel on my belly or gave me my tablets ….(pa7).Endometriosis negatively impacts on daily life and physical functioning. Severe disability in movement during the menstrual period, interference with religious practices and being upset from not doing religious duties are some of main issues found. Most patients have so much pain and discomfort that prevent them from daily activities. Based on most patient experiences this impairment is so much that makes them to be confined to bed and they are obliged to set their life plans considering the time of menstruation. Patients lose their ability in handling the affairs of life and feel that they need to be supported: I've been sick for a long time. I am so tired. I haven’t told anyone about my infertility. Everyone says “you have been married for five years, why do not you bear a baby?” I feel so bad and I cry all the time (pa6).Feelings of hopelessness and fatigue, gloomy, feeling of depression, the need for support and problems in relationships with family members due to infertility are explained by majority of participants. Long term diagnosis is time and money consuming and in addition to psychological problems due to confusion and misdiagnosis, it can also disrupt order and routine of life. One of the patients stressed that: Patients and physicians try to find a way for definite diagnosis. The seven categories identified in this theme were: 1) association the symptoms with marriage, 2) family history, 3) use of ultrasound, 4) use of laparoscopy, 5) use of imaging techniques, 6) use of biomarker and 7) confusion in diagnosis. These categories show the patients and physicians concerns about the best and the most reliable diagnostic tool.Nulliparity and late marriage, sometimes make us more suspected about endometriosis (phys5). Since virginity is very important factor in Iranian culture, sexual life starts after marriage and usually premarital sexual activity is not allowed. Thus, delayed marriage leads to late diagnosis of dyspareunia that is one of the most important symptoms of the disease. On the other hand it is believed that dysmenorrhea is normal and common during the virginity and it relieves after marriage. All of these may lead to diagnostic delay.The majority of patients mentioned that they had the symptoms before marriage. The experience of physicians implies some relation between these two: Existence of disease in other family members was stressed by many patients and physicians but negative family history does not rule out the disease.Some of the diagnostic methods and imaging techniques which are used in this matter are ultrasound, MRI, CT scan or biomarkers explained by all the patients and physicians but laparoscopy is used as the golden standard for diagnosis. Some biomarkers such as CA125 are checked as a diagnostic indicator because we expect to be faced with an increase in its level. However sometimes in the presence of disease there isn't any rising or in case of rise it is related to other disorders.We thought that the pain is due to the Intestinal colitis. After four or five years of treatment I still suffered of pain and then my doctor showed concern about endometriosis (pa4). Because these patients suffer from diverse and scattered pains, confusion in diagnosis is likely to happen. I suffered from a severe headache but my doctor diagnosed the premenstrual migraine (pa2). Patients with misdiagnosis of recurrent pelvic infections or chronic infections are treated for many years: I had the pain in my lower belly and I had to visit doctors frequently and they all said that it was pelvic infection resistant to treatment (pa6). Drug prescription, particularly analgesics or hormonal steroids in the absence of definite diagnosis, alleviates the symptoms temporarily, creates confusion in diagnosis and postpones definite diagnosis: I was told that it was normal and you must tolerate it. They prescribed analgesics or oral contraceptive pills for me (pa9).Despite all the tests that are performed to diagnose endometriosis there are many uncertainties in the diagnosis. An incorrect diagnosis and incorrect treatment followed it may lead to mismanagement: It seems that although a definite diagnosis is the aim of patients and physicians, all the above-mentioned factors can delay the diagnosis.Information obtained through interviews with physicians and patients with endometriosis reflects the fact that physical examination is used as a diagnostic method but physicians stressed that they do not use it as a confident diagnostic method however sometimes existence of pain or adhesions or tumors or uterine fixation may help. Thus this theme emerged from two categories: 1) feeling discomfort during examination and 2) physical examination findings.…. However, the physical examination is helpful in diagnosis but do not have certainty” (phys1). Some of the patients had feeling pain during examination: During the examination following the pressure into the rectum I felt a terrible pain and screamed (pa4). While some others had not mentioned it: I had no problem and did not feel any pain during the examination (pa3).The majority of physicians stressed: “To the best of our knowledge, this is the first qualitative study about patients’ and physicians’ descriptions of occurrence and diagnosis of endometriosis in Iran. The results of this study describe the perception and experiences of occurrence and diagnosis of endometriosis from the perspective of 18 participants who took part in a qualitative study.“Diagnosis of endometriosis is accompanied by perceptions and symptoms in the forms of expressing discomfort from the varied and diffused pain and a feeling of vulnerability and severe pain to the extent that it leads to struggle for relieving the pain in these patients. Another helpful condition in diagnosis of endometriosis is feeling of inability to play the role of femininity and feeling of reducing physical health and also disruption of social life which frequently refer patients to physicians; as a result physicians have been more careful and curious. Since physical examination findings are not reliable, physicians also look for a reliable diagnostic indicator such as laparoscopy which is golden standard”. This description about endometriosis diagnosis is developed for the first time in Iran and is obtained from emerging themes and represents the patients’ and physicians’ experiences in order to understand and diagnosis of endometriosis. Most of studies have limited views of disease but we tried to have an expanded and generalized presentation. Nnoaham and coworkers have recently proposed a predicting model for endometriosis based on a multicenter research [Based on the results emerged from content analysis and the themes; for the first time a description for occurrence and diagnosis of endometriosis was explored: research . Findingresearch ,24. Painresearch . Besidesresearch ,25. Adheresearch . Sometimresearch ,26. Severesearch . In thisresearch . Similarresearch . All of research .Patients make every effort to reduce their pain. They use medical and nonmedical methods to relieve pain, for example using acupuncture . In Cox’Infertility and dyspareunia are two significant factors interfering with the femininity of women living with endometriosis. They feel powerless to perform their family duties as a woman. Prevalence of infertility among women with endometriosis varies from 20% to 50% ,33. NnoaDisruption of social life was another finding of this study. Patients reported that they were unable to perform their daily activities due to pain and other complications of the disease. Similar findings were reported where reduced effectiveness and loss of work productivity were observed ,38,39.Although our purpose was not comparing patients’ and physicians’ views, physicians had less attention to social life, daily activities and communication issues. Even, Fauconnier et al. showed that different perception exist between clinicians and patients on issues such as pain . Some asResults of our study indicate that patients and physicians try to find a way for definite diagnosis. Although signs of endometriosis may be found on physical examination but it is not dependable. Ultrasonography is sometimes effective especially in the case of endometriomas of the ovaries, but it is not an acceptable diagnostic tool . CA125 mThe strengths of this study are that we have ensured a surgical diagnosis for all the women with endometriosis and almost all of them were newly diagnosed patients. Both physicians’ and patients’ participation and use of their experiences was another noticeable one. Arash hospital which we had sampling is a referral center and patients are referred there from all the cities of Iran. Moreover there is a cultural and religious attitude to the issue in present article. However, the findings of this study cannot be generalized across the endometriosis community because of cultural and religious effects.The study findings showed that perception of occurrence and diagnosis of endometriosis is rather a complex issue. However, both patients and physicians indicated that they were seeking for reliable diagnostic indicators. Perhaps the findings from this study could help to decrease the diagnostic delay in endometrosis.None of the authors have any conflicts of interest to report.HR was the main investigator and carried out the study. NT and SZ supervised the study. EM was the study advisor and involved in data analysis. EH was the statistical advisor to the study. AM critically evaluated the manuscript and contributed to the writing process and prepared the final draft. All authors read and approved the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6874/14/103/prepub


To promote effective management of cancer pain as a nationwide health policy, it is necessary to monitor the performance of health care providers in managing pain in their patients. To plan a system that monitors the performance of pain management, the exact methods of measurement, including the range of target patients, and estimate the resources must be defined. Performance in pain management can be evaluated either in all patients with cancer or restricted to patients with cancer who are already taking analgesics. Restricting the target patient group to patients on analgesics may be more efficient but the extent of that efficiency remains uncertain.Using insurance claims from eight employer-sponsored insurance companies, we analyzed data from patients (N = 2858) who had received anti-cancer treatment  for the five major cancers in Japan .Overall, 22.9% of patients received some kind of analgesic prescription in the course of a month. Lung cancer patients were more likely to be prescribed analgesic prescriptions  than patients with the other four cancers. The observed percentage of patients who received analgesic prescriptions over the study period  decreased.If we limit the target patient group to patients with cancer already on analgesics, we can reduce the number of persons to be contacted by about three-fourths, compared to assessing pain in all patients with cancer. Although we do not wish to ignore the problem of undetected pain among patients with cancer, beginning our systematic evaluation with patients with cancer already on analgesics may be a realistic option. While pain is the most focused-on part of palliative care in cancer patients , managemConcern over low opioid consumption in Japan has led policy makers to pay extra attention to pain control. The Cancer Control Act of 2007, which delegated comprehensive responsibility for cancer control to the Japanese government, specifically states that both national and local governments should “take measures to enable palliative care, such as pain control, from the early stages of cancer care processes” . And TheOne way to foster adequate pain management in hospitals throughout Japan would be to establish a system to monitor their pain management programs. Measurement and feedback of hospital performance of pain management, preferably in comparison to other medical facilities, would motivate hospitals to improve their pain management . EstabliThere are several ways to define the target patients who need pain management. The ideal way, which would be to include all patients with cancer who suffer from any kind of pain, would require a process of asking all patients with cancer (perhaps before definitive diagnoses are made) about their pain, since some patients may not have discussed their pain with their health providers. An alternative way may be to target only patients under some type of pain management or patients taking analgesic drugs. This way overlooks patients with pain not recognized by health providers, and thus fails to consider providers’ ability or efforts to thoroughly detect patients’ suffering. On the other hand, because this way does not rely on obtaining patients’ reports, it provides a more defined range of target patients and saves the time and effort of interviewing individual patients about pain.While the theoretical limitation associated with focusing on patients already being treated for pain is clear, an important unanswered question is: How much labor can we expect to save by limiting the number of target patients? We have found no studies in the literature that report the percentage of patients with cancer being treated for pain in Japan. Although surveys from other countries have reported their prevalence of pain , 2012)). Relatively small companies who do not work with associated insurance company provide coverage through the Japan Health Insurance Association. Unemployed or retired persons and persons aged 75 years or older have coverage based on their place of residence from city or region-based insurance entities, respectively.Health services are reimbursed on a fee-for-service basis according to a nationally defined fee schedule. The healthcare facilities submit claims every month for each patient. The claims list all the services and medications provided to patients in the facility as well as the diagnoses corresponding to those services and medications. For patients who receive drug prescriptions, claims for the medications are submitted by the pharmacy that has dispensed the prescription. These pharmacy claims also contain the names of the prescribing facilities, thus providing links to the prescribing claims.For our study, eight insurance companies provided data from a total of 750 000 members consisting of the employees of affiliated companies and their dependents. Among them, three insurance companies provided claims from January 2005 to December 2009 and five provided claims from January 2008 to December 2009. The claims from these eight insurance companies included a total of 84652 patients with any type of cancer diagnosis, including tentative diagnoses. To avoid ambiguity of diagnosis on the insurance claims, we analyzed data on patients who had received anti-cancer treatment for the five major cancers in Japan, namely, breast, colorectal, stomach, lung, and liver cancers. Anti-cancer treatment included surgery, chemotherapy, hormone therapy, and radiation therapy. We excluded patients who had undergone only endoscopic treatment, because we suspected that cancer painmay not have been an issue for them.Analgesic drugs were classified according to the World Health Organization Pain Control Ladder ; non-steThe proportion of analgesic prescriptions were compared between patients’ treatment phases  and primary cancer site. Definition of the treatment phase was based on the last anti-cancer therapy. For example, patients who received surgery followed by chemotherapy (at a later time) were considered to be “after surgery” for the period between surgery and chemotherapy, and “after chemotherapy” after the chemotherapy had been received. Primary cancer sites were determined on the basis of both the cancer treatment and diagnosis recorded on insurance claims. For those patients who had undergone surgery, including site-specific intervention , the primary site of cancer was considered to be the target organ. For those patients who had received only systemic chemotherapy, where the target cancer had not been clearly established, or radiation therapy where the insurance reimbursement code was the same across different target sites, the diagnoses in the insurance claims were accepted as they had been recorded. The differences in the proportions were statistically tested using the chi-square tests.The trend of prescribing analgesic drugs for cancer patients was described as the proportion of patient-prescribed analgesic drugs among the cancer patients who had used any health services during a given month. The person-month was the unit of analysis. The change in the trends was analyzed graphically. Also the beta coefficients to represent the trend was calculated using linear regression analyses where the percentage of analgesic prescriptions and the time variable were the dependent and independent variables, respectively, assuming the linearity of the relationship. Because the assumption of homoscedastic errors did not hold for some regression models, the robust standard errors were calculated with the White correction. No correlation between error terms and the independent variable was confirmed. All analyses were performed using Stata 11.2 .A total of 6656 patients had one of the five major cancers on the health insurance claims, among whom 2585 patients received treatment with surgery, chemotherapy, and/or radiotherapy during the study period, and thus were entered into the analyses. Patient characteristics are presented in Tables Our study, using health insurance claims data from employee-sponsored insurance companies, showed that about one fourth of the patients treated for the five major cancers in Japan received analgesic prescriptions. Since the patients counted in our study were in treatment, the true prevalence of pain that include patients with pain but not in treatment among these patients will be higher. Restricting our target group of patients to patients taking analgesic medications will facilitate selection of patients for evaluating the performance measurement of pain management. By selecting patients in treatment for this evaluation, we will be getting by with only one-fourth to one-fifth of the all the patients. In addition, restricting our target group to patients taking analgesic medication is likely to be more efficient for systematic evaluation purposes than identifying and assessing patients with pain from all patients with cancer.It must be noted that our study neither implies that identifying patients with untreated pain is of little value nor does it advocate limiting target patients for the monitoring of pain management. Although the prevalence of pain among Japanese patients with cancer is unknown, the prevalence of analgesic prescriptions is much lower than prevalence of pain itself reported in other countries. One systematic review showed that about half of all diseases stages and a third of patients after curative treatment reported pain , the gapWe need to implement better pain management for cancer pain nationwide. While we are not satisfied with a limited target patient group for assessment in planning a nationwide system, we understand that starting with a limited group is a realistic option. Uniform application of the assessment with clear definition is essential to encourage improvement. Even if we start small, we will eventually assess all patients with cancer who are experiencing pain and ensure that they have access to pain management and appropriate treatment.In order to work toward a nationwide pain management system for cancer pain, we need to be cautiously aware of the nature of the data to be used and the findings on opioid consumption in Japan. The decreasing trend of patients receiving analgesic drugs in the observed data may be associated with the composition of patients in treatment phases shifted from acute-phase dominant to chronic follow-up phase dominant over time. Because we enrolled patients from the month in which they began cancer therapy and followed up later, patients under observation in the early years of the study period were usually enrolled right after the treatment, making them more likely to receive analgesic medications for pain that arose from the anti-cancer treatment . In the later years of the study we observed patients both in regular follow-up and patients receiving acute treatment. Thus, a larger proportion of more stable patients in regular follow-up may have caused the overall proportion of analgesic prescriptions to decrease. Nonetheless, the decrease was not steep and therefore did not greatly influence our findings.The impact of the insurance claims on our findings also warrants mention. First, the insurance companies that provided the data were employer-sponsored. As such, they exclusively enroll employees and employees’ dependents. We suspect therefore that our target patient group tended to be younger than the average cancer patient. In fact, while the national statistics on the hospital-based cancer registries showed that most cancer patients to be in their 60s and 70s , most ofOur study showed the prevalence of analgesic prescriptions among five major cancers in Japan. When planning for a system that monitors the performance of pain management, it is important to balance the resources used with the range of the target for the measurement. The frequency of analgesic prescription provided information for an evidence-based discussion on how to restrict or broaden the target population for monitoring using available resources. Even if we decide to begin systematic evaluation with a smaller target patient group , we will do so keeping in mind that our ultimate goal is to provide pain relief to all patients with cancer in our country.


Sipuleucel-T has demonstrated improved overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC). This analysis examined the effect of sipuleucel-T on time to disease-related pain (TDRP) and time to first use of opioid analgesics (TFOA) in mCRPC using data pooled from three randomized phase III studies in men with asymptomatic or minimally symptomatic mCRPC (D9901 (NCT00005947), D9902A (NCT01133704), D9902B ).Four-hundred and twenty-eight asymptomatic patients were analyzed for TDRP; 737 patients were analyzed for TFOA. Pain status was collected using logs adjudicated by blinded, independent reviewers. Opioid use for cancer-related pain was identified from medically reviewed reports of concomitant medication. Disease-related pain was defined as pain post enrollment. TDRP and TFOA were analyzed using the Kaplan–Meier method and Cox regression.P=0.170; median TDRP 5.6 months for sipuleucel-T and 5.3 months for control, respectively), although 39.3% of sipuleucel-T-treated patients and 18.9% of control patients were pain-free at 12 months. However, there was a significant delay in TFOA with sipuleucel-T . Median TFOA for sipuleucel-T was 12.6, and 9.7 months for control, with 50.6% and 43.1% opioid-free at 12 months, respectively. Kaplan–Meier curves for both end points began to diverge at 6 months.Treatment with sipuleucel-T was not associated with a significant difference in TDRP (hazard ratio (HR)=0.819; 95% confidence interval (CI): 0.616–1.089; Sipuleucel-T was associated with longer TFOA but not significantly longer TDRP. Both end points demonstrated evidence of a delayed treatment effect, consistent with an active immunotherapy. Data regarding these attributes were prospectively collected in three clinical trials evaluating sipuleucel-T , and provided an opportunity to explore these pain-related end points.The presence of pain in patients with metastatic castration-resistant prostate cancer (mCRPC) is an adverse prognostic marker for survival.4 The efficacy and safety of sipuleucel-T in asymptomatic or minimally symptomatic mCRPC have been investigated in three phase III trials. D9901 (NCT00005947) demonstrated a significant reduction in the risk of death with sipuleucel-T versus control.4 In D9902A (NCT01133704) a trend towards improved survival was observed despite early discontinuation of enrollment.5 The pivotal IMPACT trial (D9902B (NCT00065442)) demonstrated a significant 22% reduction in the risk of death (P=0.03) with sipuleucel-T versus control and a 4.1-month improvement in median overall survival (OS).6Sipuleucel-T is an autologous cellular immunotherapy designed to stimulate an immune response against the prostate tumor antigen prostatic acid phosphatase.6 Given the similar study designs, a post hoc pooled analysis was undertaken to increase the sample size and improve the precision of treatment-effect estimates. TDRP was analyzed for all patients known to be asymptomatic at enrollment. TFOA was evaluated for all patients, irrespective of their symptomatic status at enrollment.In all three trials, TFOA and TDRP data were prospectively collected in a blinded fashion and TDRP was a prospectively defined end point.6 All trials enrolled patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1, average weekly pain score <4  at registration, and no visceral metastases. D9901/D9902A recruited only asymptomatic patients but with any Gleason score (GS). IMPACT initially enrolled only asymptomatic patients with GS ⩽7, but was amended following data review from D9901 and D9902A to include patients with any GS and minimally symptomatic disease . Pain correlating with a site of metastatic disease was allowed provided it met the above pain score criterion. TDRP was a secondary end point in D9901/D9902A, and data were intended to be pooled. Originally, in IMPACT, TDRP was a co-primary end point and TFOA was a secondary end point; both end points were removed as the protocol amendment allowed symptomatic patients and TDRP became irrelevant.n=428) included all randomized patients in D9901 (n=127) and D9902A (n=98), and asymptomatic patients from IMPACT randomized prior to the protocol amendment (n=203). The intent-to-treat population for the TFOA analysis (n=737) included all randomized patients in D9901/D9902A/IMPACT.The intent-to-treat population for the TDRP analysis (6 and were followed until disease progression (PD). After central confirmation of PD, patients were treated at the physician's discretion. Control patients could join an open-label salvage protocol and receive APC8015F, a product manufactured similarly to sipuleucel-T but from the remaining cells cryopreserved when the control was prepared.Patients were randomized 2:1 to receive sipuleucel-T or controlStudies were conducted in compliance with US Food and Drug Administration and Good Clinical Practice guidelines, and met local Institutional Review Board approvals. Written informed consent was obtained from all patients.5 For IMPACT, the PD end point included only objective PD, defined as first progression of measurable or evaluable disease confirmed by an independent, blinded review committee.6 No study used serum PSA increase to measure PD.For D9901/D9902A, the PD end point included progression of measurable or evaluable disease , spinal-cord compression or pathological fracture at known disease site(s), developing a requirement for radiotherapy, or other clinically significant disease-specific events, including disease-related pain (DRP) or other symptoms.7 DRP was considered present if the patient had unusual pain or a ⩾3-point increase in intensity at a baseline pain site. In IMPACT, pain and medication use were recorded with weekly patient-completed logs and monthly investigator-completed logs. DRP was considered present if pain was reported at a new site and the average intensity was ⩾2, and/or if existing pain intensity increased by ⩾2 points from screening. Date of pain onset was identified via a blinded, dual review of pain logs and a ‘DRP' worksheet that was completed when DRP was identified.In all studies, pain logs were collected and adjudicated by blinded, independent reviewers. DRP was defined as pain with a quality and consistency of cancer-related pain that occurred after study enrollment and anatomically correlated with the site(s) of radiographically demonstrated disease. In D9901/D9902A, onset of DRP and opioid analgesic use (OAU) were documented using a weekly log. Patients rated their pain from 0 (no pain) to 10 (pain as bad as can be imagined) for three questions from the Brief Pain Inventory.In D9901/D9902A, pain and analgesic-use status was collected until DRP occurred or for 4 weeks following PD, whichever happened first. For patients without DRP by 4 weeks after PD, data were censored at the last available pain evaluation. In IMPACT, pain and medication status was collected until DRP occurred, regardless of the time since PD. Following protocol amendment, completion of pain logs was discontinued and data were censored at the last pain evaluation for patients who had not reached the pain end point.A blinded medical review identified OAU by preferred drug names in the coded concomitant medication information on case report forms, and excluded OAU unrelated to cancer pain. OAU was excluded for procedures, rigors related to infusions, lasting ⩽2 days, or clearly unrelated to cancer.TDRP and TFOA were defined as the time from randomization to first identification of DRP or OAU, respectively.post hoc power analysis indicated there was 80% power to detect an HR of 0.67 at the two-sided α=0.05 level. Similarly, based on 240 OAU events, a post hoc power analysis indicated there was 80% power to detect an HR of 0.68 at the two-sided α=0.05 level.The individual studies were underpowered for the TDRP and TFOA end points. Accordingly, statistical analysis was performed on pooled data. The statistical analysis plan for D9901/D9902A prespecified that TDRP data were to be pooled; these combined studies had 80% power to detect a hazard ratio (HR) of 0.52 at the two-sided α=0.05 level, provided that 80 pain events were observed. Prior to amendment, IMPACT had 90% power to detect an HR of 0.562 at the two-sided α=0.01 level, provided that 193 pain events were observed. Based on the 212 DRP events observed across the three studies, a P-values, HRs and 95% confidence intervals (CIs) were derived from a Cox regression model, adjusted for baseline PSA and lactate dehydrogenase (LDH) (both log-transformed). Integrated analyses were stratified by study.TDRP and TFOA were summarized using the Kaplan–Meier method. Two-tailed Post hoc exploratory analyses were conducted using two separate Cox models, stratified by study and employing stepwise selection, to identify independent predictors of TDRP or TFOA from the following: previous chemotherapy, hemoglobin, PSA, alkaline phosphatase, LDH, age, number of bone metastases, bisphosphonate use, GS, ECOG PS, weight, time from diagnosis to randomization, previous primary radiotherapy, race (Caucasian versus others), presence of soft tissue disease, and prior radical prostatectomy. Treatment arm (sipuleucel-T or control) was included in the resulting models to assess treatment effect after adjustment.8 predicted that survival for the sipuleucel-T and control arms, respectively, was comparable for the TDRP (21.6 and 21.5 months) and TFOA (20.1 and 20.1 months) populations. Of control patients, 99 (67.8%) in the TDRP population and 165 (66.3%) in the TFOA population subsequently received APC8015F following PD.PD was documented in most of the 428 patients analyzed for TDRP, with 243/282 (86.2%) sipuleucel-T and 132/146 (90.4%) control patients progressing ; DRP wasP=0.170)  . Median P=0.170) . At 12 mP=0.170) . HoweverP<0.001); higher alkaline phosphatase ; younger age (per year decrease) ; bisphosphonate use ; and prior primary radiotherapy . When adjusting for these factors, results were comparable   .P<0.001). Median TDRP in IMPACT was 4 months. In patients with TDRP ⩽4 versus >4 months, respectively, median time to PD was 10.3 versus 34.7 weeks, and median OS was 22.3 versus 37.0 months.In IMPACT, where TDRP was recorded regardless of PD status, longer TDRP was associated with longer time to PD and OS (both n=737). OAU for reasons other than cancer-associated pain  was excluded and is summarized in Table 5. Most patients experienced PD, with 419/488 (85.9%) sipuleucel-T and 216/249 (86.7%) control patients progressing; OAU occurred in 153/488 (31.4%) and 87/249 (34.9%) patients, respectively.P=0.038)  . Median P=0.038) . TFOA reP=0.038)  similar P=0.046)  .9 and many experience associated bone pain and receive opioid analgesics.10 In addition to its obvious impact on quality of life, pain is an important prognostic factor in mCRPC. A retrospective study of 599 mCRPC patients showed a statistically significant impact of pain on survival time.1 Similarly, clinically significant pain was one of the most important independent prognostic factors for OS  in the pivotal docetaxel TAX327 study of 1006 mCRPC patients.2Approximately 90% of patients who die of prostate cancer have bone metastases,11 which is supported by the divergence of the TFOA and TDRP Kaplan–Meier curves after 6 months and the approximately two-fold increase in patients remaining DRP free at 12 months with sipuleucel-T versus control. Objective PD tended to predate DRP, which in turn preceded OAU . Given the suggested delayed effect of immunotherapy, the relative kinetics of these end points may explain the increasingly greater treatment effects observed on PD, TDRP and TFOA, successively.This analysis of pooled data from three randomized trials demonstrated a significant difference in TFOA for patients treated with sipuleucel-T versus control, but no significant difference in TDRP. Immunotherapies may show a delayed antitumor effect,12 Higher GS as an indicator for earlier TFOA is consistent with GS being a marker for more aggressive disease.8 There is no immediate explanation for the association of younger age or primary radiotherapy with shorter TDRP or TFOA. Importantly, the trend towards delayed TDRP and significantly delayed TFOA with sipuleucel-T versus control were maintained after adjusting for these factors, suggesting that any differences in baseline prognostic factors would not explain the TDRP or TFOA findings.In stepwise logistic regression analyses, several baseline factors were prognostic for earlier TDRP or TFOA. The association of higher PSA, alkaline phosphatase, LDH, number of bone metastases and ECOG PS with shorter TDRP and/or TFOA is consistent with these being baseline markers of more advanced disease. Although the shorter TDRP in patients receiving bisphosphonates seems counterintuitive, bisphosphonate treatment is more common in patients with a higher disease burden. Androgen deprivation therapy treatment is associated with a high risk of clinical fractures so current NCCN guidelines recommend that patients receiving androgen deprivation therapy should also receive bisphosphonates  when there is an absolute fracture risk.The delayed antitumor effect of sipuleucel-T may account for the greater treatment effect on later events, such as OAU (TFOA), relative to earlier events, such as DRP (TDRP), or even earlier events such as PD (time to PD). However, the lack of statistical significance versus control for TDRP could also be due to the large amount of censoring (50.5% of patients) and the relatively small sample size  to detect a true HR of 0.80).Two randomized phase III studies (NCT01057810 and NCT00861614) are currently evaluating ipilimumab versus placebo for CRPC using pain-related secondary end points. Furthermore, confirmed pain response is the primary outcome (data anticipated in Q3 2014) in the randomized COMET-2 phase III study (NCT01522443) that is evaluating cabozantinib versus mitoxantrone plus prednisone in men with previously treated symptomatic CRPC.post hoc nature. For example, while the medical review that was used to exclude OAU unrelated to cancer pain was blinded, the criteria were identified post hoc and may have led to differential exclusion favoring one arm over the other. Other limitations are the high degree of censoring and the fact that, individually, each study was not adequately powered for TDRP or TFOA analysis, requiring data pooling.This analysis has several limitations, most notably its Nevertheless, this analysis has demonstrated a significant delay in TFOA across the pooled population, irrespective of baseline symptomatic status. The TFOA findings and trend in TDRP are consistent with the delayed antitumor effect reported with immunotherapy in this patient population, and suggest that further study of clinical end points proximate to OS (such as TDRP and TFOA) is warranted.


Traditional management of wrist arthritis consists of proximal row carpectomy, partial carpal fusions, or, in the event of pancarpal arthritis, total wrist fusion. Although proximal row carpectomy and partial wrist fusions preserve some motion at the wrist while relieving pain symptoms, the quality of results obtained from these procedures is not predictable or optimal in many instances. Total wrist fusions are credited with universal pain relief at the expense of wrist motion. However, critical analysis of the results of total wrist arthrodesis shows that the results are not always consistent with what has been claimed and that pain relief is unpredictable at best. In a recent study, 14 of 22 patients who had undergone wrist arthrodesis had residual pain, and 4 of these patients had severe pain 6 years later. In another study, only 6 of 36 patients remained pain-free 4 years after wrist arthrodesis.Moreover, many patients do not like loss of motion in their wrists. In a study of wrist arthrodesis, only 40% of patients were satisfied at 1 year. In another study, 100% of patients who had wrist arthrodesis indicated that they would have a procedure performed so they could move their wrists again.Management of hip, knee, ankle, and shoulder joints has evolved from arthrodesis to arthroplasty. The wrist joint awaits the same pattern of evolution with the advent of reliable designs.In this presentation, I will first describe the design rationale of the Stryker ReMotion Total Wrist arthroplasty along with historical antecedents. Next, I will outline the technique of implantation with tips and tricks for special situations. Finally, I will discuss 10-year results and comment on future prospects of total wrist arthroplasty.


Both groups demonstrated changes in pain VAS score, grip strength, and DASH questionnaire. Lateral epicondylalgia patients who received manipulation treatment felt pain relief sooner than those who had acupuncture treatments during the first few treatments. However, both acupuncture and manipulation are effective, while the difference has no significance at the 8-week follow-up. The trial was registered with Current Controlled Trials ISRCTN81308551 on 5 February 2016.Radial bone adjustment manipulation treatment may be effective to reduce pain rapidly in lateral epicondylalgia patients and the pathological tension in the biceps brachii muscle is highly concerned. To prove this hypothesis, we conducted a randomized controlled trial and included 35 patients with lateral epicondylalgia for more than 2 months. Either manipulation treatment ( Lateral epicondylalgia is usually a self-limiting condition; however, symptoms may persist for over 1 year in up to 20% of patients –5. The mAlthough lateral epicondylalgia is highly prevalent, effective treatments are controversial, and combined nonpharmacological treatments are recommended. A recent review of nonsurgical treatments for tennis elbow includes corticosteroid injection, iontophoresis, botulinum toxin A, prolotherapy, platelet-rich plasma or autologous blood injection, bracing, physical therapy, shockwave therapy, and laser therapy; however, the results of these treatments remain nonconclusive –10. SurgWe hypothesized that pathological tension in the biceps brachii muscle is related to lateral epicondylalgia according to our clinical experience and physiopathological association. To test this hypothesis, we conducted a clinical trial and investigated the effect of radial bone adjustment therapy on pain relief during rest, daily activity, and work in patients with lateral epicondylalgia. In addition, we evaluated functional improvement and grip force change in this study and all assessments were measured in acupuncture too.In this single-center, prospective, randomized controlled trial, the enrolled patients with lateral epicondylalgia were either transferred by other doctors in Chinese medicine department or those who saw the information on the bulletin board in Chang Gung Memorial Hospital. These patients were screened for eligibility on the basis of the diagnostic criteria including (1) aggravation of the lateral elbow pain during wrist extension and relief at rest, (2) tenderness of the lateral epicondyle, and (3) positive Cozen's test. However, inclusion criteria were as follows: (1) elbow pain for >2 months, (2) unilateral elbow pain, (3) no improvement in the condition despite receiving treatment in previous 4 weeks, and (4) visual analog scale (VAS) score >30 millimeters. This study excluded patients who had central or peripheral nervous system diseases, radial nerve entrapment, inflammatory rheumatic disease, gout, or radiocapitellar osteoarthritis, underwent operation for lateral epicondylalgia, or were pregnant. After screening, the patients were randomly assigned computer-generated numbers and, then, divided into an acupuncture group and a manipulation group.Informed consent was obtained from all participants orally and in writing. The protocol of this trial is approved by the Chang Gung Memorial Foundation, Taipei, Taiwan (IRB number: 99-1544A3). Rheumatology published by the Hannover Medical School, Germany  for recording changes each time before treatment procedure in three states, rest, daily activity, and work situations, from the beginning of the study up to 8 weeks following. For functional impairment, we measured it using the Disability of Arm, Shoulder, and Hand (DASH) questionnaire (developed by the Upper Extremity Collaborative Group) , 18. PatU test was used to perform between-group comparisons of primary and secondary endpoints. All reported p values were two-sided and the value less than 0.05 seems statistically significant. No interim analysis was performed.Efficacy analyses were performed for all patients assigned to the treatment. The Wilcoxon signed rank test was used to perform within-group comparisons of primary and secondary endpoints. The Mann-Whitney Patients were enrolled from March 2011 to September 2012 and were followed up for 8 weeks after the end of treatment. Of the 53 eligible patients, 18 were excluded. The remaining 35 patients were randomly assigned to the manipulation or acupuncture group. In total, 16 patients were allocated to the manipulation group and 19 patients to the acupuncture group. In the acupuncture group, two of the 19 patients did not complete treatment because of incorrect time coordination. We used the first time data as the baseline and included the last time data in the analyses . In addip < 0.001, work: baseline: 62.13 ± 16.28 versus 8-week follow-up: 25.01 ± 15.74, p < 0.001; acupuncture: daily: baseline: 51.72 ± 23.04 versus 8-week follow-up: 29.68 ± 21.51, p = 0.002, work: baseline: 65.03 ± 25.48 versus 8-week follow-up: 33.57 ± 24.05, p < 0.001). We also found pain VAS for daily activity at the third treatment changed obviously in manipulation group, whereas acupuncture group showed no difference at the same time . No significant changes were observed in pain VAS scores at rest in the acupuncture group during 10-week period . In contrast, significant changes were observed in pain VAS scores during rest in the manipulation group  and, more interestingly, the manipulation group exhibited rapid improvement in functional impairment at the end of treatment , whereas a significant difference was observed only in the acupuncture group for grip strength (maximum) , positional faults and subluxations are the main causes of pain, and reversal of positional faults can rapidly alleviate pain and improve functional impairment , 20. TheThe biceps brachii muscle is the major supinator of elbow and it is attached to the radial tuberosity. Pathological tension of biceps brachii muscle presented by muscle spasm causing lateral rotation of the radial bone passively according to physiopathology in patients with lateral epicondylalgia . The supThe previous studies showed the pain reduction mechanism using manipulative therapy related to spinal cord hyperexcitability, especially sensory hypersensitivity exhibited in nociceptive pathway by peripheral afferent stimulation . In addiAcupuncture is also a convenient and economical option for treating lateral epicondylalgia. In a trial conducted in the Hannover Medical School, Germany, pain reduction and functional improvement of the arm were observed in early follow-up after the acupuncture treatment . The samBrain image with fMRI supports that traditional acupuncture point stimulation activates different response from stimulation at other points on same spinal segment . MoreoveAcupuncture is more impressive than manipulation in grip strength changes, especially in maximum grip strength. Since collagen type I is the major tendon structure component, the possible reason may be that acupuncture stimuli increase synthesis of collagen type I concentration and reorganize it by anti-inflammatory and mechanotransduction molecular pathways . HoweverBoth groups demonstrated well changes in DASH questionnaire and it presented improvement of quality and quantity of life and functional impairment. In our study, the patients who received manipulation treatment showed faster improvement than acupuncture group during treatment period, but both were effective at the 8-week follow-up. The possible reason may be that the subjective sense of our patients about quality of daily activity is more related to painful sensation than the real grip strength.Compared to other invasive reports, the total cost of the procedure in our study in Taiwan is approximately NT$4000 (US$120) and is covered under the National Health Insurance. This technique provides definitive intervention for recalcitrant tendinopathy without any drug or surgery, which would require huge cost and resources.Additional studies using ultrasonographic assessment for demonstrating the changes in the histology and pathology after these treatments are still warranted. Furthermore, other opioid peptides would not be antagonized by naloxone  and radiThe novel manipulation technique improved pain in patients with lateral epicondylalgia (tennis elbow) during the first few treatments till 8-week follow-up.


Objective. The aim of this preliminary study was to determine whether psychiatric disorders, psychopathological symptoms, and alexithymia are associated with endometriosis in an Italian population. Study Design. A preliminary study comprising 37 Italian patients with surgically confirmed endometriosis and 43 controls, without clinical and ultrasound signs of endometriosis, was carried out. Both patients and controls were evaluated for the presence/absence of psychiatric disorders, psychopathological symptoms, alexithymia, and pain symptoms . Results. Statistically significant differences were found between cases and controls for prevalence of mood and anxiety disorders, malfunctioning on obsessive-compulsive subscale (P < 0.01) and depression subscale (P < 0.05) of the Symptom Checklist-90-Revisited (SCL-90-R), and higher alexithymia levels (P < 0.01). Patients with endometriosis-associated pain showed greater prevalence of psychiatric disorders compared to pain-free patients but that difference was not significant. Significant correlation was found between malfunctioning in some SCL-90-R dimensions and pelvic pain, dysmenorrhea, and dyspareunia scores at the visual analog score (VAS). Conclusion. Some psychopathological aspects, such as psychoemotional distress and alexithymia, are more frequent in women with endometriosis and might amplify pain symptoms in these patients. Endometriosis is a gynecological condition characterized by the presence of ectopic endometrial tissue  outside of the uterus associated with pelvic pain and infertility . The disThe aim of the present study was to preliminarily evaluate the role of psychopathological symptoms, comorbid psychiatric disorders, and alexithymia in endometriosis patients compared with healthy women.Thirty-seven Italian Caucasian women with endometriosis (mean age 35 ± 7.6 years), ranging from unskilled workers to university graduates, were included in the study. Patients were recruited from the Department of Gynecology and Obstetrics, “Sapienza” University of Rome, Italy. Diagnosis of endometriosis was achieved by laparoscopy and histologic analysis. Twenty-one of them (56.8%) had ovarian endometrioma, while sixteen (43.2%) had ovarian endometrioma and peritoneal endometriosis. No other comorbid physical conditions were present. As healthy controls, 43 women from the same ethnic area, referred to the gynecological clinic for a gynecological control, were enrolled, mean age of 34.9 ± 10.1 years and medical history, vaginal pelvic examination, and ultrasound (US) imaging with color Doppler flow evaluation negative for endometriosis. The ethical committee of the “Sapienza” University of Rome approved the study protocol and all subjects provided their informed consent.Patients were evaluated for the presence/absence of symptoms . Pain intensity was assessed by a 10-point visual analogue scale (VAS) with 0 representing no pain and 10 representing the worst pain .Assessment of psychiatric disorders was performed using the Structured Clinical Interview for DSM IV Axis I Disorders Clinical Version (SCID-I cv)  for eachThe presence of psychopathological symptoms was investigated using the Symptom Checklist-90-Revised (SCL-90-R), a 90-item self-report instrument that has been designed to evaluate a broad range of psychological problems and symptoms of psychopathology . We consThe Toronto Alexithymia Scale (TAS-20) was used to assess alexithymia. It consists of 20 self-report items and has 3 subscales: Difficulty Describing Feelings (F1), Difficulty Identifying Feelings (F2), and Externally Oriented Thinking (F3). A TAS-20 total score ≥ 61 is diagnostic for alexithymia .χ2 or Fisher's exact tests were used to compare differences between categorical variables, whereas those between continuous variables were determined by Student's t-test or Mann-Whitney U test. Spearman's rho correlation coefficient was applied to analyze nonparametric correlations. A P value < 0.05 was considered statistically significant. Test results from the nine SCL-90-R subscales were processed by ARC90 v1.2.1 software [Basic statistical analyses were performed with the Statistical Product and Service Solutions software (SPSS) version 17.0 WIN program . The software . t = −0.034, P = 0.973), educational status , marital status , and occupational status . Pain evaluation showed higher dyspareunia and pelvic pain VAS mean scores in patients with endometriosis than in controls, while no differences were observed for dysmenorrhea VAS mean scores ; the relative percentages of each disorder are shown in P = 0.0342).The frequency of psychiatric disorders was 54.0% in patients and 18.6% in controls  and depression subscales . Mean ranks comparison performed with Mann-Whitney U test showed statistically significant differences between patients and controls group in relation to TAS-20 total score (P < 0.01), Difficulty Identifying Feeling (P < 0.05), and Externally Oriented Thinking (P < 0.01). Comparing SCL-90-R and TAS-20 results in the presence/absence of comorbid psychiatric disorder groups, no differences were found in frequency distribution and mean ranks comparison. In the patients group, the analysis of VAS mean scores  in absence/presence of comorbid psychiatric disorders , malfunctioning in SCL-90-R subscales, and alexithymia in TAS-20 showed that significant differences were present for chronic pelvic pain and dysmenorrhea  and psychopathological symptoms or VAS mean scores did not show significant results.This preliminary study aimed to explore the possible role of psychiatric comorbidity, psychopathological symptoms, and alexithymia in endometriosis and their correlation with pain symptoms.Even if in our study no statistically significant differences were observed between cases and controls regarding frequency of a specific Axis I DSM IV-TR diagnosis, the prevalence of psychiatric disorders was statistically higher in patients than in controls and a statistically significant difference was also found for mood and anxiety disorders and malfunctioning on obsessive-compulsive and depression SCL-90 subscales.In the present study psychiatric comorbidity of patients with endometriosis was lower than that reported by previous studies –17. AlthData analysis revealed some interesting results: (1) patients with endometriosis showed higher scores on TAS-20 total score, Difficulty Identifying Feeling, and Externally Oriented Thinking (that indicates an inadequate introspective ability) than controls; (2) among patients with endometriosis, greater chronic pelvic pain VAS score was observed in patients with alexithymia ; (3) a statistically significant correlation was found between TAS-20 total score, Difficulty Describing Feelings, and Difficulty Identifying Feelings and chronic pelvic pain and dyspareunia VAS scores in patients group. These findings could suggest that the difficulty to recognize feelings and emotions in endometriosis patients may facilitate somatization, that is, the expression of psychological problems on a somatic level. Similar assumptions could be done also in relation to malfunctioning in somatization and sensitivity SCL-90-R subscales, correlated with higher chronic pelvic pain and dysmenorrhea (only somatization) VAS scores. Finally, the observed greater chronic pelvic pain VAS scores in patients with malfunctioning in anxiety and obsessive-compulsive SCL-90-R subscales were in line with what was shown by previous studies regarding the possible association with the presence of psychiatric comorbidity  and pelvic pain in patients with endometriosis. In addition, our study highlighted the prevalence of a greater dysmenorrhea VAS score in patients with comorbid psychiatric disorders and those with malfunctioning in obsessive-compulsive SCL-90-R subscales, while no significant correlations were found between the type of endometriosis and the presence of psychopathological symptoms or pain symptoms.Even if in our study we could not find a specific association with certain psychopathological features and the presence of endometriosis, however the subgroups of patients with chronic pelvic pain, dysmenorrhea, and dyspareunia were characterized by the presence of a specific grade of psychopathology that could play a role in pain perception and reaction.The small sample size of this preliminary study certainly represented a limitation and did not allow us to determine a specific causality relation between some psychological features and endometriosis onset or pain perception or to exactly identify specific risk factors. Therefore, these preliminary findings need to be confirmed by further investigations and increasing the sample size.However, this study highlighted some significant characteristics. Indeed, these results suggested that some mood and psychiatric characteristics such as mood and anxiety disorders, higher alexithymia levels, and malfunctioning on obsessive-compulsive and depression dimension are more frequent in women with endometriosis than in general population. Moreover, these psychopathological conditions could be correlated with moderate-severe pain symptoms and could influence pain perception in endometriosis patients.


Objective. The objective of this study was to evaluate the regression of temporomandibular pain as a result of intra-articular injections of platelet-rich plasma (PRP) to patients with temporomandibular joint dysfunction previously subjected to prosthetic treatment. Materials and Methods. The baseline study material consisted of 10 patients, both males and females, aged 28 to 53 years, previously treated due to painful temporomandibular joint dysfunction using occlusal splints. All patients were carried out to a specialist functional assessment of the dysfunction using the Polish version of the RDC/TMD questionnaire axis I and II. Intra-articular injections were preceded by a preparation of PRP. The injection sites were determined by the method used during arthroscopic surgical procedures. Following aspiration, 0.5 mL of plasma was injected into each temporomandibular joint. Results. The comparison of the intensity of pain during all examinations suggests a beneficial effect of the procedure being performed as the mean VAS score was 6.5 at examination I, 2.8 at examination II, and 0.6 at examination III. Conclusion. Application of the intra-articular injections of platelet-rich plasma into the temporomandibular joints has a positive impact on the reduction of the intensity of pain experienced by patients treated for temporomandibular joint dysfunction. A number of conservative methods are used in the treatment of temporomandibular joint dysfunction pain syndrome, including occlusal splints of various designs, supportive physical therapy procedures, rehabilitation involving muscular training, and specialist psychological support –10.Intra-articular administration of medications is an established method of treatment, particularly in orthopedic and rheumatic disorders associated with pain, effusion, inflammation of cartilage, and bone and joint capsules as well as fibrous adhesions. Currently, agents used for intra-articular injection within the temporomandibular joint regions include hyaluronic acid and steroids , 12.Although autogenous platelet-rich plasma (PRP) concentrates were developed in the 1970s, the medical use of these materials was facilitated only by subsequent technological advances, particularly by progress in medical instrumentation. In 1997, Whitman et al. were the first to present a method for preparation and use of platelet-rich plasma to accelerate healing processes. Centrifugation of full autogenous blood yields a platelet concentrate with platelet concentration of ca. 1 million cells per cubic millimeter of plasma. The concentrate is produced in the process of collecting peripheral vein blood (most commonly from the ulnar vein) directly from patients, with blood being centrifuged during the procedure. To date, platelets were demonstrated to contain more than 30 growth factors, the most important of them being the platelet derived growth factor (PDGF), transforming growth factor (TGF), epidermal growth factor (EGF), insulin-like growth factor (IGF), and vasoendothelial growth factor (VEGF) –21.Platelets are anuclear, flat disc-shaped cells formed in bone marrow; about 30% of all platelets are found in the spleen. The life span of platelet cells ranges from 8 to 12 days; cells are eliminated by the mononuclear phagocyte system. When in the interphase, platelets have no thrombogenic potential; thrombin is required for their activation which involves a change in the shape and the release of granules. The main function of the platelets is the control of hemostasis. Platelets form hemostatic plugs at injury sites, participating in blood coagulation processes. Wound healing starts with platelet thrombus formation, platelet degranulation, and the release of growth factors. The next stage involves fibroplasia and angiogenesis followed by the synthesis of structural connective tissue elements. This leads to increased resistance to wound disruption and then to scar remodeling. New collagen is generated owing to chemotactic and mitogenic effects of FGF on fibroblasts, stimulating proliferation and differentiation of keratinocytes thanks to the presence of highly concentrated growth factors , 18.Platelet-derived growth factors contained in the concentrate are peptides that stimulate proliferation, differentiation, and migration of cells. These properties determine the usefulness of growth factors in the healing process. Most growth factors present within the platelet-rich plasma have mitogenic properties leading to an increase in the repair cell counts. Growth factors derived from centrifuged blood were used for the first time by Knighton in patients with chronic skin ulcerations .Platelet-rich plasma contains proteins that are responsible for cell adhesion, namely, fibrin, fibronectin, and vitronectin. It stimulates tissue regeneration processes by stimulating fibroblasts to produce structural proteins for use in formation of new collagen and elastin, support of remodeling and angiogenesis (formation of new vessels), and activation of mesenchymal stem cells. PRP is widely used in surgical procedures, in the treatment of burns and extensive, difficult-healing wounds, orthopedic ligament injuries, and connective tissue injuries. An additional advantage of this method is the safety of the material and a zero possibility of hypersensitivity to injected plasma. It should be kept in mind that blood and plasma may be carriers of pathogens such as HIV, CMV, EBV, or HCV, and therefore precautions should be used consisting of appropriate staff apparel and patient behavior , 21, 22.The objective of this study was to evaluate the regression of temporomandibular pain as a result of intra-articular injections of platelet-rich plasma to patients with temporomandibular joint dysfunction previously subjected to prosthetic treatment.The baseline study material consisted of 10 patients, both males and females, aged 28 to 53 years, previously treated using occlusal splints, who reported at the Consulting Room of Temporomandibular Joint Dysfunctions of the Department of Dental Prosthetics of the Jagiellonian University Medical College in Krakow between 01.09.2013 and 20.05.2014 due to painful dysfunction of the stomatognathic system.All patients were carried out to a specialist functional assessment of the masticatory organ using the Polish version of the RDC/TMD questionnaire axis I and II (examination I). The following parameters were analyzed in detail for the purposes of this study: changes in the intensity of pain as reported by the patients with regard to temporomandibular joints and stomatognathic system muscles, pain intensity characteristics, level of impairment, and grade of chronic pain , 24.The assessment involved also a subjective assessment of pain within the stomatognathic system muscles and temporomandibular joints, evaluation of the range and symmetry of mandible motion, acoustic symptoms within the temporomandibular joints, and the impact of the masticatory organ health on overall well-being , 3, 23.The inclusion criteria included temporomandibular joint dysfunction pain manifested as lack of coordination in operation of articular heads and disc (disc translocation with or without disc blockade/crackling sounds/) and dysfunctions presenting with excessive masticatory muscle tone as the dominant problem and lack of benefits from previous treatment methods. All subjects reported that the pain had sustained for at least 3 months and that they continued the prosthetic treatment.The exclusion criteria included poor overall health, unwillingness to participate, numerous dental defects, diagnosis of a connective tissue disease, and dysfunctions classified as RDC/TMD groups IIIb and IIIc. Contraindications associated with the use of platelet-rich plasma  were also taken into account , 23, 24.Intra-articular injections of platelet-rich plasma were preceded by collection of peripheral blood from the ulnar vein of the patient in accordance witj the procedures in force using single-use, closed vacuum systems and glass tubes with sodium citrate as an anticoagulant . After mThe injection sites were determined by the method used during arthroscopic surgical procedures within the temporomandibular joints. Patients were prepared for the procedure by a line being drawn on their skin between the earlobe and the outer eye corner. Three segments were marked at 10 mm intervals starting from the earlobe. The lengths of the lines were 3 mm (first line), 5 mm (second line), and 7 mm (third line). The platelet-rich plasma injection site was marked by the tip of the third line corresponding to the upper compartment and retrodiscal zone . The skiThe following parameters were assessed in the specialist baseline examination and the follow-up examinations using the RDC questionnaire: the presence and intensity of spontaneous and palpation-induced pain within temporomandibular joints and masticatory muscles, the range and symmetry of mandible motion, abduction trajectory, and the presence of acoustic symptoms within temporomandibular joints during all mandible movements and accompanying symptoms such as squeaking sounds and tinnitus in ears. In one case, classified as RDC group IIb, active unblocking of the articular joint was first performed; the patient was subsequently qualified for platelet-rich plasma injection , 23.The results were subjected to statistical analysis using the basic procedures such as determination of means, standard deviations, medians, and post hoc ANOVA Friedmana statistical significance test.The group of patients qualified for the study consisted of two males and eight females. The mean age was 37.6 years. According to the results of baseline examinations, the patients reported for prosthetic treatment for the following reasons: pain within one or both temporomandibular joints, spontaneous or occurring at mandible movements, chewing, tight jaw occlusion, or joint palpation. The pain was located in the joints or the masticatory muscles, radiating into the temporal and cranial region in 2 cases. Joint crackling sounds were heard upon mandible movements by 4 patients, while a reduced range of mandible abduction was observed in 1 patient. The following diagnoses were made on the basis of RDC/TMD questionnaire axis I survey: 1 case of group I a, 4 cases of group II a, case of group II b, and 4 cases of group III a .The comparison of the intensity of temporomandibular joint and masticatory muscles pain at baseline and follow-up examinations suggests a beneficial effect of the procedure being performed as the mean VAS score was 6.5 at examination I, 2.8 at examination II, and 0.6 at examination III. The result of subsequent investigation differs in the statistically significant way Tables  and 4. IChronic facial pain is a common cause of impairment in the everyday activities of patients and requires numerous therapeutic procedures being initiated by physicians of different dental specialties as well as by neurologists, laryngologists, maxillofacial surgeons, and psychiatrists. This suggests a need for interdisciplinary treatment due to the complex character of complaints. Temporomandibular joint pain is a special problem as the mandible motion upon chewing and talking constitutes a stimulus for a significant increase in the pain being experienced , 31–34.Acoustic symptoms and tenderness on palpation (associated with hyperactivity) of mandible lifting muscles are an evidence of overloads located within the posterior disc ligament . The area is poorly accessible for application of healing-promoting drugs and the physical therapy procedures applied in these cases are not always satisfactory.Many researchers studying PRP treatments highlight the high efficacy of this method of management of musculoarticular disorders and its safety due to the use of autologous material as well as the low costs of treatment , 35–57.Daif compared the efficacy of intra-articular injections within the upper temporomandibular joint compartment and additional injections in the articular capsule region points out the superiority of the latter method for the treatment of dysfunctions involving disc translocation with no disc blocking . PRP is Today, the use of platelet-rich plasma has been expanded no include numerous indications after orthopedic surgeries to treat sports-related injuries. PRP is widely used for tissue healing in many anatomical regions as well as in the treatment of pathological lesions of bone, cartilage, ligament, and muscle tissues. The popularity of this novel treatment method triggered a rapid increase in research. However, differences in application techniques and PRP compositions make comparisons of efficacy results difficult. Potential complications following the procedures involving PRP administration are mild and therefore this method of treatment appears to be safe. It brings various potentially positive effects for the damaged musculoskeletal system tissues. Platelet-rich plasma injection is used with increasing frequency in reconstructive orthopedic procedures , muscle injuries, dental surgeries, and implantations , 45–51. A separate opinion suggesting the lack of confirmed benefits of PRP on musculoarticular tissue healing has been presented by Willits et al., who claim that the review of PubMed and Medline data performed in April 2013 does not warrant any positive opinions on the clinical use of this method .The results of our preliminary research suggest beneficial effects of platelet-rich plasma in intra-articular injections as a supplement to the basic prosthetic treatment of temporomandibular joint dysfunction. The reduction in pain and gradual restoration of functional capabilities of the stomatognathic system as the result of the treatment of interest raises hopes that future studies would lead to establishment of appropriate management algorithms.Additional intra-articular injections of platelet-rich plasma into the temporomandibular joints have a positive impact on the reduction in the intensity of pain experienced by patients treated for temporomandibular joint dysfunction.Determination of appropriate treatment algorithm making use of intra-articular injection in patients with temporomandibular joint dysfunction pain requires further studies and longer follow-up of the study group.Conclusions are as follows.


Background. Patients diagnosed with chronic pain (CP) and rheumatoid arthritis (RA) represent two samples with overlapping symptoms, such as experiencing significant pain. Objectives. To compare the level of psychological distress among patients diagnosed CP attending a specialist pain clinic with those attending a specialist RA clinic. Measures. A cross-sectional study was conducted at an academic specialist chronic pain and rheumatology clinic. Participants. 330 participants included a CP group (n = 167) and a RA group (n = 163) completed a booklet of questionnaires regarding demographic characteristics, duration, and severity of their pain. Psychological and personality variables were compared between the CP and RA participants using a Multivariate Analysis of Covariance (MANCOVA). Results. Level of psychological distress based on the subscales of the DASS , PASS , and PCS  was significantly higher in the CP group compared to the RA group. Categorization of individuals based on DASS severity resulted in significant differences in rates of depression and anxiety symptoms between groups, with a greater number of CP participants displaying more severe depressive and anxiety symptoms. Discussion and Conclusions. This study found greater levels of psychological distress among CP individuals referred to an academic pain clinic when compared to RA patients referred to an academic rheumatology clinic. Chronic pain (CP) is a common disorder affecting up to 35% of individuals  and is aOne potential reason for the high personal and economic costs related to CP is the high prevalence of psychological distress among these individuals. Psychological factors are widely believed to play a significant role in CP . PreexisMost individuals with rheumatoid arthritis (RA) also experience CP. Andersson et al.  found thHowever, what distinguishes RA from chronic soft tissue pain disorders is the presence versus the absence of radiographically demonstrable structural abnormalities accounting for the pain. Pain among individuals diagnosed with RA is easier to define physically and pathophysiologically, through affected joint activity  and damage . Difficulties arise with regional or general musculoskeletal pain syndromes of uncertain etiology because they do not readily lend themselves to such structural diagnoses and hence specific treatment through the acute medical model. This becomes problematic when the patient is, in many cases, held responsible for his or her own pain. This is revealed when patients receive diagnoses such as malingering, hysteria, somatoform pain disorder, secondary gain, or litigation neurosis whereby the patient is seen as exaggerating their symptoms for their own personal gain rather than the pain symptoms being associated to legitimate pain . A patieFurthermore, though both groups of patients experience increased levels of disability compared to the general population, access times to receive specialised services differ. Peng et al.  found thPrevious studies have compared patients with documented sources of pain to those whose etiology of pain is less certain through samples comprised of patients with CP and RA. Generally, these studies have found significant differences between samples, whereby patients with CP experience greater pain and psychological distress than those with a diagnosis of RA; however, the increased psychological distress may be a result of the greater pain that patients diagnosed with CP report , 16.The potential lack of clear structural pathophysiological abnormalities among individuals experiencing chronic soft tissue pain along with longer wait times to be seen by a specialist may result in patients with CP experiencing greater psychological distress than those with RA. Current literature in this field often looks at one sample of patients (either those diagnosed with CP or RA) and considers a limited number of psychological variables. The current study aimed to compare patients with CP directly to those diagnosed with RA while testing a broader range of psychological variables while accounting for differences in pain. The current study hypothesizes that patients with CP will experience greater psychological distress compared to patients diagnosed with RA, even after controlling for pain intensity and demographic variables. Hence, the objective of the current study was to compare the level of psychological distress among individuals with CP attending a specialist pain clinic to patients attending a specialist RA clinic.Participants included two samples of patients, a CP group and a RA group. Patients were recruited over a period of 20 months from academic hospitals in London, Ontario. Patients with CP were recruited from an academic specialist chronic pain clinic, while patients with RA were recruited from an academic specialist rheumatology clinic. Participants with CP were included if they experienced pain for at least 3 months. Diagnosis of CP and RA was conducted by a specialist physician. Eligible participants from both study groups signed informed consent. Ethics was reviewed and approved by the Office of Research Ethics at Western University in London, Ontario, Canada.Researchers followed a similar protocol for eligible CP and RA participants. Two weeks prior to in-person clinic appointments, packages containing the study information letter, a consent form, and the first of two questionnaire booklets were mailed to each prospective CP and RA participant. Research assistants contacted patients via telephone to confirm their interest in participating and to provide answers to patients' questions. Consenting participants completed a booklet of questionnaires regarding demographic characteristics and cause, duration, and severity of their pain.The DASS-SF is a 21-item self-report questionnaire yielding separate scores for depression, anxiety, and stress over the previous week. The items are scored on a 4-point scale  where higher scores indicate greater levels of distress . The DASThe AAQ is a 9-item self-report measure of experiential avoidance, that is, unwillingness to remain in contact with distressing private experiences  and the inclination to alter the form or frequency of these experiences . RespondThe PASS-20 is designed to measure fear of pain. The PASS-20 consists of 4 subscales include avoidance, cognitive anxiety, fearful thinking, and physiological anxiety. These subscales include 5 items each where each item is rated on a frequency scale from “never” (0) to “always” (5) with scores ranging from 0 to 100. The PASS-20 has demonstrated good psychometric properties [The PCS contains 13 items assessing the tendency to misinterpret and exaggerate the threat value of pain sensations. It has good psychometric properties and includes 3 main factors: rumination, magnification, and helplessness . The PCSPain ratings for current, least, average, and worst pain were summed to yield an aggregate pain intensity score. The scale ranges from 0 to 10 with 0 indicating no pain and 10 indicating intense pain. This composite pain intensity score has been shown to be a very reliable measure of pain intensity in chronic pain patients and has been used in recent research . CronbacF-Test [Descriptive analysis was performed to compare baseline demographic factors between the groups. Psychological and personality variables  were compared between the CP and RA participants using a Multivariate Analysis of Covariance (MANCOVA) with Bonferroni adjustment for multiple comparisons and associated effect sizes were calculated. Age, gender, and pain intensity were included in the model as covariates. Patients with missing data necessary for analysis were excluded by case listwise. Preliminary tests were conducted to confirm there was no violation of MANCOVA assumptions. The homogeneity of variance assumption was violated for a number of variables so a more conservative alpha level of 0.01 was set in order to determine significance in the univariate F-Test . No othen = 163) and CP (n = 167) groups used for analysis. The impact of missing values was not significant. Chi squared results indicated that values were missing completely at random . The 330 study participants included 230 (70%) females and the mean age was 49.9 years (SD = 13.3). Level of education was similar in both groups. However, CP participants had almost double the average pain intensity as the RA participants with a significant difference between groups (t(328) = 11.21, p < 0.001). Demographic variables for each group are provided in Overall, 683 eligible patients were approached; 456 participants consented for this study. A total of 126 participants were excluded for the MANCOVA because they had incomplete measures that were necessary for analysis see . This rep < 0.001) were found between groups for AAQ, DASS, PASS, and PCS, with CP participants scoring significantly higher than participants with RA on each measure (p < 0.001). Effect sizes based on Cohen's d were calculated and ranged from 0.33 to 0.86 representing small (0.20–0.49), medium (0.50–0.79), and large effects (≥0.80) found. The greatest effect sizes were found for the PASS cognitive anxiety subscale (0.86) and the PCS helplessness subscale (0.71) while on average most effect sizes were medium  compared to RA patients . Mild to moderate levels of anxiety were greater among RA patients compared to CP patients , while the percentage of those individuals with severe and extremely severe anxiety symptoms was higher in the CP group compared to those with RA . CP patients had more mild, moderate, severe, and extremely severe stress  than RA patients . Based on our two study populations, individuals with CP experienced more severe depressive, anxiety, and stress symptoms compared to those with chronic RA.This study compares the experience of pain and psychological distress among individuals with RA compared to CP. Average pain intensity was significantly greater among CP participants than RA, with CP participants experiencing a mean pain intensity almost twice as high as RA patients. CP patients also experienced significantly more psychological distress even after controlling for age, sex, and average pain intensity. The differences between patient samples resulted in medium effect sizes, on average.Both patients diagnosed with CP and RA have been shown to experience more psychological distress than the general population . SpecifiSignificantly higher scores reflecting large and medium effect sizes in PASS cognitive anxiety and PCS among CP patients compared to those with RA suggest the use of different cognitive processing of pain among these individuals. Similarly, Gil et al.  reportedCategorization of the groups based on DASS severity revealed a higher frequency of patients with CP reporting a greater presence of depressive, anxiety, and stress symptoms. There was an absence of depressive symptoms in greater than 75% of RA patients, while only 28% of CP patients had no symptoms. Similarly, almost half the RA patients did not present with anxiety symptoms whereas only 18% of CP patients did not report anxiety symptoms. Symptoms of mild to extremely severe stress were present in only 10% of RA patients while almost 50% of CP patients reported at least mild stress. This marked difference regarding the presence of psychological distress between the two populations may in part be related to the inadequacy of treatment services available for the CP population relative to RA, although to what degree, if any, is unknown.It is unclear as to the causative relationship between pain and psychological distress in the two populations examined. CP patients may be less likely to be referred to a tertiary care clinic until pain becomes more intense and psychological distress more problematic, while RA patients tend to be referred to specialist rheumatology clinics at any symptom level . Hence, The uncertainty of a diagnosis for CP may also contribute to the increased psychological distress among CP participants compared to RA participants where a discernible organic pathology is present and can be better quantified. Chibnall et al.  found thThe current study has a number of limitations. The CP population studied came from a tertiary care clinic and may not be representative of CP patients in general although they would be representative of CP patients referred to specialists. Similarly, the RA population consisted of those seen in a specialist clinic with RA that could have been active or in remission when entered into this study. The current study did not investigate all variables that could account for the difference between the two samples. Factors such as duration of pain, disability, current employment, current litigation or workers compensation status, and interference with sleep may have a strong influence on pain intensity and psychological distress. The current study design did not allow for the examination of a causal relationship among the various variables examined. Patients willing to participate were studied cross-sectionally just before and then at their clinic appointment so cause and effect cannot be determined.Despite these limitations, results from the current study have several clinical implications. The high levels of depressive and anxiety symptoms among individuals in both populations demonstrate the need for multidisciplinary pain management, in particular psychological counselling and support, which have previously shown to be effective . The difThe current study looked at a variety of psychological variables among individuals with CP referred to an academic pain clinic compared to patients with RA referred to an academic rheumatology clinic. The measures studied included self-reported experiential avoidance, mood, fear of pain, and pain catastrophizing and among each of these variables, significant differences were found with patients diagnosed with CP scoring significantly higher on all psychological measures even after controlling for age, gender, and average pain intensity. The differences between samples based on psychological distress resulted in a number of medium effect sizes with the largest differences seen for measures of pain anxiety and pain catastrophizing. Individuals with CP were also more likely to exhibit severe to extremely severe symptoms of depression and anxiety compared to RA patients. An increased level of distress may serve to heighten chronic pain leading to a cyclical experience of distress and pain. This study points to the importance of psychological distress in both CP and RA patients in their experience of pain. Increased access to multidisciplinary services may be important in managing CP population.