The expectations of patients for managing pain induced by exercise and mobilization (PIEM) have seldom been investigated. We identified the views of patients and care providers regarding pain management induced by exercise and mobilization during physical therapy programs.We performed a qualitative study based on semi-structured interviews with a stratified sample of 12 patients (7 women) and 14 care providers (6 women): 4 general practitioners [GPs], 1 rheumatologist, 1 physical medicine physician, 1 geriatrician, 2 orthopedic surgeons, and 5 physical therapists.Patients and care providers have differing views on PIEM in the overall management of the state of disease. Patients' descriptions of PIEM were polymorphic, and they experienced it as decreased health-related quality of life. The impact of PIEM was complex, and patient views were sometimes ambivalent, ranging from denial of symptoms to discontinuation of therapy. Care providers agreed that PIEM is generally not integrated in management strategies. Care providers more often emphasized the positive and less often the negative dimensions of PIEM than did patients. However, the consequences of PIEM cited included worsened patient clinical condition, fears about physical therapy, rejection of the physical therapist and refusal of care. PIEM follow-up is not optimal and is characterized by poor transmission of information. Patients expected education on how better to prevent stress and anxiety generated by pain, education on mobilization, and adaptations of physical therapy programs according to pain intensity.PIEM management could be optimized by alerting care providers to the situation, improving communication among care providers, and providing education to patients and care providers. Society must be prepared for an aging world with an increasing demand for high-quality standards for health-related quality of life (HRQoL). Hence, handicap, particularly involving disability and restricted participation, is becoming important in connection with preventing and treating disease, and populations in developed countries are demanding increased life expectancy without disability, which is a major public health strategy -3.The prevalence of chronic painful conditions, responsible for limiting mobility and restricting participation, is increasing in aging developed countries -10. ManyAlthough these programs have been shown to reduce pain in many mid- and long-term clinical situations , they maPIEM is part of a more general problem that can be considered pain induced by care, the main components being pain induced by physical examination, administered personal care, and treatments or studies ,19.The patient point of view regarding health status and treatments has become important in decision-making procedures and has been considered a possible criterion standard to assess treatment efficacy ,21. ResuAddressing these discrepancies between patients and physicians in defining the importance of an illness associated with substantial decreases in HRQoL should lead to a paradigm shift toward a more patient-centered approach. Taking into account patient priorities and expectations may lead to a better understanding of what is important to patients -27.Despite differences between patients and their physicians in assessing what is important in health and symptom status, the views of patients and practitioners concerning the management of PIEM have been seldom studied. Qualitative research is probably the best way to understand patients' needs and contexts and could improve therapeutic strategies and their assessments, as well as adherence to treatments -30. We aThe local ethics committee is « le comité de protection des personnes Paris centre, groupe hospitalier Cochin-Broca-Hôtel Dieu ». The survey was conducted in compliance with the Good Clinical Practices and Declaration of Helsinki Principles protocol. In accordance with French national law (loi Huriet), formal approval by an ethical committee is not required for this kind of project . All patients agreed to participate and gave their written informed consent to be in the study.This was a qualitative interview study of patients and care providers performed according to guidelines for inductive qualitative research -33.Semi-structured interviews with both patients and care providers were conducted to explore patient and care provider views about PIEM and pain management. Individual behaviours (attitudes and practices), personal feelings and interpretations, social interactions and material backgrounds were specifically examined throughout the patients' therapeutic journey, to allow for a deep understanding of patient and care provider expectations.A heterogeneous sample of 12 patients and 14 care providers was selected. The sample selection was based on non-probability judgment sampling, assuring both relevance to the subject and diversity of the members selected. The sample size was determined on the basis of the principle of saturation and maximum variety sampling .31). Therefore, we relied on the professional experience and competency of the research team to determine sample size. With the expertise of the social science researchers, saturation occurs within the first 10 interviews depending on the subject studied and the heterogeneity of the group (about 5 to 15). Moreover, the main data codes were developed after about 5 or 6 interviews (in-depth interviews). We also relied on the expertise of the physician members of the research team to determine the criteria of diversification and, thus, the sample size.Saturation was only a guiding principle. This concept can provide a sample size only contingently  and physical therapists (5). We aimed for diversification of points of views and care practices by including a variety of professionals from 7 medical specialties and health care professions  and from both private and public practice.To be eligible for the study, patients had to be in physical therapy programs and experience pain during at least one session. We aimed for diversification of the patient sample according to the following criterion: age , gender , and place where the physical therapy program was performed .The patients were selected from the files of care providers identifying patients who had experienced pain during a physical therapy program. The care providers were recruited from the files of the members of the study board .After interviewing experts in the field of pain management and physical therapy and considering patient perspectives of pain induced by care management, we formulated a semi-structured interview protocol with open-ended questions. All interview protocols were as similar as possible so as to observe the range of variation of discourses and practices between medical experts and patients and to vary data sources to allow a deeper understanding of representations and practices linked to PIEM.The interview protocols were structured by combining a "funnel-shaped" structure and the "itinerary method" -36. The The interview protocols were planned as a loose list of themes and questions, interviewers continually adjusting their questions to the specific leads of the interview and pursuing unpredictable emergent data. They combined a thematic structure with chronological sequences to detail the therapeutic journey and the course of consultation. We tried to keep a similar path for all interviewees for comparison. Because these topic guides include open-ended questions, they could be presented to all interviewees, even if they relied on different individual experiences and decision processes. Of course, some chronological sequences could not be probed to the same extent with all interviewees. Example situations were for the patient journey sequence before the first physical therapy session, because physical therapists have limited insight into this part of the patient journey, and physical therapy sessions themselves, because physicians did not attend them. However, even if some interviewees had no experience with some topics, they usually had views, beliefs, or expectations about the topics, and we collected these data. To gain insights into the topic under study, we were careful to combine different types of data and collect not just opinions, beliefs, and expectations but also descriptions of effective personal practices and the contexts in which they took place.The patient interview guide was designed to collect data on the following:- The therapeutic journey, from the initial health problem to the physical therapy prescription and its organization. This gave the interviewers the opportunity to gather views and beliefs on pain and to identify and characterize previous pain experiences.- Physical therapy sessions including exercise and mobilization; their description; PIEM appearance and patients' reactions and ways of expressing this pain; effects on the patient and their interpretation of this pain; and adjustments made in response to pain. This section allowed us to probe the patient-care provider relationship and communication and their views on physical therapy.- Patient expectations related to the management of PIEM, particularly the assessment of PIEM, its prevention and treatment.The physician interview guide was designed to collect information on the following:- The physical therapy prescription process, and knowledge and views on physical therapy, specifically mobilization.- Pain induced by the exercise and mobilization prescribed. Physicians were asked to express their views on PIEM, allowing us to probe their definition of this phenomenon and the process of interpretation they relied on, including the assessment process, if one existed; the effects on the patient and care providers; how physicians were engaged in the management of this pain; prevention and treatment practices; physician views about the treatment options available; and the description of the patient-physician relationship and the physician-physical therapist relationship and process of communication.- Physician expectations and views of patient expectations.The physical therapist interview guide was designed to study the following:- The physical therapy session, in particular how prescriptions are filled and what indications are given by physicians; the decision process that governs the choice of physical therapy techniques; therapists' definitions of "mobilization techniques," how these techniques are used during the session, for what purposes, and how they are performed; the patient-therapist relationship, topics discussed, information given, and patient behaviours and demands.- PIEM and more specifically the therapist definition of PIEM and comparison with other types of pain; PIEM identification and how therapists decipher patient behaviors; PIEM assessment; PIEM effects on treatment, on patients' life, on disease; the adjustments required and the therapists' practice to relieve and prevent PIEM; and views on treatment options available. This section allowed us to probe the patient-therapist and physician-therapist relationships and procedures of communication.- Physical therapist expectations and views of patient expectations.The mean duration of these interviews was 1½ hours for patients and 1 hour for care providers.The interviews were conducted during fall 2009. All patients were interviewed at home by trained sociologists. Care provider interviews took place where they practiced.The conversations were recorded digitally, transcribed literally, and analyzed by 2 different researchers (both sociologists) who also conducted the interviews. A third socio-anthropologist (DD) validated the coding and the analysis but did not take part in the interview process. A categorizing system based on the interviews was established. This index was consequently modified, categories and subcategories added as they emerged from the thematic content analysis. In a collaborative process, researchers continually checked that they had a common understanding of the categories generated. Numerous free categories were developed from the transcripts; these were discussed, adjusted and grouped in an iterative and inductive process. All the data were coded according to the final thematic index generated, and anonymity was respected.The patient sample exhibited a diversity of professional activities  and residence . It also allowed for examining various medical situations .The care providers' sample also ensured diversity of professional contexts, institutional status  and gender (6 women).Patients considered that PIEM during physical therapy programs is only one facet of a more general problem of pain induced by care . They differentiated pain induced intentionally by care providers for diagnosis and that induced by care:"The physician examined me from all angles. He pressed hard where it hurt a lot.... I don't blame him, it's his job." "One night, nurses came because I wet my bed. They tossed me just like a pancake to change the sheets. They hurt me so much that I screamed." an extra pain" or as "too much pain" depending on the context, the impact of the patients' health condition in their everyday life, and their views on physical therapy. These factors may amplify or minimize the perception of PIEM. The occurrence of pain during a therapeutic program was cognitive dissonance for patients and a paradox, opposing the hope of getting better and the feeling of pain.The description of PIEM was polymorphic and experienced as a degradation of HRQoL. The global therapeutic context affects this experience. PIEM could be sensed as "However, the objective of the care-induced pain was a pivotal element in how patients sensed pain and experienced it. It determined the interpretation, significance, and acceptance of the situation. Therefore, PIEM can be considered to be more a social construction than a simple painful sensation or a physiological response. It is indeed a combination of different components: sensorial, emotional, and social. The social dimension involves the meaning given to pain and the contexts of interaction in which pain is expressed.part of a scarring or healing process", "a necessity in order to achieve recovery", "a useful alert to reconsider diagnosis or treatment", or a protective signal, an indication of the "limits" beyond which one must not go. PIEM was not always seen as constructive. Although some individuals interpreted it positively, it still remained an undesired experience:The significance that patients attributed to PIEM was ambivalent; PIEM could be both positive and negative for them. Among positive representations of PIEM, patients cited interpretations such as ""I don't think it is a punishment, and I don't think it's a way to transcend oneself. Pain is pain! (...) I don't need pain to get mature or to grow internally.... If it can be avoided, so much the better." PIEM could also be interpreted negatively, as care providers' lack of technical competency or lack of attention and thoughtfulness:"The day after my surgery, a physical therapist came. She was quite inhuman. I have a terrible memory of her. I had surgery on my right side and she grabbed my legs on the left side. Of course, I screamed!" PIEM was referred to as control: when interpreted positively, it was pain "under control," and when viewed negatively, it was an unsought experience, associated with fear and helplessness:"This pain (PIEM) is mostly coupled with a feeling of helplessness. It's frustrating because you don't know what ultimately comes from the pain and what comes from your feeling diminished." The impact of PIEM was complex, ranging from denial of symptoms to disruption of the therapeutic contract. When confronted with PIEM, patients did not systematically express their pain. Showing and verbalizing pain was not a neutral decision, and it could be viewed as a social and strategic decision. Strategies for emphasizing, softening, minimizing, or "silencing" were observed, depending on the sense given to the physical therapy, the pain felt, and the social context of occurrence:"Maybe I should have accepted more [than I did], or perhaps I accepted too much. (Is it difficult to judge?) Yes. It's like for syrups: before they were bitter but PIEM expression appeared to be a real issue for patients who tried to control it. Shouting might be felt as a loss of control, an inadequate verbalization, or a worthless option:"I wasn't screaming. A kid might have screamed reacting to this kind of pain but not an adult: I just gritted my teeth." "There are people who scream right away, but you shouldn't -- otherwise you can't progress.... At physiotherapy, they told me that I no longer feel the pain.... I do feel it, but I never say anything because I know that it [the physical therapy] must be done.." Expressing one's pain could be felt as socially incongruous, and patients adjusted their expression according to how they defined the PIEM and how they interpreted their social situation:"Last week, I had a crying fit at the hospital. I couldn't stop crying. That happens regularly. And yet, I wasn't off worse than before, and the worst thing is that I would hide the crying because I was in the physiotherapy room and I was afraid of being watched." The "presentation" of PIEM also depended on bystanders. For instance, one patient was allowed to express her pain by singing, because shouting was not an option for her in a care context; others limited themselves to non-verbal indicators:"During the [physical therapy] session it hurt. I was sweating [with pain]." Interactions with the health care providers affected patients' response to PIEM, sometimes encouraging patients to bear the pain and the physical therapy at the same time:"They [physical therapists] are so nice. They're working for us but they are so involved that you also want to do it for them." In some aspects, the acceptance or minimization of the expression of PIEM may be part of a specific exchange between patients and physical therapists, denoting reciprocity in the care process. The information delivered to patients was also an active part of this relationship and could have an influence:"I remember a physical therapist who told me: "we're not going to relieve you but we are going to teach you how to live with your pain". It made me think..... If they hadn't told me at the rehabilitation center to do things but to do them reasonably, I think I would have stopped immediately, saying that this pain was abnormal." Nevertheless, the occurrence of pain during a physical therapy session had negative consequences for the patient and the therapeutic contract. Patients expressed feelings of loss of confidence with the medical management of the situation and fear of reactivation of the disease:"For a while it did not hurt anymore. I began to recover. But the physical therapy, the manipulations, it woke up the pain. What bothered me most was that it (my ankle) had begun not to hurt, but the physiotherapy sessions brought back the pain. That's all I noticed." Care providers agreed that PIEM is generally not a part of their management strategies and that a generally accepted definition is lacking. When analysing the meanings of PIEM, care providers emphasized the positive dimensions of PIEM, such as pain as a "red flag" allowing for treatment adaptations or as a signal of evolution of the underlying pathology:"Pain is a limiting factor; it is an alarm system that tells you not to go further. For instance, if you consider hand surgery, it is useless to prescribe painkillers to relieve the pain, because there are things you mustn't do (and pain will stop you doing them)." "(I view PIEM differently according to the situation). It is not the same the week after the surgery as it is six weeks afterwards, when normally the pain is decreasing [and] the patient regains mobility. If the pain or the level is reversed at this time, it means that there is a problem, a complication. It can be a hematoma, an infection, or dislocation of the orthopedic material. These "virtues" seemed to have more weight than the negative dimensions of the situation. Care providers' downplaying the negative dimensions of PIEM involved a double process: the purpose of PIEM (patients suffer to get better) and the reminder of medical deontology and the absence of intentionality ("we do not do it on purpose"):"When you examine a patient, you may cause pain. There is no malice intended. It is because it helps us make a diagnosis. It's the same for physical therapy: we might actually have to cause pain. We are not trying to hurt the patient; it's to make them better.""In my mind, pain is impossible in physical therapy. It may hurt at the time but afterwards, it is so much better that it is a 'blessing in disguise'. That's why it does not even occur to me to anticipate [the pain]. I am probably wrong, but that's the way I think automatically." PIEM was identified mainly by physical therapists and less by physicians. Different modalities of pain expression were reported: clinical signs, attitudes, and verbalization. The identification of PIEM did not imply management of PIEM; the patient and physical therapist discussed the level of pain and what was acceptable to the patient before treatment might be modified.Although several care providers tended to minimize the consequences of PIEM, consequences cited were a worsening of the patient's clinical situation, fears about physical therapy, rejection of the physical therapist, and refusal of care:"I think if it's too painful, it will have psychological consequences in following up the physical therapy program. Patients will be afraid to come. They will look on physical therapy as something horrible instead of thinking it will improve (their condition)." "If you exceed the limit once, the patient may no longer want to see you. It's rare but it happens. If you simply exceed the limit once and the pain is unbearable, it's all over with the patient." Care providers admitted the existence of PIEM, but stated that it had little or no impact on their practice for managing patients' condition as compared with side effects observed with other treatments.Physical therapists were the only care providers to assess PIEM; they mainly used standardized tools such as visual analog or numeric scales, but the use of pain scales was not systematic. Physicians did not assess PIEM and had limited confidence with tools used to assess pain in general:"There are paradoxical situations: there are patients who arrive smiling but say their pain level is 10. The scale is a very specific tool. It is a valuable tool.... I stopped using those scales because of that, because it meaningless for patients." Patients recognized that pain levels are regularly assessed but had ambivalent views concerning the tools used for these evaluations, especially scales. Some patients considered these evaluations important for the care provider's comprehension of their clinical situation, whereas others questioned their use."It [pain scale] is probably useful for doctors in order to correct things. They do need benchmarks. It allows them to know how people suffer." ." The poor [care providers]! Otherwise, how can they assess [pain]?"  "It is required for the hospital service but for patients it's not very useful." . "They give you a scale and ask you to say how much pain you are feeling on a scale of 0 to 10. I refuse to rate it with a number because I can't. It can always hurt more than you think it could." Few standardized procedures exist to prevent or treat PIEM. Physical therapists, the first-line care providers dealing with PIEM, have limited treatment options. Responses to the perceived or expressed complaints include modulating the perception of pain  and pain inducer , and using pain-oriented techniques .Treatment of PIEM was subordinate to general pain management for chronic situations or for post-surgical periods. Specific treatment for PIEM was prescribed infrequently. Pharmacological and nonpharmacological options for PIEM related to the general treatment of the underlying clinical situation . Thus, PIEM treatment depended on physicians' choices for general pain management, but patient impressions of pain killers also influenced PIEM treatments:"I avoid drugs; you know they're not good. If you take a paracetamol as soon as you have a headache, sooner or later your body will adapt to it, and instead of 500 mg, it will ask for more... The way I see it, you could say that it's part of our diet.... I am not happy when I leave the drugstore with a huge bag!" "Morphine terrifies me. Even the term is terrible! A light death, a small death, an adorable death." These impressions were organized around central themes:- toxicity"On one hand, drugs mess you up you, and on the other, they treat you. I am sure of that... but I do look at the leaflets in order to see if I'm not going to be poisoned." . " They think they're harmful in the long run. They say they don't want to take them anymore.." - fear of loss of efficacy with time"And you get used to drugs; your blood must get used to them, because before, they had more effect on me." - perception of lack of efficacy of over-the-counter pain medications" No, I didn't get anything. (You say you're taking paracetamol?) Ah, if that's what you mean by treatment, well then yes: I'm taking paracetamol but it's not doing anything for me." - and severe side effects with opioids:"They asked me if I wanted morphine... it took me 8 days to get my intestinal tract back in order." ."It made me nauseous though; it caused vomiting." The negative views of pain killers influence compliance:"I am a bit anti-medicine, so the less I take, the better I feel." Compliance with prescribed treatments also related to dosage adapted to pain level, occurence of side effects, and perceived efficacy.GPs did not mention the possibility of PIEM, and only some rehabilitation units in tertiary care hospitals proposed standardized procedures.We observed three different types of practices concerning PIEM prevention. One was the absence of any consideration of this topic by GPs, who stated that they did not consider the situation, and by physiotherapists, who stated that they did not induce pain with the techniques they use:" I never tell my patients that physiotherapy can hurt simply because I don't think of it. Moreover, I don't know whether it will hurt or not." "During the session, I try to stop before pain occurs or to fight against pain. My technique is to be of benefit, to relieve, not to work through pain.... The first thing you learn in your studies when you are a physiotherapist is to work without provoking pain. That said, there are some big brutes, fewer and fewer I think.... who force even when it hurts... but for me, there's no point in that." from time to time") and not standardized. It concerned patients who feared physical therapy, with specific painful situations, such as with adhesive capsulitis or certain surgeries that require early exercise:Another practice identified is selective PIEM prevention. Prevention is not systematic (""(Do you prescribe something to prevent pain during physiotherapy sessions?) Sometimes I warn my patients. I tell them to take a painkiller one hour before the session or an anxiolitic to relax. It is because I am an old physician.." " We do it from time to time. Again, our treatments are really individualized. If we think that the therapy is going to be painful, we give painkillers with a specific schedule." "(Do you make these prescriptions to anticipate or to treat the pain induced by physiotherapy?) It depends. Some exercise programmes are more painful than others. If I take my last patient, whom I've treated for shoulder pain, I did prescribe morphine. She was close to adhesive capsulitis...I had to act quickly to free the shoulder, and I told her to take pain killers, in this case morphine." The third practice was a standardized protocol of prevention proposed by some GPs and in some rehabilitation units:"When I prescribe physiotherapy, I also prescribe analgesics. I explain to the patient that he may experience pain and that he will have to take his treatment. I also prescribe non-steroidal anti-inflammatory drugs. I tell my patients that it is temporary, that it is for 2 or 3 days when it is most painful.. I also explain to them that they should tell the physiotherapist when it hurts." The presence or absence of PIEM prevention procedures seemed to depend less on the status of the institution of the care provider and more on the sensitivity of the care provider to pain management.Poor coordination of care is a factor that may worsen PIEM management. Multiple care providers are involved in PIEM management and follow-up. Nurses, physiotherapists, surgeons, anesthetists, and specialists may be involved in the care of inpatients, with only primary care physicians and physiotherapists involved in the care of outpatients. For inpatients as well as outpatients, PIEM follow-up was characterized by poor transmission of information, in part because of professional compartmentalization:"(How does communication with physicians work?) In surgery units, it is very difficult. If it's urgent, we phone; otherwise we look for them in the corridors, we run after them. It's not very easy, but that's how it is; you can lose a day of treatment for example." "When we arrive in the morning, we discuss patients with nurses to schedule our intervention between dressing changes, and we manage to reschedule physiotherapy according to analgesics prescription (Is that easy to do?) No, it's not always easy. You have to be organized." A lack of human resources was also mentioned:"We have analyzed our practice for pain management after total knee replacement. We realized that we were not efficient and that our pain management was not satisfactory. (Why?) I think that it is a matter of number of physicians. Here there is one and a half physician for 75 patients. The physiotherapists do not always find us." .Information about PIEM was transmitted mainly in rehabilitation units, but it might be partial or delayed. For outpatients, there was practically no transmission of information between GPs and physiotherapists, except for situations of significant medical complications.Patient expectations about PIEM management included more information and transparency from care providers about what factors induced pain, how to assess pain, and whether it requires a specific treatment:"There is no debriefing on this.... The first day and the last day, we fill in a little questionnaire for the physician to assess the impact of pain on our everyday activities. We fill it in, but it's the same, we don't get any feedback. I would have liked it, for example, if someone had told us about our progress after the sessions" They also expected education on how to better prevent stress and anxiety generated by pain, counseling on how to anticipate PIEM and on mobilization, and accurate adaptations of physical therapy programs according to pain intensity. These expectations were modulated by patients' own interpretations and behaviors concerning pain in general and PIEM. Some patients were fatalistic about PIEM:"I think it's better to do the physiotherapy session without medication. That way if there is a problem you can feel it. If it hurts, it is better to take analgesics after pain occurs, because if you take it before and there is a problem, you won't feel it." "In any case, even at home, I can't control pain, and I don't see how I could do so during physiotherapy sessions." .Not all patients suggested that care providers should be more involved in PIEM recognition and management.Expectations about pain killers were heterogeneous. The criteria mentioned were efficacy, rapidity of action, absence of side effects, and methods of administration. For over-the-counter drugs and acetaminophen, expectations were mainly for more efficacy, whereas for opioids, they were mainly for fewer side effects:"Paracetamol. It might be worse if I didn't take it, but it is totally inefficient" ."I had a lot of pain killers. Paracetamol and codeine didn't do any good. When I was on these prescriptions, sometimes I didn't take anything because I figured 'if that's what a pain reliever is...' I don't take medicine if it does nothing for me." "I couldn't stand tramadol. I was dizzy, I threw up, and I didn't even know my name anymore." "I felt nauseous, I even threw up, and the last time I took tramadol, I took 2 tablets and I was completely drowsy, really, really sleepy but when I was taking 6 tablets a day, I didn't experience those side effects." Care providers had few expectations about PIEM management or specific continuing education programs on PIEM, either because they were satisfied with actual practice or not sensitized to PIEM. They did express a need for tools or procedures to better identify, assess, and follow PIEM:"I don't really know how to measure the pain... It is just like these super PAS scales from 0 to 10, but you'll never manage to get an orthopaedic surgeon to keep this thing in his pocket. Even my goniometer, that I use every day, I can't keep it in my pocket." "For pain assessment, there have been policies that were widely circulated that might give you a false good conscience, saying 'I've used my little EVA scale, so there, there's no problem'". Care providers' opinions about pain killers strongly depended on the images reflected and opinions expressed by patients, and the criteria that they mentioned were similar to those defined by patients.As for continuing medical education programs, care providers mentioned the already large number of educational programs and their limited time to participate in these programs:"We are so overwhelmed. We choose one or two and that's it. It is impossible to manage if you get in any deeper." Several physicians pointed out the need for a large sensitization campaign on pain before proposing specific educational programs on PIEM. Physicians expressed a need for better education on the pharmacokinetics of analgesics and on prescriptions for physiotherapy:"My expectation would be to have explanations on drug therapies for pain, their side effects, those I can associate. I'm missing that. I receive physician visitors from the industry, but that's not enough." Education on the patient-physician relationship concerning pain management was also mentioned:" I think the psycho-behavioural approach is important. It's important for almost everyone. The relationship you have with the patient has a great influence on pain. A relationship of trust can help them forget about pain and concentrate on movement." Physicians insisted on the need for educational programs aimed at increasing competency rather than knowledge and on interdisciplinary programs because PIEM management implies different and complementary skills.To our knowledge, this is the first qualitative study of patient and care provider views of PIEM. Our results suggest an important lack of knowledge and recognition of this situation by care providers not directly involved in physical training or physiotherapy programs.Even though patients had ambivalent and heterogeneous views about PIEM, the occurrence of PIEM can be considered a serious adverse event because of its negative consequences on patients and on their therapeutic contract with care providers, which can lead them to suspend or end treatment, lose confidence in medical management, and return to the condition of chronic pain.Care provider views of PIEM differed from those of patients. PIEM was sometimes viewed negatively due to lack of competency of a single and isolated professional and therefore a relatively infrequent situation or to particular situations with patients highly vulnerable to pain. In the latter case, the PIEM importance was minimized, and some care providers indicated that the risk of PIEM was more that it would slow recovery than slow the treatment process.Our results also suggest that PIEM assessment is far from optimal because of care provider low confidence in assessment tools and patient ambivalent views of the usefulness of assessment. One barrier to the assessment of PIEM is patient lack of comprehension of the therapeutic objectives of this assessment, which sometimes leads to passive submission behaviors regarding PIEM assessment and can in turn be harmful to the quality of the assessment. The process of evaluation could be improved by recognizing its utility for therapeutic decisions, improving the quality of the patient-physician relationship, clarifying its use to patients, and proposing more relevant assessment tools to patients and care providers.Our results reveal several barriers to specific PIEM treatments. Physiotherapists are care providers who frequently deal with PIEM. Although they have access to non pharmacological options such as physical and cognitive techniques, education received on this topic is at least limited. Cooperation among care providers is needed to efficiently deal with this clinical situation. However, lack of communication among care providers seemed greater than the existence of structured protocols to prevent or treat PIEM. In addition, by nature, the physiotherapist's work depends on patient cooperation, and one of the treatment options available is to modulate factors inducing pain, which leads patients to discontinue mobilization exercises. Another barrier is patient and physician global negative view of pain killers. We also observed these negative views of pain killers among French patients with knee osteoarthritis . The triTo help physical therapists manage the emotional and cognitive aspects of PIEM, educational programs during their initial education or later continuing education could be proposed. In addition, educational programs for physicians should increase their knowledge of non pharmacological options for management of PIEM which should lead to propose cognitive and coping strategies more often to better manage PIEM. Similar barriers  and poteSome obstacles to PIEM prevention are organizational constraints, such as the lack of human resources, mainly in institutions, and care planning, such as communication among nurses, physicians, and physiotherapists. PIEM prevention could be facilitated by better organization of medical care (prescription and follow-up), providing patients with specific educational programs about cognitive and coping strategies to alleviate pain and about painkillers and their use, and care provider training in non pharmacological treatment options and the pharmacokinetics of analgesics. PIEM follow-up is characterized by poor transmission of information among care providers, and one way to optimize this transmission might be the systematization of standardized information to be circulated among the patients and care providers involved in the process. However, this approach cannot be optimal without care providers being involved in the process, and facilitators for the adoption of these procedures have yet to be determined.Patients' expectations concerning PIEM have two main aspects: global management and specific treatments. Expectations concerning managing PIEM are mainly related to the implications of treatment and more communication between patients and care providers. To be effective, a strategy aimed at optimizing this process would lead to a "win-win" situation for both patients and care providers. Expectations concerning specific treatments may appear unrealistic, which points to the need for more education and counseling.The lack of care providers' expectations about PIEM is the result of the lack of knowledge about the situation and the tendency to minimize its impact on patients and on disease management. Their expectations mainly concern the need for formalized support for the identification, assessment, and management of PIEM. However, care providers did not spontaneously express a need for specific continuing medical education on this topic. When it was suggested to them by interviewers, care providers mentioned the large range of programs already available, and they insisted on the need for prior sensitization about the general management of pain and a pragmatic approach to increase their skills. Thus, increasing care providers' adherence to and use of education programs on this topic should emphasize the interest for both patients and care providers in better identifying and managing PIEM.Our work has limitations. The first is that we restricted our investigation to a French context. How the health care system is organized and the cultural context in France probably affect views and expectations in this field. Transcultural qualitative studies are needed to address this question. Moreover, we did not search for non-confirming cases. Another limitation is our rather small sample of patients and practitioners. Therefore, we cannot exclude that this study might under represent the range of views that patients and care providers have of PIEM. However, we tried to stratify this sample to reflect diversity, as recommended for qualitative studies expecting a range of representations, practices, interactions, and expectations of a subject .Finally, this work underlines the views that patients and care providers have of PIEM, which limit the management of PIEM more than the material constraints or the social dynamics of the patient-care provider relationship. Ethnographical observations are necessary to probe the logic underlying these relationships and detail potential value conflicts .Patients and care providers have differing views of PIEM in the overall management of disease. PIEM management could be optimized by sensitizing care providers to the situation; improving communication among care providers; providing information and education to patients and care providers to recognize, assess, prevent and treat PIEM; and elaborating and proposing standardized structured procedures to manage this particular clinical situation. The appropriation, mobilization, and efficacy of information and education for care providers and patients need further investigation.Financial competing interestsThis work was funded by Bristol-Myers Squibb. SA, DD, ASB and SP received honoraria from BMS. EB is employed by BMS.There is no other competing financial interestNon-financial competing interestsThe author declares that they have no competing interests.SA, DD, MMLC, EB, FR, and SP contributed to Conception and design of the semi-structured interview study, SA and ASB to data collection, SA, DD, ASB, and SP to data analysis, SA, MMLC, and SP to drafting the manuscript, DD, ASB, FR, and EB to critical review of the manuscript. All authors read and approved the final manuscript.1 Phonetically, in French, the word "morphine" sounds like "death" (mort) and (fine), which means "fine", "exquisite", "thin", "small" and led the patient to associate "morphine" with "a little death". Etymologically, the word refers to the Greek name for the God of Dreams, Morpheus.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/12/172/prepub


The aim of this study was to compare the efficacy of diclofenac, for the treatment of acute pain originated by lower-limb fracture and surgery, with that of diclofenac plus B vitamins. This was a single-center, prospective, randomized, and double-blinded clinical trial. Patients with lower-limb closed fractures rated their pain on a 10 cm visual analog scale (VAS). Patients were then randomized to receive diclofenac or diclofenac plus B vitamins  intramuscularly twice daily. Patient evaluations of pain intensity were recorded throughout two periods: twenty-four hours presurgery and twenty-four hours postsurgical. One hundred twenty-two patients completed the study. The subjects' assessments of limb pain on the VAS showed a significant reduction from baseline values regardless of the treatment group. Diclofenac plus B vitamins combination was more effective to reduce the pain than diclofenac alone. The results showed that the addition of B vitamins to diclofenac increased its analgesic effect. The novelty of this paper consists in that diclofenac and diclofenac plus B vitamins were useful for treatment of acute pain originated by lower-limb fracture and surgery. A number of situations are prone to develop pain symptomatology, such as tissue degeneration, infection, inflammation, cancer, trauma, surgery, and limb fractures. Each of these physiological abnormalities requires a therapeutic approach different from the last. In acute pain, caused by fracture and/or surgery, several classes of analgesics have been utilized. These basic remedies for analgesia, however, are still confined to a small number of medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), local anesthetics, and opioids. In addition, most of these drugs have side effects, limiting their use in clinical practice , 2. The clinical use of combinations of analgesic agents has increased significantly in the last few years. The purpose is to associate two or more drugs with different mechanisms of action, in hopes of achieving a synergistic interaction that yields a sufficient analgesic effect with low doses of each agent, therefore, reducing the intensity and incidence of untoward effects . B vitamins are a water-soluble group of vitamins including thiamine, riboflavin, niacin and niacinamide, pyridoxine, cobalamin, folic acid, pantothenic acid, biotin, choline, inositol, and para-aminobenzoic acid (PABA). In particular, some of these B vitamins  have been used, not only in the treatment of pain and inflammation resulting from vitamin deficiency but also alone or in combination with diclofenac or other NSAIDs for various painful diseases such as polyneuropathies, degenerative diseases of the spinal column, rheumatic diseases lumbago and pain originated from tonsillectomy –8. HowevThis was a single-center, prospective, randomized and double-blinded clinical trial. The study was carried out at the Hospital General SSH Pachuca, Hidalgo, Mexico from January 2008 to February 2010. The study protocol was approved by the Ethic and Investigation Committees from the Hospital General SSH Pachuca, Hidalgo, Mexico as well as this was conducted according to the Declaration of Helsinki.The participants of the study were patients with lower-limb closed fractures, ranging in age from 18 to 55 years, with acute pain ≥5 cm according to a 10 cm visual analog scale , good health determined by clinical history and laboratory studies, without sanguineous dyscrasias or hypersensitivity to drugs to be employed, and who consented to participate voluntarily. After giving their consent, patients rated their pain on a VAS, and they were then randomized into one of two groups receiving 75 mg diclofenac or 75 mg diclofenac plus B vitamins  twice daily . Patient evaluations of pain intensity were recorded throughout two periods: twenty-four hours presurgical and twenty-four hours postsurgical. Twenty-four hours after the first drug administration, patients underwent elective lower-limb surgery. Standardized general anesthetic techniques were used for all patients. Patients received 50 mg ranitidine intravenously twice a day throughout the study. If the pain was not controlled after two hours, patients received rescue treatment with morphine. At the end of the study, the improvement in pain levels was evaluated by a Likert scale. The categorical Likert response alternatives consisted of four descriptions. Responses were rated 0–3: 0 = complete relief, 1 = moderate relief, 2 = slight relief, 3 = without relief. Gastrointestinal side effects, rash, or spontaneous complaints of other adverse effects such as postsurgical bleeding problems during the postoperative phase were registered. t student and a nonparametric statistical analysis, the Mann-Whitney U test. P < 0.05 was required for significance.Data are shown as the mean ± SEM. Data were evaluated using P > 0.05). One hundred twenty-two patients completed the study, sixty-two in the diclofenac group  and sixty in the diclofenac with B vitamins group . The mean ± standard deviation age in the diclofenac group was 37.9 ± 10.5 years and 35.0 ± 8.8 years in the diclofenac plus B vitamins group, which does not represent a significant difference between the groups (P > 0.05).In the study presented here, all patients received medication for forty-eight hours and the acute pain induced by lower-limb fracture and surgery was monitored and recorded. The lower-limb fractures that the patients presented with were 8 fractures of the patella, 47 ankle fractures, 24 tibia shaft fractures, 14 tibial plateau fractures, 20 diaphyseal fractures of the femur, 6 subtrochanteric femoral fractures, 2 fractures of the calcaneus, and 1 fracture of the talus. There was no statistically significant difference in the type of fracture and gender between the two treatment groups (P < 0.05) (P < 0.05) (P > 0.05).The subjects' assessment of limb pain on the VAS in both treatments showed a significant reduction from baseline at 4, 8, 12, 24, 36, and 48 hours after treatment. Diclofenac plus B vitamins was more effective to reduce the pain than diclofenac alone at 8, 12, 24, 36, and 48 hours after treatment ( < 0.05) . However < 0.05) . The valRescue treatments were not applied. All the patients reported pain in the administration site, but generally speaking, all the regimens were well tolerated. None of the patients had any bleeding complication or gastrointestinal complain before or after surgery.Fractures of the lower limb are common, especially in the elderly, and are often associated with considerable morbidity and lengthy hospitalization. The immediate goal of treating acute lower-limb fractures is to decrease pain and swelling as well as to protect adjacent structures from further injury. For this reason, after immobilization of the lower limb, NSAIDs are invaluable in treating these musculoskeletal conditions, primarily due to their analgesic and anti-inflammatory effects. Unfortunately, NSAIDs propensity to cause gastrointestinal damage and patient discomfort limits their use. It is known that as many as two to four percent of patients who take NSAIDs during long-term therapy may have serious gastrointestinal side effects such as perforation, ulceration, or bleeding , 11. An In the present study, both diclofenac and diclofenac plus B vitamins were able to produce an analgesic effect in patients with acute pain originating from lower-limb fracture and surgery. Likewise, at certain points of time the diclofenac-B vitamins combination provided a significantly greater analgesia than the single-agent diclofenac. In this last case, B vitamins potentiated the analgesia produced by diclofenac. There is evidences that B vitamins in their separate forms  have antinociceptive or analgesic effects. In this regard, in animal experiments, thiamine (B1 vitamin) was able to produce antinociception in the model of pain induced by acetic acid in mice, in the second phase of the formalin test in mice and in the model of pain induced by electrical stimulation of afferent fibers . ClinicaThe increased analgesia with the diclofenac-B vitamins combination differs from the similar analgesic effects observed with diclofenac alone and diclofenac plus B vitamins in the treatment of acute postoperative pain after tonsillectomy ; probabl+-gated channels in sensory neurons, increase the concentration of kynurenate (an endogenous antagonist of NMDA receptors), stimulate the nitric oxide-cGMP-K+ channels pathway, and activate metformin- and phenformin-dependent mechanisms to induce antinociception [Diclofenac is an NSAID that exhibits potent analgesic and anti-inflammatory properties. It is known that diclofenac as well as other nonselective NSAIDs are able to impair prostaglandin synthesis by inhibiting the cyclooxygenase isozymes COX-1 and COX-2 in injured tissues and in the central nervous system. However, there is also evidence that diclofenac exhibits additional prostaglandin-independent properties that mediate its antinociceptive effects. For instance, diclofenac is able to inhibit Hiception –23. On tiception , 25. Regiception , 27. Furiception  and reduiception . More reiception , 31. Howiception . In lighPatients often experience unpredictable therapeutic and diagnostic procedural-related pain in emergency rooms that can be associated with considerable stress and anxiety . AlthougOne weakness of our study was that participants had different types of lower-limb fractures and surgeries, and this diversity could have affected the results in favor of providing a better analgesic effect with the combination of diclofenac with B vitamins. However, it was noted that although the patients had different types of fractures, there was no statistically significant difference in the level of pain that both groups of patients presented with on their admission. Therefore, it is necessary to evaluate the effectiveness of this combination in a particular type of fracture or surgery, either member. In conclusion, the present study gives evidence that the combination of diclofenac plus B vitamins could be a safe and inexpensive postsurgical analgesic strategy. Likewise, it is necessary to undertake controlled studies using this combination in different states of acute postsurgical pain to demonstrate its security and efficacy.


Electrical stimulation of central nervous system areas with surgically implanted stimulators has been shown to result in pain relief. To avoid the risks and side effects of surgery, transcranial direct current stimulation is an option to electrically stimulate the motor cortex through the skull. Previous research has shown that transcranial direct current stimulation relieves pain in patients with fibromyalgia, chronic neuropathic pain and chronic pelvic pain. Evidence indicates that the method is pain free, safe and inexpensive.A randomised controlled trial has been designed to evaluate the effect of transcranial direct current stimulation over the motor cortex for pain reduction in patients with chronic low back pain. It will also investigate whether transcranial direct current stimulation as a prior treatment enhances the symptom reduction achieved by a cognitive-behavioural group intervention. Participants will be randomised to receive a series of 5 days of transcranial direct current stimulation  or 20 mins of sham stimulation; followed by a cognitive-behavioural group programme. The primary outcome parameters will measure pain  and disability (Oswestry Disability Index). Secondary outcome parameters will include the Fear Avoidance Beliefs Questionnaire, the Funktionsfragebogen Hannover (perceived function), Hospital Anxiety Depression Scale, bothersomeness and Health Related Quality of Life (SF 36), as well as Patient-Perceived Satisfactory Improvement. Assessments will take place immediately prior to the first application of transcranial direct current stimulation or sham, after 5 consecutive days of stimulation, immediately after the cognitive-behavioural group programme and at 4 weeks, 12 weeks and 24 weeks follow-up.This trial will help to determine, whether transcranial direct current stimulation is an effective treatment for patients with chronic low back pain and whether it can further enhance the effects of a cognitive behavioural pain management programme. Trial registration: Current Controlled Trials ISRCTN89874874. A literature review  on the eImaging studies have revealed that pain is accompanied by an extensive reorganisation of the brain. Changes in chronic back pain patients are structural ,4 and fuIf a chronic pain conditions is regarded as non-specific  and doesTranscranial direct current stimulation (tDCS) is a non-invasive alternative that applies weak electrical currents (1-2 mA) through the skull to modulate the activity of neurons in the brain .A current systematic review of the literature  concluded that anodal tDCS had a pain reducing effect in patients with chronic pain due to spinal cord injury ,17, fibrA trial with high methodological quality is needed to determine whether tDCS is effective in the reduction of pain in chronic pain patients.This trial will evaluate the effect of tDCS on pain and disability of patients with non-specific CLBP and investigate whether tDCS as a prior treatment enhances the symptom reduction achieved by a cognitive-behavioural group intervention.Double-blind single-centre randomised controlled trial with two study arms  Figure .Participants will be allocated to groups  using computer generated randomisation lists, stratified for high (51-100) and low (20-50) average pain intensities over the past 24 hours. Block randomisation (blocks of 20) was chosen to allow for equal numbers in each group at regular time intervals.Allocation concealment and blinding (patient and therapist providing the intervention) is secured, since the randomisation lists consist of 70 different number codes for each group. Following consent at recruitment, participants will be given the next available code from the randomisation list. The stimulation code will be entered into the tDCS device to initialise the stimulation procedure. According to the entered code the device produces an active or a sham stimulation paradigm. Only the independent researcher (CW) will have access to the list that unblinds the allocation to either tDCS or sham stimulation group.The stimulation period is followed by a four week cognitive-behavioural group therapy.Patients will be recruited and treated at a back pain clinic in North Germany.Patients will be eligible if they satisfy the following criteria:• Aged 18 - 65 years• Categorised as suitable for a pain management programme• Have non-specific CLBP◦ with a minimum of 3 months of low back pain without any relevant ongoing pathologies such as acute disc prolapse, acute inflammation, bone fractures, spondylolisthesis or general health restrictions that require medical attention• Are waiting to attend a cognitive-behavioural group programme at a back pain clinic in North Germany.• Provide written consentPotential participants will be excluded if they have any of the following:• Other chronic pain syndromes• spinal surgery in the past 6 month• Neurological disease• Psychiatric disease• Does not understand German• Pregnant or likely to become pregnant during the trial• Alcohol-, drug-, medication abuseMedication intake is not listed as an exclusion criterion but type and dosage of medication will be recorded and any change in medication documented.tDCS is produced by a battery driven small stimulator box and is applied to the skull via sponge electrodes. The equipment is portable and of relatively low cost. Application is easy and safe ,25. Acro2) sponge electrodes, soaked in a saline solution will be placed over the stimulation sites and held in place by an elastic bandage. The anode (positively charged electrode) will be placed over the left primary motor cortex (M1), while the cathode (negatively charged electrode) will be placed above the right eyebrow. This electrode arrangement has been shown to induce excitability changes in the primary motor cortex [All participants will receive 20 mins of anodal tDCS  with an intensity of 2 mA, on 5 consecutive days. This dosage has been identified in a systematic review of the current available evidence as the stimulation parameters used in the majority of trials . Large size  will be applied over the motor cortex on the left side of the skull, until a twitching of the right index finger is observed.An identical procedure will be used for the sham stimulation, but the DC stimulator will not deliver an active stimulation paradigm.The sham paradigm initially produces a direct current, but switches off automatically after 30 seconds. Participants perceive a tingling sensation identical to that perceived during the real stimulation. This short stimulation does not result in any neurophysiological changes. The method has been shown to be a reliable placebo condition . HoweverThis pain management programme is the standard care for patients at the back pain clinic involved in the study. The effectiveness of interdisciplinary group programmes for the treatment of non-specific CLBP has been demonstrated by a number of publications -31. A maThe programme will be delivered by an interdisciplinary team of orthopaedic consultants, physiotherapists, psychologists and sports therapists who deliver this programme routinely to patients at the clinic.tDCS and the cognitive-behavioural group programme aim to influence different factors associated with non-specific CLBP. While tDCS is believed to directly influence pain processing within the central nervous system, the cognitive-behavioural programme is targeting disability, beliefs and other psychosocial aspects of the pain experience. Therefore, two primary outcome measures will be used to assess the effect of tDCS as well as of the cognitive-behavioural group programme:Pain: Visual analogue (VAS 0-100) or numerical rating scale (NRS 0-10) over the past 24 hours. 0 indicates no pain and 100 or 10 indicates the worst imaginable pain.• VAS was used in previous trials on tDCS for the relief of chronic pain ,18,21. MDisability: Oswestry Disability Index [• ty Index . The maxValidated in German . The cutPatient-perceived satisfactory improvement (PPSI): Participants' perceived global rating of overall change (from baseline) will be recorded on a 5-point Likert-type scale  [•  better) . This meBothersomeness: A second global score that will be used is "bothersomeness". This single question ("how bothersome is your pain today?") tool gives 5 answering options: "not at all," "slightly," "moderately," "very much," and "extremely" [• tremely" .General health and health-related quality of life: SF 36 has been widely used in study populations with chronic pain [• nic pain -40. It hnic pain .Perceived restriction of function: The Funktionsfragebogen Hannover (FfbH-R) consists of 12 items that ask about the patient's capacity to perform daily life activities. It has been designed to reflect the limitations, a back pain patient may typically experience. The answers are rated in a 3 point scale . Validity and reliability has been established [• ablished .Fear avoidance beliefs: Fear avoidance beliefs questionnaire (FABQ) developed by Waddell et al. [• l et al. ,44 transl et al. . Fear avl et al.  althoughl et al. . Since pAnxiety and Depression: Hospital anxiety and depression scale (HADS) [• e (HADS) . Analog The sample size calculation was based on published minimum clinically relevant change recommendations of 15 mm on a 0-100 mm VAS  and 8 poData will be digitalised from the paper version (source data) into Microsoft excel spreadsheets by a blinded investigator.Data analysis will be conducted using SPSS 18 for Apple Macintosh. The primary analysis will use a general linear model to compare between-group effects on the primary outcome measure, at 4 weeks, 12 weeks and 24 weeks follow-up, with baseline values as covariate. Similar analyses will be conducted on appropriate secondary outcomes, or non-parametric tests as appropriate (e.g. on PPSI).Conduct of the study will be in accordance with the Declaration of Helsinki . The proThe proposed study presents the first high quality randomised controlled trial on tDCS for the reduction of chronic pain. As identified in a recently published Cochrane review  and a syChronic low back pain patients have been included in two of the existing trials on various chronic pain conditions ,23 but nThe choice of outcome parameters was based on the review of previous publications on comparable study populations/interventions. A range of identified measurement tools was monitored over a 3 month period in the back pain clinic. These included the Short Form McGill Pain Questionnaire , the VisHowever, the study is limited to investigate the short term effects of tDCS and the combination of tDCS and a cognitive-behavioural group programme. Since all patients will receive the group programme following the stimulation period, no long term effects of tDCS alone can be measured. The group programme is currently the standard care for patients attending the back pain clinic and ethical as well as health insurance reasons required that all patients receive the group programme as soon as possible. It was therefore not feasible to include a third group receiving tDCS alone or to postpone the group programme until long term measurements were taken.The authors declare that they have no competing interests.KL participated in the study design and drafted the manuscript. AR participated in the design and helped to draft the manuscript. CW participated in the design, helped to draft the manuscript, and performed the statistical analysis. TPJ participated in the sequence alignment. GM participated in the study coordination. AM conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/12/290/prepub


Objective: An examination of whether oxycodone/naloxone prolonged-release tablets (OXN PR) can improve constipation and maintain analgesia, compared with oxycodone prolonged-release tablets (OxyPR) in patients with moderate/severe cancer pain.Methods: Randomized, double-blind, active-controlled, double-dummy, parallel-group study in which 185 patients were randomized to receive up to 120 mg/day of OXN PR or OxyPR over 4 weeks. Efficacy assessments included Bowel Function Index (BFI), Brief Pain Inventory Short-Form (BPI-SF), laxative and rescue medication use. Quality of life (QoL) and safety assessments were conducted.Results: After 4 weeks, mean BFI score was significantly lower with OXN PR; mean total laxative intake was 20% lower with OXN PR. Mean BPI-SF scores were similar for both treatments and the average rate of analgesic rescue medication use was low and comparable. QoL assessments were stable and comparable with greater improvements in constipation-specific QoL assessments with OXN PR. Overall, rates of adverse drug reactions were similar.Conclusions: OXN PR provides superior bowel function in cancer pain patients, compared with OxyPR, without compromising analgesic efficacy or safety. This study confirms that OXN PR is well tolerated and efficacious in cancer pain patients and results are in line with those seen in non-malignant pain patients. Pain is a particular concern for cancer patients, having a significant impact on quality of life.11 Consequently, patients can experience constipation, gastro-oesophageal reflux, abdominal cramping, spasm and bloating; collectively these symptoms are known as opioid-induced bowel dysfunction.13 Opioid-induced constipation (OIC) is the most frequently reported and persistent adverse event (AE) in patients receiving opioid analgesia.14The effects of opioids are determined by the location of opioid receptors. Activation of opioid receptors in the central nervous system results in analgesia, but activation of opioid receptors in the gut wall leads to reduced gut motility, delayed gastric emptying, increased sphincter tone and slower gut transit time.15 Laxatives are frequently used and can be effective, although many patients still do not achieve adequate symptom relief, as they fail to address the underlying opioid-related mechanisms.17 Use of peripherally acting opioid antagonists has been identified as a promising approach; these agents specifically target gastrointestinal (GI) receptors without limiting the central analgesic activity of opioids.19 Naloxone is a peripherally acting opioid antagonist with low systemic bioavailability (<3%) following oral administration, due to extensive first-pass hepatic metabolism.22 Consequently, orally administered naloxone acts almost exclusively on opioid receptors in the GI tract.23 Targeting peripheral receptors whilst sparing central analgesic function through combining naloxone with oxycodone has emerged as a promising approach for managing OIC, and generated much academic and clinical interest.24Current management strategies for OIC are non-specific, often ineffective and are largely lacking a good evidence base.27 plus a prospectively planned pooled analysis of two of these studies,28 have already confirmed analgesic efficacy of the combination of prolonged-release (PR) oxycodone/naloxone (OXN PR), while also demonstrating benefits in terms of bowel function versus oxycodone PR (OxyPR) alone. Importantly, OXN PR did not lead to a reduction in analgesic efficacy, compared with OxyPR. Moreover, high analgesic efficacy and a positive effect on bowel function associated with OXN PR have been shown in a long-term study,29 and in a large observational study.30 The trials described above have demonstrated the benefits of the combination of oxycodone with naloxone in patients with chronic non-cancer pain. Because opioid drugs are recommended for the management of moderate/severe pain in cancer patients,31 the aim of the current study was to investigate whether OXN PR can also improve constipation and maintain analgesia, compared with OxyPR, in the cancer pain patient population.Three large, randomized, placebo-controlled Phase III trials in patients with non-cancer pain,32 was a 4-week, international, multicentre, randomized, double-blind, active-controlled, double-dummy, parallel-group, Phase II study, designed to evaluate the safety and efficacy of OXN PR in patients with moderate/severe chronic cancer pain. The study was initiated on 2 November 2007 and the extension phase was completed on 17 August 2010. Following the screening period (3–10 days before randomization), eligible patients stopped their pre-study opioid and laxative medication and were randomized (on Day 1/Visit 2) to switch directly to either OXN PR or OxyPR during the 4-week double-blind treatment phase. During the core phase of the study, all subjects, investigators and sponsor personnel were blinded. Treatments were masked in a double-dummy fashion, whereby subjects randomized to receive OXN PR were given OXN PR and OxyPR placebo, and subjects randomized to receive OxyPR were given OxyPR and OXN PR placebo. Patients attended three further clinic visits , and received four additional telephone calls . Patients could enter an open-label extension phase, the details and results of which will be reported separately. The study was performed in full compliance with applicable Good Clinical Practice33 and regulations, and in accordance with the Declaration of Helsinki.34The OXN2001 trial 37 compared with patients taking OxyPR alone; and (ii) to compare efficacy for management of chronic cancer pain, as assessed by the Brief Pain Inventory–Short Form (BPI-SF).38 The secondary objectives included a comparison of effects on laxative and rescue medication use, quality of life (QoL) and safety. Regardless of treatment group, patients were titrated up to a maximum of 120 mg/day oxycodone PR (if required). Open-label oxycodone immediate-release capsules (OxyIR) were available to patients as rescue medication, up to a maximum of six doses per 24 h. Patients who needed to titrate up to oxycodone PR 120 mg/day and who regularly required two or more rescue doses of OxyIR were withdrawn from the study. Bisacodyl tablets were available as laxative rescue medication, up to a maximum of five doses within seven consecutive days.There were two primary objectives: (i) to determine whether patients with moderate/severe cancer pain taking OXN PR experience an improvement in symptoms of constipation, as measured by the validated Bowel Function Index (BFI),Eligible patients were aged ≥ 18 years, with a diagnosis of cancer and a documented history of moderate/severe, chronic cancer pain, requiring round-the-clock opioid therapy . Subjects had to be willing and able  to participate in all aspects of the study, including use of medication, completion of subjective evaluations, attending scheduled clinic visits, completing telephone contacts, and compliance with protocol requirements as evidenced by providing written, informed consent. Patients were excluded from the study for the following reasons: evidence of clinically unstable disease or significant cardiovascular, renal, hepatic or psychiatric disease; clinically significant GI disease, or significant structural abnormalities of the GI tract; cyclic chemotherapy within 2 weeks before screening visit or planned during the core study (shown in the past to influence bowel function); radiotherapy that would influence bowel function or pain during the double-blind phase.37 pain control (BPI-SF),39 use of rescue medication and use of laxative medication during the last 7 days were performed at each clinic visit. The co-primary efficacy variable was average pain over the last 24 h based on BPI-SF (non-inferiority bound 1.0). Co-primary efficacy assessments were based on changes from baseline after 4 weeks of treatment.Evaluations of bowel function (BFI),40 and European Organization for Research and Treatment of Cancer QoL Questionnaire-Core 30 (EORTC QLQ-C30)42 were conducted at screening and study end. In addition, Patient Assessment of Constipation Symptoms (PAC-SYM) was conducted at screening, randomization and 4 weeks.43 Adverse events were noted at every assessment post-randomization. In addition, vital signs, clinical laboratory tests, physical examinations and 12-lead electrocardiographs (ECGs) were conducted throughout the study. Patients were followed up regarding AEs and adverse drug reactions (ADRs) after study completion. At randomization, Days 2, 4, 6 and 8, patients were asked about symptoms of opiate withdrawal .44Quality-of-life assessments, including the European QoL (EuroQoL) EQ-5D instrumentα = 0.05 assuming a common standard deviation (SD) of 26.Patients were assigned to treatments  using a pseudo-random number generator in a computer program. During visit 2, eligible subjects were randomized to one of two treatment groups (i.e. OXN PR or OxyPR) according to a randomization schedule prepared by the Clinical Supplies Department of the Sponsor or an associated company. Treatment assignments were randomized within blocks of fixed size. No stratification was done. The study was designed to have a power of 80% to detect a treatment difference of 12 on the BFI on a two-sided level of significance of α = 0.05 assuming a non-inferiority bound of 1.0 and a common SD of 2.0.Non-inferiority of OXN PR to OxyPR regarding pain intensity could be concluded on a one-sided level of significance of t-tests were performed at the 5% significance level.For the primary analyses, analysis of covariance (ANCOVA) was used to compare treatments regarding primary and co-primary endpoints at 4 weeks, adjusting for baseline observation, and using the last observation carried forward (LOCF) approach for missing values. For the BFI, the null hypothesis was a zero difference (on average) between treatment groups at the final visit. The alternative hypothesis was that there is a difference between the treatment groups. Two-sided tests were performed at the 5% significance level. For BPI-SF, the null hypothesis was a difference of −1 (on average) between treatment groups at the final visit, in favour of Oxy PR (OXN PR inferior to OxyPR). The alternative hypothesis was a difference greater than −1 (OXN PR non-inferior to Oxy PR). One-sided Additional sensitivity analyses were performed for co-primary endpoints using the same ANCOVA analyses on the non-LOCF data and baseline observation carried forward (BOCF) data. Mixed-effects models for repeated measures (MMRM) analyses were also conducted, adjusting for visit and treatment × visit interaction, and assuming a constant treatment effect over visits in respective MMRM analyses. For other efficacy outcomes and safety data, summary statistics were produced.n = 20; OxyPR, n = 12).Of 224 enrolled patients, 185 were randomized, 184 were part of the double-blind safety population and 183 were included in the full analysis population I; the full analysis population II consisted of 157 patients and the per-protocol population of 133 patients. During the blinded data evaluation it was recognized that 28 patients randomized dropped out early but not due to AE constipation and not due to lack of effect. It was decided at a blinded stage to exclude those subjects from the full analysis population I as those patients would not give valid information about the drug effects regarding BFI if the distribution was not equal in both treatments arms. The primary analysis (superiority testing) of BFI was performed in an intention-to-treat manner on the full analysis II population. The patient dispositions and study populations are shown in Demographic characteristics were well balanced between treatment groups. The only exception to this was a slightly higher percentage of patients aged ≤ 65 years in the OXN PR group, compared with the OxyPR group , and had similar mean (SD) durations of study participation  and daily doses .35 It is a three-item questionnaire that takes into account subjective criteria often reported by the patient. Using analysis of standard error of measurements and one-half SD characteristics of each BFI component, Rentz et al. reported that changes in BFI score ≥12 points represent clinically meaningful changes while score changes of less than 7.5 points are unlikely to be clinically meaningful in patient’s perception of their bowel habits.35 At randomization, mean (SD) BFI values were high and comparable in the OXN PR and OxyPR groups , and similar to baseline assessments in previous OXN PR Phase III trials,27 indicating that patients suffered from constipation caused or aggravated by opioid medication. The difference in change from baseline in BFI score (ΔBFI) between groups was statistically significant  These findings were underlined by the results of MMRM , MMRM , BOCF . A statistically significant difference between treatments in favour of OXN PR was observed already at week 1. Taking all analyses into account, OXN PR is both statistically significantly superior in respect to BFI and has also demonstrated a change that is clinically relevant.Perception of constipation varies from patient to patient and results from three randomized controlled trials have shown that the BFI is a validated, easy-to-use questionnaire for the measurement of opioid induced constipation.p < 0.01). Non-inferiority in pain was further supported by sensitivity analyses, including MMRM, LOCF and BOCF.At randomization, mean (SD) BPI-SF scores were comparable for OXN PR and OxyPR treatment groups (4.16 [1.87] vs. 4.18 [1.87]). There was a slight decrease in mean BPI-SF scores, which was similar between groups. After 4 weeks of treatment, mean (SD) BPI-SF scores remained comparable between OXN PR and OxyPR groups (3.50 [1.88]) and 3.52 [1.80]; p = 0.17). The need for rescue analgesic medication was generally low in both treatment groups throughout the double-blind phase, in terms of both frequency (less than one intake/day) and dose. Differences between groups were not significant for either variable . Over 4 weeks of treatment, PAC-SYM scores improved in both groups, but the degree of improvement at endpoint was significantly greater for OXN PR than for OxyPR, in terms of total symptom score (p = 0.014) and frequency of symptoms  total laxative  intake was 20% lower in the OXN PR group than the OxyPR group , but the difference was not statistically significant  index score was 0.50 (0.33) for OXN PR and 0.49 (0.38) for OxyPR. All mean (SD) EORTC QLQ-C30 scores were comparable between treatment groups at randomization. Mean pain subscore improved in both groups. Importantly, the mean (SD) constipation subscore in the OXN PR group was 44.32 (35.16) after 4 weeks of treatment , compared with a subscore of 59.78 (35.13) in the OxyPR group . The improvement in this quality of life measure correlates well with the improvement seen measured by the BFI (R = 0.71)The proportion of patients who experienced AEs or ADRs was generally similar for OXN PR and OxyPR groups . Approxin = 16; cardiac disorders n = 2). There were no clinically important changes in vital signs, laboratory values, ECG assessments or modified SOWS observed. Mean (SD) SOWS values at baseline were 8.01 (7.76) and 8.90 (7.81) for OXN PR and OxyPR, respectively. These remained stable throughout the assessment period .The incidence of serious ADRs was low in both groups . In tota45 but are associated with AEs such as constipation. Results from this study demonstrate that OXN PR provides comparable analgesia to OxyPR for patients with moderate/severe cancer pain, whilst significantly improving bowel function and reducing symptoms of constipation.Opioids are widely recommended to relieve pain in cancer patients,10 Primary efficacy findings were underlined by significant differences in PAC-SYM domain scores in favour of OXN PR.OXN PR was superior to OxyPR with respect to bowel function, particularly reducing constipation, as measured by the BFI. Importantly, the difference between the two treatments was both statistically significant and clinically relevant and, moreover, achieved with less laxative use with OXN PR (20% less). In fact, there was already a statistically significant benefit in BFI score for OXN PR, compared with OxyPR, after 1 week. Overall, achieving this improvement in BFI with reduced laxative use in the OXN PR group, in such a short time frame, is encouraging, considering the severity of underlying disease and the negative impact of constipation on the lives of cancer patients.With respect to the co-primary endpoint of pain relief, OXN PR was non-inferior to OxyPR, as measured by BPI-SF. Rescue analgesic use was low and comparable between groups throughout the double-blind phase, showing that patients were effectively titrated to a stable dose of study medication, and that comparable analgesic efficacy of OXN PR and OxyPR was not influenced by differential use of rescue analgesic medication.General QoL results using EQ-5D and EORTC QLQ-C30 were similar for OXN PR and OxyPR treatments over time. However, results of the specific EORTC QLQ-C30 constipation subscore indicated that OXN PR patients had a superior outcome, compared with OxyPR patients. This could contribute towards an improved quality of life for many patients with chronic cancer pain treated with OXN PR.27 There were slightly more total GI disorders observed in the OXN PR group; however, the incidence of the most frequent AEs such as abdominal pain, worsened constipation, diarrhoea and vomiting were comparable, whilst nausea was reported less commonly in the OXN PR group. Therefore, the slightly higher number of total GI disorders in the OXN PR group is explained by the sum of less frequent AEs. It is possible that GI-related AEs indicate return of more active bowel function (as is aimed for when treating constipated patients), which has also been documented after use of other peripherally acting opioid antagonists, such as methylnaltrexone.46 In a study comparing methylnaltrexone with placebo, in patients receiving the active drug, abdominal pain also occurred more frequently. In addition, more flatulence and nausea were reported for methylnaltrexone;46 this was not seen with OXN PR in the study described here. There were no clinically relevant changes in laboratory values or vital signs related to study medication. Mean modified SOWS values were low and comparable in both groups. In summary, the results suggest that switching from other opioids to oxycodone – as either OXN PR or OxyPR – was generally safe and well tolerated by patients in this trial, with switching to OXN PR giving the added benefit of reduced OIC complications.There were slightly more dropouts due to AEs in the OXN PR group, although the overall incidence of AEs was comparable between treatment groups. Most frequently reported ADRs were consistent with the known safety profile of the opioid analgesic class of drugs, and with those seen in previous Phase III trials of OXN PR in patients with non-cancer pain.47 This timeframe is also deemed adequate for observing differences in constipation based on previous Phase II48 and Phase III data.27The findings of this study should be interpreted within the context of the trial design and patient population. The double-blind phase had a duration of 4 weeks to allow for assessment of analgesic effect, consistent with European Medicines Agency guidelines on clinical studies of chronic moderate/severe cancer pain.49 Additional assessments showed that there was no correlation between BFI score at study end (LOCF) and age (data not shown).Although the demographic profile of both treatment groups was generally similar there was a slightly higher percentage of patients aged ≤ 65 years in the OXN PR group than in the OxyPR treatment group. However, this difference is not clinically relevant, as results from previous clinical studies have demonstrated that the efficacy and safety of OXN PR in older patients is similar to that in younger patients.15 The new targeted approach of administering peripherally acting opioid antagonists is effective and is supported by extensive clinical trial data. Previous attempts to use immediate-release naloxone were unsuccessful because of reversal of analgesia; and the only other licensed peripherally acting opioid antagonist, methylnaltrexone, has to be given by injection.46 The present trial has shown that oral OXN PR tablets are well tolerated and can effectively and conveniently provide targeted treatment of OIC at a dose range which includes a substantial proportion of patients with cancer pain.Opioid-induced bowel dysfunction is common and adds to the burden of living with chronic pain. Current oral and rectal laxatives are often ineffective and do not have a good evidence base.In this study of patients with OIC and moderate/severe cancer pain, patients who were switched directly from other opioids to OXN PR experienced a similar analgesic effect as well as a statistically significant and clinically relevant improvement in bowel function, compared with those switched to OxyPR. Overall, these data are in line with results of previous Phase III trials demonstrating analgesic efficacy and tolerability of OXN PR, suggesting that the combination of oxycodone and naloxone is suitable across the spectrum of patients with cancer and non-cancer pain.


Patients experiencing lower body pain resulting from bone metastases have greater levels of functional interference than those with upper body pain. The purpose of this study was to assess the levels of interference caused by pain after treatment with conventional radiotherapy using the Brief Pain Inventory (BPI) and to validate this tool for telephone use. After radiotherapy, a total of 159, 129, and 106 patients completed the BPI over the telephone at months 1, 2, and 3, respectively. Cronbach's alpha, confirmatory factor analysis, and discriminant validity tests were performed to assess the validity of the BPI. One-way ANOVA was used to compare BPI scores. There was no statistically significant difference in functional interference among patients after treatment. Internal consistency of the BPI was high. Functional interference may be inherently higher in patients with pain in the lower body. Telephone use of the BPI is reliable and recommended in this population. Bone metastases can occur in up to 70% of patients with advanced cancer , and theBone metastases have received much attention in the literature regarding effective treatments and management of pain resulting from the disease , 7–9. ThThe Brief Pain Inventory (BPI), developed by Cleeland and Ryan , has beeThe BPI is usually administered to patients prior to treatment in person. When following palliative patients, it is beneficial to reduce their number of visits to a health care centre. Studies in the past –15 have The Rapid Response Radiotherapy Program (RRRP) at the Odette Cancer Centre, Toronto, Canada provides rapid access to palliative radiotherapy. During the period lasting from May 2003 to June 2007, patients with bone metastases referred to the RRRP and subsequently treated with palliative radiotherapy were screened for eligibility for this prospective study assessing pain and functional interference using the Brief Pain Inventory (BPI). The institution's research ethics board had approved this study prior to commencement. Baseline data was collected, and patients were followed at four-week intervals following the end of radiotherapy for a total of 12 weeks . Patients were contacted by telephone for these followups by a trained research assistant. The BPI questions were read out loud, and the patient did not have a physical copy present when answering the items.The BPI is a validated multidimensional pain assessment tool developed by Cleeland and Ryan  which isThree questions regarding pain intensity and seven regarding pain interference are rated on an ordinal numerical scale with anchors of 0 (no pain/interference) to 10 (maximum pain/interference). Pain intensity is measured according to the worst pain experienced in the last three days, average pain in the last three days, and current pain. Pain interference assesses how that pain has affected general activity, mood, walking ability, normal work, relations with others, sleep, and enjoyment of life.Demographic results were expressed as means, standard deviations (SD), medians and interquartiles for continuous variables, and proportion for categorical values. Patients with complete data (no missing items on the BPI) were used for analysis. All analyses were repeated at all three follow-up intervals where data was collected. All analyses  were used to validate the psychometric properties of the BPI.Patients were separated into groups based on the location of pain: upper or lower skeletal metastases. Upper pain included patients receiving treatment to cervical or thoracic spine, shoulder girdle/upper extremity, ribs, and skull. Those receiving treatment to the lumbar spine, sacrum, or any of the pelvic girdle , femur , and tibia were classified as having “lower skeletal pain”. Those receiving treatment to the thoracolumbar spine were excluded from this portion of the analysis to prevent inaccurate reporting of pain location. One-way ANOVA was applied for comparing mean scores of BPI subscales in patients with lower or with upper skeletal bone metastases at different follow-ups and also at baseline.With two- and three-factor analysis, item-item correlations were examined to identify redundant questions. Standardized Cronbach's alpha was applied to estimate internal consistency within each subscale . ChangesCFA was used to examine the structure of the BPI as a single construct , two-factor (pain and interference), and three-factor model  for each follow-up period  . CovariaR-squared and t-statistic), and composite reliability were provided for the best two-factor and three-factor models. Composite reliability is a measure of the overall reliability of a collection of heterogeneous but similar items. The minimum acceptance level of composite reliability is 0.70, and the minimum critical t value is 3.29 for P = .001. Standardized factor loadings, associated statistics  were carried out to further evaluate highly correlated factors within the three-factor model. The variance extracted estimates the amount of variance that is explained by an underlying factor in relation to the amount of variance due to measurement error. Fornell and Larcker suggested that constructs should exhibit estimates of 0.50 or larger . It shouP  value of less than  .05 was considered as statistically significant.All analyses were performed using Statistical Analysis System (SAS version 9.2 for Windows) software. Confirmatory factor modeling was carried out using SAS covariance analysis of linear structural equations (PROC CALIS). A two-sided A total of 212, 159, and 133 patients at weeks 4, 8, and 12, respectively, had at least partial data. Of these patients, 159 (75%), 129 (81%), and 106 (80%) had complete data at weeks 4, 8, and 12, respectively, and this cohort formed the study population for analyses on pain and interference. Of the study population at week 4, median age was 65 (range: 30–89), 88 of patients (55%) were male, and 94 patients (60%) were classified as having lower body pain . At weekP  values not statistically significant). At week 8, mean values for pain, activity, and affect in patients with lower skeletal pain were 3.69, 4.63, and 3.39, respectively, in comparison to 3.42, 3.57, and 2.98 for those with upper skeletal pain . At 12 weeks posttreatment, pain was significantly worse for patients with upper skeletal pain than those with lower skeletal pain (P = .0278), but interference levels (both activity and affect) were similar.Analysis of baseline data showed that patients with lower skeletal pain had significantly greater activity interference than those with upper skeletal pain; this is similar to the result obtained by Wu et al.  in theirThere was internal consistency among all items except sleep at each follow-up period. Improvement in correlation was seen at each follow-up period and in both two- and three-factor subscales when the sleep item was improved. Alpha for two-factor analysis improved from 0.48 to 0.91 at 4 weeks, 0.54 to 0.91 at 8 weeks, and finally, 0.56 to 0.91 at 12 weeks. For the three-factor analysis, removal of sleep from the activity subscale improved alpha from 0.45 to 0.87 at 4 weeks, 0.48 to 0.90 at 8 weeks, and 0.53 to 0.90 at 12 weeks . In all In general, both the two-factor and the three-factor models demonstrated reasonably high levels of internal consistency, composite reliability, and convergent validity Tables  and 5. TFactor loading and associate statistics for the best two-factor and three-factor analyses were constructed at each follow-up period. The correlation between grouped items  was high for all three data sets  test indicated correlation of 0.88, 0.87, and 0.85 at weeks 4, 8, and 12, respectively, , the Chi-square difference test demonstrated significance between mixed and separated support at all followups. The variance-extracted test failed to confirm discriminant validity for all three sets of data. Despite these results, the combination of different analyses confirmed the validity of the construct since reasonably high levels of internal consistency, composite reliability, and convergent validity were present at weeks 4, 8, and 12. Although the two-factor model is adequate, the three-factor model is preferred since fewer covariance terms were needed to fit the model. Furthermore, this model satisfies an additional IMMPACT recommendation.Functional interference is a significant component of quality of life in advanced cancer patients which has seldom been addressed in the literature. It has been shown that improvement in metastatic bone pain will similarly improve functional interference as a result of this pain . The BPIThe fact that interference levels are worse in lower skeletal pain patients prior to radiotherapy suggests that in general people exhibiting lower body pain will have more functional interference than those with upper body pain, not only inclusive to patients with bone metastases pain. Studies, however, have suggested that there is an inherent difference among pain interference between cancer and noncancer patients  meaning The BPI has been used in numerous studies via telephone, to assess a patient's response to treatment. Although the questions remained the same whether asking a patient across the phone or in person, the differences in setting may affect responses and consequently the validity of the BPI. When comparing the statistical analyses to results of Wu et al., who validated the BPI in patients with bone metastases physically in clinic with the same methods , the simThe sleep item of BPI contributes little to both the activity or affect subscales of three-factor analysis and interference in general in the two-factor analysis. Previous papers have also noted this difference when conducting an analysis of the BPI , 22–24. A further point of research would be to test the correlation of the BPI with other musculoskeletal functional scales, such as the Western Ontario and McMaster University Osteoarthritis Index (WOMAC)  and the The BPI is a valid and reliable tool for use across the telephone and should be the preferred mode of contact when following up with advanced cancer patients. CFA of the BPI demonstrates validity with both the two- and three-factor models; however, the latter is preferred as fewer covariance terms are needed to fit the model and it satisfies an additional IMMPACT factor. Patients with lower skeletal pain resulting from bone metastases should receive prompt treatment to reduce their functional interference and improve their overall quality of life. The preferred modality for following palliative patients with quality-of-life assessments should be via the telephone as it reduces the travelling burden associated with multiple visits to a health care setting.The authors have no conflict of interests to disclose.