Background: Patients suffering from chronic pain frequently ask pharmacists for advice.Aims: This study was prompted by inadequacies in the available body of literature reporting on pharmacists’ experiences with providing care for patients with chronic pain in the community setting.Methods: A qualitative investigation of Ontario community pharmacists’ experiences was carried out. Participants were interviewed using a semistructured guide. Interviews were analyzed using thematic analysis, influenced by grounded theory.Results: This study revealed that pharmacists were knowledgeable and empathetic toward patient concerns. Challenges in their role included financial factors, patient access to multimodal treatment options, potential for harm associated with opioid use, inadequate monitoring, and gaps in training.Conclusions: This study reports community and Family Health Team pharmacists’ experiences caring for patients with chronic pain and perceptions of their professional role, including strengths and limitations, and identifies perceived challenges in the health care system. As highly accessible medication experts, pharmacists can assist patients with individualizing their therapy based on their comorbid conditions, concurrent medications, and other specific needs, expectations, and goals. Pharmacists routinely provide information on opioid therapy, benefits and risks, overdose identification and management, and proper storage and disposal.13 Patients in pharmacy settings feel ready to discuss and accept written information on related risks such as substance use disorders.14 Other services that pharmacists can provide include optimizing patients’ therapy through pain assessment, medication review, monitoring for interactions, ensuring appropriate dosing, and consulting on switching or tapering of medications such as opioids.13 However, the pharmacist’s role in the management of chronic pain remains largely unstructured and underinvestigated. Gaps in knowledge exist, with fewer than half (48%) of pharmacists reporting being familiar with the Canadian opioid guidelines and only 52% able to state the recommended opioid watchful dose.7Pharmacotherapy is a key component of chronic pain management, and patients frequently seek advice from pharmacists.15 and there is evidence that those beliefs can be influenced by the information and advice presented to patients about their pain by a health care provider.16 For example, in chronic lower back pain, both the patients’ perceptions of their condition and health care providers’ beliefs and attitudes, such as whether a patient is likely to be difficult to treat, can influence treatment decisions.18The beliefs and attitudes of both pharmacists and patients can affect the care provided and the outcomes of that care. Treatment outcomes have been shown to be affected by patients’ initial beliefs and expectation of success for a given pain treatment,Although pharmacists’ perceptions and beliefs regarding chronic pain might contribute to the formulation of treatment decisions and to the information provided to patients, the content of those perceptions and beliefs has not been investigated. Therefore, the aim of this study is to explore the perceptions, beliefs, and experiences of pharmacists regarding patients with chronic non-cancer pain. This includes pharmacists’ understanding of their role in providing care to patients with chronic pain, their perceptions of patients with chronic pain, and their experience of communication with prescribers in the context of providing care to patients with chronic pain.Due to the lack of previous research on the topic, we chose a qualitative, exploratory study design to address the question under study and used one-on-one interviews with a small sample of community pharmacists to facilitate a detailed examination of pharmacists’ perspectives.We used a purposive sampling strategy to recruit Ontario-licensed pharmacists who were actively practicing in a community pharmacy or on a Family Health Team. In the province of Ontario, Family Health Teams are practice settings that can include nurse practitioners, registered nurses, social workers, and dietitians as well as physicians and pharmacists. We recruited participants by means of a recruitment poster and invitation letters sent by e-mail through the Ontario College of Pharmacists’ database of pharmacists who had provided consent to be contacted for research purposes. We screened participants for eligibility, excluding those not practicing or practicing in other settings, such as hospitals, nursing homes, or pharmaceutical companies. No incentives were provided for participation in the study. We obtained approval of the study by the University of Waterloo Human Research Ethics Committee and written consent from all study participants.19We collected data through individual semistructured interviews. This format provides the interviewer with enough flexibility to explore emergent lines of inquiry, while also keeping the interview fairly focused on the general topic. A major benefit of this method is that the flexible format helps develop rapport and gain participants’ trust by being fairly conversational, as well as allowing researchers to explore participants’ responses in depth.20 A core element of the grounded theory approach is that theoretical propositions or relationships are developed throughout the data collection and analysis process, rather than proposed a priori to be tested. Our research was also intended to be exploratory and fairly descriptive rather than concerned with developing a theoretical framework. However, it was important for us to approach the research without strong expectations about pharmacists’ experience and to let themes emerge from the research process. Because three of the authors, including the main interviewer, are pharmacists, it was impossible not to have some preconceptions about pharmacists’ perceptions. Contrary to the original formulations of grounded theory, we consulted previous research in the area in advance.Our approach was influenced by grounded theory, which has become a widely used framework for qualitative research in the social and health sciences.A primary interview guide was developed by research team members based on the previous body of literature in chronic pain management. In this stage, having both pharmacist and non-pharmacist team members helped avoid unintentionally incorporating assumptions about pharmacy practice into the questions. This interview guide was then revised after the first three interviews with pharmacists. The initial and final interview guides covered seven main topics for discussion; an introduction with specific questions about the pharmacists’ current practice and length of experience, their feelings towards patients with chronic pain, perceived concerns, thoughts and beliefs regarding the use of opioids for chronic pain, experience with communication with healthcare providers within the context of chronic pain treatment, challenges encountered and pharmacist training regarding chronic pain .Table 1.We conducted interviews from June to September 2016, either in person or by telephone, according to pharmacists’ schedules. A single interviewer conducted all but one interview; two team members were present for the first interview. Interviews lasted 40 to 90 min and were audio recorded. We transcribed the recordings verbatim using NVivo qualitative analysis software v11 for coding .21 As in grounded theory, each interview transcript was coded immediately after collection to identify salient themes, with the coding structure modified as new themes emerged. We followed this open coding with axial and selective coding to identify and refine new themes.21 However, the analysis is best described as thematic analysis because the emphasis was not on the development of theory as such, and the themes that were developed were mainly descriptive.22Our analysis method was also influenced by the constant comparison method of grounded theory.To help ensure rigor in the data collection and analysis and to avoid unintentional bias due to our own perspectives and experiences, we made use of the diversity of the research team in several ways. The first interview was conducted by two team members, a pharmacist and a non-pharmacist social scientist, who then met to discuss the contents of the interview guide and initial impressions regarding possible themes. After being transcribed, the first two interviews were independently coded by two researchers, who then compared their coding structures to test the conceptual validity and completeness of the set of themes that had been identified. The subsequent interviews were then coded by the main interviewer after transcription. The coding of these interviews was reviewed by a third team member for consistency. The entire research team reviewed and commented on the final set of themes.19 As with much research in health care services, our purposive sampling was not strictly theoretical.23 Recruitment continued, concurrent with the analysis, but additional participants were not specifically selected for theoretical reasons but to ensure that thematic saturation was reached; that is, until no substantial new information about themes was generated by additional interviews.21Grounded theory generally calls for theoretical sampling, in which additional data are collected based on the emerging themes in the analysis and researchers direct the sampling procedure to further develop the theory.25 In this case, the relative consistency of the views of the pharmacists and the straightforward nature of the interview questions likely contributed to saturation being reached with this small sample.We conducted three in-person interviews and nine one-on-one telephone interviews. We reached data saturation by the ninth interview, and the final three interviews did not identify any additional themes. In previous research exploring perspectives of community pharmacists and other medical personnel, saturation has been met with similar sample sizes (<20 participants).We interviewed 12 pharmacists. The mean age of participants was 46 years (range 27–63). Of the 12 participants, 66% were female, and participants had been practicing pharmacists for 19 years on average: 17 years for those with Family Health Team backgrounds  and 20 years for community pharmacists (the remainder of participants). Most participants had a bachelor of pharmacy degree (8 participants) and only 17% of participants had residency training (2 participants) or doctor of pharmacy degrees (2 participants). Topics discussed and themes identified from the qualitative analysis are shown in 26 Some expanded their definition of chronic pain by commenting on associated issues such as anxiety, depression, disability, and impaired quality of life.P3: Chronic is associated with long-term, so we’re dealing with pain that is due to a physical condition that’s … maybe lasting for a couple of months. We’re dealing with a full spectrum of symptoms from anxiety, from depression, from even organic effects on blood pressure and sugar control.Participant pharmacists did not differ greatly in their understandings of what constituted chronic pain. When asked how they would define chronic pain, almost all mentioned the core characteristics of chronic pain: unknown etiology and chronicity (exceeding 3–6 months).P5: [They] look like they have a black cloud over their head. They always look sad, they look depressed. They look unhappy. The people with true chronic pain, their quality of life, their joy in life, is not sustained.P7: They want to know what they are; they have an anxiety because having pain is not normal for them. They don’t know if it’s good or bad. So, that’s if it’s a new pain. But if it’s not a new pain and they have been having pain for a long time, then their first mention—it’s inconveniencing them.P9: They have many concerns, you know, stemming from their pain. Not just that their pain is not controlled but that they cannot function and, you know, have a good quality of life.With only one exception, pharmacists described feelings of empathy toward patients with chronic pain and expressed their thoughts on their patients’ perceived desires . In their experience, the distress of pain and disability was visible in their patients’ appearance. This perception induced a feeling of empathy toward patients with chronic pain. The pharmacist participants thought that the most distressing part of chronic pain for patients was inadequate pain control intertwined with the chronicity of the pain.P5: I had one doctor tell me, he had a patient who was in her 80s, and he said, “She’s going to fire me, as a doctor! She’s been my patient for over 40 years and she threatened to fire me!” So, you know, I think that doctors do get a problem with their patients and they don’t want to upset them either, you know, if you have a nice guy as a doctor.Pharmacists perceived that patients seeking drugs sometimes place pressure on physicians to prescribe opioids. In these cases, patients insist on having opioids prescribed for their pain and might even threaten their prescribers.P1: I think there is something about being seen, being heard, being understood, being validated, and having a place where they are believed. And some days I think that that’s the therapy and that’s in and of itself.P3: Lots of these patients are concerned with how they feel when they approach their health care provider or their pharmacist for their prescriptions.Participants also believed that because pain is a subjective feeling, it might not be well understood by those who have not experienced chronic pain. The subjective characteristic of pain was described as being emotionally challenging for patients because they frequently encounter skepticism or misunderstanding related to their pain. Pharmacists reported that patients with chronic pain often expect their families, as well as society in general, to believe their accounts of pain and to validate their experiences and expect their health care providers to hear their concerns and to do their best to control their pain.The pharmacists in this study described their role in providing care to patients with chronic pain as including several dimensions. These included the assessment and management of pain, especially when assisting patients with selecting over-the-counter analgesics or dispensing prescribed medications for pain. Respondents reported routinely inquiring about the severity, duration, and possible etiology of pain when assessing patients’ pain to determine the best course of action for the patient, including recommending nonprescription options for treating pain.P8: I think that it’s something that needs to be addressed, perhaps holistically—more than just prescribing painkillers.Pharmacists in this study also saw their role as being part of a comprehensive approach to pain management, which included collaboration with prescribers and other health care professionals. All participating pharmacists stated that if a referral were necessary they would refer the patient to his or her family physician. Study participants frequently spoke of the physical, psychosocial, vocational, and social aspects of chronic pain and believed that treatment of chronic pain should not be limited to prescribing of medications. Chronic pain and its associated health conditions, such as depression and anxiety, that impact patients’ lives should, they felt, be addressed by a variety of health care professionals, including physiotherapists, psychotherapists, nurses, social workers, and occupational therapists.Finally, pharmacists felt that they played a significant role in advising and educating patients about pain management, including face-to-face consultations with a focus on education about pain, medications used in the treatment of pain, and nonpharmacological measures such as keeping a pain diary, lifestyle changes, and better understanding additional resources, such as websites.P1: Are you moving more? Are you doing more in your day? No? Do you think this is really giving you much more in your quality of life and you being able to participate? If you’re not improving function, then [the medication is] not worth having.Unrealistic expectations about chronic pain management and the inadequate use of alternatives for opioids were two parameters that pharmacist participants felt often led to inappropriate use of medications, particularly opioids. Because most patients do not achieve complete resolution of their pain even with opioid medications, several participants felt that patients should receive education to help them to have realistic expectations about their pain and that chronic pain management should focus on functionality.P10: Now this patient will approach the nearby pharmacy and will buy whatever he wants, but we missed our customer.There were a number of factors that pharmacists believed may hinder their ability to fulfill their perceived role. These included financial factors, particularly the fact that the sale of medications is the primary source of income for community pharmacists. This was seen as sometimes being a barrier to pharmacists being effective in finding nonpharmacological options. For example, one described how, if they refused the sale of large quantities of opioid products that are available for purchase without a prescription, patients might take their business elsewhere.The cost of medications was also seen as a barrier to pharmacists fulfilling their role in care of patients with chronic pain. Because non-opioid therapeutic options such as pregabalin, or non-drug interventions such as physiotherapy, are expensive and typically not covered by government health care plans, opioids are a less costly option for the management of chronic pain, encouraging physicians to prescribe opioids. Pharmacist participants also emphasized that patients with chronic pain often did not have adequate support from the government or the framework within which the health care system exists, as evidenced by the lengthy wait times for consultations with pain specialists.P9: Treatment is complex and multifactorial and drugs are a small part of a successful treatment plan and the other parts are kind of expensive—things like physio, occupational therapy. And it might, it’s kind of in a way, it’s hard to measure too. So, you know, like it’s easy for the province to look at wait times for hip replacement. Although I guess they could look at wait times for chronic pain clinics, this is like they do not open a can of worms.Although the necessity of a comprehensive approach was clear to participants, they believed that this was best achieved in medical centers in which health care professionals work together to serve patients with chronic pain. They believed that even though chronic pain is a multidimensional health condition that requires a multimodal approach through collaboration of several health care providers, there is insufficient budget allocated by the government to cover multimodal collaborative care services.P4: Just in case people ask a question and go to another pharmacy down the street—which often happens—and somebody says to them something completely different. And that doesn’t look as professional.P2: We learn it all in school, but some of us graduated 2 years ago, some 10 years ago, some 20, some 30. So, a refresher would be good to boost that confidence and to do that.P6: If you have a very good knowledge of pain and the management, then it will definitely help you to communicate better with physicians in terms of also recommending alternatives or you have a better idea about the dosing and other alternative options as well. So, it’s a combination of both—the knowledge and the communication together.Another important barrier to pharmacists fulfilling their role in care for patients with chronic pain was knowledge among pharmacists themselves. Almost all pharmacist participants believed that there was a wide range in pharmacist knowledge about chronic pain management and that, in general, pharmacists needed more training in several areas, including pain assessment, pharmacologic and nonpharmacologic treatments, and communication skills. Differences in knowledge between pharmacists was thought to lead on occasion to contradictory recommendations to patients, adversely affecting pharmacists’ credibility and patients’ trust. In the perspective of some participants, this inconsistency might arise from pharmacists’ different educational experiences, and this was thought to differ with time since graduation. Several pharmacists described a difference in knowledge between pharmacists who had graduated within the previous few years and members of cohorts that graduated 10 or 20 years prior. However, participants felt that these knowledge gaps could be bridged by continuous education programs.P5: Pharmacists aren’t taught to recognize suspicious prescribing methods, and we aren’t taught what to do about it.P4: Like, if someone came in, how would you catch it or how would you respond? Because no one taught us, like do I call the police, do I—like even now, to this day I don’t know if I’m legally obliged to call the police if we catch them. I would think yes, but the thing is how would you do so? Like you need to run through some scenarios, because when it actually does happen to you in real life.Gaps in knowledge related to regulation were another factor perceived to hinder pharmacists in performing their role. Pharmacists expressed a need for more knowledge and training in legal issues associated with narcotics. Respondents reported that many pharmacists are not confident in their ability to react in an optimal manner to forgeries or to report misconduct of health care professionals to authorities.P3: We’re being asked to be the gatekeepers and making sure that we’re dispensing properly.Another factor perceived to hinder pharmacists’ performance of their role was the risk of opioid misuse disorder. The potential risk for misuse was the most frequently stated concern of pharmacists related to opioid use and was associated with a strong sense of responsibility to minimize risks for patients. From their perspective as gatekeepers for opioid use, the pharmacists in our study believed that they had a responsibility for the health and safety of their patients as well as society. Participants felt a need to balance risk of misuse with providing relief from pain for their patients and described themselves as exercising caution in monitoring the appropriateness of medications.P9: I don’t think we’re very systematic in assessing for addiction. The pain specialist that I work with, she is systematic—she does that with every patient—but family doctors are not.P3: The other one is limiting quantities; I think that’s extremely important. Physicians need to be more aware of quantities. Physicians need to be more aware of refill frequency.From the pharmacists’ perspectives, inadequate monitoring of efficacy and safety for patients receiving opioid therapy stem from several factors: insufficient time, inadequate communication systems between health professionals, pressure from patients seeking medication, and pharmacy finances . They believed that family physicians do not currently allocate enough time to addressing the multiple issues related to the use of opioids; our respondents felt that physicians often did not have sufficient time to review medical records of patients who were prescribed opioids to determine potential for risk of misuse. They believed that, in the context of insufficient monitoring, strategies to reduce the potential of opioid misuse should be used, such as limiting the permitted quantity of opioids in a prescription and/or limiting prescribing to health care providers with specific qualifications in opioids.Almost all pharmacists in this study stated that they had good communication with physicians, preferring to communicate with physicians by fax, with the exception of one Family Health Team pharmacist who preferred face-to-face communication. Reasons for contacting a physician included correcting errors in prescriptions, such as improperly ordering refills for opioids, incorrect amounts of medications, typos, or a lack of physician signature. Pharmacists also communicated with physicians to discuss drug interactions, to confirm opioid dose conversions, and to answer questions from physicians inquiring about the availability of medications and available dosage forms. Despite this good communication, there was a lack of a dedicated communication system enabling pharmacists and physicians to update patient information. A common example cited was patients’ use of multiple walk-in clinics to obtain multiple prescriptions, without any of the prescribers or pharmacists being aware of the overlap of service.P5: If they are an empathetic doctor who gives each patient more than their 5 or 10 minutes, then usually they’re willing to accept suggestions. But if they’re a “you get 5 minutes and you’re out the door/one-problem doctor,” then I usually find that they are not responsive to any suggestions from a pharmacist.Participants believed that communication between pharmacists and physicians had improved over the previous 20 years. All pharmacist respondents had positive comments regarding their communication with physicians, although they did indicate that barriers for effective communication with physicians continue to exist. Almost all participant pharmacists believed that physicians were generally not very accessible, particularly those physicians working in hospitals for whom direct office contact information is often unavailable. Pharmacists perceived some physicians to be uncooperative, and they identified several characteristics they thought typified these uncooperative physicians. Pharmacists perceived younger physicians as well those who were trained in a team-focused environment as more communicative and receptive to pharmacists’ comments. Additionally, pharmacists felt that the personality of the individual physician played a role, explaining that some people are less communicative by nature. Pharmacists generally thought that physicians who were empathetic and spent more time on their patients were also more likely to be receptive to pharmacists’ comments. As one commented,P1: So, pharmacists are often bound by little picky details that they have to ensure that are done, and physicians may not be aware of that. And with a doctor who is in a high-stress area—and pharmacists are too—they won’t realize why they are getting these messages and why these things need to be changed.Trust between pharmacists and physicians was seen as playing a pivotal role in communication. Pharmacists believed that trust develops over time and that it was the responsibility of pharmacists to make physicians familiar with the profession of pharmacy and their scope of practice, as well as to provide physicians with appropriate recommendations.To the best of our knowledge, this is the first qualitative study to investigate pharmacists’ perceptions and experiences with providing care to patients with chronic pain in a community setting. Participating pharmacists were knowledgeable about chronic pain and the challenges of providing care to patients with chronic pain. Adequate monitoring, appropriate use of medications and drug information resources, and patient education were identified as factors important for the effective and safe management of chronic pain.27 In contrast, key opioid treatment goals include pain relief, improved quality of life, and improved functional capacity.27 Patients who have function-focused expectations about chronic pain management report improved experience of pain and reduced risk of side effects and addiction.30 This suggests that educating patients about the characteristics of chronic pain and its management and defining pain relief along with functionality as the ultimate treatment goals will lead to realistic expectations about treatment and result in a more balanced use of medications and potentially reduced dependence on opioids.Patients’ unrealistic treatment expectations, inadequate access to alternative treatments for opioids, and the lack of a comprehensive approach to pain management were identified as factors that can impede management. Because there is a fine line between effective pain control and impaired functionality due to opioid safety risks, unjustified long-term opioid therapy can be associated with poor self-rated health, being unemployed, higher use of the health care system, and reduced quality of life.31 and an eight-year follow-up study that reported that only 34.6% of patients were pain free.32Participating pharmacists also recognized and were empathetic to patients’ concerns about lack of pain control, as well as lack of family, social, and government supports, such as inadequate access to expert health care and collaborative team-based care , which add to the distress of patients with chronic pain. These beliefs were well founded and are supported by the results of a four-year follow-up study that found that two thirds of patients do not receive adequate pain management34 There is evidence that this expanded role is effective in providing better outcomes for patients. Pharmacists can help reduce the strength of pain medication and frequency of use while maintaining pain management.35 Delivering patient education can reduce pain intensity and reduce adverse events,36 decrease the cost of pain management,37 and help reduce the frequency of harmful medication combinations .38Driven by the ongoing expansion of pharmacists’ scope of practice and the development of pharmaceutical care, it is expected that the role of pharmacists will continue to move from medication-oriented dispensing toward a more comprehensive patient-centered model of practice in which pharmacists use their expertise to assist patients in addressing their pain, rather than simply dispensing medications.39 Despite the lack of data to support long-term efficacy and safety of opioids for chronic pain,28 the pharmacists in this study were very concerned that the use of opioids for chronic non-cancer pain is continuing to increase. Similar findings have been found in a 2011 survey of Ontario pharmacists, who voiced a concern for patients on opioids.13 Previously surveyed Canadian pharmacists have also expressed low confidence in their ability to identify patients with potential prescription drug misuse and addiction.40 Targeted curriculum education and training postgraduation were suggested as potential solutions to help build pharmacist capacity in this area.Pharmacists are still at the early stages of this transition. In this study, pharmacists felt that their ability to perform these expanded roles was limited by various barriers. One important barrier was the risk of potential harm associated with opioid use and confidence in managing this risk. Canada is the world’s second largest per capita consumer of opioids.34 Adequate monitoring ensures that signs of aberrant drug behavior will be recognized as soon as possible by pharmacists, who can then initiate early intervention strategies.41 However, pharmacists consider their workload in community pharmacies, gaps in communications with prescribers, and the fact that medication sales are the primary source of income for pharmacies as barriers to managing potential misuse and diversion of opioids at the pharmacy level. One suggested solution is reimbursement for the documenting and monitoring of opioid prescriptions, to empower pharmacists to better assume the shared role of stewards for opioid medications.Recent Canadian guidelines for opioids for chronic non-cancer pain and draft regulations to expand the scope of pharmacists’ practice encourage pharmacists to take more responsibility for appropriate use of medications and patient monitoring for common diseases and potentially risky medications like opioids.43 A number of non-opioid medications and interventions have demonstrated effectiveness in chronic pain disorders.45 Moreover, non-opioid medications and interventions for the management of chronic pain can produce better functional outcomes than opioids, being outperformed only by strong opioids for pain relief.48 Because chronic pain is disabling, with up to 25% of patients losing their jobs,46 expanded access with financial support is vital to widening therapeutic options for pain management.Although a multimodal approach is recommended by best practice, participants felt that lack of access is a barrier to formulating a comprehensive approach. This is reflected in previous research showing that lack of insurance coverage for alternative medications or treatment approaches is a core concern that can lead to inappropriate pain management.49This study captured the perspectives and opinions of Ontario pharmacists working in a community setting or in a Family Health Team. These opinions may not be representative of pharmacists in other provinces because the pharmacist role varies provincially. Additionally, the use of two different interview modes (in person and telephone) might have influenced the results, although research suggests that such an effect might not be substantial.To conclude, this study describes community and Family Health Team pharmacists’ experiences caring for patients with chronic pain and perceptions of their professional role and identifies perceived challenges in the fulfillment of this role. Participants suggested future action in building pharmacist capacity, making system-based changes to empower pharmacists in providing collaborative team-based care, and improving funding for nonmedicinal and non-opioid pain treatments.


However, both groups demonstrated comparable (p > 0.05) post-operative pain relief over the other aforementioned allocated time intervals. In conclusion, the diclofenac potassium group had slightly better control over post-operative pain than the group receiving loxoprofen sodium.One of the most common post-operative complications of tooth extraction is pain. Oral analgesics, namely loxoprofen sodium and diclofenac potassium, are often prescribed; however, the efficacy of these drugs irrespective of gender and type of extraction has not been tested. Therefore, this study aimed to compare the efficacy of these two drugs in post-dental extraction pain relief among male and female patients in cases of simple and surgical tooth extraction. A single-center, triple-blind, randomized clinical trial was conducted among 100 male and female patients who underwent tooth extraction at Taibah University Dental College and Hospital in Al-Madinah, Saudi Arabia. The patients reported their pain post-operatively after 6 hours and every 12 h for 3 days using the Verbal Descriptor Scale . Descriptive statistics and chi-square tests were run to analyze the data. An equal number of patients received either the drug loxoprofen sodium or diclofenac potassium and completed the study follow-up. Patients allocated to the diclofenac potassium drug group after 36 h were statistically significantly in their reporting of “no pain” and “mild pain” compared to patients allocated to the loxoprofen sodium group (86% vs. 66%, respectively;  Tooth extraction remains a common procedure in dentistry. The most common cause for tooth extraction is dental caries , though A recent study indicated that the intensity of pain reaches its maximum score in the first 24 h after surgical tooth extraction using the McGill Pain Questionnaire . The higLack of dental pain management guidelines, lack of awareness among dentists and a lack of prescription controls for pain medications in practice cause dentists to fall victim to pharmaceutical companies, and “trial-and-error” became the predominant practice. This subjective method of prescribing medication needs to be replaced by safe prescribing practices that take into account patient variability and include a discussion about the type of dental procedure and effective pain relief to provide the best care for patients .Notably, in Saudi Arabia, diclofenac potassium was found to be more effective than paracetamol or ibuprofen for moderate to severe post-operative pain . The limTwo oral analgesics were chosen in this study to elucidate the most effective analgesics prescribed by dentists for reducing pain after tooth extraction; they were also chosen for their efficiency, potency and availability in pharmacies for all patients in Saudi Arabia, specifically Al-Madinah. The two randomly distributed analgesics used in this study were loxoprofen Roxonin 60 mg) and diclofenac potassium (Rapidus 50 mg). Loxoprofen 60 mg is a tablet that contains loxoprofen sodium hydrate as an active ingredient. It is intended for relief of inflammation and pain in rheumatoid arthritis, osteoarthritis, toothache and acute upper respiratory tract inflammation as well as relief of post-operative, post-traumatic or post-dental extraction pain and inflammation . Diclofe0 mg and The aim of this study was to assess the efficacy of orally administered loxoprofen sodium compared with diclofenac potassium, among male and female patients with simple and surgical tooth extraction, on post-dental extraction pain. The hypothesis in this study was that no difference would be found between diclofenac potassium and loxoprofen sodium oral analgesics for controlling post-dental extraction pain irrespective of gender and type of extraxtion .This was a single-center, triple-blinded, randomized clinical trial in two groups that took place at Taibah University Dental College and Hospital in Al-Madinah, Saudi Arabia, over the period between February 2018 and March 2018. Based on previous studies and the formula provided on the OpenEpi website, the sample should include 50 participants. In this study, the sample size was increased to 100 participants to allow for the inclusion of all types of extraction .http://www.isrctn.com/ISRCTN62004181) and adhered to CONSORT guidelines . The study was conducted in accordance with the principles of the World Medical Association of Helsinki; written consent was obtained from the participants after they were informed of the study’s objectives, methods and possible risks. Participation in this study was voluntary and patients had the right to withdraw at any time, without changes to the quality of their treatment. Confidentiality was assured, as every questionnaire was anonymous and coded . The study was registered at the International Standard Randomized Controlled Trials Registry  by means of drawing lots. The two groups were coded as A and B. The codes of the drugs were kept by an independent monitor and were not revealed until after data analysis. The researcher, clinicians and patients were blinded to the codes of the drugs A and B during the course of the study. When the participant opened the envelope, he/she found instructions on how to take the medicine according to the manufacturer’s specifications.In oral surgery, administration of LA is considered a common procedure before tooth extraction . For theThe pain assessment was carried out 6 hours post-dental extraction and every 12 h thereafter on the same day of extraction and the following two days, because the highest pain point is between 6 to 8 h after extraction and intensity of pain has been shown to reach its maximum in the first 24 h ,6. The pp < 0.05. To allow for the discussion of the post-operative pain, the drug codes  were released at the completion of the data analysis by the independent personnel.The statistical package for social sciences version 16  was used for data analysis. The categorical data  was presented as frequency with percentages (F [%]). Bivariate analysis chi-squared tests or Fisher’s exact test were run as appropriate to identify any statistically significant association between type of drug and post-operative severity of pain as well as to identify differences in pain severity within each drug group . The “no pain” and “mild pain” were collapsed into simply “no pain,” and “moderate pain‘‘ and ‚‘severe pain” into “pain” due to the small sample size and to ease interpretation of the results. The difference was considered significant at p = 0.688) for gender randomized in both drugs nor for age (p = 0.449). Of the patients in the study sample, 80% (n = 80) used the drugs after simple extraction (anterior and posterior teeth) and only 20% (20) patients used these drugs for other types of extractions of posterior teeth  of the latter types of extractions were randomized into both drug groups.Of the 100 recruited patients, 54 (54%) were males and 46 (46%) females. The age groups of participating patients were as follows: 18–30 years old (26%), 31–40 years old (24%), 41–50 years old (29%) and 50–70 years old (21%). As shown in p =0.398). The percentage of “no pain” perception was increasingly reported over time for both drugs. As shown in p > 0.05) in post-operative pain perceptions among the loxoprofen sodium and diclofenac potassium groups over the allocated time intervals, except on day two (after 36 h). A statistically significantly number of patients receiving diclofenac potassium reported “no pain” compared to patients receiving loxoprofen sodium drug .Post-operative pain was reported by the patients on the day of the extraction and the following two days. Comparable percentages of “no pain” perception 6 hours after extraction were reported by both drug groups (p > 0.05) between males and females for all time intervals .For the comparison of the post-operative pain perception between genders within each drug group, there were non-significant differences . Our findings align with previous studies that have discussed the differences between some NSAIDs. One such study compared ibuprofen, paracetamol and diclofenac potassium after deep cavity preparation and third molar extraction, in which it was concluded that diclofenac potassium has better pain control over post-operative pain . This isFurthermore, comparing our results with a randomized, triple-blind clinical study comparing the efficacy of an NSAID drug and a combination of NSAID plus tramadol/acetaminophen showed that both groups had good pain control after lower third molar extraction and that the difference is not clinically relevant . AdditioThe strengths of the study were as follows: First, the drugs used were triple blinded , which likely reduced assessment bias and increased the accuracy and objectivity of clinical outcome findings. Second, both genders and types of extractions  were included. Third, we adopted a patient-centered health outcomes assessment in the form of patient-reported post-operative pain. As for the study limitations, the sample size was considered small . In addition, the use of the Visual Descriptive Scale for pain assessment instead of the Visual Analogue Scale may have obscured a thorough assessment of pain trends; however, we anticipated that patients attending the service would be less likely to conceptualized the numerical and linear scale. Finally, confounding factors such as smoking, socioeconomic status and patient weight and their role in pain perception were not investigated within the context of the study.Among this study sample, the two randomly distributed analgesics  were both shown to significantly reduce post-operative pain irrespective of gender or type of dental extraction. Notably, diclofenac potassium demonstrated slightly better post-operative pain relief than loxoprofen sodium.


The objective in this study is to assess the short-term effects of a single-session mobilization in addition to subacromial corticosteroid (SACS) injection in impingement syndrome.The study was designed as a prospective randomized controlled single-blind, parallel group clinical trial. Patients  were divided randomly into two groups equally. Forty-two patients in Group 1 received mobilization and SACS injection, whereas 42 patients in Group 2 only received SACS injections. A single SACS injection was applied in all patients. Mobilization was administered as a single session right after SACS injection. Patients’ evaluations were performed measuring active range of motion (AROM), visual analogue scale (VAS) during activity and rest, and Disabilities of Arm, Shoulder, and Hand Score (DASH) prior to treatment and in the first and fourth weeks following the treatment.Both groups showed significant improvement in terms of AROM, VAS, and DASH scores in each evaluation step (P < 0.05). Visual analogue scale activity in the first week was significantly better in Group 1 (P = 0.028). Also, flexion and abduction degrees showed significantly better outcomes in Group 1 . Addition of single-session mobilization might provide rapid improvement in flexion and abduction as well as early pain relief following SACS injections. Shoulder pain is a common problem in the general population. About half of the population suffers from shoulder pain and the most frequent cause of shoulder pain is defined as subacromial impingement syndrome (SIS) . In this condition, the shoulder pain seen in arm elevation is due to the narrowing of the space between the coracoacromial arch and the humerus, trapping the subacromial/subdeltoid bursae, rotator cuff tendons, and the long head of the biceps. Main treatment goals are reducing the pain and improving shoulder function [3]. The first line of treatment includes conservative treatment modalities such as nonsteroidal antiinflammatory drugs (NSAIDs) and physical therapy [4]. In addition, alternative noninvasive treatment methods such as subacromial corticosteroid (SACS) injections, exercise, application of heat and electricity, elastic therapeutic taping, acupuncture, and manual therapy (MT) were also recommended in the previous studies on this subject [5]. Subacromial corticosteroid and local anesthetic injections were demonstrated both as a diagnostic and treatment method in SIS . They were found to be more effective than placebos, exercises, and physiotherapy in this condition .Mobilization is a well-known treatment method for shoulder pain [8]. There are no previous studies about the additional effect of mobilization on SACS injection in SIS. Mobilization is a treatment method which requires adherence, continuity, time, and physician experience on the subject. Although there are virtually no side effects attributed to this method, which is a clear advantage over other treatment options, the fact that it is a time-consuming method makes this option less favored in Turkey where there is a dense patient population. For this reason, we wanted to conduct research on the question of whether a single-session of mobilization treatment which does not require follow-up and is not time-consuming can provide additional benefit to SACS injection in SIS management. Our main objective in this study is to assess the effect of a single-session mobilization treatment in addition to SACS injection on pain severity, joint mobility, and functional status in the short-term using objective testing methods.The study was designed as a prospective randomized controlled  single-blind, parallel group clinical trial in the Giresun University Faculty of Medicine’s Physical Medicine and Rehabilitation Department. Ethics approval for the study was obtained from the Ethics Committee of Giresun University with decision number KAEK-46. The patients included were over 18 years of age without any significant shoulder trauma, and were diagnosed with SIS , supplemented by ultrasonography (USG) findings  in our clinic between June 2017 and September 2018. All patients had shoulder X-rays from the front and the rear to eliminate bone pathologies. Patients with main complaints of shoulder pain caused by neck problems, with acromioclavicular pathology and with other primary shoulder disorders including adhesive capsulitis or suspected full-thickness cuff-tear on USG, were excluded from the study. Adhesive capsulitis was diagnosed if there was range of motion (ROM) limitation of the shoulder to all directions both active and passive with external rotation reduced by at least 50% and elevation <100° compared with the normal side in the absence of bone pathology. Patients with a history of inflammatory arthritis, fracture, infection, malignancy, ipsilateral shoulder surgery, shoulder injection, or shoulder-focused exercise program history within 6 months were excluded from the study, as were those for whom SACS injections were contradicted and patients on a surgery waiting list [9]. G Power 3.1 software was used to calculate the required sample size. Based on a power of 80% and 5% level of significance, we calculated that the total sample size required was 72 [10]. Assuming a 10% loss to follow-up, the final sample size required was 80 patients for randomization. Following exclusion, 84 patients in total were included in the study. All participants signed an informed consent form before participating in the study.Patients were divided randomly into two groups equally. Group 1 consisted of 42 patients who received one session of mobilization (OSM) and SACS treatment (OSM group) whereas Group 2 (n = 42) consisted of patients who only received SACS injections (SACS group). Randomization was done using a computer with assignments placed in opaque and sequential numbered envelopes by an off-site researcher who was not involved with patient care or follow-up. A single SACS injection (20 mg triamcinolone hexacetonide) was applied via palpation-guided posterolateral approach in all patients . Mobilization was administered as a single session right after SACS injection. Glenohumeral anterior, posterior and inferior gliding, posterior capsule mobilization, and scapulothoracic joint mobilizations were done by a clinician who was trained and experienced in the application of this method . To avoid bias, clinical examination (F.K.), diagnosis (F.K.), assessment (İ.F.S.), mobilization (A.T.), and SACS injection (İ.İ.) were all performed by the same physiatrists. The researcher who reviewed pre- and posttreatment outcomes was blind to the treatment methods used on the patient.Exercise programs  were prescribed to all patients following baseline assessment. Isotonic exercises were avoided for 2 weeks following SACS injections. Participants were instructed to rest and perform Codman’s pendulum exercises during the first 15 days. Postinjection care advice and exercise leaflets were provided to all patients. The leaflet included information about shoulder anatomy and SIS in addition to simple self-help messages about pain relief (including application of cold packs) and activities. The exercise program included a small number of standardized exercises focusing on specific muscle strengthening and ROM improvement. Patients were supervised weekly to ensure that the exercises were performed correctly and for patient adherence to the treatment. Patients were allowed to use acetaminophen and this amount was recorded. Occurrences of all potential adverse events from all interventions were also monitored closely.The evaluation of patients was done measuring active ROM , a visual analogue scale (VAS) during activity and rest, and the Disabilities of Arm, Shoulder, and Hand Score (DASH) [11] prior to treatment and in the first and fourth weeks following the treatment. Pain levels during activity and rest periods were assessed using the VAS, which is a 10-cm continuous scale. The patients were asked to mark a location on the VAS scale according to their pain intensity  [12].Active ROM degree measurement  was done with the patient seated using a plastic universal goniometer according to the evaluation method [13]. The normal shoulder flexion and abduction range was defined as 180° whereas the external an internal rotation was defined as 90° [14].The DASH was used for functional disability assessment. The main part of DASH is a 30-item disability/symptom scale concerning the patient’s health status during the preceding week. The items evaluate the degree of difficulties seen in performing different physical tasks due to arm, shoulder, or hand issues (n = 21); the severity of each symptom such as pain, activity-related pain, tingling, weakness, and stiffness (n = 5); and the condition’s impact on social activities, sleep, and self-image (n = 4). Each item has five response options. The scores for all items are used to calculate a scale score ranging from 0 (no disability) to 100 (very severe disability) [15]. The score calculated is called the DASH score. In this study, we employed the Turkish version of DASH [16].Both groups were compared in terms of demographic properties and continuous variables. In addition, differences between evaluation steps for each group were also reviewed. Baseline variable comparison between the groups was done using independent t tests or Mann–Whitney U tests for continuous variables and using the chi-square test of independence for categorical variables. Intergroup differences in mean change from baseline to each treatment period were compared using repeated measures ANOVA with adjustments for baseline levels of outcome measures. All statistical analyses were performed using SPSS 16.0 for Windows . Statistical significance level was set as P < 0.05.Out of 126 patients assessed for eligibility, 84 patients met the eligibility criteria for the study and were randomized. Two patients in Group 1 and two patients in Group 2 were lost during follow-up due to personal issues. None of the participants reported an adverse effect associated with SACS injection or OSM. None of the participants came back for repeated injections during the study. Data obtained from 80 patients in total were analyzed. Demographic data analysis showed no statistically significant difference between the groups in terms of age, sex, and duration of the disease. When the occupations of the participants were examined, it was found that the blue collar workers were significantly more common in the OSM group and white collar workers were significantly more common in the SACS group (Table 1). Both groups showed significant improvement in terms of AROM, VAS pain, and DASH scores in each evaluation step (P < 0.05) (Tables 2 and 3). The VAS activity in the first week following treatment was significantly better in the OSM group (P = 0.028). Flexion and abduction degrees showed significantly better outcomes in the OSM group as well . Acetaminophen usage was similar in both groups (P = 0.448) and no side effects were observed in both groups during the study period.To the best of our knowledge, this is the first study that shows the additional benefits of mobilization used with SACS injection on pain, function, and ROM in SIS patients. Moreover, the significant point that differentiates our study from other studies is that the mobilization was performed as a single session right after injection. It can be argued that adding OSM to SACS injections might be beneficial in reducing pain in the acute period as compared to SACS injections alone, therefore allowing the patient a faster return to normal life. Although the OSM group showed better improvement in the short-term in terms of flexion, abduction, and pain during activity, this difference dissipated over time. Although mobilization is a safe and reliable treatment method with almost no side effects at all, it is not very popular among physicians in Turkey due to its time-consuming nature, which is not very practical in a very dense patient population. For this reason, we wanted to eliminate this time-consuming step by using OSM to supplement SACS injections to see if any other improvements can be seen with this practice. We were able to see that adding OSM to SACS injections in SIS patients caused an improvement in pain and ROM in the first week when compared to SACS injections alone. This allows the patient to return to normal life faster, eliminate workforce loss, and improve the patient’s mood due to a speedy recovery from pain and function loss due to the condition.Subacromial corticosteroid injection is a well-known and effective method used in diagnosis and treatment for many years in SIS. Corticosteroids, such as triamcinolone, reduce pain with antiinflammatory and analgesic effects [17]. The MT and exercise are common treatment methods for SIS as a part of physical therapy. Improving function and ROM and decreasing pain are the main goals of both treatments . A recently published metaanalysis reported that corticosteroids were superior to control and physical therapy modalities, but only during a short-term follow-up period. In addition, exercise was found to be superior to doing nothing and specific exercises were superior to nonspecific ones. The MT was superior to doing nothing for pain and MT in addition to exercise was also found to be superior to nonspecific exercise alone during a short-term follow-up period [8]. A recent trial compared SACS injection plus MT-exercise versus MT-exercise alone for SIS and determined similar improvements in pain and function at 3 months; however, in the injection group, pain and disability showed a more rapid improvement [20]. Another study divided subacromial pain syndrome patients into two groups, and treated the first group with SACS injections and the second group with SACS injections plus exercise using USG to assess patients’ conditions. The authors reported no significant additional benefit of exercise in pain severity or subacromial bursa USG appearance [21]. In our study, we found that both SACS and SACS with OSM were effective in reducing pain and increasing joint ROM in the first and fourth weeks of treatment. Although there are some studies that assess the additional benefits of exercise treatment in corticosteroid injection treatments, there are no data in other studies about the additional effect of OSM over SACS injection in SIS cases. When the additional effect of OSM was assessed in the first week of treatment, we were able to see that the ROM in flexion and abduction had an increase and VAS activity scores were better in the OSM plus SACS injection group. However, no statistically significant difference was found between the groups in terms of ROM and VAS scores in the fourth week of treatment. These results showed that rapid functional improvement might be achieved in a shorter period of time in the OSM plus SACS injection group.Corticosteroid injections are associated with a number of side effects including infection-sepsis, skin issues , lipoatrophy, hemorrhage, postinjection flare-ups, and pain at the injection site . In our study, none of the participants reported adverse effects associated with SACS injection or OSM.One of the limitations of our study is that we were not able to clearly determine if the effect was due to the natural course of the illness or the placebo effect of the interventions. Another limitation is that mobilization treatment was done as a single-session treatment whereas normally it would require multiple sessions over a relatively longer period of time. As mentioned above, our main objective was to answer the question of whether we could transform mobilization treatment into an effective form that did not require longer treatment periods to be used by physicians with a limited amount of time. Finally, another limitation was that we were only able to observe the effects of the treatment in the short-term. We will see if the outcomes are sustainable in the long-term in our routine follow-up period. Even though the subject number was determined by power analysis, such studies should be performed with longer series so as to avoid interpretation limitations and allow the generalization of the results. Moreover, the follow-up periods should be extended to produce more valid and informative results, as well.In conclusion, addition of OSM might provide rapid improvement in flexion and abduction as well as early pain relief following SACS injections in SIS. It is clear that more studies with longer follow-up periods and with repeating mobilization treatment sessions are essential to clearly grasp this subject.All participants signed an informed consent form before participating in the study.Ethics approval for the study was obtained from the Ethics Committee of Giresun University with decision number KAEK-46.


Postoperative acute pain is a common issue following thoracic surgery. Acupotomy is a common and safe intervention method for pain treatment in clinical practice. In previous preliminary experiments, we found that acupotomy has a good clinical effect and good safety in the treatment of pain after thoracoscopic surgery. However, due to a lack of a rigorous design and an adequate sample size, its efficacy still requires further confirmation. The purpose of this study will be to explore the efficacy and safety of acupotomy combined with patient-controlled analgesia (PCA) for the treatment of pain after video-assisted thoracic surgery (VATS).The study will be a single-centre, parallel group, randomized controlled trial.Seventy patients with significant pain after thoracoscopic surgery with a visual analogue scale (VAS) score ≥ 7 will be included and randomly distributed into two groups: G1, the acupotomy combined with PCA group; and G2, the conventional PCA group. The primary outcome measure is pain scores at rest and coughing evaluated with the VAS by a blinded observer in the postanaesthesia care unit (PACU) and postoperatively at 1, 2, 4, 8, 12, 24, 48, and 72 h. The secondary outcome measures are postoperative requirements for rescue analgesia, the cumulative amount of self-administered analgesics, the level of sedation (LOS), the Bruggemann comfort scale (BCS), and the functional activity score (FAS) concerning adverse effects and patient satisfaction.This trial has the potential to identify an innovative and effective analgesic method for postoperative pain management for VATS. The findings may advocate for the inclusion of the treatment of comorbid pain after thoracoscopy in current pain management practice guidelines.ChiCTR1900027191. Registered on 4 November 2019Chinese Clinical Trial Registry  Postoperative acute pain is a common issue following thoracic surgery . AlthougPatient-controlled analgesia (PCA) is a personalized strategy involving various opioids that allows patients to administer analgesics as needed and has been demonstrated to be effective for postoperative pain management under diverse conditions , 8. In aHowever, most of these modalities are technically complex and present a high risk and/or carry a high risk of serious side effects such as epidural haematomas, dural puncture, nerve injuries, pneumothorax, hypotension, infection, respiratory depression, cough suppression, coagulopathy, local anaesthetic toxicity, and renal impairment , 13. TheAcupotomy, which is widely used in Korea and China as a special form of acupuncture with characteristics of surgical procedures, is widely used for musculoskeletal conditions and is considered an excellent treatment for pain relief . The anaThus, in this trial, we combined acupotomy with PCA to form a multimodal analgesia regimen and designed a randomized controlled trial to explore its efficacy and safety in the treatment of pain after VATS.This study will use a single-centre, parallel group, randomized controlled trial to explore the efficacy and safety of acupotomy combined with PCA for the treatment of pain after VATS. The study will be carried out at Fujian Provincial Hospital and has been registered with the Chinese Clinical Trial Registry (ChiCTR1900027191).After eligibility screening and written informed consent provision, eligible participants after thoracoscopic surgery will be randomly distributed into two postoperative analgesia groups: G1, the acupotomy combined with PCA group; and G2, the conventional PCA group. In addition to the abovementioned analgesic regimen, all subjects will receive conventional postoperative treatment, including health education and conventional medical therapy. This protocol design adheres to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Checklist . Therefore, 70 participants will be recruited, with 35 participants in each group.Based on the results of our preliminary experiments, the visual analogue scale (VAS) scores (mean difference ± SD) at rest for postoperative day 1 were 3.47 ± 1.39 in the conventional PCA group and 2.34 ± 1.21 in the acupotomy combined with PCA group. We input these data into the G-power 3.1.9.2 software  to calculate the sample size. We obtained a calculated effect size of 0.867 for this outcome after the intervention. A sample size of 70 participants is required to sufficiently detect a target effect size (0.8) with a type 1 error of 5% ; clinically significant neurological, cardiovascular, renal, and hepatic diseases; an inability to remove the tracheal catheter or to correctly use the PCA pump after surgery; psychiatric illnesses that would interfere with the perception and assessment of pain; and pain-killer use within a week before surgery.Seventy patients with lung cancer, an American Society of Anesthesiologists physical status I–II, an age of 30–70 years, and a VAS score ≥ 7 who are selected for VATS lobectomy will be recruited for this clinical study. They will also be required to be able to communicate well and understand how to score their pain level. All eligible participants who meet the study inclusion criteria will be identified through the Division of Thoracic Surgery. The study exclusion criteria are coagulation disorders; neuropathy; infections at the site of acupotomy; obesity  statistical software to create a randomization sequence generated by an independent statistician. The randomization sequence will assign patients on the basis of a 1:1 ratio to either the intervention group (acupotomy combined with PCA group) or the control group . The allocation sequence  will be concealed from the researchers who are responsible for enrolling and assessing participants in sequentially numbered, opaque, sealed, and stapled envelopes. The project manager will evaluate the baseline information of eligible participants and then inform them of the group to which they are assigned. Study personnel involved in recruitment, screening, data collection, and data entry will be blinded to group assignments. Due to the nature of the intervention, blinding the participants is impossible.2), and end-tidal carbon dioxide tension (PETCO2).All patients will be expected to avoid preoperative use of pain medication. After entering the operating room, clinicians will regularly monitor the patients’ blood pressure, electrocardiography, pulse oxygen saturation  doctors with nearly 30 years of clinical experience in acupuncture and 5 years of acupotomology experience will perform all acupotomy procedures. The doctors will not be involved in evaluating the effects of treatment. A flat-head screw-driver-shaped stainless-steel disposable acupotomy needle  will be used. Acupotomy will be performed in the lateral position. An iodine antiseptic will be used to sterilize the area for acupotomy. We will not anaesthetize the skin. The needle will be inserted at a position 0.5–1.5 in. away from the spinous process at the T4–T7 level on the painful side of the chest, 50–60 mm under the skin and in a direction parallel to the muscle fibres. The practitioner will stop advancing the acupotomy needle when resistance at the needle point is felt. The practitioner will move the needle point around in different directions to stimulate the soft tissue 3–5 times until the tenderness disappears. Then, the needle will be pulled out, and gauze will be applied to the site to prevent bleeding.2) will be monitored and recorded every 5 min for at least 30 min. When the patients’ vital signs are stable and they are able to communicate easily, a series of clinical-scale evaluations and analgesia will be evaluated and recorded. The primary outcome measure of this study is the postoperative pain intensity score. Pain scores (VAS) in the PACU and postoperatively at 1, 2, 4, 8, 12, 24, 48, and 72 h at rest and coughing in each group will be assessed. The VAS ranged from 0 = no pain to 10 = unbearable pain. The mean value and standard deviation will be used for descriptive analysis. The primary outcomes of this study were the resting and dynamic pain scores, which were recorded using a VAS. The secondary outcome measures are postoperative requirements for rescue analgesia, the cumulative amount of self-administered analgesics, the level of sedation (LOS), the Bruggemann comfort scale (BCS), and the functional activity score (FAS) concerning adverse effects and patient satisfaction.When patients are transferred to the PACU, vital signs . The observer who records the postoperative data will also be blinded to the group assignments.During the course of the study, researchers will record any AEs and then comprehensively evaluate the correlations between these AEs and the clinical intervention. To our knowledge, acupotomy may cause discomfort or bruising at the sites of needle insertion, nausea, or faintness after each treatment. No other serious adverse reactions caused by acupotomy have been reported to date. No harm or compensation is anticipated for trial participation. Meanwhile, if any AE occurs, the investigator will take proper measures to ensure the safety of participants; all details will be written down carefully.The experimental data will be carefully entered into an electronic case report form (CRF). To guarantee the data quality, we will appoint a dependent research assistant (RA) to be responsible for the quality control during the data collection process. Participant identification and privacy information will be deleted from all study documents to protect confidentiality. All outcomes will be manually double-checked, and a second independent data entry will be conducted to promote data quality. After data storage, only researchers directly involved in the data analysis will be permitted to access to the final trial dataset. During the study, an independent data and safety monitoring board (DSMB) of the scientific research department of Fujian Provincial Hospital will be responsible for monitoring the safety, progress, study integrity, and design aspects of the trial. Drop-outs and withdrawals from the trial will be recorded throughout the intervention, and the data will be collected in the CRF and used for the final statistical analysis. No conflict of interest with the sponsors or researchers exists.t test, as appropriate. Categorical variables will be presented as numbers and percentages and analysed by Fisher’s exact test or the chi-squared test. Repeated measurements will be analysed using two-way ANOVA, and Tukey’s test will be used for post hoc testing. All statistical tests will be performed with a bilateral test, and P ≤ 0.05 will be considered as statistically significant.The statistical analysis will be carried out using SAS (SAS 9.2) statistical software. All allocated subjects with available data will be analysed, i.e. on the basis of the intention-to-treat principle. The continuous variables will be presented as the means ± SDs (standard deviations) or the medians (25th to 75th centiles) and compared using the two-tailed Mann-Whitney test or Student’s This prospective randomized control study aims to evaluate the effects of acupotomy combined with PCA  on postoperative pain, functional recovery, postoperative adverse effects, and patient satisfaction among patients undergoing VATS with poorly controlled postoperative pain. Despite the application of minimally invasive techniques, improved administration of analgesic drugs, and combined use of analgesic drugs, the postoperative pain of some patients after thoracoscopic surgery is not well controlled .As a concept for a multimodal perioperative analgesic regimen, the options for postoperative analgesia must be effective with minimal side effects and aim to decrease the potentially harmful consequences of thoracic surgery on immediate and long-term patient well-being , 24. MorPCA is a common analgesic method after thoracoscopic surgery in clinical practice , 28, andIn this study, we will use a combination of patient-reported subjective evaluation scales and objective statistical evaluation indicators of the effect of analgesic use to verify the effect of acupotomy combined with PCA on pain after thoracoscopy, thus increasing the reliability of the research results. In addition, early rehabilitation of postoperative limb function is also an important part of evaluating the effect of surgical treatment. In this study, the FAS scale will be used to evaluate the recovery of upper limb motor function in patients after thoracoscopic surgery. At the same time, we will also focus on evaluating adverse reactions and patient satisfaction. To the best of our knowledge, this will be the first randomized controlled trial to study the effect of a combination of acupotomy and PCA on the management of postoperative pain and functional recovery in this population.The major limitation of this protocol is its non-double-blind design. Nevertheless, we have taken some remedial measures to further ensure the quality of the research. For instance, patients will be allocated using a computerized randomization schedule to receive either of two techniques, which may control for selection bias. Moreover, the outcome assessors and statistical analysts will be blind to the intervention, which may control for report bias. Another limitation of this study is that no blank control group was established to exclude the placebo effect. We will consider this issue in the next more rigorous experimental design. This study also lacks long-term follow-up observations and assessments. The 3-day continuous observation period reflects the real-world clinical practice of the observation of acute analgesia after thoracoscopy and is sufficient to confirm the clinical efficacy and safety of acupotomy combined with PCA in the short-term treatment of pain after thoracoscopy.In conclusion, our results may offer an innovative strategy for improving postoperative pain control that could have a substantial impact on postoperative care and quality of life for patients undergoing VATS.Protocol number: version 2.0-2019.12.01. Recruiting start date: December 5, 2019. Expected study completion date: December 2021. In case of any changes to the protocol, we will notify the relevant parties  through e-mail or letter.Additional file 1. SPIRIT checklist.Additional file 2. Acupotomy operation


We aim to measure dietary inflammatory index (DII) and its association with functional status, pain intensity and quality of life (QOL) in patients with knee osteoarthritis (KOA). Dietary information from 220 qualified patients with KOA was collected by a 168-item food frequency questionnaire. The functional status, pain intensity and QOL were evaluated by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire, Visual Analogue Scale (VAS) and SF36 questionnaire respectively.trend = 0.091 and 0.181, respectively). After adjustment, a significantly increased severe pain odds was observed in the highest tertile of DII score in comparison with the lowest tertile .Linear regression analysis showed that the DII was significantly associated with VAS , and physical function , emotional wellbeing  and pain  scales and physical health  subscale of QOL after adjusting for age, sex, body mass index, and physical activity. There was no significant differences concerning WOMAC across the DII tertiles with and without adjustment to probable confounders (P Knee osteoarthritis (KOA) is a musculoskeletal disorder of an inflammatory nature that affects people around the world, causing pain, physical disability, and lowering the quality of life (QOL) . PreviouVarious studies have shown that one’s dietary habits play an important role in regulating chronic inflammation , 5 and dConsidering the importance of the topic and rarity of studies in this area, especially in patients with KOA, this study was designed to firstly identify the DII in patients with KOA, and secondly, the association of DII with functional status and pain intensity and QOL in these patients.This descriptive cross-sectional study was conducted on 220 individuals with KOA during the March-September 2018. Participants were selected via proportional random sampling from the health centers of Tabriz City and then phoned, a summary explanation of the objectives and process of the research were described and, if they agreed to contribute in the study, they were requested to be present at the selected time in the center.Diagnosis of primary KOA defined by the American College of Rheumatology classification criteria , age 45 Follow a special dietary pattern for medical or other reasons, subjects with neuropathy and sensory impairment, body mass index (BMI) ≥ 35, history of knee joint injection in the last 6 months or the use of corticosteroid medications for a recent month, people who are unable to cooperate in completing questionnaires and procedures for any reason.A validated 168 items semi-quantitative food frequency questionnaire (FFQ)  was usedDietary intakes of 29 abovementioned food parameters were used to calculate the DII. In order to reduce between-subject variation, dietary intake was adjusted to the total daily energy intake using residual method . The fooFor all participants, the demographic information was gathered via a general information questionnaire. Body weight and height were measured by digital scale  and a non-stretched tape measure , respectively. The Persian version of International Physical Activity Questionnaire (IPAQ) was applied to measure physical activity , 18.VAS  was applied to measure the pain intensity in the participants. The validity of using this scale for assessing the pain intensity has been demonstrated in the studies .WOMAC index was applied to measure the functional status of participants by considering twenty-four items categorized into three subscales: pain (5 items), stiffness (2 items) and physical function (17 items) . It is oThe Persian version SF36 was used to measure QOL in participants. The questionnaire has 36 questions, which assesses eight different areas of health with respect to the physical and emotional aspects. Likert scales and yes/no options are applied to evaluate function and well-being. Scales are standardized with a scoring process to achieve a total score fluctuating from zero to 100. Its validity and reliability have been established in Iran .The 168-item semi-quantitative FFQ, categorizes the food items into twenty-two groups. It has been recommended that the sample size for such studies to be considered as ten subjects per variable . ConsequNormal distribution of variables was tested using Kolmogorov–Smirnov test. Linear regression and Chi square tests were applied to examine the trend of continuous and categorical variables across DII tertiles, respectively. The relationships between the DII score and pain intensity, functional disability and QOL were analyzed by linear regression analysis  and 95% confidence interval (CI) of severe pain and disability across DII tertiles were measured by logistic regression analysis, whereas the lowest tertile of DII considered as the reference. The SPSS version 17.0  has been used to analyze data.From 348 subjects who were screened, a total of 220 patients with KOA were qualified for inclusion in the investigation. Demographic characteristics of the participants according to the DII tertiles are shown in Table Data on the pain intensity, functional status and scales and subscales of QOL in the patients across the DII tertiles are shown in Table Crude and adjusted odds ratios and 95% confidence intervals for the association between DII and severe pain and disability according to tertiles of DII score in patients with KOA are presented as Table The present study found that consuming a diet with higher DII score was related with higher pain intensity and lower QOL. After adjusting for potential covariates, KOA patients with the highest DII score had significantly higher VAS, and lower QOL in terms of PF, RP, SF and P scales and PH subscale. In this study, we observed that higher DII of diet was associated with 48% higher likelihood of having severe pain in patients with KOA. However DII score was not significantly associated with functional status measured by WOMAC the patients. These findings reinforce the rising body of evidences on the promising role of foods with lower inflammatory capacity in decreasing the odds of severe symptoms of KOA.The effect of diet on the inflammatory markers such as CRP has been well recognized in numerous observational investigations, with utmost investigations indicating that healthier diets may be related with lesser inflammation –28. In rStudies investigating the relationship between DII and OA are rare. Along with the results of this study, in A large cross-sectional study, Veronese et al.  showed tTo our knowledge, our study is the first that examined the relationship between DII score and scales and subscales of QOL. However, the association of systemic inflammation with high levels of inflammatory and pro-inflammatory cytokines with reduced QOL in general and specific components including pain, physical and emotional health have been shown in previous studies –39.In conclusion, DII score was associated with pain intensity (VAS) and PF, RP, and P scales and PH subscales of QOL in patients with KOA with and without adjustment for age, sex, BMI and physical activity. Higher DII in the diets was related with higher odds of severe pain in patients with KOA.First, we can’t conclude confident cause and effect associations because of the cross-sectional design of the study. Relatively small sample size in second limitation. Third, the possibility of recall bias should be considered. Fourth, in our study, data are available on 29 of the 45 food parameters; lack of data on the residual food parameters intake is a limitation. Fifth, self-reported dietary approaches such as FFQ are exposed to bias, the incapability to quantity this bias and adjust for it is a limitation.Additional file 1. Standardized regression coefficients (B) and their standard error (SE) and p value of the association between DII score and pain intensity, functional status and quality of life in patients with knee osteoarthritis.


Intra-articular injections may be useful in terms of pain and functional status, in knee osteoarthritis (OA). Besides hyaluronic acid (HA) and platelet-rich plasma (PRP), peptide molecules recently begin to be used. The aim of this study was to compare the efficacy of intra-articular peptide Prostrolane® (CAREGEN Co. Ltd.) injection with that of the HA and PRP in the persons with OA.Fifty-four patients with OA were included in this prospective, randomized study. Patients were randomized into three groups as intra-articular HA, peptide, and PRP groups. Paracetamol was permitted three times a day to all groups. All the patients were evaluated by the Western Ontario and McMaster Universities Arthritis Index (WOMAC), Health Assessment Questionnaire (HAQ), and visual analogue scale (VAS) at rest and during movements. Measurements performed at the baseline, after the first week of injection, and at the first and third months of follow-up.p < 0.05). There were no statistically significant differences between the groups in terms of first week pain relief (p > 0.05). WOMAC pain, stiffness, function, and total scores were improved significantly in all the groups a week after the injections (p < 0.05). Improvement continued at the third month control; however, the improvement in the WOMAC pain score was significantly better in the peptide group at the third month control (p < 0.05). The decrease in the rest and movement pain was continued for 3 months except the HA group’s rest pain. There were no differences among the groups for all measurements, except for the WOMAC pain score at 3 months after treatment, which was significantly lower in the peptide group.Mean age was 55.8 ± 8.9 years. Forty-four (81.6%) were women. A week after the injections, rest and movement pain severity was measured by VAS decreased significantly in all the study groups (As a result, pain relief and functional improvement were obtained after the intra-articular HA, peptide, and PRP injections in OA, and decrease in pain was better in the peptide group. Knee osteoarthritis (OA) is the most common cause of chronic arthritis and is associated with severe pain, disability, loss of function, and adverse effects on quality of life –3. IntraThe comparison of the effects of intra-articular PRP and HA is controversial in knee OA , 15–17. However, peptides have been considered to have limited treatment potential due to various disadvantages including molecular instability, short plasma half life, lack of specificity, and poor oral bioavailability. The introduction of systems facilitating increased bioavailability and persistence in the recent years has shown particular promise for the treatment of various conditions, especially OA . An intrFifty-four patients were included in this prospective randomized study. Patients were selected from 120 patients who admitted to the outpatient clinic of a hospital with symptomatic knee osteoarthritis between January 2018 and June 2018. Flow chart according to the Consort diagram [The knee roentgenograms  of all patients were evaluated by the same physician. The inclusion criteria were having symptomatic chronic knee OA > 1 year, being radiologically Kellgren–Lawrence Grade 2–4 , 18 yearn = 18) received peptide, Group 2 received  HA, and Group 3 received  PRP. The injections were performed when the patient is laying in supine position with the knee in semi-flexion. Peptide, HA, or PRP injections were administered under sterile conditions using a needle via the classic suprapatellar approach for intra-articular injection. All patients were prohibited from using NSAIDs or corticosteroids. Paracetamol was permitted three times a day, along with the application of an ice pack for pain at the injection site in all groups.The patients were randomly assigned into three groups using a computer-based protocol for the three kinds of single-dose intra-articular injection. All the products were provided free of charge by Intraline Company. The patients were called to the clinic for intra-articular injections: Group 1 , oligopeptide-92, nanopeptide-25, octapeptide-11, heptapeptide-16, and decapeptide-23, which is also available in a pre-filled syringe.N-acetyl glucosamine in phosphate-buffered saline, which is available in a pre-filled syringe. The molecular weight of the product is between 1,700,000 and 2,100,000 kDa.Group 2 received hyaluronic acid injections. Biometics® is a solution containing linear macromolecular mucopolysaccharide hyaluronate consisting of disaccharide units of glucuronic acid and Group 3 received the PRP injection. I-Stem® was used as a PRP kit. 21-gauge needles were used to prevent rupture of erythrocytes. For PRP preparation, 2.2 cc anticoagulant + 17 cc blood is taken for women, and 2.2 cc anticoagulant + 16 cc blood is taken for men. An air hole is opened with a 90-mm needle (moved to the left and right). Blood is injected into the kit with a 90-mm-long needle. The solution is then centrifuged at 3000 RPM in fixed-angle centrifuges and 3400 RPM in swing-rotor centrifuges for 6–7 min by placing it opposite the balance kit. After centrifugation, the kit is removed without shaking. Using a 2–3 cc injector, the buffy coat layer immediately above the erythrocytes is first taken using the tornado technique with the tip of a 50-mm needle, and 2–3 cc is then taken with the plasma injector. In this way, 2–3 ml PRP containing the buffy coat is obtained.Clinical parameters were recorded. Primary outcome of the study was the pain severity as measured by the visual analogue scale (VAS) rest and movement scores. Knee pain was evaluated with the 10-cm horizontal VAS . Secondary outcome measures were Western Ontario and McMaster Universities Arthritis Index (WOMAC) , LequesnAll the measurements were performed by blind clinicians at the baseline, at the end of the 1st week after injection, first and third month follow-up to all groups.Written informed consent was obtained from all the participants. The ethics committee of Kanuni Sultan Suleyman EAH, University of Health Sciences, Turkey, and health authority approved the study protocol.U tests were used to analyze quantitative independent data. The Wilcoxon test was used for the analysis of the dependent quantitative data. The chi-square test was used to analyze qualitative independent data, and Fischer’s test was used when the chi-square test conditions were not met. In all analyses, a value of p < 0.05 was accepted as statistically significant.The SPSS version 10.0 software program was used for the statistical analyses. Average, standard deviation, median lowest, highest, frequency, and ratio values were used for the descriptive statistics of the data. The distributions of the variables were measured with the Kolmogorov Smirnov test. The Kruskal-Wallis and Mann-Whitney p > 0.05). The mean age in the peptide group was significantly higher (p < 0.05) than that of the PRP group.Mean age was 55.8 ± 8.9 years. Forty-four were women. Clinical characteristics are shown in Table There is no warmth, joint deformity, neurologic deficit at baseline examination in all groups, and ACL and Apley tests were negative in all patients at baseline.p < 0.05). VAS resting scores improved significantly in the groups except HA group, in the third month. VAS resting scores in the peptide group showed a statistically significant improvement compared to those of the other groups at 3 months control (p < 0.05)  Table .Table 2Vp < 0.05). WOMAC pain score was significantly lower in the peptide group compared to the HA and PRP groups at 3 months control (p < 0.05) (Table p > 0.05)  Table . There w5) Table .p < 0.05). There was no significant difference in terms of the Lequesne Knee Pain Function scores between the groups (p > 0.05)  Table .Table 3Lp < 0.05). No significant difference was found in the groups at the control visits in terms of the HAQ scores (p > 0.05)  Table .Table 4HThere were no side effects and no dropouts in the treatment groups.p < 0.05).In this study, a single dose of intra-articular PRP, HA, or peptide injection provided satisfactory results in terms of pain and function in knee OA. The follow-up parameters were improved at the first week after treatment in all the groups. Pain and knee functions as measured by VAS, WOMAC, HAQ, and Lequesne Index were significantly improved after the treatment. This benefit was maintained up to the first 3 months. The only exception was that VAS resting scores in the 3 months were not significantly decreased in HA group. Pain severity as measured by VAS resting scores and WOMAC showed better improvement at 3 months control in the peptide group (There are previous studies comparing PRP, HA, or combined treatments in the literature –17, 25; Both of intra-articular PRP and HA injections are thought to be effective for pain and quality of life in OA , 27–29. Intra-articular peptide injection is thought to inhibit cartilage degeneration in a mouse experimental knee OA model . AdditioIn our study, all the groups showed similar well-being in terms of VAS movement pain, HAQ, Lequesne and WOMAC scores except pain score, and no statistically significant differences were found among the groups. Peptide injection provided better results in terms of resting pain and WOMAC pain score at the 3 months control. Peptides may help better pain control, because of the different action mechanisms in the knee joint. However, we cannot declare these effects strongly due to the limited patient number and relatively short follow-up period in this study. Maybe, our study provides a basis for future studies comparing HA, PRP treatment, and peptides.In this study, some of the patients had mild to moderate knee OA but some of them had severe OA radiologically. Also, the patients with advanced osteoarthritis who did not want surgical procedures were included in this study; however, we know that the intra-articular injections are more successful in patients with mild to moderate knee OA.There are some limitations of this study. The first one is absence of a placebo group. Other limitations are small sample size of groups, failure to establish blindness, and the lack of imaging because of the relatively short follow up duration and biochemical cartilage morphology examinations. Future studies and comparing the clinical and histopathological features of the three injection groups may help to clarify our findings.In conclusion, intra-articular HA, PRP, and peptide injections were found to be useful for pain relief and functional improvement in this study. Peptide injection might be an alternative in the patients with knee OA.