Dry eye and glaucoma are two frequently encountered ocular conditions, which can lead to substantial morbidity and decreased quality of life. Patients on topical glaucoma medications are known to be at greater risk for ocular surface symptoms. Veterans seen in the eye clinics at the Miami Veterans Affairs Hospital from January to July 2016 completed surveys assessing dry eye and ocular pain symptoms, including the five item Dry Eye Questionnaire (DEQ5). A total of 62 patients with glaucoma completed the survey. Of those, 52 were on glaucoma medications at the time of the survey, with the majority requiring more than one medication to control intraocular pressure. The frequency of mild or greater dry eye symptoms (defined as DEQ5 >6) tended to increase with increasing medication burden, and patients on brimonidine were more likely to report a DEQ5 >6. Patients on three or more glaucoma medications were more likely to report symptoms of shooting pain, dryness, and itchiness. Patients using timolol were more likely to report throbbing and pain by light, while those on latanoprost reported stinging. Our data support an association between increasing number of glaucoma medications and worsening of dry eye symptoms. Patient and medication-associated symptoms can be used to tailor individual medication regimens. Glaucoma is an optic neuropathy defined by optic disc cupping, characteristic visual field defects, and often an increase in intraocular pressure. It remains a leading cause of irreversible blindness, with an estimated 60.5 million people affected worldwide ,2. The bDry eye often presents with symptoms of discomfort and blurred vision. It is seen more commonly in the elderly population, with an estimated prevalence of approximately 19% in those over the age of 75 . As the Prior studies at the Miami Veterans Affairs Hospital have shown a high prevalence of dry eye in the veteran population . In thesThis is a single-center, cross-sectional study of patients evaluated at the Miami Veterans Affairs Hospital between January 2016 and July 2016. Patients seen in the ophthalmology and optometry clinics over the designated time period were invited to complete standardized eye questionnaires, including the DEQ5, OSDI, NPSI-Eye, and sf-MPQ, to assess their dry eye and ocular pain symptoms. These surveys were modified for the eye and are validated forms designed to evaluate dry eye and ocular pain symptoms. The DEQ5 questionnaire assesses the frequency and intensity of dry eye symptoms, with scores ranging from 0 (no symptoms) to 22 (severe symptoms), and a score of >6 indicating mild or greater dry eye symptoms. The OSDI survey is a 12 item questionnaire assessing dry eye symptoms  and the effect on vision. The sf-MPQ survey evaluates the severity of 15 pain and affective descriptors . Additional pain descriptors found in other DE questionnaires were added to the sf-MPQ survey, including dryness, itchiness, irritating, piercing, and stinging. The NPSI-Eye is a validated 10 item tool to assess neuropathic pain (including the symptom of pins and needles) . The queAfter administration of the surveys, the medical records of patients completing the questionnaires were retrospectively reviewed for baseline characteristics and demographics including age, sex, diagnosis of glaucoma, number and type of glaucoma medications used, and a history of glaucoma surgery or laser. The only combination glaucoma medication used at this institution was dorzolamide/timolol, which was recorded as the two separate components for the purposes of this study. Systemic comorbidities were also examined, including a history of post-traumatic stress disorder, depression, headaches, migraines, back pain, fibromyalgia, sleep apnea, diabetes, and hypertension. Exclusion criteria included current contact lens use, active infection, presence of pterygium or corneal edema, history of refractive surgery, eyelid pathology , and cataract surgery within the preceding 6 months. Systemic exclusion criteria included a diagnosis of Sjögrens syndrome, human immunodeficiency virus, sarcoidosis, graft-versus-host disease, or collagen vascular disease.® Excel Version 16.16 and SAS version 9.4 . Independent samples t-test, Mann–Whitney U, Jonckheere-Terpstra, chi square, Fisher’s exact tests, Spearman and Kendall correlations, and logistic regression were used as appropriate to compare variables of interest. A p-value < 0.05 was considered statistically significant. The project was started as a quality assurance study. The Bruce W. Carter VA Medical Center later approved the retrospective review of patient questionnaires and charts. The research adhered to the tenets of the Declaration of Helsinki and complied with the Health Insurance Portability and Accountability Act of 1996.Statistical analysis was performed using Microsoftn = 58, 93.5%) and the average age was 72 years old .A total of 151 patients were seen in the ophthalmology and optometry clinics at the Miami Veterans Affairs Hospital and completed the dry eye and ocular pain questionnaires over the designated time period. Sixty-two of these patients (41.1%) had a known diagnosis of glaucoma at the time of survey administration and met the inclusion criteria . The majn = 40), followed by latanoprost (n = 39), dorzolamide (n = 36), and brimonidine (n = 22). The majority of patients required more than one topical glaucoma medication to control intraocular pressure: 1 medication (n = 9), 2 medications (n = 11), 3 medications (n = 22), and 4 medications (n = 10). Of the 22 patients on brimonidine, none were on brimonidine alone, and all were on three or more glaucoma medications. Of the 40 patients on timolol, only one (2.5%) was on timolol alone, and of the 39 patients on latanoprost, eight (21%) were on latanoprost alone. A total of 18 patients had a history of prior incisional glaucoma surgery, with eight patients having undergone trabeculectomy and 13 patients having had tube shunt surgery. Eleven patients had a history of laser trabeculoplasty.Fifty-two patients were on glaucoma medications at the time of the survey administration (83.9%). The most commonly used medication was timolol (p = 0.004) (p = 0.004). Additionally, those patients on three or more glaucoma medications tended to report more severe dry symptoms, with an average DEQ5 score of 8.5 in patients on no medications, 7.4 in patients on 1–2 medications, and 9.9 in patients on 3–4 medications. Overall, individuals with a DEQ5 ≤6 (n = 16) were on an average of 1.7 medications, while those reporting a DEQ5 >6 (n = 46) were on an average of 2.5 medications (p = 0.03).All patients completed the DEQ5 questionnaire. Patients on three or more glaucoma medications at the time of survey administration were more likely to have a DEQ5 >6, indicating mild or greater dry eye symptoms: 50.0% on 0 medications, 44.4% on one medication, 45.5% on two medications, 86.4% on three medications, and 70.0% on four medications (= 0.004) . In totap = 0.03). There was a trend for those on brimonidine to more frequently report a DEQ5 >6 compared to those on other glaucoma eye medications: 81.8% on brimonidine, 72.5% on timolol, 69.4% on dorzolamide, 69.2% on latanoprost. When considering both each individual medication and number of medications in a forward stepwise multivariable analysis, only brimonidine remained significantly associated with mild or greater dry eye symptoms .Patients on brimonidine were more likely than those not on brimonidine to report mild or greater dry eye symptoms, as defined by a DEQ5 >6 , irritating (n = 29), dryness (n = 28), and aching (n = 21). Patients on three or more glaucoma medications were more likely than patients on fewer medications to report symptoms of shooting pain , dryness , and itchiness . Medication-specific ocular pain symptoms were also investigated (p = 0.03) and pain by light . Patients using latanoprost were more likely than those not using latanoprost to report stinging .Ocular pain surveys were reviewed to analyze symptom-specific complaints. Specifically, the results of the sf-MPQ, OSDI, and NPSI-Eye survey were used to evaluate pain and effective symptoms. The most common descriptors reported by surveyed glaucoma patients included itchiness (stigated . Those pp = 0.04). There was a moderately significant association between depression and latanoprost use, compared to those not on latanoprost . There was no association between specific glaucoma medication use and the concomitant use of antidepressant medication and anti-anxiety medications.The association between glaucoma medication use and the presence of certain systemic comorbidities  was investigated, and those comorbidities reaching statistical significance are presented in For each specific ocular pain and systemic comorbidity found to be statistically associated with one of the four glaucoma medications used in our series , a univaGlaucoma and ocular surface disease are two frequently encountered ocular conditions, which account for a substantial number of office visits and can lead to patient morbidity. While many studies have shown a correlation between the use of glaucoma medications and the incidence of dry eye disease, none have evaluated specific ocular pain descriptors to better quantify and understand medication-associated symptoms. The use of validated tests in this study  allowed for both the evaluation of dry eye symptoms and pain-specific descriptors.The majority of patients in our series required the use of topical pressure lowering eye medications for treatment of their glaucoma. The most commonly used eye medication was timolol, followed closely by latanoprost and dorzolamide. Fewer than half of patients were using brimonidine at the time of survey administration. These prescription patterns mirror other epidemiological studies, which have shown topical beta blockers and prostaglandin analogs to be the most commonly used glaucoma medications ,19,20. TThe DEQ5 survey was administered to all patients to better assess the frequency and intensity of their dry eye symptoms. Those patients on three or more glaucoma medications were more likely to report the presence of mild or greater dry eye symptoms (measured by a DEQ5 >6) and more severe symptoms (measured as a higher DEQ5 score) than those patients on a fewer number of mediations. This corroborates prior studies, which have shown a higher frequency of dry eye symptoms in patients on glaucoma medications, with increased incidence and severity amongst those using multiple medications ,8,16. AlInterestingly, patients using brimonidine at the time of survey administration were statistically more likely than those not on brimonidine to report a DEQ5 >6. Brimonidine, an alpha-2-adrenergic receptor agonist, is known to have a number of ocular side effects, including conjunctival hyperemia, allergic conjunctivitis, and ocular pruritis, which limits its use in some patients . As prevUnique to our study was the use of standardized surveys to investigate patient-specific descriptors of ocular pain. Patients with glaucoma in our series most commonly described symptoms of itching, irritation, dryness, and aching. Those patients on three or more glaucoma medications were statistically more likely to report symptoms of shooting pain, dryness, and itching compared to those on fewer topical medications. Interestingly, patients using timolol were more likely to report symptoms of throbbing and pain by light compared to those not on timolol. Timolol, a medication which has been used for decades in the treatment of glaucoma, is a non-selective beta-adrenergic blocker which lowers intraocular pressure by decreasing the production of aqueous humor in the eye. Known side effects include central nervous system changes , cardiovascular effects (bradycardia and hypotension), respiratory complications (bronchospasm), and ocular side effects, including deep orbital pain and burning ,30. ThouInterestingly, further investigation of these medication-associated pain descriptors in a bivariate model, which included brimonidine as the second explanatory variable, showed that brimonidine had an odds ratio of less than 1.00 for the descriptors analyzed (suggesting that use of brimonidine is associated with reduced odds of experiencing this ocular pain symptom). This was particularly true for pain by light and stinging, for which there were clinically significant decreased odds of approximately one-half in those patients on brimonidine. Therefore, while patients using brimonidine were at increased odds of dry eye symptoms (DEQ 5>6), they were less likely to report these specific pain descriptors. It is plausible that this may represent a case of reverse causality, with physicians being less likely to prescribe brimonidine to those patients with specific ocular pain symptoms.The relationship between multiple systemic comorbidities and glaucoma medication use was evaluated. Patients in our series on latanoprost tended to have a more frequent diagnosis of depression, which was of borderline significance. Traditionally, topical beta-blockers (timolol) have been associated with symptoms of depression, memory loss, and disorientation . While iPatients on three or more glaucoma medications are more likely to have dry eye symptoms compared to those patients on fewer medications. They are also more likely to report specific ocular surface symptoms of dryness, shooting pain, and itchiness. This is the first study to use validated ocular pain surveys to assess patient-specific symptoms. The use of brimonidine was shown to be associated with a higher frequency of dry eye symptoms and a more frequent history of headaches. Patients on timolol were more likely to report throbbing and pain by light, while those on latanoprost reported more stinging. Dorzolamide was not associated with any specific increase in ocular pain descriptors. Given the known association between glaucoma medications and ocular surface disease, providers should actively assess dry eye symptoms in their glaucoma patients, note patient-specific pain descriptors, and tailor a medication regimen based on a patient’s individual complaints. More research is needed to understand the associations between glaucoma medications and dry eye symptoms, including how dry eye symptoms and medication intolerability may accelerate the transition from medically treated to surgically treated glaucoma.


Pain catastrophizing contributes to acute and long-term pain after knee arthroplasty (KA), but the association between pain catastrophizing and physical function is not clear.We examined the association between preoperative pain catastrophizing and physical function one year after surgery, as well as differences in physical function, pain and general health in two groups of patients with high and low preoperative pain catastrophizing score.We included 615 patients scheduled for KA between March 2011 and December 2013. Patients completed The Pain Catastrophizing Scale (PCS) prior to surgery. The Oxford Knee Score (OKS), Short Form-36 (SF-36) and the EuroQol-5D (EQ-5D) were completed prior to surgery, and 4 and 12 months after the surgery.Of the 615 patients, 442 underwent total knee arthroplasty (TKA) and 173 unicompartmental knee arthroplasty (UKA). Mean age was 67.3 (SD: 9.7) and 53.2% were females. Patients with PCS > 21 had statistically significantly larger improvement in mean OKS for both TKA and UKA than patients with PCS < 11; 3.2  and 5.4 , respectively. Furthermore, patients with preoperative PCS > 21 had statistically significantly lower OKS, SF-36 and EQ-5D and higher pain score than patients with PCS < 11 both preoperatively and 4 and 12 months postoperatively.Patients with high levels of preoperative pain catastrophizing have lower physical function, more pain and poorer general health both before and after KA than patients without elevated pain catastrophizing.The online version of this article (10.1186/s12891-019-2787-6) contains supplementary material, which is available to authorized users. For persons with end-stage knee osteoarthritis, knee arthroplasty (KA) is common treatment for pain and disability when non-surgical management is no longer effective. Improvement in function and durability of total knee replacement (TKA) procedures has been documented by several researchers –3. AlthoSeveral risk factors for poor outcome after KA are found. These factors can be divided into physical and psychological predictors. The former include young age, female gender, obesity, severe preoperative knee pain and other painful joints –8. The lStudies have found pain catastrophizing to be a consistent psychologic predictor of persistent pain six months to two years after TKA –12, whilPain catastrophizing is characterized as negative emotional and cognitive responses to actual or anticipated pain. It is often described as a set of maladaptive beliefs and consist of several components such as rumination, helplessness in coping with pain, excessive worry and exaggerated attention against pain-related thoughts . FurtherDespite the hypothesized association between pain catastrophizing and disability we only identified two studies that directly assessed the role of pain catastrophizing on physical function after KA , 12. TheThe study is a prospective observational cohort study. All patients were recruited between March 2011 and December 2013. Eligibility criteria included being listed for a primary unicompartmental knee arthroplasty (UKA) or a TKA. Patients who did not speak or read Danish or did not attend the preoperative education day were not included. If a patient had undergone primary TKA or UKA in the contralateral limb during the study period, the patient only participated in the study with data from the first KA to avoid multiple observations on some patients. All surgeries were performed by 4 highly experienced knee arthroplasty surgeons.The patients completed the 4 questionnaires: Pain Catastrophizing Scale (PCS), Oxford Knee Score (OKS), The Physical Function domain of Short Form-36 (SF-36 (PF)) and EuroQol 5D (EQ-5D) at the time of their preoperative education day approximately one week before KA. Furthermore, they completed OKS, SF-36 (PF) and EQ-5D at the time of their postoperative follow-up, 4 and 12 months after KA. Additional preoperative variables collected from the Lundbeck Foundation Centre for Fast-Track Hip and Knee replacement database (LCDB) to control for confounding were: age, gender, body mass index (BMI), alcohol consumption, smoking, living alone and co-morbidity .The Pain Catastrophizing Scale (PCS) consists of 13 questions addressing feelings and thoughts related to the experience of pain . The PF domain consists of 10 questions and is scored on a scale from 0 to 100, with 100 indicating no problems .The EQ-5D is a standardised generic measure of self-reported general health and consists of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression .Statistical analysis was performed using STATA 15. We used visual QQ-plots to determine if data were normally distributed or not and descriptive statistics to summarise patient characteristics and baseline data. Categorical data are presented as number and percentage, and continuous data are presented as mean and standard deviation (SD), if normally distributed, and median and interquartile range (IQR), if not normally distributed. The PCS was divided into three groups with cut-off at PCS < 11 and PCS > 21. Numbers of co-morbidities were summed and dichotomized 0 or ≥ 1. Pain was dichotomized in “no pain” (none/very mild/mild) and “pain” (moderate/severe). Missing values were filled in with mean values as described in the manuals if less than half of the answers were missing in the SF-36 (PF) , 23.p-value of < 0.05 was considered significant for all statistical tests. 95% confidence interval was defined as (95% CI).We used multiple linear regression to determine the association between preoperative PCS and change in OKS score from pre- to 12 months postoperatively. The baseline characteristics presented in Table To test the association between preoperative PCS and pain after 12 months, we used logistic regression.Differences in the OKS and the SF-36 between patients with high and low pain catastrophizing score were measured using linear mixed effects model with a random person level and systematic effects of BMI, time, group and the interaction between time and group. Model validation was performed by comparing observed and expected within-subject standard deviations and correlations and by inspecting QQ-plots.Differences in pain and the EQ-5D between patients with high and low pain catastrophizing score were measured using chi square test and Wilcoxon signed-rank test.p = 0.15) and gender (p = 0.07) between the patients excluded and the patients in the final study group. Although there was a trend indicating that the female ratio is lower in the final study group than in the patients excluded. Furthermore, we found no differences between the two groups in PCS (p = 0.61) or OKS (p = 0.16) .Figure The patient characteristics at baseline are presented in Table Preoperative pain catastrophizing was associated with the change in the OKS 12 months after the operation  point lower OKS score preoperative and 3.9 95% CI: 2.2, 5.5) point lower score after 12 months than “non-catastrophizers” . Patients with UKA reported better function in the OKS and the SF-36 (PF) and less proportion of patients reported moderate/severe pain than the TKA patients. This applied to both “catastrophizers” and “non-catastrophizers”.Both patients with TKA and UKA experienced the largest improvements from preoperatively to 4 months postoperatively with smaller improvements thereafter  and EQ. 5D scores and more pain both preoperatively and 4 and 12 months postoperatively.The current evidence regarding the potential impact of PCS on physical function is conflicting. Sullivan et al. found that pain catastrophizing predicted both pain and function 12 months after TKA . Riddle Contrary to our expectation, we found that “catastrophizers” reported significantly larger improvements in mean OKS TKA; 3.2  than “non-catastrophizers”, possibly because their preoperative score on the OKS scale was lower. We know that the expected score change depends on the preoperative score, and that patients with lower preoperative physical function normally improve more than patients with higher physical function , 25.Based on the patients’ preoperative OKS score, Murray et al. reported from the Knee Arthroplasty Trial mean OKS data before and after TKA divided into 10 subgroups based on OKS score and our results are similar indicating that the difference in preoperative score may be one of the reasons for the larger improvement among “catastrophizers” . WhetherFurthermore, a difference of 5 points in the OKS between the two groups is a minimal important difference in change score from baseline . The meaLazaradoi et al. followed 121 patients with knee osteoarthritis in a period of seven days and found that daily physical activity was associated with higher levels of knee pain among patients with high PCS than among patients with low PCS . In the In the present study we decided to split the patients into three groups of equal size based on their PCS score. The reason for this is that we wanted to study the patients in subgroups based on evidence saying that patients with higher scores have poorer outcomes and that up to one third of the patients report poor outcome. We are aware that our cut-points are based on a statistical dichotomization and that the PCS manual define patients with a PCS > 30 to be at high risk of developing chronic pain, but only 91 of the patients in this study reported a PCS > 30 and this gives us too few patients in the high group too divide the patients into TKA and UKA. Additional analysis made with cut-off scores at 21 and 30 as recommended by the manual did not change the results Additional file 2:Additional analysis. Analysis with PCS cut-off score at 21 and 30. (DOCX 16 kb)


Patellofemoral pain (PFP) is a common and complex condition. The diagnosis and causal mechanisms are not well understood and therefore the long-term prognosis tends to be poor. Exercise is currently the only evidence-based treatment strategy suggested to improve pain and function in the long term. However, no qualitative studies have been conducted to establish patients’ perceptions of recovery in the long term following an exercise intervention.To measure self-reported recovery on a 7-point Likert scale in 31 participants with PFP 6 months after a 6-week physiotherapy intervention. To explore the subjective accounts of patients who received a physiotherapy intervention for PFP, regarding their expectations and perceptions of recovery.Semi-structured exit interviews were conducted electronically 6 months after intervention to ascertain the patients’ perspectives on whether expectations of treatment were met, and factors that influenced their recovery experience.Quantitative analysis of self-reported recovery on a 7-point Likert scale showed that 48.4% of participants felt that they were ‘recovered’. Qualitative analysis showed three main categories: expectations of treatment, perceptions of recovery and changes in functional abilities.Clinicians should address patients’ expectations of treatment and include the patients in decision-making regarding their treatment. Long-term follow-up is essential to ensure that treatment effects have been maintained, and this should include information about patients’ self-reported recovery.This study suggests that patients’ expectations of treatment and perceptions of recovery from PFP may influence prognosis. Clinicians need to collaborate with patients and involve them in decision-making to achieve their goals. An individualised treatment approach is essential to adequately address patients’ experiences, priorities and beliefs. Patellofemoral pain (PFP) is a common and disabling condition amongst adults and adolescents and may account for up to 17% of all knee-related complaints seen in primary healthcare clinics  were conducted 6 months after the intervention period had ended. The follow-up interviews took no longer than 10 min to complete. The interviewer recorded the exact responses on a hard copy of the questionnaire for each participant. The responses were written down or recorded and typed immediately following the interview. Data collection through telephonic interviews, as an alternative to real-time personal interviews normally preferred in qualitative research, is acceptable, time efficient and economical .A thematic analysis approach was used to analyse the qualitative data. This is an independent approach within the descriptive qualitative methodologies commonly used to identify, analyse and report common themes within a set of data  with unilateral PFP  were included in our study. The average age was 30(±8.4) (range 14-40), the mean height was 170.1(±10.4) cm and the mean weight was 77.5 (±25.7) kg. Twenty-five (80.6%) of the participants were active and participated in a sport or athletic activity regularly. The majority of the participants were working adults (74.2%); however, we also included six school-aged adolescents (19.4%) between the ages of 14 and 19 and two full-time university students (6.5%). The average duration of symptoms was 16.5 months and 68% of the participants had tried previous treatment such as massage, physiotherapy, biokinetics, taping, pain medication and strength training, as shown in As seen in When asked retrospectively to describe why they had initially chosen to participate in the study, half of the participants had the goal of returning to sport or a specific activity after the intervention. The patients’ expectations prior to participation are summarised in ‘I wanted to go back to competing for my university cross-country team.’ ‘I am an active person and my pain impairs my functioning and enjoyment of life.’ About a third of participants were mainly concerned with pain relief (29%).‘I wanted to finally be relieved of this ongoing pain.’ Twenty-six per cent of participants wanted to be educated regarding the cause of their ongoing pain.‘I want to understand the cause of the injury and how to prevent it from occurring in the future.’ Sixteen percent of the participants wanted to learn appropriate exercises that would allow for appropriate self-management of the condition.‘I want to learn better training and preparation strategies for running and how to stretch better.’ A small percentage (6.5%), were already active but wanted to reach specific sport performance goals.‘Although I was new to running, I had a dream to run a marathon. I could not achieve this with the knee pain I was experiencing.’ Most of the participants (80.6%) reported that at least one of their main expectations or goals had been met 6 months after the intervention period. Patients’ perceptions of recovery following the intervention are summarised in ‘I ran my first half marathon in February 2017 and it was the first time that I could run without experiencing pain in my knee.’ One-third (32.3%) described one of their main expectations or goals as partially or somewhat achieved.‘I have gone back to mountain biking, but not ballroom dancing.’ Two participants (6.5%) did not feel that they had recovered or that their expectations had been met six months after intervention.‘The pain with horse-riding is the same.’ Three participants (9.7%) mentioned that although their knee pain had subsided they were struggling with other injuries, such as iliotibial band syndrome, foot pain and Achilles tendon pain. The pain had developed on the opposite side to the knee pain in all three cases.‘My knee is no longer painful, but I have now developed an Achilles tendon problem on my left leg (opposite side to the knee pain).’ The final category that was identified was patients’ descriptions of the activities that were easier or more difficult following the intervention. Twenty-nine participants (93.5%) reported improvements in activities of daily living that they previously found difficult. These activities included sitting with legs crossed, stair climbing, running, jumping, squatting, weight training, cycling, standing, walking and lunging. Of these, 10 participants (32.3%) reported that all activities were easier.However, 13 (42%) patients reported that they were still struggling with an activity that they had previously found difficult. These activities include squatting, lunging, weight lifting, prolonged sitting, jumping kneeling, stair climbing and squash.Two patients reported that their fear avoidance had been addressed and that they were no longer afraid to do certain activities.‘In the past I was very afraid to perform any sudden or fast movements. This is now easier, and my knee is more stable.’ A major challenge in the treatment of PFP is that participants tend to improve with exercise but don’t recover fully  reported that they had ‘recovered fully’ at 6 months after intervention as measured on the 7-point Likert scale. Addressing fear-avoidance behaviours using a cognitive behavioural approach is an important component of treatment and may influence patients’ long-term perception of recovery as they realise that these activities will not cause permanent damage to their knees (Smith et al. Five participants wanted to learn exercises to self-manage their pain. Promoting self-efficacy is an important component of rehabilitation programmes for chronic musculoskeletal pain (Miles et al. Education may promote self-efficacy and help to address fear avoidance (Barton & Rathleff Three patients reported that they were experiencing secondary injuries following the intervention period, despite improvements in knee symptoms. It has been suggested that biomechanical approaches to treatment could, in some cases, result in a carry-over effect to other locations if patients overcompensate on certain features (Smith et al. Patients’ expectations of treatment need to be specifically elicited and addressed by clinicians. A focus on addressing functional ability and getting patients back to activities that add value to their lives is more important than complete resolution of pain, especially in chronic cases where multiple factors may be contributing to the ongoing pain (Medina-Mirapeix et al. Objective measures of recovery are important; however, clinicians should not neglect subjective opinions of how patients are feeling about their recovery. It is important to establish whether the patient feels that they have progressed in their recovery, regardless of whether their objective measures such as strength and motional analysis findings have shown improvements. Physiotherapists need to identify which measurable outcomes are most meaningful to the patient.There are several limitations related to the chosen study design and the approach used. A limitation of the retrospective nature of the qualitative interviews is the extent to which participants remember their feelings at the onset of the study (Ashby & Schoon The telephonic mode in which the interviews were conducted has limitations. Although patients might feel more comfortable with the increased anonymity in telephonic interviews; it deprives the interviewer of seeing the participants’ non-verbal cues and body language (Sturges & Hanrahan The participants had previously received a biomechanical exercise intervention as exit interventions were part of this larger study. All of the included participants presented with biomechanical contributing factors on initial assessment and the sample mainly consisted of active and working individuals. It is therefore unclear if these findings can be extrapolated to populations with different functional goals, and if including a broader range of participants could alter the findings in future research.We have identified expectations that could be generalised to other participants; however, how these factors influence recovery and prognosis remains unknown. Our study showed that the majority of patients improved in terms of function and self-reported recovery at a 6-month follow-up. However, it is unclear how this compares to other exercise interventions and if the effects would be maintained at 12 months or even a few years later. These limitations should be addressed in future research.The treatment of PFP is challenging and complex, given its propensity to become chronic. PFP is a multifactorial condition with many possible contributing factors (Davis & Powers Therapists’ communication behaviours need to support patients’ psychological needs and motivate them to change their health-related behaviours and accept responsibility for their health in a non-judgemental way (Lonsdale et al. The diagnosis and causal mechanisms of PFP are not well understood and, therefore, the long-term prognosis tends to be poor. Most of the research on PFP to date has focused on quantitative, objective studies, where patients’ subjective experiences are neglected. As the condition tends to become chronic, fear-avoidance behaviours, and barriers to adherence should be included in treatment. Clinicians should consider each patient’s goals, address expectations and facilitate patients to take responsibility for their recovery in order to achieve better outcomes. Future research on individualised treatment that includes addressing psychological contributing factors should be investigated as these need to be included in the holistic management of this condition.


Are concerns about the opioid epidemic in the United States and the heightened oversight and restrictions on prescribing opioids associated with changes in the management of acute and chronic pain for patients with sickle cell disease?This qualitative study interviewed 15 adults with sickle cell disease. Participants reported that they face increased barriers to the use of opioids for pain management, that their physicians exclusively focus on opioid dosage without establishing a multimodality pain management plan, and that they lack access to nonopioid therapies.Adult patients with sickle cell disease should be included in establishing goals for managing pain and improving functionality using multimodality approaches. This qualitative study interviews patients with sickle cell disease and identifies their views on how the current US opioid epidemic has affected the management of chronic and acute pain related to their disease. The hallmark of sickle cell disease (SCD) is vaso-occlusive pain that may be acute and episodic or may progress to chronic, persistent pain with unpredictable and disabling exacerbations. Patients with SCD rely on opioids almost exclusively for acute and chronic pain management.To understand how the current opioid epidemic and subsequent guidelines from the Centers for Disease Control and Prevention are associated with the management of acute and chronic pain for patients with SCD.Qualitative study using semistructured interview guides. Interviews 1 hour or longer were conducted over the telephone. Participants were adults (aged ≥18 years) diagnosed with SCD who experienced pain on 3 or more days per week recruited from national SCD conferences, symposiums, and 2 sickle cell clinics. Open coding analysis facilitated thematic analysis of interview transcripts. Data collection took place from May 2017 to June 2018.Participant perspective of any changes to their pain management associated with the 2016 guidelines from the Centers for Disease Control and Prevention.The 15 adults interviewed had a median (range) age of 32 (21-52) years; 13 (87%) were female; and all were of African American race/ethnicity. Participants reported that recently their opioid prescriptions had become more restrictive, were more closely monitored, and were increasingly difficult to fill in pharmacies. Participants also described increased stigmatization about opioid use and that their medical care was being affected by the physician’s exclusive focus on reducing pain medication use. There was an emerging interest among adult patients in the consideration of the use of alternative therapies, including marijuana, to manage pain.These findings suggest that from the perspective of adults living with SCD, the opioid epidemic may have negatively affected patients’ care by increasing barriers to opioids. Patients reported decreased opioid dosing, increased stigmatization regarding opioid use, physician preoccupation with opioid dosage interfering with comprehensive care, and lack of access to alternative therapies. Using rigorous qualitative research methods, we sought to obtain the perspective of adult patients with SCD on their experience of pain, their interaction with the health care system, and their perception of how the CDC guidelines affected the management of their acute and chronic pain.COREQ) reporting guideline.9We recruited individuals aged 18 years or older with SCD who were attending national conferences and 2 sickle cell clinics and from those who self-referred themselves to this study, which was approved by the Emory University institutional review board. Participants were enrolled following in-person or telephonic verbal consent. One investigator conducted semi-structured qualitative interviews with participants either in person or over the telephone. All participants received a $25 gift card for participation. Results are reported in compliance with the Consolidated Criteria for Reporting Qualitative Research  experiences, and the participant’s thoughts concerning the opioid epidemic and how it had influenced their care.10 Coding concepts were derived from the participant responses and categories developed from these concepts with prevalence determined by content analysis, which quantifies the coding schemes and allows identification of the most prevalent of emerging patterns.11 Thematic analysis was then used as a descriptive analytical approach to illustrate the major themes.11All interviews were transcribed verbatim. We used NVivo software version 11  to perform the line-by-line coding.12 that is, understanding how the participants’ point of view addresses our research question. The objective was to understand the constructed view of the participants’ social world rather than generalizing it to the population.13 Because rigorous analysis runs concurrently with data collection for concept-gathering studies, smaller sample sizes are advantageous for greater involvement of the investigator.14 In qualitative research, robust coding schemes can establish data saturation with concepts ceasing to offer any new perspective on the research question after 6 to 12 interviews.14To achieve in-depth analysis, we focused on a sample of 15 participants. In qualitative interviewing, a small sample allows for a more authentic account,As themes developed, investigators discussed and substantiated each with examples provided. The lead coder (C.B.S.) developed the initial coding scheme and shared the coding scheme with the second coder (D.R.). The second coder coded 20% of the sample. We then compared the number of occurrences of content and calculated a percentage of agreement. There was 90% agreement between the 2 coders identifying the same content coded.We approached 21 potential participants, all of whom initially agreed to participate and provided their contact information. Six individuals who had expressed initial interest were not reachable by telephone or email for consent. Twelve participants were recruited from conferences and 3 from clinics. Once they had consented, no participants dropped out of the study. Two participants whose interviews did not specifically address the opioid epidemic were recontacted for follow-up questions.We interviewed 15 adults . Five were employed full time or part time and 10 received Social Security disability benefits. All participants self-reported that their genotype was HbSS, HbSC, and/or HbS-β-thalassemia. Participants were interviewed in person and over the telephone. Across these interview methods, there were no discernible differences in participant narrative. The median (range) length of the participant interviews was 52 minutes .All participants reported pain on 3 or more days per week and had a current prescription for opioids to treat their pain. Regular prescriptions of opioids were started in 12 participants in childhood or adolescence and 3 in adulthood.Three themes emerged from the analysis. First, participants reported that recently their opioid prescriptions have become more restrictive, more closely monitored, and increasingly difficult to fill in pharmacies. Second, participants believed that their physician’s exclusive focus on reducing pain medication resulted in further stigmatization and decreased attention to patient’s overall medical care. Third, there was an emerging interest among adult patients in the consideration of the use of alternative therapies, including marijuana, to manage pain. In many cases, patients felt forced to pursue nonopioid approaches because of issues with access to opioids.Participants reported being under increasing pressure to sign a treatment agreement, despite, in some cases, having received opioids to treat pain for several years from the same practice. Overall, 10 participants (67%) currently had a signed agreement with their physicians for opioid prescriptions, 8 of them within the year prior to the interview.Participants understood that the primary objective of the treatment agreement was to ensure that patients do not sell their opioids or go “doctor shopping.” Participants indicated that while they had conversations with their physician about dependence on opioids and the need for reductions in their opioid prescriptions, they did not have conversations about comprehensive evaluation and management of pain, including the use of alternative therapies.The reduction in prescriptions resulted in participants rationing their pain medication and being unable to increase their dosage at the onset of a pain crisis or in the presence of a trigger for crisis such as cold weather.One participant stated, “When something stresses me out maybe they used to do every 2 weeks of getting my medication. Now it’s down to once a month or they [the physician] may say instead of third of the pills [30 pills], we’re only going to give you 15. So, it [the opioid epidemic] has definitely affected me personally and I hate that. Like, I know the wintertime is one of the worse times for me. This winter [state] had one of the worse winters we’ve had.”Frequently, participants described their treatment history with the phrase “used to” to convey that their regular clinician had recently changed their opioid prescription. Additional barriers included limits to the number of opioid prescriptions permissible by their health insurance company or their pharmacy stocking inadequate supplies of opioids. A participant stated, “There was some law…that had changed earlier this year, they wanted to ask my doctor questions on why I needed so much medicine. I have Medicaid.” Another participant stated, “I went to 10 pharmacies in 1 day to get an oxycodone prescription. They told me that they only order a certain amount.”Participants believed that opioid prescribing in the ED had also changed. Most participants lacked an established pain protocol for the ED and believed that health care professionals were not well versed in the management of SCD pain. One participant stated, “You have those [ED physicians] that they’re so limited in education that they’re skeptical about following your own protocol. It’s like my doctor wrote that protocol. You’re [ED physician] putting me in harm’s way, but of course they’re not familiar with the dosage you are on, things of that sort, so your safety becomes a prohibiting factor to them. There are specific protocols but they’ll ignore it.”In the ED, participants also reported having to negotiate for their usual dose of opioids. At times, a shortage of hydromorphone was cited as a reason for reducing the dosage or prescribing another opioid. One participant stated, “Many people that have sickle cell are allergic to morphine and they don’t have Dilaudid so now we have to play Russian roulette and take the morphine. I think it is the worst thing to ever happen, I think it is beyond cruel.”Participants suspected during the shortage of hydromorphone that the hospital staff was reserving the drug for patients with conditions other than SCD. For example, ED staff advised that they do not have hydromorphone in the ED; however, when the patient with SCD was hospitalized, hydromorphone was available.Participants observed that the preoccupation with monitoring and limiting prescriptions was preventing their physician from providing comprehensive care, including the management of pain and comprehensive care of their disease. One participant stated, “They just ask me what my pain is. They ask me how my pain is. You okay with just using morphine? Yes. Okay and that’s about it and they take my blood work. That’s all the conversation I have. I’ve never had any real in-depth conversation concerning pain management.”Participants believed they should have interactive conversations with their physician regarding disease management. Two younger participants reported that they were used to having these conversations with their pediatric hematologist, but they were less likely to occur with their adult hematologist.The preoccupation with opioid monitoring occurred in the ED as well, with ED physicians, instead of taking patients’ reported pain at face value, preferring to wait for blood work to determine whether the patients were actually “sickling.” Consequently, participants felt they continued to be stigmatized as drug seekers and attributed the stigma to 2 primary factors, lack of knowledge among ED physicians in the management of SCD pain and racial bias. Overall, participants expressed the most dissatisfaction with ED physicians’ lack of SCD-related knowledge. They felt that if the physician and staff knew how to treat SCD complications, then they would not question their complaints of pain and stigmatize them as drug seekers. One participant stated, “In pediatrics they teach us ‘know your numbers, know where you don’t do well, know what medications that you take.’ Like that’s supposed to be a help, but when we go in [the ED] as adults and we do that then it’s like ‘whoa we got a drug seeker here!’ Because I’m only here because I’m seeking drugs…, ‘you got a drug seeker!’”Participants use nonpharmacological approaches such as hot baths and warm compresses, meditation, reading, praying, music, and art to manage pain and reported interest in other nonpharmacological approaches, such as acupuncture and physical therapy. Frequently, these modalities were cost-prohibitive for individuals with Medicaid. One participant stated, “Yes, I really liked the acupuncture but the crazy thing; my insurance company would not pay for that. Now that’s the part that tripped me out because you guys, they [physicians] don’t want us on opioids like that but yet they’re not willing to pay for alternative medicine, you know. I can’t afford $120 every time I’m in pain [and] want to go get acupuncture.”Participants also volunteered that marijuana was the most common nonopioid pharmacological approach considered. Six participants reported they had tried or currently use marijuana, in varying frequency, to ease SCD chronic pain. Some participants who used marijuana did so owing to increased restrictions and overall difficulties maintaining opioid therapy. A participant stated, “Yes, the hydrocodone pills. Because once CVS got their first prescription there’s only just that 1 prescription and then I needed a refill or whatever [after taking public transportation to pharmacy]. I had to like go back to my clinic and tell them I need a refill. They have to send it upstairs [and] I had to take it up there myself. Then I have to take the [public transportation] and this paper back to CVS. Then CVS said they’re missing something so I had to go back to my clinic. Honestly, really and truly, I do not use my pain medicine [opioids]…I smoke [marijuana].” For this patient, marijuana offered the least restrictive alternative to manage pain.Other participants sought marijuana to avoid the adverse effects of opioid therapy. One participant stated, “They had me on 180 milligrams of oxycodone and 30 milligrams of methadone. That was my pain regimen at home every day. I went from a very social person to a very isolated person and I would sleep all the time. I told my family, my pastor, and friends I am really close to [about using marijuana]. I only vape when I am in pain or when I feel it so it is not an everyday thing for me. I won’t say I was able to replace all my medicine except for the muscle relaxer but no more opioids. As of right now, I’m not affected by the opioid epidemic because I took myself out of it.”Those not using marijuana cited concerns with how to gain access to medical marijuana and concerns with the unknown effects of the drug. A participant stated, “You can get medical marijuana in [home state] but the only problem is that it is going to be a hell of a time finding a doctor who’s going to write you a prescription for it.”While mostly used for pain, participants also reported that the drug eased their depression and anxiety. Participants also reported that marijuana provides relief without the opioid adverse effects of severe constipation and grogginess and may allow them to reduce or eliminate opioids altogether.The participants who were interested in learning more about using marijuana were worried about using the drug, especially without physician monitoring. Participants were familiar with the effects of long-term opioid use. Owing to the risk of acute chest syndrome, participants expressed concern about smoking marijuana.20 That most participants who signed an agreement with their physician to maintain opioid therapy only did so in the last year and that they “used to” get more opioid prescriptions in the past suggests a recent change in their care. Thus, our study provides the patient perspective on how concerns about the opioid epidemic may have adversely affected the efforts of patients with SCD to seek medical care and pain management.To our knowledge, this is the first investigation to use rigorous qualitative methods to examine the perspective of adult patients with SCD on the impact of the national opioid epidemic and the CDC guidelines on their care and experience in health care settings. In the view of the participants, this has led to decreased access to opioids, increasing stigmatization, and impaired delivery of care, all pushing them to seek alternatives with little guidance or support. Thus, patients experience systemic barriers to managing acute and chronic pain and receiving comprehensive care for their SCD. Participants in this study described how the physician’s lack of understanding about pain from SCD results in lack of sensitivity to patient’s pain, not involving the patient in decision making, and consequently undertreating pain. These findings are concordant with results of survey-based studies examining quality of life for adults living with SCD.21 recommend that patients should receive multiple modalities of care and state that the goal of the opioid component of treatment is to manage pain while maintaining functionality.The intended audience of the CDC guidelines is primary care physicians prescribing opioids for chronic pain or pain conditions lasting more than 3 months. For circumstances outside the scope of these guidelines, such as receiving care for SCD in an ED, the guidelines recommend that physicians refer to guidelines written specifically for these scenarios. The National Heart, Lung, and Blood Institute guidelines3 They are based on the assessment that there is a lack of evidence demonstrating the long-term benefits of opioids to treat chronic pain, that long-term opioid use is potentially harmful, and that there is some evidence of benefits of nonpharmacologic and nonopioid pharmacologic treatments compared with long-term opioid use. The guidelines recommend that clinicians should consider opioid therapy only if the expected benefits to both pain and function are anticipated to outweigh risks to the patients, and that if opioids are used, they should be combined with nonpharmacologic therapy and nonopioid pharmacologic therapy. Furthermore, they recommend that before starting opioid therapy for chronic pain, clinicians should establish treatment goals with all patients, including realistic goals for pain and function, and only continue opioid therapy if there is clinically meaningful improvement in pain and function that outweighs risks to patient safety. This qualitative study did not provide any evidence that physicians were routinely involving patients in discussions of this type or are combining nonpharmacologic therapy and nonopioid pharmacologic therapy such as nonsteroidal anti-inflammatory drugs, anticonvulsants, and antidepressants. These findings underscore the need for further education of physicians about the intent of the CDC’s recommendations. Clinicians should engage patients in a dialogue to establish goals for pain relief and functionality, jointly identify what works and what does not, and, together, formulate a multimodality approach to pain management. For patients with SCD who receive Medicaid,23 there is limited access to nonpharmacological therapies because Medicaid may not cover these therapies.25The CDC guidelines are intended to be voluntary and are not prescriptive.26 Each state determines the medical conditions allowable and method of consumption for the drug, with only 4 states listing SCD as one of the approved indications. While clinical studies report moderate effectiveness of marijuana in the treatment of various chronic conditions,30 including chronic pain, where it may be opioid-sparing,31 there is little research on its effectiveness in treating SCD pain. Roberts et al32 reported that approximately 40% of participants with SCD report using marijuana. Participants in this study cited lack of access to, the unacceptable adverse effects of, and a desire to be free of opioids as reasons for considering the use of marijuana.Several participants viewed marijuana as a potential means of addressing pain without the adverse effects associated with opioids. Medical marijuana is currently legal in almost all US states, but possession remains a federal offense.33 In 4 states, Medicaid covers acupuncture for back pain and migraine, but no state covers this intervention for SCD.37 There are limited data available on the efficacy of acupuncture in the management of pain in SCD.38Participants also considered physical therapy and acupuncture as potential treatments for managing pain, but access to these interventions may be limited by lack of coverage by Medicaid.40 Of the 16 000 deaths attributed to opioid overdose in 2013,41 only 10 occurred in patients with SCD.41 Nonetheless, racial minorities are more likely to be perceived as addicted to opioids and exhibiting drug-seeking behavior in the ED.42 Race may influence how health care professionals view and treat patients with SCD43 and their attitude toward patients’ accounts of intensity of pain.44 Participants in this study believed that their race was an influential factor in negative experiences in the ED and that physicians who were knowledgeable about SCD were less likely to exhibit racial bias toward patients with SCD.45Individuals self-identifying as white non-Hispanic are more likely to be prescribed and engaged in long-term use of opioids compared with other racial/ethnic groups.There are several limitations to this study. Female patients were overrepresented in the sample. It is possible that a more representative sample could potentially reveal different themes. Participants were recruited from among the attendees at national sickle cell disease conferences and may have been more activated in regard to disease self-management, had access to more resources, and have been less representative of the general population of patients with SCD. Lacking access to participants’ medical records, the investigative team had no way to independently verify participants’ accounts of experience with opioids.This study suggests that from the perspective of adult patients, the opioid epidemic may have negatively affected the care of patients with SCD by increasing barriers to care. Patients reported decreased access to opioids, increased stigmatization regarding opioid use, and physician preoccupation with opioid dosage without attention to multimodality care or alternative therapies. Further research is required to generate a better understanding of the mechanisms underlying the transition from acute episodic to chronic persistent pain in SCD and the management of chronic pain, including the use of nonopioid pharmacological and nonpharmacological approaches.


This study is an illustration of how social media networks like Twitter can be used to better understand the relationships, language gaps, and shared resources between pain patients and providers and offers a template for using digital social network (Twitter) interactions to research other difficult-to-treat or rare disease states.The objective of this study was to understand how pain patients and health care providers (HCPs) are engaging on Twitter and what insights this engagement might provide. By identifying how information is spread by and between these audiences, organizations such as patient advocacy groups may be better poised to develop and share materials that facilitate online communication between HCPs and pain patients, with an end goal of improving a shared decision-making process around pain management. We analyzed the Twitter audiences most engaged on pain topics by conducting a Social Network Analysis (SNA) of a large network of connected users on Twitter. The analysis segmented users based on the sources they cited and measured their influence based on who follows them. As a point of comparison, we also conducted an SNA of Twitter audiences most engaged on oncology topics. Oncology was chosen as a comparison due to what was perceived to be a highly developed online network of both patients and physicians. The populations included in this research included 12,086 accounts that were highly engaged on pain-related topics, and 12,617 accounts that were highly engaged on oncology-related topics. Network statistics were generated for variables including: word use, sources cited, retweets, and mentions. We also statistically analyzed the Twitter follow relationships among select HCPs and patient groups within each SNA. The creation of separate pain and oncology SNAs allowed the team to compare relationships and engagement related to these topics. We found that on Twitter, pain patients and providers appear to interact less than oncology patients and providers. Pain patients do not appear to follow medical professionals or share medical or health-related information on Twitter to the same extent as oncology patients. In addition, we found that pain patients do not communicate on Twitter in the same language as HCPs. Our results are important because they underscore that challenges in communication are not just problematic in face-to-face interactions, but also in digital social network (Twitter) interactions, serving as an additional roadblock to what can be shared decision-making opportunities around pain management. Contributing to this roadblock is access to quality information and a potential need for an online, evidence-based resource hub that could benefit the pain patient community in the same way that  Pain is the most common reason for seeking medical care, and approximately 25 million American adults suffer from daily chronic pain . With AmTo improve health outcomes among pain patients, there is a need to understand how patients and health care practitioners (HCPs) communicate about pain management or treatment plans . Due to Research has found that a shared decision-making approach to pain management—an approach that involves engaged collaboration between patients and HCPs—is an important part of an overall pain treatment plan . But theTo add complexity to these patient‒provider conversations, health discussions are not just taking place in physicians’ offices. Digital platforms, such as websites and social media sites , have become places where people not only find health information, but where they congregate, connect, and discuss their health questions and concerns with others who may be experiencing similar circumstances . “One-inThe trend continues with the next generation. Not only are 9 out of 10 teens and young adults going online for health information, “about four in ten (39%) say they have gone online to try to find people with health conditions similar to their own, using methods such as participating in online forums or closed social media groups on specific issues, doing hashtag searches on social media, or following people with similar health conditions,” according to a 2018 report from Hopelab and Well Being Trust .In addition, learning networks  have been used in health care settings to connect knowledgeable communities—patients, providers, and researchers—to work on solutions for difficult-to-treat conditions . ResearcAs a result, as people turn toward the internet for their health information, for community, and for connection, it’s important to study their online behaviors—how and where people get their information—in an effort to improve how that information is delivered and consumed. The need for quality, evidence-based resources is not going unseen. A call to assess patient education materials and decision support resources as key components for effective pain care were reflected in the 2018 Federal Pain Research Strategy issued by the National Institutes of Health .This paper seeks to closely examine how pain patients and providers communicate on Twitter and to explore how these conversations might help inform the information needs of pain patients.Twitter is an online news and social networking platform where users post and interact using messages called “tweets.” While it is not the most used social network, it has the research advantage of consisting of conversations and follow relationships that are almost entirely in the public domain. Twitter’s use by health professionals is documented  and thouTwitter users create their own lenses to view the rest of the platform. By choosing users to follow, they are creating blinders with which they only view content based on the interests of the people they follow. This behavior allows for analysis on how health communicators can effectively share information with specific audiences or view the ways information flows. Twitter also has an advantage in that users tend to cite other publications in their tweets, such as via linking a URL or mentioning the publication’s account.Despite limited character allowances in tweets, the ability to add citations brings in large amounts of meaningful data. In fact, recent research shows that Twitter citations of medical research accurately predicts the citations of those publications in future published articles , 22.In face-to-face interactions between patients and HCPs, research has found that differences in points of view , as wellDefine the differences and similarities in Twitter relationships and identify what the similarities and differences in engagement among patients and HCPs within a sample of social media accounts tell us.Compare word use and citations among pain patients and HCPs. This evaluation focused on comparing the types of information sources that these audiences are sharing . This analysis allowed us to evaluate whether both groups are sharing medically focused sources, or whether one or both groups may be sharing more general or consumer-focused sources of information. As part of this analysis, we also evaluated the extent to which both audiences are discussing pain-related topics, to confirm that a high amount of their respective citations were likely shared in relation to pain-focused topics.Outline the challenges and limitations in addressing any differences between the audiences evaluated.Our research aims to define the audiences with whom patients and HCPs engage online and the information they share about pain management, specifically on Twitter. To define the audiences, we worked with Graphika Inc. to analyze the Twitter audiences most engaged in pain and oncology topics by conducting two separate Social Network Analysis (SNA) maps focused on these respective topics. We assessed the structure of Twitter relationships within the Pain and Oncology SNAs and compared the strength of the relationships between the patient and HCPs audiences within each SNA. This analysis was primarily focused on evaluating whether any potential gaps in communication exist between the patient and HCP audiences in the Pain SNA, when compared with the Oncology SNA. The creation of two separate SNAs provided comparisons between the audiences engaged on these issues, allowing us to define trends related to the communication patterns of the audiences within each map. While the main focus of the research was on the Pain SNA, oncology was chosen as a comparison due to what was perceived to be a highly developed online network of both patients and physicians.An SNA is the analysis and visualization of large networks of connected users on Twitter, and it provides insight into the social engagement of accounts focused on the specific topics and flow of information between these accounts. Network analysis has been used frequently in past research to study health-related issues and is an “approach to research that is uniquely suited to describing, exploring, and understanding structural and relational aspects of health .” SNAs oTo begin the creation of the SNA maps, we generated “seed lists” by compiling a sample of accounts with a focus on topics related to pain and oncology. The pain seed list (12 users) was smaller than the oncology seed list (22 users) as there were fewer accounts that were focused just on the subject matter. Starting with this list, all their followers, the users they followed, and individual tweets were collected. Collection also included new accounts discovered during the mining process.The Twitter dataset was collected using Twitter’s Streaming Application Program Interface (API). To determine the placement of users into clusters, Graphika’s algorithm was utilized. This algorithm, which has been used in previous research focused on social network analysis, also generated network statistics, including measurements of influence based on follow relationships within the map .A Fruchterman-Reingold visualization algorithm was used in both maps to represent the patterns of connection between these accounts. It arranges the accounts in a visualization through a centrifugal force that pushes nodes to the edge and a cohesive force that pulls strongly connected nodes together.This method of segmenting users and generating broad observations about associations is an iterative process drawing on qualitative, quantitative, and computational methods. To create a map of segments and groups, we used a bipartite graph to provide a structural similarity metric between the accounts within the map, which is used in combination with a clustering algorithm to segment the map into distinct communities. Hierarchical agglomerative clustering was used to automatically generate segments and groups from sampled data.The identification of which audiences  each cluster was composed of was determined through reviewing the following: the members of the clusters (self-reported Twitter data); the sources they cited; the users they mentioned; and the users they followed. The review of the clusters was completed by prioritizing the users within each cluster who had the largest number of followers within the map.The outcome of this process was the creation of two separate SNA maps, focused on pain and oncology. The top accounts—12,086 accounts in the Pain SNA and 12,617 accounts in the Oncology SNA, as determined by those most well-connected to others in the SNA—were included in this research. Network statistics were generated for variables, including word use, sources cited, retweets, and mentions. The sources that each of the audiences cited  are all engaged on pain topics, but for the most part are not directly engaged with patient‒HCP communication. However, it should be noted that most of the Health Industry audience is composed of the pharmaceutical industry, which is highly engaged with the HCP audience.The Oncology SNA  is comprThe HCPs  are concThe follow relationships between audiences were compared by collecting the total follows between groups, and then applying a density measure to correct for disparate audience sizes. The density measure normalized the data by weighting the total follows between each audience in accordance with its number of members. The normalization process assured that the size of a specific audience did not influence the findings on how audiences interacted, as the goal was to understand how members of an audience interacted with members of the other audiences.For example, within The following figures are visualizations of the comparative follow patterns between the select SNA audiences that are discussed within this section.Chronic pain patients follow other pain patients at a statistically higher rate than the amount, on average, that they follow all accounts within the Pain SNA map. Similarly, cancer patients are more likely than average to follow other cancer patients, when compared to a random mixing baseline . They alChronic pain patients are less likely to follow other chronic pain patients than cancer patients are to follow other cancer patients . HoweverChronic pain patients and cancer patients are similarly likely to follow general HCPs Figs  and 7. BPain and cancer specialists show similar follow patterns Figs  and 7. LWhile the SNAs have slightly different audience labels, both the Health Industry audience in the Pain SNA and the Oncology SNA’s Life Sciences audience include the pharmaceutical industry. Please note, however, that as the name reflects, the Life Sciences audience in the Oncology SNA includes a large group of researchers.The nonspecialist HCPs’ Figs  and 7 reUnlike other audiences, the nonpharmacologic pain providers appear to be somewhat insular, in that they appear to be more likely to follow members within the same audience than all other audiences in the SNA . This pacancer.gov at higher rates than chronic pain patients.As we examined the chronic pain SNA, we found that chronic pain patients follow each other at higher-than-average rates compared with a random mixing baseline, which suggests that they often get information from like-minded accounts; they also are more likely than oncology patients to cite consumer-focused information sources. They also appear to be engaged on general topics, such as pop culture, and topics related to nonpharmacologic pain treatment sources . In compWe then analyzed language use within the Pain SNA patient and provider audiences to gain further insights into the similarities and potential gaps between these audiences. In order to confirm that the initial analysis captured the pain conversation and to summarize the thousands of tweets that took place in the Pain SNA, the top 12,000 pairs of words were generated and ranked within each audience. Common word pairs that had no significance  were removed, as were proper nouns.While many words such as “health care” were used across the audiences, chronic pain patients were both focused on chronic pain and illness and most likely to use terms tied to feelings . Specialist HCPs (both those involved in Pain Medicine and Nonpharmacologic Pain Treatment) had different lexicons in talking about pain. The information and media sources cited in audience members’ tweets indicate which of these sources have the most influence over each audience. Understanding the URL citations by each cluster cites, compared to the URL citations of other clusters, provides insight into the type of content shared on Twitter by pain patients and providers.As not every tweet contains a URL citation, we expanded the collection period to nine months, which enabled the collection of 363,733 citations of 23,753 sources across all audiences in the Pain SNA, and then ranked which sources were used by each audience.nytimes.com), only HCPs cite sources related to health care, including sources such as statnews.com and khn.org . Pain patients do not cite medical or health resources. The pain patients’ behavior of citing consumer sites, in combination with their focus on pain-related words within discussions, indicates that their online behavior appears to focus on pain, but they may not have adequate medically focused resources to cite. In While both patients and HCPs often post stories from large, traditional media sources Click here for additional data file.S2 File(DOCX)Click here for additional data file.S3 File(DOCX)Click here for additional data file.S4 File(DOCX)Click here for additional data file.S5 File(XLSX)Click here for additional data file.


The sub hepatic drain is often placed after laparoscopic cholecystectomy is considered to affect post operative infection, pain and sub hepatic collections. The objective of this study was to compare the degree of postoperative pain in patients with routine drainage with those without it after elective, uncomplicated laparoscopic cholecystectomy.th June 2015 to 8th December 2015 at Military Hospital Rawalpindi. Sample calculated with WHO calculator and consecutive non probability random sampling used to divide 170 patients undergoing laparoscopic cholecystectomy in two groups. One group had routine sub hepatic drain and other didn’t. Degree of postoperative pain was assessed according to VISUAL ANALOGUE SCALE by duty doctor at 24 hours. Data was collected and analyzed applying chi square test and p value was <.05 considered statistically significant.This randomized control trial (RCT) was done over six months from 9Our results demonstrated that intensity of post operative pain in routine drainage group is higher as compared to non drainage group after elective, uncomplicated laparoscopic cholecystectomy.Routine placement of sub hepatic drain in elective uncomplicated laparoscopic cholecystectomy should be avoided to reduce post-operative pain. Cholelithiasis is a common problem among masses and two to three percent of asymptomatic patients become symptomatic each year.In a study conducted by Shamim M et al postoperative pain was 18.99% in drain group and 5.66% in group without drainage.8The rationale of the study was to assess the severity of postoperative pain in drain group and compare it with non drain group to carry out analysis and apply it in our routine work. It would direct us to counter postoperative pain if cause seems to be routine sub hepatic drainage.th to December 8th 2015 and was a randomized controlled trial. Our sample calculated by WHO calculator, came as 170 with 85 in group one and 85 in group two. Level of significance was 5% and Power of the test was 80% with anticipated P1 and P2 at 18.99 and 5.66 respectively. Inclusion criteria comprised of all patients undergoing elective laparoscopic cholecystectomy including both genders. Age limit of 30-55 years was applied. Exclusion criteria comprised of those patients converted to open cholecystectomy, Immunocompromised and requiring critical care. It also included Patients with neuralgias and with complications like post operative hemorrhage or biliary leakage.Our study was carried out at Department of Surgery Military Hospital Rawalpindi for a period of six months from June 9After approval of the study by the institution’s research ethics committee, the patients meeting inclusion criteria were enrolled in the study after explaining the procedure to them in the language they understood and informed written consent was taken. Demographic information like age, gender and address was endorsed in a predesigned Performa and telephone numbers were also taken for follow up. Consecutive non-probability sampling technique was applied and the patients undergoing elective laparoscopic cholecystectomy, meeting inclusion criteria were assigned randomly to one of the two groups. Group one received sub hepatic drain during the operation and group two had no sub hepatic drainage. Degree of post operative pain was assessed according to Visual Analogue Scale by duty doctor at 24 hours in both groups. Patients developing complications such as biliary leak and hematoma were omitted from the study.Data was recorded on separate forms. Data collected through Performa was entered into SPSS version 17.0 and analyzed through its statistical package. Descriptive statistics were used to calculate quantitative and qualitative variables. Qualitative variables like gender were measured in frequency percentages. Quantitative variable, pain was measured as mean pain score with VAS. Chi square test was applied to compare frequency of pain between the two groups. P value of ≤0.05 was considered significant. Effect modifiers like age gender were controlled by stratification. Ethical issues were maintained by informing about factors such as data coding, disposal, sharing and archiving.Age distribution of the patients was done showing that 15.29%(n=26) were between 30-35 years of age, 18.82% (32) were between 36 to 40 years, 10.58% (n=18) between 41 to 45 years of age, 22.35% n= 38 between 46 – 50 years and 32.94% n=56 between 51 to 55 years of age, mean ± SD was calculated as 46 ± 7.65 years for Group-I and 47±7.63 years for Group-II years.Patients were distributed according to gender, it shows that 21.17%(n=36) were males while 78.82%(n=134) were females of the total sample. In Group-I females were 38.82%(n=66) and males were 11.17%(n=19). In Group-II females were 39.41%(n=68) and males were 10% (n=17).Frequency of significant pain score in Group-I was 21.17% n=18 and frequency of significant pain score in Group-II was 5.88% n=5. The combined frequency of significant pain score in both groups combined was 13.52 % n=23. P value was 0.0035.Cholelithiasis is a major problem in the western population and also in our part of the world. It has been traditionally treated with open cholecystectomy. Routine drainage of the sub hepatic space has been a surgical trend of open cholecystectomy, carried on to the era of laparoscopic surgery without substantial evidence. The sub hepatic drain is placed to drain blood, bile and serous fluid from that space and is an early warning system for detection of operative complications such as blood collection or biliary leak. In a study done by Antoniou S, Pain scores were significantly higher in the drainage group both at 6-12h  and at 12-24h after surgery . This was also comparable with our results where significant pain was higher in drain group (p=0.0035).11Laparoscopic cholecystectomy (LC) has largely replaced conventional cholecystectomy in the past decade and is the gold standard now.Our study shows that 21.17 %(n=36) were male while 78.82%(n=134) were females. Frequency of significant pain score in Group-I was 21.17% n=18 and frequency of significant pain score in Group-II was 5.88% n=5. The frequency of significant pain score in both groups combined was 13.52% n=23. P value was 0.0035 indicating significant statistical difference. Pain in the drain group was significantly higher after observation at 24 hours.The results of our study were similar to study done by Shamim M, published in Indian journal of surgery. According to his study significant pain was 18.99% in drain group comparable to our result of 21.17% in drain group, whereas his results for significant pain were 5.66%, very close to our 5.88% in non drain group.Results of majority of the studies conducted in different populations of the world in establishing role of sub hepatic drain in laparoscopic cholecystectomy patients revealed that it is associated with significant postoperative pain, increases discomfort as well as hospital stay for the patients.We are of the opinion that routine placement of sub hepatic drain after laparoscopic cholecystectomy should be restrained and discouraged to allow the patients smooth and pain free recovery.Our patients were not followed in long term for pain and other long term complications such as adhesions, port site hernias and intestinal obstruction. Study was done in military set up and targeted specific class of patients. Moreover it was one at Rawalpindi so patients in this particular area were enrolled and results may not be generalized for entire Pakistani population.The results of our study are in accordance with the majority of studies on this subject and we concluded that the frequency of post operative pain in routine drainage group after elective laparoscopic cholecystectomy is higher as compared to non drainage group and routine placement of sub hepatic drain in elective uncomplicated laparoscopic cholecystectomy should be avoided to reduce post operative pain. However, post operative complications such as sub hepatic abscess, hematoma and bilioma may alter the outcome.FN: Conceived, designed, analyzed data and prepared manuscript.MRK: Edited manuscript did literature search.FUN: Performed data collection and proof reading of manuscript.


Tapentadol is a centrally acting analgesic with μ‐agonistic activity combined with noradrenaline reuptake inhibition. Its mechanism of action relies on improvement of descending pain inhibition. In the current study, tapentadol's ability to enhance conditioned pain modulation  was evaluated in fibromyalgia patients with absent or reduced CPM responses.A total of 34 fibromyalgia patients completed this double‐blind trial. Patients were randomized to receive treatment with tapentadol sustained‐release or placebo for a 3‐month period with 1‐month follow‐up. At baseline, the cornea nerve fibre state (CNFS) was quantified to determine the presence of nerve fibre pathology and assess its value in the prediction of the analgesic response.p = 0.042). No treatment effect was observed for the absolute pain scores, however, analgesia responder rate analyses demonstrated a treatment effect in favour of tapentadol. Pain relief (a reduction in pain score ≥ 30%) was predicted by the presence of a normal CNFS (p = 0.035). Patients with an abnormal CNFS had no analgesic effect from tapentadol despite an increase in CPM.Tapentadol significantly increased CPM responses during treatment with an average increase from baseline of 20.5 ± 12.5% (tapentadol) versus 3.0 ± 11.2% (placebo; In chronic pain patients with fibromyalgia, the increase in endogenous pain inhibition by tapentadol was translated into analgesia in patients with a normal CNFS. In those with abnormal CNFS, tapentadol treatment was without analgesic effect.In this double‐blind randomized placebo‐controlled trial, we showed that tapentadol significantly enhanced the descending pain inhibition in fibromyalgia patients. Tapentadol‐induced pain relief was only present in patients with a normal CNFS. The study protocol was approved by the local Committee on Medical Ethics and the Central Committee on Research Involving Human Subjects in The Hague. From all patients included in the study, oral and written informed consent was obtained after written information was provided and before enrolment in the study. The study was registered at the trial register of the Dutch Cochrane Centre under identifier 6090 and at the EU clinical Trials register with identification number 2015‐005258‐37 on 18 November 2015. The study was performed between March 2016 and March 2018. All procedures were performed in compliance with the current revision of the Declaration of Helsinki and Good Clinical Practice guidelines.2.22, the presence of any medical disease , pregnancy or lactation, a history of psychosis, a history of illicit drug or alcohol abuse and the use of benzodiazepines. Patients were asked to stop any current pain medication for at least 4 weeks before the start of the study screening.Forty patients with fibromyalgia (diagnosed by a rheumatologist) were recruited to participate in the study. Patients were suitable for inclusion if they had a pain score of at least 5 of 10 for most of the day and met the 2010 American College of Rheumatology diagnostic criteria , patients were included in the study. After inclusion, patients were randomized to either receive a 12‐week daily tapentadol sustained release  or placebo treatment. Randomization was performed by a third party (independent investigator) using a computer‐generated randomization list. This list was transferred to the local pharmacy, which was responsible for dispensing of study medication. Tapentadol and placebo tablets were repackaged by the pharmacy for identical appearance. Treatment was started at a dose of 50 mg twice daily and weekly increased by 50–100 mg per day depending on the degree of pain relief and side effect profile to a maximum of 250 mg two times a day. In case of unacceptable side effects, dosages were decreased to a dose were side effects were acceptable. Visits 2, 3 and 4 were planned respectively 1, 2 and 3 months after the start of treatment. Visit 5 was planned 1 month after treatment ended. During these visits, CPM tests were performed and pain scores were obtained . Furthermore, patients were contacted on a weekly basis by telephone to query for pain scores and side effects.2.4The CPM paradigm was performed as described previously  with and without the conditioning stimulus (cold pain) was determined using the slider of the computerized potentiometer. For the test stimulus, the temperature of the heat probe increased with 1.5°C/s from baseline (32°C) to the target temperature for 10 s after which the temperature rapidly returned (6°C/s) to baseline. The conditioning stimulus was applied 25 s before the start of the test stimulus and ended simultaneously with the test stimulus. Patients were specifically instructed to only rate the pain intensity level of the test stimulus.2.5To quantify spontaneous pain scores, the PainDetect questionnaire was used. This questionnaire is a screening tool to detect pain intensity and the presence of neuropathic pain symptoms. It assesses current pain intensity, pain intensity during the last 4 weeks, pain localization and pain qualification . Pain intensity was scored using the VAS, which comprises a 100 mm line where the left side end indicates no pain and the right end side indicates the worst pain imaginable. Patients were asked to mark the line at a point that corresponded with their pain intensity level. The PainDetect questionnaire includes a neuropathic symptom score that ranges from 0 to 38 points, were 0–12 points indicates the absence of neuropathic pain, 13–18 points indicates that a neuropathic component may be present and 19–38 points indicates that a neuropathic component is likely present.2.6CCM was performed on both eyes using the Rostock Cornea Module of the Heidelberg Retina Tomograph III . After topical anaesthesia of both eyes the microscope was placed at the surface of the cornea apex and images were acquired with a 400 × 400 µm field of view and quantified using ACCmetrics software . Next, 3–10 representative, high‐quality images per eye were manually selected by a blinded investigator, which were used for quantification of the cornea nerve fibre length (CNFL), cornea nerve fibre density (CNFD) and cornea nerve branching density (CNBD). Each of these parameters for small nerve fibre pathology of the cornea were then compared to a reference value set published by Tavakoli et al. . Small n2.7SD and to compensate for expected drop outs due to the long study period.We did not perform a formal sample size analysis as no data were available on the efficacy of tapentadol on CPM in fibromyalgia patients. Based on the results of a previous study  compared to baseline. A Kolmogorov–Smirnov test was used to compare treatment distributions. CCM responses  between the different treatment responder groups and the correlation between CCM and the neuropathic symptom score of the PainDetect questionnaire were compared with a Fisher's exact test. A binary logistic regression was used to determine whether the CNFS was able to predict treatment responses where a treatment responder was defined by a reduction in pain reporting of at least 30%. SPSS  was used for all analyses, p‐values < 0.05 (two‐tailed) were considered significant. All data are reported as mean ± SD unless otherwise stated.All variables were screened for missing data, distribution abnormalities and outliers. Baseline characteristics were analysed with the appropriate parametric or non‐parametric tests. CPM responses were calculated using the area under the curve values of the electronic collected VAS data during the test stimulus with and without the conditioning stimulus. Averages of the three AUC responses per condition were calculated. To correct for variation in the magnitude of the responses between sessions and between subjects the relative CPM was calculated as: CPM% = [(mean AUC without CS − mean AUC with CS)/(mean AUC without CS)] × 100. The overall treatment effect (corrected for baseline) on the CPM% responses and the spontaneous pain scores (visits 1–4) were analysed using a mixed model with treatment as fixed effect and patient as random effect to account for repeated measurements over time. Similar analyses were performed on the CPM% responses and pain scores as function of CCM. The absolute pain scores were correlated to the CPM% responses and the neuropathic symptom score of the PainDetect questionnaire by Spearmans 3p = 0.005). Furthermore, although not significant, more patients in the tapentadol group reported opioid related side effects.A total of 67 patients were assessed for eligibility of whom 27 were excluded because they did not meet the inclusion criteria; 40 patients were randomized to treatment. Six patients  did not complete the study period mostly due to unacceptable side effects. Since this occurred in the first weeks of treatment (before the measurement at month 1), analysis was performed only on the patients who completed the whole study period. See Figure 3.1p = 0.708), which induced pain scores of respectively 61.3 ± 17.4 mm and 57.9 ± 15.4 mm (p = 0.655). Average cold pain temperatures were for the tapentadol group 11.5 ± 6.3°C and 11.2 ± 6.7°C for the placebo group (p = 0.896). Corresponding pain scores were 40.0 ± 1.7 mm and 42.0 ± 1.9 mm respectively (p = 0.723). Before treatment no difference was observed in the magnitude of the CPM responses between the two treatment groups with a CPM% score of −4.0 ± 17.4% for the tapentadol group and 1.8 ± 13.9% for the placebo group (p = 0.297). CPM% responses increased during treatment with tapentadol with an average increase compared to baseline of 20.5 ± 12.5% for tapentadol compared to 3.0 ± 11.2% for placebo . Overall, no significant difference in pain scores were observed during the 3‐month treatment period between tapentadol and placebo . No correlation was observed between pain scores and the neuropathic symptom score.Average spontaneous pain scores did not differ between the two groups before the start of treatment with a reported VAS score of 62.0 ± 13.1 mm for the tapentadol group and 62.1 ± 14.0 mm for the placebo group . The correlation still existed when the treatment responder groups were analysed separately, but at a borderline significant level probably due to the smaller sample size  were taken together (3.4p = 0.041). In the placebo group CCM images were similarly affected in both responder groups: 33.3% of the treatment responders (two of six) and 28.5% of the treatment non‐responders (4 of 13) had normal CCM images  with a normal CNFS as predictor for tapentadol induced analgesia. CCM was not able to predict treatment effects in patients treated with placebo (p = 0.465). In Figure p = 0.104). No correlation was observed between CCM status and the neuropathic symptom score at baseline (p = 0.580).Before the start of treatment each patient was photographed using CCM to evaluate the quantity and quality of the small nerve fibres in the cornea. Abnormal CCM images were observed in 38% of patients  treatment. As discussed earlier, it is important to stratify patients in homogeneous subgroups according to patterns of disease symptoms, (psycho)physical tests and underlying pathology  may be interpreted with reasonable reliability. The study was not powered to detect a difference in pain reporting and significant analgesic responses are not expected with these low numbers. Our secondary outcome measurement, the ability of the CNFS to predict treatment efficacy should be seen as hypothesis generating and needs further research in a large patient population to confirm or disclaim our findings. Another limitation of our study is that our conclusions are restricted to fibromyalgia patients with an impaired CPM response. It is of interest to assess tapentadol's analgesic efficacy in patients with fibromyalgia and normal CPM responses, and determine the role of the cornea nerve state on response efficacy.Finally, it is important to discuss the use of tapentadol in this patient population in light of the current opioid epidemic. Tapentadol is a bifunctional analgesic at two distinct (one opioid and one non‐opioid) receptors to induce synergistic analgesic responses . All authors report no conflict of interest regarding the topic of this study.TvdD and MvV participated in patient management and data collection. TvdD, AD and MN performed the analyses. All authors discussed the study results and commented on the manuscript.