Leg pain can be caused by both lumbar spinal disease and chronic venous disorder (CVD) of leg veins, but their clinical differences have not been thoroughly investigated. This study aimed to determine the incidence of CVD among patients visiting a spine center for leg pain. A total of 196 cases underwent ultrasound examination with a diagnosis rate were 85.7% (168 cases). CVD-diagnosed cases were divided into two groups based on the severity of lumbar spinal disease. The Clinical grades, symptom areas, and symptom types were compared. The differences in symptom improvements with vasoactive medication were also assessed. The most common symptom area was calf then the foot in CVD, while calf then thigh in lumbar spinal disease. Tingling-paresthesia was the most common symptom type for both, with pain and cramping similarly common in CVD and pain more common than cramping in lumbar spinal disease. Considering that the majority of CVD cases (78.6%) had minor cutaneous changes and almost half of cases (41.7%) had refluxes only in tributaries, significant differences in symptom improvement in CVD-dominant group suggested that early-stage venous reflux is a symptomatic disease and a possible cause of leg pain and other symptoms. Patients with leg pain usually seek relief from lumbar spinal pain by visiting spine centers. However, not every patient is fortunate enough to receive a clear lumbar diagnosis. Leg pain can be caused by other disease conditions such as arterial occlusion, peripheral neuropathy, deep vein thrombosis, knee or hip arthrosis, cellulitis, Baker’s cyst, muscular injury, tumor or infection, arterial aneurysm, and Achilles tendon inflammation or rupture5.CVD is caused by chronic dysfunctions of the venous valves and resulting reflux of blood in the superficial veins of the legs. Its clinical importance is often ignored despite being a common disease. A population-based, cross-sectional study showed 22.6% of participants had varicose veins in Clinical, Etiology, Anatomic, Pathophysiology (CEAP) grade C2-6, and venous disorders had significant association with several leg symptoms such as itching, feeling of heaviness or tightnessLumbar spinal disease and CVD present similar clinical symptoms on legs, but there are no clear and acceptable symptomatic criteria to differentiate two conditions and their clinical relationship has not been addressed due to different clinical disciplines associated with each disease. The present study was planned to determine the incidence of CVD among patients visiting a spine center for leg pain, to distinguish it from lumbar spinal disease, and to highlight the importance of early-stage CVD as a potential cause of leg pain.This study was designed as a cross-sectional study to investigate the prevalence of CVD among patients with leg pain visiting a spine center and to compare it with lumbar spinal disease. All methods were carried out in accordance with relevant guidelines and regulations and informed consent was obtained from all subjects and/or their legal guardians.The inclusion criteria were based on patients’ symptoms and history of illness. Patients were included if they experienced leg pain combined with common clinical features of CVD, such as atypical radiculopathy mismatching dermatome level, cutaneous changes like telangiectasia, reticular veins or varicose changes, cramping, coldness, morning heaviness, nocturnal aggravation of symptoms, and chronic leg pain persisting over years.The exclusion criteria were applied to patients presenting with definite radiculopathy symptoms and root irritation signs examined by straight leg raising test and femoral nerve stretching test, along with corresponding motor weakness. Cases with a history or diagnosis of arterial occlusion or deep vein thrombosis in the lower extremities were also excluded.A total of 196 patients were recruited and underwent lower extremity ultrasound examinations from January to December 2021. All ultrasound examinations were performed by the first author, who had more than six months of experience in CVD ultrasound diagnosis.The sample size of 196 patients was smaller than the calculated value for a 95% confidence level and a 5% margin of error. However, it was deemed to sufficient to provide initial insights into the study objectives.6. All patients’ CEAP grades were recorded and classified.The CEAP grade is a well-known clinical grade system for CVD that classifies it as follows: C0: no visible or palpable signs, C1: telangiectasias (veins less than < 1 mm), reticular veins (1–3 mm in diameter), C2: varicose veins (> 3 mm), C3: edema, C4: secondary skin alterations. C4a: pigmentation and eczema, C4b: lipodermatosclerosis or white atrophy, C5: healed ulcer, and C6: open ulcerThe areas of symptom complaints were classified as low back, buttock, thigh, knee, calf, and foot. The types of symptoms were classified as pain, tingling-paresthesia, hypoesthesia, cramping, coldness, heat, swelling, and weakness. Each patient could have more than one symptom area and type of symptom manifestation.The CVD diagnosis groups were classified according to the ultrasound findings, which were classified as follows: VD0 for no CVD finding, VD1 for venous reflux only in tributaries and perforators, VD2 for venous reflux in major veins such as great saphenous vein (GSV) or small saphenous vein (SSV) and varicose vein, and VD3 for venous reflux in major veins, tributaries, and perforators.7. The lumbar spinal disease groups were classified by combining severities of two diseases as follows: LD0 for no definite disc protrusion or spinal canal narrowing, LD1 for mild disc bulging or stenosis grade A and B which unlikely to cause any leg symptoms, LD2 for moderate disc protrusion or stenosis grade C which potentially to cause leg pain, and LD3 for ruptured disc or stenosis grade D.The lumbar disc herniation and the lumbar spinal stenosis were included in the lumbar spinal disease diagnosis group based on magnetic resonance imaging (MRI) findings. The lumbar disc herniation was categorized according to the degree of disc protrusion. The lumbar spinal stenosis was graded based on the presence of cerebrospinal fluid (CSF) signal as follow: Grade A for clearly visible CSF inside the dural sac, Grade B for individualized rootlets occupying the entire dural sac, Grade C for homogeneous gray signal dural sac with no visible CSF signal and unrecognizable rootlets, and Grade D for the absence of posterior epidural fatNone of cases had any history or diagnosis of arterial occlusion or deep vein thrombosis in the lower extremities.CVD-diagnosed cases (VD123) were divided into two groups for comparison analysis based on the severity of lumbar spinal disease. The first group, CVD-dominant group (VDG), had a lower degree of lumbar spinal disease and symptoms were believed to be caused by CVD. The second group, lumbar spinal disease-dominant group (LDG), had a higher degree of lumbar spinal disease, and patients’ symptoms were thought to be influenced by the lumbar spinal diseases.Vasoactive medications were provided to the cases diagnosed with CVD, but surgical management for CVD was not performed, which could be a limitation in improving symptoms, especially in severe cases of CVD. To compensate for this limitation, the trends of symptom improvement graphs were compared between the two groups.Symptom improvements were assessed at the first follow-up visits within a two-month period and were categorized as excellent, good, or poor based on the patients’ own descriptions of their symptoms. The visual analog scale (VAS) or numeric rating scale (NRS) was irrelevant and not used because CVD symptoms include pain as well as a variety of other symptoms. It was hypothesized that if there was significant difference in vasoactive medication effect between the VDG and LDG, it could provide indirect evidence for the existence of venous pain in patients presenting to the spine center with leg pain.The estimation of vasoactive medication effect could be affected by several factors such as pain medication, neuropathic medication, pain block, and lumbar surgery. Pain medications (PM) were graded according to its strength as follows: PM0 for no pain medication, PM1 for NSAIDs , PM2 for weak opioids , and PM3 for strong opioids. Neuropathic medications (NM) were graded as follows: NM0 for no neuropathic medication and NM1 for gabapentin or pregabalin. These factors were included in the group comparisons to estimate the effect of vasoactive medication.The ultrasound examinations were conducted in an erect position along the pathway of the GSV, SSV and their major tributaries from the inguinal to the lower medial calf, posterior knee to posterior calf, and lateral knee to calf. The B mode ultrasound examinations were started to find the proximal junction of the saphenous vein at the inguinal area for GSV and the posterior knee for SSV. Venous refluxes were assessed using a manual compression-and-release maneuver. An assistant made an upward venous flow by manually compressing and releasing more distal leg from the test site. Upward flow and following venous flow were examined by real-time simultaneous Color and Pulsed Wave Doppler mode. A positive finding was defined as the presence of reflux flow for more than one second of reflux flow in major saphenous veins, and for at least half a second of reflux in tributaries and perforators. The examination was carried out using both a linear probe  and a hockey-stick probe .The frequency data were displayed without statistical comparison. Chi-square tests were used for comparing categorical variables, and a p-value of < 0.05 was considered statistically significant. The analyses were performed using the IBM SPSS Statistics software, version 25.The study was approved by the local ethics committee (PSSH 0475–202207-HR-10) of the Pohang Strokes and Spine Hospital in July 2022.Among 196 inclusion cases, 54 cases (27.6%) were men and 142 (72.4%) were women, with ages ranging from 25 to 84 years old (mean 61.3 ± 12.0). Symptoms on the right leg were observed in 20.4% (40 cases) and 23.0% (45 cases) were on the left leg. Bilateral symptoms were present in 56.6% (111 cases). The most common CEAP grade was C0 , and sum of C0 and C1 was 78.6% (154 cases). Most patients reported symptom duration of longer than one month , with 57.7% (113 cases) lasting more than one year (Table The ultrasound CVD diagnosis rate were 85.7% (168 cases), with negative findings in only in 14.3% 28 cases). Within diagnosis group from VD1 to 3, VD1 accounted for 41.7% (70 cases), VD2 for 19.0% (32 cases), and VD3 for 39.3% (66 cases) . LD1 was present in 11.7% (23 cases), LD2 in 30.6% (60 cases), and LD3 in 32.1% (63 cases). Assuming LD2-3 could cause significant leg pain, 62.7% (123 cases) of the cases were found to be affected by lumbar spinal diseases.Electromyography (EMG) was performed on 76 cases, accounting for 38.8% of the total cases, and radiculopathy findings were present in 50.0% (38 cases). Most of the cases with radiculopathy were LD2 and LD3, indicating that the most common accompanying disease was lumbar spinal disease   Table . This meWhen comparing the frequencies of symptom manifestations between the VDG VD123-LD01) and LDG (VD123-LD23), it was found that the calf was the most common symptom area for both groups. In the VDG, the second most common area was the foot, whereas in the LDG, it was the thigh. Regarding the types of symptoms, tingling-paresthesia was the most common for both groups, In the VDG, pain and cramping occurred with similar frequencies as the second most common symptoms, while in the LDG, pain was more common than cramping  were enrolled for the vasoactive medication effect evaluation except 23 cases (13.7%) of follow-up loss. Excellent symptom improvements were observed in 44.1% (64 cases), while 29.0% (42 cases) were rated as good, and 19.9% (39 cases) were rated as poor.There was a statistically significant difference in symptom improvement between the VDG VD123-LD01) and LDG (VD123-LD23). The rate of excellent symptom improvement rate was much higher in the VDG  than in the LDG . When the definition of group comparison was changed to the VDG (VD123-LD012) and LDG (VD123-LD3), the difference was similarly significant  of the 145 enrolled cases. This variable had a low value as a separate interfering factor for the group comparison because most pain block cases also took pain medications. The influence of pain block variable could be included in the pain medication variable.The lumbar surgery was performed on 6.2% (9 cases) of the 145 enrolled cases within six months of vasoactive medication. It was assumed the frequency of lumbar surgery was too small to have a significant impact on the outcome of symptom improvement.8. The Vein Consult Program enrolled 91,545 subjects through 6232 general practitioners, the worldwide prevalence was found to be 83.6% , and 41.4% of these patients had early-stage CVD (C0–1)9. The present study focused on patients who visited a spine center due to leg pain and related symptoms. The prevalence of C1-6 was 53.1%, with higher than C2 was only 21.4%. Early-stage CVD (C0-1: 78.6%) was more dominant than other grades, indicating that a significant proportion of patients with C0-1 had leg symptoms. Patients with higher than C2 were more likely to seek venous treatment rather than visit a spine center, as venous pathology was more visible, and patients were able to recognize problems related to CVD.CVD is a common pathologic condition, but its clinical importance is not widely recognized. In a survey conducted in Belgium and Luxembourg, a total of 6009 patient were included by 406 general practitioners and the prevalence (C1-6) was found to be high at 61.3%5. Another study showed that heavy legs, pain, and sensation of leg swelling were the most common complaints among the 3889 symptomatic patients8. While it is obvious that CVD is a major cause of various leg symptoms, more than half (62.7%) of the cases in this study were found to be influenced by lumbar spinal disease. Although the symptoms of two diseases were similar, characteristic differences could be found  scan is useful for visualizing entire vascular pathway and tortuous varicose change of leg veins Fig. c. It has12. The comparison analysis of symptom improvement for VD1 showed significant differences, indicating that these small refluxes could be a causative factor of the leg pain (Table The diagnosis rate in the present study was much higher 85.7%) than in other studies, because the reflux confined to tributaries and perforators was included as a diagnosis group (VD1). Up to 41.7% of the diagnoses were due to refluxes in tributaries and perforators (VD1), while 58.3% were in major veins VD2-3) , and the spinal and dural sac space was associated with neurological claudication16. Common degenerative leg diseases such as knee or hip arthrosis can also present typical symptoms of CVD4.Although excluded in the present study, other vascular diseases such as peripheral arterial disease and deep vein thrombosis can cause similar leg pain that worsens with walking. However, femo-gluteal fatigability or pain and impotence, which are early signs of Leriche’s syndrome, have also been attributed to co-existing lumbar spinal diseaseAlready progressed and clinically clear CVD patients will seek vascular diagnosis and treatment. However, early-stage CVD usually doesn’t have noticeable cutaneous changes, and patients may be unaware of the underlying the cause of their pain. These symptoms can easily be mistaken for lumbar spinal disease or considered as a part of the lumbar symptoms during the assessment of the condition. Considering that the majority of cases in the present study (78.6%) were C0-1 grade and almost half of the diagnosed cases (41.7%) were in the VD1 group, significant differences in symptom improvement between VDG and LDG provide evidence for the presence of venous pain in early-stage CVD. Simply, clinically hidden small or early-stage venous refluxes can be a cause of leg pain.When cases taking pain and neuropathic medications were excluded from the comparison, the count of LDG was prominently lower than that of VDG Table e, f. ThiThe present study had several limitations. It was non-randomized and observational study. A control group without CVD was not included for specific comparison. Only short-term medical treatment was included, and more invasive treatment was not. The comparison variables were categorial, further statistical analysis using continuous variables should be developed. Randomized case–control trials should be evaluated to provide more definite conclusions.CVD is not uncommon condition among patients visiting a spine center for leg pain. While the clinical presentation of CVD is similar to that of lumbar spinal disease, it has a few distinguishable clinical features. CEAP C0-1 grades and refluxes confined solely to tributaries and perforators are not asymptomatic condition, it can cause leg pain and various other symptoms. Evaluating early-stage CVD can reveal another clinically hidden cause of leg pain when assessing the lumbar spinal disease.


Coccydynia is defined as pain in the coccyx. We investigated the effect of radial extracorporeal shockwave therapy (rESWT) in the management of coccydynia.In this prospective study, patients (≥18 years) diagnosed with coccydynia at a sports clinic located in Thessaloniki, Greece, were eligible for rESWT treatment when they reported a visual analogue scale (VAS) pain level ≥6. Treatment sessions were once weekly and ended when VAS pain levels decreased to ≤3. Recurrence rates were documented at 3-month and 12-month follow-ups.r=0.701, P=0.005). Pairwise comparison highlighted significant reductions in VAS pain levels between each stage of treatment (P<0.001).Fourteen patients were treated using rESWT. The mean age and symptom duration of our cohort was 33.6±7.9 (range: 20–45) years and 9.4±8.5 (range: 3–36) months, respectively. The mean number of treatment sessions per patient was 6.4±1.6 (range: 4–8). The mean device pressure, frequency, and number of pulses was 1.2±0.1 (range: 1–1.4) bar, 5.0±0.1 (range: 5–6) Hz, and 2082±74.8 (range: 2000–2300) pulses, respectively. Treatment alleviated pain in all patients, and no recurrence of symptoms was reported during follow-up. There was a positive correlation between symptom duration and the number of treatment sessions (Our study affirms the safety and efficacy of rESWT in managing coccydynia. HighlightsRadial extracorporeal shockwave therapy (rESWT) offers an alternative and non-invasive means of treatment for coccydynia.Treatment can be adapted by altering device parameters in line with patients’ pain tolerance and treating patients over a variable number of sessions.Pain-adapted intervention protocols may optimise pain management and lower the risk of symptom recurrence.Randomised controlled trials comparing rESWT efficacy with other surgical and non-surgical modalities are needed.1. It serves as the attachment site for several pelvic structures and possesses an extensive nerve supply2. Coccydynia is five times more common in women than men, although its exact prevalence is unclear4. Factors associated with the development of coccydynia include obesity, prolonged sitting, and childbirth4. Degenerative joint disease is also thought to increase risk1. The most common presentation is following a traumatic event, typically a backwards fall1.Coccydynia, or coccygodynia, refers to pain in the coccyx (tailbone). The coccyx is a triangular-shaped bone in the lowermost region of the spine and is composed of three to five individual segments3. Physiotherapy and manipulative therapy are also popular treatment options5. Steroid and anaesthetic injections may be useful in patients who do not respond to these methods, but there is controversy surrounding the optimal site for injection1. Surgical coccygectomy is performed in treatment-resistant cases, and whilst outcomes are generally good-to-excellent, the incision is made close to the anal canal and can make subsequent care challenging7.Most cases of coccydynia can be managed conservatively with rest, anti-inflammatory medications, seating aids, and warm baths8. Devices are placed against the skin and deliver impulses of energy to injured tissue at a given pressure (bar) and frequency (Hz)11. The exact mechanism of action of ESWT remains unknown; however, biological responses are proposed to be mediated by mechanotransduction and include tissue regeneration, wound healing, angiogenesis, and neovascularisation15. Altogether, this can result in significant pain alleviation12. There are two types of ESWT: focused (fESWT) and radial (rESWT). These differ marginally in terms of shockwave production and energy delivery8. In practice, rESWT devices are smaller, cheaper, and easier to use8. Moreover, rESWT has proven to be successful in the management of musculoskeletal disorders such as plantar fasciitis18, calcific shoulder tendinopathy20, trigger digit21, sesamoid osteonecrosis22, patellar tendinopathy23, medial tibial stress syndrome26, and lateral epicondylitis28.Extracorporeal shockwave therapy (ESWT) is a physical agent modality that offers an alternative and non-invasive means of treatment for coccydynia32. One study found rESWT to be more effective than steroid injections for pain relief over 6 months of observation32. A recent systematic review reported that shockwave therapy offered the second-greatest improvements in pain among all available treatment options33. However, research on the subject remains limited. Furthermore, most of the available studies adopt a ‘one size fits all’ approach by treating patients at a single dose over a predetermined number of sessions. The research objectives of this study were: (i) determine whether a pain-adapted protocol of rESWT is effective in treating coccydynia, (ii) assess for a relationship between treatment duration and symptom intensity, and (iii) monitor patients for possible adverse effects of treatment.Previous literature has highlighted the benefit of rESWT for coccydynia34, Supplemental Digital Content 1, http://links.lww.com/MS9/A206.This prospective study was reported in line with the PROCESS (Preferred Reporting Of CasE Series in Surgery) Guideline35. Anteroposterior and lateral radiographs of the lumbar spine and coccyx were obtained to assess the position of the coccyx and rule out coccygeal dislocations. Magnetic resonance imaging scans were also performed to exclude other pathologies of the lumbar spinal cord, coccyx, and associated soft tissue. Treatment options, including the use of rESWT, were discussed with patients if they reported a visual analogue scale (VAS) pain level ≥6. Patients aged ≥18 years were eligible for the study. Exclusion criteria were: local or systemic neurological disease, rheumatological disease, malignant disease, previous spinal surgery or spinal disease, coagulopathies, pregnancy, recent (≤6 weeks) trauma to the coccyx, and coccygeal dislocations.Patients presenting to a sports clinic located in Thessaloniki, Greece, between January 2017 and December 2020 were diagnosed with coccydynia by a consultant sports physician (N.M.) following focused clinical history, examination, and imaging. Physical examination included inspection of the overlying skin and palpation, which revealed localised focal tenderness in the region of the coccyx36. All treatments were performed after verbal and written informed consent had been obtained. The probe was placed on the skin at 90° to the coccyx in the sagittal plane29. Ultrasound gel was applied to the skin before treatment to reduce energy loss from the device. Local anaesthesia is known to lower the efficacy of treatment and was therefore not used37. Treatment sessions took place once a week to allow for adequate periods of recovery and healing for at least three sessions. Any ongoing treatments for coccydynia were stopped, and patients were advised against the use of non-steroidal anti-inflammatory drugs.Treatment was administered to the maximal point of tenderness exactly over and posterior to the coccyx by the same consultant sports physician, using the Storz Medical Masterpuls MP200  rESWT device22. Pressure, frequency, and the number of pulses were adjusted between sessions in line with patients’ pain tolerance. Pain tolerance is the duration of time until an individual can no longer withstand an unpleasant stimulus and reflects the greatest level of discomfort they are willing to endure39. Tolerance is of particular value in coccydynia, given that pain is the most common presenting symptom and its management is the primary goal of treatment.The rESWT device was set to a minimum pressure and frequency of 1 bar and 5 Hz, respectively. Each session included the delivery of at least 2000 pulses. These parameters were set based on the experience of our authors with previous cases of coccydynia and mirror those utilised in similar rESWT research41. Patients were asked their pain level before treatment at each session, although this did not form part of our formal data collection. Treatment continued until patients reported a VAS pain level ≤3, at which point they were discharged from the clinic42.VAS pain levels were used to monitor patient response and clinical improvement throughout treatment, with patients ranking the severity of their pain at rest between ‘no pain’ (0) and ‘worst imaginable pain’ (10)The main outcome measure of this study was pain management. Each patient provided a baseline VAS pain level based on their initial symptomology. Follow-up measurements were taken immediately after the cessation of treatment, at 3 months posttreatment, and at 12 months posttreatment. Symptom resolution and disease recurrence were monitored during this period. The mean device pressure and frequency, number of pulses, and number of rESWT sessions were also documented using electronic device records.P<0.001). The repeated measures ANOVA  procedure (Friedman) was used to test for significant reductions in VAS pain levels. Pairwise comparisons using Durbin–Conover measured differences in VAS at each stage of follow-up when compared with baseline scores. Spearman’s rank correlation coefficient was used to assess the correlation between variables. A predefined confidence level of 95% (α=0.05) was set for all statistical analyses.Descriptive statistical analysis was carried out using Microsoft Excel , IBM SPSS Statistics Version 27 , and Jamovi . The variables analysed did not meet the normality assumption, which was performed using the Shapiro–Wilk test (Fourteen patients were included in the study. The cohort comprised five (36%) men and nine (64%) women, with a mean age of 33.6±7.9 (range: 20–45) years. The average duration of symptoms before rESWT was 9.4±8.5 (range: 3–36) months Table .r=0.701, P=0.005).The mean number of rESWT sessions was 6.4±1.6 (range: 4–8). The median number of sessions was 6.5 . Five patients (36%) underwent eight sessions, two (14%) underwent seven sessions, two (14%) underwent six sessions, three 21%) underwent five sessions, and two (14%) underwent four sessions (Table 1% underwhttp://links.lww.com/MS9/A207).The mean pressure and frequency of the rESWT device over the course of all treatments were 1.2±0.1 (range: 1–1.4) bar and 5.0±0.1 (range: 5–6) Hz, respectively. The median pressure and frequency was 1.2  bar and 5.0  Hz, respectively. The mean number of pulses delivered per session was 2082±74.8 (range: 2000–2300) pulses. The median number of pulses per session was 2000  pulses (Table http://links.lww.com/MS9/A207).The mean and median pretreatment VAS was 7.4±0.7 (range: 6–8) and 7.5 , respectively. The mean and median VAS immediately posttreatment was 1.6±0.7 (range: 1–3) and 1.5 , respectively. The mean and median VAS at 3-month follow-up were 0.9±0.7 (range: 0–2) and 1.0 , respectively. The mean and median VAS at 12-month follow-up was 0.3±0.5 (range: 0–1) and 0.0 , respectively  value of 38.7 (P<0.001). The pairwise comparison revealed significant reductions in VAS pain levels between each stage of treatment (P<0.001) , frequency (5–21 Hz), number of pulses (2000–3000 pulses), and number of sessions ranged considerably. To our knowledge, this study is the first to deliver a pain-adapted protocol of rESWT. We achieved this by (i) adjusting rESWT device parameters in line with patients’ pain tolerance and (ii) continuing treatment until a VAS pain level ≤3 was reported. We believe that continuing treatment until a low level of pain is achieved is relevant to the favourable outcome of this study.The value of rESWT for coccydynia has been highlighted in a handful of studies43. To illustrate, if a patient found the same dose of treatment to be less painful at a later session compared to an earlier session, then device parameters may be increased. Alternatively, if a patient finds treatment uncomfortable at a particular dose, then device parameters may be lowered. A 2007 study also observed the greatest reductions in pain when patients with chronic heel pain were treated with ‘maximum tolerable’ energy densities, compared to a fixed protocol44.Treating patients according to pain tolerance is common with the use of shockwave therapy. Numerous regimes in a 2013 systematic review described making dose alterations ‘as tolerated’ when treating soft tissue conditions19. Higher device pressures are said to increase pain; therefore, our approach may also make treatment more comfortable for patients45. The mean device frequency increased by a maximum of 0.2 Hz (5–5.2 Hz), and the mean number of pulses per session increased by a maximum of 8.95% (2000–2179 pulses). An increased number of larger cavitation bubbles – and resultant shockwaves – are generated at lower frequencies, which may explain the findings of one study, where the device frequency was set to 21 Hz, and increases in pain were reported at the 7-month follow-up46. In contrast, no symptom recurrence was present in our study. The number of pulses per session increased only between sessions numbers two and six, and with careful consideration of energy accumulation in those who had more than six sessions.The mean device pressure in this study increased by a maximum of 0.2 bar (1.1–1.3 bar). Whilst this may be an arguably insignificant change, it is worth noting the positive outcomes observed at lower overall device pressures31. Given the symptom control and lack of recurrence in our cohort, we may argue for the number of treatment sessions to be dictated by patients’ pain levels, as this appears to be the most important indicator of successful treatment. Pain levels after treatment and during follow-up were also lower in our cohort compared to others.Patients were discharged from the clinic once their VAS pain level reached ≤3. This meant that they all underwent at least four, and no more than eight, treatment sessions. In contrast, previous studies administered treatment over a predetermined number of sessions29. Equally, we acknowledge that complete symptom resolution (VAS=0) was not achieved among our entire sample, and, in fact, no patient was completely pain-free immediately posttreatment (VAS 1-3). While the long-term effect of rESWT can be observed during follow-up, four patients remained symptomatic (VAS=1) at 12 months. This suggests that while treatment may have been successful, it did not always eradicate pain. A lengthier follow-up period may have highlighted further decreases or recurrences in VAS; however, 12 months can be considered adequate, given the nature and conditions of this study.Yet, inadequate pain relief among patients was observed in another study that continued rESWT until VAS pain levels were ≤3r=0.701). There were seven patients who underwent either seven or eight sessions, all of whom reported pain for more than 6 months. However, symptom duration did not appear to be reflected in pretreatment VAS. The remaining patients, whose symptomologies ranged from 3–6 months, required no more than six sessions. This suggests that patients with chronic symptoms (>6 months) at presentation are likely to require more rESWT sessions.Our analyses found a strong positive correlation between symptom duration and the number of treatment sessions required  comparing rESWT with other management options for coccydynia and comparing different rESWT protocols.Despite its poorly understood mechanism of action, rESWT continues to serve as a safe and effective management option for coccydyniaWe acknowledge some limitations of this study. Firstly, the number of patients included was small because coccydynia is a condition of low incidence. Secondly, our analysis must be interpreted with some degree of caution. Although a single modality was delivered, we cannot be certain that there were no alternative explanations for the effects observed. Additionally, VAS pain levels during treatment were not formally recorded. VAS was also the only measure used to assess patients’ pain tolerance. Employing a second tool to confirm the decrement of intensity may have strengthened our conclusions regarding the efficacy of rESWT. Other outcomes, such as quality of life and disability, have featured in similar research and assessed using scales such as SF-36 and Oswestry Disability Index, respectively.We had identified a high success rate and no recurrence of disease at 12-month follow-up when coccydynia patients were treated with a pain-adapted protocol using rESWT. Our results align with the current evidence base recognising rESWT as a conservative management option for coccydynia and also suggest that adjusting the number of treatment sessions and doses during treatment in line with patients’ pain tolerance may optimise pain management and lower the risk of recurrence. This may also make treatment more comfortable for patients. More RCTs are needed to compare the effect of rESWT on other surgical and non-surgical treatment modalities.Ethical approval was granted by the Thessaloniki Clinic Institutional Review Board (ART No. 2016-09).Written informed consent was obtained from the patient for publication and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.This paper received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors affirm that this manuscript is an honest, accurate, and transparent account of the study being reported, that no important aspects of the study have been omitted and that any discrepancies from the study as planned  have been explained.N.M.: set up and carried out the study; K.S.L. drafted the manuscript. All authors contributed to the writing of the manuscript, revised the draft manuscript, and approved the final version.The authors declare that they have no conflicts of interest.Name of the registry: ClinicalTrials.gov.Unique identifying number or registration ID: NCT05753514.https://clinicaltrials.gov/ct2/show/NCT05753514.Hyperlink to your specific registration (must be publicly accessible and will be checked): ha16657@qmul.ac.uk; Nikos Malliaropoulos, E-mail: contact@sportsmed.gr; Georgios Bikos, E-mail: bikosg77@yahoo.gr; Heinz Lohrer, E-mail: Heinz.Lohrer@esn-ortho.de.Kabir Singh Lota, E-mail: The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.Not applicable.


Thus, this study aimed to investigate patient's satisfaction with their post-operative pain management and its determinants among surgically treated patients in a specialized hospital within Ethiopia.an institutional-based prospective cross-sectional study was conducted in the surgical ward of Ayder Comprehensive Specialized Hospital. Data were collected using a semi-structured questionnaire, which was an adoption of the 2010 version of the American Pain Society Patient Outcome Questionnaire, and by reviewing the medical charts of the patients. A stepwise linear regression model was used to analyze the data.2= 0.084, P=0.02).among the 144 patients approached in this study, 112 (77.8%) of them categorized their postoperative pain as moderate to severe. The mean patient satisfaction with their pain management was 7±2.3 on 0-10 numerical rating scale. Despite high levels of pain, the majority of patients  were moderately or completely satisfied with their pain management. Stepwise linear regression analysis found that the determinants of patients' satisfaction were prior chronic pain, prior surgical history, and substance use  = 5.364, adjusted Rthe patients were moderately and completely satisfied with their pain management in spite of expressing moderate and severe level of pain intensity. Pain still remains a concern among surgical patients, and effective pain management strategies should be practiced to manage pain and its functional interferences more effectively. Post-operative pain (POP) is prevalent among surgical patients and is a persistent challenge to the medical community despite efforts to advance pain management protocols in surgical patients . EffectiThe subjective and complex character of pain presents obstacles to assessment and management by health care professionals, which demands a patient-centered assessment. Limited research has been carried out exploring patient experiences despite the clinical importance of pain management ,12. PatiStudy design and area: a prospective cross-sectional study was conducted in the surgical ward of Ayder Comprehensive Specialized Hospital (ACSH) which is found in Mekelle city, Northern Ethiopia. It is one of the largest referral and teaching hospital in Northern Ethiopia providing health services for a catchment population of about 10 million people. The hospital has 500 beds with an average of 280 operations being carried out weekly. The hospital did not have any standardized procedures for management of pain and routine pain management protocols were being followed in the hospital.Study participants: the source population was constituted of all patients who underwent surgical procedures in ACSH. All surgically treated patients, who were admitted in the hospital from March 25th to May 25th, 2017 and who fulfilled the inclusion criteria, were included in the study. The inclusion criteria were patients who had undergone any type of surgery, who were alert and active to respond, who were 18 years and above. The exclusion criteria were patients who were in critical situation (unable to communicate), patients who underwent emergency surgery, and patients who were admitted to intensive care unit or with known mental health disorders . Moreover, those patients that have been discharged overnight were excluded.2)2 p (1-p)]/d2, where n= minimum sample size, Z1-aα/2 at 95% confidence interval=1.96, p=estimated level of patient satisfaction with POP management (91%) taken from a study conducted in Jimma [Sample size was computed using a single population proportion sample size estimation formula. For population >10,000, the formula can be provided as n = [ [(APSPOQ) . The queThe revised APSPOQ items are mainly based on an 11-point numerical rating scale (NRS: scores from 0-10). Patients severity of pain (pain intensity) was measured as NRS score which ranges from 0 = “no pain” to 10 = “worst pain possible”. The proportion of time the surgical patient had spent in severe pain after surgery was measured from 0% = “never in severe pain” to 100% = “always in severe pain.” Pain interference was recorded as functional disability due to pain (NRS score from 0 = “did not interfere” to 10 = “completely interfered”) and the effect of pain on mood and emotion like feeling of anxious, depressed, frightened and helpless was measured using NRS score from 0 = “not at all” to 10 = “extremely”. Patient perception of care was measured as the degree of pain relief obtained through combined medicine and non-medicine pain treatment (NRS score from 0% = “no relief” to 100% = “complete relief”). Patient's requests for stronger analgesics and information about their pain treatment options  were detailed as “yes” or “no.” Degree of satisfaction with the outcomes of pain management was measured as an NRS score from 0 = “extremely dissatisfied” to 10 = “extremely satisfied.”For the sake of validation and consistency in data collection, the questionnaire was pretested in 10% of patients  and amendments were made accordingly. A data abstraction checklist was also developed by retrieving reputable literatures to extract relevant information. Patients' satisfaction was the primary outcome of the study and level of pain intensity, socio-demographic characteristics, and substance use were considered as the independent variables. The statistical analysis was carried out using Statistical Package for Social Sciences (SPSS) Version 21 software. First, the data were edited and checked for completeness and consistency then entered into SPSS for analysis. Simple descriptive statistics, including frequencies, percentages, means and standard deviation, were computed to summarize the socio-demographic and clinical characteristics of the study participants. Categorical variables were expressed with frequencies and percentages, while continuous variables were expressed as means ± standard deviations. A stepwise linear regression model was used for analyzing the data. All statistical analyses were performed and a p-value of less than 0.05 was considered as statistically significant.Operational definitions: Pain was defined as an unpleasant sensory and emotional experience associated with actual and potential tissue damage [Mild pain was defined as when the American Pain Society Patient Outcome Questionnaire (APSPOQ) score is from 1-3. Moderate pain when APSPOQ score is from 4-6 and severe pain when APSPOQ score is from 7-10. Participants who score APSPOQ of zero (0) were considered as having no pain [Null, mild, moderate and full patient satisfaction was defined when APSPOQ pain satisfaction score was 0, 1-4, 5-6 and 7-10 respectively [e damage . Mild pa no pain . Null, mectively .Ethical considerations: ethical clearance was secured from the Institutional Review Board of the College of Health Sciences, Mekelle University. Written consent was obtained from all the study participants after explaining the main aims and purposes of the study. Moreover, the study participants were informed about their full right to terminate the study at any time. Confidentiality and privacy of the participants were also maintained. During the data collection process, data of patients who were at any risk of complications due to pain were shared with their healthcare providers for possible interventions.Socio-demographic characteristics: a total of 144 patients participated in this study achieving a 100% response rate. The majority (66%) of the study participants were males and the mean age of the patients were 39.1 ± 14.4 years, ranging from 19 to 76 years. Three-quarters of the participants were married and farmers. Almost half (47.9%) of the patients did not have a formal education  of them received anti-pain medications within 15 minutes of complaint of pain. More than half  of the patients never asked for analgesic during their hospitalization whereas 2 (1.4%) patients never received the analgesic medications they requested. Forty-one patients (28.5%) needed strong medication for their pain relief and 32(22.2%) used non- pharmacological methods to relieve their pain  did not use non-pharmacological methods of pain management. Among the total study participants who used non-pharmacological methods of pain management, 43.75%, 12.5%, and 12.5 %, listened to music, used relaxation, and listened to music and prayed to relieve their pain respectively. The majority (92.4%) of the study participants experienced varying degrees of POP within 24 hours of surgical procedures whereas 7.6% of the surgical patients did not experience any sort of pain. Concerning the degree of post-operative pain, 14.6%, 39.6% and 38.2% had experienced mild, moderate and severe pain respectively. The mean of pain interference over the 24 hours in increasing order were: falling asleep (2±2.2), staying asleep (2.2±2.5), activities in bed (6.9±3), and activities out of bed (7.5±3.1). Pain caused patients to feel: anxious (2+2.5), depressed (2.4± 2.8), frightened (1.6±2.6) and helpless (0.9±1.7). Nausea, drowsiness, itching and dizziness were some of the side effects experienced by the patients when they received the anti-pain medications.Patients' satisfaction with pain management and its predictors: the level of patient satisfaction with their POP management in this study is presented in 2= 0.084, P=0.02). Patients with prior chronic pain are more satisfied  than those patients without prior chronic pain. Patients who use substance were more satisfied with their pain management protocols than those patients who did not use substance . On the other hand, patients with prior history of surgery are less satisfied compared with patients that did not have surgical history   =5.364, Adjusted RP=0.029) .Attitude and belief of patients on pain management: the attitude and beliefs of patients on their pain management are summarized in Surgical patients in this study reported high levels of post-operative pain. Almost 92.4% of the patients studied had some sort of pain after 24 hours of surgery with 39.6% and 38.2% having moderate and severe pain respectively. Despite high reporting of moderate (61.8%) and severe pain (28.5%) the respondents were completely or moderately satisfied with their pain management respectively. This paradoxical high satisfaction of patients despite high reports of post-operative pain is supported by different literature. There is growing evidence of patient satisfaction with pain relief despite high pain score reports ,17. ThusThere was no significant difference in patients' satisfaction regardless of the variation in pain intensity level  =1.609, P=0.190). This finding is consistent with previous studies 0 =1.609,. This diThe majority (58.3%) of the patients never requested any pain medication. This finding showed that patients of the current setting were less likely to request anti-pain medication in comparison to patients from other countries -29, evenThis study demonstrated that substance use , prior chronic pain  and prior surgical history  were strong predictors of patients' satisfaction with their pain management. This result is in contrast with the findings of some previous studies ,24,26. TThis study demonstrated a high level of patients' satisfaction with their pain management despite the majority of the patients complained of moderate and severe pain intensity. This finding indicates the need for future in-depth studies on this 'disconnect'. The study also showed the lack of inclusiveness of non-pharmaceutical interventions in the pain management strategies in the hospital. In part, this may reflect the lack of standard guidelines for pain management in this setting and for training of patients and health professionals on the merits of alternative approaches to post-operative pain management.There is paradoxically high level of patient satisfaction despite majority of the surgically treated patients experienced moderate to severe degree of pain;Sophisticated non-pharmacological pain treatment protocols are used especially in developed countries like USA and China.This study determines the predictors of patient satisfaction i.e. substance use, prior chronic pain and prior surgical history;Non-pharmacological methods of pain management were found low in this study and this indicates there is a disjoint between the medical staff and the patient needs;This study reveals surgical patients had less involvement in their pain management and, due to high level of barriers and they are less likely to communicate their concerns and their needs to their healthcare providers.


T test, Mann–Whitney U test and Chi-square test. Results: There were statistically significant differences between the two groups both in the PRS and FLACC ratings. Both in subjective and objective pain evaluations, significantly higher pain ratings were observed in the group without topical anesthesia. There was also a statistically significant difference in terms of patients’ parents’ judgment, as in the group with the use of topical anesthetic the level of parental satisfaction is statistically higher. Conclusion: The experimental anesthetic has proved very effective in its use as a topical gel in both pain measurement scales, thus validating its use on the oral mucosa, for its pharmacological and psychological effect, in the total absence of local and systemic side effects.The aim of the present study was to test a new topical anesthetic gel with a different formulation  to analyze its effectiveness in pain control, during the subsequent injection of local anesthetic, and the presence of any side effects. Methods: The study’s research design was a randomized controlled clinical trial on 300 children, aged 5–8 years, divided into two groups, each of 150 patients, according to pre-injection procedures . The injection pain was analyzed using the Wong-Baker Faces Pain Rating Scale (PRS) and the Face, Legs, Activity, Cry, Consolability Scale (FLACC). At the end of the procedures, patients’ parents’ satisfaction was recorded. The data were analyzed using the Student’s  The term anesthesia generically indicates the abolition of sensitivity, consciousness and pain, associated with muscle relaxation. Anesthesia is generally divided into two main strands: local and general anesthesia. Local anesthesia (LA) is a form of anesthesia used to anesthetize and thus inhibit pain on small areas of the body; it requires infiltration of an anesthetic drug through the skin or subcutaneous area to be treated. The use of local anesthesia has only specific contraindications and does not imply the loss of consciousness of the patient, who remains alert as the drugs remain confined to the affected area without exhibiting any direct action on the central nervous system.When a correct dosage is used, the most annoying side effect associated with local anesthesia is pain at the injection site. Indeed, it is known that in an entire dental treatment the anesthetic injection is the part that causes the most fear. Local anesthesia, particularly in children, is associated with high levels of anxiety and correct administration is essential for optimal behavioral management . UnfortuAt the time of dental anesthesia, therefore, children could typically have a negative reaction to this procedure, from the young patient’s loss of compliance to extreme reactions, in which the child becomes uncontrollable and combative, which could make it impossible for the dentist to continue with the pre-established dental treatment . HoweverTo reduce the inconvenience of injection fear, especially in pediatric populations, the local anesthesia technique can be combined with topical anesthesia. Topical (or surface) anesthesia is a reversible abolition of sensitivity in a small part of the body by external and localized administration of anesthetics in the form of creams, ointments, gels or sprays, usually on an area of skin or mucosa. The intensity of anesthesia is weak, but it is easy to administer and can reduce the pain caused by needle injections, having minimal side effects, and can therefore lead to improved behavior toward dental treatment ,12. The The anesthetics used for the topical technique have clear differences from those used for infiltration anesthesia: the molecules used for topical anesthesia must have a high permeability of the mucosa to increase the anesthetic effect, in order to block the more superficial free nerve terminals. For this same reason, vasoconstrictors are not added to topical anesthetic mixtures because they undermine this mucosal permeability. Additionally, topical anesthetic formulations typically have higher concentrations than injectables to promote diffusion after passing through the mucosa . As the There is a wide range of applications for topical anesthesia, such as before needle insertion, as mentioned above, simple extraction of primary tooth, placement of rubber-dam clamp or orthodontic bands and to inhibit of vomiting. For this reason, topical medications can be administered in different ways, through the use of sprays, gels, solutions, ointments and patches. For each application there is a preferable way of administration . Spray aThe aim of this study was to test a new topical anesthetic gel with a different formulation  to analyze the effectiveness in pain control and the presence of any side effects.The study’s research design was a randomized controlled clinical trial with children, aged 5–8 years, conducted from February 2020 to December 2021. A minimum sample size of 267 subjects was determined via the G*Power software program . At the beginning of the study, a total of 333 children were recruited, calculating possible losses due to the exclusion criteria. The protocol of the study was approved by the Research and Ethics Committee of the University of Naples Federico II (Prot. N. 23/2019).The operations were conducted in the Pediatric Dentistry Center in Sedation of Naples and supported by the UNESCO Chair in Health Education and Sustainable Development of ‘Federico II’ University of Naples between February and September 2022 by six pediatric dentist operators. All examiners were calibrated on pain recording at the UNESCO Chair of Naples and the kappa test revealed a final score of k = 0.90 (CI 95% 0.795–0.952).All patients had never undergone infiltrative anesthesia. We selected patients who needed treatment that required anesthesia, but without pain at the time of the first visit. Therefore, we excluded patients who presented inflammatory or infectious processes (such as irreversible pulpits or abscesses) at the time of the treatment. Among the exclusion criteria based on medical history, there was also a history of allergies, the presence of chronic pathologies and the use of medications (such as NSAIDs or corticosteroids) at the time of treatment. After exclusion, the final sample size was 300 children.A written informed consent, with an explanation of potential risks and benefits, was discussed and obtained from each parent of all eligible children who agreed to participate.Group A:  The injection site has dried out, and experimental strawberry-flavored topical anesthetic gel  was applied with a cotton pellet, using moderate pressure with rubbing circular motion for 30–45 s to a confined site and left for about 5 min, before local injection.Group B: .In this randomized clinical research, patients were divided into two groups, each of 150 patients, according to pre-anesthesia procedures :Each patient received an injection of LA solution  using a 27-gauge dental needle, as follows: the patient opened the mouth, and, using reassuring language, the patient’s lip was lifted keeping the tissue taut, the needle was inserted parallel to the long axis of the tooth at the level of the mandibular or maxillary fornix, the injection was carried out at a flow rate of 1 mL/min and, finally, the needle was gently removed.The effectiveness of pre-anesthesia methods on injection pain was assessed subjectively and objectively and then a judgment was asked of the children’s parents.Subjective assessment: The WBFRRS, or Wong-Baker Faces PRS  was used for subjective assessment . It is aObjective assessment: The FLACC  scale was used for objective assessment . The FLAPatients’ parents’ judgment: at the end of the procedures, parents, who remained in the same room as the child for the duration of the treatment session, were asked whether or not they were satisfied with the procedure and their answers were recorded.T test was used to evaluate the differences between groups, in terms of both pain scales ratings. The relationship between pain ratings and gender was evaluated with the Mann–Whitney U Test. The Chi-square test was used to compare the distribution of parents’ patient judgment. The significance level (α) was set to 0.05. Only patients with complete data on all analyzed variables were included in the analysis; those with incomplete data were excluded.Data obtained were statistically analyzed with Stata software . The Student’s The trial was completed with good compliance. No allergic reactions or side effects were observed.p > 0.05) in both the PRS and FLACC scales.Three hundred children—142 girls (47%) and 158 boys (53%)—aged between 5 and 8 years (6.37 ± 0.46) were included in this study. The relationship between pain ratings and gender has not been included in the tables, as the Mann Whitney U test showed that there are no statistically significant differences (p < 0.001) and FLACC (p < 0.001), showed statistically significant differences between the two groups  was lower than that of Group B (4.35 ± 2.60). More precisely, the number of “no hurt” ratings was lower in Group A than in Group B  and the number of “hurts worse” ratings was lower in Group A than in Group B  .Likewise, on the FLACC scale, the number of “no pain” ratings was higher in Group A than in Group B . In addition, the number of “severe pain” ratings was lower in the Group A than in Group B  . Thus, lp < 0.001). As shown in There was also a statistically significant difference in terms of parents’ patient judgment, according to the Chi-square test  in the literature have been inconsistent and have divergent results, Many providers are using those for periodontal and orthodontic procedures instead of traditional local anesthetic injections ,28,29,30In this study, the results presented in All these data are then confirmed in the satisfaction questionnaire delivered to the parents of the patients: the percentage of parents not satisfied with the procedure in the group with the experimental topical gel is only 17%, while in the group with exclusively infiltrative anesthesia the unsatisfied parents comprise as much as 60%. All these results occurred with the total absence of both local and systemic side effects in all patients to whom the experimental formulation was administered and, moreover, operators noted that the strawberry flavor made it particularly pleasant to use for children in group A.Pain management during the injection of local anesthetic is a fundamental step of treatment in a pediatric patient and, when it cannot be avoided, always represents a critical moment for dentists, as the outcome of the anesthesia will influence the relationship with the young patient, who, in the event of a positive outcome, will have greater confidence in subsequent therapeutic sessions.In this study we evaluated the use of a new formulation of topical anesthetic, using the main pain assessment scales as parameters. The data obtained proved to be satisfactory with excellent values in terms of the efficacy of the anesthetic in reducing pain, compared with the control group, and the total absence of side effects. Further studies will be needed, especially by comparing this formulation with others on the market  and with a placebo group, in order to validate its possible superiority over others and to show a dose-response effect, i.e., whether the 10%/10% gel worked better than the 2.5%/2.5% gel.The experimental anesthetic has proved very effective in its use as a topical gel both in the subjective scales and in the objective pain measurement scales, thus validating its use on the oral mucosa, for its pharmacological and psychological effect, in the total absence of both local and systemic side effects. Therefore, the use of a topical anesthetic should always be recommended before performing a local anesthetic injection in the pediatric population, to decrease discomfort and for optimal behavioral outcomes. Furthermore, the procedure led to a high level of parental satisfaction.


Previous To describe in depth the evolution of QoL, pain- and activity-related domains and questions for pediatric, adolescent, and adult patients with hemophilia B treated with rFIXFc prophylaxis.post hoc analysis of data from a series of clinical trials.A post hoc, long-term analysis assessed patient-reported outcomes (PROs) from the Kids B-LONG (NCT01440946: pediatric) and B-LONG (NCT01027364: adults and adolescents) parent studies and the B-YOND  extension study.This p ⩽ 0.01), as were the subdomains ‘physical health’ , ‘sports and leisure’ , ‘treatment’ , and ‘view of self’ . Thirty pediatric patients that started in the Kids B-LONG study were assessed, with a median (min–max) duration of follow-up of 36.7 (9.0–59.9) months. The high level of satisfaction demonstrated by the PROs at baseline was maintained.Ninety-two adult and adolescent patients that started in the B-LONG study were assessed, with a median (range) duration of follow-up of 58.9 (0.0–78.4) months. The Haem-A-QoL total score was significantly reduced from baseline by 4.45  that works properly, so they need to be given additional FIX to help their blood clot. Recombinant factor IX Fc fusion protein (rFIXFc), is an extended half-life  treatment for hemophilia B. People with hemophilia B can experience episodes of bleeding, which can result in other symptoms, including pain, difficulty participating in sport, and poor mental health. This study shows that regularly taking rFIXFc over approximately 5 years to prevent or treat bleeds could also help to make these other symptoms better. The majority of clinical bleeding episodes occur in the large mobile joints, and these hemarthroses can progress to synovial hypertrophy and irreversible joint damage. Hemarthrosis typically presents as acute pain and inflammation, due to distension of the joint capsule and functional disability, with repeated subacute episodes leading to hemophilic arthropathy with persistent pain in the joint during physical activity and, in some cases, at rest.Repeated bleeding episodes, along with prolonged bleeding after injury, are the hallmarks of hemophilia B. it is possible that coping strategies adopted by patients to deal with chronic pain may mask the full extent of the physical and mental burden. Furthermore, it has been shown that patients with severe hemophilia have poorer health-related quality of life (HRQoL) compared with the reference population. Measuring pain and quality of life (QoL) is subjective and personal, with patients describing hemophilia-associated pain as ‘intolerable, unbelievable and like being shot’. Patient-reported outcome (PRO) measures, such as Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL), European Quality of Life Five Dimension (EQ-5D-3L), the Hemophilia-specific Treatment Satisfaction Questionnaire (HEMO-SAT), and the Canadian Haemophilia Outcomes–Kids’ Life Assessment Tool (CHO-KLAT), can help to quantify treatment benefit from the patient perspective.While enduring and debilitating pain is well documented in patients with hemophilia, overall activity levels are lower than the healthy control population, despite advances in treatment allowing more patients to participate in physical activities. Indeed hemarthrosis is reduced and HRQoL improved by regular prophylaxis, regardless of age. Physical activity has the potential to improve pain and health status, reduce the risk of bleeding, and improve mental health.811 Therefore, early intervention is needed to prevent bleeding, promote physical activity, and improve general health. In support of this, prophylaxis initiated early in life has been associated with a reduction in bleeding and promotes psychosocial wellbeing and QoL. Moreover, a study of patients who did not initiate prophylaxis, at or before the age of 3, perceived that mental and physical health was poorer than the reference population. The current treatment goal is to relieve both physical and mental burden, resulting in living with a ‘hemophilia-free mind’.While physical activity is endorsed for patients with hemophilia,16 The safety and efficacy of rFIXFc was demonstrated in three phase III trials of previously treated pediatric  and adolescent/adult patients  with severe hemophilia B (defined as endogenous FIX ⩽2 IU/dl), with patients completing the studies eligible to participate in the B-YOND long-term extension study. The long-term safety and efficacy of rFIXFc was confirmed when patients from Kids B-LONG and B-LONG were followed, on average, for 4 or 5 years, respectively, in the extension trial .Recombinant factor IX Fc fusion protein (rFIXFc) is an extended half-life (EHL) factor IX (FIX) replacement therapy approved for the on-demand and prophylactic treatment of patients of all ages with hemophilia B.Post hoc analyses using data from the B-LONG trial for adults and adolescents highlighted improvements in both pain and physical activity  irrespective of their treatment regimen prior to receiving rFIXFc. Results from Haem-A-QoL demonstrated that patients reported meaningful improvements in ‘Total score’, and the subdomains ‘Physical health’ and ‘Sports and leisure’, which were maintained over 24 months in an interim assessment of BYOND.post hoc analysis of data from the Kids B-LONG, B-LONG, and BYOND studies. A range of PROs were used to describe in depth the evolution of QoL, pain- and activity-related domains and questions for pediatric, adolescent, and adult patients with hemophilia B treated with rFIXFc prophylaxis.This study presents a 1719 Briefly, in Kids B-LONG, previously treated (with any recombinant or plasma-derived FIX product) children [<12 years of age with ⩾50 prior exposure days (EDs) to FIX] with severe hemophilia B (defined as endogenous FIX ⩽2 IU/dl) were given prophylactic rFIXFc once weekly with a starting dose of 50–60 IU/kg, up to a maximum dose of 100 IU/kg and a maximum frequency of twice weekly. In B-LONG, previously treated adult and adolescent patients (⩾12 years of age with ⩾100 prior EDs to FIX) with severe hemophilia B were assigned to one of four treatment arms: weekly dose-adjusted rFIXFc prophylaxis (50 IU/kg starting dose), interval-adjusted rFIXFc prophylaxis (100 IU/kg every 10 days to start), on-demand treatment , or treatment as part of perioperative care.The study designs of Kids B-LONG, B-LONG, and B-YOND have been previously published. Patients received weekly prophylaxis (20–100 IU/kg every 7 days), individualized interval prophylaxis (100 IU/kg every 8–16 days or twice monthly), modified prophylaxis , or on-demand  treatment. Switching treatment regimen was permitted upon enrollment or any time during B-YOND at the investigator’s discretion to achieve the lowest effective dose resulting in an FIX trough level of 1–3 IU/dl along with dose adjustments to target trough levels up to 5 IU/dl (or >5 IU/dl for modified prophylaxis) if warranted by bleed history or activity level.The B-YOND study enrolled eligible subjects who completed either B-LONG or Kids B-LONG .19 PatPain, physical functioning and activity were assessed on an approximately 6-month basis by Haem-A-QoL  based on the validated performances of these questionnaires in different age groups, EQ-5D-3L , EQ-5DY , HEMO-SAT , and CHO-KLAT  or discontinued. While most patients continued through to B-YOND, not all patients did, and therefore the end of study could occur during either Kids B-LONG, B-LONG, or B-YOND. No values were recorded for EQ-5D-3L in adults and adolescents during the B-LONG study as this was not part of the protocol; therefore, the BYOND 6-month values were used as a baseline. The main analysis included patients who started weekly dose-adjusted or interval-adjusted rFIXFc prophylaxis (adults and adolescents only) and completed the Haem-A-QoL and EQ-5D-3L questionnaires in the adult and adolescent population; and HEMO-SAT, CHO-KLAT, and EQ-5DY in the pediatric population. The sensitivity analysis included all patients who started prophylaxis in Kids B-LONG or B-LONG and were followed until switch to modified prophylaxis .Descriptive analysis of categorical variables was reported using number of subjects and percentages; continuous variables were reported, mean, standard deviation, median, percentiles (25.00% and 75.00%), minimum, and maximum. Change over time was assessed by comparing individual patient values at each time point with their baseline level , as patient numbers changed during the course of the study. For categorical variables, paired McNemar tests were used (a continuity correction was applied when any of the cell counts were <). The Wilcoxon signed rank test was used for continuous variables. All data processing and analyses were to be performed using SAS software version 9.4 or higher  and RStudio Software version 4.0.4.1719 There was a fairly even split between adults and adolescents by previous treatment regimens prior to receiving rFIXFc, whereas all children were previously treated with prophylaxis (n = 92), 14 patients were excluded from the sensitivity analysis  due to switching to modified prophylaxis. In the pediatric population (n = 30), two patients were excluded from the sensitivity analysis  due to switching to modified prophylaxis.Patient demographics have been published previously.phylaxis . Ninety-n = 59; p ⩽ 0.01) at the end of study compared with the baseline. The mean (SD) reduction from baseline to end of study (which could refer to any time point during B-LONG or B-YOND) in the Haem-A-QoL subdomain ‘feeling’ was 4.26 ; in the subdomain ‘physical health’ was 9.1 ; in the subdomain ‘sports and leisure’ score was 11.25 ; in the subdomain ‘treatment’ was 2.69 ; and in the subdomain ‘view of self’ was 5.81  .Statistically significant and sustained improvements were observed in mean [standard deviation (SD)] Haem-A-QoL total score, with a reduction of 4.45 .No significant difference at any time point was shown for family planning, partnership, and sexuality and future . Significant improvements were observed in Haem-A-QoL items ‘I had to avoid sports like football’, ‘I had difficulty walking as far as I wanted to’, ‘It was painful for me to move’, ‘My swellings hurt’, and ‘I had pain in my joints’, but baseline to end of study were not significant . No significant improvements were observed in the Haem-A-QoL item ‘I didn’t have the freedom to travel where I wanted’ .Significant and sustained improvements were found in Haem-A-QoL items, ‘I had to avoid sports that I like because of my hemophilia’, ‘I played sports just as much as others’, ‘I was annoyed about the amount of time spent having the injections’ and ‘It was necessary for me to plan everything in advance’ , although there were no significant changes for ‘Factor injections were a bother for my son’ from the caregiver’s perspective. No significant results were observed in any other item, although for all items apart from ‘It bothered me that I couldn’t play the sports that I like’ and ‘It bothered my son that he couldn’t play the sports that he likes’, initial satisfaction levels at baseline were high .usual activities and 16.00% of patients reporting ‘some or severe problems’ with pain/discomfort.The percentage of pediatric patients directly reporting having no problem with pain/discomfort or usual activities was maintained over the course of the study, but no significant improvements were demonstrated. The proportion of patients with no problems at baseline was high , with onpost hoc analysis of Kids B-LONG, B-LONG, and B-YOND data, PROs assessing QoL measures of pain and physical activity demonstrated at least a maintenance of baseline scores and, in some incidences, a significant and sustained improvement over approximately 5 years. In the pivotal studies upon which this post hoc analysis is based, bleeding rates were reduced from the levels recorded prior to the parent study,18 and remained low in the study extension. Given the well-documented link between bleeding and pain, the results of this study were expected and add to the already published data that demonstrate the ability of rFIXFc to improve HRQoL, with reduced dosing frequency and a good tolerance profile.1723In this  and the interim analysis of the BYOND study. There is a paucity of data on the impact of prophylaxis with EHL FIX products on HRQoL in patients with hemophilia B, making it difficult to ratify these results against previous studies. As the emphasis shifts away from focusing solely on bleed prevention toward a more holistic approach for treating hemophilia B, the impact of successful treatment on HRQoL will be revealed.Haem-A-QoL improvements in adults and adolescents were maintained over time for the total score and the domains sports and leisure, physical health, feeling, and view of self; confirming both the results from the initial B-LONG study,There was consistent improvement and maintained benefit of prophylaxis with rFIXFc in adults and adolescents on the Haem-A-QoL items relating to pain and activities . An increase over time was observed in the proportion of adult and adolescent patients never/rarely/seldom reporting difficulties walking as far as they wanted, pain in their joints, pain when moving, painful swellings, and avoidance of sport.The lack of adult and adolescent EQ-5D-3L results from B-LONG meant that any initial improvements from rFIXFc prophylaxis in the first 18 months were not captured, preventing any analysis of change from baseline. However, the EQ-5D-3L results for adults and adolescents showed that the proportion of patients reporting pain/discomfort and problems with usual activities was sustained over time from B-YOND month 6 to B-YOND end of study (data not shown). Similarly, the EQ-5D-3L results for pediatric patients showed minimal change from baseline to end of study, reflecting the maintenance of the relatively high baseline scores. The low number of pediatric patients reporting problems at baseline resulted in a ceiling effect, limiting that variability of the results, and leaving little room for improvement.post hoc analysis suggest that there is a general improvement in levels of pain and physical activity upon initiating prophylactic treatment with rFIXFc, which is maintained, with long-term improvements observed in patient esteem and satisfaction. Therefore, successful, long-term, prophylactic treatment of patients with hemophilia B may well be pivotal in the goal of ‘living with a hemophilia-free mind’.The results of this 26 This is unsurprising given that the progression of joint damage, and therefore the subsequent joint pain, can be delayed but not halted. Further research is needed to understand the association between declining HRQoL and age of patients.In pediatric patients treated with rFIXFc prophylaxis, high satisfaction levels were maintained, with improvements seen relating to factor injections from both the caregiver (HEMO-SAT) and child’s (CHO-KLAT) viewpoint. The lack of significant improvement may be a result of the ceiling effect, or it could be attributed to age, as pain has a tendency to increase and QoL has a tendency to decrease in the adult population compared with the pediatric population.This study had limitations, including the lack of a comparator and the decline in patient numbers over time, primarily throughout B-YOND due to the planned end of study upon rFIXFc becoming commercially available, which was at different timepoints in the participating countries. In addition, the high baseline scores and small sample size for pediatric patients limited the conclusions that could be drawn. There are also limitations related to the use of PROs and the validity of grouping reporting levels. Assessing pain and physical activity with PROs, where responses are subjective and are not set against an objective baseline, limits the ability to draw absolute conclusions. In addition, the averaging of whole integers results in numerical scores that cannot distinguish between a patient who always has a problem on one item and a patient who occasionally has problems across many items, limiting the potential to analyze individual domains from a patient’s overall scores.Long-term rFIXFc prophylaxis reduces perceived pain and increases levels of physical activity in adult and adolescent patients with hemophilia B and maintains high QoL scores in pediatric patients. The analyses of subdomains within PRO instruments highlight the relevance of pain and physical health  as the concepts most sensitive to change with prophylaxis treatment and indicate the potential for improving long-term QoL in patients with hemophilia B.Click here for additional data file.Supplemental material, sj-docx-1-tah-10.1177_20406207231170701 for Recombinant factor IX Fc prophylaxis reduces pain and increases levels of physical activity, with sustained, long-term improvements in patients with hemophilia B: post hoc analysis of phase III trials using patient-reported outcomes by Jan Astermark, Cédric Hermans, Monia Ezzalfani, Alaeddine Sidhom, Sylvaine Barbier, Nana Kragh, Aletta Falk and Daniel Eriksson in Therapeutic Advances in Hematology


Data indicates that clinicians might be under-prescribing opioids for patients with chronic cancer pain, and this could impact adequate chronic pain management. Few studies have sought to understand healthcare provider (HCP) perceptions and practices regarding the prescription of opioids for chronic pain. We assessed HCP perceptions and practices regarding opioid prescription for patients with chronic pain since the onset of the COVID-19 pandemic.An anonymous cross-sectional survey was conducted among 186 HCPs who attended an opioid educational event in April 2021 and 2022.61/143(44%) opioid prescribers reported reluctance to prescribe opioids for chronic pain. In a multivariate logistic model, younger participants  and pain medicine clinicians  were less reluctant, whereas providers who worry about non-medical opioid use (NMOU) were more reluctant to prescribe opioids . 53/143(37%) respondents had experienced increased challenges regarding opioid dispensing at pharmacies, and 84/179(47%) reported similar experience by their patients. 54/178(30%) HCPs were aware of opioid-related harmful incidents to patients or their families, including incidents attributed to opioid misuse by a household or family member.A significant number of opioid prescribers were reluctant to prescribe opioids for patients with chronic pain. Many reported challenges regarding dispensing of opioids at the pharmacies. These may be unintended consequences of policies to address the opioid crisis. Future measures should focus on addressing regulatory barriers without undermining the gains already made to combat the opioid crisis. Prescription opioids remain the cornerstone of cancer pain management. RegrettaA careful balance of the judicious use of opioids with their risk for non-medical use among patients with chronic pain is therefore critically needed. It starts by gaining a broad understanding of provider perceptions and practices related to opioid prescriptions, especially after the onset of the COVID-19 pandemic. However, this has not been sufficiently examined in literature. The main objective of our study was to assess the reluctance among healthcare providers to prescribe opioids to patients with chronic pain since the onset of the COVID-19 pandemic. We also assessed other opioid prescribing practices and perceptions among healthcare providers.This was an anonymous cross-sectional survey conducted among healthcare providers who attended the Interdisciplinary Pain and Opioid Crisis Seminar, a one-and-a-half-day educational event organized annually by the Department of Palliative, Rehabilitation and Integrative Medicine at the University of Texas MD Anderson Cancer Center in April 2021 and 2022. Event attendees were health care providers who prescribed opioids , administered opioids , or were involved with patients on opioids .Eligible participants were seminar attendees who could understand, read, write, or speak English, and were willing to participate in the survey. Participants received an email on the eve of the event asking them to complete an anonymous web-based survey. Those who were unable to complete the survey received daily email reminders up to 3 days after the end of the meeting. Participants were informed that survey participation was voluntary. The web-based survey was developed using Qualtrics and consisted of a questionnaire developed by the study investigators.Opioid Prescribing Survey (APPENDIX A) was developed by study investigators  after a thorough review of previous studies that assessed healthcare providers’ beliefs and attitudes towards opioid prescribing for patients with chronic pain.[The nic pain.–15 This nic pain., 15 and nic pain. The survWe calculated the percentage of responders who selected ‘agree’ or ‘strongly agree’  along with a 95% confidence interval. With an estimated 200 responses to each question, the confidence intervals were expected to be no wider than 14% (4 * sqrt (0.5*0.5/200)). Descriptive statistics such as frequency and percentage for categorical data, and median with interquartile range (IQR) for continuous variables, were used to summarize the participants’ survey responses. Chi-squared test was used to assess the association between categorical variables. Logistic regression was fit using participant characteristics  as independent variables and the primary outcome of interest (providers’ reluctance to prescribe opioids) as the dependent variable. Independent variables with coefficient q-value  less than 0.1 were considered of interest. P-values less than 0.05 were considered statistically significant. The data were analyzed with R version 4.1.1.Overall, 207 of 387 (54%) survey recipients completed the survey. Twenty-one non-US respondents were excluded from the analysis because they were from countries with limited experience and exposure to issues related to prescription opioids and were likely to have varied views that might not be applicable in the US. One hundred and eighty-six participants were therefore included in the analysis. Participants’ demographic and clinical characteristics are summarized in Akaike Information Criteria (AIC) was used to select the best multivariate logistic regression model to associate provider demographic variables and prompt responses with reluctance to prescribe opioids. In this study, a significant number of opioid prescribers felt comfortable prescribing opioids but were increasingly worried about NMOU in their patients, and many felt reluctant to prescribe opioids for chronic pain since the onset of COVID-19 pandemic. Healthcare providers are understandably cautious about prescribing opioids for their patients due to several reasons. Prescription opioids are noted to play a major role in the opioid crisis, which was exacerbated by the COVID-19 pandemic., 6, 16 ROne strategy to increase provider confidence and willingness to prescribe opioids for patients with chronic pain is to increase interdisciplinary clinical support for prescribers. Studies have shown that clinicians perceive caring for patients with NMOU behavior as stressful and time consuming., 26 ThisParticipants were generally more concerned about their patients’ mental health since the onset of the COVID-19 pandemic. Theis is probably because the pandemic led to increased rates of depression and anxiety which are common co-occurring conditions among patients at risk for opioid use disorder., 30 DataA significant number of survey respondents recounted their patients’ increased difficulties with filling their opioid prescriptions as well as their own challenges working with pharmacies to dispense opioid prescriptions. This may be another undesirable consequence of measures implemented to address the opioid crisis. Recently, there has been an increase in the number of state and insurance limitatiTramadol was the most prescribed opioid among survey respondents. This is consistent with prior research which found that tramadol is increasingly being prescribed for patients with chronic cancer pain after hydrocodone was reclassified as a scheduled II opioid in October 2014. Perhaps,A significant number of participants reported opioid-related harmful incidents in their patients that were attributed to opioid misuse by a household or family member. This important finding illustrates the fact that the risk related to NMOU transcends the individual to affect those around them. Clinicians should therefore be aware of the potential broader repercussions with unsafe prescribing practices. Family members and caregivers caring for patients with chronic cancer pain may have increased access and exposure to substantial amounts of opioids. Over half of the 3.8 million Americans who misuse prescription opioids obtain the medication from a friend or relative. This furOne limitation of our study is that participants were recruited from a single opioid educational event. The findings may therefore not be generalizable to other participants in different settings. Second, details of the reasons why participants were reluctant to prescribe opioids was not captured in real time. Future studies should aim at specifically obtaining such important information directly from participants since this will be critical in increasing understanding of provider challenges with opioid prescriptions. Third, the study findings were based on participant self-report which might not necessarily represent the actual opioid prescribing practices of the study participants.Healthcare providers were frequently comfortable prescribing opioids for chronic pain but reluctant to do so. Many reported frequent challenges that they and their patients faced when filling opioid prescriptions at the pharmacies. Tramadol, a weak opioid with notable side effect profile, was the most prescribed opioid among prescribing participants. These findings might be unintended consequences of policies implemented to combat the opioid crisis. Future studies should therefore focus on strategies to reduce barriers to effective opioid pain management without undermining the progress that has been made thus far to mitigate NMOU and combat the opioid overdose crisis.