The relationship tested was statistically significant (p < 0.001), and the strength of the relationship was high (rc = 0.695). The average level of low back pain among PwMS was 4.7 out of 10 on the VAS. The prevalence of LBP was higher in female patients (p < 0.001), patients with a secondary progressive form of MS (p < 0.001), and patients with a longer duration of disease (p < 0.05). The most widely used methods for treating LBP were kinesitherapy and manual therapy. Conclusions: LBP is common in patients with multiple sclerosis. Female sex, a secondary progressive form of MS, and a longer duration of disease increase the risk of LBP. It is important to implement properly planned physiotherapy activities and educate patients on how to combat LBP.Background: The purpose of this study was to evaluate the intensity and frequency of low back pain (LBP) in people with multiple sclerosis (PwMS) and patients’ knowledge of physiotherapeutic methods for combating LBP. Methods: This study included all MS patients attending consecutive follow-up visits for treatment related to MS between March and May 2023. Only current pain sensations in the lumbar spine were taken into account. The inclusion criteria were age 18–60 years, a definite diagnosis of MS according to the 2017 McDonald criteria, treatment with disease-modifying drugs (DMTs), and consent to participate in the study. This study was carried out using an original survey questionnaire and a Visual Analogue Scale. PwMS were divided into three age groups: 18–30 years, 31–50 years, and over 50 years. Results: Ninety PwMS (68 women and 22 men) were included in the study. The mean duration of the disease was 9.5 ± 4.9 years, and the mean EDSS was 3.5 ± 1.6. Most patients had a relapsing-remitting form of the disease. Overall, 68.9% of PwMS felt low back pain ( Spinal pain  is a term that describes a feeling of pain along the spine and paraspinal muscles that is either chronic (long-term occurrence for 3 months) or acute . It is one of the most common disorders of the musculoskeletal system in adults, and more than three quarters of the global population suffers from this disorder or will suffer from this disorder at least once in their lives. According to available epidemiological data, approximately 90% of cases involve pain of unknown etiology, and the potential hypothesis is largely related to overload, for example, heavy physical work, other comorbidities, a sedentary lifestyle, psychosocial disorders, or obesity. The problem can affect any of the five sections of the spine, but the vast majority of patients report problems in the lumbar-sacral and cervical areas. Furthermore, spinal disorders can be related to a lack of physical activity during the day , a sedentary lifestyle, and remote work, all of which significantly contribute to progressive pain ,2,3.Low back pain (LBP) is a multifactorial global disease and one of the three most common causes of disability in Poland (just after ischemic heart disease and stroke). According to data in 2017, a problem in the lower spine was reported in approximately 7.5% of the global population (approximately 577 million people) . This heA crucial issue worth mentioning in the context of low back pain is the number of hospitalizations due to this health problem. Hospitalizations are prevalent in women in retirement (over 60 years of age) and in men before retirement (below 65 years of age). Furthermore, in recent years, there has been an increase in hospitalizations due to lumbar spine pain among rural residents, both among women and men. The reasons for this phenomenon can be related to difficult working conditions  or socioeconomic conditions . The hospitalization rate for LBP in Poland is the lowest in Europe, but it should be noted that the average hospitalization time is statistically longer than in other European and non-European countries. The early implementation of physical therapy and preventive methods is important for the continued functioning of patients. A big problem in Poland is the lack of public health education and knowledge on how to counteract spine pain. It is estimated that half of the population with this health problem decides to seek the help of a specialist only when pain significantly prevents them from functioning in professional and/or social environments .Multiple sclerosis is a progressive and inflammatory demyelinating disease of the nervous system that affects a large number of young people, regardless of location (both in developed and developing countries), making it a global disease to a large extent .The cause of its occurrence is still unclear, but the analyzed literature indicates that great diversity and the influence of external factors contribute to the development of the disease. Currently, the number of people suffering from multiple sclerosis in the world is approximately 2.8 million, with an average incidence of 35.9 cases per 100,000 inhabitants. However, the highest incidence is recorded in European areas . The most common information about multiple sclerosis is that this disease occurs more often in women (2:1) than in men. Patients with multiple sclerosis more often learn about their disease between the ages of 25 and 35 (average age of diagnosis is 32), and a diagnosis is associated with numerous changes in patients’ lives .Among the numerous symptoms and ailments, PwMS often complain of various types of pain. The frequency of different types of pain is estimated to range widely from 29 to 86% . The mosThe purpose of this study was to evaluate the intensity and frequency of low back pain in patients with multiple sclerosis and to evaluate the knowledge of patients about physiotherapeutic methods for combating LBP.(1)0—without pain;(2)1–3—mild pain;(3)4–7—moderate pain;(4)8–9—severe pain;(5)10—unbearable pain .This study included all MS patients attending consecutive follow-up visits related to DMT (disease-modifying therapy) between March and May 2023. Each patient had a definite diagnosis of MS according to the 2017 McDonald criteria . All patUsing a self-administered questionnaire prepared for this study, information regarding the basic personal data and the current situation of the patients , information about their disease , and their knowledge about the methods of physiotherapy were collected.The inclusion criteria included age 18–60 years, a definite diagnosis of multiple sclerosis according to the 2017 McDonald criteria, treatment with disease-modifying drugs (DMTs), and consent to participate in the study. The exclusion criteria of this study were age under 18 and over 60, a traffic accident within the last year, active cancer, and other serious additional diseases causing pain or requiring surgery of the lumbar spine. In addition, people were excluded from the study if they did not consent to participate, withdrew from the study, reported a deterioration of their health, or reported that unexpected accidents occurred.Participants gave written informed consent to participate in the study, which was free and voluntary. They were informed why their consent was needed, and each stage of the study was explained. Each participant was informed about how this scientific study would be conducted and about the precautions that would be taken throughout. All participants were informed that they could stop the study at any time. Each participant obligatorily agreed to the use and analysis of anonymous data collected for this study. The researchers associated with this study had access to the research data. All research documentation containing personal data was protected. Each participant whose data were entered into the system was given a unique number, making it impossible to identify them. Participants also gave written consent to the publication of the research results in the form of a scientific article. This study was carried out according to the Declaration of Helsinki and in accordance with the applicable law in the Republic of Poland. The Ethics Committee did not require patient consent because this study was a pilot study, not a medical experiment. For this reason, we did not seek the approval of the Commission.t-test was applied since the groups were of similar sizes. To verify the secondary hypotheses, the same method was applied for the comparison of quantitative variables  between the groups, and a contingency table analysis with chi-square analysis was performed to compare the groups in terms of nominal and ordinal variables . The magnitude and clinical relevance of the scores were evaluated based on effect size statistics. According to Cohen’s benchmarks, a value of 0 to 0.20 denotes a negligible effect size, a value of 0.21 to 0.5 denotes a small effect size, a value of 0.51 to 0.80 denotes a medium effect size, and a value > 0.80 denotes a large effect size.Statistical description techniques and the Shapiro–Wilk test of normality were applied for descriptions of the groups and the variables. The main research hypothesis was tested by comparing the average results of the two groups. The parametric Student’s www.statsoft.pl), and p-values < 0.05 were considered statistically significant.All statistical analyses were performed using the STATISTICA 13.3PL software , with a smaller group of people living in rural areas . For both women  and men , the most common place of residence was urban areas. Rural areas were inhabited by 22.1% (n = 15) of the women and 22.7% (n = 5) of the men. When asked about education, most respondents declared that they had completed secondary school  and higher education . The demographic and clinical data are presented in This study involved 90 people with multiple sclerosis aged 18 to 60 years (mean age 42.4 ± 12.6). The mean duration of disease was 9.5 ± 4.9 years, and the mean EDSS was 3.5 ± 1.6. Overall, 74.4% of the patients had a relapsing-remitting form, and 17.8% had a secondary progressive form. The respondents were divided into three age groups: 18–30 years old , 31–50 years old , and over 50 years old . The vast majority of the group was women , with a smaller group of men . Most of the respondents lived in small or large cities (n = 62), while no problem was observed in 31.1% of the patients (n = 28). Significant differences were found depending on the gender of the respondents. Pain in the lumbar spine was reported more frequently by women  than by men . A total of 17.7% (n = 12) of women and 72.7% (n = 16) of men did not report this health problem. The relationship tested was statistically significant , and the strength of the relationship was high (rc = 0.695). The prevalence of low back pain was higher in patients with a secondary progressive form (p < 0.001) and a longer duration of disease (p < 0.05).Most of the patients who participated in this study reported pain in the lumbar spine. LBP was felt by 68.9% of the patients (p < 0.001), secondary progressive form of MS (p < 0.001), female sex (p < 0.001), and LBP, with effect sizes in the range of 0.66–1.12 for Cohen’s values. Significant relationships between disease duration (p = 0.023) and EDSS score (p = 0.015) and LBP were also observed, while no significant associations were found between male sex, relapsing-remitting MS, and primary progressive MS. Detailed results are presented in The results of this study showed significant associations between age , more than 31.11% (n = 28) of the patients reported no recent pain in the lumbar spine. Mild and very severe pain were reported by the same number of patients . Moderate pain was recorded in 26.67% of the patients (n = 24), and the most severe pain, preventing daily functioning and professional work, was recorded in 6.67% of the patients (n = 6). Significant differences in the intensity of lumbar spine pain were found across the sex groups. Women  reported lumbar spine pain (from 1 to 10 on the VAS) much more frequently than men . Pain was not observed in 17.65% of the women (n = 12) and 72.73% of the men (n = 16). Women most frequently reported pain of moderate intensity  and mild intensity . Very severe pain and the most intense pain affected 19.12% (n = 13) and 7.35% (n = 5.56%) of the women, respectively. Men most often reported severe pain , and mild, moderate, and very severe pain was observed in only one man . The average level of low back pain among these MS patients was 4.7 out of 10 on the VAS. The relationship tested was statistically significant , and the strength of the relationship was medium (rc = 0.466). Detailed results are presented in In the entire study group . A total of 65.55% of patients with multiple sclerosis believed that the best and most effective physiotherapeutic treatment for lumbar spine pain is manual therapy. Kinesiotherapy also ranked very high, with a score of 66.33%. Much less frequently, the respondents mentioned deep tissue massage (30.00%), trigger-point therapy (26.67%), and kinesiotaping (24.44%). The respondents considered ultrasound treatment (2.22%) and heat therapy (8.89%) to be the least effective methods to combat lumbar spine pain. Electrotherapy (16.68%) and laser therapy (12.22%) also had low values. Concerning the use of physiotherapeutic treatments for lumbar spine pain, the respondents had most often used kinesitherapy (71.11%), manual therapy (46.67%), electrotherapy (43.33%), or laser therapy (36.67) at least once. The methods that were chosen least frequently were trigger-point therapy (10.00%), kinesiotaping (14.44%), and deep tissue massage (16.67%). The least frequently chosen physical treatments were ultrasound treatment (12.22%) and heat therapy (13.33%). The results are presented in Lower back disorders are a civilized and global problem that affects the vast majority of the population at least once in their life, regardless of sex or age. Differences in the appearance of this health problem are evident, especially among professionally active people, and may be related to a sedentary lifestyle or a lack of physical activity in daily life . The maiWhen it comes to the presence of pain in patients with multiple sclerosis, scientific studies and clinical reports often show an inconsistent picture. Pain is often neuropathic and may affect more than 80% of patients, especially in the form of pain in the upper and/or lower limbs, neuralgia, spinal pain syndromes , or headaches . A revieIn previous studies, the average age of patients with multiple sclerosis participating in studies related to lumbar spine pain ranged from 30.4 years to as much as 54.9 years ,23,24,25p < 0.001) and a longer duration of disease (p < 0.05). The differences between the groups may be due to different conditions, as identified in the Bento et al. study. Low back pain has been associated with older age, low levels of education, hypertension, and smoking in men. However, occupational and ergonomic factors are a more common cause of pain in women [The examination of lumbar spine pain was carried out using various methods and tools. Authors and researchers most often used numerical scales, questionnaires, and proprietary questionnaires to assess lumbar spine pain in people with multiple sclerosis. A Visual Analogue Scale was used in this study, as used by the authors of the abovementioned studies ,26,28. Iin women . Howeverin women . Sociodein women , as wellin women . Sleep din women .Most guidelines for the treatment of low back pain recommend maintaining physical activity and selecting the parameters, duration, and type of exercise depending on patients’ functional status ,35. The In the treatment of patients with LBP, it is recommended to use techniques from the field of manual therapy, in particular manipulation , mobilizDespite the use of numerous physiotherapeutic treatments, it is worth mentioning treatments that are not recommended in the case of low back pain. It is not recommended to use stabilizing belts and corsets ,45,46, fThe interdisciplinary rehabilitation process should include cognitive behavioral therapy  and be sAn in-depth analysis of the available scientific literature allowed us to find information on physiotherapeutic methods used for treating low back pain in people with multiple sclerosis. The Al-Smaidi study involved 15 people who were divided into three groups and underwent appropriate therapy with the use of TENS currents. The first group consisted of people who received low-frequency TENS currents , the second group consisted of people who received high-frequency TENS currents , and the third group (control) did not receive electrotherapeutic stimuli. These patients were treated for a maximum of 10 weeks, and the frequency of treatments was twice a week for 45 min. Test scores were measured using the Roland Morris Disability Questionnaire, Short Form-36, the McGill Questionnaire, and a Visual Analog Scale. The researchers concluded that the use of TENS currents was effective in the treatment groups when compared to the control group, particularly in reducing VAS scores. However, despite this novel approach, the results were statistically insignificant . The aboThe high incidence of pain reduction indicates the importance of regular physiotherapeutic treatments . ImportaIn our study, the main limitations were the small size of the study group and the lack of a control group. This study also had a limited time frame, and not all patients agreed to participate in it. These were only patients taking DMTs, while some untreated patients were not included in the study. The inclusion criterion of age up to 60 years also excluded several patients from the study. The conditions of some people did not allow them to participate in the study. Moreover, people with lumbar spine injuries had to be excluded from the study, which made it impossible to collect a sufficiently large sample size . Moreover, the assessment of pain was limited only to a VAS; other more extensive scales, such as the Self-Complete of Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS), the McGill–Melzack Questionnaire, the Brief Pain Inventory (Short Form), the Oswestry Disability Index (ODI), the painDETECT, the Quebec Back Pain Disability Scale, the Roland–Morris Disability Questionnaire, and the Laitinen Scale, could provide a broader view of the nature of LBP. This study focused on estimating the incidence of LBP in MS patients, ignoring the aspects of the impact of pain on quality of life. This topic, according to the authors, exceeded the scope of this publication, and it was decided that it would be the subject of another report.According to population-based studies, the annual incidence of a first episode of LBP ranges from 6.3% to 15.4%, while the cumulative incidence of a first or any episode ranges from 1.5% to 36% . Multipl


Chronic back pain (CBP) constitutes one of the most common complaints in primary care and a leading cause of disability worldwide. CBP may be of mechanical or inflammatory character and may lead to functional impairment and reduced quality of life. In this study, we aimed to assess and compare burden of disease, functional capacity, quality of life and depressive symptoms in axial spondyloarthritis (axSpA) patients with orthopedic chronic back pain patients (OBP). We further aimed to identify factors associated with quality of life.Cross-sectional survey of a cohort of 300 CBP patients including 150 patients from a University Hospital Orthopedic Back Pain Outpatient Clinic with OBP and 150 patients with confirmed axSpA from a University Hospital Rheumatology Outpatient Clinic. Questionnaire-based assessment of pain character , functional status , quality of life (WHOQOL-Bref) and depressive symptoms (Phq9) and retrospective medical chart analysis.p < 0.001). In a multivariate regression model, depressive symptoms, mechanical back pain, pain level and age were negative predictors of subjective quality of life, whereas functional capacity was a positive predictor.Both, OBP and axSpA patients reported on average intermediate pain levels of mostly mixed pain character. Both groups demonstrated a reduced health-related quality of life and the presence of depressive symptoms. However, axSpA patients reported a significantly better subjective quality of life, more satisfaction with their health status and better functional capacity compared to OBP patients (all Chronic back pain was associated with a high morbidity and reduced quality of life regardless of pain character. We identified multiple factors associated with reduced quality of life. Awareness and addressing of these factors may help to overcome unmet needs and improve quality of life for these patients. LifetimRegarding pain character, back pain can be broadly categorized as mechanical, inflammatory or referred back pain. Mechanical back pain is responsible for approximately 97% of chronic back pain cases, while non-mechanical causes include rheumatic diseases, vascular or malignant causes or infections . MechaniChronic back pain may have a major impact on health-related quality of life (QoL) . Among oWithin this study, we aimed to assess the pain character, burden of disease, functional status, QoL, symptoms of depression and sex differences in a cohort of 300 back pain patients including 150 patients with orthopedic back pain (OBP) causes and 150 patients with axSpA and identify factors associated with QoL.2.2.1.For this cross-sectional study, a total of 300 chronic back pain patients were recruited, including 150 patients from the from the Orthopedics outpatient clinic and 150 patients from the Rheumatology outpatient clinic of the University Medical Center Freiburg, Freiburg, Germany. Consecutive patients presenting to the Rheumatology outpatient clinic with axSpA, respectively all patients presenting to the Orthopedic Outpatient clinic due to chronic back pain were asked to participate in the study. AxSpA patients had to fulfil the modified New York (mNY) or Assessment of Spondyloarthritis International Society (ASAS) criteria. OBP patients needed to suffer from back pain for at least 6 weeks. Specific diagnoses of OBP patients are listed in section 3.1. This study was conducted under the ethics protocol 37/17 of the ethics committee of the University of Freiburg, Germany. Patients gave their consent according to International Conference on Harmonization Good Clinical Practice (ICH GCP) guidelines. The results section of this manuscript comprises a detailed description of the patient cohort.2.2.2.2.1.Pain intensity was assessed on a visual analogue scale of 0-100 mm, representing a continuum between “no pain” and “worst imaginable pain.”To screen for symptoms of inflammatory back pain, the Inflammatory Back Pain questionnaire consisting of 5 items was used . The queTo further characterize lower back pain, the Mechanical and Inflammatory Low Back Pain Scale  was employed . The MAIpain and gives a maximum score of 13 points. Scoring was conducted according to the instructions provided by Riksman et al. Mean scores of Part A and Part B were used as cut-offs. Patients with greater than mean scores in one and less than mean in the other subscale were classified as purely inflammatory or purely mechanical back pain. All other patients were classified as having “mixed” back pain.Disease activity was furthermore measured with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) , which c2.2.2.Functional capacity was assessed with the help of Bath Ankylosing Spondylitis Functional Index (BASFI), which constitutes a validated instrument for the assessment of functional status and impairment in axSpA patients . The BASFurthermore, functional capacity in everyday life was additionally assessed employing the Functional Questionnaire Hannover , which constitutes a tool developed in Germany to assess functional capacity in patients with rheumatic diseases or other joint problems . The FFb2.2.3.To assess QoL, the WHO-QOL-Bref questionnaire was used , which constitutes a validated and well-established instrument for the assessment of subjective QoL . The que2.2.4.Depressive symptoms were assessed with the Patient Health Questionnaire 9 (Phq9), which comprises 9 items to screen for depression . Symptom2.3.In addition, retrospective medical chart analysis was performed to confirm the diagnosis, collect data on current or recommended therapies as well as disease duration for OBP and axSpA patients. Furthermore, demographic data on sex, age, height, body weight, body mass index (BMI), smoking status as well as highest educational degree  were collected.2.4.t-test was used for normally distributed variables and Welch’s t-test for variables with unequal variance.Descriptive statistics such as percentages, mean and standard variation were employed to depict demographic variables and disease characteristics. Chi-square test was used to compare categorical variables. For continuous variables, Student’s p < 0.05.Multivariate linear regression was employed to predict factors independently associated with subjective QoL. Models were constructed by stepwise backwards elimination. The statistical level of significance was set at Jamovi. (Version 2.3) [Computer Software], retrieved from)Statistical analyses were performed using GraphPad Prism software version 9.5.1 for Mac, GraphPad Software, San Diego, California United States”3.3.1.n = 150) patients had degenerative disc disease/spinal disc herniation (n = 39), sacroiliac joint syndrome (n = 19), vertebral fractures (n = 17), spinal stenosis (n = 16), facet syndrome/osteoarthritis (n = 15), cervical syndrome/thoracic spine syndrome/lumbar syndrome (n = 14), postoperative complaints after spinal surgery (n = 13), spondylolisthesis (n = 7), scoliosis (n = 5) and spondylitis/spondylodiscitis (n = 5).A total of 300 patients with back pain were surveyed, including 150 patients consulting the orthopedic outpatient clinic due to back pain and 150 patients with confirmed axSpA from the rheumatology outpatient clinic. In the OBP cohort (n = 150), axial involvement was present in 100% of patients, peripheral arthritis in 42%, enthesitis in 26% and dactylitis in 6.7% of patients. History of uveitis/eye involvement occurred in 20.7%, psoriasis in 19.5% and inflammatory bowel disease in 5.3% of patients. HLA B27 positivity was confirmed in 74.3% of patients and 29.5% had a positive family history. Mean disease duration was 10.9 years .In the axSpA cohort .Out of the 300 surveyed patients, 57.3% were male  and 42.7% female . Mean age of axSpA patients was 48.99 years  compared to 56.74 years  in the OBP group (p = 0.018).Regarding the highest educational degree, 59.9% of the patients interviewed had a lower or intermediate secondary school-leaving qualification . A polytechnic entrance qualification or high school diploma were reported as the highest educational degree by 15.4% of the patients . In total, 21.6% had a polytechnic or university degree or were postgraduated  whereas 3.5% of the patients had no school-leaving qualification . Overall, the SpA patients thus possessed a slightly higher level of education than the OBP patients , 18.4% a conventional synthetic (cs)DMARD and 15.0% NSAIDs while 12.9% did not receive any therapy. In the OBP group, 22.7% underwent surgery for their back problems and 16% received an injection therapy of facet or SI joints. Physiotherapy and analgesics were recommended in 52 and 5.3% received orthopedic aids . Further investigations or no specific therapy were recommended in 4% of patients.3.2.p = 0.051, see p < 0.001). Morning stiffness did not differ significantly between both groups . Awakening due to back pain was frequent in both subgroups . Improvement with exercise was significantly more common in the axSpA cohort , whereas the OBP patients significantly more often reported continuous pain . In the cohorts of OBP and axSpA 75.0 and 80.3% of patients reported an improvement on NSAID treatment (p = 0.312), respectively.Regarding their current pain intensity, both the OBP and the axSpA cohorts reported on average moderate pain levels. Pain intensity was slightly higher in the OBP group, marginally missing level of significance . However, 47.3% of OBP patients reached three or more points, suspicious of spondyloarthritis . In the BASDAI, the OBP patients averaged 4.37 points, compared to 3.66 points in the axSpA patients (p = 0.013).On the Inflammatory Back Pain questionnaire, the OBP patients scored an average of 2.42 points compared to 3.23 points in the axSpA cohort (p = 0.469). In Part B, which relates to mechanical back pain, the OBP cohort averaged 7.38 points out of a possible 13 points, compared to a mean of 5.68 points in the axSpA cohort (p < 0.001). According to the analysis after Riksman et al. (p = 0.023).To further differentiate inflammatory and mechanical lower back pain, the MAIL-Scale questionnaire was used. In Part A, which assesses characteristics of inflammatory low back pain, OBP patients scored an average of 6.87 points whereas axSpA patients scored 6.53 out of a possible 16 points (p < 0.001). 35.7% of the OBP and 15.4% of SpA patients had a clinically relevant functional impairment . OBP patients scored an average of 3.88 in the BASFI compared to 2.95 points in the axSpA cohort (p = 0.002).Regarding functional capacity, the OBP cohort reached on average 69.7% in the FFbH, measuring functional capacity in everyday life, compared to 80.8% in the axSpA cohort , see also p < 0.001, norm 70.6 points). Also in the environment domain the OBP patients scored significantly lower than the axSpA patients (p < 0.001). Regarding social relationships, there were no significant differences between both groups . Satisfaction with health was significantly worse in the OBP cohort than in the axSpA cohort (p < 0.001).The WHOQOL-BREF questionnaire was used to assess QoL parameters in five domains: global, physical, psychological, social and environmental. Perceived QoL was rated significantly worse by OBP patients compared to axSpA patients (p = 0.006). Moderate to severe depressive symptoms could be detected in 42.9% of OBP, respectively 25% of axSpA patients (see p = 0.019), dejection, melancholy or hopelessness (p < 0.001) and little interest or pleasure in activities (p < 0.001).In the PhQ9, which assesses signs of depressive symptoms, the axSpA patients scored an average of 6.71 points, while the OBP patients reached on average 8.50 points and thus showed significantly more depressive symptoms (ents see . OBP patp < 0.001). Functional limitation in everyday life (FFbH) also correlated significantly with all four domains  as well as with subjective QoL (Q1) and satisfaction with health  = 29.60, p < 0.001. The results for individual predictors are shown in To determine factors predicting subjective QoL, a linear regression was conducted using stepwise backwards elimination, adjusting for sex, BMI and smoking status. The model explained 55.6% of variance in subjective QoL, adj. In addition, separate multivariate models were calculated for the axSpA and OBP subgroups. For axSpA, disease activity assessed by BASDAI score, depressive symptoms, age and functional capacity were significant predictors of subjective QoL, whereas in OBP patients depressive symptoms, functional capacity and pain assessed on a visual analogue scale were significant predictors. The results for individual predictors are shown in the middle and bottom panel of 3.5.p = 0.001) and reported significantly worse QoL with respect to all four domains of QoL compared to men  as well as significantly more depressive symptoms than male patients (p = 0.002). Reported pain intensity did not differ significantly between male and female patients (p = 0.150).Female patients were significantly less satisfied with their health compared to male patients , while domains of QoL and functional capacity did not differ significantly compared to their male counterparts.However, when stratifying the data by diagnosis, it could be shown that sex differences are in fact more pronounced in axSpA patients than in OBP patients . Nonethe4.Chronic back pain constitutes a significant worldwide health burden. Healthcare costs as well as societal costs caused by lost productivity are substantial and growing , 29. TheIn both groups, the great majority of patients reported pain of mixed pain character, i.e., neither purely inflammatory nor purely mechanical symptoms of back pain. Furthermore, almost half of OBP patients reached 3 or more points in the inflammatory back pain questionnaire, suspicious of spondyloarthritis, despite having a clear orthopedic etiology of back pain. This mirrors the data of Riksman et al., who were unable to clearly discriminate between mechanical and inflammatory back pain by questionnaire in a chiropractic setting . This ovIn this study, OBP patients were significantly older, had a significantly worse functional capacity in everyday life and a lower educational status than axSpA patients. This is in line with other studies reporting mechanical/orthopedic chronic back pain to be associated with age and inversely associated with educational degree , 32. In Previous studies have shown that even patients with low-level but chronic back pain report an impaired QoL . In thisPain and disability were also identified as prominent predictors of lower QoL in other studies on chronic back pain . In axSpWhile in our multivariate regression model sex was not an independently associated factor, it has furthermore been shown for both, chronic mechanical back pain and axSpA, that female patients report a reduced QoL compared to male patients , 41. AlsProinflammatory cytokines and chronic inflammation have been implicated in the development of pain as well as depression. Nonetheless, in this study axSpA patients showed fewer depressive symptoms than OBP patients. However, independently of back pain character, depressive symptoms were common in this cohort. Similarly, a Canadian study reported a rate of major depression of 19.8% for chronic back pain patients . In otheLimitations of this study include the monocentric study design, which led to a comparatively small patient number, as well as the questionnaire-based approach. Furthermore, it needs to be taken into account that the great majority of axSpA patients were under treatment, whereas the orthopedic cohort was a mixed cohort of treated and untreated patients at the time of survey owing to the study design. The cross-sectional approach does not allow to capture potential improvement over time with recommended treatments especially in the orthopedic cohort with patients undergoing surgery or injection therapy. At this point we also want to underline again that with increasing age and disease duration axSpA patients may also have mechanical or unspecific back pain. Furthermore, the university hospital setting may have led to a bias and data might not be directly transferable to other outpatient settings or GP practices.In conclusion, in this study chronic back pain was associated with a high morbidity, reduced QoL and increased depressive symptoms regardless of the pain character, with significant differences between male and female patients. Awareness and addressing of the predisposing factors identified in this study may help to overcome unmet needs and improve QoL for these patients.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.This study was conducted under the ethics protocol 37/17n of the ethics committee of the University of Freiburg, Germany. Patients gave their written informed consent to participate according to International Conference on Harmonization Good Clinical Practice (ICH GCP) guidelines.NV, RV, JT, SF, GH, DE, and LE designed and supervised the study and gave critical input. SH, SF, NV, NF, NC, MS, IR, and JT recruited, consented and cared for the patients enrolled in this study and provided clinical information. NF, SH, and NV analysed the data. NF and NV wrote the manuscript. All authors read and approved the final manuscript.Parts of this study were financially supported by an unrestricted grant from Novartis Pharma GmbH, Germany. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.NV: Speaker honoraria: AbbVie, Novartis, UCB, Bristol-Myers-Squibb, Pfizer; Advisory boards: AbbVie, Novartis, UCB; Research grants: Bristol-Myers-Squibb, Novartis, Pfizer. JT: Speaker honoraria: GSK, BMS, Astra-Zeneca, Abbvie, UCB, Lilly; Advisory boards: Novartis, GSK, Astra-Zeneca, Lilly. Grant/research support from: BMS, Novartis. RV: Speaker fees: AbbVie, Amgen, BMS, Boehringer-Ingelheim, GSK, Janssen-Cilag, Hexal, Novartis, Pfizer, Roche; Advisory boards: AbbVie, Amgen, Boehringer-Ingelheim, BMS, GSK, Janssen-Cilag, Hexal, Neutrolis, Novartis, Sanofi, Takeda; Unrestricted research grants: Amgen, BMS, Novartis, Pfizer. NF received travel grants from AbbVie, Janssen, Sobi, Pfizer.The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Headaches are frequent neurological disorders that are yet to be unveiled and treated comprehensively worldwide. Bearing in mind that the distribution of headache subtypes in neurology clinics (NC) is essential for planning appropriate diagnostic and therapeutic approaches, the primary goals of this multi-centric study are to carry out inter-regional comparisons by using current diagnostic criteria with evaluations of neurologists to delineate headache burden.A cross-sectional study between April 1 and May 16, 2022 was conducted with the participation of 13 countries from the Middle East, Asia, and Africa. Patients were included in the study on a specific day each week during five consecutive weeks. All volunteers over the age of 18 and whose primary cause for admission was headache were examined. The patients admitted to NC or referred from emergency services/other services were evaluated by neurologists by means of the International Classification of Headache Disorders (ICHD-3) criteria.p < 0.001).Among the 13,794 patients encountered in NC, headache was the primary complaint in 30.04%. The headache patients’ mean age was 42.85 ± 14.89 (18–95 years), and 74.3% were female. According to the ICHD-3 criteria, 86.7% of the main group had primary headache disorders, 33.5% had secondary headaches, 4% had painful cranial neuropathies along with other facial and headaches, and 5.2% had headaches included in the appendix part showing some overlapping conditions. While the most common primary headache was migraine without aura (36.8%), the most common secondary headache was medication-overuse headache (MOH) (9.8%). Headaches attributed to COVID-19, its secondary complications, or vaccines continue to occur at rates of 1.2%-3.5% in current neurology practice. Pain severity was significantly lower in Ivory Coast and Sudan than in Türkiye, Turkish Republic of Northern Cyprus, Iran, Egypt, Senegal, Tatarstan, and Azerbaijan (The study showed that migraine is still the most common motive for admissions to NC in different regions. Furthermore, MOH, an avoidable disorder, is the most common secondary headache type and appears to be a significant problem in all regions. Remarkably, pain perception differs between regions, and pain intensity is lower in Africa than in other regions.The online version contains supplementary material available at 10.1186/s10194-023-01555-8. Despite some regional differences, headache disorders are a global problem affecting people of all ages and races with different incomes and geographic regions . In the Information on the epidemiology of neurological disorders, especially in developing countries, is limited due to the limited resources and the need for trained health workers and neurologists . HeadachThe aim of this study is to determine the distribution of headache in different service areas in NC according to the ICHD-3 criteria  through This study was designed as a multinational, multicentered and cross-sectional. The patients were admitted to the study on a particular day each week for five consecutive weeks between April 01 and May 16, 2022. The days of the study were selected using the “Research Randomizer Program”. Trained neurologists evaluated all patients. Prior to the study, all researchers underwent a reconstructed briefing about the ICHD-3 criteria. Current diagnostic criteria were applied for headaches attributed to Coronavirus disease 2019 (COVID-19), headaches attributed to complications secondary to COVID-19, and headaches attributed to the COVID-19 vaccine. All volunteer patients over 18 years old and whose primary reason for admission was headaches were included in the study. The researchers received online informed consent forms from all volunteered patients. Patients not reporting headaches at admission, being younger than 18 years, and did not agree to participate in the study were excluded. A structured, standardized questionnaire was applied to the volunteers participating in the study , 70 researchers from 13 countries were able to take an active part in the research. Since 83% of the patients participating in the study were from Türkiye, Türkiye was evaluated separately to analyze the data more accurately. Ivory Coast, Chad, Senegal, Sudan, Ethiopia, and Morocco from Africa; Egypt and Iran from the Middle East; Tatarstan, Turkish Republic of Northern Cyprus, Azerbaijan, and Mongolia from Asia joined the study  refused to participate in the study.Headache rates observed in NC in the Middle East, Asia, and Africa have been shown in Fig. p = 0.004). There was no difference between primary and secondary headaches regarding age, gender, and pain intensity. However, lifetime pain duration in primary headaches was 5.80 ± 8.40 years, and it was longer than secondary headaches (4.51 ± 7.20 years) (p = 0.036).The mean age of the participants was 42.85 ± 14.89 (18–95 years), and 74.3% were female patients. The number of painful days in the previous month was 11.73 ± 10.41, and the lifetime painful period was 5.69 ± 8.34 years. Pain intensity measured by numbered visual scale (NVS) was 7.03 ± 1.73. Combined headache types (more than one subtype of headache diagnosis) were present in 36.1% of the patients. Primary headache disorders (Part I in ICHD-3) comprised 23.4% of all evaluated patients in NC, and 86.7% of all the patients admitted with headaches. Among patients with a primary headache disorder, 75.2% were female. The distribution of headache rates by diagnostic categories, regions, and demographic characteristics is given in Table p < 0.001). When analyzed separately according to the countries, pain severity was significantly lower in Ivory Coast and Sudan than in Türkiye, Turkish Republic of Northern Cyprus, Iran, Egypt, Senegal, Tatarstan, and Azerbaijan . Total lifetime pain duration was 5.84 ± 8.43 years in Türkiye while it is 7.57 ± 10.30 years in the Middle East; 4.71 ± 7.62 years in Asia; and 2.80 ± 3.93 years in Africa. Unlike the lifetime pain duration being significantly longer in the Middle East than in the other regions, it is seen that patients in Turkey are likely to suffer from pain longer in Türkiye than in Africa (p < 0.001). While the mean lifetime pain duration of both primary and secondary headaches was substantially more prolonged in the Middle East than in the other regions, it was longer in Türkiye than in Africa (p < 0.001). The severity of primary headaches was milder in Africa when compared to the other regions (p < 0.001). The severity of secondary headaches in Africa was again found to be significantly lower than the regions of Türkiye and Asia (p < 0.013).Headache severity measured with NVS seems to differ according to the regions. Pain intensity was significantly lower in the African region compared to the other regions . The most common secondary headache diagnosis was medication-overuse headache (MOH) (9.8%). The most common combination of headaches was between migraine and MOH with a rate of 5.7%. MOH headache was observed in 10% of patients with migraine and 11.9% of patients with TTH. Migraine and TTH were observed in an integrated manner in 5.53% of patients with headaches. The mean ages in migraine and TTH patients were 42.33 ± 14.53 and 43.79 ± 15.20. The mean age of onset of headache was 36.08 ± 15.70 in migraine patients and 38.33 ± 16.35 in TTH patients. The distribution of migraine and TTH according to the regions was specified in terms of frequency, age, gender, headache frequency, severity, and lifetime pain duration in Table p < 0.05). The findings in the analysis are found to be significant. The mean age of onset of headache was 36.08 ± 15.70 in migraine patients, and in terms of gender there was no difference across the regions. It was statistically significant that the migraine headache frequency was higher in the Middle East than in all regions, and the frequency in Türkiye was more than in Africa (p < 0.001). The headache severity was lower in Africa than in all regions, which was statistically significant (p < 0.001). Lifetime pain duration was significantly shorter in Africa than in the Middle East and Türkiye (p < 0.001)  Table .p = 0.003). Besides, it was statistically significant that TTH was more common in women in Türkiye, the Middle East, and Africa than in Asia (p = 0.03). The mean age of onset of headache was 38.33 ± 16.35 in TTH patients. It was statistically significant that the TTH headache frequency was less in Africa than in all regions (p < 0.001). Headache severity was lower in Africa than in the Middle East (p < 0.024), and there was no difference across the regions regarding lifetime pain duration (p  =0.098) , and the criteria specified were A11.2.4 Headache attributed to upper cervical radiculopathy, A12.4 Headache attributed to separation anxiety disorder, A12.5 Headache attributed to panic disorder, A12.9 Headache attributed to a post-traumatic stress disorder, A5.8 Acute headache attributed to other trauma or injury to the head and/or neck. According to the ICHD-3 criteria, no significant difference was observed in all the regions regarding the incidence of headache subtypes except migraine and TTH.Headache disorders remain to be under-recognized and undertreated especially in developing populations , 8–12. TIn our study, the female-male (F: M) proportion was 2.9:1 in patients who applied to the outpatient clinic with headaches, and there was no difference with respect to the regions regarding gender distribution . The pain was highly severe in 18% of the patients, severe in 47%, moderate in 34%, and mild in 1%. Severe pain rates reported in previous studies were 9.3% in China , 41.5% iPain perception and response mechanisms differ among individuals  and are In our study lifetime pain duration of the patients admitted to NCs was significantly longer in the Middle East than in the other regions. The duration of pain is longer in Türkiye than in Africa. The differences in lifetime pain duration can be caused by various factors such as sociocultural, economic, and educational differences. Mechanisms of coping with pain and the duration may indirectly be reflected in personal and cultural differences. For example, a study performed on older Korean women revealed that patients associated a different meaning to pain. According to them, chronic pain is an inevitable consequence of aging and is not considered a problem to be solved . South AAmong patients with headaches, the rate of primary headaches was 50.1% in China , 52.9% iAs far as the global prevalence estimate of TTH is 22%, that of migraine is 15%  is conceTACs were detected at a rate of 3.5%, and other primary headache disorders were measured at a rate of 2.9% by neurologists in our study. It was remarkable that there was no significant difference across the regions.Secondary headaches were found at a rate of 20.1% in Iran  and in BThe prevalence of Post-traumatic headaches is estimated to be approximately 4% of all symptomatic headaches . GeneralAnother critical issue is “Headache due to substance (use) or withdrawal.” The population prevalence of MOH, a sub-title of this group, is approximately 1% , 62 and The epidemiology of headaches in Africa involves more secondary headaches primarily due to tropical neuro infections such as malaria and meningitis . HoweverIn our study, “Especially people with primary headache disorders experience a headache more commonly than the general population in the acute phase of COVID-19 and after vaccination . KnowledSynchronized evaluation of patients in different geographic locations by neurologists with a clear protocolDelivering preliminary training on ICHD-3 criteria to physicians before the study,Including not only outpatients but also patients referred from emergency and other services within the work experience of neurologists are to be evaluated.Including regions that represent a significant part of the world’s geography and are not frequently represented in previous studies.Revealing the significant difference in the pain severity in different countries by adhering to the same scale.Reporting the current frequencies of headaches related to COVID-19 disease, its secondary complications, and its vaccine-related headaches in NCs in different parts of the world.We can list the strengths of our work as follows.Although this study is carried out in large geography, more countries and centers are required to represent the relevant regions fully. Although it is a disadvantage that factors such as race, sociocultural level, and education that may affect the analysis were not questioned in the study, it is inferred that the individuals included in the survey generally represent ethnicity in the relevant regions. Since our research is hospital-based, it is not appropriate to generalize its results to the population. Besides, there is easy access to different subspecialties in Iran, especially in big cities, so headache sufferers usually go to headache specialists. Therefore the recorded cases from centers in Iran may not precisely reflect the rate of headache patients in the general clinics there.One out of every three patients who applied to neurology clinics complained of headaches. Compared to previous studies, the increase in the rate of patients with primary headaches among patients with headaches is remarkable. Pain intensity was lower in the African region compared to the other regions. Lifetime pain duration is significantly longer in the Middle East than in the other regions as it is in Türkiye than in Africa indicating various motives such as healthcare system regulations and sociocultural, economic, and educational factors.Migraine headaches are more common in Africa than in Türkiye and Asia and in the Middle East than in Türkiye. TTH has been observed at a higher rate in Türkiye than in Africa and the Middle East. MOH is an increasing problem in all regions and is the most common type of secondary headache. Although this study reveals that the diagnostic capacity of the ICHD-3 criteria is high, it is valuable as it supports the evaluation of some additional criteria in future classifications bearing in mind the prevalence of increased headaches in NCs after the COVID-19 pandemic is important for developing diagnosis and treatment strategies.Additional file 1.


Chronic pain is among the most common conditions presenting to primary care and guideline-based care faces several challenges. A novel pain management program, Video-Telecare Collaborative Pain Management (VCPM), was established to support primary care providers and meet new challenges to care presented by the COVID-19 pandemic.The present single-arm feasibility study aimed to evaluate the feasibility and acceptability of VCPM and its components among U.S. veterans on long-term opioid therapy for chronic pain at ≥ 50 mg morphine equivalent daily dose (MEDD). VCPM consists of evidence-based interventions, including opioid reassessment and tapering, rotation to buprenorphine and monitoring, and encouraging behavioral pain and opioid-use disorder self-management.MEDD = -58.1 vs. -8.40). Finally, 29 referrals were placed for evidence-based non-pharmacologic interventions.Of the 133 patients outreached for VPCM, 44 completed an initial intake (33%) and 19 attended multiple VCPM appointments (14%). Patients were generally satisfied with VCPM, virtual modalities, and provider interactions. Nearly all patients who attended multiple appointments maintained a buprenorphine switch or tapered opioids , and buprenorphine switches were generally reported as acceptable by patients. Patients completing an initial intake with VCPM had reduced morphine equivalent daily dose after three months (means = 109 mg MEDD vs 78 mg), with greater reductions among those who attended multiple appointments compared to intake only (ΔPre-defined feasibility and acceptability targets for VCPM and its components were broadly met, and preliminary data are encouraging. Novel strategies to improve enrollment and engagement and future directions are discussed. Chronic pain is among the most commonand debilitating conditions in the U.S. and worldwide , 2, and The COVID-19 pandemic disrupted in-person healthcare, including access to many non-pharmacologic pain management approaches. This led to an urgent need for adaptation of clinical care, particularly for patients with chronic pain prescribed LTOT whose access to evidence-based pain care may be limited due to public health precautions. To address primary care and COVID-19 related challenges, we aimed to evaluate the feasibility and acceptability of a program called Video-Telecare Collaborative Pain Management (VCPM) in preparation for a larger-scale trial. VCPM comprises three evidence-based components: opioid reassessment and tapering, buprenorphine switch and monitoring, and behavioral pain and OUD self-management .This single-arm feasibility study was funded as a Veterans Health Administration (VHA) Health Services Research & Development Rapid Response Project , a rapid funding initiative to respond to challenges related to the COVID-19 pandemic. The study took place in two VHA healthcare systems located in the northeast and mountain regions and was deemed quality improvement by the two participating VHA Institutional Review Boards.Eligible patients were Veterans on LTOT for chronic pain at ≥ 50 mg morphine equivalent daily dose (MEDD). Exclusion criteria included a diagnosis of dementia or moderate-severe cognitive impairment, unstable or severe untreated psychiatric disorder or medical disease that required hospitalization, documentation of suspected controlled substance diversion, or inability to communicate by phone. Eligible patients were identified through referrals from primary care providers to the participating VHA site’s pain management teams (PMTs) or through direct patient outreach using internal opioid risk reports to identify potentially eligible patients.VCPM is a multicomponent intervention led by pain-trained clinical pharmacy practitioners (CPPs) and supported by a collaborating physician, modeled after the collaborative care intervention in the SPACE trial . The phyEligible patients received an information packet via mail or email and were then contacted by study staff to schedule an intake evaluation with the CPP. In collaboration with the supporting physician, a pain management plan was created and presented to the patient . For data collection purposes, duration of active intervention was set for 90 days with follow-ups increasingly spaced-out over time, though duration of intervention and frequency of follow-ups were ultimately determined on a case-by-case basis according to patient’s clinical situation . Patient preference was incorporated into virtual treatment modality (video vs. telephone) and information receipt . If a patient declined follow-up, VCPM recommendations were sent to their primary care provider. Patients also completed outcome measurements three months after their baseline visit.The primary outcomes of interest were feasibility and acceptability of VCPM, measured by 1) number of referrals through participating PMTs or direct outreach, 2) enrollment as determined by completion of a VCPM intake, 3) continued engagement with the VCPM program , and 4) patient-reported acceptability. Feasibility and acceptability of opioid reassessment and taper or buprenorphine switch were based on the total number of patients who engaged in an opioid taper or buprenorphine switch. Acceptability of VCPM was assessed using an 18-item questionnaire assessing the impact of COVID-19, healthcare-related use of technology, and questions regarding satisfaction with virtual visits, the VCPM pain management model, and buprenorphine . Questions included willingness to engage with VCPM or to trial buprenorphine, success of interventions, and confidence in recommending the intervention . We used electronic health record data and follow-up phone evaluations to collect additional data.We obtained data through chart review of electronic health records and review of provider documentation. Variables of interest included demographic data, VHA service connection, pain generator, medical and mental health comorbidities (aggregated into risk index for overdose or serious opioid‐induced respiratory depression (RIOSORD) comorbidities , substanThe PEG-3 is a reliable and valid three-item measure of pain intensity, interference with enjoyment of life, and interference with general activity . Items aThis study utilized a modified version of the 14-item QQPPI , a measuFeasibility and acceptability outcomes were evaluated based on descriptive statistics with defined a priori criteria, used to determine whether further evaluation was warranted. Poor feasibility or acceptability were defined as follows: 1) the majority of patients declining to trial a buprenorphine switch (> 50%), 2) low treatment satisfaction (> 50% negative satisfaction), or 3) low engagement in follow-up (< 50% attending follow-up). Given the nature of this small pilot quality improvement project, secondary outcomes were evaluated using descriptive statistics only. Analyses were performed using SPSS for Windows .VCPM patients were primarily male  and white , with a mean age of 63.5 years (SD = 8.5), and about half were from urban locations (55%)  and 19 continued VCPM engagement past intake (14%). Approximately three-quarters (32/44) of patients who completed intake evaluations completed follow-up evaluations.n = 16) compared to those who were seen for multiple appointments (n = 16). Patients who continued in VCPM beyond the intake evaluation rated VCPM as more successful (means = 6.9 vs 4.1) and reported higher satisfaction with provider interactions (means = 70.2 vs 64.1) compared to those who completed an intake evaluation only.Patients reported high satisfaction with both video visits (mean = 4.3/5) and phone visits (mean = 4.0/5), high willingness to engage with VCPM  and confidence in recommending the program , with no difference in satisfaction between those completing only an intake evaluation (n = 9) rated, on average, their willingness to try buprenorphine as 7.8/10, view of buprenorphine as successful as 6.5/10, and confidence in recommending buprenorphine as 6.5/10.Individuals who continued engagement in VCPM had high rates of trialing buprenorphine  and of either maintaining a buprenorphine switch  or tapering full-agonist opioids  after three months. Those who trialed buprenorphine and completed the three-month survey (MEDD = -58.1 vs -8.40).Individuals who completed the VCPM intake evaluation reduced their MEDD three months later (means = 109 mg MEDD at intake vs 78 mg MEDD three months later). Individuals who continued engaging with VCMP for multiple appointments, compared to those who attended only an intake evaluation, exhibited a larger MEDD reduction after three months  went to complementary and integrative health programs , followed by physical therapy , behavioral interventions , and interventional pain programs .On the three-month survey, individuals who continued VCPM engagement compared to those completing only the initial evaluation reported a lower pain intensity (6.1 vs 7.1/10), pain interference with enjoyment of life (6.0 vs 8.3/10), and pain interference with general activity (5.9 vs 7.4/10). When describing how pain has changed over the last three months, 44% of those who continued engagement reported improvement while 25% reported worsened pain. Among those who completed an intake evaluation only, 19% reported improvement and 38% reported worsened pain over the last three months.The current quality improvement project examined the feasibility and acceptance of a novel virtual care model of pain management utilizing well-established components including opioid reassessment and tapering, buprenorphine switch and monitoring, and behavioral pain and OUD self-management –16.Broadly, the project met the identified a priori feasibility and acceptability criteria for the virtual delivery component. Across 17 months, 133 Veterans were identified as eligible for VCPM, resulting in 44 intake evaluations . Of those who completed an intake evaluation, 19 patients also received follow-up care from a VCPM CPP . The project succeeded in engaging rural Veterans who made up nearly 50% of the sample, notable in the context that, only 14% of patients with an assigned primary care provider among these two participating VHA systems are in rural areas , 22. HowAmong those enrolled, acceptability of VCPM was high, with robust satisfaction for both virtual care modalities . Patients reported high willingness to engage with virtual care and confidence recommending the program. As would be expected for individuals choosing to engage with the program, those who attended multiple appointments with the CPP generally rated the program as more successful than those completing only an intake evaluation. Future efforts will focus on understanding reasons for lack of engagement.Similarly, a priori criteria for success of the buprenorphine switch component of VCPM were largely met. Among those engaged in VPCM, over half trialed buprenorphine and nearly all of those maintained their buprenorphine regimen at three-month follow-up. From a harm-reduction standpoint, VCPM was successful in tapering opioids or transitioning to buprenorphine with a majority of patients. Acceptability of the buprenorphine switch was generally favorable, with patients reporting moderate or high willingness to trial buprenorphine, view of the buprenorphine switch as successful, and confidence recommending to a friend.Preliminary findings are encouraging, as individuals who continued to engage with VCPM exhibited greater MEDD reductions and indications of improved pain outcomes compared to those completing only a baseline intake. It is important to note, however, the single-arm nature and emphasis as a quality improvement project preclude comparisons to traditional, in-person pain management interventions.The present quality improvement project provides initial support for VCPM and the virtual delivery of multi-modal pain management interventions. Within the VHA system, virtual interventions offer the ability to markedly increase the reach of programs designed to assist primary care providers, particularly among regions where maintaining a specialized care team is difficult. Larger effectiveness trials are needed to 1) compare VCPM to other pain management interventions and 2) ensure non-inferiority of virtual interventions and 3) evaluate VCPM among more diverse populations .


Opioid use has come under increasing scrutiny, driven in part by the opioid crisis and growing concerns that up to 6% of opioid-naïve patients may become chronic opioid users. This has resulted in a revaluation of perioperative practice. For this reason, we implemented a multidisciplinary pathway to reduce perioperative opioid usage through education and standardization of practice.p < 0.15 included in the final model and using post-operative opioid use  as the primary outcome.A single-centre retrospective evaluation was performed after 1 year, comparing the outcomes to those of the 2 years prior to pathway implementation. Comparisons were made between pre- vs. post pathway change by 2:1 propensity matching between cohorts. Univariate linear regression models were created using demographic variables with those that were p < .001, as was post-operative opioid use for the duration of the hospitalization, 46.3 mg (49.5) vs. 35.49 mg (43.7) OME, p = 0.002. In subgroup analysis of those that received some intraoperative opioids (n = 152) and those that received no opioids (n = 34), we found that both groups required fewer opioids in the post-operative period 47.0 mg (47.7) vs. 32.4 mg (40.6) OME, p = 0.001, + intraoperative opioids, 62.4 mg (62.9) vs. 35.8 mg (27.7) OME, p = 0.13, - intraoperative opioids. Time to discharge from the PACU was reduced in both groups 215 min (199) vs. 167 min (122), p < 0.003, + intraoperative opioids and 253 min (270) vs. 167 min (105), p = 0.028, - intraoperative opioids. The duration of time until meeting discharge criteria from PACU was 221 min (205) vs. 170 min (120), p = 0.001. Hospital length of stay (LOS) was significantly reduced 1.4 days (1.3) vs. 1.2 days (0.8), p = 0.005. Both sub-groups demonstrated reduced hospital LOS 1.5 days (1.4) vs. 1.2 days (0.8), p = 0.0047, + intraoperative opioids and 1.7 days (1.6) vs. 1.3 days (0.9), p = 0.0583, - intraoperative opioids. Average pain scores during PACU admission and post-PACU until discharge were not statistically different between cohorts.We found that intraoperative opioid use was significantly decreased 38.2 mg (28.3) vs. 18.0 mg (40.4) oral morphine equivalents (OME), These findings underscore the effectiveness of a multidisciplinary approach to reduce opioids. Furthermore, it demonstrates improved patient outcomes as measured by both shorter PACU and almost 50% reduction in perioperative opioid use whilst maintaining similar analgesia as indicated by patient-reported pain scores.The online version contains supplementary material available at 10.1186/s13741-023-00331-1. Perioperative opioid use has come under increasing scrutiny, driven largely by worsening trends in opioid-related adverse events (ORAEs)  and timing. In 50 cases reviewed, we observed patients receiving on average 250 mcg of fentanyl and almost 2 mg of hydromorphone during an average case length of 103 min. Moreover, the use of non-opioid analgesics was inconsistent and largely considered an ‘afterthought’ (author’s unpublished data). This variability in practice may further contribute to the opioid crisis  have been reported in the literature  pathway.Based on the desire to improve patient care and provide a more standardized approach across practitioners, we established an anaesthesiology-led, multidisciplinary group comprised of urological surgeons; nurse practitioners; nurses from the surgery clinics, PACU, and hospital wards; and pharmacists, in order to design our analgesic care pathway for robotic prostatectomies see Fig. . We emplThis pathway went into practice on August 1, 2017, following 1 month of education in the form of formal presentations, lectures, and written communication. We confirmed wide-spread understanding and adoption among the stakeholders through continual education and support during implementation and establishment. The pathway then became the standard of practice for patients undergoing robotic prostatectomies at our institution.After obtaining internal review board approval for a quality improvement review, we surveyed the medical records of all patients that underwent robotic prostatectomy at our institution between September 1, 2017, and September 1, 2018. Data from the medical records for patients undergoing the same procedure between July 1, 2015, and July 31, 2017, were reviewed and used as a comparison for post-implementation care. Demographic data was collected on all patients in addition to factors that commonly associate with the perception of pain, including histories of chronic pain, anxiety, depression, and prior drug use . Patients were not consistently nor uniformly instructed about expectations for their recovery and the anticipated pain levels after the procedure. Multimodal, non-opioid analgesic use was infrequent and sporadic among the care team, during all phases of care.We previously published our protocols for opioid-reduction/opioid-free anaesthesia  as the outcome and each of the demographic variables above as well as intraoperative opioids and time (pre vs. post pathway change). Any variable p-value < 0.15 in the univariate analysis and were included in the initial multivariable model. The final multivariable model includes time (pre vs. post), intraoperative opioid use, age, race, ASA score, smoking status, chronic pain, history of chronic pain, and history of anxiety. The SQUIRE checklist was used in the preparation of this manuscript . The opioids used within the post-operative period included hydromorphone, fentanyl, oxycodone, morphine, and methadone.Post-operative opioid administration, which remained available to all patients PRN, was significantly reduced over the entire duration of the hospitalization  vs. those who did not receive intraoperative opioids  and . The duration of time until meeting discharge criteria from PACU was most prominent, saving an average of 51 min  was significantly reduced in both groups . Both groups had reduced hospital LOS [ and ]  analgesics  (Chia et al. Recent work published by Purdon et al. (Santa Cruz Mercado et al. Classic studies have demonstrated that the knowledgeable patient requires less analgesia in the post-operative period and at the same time experiences significantly less pain than the less-informed patient, and more recent investigations have supported the conclusion that preoperative information will aid coping, reduce preoperative anxiety, and may also enhance postsurgical recovery (Kehlet and Wilmore Anaesthesiologists are leading experts in pain medicine, and through evidence-based implementations such as ERAS and multimodal anaesthesia, the specialty is helping to address the opioid crisis by reducing the amount of opioid used in the perioperative period whilst still maintaining adequate acute pain control. The time has come to change the foundations of our practice from that of an opioid-based one to that of a multimodal and multidisciplinary practice Fig. , whereinPerioperative physicians and anaesthesiologists should continue to pursue evidence-based research to assist with the opioid epidemic from a broad, perioperative population health approach. We share the responsibility with the rest of the medical community not only to decrease the financial burden on society and on hospitals but also to assist in solving the epidemic, which has now become the number one accidental cause of death in the USA. In addition to the more pragmatic benefits of decreased PACU/hospital LOS, decreased opioid use and fewer opioid-related side effects improve patient outcomes, sometimes substantially — making an ORA/OFA approach favourable from that viewpoint.We acknowledge several limitations of our study, one being its retrospective nature. Whilst our pathways essentially moved opioids in the position of a ‘rescue’ medication, the lower use of opioids during the post-operative period cannot solely be interpreted as less need for rescue medication, nor can its use suggest increased need. These questions are best answered via prospective study. Moreover, as pain scores were similar between cohorts, we do not know if the administration of opioids was given at the request of the patient or given based on beliefs and biases of members of the care team. Future studies will require not only capturing pain scores specifically but also patient’s expectations on pain, requests by patients for rescue medications, and data on provider’s interpretation and biases in pain management. Another critical limitation of our study is that we do not have access to long-term follow-up care and therefore are unable to report on the long-term use of opioids. Future work will include long-term follow-up to specifically address long-term opioid use as well as functional recovery in these patients.The collaborative efforts of all the members of the care teams that interact with surgical patients undergoing robotic prostatectomies, acting in a mindful, planned manner, were able to decrease opioid use, hospital, and PACU LOS and reduced opioid-related side effects. This teamwork allowed for consistency of practice, minimized variability, and allowed providers the ability to individually address needs as they arose within a guided framework of care. We believe that this type of approach is translatable across specialties. However, prospective studies are urgently needed to further evaluate the role of opioid-reduction pathways and opioid-free anaesthesia on a patient’s long-term outcomes.Additional file 1: Table 1. Opioid Free Pathway during the perioperative period. Table 2. Script elements to align expectations for OFA in Robotic Prostatectomies.


Anxiety contributes to postsurgical pain, and midazolam is frequently prescribed preoperatively. Conflicting results have been described concerning the impact of midazolam on pain. This study aims to evaluate the effect of systemic midazolam on pain after open inguinal hernia repair, clarifying its relationship with preoperative anxiety. A prospective observational cohort study was conducted in three Portuguese ambulatory units between September 2018 and March 2020. Variable doses of midazolam were administered. Postsurgical pain was evaluated up to three months after surgery. We enrolled 306 patients and analyzed 281 patients. The mean preoperative anxiety Numeric Rating Scale score was 4 (3) and the mean Surgical Fear Questionnaire score was 22 (16); the mean midazolam dose was 1.7 (1.1) mg with no correlation to preoperative anxiety scores. Pain ≥4 was present in 67% of patients 24 h after surgery and in 54% at seven days; at three months, 27% were classified as having chronic postsurgical pain. Preoperative anxiety correlated to pain severity at all time points. In multivariable regression, higher midazolam doses were associated with less pain during the first week, with no apparent effect on chronic pain. However, subgroup analyses uncovered an effect modification according to preoperative anxiety: the decrease in acute pain occurred in the low-anxiety patients with no effect on the high-anxiety group. Inversely, there was an increase in chronic postsurgical pain in the very anxious patients, without any effect on the low-anxiety group. Midazolam, generally used as an anxiolytic, might impact distinctively on pain depending on anxiety. Anxiety is reported by most patients as the worst aspect of the perioperative period . ExcessiMidazolam is a γ-aminobutyric acid type A (GABA A) receptor modulator, binding to a specific benzodiazepine site. It is popular due to combining anxiolytic, sedative, hypnotic, anticonvulsant, muscle relaxant, and anti-emetic properties with rapid onset, short half-life and good safety profile ,7,8. TheA possible explanation for such inconsistent results might be that different timings and/or surrogates of pain were used or that anxiety could have confounded or modified this effect. Acute pain is influenced by multiple endogenous, physical, and emotional factors. State anxiety is indeed one of the most significant predictors of postsurgical pain .Following previous results, where we found that midazolam was associated to increased postsurgical pain in ambulatory knee arthroscopy , we hypoclinicaltrials.gov accessed on 17 April 2018 (NCT03499730) by principal investigator Caroline Dahlem. Ethical approval for this study was provided by the Ethical Committees of Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia; Centro Hospitalar do Baixo Vouga, Aveiro; and Centro Hospitalar Entre Douro e Vouga, Santa Maria da Feira, Portugal. Written informed consent was obtained from all study participants. This manuscript adheres to the applicable STROBE guidelines.This multicentre prospective observational cohort study was preregistered prior to patient enrollment at clinicaltrials.gov accessed on 17 April 2018 (NCT03499730).This multicentric prospective observational cohort study was registered at Setting: three ambulatory surgery units serving different populations from Portugal; patients were recruited between 12 September 2018 and 5 March 2020.Inclusion criteria: adult patients scheduled for open inguinal hernia repair who agreed to participate and sign an informed consent form. Exclusion criteria included psychiatric disorders or alcoholism; illiteracy or a poor understanding of the Portuguese language; a history of chronic pain under opioid treatment; recurrent hernia; and simultaneous bilateral surgery.We chose to study patients submitted to open inguinal hernia repair, as this is a common ambulatory surgical procedure and most patients experience both acute and chronic postsurgical pain .−1 of fentanyl and 1–2 mg.Kg−1 of propofol, and maintained with sevoflurane through a laryngeal mask. Anti-emetics were administered according to risk factors. Spinal anesthesia was performed with 8–9 mg of 0.5% hyperbaric bupivacaine in lateral decubitus. At the end of surgery, all patients received local wound infiltration with 10 mL of ropivacaíne 0.75%, 1 g of IV acetaminophen, and 30 mg of ketorolac, and rescue analgesia was given in the recovery room with 2 mg.Kg−1 of tramadol. All patients received take-home oral analgesia: 1 g of acetaminophen (6/6 h), 400 mg of ibuprofen (8/8 h), and 50 mg of rescue tramadol (8/8 h). If there was an intolerance or allergy, ketorolac and/or ibuprofen were replaced by 2 g of metamizole. All centers used a polypropylene Bard® Mesh Perfix Plug for surgery .All patients had a standard preoperative assessment with an anesthesiologist several weeks before surgery. Before arrival at the operating room, patients received preoperative medication: 10 mg of metoclopramide, 40 mg of esomeprazole, and variable doses of intravenous (IV) midazolam. The attending anesthesiologist would define the midazolam dosage according to his own criteria (from none to any dosage) as well as the anesthesia protocol . General anesthesia was induced with 2–2.5 μg.KgThe predictor variable was the total IV midazolam dose in mg. The primary outcome was postsurgical pain evaluated by an 11-point numeric rating scale (NRS) (0–10) by telephone interview at three different follow-up points: 24 h, 7 days, and 3 months after surgery. Secondary outcomes included: total analgesic consumption at 24 h and 7 days; adverse events; patient satisfaction; and Global Surgery Recovery Index (GSRI) scores. We considered preoperative anxiety as the main confounder because it might interfere with both midazolam dosage and postsurgical pain. Other variables that considered potential confounders were preoperative pain, sex, ambulatory unit, chronic benzodiazepine consumption, smoking, and the type of anesthesia. Chronic postsurgical pain (CPSP) was defined according to ICD-11 as pain that developed or increased in intensity after surgery and persisted for at least 3 months .Age, weight, height, sex, smoking status, employment status, education level, preoperative pain, and anxiety were assessed by a self-reported preoperative questionnaire on the day of surgery, supported when needed by one of the study investigators. Preoperative anxiety was assessed both as an 11-point NRS, from 0 to 10, and via the Surgical Fear Questionnaire (SFQ), validated for the Portuguese population. It consists of two subscales: fear of the short- and long-term consequences of surgery . A simplThe sample size was calculated considering a power of 80%, α = 0.05, a mean 24 h postsurgical pain NRS of 4.5 (1.5) , and an ® SPSS®  considering a significance level of p = 0.05. Categorical variables are presented as n (%) and compared using the Pearson chi-square test. Pain and anxiety scores were considered continuous variables. Continuous variables were considered normally distributed when skewness and kurtosis varied between −0.7 and 0.7; these data are presented as mean (SD) values and compared using Student’s t-test or one-way ANOVA. Other continuous variables are presented as median [IQR]. All tests are two-sided and referenced in tables. Missing data were not replaced and outlying data were not removed. When appropriate, age, body mass index (BMI), and pain and anxiety scores were transformed into categorical variables. Preoperative pain was defined as NRS ≥ 4 and significant postsurgical pain was defined as NRS ≥ 4. For age and SFQ anxiety scores, groups were defined using the terciles; for BMI, the mean value was used. Pearson correlation was used to assess the association between anxiety scales, postsurgical pain, midazolam dosage, and analgesic consumption. Due to the uneven administration of midazolam among some groups of patients, the effect of midazolam on pain was searched for through multivariable logistic regression models. Preoperative pain, anxiety SFQ, sex, age, ambulatory unit, and the type of anesthesia were forced into all logistic models, as they were considered major potential confounders due to possible influence on both midazolam dose and postsurgical pain. In the models, we also included variables that were significantly associated with the pain outcome variables (if p < 0.1). Multicollinearity was assessed in all models; all predictor variables had a variance inflation factor < 2. Estimates of adjusted odds ratios (adj ORs) with 95% confidence intervals (95% CI) are presented. While running these logistic regression models, an interaction of midazolam with preoperative anxiety was significant for some pain outcomes. To clarify this interaction, we ran the same models separately on the anxiety subgroups, defined by the terciles of the SFQ scores. We also explored subgroups and effect modification according to sex, the type of anesthesia, and the ambulatory unit.Statistical analyses were performed using IBMThree hundred and six patients were enrolled between 12 September 2018 and 5 March 2020; unit 3 stopped enrollment earlier than planned due to SARS-CoV-2 pandemic restrictions. A total of 267 patients completed the three months follow-up and 281 were analyzed. The study flow chart is presented in p < 0.001). The median preoperative pain NRS was 1 , p < 0.001), 7 days , and 3 months . Analgesic consumption at 24 h and 7 days did not consistently correlate with pain intensity at those time points but was significantly different across surgical units (p < 0.001).Moderate-to-severe pain was present in 67% of patients 24 h after surgery and in 54% of patients at seven days; on the first postoperative day, 11% needed rescue analgesics more frequently if they operated under general rather than spinal anesthesia  and any pain at 7 days decreased by 0.418 (0.175–0.997). Midazolam did not seem to influence chronic pain in the overall analysis. However, subgroup analysis suggests that the positive effect of midazolam on pain only benefitted the low-anxiety patients. If SFQ < 12, for each mg of midazolam, the odds of reporting significant pain at seven days decreased by 0.289 (0.117–0.713). On the contrary, midazolam was associated with increased CPSP exclusively in the highly anxious patients; if SFQ > 28, for each mg of midazolam, the odds of developing CPSP at three months increased by 2.124 (1.026–4.397). Results of the logistic regression models are presented in In this study, midazolam was associated with decreased acute pain after ambulatory open inguinal hernia repair; each mg of midazolam significantly reduced the likelihood of reporting pain in the first week. This analgesic effect of midazolam has been described by other authors ,12,13. HOn the other hand, midazolam was associated with increased CPSP, but only in the high-anxiety patients; each mg of midazolam doubled the odds of CPSP at three months, without any effect on the low-anxiety group. To our knowledge, no previous study has addressed the effect of midazolam on chronic pain and its effect modification dependent on preoperative anxiety.This effect modification is consistent across several outcomes and cut-offs for anxiety and is also present whether we use the SFQ or the NRS to measure anxiety. However, subgroup analysis implied a loss of statistical power, which might be why we failed to find a significant effect of midazolam on acute pain in high-anxiety patients or on CPSP in low-anxiety patients. Kain and colleagues were the only authors to previously explore the effect of midazolam on pain, separately analyzing the subgroups based on trait anxiety; however, they did not find any significant effect of midazolam on pain up to one month after surgery .−1) [Increased pain perception in volunteers sedated with midazolam has been previously described . We have−1) ,13. Agai−1) ,13.The major strengths of our study are a 3-month follow-up and the separate analyses by subgroups of state anxiety. This scrutiny of data clarified that anxiety appears as an effect modifier of the impact of midazolam on postsurgical pain. Though anxiety is a known risk factor for postsurgical pain, it is unclear how it mediates the effect of midazolam.The answer might be in the GABA receptors, about which knowledge is continuously being updated. GABA A receptors are the major inhibitory neurotransmitter receptors in the human brain, being involved in inhibitory pain pathways. Midazolam modulates GABA A activity, facilitating channel opening, but different receptor subtypes produce different clinical effects . MidazolFurther research investigating the effect of variable midazolam doses on postsurgical pain in different anxiety populations might clarify our results.Concerning patient recruitment, one of the units stopped enrollment due to SARS-CoV-2 pandemic restrictions. Although we enrolled a total of 296 patients, a more even distribution across units would allow for more robust external validity of the results. The low education level of our sample, particularly among the elderly, might have contributed to missing data in anxiety and pain questions; some patients needed help to complete questionnaires, which could, to some extent, influence their responses. A total of 14 patients had incomplete follow-ups, meaning that they did not answer all three follow-up telephone contacts, though all available data were included in each analysis. Concerning outcomes, we observed that analgesic doses were not consistently related to pain scores but instead were mainly dependent on routines and usual practice of each unit; thus, we decided not to use analgesic consumption as a surrogate for pain and to include the ambulatory unit as a variable in all regression models. Finally, we did not evaluate depression, pain catastrophizing, or trait anxiety, as this would increase the length and complexity of the questionnaire. However, measured state anxiety was similar to state anxiety in other populations . Acute aIncluding patients submitted to either spinal or general anesthesia under variable doses of midazolam (0–5 mg), from three different units, might have increased the risk of bias and confounding. The type of anesthesia and ambulatory unit are external factors that could simultaneously influence midazolam dose and postsurgical pain through minor variations in the surgical technique; on the other hand, a multicentre study with different populations might result in more generalizable results. Being an observational study, the lack of a formal control group  and a strict single anesthetic protocol was counterbalanced with thorough multivariable regression models, analyzing midazolam as a continuous variable and adjusting for both the type of anesthesia and ambulatory unit. Interestingly, midazolam dose did not relate to preoperative anxiety (attending anesthesiologists did not have access to the preoperative questionnaire). Previous authors have shown that anesthesiologists do not correctly evaluate patient preoperative anxiety ,27. TherWe know that a randomized controlled trial (RCT) could decrease bias and better show a cause–effect relationship between midazolam and pain. However, we opted for an observational study because, in our setting, this was the most feasible to carry through. Midazolam is in such common use and, being a prospective study, we tried to measure all confounding variables to capture results in real clinical scenarios.Our results uncover an effect modification of midazolam on postsurgical pain, depending on patient preoperative anxiety levels. Midazolam does not seem to attenuate the well-known hyperalgesic effect of high anxiety on postsurgical pain; paradoxically, it might be analgesic in low-anxiety patients and hyperalgesic in the very anxious ones. These results raise a new issue regarding perioperative care: midazolam, generally used as an anxiolytic, seems to only benefit the low-anxiety patients. We recommend that anesthesiologists actively measure preoperative anxiety and consider alternative strategies to reduce it, as midazolam seems to neither consistently reduce pain nor anxiety in ambulatory surgery. Further research should focus on the effect of variable midazolam doses on postsurgical pain in different anxiety populations, preferably with an RCT.