Background: Fibromyalgia is characterized by chronic widespread pain, which has been linked to neuroinflammation. Hematological indices, i.e., neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV) have been shown to be effective markers in neurological diseases like depression.Aims: To study the association between fibromyalgia severity and the hematological indices .Subjects and Methods: This was a hospital-based cross-sectional study of fibromyalgia patients satisfying the 2016 modification of the 2010/11 ACR criteria. Demographic and clinical characteristics were recorded along with fibromyalgia outcomes and hematological indices. Statistical analysis was done using descriptive statistics, ROC analysis using the Youden index, and Pearson and Spearman correlations.Results: A total of 266 patients were recruited. The (mean ± S.D) NLR, MPV, and PLR were 1.92 ± 1.26, 8.94 ± 1.25, and 119.48 ± 76.91, respectively. Patients with severe visual analog scale (VAS) pain scores had lower MPV (8.8 ± 1.3) than those with mild/moderate pain . MPV showed a mild negative correlation with the Fibromyalgia Impact Questionnaire-Revised (FIQR) score (R2 -0.31 p 0.004). MPV threshold of 8.95 was discriminated severely from mild/moderate VAS-pain score with a sensitivity of 52.3 % and specificity of 66.7%.Conclusions: MPV can possibly be considered as a biomarker for predicting pain severity in fibromyalgia. Given its inexpensive nature, MPV can be used as a cost-effective method to assess fibromyalgia severity in rural India. Fibromyalgia typically presents as chronic widespread musculoskeletal pain syndrome and is often accompanied by fatigue, insomnia, cognitive disturbances, and multiple somatic symptoms. It occurs more commonly in women with its prevalence in different countries varying between 1-3% of the general population. The exact mechanisms that lead to the development of fibromyalgia are unknown but the key etiopathology mechanisms are alterations in cortical and spinal pain processing along with small fiber neuropathy . SystemaIncreasingly, the role of non-traditional hematological indices in identifying systemic inflammation is being studied. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV) are three of the most commonly studied hematological indices with higher NLR, PLR, and MPV values being suggestive of underlying inflammation. These indices are cost-effective and readily available in all patients .There are few studies that have studied these hematological studies in fibromyalgia and, to the best of our knowledge, no previous studies have studied the relation between NLR, PLR, and MPV with fibromyalgia disease severity. The aim of our study was to investigate associations between fibromyalgia outcome measures and the hematological indices .Study population and designThe study was a hospital-based cross-sectional study conducted at Amrita Institute of Medical Sciences, Kochi, Kerala, India. The study was approved by the Institutional Ethics Committee of Amrita Institute of Medical Sciences, Kochi, Kerala, India (IRB-AIMS-2020-458), and data were retrospectively collected using hospital electronic medical records for the period of June 2018 to June 2020. The diagnosis of fibromyalgia was made using the 2016 modification of the 2010/11 American College of Rheumatology (ACR) criteria. These were patients seen in the Rheumatology clinic for fibromyalgia. Other possible causes of chronic pain were excluded through clinical and laboratory tests, while the causes of inflammation and infection were ruled out. Patients with type 2 diabetes mellitus hypothyroidism, hyperthyroidism, inflammatory rheumatic disease, and autoimmune disease were not included in the study. Patients with a history of major depression, cerebrovascular events, and malignancy were excluded from the study. Patients were also excluded if they had cardiovascular disease, hypertension, peripheral artery disease, active chronic obstructive lung disease, heart failure, chronic kidney disease, diabetes mellitus, pulmonary or neurological disease, peripheral neuropathy, hepatic disease, or history of alcohol abuse. Demographic, biochemical parameters, and disease outcome measures Routine demographic and clinical details were assessed for every patient. Hematological parameters were collected from the records. All tests were analyzed using a hematology analyzer, CELL-DYN® 3700 , within 30-45 minutes after the blood was collected. Hemoglobin values were expressed in g/dL. Leucocyte, neutrophil, lymphocyte, and platelet counts were recorded and expressed in 10^3/μL. NLR and PLR were calculated using the results of these parameters. To assess fibromyalgia severity, the outcomes used were the visual analog scale (VAS) pain score and Fibromyalgia Impact Questionnaire-Revised (FIQR) score. FIQR is the latest validated composite patient self-reported instrument that assesses the impact of fibromyalgia symptoms and functional impairment. VAS pain score of 6 was considered to be severe pain.Statistical methodsDescriptive statistics for the constant variables were expressed as mean and SD while the categorical variables were expressed as numbers and percentages. Pearson and Spearman correlation tests were done to determine the relationship between the hematological indices  with categorical land non-categorical pain scores, respectively. In addition, the Mann-Whitney U test was used to assess the relationship between these indices with the categories. Receiver operating characteristic (ROC) curve analysis was used to investigate for significant indices as to whether it could distinguish between severe pain and mild/moderate pain on the VAS pain scale. Youden's index was assessed to identify the optimum cut-off to distinguish severe from mild/moderate pain. The statistical analyses and graphical plotting were performed using SPSS for Windows, Version 16.0 , and a p-value of less than 0.05 value was considered to be statistically significant with all statistical tests performed were two-tailed.We recruited 266 patients for this study. The baseline demographics along with the disease outcome measures and biochemical indices are shown in Table A significant mild negative correlation was found between FIQR score and MPV and is graphically shown in Figure ROC analysis was done based on MPV in discriminating severe pain from mild/moderate pain. The AUC of this curve was 0.591 (95%CI 0.519-0.662). From the Youden's index, the optimal MPV threshold of 8.95 was found to discriminate severe pain from mild/moderate pain on the VAS pain score with a sensitivity of 52.3% and specificity of 66.7%.In this study, we evaluated novel hematological indices (NLR and PLR) along with MPV in fibromyalgia patients and studied their associations with pain severity. Our study shows that of the three indices evaluated, it is MPV that shows associations with the severity of fibromyalgia more than NLR or PLR indices. The MPV showed a mild negative correlation with both FIQR (p=0.004) and reported pain in fibromyalgia. Though the correlation between MPV and VAS pain score is significant (p = 0.016); this relation is not clinically significant. However, it was noted that the absolute MPV value tended to be lower in patients with severe pain of VAS pain scores. This is the first study to the best of our knowledge that has studied the association between hematological indices and pain severity in fibromyalgia.The association between MPV and pain severity could be related to the cytokine signatures reported in fibromyalgia. We have already mentioned the nature of IL-6 and IL-8 in fibromyalgia syndrome (FMS); however, these cytokines have systemic knock-down effects. IL-8 and IL-6 are associated with platelet hyperactivity and peripheral activation in the nervous system of platelets in fibromyalgia due to the cytokines could lead to a lower MPV centrally. This phenomenon has been reported in other studies on diseases with over systemic inflammation  where the lower MPV level surrogates an active and/or chronic inflammatory state in the body . In the In comparison to other cohorts, the ranges of NLR, PLR, and MPV reported in our study are comparable Table . AnotherAn important domain to consider here is the link between atherosclerotic disease and MPV. It is well known that MPV is raised in atherosclerotic cardiovascular disease and cerebrovascular ischemia. A study by Su et al. points to a significantly increased risk of coronary heart disease in patients with fibromyalgia . FurtherOur study is not, however, without limitations. The retrospective design of the study fails to discount patients who have other causes of hemogram alterations like viral fever, drugs, and smoking. Further prospective studies can assess this flaw. Such studies can simultaneously also assess the cardiovascular risk status and cytokine profiles to improve the clinical relevance.From the current study, an inference can be made that there is a relation between MPV and fibromyalgia severity. The other hematological markers do not show any relation with disease severity. The importance of MPV could be linked with IL-8, which is a key factor for both platelet activity and fibromyalgia etiopathology. This study also suggests that MPV is a cost-effective tool that can be utilized to diagnose or stratify the severity of fibromyalgia even in the peripheral centers of rural India. Future long-term follow-up studies can better substantiate this study.


Introduction: With an increasingly ageing population, there is a growing impact of fragility hip fracture on the healthcare system and on society as a whole. Oral and injectable analgesics are often insufficient whilst traction and regional blocks do not allow patients to be discharged easily. While the conventional approach of ultrasound-guided anterior hip pericapsular neurolysis can help a lot of inoperable hip fracture patients to relieve their fracture pain and facilitate subsequent nursing care, enormous technical challenges are encountered in some cases. In this retrospective case study, we evaluated the overall pain and functional outcomes of our modified approach of anterior hip pericapsular neurolysis for inoperable hip fractures using the IDEAL framework. Method: This retrospective case series studied patients with acute inoperable hip fracture who received the modified approach of anterior hip pericapsular neurolysis from January 2018 to June 2019 according to the IDEAL recommendations. The modified approach consisted of pericapsular nerve group (PENG) injection, iliopsoas plane infiltration, and the sagittal approach of obturator nerve articular branches (ONAB) injection. Subsequent alcohol neurolysis would be performed in the same setting if there were positive diagnostic blocks. Assessments were carried out on post-intervention day 5. The primary outcome was pain intensity during hip flexion at 80 degrees in the recumbent position and during gentle hip internal and external rotation using an appropriate pain scoring tool. The secondary outcomes were the range of tolerable hip flexion and occurrence of any lower limb neurological deficit because of the procedure. Interim outcomes were also briefly evaluated. Results: Among the 74 patients who were reviewed in the study period, the median dynamic pain at hip flexion 80° (p < 0.001) and on gentle hip external and internal rotation (p < 0.001) was significantly reduced from a composite score of 3 (severe pain) to 1 (mild pain) on post-intervention day 5 after the modified approach of hip neurolysis. This translated to 72% of patients achieving satisfactory pain control, which was defined as a composite pain score of ≤1 on hip flexion at 80°. Functionally, the mean range of tolerable hip flexion significantly improved from 39.7° at baseline to 74° on post-intervention day 5 (p < 0.001). Transient and reversible hypotension was seen in about 10% of the patients. No other major procedural adverse event was noted. Interim follow-up at 4–6 months post-intervention revealed that more than 95% of patients continued to have satisfactory dynamic pain control . According to the IDEAL classification, this study could be ranked as stage 2a (development). Conclusions: Our findings suggested that anterior hip pericapsular neurolysis using a modified approach could offer consistent and satisfactory analgesic and functional benefits to a majority of patients with inoperable hip fractures during the interim of the fracture healing process, and it was potentially safer than the conventional approach. This technique might have achieved its readiness to proceed to the next stage of research according to the IDEAL framework. The growing impact of fragility hip fracture on the healthcare system and on society has become a major concern worldwide. Despite the advances in perioperative medicine and anaesthetic care, a minority of frail patients are still too ill to be surgical candidates. Hip fracture analgesia generally includes non-pharmacological modalities, oral and injectable analgesics, traction and regional nerve block ,2. HowevWe hence developed a novel modified approach to tackle these clinical challenges in late 2017. From January 2018 onwards, as a standard institutional practice, we fine-tuned our technique of anterior hip pericapsular neurolysis that was originally published in our first case series . The modThis was a preliminary retrospective analysis of the outcomes of a modified approach of alcohol neurolysis of the femoral nerve articular branches (FNAB), accessory obturator nerve, and the obturator nerve articular branches of the hip joint in the format of case series. The study design followed the IDEAL framework.Hip fracture patients were evaluated by an anaesthetist and an orthopaedic surgeon. In the case that the patients were considered as too risky for operative management, conservative management would be considered with referral to the pain management unit in our institution. From January 2018 to June 2019, all such patients presenting to the pain management unit were evaluated for hip neurolysis. This treatment option was based on our previous satisfactory experience [For eligible patients, written informed consent was sought from the patients, their powers of attorney, or legal caregivers subject to the cognitive status of patients. The informed consent process consisted of the purpose of the intervention, a brief explanation of how we performed the intervention, the pros and cons of this intervention, and the potential risks which included but were not limited to the following: treatment failure, procedural discomfort, wound infection, wound hematoma, vascular injury, transient neuritis, systemic side effects of alcohol injection and allergy. As per our institutional practice, this intervention was arranged as an emergency procedure in the hospital emergency operation list and was performed in either the operation theatre or in the regional block corner in our operation suite during office hours. It was performed by a pain specialist or anaesthesia specialist who was under pain medicine training, with the support from one or two pain nurses.Institutional approval of the study was sought from the New Territories West Cluster (NTWC) Research and Ethics Committee, Hospital Authority, Hong Kong (ref no.: NTWC/REC/21063).In addition to the classical PENG injection, our modified approach highlighted the addition of pericapsular infiltration in the iliopsoas plane to cover the low articular branch of the femoral nerve and a sagittal approach to target the ONAB. The algorithm was still used to perform diagnostic blocks, followed by alcohol neurolysis 10 min later for those with a positive diagnostic block in the same setting under real-time ultrasound guidance . In the modified approach, the procedure consisted of 3 needle insertions with the use of 22-gauge 10 cm Quincke needles. The first needle for the high femoral nerve articular branches (high FNAB branches) and AON was inserted in the same way as the PENG approach between the anterior inferior iliac spine (AIIS) and the iliopubic eminence (IPE) deep to the psoas tendon . A seconStandard monitoring with electrocardiogram were routinely applied to all patients, and a functioning intravenous access was ensured before the intervention commenced. A pain nurse was responsible for monitoring the clinical status of patients and their vital signs. Resuscitation drugs  and sedative drugs (midazolam) were on standby for every patient.Following the procedure, the follow-up assessments were performed by pain nurses 20 min after the neurolytic procedure and on post-intervention day 5 at the hospital. We measured tolerable passive hip flexion with a goniometer, as well as pain intensity during hip flexion at 80 degrees in the recumbent or semi-recumbent position and upon gently rotating the hip internally and externally. We also documented any lower limb neurological deficit along the femoral nerve and obturator nerve distribution by checking the cold sensation to ice.In this patient population, it is not uncommon to have cognitive impairment, leading to difficulty in applying a single pain assessment tool towards them. As such, the Numeric Rating Scale (NRS), Verbal Descriptive Scale (VDS), or Pain Assessment in Advanced Dementia Scale (PAINAD) was used when appropriate. While NRS and VDS are popular pain assessment tools, older adults preferred the VDS when given a choice ,9,10,11.The primary outcome measure was the dynamic pain score on hip flexion to 80 degrees on post-intervention day 5 compared with that before pain intervention. Subject to their cognitive status, one of the above pain assessment scales was used as applicable. The secondary outcomes were the dynamic composite pain score on gentle external and internal hip rotation which referred to rotating the hip gently until an obvious hip rotation was observed and usually involved 5 degrees of movement, and the tolerable hip flexion measured by a goniometer on post-intervention day 5 compared with those before neurolysis. The range of movement served as the functional outcome assessment. The percentage of patients who could achieve a satisfactory pain control, which is defined as a composite pain score 0–1 at hip flexion 80 degrees, was also evaluated. Interim outcomes on dynamic pain control were also evaluated in the outpatient clinic at post-intervention 4 to 6 months. Adverse events were defined as unfavourable and/or unintended findings , or symptoms associated with the study procedure.The number of patients recruited in this retrospective study was reported. Wilcoxon signed rank test was used to compare the median dynamic composite pain scores with the baseline. T test was used to analyse the mean degree of tolerable hip flexion. SPSS version 26  was used for analyses.p < 0.001). The median composite pain score during gentle hip internal and external rotation reduced from 3 at baseline to 1 on post-intervention day 5 (p < 0.001) (p < 0.001). The mean of differences between day 5 and baseline was 34.3°   . Functio.8–39.8) .If we set our criterion of satisfactory pain control as a composite pain score ≤ 1 on hip flexion 80 degrees, 72% of the patients would meet this criterion. During the interim follow-up at 4 to 6 months after intervention, 47 patients attended and 45 of them reported satisfactory dynamic pain control (composite pain score ≤ 1) on hip flexion and gentle hip external and internal rotation. Among these 47 patients, 32 suffered from fracture neck of femur whilst 15 suffered from trochanteric fracture. The remaining patients either defaulted or passed away. The two patients who still suffered from significant hip pain were from the fracture neck of femur group.We observed that around 50% of patients experienced a transient burning sensation which lasted for a few minutes after alcohol injection and then subsided spontaneously. However, we did not notice any recurrence of such burning sensations after the local anaesthetic effect wore off. There were seven patients (around 10%) who developed transient hypotension in the post-anaesthetic care unit (PACU) after the neurolytic procedure. All responded to fluid therapy and vasopressor treatments and could be discharged to the general ward afterwards. There was no report of lower limb sensory deficit as a result of femoral or obturator nerve block in all patients on post-intervention day 5. The overall 30-day mortality rate was 12.5%.Regarding the IDEAL evaluation, this study was classified as stage 2a (development). Despite a retrospective nature of the study, it fulfilled the criteria of stage 2a (development) in terms of the number of patients according to a previous report implementing the IDEAL framework by Gerullis et al. . It provWith the increasing elderly population globally, anterior hip neurolysis under ultrasound guidance has provided an important treatment option in the management of fragile hip fracture patients with severe comorbidities, and the results in our study were consistent with those in our first case series of anterior hip pericapsular neurolysis via the conventional approach . Both thWe arbitrarily selected 80 degrees as the cut-off for our hip flexion assessment because this degree of hip flexion would indicate the ability of sitting up comfortably. Pain control during hip rotation could reflect comfort in bed turning during nursing care. Since it usually takes several days for the full effects of alcohol neurolysis to be seen , post-inThe two patients who persisted to have significant pain in long-term follow-up suffered from fracture neck of femur. It is well recognized that there was a 10–30% risk of non-union, subsequently avascular necrosis in femoral neck fracture despite surgery ,21,22. TMotor assessment was an important area to illustrate in this motor-sparing technique. Nonetheless, it was challenging to objectively assess motor function in this group of patients since quite a few of them were cognitively impaired and there might have been significant pre-existing muscle wasting in some patients. Spontaneous lower limb movement might illustrate the integrity of motor function, but it was by all means non-specific to the femoral and obturator nerves. The disruption of lower limb mechanics as a result of fracture might also hinder lower limb movement. As such, we chose to use sensory testing by cold sensation as a surrogate to the integrity of the motor branch of the femoral and obturator nerves.While the high FNAB branches consistently course over the periosteal surface of the pubis between the AIIS and IPE, the low FNAB branches are fewer in number and pierce the iliopsoas before reaching the iliofemoral ligament, and there is no relation to any sonographically identifiable landmark ,24,25. TOur modified approach to the ONAB would have the following advantages over the ordinary oblique approach published in our first case series . First, Transient burning sensation immediately after alcohol injection is a potential pitfall of this treatment modality despite the prior local anaesthetic injection. According to our study, this side effect was transient and could be much minimized if we waited adequately after local anaesthetic injections. Prior explanation to patients could also facilitate tolerance to the transient discomfort. The absence of subsequent recurrence of burning sensation could be explained by the absence of skin innervation from the articular branches. More burning discomfort would result from absolute alcohol injection if a lower volume of local anaesthetics is injected beforehand. This, however, can yield a higher final alcohol concentration. It is commonly believed that a resultant concentration of at least 50% alcohol is required for a long-lasting neurolytic effect . RegardiSince it was difficult to standardize perioperative analgesics in this group of patients and it was also common for them to have multiple analgesics for other pain conditions, perioperative analgesic consumption was not evaluated.Methodology wise, we adopted a new reporting approach, the IDEAL framework that was proposed in 2009 by McCulloch et al. . This deThere are several limitations in this study. First, it was a retrospective case study, and this was subject to various biases. Second, the retrospective nature was not a desirable research format for the IDEAL classification stage 2a. Third, although the sagittal approach of targeting ONAB with a caudal-to-cephalad needle trajectory can avoid femoral vessels and ONAB can be better visualized, it is still unknown about the desired volume of absolute alcohol balancing the safety of obturator main trunk involvement and the maximum analgesic benefit. Other limitations included a lack of documentation of perioperative analgesic consumption, which might lead to biases in interpreting our composite pain score and a lack of formal testing of motor nerve integrity, such as a nerve conduction study that might be overlooked by simple clinical examination in cognitively impaired patients. Finally, it is also unknown about the desired injectate volumes for iliopsoas infiltration and PENG injection to faithfully cover all articular branches while minimizing the systemic side effects of absolute alcohol.We conclude that anterior hip neurolysis by our novel modified approach  provided satisfactory and consistent analgesic and functional benefits to the majority of patients with inoperable hip fractures. Compared with the classical approach (PENG approach and oblique approach to ONAB), this modified approach can offer a better safety profile theoretically. According to the IDEAL framework, despite some pitfalls, our study has shown the safety and stability of the modified anterior approach and can be classified as stage 2a. Complemented by our other retrospective case series on posterior hip pericapsular neurolysis , this ch


Patients with zoster-associated pain exhibit a variety of sensory symptoms and forms of pain and complain of different pain patterns. The purpose of this study is to subgroup patients with zoster-associated pain who visited a hospital using painDETECT sensory symptom scores, analyze their respective characteristics and pain-related data, and compare similarities and differences among the groups.The characteristics of 1,050 patients complaining of zoster-associated pain and pain-related data were reviewed retrospectively. To identify subgroups of patients with zoster-associated pain according to sensory symptom profiles, a hierarchical cluster analysis was performed based on the responses to a painDETECT questionnaire. Demographics and pain-related data were compared among all subgroups.Patients with zoster-associated pain were classified into 5 subgroups according to the distribution of sensory profiles, with each subgroup exhibiting distinct differences in the expression of sensory symptoms. Patients in cluster 1 complained of burning sensations, allodynia, and thermal sensitivity, but felt numbness less strongly. Cluster 2 and 3 patients complained of burning sensations and electric shock-like pain, respectively. Cluster 4 patients complained of most sensory symptoms at similar intensities and reported relatively strong prickling pain. Cluster 5 patients suffered from both burning and shock-like pains. Patient ages and the prevalence of cardiovascular disease were significantly lower in cluster 1. Patients in clusters 1 and 4 reported longer pain duration compared with those in clusters 2 and 3. However, no significant differences were found with respect to sex, body mass index, diabetes mellitus, mental health problems, and sleep disturbance. Pain scores, distribution of dermatomes and gabapentinoid use were also similar among the groups.Five different subgroups of patients with zoster-associated pain were identified on the basis of sensory symptoms. A subgroup of younger patients with longer pain duration showed specific and distinct symptoms, such as burning sensations and allodynia. Unlike patients with acute or subacute pain, patients with chronic pain were associated with diverse sensory symptom profiles. Cases of herpes zoster occur in at least 1 million people in the United States every year, and the incidence rate has been increasing worldwide over the past 20 years .Patients with zoster-associated pain, including herpes zoster infection and PHN, complain of diverse patterns of sensory symptoms despite the common cause of the pain. Some patients complain strongly of spontaneous pain, tingling sensations, and electric-shock-like pain, while others suffer from hypersensitivity to light touch or temperature. A simple and validated patient-reported screening questionnaire, painDETECT, can detect these characteristic sensory abnormalities , 5. ReseThe goal of this study is to classify patients with zoster-associated pain into groups that clearly represent each characteristic using a cluster analysis technique and to identify any similarities and differences in the characteristics of each cluster groups.This study was approved by the Institutional Review Board of Yonsei University Health System, Seoul, Republic of Korea (No. 4-2022-0819). As it is a retrospective observational study, the requirement for obtaining informed consent from the patients was waived. This manuscript complies with the STROBE checklists applicable to observational studies. Adult patients who complained of zoster-associated pain at their first visit from January 2016 to August 2021 were enrolled. Patients with incomplete medical records or those who did not complete the painDETECT questionnaire were excluded.Sensory symptom profiles due to herpes zoster were described using the painDETECT questionnaire during the patient's first visit to our clinic. Patients complaining of neuropathic pain caused by herpes zoster freely described their symptoms and filled out the validated Korean version of the painDETECT questionnaire under the supervision of a researcher . The quePatient characteristics and pain-related data were gathered from electronic medical records. Patient characteristics included age, sex, body mass index (BMI), presence of diagnosed comorbidities, and sleep disturbances. Diagnosed comorbidities included cardiovascular disease, diabetes mellitus, and mental health problems that required continuous medical intervention with regular hospital visits. Mental health problems were defined as those requiring psychiatric treatment or medication due to depression, anxiety, and stress over the past year. Average and maximum pain scores using a numeric rating scale (NRS), duration of pain, dermatomes, and the use of a gabapentinoid at the time of visit were identified as pain-related factors. The duration of pain was classified into < 1 month (acute), 1–3 months (subacute), and ≥ 3 months (chronic).post hoc test or a chi-squared post hoc difference was used to determine the intergroup difference between the mean of the groups when significant differences existed. Statistical Package for the Social Sciences, version 26.0  was used to analyze the data. A P < 0.05 was considered statistically significant.Continuous variables were shown as mean ± standard deviation (SD), and categorical variables was tabulated using numbers (percentage). The normality of distribution was evaluated using a Shapiro–Wilk test. Differences among the cluster groups were analyzed using one-way analysis of variance and chi-squared tests. A Tukey's A hierarchical cluster analysis was performed for subgrouping according to relevant sensory symptoms of zoster-associated pain . A hieraThe cluster is represented by a pattern of questionnaire scores, indicating the typical pathological structure of each group. All profiles were given individually adjusted scores (see above). Heuristic interpretations of clusters were provided by experts. Statistical analysis was not performed because this was a heuristic approach.During the study period, 1,434 patients visited our clinic for zoster-associated pain. Among these patients, 384 met the exclusion criteria, leaving 1,050 patients in the analysis .2. Cardiovascular disease, diabetes mellitus, and mental health problems were reported for 362, 207, and 166 patients, respectively, and more than 50% of the patients complained of sleep disturbances. The mean average pain score was 5.57 and the maximum pain score was 6.29 on the NRS. A total of 302 patients were assessed at < 1 month after zoster infection, 315 patients had passed 1–3 months, and 433 patients complained of pain for more than 3 months. There were 201 patients with zoster in the trigeminal and facial nerve areas, 167 with zoster in the cervical dermatomes, 546 in the thoracic dermatomes, and 136 in the lumbosacral dermatomes. Approximately 80.6% of patients were taking a gabapentinoid to relieve pain.Demographic profiles and pain-related data for these patients are shown in A cluster analysis was performed using the Korean version of painDETECT to identify the subgroups of patients showing typical sensory neuropathic symptoms as 5 distinct clusters . Patientp = 0.001; cluster 1 vs. 3, p = 0.002; cluster 1 vs. 4, p = 0.006; cluster 1 vs. 5, p = 0.009) and the prevalence of cardiovascular disease  were significantly lower in cluster 1 than those in the other clusters. In addition, clusters 1 and 4 had a relatively high proportion of patients complaining of pain for more than 3 months (chronic) compared to clusters 2 and 3 . However, there were no significant differences in sex, BMI, medical comorbidities including diabetes mellitus and mental health problems, and sleep disturbance between clusters. Also, the average and maximum pain scores on the NRS, the dermatomes to which the lesion belongs, and the use of gabapentinoids were similar between cluster groups.A comparison was conducted to determine whether there was a difference in the characteristics and pain-related data of the patient groups between the 5 clusters . PatientPatients with zoster-associated pain account for a large proportion of those with neuropathic-like pain symptoms. Despite an increased understanding of the pathophysiological mechanism of neuropathic pain, treatment of zoster-associated pain remains challenging and insufficiently effective. This study was designed to classify patients with zoster-associated pain based on abnormalities in sensory symptoms because it would be ideal and effective to stratify patients according to the pain mechanism .Distinct sensory abnormalities associated with pain perceived by patients can be self-assessed, and they are largely divided into spontaneous sensory sensation , stimulus-evoked positive sensory symptoms , and stimulus-evoked negative sensory symptom (numbness) , 16. TheAn analysis of patients with zoster-associated pain on the basis of sensory phenotype found that patients in cluster 1 suffered primarily from thermally evoked pain and mechanical allodynia, but not numbness. Allodynia is due to central spinal cord sensitization and is induced by activation of touch-sensitive cutaneous Aβ-fibers that terminate in synapses of nociceptive second-order neurons in the central nervous system . ThermalIn the present study, the patients belonging to cluster 1 were younger than those of the other clusters. Although results conflicted depending on the animal model and experimental stimuli, preclinical data suggest that advanced age may be related to increased pain sensitivity . HoweverThis study has several limitations. As a retrospective study conducted in a single center, selective bias or information bias is possible. PainDETECT is a reliable questionnaire to assess differences in sensory perception intensity, but there is a paucity of interpretation of evoked pain and negative symptoms. Also, pain perceptions are subjective and could be confounded by personal factors . To miniIn conclusion, despite the common cause of the pain, some differences in the distribution of sensory profiles were evident among patients with zoster-associated pain. In particular, a subgroup with younger patients who experienced longer durations of pain reported specific and distinct positive symptoms, such as burning sensations and allodynia. Unlike patients with acute or subacute pain, patients with chronic pain were associated with diverse sensory symptom profiles. These results indicate that patients can be subgrouped according to patient-reported sensory symptoms of zoster-associated pain, although the central and peripheral mechanisms of pain vary among subjects. This approach may help determine the most appropriate pain treatment for each individual of this population.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Institutional Review Board of Yonsei University Health System, Seoul, Republic of Korea. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.Conceptualization, writing—review and editing, and supervision: SHK and KBY. Software and validation: HJK and MK. Formal analysis and data curation: HJK and YSY. Writing—original draft preparation: HJK and SHK. Project administration and methodology: HJK. Funding acquisition: SHK. All authors contributed to the article and approved the submitted version.


This study has two aims: to evaluate long‐term chronic pain and complications after circular incision transabdominal preperitoneal inguinal hernia repair (C‐TAPP) and compare outcomes of unilateral and bilateral inguinal hernia cases.A postoperative patient questionnaire was used to evaluate pain and complications in 1546 patients who underwent C‐TAPP for simple inguinal hernia. Questions concerned satisfaction with surgery, pain at rest, pain at movement, mesh discomfort on a 10‐point scale, and complications, such as recurrence. Patients were classified into unilateral (U Group) and bilateral (B Group) groups, and propensity score matching was performed to compare long‐term chronic pain and complications.P = .726), at movement (P = .712), or mesh discomfort (P = .981) were detected between the U and B groups. Postoperative complications occurred in 2.1% of all patients, and the recurrence rate was 0.3%. In the post‐match comparison, no differences in complications with Clavian‐Dindo classification ≥III  were detected.The questionnaire return rates were 77.5% (1034 cases) and 79.9% (135 cases) in unilateral and bilateral cases. The frequency of moderate‐to‐severe (≥4 points) pain at rest, pain at movement, and mesh discomfort were 3.2%, 3.6%, and 4.5%, respectively. After propensity score matching, no significant differences in pain at rest (C‐TAPP, which focuses on the layered structure, showed acceptable results for long‐term chronic pain. Bilateral cases did not have worse pain or complications compared to unilateral cases. Circular incision TAPP, which focuses on the layered structure, showed acceptable results for long‐term chronic pain. Bilateral cases did not have worse pain or complications compared to unilateral cases. We often experience the incidental finding of an asymptomatic inguinal hernia on the contralateral side during surgery. In such cases, there is no clear conclusion about whether both sides should be repaired simultaneously. Whether there is a difference in complications and pain between bilateral and unilateral cases affects the decision of the initial surgical plan. However, only a few studies have examined the impact of bilateral cases on postoperative complications and pain compared with unilateral cases.In this study, we conducted a postoperative questionnaire survey to evaluate the surgical results of C‐TAPP, in terms of chronic pain and recurrence, and compared unilateral and bilateral cases.Unlike cancer surgery, few institutions conduct long‐term surveillance for inguinal hernia repair; thus, visiting the hospital for follow‐up is difficult. Postoperative questionnaires are a common method to investigate the long‐term prognosis when patients do not visit the hospital for follow‐up.22.1We performed 2141 inguinal hernia repair procedures  in inguinal hernia patients aged 16 years or older at our institution from April 2006 to March 2014. Patients undergoing emergency surgery, anterior approach, post‐prostatectomy, recurrent surgery, and simultaneous other surgeries were excluded . As a result, 1681 patients  who underwent TAPP for simple inguinal hernia were included in the study. A postoperative inguinal hernia questionnaire was used to collect data. Unilateral cases were defined as the Unilateral Group (U Group), and bilateral cases were defined as the Bilateral Group (B Group). The protocol for this research project has been approved by a suitably constituted Ethics Committee of the institution and it conforms to the provisions of the Declaration of Helsinki . As this is a retrospective study, patient consent was obtained on an opt‐out basis.2.2We used a circular incision around the peritoneal processus vaginalis Figure . The per2.3The mesh was placed in a layer as far away from the nerves as possible. On the dorsal side, the mesh was placed between the preperitoneal fascia areolar layer and the peritoneum. On the head side, the mesh was placed between the APRS and the preperitoneal fascia areolar layer Figure .2.4Blood tests were performed before and the day after the surgery. Basically, the patient was discharged from the hospital the day after surgery. At the time of discharge, 10 doses of oral NSAIDs were prescribed for the patient. If no abnormalities occurred, the follow‐up period was set at 3 months postoperatively, and the follow‐up period was extended for symptomatic patients. The patients were advised to visit our outpatient clinic if any symptoms occurred after the follow‐up.2.5The presence or absence of recurrence after the follow‐up period was included in the questionnaire. Questions about surgical satisfaction , pain at rest and pain at movement according to the Numeric Rating Scale (NRS) , and mesh discomfort  were also included in the questionnaire Figure .19 The2.6The first questionnaire was sent by mail 1 year after the end of the study period, excluding patients whose deaths were confirmed in the hospital's medical records. For those cases that did not reply, the questionnaire was resent after 1 year and 11 months. For those cases that did not return the second questionnaire, we requested contact by phone. Patients with recurrence (on the questionnaire) were checked by telephone and examined in the outpatient clinic if necessary.2.7U tests were used for continuous variables. Wilcoxon rank‐sum tests were used for pain level and satisfaction in the questionnaire. A significant difference was defined as P < .05.Statistical analyses were performed using the statistical software, EZR.33.1The number of cases in the questionnaire study is shown in the flowchart Figure . A total3.2Among the 1501 unilateral cases selected, 45 deaths were confirmed by medical records, and 1456 questionnaires were prepared. However, the addresses on 82 of these were invalid, leaving 1374 questionnaires that were mailed. Twenty‐three of the surveyed patients were confirmed to be deceased by the questionnaire, and 17 patients were unable to answer due to dementia. Of the remaining questionnaires, 1034 were returned and 300 cases were not returned. The response rate was 77.5%.3.3Among the 180 cases selected, no deaths were confirmed by our medical records and eight patients had unknown addresses. Therefore, 172 questionnaires were sent out. Three patients were unable to answer the questionnaire due to dementia. Of the remaining questionnaires, 135 were returned and 34 were not returned. The response rate was 79.9%.3.4Patient backgrounds before and after propensity score matching were categorized into Unilateral Cases (U Group) and Bilateral Cases (B Group), as shown in Table 3.5P < .001). No significant differences in the amount of bleeding, postoperative hospital stay, the proportion able to be discharged on the day after surgery, intraoperative complications, postoperative complications, and frequency of complications (Clavian‐Dindo classification ≥III) were detected between the two groups .Chronic pain of inguinal hernia is generally defined as pain that persists for at least 3 months after surgery.Interestingly, no differences in the rate of chronic pain were detected between groups U and B. We assumed that the rate of chronic pain would increase with repairs for two lesions, but no differences were detected. In TAPP, a contralateral inguinal hernia may be found incidentally at the time of surgery, even if the patient is asymptomatic. However, significantly higher postoperative complications and reoperation rates have been reported when repairing bilateral cases, which are disadvantages of simultaneous repair.The degree of a patient's preoperative symptoms may affect the postoperative symptoms. However, since this was an 8‐year retrospective study, quantitative data on preoperative symptoms were not collected. In addition, the number of analgesic medications, which is the most objective assessment of pain, could not be accurately measured because of the long‐term follow‐up of patients with chronic pain. To simplify the questionnaire, we did not ask questions about neuralgia and numbness. The questionnaire was designed to be as simple as possible, but there were a few missing answers, mainly from the elderly. Although we tried to confirm the results by phone calls and other means, few cases could not be confirmed. These points may be the limitations of this study. Another limitation of this study was that this was a single‐center study, although the number of cases was not small. In the future, a system to follow up patients on a large scale, such as the creation of a nationwide registry of patients, should be established and examined.In conclusion, we performed C‐TAPP with emphasis on the layered structure. The results showed that the frequencies of moderate‐to‐severe long‐term pain at rest, pain at movement, and mesh discomfort were 3.2%, 3.6%, and 4.5%, respectively. Postoperative complications occurred in 2.1% of patients, and the recurrence rate was 0.3%. No differences in pain and complications were detected between the U and B groups before or after propensity score matching. The results of C‐TAPP are acceptable as a standard TAPP technique, and bilateral TAPP is not worse than unilateral TAPP in terms of pain and complications.Conflict of Interest: Authors declare no conflict of interests for this article.Informed Consent: As this is a retrospective study, patient consent was obtained on an opt‐out basis.Approval of the Research Protocol: The protocol for this research project has been approved by a suitably constituted Ethics Committee of the institution and it conforms to the provisions of the Declaration of Helsinki. Ethics Review Committee of Kariya Toyota General Hospital, Approval No. 205.


Pain is a fearful yet common symptom among lung cancer patients. This multicenter, cross‐sectional study was conducted to examine the current status of pain prevalence and management in lung cancer patients in northern China.A total of 18 hospitals across northern China were selected. Patients with primary lung cancer who visited the outpatient clinic or were admitted in the wards on a preplanned day were invited to complete a questionnaire. Meanwhile, physicians who had experience of treating primary lung cancer patients were also surveyed.A total of 533 patients and 197 physicians provided valid responses to the survey, of which 45.4% (242/533) of patients reported pain during the course of disease and 24.2% (129/533) of patients had experienced pain within the past 24 h. The mean average pain intensity by the brief pain inventory was 3.47 ± 1.55. The binary logistic regression analysis showed female gender and stage IV disease were significantly associated with the presence of pain. A total of 74.4% (96/129) of patients reporting pain within 24 h were taking analgesics. The most common reason for patients not using analgesics was that the pain was tolerable (48.2%), while the most common barriers to prescribing opioids as reported by physicians were fear of adverse reactions (43.7%) and fear of addiction (43.1%).Despite recognition of the importance of pain control by most physicians and an improvement in cancer pain management, inadequate treatment of cancer pain still exists in lung cancer patients in northern China. High‐quality pain education for both patients and physicians is needed in the future. We conducted a multicenter, cross‐sectional study in 18 hospitals across northern China to evaluate the prevalence and management of pain in lung cancer patients. Among the 533 patients surveyed, 45.4% (242/533) suffered pain in the course of their disease. Meanwhile, 24.2% (129/533) experienced pain within 24 h, only 74.4% (96/129) of whom were taking analgesics, suggesting inadequate treatment of cancer pain. There is still need for high‐quality pain education for patients and physicians. Lung cancer is one of the leading cancer entities and mortality worldwide, with an estimated 2.2 million new cancer cases and 1.8 million deaths in 2020.Although the influences of pain on clinical outcomes have attracted growing attention, undermanaged pain is still common in cancer patients. The major barriers to adequate pain control involve the physicians, patients, and healthcare system. Common professional‐related barriers include poor assessment of pain, inadequate knowledge and skill, and reluctance to prescribe opioids. From the patients' perspective, the barriers include cognitive factors (concern regarding disease progression or addiction), affective factors , and adherence to analgesic regimens.At present, data are lacking on the status of cancer‐related pain in Chinese lung cancer patients, including the prevalence, evaluation and management of cancer‐related pain, the reasons for undermedication, and patients' perception and physicians' knowledge of pain control. Although much effort has been devoted to uncover the underlying association between clinical‐pathological characteristics and treatment outcomes of lung cancer patients, few studies have investigated the possible factors affecting the incidence of lung cancer‐related pain, such as age, gender, stage of cancer and history of smoking. Therefore, we initiated a cross‐sectional study by questionnaire survey of participating patients and physicians from multiple centers in northern China, to evaluate the prevalence and characteristics of lung cancer‐related pain, the correlation between pain and clinicopathological factors, and the attitudes of patients and physicians towards pain control.A total of 18 participating centers in northern China were selected from January 16, 2018 to January 29, 2018, based on convenience sampling from two municipalities (Beijing and Tianjin), three provinces , and one autonomous region (Inner Mongolia). Each center performed the study on a single, prespecified day determined by randomization. Two sets of questionnaires were designed for patients and physicians, respectively, and distributed in the clinics and wards of relevant departments that treated lung cancer patients . The inclusion criteria of patients were: (1) pathologically diagnosed with lung cancer, (2) visited the outpatient clinic or admitted in the relevant wards, (3) had sufficient knowledge of spoken and written Chinese, and (4) consented to participate in the study. Physicians who had experience of treating primary lung cancer were surveyed.Questionnaires for patients included demographic data, presence and intensity of cancer pain, details of management, attitudes toward usage of analgesics, level of satisfaction with pain control, and their access to cancer pain education. The intensity of cancer‐related pain was evaluated with the brief pain inventory–short form (BPI‐sf). Questionnaires for physicians focused on previous education with pain control, and routine practice with assessment, management, follow‐up, and patient education of cancer pain. The responses to the questionnaire were collected in the form of face to face interview.χ2 test. A binary logistic regression model was established, using the presence of pain as the dependent variable and the categorized clinicopathological characteristics as the independent variables. All probability values are two‐sided, and p < 0.05 was considered statistically significant. All analyses were performed using SPSS software, version 22.0 (SPSS Inc).Patient characteristics were summarized using absolute numbers and percentages. Normal distribution of data is presented as mean ± standard deviation (SD). To identify factors significantly associated with the presence of cancer‐related pain, clinicopathological characteristics including gender, age, pathological type of lung cancer, smoking status and TNM stage were first categorized and examined by The study questionnaires were collected from 533 patients and 197 physicians who provided complete and valid responses. The mean age of the patients was 59.1 years range: 23–84), among whom 354 (66.4%) were male. A total of 166 patients (31.1%) were surveyed in the outpatient clinic, 367 patients (68.9%) were from the inpatient wards. Most patients had adenocarcinoma , and 310 patients (58.2%) presented with stage IV disease. Most of the physicians were medical oncologists . The demographic characteristics of the patients and physicians are summarized in Tables 3–84, amoAmong the 533 lung cancer patients, 242 patients (45.4%) experienced pain during the course of disease, 291 patients did not. A total of 125 patients (51.7%) experienced pain in one body site, 76 patients (31.4%) had pain in two body sites. The most common sites of pain were chest in 117 patients (48.3%), back in 81 patients (33.5%), and waist and abdomen in 39 patients (16.1%). The cancer pain was most frequently described as dull  or swelling pain . A total of 129 patients (24.2%) experienced pain within 24 h before survey, the mean average pain intensity (API) was 3.47 ± 1.55, and API was severe (7–10 points) in seven patients, moderate (4–6 points) in 46 patients, and mild (1–3 points) in 76 patients. The major characteristics of pain are summarized in Table n = 242) and patients without pain group (n = 291). The association of pain with the major clinicopathological characteristics of patients are listed in Table p = 0.020; TNM stage, p < 0.001). We then identified that gender (p = 0.040) and TNM stage (p = 0.007) significantly affected the presence of pain using a binary logistic regression model. As shown in Table Patients were divided into two groups based on whether they experienced pain: patients with pain group n = 22 and patn = 96) in the 129 patients who reported pain within the past 24 h, and 28.3% (n = 32) in the 113 patients who had experienced pain but not within the past 24 h. Notably, among the 33 patients who had pain within 24 h but were not taking analgesics, 17 reported the worst pain intensity of 4–6. The most common reason for not taking analgesics from the patients' responses was “can tolerate pain on own” . Seventy‐three out of the 108 patients using opioids reported constipation as one of the side effects, and 66 of them reported that physicians prescribed laxatives to relieve constipation.In the patients' survey, 95.0% patients (230/242) reported pain to physicians, and 83.1% patients (201/242) responded that their physicians would actively inquire and assess pain. A total of 52.9% patients (128/242) were taking analgesics for cancer pain, 44.6% patients (108/242) were receiving opioids. Specifically, the percentage of patients taking analgesics was 74.4% (Eighty‐seven (77.0%) out of the 113 patients who had experienced pain but not within the past 24 h were satisfied with their pain control, 18 patients (15.9%) were neutral, while eight patients did not provide an answer. Out of the 129 patients who had pain within the past 24 h, 73 (56.6%) were satisfied, 26 (20.2%) were neutral, 26 (20.2%) did not respond to the question, and four (3.1%) were dissatisfied. Of these, two patients reported the analgesics were not effective, whereas the other two thought their pain had been overlooked by physicians.A total of 85.8% of physicians (169/197) reported that pain management was included as part of medical education, and 94.9% of physicians (187/197) had received continuing medical education (CME) regarding cancer pain management. A total of 59.4% of physicians (117/197) agreed to carry out at least 5 h of cancer pain CME every year. However, only 46.2% of physicians (91/197) actually received over 5 h of cancer pain CME during the past year, and 88.8% (175/197) of physicians reported that they referred to mainstream guidelines for cancer pain management, including the World Health Organization Cancer Pain Relief , the Chinese Guidelines for the diagnosis and treatment of cancer pain , and the National Comprehensive Cancer Network guidelines for adult cancer pain .A total of 84.7% of physicians 167/197) conducted pain‐screening routinely, while 9.6% (19/197) only did it “sometimes.” Numeric rating scale (NRS) was most commonly used for pain assessment , followed by visual analog scale (VAS), verbal rating scale (VRS) and BPI. A total of 18.3% (36/197) of physicians could control patients' pain within 1 day upon appropriate medication, while 72.6% (143/197) of physicians required 2–3 days, and 96.4% (190/197) of physicians were satisfied with cancer pain management. A total of 89.3% (176/197) of physicians agreed that opioids were the first‐line analgesics in cancer patients with moderate–severe pain, and 85.8% (169/197) preferred oral opioids . The most common barriers to prescribing opioids as reported by physicians were patients' fear of adverse reactions , patients' fear of addiction , and worry by physicians that adverse reactions may not be tolerated  of physicians declared that they provided education on pain management to patients. The content of patient education included general knowledge of pain, assessment and treatment options of pain, and management of adverse reactions with analgesics. The frequencies of follow‐up with outcomes of pain relief were once every week for 80 physicians (40.6%), once every month for 76 physicians (38.6%), and once every 1–3 months for 21 (10.7%) physicians. Seven physicians (3.6%) reported the follow‐up interval of more than 3 months, while 13 physicians (6.6%) did not follow up their pain control outcomes.Pain is one of the most common symptoms in cancer patients, and it can be secondary to malignant tumors or treatment, which seriously affects the quality of life of patients. Pain has been thought to affect survival in cancer patients, although the mechanism remains unknown. A meta‐analysis demonstrated that pain was a prognostic factor for shorter survival, in addition to demographic and clinical factors.In the present cross‐sectional study, one important finding was that 45.4% of lung cancer patients reported suffering from pain, which may represent a period prevalence. Meanwhile, 24.2% of patients had pain within 24 h, this was regarded as a point prevalence, reflecting patients immediately in need of appropriate pain control. Two systemic reviews conducted in the western hemisphere have reported that the overall prevalence of pain in lung cancer patients was 47% and 55% in 2004 and 2007, respectively.In the present study, chest was the most common site of pain, which could be the result of pleural involvement or bone metastasis. Moreover, it has been found that roughly half of patients who underwent thoracic surgery reported clinically significant pain, while its management was not sufficient to result in acceptable outcomes.Risk factors for the development of pain had been investigated in malignancies other than lung cancer. For instance, in a previous study, higher BMI, fewer schooling years, not smoking, chemotherapy, hormone therapy, and radiotherapy were significantly associated with higher odds for the development of chronic pain in breast cancer patients.Lack of time and knowledge about cancer pain assessment and management in healthcare providers are the leading causes for inadequate pain control among oncology patients.Physicians' considerations when prescribing opioids to patients were fear of addiction and adverse reactions, and these findings are consistent with previous studies of the major barriers of cancer pain management.Our study had limitations. The cross‐sectional design was incapable of showing the evolution of lung cancer pain prevalence and management over time. Additionally, most centers were tertiary hospitals with relatively high standards of care, and convenience sampling might have introduced selection bias.In conclusion, despite the recognition of the importance of pain control by most physicians and an improvement in cancer pain management, inadequate treatment of cancer pain still exists in lung cancer patients in northern China. As the largest epidemiology study evaluating pain in Chinese lung cancer patients to date, this study has provided some key facts to understand the current status of pain management in a common malignancy. In the future, efforts should be made to improve the quality of pain management education for lung cancer patients and physicians.The authors declare that there are no conflicts of interest.


The use of opioids to treat pain can increase the risk of long-term opioid dependency and is associated with negative patient outcomes. The objective of this study was to present the initial results following the implementation of Emergency-Department Alternatives to Opioids (ED-ALTO), a program that encourages the use of non-narcotic medications and procedures to treat pain in the Emergency Department (ED). We used a pre- and post-implementation study design to compare in-ED opioid utilization, as well as ED-ALTO medication and procedure use in the year before and after the program’s implementation. After ED-ALTO’s implementation, there was a decrease in opioid utilization in the ED and an increase in ED-ALTO medication use. Additionally, there was an increase in ED-ALTO procedure utilization and the complexity of conditions treated with ED-ALTO procedures, including the use of regional nerve blocks for shoulder dislocations and hip and rib fractures. In 8 of the 12 months following ED-ALTO’s implementation, a lower proportion of patients receiving ED-ALTO procedures received an opioid, and the opioid dosage was lower compared to patients with the same diagnoses who received standard care. The continued expansion of ED-ALTO programs across the US may serve as a mechanism to reduce opioid utilization and safely and successfully treat pain in ED settings. Pain is one of the most common reasons patients seek emergency medical care; accordingly, pain-related complaints account for up to 42% of all Emergency Department (ED) visits in the United States ,2. In orInnovative programs that encourage the use of non-narcotic medications and procedures to treat pain in the ED have recently been evaluated ,9,10,11.While several published studies have demonstrated success through the use of ED-ALTO programs, no studies have evaluated ED-ALTO programs utilizing a combination of both medication- and procedure-based approaches to the treatment of pain. The objective of this study is to present the initial results of the implementation of a multi-faceted ED-ALTO program at a Level I Trauma Center ED located in the Southeastern US that utilizes alternative medication- and procedure-based approaches to manage pain in the ED. This program includes systematic training to create a culture of change within our ED and create sustainable, opioid-free treatment options to help treat various pain complaints commonly cared for in the ED.The ED-ALTO study was implemented on 1 August 2021, within a large, Level 1 Trauma Center in South Carolina in the Southeastern part of the United States. This research implemented a pre- and post-implementation study design comparing in-ED opioid utilization as well as ED-ALTO medication and procedure use. Data collection took place 12 months before the intervention and 12 months following implementation to reduce seasonal variability. The primary study location’s ED is a regional tertiary care referral center for the largest health system in the state. The ED sees approximately 100,000 adult patients a year and contains a three-year emergency medicine residency program with thirty residents. This study was approved by the Prisma Health-Upstate Institutional Review Board.English-speaking adult patients presenting to the ED with pain-related conditions were eligible for ED-ALTO treatment. Our intervention targeted low-acuity pain conditions; therefore, patients with an Emergency Severity Index (ESI) below 3 were not eligible. The ESI is a triage tool that uses five levels from 1 (most urgent) to 5 (least urgent) to estimate the severity of illness and resource needs. Additionally, patients who were incarcerated or otherwise unable to provide informed consent to participate were excluded. Study personnel were on-site in the ED one day a week to identify and enroll eligible patients for ED-ALTO medication and procedure use. On enrollment days, study personnel monitored the ED track-board in real time for patients arriving with a pain complaint or were contacted by an ED physician for a patient consult within the electronic health record (EHR) system. If the patient was deemed eligible, the study coordinator would approach the patient to explain the study and ask for their consent to participate.ED-ALTO therapies included the use of alternative medications and procedures to treat pain. A specific order set containing various medication choices based on a previous publication  was addePhysicians’ education with respect to ED-ALTO medications and procedures was provided through multiple channels, including (1) direct bedside training, (2) live lectures/simulation education, and (3) asynchronous recoded video lectures, simulation sessions, and reading materials. Direct bedside training was provided on our scheduled “Opioid-free days”, which occurred one day a week. The goal of “Opioid-free days” was to encourage the use of ED-ALTO therapies on these days and reduce opioid prescription. On “Opioid-free days”, direct bedside support, training, and education was provided by two physicians: the Division Head of Anesthesia and Pain Management for the health system (K.W.) and a local practitioner of Acupuncture and Oriental Medicine (W.H.). On the “Opioid-free days”, these physicians were available from 10 a.m.–6 p.m. to provide direct procedural support and bedside training to the attending ED physicians, resident physicians, physician assistants, and nurse practitioners performing ED-ALTO procedures for patients.® , and included patient demographics, use of ED-ALTO medications, procedures, and opioid utilization. Encounter-level data elements included date of service, principal visit diagnosis, age, payer status, disposition, and patient sex. T-tests and Chi-square tests were performed to assess differences in the pre- and post-implementation samples as well as the utilization of opioids and ED-ALTO medications. Statistical significance was set at p < 0.05. The frequency of ED-ALTO procedure use was reported by diagnoses groups for the pre- and post-implementation periods.Data were collected for 12 months pre-implementation from 1 August 2020, to 30 July 2021, and for the same 12-month period after implementation, which was from 1 August 2021, to 30 July 2022. Data were provided from the EHR, EpicWe conducted a matched analysis in the post-intervention period. We found all diagnoses codes for patients receiving ED-ALTO procedures and matched them to patients with the same diagnoses that did not receive ED-ALTO procedures and received standard care see . In the p < 0.01) and a lower proportion were admitted to the hospital directly following their ED visit . In general, the ED patient population appeared similar in the pre- and post-implementation periods. The patients presenting to the ED in the pre- and post-implementation periods were not meaningfully different. On average, the patients presenting to the ED were 51 years of age and 50% were female. The majority of patients were White (62%) or Black (27%), and 50% were publicly insured, followed by 26% of the sample that had private health insurance. In the post-implementation period, a slightly higher proportion of patients had public insurance . The overall utilization of opioids decreased in the post-implementation period from 17.7% to 16.5% (p < 0.01), with significant reductions in the use of Dilaudid  and Hydrocodone . Among the patients receiving opioids, the average MME received increased in the post-implementation period .In the pre-implementation period, a total of 98 ED-ALTO procedures were performed. After implementation, the total frequency of ED-ALTO procedures performed was 167. Prior to the ED-ALTO program’s implementation, neither acupuncture nor electrostimulation, either through TENS or PENS, had ever been utilized in this ED. After implementation, acupuncture was used to treat joint pain, lower back pain, and abdominal pain. Similarly, the use of trigger point injection was increased in the post-implementation period and its use was also extended outside of the treatment of headaches to include abdominal and back pain.The use of nerve blocks saw an expansion in both overall frequency and clinical condition complexity, with an expanded use of the more complex regional nerve blocks. In the pre-intervention phase, digital nerve blocks were the primary nerve blocks used. These are commonly used for injuries of the hand, wrist, or fingers. Suprascapular, axillary, fascia iliaca, and erector spinae plane regional nerve blocks were all introduced as part of this program and used in the post-implementation period to treat fractures of the femur/hip and ribs as well as shoulder dislocations. Compared to the patients with the same diagnoses who received standard care, in 8 of the 12 months following ED-ALTO’s implementation, a lower proportion of patients receiving ED-ALTO procedures received an opioid in the ED . In montSimilarly, compared to the patients with the same diagnoses who received standard care, the patients who received an ED-ALTO procedure had lower average opioid MME in 8 of the 12 months after the study’s implementation .Our results reflect the first-year results from the implementation of a multi-faceted ED-ALTO program carried out in the Southeastern United States. Our ED-ALTO program includes expanded interventions including both medications and procedure-based approaches to treating pain in the ED. Following implementation, we demonstrated an overall ED-level decrease in opioid utilization with a concomitant increase in the use of ED-ALTO medications and procedures. Among the patients receiving ED-ALTO procedures, in 8 of the 12 months following the program’s implementation, opioid utilization and dosage was lower compared to patients with similar conditions receiving standard care.The ED-ALTO programs initiated within other institutions in the United States have focused on medication-based changes to the treatment of pain ,9,10,11.Our program encouraged providers to implement ED-ALTO alternatives as a first-line treatment for varied pain complaints. Providers were encouraged to start with ED-ALTO alternatives during the initial patient evaluation, which might have occurred while waiting for diagnostic imaging and reports. The majority of ED-ALTO interventions were applied for appropriate, expected diagnoses. However, the push to initiate the treatment of symptomatic pain, as opposed to a final diagnosis, did result in some cases in which final diagnoses might be considered inappropriate for alternative treatments. However, all interventions were applied in a timely manner without the delay of other care, including opioids when needed. In many cases, patients’ pain was successfully treated with ED-ALTO interventions that have a very low risk of complications.We observed that among the patients receiving an opioid, the average MME increased in the post-implementation period. One potential explanation for this finding is that as an increased number of lower-acuity patients are treated with ED-ALTO procedures and medications, the remaining pool of patients presenting with pain will be comprised of patients with more severe conditions and injuries that require higher opioid dosage. Currently, the ED-ALTO protocols are focused on decreasing the widespread and often indiscriminate use of opiates in lower acuity patients (ESI 3-5). Higher-acuity patients were not eligible for this study. However, the success of ED-ALTO therapies for lower-acuity patients suggests that some of these approaches may be applicable to higher-acuity patient populations as well. In particular, nerve blocks, in the presence of dislocations and fractures, can provide targeted pain relief without the negative side effects associated with opiates.Our ED-ALTO program includes multi-faceted training with which to create a culture of change within the ED and create sustainable, multi-modal, opioid-free treatment options to help treat various pain complaints commonly cared for in the ED. We adopted a model using “Opioid-free days”, in which bedside support was available from physicians with expertise in pain management and acupuncture. During those “opioid-free days”, we administered bedside training to available physicians. We believe a hands-on training approach is necessary for initiating a change in practice patterns and allowing ED physicians to feel comfortable performing new procedures.There are several limitations associated with this study. Due to the design of this study, it is possible that the statistically significant reduction in opioid utilization we observed after ED-ALTO’s implementation may be due to overall historical trends and the national focus on decreasing opioid use. Our current analysis cannot isolate the effect of our ED-ALTO intervention on opioid practices. Although, we did find an increase in the frequency of ED-ALTO procedures and medication use, which cannot be excluded as a potential factor related to the observed reduction in opioid use. Furthermore, Year 1 of this study occurred during the ongoing COVID-19 pandemic, which created unique challenges for ED research. The COVID-19 pandemic and patient surges often limited ED-ALTO enrollment and eligible patient populations, thus limiting our sample size in Year 1. Furthermore, the overall climate of lockdowns likely prevented certain injuries and exposures, which changed the typical care-seeking patterns and the patients visiting the ED. Additionally, it is possible that the Epic report data used for this analysis may include opioid utilization that was not dispensed in the ED. In Month 9 following ED-ALTO’s implementation, we found that there was one patient with very high opioid utilization. It was later identified that opiate orders were completed in the ED but originated from inpatient orders while a patient was awaiting transport to their final inpatient unit. Therefore, further analysis may reveal an even greater decrease in opioid utilization and MME levels in ED-ALTO-treated patients.Finally, the unpredictable nature of the complaints presenting to the ED, the pace of care within the ED setting, and the broad ED-ALTO medication order set makes it difficult to attribute all the results regarding the patients receiving ED-ALTO medications to our study efforts. The development of the medication order set was designed to make the prescription of alternative medications more accessible. While it is our intent to increase the use of alternative medications and procedures to treat pain, much of the use of ED-ALTO medications occurred outside of consenting and enrolled patients.The opioid crisis continues to be a significant problem in the US, and overdose deaths are on the rise. While pain is a major reason why patients seek care in the ED, it is unnecessary for the successful treatment of pain to be solely focused on the use of opioids, which have many negative side effects. The continued expansion of ED-ALTO programs across the US may serve as a mechanism with which to reduce opioid utilization and successfully help patients control pain. Although our program is in its early stages of implementation, we believe it is showing early success with respect to reducing opioid utilization. We have initiated patient follow-up surveys after ED discharge to assess pain scores for patients receiving ED-ALTO procedures and medications, and we hope to use these data in the future to highlight the effectiveness of ED-ALTO treatments for acute pain in the ED.


Musculoskeletal pain is one of the leading complaints in the ambulatory setting. There are many ways to treat it, including pharmacologic and non-pharmacologic approaches. Dry needling (DN) is an option that is easy to learn, cheap and has a good safety profile. The aim of this study was to assess the association between DN performed by GPs for acute myofascial pain syndrome (MPS) and pain relief and to evaluate factors associated with treatment success.In this prospective cohort study, two GPs performed DN in their clinics. Patients were asked to rank their pain using the Short-Form McGill Pain Questionnaire (SF-MPQ) before, 10-min and 1-week after the procedure. The SF-MPQ index consists of 3 parts; visual analog scale (VAS), pain rating index (PRI) and present pain intensity (PPI).Logistic regressions were performed to assess the variables associated with short- and medium- term success.P < 0.05. PRI was 17 ± 9.1 (before), 10.8 ± 8.5 (10-min after) and 5.1 ± 6.5 (1-week after), P < 0.05. PPI was 2.6 ± 1.0 (before), 1.7 ± 1.0 (10-min after) and 1.1 ± 1.2 (1-week after), P < 0.05.Fifty two patients were recruited from September 2019 until August 2020. VAS was 6.0 ± 2.3 (before), 4.1 ± 2.5 (10-min after) and 2.6 ± 2.71 (1-week after), Short-term success was associated with the physician who performed the procedure  and with the use of a single needle (vs. multiple needles inserted) . Medium-term success was associated with being a native born (non-immigrant), OR 8.59, 95% CI 1.11,66.28 and with high level of initial pain, OR 11.22, 95% CI 1.82,69.27.Our study demonstrated improvement in acute pain 10-min and 1-week after DN performed by a GP, in all parts of the SF-MPQ. Therefore, we believe DN is a good therapeutic option for GPs to aid patients suffering from MPS.The online version contains supplementary material available at 10.1186/s12875-022-01951-0. Pain is one of the leading complaints in the ambulatory setting. The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 demonstrated that low back pain, neck pain and other musculoskeletal pain complaints are the leading causes of morbidity globally in terms of years lived with disease [Myofascial pain syndrome (MPS) is a potential cause of musculoskeletal pain . MPS is The effectiveness of DN was examined in many studies. Most systemic reviews and meta-analysis recommended DN for treating acute and chronic pain in patients with temporomandibular joint dysfunction , upper-qSide effects of dry needling include minor adverse events such as mild bleeding (16%), bruising 7.7%) and pain during DN (5.9%). Major adverse events such as pneumothorax or hemothorax are rare (< 0.1%) [.7% and pIn 2015, the Israeli society of Musculoskeletal Medicine released a position paper concerning intra-muscular stimulation (IMS), written by six experts, using the Delphi procedure . The genIn 2017, Maccabi Healthcare Services, the second largest health maintenance organization (HMO) in Israel, launched DN courses for GPs. The basic course consists of 3 sessions of 10 academic hours each. Every GP who attends the course is afterwards certified to treat their patients with DN. Since, there has been an increase in the number of certified physicians, from 107 in 2017 to 199 in 2020 as well as an additional increase in the number of DN procedures, from 7,644 in 2017 to 10,647 in 2020 .The aim of this study was to assess the association between DN performed by GPs for acute MPS and short- and medium-term pain relief. Secondary aim was to evaluate factors that are associated with treatment success.This is a prospective cohort study. Two GPs who regularly treat patients with DN in their clinics invited eligible patients to participate in the study. Participation was voluntary and patients who refused to take part were still treated with DN. Patients who agreed to take part in the study were given full explanation on the procedure of DN and possible side effects and signed a written informed consent statement. Patients were asked to rank their pain using the Short-Form McGill Pain Questionnaire (SF-MPQ) before, 10 min after and 1 week after the procedure. The study was approved by the ethical committee of Bait Balev , ID 0017–19-BBL. All data was saved anonymously.DN was performed by two GPs, one is a specialist with 3 years of experience with DN and 8 years working in the same clinic and the other a resident, with 4 years of experience with DN but only 1 year working in the clinic. The GPs who performed DN chose the muscles to be treated based on the patient's complaints and findings of the physical examination. The length of the needle used for DN varies according to the muscle location, from 30 to 120 mm, and the diameter was 0.3 mm. Insertion of the needle was deep and perpendicular except for the back area, where it was oblique to the skin.Inclusion criteria were age > 18 years old, Hebrew speakers, acute MPS (less than a week from onset) and consent to take part in the study. Exclusion criteria were pregnancy, local infection, hemophilia, anti-coagulants use, local mass in the site of insertion, a contagious disease , having orthopedic implants or having undergone lymph node dissection. Follow-up of patients was done via telephone by the lead researcher.The diagnosis of MPS in this study relies on specific finding in the physical examination and clinical judgment of the physicians. The findings relevant for MPS in the physical examination include identification of a taut band and intentionally producing the pain by application of pressure to a point of tenderness within the band , 27.The outcome variables were the SF-MPQ which consists of three distinct parts; First, pain rating index – which includes 15 words describing pain , each rated on intensity scale of 0 (none) to 3 (severe). Total scores range from 0 to 45. Second, present pain intensity which represents the amplitude of pain from 0 (no pain) to 5 (excruciating pain) and third, a 10 cm visual analog scale (VAS) for average pain , 29. TheIndependent variables included were sociodemographic and DN related variables; sociodemographic data were collected for all participants including gender, age, marital status, country of birth (native born vs. other), socioeconomic status  to 10, (highest)). Smoking status and DN related variables were also collected, including exact site of DN, single vs. multiple needles inserted, the physician who performed the procedure and the baseline VAS .Sample size was calculated based on assumptions of pain rating index of 30 before DN and 25 after DN (with SD of 7) and VAS of 6 before DN and 4 after DN with a power of 90%, p value < 0.001 and a correlation of 0.4 assumed between both tests. These assumptions yield a sample size of 50 patients.For each part of the SF-MPQ a mean and standard deviation were produced . Change was estimated using ANOVA with Bonferroni correction;10 min after compared to the baseline (short-term effect), 1-week after compared to the baseline (medium-term effect) and 1-week after compared to 10 min after. A success was defined has having at least 2 measures that have improved (out of the three parts of the SF-MPQ). A continuous success was considered success in both short- and medium-term indices. A logistic regression was performed to assess what variables are associated with short-term, medium-term, and continuous success, using the Forward approach. Analyses were performed using SPSS Statistics, version 27.From September 2019 to August 2020, 55 patients were recruited  and 1.1 ± 1.2 1-week after (Table P < 0.05.VAS was 6.0 ± 2.3 A logistic regression for short-term success (improvement after 10-min) showed that 2 factors were associated with it; the physician who performed the procedure  and single needle inserted (vs. multiple needles) . Medium-term success  was associated with being a native born   and high level of initial pain . Continuous success was associated with insertion of one needle, compared to multiple needles .Our study demonstrated improvement in acute MPS 10-min after and 1-week after DN. Improvement was demonstrated in all parts of the SF-MPQ . Short-term success was associated with the physician who performed the procedure and the insertion of a single needle (vs. multiple needles). Medium-term success was associated with being a native born and with higher levels of baseline pain (as evident by a VAS level higher than 5). Continuous success was associated with insertion of one needle (vs. multiple needles).In this study we explored the effectiveness of DN when performed by GPs in their clinics. Most research conducted on DN focuses on other health care providers who perform this intervention (physiotherapists and consultant physicians). The only data we found about DN in family practice is a review published by the Journal of the American Board of Family Medicine in 2010 . In thisOur findings on the effectiveness of DN support the body of knowledge that DN can be considered as a good treatment for acute pain . The sucHigh intensity of pain before the procedure, as indicated by a VAS of 6 or more, was associated with medium-term success. This might suggest that DN is more effective in alleviating pain when it is severe in the first place.We believe that certain aspects of DN performed specifically by GPs should be addressed. Firstly, continuity of care, which is a fundamental aspect of primary care can augment the success of the procedure . In our Preferences of patients might also be different when GPs perform DN compared to other health care workers; our study demonstrated that insertion of 1 needle (vs. multiple needles) was associated with short-term and continuous success, contrary to a meta-analysis that found the effect of acupuncture increased when more needles were inserted . This maThis study examines the effect of DN performed by GPs in their clinics. This is unlike most studies, which examine DN use by physiotherapists or physicians that are not necessarily GPs. As this procedure is widely and increasingly used by GPs, this is an important aspect of the research on the effectiveness of DN. The use of a validated scale for pain, the SF-MPQ, increases the validity of this study. Measuring the effect of DN both in short- and medium-term is another strength of this study.This study did not include a control group, and thus the treatment cannot be compared to other treatment options or to sham-therapy. Additionally, patients were treated by two GPs in the southern district of Israel; the population of patients does not represent the whole Israeli population, which may affect the results found. Both physicians who performed the DN also treat patients for other medical problems. This may influence patients’ satisfaction and pain. The specialty status of the GPs  might also have impacted the results. Another limitation is the lack of follow-up with patients who declined to participate; thus, a possible selection bias might exist.DN is a good therapeutic option for GPs to aid patients suffering from acute pain. All SF-MPQ parameters of pain improved significantly, both in short- and medium-term. The physician who performed the procedure was associated with short-term and continuous success rates. Initial high intensity pain (VAS > 5) was associated with medium-term success. Considering it is a low-cost method and relatively easy skill to impart, it should be encouraged by policy makers to increase its availability to patients. This can be done by exposing students, residents and specialists to this skill. Further research should explore the effectiveness of DN shortly after having learned the method and by a larger group of GP participants in different settings. Future studies may prefer to choose algometry as a method to assess pain rather than questionnaires as we had chosen.Additional file 1. Dataset - IMS.