Somatosensory deficits and abnormal pain sensitivity are highly prevalent among stroke survivors, which negatively impacts their quality of life and recovery process. However, the factors for pressure pain threshold (PPT) and somatosensory abnormalities in post-stroke elderly remain unknown. The aim of this study was to explore the effects of age, side and other functional conditions, such as spasticity and motor functions, on PPT and sensory abnormalities among elderly after stroke.The cross-sectional study finally included 43 post-stroke elderly aged over 60 and assessed the PPT of 14 bilateral muscles widely located in the whole body by using a digital force gage. Meanwhile, spasticity, motor function, joint pain and activity of daily living (ADL) were evaluated by the Modified Ashworth scale, Fugl-Meyer, and Barthel Index, respectively. All participants were divided into higher-aged and lower-aged groups based on the median age of all of them.p < 0.05). Furthermore, the somatosensory abnormalities in the affected side, particularly hypoalgesia, were more frequent in higher-aged than lower-aged patients in most assessed muscles. Meanwhile, patients with spasticity showed more increment of PPTs in affected muscles around the knee joint than patients without spasticity (p < 0.05). Patients with better motor functions, less joint pain and higher ADL performed less bilateral differences of PPTs than other patients in some muscles (p < 0.05).Higher age tended to be associated with higher sensitivity but not significant except for one upper limb muscle, and the affected side showed significantly higher PPTs than the unaffected side in three out of seven muscles (The age and side differences of mechanical pain sensitivity were found among post-stroke elderly. Older patients show higher sensitivity in both sides compared with the younger ones, and the affected side of the elder shows more somatosensory abnormalities, particularly hypoalgesia, than that of the younger ones. Post-stroke elderly in good functional conditions, such as normal muscle tone, better physical function and daily activities, and less joint pain, seems to have more equal pain sensitivity between both sides than those in poor conditions.The online version contains supplementary material available at 10.1186/s12877-022-03515-4. Stroke is a high-prevalence disease worldwide, which causes around 110 million disability-adjusted life years and 5.5 million deaths in a single year . NeuroloMany previous studies have researched pain perception in different populations. According to Mücke et al., the increases in thermal and vibration pain perception were strongly associated with aging, which indicates that age is positively associated with pain perception in healthy population . MoreoveThis study aimed to explore the age and side effects on pressure pain sensitivity in elder stroke survivors through assessing the PPT of large muscles located all over the body in affected and unaffected sides among 43 patients aged over 60. Moreover, this study aimed to evaluate the relationships between pain sensitivity for pressure stimuli and functional conditions, such as spasticity, motor functions and ADL, in elderly after stroke.Forty-three participants were involved in this cross-sectional study. Fourteen points in twelve muscles on both sides, including the middle deltoid muscles (MD), biceps brachii muscles (BB), erector spinae muscles (ES) at the second and fourth lumbar vertebra (L2 and L4) levels, rectus femoris muscles (RF), biceps femoris muscles (BF), and medial gastrocnemius muscles (MG), were selected to evaluate PPT. In addition, spasticity, motor function, joint pain, and ADL were evaluated by the Modified Ashworth Scale (MAS), upper limb (FM-UL), lower limb (FM-LL), motor function (FM-MF), and joint pain (FM-JP) subscales of Fugl-Meyer Assessments and Barthel Index, respectively. In addition, other baseline information was collected for further exploration. The study was approved by Human Ethics Committee of the First Rehabilitation Hospital of Shanghai (YK-2020–01-030). All willing participants signed informed consent forms.According to the mean values and standard deviation values from a previous study, G*Power was used to evaluate the sample size, with Mann–Whitney U test, α = 0.05, power = 0.8, allocation ratio N2/N1 = 1. The total sample size was 36 with an actual power of 0.81 . This st2 rubber tip at a stable speed until the PPT was reached. The apparatus showed a good-to-excellent test–retest and inter-rater reliability based on the previous research  and has been widely applied to the clinical measurement of PPT [2, which ranged from 0 to 14 kgf/cm2. In addition, MAS was used to measure the spasticity of flexors or extensors in different joints by moving the patient limb from a position of maximal flexion to maximal extension or moving through opposite direction. Moreover, motor functions of the upper and lower limb, such as active movement of the shoulder and hip, were evaluated by FM-UL and FM-LL, respectively. Afterward, the overall motor function (FM-MF) was calculated by the sum of FM-UL and FM-LL. The FM-JP was applied by recording pain severity during passive joint movement. Finally, the ADL, such as dressing, transfers and stairs, was evaluated by the Barthel Index.PPT was defined as the turning point when pressure sensation transformed into pain sensation . PPT asst of PPT , 22. TheBefore the PPT test, participants were instructed to lie on a bed in supine position and informed with the procedures of the following PPT test. Five-time practice was available for participants to get familiar with it. Participants were required to give their response as soon as they feel the sensation transforming. After practice, palpation conducted by the operator was required to help mark the test points on the belly of targeted muscles. The muscle belly was selected in this study because muscle tissue showed the least changes of PPT when different kinds of evaluation apparatus and circumstances were applied, which might indicate a better consistency in various clinical practices compared with other tissues  , 12. AllSPSS statistics  was applied to analyze the data. All participants were divided into the lower-aged group and higher-aged group in accordance with the median age (median age = 71). The Mann–Whitney U test and Chi-square test were used to detect any differences for qualitative and quantitative demographics between two groups, respectively. Adjusted liner regression analysis was used to detect the association between age and PPT values and the adjusted factors were sex, body mass index, and stroke type. In comparing PPT values between the unaffected and affected sides, normal transformation and paired-sample T test were performed.In a previous study , pressurExcept for the ratio, the absolute difference values of PPT between the affected and unaffected sides were calculated to present the bilateral differences. Subsequently, based on the MAS results of flexors and extensors at different joints to detect the effect of muscle spasticity on PPTs, all participants were divided into two groups, normal group (MAS = 0) and spasticity group (MAS > 0). The Mann–Whitney U test was applied to find the PPT differences between normal and spasticity groups. Finally, a two-tailed spearman test was used to find the correlation between the functions and PPT based on the results from functional scales. Notably, the Chi-Square test was applied to detect any sex imbalance between the normal group and spasticity group because sex has been demonstrated to be a factor for PPT in previous research. Similarly, the correlations between PPT and functions among male and female participants were provided separately.2. No significance of demographic characteristics was found between the lower-aged group and higher-aged group.Forty-three patients were included in the study and the baseline information of them is demonstrated in Table p > 0.05) in the regressions except for the BB in the unaffected side (p = 0.028). In addition, nearly all PPT values in the affected side were higher than those in the unaffected side not only in all participants but also in different age groups. In all participants, side differences of BB, ES (L4), and MG were significant (p < 0.05). Furthermore, one out of seven muscles (BB) showed a side difference in the lower-aged group (p < 0.05), whereas three out of seven muscles  showed this difference in the higher-aged group (p < 0.05). Almost all significant side differences were found in muscles located in the upper and lower extremities instead of the trunk.The associations between age and PPT of different muscles are provided in Table SDifferent from comparison between two sides among all patients, the results of hyperalgesia and hypoalgesia analyses providing the side comparison at individual level are demonstrated in Table Outcome with significant differences between the normal and spasticity groups based on MAS is reported in Table p < 0.05) between bilateral difference and functional scales (Fugl-Meyer and Barthel Index) are illustrated in Figs. r =  − 0.371, p = 0.014) and FM-MF . In addition, bilateral difference of MG weakly correlated with FM-LL , FM-MF , FM-JP , and Barthel Index . Furthermore, a weak relationship was observed between the bilateral difference of BB and FM-JP , and a moderate correlation was found between that of ES (L4) and FM-JP .Significant correlations p < 0.0 between The study evaluated pain sensitivity for pressure stimuli among 43 stroke survivors over 60 years old. The results showed that higher age might be more sensitive to pressure pain in both sides despite no significances except for one upper limb muscle, whereas older elderly was at higher risk of sensory loss and hypoalgesia in the affected side when compared with the unaffected side. Furthermore, participants with normal muscle tone, less joint pain, and high level of motor function and ADL performed more symmetrical pain perception between the affected and unaffected sides.Nearly all PPT values in affected muscles were higher than those in unaffected muscles, which might indicate an extensive pressure pain sensory loss on the hemiplegic side in patients with stroke. Some previous studies have revealed that somatosensory performance, including tactile, electrical and pressure sensation, in the hemiplegic side decreased compared with the unaffected side , 24, whiParticipants with higher age tended to be more sensitive to pressure pain either in the affected or unaffected sides. Although these associations were not significant except for one upper limb, unaffected BB, this finding is supported by a previous study by Lin C-H et al. They measured the PPT of muscle tendon and bony prominences and reported that higher-aged post-stroke patients had a higher sensitivity to pressure pain but not to heat pain in both sides than lower-aged patients, which indicated the existence of age effect on pain threshold. This effect varied from different characteristics of pain stimuli . SimilarFurthermore, lower- and higher-aged post-stroke elderly showed a similar trend with all patients, which is pain threshold had a tendency to increase in the affected side compared with that in the unaffected side. In particular, older old patients after stroke had more muscles that showed significant difference between the two sides than younger old. This finding indicated that higher-aged stroke survivors were more likely to have sensory loss on their affected side. Similarly, hypoalgesia in the affected side was more frequently observed in higher-aged than in lower-aged post-stroke patients, which indicated a consistent trend. This age differences could be explained on the basis of the activity level. Carey et al. stated that the daily activities of stroke survivors with sensory loss in the affected side were significantly reduced compared with those without sensory loss . MeanwhiIn addition, the proportion of hyperalgesia in MD in lower-aged patients was higher than that of hypoalgesia, although hyperalgesia in most muscles was relatively less frequent than hypoalgesia. This difference in tendency might be due to the high prevalence of post-stroke shoulder pain. Large amounts of previous studies reported that post-stroke shoulder pain is a common complication with shoulder tissue injury among post-stroke patients, with a 40% prevalence , 29. FroWith regard to muscle locations, trunk muscles were less likely to have sensory abnormality compared with extremity muscles. Based on a study tracing the related pain of patients one year after stroke, the lower extremity was one of the common pain-stricken regions among all post-stroke survivors . MoreoveThis study found that post-stroke patients with spasticity of knee flexors and extensors showed significantly higher ratio of PPT than patients without spasticity, which indicated a relative hyposensitivity of pressure pain in affected RF muscles. This finding indicates that spasticity may be associated with sensory loss, particularly in the lower limbs. Some previous studies have reported the similar phenomenon. Peter et al. stated that patients with hemi-hypesthesia were at significantly high risk of potential upper and lower limb spasticity in the future . SimilarMultiple correlations were found between PPT and functional condition. To be specific, patients with good function are associated with symmetrical pain perception between both sides. Previously, the severity of sensory deficits was proven to be a prognostic factor to predict post-stroke recovery through a large sample regression model , 41. OthA more symmetrical pain perception in both sides was found in stroke survivors with less joint pain. Considering that the FM-JP detects joint pain during movement, spasticity characterized by velocity-dependent might primarily account for the induction of pain. Thus, patients with severe spasticity seems to report more joint pain. As mentioned previously, this study reported that patients with spasticity suffered from more sensory loss in the affected side and larger bilateral difference, which is consistent with this finding. Furthermore, the recovery of mechanical pain perception in affected side was associated with the improvement of daily activity. Similarly, previous research indicated that proprioception and tactile sensation deficits were weakly-to-moderately related to independent ADL and recovery of ADL in post-stroke patients, and the combination of two sensations was more strongly associated with daily activity , 46. MeaThere are some limitations in this study. Firstly, the sample size was small, even though it satisfied the sample size calculation. More participants may provide more information about mechanical pain threshold in difference age ranges in post-stroke elderly and increase the reliability of the results. Meanwhile, the study did not consider the potential influence of stroke type or stroke volume size or location on pressure pain sensitivity, which should be further researched through subgroup analysis or other statistical methods with larger sample size. Thirdly, the study reported the correlation between pain sensitivity and motor function, joint pain condition, and basic ADL, whereas the correlation with more other functional conditions, such as instrumental ADL, mental health, and quality of life were not provided. In future research study, more relationship between pain sensitivity and other functional condition in post-stroke elderly should be explore, and regression analysis could be performed to provide more information.The findings in this study could provide more information about somatosensory performance in post-stroke elderly for clinical staff, which emphasize that older patients are at high risk of hyposensitivity or hypoalgesia in their affected side. Sensory training should be integrated into the rehabilitation prescription for post-stroke elderly, which may be beneficial to preventing potential central or peripheral sensitization, and improving motor function and ADL simultaneously.This study explored the age effect of pain sensitivity in post-stroke elderly, which indicated that higher age might be more sensitive to pressure pain both in the affected and unaffected sides but not significant except for one upper limb muscle. Moreover, hyposensitivity and even hypoalgesia were more frequently located at some affected muscles in older elderly than in younger elderly after stroke. Furthermore, post-stroke spasticity seemed to be related with sensory loss in the affected side at knee joint. Elderly after stroke with better motor function, less joint pain during movements, and higher level of ADL showed less sensory loss during pain perception in affected muscles and a more symmetrical pain perception between both sides. In the future, studies involving a large sample size and evaluating more functional conditions in healthy and post-stroke elderly are required.Additional file 1. Associations between age and PPTs in the affected and unaffected sides in Table S1. All comparisons of bilateral difference and ratios of PPTs between patients with normal muscles tone and those with spasticity are demonstrated in Table S2. The associations between PPTs and functional conditions are shown in Table S3. The associations between the subscales of Fugl-Meyer Assessment and ratio of PPTs were illustrated in Figures S1, S2, S3, S4, and S5.


ClinicalTrials.gov Identifier: NCT04916249) to assess the efficacy and safety of the pain-relieving plaster for temporary pain relief among cancer survivors with chronic musculoskeletal pain. Under ethical approval from the Institutional Review Board at the Memorial Sloan Kettering Cancer Center, we will enroll eligible cancer survivors who have a clinical diagnosis of moderate to severe chronic musculoskeletal pain in this study. We use a central randomization system to allocate the eligible participants to either the treatment or the control group in a 1:1 ratio, with stratification by baseline opioid use. We will instruct the participants to apply the herbal patch  or placebo patch daily at the focal area with worst pain for 14 consecutive days. Study physician, participant, outcome assessor, and biostatistician are blinded to the group allocation. The primary outcome is pain severity measured by the Brief Pain Inventory on Days 2–7. Secondary outcomes include changes in insomnia, anxiety, depression, fatigue, pressure pain threshold, pain medication use, and global impression of change. We will also monitor the adverse events throughout the study period. Statistical analysis will follow the intention-to-treat principle and linear mixed modeling will be used. With rigorous design and implementation, this randomized, placebo-controlled trial will provide the initial evidence on the efficacy and safety of the pain-relieving plaster for pain relief among cancer survivors with chronic musculoskeletal pain.Chronic pain is common and debilitating in cancer survivors. Tibetan herbal pain-relieving plaster is used as an external analgesic to treat musculoskeletal pain in China; however, its safety and efficacy have not been evaluated via clinical trials in cancer survivors. We designed this Phase II randomized, double-blind, placebo-controlled trial ( In the United States (U.S.), the number of cancer survivors exceeded 16.9 million in 2019, which is projected to reach 22.1 million by 2030 . One in In the Asia-Pacific region and the U.S., Tibetree Pain-Relieving Plaster (PRP) –a patented herbal medicine made with 1% Camphor (Cinnamomum camphora (L.) Nees and Eberm) and other herbal species –is used This is a prospective, single-center, two-arm, randomized, placebo-controlled trial comparing Tibetree PRP with a placebo control plaster for pain relief in cancer survivors. We plan to enroll 66 eligible patients who completed active cancer treatment and have no evidence of disease, with moderate-to-severe musculoskeletal pain for at least 3 months, from the Memorial Sloan Kettering (MSK). We use a central randomization system to allocate the participants to the experimental or control group in a 1:1 ratio. In the experimental group, patients will be instructed by a study physician/investigator to topically administrate PRP at the worst pain area daily for 14 days. In the control group, patients will be instructed by the same clinician to use the placebo patch at the same frequency for the same time course. The placebo patch mimics the color, smell, dose form, and package of the true patch. The primary outcome is pain severity measured by the brief pain inventory (BPI) at days 2–7. Secondary outcomes include pain severity measured at other time points, pain interference, fatigue, insomnia, anxiety and depression, global impression of change, treatment expectancy, and pressure pain threshold .• Inclusion Criteria: 1) Age ≥18 years or older; 2) A diagnosis of cancer with no restrictions placed on type of cancer or stage. Eligibility criteria will not be restricted to MSK confirmed biopsy/diagnosis; 3) Completed active treatment  at least 1 month prior to study initiation (patients on continued hormone treatment or maintenance targeted therapies will not be excluded); 4) Patients currently have no evidence of disease; 5) Ambulatory ; 6) Having a focused location of regional musculoskeletal pain  that can be covered by one patch of PRP; 7) Worst pain score  ≥ 5 in the preceding week; and 8) Pain for at least 3 months and at least 15 days with pain in the preceding 30 days; and 9) Willingness to adhere to and understanding of all study-related procedures, including randomization to one of the two possible treatment groups; (10) Able to understand informed consent and provide signed informed consent form.• Exclusion Criteria: 1) Patients with non-musculoskeletal pain syndromes  will be excluded if these are the sole source of pain but can be present as co-morbid conditions as long as the patient has a primary musculoskeletal pain condition defined as above; 2) Patients have generalized musculoskeletal pain such as fibromyalgia; 3) Use of corticosteroid drugs by any route of administration within 30 days; 4) Patients with significant self-reported skin disorders; 5) Patients with open wounds, infections, skin trauma at skin overlying area of pain; 6) Patients with documented history of skin sensitivity to adhesive or allergic reaction to other patches or topical analgesics; 7) Patients with documented skin allergic reaction to plants or herbs; 8) Patients who are in active treatment ; 9) Plan to change or initiate other pain medications or interventions . Patients may remain on their current pain regimen.We will enroll cancer survivors with chronic musculoskeletal pain from MSK and the local areas. The following criteria are used to determine the eligibility of a participant.clinicaltrials.gov. Additionally, printed materials will be posted in clinic areas .Our primary recruitment approach will use a population-based strategy via sending recruitment letters to potential participants. Potential candidate will be identified through Dataline querying at MSK by an analyst. Our clinical research coordinators (CRC) (KC) will reach out to potential participants identified or referred to the study coordinator by protocol investigators or other MSK healthcare providers. We will also enroll self-referred participants. Information about the protocol will be provided in lay language on MSK’s web site and on A CRC will screen potential interested and eligible patients, and schedule screening and consenting appointments. A study investigator will confirm each patient’s eligibility and complete a protocol-specific Eligibility Checklist to ensure that all institutional requirements necessary to enroll the participant to the study have been completed. A CRC specially trained for the study will obtain informed consent. After establishing eligibility and consenting, the study staff will register participants through the Clinical Trials Management System (CTMS).Participants will be randomized in a 1:1 ratio to the PRP or placebo plaster groups using MSK’s Clinical Research Database (CRDB), a secure computer system that ensures full allocation concealment. Permuted block randomization methods with stratification by baseline opioid use (yes/no) will be utilized. Participants’ treatment assignments can be viewed in the CRDB only by the hospital pharmacists who are dispensing the study medication.The CRCs, patients, clinicians, PI, co-investigators, biostatisticians will be blinded to the group allocation. The MSK research pharmacy will maintain the randomization and distribution list of the PRP and placebo medications. Pharmacist who dispenses the patches will have no contact with patients and a study clinician will pick up the plasters from the pharmacy and distribute them to patients on their Day 1 visit.• PRP: Each participant will receive 14 plaster packages in a single box in the PRP group from our study clinician (MY). Each package includes a light brown plaster (1.2 g/patch) and a small white plastic bag of dark yellow herbal liquid (1% camphor [Cinnamomum camphora (L.) Nees and Eberm], 2.5 ml/bag). The plaster is composed of a paper-based hypoallergic medical adhesive (122 mm × 145 cm) and at its center a single layer (thickness 0.8 mm) of sealed cotton pad (50 mm × 70 mm) with herbal powders inside. The herbal components of PRP are detailed in • Placebo: The placebo plaster lacks the active ingredients but are otherwise identical to the true patch in appearance. The placebo pouch contains liquid made up of purified water, sodium methyl para-hydroxybenzoate, sodium propyl 4-hydroxybenzoate, sodium dodecyl sulfate, and tartrazine. The placebo herbal powders in the plaster are composed of plant fiber, light yellow dye, yellow dye, egg yolk powder, cocoa powder, pumpkin powder, and active charcoal. Tibet Cheezheng Tibetan Medicine Co. Ltd.  manufactured both the real and the placebo patch .On Day 1, the study clinician will help the patient identify a focused body area where the patient reports worse pain. This will be the area for the patch to be applied. The study clinician will demonstrate the patient how to appropriately apply the patch. To use, we advise each patient to adopt the following procedures: 1) clean the skin of the affected area, 2) remove the plastic film from plaster, 3) squeeze the diluents contained in the plastic bag onto the middle of the pad, and 4) apply the plaster on the affected area. We remind all patient that a patch should not be worn for more than 6 h to avoid any potential skin irritation or unknown side effects. The fidelity of treatment is ensured by drug use compliance recording form which is automatically sent to patient daily through the REDCap system. In the following days, patients are required to apply only one patch daily at the fixed pain area. At the end of the study, we also require all patients to return the drug box and any unused patches.The primary outcome is pain severity measured with the Brief Pain Inventory (BPI) at days 2–7. The BPI is a 11-item pain instrument validated to quantify pain severity (4 items) and pain interference (7 items). It is one of the most widely used instruments to measure pain in patients and has been demonstrated to be a reliable, valid, and responsive measure . We defi• Pain severity and interference measured by the BPI at day 14.• Patients’ Global Impression of Change (PGIC) is a one item survey that will be used to define a clinically important change in pain from the patient’s perspective . Patient• Brief Fatigue Inventory (BFI) will be used to determine the effect of treatments on fatigue. This 9-item instrument was designed to assess one construct of fatigue severity in cancer and non-cancer populations. Three items ask patients to rate the severity of their fatigue at its “worst,” “usual,” and “now” during normal waking hours, with 0 being “no fatigue” and 10 being “fatigue as bad as you can imagine.” Six items assess the amount that fatigue has interfered with different aspects of the patient’s life during the past 24 h. The interference items are measured on a 0–10 scale, with 0 being “does not interfere” and 10 being “completely interferes” . A compo• Insomnia Severity Index (ISI) will be used to measure subjective insomnia severity. The ISI has seven items rated on a 5-point Likert response scale , yielding a total score ranging from 0 to 28 with higher scores representing more severe insomnia symptoms. The usual recall period is the “last month”; however, we will use a modified recall period of “the past week” to match our assessment schedule. The ISI authors suggest the following guidelines for interpreting the ISI total score: < 8, no clinically significant insomnia; 8-14, subthreshold insomnia; 15-21, clinical insomnia (moderate severity); >21, clinical insomnia (severe).. The ISI• Hospital Anxiety and Depression Scale (HADS) will be used to explore the effect of treatments on psychological distress. HADS is a 14-item scale with seven items measuring depression and seven items measuring anxiety. Each item is answered by the patient on a four-point (0–3) response category so possible scores range from 0-21 for anxiety and depression, with higher scores indicating higher symptomatology. Established cutoffs are: 0–7 not significant; 8–10 subclinical; and 11–21 clinically significant depression/anxiety.. Factor • Patient Reported Outcomes Measurement Information System (PROMIS®) Scale v1.2 - Global Health is a brief instrument composed of 10 items that demonstrates adequate reliability and validity  as a mea• MAO Expectancy of Treatment Effects (METE) has four items originally developed as the Acupuncture Expectancy Scale (AES) by Mao et al. It has d• Mao Expectancy of Side Effects of Treatment (MESET) measures the expectations of side effects and therapeutic effects of the study intervention.. The sco• Pressure Pain Threshold: This is a study measure that a study investigator will administer. Pressure algometry is a reliable measure of pressure pain threshold. Two types of algometers will be used in this trial:2/sec increment at the tissue located at or surrounding the tested site with the tip of the algometer. The test will be terminated when participants reach their pain threshold or a pressure of 10 kgf/cm2. The test will be repeated three times per site, and we will take the mean threshold for analysis, measured as kgf/cm2. The test will be conducted three times during the study: before patch application at baseline; 45 min after patch application at baseline and at the primary endpoint (Day 7).(1) the FPX Wagner algometer: We will use a digital pressure algometer, FPX , to apply pressure at the site of pain (the tender points of tissue where the patient experiences the worst pain) and two pain-neutral areas (thumbnail bed and trapezius) to derive the pressure pain threshold (the first pressure that is perceived as painful) shown to be predictive of analgesic effects . The cli2/s ramp rate) at 20 s intervals, beginning at 0.25 kgf/cm2 and increasing in 0.25–0.50 kgf/cm2 steps. Pain intensity will be rated after each stimulus on a 0–100 Numerical Rating Scale. The test will be terminated when participants reach their tolerance or 10 kgf/cm2. PPT test with the MAST system will be conducted once before patch application at baseline only. The validity of testing pressure pain threshold with the MAST system has been demonstrated extensively ((2) the MAST system: We will use the MAST System   to applyensively . We will• Study Allocation Belief: This is a patient-reported outcome that asks patient to guess which treatment they have received during the study to assess the adequacy of blinding.• Pain Medication Diary: Name of pain medication, the dosage/strength, number of days patients took the medication and how many pills were taken were collected in the Pain Medication Diary. A pain medication usage score was calculated according to the method developed by Robinson-Papp et al. .• Adverse events: We will document all related adverse events and report any related serious adverse event promptly to IRB.The main objective of this study is to provide preliminary data on the effect of PRP in reducing musculoskeletal pain compared to placebo plaster. We conservatively anticipate lost to follow up to be at most 10% by day 7. To ensure adequate power to compare arms on our secondary symptom endpoints, we will enroll 66 patients to obtain at least 60 patients evaluable for these secondary symptom endpoints. Our sample size will provide sufficient statistical power to detect clinically relevant effect sizes for our primary pain outcome between PRP vs. placebo plaster (primary objective). We present our power considerations for an ANCOVA regression model , which we will apply to our primary pain endpoint as well as to the secondary symptom endpoints. However, our analysis method for our primary endpoint (linear mixed model) will be able to detect a slightly smaller effect size than presented here. For our sample size/power considerations, we calculated the smallest standardized effect size we will be able to detect with 0.80 power, given a sample size of 60. With 30 participants in each of the two arms, we will have power of 0.80 to detect an effect size of 0.74  between the two arms at Day 7, using a two-sided test with alpha of 0.05 in a regression model controlling for baseline score. This 0.74 effect size is considered a moderate-to-large effect size by convention. Given the standard deviation of the BPI pain severity subscale typically ranges between 2 and 3, this effect size translates to a mean difference between the arms of around 1.5 to 2.25 points on the 0–10 BPI scale. A 1-point difference in BPI severity is clinically important . In addiWe describe the analysis for the primary objective below using the intention-to-treat (ITT) principle. We will also perform a per-protocol sensitivity analysis among treatment and assessment completers, but study conclusions will be based upon the ITT analysis results.All randomized patients will have a baseline pain assessment, and those with at least one post-baseline BPI assessment on or before Day 7 will be included in the analysis of the primary objective using the modified ITT principle . Secondary outcome such as insomnia, anxiety, depression, fatigue, and quality of life are measured at baseline, Day 7, and Day 14. The analysis population for these endpoints will include patients who complete the baseline and one or both of the Day 7 and Day 14 assessments. Pressure pain threshold is measured at baseline before patch application, baseline 45 min after patch application and Day 7. The analysis population for this endpoint will include patients who complete the test at baseline before patch application and one or both of the other two timepoints. Additionally, all patients who apply at least 1 of the study plasters will be included in the analysis of safety.We will plot the outcome measure trajectories by randomization arm over time and summarize each outcome measure at each assessment time by treatment arm using descriptive statistics. We expect patients’ pain levels to decrease upon first application of the PRP and then stay at a similarly decreased level with continued use over the study period. Accordingly, we will test for differences between the two study arms in post-Baseline BPI severity using a linear mixed model (LMM) predicting post-Baseline BPI severity as a function of treatment arm, controlling for Baseline BPI severity, assessment time, and randomization strata . The test of differences between randomization arms with respect to the outcome will be based on the coefficient for treatment arm in this LMM. For our test of differences between the arms in the primary endpoint (Day 2–7 BPI severity), the LMM will have BPI severity assessments through Day 7. We will fit a similar model with BPI assessments through Day 14, but the Day 7 model will be our primary test of efficacy.To enhance patient-centered data interpretation and decision-making, we will also perform responder analyses by considering those who experienced 30% or greater reduction in BPI severity as responders at the primary end point/Day 7 and at the end of treatment/Day 14.. We willThe number and percent of adverse events within each treatment arm will be reported by grade. We will compare changes between the arms in insomnia, anxiety, depression, fatigue, quality of life, and pain medication usage scores using linear regressions predicting these endpoint scores at Day 7 and Day 14 (separate models) as a function of treatment arm, controlling for baseline score and randomization strata. This is equivalent to an ANCOVA model. The same analysis will be performed for PPT for the baseline (45 min after patch application) and Day 7 assessments, controlling for the pre-patch baseline assessment. We will summarize responses to the PGIC at days 2, 7, and 14 using frequencies and percentages by arm, and test for differences between arms using chi-square tests. To obtain estimates of the correlation of treatment expectancy and treatment response, we will fit a LMM similar to that specified for the primary objective, but with the addition of METE score and the interaction between treatment arm and METE score. To evaluate whether PPT predicts treatment response, we will fit a LMM similar to that specified for the primary objective, but with the addition of baseline (pre-patch) PPT score and the interaction between treatment arm and PPT baseline (pre-patch) score. Pain response variations in associated with other variables, such as sex, race/ethnicity, or age, may be addressed in post hoc analyses.The current opioid epidemic has presented enormous challenges to the management of pain among cancer survivors . ComplemIn real-world practice, PRP used as a topical analgesic confers pain relief and clinical benefits that are comparable to oral analgesics to cancer patients . ClinicaResults of our study will contribute to understanding the efficacy and safety of PRP for temporary pain relief among cancer survivors with chronic musculoskeletal pain. Our systematic review of randomized controlled trials showed that PRP compared to analgesic medications such as Diclofenac or NSAIDs may lead to greater improvements in pain outcomes in acute low back pain patients . BuildinPain and comorbid symptoms like insomnia and depression may share common neurobiological pathways . Recent Although PRP may not impose serious side effects when used as a topical analgesic among chronic pain populations, moderate skin irritations were reported in observational studies, including skin dryness, redness, and blistering in the area where patch is applied . As pharWe are currently enrolling patients. We designed this study in full compliance with the Declaration of Helsinki and the principles of Good Clinical Practice to maximize the protection of patient rights and health. The Institutional Review Board (IRB) at MSK reviewed and approved all procedures stated in this study protocol version 5.14 (27 May 2021) . All eligible patients provide written consent or a signed e-consent form prior to the initiation of any study procedures. All patient data will be protected under the MSK CRDB and the REDCap systems. MSK Data and Safety Monitoring Committee oversees the study and initiates review from the enrollment of the first participant, till the protocol has closed to accrual. Results of this study will be disseminated through poster/oral presentations at regional/international conferences and peer-reviewed journals.


Background: Low back pain affects the lives of millions of people in the United States and the world. Not only does low back pain affect the quality of life for the individual patient, but it also accounts for many emergency department and health care visits. For a subset of patients, conservative measures such as medications and physical therapy, nonsurgical interventions, and surgery are not effective. Peripheral nerve stimulation is an emerging treatment option for patients with chronic low back pain. This case series assesses 6 patients’ experiences with lumbar level peripheral nerve stimulation.Case Report: Three male and 3 female patients underwent lumbar level peripheral nerve stimulation as a treatment for chronic low back pain. The average age of the patients was 63.5 years, and they demonstrated an average pain reduction of 64.8%.Conclusion: This series provides evidence that lumbar level peripheral nerve stimulation may be an efficacious treatment for chronic low back pain that is refractory to conservative measures. Large studies are needed to assess the outcomes and durations of improvement associated with this treatment. Chronic back pain is described as pain that persists for 12 or more weeks.3 A systematic review of 9 studies assessing the prevalence of chronic low back pain found the prevalence to be between 3.9% and 20.3%.13Low back pain affects millions of people across the globe, increasing in prevalence with age and peaking between the ages of 80 to 89 years with a higher incidence in females.14 Nonsteroidal anti-inflammatory drugs, acetaminophen, skeletal muscle relaxants, acupuncture, superficial heat, physiological therapy, interdisciplinary rehabilitation, exercise therapy, spinal manipulation, opioids, brief individualized educational interventions, benzodiazepines, massage, and yoga have all been found to have a moderate net benefit.14Medications, physical therapy, nonsurgical interventions, and surgery are treatment options for low back pain. Minimally invasive interventions include exercise, acupuncture, functional restoration, progressive relaxation, self-care options, traction, spa therapy, and massage.15 While these more invasive treatment modalities may be a patient's only remaining recourse for intractable low back pain, complications associated with each option must be considered. Failed back surgery syndrome is a common complication of lumbar surgeries in which patients experience persistent, even aggravated, low back pain following surgical intervention.16 Peripheral nerve stimulation (PNS) offers an appealing alternative to these more invasive treatment modalities because the procedure is safe, minimally invasive, and reversible.16For patients refractory to these treatment options, radio-frequency ablation, surgery, and permanently implanted neuromodulation systems are used to treat chronic low back pain.17 Multiple prospective studies have been conducted to assess the effectiveness of PNS in patients with intractable low back pain, and all have found the procedure to be safe and effective in improving both pain and quality of life.20In PNS, small electrodes are placed next to a peripheral nerve. Electrical pulses delivered through the electrodes stimulate the desired nerve for 60 days and then the electrodes and PNS device are removed. For some patients with chronic low back pain, PNS has been shown to provide significant improvements in patient quality of life and pain reduction lasting at least 12 months.22 the results of these studies suggest that PNS should be considered as an intervention for these patients more often and perhaps earlier in their course of treatment. Studies by Kumar et al23 and van Gorp et al24 found that intervention with neuromodulative treatment, such as PNS, is associated with greater likelihood of pain relief and greater improvement in general health status overall. Despite the promising evidence surrounding PNS for use in patients with chronic low back pain, the procedure has associated complications, including lead migration, skin erosion, wound infection, dural puncture, and neurologic injury.25 Complication rates across studies range from 9% to 20% of patients.20 Ongoing investigation of these complications is critical to provide further evidence of the safety of PNS.Because impaired quality of life is one of the most prevalent negative impacts of chronic back pain,This case series underwent institutional review board review and received an exemption. All patients who underwent PNS implant met our defined criteria for chronic low back pain refractory to conservative management. Patients were considered eligible for intervention if they experienced nonspecific low back pain for at least 5 days per week for more than 2 months and did not experience relief following conservative management with a combination of pharmacotherapy, physical therapy, transcutaneous electrical nerve stimulation (TENS) units, chiropractics, sacroiliac joint injections, radiofrequency ablation, heat and ice, and rest. Prior to intervention, serious etiologies of low back pain, such as cauda equina syndrome or cancer, were ruled out.15 was used to place the SPRINT PNS System . Patients underwent fluoroscopy-guided percutaneous lead placement targeting the medial branch nerves at the lumbar levels at the center of the painful region. Correct placement was determined through ultrasound visualization of activation of the lumbar multifidi, and the leads were secured with surgical glue. The leads were then connected to wearable stimulators.For each of the 6 cases presented in this series, the approach described by Deer et alA 66-year-old male with a history of hypertension, obesity, degenerative joint disease of the lumbar spine, and depression presented to the interventional pain clinic with a 30-year history of left-sided low back pain. The patient had a history of multiple accidents, including falling off a ladder that resulted in multiple fractures. The patient rated his pain at 3/10 on the visual analog scale (VAS) and described it as a constant “achy” pain that worsened with movement and had been worsening during the prior few years. The patient experienced minimal relief with pharmacotherapy and conservative management.The patient underwent implantation of a SPRINT peripheral nerve stimulator targeting the left median nerves at the L4 and L5 levels . The patA 63-year-old male with a history of hypertension, hypogonadism, foraminal stenosis of the lumbar spine, obesity, and bilateral sciatica presented to the interventional pain clinic with progressing chronic low back and buttock pain following a lumbar laminectomy in 2019. He rated his right low back pain at 9/10 on the VAS and described it as a constant “sharp” pain radiating through the right thigh. The patient experienced minimal relief with pharmacotherapy, physical therapy, L4-L5 laminectomy, left facetectomy with interbody fusion, and C2-C7 cervical fusion.The patient underwent implantation of a SPRINT peripheral nerve stimulator bilaterally at the level of L4 . Eleven A 66-year-old female with a history of hypertension, obesity, anxiety, stage IIIC high grade serous ovarian carcinoma, breast cancer, and osteopenia presented to the interventional pain clinic with chronic low back pain and foot/ankle/calf chemotherapy-induced peripheral neuropathy. She rated her pain as 6/10 on the VAS and described the pain as a band across her low back that was occasionally sharp and constantly “achy.” The patient experienced minimal relief with rest, Salonpas Pain Relief Patches (Hisamitsu America Inc.), TENS unit, pharmacotherapy (except gabapentin which provided some relief), physical therapy, chiropractic intervention, acupuncture, sacroiliac joint injections, and lumbar interspinous injection at L3-L4 and L4-L5.The patient underwent implant of a SPRINT peripheral nerve stimulator bilaterally at the level of L4 . Ten dayA 70-year-old female with a history of hypertension, nerve entrapment syndrome, osteopenia, and degenerative joint disease of the lumbar region presented to the interventional pain clinic with chronic “achy” axial back pain that was worse on the right. The patient rated her pain as 10/10 when she presented to the clinic, although historically the pain was intermittent, improving to 0/10 at its best. The pain improved with rest and worsened with twisting, bending, sweeping, and vacuuming. The patient experienced minimal relief with pharmacotherapy, steroid injections, and lumbar medial branch radiofrequency ablation.The patient underwent implant of a SPRINT peripheral nerve stimulator bilaterally at the level of L4 . Eleven A 48-year-old male with a history of hypertension, morbid obesity, and osteoarthritis presented to the interventional pain clinic with chronic bilateral low thoracic back pain resulting from a vehicular accident. The patient rated his pain as 6/10 on the VAS and described it as sharp and tight, with the location around the ribcage bilaterally and the feeling “like I am doing sit-ups.” The pain was constant but worsened with sitting too long and twisting. Pain was improved by lying down. The patient experienced minimal relief with pharmacotherapy.The patient underwent bilateral L3 SPRINT peripheral nerve stimulator implant . The patA 68-year-old female with a history of hypertension, obstructive sleep apnea, and anxiety presented to the interventional pain clinic with a 3-year history of chronic low back pain. Her pain was axial; she described it as burning and sharp and rated it at a constant 6-10/10 on the VAS with a band-like shape in her lower back with no referral pattern. The patient experienced minimal relief with pharmacotherapy, dry needling, physical therapy, and L4-S1 bilateral radiofrequency ablation. The patient found some relief with a sacroiliac joint injection, lumbar trigger point injections, and bilateral greater trochanteric bursa injections.The patient underwent bilateral L4 SPRINT peripheral nerve stimulator lead placement . Eleven The 6 cases are summarized in the All of the patients presented in this series reported a decrease in pain scores with implantation of a PNS device. The average percent pain reduction among the 6 patients was approximately 64.8%, equating to a mean pain score drop of 4.9. Two patients had better pain relief with the device in place. One of the 6 procedures targeted L3 bilaterally, 4 of the 6 targeted L4 bilaterally, and 1 targeted both L4 and L5 on the left side.2), and 2 of the 6 presented with a history significant for anxiety. The average age for the 6 patients was 63.5 years, with an age range of 48 to 70 years. These cases provide data on potential variables for predicting the efficacy of PNS in treating back pain.All 6 patients—3 males and 3 females—presented with a medical history including hypertension, 5 of 6 were obese (body mass index >30 kg/m26 Additionally, randomized controlled trials conducted by van Gorp et al reported that the only other factor associated with effectiveness of PNS was time since onset of pain, finding that quicker intervention with PNS showed greater likelihood of pain relief.24 Future clinical trials should investigate the impact of obesity, hypertension, and other chronic conditions on the efficacy of PNS. Patients whose pain is directly impacted by a chronic condition such as obesity might experience a difference in benefit from PNS intervention vs patients without chronic conditions.As with any procedure, identifying the ideal patient population to undergo PNS for chronic low back pain is essential. Evidence suggests that younger patients have improved pain reduction as a result of PNS vs older patients.Because lumbar level PNS is a relatively new procedure, all negative side effects need to be documented in the literature. Negative observations from these 6 patients following PNS placement included abnormally awakening at night, a mild rash at the dressing site, difficulty changing dressings, accidental removal of leads, and some pressure at the site of implantation. The literature on PNS use in patients with low back pain does not include investigation of the etiology of such negative effects, and although these negative side effects are minor, further investigation of them in clinical studies is important to confirm PNS as a safe option for patients. Positive effects other than pain reduction reported by the patients in this series were improved sleep, the ability to stand for longer periods without pain, and functional improvement.27 With PNS implantation for low back pain, not only are medial branch nerves targeted, but the intrinsic back muscle—the multifidus—is also stimulated. Wallwork et al showed that people with chronic low back pain have smaller multifidus muscles compared to healthy individuals.28 The placement of the PNS lead is typically in the substance of the multifidus muscle and to identify correct placement, stimulation resulting in selective unilateral multifidus activation is visualized on ultrasound.29The mechanism of pain relief provided by PNS remains poorly understood. The gate control theory postulates that the pain relief provided by neuromodulation interventions arises from the inhibition of A-delta and unmyelinated C fibers via subcutaneous stimulation of myelinated A-beta fibers within the spinal cord by devices such as peripheral nerve stimulators.16 While all patients included in this case series experienced pain relief from PNS placement, future clinical studies should investigate the patient history and demographic factors associated with decreased efficacy of pain reduction via PNS along with analyzing the duration of its effect.Some patients do not experience effective pain relief from PNS. In their study regarding the safety and efficacy of PNS, Ishak et al hypothesized that patients with a history of large skin incisions and multilevel surgical preparations may not benefit from PNS because of irritation of subcutaneous nerves that modifies the ability of terminal sensory afferent nerves to depolarize in the presence of the electrical field generated by PNS devices.Patients with refractory chronic low back pain may find pain relief and functional improvement with PNS of the medial branch nerves at the lumbar spine level. This 6-case series suggests the potential for not only a large reduction in pain but also an increase in daily living function. These 6 patients showed an average pain reduction of 64.8% with minimal side effects. Further research needs to be conducted to assess the efficacy of using PNS as a treatment for chronic lower back pain in a larger population, the severity of less common complications, and the impact that variables such as sex and obesity have on the effectiveness of PNS. Additionally, further research should be conducted to improve this procedural technique to maximize its effectiveness, minimize any complications, and assess the duration of its potential relief.


Irritable bowel syndrome (IBS) is a chronic disease leading to abdominal pain that is often related to psychological distress. The aim of the study was to investigate the temporal relationships between abdominal pain and psychological variables in patients with IBS.This longitudinal diary study included eight patients from a waiting group, recruited in the frame of a pilot intervention study. During their waiting time of 3 months the patients answered questions daily regarding somatic and psychological variables using an online diary. All patients were considered and analyzed as single cases. The temporal dynamics between the time series of psycho-somatic variables were analyzed using a vector autoregressive (VAR) modeling approach.r = 0.40 to r = 0.94). Altogether, n = 26 significant lagged relationships were identified; n = 17 (65%) indicated that somatic values were predictive of psychological complaints on the following days. N = 9 (35%) lagged relationships indicated an opposite relationship in that psychological complaints were predictive of somatic symptoms. Three patients showed a significant positive same-day correlation between abdominal pain and use of a positive coping strategy. However, significant lagged relationships in two patients showed that for these patients the use of positive thinking as a coping strategy was unhelpful in reducing pain on the following days.For all patients, positive same-day correlations between somatic and psychological time series were observed. The highest same-day correlations were found between somatic symptoms and pain-related discomfort (In patients with IBS abdominal symptoms appear to be closely related to psychological symptoms. For some patients, somatic complaints predict psychological complaints, in other patients the directionality is opposite. The impact of coping strategies on somatic symptoms varies among patients, therefore their role for a possible reduction of pain should be further explored. The results suggest the need of characterizing patientsindividually for effective health interventions. Individual time series analyses provide helpful tools for finding reasonable person-level moderators. Irritable bowel syndrome (IBS) affects about 8% of the European population  and is mvia mast cell activation , assessed by using a longitudinal, observational design. ROME-III criteria were collected by a questionnaire and validated in a telephone interview prior to patient inclusion. According to ROME-III an IBS can be diagnosed when a patient has recurrent abdominal pain or discomfort at least 3 days per month associated with 2 or more of the following: (1) improvement with defecation, (2) onset associated with change in frequency of stool, (3) onset associated with a change in form (appearance) of stool. The criteria must be fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis . DiagnosAll patients were recruited by way of an appointment in the outpatient specialty clinic of the Department of General Internal Medicine and Psychosomatics, University Hospital Heidelberg, for functional gastrointestinal disorders, before the start of a pilot intervention , 29.Written informed consent was obtained; the study was approved by the medical ethics committee of the University Hospital Heidelberg.In the course of their waiting time patients answered questions daily using an online diary that included somatic, psychological, and coping variables. All patients filled in the online diary over a period of 3 month between 07/2014 and 05/2015 (different start times). The number of measurement days per patient varied between 68 and 94, thus fulfilling the requirements for the application of a comprehensive time series analysis approach .Patients were given information about the online diary and were asked to complete it daily (between 4 and 12 p.m.). The diary questions referred to questions from validated questionnaires, shortened so that a completion time of 5–10 min could be achieved. A visual analog scale (VAS) with bipolar levels was used by the patients and later transcribed into a numeric scale (1–101). In addition, patients were provided an opportunity to write a short free text in the diary.The items included in the analysis are shown in In the following, we briefly describe the patients including their disorder history, comorbidities, and the free-text diary data in order to provide some information for the interpretation of the individual time series analyses. All patients were German and can be described as typical patients with IBS treated in our outpatient clinic: They suffer from various somatic and psychological comorbidities and show a high burden of complaints .P1 was a man in his late 40s, employee, suffering from diarrhea-dominant IBS and gluten-sensitivity (no celiac disease) for 2 years. His symptoms had begun following a career change that was associated with increased stress levels. He reported that he was under a high pressure to perform - also reflected in the diary data. Several peaks of abdominal pain  were related to an actual high stress situation on his job. In addition, episodes of less or no pain were associated with periods when the patient was on vacation and /or thinking about other things than work (days 54–65). Other stressors (such as a sick child or trying gluten) appeared not to be associated with pain.P2 was a woman in her late 20s, employee, suffering from diarrhea-dominant IBS (main symptom pain), fructose malabsorption, depression, and social phobia. Fructose malabsorption is common in IBS and does not rule out the diagnosis of irritable bowel syndrome, particularly when improvement is not obtained following an appropriate diet  she described how good everything was—apart from the symptoms. However, in her contact to our outpatient clinic she also assumed a connection between IBS-symptoms, stress, tension and regrets regarding her work.P4 was a man in his late 30s, employee, with mixed-type IBS, sorbitol intolerance, suspected wheat/gluten-sensitivity, reflux esophagitis, and a depression diagnosis. The patient used the free text for only the first 5 days, describing his work as challenging. During the appointment in our outpatient department he described an inner restlessness and nervousness. He generally attributed improvements in health to natural remedies and nutritional advice.P5 was a woman in her early 20s, student, with mixed-type IBS, functional dyspepsia, lactose intolerance, bronchial asthma, depression, and suspected emotionally unstable personality disorder. An atypical eating disorder had also been discussed. She suffered from IBS for several years and described ongoing fears of being unable to cope with her symptoms. She was very afraid of bodily changes  and of other people's reactions. In the free text of the diary she expressed her impairment and insecurity also reflected in the data by high pain scores or high daily impairment .P6 was a woman about age 30, employee, with mixed-type IBS, fructose malabsorption, and tension headache. Since attending school, she had symptoms that had worsened over the past years. She described feelings of social anxiety in relation to her complaints that were also reflected in the free text of her diary. Her fear and shame were related to other people, who, she feared, might notice that something was wrong . Apart from this anxiety, she described an increase in symptoms due to menstrual cramps (day 15), and problems at work (day 16). Interestingly, her time series indicated an improvement regarding IBS symptoms and daily impairment when she described almost no positive events .P7 was a woman about age 50, employee, with unsubtyped IBS , sorbit malabsorption, fibromyalgia, and depression. Symptoms had started a long time ago with an onset of more severe symptoms approximately 7 years ago. She described that her complaints were aggravated by nervousness and gas-forming food. Additional stress factors, as described, were a difficult childhood and an unfulfilled desire to have children. In the free text of the diary she frequently reported complaints such as tiredness, pain , and bloating as well as having negative feelings  She very rarely reported positive feelings.P8 was a man about age 50, unemployed, on sick leave for several months, with diarrhea-dominant IBS, lactose intolerance, and severe depression. He described that symptoms began more than 20 years ago and that they could be controlled only minimally by medication (loperamide). He completed the free text diary for only the first few days. He indicated better episodes such as symptom improvement of diarrhea, anxiety, or depression  and worse episodes due to ineffective medication  or thinking about problems (day 14).The analyses were conducted using the R software. For further descriptions, more elaborate explanations regarding time series analysis, and implementations of all analyses with the R software we refer to further literature , 34, 35.The left part of r = 0.40 and r = 0.80. This means that for all patients, high values in abdominal pain were associated with high values in DI on the same day.The right section of For four patients  the IRFs indicated significant temporal relations between somatic time series. For example, abdominal pain measures of patient 7 depended linearly and positively on previous day values of IBS associated daily impairment: Step 1 IRF=0.49, 95% CI=.The free text of the patients' diaries is mainly reflected in the time series data .r = 0.40 to r = 0.97. The amount of explained variance (R2) from linear regressions, with psychological measures as dependent variables and somatic variables as predictors, varied from 2 (patient 2) to 94% .r = 0.25 to r = 0.42. For four patients (P1–P4), somatic symptoms were followed by more coping next day with 5 to 17% of explained variance. In only two patients  the use of coping strategies was temporally predictive for abdominal pain on the next day. However, and unexpectedly, for these patients a more frequent use of coping strategies was followed by an increase in abdominal pain on the next day (with 5–6% of explained variance in AP).For three of the patients , significant positive same-day correlations were observed: This study investigated the daily temporal relationships between somatic and psychological variables in patients with IBS. Of note is the fact that in some aspects the patients presented quite similar patterns in cross-correlations whereas in other aspects the results differed widely across patients. Therefore, the patterns that were noted for the majority of patients will be reviewed first, while the individual patterns of illness and coping will be discussed afterwards.The somatic time series of all patients (except P5) remained stationary during the observation period - that is, time series exhibited no trends in this study period where the patients were waiting for the beginning of a group program and did not receive additional psychotherapeutic treatment. This corresponds to previous studies describing IBS as a chronic disease. Only 55% of IBS-patients report a remission over a period of more than 10 years .For all patients, strong positive same-day correlations of abdominal pain (AP) and IBS-associated daily impairment (DI) were observed. Not only does this result reflect the strong association between pain and daily impairment, but it also indicates that the self-reported diary scores are valid. For P1, P3, P5, and P7 the temporal relationship between AP and DI were significant in the direction that a higher symptom score in DI was followed by a higher AP score; thus, in 50% of the patients, higher daily impairment appears to trigger higher abdominal pain. For P2, P4, and P6, the direction of the temporal relationship between AP and DI was the reverse, but only as a trend.All patients showed high positive same-day correlations between IBS associated daily impairment and psychological variables such as nervousness, depressiveness, or hopelessness. We can therefore conclude that all of the included IBS patients were psychologically burdened on days with higher somatic symptoms. In addition, for all patients, somatic symptoms were most strongly related to pain-associated discomfort. This may confirm the validity of the diary entries.Regarding the temporal relationships between somatic symptoms and coping strategies, we were unable to replicate the results of a previous single case analysis for all patients . Only twFurther, for all patients, significant temporal relationships were found between somatic and psychological variables. In 6 patients, an increase in psychological variables such as nervousness or tension significantly predicted an increase in abdominal pain or irritable bowel related somatic impairment on the following days. For two patients the opposite was true: here, higher scores in psychological variables predicted a decrease in pain or somatic impairment on the following days. These results are partly in contrast to a previous study using ESM in IBS patients reporting that daily life stress predicted a decrease in abdominal pain . Vice veIn our study, the direction of the temporal relationship between somatic and psychological variables varied across patients and individual patterns were clearly visible.In his diary free text P1 expressed the insight that the severity of his IBS symptoms could be related to stress. This was reflected in the time series data by high same-day correlations between DI and tension as well as DI and nervousness. For this patient, higher AP on 1 day was followed by higher depressiveness on the next day. However, there appeared to be a mutual relationship between somatic and psychological variables because a higher score in hopelessness was followed by higher IBS related impairment. The time series data of AP and DI showed clear peaks of increased discomfort that decreased shortly afterwards.Results for P2 showed a high same-day correlation between somatic complaints and catastrophizing. In her case, abdominal pain was followed by depressiveness, while higher catastrophizing predicted higher daily impairment on the following days. Interestingly, this patient reported visiting her general practitioner, as well as various medical specialists quite frequently. According to her story, the doctors continued to give her diagnostic information instead of introducing another perspective of IBS symptoms. This approach is often used by doctors who frequently experience patients with medically unexplained physical symptoms as difficult . HoweverP3 described, almost exclusively, positive feelings and events. However, we found a mutual relationship between catastrophizing and pain. A higher pain score predicted more catastrophizing at 4 days later whereas a higher catastrophizing score was followed by less pain at 4 days later. For this patient, one could hypothesize that admitting negative feelings could lead to more self-acceptance and relief. Exaggerated positive thinking can be a denial, thus avoiding measures to reduce pain and relieve stress. Furthermore, the suppression of emotional expression and unwanted thoughts have been shown to be correlated to higher physiological arousal and psychopathology .P4 was a patient who mainly attributed his complaints to physical causes. However, his diary data showed a strong same-day correlation between tension and somatic symptoms. In addition, increased tension was followed by stronger pain at 3 days later. This could reflect an inability to link psychological processes to physical ones and vice versa; this is often observed in IBS .P5 was a patient who was completely focused on her body. Her symptoms and her fears  could also be signs of an eating disorder. Comorbid eating disorders are common in patients with functional gastrointestinal diseases (up to 10% in our outpatient clinic) ; a conneP6 reported profound social fears in relation to her IBS symptoms. Her diary data showed high same-day correlations between somatic symptoms and hopelessness in addition to catastrophizing. Interestingly, in this patient an increase in nervousness was followed by a decrease in DI on the next day. In the free text the patient frequently described social anxiety and the specific fear that, in social contexts, she would have to rush to a toilet. The latter is often described by IBS patients  and may P7 was aware of the connection between her life stressors and (the following) somatic complaints. This was reflected in the time series data by high same day correlations between somatic complaints and psychological variables. This patient also had a diagnosis of depression - also common among IBS patients. Her diary data showed that higher depressiveness on one day was followed by an increase in pain on the next day; conversely, a higher score in pain on one day was followed by a decrease in nervousness 2 days later. One could thus speculate that the pain symptoms played a part in the mood regulation of the patient.P8 was on sick leave for several months; the comorbid diagnosis of depression contributed to his symptom burden. Interestingly, for this patient, time series analyses showed that increased daily impairment was followed by decreased depressiveness and nervousness at 4 days later. A previous study found that more than 40% of the patients on longer sick leave reported feelings of guilt . It is pvia the (microbiota-) gut-brain axis. Psychological stress can lead to an activation of the autonomic system, the HPA-Axis, or the immune system resulting in increased IBS symptoms (via mast cell activation to increased IBS-symptoms on the following day).When looking at all of the patients and their diverse courses of illness, emotions, and time series, it becomes clear that IBS is not expressed as a single type of IBS. Still, it is possible to draw a few conclusions for the entire group of examined patients: High same-day correlations between somatic and psychological time series (including negative coping) suggest a strong association between these complaints for all patients. This close relationship is also indicated by the day-lagged data, indicating a mutual relationship between somatic and psychological complaints. Possible physiological mechanisms linking somatic and psychological complaints in IBS patients can be explained symptoms , 14. VicOur study has several limitations. Firstly, we examined only eight patients who suffered from IBS. As inter-individual variability can be accentuated and obliterated by a small sample size, the generalizability of the results is limited. Secondly, we analyzed associations with abdominal pain because it is the cardinal symptom of IBS. However, symptoms such as diarrhea, urgency, or the feeling of not being able to empty the bowels can be equally disturbing for the patients. The results – particularly the determined associations between coping strategies and symptoms – are therefore limited and only valid in regard to the cardinal symptom, abdominal pain. Thirdly, we were able to detect day-to-day changes only; shorter periods of time could not be captured. Nevertheless, previous studies focused mainly on longer time periods or had no longitudinal data at all. As a result, this approach is still more advantageous in terms of capturing the direct relationships. Finally, it is possible that irritable bowel symptoms and psychological variables were driven by factors that were not captured in the data set such as stressful life events that had occurred prior to the study. However, the most significant strength of our study is that we, by examining all patients individually, could show a clear picture of the patients and their differences, even if our conclusions are highly speculative. The high data density per patient is helpful as IBS is a complex illness with, in all likelihood, heterogeneous genesis and factors.This study has several implications: Clinicians and researchers should be aware of the great variability of patients with IBS; patients may present their fears, triggers, emotions, and coping strategies in a multiplicity of ways. While some strategies may be helpful for certain patients , this approach has no or even a reverse effect in others. Therefore, a very accurate anamnesis should always be taken, and the therapy should be adapted to the individual patient's needs. As a result, the direction of the effect is highly relevant in deciding whether therapy should focus primarily on IBS symptoms or on the psychological distress. For future research on patients with IBS it is important to be aware of the dilution and loss of data in aggregated data analysis. The varying patterns of psycho-somatic symptoms and dynamics indicate that individual factors are moderating the interdependency of psychological and somatic symptoms. Possible person-level moderators, in our sample, could be a high pressure to perform , illness worries (P2), neglect of feelings (P3), eating disorder (P5), social anxiety (P6), biographical stressors (P7), or resignation (P8). It could be important to more closely investigate these person-level moderators in order to generate a better understanding of the diverse mechanisms in IBS and to apply appropriate therapeutic strategies.In the IBS cases here presented, we found a high correlation between somatic and psychological complaints, as was also represented in day-lagged relationships. The patients exhibited a wide variety of their particular course of illness. Our study supports the finding that patients with IBS are a heterogeneous group, and that individualized biopsychosocial explanatory models and treatment concepts are needed.The raw data supporting the conclusions of this article will be made available by the authors upon request, without undue reservation.The study was reviewed and approved by the Ethics Committee of the University Hospital, Heidelberg.BW, FE, ES-K, and RS conceived and designed the study. FE, SB, ES-K, and RS collected the data. TS statistically analyzed and all authors interpreted the data. FE, BW, and TS drafted the manuscript. All authors critically revised the manuscript and provided important intellectual content and approved the final version.The study was supported by the Medical Faculty of the University of Heidelberg, Postdoctoral Fellowship Program. For the publication fee we acknowledge financial support by Deutsche Forschungsgemeinschaft within the funding programme Open Access Publikationskosten as well as by Heidelberg University.The 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.


To determine the proportion of patients admitted to the hospital for back pain who have nonserious back pain, serious spinal, or serious other pathology as their final diagnosis. The proportion of nonserious back pain admissions will be used to plan for future ‘virtual hospital’ admissions. Electronic medical record data between January 2016 and September 2020 from three emergency departments (ED) in Sydney, Australia were used to identify inpatient admissions. SNOMED-CT-AU diagnostic codes were used to select ED patients aged 18 and older with an admitting diagnosis related to nonserious back pain. The inpatient discharge diagnosis was determined from the primary ICD-10-AM codes by two independent clinician-researchers. Inpatient admissions were then analysed by sociodemographic and hospital admission variables. A total of 38.1% of patients admitted with a provisional diagnosis of nonserious back pain were subsequently diagnosed with a specific pathology likely unsuitable for virtual care; 14.2% with a serious spinal pathology  and 23.9% a serious pathology beyond the lumbar spine . A total of 57% of admissions were identified as nonserious back pain, likely suitable for virtual care. A challenge for implementing virtual care in this setting is screening for patients with serious pathology. Protocols need to be developed to reduce the risk of patients being admitted to virtual hospitals with serious pathology as the cause of their back pain.The online version contains supplementary material available at 10.1007/s10067-022-06054-w. Guidelines for managing low back pain recommend that it should be managed in primary care , howeverDevelopment of clinical pathways allowing for avoidance of ‘traditional admission’ is urgently needed. A potential solution is to offer a ‘virtual hospital’ model of care to select patients who would do well with this approach . The virEstimates for the prevalence of serious spinal pathology in patients presenting with back pain to the ED are higher than those for patients presenting to primary care. A systematic review of 22 studies in the ED reported rates of 2.5 to 5.1% in prospective and 0.7 to 7.4% in retrospective studies for pathologies requiring immediate or urgent treatment . These eAt present, no study has focussed on the discharge diagnoses of patients who were admitted, via the ED, with a provisional diagnosis of nonserious back pain. Understanding the prevalence and profile of these patients may lead to a better understanding of the feasibility of a virtual hospital model care as an alternative to inpatient admission for back pain. Thus, in this study, we determined the proportion of patients admitted with nonserious back pain who received a discharge diagnosis of serious spinal or non-spinal pathologies or other musculoskeletal conditions. We also examined the specific pathologies within these broad categories and the patient characteristics associated with these categories.We followed the Reporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement . Approvai.nonspecific back painii.radicular back painiii.serious spinal pathologyiv.serious pathology beyond the lumbar spinev.other musculoskeletal conditions We accessed electronic medical record data for the three SLHD EDs between January 2016 and September 2020. SNOMED-CT-AU diagnostic codes were used to select ED patients aged 18 and older with an admitting diagnosis related to nonserious back pain  . The disCategorisation of primary ICD-10-AM codes was completed independently by two experienced clinicians, and any disagreements were resolved by consensus reviewing the inpatient electronic medical record of such patients. ICD-10-AM sub-categories were created for two categories: ‘serious spinal pathologies’ and ‘pathology beyond the lumbar spine’, to ascertain the prevalence of specific pathologies.Socio-demographic variables such as age, sex, and postcode were collected. Patient postcode was linked to SEIFA (Socio-Economic Indexes for Areas) categories and clustered by deciles 1–5 and 6–10, as a proxy for socioeconomic status. Data regarding ED admission included mode of arrival (ambulance or non-ambulance), and Australasian triage scale category (1–5). Hospital length of stay in the ED as well as on the ward was also collected.We included 1982 admissions from ED with a provisional diagnosis of nonserious back pain. These admissions were coded to 394 unique ICD-10-AM diagnostic codes and distributed to the five broad categories  of admissions were identified as nonserious back pain, likely suitable for virtual care. These patients had a mean age of 70 [51–82], 41% were female, with 73.4% living in areas with a higher average socioeconomic index (6–10). Postcode data were missing for 30 admissions. 61.6% of nonserious back pain patients arrived by ambulance, with 53% being triaged as ATS 3, classified as severe pain  and infection (2.1%), and the most common serious pathologies beyond the spine were pathological fracture (7.3%) and infection (4.3%).In those aged ≥ 65, serious spinal pathology had a prevalence rate of 16.2%, compared to 10.6% in those under 65. Pathologies beyond the lumbar spine were also more prevalent at 26.6% in those aged ≥ 65, compared to 18.9% of those younger than 65. 5.0% of all admissions were for a nonserious musculoskeletal condition beyond the lumbar spine.Over half the admissions from ED with a provisional diagnosis of nonserious back pain had an equivalent discharge diagnosis and so are likely to be suitable for a virtual hospital model of care. However, a significant proportion of patients admitted with nonserious back pain were subsequently diagnosed with a specific pathology likely unsuitable for virtual care; 14.2% with a serious spinal pathology and 23.9% with a serious pathology beyond the lumbar spine. The most common serious spinal pathologies were fracture (8.7%) and infection (2.1%), and the most common serious pathologies beyond the spine were pathological fracture (7.3%) and infection (4.3%). These results suggest that patient selection would be key to the successful implementation of a virtual hospital model of care as an alternative to inpatient admission for LBP.This is the first study to investigate discharge diagnoses in patients who presented to ED with back pain and were admitted as inpatients with a provisional diagnosis of nonserious LBP. A strength of the study is that we sourced hospital admission data over a 4.75-year period, with a large sample size drawn from three university teaching hospitals in Sydney. We do acknowledge that rates of specific pathologies may be different in other health districts. Detailed consideration of ICD-10-AM codes by two experienced clinicians increased the precision of the diagnostic data we extracted. However, ICD-10-AM codes are applied by administrative staff to diagnostic information in the electronic medical record, therefore there is potential for error in the initial clinical coding. We are unable to report on rates of serious pathology ‘red flags’, as this data was not extracted from medical records.This study did not consider other criteria to judge a patient’s suitability for virtual care. We understand that comorbid health conditions, patients’ existing social support and ability to navigate virtual care, as well as preferences, would all influence whether a patient would be suitable. We plan to evaluate these issues in a separate series of studies.An Australian study of 712 admissions via ED to general medical or rheumatology wards over 36-months [Our results would suggest that up to 57% of ED LBP patients who are currently admitted as an inpatient may be suitable for virtual hospital care, which is ~ 250 patients per year. We have previously shown that each of these admissions typically costs ~ $A15,000 , meaningA key clinical challenge in implementing virtual hospital care is the differential diagnosis of nonserious, serious spinal, and non-lumbar pathologies in those presenting to ED with back pain. Protocols need to be developed to reduce the risk of patients being admitted to virtual hospitals with serious pathology as the cause of their back pain. Transfer to virtual care from ED short-stay units or the inpatient ward, once laboratory tests and imaging results are available to confirm nonserious back pain, maybe a suitable clinical pathway. We plan to evaluate the implementation of a virtual hospital model of back pain in the Sydney Local Health District in 2022.Supplementary file1 (DOCX 32 kb)Below is the link to the electronic supplementary material.


Background and objectives: Fragility fractures of the pelvis (FFP) are of increasing interest lately, being associated with a loss of mobility and affecting the quality of life. The aim of our study was to investigate the effect of FFP on disability and pain in patients, after one year since injury. Materials and Methods: In the study, we included 76 patients diagnosed with FFP, who were admitted to our trauma department between January 2016 and January 2019, and were above 65 years of age. The Von Korff pain intensity and disability scores were calculated in the hospital at 6 months and after 1 year. Results: Fifty-four patients were female (71%), with an average age of 75.9 ± 7.19 years. Twenty-two patients were male (29%) and had a mean age of 77.22 ± 7.33 years. We did not record significant differences regarding age between the men and women (p > 0.05). Significant improvements appeared between the baseline and the 6 month follow-up; the average pain intensity score at 6 months was 44.94 (SD 21.20) (p < 0.001), and the disability score was 54.30 (SD 21.62). The following average pain intensity and disability scores after 12 months were similar to the values at6 months: 44.48 (SD 21.74) for pain intensity and 52.36 (SD 24.53) for disability. The Von Korff pain score at 6 months and after 1 year depends on gender and on the initial Von Korff pain score (p = 0.02). The Von Korff disability score at 6 months depends on gender, the baseline pain score and the baseline disability score (p = 0.001). Conclusions: our patients reported long-lasting pain that had a severe effect on their daily routines, and they could not return to their normal status prior to injury. Because of the high life expectancy in our population, fragility fractures have become more frequent . Bone frFragility fractures are defined as fractures that occur following a low-energy trauma . The fraThe priority in the treatment of fragility fractures of the pelvis (FFP) is pain control and the restoration of mobility. Bone strength and bone morphology are restored by means of conservative and surgical management. Pharmacotherapy is involved in bone resorption through anti-resorptive and anabolic medication. Agents such as calcium, bisphosphonates, denosumab, selective estrogen receptor modulators and estrogen hormone therapy  inhibit bone resorption, and agents such as teriparatide and abaloparatide promote bone mass formation.A third anabolic product (romosozumab) is in the FDA approval procedure ,6. OsteoPain and disability are the primary problems caused by FFP in elderly people. Many studies indicate long periods of immobility and, therefore, a lack of independence for patients who suffer from FFP ,11,12. TIn recent years, there has been an increased frequency of fragility fractures in the elderly. These events are associated with prolonged hospitalizations, disability, morbidity and last, but not least, mortality. In this context, the aim of our study was to investigate the effect of FFP on disability and pain in patients, after one year since injury.In our observational study, we enrolled patients with an age higher than 65 years, who were admitted to our hospital with FFP, from January 2016 to January 2019. Only the patients who were treated conservatively were recruited. The fractures were diagnosed by X-ray or CT scan. Exclusion criteria for the patients included treatment with anti-osteoporotic drugs or prior pelvic fractures. We also ruled out pelvic fractures due to high-energy mechanisms or metastatic pathology. We informed all our patients about information regarding the study and provided invitations for participation. For those who agreed to take part in the study, questionnaires were given to them during hospital admission. Upon admission, each patient was given an anticoagulant and analgesic regimen. The analgesic therapy and cocktail were adapted according to the pathology of each patient and to their tolerance to these drugs. The analgesic regimen consisted of Urgendol, Quamatel, Ketoprofen and Perfalgan, all in a two-vial dosage. The evaluations at 6 and 12 months were conducted by interviewing patients by phone. Informed consent was obtained from all patients who accepted to participate in our study. The research was carried out in conformity with the Declaration of Helsinki and authorized by the Ethical Board of the Emergency Hospital “Sf. Spiridon” in Iasi (8 October 2019).Von Korff et al.  developep < 0.05.We used SPSS version 18 for the statistical analysis. Data were presented as mean ± standard (SD) deviation or percentage (±SD). Statistical significance was defined as a The multiple correlation coefficient, as a measure of the association between y and the set of variables x, introduces the multiple correlation coefficient, denoted by R. It can be defined as the maximum simple correlation coefficient (Pearson) between y and a linear combination of variables x. This explains why the calculated value of R is always positive and tends to increase as the number of independent variables increases. The least squares method can, thus, be thought of as a method that maximizes the correlation between the observed values and the estimated values (those representing a linear combination of variables x). An R value close to 0 denotes an insignificant regression, meaning that the predicted regression values are not any better than those obtained by a random approximation (or based only on the distribution of y).From January 2016 to January 2019, we admitted 112 patients with FFP to our hospital. A total of 29 patients refused to participate and were excluded. Ultimately, we included 83 patients in the study. Only 76 patients responded to the questionnaires at all three evaluations; 5 did not respond to the questionnaires at all and 2 died during the follow-up period.p > 0.05). The mean age of the patients was 76.28 ± 7.26 years. We did not record significant differences regarding age between the men and women  are presented in Following the Rommens and Hofmann classification of the FFP, 28 patients had FFP type Ia lesions , 2 had FFP type Ib lesions , 2 had FFP type IIa lesions , 25 had FFP type IIb lesions , 13 had FFP type IIc lesions , 2 had type IIIa lesions , 1 had a type IIIb lesion , 2 had type IIIc lesions , and 1 had a type IVb lesion  . The disThe results of the questionnaires at all three evaluation times are presented in The data are given as mean ± SD, and the P values represent the differences between 6 months, 1 year and baseline.The distribution of Von Korff pain and disability scores during the first year after injury can be observed in p < 0.001), and remained elevated at the 1-year follow-up, at 11.8%.The initial pain intensity score was found to be between 75 and100 in 45 patients (59.2%), between 50 and75 in 25 patients (32.9%), and between 25 and50 in 4 patients (5.3%). Only 2 (2.6%) patients had a score of less than 25 points. Pain severity decreased considerably at the 6-month follow-up, from 59.2% to 10.5% .A percentage of 74.2% of the variation in pain scores at 6 months is explained by the variables gender and baseline Von Korff pain scores (p = 0.087).Only 29.4% of the variation in disability scores at 6 months is correlated with the variables gender and baseline Von Korff pain and disability score, but the result was not statistically significant . The disability score at 6 months is dependent on sex . The disability score at 12 months apparently does not depend significantly on sex, the baseline pain score or the baseline disability score (p = 0.662).The specific analyses showed that the Von Korff pain score at 6 months and after 1 year depends on sex and on the initial Von Korff pain score  was significantly higher than in males (29%). In a retrospective analysis of 245 patients with FFP, a similar distribution was found when patients were stratified by sex .Most of the studies referring to the follow-up of patients who suffered from FFP were focused on the functional outcome and mortality rate ,25,26,27p < 0.001). At the one-year follow-up, the pain intensity score (44.48 ± 21.74) was low compared to baseline , but had not significantly changed from the 6-month follow-up. The pain levels after 6 months and after 12 months were very similar. This indicates that the pain intensity diminished earlier. In further studies, we suggest that the researchers evaluate the pain intensity at earlier times  to have a better idea of the natural course of pain intensity after FFP.The results of our study show an important decrease in the pain intensity score (44.94 ± 21.20) at 6 months, compared to baseline (73.19 ± 18.21, Similar results were also obtained when assessing the Von Korff disability score. Suzuki et al. reported similar results when they evaluated the course of pain intensity and degree of disability in the first year after acute vertebral compression fractures were treated non-surgically .The participants who underwent our questionnaires and were involved in the study, and who described an active lifestyle prior to their fragility fracture, reported being unable to achieve similar resistance levels and intensity regarding physical activities.Although the intensity of the pain decreased compared to baseline, some pain remained, which had a negative impact on their quality of life.A study about the experience of women who suffered from post-menopausal vertebral fractures reported that pain from their fracture severely restricted their routine social activities . The paiThe development of rehabilitation strategies that alleviate pain and improve the quality of life for patients suffering from FFP is a major necessity. New rehabilitation strategies that alleviate pain and improve the quality of life require a combination of therapeutic exercise with continuous radiofrequency or the administration of food supplements ,31,32.This study has limitations. The patients were not clinically consulted to assess the outcomes. Our study highlights the importance of the diagnosis and treatment of osteoporosis to reduce and prevent the risk of FFP. To reduce healthcare-related costs in the future, it is important to focus on the prevention of falls and osteoporosis.The questionnaire of Von Korff is very simple. A more detailed questionnaire could provide the researcher and reader with a more differentiated view of what kind of disability is permanent. The therapists could develop specific treatment protocols with this new knowledge.The patients included in our study reported long-lasting pelvic pain, which they described as disturbing, and they reported that this pain affected their daily activities- and that they were ultimately unable to achieve the same quality of life. It is clear from our results that FFP is directly related to the loss of social and physical independence. Efforts are needed to prevent pelvic insufficiency fractures. The development of rehabilitation strategies that alleviate pain and improve the quality of life for patients suffering from FFP is a necessity.