Literature Review: Mechanism, Indications, and Clinical Efficacy of Peripheral Nerve Stimulators in Lower Extremity Pain.

PURPOSE OF REVIEW: Lower extremity pain is deemed by Center for Disease Control and Prevention (CDC) to be a significant source of chronic pain in adults. If not appropriately managed, patients are subjected to risks of prolonged musculoskeletal dysfunction, disruption to quality of life, and elevated healthcare expenditures. Peripheral nerve stimulation (PNS) has shown great potential in recent years demonstrating efficacy in multiple diagnoses ranging from acute post-surgical pain to complex regional pain syndrome (CRPS). This study seeks to delineate efficacy of peripheral neuromodulation in the context of chronic lower extremity pain. RECENT FINDINGS: Prevailing clinical studies demonstrate evidence levels ranging from II to V (Oxford Centre of Level of Evidence) in lower limb PNS, attaining positive outcomes in pain scores, opioid use, and quality of life measures. Nerves most frequently targeted are the sciatic and femoral nerves with post-amputation pain and CRPS most commonly investigated for efficacy. PNS is a promising therapeutic modality demonstrated to be effective for a variety of nociceptive and neuropathic pain conditions in the lower extremity. PNS offers chronic pain physicians a powerful tool in the multi-modal management of lower limb chronic pain.

Benefits of home-based foot neuromuscular electrical stimulation on self-reported function, leg pain and other leg symptoms among community-dwelling older adults: a sham-controlled randomised clinical trial.

INTRODUCTION: Lower leg pain and symptoms, and poor leg circulation are common in older adults. These can significantly affect their function and quality of life. Neuromuscular electrical stimulation (NMES) applied via the feet as 'foot NMES' activates the leg musculovenous pump. This study investigated the effects of foot NMES administered at home using Revitive® among community-dwelling older adults with lower leg pain and/or other lower leg symptoms such as cramps, or sensations of tired, aching, and heavy feeling legs. METHODS: A randomised placebo-controlled study with three groups (2 NMES, 1 Sham) and three assessments (baseline, week 8, week 12 follow-up) was carried out. Self-reported function using Canadian occupational performance measure (COPM), leg pain, overall leg symptoms score (heaviness, tiredness, aching, or cramps), and ankle blood flow were assessed. Analysis of covariance (ANCOVA) and logistic regression were used to compare the groups. Statistical significance was set at p < 0.05 (two-sided 5%). RESULTS: Out of 129 participants enrolled, 114 completed the study. The improvement in all outcomes were statistically significant for the NMES interventions compared to Sham at both week 8 (p < 0.01) and week 12 (p < 0.05). The improvement in COPM met the minimal clinically important difference (MCID) for the NMES interventions compared to Sham at both week 8 (p < 0.005) and week 12 (p < 0.05). Improvement in leg pain met MCID at week 8 compared to Sham (p < 0.05). Ankle blood flow increased approximately 3-fold during treatment compared to Sham. Compliance with the interventions was high and no device-related adverse events were reported. CONCLUSIONS: The home-based foot NMES is safe, and significantly improved self-reported function, leg pain and overall leg symptoms, and increased ankle blood flow compared to a Sham among older adults. TRIAL REGISTRATION: The trial was prospectively registered in ISRCTN on 17/06/2019 with registration number ISRCTN10576209. It can be accessed at https://www.isrctn.com/ISRCTN10576209 .

Characteristics in patients with very early therapeutic response of condoliase chemonucleolysis for lumbar disc herniation.

INTRODUCTION: Treatment of lumbar disc herniation (LDH) using condoliase chemonucleolysis (CC) requires more time than surgery to demonstrate therapeutic effects. This study aimed to identify patients who show significant improvement in leg pain very early after CC and to determine pretreatment factors that can predict a very early therapeutic response. METHODS: The study included 52 patients who underwent CC for treatment-resistant LDH. Scores for low back and leg pain measured by a numerical rating scale were assessed at four time points (1 day, 1 week, 1 month, and 3 months after CC). Patients who reported subjective pain relief the day after treatment and further exhibited an improved straight leg raising (SLR) angle compared to pretreatment were classified as "very early responders (VER)". RESULTS: Of the 52 patients, 39 (75%) were VER, and 13 (25%) were non-VER. The VER showed earlier improvement in leg pain. The VER had a significantly higher proportion of positive SLR test patients (p = 0.01) and a significantly smaller pretreatment SLR angle compared to the non-VER (VER vs. non-VER: 40.6 ± 19.0 vs. 63.1 ± 16.9, p < 0.001). There were no significant differences in the level, type, and size of LDH and the disc regression rate between the two groups. CONCLUSIONS: Patients with a smaller pretreatment SLR angle are more likely to experience very early or early symptomatic relief, with a significant and sustained reduction in leg pain up to 3 months after CC treatment.

Prevalence of weakness and factors mediating discrepancy between reported and observed leg weakness in people with sciatica.

PURPOSE: To establish the prevalence and agreement between reported and observed leg weakness in people with sciatica. To establish which factors mediate any identified difference between reported and observed leg weakness in people with sciatica. METHODS: 68 people with a clinical diagnosis of sciatica, records from spinal service, secondary care NHS Hospital, England, UK reviewed. Primary outcome measures were the sciatica bothersome index for reported leg weakness and the Medical Research Council scale for observed weakness. Agreement was established with Cohen's Kappa and intraclass correlation coefficient. Potential factors that may mediate a difference between reported and observed weakness included leg pain, sciatica bothersome index sensory subscale, age, hospital anxiety and depression subscale for anxiety. RESULTS: 85% of patients reported weakness but only 34% had observed weakness. Cohen's Kappa (0.066, 95% CI - 0.53, 0.186; p = 0.317)] and ICC 0.213 (95% CI - 0.26, 0.428, p = 0.040) both showed poor agreement between reported and observed weakness. The difference between reported and observed measures of weakness was mediated by the severity of leg pain (b = 0.281, p = 0.024) and age (b = 0.253, p = 0.042). CONCLUSION: There is a high prevalence of reported leg weakness in people with sciatica, which is not reflected in observed clinical measures of weakness. Differences between reported and observed weakness may be driven by the severity of leg pain and age. Further work needs to establish whether other objective measures can detect patient reported weakness.

Post-operative shift in pain profile following fusion surgery for adult spinal deformity: a cluster analysis.

PURPOSE: Adult spinal deformity (ASD) is associated with a combination of back and leg pain of various intensities. The objective of the present study was to investigate the diverse reaction of pain profiles following ASD surgery as well as post-operative patient satisfaction. METHODS: Multicenter surveillance collected data for patients ≥ 19 years old who underwent primary thoracolumbar fusion surgery at > 5 spinal levels for ASD. Two-step cluster analysis was performed utilizing pre-operative numeric rating scale (NRS) for back and leg pain. Radiologic parameters and patient-reported outcome (PRO) scores were also obtained. One-year post-operative outcomes and satisfaction rates were compared among clusters, and influencing factors were analyzed. RESULTS: Based on cluster analysis, 191 ASD patients were categorized into three groups: ClusterNP, mild pain only (n = 55); ClusterBP, back pain only (n = 68); and ClusterBLP, significant back and leg pain (n = 68). ClusterBLP (mean NRSback 7.6, mean NRSleg 6.9) was the oldest 73.4 years (p < 0.001) and underwent interbody fusion (88%, p < 0.001) and sacral/pelvic fixation (69%, p = 0.001) more commonly than the other groups, for the worst pelvis incidence-lumbar lordosis mismatch (mean 43.7°, p = 0.03) and the greatest sagittal vertical axis (mean 123 mm, p = 0.002). While NRSback, NRSleg and PRO scores were all improved postoperatively in ClustersBP and BLP, ClusterBLP showed the lowest satisfaction rate (80% vs. 80% vs. 63%, p = 0.11), which correlated with post-operative NRSback (rho = -0.357). CONCLUSIONS: Cluster analysis revealed three clusters of ASD patients, and the cluster with the worst pain back and leg pain had the most advanced disease and showed the lowest satisfaction rate, affected by postoperative back pain.

The association of the STarT Back Screening Tool and type of leg pain with low back pain disability trajectories: a prospective cohort study.

BACKGROUND: Multiple factors influence the recovery process of low back pain (LBP). The identification and increased knowledge of prognostic factors might contribute to a better understanding of the course of LBP. The purpose of this study is to investigate the association of the STarT Back Screening Tool (SBST) risk score and the type of leg pain (non-radiating LBP, referred non-radicular, and radicular radiating leg pain) with the disability trajectory (at baseline, the slope, and recovery at one year) in adults with low back pain. METHODS: This is a prospective cohort study in 347 patients with low back pain who sought physiotherapy care at three primary care practices in the Netherlands. Linear mixed models were estimated to describe the association of the SBST risk score and the type of leg pain with disability at baseline, the slope in the disability trajectory, and at twelve months follow-up. RESULTS: A medium/high risk score on the SBST is associated with higher baseline disability scores on the Oswestry Disability Index (ODI), faster initial recovery, and still a higher disability ODI score at 12 months follow-up. Non-radicular referred and radicular radiating leg pain were associated with worse baseline disability ODI scores in LBP. This association was not present for the initial recovery or at the 12 months follow-up. CONCLUSION: The SBST is associated with the LBP recovery trajectory. The SBST might be a useful tool to predict the disability trajectory in a heterogeneous group of people with low back pain in primary care and might, therefore, be recommended in future clinical practice guidelines. The type of leg pain was not associated with the recovery trajectory of LBP. Future research might focus on evaluating different types of leg pain. TRIAL REGISTRATION: Clinicaltrials.gov: 109,643.

Leg Pain-An Unexpected Twist.

BACKGROUND: Obturator hernia is a rare condition, often presenting with non-specific symptoms, such as thigh pain, groin pain, nausea, or vomiting. Obturator hernias are most common in thin, elderly women. Oftentimes, they are diagnosed late in the disease course resulting in complications and high morbidity and mortality. CASE REPORT: We present the case of a 75-year-old female who presented with right thigh pain with no other symptoms. After computed tomography (CT) of the abdomen/pelvis, the patient was found to have an incarcerated obturator hernia complicated by a small bowel obstruction, ultimately requiring urgent surgical intervention. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Given the very general symptoms associated with the condition, the diagnosis of obturator hernia can easily be missed, leading to a delayed diagnosis, more complications, and a higher morbidity and mortality rate. Due to the risk associated with a delayed diagnosis, it is important for emergency physicians to maintain a high clinical suspicion for the diagnosis.

Low-energy differential target multiplexed SCS derivative reduces pain and improves quality of life through 12 months in patients with chronic back and/or leg pain.

INTRODUCTION: Energy-reducing spinal cord stimulation (SCS) approaches have the potential to impact patient experience with rechargeable and non-rechargeable SCS devices through reducing device recharge time or enhancing device longevity. This prospective, multi-center study evaluated the safety, effectiveness, and actual energy usage of differential target multiplexed (DTM) endurance therapy, a reduced energy DTM SCS derivative. METHODS: Subjects who reported an overall pain visual analog score (VAS) of ≥6/10 cm and an Oswestry Disability Index score of 21-80 out of 100 at baseline with moderate to severe chronic, intractable back and/or leg pain were eligible. Evaluation visits occurred at 1, 3, 6, and 12 months post-device activation. The primary objective was to characterize change in overall pain intensity, as measured by VAS, from baseline to 3-month visit. RESULTS: Fifty-seven subjects enrolled at 12 US sites from November 2020 through June 2021, 35 were implanted with a rechargeable SCS device, and 27 completed the 12-month visit. Subjects experienced a 50.4% mean reduction in overall pain from baseline at the 3-month follow-up that was sustained through 12 months. Additional outcomes including changes in overall, back, and leg pain intensity, quality of life, disability, therapy satisfaction, safety, and current battery usage are shown through 12-month follow-up. CONCLUSION: The use of DTM endurance SCS therapy in this study resulted in reductions in pain relief through 12 months, demonstrating that energy-reducing stimulation patterns can provide clinical benefit. Clinically effective, reduced energy SCS derivatives have the potential to impact patient experience through either reduced recharge requirements or increased device longevity.

To fuse or not to fuse: The elderly patient with lumbar stenosis and low-grade spondylolisthesis. Systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The optimum surgical intervention for elderly patients with lumbar spinal stenosis (LSS) and low-grade degenerative-spondylolisthesis (LGDS) has been extensively debated. We conducted a systematic review and meta-analysis of randomised-controlled-trials (RCTs) comparing the effectiveness of decompression-alone against the gold-standard approach of decompression-with-fusion (D + F) in elderly patients with LSS and LGDS. METHODS: A systematic literature search was performed on published databases from inception to October-2021. English-language RCTs of elderly patients (mean age over-65) with LSS and LGDS, who had undergone DA or D + F were included. The quality and weight of evidence was assessed, and a meta-analysis performed. RESULTS: Six RCTs (n = 531; mean age: 66.2 years; 57.8% female) were included. There was no difference in visual-analogue-scale (VAS) scores of back-pain (BP) or leg-pain (LP) at mean follow-up of 27.4 months between both DA and D + F groups (BP: mean-difference (MD)0.24, 95%CI: -0.38-0.85; LP MD:0.39, 95%CI: -0.34-1.11). No difference in disability, measured by Oswestry-Disability-Index scores, was found between both groups (MD:0.50, 95%CI: -3.31-4.31). However, patients in DA group had less hospital complications and fewer adverse events (total-surgical-complications OR:0.57, 95%CI: 0.36-0.90), despite a higher rate of worsening DS (OR:3.49, 95%CI: 1.05-11.65). No difference in BP or LP was found in subgroup-analysis of open-laminectomy compared to posterolateral-fusion (PLF) (BP: MD: -0.24, 95%CI: -1.80-1.32; LP MD:0.80, 95%CI: -0.95-2.55). CONCLUSIONS: DA is not inferior to D + F in elderly patients with LSS and LGDS. DA carries a lower risk of hospital complications and fewer adverse events, however, surgeons should weigh these findings with the increased risk of DS progressing post-operatively.

Comparison Between Musculoskeletal Pain and Gender-Specific, Non-gendered Job-Exposure Matrix and Self-reported Exposures in CONSTANCES.

PURPOSE: Musculoskeletal disorders (MSDs) are common worldwide and gender differences exist in terms of prevalence and disability. MSDs are a leading cause of sick leave and physical work exposures. To assess the association between physical exposures assessed by the gender-specific CONSTANCES Job-Exposure Matrix (JEM) and musculoskeletal pain in six areas: neck pain, shoulder pain, elbow/arm pain, hand/wrist pain, low back pain, knee/leg pain; and to compare the results with those obtained using the non-gendered CONSTANCES JEM and with individual self-report exposures. METHODS: We included 48,736 male and 63,326 female workers from the CONSTANCES cohort (France). The association between 27 physical exposures and musculoskeletal self-reported pain in six body areas was assessed using logistic regression. We conducted the analysis with three types of exposures: (1) individual self-reported exposures; (2) gender-specific CONSTANCES JEM; (3) non-gendered CONSTANCES JEM, and adjusted for age and Body Mass Index (BMI). Analyses were stratified by gender. RESULTS: The associations to the gender-specific and non-gendered JEM were similar. The odds ratios using individual self-reported exposures were comparable to the JEM-based associations, with the exceptions of the exposures 'change tasks', 'rest eyes' and 'reach behind'. In some comparisons, there were differences in the direction and/or significance of effects between genders (regardless of whether the JEM used was gender-specific or not). CONCLUSION: The gender-specific and non-gendered JEMs gave similar results, hence, developing physical work exposures JEMs that are gender-specific may not be essential. However, when predicting musculoskeletal pain, it seems relevant to stratify the analysis by gender.

Prevalence and severity of restless leg syndrome in patients with spinal cord injuries.

OBJECTIVE: To determine the prevalence of restless leg syndrome in patients with spinal cord injury using a consensus criterion. METHODS: The cross-sectional study was conducted from November 29, 2018, to February 28, 2021 at the departments of Neurology and Orthopaedic Surgery, King Edward Medical University, Mayo Hospital, Lahore, Pakistan, and comprised patients of either gender aged 18-80 years having spinal cord injuries. All the patients were interviewed using a 10-item questionnaire, and were assessed using the five-point consensus criteria of the International Restless Leg Syndrome Study Group. Data was analysed using SPSS 20. RESULTS: Of the 253 patients, 128(50.6%) were males and 125(49.4%) were females. The overall mean age was 38.6±14.2 years. Restless leg syndrome was present in 116(45.8%) patients, and 64(55.2%) of them were males (p>0.05). The mean duration of the symptoms was 18.9±16.9 months. Causes of spinal cord injury included metastasis 28(11.1%) multiple sclerosis 32(12.6%), neuromyelitis optica spectrum disorders 68(26.9%), tuberculous spondylitis 85(33.6%), trauma 24(9.5%) and viral myelitis 16(6.3%). CONCLUSIONS: Restless leg syndrome was prevalent in less than half the patients having spinal cord injury. It was more prevalent in males compared to females, but the difference was not significant.

Effects of administration of α2 adrenergic receptor agonist into psoas major muscle on inflammatory pain induced by injection of complete Freund's adjuvant in rats.

α2 adrenergic agonists are widely used in clinical anesthesia and ICU sedation owing to their effective sedative and analgesic effects. Lumbago and leg pain is the most common clinical pain disease. Studies have reported that lumbago and leg pain is associated with dysregulation of paravertebral muscles, especially psoas major muscles. In the present study, a unilateral lower extremity chronic inflammation and pain model was established by subcutaneous administration of low-dose complete Fredrin's adjuvant (CFA) into the posterior paw of rats. α2 adrenalin receptor agonist was then injected into the psoas major muscle. Behavioral tests were conducted for 21 days. Psoas major muscle tissue was harvested for evaluation of biochemical indexes related to pain. The effect of α2 adrenergic receptor agonist injected into psoas major muscle on chronic inflammatory pain of lower extremities in rats was explored. The results showed that injection of α2 adrenergic receptor agonist into the psoas major muscle relieved CFA-induced mechanical hyperalgesia. Administration of α2 adrenergic receptor antagonist yohimbine reversed the analgesic effect of α2 adrenergic receptor agonists. Administration of dexmedetomidine into psoas major muscle downregulated the levels of norepinephrine, interleukin-6 and tumor necrosis factor-α in tissues. The findings of the present study show that administration of α2 adrenoceptor agonists into the psoas major muscle relieves chronic inflammatory pain induced by CFA. Local injection of dexmedetomidine also exerted anti-inflammatory and anti-sympathetic effect by activating α2-adrenoceptor in the psoas major muscle.

Vibrio vulnificus necrotizing fasciitis with sepsis presenting with pain in the lower legs in winter: a case report.

BACKGROUND: Vibrio vulnificus infections develop rapidly and are associated with a high mortality rate. The rates of diagnosis and treatment are directly associated with mortality. CASE PRESENTATION: We describe an unusual case of a 61-year-old male patient with chronic liver disease and diabetes who presented with a chief complaint of pain in both lower legs due to V. vulnificus infection in winter. Within 12 h of arrival, typical skin lesions appeared, and the patient rapidly developed primary sepsis. Despite prompt appropriate antibiotic and surgical treatment, the patient died 16 days after admission. CONCLUSION: Our case findings suggest that V. vulnificus infection should be suspected in patients with an unclear infection status experiencing pain of unknown origin in the lower legs, particularly in patients with liver disease or diabetes, immunocompromised status, and alcoholism.

The effect of gender on intramuscular pressure in patients with chronic exertional compartment syndrome of the lower leg.

This study aimed to compare intramuscular pressure (IMP) in all four compartments of the lower leg between men and women in patients with suspected chronic exertional compartment syndrome (CECS), and to assess possible effects of gender in relation to covariation factors. A consecutive series of patients with exertional leg pain (n = 962, median age 27 years, 56.2% women) underwent IMP measurements between 2009 and 2019. The CECS diagnosis was confirmed (n = 491, 48% women) or ruled out (n = 471, 65% women) based on the patient's history, clinical examination, and IMP measurements. IMP values of the compartments were compared between genders. A multiple linear regression analysis was performed for IMP in the anterior and lateral compartments, where the number of patients was large enough to investigate the possible impact of other factors such as height, age, and duration of pain. Among those with a confirmed CECS diagnosis, one-minute post-exercise IMP was significantly lower in women than in men for all four muscle compartments: anterior (median [range] mmHg 44 [24-120] vs. 50 [24-130]), lateral (35 [20-89] vs. 40 [26-106]), deep posterior (31 [25-36] vs. 34 [24-53]), and superficial posterior (32 [27-39] vs. 37 [22-54]). In the multiple regression analysis, gender differences remained significant in the anterior compartment but not the lateral compartment, where only height remained a significant predictor of IMP. Gender should be considered when using cut-off values for IMP in diagnosing CECS, especially for the anterior compartment.

Cross-Cultural adaptation and validation of the Exercise-Induced Leg Pain questionnaire for Spanish speaking patients.

OBJECTIVES: To cross-culturally adapt and validate a Spanish version of the Exercise-Induced Leg Pain questionnaire. DESIGN: Clinical measurement study. PARTICIPANTS: The validity and reliability of the adapted version were assessed in four groups of 40 patients with exercise-induced leg pain, 40 physically active healthy individuals (control group), 40 athletes with other leg conditions and 40 athletes, military personnel and candidates with no history of injury (risk group). MAIN MEASURE: Exercise-Induced Leg Pain questionnaire. REFERENCE MEASURES: Spanish version of the Short-Form 36 and Schepsis postsurgical classification scale. RESULTS: In patients with exercise-induced leg pain, the mean age was 24.9 (± 6.7) years and the mean score of the questionnaire was 62.8 (± 10.9). The standard error of measurement and minimum detectable change threshold were 1.67 and 4.63 points, respectively. Excellent internal consistency (Cronbach's α = 0.942) and test-retest reliability (intraclass correlation coefficient = 0.995) were found. The exploratory and confirmatory factor analyses indicated that a one-factor solution explained 66.84% of the variance. For construct validity, 87.5% of the previously stated hypotheses were fulfilled between the total score of the questionnaire and Short-Form 36 dimensions. Concurrent validity, assessed by the Schepsis scale, was almost perfect (r = 0.92, p < 0.001). The predictive validity of the questionnaire was demonstrated using the receiving operating curve (area of 0.992; 95% CI: 0.983-1, p < 0.001). CONCLUSION: The Spanish version of the Exercise-Induced Leg Pain questionnaire resulted in a reliable and valid instrument to assess patients with exercise-induced leg pain.

Patients with no preoperative back pain have the best outcome after lumbar disc herniation surgery.

PURPOSE: Most patients with lumbar disc herniations requiring surgery have concomitant back pain. The purpose of the current study was to evaluate the outcome of surgery for lumbar disc herniations in patients with no preoperative back pain (NBP) compared to those reporting low back pain (LBP). METHODS: 15,418 patients surgically treated due to LDH with primary discectomy from 1998 until 2020 were included in the study. Self-reported low back pain assessed with a numerical rating scale (NRS) was used to dichotomize the patients in two groups, patients without preoperative back pain (NBP, NRS = 0, n = 1333, 9%) and patients with preoperative low back pain (LBP, NRS > 0, n = 14,085, 91%). Patient reported outcome measures (PROMs) collected preoperatively and one-year postoperatively were used to evaluate differences in outcomes between the groups. RESULTS: At the one-year follow-up, 89% of the patients in the NBP group were completely pain free or much better compared with 76% in the LBP group. Significant improvement regarding leg pain was seen in all measured PROMs in both groups oneyear after surgery. In the NBP group, 13% reported clinically significant back pain (NRS difference greater than Minimally Clinical Important Difference (MICD)) at the one-year follow-up. CONCLUSIONS: Patients without preoperative back pain are good candidates for LDH surgery. 13% of patients without preoperative back pain develop clinically significant back pain one-year after surgery.

Clinical pathways for the management of low back pain from primary to specialised care: a systematic review.

PURPOSE: Clinical pathways for low back pain (LBP) have potential to improve clinical outcomes and health service efficiency. This systematic review aimed to synthesise the evidence for clinical pathways for LBP and/or radicular leg pain from primary to specialised care and to describe key pathway components. METHODS: Electronic database searches (CINAHL, MEDLINE, Cochrane Library, EMBASE) from 2006 onwards were conducted with further manual and citation searching. Two independent reviewers conducted eligibility assessment, data extraction and quality appraisal. A narrative synthesis of findings is presented. RESULTS: From 18,443 identified studies, 28 papers met inclusion criteria. Pathways were developed primarily to address over-burdened secondary care services in high-income countries and almost universally used interface services with a triage remit at the primary-secondary care boundary. Accordingly, evaluation of healthcare resource use and patient flow predominated, with interface services associated with enhanced service efficiency through decreased wait times and appropriate use of consultant appointments. Low quality study designs, heterogeneous outcomes and insufficient comparative data precluded definitive conclusions regarding clinical- and cost-effectiveness. Pathways demonstrated basic levels of care integration across the primary-secondary care boundary. CONCLUSIONS: The limited volume of research evaluating clinical pathways for LBP/radicular leg pain and spanning primary and specialised care predominantly used interface services to ensure appropriate specialised care referrals with associated increased efficiency of care delivery. Pathways demonstrated basic levels of care integration across healthcare boundaries. Well-designed randomised controlled trials to explore the potential of clinical pathways to improve clinical outcomes, deliver cost-effective, guideline-concordant care and enhance care integration are required.

The Preferential Use of Anakinra in Various Settings of FMF: A Review Applied to an Updated Treatment-Related Perspective of the Disease.

Familial Mediterranean fever (FMF), the most frequent monogenic autoinflammatory disease, is manifested with recurrent and chronic inflammation and amyloid A (AA) amyloidosis, driven by overproduction of interleukin 1 (IL-1) through an activated pyrin inflammasome. Consequently, non-responsiveness to colchicine, the cornerstone of FMF treatment, is nowadays addressed by IL-1- blockers. Each of the two IL-1 blockers currently used in FMF, anakinra and canakinumab, has its own merits for FMF care. Here we focus on anakinra, a recombinant form of the naturally occurring IL-1 receptor antagonist, and explore the literature by using PubMed regarding the utility of anakinra in certain conditions of FMF. Occasionally we enrich published data with our own experience. To facilitate insights to anakinra role, the paper briefs some clinical, genetic, pathogenetic, and management aspects of FMF. The clinical settings of FMF covered in this review include colchicine resistance, AA amyloidosis, renal transplantation, protracted febrile myalgia, on- demand use, leg pain, arthritis, temporary suspension of colchicine, pediatric patients, and pregnancy and lactation. In many of these instances, either because of safety concerns or a necessity for only transient and short-term use, anakinra, due to its short half-life, is the preferred IL-1 blocker.

Systematic Review of Patient-Reported Outcome Measures for Patients with Exercise-Induced Leg Pain.

Background and Objectives: To determine the most commonly used patient-reported outcome measures (PROMs) in exercise-induced leg pain (EILP) and to identify specific PROMs for EILP in order to evaluate their psychometric properties and methodological quality. Materials and Methods: A strategic search was performed in different databases to identify and extract the characteristics of studies based on the use of PROMs in patients with EILP. Specific PROMs were evaluated according to the Terwee et al. and COSMIN criteria. Results: Fifty-six studies were included in the review. The Medial Tibial Stress Syndrome Score (MTSSS), Lower Extremity Functional Scale (LEFS) and Exercise-Induced Leg Pain Questionnaire (EILP-Q) were identified as specific PROMs for EILP. The Visual Analog Scale (VAS) was the most widely used instrument in the assessment of EILP. The methodological quality assessment showed six positive values for the LEFS, four for the MTSSS and three for the EILP-Q for the eight psychometric properties analyzed according to the COSMIN criteria. The evaluation of the nine psychometric properties according to Terwee showed five positive values for the LEFS and MTSSS, and three for the EILP-Q. Conclusions: The overall methodological quality of the PROMs used was low. The VAS was the most widely used instrument in the assessment of EILP, and the LEFS was the highest quality PROM available for EILP, followed by the MTSSS and EILP-Q, respectively.

Differences in Gene Expression of Endogenous Opioid Peptide Precursor, Cannabinoid 1 and 2 Receptors and Interleukin Beta in Peripheral Blood Mononuclear Cells of Patients With Refractory Failed Back Surgery Syndrome Treated With Spinal Cord Stimulation: Markers of Therapeutic Outcomes?

OBJECTIVE: The use of spinal cord stimulation for patients with failed back surgery syndrome (FBSS) is very common. In order to better understand the mechanisms of action of spinal cord stimulation (SCS), our aim was to determine potential changes in relative gene and protein expression in the peripheral blood mononuclear cells (PBMCs) of patients as potential biomarkers of disease outcomes and potential new targets for therapy. METHODS: Twenty-four patients with diagnosis of FBSS refractory to conservative therapy for at least six months were included in the study. Clinical evaluation in this study included validated questionnaires. Blood samples (10 mL) were collected five times from baseline until two months after implant of the leads. Proenkephalin (PENK), cannabinoid receptors CB1 and CB2, and interleukin 1ß (IL 1ß) were analyzed. Each patient served as his/her own control by comparing the samples collected at different time points against the baseline sample collected at T0. RESULTS: A total of 16 patients met all relevant criteria during the whole study and were assessed. Only PENK showed significant changes over time (Friedman p = 0.000). A positive correlation was observed between changes in visual analog scale (VAS) scores and PENK and a negative correlation between changes in PENK and Short Form-12 (SF-12) mental component score (MCS) scores, as well as between changes in IL 1ß and Pain Detect Questionnaire (PD-Q) scores. As PENK changes increased, so did pain (VAS). As changes in PENK increased, SF-12 MCS health worsened. As changes in IL 1ß increased, PD-Q values decreased. No severe adverse events occurred. CONCLUSIONS: Previously unknown effects of SCS on levels of PBMCs biomarkers are demonstrated. The findings of our research suggest a potential for useful integration of genome analysis and lymphocyte expression in the daily practice of neurostimulation for pain management and represent a novel road map in the light of the important questions that remain unanswered.