Improving access to chronic pain care with central referral and triage: The 6-year findings from a single-entry model.

Background: Despite the established efficacy of multidisciplinary chronic pain care, barriers such as inflated referral wait times and uncoordinated care further hinder patient health care access. Aims: Here we describe the evolution of a single-entry model (SEM) for coordinating access to chronic pain care across seven hospitals in Toronto and explore the impact on patient care 6 years after implementation. Methods: In 2017, an innovative SEM was implemented for chronic pain referrals in Toronto and surrounding areas. Referrals are received centrally, triaged by a clinical team, and assigned an appointment according to the level of urgency and the most appropriate care setting/provider. To evaluate the impact of the SEM, a retrospective analysis was undertaken to determine referral patterns, patient characteristics, and referral wait times over the past 6 years. Results: Implementation of an SEM streamlined the number of steps in the referral process and led to a standardized referral form with common inclusion and exclusion criteria across sites. Over the 6-year period, referrals increased by 93% and the number of unique providers increased by 91%. Chronic pain service wait times were reduced from 299 (±158) days to 176 (±103) days. However, certain pain diagnoses such as chronic pelvic pain and fibromyalgia far exceed the average. Conclusions: The results indicate that the SEM helped reduce wait times for pain conditions and standardized the referral pathway. Continued data capture efforts can help identify gaps in care to enable further health care refinement and improvement.

Contexte: Malgré l'efficacité établie des soins multidisciplinaires dans le traitement de la douleur chronique, des obstacles tels que des délais d'attente prolongés et l'absence de coordination des soins entravent davantage l'accès des patients aux services de santé.Objectifs: Nous décrivons ici l'évolution d'un modèle à entrée unique visant à coordonner l'accès aux soins pour la douleur chronique dans sept hôpitaux de Toronto. Nous examinons également l'effet de ce modèle sur les soins aux patients six ans après sa mise en œuvre.Méthodes: En 2017, un modèle à entrée unique novateur a été mis en place pour orienter les patients souffrant de douleur chronique à Toronto et dans les régions avoisinantes. Les patients sont reçus de manière centralisée, triés par une équipe clinique et un rendez-vous leur est attribué en fonction du degré d'urgence et de l'établissement de soins ou du prestataire le plus approprié.Pour évaluer l'impact du modèle à entrée unique, une analyse rétrospective a été entreprise afin de déterminer les schémas de consultation, les caractéristiques des patients et les temps d'attente pour les demandes de consultation au cours des six dernières années.Résultats: La mise en œuvre d'un modèle à entrée unique a permis de rationaliser le nombre d'étapes du processus de demande de consultation et a conduit à l'élaboration d'un formulaire de demande de consultation normalisé comprenant des critères d'inclusion et d'exclusion communs à tous les sites. Au cours de la période de six ans, le nombre de demandes de consultation a augmenté et le nombre de prestataires uniques a augmenté de 91 %.Les temps d'attente pour les services de traitement de la douleur chronique ont diminué de 299 (±158) jours à 176 (±103) jours. Cependant, certains diagnostics de douleur, comme la douleur pelvienne chronique et la fibromyalgie, dépassent de loin la moyenne.Conclusions: Les résultats indiquent que le modèle à entrée unique a contribué à réduire les temps d'attente pour les affections douloureuses et à normaliser le parcours de consultation. La poursuite des efforts de collecte des données peut aider à recenser les lacunes dans les soins, permettant ainsi une amélioration continue des soins de santé.

Nuclear-localized androgen receptor content following resistance exercise training is associated with hypertrophy in males but not females.

Androgen receptor (AR) content has been implicated in the differential response between high and low responders following resistance exercise training (RET). However, the influence of AR expression on acute skeletal muscle damage and whether it may influence the adaptive response to RET in females is poorly understood. Thus, the purpose of this exploratory examination was to 1) investigate changes in AR content during skeletal muscle repair and 2) characterize AR-mediated sex-based differences following RET. A skeletal muscle biopsy from the vastus lateralis was obtained from 26 healthy young men (n = 13) and women (n = 13) at baseline and following 300 eccentric kicks. Subsequently, participants performed 10 weeks of full-body RET and a final muscle biopsy was collected. In the untrained state, AR mRNA expression was associated with paired box protein-7 (PAX7) mRNA in males. For the first time in human skeletal muscle, we quantified AR content in the myofiber and localized to the nucleus where AR has been shown to trigger cellular outcomes related to growth. Upon eccentric damage, nuclear-associated AR (nAR) content increased (p < .05) in males and not females. Males with the greatest increase in cross-sectional area (CSA) post-RET had more (p < .05) nAR content than females with the greatest gain CSA. Collectively, skeletal muscle damage and RET increased AR protein, and both gene and hypertrophy measures revealed sex differences in relation to AR. These findings suggest that AR content but more importantly, nuclear localization, is a factor that differentiates RET-induced hypertrophy between males and females.

Evidence for an association of serum microanalytes and myofascial pain syndrome.

BACKGROUND: Myofascial Pain Syndrome (MPS) is a common pain disorder. Diagnostic criteria include physical findings which are often unreliable or not universally accepted. A precise biosignature may improve diagnosis and treatment effectiveness. The purpose of this study was to assess whether microanalytic assays significantly correlate with characteristic clinical findings in people with MPS. METHODS: This descriptive, prospective study included 38 participants (25 women) with greater than 3 months of myofascial pain in the upper trapezius. Assessments were performed at a university laboratory. The main outcome measures were the Beighton Index, shoulder range of motion, strength asymmetries and microanalytes: DHEA, Kynurenine, VEGF, interleukins (IL-1b, IL-2, IL-4, IL-5, IL-7, IL-8, IL-13), growth factors (IGF-1, IGF2, G-CSF, GM-CSF), MCP-1, MIP-1b, BDNF, Dopamine, Noradrenaline, NPY, and Acetylcholine. Mann-Whitney test and Spearman's multivariate correlation were applied for all variables. The Spearman's analysis results were used to generate a standard correlation matrix and heat map matrix. RESULTS: Mean age of participants was 32 years (20-61). Eight (21%) had widespread pain (Widespread Pain Index ≥ 7). Thirteen (34%) had MPS for 1-3 years, 14 (37%) 3-10 years, and 11 (29%) for > 10 years. The following showed strong correlations: IL1b,2,4,5,7,8; GM-CSF and IL 2,4,5,7; between DHEA and BDNF and between BDNF and Kynurenine, NPY and acetylcholine. The heat map analysis demonstrated strong correlations between the Beighton Index and IL 5,7, GM-CSF, DHEA. Asymmetries of shoulder and cervical spine motion and strength associated with select microanalytes. CONCLUSION: Cytokine levels significantly correlate with selected clinical assessments. This indirectly suggests possible biological relevance for understanding MPS. Correlations among some cytokine clusters; and DHEA, BDNF kynurenine, NPY, and acetylcholine may act together in MPS. These findings should be further investigated for confirmation that link these microanalytes with select clinical findings in people with MPS.

Symptoms and disease severity in lung transplant candidates co-managed with palliative care.

BACKGROUND: Lung transplant (LTx) candidates experience significant respiratory symptoms often necessitating palliative care (PC) support. We aimed to describe symptoms experienced by interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD) LTx candidates referred for PC using the Edmonton Symptom Assessment System (ESAS) and to assess the change in ESAS in relation to pre-LTx exercise capacity, oxygen requirements, and respiratory exacerbations. Understanding symptom trajectory of these two patient groups will help inform PC management. METHODS: Single centre, retrospective cohort of 102 ILD and 24 COPD LTx candidates who were assessed in the Toronto Transplant PC Clinic (TPCC) from 2014-2017. Chi-square and t-tests were used to compare clinical characteristics, physiological parameters, and ESAS scores. RESULTS: The most common symptom in ILD and COPD patients was dyspnea (median score of 8, cough 7, fatigue 6). ILD patients reported higher cough scores (7 vs. 4, P<0.001). There was no association between the change in ESAS domains and six-minute walk distance (6MWD), oxygen requirements, or respiratory exacerbations, despite increased oxygen requirements and a greater decline in 6MWD in ILD compared to COPD pre-LTx (-47 vs. -8 meters, P=0.01). ILD candidates who were delisted/died compared to those transplanted, experienced worse depression (median ESAS; 4.5 vs. 1), anxiety (5.5 vs. 2) and dyspnea (9.5 vs. 8); P<0.05. CONCLUSIONS: ILD patients had similar symptoms as COPD patients, despite increased oxygen requirements and decreasing 6MWD pre-LTx. This study highlights the importance of symptom management of LTx candidates co-managed with PC, independent of traditional measures of disease severity.

Effects of Distinct Force Magnitude of Spinal Manipulative Therapy on Blood Biomarkers of Inflammation: A Proof of Principle Study in Healthy Young Adults.

OBJECTIVES: The purpose of this preliminary study was to determine the influence of thoracic spinal manipulation therapy (SMT) of different force magnitudes on blood biomarkers of inflammation in healthy adults. METHODS: Nineteen healthy young adults (10 female, age: 25.6 ± 1.2 years) were randomized into the following 3 groups: (1) control (preload only), (2) single thoracic SMT with a total peak force of 400N, and (3) single thoracic SMT with a total peak force of 800N. SMT was performed by an experienced chiropractor, and a force-plate embedded treatment table (Force Sensing Table Technology) was used to determine the SMT force magnitudes applied. Blood samples were collected at pre intervention (baseline), immediately post intervention, and 20 minutes post intervention. A laboratory panel of 14 different inflammatory biomarkers (pro, anti, dual role, chemokine, and growth factor) was assessed by multiplex array. Change scores from baseline of each biomarker was used for statistical analysis. Two-way repeated-measures analysis of variance was used to investigate the interaction and main effects of intervention and time on cytokines, followed by Tukey's multiple comparison test (P ≤ .05). RESULTS: A between-group (800N vs 400N) difference was observed on interferon-gamma, interleukin (IL)-5, and IL-6, while a within-group difference (800N: immediately vs 20 minutes post-intervention) was observed on IL-6 only. CONCLUSION: In this study, we measured short-term changes in plasma cytokines in healthy young adults and found that select plasma pro-inflammatory and dual-role cytokines were elevated by higher compared to lower SMT force. Our findings aid to advance our understanding of the potential relationship between SMT force magnitude and blood cytokines and provide a healthy baseline group with which to compare similar studies in clinical populations in the future.

Validity and Diagnosis in Physical and Rehabilitation Medicine: Critical View and Future Perspectives.

ABSTRACT: Obtaining a diagnosis is an essential and integral part of physical and rehabilitation medicine in practice and research. Standardized psychometric properties are required of any classifications, diagnostic criteria, and diagnostic rules used. Physicians and researchers, in physical and rehabilitation medicine, need to understand these properties to determine the accuracy and consistency of their diagnosis. Although chronic musculoskeletal pain disorders are among the highly prevalent disorders seen in physical and rehabilitation medicine, limitations regarding existing diagnostic criteria for chronic musculoskeletal pain disorders still exist. Hence, the quest for developing diagnostic tools for chronic musculoskeletal pain that align with the standard properties remains open. These are discussed with an example for existing diagnostic criteria for fibromyalgia. This article primarily aimed to provide an overview of standard psychometric properties. A secondary aim was to critically appraise the tools currently used to diagnose chronic musculoskeletal pain disorders. The challenges and limitations of existing diagnostic tools are discussed. Potential approaches on how to improve the conceptualization of the construct of musculoskeletal pain disorders are also discussed. Adopting a network perspective, for example, can better constitute the disease instead of a single known underlying etiology for persistent or recurrent pain symptoms.

Potential role of blood biomarkers in patients with fibromyalgia: a systematic review with meta-analysis.

ABSTRACT: Fibromyalgia (FM) is a complex chronic pain condition. Its symptoms are nonspecific, and to date, no objective test exists to confirm FM diagnosis. Potential objective measures include the circulating levels of blood biomarkers. This systematic review and meta-analysis aim to review studies assessing blood biomarkers' levels in patients with FM compared with healthy controls. We systematically searched the PubMed, MEDLINE, EMBASE, and PsycINFO databases. Fifty-four studies reporting the levels of biomarkers in blood in patients with FM were included. Data were extracted, and the methodological quality was assessed independently by 2 authors. The methodological quality of 9 studies (17%) was low. The results of most studies were not directly comparable given differences in methods and investigated target immune mediators. Thus, data from 40 studies only were meta-analyzed using a random-effects model. The meta-analysis showed that patients with FM had significantly lower levels of interleukin-1 ß and higher levels of IL-6, IL-8, tumor necrosis factor-alpha, interferon gamma, C-reactive protein, and brain-derived neurotrophic factor compared with healthy controls. Nevertheless, this systematic literature review and meta-analysis could not support the notion that these blood biomarkers are specific biomarkers of FM. Our literature review, however, revealed that these same individual biomarkers may have the potential role of identifying underlying pathologies or other conditions that often coexist with FM. Future research is needed to evaluate the potential clinical value for these biomarkers while controlling for the various confounding variables.

Differences and similarities among questionnaires to assess pain status in chronic widespread pain population: a quantitative analysis.

OBJECTIVE: In clinical practice, multiple questionnaires are often used as part of the diagnosis of chronic widespread pain. Body Surface Area (BSA), Visual Analogue Scale (VAS), Fibromyalgia Diagnostic Criteria (FDC) and Central Sensitization Inventory (CSI) have all been used as screening tools to assess pain status in individuals with widespread pain. However, substantial overlap can be observed among these commonly employed questionnaires. This study aimed to quantitatively determine the most independent and dependent clinical characteristics obtained through these questionnaires and to examine potential redundancies. METHODS: Seventy-nine participants with widespread pain, 61 females and 18 males, from a chronic pain outpatient clinic were recruited. The FDC, BSA, VAS and the CSI were measured for all participants. A principal component analysis (PCA) using a varimax rotation was used to determine which clinical measures represented separate constructs of widespread pain. This was followed by a regression analysis to assess redundancy between the constructs and related pain characteristics. RESULTS: The identified three-component PCA solution was characterized by (1) the FDC and CSI score, (2) the VAS score and (3) the BSA score. This indicates that the BSA and the VAS scores capture independent patient information. From the regression analysis, the FDC and CSI scores shared approximately 80% of the variance, indicative of substantial overlap between scores. CONCLUSION: Our findings demonstrated that BSA and VAS scores were independent clinical measures of widespread chronic pain, while the FDC and CSI scores were not independent, were highly correlated and provided redundant information. Clinicians should continue using both the BSA and VAS; however, either only FDC or CSI will be beneficial during clinical assessment of widespread chronic pain.

Re-Examining Myofascial Pain Syndrome: Toward Biomarker Development and Mechanism-Based Diagnostic Criteria.

PURPOSE OF REVIEW: We discuss the need for a mechanism-based diagnostic framework with a focus on the development of objective measures (e.g., biomarkers) that can potentially be added to the diagnostic criteria of the syndrome. Potential biomarkers are discussed in relation to current knowledge on the pathophysiology of myofascial pain syndrome (MPS), including alterations in redox status, inflammation, and the myofascial trigger point (MTrP) biochemical milieu, as well as imaging and neurophysiological outcomes. Finally, we discuss the long-term goal of conducting a Delphi survey, to assess the influence of putative MPS biomarkers on clinician opinion, in order to ultimately develop new criteria for the diagnosis of MPS. RECENT FINDINGS: Myofascial pain syndrome (MPS) is a prevalent healthcare condition associated with muscle weakness, impaired mood, and reduced quality of life. MPS is characterized by the presence of myofascial trigger points (MTrPs): stiff and discrete nodules located within taut bands of skeletal muscle that are painful upon palpation. However, physical examination of MTrPs often yields inconsistent results, and there is no gold standard by which to diagnose MPS. The current MPS diagnostic paradigm has an inherent subjectivity and the absence of correlation with the underlying pathophysiology. Recent advancements in ultrasound imaging, systemic biomarkers, MTrP-specific biomarkers, and the assessment of dysfunction in the somatosensorial system may all contribute to improved diagnostic effectiveness of MPS.

A randomized double blinded placebo controlled study to evaluate motor unit abnormalities after experimentally induced sensitization using capsaicin.

Central sensitization is a condition that represents a cascade of neurological adaptations, resulting in an amplification of nociceptive responses from noxious and non-noxious stimuli. However, whether this abnormality translates into motor output and more specifically, ventral horn abnormalities, needs to be further explored. Twenty healthy participants aged 20-70 were randomly allocated to topical capsaicin or a placebo topical cream which was applied onto their left upper back to induce a transient state of sensitization. Visual analogue scale (VAS) ratings of pain intensity and brush allodynia score (BAS) were used to determine the presence of pain and secondary allodynia. Surface electromyography (sEMG) and intramuscular electromyography (iEMG) were used to record motor unit activity from the upper trapezius and infraspinatus muscles before and twenty minutes after application of capsaicin/placebo. Motor unit recruitment and variability were analyzed in the sEMG and iEMG, respectively. An independent t-test and Kruskal-Wallis H test were performed on the data. The sEMG results demonstrated a shift in the motor unit recruitment pattern in the upper trapezius muscle, while the iEMG showed a change in motor unit variability after application of capsaicin. These results suggest that capsaicin-induced central sensitization may cause changes in ventral horn excitability outside of the targeted spinal cord segment, affecting efferent pathway outputs. This preclinical evidence may provide some explanation for the influence of central sensitization on changes in movement patterns that occur in patients who have pain encouraging of further clinical investigation.Clinical Trials registration number: NCT04361149; date of registration: 24-Apr-2020.

Fibromyalgia and Nociceptive Flexion Reflex (NFR) Threshold: A Systematic Review, Meta-Analysis, and Identification of a Possible Source of Heterogeneity.

BACKGROUND: The nociceptive flexion reflex is a physiological, polysynaptic reflex and refers to the level that an appropriate withdrawal response activates when a painful stimulus is detected. The nociceptive flexion reflex threshold (NFRthr) is defined as the lowest noxious stimulation intensity required to trigger a reflex motor response. Despite wide utilization and reports of the NFRthr, there has been no consensus on a standard and/or best method in assessment of the NFRthr. OBJECTIVE: To systematically review the literature that compared the NFRthr between individuals with fibromyalgia (FM) and healthy controls; and to identify a source of heterogeneity in these trials. METHODS: Employing the Cochrane methodology, we systematically searched Ovid MEDLINE, Embase, Cochrane Clinical Answers, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and PsycINFO for clinical case-controlled trials assessing the NFRthr in individuals with and without fibromyalgia from inception to July 2019. Selected articles were passed for data extraction and meta-analyses. We utilized the random-effects model for meta-analysis assuming the true effect size may vary between studies. The sample sizes as a possible source of heterogeneity in multiple meta-regressions were investigated. This systematic review and meta-analysis were registered in PROSPERO before data extraction. RESULTS: Nine studies met our criteria and were included in the meta-analysis. Methodologies and settings varied between studies, eg, stimulation intensity, duration, and the current increments. Only two articles comprehensively described and reported details about electromyogram amplification, latency, and sampling rate. Evidence from 423 patients with fibromyalgia and 326 healthy individuals suggested that there may not be a meaningful decreased NFRthr in patients (overall mean difference = -3.16; 95% CI:-6.82 to 0.50; Z = 1.69; P=0.09). Published effect sizes were not homogenous (I2 = 0.91, τ 2 = 25.04, χ 2 = 91.22, df = 8, P < 0.00001). The multiple meta-regression analyses indicated that total and female sample sizes might be the main sources of heterogeneity for the effect sizes SStotal = -0.0570, P = 0.040; SSfemale = -0.0569; P = 0.047. CONCLUSION: Evidence suggests that the nociceptive flexion reflex threshold may not be different between patients with fibromyalgia and healthy controls. A unified and rigorous methodology and sample size calculation (probably sex specific investigation) is required for the assessment of nociceptive flexion reflex threshold in patients with fibromyalgia.

A theoretical framework to improve the construct for chronic pain disorders using fibromyalgia as an example.

Fibromyalgia (FM) is a frequent, complex condition of chronic musculoskeletal pain with no evidence for biological correlates. For this reason, despite many efforts from the medical community, its construct still appears ill defined. Promising candidate biomarkers are critically reviewed. A research agenda is proposed for developing a clearer construct of FM. The ideal theoretical framework is one of overcoming the illness-disease dichotomy and considering reciprocal interactions between biology and behaviour. This approach may foster research in other fields of pain medicine and of medicine in general.

Nociceptive Flexion Reflex Threshold in Chronic Pain Patients: A Needed Update for the Current Evidence.

BACKGROUND: The nociceptive flexion reflex is a physiological, polysynaptic reflex triggered by a nociceptive stimulus activating a withdrawal response. In chronic musculoskeletal-related pain conditions, a decreased nociceptive flexion reflex threshold has been suggested as a possible recognition evidence for central sensitization that may cause alteration of central nervous system processing. OBJECTIVE: The aim of the study was to systematically review reported comparisons of the nociceptive flexion reflex threshold in chronic pain patients and healthy individuals. METHODS: Electronic databases covering studies published between January 1990 and December 2019 were systematically searched. After application of exclusion criteria, 20 studies including 28 trials were included in this review. For meta-analysis, we used a random-effects model and funnel plot for publication bias. This research was registered at PROSPERO (CRD42019140354). RESULTS: Compared with healthy controls, standardized mean differences in nociceptive flexion reflex threshold were significantly lower in the total sample of chronic pain patients. Subgroup analysis indicated a homogenous decreased nociceptive flexion reflex threshold in studies reporting fibromyalgia, chronic pain, and joint pain while heterogeneity existed in other included pain conditions. CONCLUSIONS: A lower nociceptive flexion reflex threshold in patients experiencing chronic pain conditions may imply hyperexcitability in central nervous system processing. As a preliminary study, the findings would act as a basis for developing a methodology assisting current clinical practices.

The Levels of Insulin-Like Growth Factor in Patients with Myofascial Pain Syndrome and in Healthy Controls.

BACKGROUND: Insulin-like growth factor-1 (IGF-1) plays an important role in muscle maintenance and repair. The role of IGF-2 in the muscle is less clear. OBJECTIVE: To compare the levels of IGF-1 and IGF-2 in participants with acute myofascial pain syndrome (MPS) versus healthy controls and to determine whether age, gender, body mass index (BMI), region of pain, and pain intensity are associated with IGF levels. DESIGN: A case-control study design included a total of 74 participants. SETTING: Hospital emergency department. PARTICIPANTS: Participants presenting with acute MPS (n = 43) and non-MPS controls (n  =  31). MAIN OUTCOME MEASURES: Serum IGF-1 and IGF-2 (pg/mL) were measured in participants with MPS within 24 hours of symptom onset, and in non-MPS controls. Group and gender differences in serum IGF-1 and IGF-2 were assessed, with group and gender as factors, while controlling for age and BMI. RESULTS: The mean IGF-1 levels were not significantly different between MPS and controls (88 554.1, confidence interval [CI], 79 724.4-97 383.7 vs. 97 911.2, CI, 85 322.8-110 493.6). Significant differences were also not observed in IGF-1 levels between men and women with MPS nor between men and women in the control group. Mean levels of IGF-2 were significantly lower in patients with MPS than in controls (226 608.9, CI, 180 057.3-273 160.5 versus 460 343.9, CI, 387 809.4-532 878.2, P < .001). There were no significant gender differences in the levels of IGF-2 in patients with MPS. Mean IGF-2 levels (pg/mL) of men and women with MPS were lower (253 343.0, CI, 179 891.0-326 795.0, and 204 524.2, CI, 141 176.4-267 872.0, respectively) than those of healthy men and women (428 177.2, CI, 368 345.7-488 008.6, and 511 274.4, 355 178.6-687 370.1, respectively). Lower BMI and younger age were associated with higher levels of IGF-2. Pain intensity was associated with IGF-2 but not with IGF-1, whereas region of pain was not associated with either IGF-1 or IGF-2 levels. CONCLUSIONS: IGF-2 levels were lower in patients with acute MPS versus healthy controls with no gender differences, and IGF-1 levels were not different among the groups. Future studies should investigate the role of IGF-2 in muscle maintenance and repair in MPS.

Interrupting prolonged sitting with repeated chair stands or short walks reduces postprandial insulinemia in healthy adults.

We determined if interrupting prolonged sitting with practical "activity snacks" could reduce postprandial glycemia and insulinemia in healthy adults. Fourteen participants (7 males, 7 females; 24 ± 5 yr; 25 ± 5 kg/m2; 40 ± 8 mL/kg/min; 7,033 ± 2,288 steps/day) completed three 7.5-h trials in a randomized order consisting of uninterrupted sitting (SIT), sitting with intermittent (every 30 min) walking (WALK; 2 min at 3.1 mph), or sitting with intermittent squats (SQUAT; 15 chair stands with calf raise). Mixed-macronutrient liquid meals provided 20% ("breakfast") and 30% ("lunch") of daily energy needs to mimic Western meal patterns. Blood samples were obtained for analysis of postprandial plasma glucose and insulin concentrations, and skeletal muscle biopsy samples were collected to measure markers of contraction- and insulin-mediated glucose uptake signaling. Postprandial glucose and insulin did not differ across conditions following breakfast. After lunch, peak insulin concentration was lower in SQUAT (52 ± 27, P < 0.01) and WALK (62 ± 35, P < 0.05) compared with SIT (79 ± 43 µIU/mL). The insulin incremental area under the curve (iAUC) 1 h following lunch was 37 and 29% lower in SQUAT (P < 0.01) and WALK (P < 0.05) compared with SIT, respectively; however, 3-h insulin iAUC was reduced in SQUAT only (24% vs. SIT, P < 0.05). The 3-h insulin:glucose iAUC was reduced following lunch in both SQUAT (30%) and WALK (23%) compared with SIT (P < 0.05). Phosphorylation of AKTThr308, AKTSer473, and AS160Ser318 was not different between conditions (P > 0.05). Interrupting prolonged sitting with short walks or repeated chair stands reduces postprandial insulinemia in healthy adults. Our results may have implications for mitigating cardiometabolic disease risk in adults who engage in periods of prolonged sitting.NEW & NOTEWORTHY Breaking up prolonged sitting with intermittent walking breaks can improve glycemic control. Here, we demonstrated that interrupting prolonged sitting every 30 min with 1 min of repeated chair stands was as effective as 2-min treadmill walks for lowering postprandial insulinemia in healthy adults. Markers of contraction- and insulin-mediated muscle glucose uptake were unchanged. Repeated chair stands as a form of body-weight resistance activity may represent a cost- and space-efficient activity break for mitigating cardiometabolic-disease risk.

Machine Learning Diagnostic Modeling for Classifying Fibromyalgia Using B-mode Ultrasound Images.

Fibromyalgia (FM) diagnosis remains a challenge for clinicians due to a lack of objective diagnostic tools. One proposed solution is the use of quantitative ultrasound (US) techniques, such as image texture analysis, which has demonstrated discriminatory capabilities with other chronic pain conditions. From this, we propose the use of image texture variables to construct and compare two machine learning models (support vector machine [SVM] and logistic regression) for differentiating between the trapezius muscle in healthy and FM patients. US videos of the right and left trapezius muscle were acquired from healthy (n = 51) participants and those with FM (n = 57). The videos were converted into 64,800 skeletal muscle regions of interest (ROIs) using MATLAB. The ROIs were filtered by an algorithm using the complex wavelet structural similarity index (CW-SSIM), which removed ROIs that were similar. Thirty-one texture variables were extracted from the ROIs, which were then used in nested cross-validation to construct SVM and elastic net regularized logistic regression models. The generalized performance accuracy of both models was estimated and confirmed with a final validation on a holdout test set. The predicted generalized performance accuracy of the SVM and logistic regression models was computed to be 83.9 ± 2.6% and 65.8 ± 1.7%, respectively. The models achieved accuracies of 84.1%, and 66.0% on the final holdout test set, validating performance estimates. Although both machine learning models differentiate between healthy trapezius muscle and that of patients with FM, only the SVM model demonstrated clinically relevant performance levels.

Variability in skeletal muscle fibre characteristics during repeated muscle biopsy sampling in human vastus lateralis.

The percutaneous muscle biopsy procedure is an invaluable tool for characterizing skeletal muscle and capillarization. Little is known about methodological or biological variation stemming from the technique in heterogeneous muscle. Five muscle biopsies were taken from the vastus lateralis of a group of young men (n = 29, 22 ± 1 years) over a 96-h period. We investigated the repeatability of fibre distribution, indices of muscle capillarization and perfusion, and myofibre characteristics. No differences between the biopsies were reported in myofibre type distribution, cross-sectional area (CSA), and perimeter. Capillary-to-fibre perimeter exchange index and individual capillary-fibre contacts were unchanged with respect to the location of the muscle biopsy and index of capillarization. The variability in the sampling distribution of fibre type specific muscle CSA increased when fewer than 150 muscle fibres were quantified. Variability in fibre type distribution increased when fewer than 150 muscle fibres were quantified. Myofibre characteristics and indices of capillarization are largely consistent throughout the vastus lateralis when assessed via the skeletal muscle biopsy technique. Novelty Markers of muscle capillarization and perfusion were unchanged across multiple sites of the human vastus lateralis. Myofibre characteristics such as muscle cross-sectional area, perimeter, and fibre type distribution were also unchanged. Variation of muscle CSA was higher when fewer than 150 muscle fibres were quantified.

Incapacitating pain from Tenofovir Induced Hypophosphatemic Osteomalacia in a Hemophilia Patient - A Case Report.

Background: Pain in patients with hemophilia is common and usually a result of arthropathy. Clinicians should, however, consider a wide range of etiologies for pain in patients with hemophilia including infection, osteoporotic fractures, arthritis, and osteomalacia. Aims: This case demonstrates an instance of poorly localized back and hip pain, severe enough to prevent ambulation, caused by hypophosphatemic osteomalacia due to tenofovir treatment for blood transfusion acquired Human Immunodeficiency Virus (HIV) in a patient with hemophilia A. Methods: Case Report. Results: With termination of tenofovir treatment, this patient returned to baseline function. Conclusion: This report serves to emphasize the need for accurate diagnosis of pain in hemophilia patients, especially among the aging demographic of people with hemophilia in which there is a significant likelihood of an HIV infection and among patients who may be on Pre-exposure Prophylaxis (PrEP) or clinical trials involving tenofovir.

Contexte: La douleur chez les patients hémophiles est courante et résulte généralement d'une arthropathie. Les cliniciens doivent cependant envisager un large éventail d'étiologies pour la douleur chez les patients hémophiles y compris l'infection, les fractures ostéoporotiques, l'arthrite et l'ostéomalacie.Buts: Ce cas montre un exemple de douleur mal localisée au dos et à la hanche, suffisamment grave pour empêcher la marche, provoquée par une ostéomalacie hypophosphatémique attribuable au traitement par ténofovir pour le virus de l'immunodéficience humaine (VIH) acquis par transfusion sanguine chez un patient atteint d'hémophilie A.Méthodes: Rapport de cas.Résultats: Avec l'arrêt du traitement par ténofovir, ce patient a récupéré sa capacité fonctionnelle de départ.Conclusion: Ce rapport souligne la nécessité d'un diagnostic précis de la douleur chez les patients hémophiles, en particulier parmi la population vieillissante des personnes atteintes d'hémophilie chez qui il existe une forte probabilité d'infection au VIH et parmi les patients auxquels la prophylaxie pré-exposition (PrEP)est administrée ou qui participent à des essais cliniques impliquant le ténofovir.

Consistent expression pattern of myogenic regulatory factors in whole muscle and isolated human muscle satellite cells after eccentric contractions in humans.

Skeletal muscle satellite cells (SC) play an important role in muscle repair following injury. The regulation of SC activity is governed by myogenic regulatory factors (MRF), including MyoD, Myf5, myogenin, and MRF4. The mRNA expression of these MRF in humans following muscle damage has been predominately measured in whole muscle homogenates. Whether the temporal expression of MRF in a whole muscle homogenate reflects SC-specific expression of MRF remains largely unknown. Sixteen young men (23.1 ± 1.0 yr) performed 300 unilateral eccentric contractions (180°/s) of the knee extensors. Percutaneous muscle biopsies from the vastus lateralis were taken before (Pre) and 48 h postexercise. Fluorescence-activated cell sorting analysis was utilized to purify NCAM+ muscle SC from the whole muscle homogenate. Forty-eight hours post-eccentric exercise, MyoD, Myf5, and myogenin mRNA expression were increased in the whole muscle homogenate (~1.4-, ~4.0-, ~1.7-fold, respectively, P < 0.05) and in isolated SC (~19.3-, ~17.5-, ~58.9-fold, respectively, P < 0.05). MRF4 mRNA expression was not increased 48 h postexercise in the whole muscle homogenate (P > 0.05) or in isolated SC (P > 0.05). In conclusion, our results suggest that the directional changes in mRNA expression of the MRF in a whole muscle homogenate in response to acute eccentric exercise reflects that observed in isolated muscle SC.NEW & NOTEWORTHY The myogenic program is controlled via transcription factors referred to as myogenic regulatory factors (MRF). Previous studies have derived MRF expression from whole muscle homogenates, but little work has examined whether the mRNA expression of these transcripts reflects the pattern of expression in the actual population of satellite cells (SC). We report that MRF expression from an enriched SC population reflects the directional pattern of expression from skeletal muscle biopsy samples following eccentric contractions.

Toward a phenomic analysis of chronic postsurgical pain following cardiac surgery.

Background: Despite the same surgical approach, up to 40% of patients develop chronic postsurgical pain (CPSP) following cardiac surgery, whereas the rest are chronic pain free. This variability suggests that CPSP is controlled partially through genetics, but the genes for CPSP are largely unknown. Aims: The aim of this study was to identify potential CPSP phenotypes by comparing patients who developed CPSP following cardiac surgery vs. those who did not. Methods: A research ethics board-approved, cross-sectional study of post-cardiac surgery pain was conducted at Toronto General Hospital from 2011 to 2015. Patients were recruited to complete a short survey of chronic pain scores and the Short-Form McGill Pain Questionnaire-2. A subset of patients completed a longer survey of eight validated pain phenotyping questionnaires and/or four psychophysical assessments. All surveys and psychophysical testing were conducted after surgery. Patients were stratified by presence of chronic pain and groups were compared using descriptive statistics. Results: Six hundred forty-three patients completed the short form survey. The mean postsurgery assessment time was 41.5 (SD = ±25.1) months. Over a quarter (27.8%) reported CPSP at the chest as a consequence of their surgery. Of patients reporting CPSP, 46.6% reported mild pain (0-3), 35.8% reported moderate pain (4-7), and 17.6% reported severe pain (7-10) in accordance with the numerical rating scale. Patients with moderate and/or severe CPSP were younger, had a greater body mass index, and had higher anxiety sensitivity, pain catastrophizing, and somatization scores. Conclusions: Chronic pain levels after cardiac surgery are associated with anxiety, catastrophizing, and sensory abnormalities in body parts outside the field innervated by injured nerves, indicating the presence of widespread central sensitization to incoming sensory inputs from intact nerves.

Contexte: Malgré qu'ils aient été soumis à la même approche chirurgicale, jusqu'à 40 % des patients souffrent de douleur chronique postopératoire après une chirurgie cardiaque, tandis que le reste des patients n'en souffrent pas. Cette variabilité porte à croire que la douleur chronique postopératoire est en partie maitrisée génétiquement, mais les gènes en cause dans la douleur chronique postopératoire sont très peu connus.But: Identifier les phénotypes de douleur chronique postopératoire possibles en comparant des patients souffrant de douleur chronique postopératoire à des patients n'en souffrant pas après une chirurgie cardiaque.Méthodes: Une étude transversale de la douleur après une chirurgie cardiaque approuvée par la commission d'éthique de la recherche a été menée à l'Hôpital général de Toronto de 2011 à 2015. Les patients ont été recrutés pour répondre à un court questionnaire portant sur les scores de douleur chronique et à une version abrégée du McGill Pain Questionnaire-2. Un sous-ensemble de patients a répondu à une enquête plus longue comprenant huit questionnaires validés portant sur le phénotypage de la douleur et/ou sur quatre mesures psychophysiques. Tous les questionnaires et les tests psychophysiques ont été menés après la chirurgie. Les patients ont été stratrifiés en fonction de la présence de douleur chronique et les groupes ont été comparés à l'aide de statistiques descriptives.Résultats: 634 patients ont répondu à la version courte de l'enquête. Le temps moyen de l'évaluation post-chirurgie était de 41,4 mois (écart-type ± 25,1). Plus d'un quart (27,8%) des participants ont rapporté de la douleur chronique postopératoire au thorax en tant que conséquence de la chirurgie. Parmi les patients rapportant de la douleur chronique post-opératoire, 46,6 % ont rapporée une douleur faible (0-3), 35,8 % ont rapporté de la douleur modérée (4-7) et 17,6 % ont rapporté de la douleur sévère (7-10), selon l'échelle d'évaluation numérique. Les patients souffrant de douleur chronique postopératoire de modérée à sévère étaient plus jeunes, avaient un indice de masse corporelle plus élevé et obtenaient des scores plus élevés en ce qui concerne la sensibilité à l'anxiété, la catastrophisation de la douleur et la somatisation.Conclusion: Les niveaux de douleur chronique après une chirurgie cardiaque sont associés à l'anxiété, à la catastrophisation et à des anomalies sensorielles dans des parties du corps à l'extérieur de la zone innervée par les nerfs par les nerfs endommagés, ce qui indique la présence d'une sensibilisation centrale généralisée aux signaux sensoriels provenant des nerfs intacts.