Is there any benefit of adding a central nervous system-focused intervention to a manual therapy and home stretching program for people with frozen shoulder? A randomized controlled trial.

BACKGROUND: Frozen shoulder (FS) is a highly disabling pathology of poorly understood etiology, which is characterized by the presence of intense pain and progressive loss of range of motion. The aim of this study was to evaluate the effect of adding a central nervous system (CNS)-focused approach to a manual therapy and home stretching program in people with FS. METHODS: A total of 34 patients with a diagnosis of primary FS were randomly allocated to receive a 12-week manual therapy and home stretching program or manual therapy and home stretching program plus a CNS-focused approach including graded motor imagery and sensory discrimination training. The Shoulder Pain and Disability Index score, self-perceived shoulder pain (visual analog scale score), shoulder range of motion, and the Patient-Specific Functional Scale score were measured at baseline, after a 2-week washout period just before starting treatment, after treatment, and at 3 months' follow-up. RESULTS: No significant between-group differences in any outcome were found either after treatment or at 3 months' follow-up. CONCLUSION: A CNS-focused approach provided no additional benefit to a manual therapy and home stretching program in terms of shoulder pain and function in people with FS.

Comorbidities Drive the Majority of Overall Mortality in Low-Risk Mucinous Pancreatic Cysts Under Surveillance.

BACKGROUND & AIMS: The Charlson Comorbidity Index (CACI) has been suggested as a tool to determine comorbidity burden and guide management for patients with mucinous pancreatic cysts (Intrapapillary Mucinous Neoplasms and Mucinous Cystic Neoplasms), but has not been studied well among "low-risk" mucinous pancreatic cysts i.e. without worrisome features (WF) and high-risk stigmata (HRS). This study sought to determine the comorbidity burden among surveillance population of low-risk pancreatic cysts and provide their follow-up mortality outcomes. METHODS: A single center study retrospectively reviewed a prospective pancreatic cyst database and included individuals with low-risk cysts undergoing serial imaging during 2016. Electronic medical records were reviewed to determine their baseline age-adjusted CACI (age-CACI). After 4 years, their progression to WF, disease specific (pancreatic malignancy-related, DSM), extra-pancreatic (EPM), and overall mortalities (OM) were determined using Kaplan-Meir Survival Analysis. RESULTS: 502 individuals underwent prospective surveillance. The study included 440 individuals with low-risk suspected or presumed mucinous cysts and excluded 50 and 12 individuals with WF and HRS respectively. Over a median follow-up of 56 months, 12 WF progressions, 2 DSMs, 42 EPMs, and 44 OMs were observed. Baseline age-CACI had good predictive capacity for 4-year EPM (Area-Under Curve: 0.87; p< .0001). The median age-CACI of 4 enabled cohort stratification into Low (age-CACI <4) and High CACI (age-CACI ≥4) groups. A significantly higher OM (p< .001) was observed among the High CACI group as compared to the Low CACI group. CONCLUSION: Through real-time application of CACI to patient outcomes, our analysis supports incorporation of this comorbidity assessment tool in making shared surveillance decisions among low-risk pancreatic cyst population.

Bioavailability of once-daily tacrolimus formulations used in clinical practice in the management of De Novo kidney transplant recipients: the better study.

Multicenter, prospective, observational study to compare the relative bioavailability of once-daily tacrolimus formulations in de novo kidney transplant recipients. De novo kidney transplant recipients who started a tacrolimus-based regimen were included 14 days post-transplant and followed up for 6 months. Data from 218 participants were evaluated: 129 in the LCPT group (Envarsus) and 89 in the PR-Tac (Advagraf) group. Patients in the LCPT group exhibited higher relative bioavailability (Cmin /total daily dose [TDD]) vs. PR-Tac (61% increase; P < .001) with similar Cmin and 30% lower TDD levels (P < .0001). The incidence of treatment failure was 3.9% in the LCPT group and 9.0% in the PR-Tac group (P = .117). Study discontinuation rates were 6.2% in the LCPT group and 12.4% in the PR-Tac group (P = .113). Adverse events, renal function and other complications were comparable between groups. The median accumulated dose of tacrolimus in the LCPT group from day 14 to month 6 was 889 mg. Compared to PR-Tac, LCPT showed higher relative bioavailability, similar effectiveness at preventing allograft rejection, comparable effect on renal function, safety, adherence, treatment failure and premature discontinuation rates.

Digital pain extent is associated with pain intensity but not with pain-related cognitions and disability in people with chronic musculoskeletal pain: a cross-sectional study.

BACKGROUND: To evaluate whether digital pain extent is associated with an array of psychological factors such as optimism, pessimism, expectations of recovery, pain acceptance, and pain self-efficacy beliefs as well as to analyse the association between digital pain extent and pain intensity and pain-related disability in people with chronic musculoskeletal pain. METHODS: A descriptive cross-sectional study conducted in a primary health care setting was carried out including 186 individuals with chronic musculoskeletal pain. Patient-reported outcomes were used to assess psychological factors, pain intensity, and pain-related disability. Digital pain extent was obtained from pain drawings shaded using a tablet and analysed using novel customized software. Multiple linear regression models were conducted to evaluate the association between digital pain extent and the aforementioned variables. RESULTS: Digital pain extent was statistically significantly associated with pain intensity. However, digital pain extent was not associated with any psychological measure nor with pain-related disability. DISCUSSION: The results did not support an association between digital pain extent and psychological measures.

Differences in Coracohumeral Distance Between the Symptomatic and the Asymptomatic Shoulder in Patients With Unilateral Shoulder Pain and in Healthy Participants: A Cross-Sectional Study.

OBJECTIVES: The aim of this study was to analyze whether differences in the coracohumeral distance (CHD) exist between the symptomatic and the asymptomatic shoulder in patients with subacromial pain syndrome and compare with the shoulder of control participants. METHODS: This was a cross-sectional, observational study. A sample comprising 62 participants with subacromial pain syndrome was recruited from 3 different primary care centers. The CHD was determined from standardized ultrasonography measures performed on both shoulders at 0° and 60° of shoulder abduction, whereas the dominant arm was measured for the control participants. RESULTS: Statistically significant differences in CHD at 0° and 60° were found between the symptomatic and control shoulders (P = .011/P = .002) and between the contralateral asymptomatic shoulder and controls (P = .026/P = .007). CONCLUSION: We found differences in CHD at 0° and 60° of shoulder elevation between both the affected and the nonaffected shoulders when compared with healthy shoulders. These results suggest that CHD may be a contributing factor in chronic shoulder pain.

Arterial blood stealing as a mechanism of negative BOLD response: From the steady-flow with nonlinear phase separation to a windkessel-based model.

Blood Oxygen Level Dependent (BOLD) signal indirectly characterizes neuronal activity by measuring hemodynamic and metabolic changes in the nearby microvasculature. A deeper understanding of how localized changes in electrical, metabolic and hemodynamic factors translate into a BOLD signal is crucial for the interpretation of functional brain imaging techniques. While positive BOLD responses (PBR) are widely considered to be linked with neuronal activation, the origins of negative BOLD responses (NBR) have remained largely unknown. As NBRs are sometimes observed in close proximity of regions with PBR, a blood "stealing" effect, i.e., redirection of blood from a passive periphery to the area with high neuronal activity, has been postulated. In this study, we used the Hagen-Poiseuille equation to model hemodynamics in an idealized microvascular network that account for the particulate nature of blood and nonlinearities arising from the red blood cell (RBC) distribution (i.e., the Fåhraeus, Fåhraeus-Lindqvist and the phase separation effects). Using this detailed model, we evaluate determinants driving this "stealing" effect in a microvascular network with geometric parameters within physiological ranges. Model simulations predict that during localized cerebral blood flow (CBF) increases due to neuronal activation-hyperemic response, blood from surrounding vessels is reallocated towards the activated region. This stealing effect depended on the resistance of the microvasculature and the uneven distribution of RBCs at vessel bifurcations. A parsimonious model consisting of two-connected windkessel regions sharing a supplying artery was proposed to simulate the stealing effect with a minimum number of parameters. Comparison with the detailed model showed that the parsimonious model can reproduce the observed response for hematocrit values within the physiological range for different species. Our novel parsimonious model promise to be of use for statistical inference (top-down analysis) from direct blood flow measurements (e.g., arterial spin labeling and laser Doppler/Speckle flowmetry), and when combined with theoretical models for oxygen extraction/diffusion will help account for some types of NBRs.

Intervention Therapies to Reduce Pain-Related Fear in Fibromyalgia Syndrome: A Systematic Review of Randomized Clinical Trials.

OBJECTIVE: This systematic review aimed to evaluate the effectiveness of different interventions at reducing pain-related fear in people with fibromyalgia and to analyze whether the included trials reported their interventions in full detail. DESIGN: Systematic review. SETTING: No restrictions. METHODS: The Cochrane Library, CINAHL, EMBASE, PsycINFO, PubMed, and Scopus were searched from their inception to April 2020, along with manual searches and a gray literature search. Randomized clinical trials were included if they assessed pain-related fear constructs as the primary or secondary outcome in adults with fibromyalgia. Two reviewers independently performed the study selection, data extraction, risk-of-bias assessment, Template for Intervention Description and Replication (TIDieR) checklist assessment, and grading the quality of evidence. RESULTS: Twelve randomized clinical trials satisfied the eligibility criteria, including 11 cohorts with a total sample of 1,441 participants. Exercise, multicomponent, and psychological interventions were more effective than controls were in reducing kinesiophobia. However, there were no differences in decreasing kinesiophobia when self-management and electrotherapy were used. There were also no differences between groups with regard to the rest of the interventions and pain-related constructs (fear-avoidance beliefs, fear of pain, and pain-related anxiety). However, a serious risk of bias and a very serious risk of imprecision were detected across the included trials. This caused the overall certainty of the judged evidence to be low and very low. Additionally, the included trials reported insufficient details to allow the full replication of their interventions. CONCLUSIONS: This systematic review shows that there are promising interventions, such as exercise, multicomponent, and psychological therapies, that may decrease one specific type of fear in people with fibromyalgia, i.e., kinesiophobia. However, because of the low-very low certainty of the evidence found, a call for action is needed to improve the quality of randomized clinical trials, which will lead to more definitive information about the clinical efficacy of interventions in this field.

Self-efficacy beliefs mediate the association between pain intensity and pain interference in acute/subacute whiplash-associated disorders.

PURPOSE: To evaluate whether a set of pre-accident demographic, accident-related, post-accident treatment and psychosocial factors assessed in people with acute/subacute whiplash-associated disorders (WAD) mediate the association between pain intensity and: (1) pain interference and (2) expectations of recovery, using Bayesian networks (BNs) analyses. This study also explored the potential mediating pathways (if any) between different psychosocial factors. METHODS: This was a cross-sectional study conducted on a sample of 173 participants with acute/subacute WAD. Pain intensity, pain interference, pessimism, expectations of recovery, pain catastrophizing, and self-efficacy beliefs were assessed. BN analyses were conducted to analyse the mediating effects of psychological factors on the association between pain intensity and pain-related outcomes. RESULTS: The results revealed that self-efficacy beliefs partially mediated the association between pain intensity and pain interference. Kinesiophobia partially mediated the association between self-efficacy and pain catastrophizing. Psychological factors did not mediate the association between pain intensity and expectations of recovery. CONCLUSION: These results indicate that individuals with acute/subacute WAD may present with lesser pain interference associated with a determined pain intensity value when they show greater self-efficacy beliefs. As the cross-sectional nature of this study limits firm conclusions on the causal impact, researchers are encouraged to investigate the role that patient's self-efficacy beliefs play in the transition to chronic WAD via longitudinal study designs.

Interferon beta 1a (Rebif®) in relapsing remitting multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease that affects the central nervous system. It is the second cause of neurological disability in young adults. The exact cause of the disease remains unknown and there is no curative treatment. It is imperative to evaluate the efficacy of newest, biotechnological products modifying the disease. This study was designed to evaluate the use of interferon beta 1a (Rebif®) in patients with relapsing remitting MS treated at International Center for Neurological Restoration. Thirty-one patients with relapsing remitting MS, between 10 and 65 years of age, four males and 27 females, were treated with Rebif® three times per week during 1 year. The safety of the treatment was evaluated based on the adverse events and the efficacy based on the disability scale score, the number of attacks and the number of lesions at magnetic resonance imaging (MRI). The public clinical trial is registered in Cuba (Number B-10-030-L03). Adverse effects occurred in 75% of the cases, but they were mild. A significant reduction in the number of attacks, the disability scale score and the number of lesions at MRI were observed in patients with relapsing remitting MS treated with Rebif®. The use of interferon beta 1a showed safety and efficacy in the treatment of patients with relapsing remitting MS.

Morphological Characteristics of Passive and Active Structures of the Foot Across Populations With Different Levels of Physical Activity.

BACKGROUND: Imaging diagnosis plays a fundamental role in the evaluation and management of injuries suffered in sports activities. OBJECTIVE: To analyze the differences in the thickness of the Achilles tendon, patellar tendon, plantar fascia, and posterior tibial tendon in the following levels of physical activity: persons who run regularly, persons otherwise physically active, and persons with a sedentary lifestyle. DESIGN: Cross-sectional and observational. PARTICIPANTS: The 91 volunteers recruited from students at the university and the Triathlon Club from December 2016 to June 2019. The data were obtained (age, body mass index, and visual analog scale for quality of life together with the ultrasound measurements). RESULTS: Tendon and ligament thickness was greater in the runners group than in the sedentary and active groups with the exception of the posterior tibial tendon. The thickness of the Achilles tendon was greater in the runners than in the other groups for both limbs (P = .007 and P = .005). This was also the case for the cross-sectional area (P < .01) and the plantar fascia at the heel insertion in both limbs (P = .034 and P = .026) and for patellar tendon thickness for the longitudinal measurement (P < .01). At the transversal level, however, the differences were only significant in the right limb (P = .040). CONCLUSION: The thickness of the Achilles tendon, plantar fascia, and patellar tendon is greater in runners than in persons who are otherwise active or who are sedentary.

A phylogenomic approach reveals a low somatic mutation rate in a long-lived plant.

Somatic mutations can have important effects on the life history, ecology, and evolution of plants, but the rate at which they accumulate is poorly understood and difficult to measure directly. Here, we develop a method to measure somatic mutations in individual plants and use it to estimate the somatic mutation rate in a large, long-lived, phenotypically mosaic Eucalyptus melliodora tree. Despite being 100 times larger than Arabidopsis, this tree has a per-generation mutation rate only ten times greater, which suggests that this species may have evolved mechanisms to reduce the mutation rate per unit of growth. This adds to a growing body of evidence that illuminates the correlated evolutionary shifts in mutation rate and life history in plants.

Blood Chromogranin A Is Not Effective as a Biomarker for Diagnosis or Management of Bronchopulmonary Neuroendocrine Tumors/Neoplasms.

BACKGROUND: Identification of circulating tumor markers for clinical management in bronchopulmonary (BP) neuroendocrine tumors/neoplasms (NET/NEN) is of considerable clinical interest. Chromogranin A (CgA), a "universal" NET biomarker, is considered controversial as a circulating biomarker of BPNEN. AIM: Assess utility of CgA in the diagnosis and management of BPNEN in a multicentric study. MATERIAL AND METHODS: CgA diagnostic metrics were assessed in lung NET/NENs (n = 200) and controls (n = 140), randomly assigned to a Training and Test set (100 BPC and 70 controls in each). Assay specificity was evaluated in neoplastic lung disease (n = 137) and nonneoplastic lung disease (n = 77). CgA efficacy in predicting clinical status was evaluated in the combined set of 200 NET/NENs. CgA levels in bronchopulmonary neuroendocrine tumor (BPNET) subtypes (atypical [AC] vs. typical [TC]) and grade was examined. The clinical utility of an alteration of CgA levels (±25%) was evaluated in a subset of 49 BPNET over 12 months. CgA measurement was by NEOLISATM kit (EuroDiagnostica). RESULTS: Sensitivity and specificity in the training set were 41/98%, respectively. Test set data were 42/87%. Training set area under receiver operator characteristic analysis differentiated BPC from control area under the curve (AUC) 0.61 ± 0.05 p = 0.015. Test set the data were AUC 0.58 ± 0.05, p = 0.076. In the combined set (n = 200), 67% BPNET/NEN (n = 134) had normal CgA levels. CgA levels did not distinguish histological subtypes (TC vs. AC, AUC 0.56 ± 0.04, p = 0.21), grade (p = 0.45-0.72), or progressive from stable disease (AUC 0.53 ± 0.05 p = 0.47). There was no correlation of CgA with Ki-67 index (Pearson r = 0.143, p = 0.14). For nonneoplastic diseases (chronic obstructive pulmonary disorder and idiopathic pulmonary fibrosis), CgA was elevated in 26-37%. For neoplastic disease (NSCLC, squamous cell carcinoma), CgA was elevated in 11-16%. The neuroendocrine SCLC also exhibited elevated CgA (50%). Elevated CgA was not useful for differentiating BPNET/NEN from these other pathologies. Monitoring BPNET/NEN over a 12-month period identified neither CgA levels per se nor changes in CgA were reflective of somatostatin analog treatment outcome/efficacy or the natural history of the disease (progression). CONCLUSIONS: Blood CgA levels are not clinically useful as a biomarker for lung BPNET/NEN. The low specificity and elevations in both nonneoplastic as well as other common neoplastic lung diseases identified limited clinical utility for this biomarker.

Sedation During Endoscopy in Patients with Cirrhosis: Safety and Predictors of Adverse Events.

BACKGROUND: Sedation during endoscopy in cirrhotic patients is typically via moderate sedation, most commonly using a combination of a benzodiazepine (i.e., midazolam) and narcotic (i.e., fentanyl) or with propofol using monitored anesthesia care (MAC). Here, we examined the safety of moderate sedation and MAC in patients with cirrhosis. METHODS: This retrospective cohort study of cirrhotic patients undergoing endoscopy from a large academic medical center between 2010 and 2014 examined extensive clinical data including the following: past history, physical findings, laboratory results, and procedural adverse events. Adverse events were defined a priori and included hypoxia, hypotension, bleeding, and death. RESULTS: We identified 2618 patients with cirrhosis who underwent endoscopic procedures; the mean age was 56 years, 36% were female, the mean Child-Pugh score was 9.3 (IQR: 8, 11), and Charlson Comorbidity Index score was 3.2 (IQR: 1, 4); 1157 had MAC; and 1461 had moderate sedation. There was no difference in the frequency of adverse events in MAC and moderate sedation groups, with a total of 15 adverse events (7/1157 MAC and 8/1461 moderate sedation). The most common procedure performed was esophagogastroduodenoscopy (EGD, n = 1667) and was associated with 10 adverse events. Overall, adverse events included bradycardia (1), hypoxia (7), bleeding (5), laryngospasm (1), and perforation (1). The frequency was similar for EGD, ERCP, and colonoscopy-each at a rate of 0.6%. CONCLUSIONS: Adverse events in cirrhotic patients undergoing endoscopy appeared to be similar with moderate sedation or MAC, and the frequency was the same for different types of procedures.

Conservative Interventions Reduce Fear in Individuals With Chronic Low Back Pain: A Systematic Review.

OBJECTIVE: To systematically review and critically appraise the effectiveness of conservative and surgical interventions to reduce fear in studies of people with chronic low back pain, based on the analysis of randomized controlled trials for which fear was a primary or secondary outcome. DATA SOURCES: Electronic databases PubMed, CINAHL, PsycINFO, PEDro, and CENTRAL, as well as manual searches and grey literature were searched from inception until May 2019. STUDY SELECTION: Randomized controlled trials analyzing the effectiveness of conservative and surgical interventions to reduce fear were included. DATA EXTRACTION: Two reviewers independently conducted the search strategy, study selection, data extraction, risk of bias assessment, and quality of the evidence judgment. DATA SYNTHESIS: Sixty-one studies (n=7201) were included. A large number of fear-related search terms were used but only 3 fear constructs (kinesiophobia, fear-avoidance beliefs, fear of falling) were measured in the included studies. Multidisciplinary and psychological interventions as well as exercise reduced kinesiophobia. Fear-avoidance beliefs were reduced by the aforementioned interventions, manual therapy, and electrotherapy. A multidisciplinary intervention reduced the fear of falling. There was moderate evidence of multidisciplinary interventions and exercise to reduce kinesiophobia. There was moderate evidence of manual therapy and electrotherapy to reduce fear-avoidance beliefs. CONCLUSIONS: The present systematic review highlights the potential effectiveness of conservative interventions to reduce kinesiophobia and fear-avoidance beliefs in individuals with chronic low back pain. This information can help health professionals to reduce fear when treating patients with this condition.

Is kinesiophobia and pain catastrophising at baseline associated with chronic pain and disability in whiplash-associated disorders? A systematic review.

BACKGROUND: Kinesiophobia and pain catastrophising may be associated with patients' transition from having acute to chronic pain following a whiplash injury. OBJECTIVE: To systematically review and critically appraise the literature to determine whether kinesiophobia and pain catastrophising are associated with greater likelihood of patients developing chronic pain and disability following a whiplash injury. DESIGN: A systematic review of the literature DATA SOURCES: Electronic searches of PubMed, AMED, CINAHL, PsycINFO, and PubPsych, and grey literature were undertaken from inception to September 2017. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Study selection was based on longitudinal studies evaluating how kinesiophobia and/or pain catastrophising at baseline are associated with pain intensity, disability or both after a whiplash injury. RESULTS: We included 14 longitudinal studies that described 12 independent cohorts with a total sample of 2733 participants with whiplash-associated disorder. Kinesiophobia at baseline was not associated with pain intensity over time (three studies). Whether kinesiophobia at baseline was associated with disability was unclear as results were conflicting (six studies). There were also conflicting results when we examined the association between pain catastrophising and both pain intensity (five studies) and disability (eight studies). SUMMARY/CONCLUSIONS: Kinesiophobia at baseline was not associated with pain intensity over time. There were conflicting results for the remaining analyses. The size of the associations was small. The overall quality of the evidence was very low. TRIAL REGISTRATION NUMBER: CRD42016053864.

Is There Any Association Between Foot Posture and Lower Limb-Related Injuries in Professional Male Basketball Players? A Cross-Sectional Study.

BACKGROUND: Several studies have shown that foot posture is related to the incidence of ankle sprains in athletes and in nonathletic populations, but this association has not previously been considered in basketball players. This study investigates the relationship between foot posture and lower limb injuries in elite basketball players. DESIGN AND METHOD: Two hundred twenty participants were recruited as a convenience sample. The players had a mean age of 22.51 ± 3.88 years and a body mass index of 23.98 ± 1.80. The players' medical records were accessed from the preceding 10 years, and injuries were recorded according to their location (knee, foot, and/or ankle). In addition, the Foot Posture Index (FPI) was scored for each player, and their playing positions were noted. RESULTS: An average FPI score of 2.66 was obtained across all players, with guards presenting a significantly lower average FPI of -0.48 (P < 0.001) compared with the rest of playing positions, indicating a more supinated foot. However, center players presented an average FPI of 5.15 (P < 0.001), indicating a more pronated foot. The most common injuries observed were lateral ankle sprain (n = 214) and patellar tendinopathy (n = 126). Patellar tendinopathy was more common in supinated feet (30.08%) compared with 20.7% and 19.8% in pronated and neutral feet, respectively. CONCLUSIONS: The most common lower limb injuries observed in basketball players were lateral ankle sprain and patellar tendinopathy. Patellar tendinopathy was more commonly associated with the supinated feet. Guard players tended to have a more supinated foot, whereas centers presented a more pronated foot.

Association of Both Scapular Upward Rotation and Scapulothoracic Muscle Lengths With Shoulder Pain, Function, and Range of Movement.

OBJECTIVE: Our aim was to analyze whether shoulder pain is related to scapular upward rotation (SUR) or to the lengths of the pectoralis minor and levator scapulae muscles. METHODS: This cross-sectional, observational study was carried out in 3 primary-care centers; 54 individuals with chronic shoulder pain participated. Scapular upward rotation and the lengths of the pectoralis minor and levator scapulae muscles were assessed. RESULTS: The level of association was small between shoulder pain and function and (1) the lengths of the pectoralis minor (r = 0.08, P = .93) and levator scapulae (r = -0.01, P = .57) muscles and (2) SUR at 45° (r = 0.17, P = .21), 90° (r = 0.08, P = .57), and 135° (r = 0.10, P = 0.45) of shoulder elevation. CONCLUSION: The relationship was small between shoulder pain and function and (1) SUR (45°, 90°, and 135° of shoulder elevation) and (2) the lengths of the pectoralis minor and levator scapulae muscles. Thus, the use of SUR and pectoralis minor and levator scapulae lengths in shoulder assessment should be undertaken with caution. Other factors such as psychological factors, central/peripheral sensitization, and intrinsic properties of the tissue have to be taken into account.

Kinesiophobia Is Associated With Pain Intensity and Disability in Chronic Shoulder Pain: A Cross-Sectional Study.

OBJECTIVE: Kinesiophobia is a clinically relevant factor in the management of chronic musculoskeletal pain. The aim of this study was to explore the cross-sectional association between kinesiophobia and both pain intensity and disability among individuals with chronic shoulder pain. METHODS: A total of 65 participants with chronic unilateral subacromial shoulder pain were recruited from 3 primary care centers. The Shoulder Pain and Disability Index assessed pain intensity and disability. The Tampa Scale for Kinesiophobia short form assessed the presence of kinesiophobia. A linear multivariable regression analysis evaluated the potential association between kinesiophobia and range of movement free of pain with pain intensity and disability. The analysis was adjusted for sex and age. RESULTS: In the linear multivariable regression analysis, only greater kinesiophobia (standardized ß = 0.35, P < .01) and sex (standardized ß = -0.29, P < .01) contributed to explain 19% of the variance in shoulder pain and disability scores. CONCLUSION: This cross-sectional study provides preliminary evidence about the association between kinesiophobia and pain intensity and disability among individuals with chronic shoulder pain. However, our findings only contributed to explain 19% of the variance in shoulder pain and disability scores.

NETest Liquid Biopsy Is Diagnostic of Lung Neuroendocrine Tumors and Identifies Progressive Disease.

BACKGROUND: There are no effective biomarkers for the management of bronchopulmonary carcinoids (BPC). We examined the utility of a neuroendocrine multigene transcript "liquid biopsy" (NETest) in BPC for diagnosis and monitoring of the disease status. AIM: To independently validate the utility of the NETest in diagnosis and management of BPC in a multicenter, multinational, blinded study. MATERIAL AND METHODS: The study cohorts assessed were BPC (n = 99), healthy controls (n = 102), other lung neoplasia (n = 101) including adenocarcinomas (ACC) (n = 41), squamous cell carcinomas (SCC) (n = 37), small-cell lung cancer (SCLC) (n = 16), large-cell neuroendocrine carcinoma (LCNEC) (n = 7), and idiopathic pulmonary fibrosis (IPF) (n = 50). BPC were histologically classified as typical (TC) (n = 62) and atypical carcinoids (AC) (n = 37). BPC disease status determination was based on imaging and RECIST 1.1. NETest diagnostic metrics and disease status accuracy were evaluated. The upper limit of normal (NETest) was 20. Twenty matched tissue-blood pairs were also evaluated. Data are means ± SD. RESULTS: NETest levels were significantly increased in BPC (45 ± 25) versus controls (9 ± 8; p < 0.0001). The area under the ROC curve was 0.96 ± 0.01. Accuracy, sensitivity, and specificity were: 92, 84, and 100%. NETest was also elevated in SCLC (42 ± 32) and LCNEC (28 ± 7). NETest accurately distinguished progressive (61 ± 26) from stable disease (35.5 ± 18; p < 0.0001). In BPC, NETest levels were elevated in metastatic disease irrespective of histology (AC: p < 0.02; TC: p = 0.0006). In nonendocrine lung cancers, ACC (18 ± 21) and SCC (12 ± 11) and benign disease (IPF) (18 ± 25) levels were significantly lower compared to BPC level (p < 0.001). Significant correlations were evident between paired tumor and blood samples for BPC (R: 0.83, p < 0.0001) and SCLC (R: 0.68) but not for SCC and ACC (R: 0.25-0.31). CONCLUSIONS: Elevated -NETest levels are indicative of lung neuroendocrine neoplasia. NETest levels correlate with tumor tissue and imaging and accurately define clinical progression.

Role of kinesiophobia on pain, disability and quality of life in people suffering from chronic musculoskeletal pain: a systematic review.

OBJECTIVE: (1) To explore the level of association between kinesiophobia and pain, disability and quality of life in people with chronic musculoskeletal pain (CMP) detected via cross-sectional analysis and (2) to analyse the prognostic value of kinesiophobia on pain, disability and quality of life in this population detected via longitudinal analyses. DESIGN: A systematic review of the literature including an appraisal of the risk of bias using the adapted Newcastle Ottawa Scale. A synthesis of the evidence was carried out. DATA SOURCES: An electronic search of PubMed, AMED, CINAHL, PsycINFO, PubPsych and grey literature was undertaken from inception to July 2017. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Observational studies exploring the role of kinesiophobia (measured with the Tampa Scale for Kinesiophobia) on pain, disability and quality of life in people with CMP. RESULTS: Sixty-three articles (mostly cross-sectional) (total sample=10 726) were included. We found strong evidence for an association between a greater degree of kinesiophobia and greater levels of pain intensity and disability and moderate evidence between a greater degree of kinesiophobia and higher levels of pain severity and low quality of life. A greater degree of kinesiophobia predicts the progression of disability overtime, with moderate evidence. A greater degree of kinesiophobia also predicts greater levels of pain severity and low levels of quality of life at 6 months, but with limited evidence. Kinesiophobia does not predict changes in pain intensity. SUMMARY/CONCLUSIONS: The results of this review encourage clinicians to consider kinesiophobia in their preliminary assessment. More longitudinal studies are needed, as most of the included studies were cross-sectional in nature. TRIAL REGISTRATION NUMBER: CRD42016042641.