The changes of blood-based inflammatory biomarkers after non-pharmacologic interventions for chronic low back pain: a systematic review.

BACKGROUND: Chronic low back pain (CLBP) is a prevalent and debilitating condition, leading to significant challenges to both patients and the governmental healthcare system. Non-pharmacologic interventions have received increasing attention as potential strategies to alleviate chronic low back pain and improve patient outcomes. The aim of this systematic review was to comprehensively assess the changes in blood inflammatory biomarkers after non-pharmacologic interventions for CLBP patients, thus trying to understand the complex interactions between non-pharmacologic interventions and inflammatory biomarker changes in CLBP. METHODS: A thorough search (from January 1st, 2002 to October 5th, 2022) of PubMed, Medline (platform Web of Science), and the Cochrane Library (platform Wiley Online Library) were conducted, and inclusion criteria as well as exclusion criteria were refined to selection of the studies. Rigorous assessments of study quality were performed using RoB 2 from Cochrane or an adaptation of the Downs and Black checklist. Data synthesis includes alterations in inflammatory biomarkers after various non-pharmacologic interventions, including exercise, acupressure, neuro-emotional technique, and other modalities. RESULTS: Thirteen primary studies were included in this systematic review, eight randomized controlled trials, one quasi-randomized trial, and four before-after studies. The interventions studied consisted of osteopathic manual treatment (one study), spinal manipulative therapy (SMT) (three studies), exercise (two studies), yoga (two studies) and acupressure (two studies), neuro-emotional technique (one study), mindfulness-based (one study) and balneotherapy study (one study). Four studies reported some changes in the inflammatory biomarkers compared to the control group. Decreased tumor necrosis factor-alpha (TNF-α) after osteopathic manual treatment (OMT), neuro-emotional technique (NET), and yoga. Decreased interleukin (IL)-1, IL-6, IL-10, and c-reactive protein (CRP) after NET, and increased IL-4 after acupressure. Another five studies found changes in inflammatory biomarkers through pre- and post-intervention comparisons, indicating improvement outcomes after intervention. Increased IL-10 after balneotherapy; decreased TNF-α, IL-1ß, IL-8, Interferon-gamma, interferon-γ-induced protein 10-γ-induced protein 10 after exercise; decreased IL-6 after exercise and SMT; decreased CRP and chemokine ligand 3 after SMT. CONCLUSION: Results suggest a moderation of inflammatory biomarkers due to different non-pharmacologic interventions for CLBP, generally resulting in decreased pro-inflammatory markers such as TNF-α and IL-6 as well as increased anti-inflammatory markers such as IL-4, thus revealing the inhibition of inflammatory processes by different non-pharmacologic interventions. However, a limited number of high-quality studies evaluating similar interventions and similar biomarkers limits the conclusion of this review.

Insights into pain distraction and the impact of pain catastrophizing on pain perception during different types of distraction tasks.

Introduction: Distraction is commonly used to reduce pain, but the effectiveness of distractions remains inconclusive. Studies have shown that pain catastrophizing could modulate the effectiveness of distraction strategies. The present study aimed to compare various distraction tasks, then control for pain catastrophizing, and examine how this relationship varies with pain intensity and unpleasantness across different distraction tasks. Methods: Forty-one pain-free participants (aged 27.00 ± 5.41) were recruited for a cross-sectional study. Four types of distraction (cognitive, sensory, emotional, and social) were presented, while moderate pain intensity was induced by electrical stimulation. Before starting the experiment, moderate pain intensity was individually calibrated as six on the Numerical Pain Rating Scale (NRS) to control individual differences in pain sensitivity. Each participant performed all four distraction tasks in a random order. NRS measured pain assessment. Pain catastrophizing was measured by the Pain Catastrophizing Scale (PCS). A repeated measure ANCOVA was conducted to examine the effects of pain dimensions during distraction tasks as a within-subject and pain catastrophizing as a covariate factor. Results: A significant difference was observed in the pain intensity and unpleasantness during cognitive distraction. After controlling for PCS, there were diverse associations between PCS and pain intensity across distinct distraction tasks: social vs. sensory, and cognitive vs. sensory distraction. A consistent pattern in pain unpleasantness emerged with minor variations. This interaction underscored notable distinctions between social vs. sensory and emotional distractions, as well as between cognitive vs. sensory and emotional distractions. However, only the correlation in social distraction remained significant in both pain dimensions. Discussion: Our findings reveal that the link between PCS and pain dimensions varies across different distraction tasks, suggesting diverse interactions. Particularly, social distraction, characterized by both emotional and cognitive states, proves beneficial with lower PCS scores; however, this advantage diminishes as PCS scores increase.

Dose-response relationship and effect modifier of stabilisation exercises in nonspecific low back pain: a project-wide individual patient data re-analysis on 1483 intervention participants.

ABSTRACT: This planned MiSpEx-Network reanalysis was designed to derive a dose-response relationship under consideration of further effect modifiers in exercises on low back pain. One thousand four hundred eighty three intervention participants with low back pain (mean age, 40.9 years [SD 14 years]) performed stabilisation exercises (3 weeks supervised, 9 weeks self-administered). Patients reported pain intensity, disability, and disability days at baseline, 3 weeks, 12 weeks, and 6 months post randomisation. Exercise characteristics and effect modifiers were prospectively monitored. Beyond the comparison to the results of the control group, linear mixed models were calculated to determine a dose-response relationship. The interventions led to small but significantly larger symptom reductions than in the control group at each measurement. Longer durations of the intervention led to larger symptom reductions. Higher exercise frequencies were associated with a decrease in pain intensity: to train once more per week led to a mean decrease of 0.93 points in pain intensity [95% CI = -1.54 to -0.32]. Disability days were also impacted (estimate = -0.07 [-0.14 to 0.00]), but disability was not (-0.09 [-0.67 to 0.48]). Adding perturbation was superior to adding stretching or a behavioural module. The relationships were robust when additional effect modifiers were considered and against the control group' effects. The odds ratio for a clinically important effect with higher exercise frequencies decreased at 3 weeks (OR = 0.71 [0.618-0.813] for >2.5*week -1 ) and increased at 12 weeks (1.13 [1.006-1.270], >1.5*week -1 ). Using longer intervention durations, adding a perturbation component to the stabilisation trainings and using higher frequencies (up to a certain point) may lead to an even more beneficial response on exercise in patients with low back pain. Developing strategies to maintain a training frequency of at least 2 times per week may be relevant in stabilisation exercises to treat low back pain.

Association of primary allostatic load mediators and metabolic syndrome (MetS): A systematic review.

Allostatic load (AL) exposure may cause detrimental effects on the neuroendocrine system, leading to metabolic syndrome (MetS). The primary mediators of AL involve serum dehydroepiandrosterone sulfate (DHEAS; a functional HPA axis antagonist); further, cortisol, urinary norepinephrine (NE), and epinephrine (EPI) excretion levels (assessed within 12-h urine as a golden standard for the evaluation of the HPA axis activity and sympathetic nervous system activity). However, the evidence of an association between the primary mediators of AL and MetS is limited. This systematic review aimed to critically examine the association between the primary mediators of AL and MetS. PubMed and Web of Science were searched for articles from January 2010 to December 2021, published in English. The search strategy focused on cross-sectional and case-control studies comprising adult participants with MetS, obesity, overweight, and without chronic diseases. The STROBE checklist was used to assess study quality control. Of 770 studies, twenty-one studies with a total sample size (n = 10,666) met the eligibility criteria. Eighteen studies were cross-sectional, and three were case-control studies. The included studies had a completeness of reporting score of COR % = 87.0 ± 6.4%. It is to be noted, that cortisol as a primary mediator of AL showed an association with MetS in 50% (urinary cortisol), 40% (serum cortisol), 60% (salivary cortisol), and 100% (hair cortisol) of the studies. For DHEAS, it is to conclude that 60% of the studies showed an association with MetS. In contrast, urinary EPI and urinary NE had 100% no association with MetS. In summary, there is a tendency for the association between higher serum cortisol, salivary cortisol, urinary cortisol, hair cortisol, and lower levels of DHEAS with MetS. Future studies focusing on longitudinal data are warranted for clarification and understanding of the association between the primary mediators of AL and MetS.

Training intervention effects on cognitive performance and neuronal plasticity-A pilot study.

Studies suggest that people suffering from chronic pain may have altered brain plasticity, along with altered functional connectivity between pain-processing brain regions. These may be related to decreased mood and cognitive performance. There is some debate as to whether physical activity combined with behavioral therapy (e.g. cognitive distraction, body scan) may counteract these changes. However, underlying neuronal mechanisms are unclear. The aim of the current pilot study with a 3-armed randomized controlled trial design was to examine the effects of sensorimotor training for nonspecific chronic low back pain on (1) cognitive performance; (2) fMRI activity co-fluctuations (functional connectivity) between pain-related brain regions; and (3) the relationship between functional connectivity and subjective variables (pain and depression). Six hundred and sixty two volunteers with non-specific chronic low back pain were randomly allocated to a unimodal (sensorimotor training), multidisciplinary (sensorimotor training and behavioral therapy) intervention, or to a control group within a multicenter study. A subsample of patients (n = 21) from one study center participated in the pilot study presented here. Measurements were at baseline, during (3 weeks, M2) and after intervention (12 weeks, M4 and 24 weeks, M5). Cognitive performance was measured by the Trail Making Test and functional connectivity by MRI. Pain perception and depression were assessed by the Von Korff questionnaire and the Hospital and Anxiety. Group differences were calculated by univariate and repeated ANOVA measures and Bayesian statistics; correlations by Pearson's r. Change and correlation of functional connection were analyzed within a pooled intervention group (uni-, multidisciplinary group). Results revealed that participants with increased pain intensity at baseline showed higher functional connectivity between pain-related brain areas used as ROIs in this study. Though small sample sizes limit generalization, cognitive performance increased in the multimodal group. Increased functional connectivity was observed in participants with increased pain ratings. Pain ratings and connectivity in pain-related brain regions decreased after the intervention. The results provide preliminary indication that intervention effects can potentially be achieved on the cognitive and neuronal level. The intervention may be suitable for therapy and prevention of non-specific chronic low back pain.

Stress Management in Pre- and Postoperative Care Amongst Practitioners and Patients in Cardiac Catheterization Laboratory: A Study Protocol.

Background: As the number of cardiac diseases continuously increases within the last years in modern society, so does cardiac treatment, especially cardiac catheterization. The procedure of a cardiac catheterization is challenging for both patients and practitioners. Several potential stressors of psychological or physical nature can occur during the procedure. The objective of the study is to develop and implement a stress management intervention for both practitioners and patients that aims to reduce the psychological and physical strain of a cardiac catheterization. Methods: The clinical study (DRKS00026624) includes two randomized controlled intervention trials with parallel groups, for patients with elective cardiac catheterization and practitioners at the catheterization lab, in two clinic sites of the Ernst-von-Bergmann clinic network in Brandenburg, Germany. Both groups received different interventions for stress management. The intervention for patients comprises a psychoeducational video with different stress management technics and additional a standardized medical information about the cardiac catheterization examination. The control condition includes the in hospitals practiced medical patient education before the examination (usual care). Primary and secondary outcomes are measured by physiological parameters and validated questionnaires, the day before (M1) and after (M2) the cardiac catheterization and at a postal follow-up 6 months later (M3). It is expected that people with standardized information and psychoeducation show reduced complications during cardiac catheterization procedures, better pre- and post-operative wellbeing, regeneration, mood and lower stress levels over time. The intervention for practitioners includes a Mindfulness-based stress reduction program (MBSR) over 8 weeks supervised by an experienced MBSR practitioner directly at the clinic site and an operative guideline. It is expected that practitioners with intervention show improved perceived and chronic stress, occupational health, physical and mental function, higher effort-reward balance, regeneration and quality of life. Primary and secondary outcomes are measured by physiological parameters (heart rate variability, saliva cortisol) and validated questionnaires and will be assessed before (M1) and after (M2) the MBSR intervention and at a postal follow-up 6 months later (M3). Physiological biomarkers in practitioners will be assessed before (M1) and after intervention (M2) on two work days and a two days off. Intervention effects in both groups (practitioners and patients) will be evaluated separately using multivariate variance analysis. Discussion: This study evaluates the effectiveness of two stress management intervention programs for patients and practitioners within cardiac catheter laboratory. Study will disclose strains during a cardiac catheterization affecting both patients and practitioners. For practitioners it may contribute to improved working conditions and occupational safety, preservation of earning capacity, avoidance of participation restrictions and loss of performance. In both groups less anxiety, stress and complications before and during the procedures can be expected. The study may add knowledge how to eliminate stressful exposures and to contribute to more (psychological) security, less output losses and exhaustion during work. The evolved stress management guidelines, training manuals and the standardized patient education should be transferred into clinical routines.

Stress and Pain. Predictive (Neuro)Pattern Identification for Chronic Back Pain: A Longitudinal Observational Study.

Introduction: Low back pain (LBP) leads to considerable impairment of quality of life worldwide and is often accompanied by psychosomatic symptoms. Objectives: First, to assess the association between stress and chronic low back pain (CLBP) and its simultaneous appearance with fatigue and depression as a symptom triad. Second, to identify the most predictive stress-related pattern set for CLBP for a 1-year diagnosis. Methods: In a 1-year observational study with four measurement points, a total of 140 volunteers (aged 18-45 years with intermittent pain) were recruited. The primary outcomes were pain [characteristic pain intensity (CPI), subjective pain disability (DISS)], fatigue, and depressive mood. Stress was assessed as chronic stress, perceived stress, effort reward imbalance, life events, and physiological markers [allostatic load index (ALI), hair cortisol concentration (HCC)]. Multiple linear regression models and selection procedures for model shrinkage and variable selection (least absolute shrinkage and selection operator) were applied. Prediction accuracy was calculated by root mean squared error (RMSE) and receiver-operating characteristic curves. Results: There were 110 participants completed the baseline assessments (28.2 ± 7.5 years, 38.1% female), including HCC, and a further of 46 participants agreed to ALI laboratory measurements. Different stress types were associated with LBP, CLBP, fatigue, and depressive mood and its joint occurrence as a symptom triad at baseline; mainly social-related stress types were of relevance. Work-related stress, such as "excessive demands at work"[b = 0.51 (95%CI -0.23, 1.25), p = 0.18] played a role for upcoming chronic pain disability. "Social overload" [b = 0.45 (95%CI -0.06, 0.96), p = 0.080] and "over-commitment at work" [b = 0.28 (95%CI -0.39, 0.95), p = 0.42] were associated with an upcoming depressive mood within 1-year. Finally, seven psychometric (CPI: RMSE = 12.63; DISS: RMSE = 9.81) and five biomarkers (CPI: RMSE = 12.21; DISS: RMSE = 8.94) could be derived as the most predictive pattern set for a 1-year prediction of CLBP. The biomarker set showed an apparent area under the curve of 0.88 for CPI and 0.99 for DISS. Conclusion: Stress disrupts allostasis and favors the development of chronic pain, fatigue, and depression and the emergence of a "hypocortisolemic symptom triad," whereby the social-related stressors play a significant role. For translational medicine, a predictive pattern set could be derived which enables to diagnose the individuals at higher risk for the upcoming pain disorders and can be used in practice.

Translation and Adaptation of the French Version of the Risk Stratification Index, a Tool for Stratified Care in Chronic Low Back Pain: A Pilot Study.

Background and Objectives: Low back pain is a worldwide health problem. An early diagnosis is required to develop personalized treatment strategies. The Risk Stratification Index (RSI) was developed to serve the purpose. The aim of this pilot study is to cross-culturally translate the RSI to a French version (RSI-F) and evaluate the test-retest reliability of RSI-F using a French active population. Materials and Methods: The RSI was translated from German to French (RSI-F) based on the guidelines of cross-cultural adaptation of self-report measures. A total of 42 French recreational athletes (age 18−63 years) with non-specific low back pain were recruited and filled in the RSI-F twice. The test-retest reliability was examined using intraclass correlation coefficient (ICC1,2) and Pearson correlation coefficient. Results: Finally, 33 questionnaires were analyzed (14 males and 19 females, age 31 ± 10 years, 9.5 ± 3.2 h/week of training). The test-retest of RSI-F CPI and DISS were excellent (CPI: ICC1,2 = 0.989, p < 0.001; r = 0.989, p < 0.001; DISS: ICC1,2 = 0.991, p < 0.001; r = 0.991, p < 0.001), as well as Korff pain intensity (ICC1,2 = 0.995, p < 0.001; r = 0.995, p < 0.001) and disability (ICC1,2 = 0.998, p < 0.001; r = 0.998, p < 0.001). Conclusion: The RSI-F is linguistically accurate and reliable for use by a French-speaking active population with non-specific low back pain. The RSI-F is considered a tool to examine the evolution of psychosocial factors and therefore the risk of chronicity and the prognostic of pain. Further evaluations, such as internal, external validity, and responsiveness should be evaluated in a larger population.

The prevalence of chronic ankle instability in basketball athletes: a cross-sectional study.

BACKGROUND: Ankle sprain is the most common injury in basketball. Chronic ankle instability develops from an acute ankle sprain may cause negative effects on quality of life, ankle functionality or on increasing risk for recurrent ankle sprains and post-traumatic osteoarthritis. To facilitate a preventative strategy of chronic ankle instability (CAI) in the basketball population, gathering epidemiological data is essential. However, the epidemiological data of CAI in basketball is limited. Therefore, this study aims to investigate the prevalence of CAI in basketball athletes and to determine whether gender, competitive level, and basketball playing position influence this prevalence. METHODS: In a cross-sectional study, in total 391 Taiwanese basketball athletes from universities and sports clubs participated. Besides non-standardized questions about demographics and their history of ankle sprains, participants further filled out the standard Cumberland Ankle Instability Tool applied to determine the presence of ankle instability. Questionnaires from 255 collegiate and 133 semi-professional basketball athletes (male = 243, female = 145, 22.3 ± 3.8 years, 23.3 ± 2.2 kg/m2) were analyzed. Differences in prevalence between gender, competitive level and playing position were determined using the Chi-square test. RESULTS: In the surveyed cohort, 26% had unilateral CAI while 50% of them had bilateral CAI. Women had a higher prevalence than men in the whole surveyed cohort (X2(1) = 0.515, p = 0.003). This gender disparity also showed from sub-analyses, that the collegiate female athletes had a higher prevalence than collegiate men athletes (X2(1) = 0.203, p = 0.001). Prevalence showed no difference between competitive levels (p > 0.05) and among playing positions (p > 0.05). CONCLUSIONS: CAI is highly prevalent in the basketball population. Gender affects the prevalence of CAI. Regardless of the competitive level and playing position the prevalence of CAI is similar. The characteristic of basketball contributes to the high prevalence. Prevention of CAI should be a focus in basketball. When applying the CAI prevention measures, gender should be taken into consideration.

Lipid Biomarkers in Depression: Does Antidepressant Therapy Have an Impact?

Studies have revealed mixed results on how antidepressant drugs affect lipid profiles of patients with major depression disorder (MDD). Even less is known about how patients respond to a switch of antidepressant medication with respect to their metabolic profile. For this, effects of a switch in antidepressants medication on lipid markers were studied in MDD patients. 15 participants (females = 86.67%; males = 13.33%; age: 49.45 ± 7.45 years) with MDD and a prescribed switch in their antidepressant medication were recruited at a psychosomatic rehabilitation clinic. Participants were characterized (with questionnaires and blood samples) at admission to the rehabilitation clinic (baseline, T0) and followed up with a blood sample two weeks (T1) later. HDL, LDL, total cholesterol, and triglycerides were determined (T0), and their change analyzed (Wilcoxon test) at follow up (T1). Decrements in HDL (p = 0.041), LDL (p < 0.001), and total cholesterol (p < 0.001) were observed two weeks after a switch in antidepressant medication. Triglycerides showed no difference (p = 0.699). Overall, LDL, HDL, and total cholesterol are affected by a change in antidepressant drugs in patients with MDD. These observations are of clinical relevance for medical practitioners in the planning and management of treatment strategies for MDD patients.

Cross-cultural adaptation, reliability, and validation of the Taiwan-Chinese version of Cumberland Ankle Instability Tool.

PURPOSE: To cross-cultural translate the Cumberland Ankle Instability Tool (CAIT) to Taiwan-Chinese version (CAIT-TW), and to evaluate the validity, reliability and cutoff score of CAIT-TW for Taiwan-Chinese athletic population. MATERIALS AND METHODS: The English version of CAIT was translated to CAIT-TW based on a guideline of cross-cultural adaptation. 77 and 58 Taiwanese collegial athletes with and without chronic ankle instability filled out CAIT-TW, Taiwan-Chinese version of Lower Extremity Functional Score (LEFS-TW) and Numeric Rating Scale (NRS). The construct validity, test-retest reliability, internal consistency and cutoff score of CAIT-TW were evaluated. RESULTS: In construct validity, the Spearman's correlation coefficients were moderate (CAIT-TW vs LEFS-TW: Rho = 0.39, p < 0.001) and strong (CAIT-TW vs NRS: Rho= 0.76, p < 0.001). The test retest reliability was excellent (ICC2.1 = 0.91, 95% confidential interval = 0.87-0.94, p < 0.001) with a good internal consistency (Cronbach's α: 0.87). Receiver operating characteristic curve showed a cutoff score of 21.5 (Youden index: 0.73, sensitivity: 0.87, specificity 0.85). CONCLUSIONS: The CAIT-TW is a valid and reliable tool to differentiate between stable and instable ankles in athletes and may further apply for research or daily practice in Taiwan.Implications for rehabilitationFor athletes, chronic ankle instability is prevalent and causes negative sequela, such as lowered quality of daily life, affected functional performance, and may cause post traumatic osteoarthritis.The psychometric properties of the Taiwan-Chinese version of the Cumberland Ankle Instability Tool showed moderate to strong construct validity, excellent test retest reliability, a good internal consistency and a cutoff score of 21.5.The validity and reliability of the Taiwan-Chinese version of the Cumberland Ankle Instability Tool are to enable clinicians to evaluate and manage ankle instability in Taiwanese who speaks Mandarin Chinese.

RENaBack: low back pain patients in rehabilitation-study protocol for a multicenter, randomized controlled trial.

BACKGROUND: Millions of people in Germany suffer from chronic pain, in which course and intensity are multifactorial. Besides physical injuries, certain psychosocial risk factors are involved in the disease process. The national health care guidelines for the diagnosis and treatment of non-specific low back pain recommend the screening of psychosocial risk factors as early as possible, to be able to adapt the therapy to patient needs (e.g., unimodal or multimodal). However, such a procedure has been difficult to implement in practice and has not yet been integrated into the rehabilitation care structures across the country. METHODS: The aim of this study is to implement an individualized therapy and aftercare program within the rehabilitation offer of the German Pension Insurance in the area of orthopedics and to examine its success and sustainability in comparison to the previous standard aftercare program. The study is a multicenter randomized controlled trial including 1204 patients from six orthopedic rehabilitation clinics. A 2:1 allocation ratio to intervention (individualized and home-based rehabilitation aftercare) versus the control group (regular outpatient rehabilitation aftercare) is set. Upon admission to the rehabilitation clinic, participants in the intervention group will be screened according to their psychosocial risk profile. They could then receive either unimodal or multimodal, together with an individualized training program. The program is instructed in the clinic (approximately 3 weeks) and will continue independently at home afterwards for 3 months. The success of the program is examined by means of a total of four surveys. The co-primary outcomes are the Characteristic Pain Intensity and Disability Score assessed by the German version of the Chronic Pain Grade questionnaire (CPG). DISCUSSION: An improvement in terms of pain, work ability, patient compliance, and acceptance in our intervention program compared to the standard aftercare is expected. The study contributes to provide individualized care also to patients living far away from clinical centers. TRIAL REGISTRATION: DRKS, DRKS00020373 . Registered on 15 April 2020.

Mobile diagnostics and consultation for the prevention of the metabolic syndrome and its secondary diseases in Brandenburg-study protocol of a regional prospective cohort study: the Mobile Brandenburg Cohort.

BACKGROUND: The metabolic syndrome (MetS) is a risk cluster for a number of secondary diseases. The implementation of prevention programs requires early detection of individuals at risk. However, access to health care providers is limited in structurally weak regions. Brandenburg, a rural federal state in Germany, has an especially high MetS prevalence and disease burden. This study aims to validate and test the feasibility of a setup for mobile diagnostics of MetS and its secondary diseases, to evaluate the MetS prevalence and its association with moderating factors in Brandenburg and to identify new ways of early prevention, while establishing a "Mobile Brandenburg Cohort" to reveal new causes and risk factors for MetS. METHODS: In a pilot study, setups for mobile diagnostics of MetS and secondary diseases will be developed and validated. A van will be equipped as an examination room using point-of-care blood analyzers and by mobilizing standard methods. In study part A, these mobile diagnostic units will be placed at different locations in Brandenburg to locally recruit 5000 participants aged 40-70 years. They will be examined for MetS and advice on nutrition and physical activity will be provided. Questionnaires will be used to evaluate sociodemographics, stress perception, and physical activity. In study part B, participants with MetS, but without known secondary diseases, will receive a detailed mobile medical examination, including MetS diagnostics, medical history, clinical examinations, and instrumental diagnostics for internal, cardiovascular, musculoskeletal, and cognitive disorders. Participants will receive advice on nutrition and an exercise program will be demonstrated on site. People unable to participate in these mobile examinations will be interviewed by telephone. If necessary, participants will be referred to general practitioners for further diagnosis. DISCUSSION: The mobile diagnostics approach enables early detection of individuals at risk, and their targeted referral to local health care providers. Evaluation of the MetS prevalence, its relation to risk-increasing factors, and the "Mobile Brandenburg Cohort" create a unique database for further longitudinal studies on the implementation of home-based prevention programs to reduce mortality, especially in rural regions. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00022764 ; registered 07 October 2020-retrospectively registered.

Sustainability of a Motor Control Exercise Intervention: Analysis of Long-Term Effects in a Low Back Pain Study.

Development of chronic pain after a low back pain episode is associated with increased pain sensitivity, altered pain processing mechanisms and the influence of psychosocial factors. Although there is some evidence that multimodal therapy (such as behavioral or motor control therapy) may be an important therapeutic strategy, its long-term effect on pain reduction and psychosocial load is still unclear. Prospective longitudinal designs providing information about the extent of such possible long-term effects are missing. This study aims to investigate the long-term effects of a homebased uni- and multidisciplinary motor control exercise program on low back pain intensity, disability and psychosocial variables. 14 months after completion of a multicenter study comparing uni- and multidisciplinary exercise interventions, a sample of one study center (n = 154) was assessed once more. Participants filled in questionnaires regarding their low back pain symptoms (characteristic pain intensity and related disability), stress and vital exhaustion (short version of the Maastricht Vital Exhaustion Questionnaire), anxiety and depression experiences (the Hospital and Anxiety Depression Scale), and pain-related cognitions (the Fear Avoidance Beliefs Questionnaire). Repeated measures mixed ANCOVAs were calculated to determine the long-term effects of the interventions on characteristic pain intensity and disability as well as on the psychosocial variables. Fifty four percent of the sub-sample responded to the questionnaires (n = 84). Longitudinal analyses revealed a significant long-term effect of the exercise intervention on pain disability. The multidisciplinary group missed statistical significance yet showed a medium sized long-term effect. The groups did not differ in their changes of the psychosocial variables of interest. There was evidence of long-term effects of the interventions on pain-related disability, but there was no effect on the other variables of interest. This may be partially explained by participant's low comorbidities at baseline. Results are important regarding costless homebased alternatives for back pain patients and prevention tasks. Furthermore, this study closes the gap of missing long-term effect analysis in this field.

Psychosocial Moderators and Mediators of Sensorimotor Exercise in Low Back Pain: A Randomized Multicenter Controlled Trial.

The effects of exercise interventions on unspecific chronic low back pain (CLBP) have been investigated in many studies, but the results are inconclusive regarding exercise types, efficiency, and sustainability. This may be because the influence of psychosocial factors on exercise induced adaptation regarding CLBP is neglected. Therefore, this study assessed psychosocial characteristics, which moderate and mediate the effects of sensorimotor exercise on LBP. A single-blind 3-arm multicenter randomized controlled trial was conducted for 12-weeks. Three exercise groups, sensorimotor exercise (SMT), sensorimotor and behavioral training (SMT-BT), and regular routines (CG) were randomly assigned to 662 volunteers. Primary outcomes (pain intensity and disability) and psychosocial characteristics were assessed at baseline (M1) and follow-up (3/6/12/24 weeks, M2-M5). Multiple regression models were used to analyze whether psychosocial characteristics are moderators of the relationship between exercise and pain, meaning that psychosocial factors and exercise interact. Causal mediation analysis were conducted to analyze, whether psychosocial characteristics mediate the exercise effect on pain. A total of 453 participants with intermittent pain (mean age = 39.5 ± 12.2 years, f = 62%) completed the training. It was shown, that depressive symptomatology (at M4, M5), vital exhaustion (at M4), and perceived social support (at M5) are significant moderators of the relationship between exercise and the reduction of pain intensity. Further depressive mood (at M4), social-satisfaction (at M4), and anxiety (at M5 SMT) significantly moderate the exercise effect on pain disability. The amount of moderation was of clinical relevance. In contrast, there were no psychosocial variables which mediated exercise effects on pain. In conclusion it was shown, that psychosocial variables can be moderators in the relationship between sensorimotor exercise induced adaptation on CLBP which may explain conflicting results in the past regarding the merit of exercise interventions in CLBP. Results suggest further an early identification of psychosocial risk factors by diagnostic tools, which may essential support the planning of personalized exercise therapy. Level of Evidence: Level I. Clinical Trial Registration: DRKS00004977, LOE: I, MiSpEx: grant-number: 080102A/11-14. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00004977.

Extracellular Vesicles: Potential Mediators of Psychosocial Stress Contribution to Osteoporosis?

Osteoporosis is characterized by low bone mass and damage to the bone tissue's microarchitecture, leading to increased fracture risk. Several studies have provided evidence for associations between psychosocial stress and osteoporosis through various pathways, including the hypothalamic-pituitary-adrenocortical axis, the sympathetic nervous system, and other endocrine factors. As psychosocial stress provokes oxidative cellular stress with consequences for mitochondrial function and cell signaling (e.g., gene expression, inflammation), it is of interest whether extracellular vesicles (EVs) may be a relevant biomarker in this context or act by transporting substances. EVs are intercellular communicators, transfer substances encapsulated in them, modify the phenotype and function of target cells, mediate cell-cell communication, and, therefore, have critical applications in disease progression and clinical diagnosis and therapy. This review summarizes the characteristics of EVs, their role in stress and osteoporosis, and their benefit as biological markers. We demonstrate that EVs are potential mediators of psychosocial stress and osteoporosis and may be beneficial in innovative research settings.

The epidemiology of chronic ankle instability with perceived ankle instability- a systematic review.

BACKGROUND: Chronic ankle instability, developing from ankle sprain, is one of the most common sports injuries. Besides it being an ankle issue, chronic ankle instability can also cause additional injuries. Investigating the epidemiology of chronic ankle instability is an essential step to develop an adequate injury prevention strategy. However, the epidemiology of chronic ankle instability remains unknown. Therefore, the purpose of this study was to investigate the epidemiology of chronic ankle instability through valid and reliable self-reported tools in active populations. METHODS: An electronic search was performed on PubMed and Web of Science in July 2020. The inclusion criteria for articles were peer-reviewed, published between 2006 and 2020, using one of the valid and reliable tools to evaluate ankle instability, determining chronic ankle instability based on the criteria of the International Ankle Consortium, and including the outcome of epidemiology of chronic ankle instability. The risk of bias of the included studies was evaluated with an adapted tool for the sports injury review method. RESULTS: After removing duplicated studies, 593 articles were screened for eligibility. Twenty full-texts were screened and finally nine studies were included, assessing 3804 participants in total. The participants were between 15 and 32 years old and represented soldiers, students, athletes and active individuals with a history of ankle sprain. The prevalence of chronic ankle instability was 25%, ranging between 7 and 53%. The prevalence of chronic ankle instability within participants with a history of ankle sprains was 46%, ranging between 9 and 76%. Five included studies identified chronic ankle instability based on the standard criteria, and four studies applied adapted exclusion criteria to conduct the study. Five out of nine included studies showed a low risk of bias. CONCLUSIONS: The prevalence of chronic ankle instability shows a wide range. This could be due to the different exclusion criteria, age, sports discipline, or other factors among the included studies. For future studies, standardized criteria to investigate the epidemiology of chronic ankle instability are required. The epidemiology of CAI should be prospective. Factors affecting the prevalence of chronic ankle instability should be investigated and clearly described.

Which Functional Outcomes Can be Measured in Low Back Pain Trials and Therapies?: A Prospective 2-Year Factor-, Cluster-, and Reliability-Multicenter Analysis on 42 Variables in 1049 Individuals.

STUDY DESIGN: Prospective 2-year factor-, cluster-, and reliability-multicenter analysis. OBJECTIVE: To provide evidence on the uniqueness and usefulness of a set of potential relevant functional outcomes. SUMMARY OF BACKGROUND DATA: A very high number of functional outcomes that can be utilized as variables in low back pain (LBP) trials exists. METHODS: Participants (n = 1049) with and without current LBP were included. At 7 visits (baseline, 4 wk, 3 mo, 6 mo, 9 mo, 1 yr, and 2 yr), 42 different functional outcomes were assessed. Two exploratory factor analyses (for baseline-values and for changes scores to 3 mo post-baseline) were calculated (maximum likelihood extraction, varimax factor rotation). The strongest factor-loading outcomes were selected for the following hierarchical cluster analyses (average linkage, Euclidean distance measure). For each cluster, time point, and outcome, reliability analyses were subsequently calculated using intraclass correlation coefficients, standard error of measurements and coefficients of variation. RESULTS: The factor analysis for the cross-sectional values revealed 9 factors with a cumulative variance explanation of 61.7% and 13 unique ones. The change-score factor analysis revealed nine factors with a total variance explanation of 61.8%, seven outcomes were unique. Ten outcomes were important for both cross-sectional and change-score analyses, 11 were most valuable for cross-sectional and four for the change scores. Patients with pain grades 1 to 3 show comparable patterns (cluster 2). Grade 0 (cluster 1) and grade 4 (cluster 3) are unique and cannot be cumulated with other grades. Most biomechanical outcomes were highly reliable and display low measurement errors. CONCLUSION: We found 25 potentially meaningful functional outcomes in the context of objective functional measurements (such as trunk range of motion, dynamic and static balance, strength, and muscle fatigue resistance) and body characteristics. The present framework may help to select appropriate functional outcomes and rate effects beyond the known core set of outcomes.Level of Evidence: 1.

Motor Control Stabilisation Exercise for Patients with Non-Specific Low Back Pain: A Prospective Meta-Analysis with Multilevel Meta-Regressions on Intervention Effects.

Low-to-moderate quality meta-analytic evidence shows that motor control stabilisation exercise (MCE) is an effective treatment of non-specific low back pain. A possible approach to overcome the weaknesses of traditional meta-analyses would be that of a prospective meta-analyses. The aim of the present analysis was to generate high-quality evidence to support the view that motor control stabilisation exercises (MCE) lead to a reduction in pain intensity and disability in non-specific low back pain patients when compared to a control group. In this prospective meta-analysis and sensitivity multilevel meta-regression within the MiSpEx-Network, 18 randomized controlled study arms were included. Participants with non-specific low back pain were allocated to an intervention (individualized MCE, 12 weeks) or a control group (no additive exercise intervention). From each study site/arm, outcomes at baseline, 3 weeks, 12 weeks, and 6 months were pooled. The outcomes were current pain (NRS or VAS, 11 points scale), characteristic pain intensity, and subjective disability. A random effects meta-analysis model for continuous outcomes to display standardized mean differences between intervention and control was performed, followed by sensitivity multilevel meta-regressions. Overall, 2391 patients were randomized; 1976 (3 weeks, short-term), 1740 (12 weeks, intermediate), and 1560 (6 months, sustainability) participants were included in the meta-analyses. In the short-term, intermediate and sustainability, moderate-to-high quality evidence indicated that MCE has a larger effect on current pain (SMD = -0.15, -0.15, -0.19), pain intensity (SMD = -0.19, -0.26, -0.26) and disability (SMD = -0.15, -0.27, -0.25) compared with no exercise intervention. Low-quality evidence suggested that those patients with comparably intermediate current pain and older patients may profit the most from MCE. Motor control stabilisation exercise is an effective treatment for non-specific low back pain. Sub-clinical intermediate pain and middle-aged patients may profit the most from this intervention.

Personalized Treatment Suggestions: The Validity and Applicability of the Risk-Prevention-Index Social in Low Back Pain Exercise Treatments.

Background: The back pain screening tool Risk-Prevention-Index Social (RPI-S) identifies the individual psychosocial risk for low back pain chronification and supports the allocation of patients at risk in additional multidisciplinary treatments. The study objectives were to evaluate (1) the prognostic validity of the RPI-S for a 6-month time frame and (2) the clinical benefit of the RPI-S. Methods: In a multicenter single-blind 3-armed randomized controlled trial, n = 660 persons (age 18-65 years) were randomly assigned to a twelve-week uni- or multidisciplinary exercise intervention or control group. Psychosocial risk was assessed by the RPI-S domain social environment (RPI-SSE) and the outcome pain by the Chronic Pain Grade Questionnaire (baseline M1, 12-weeks M4, 24-weeks M5). Prognostic validity was quantified by the root mean squared error (RMSE) within the control group. The clinical benefit of RPI-SSE was calculated by repeated measures ANOVA in intervention groups. Results: A subsample of n = 274 participants (mean = 38.0 years, SD 13.1) was analyzed, of which 30% were classified at risk in their psychosocial profile. The half-year prognostic validity was good (RMSE for disability of 9.04 at M4 and of 9.73 at M5; RMSE for pain intensity of 12.45 at M4 and of 14.49 at M5). People at risk showed significantly stronger reduction in pain disability and intensity at M4/M5, if participating in a multidisciplinary exercise treatment. Subjects at no risk showed a smaller reduction in pain disability in both interventions and no group differences for pain intensity. Regarding disability due to pain, around 41% of the sample would gain an unfitted treatment without the back pain screening. Conclusion: The RPI-SSE prognostic validity demonstrated good applicability and a clinical benefit confirmed by a clear advantage of an individualized treatment possibility.