Effect of sense of coherence on long-term work participation among rehabilitation patients: a longitudinal study.

OBJECTIVE: To investigate the causal effect of sense of coherence on long-term work participation after rehabilitation, including stratification by age and diagnoses. DESIGN: Longitudinal cohort study. PARTICIPANTS: Patients aged ≤ 60 years, employed and accepted for somatic interprofessional rehabilitation in 2015 (n = 192). METHODS: Patients reported sense of coherence before rehabilitation in 2015 and mental and physical functioning in 2016. Register data were used to measure work participation during 2018 and days working without social security benefits during 2016-18. Regression models were used to explore the total effect of sense of coherence and the possible mediation of functioning. Results are reported as odds ratios (95% confidence intervals). RESULTS: During 2018, 77% of the total study cohort participated in work activities. The subgroup with musculoskeletal diagnoses had the fewest days of working without social security benefits. A causal relationship was found between sense of coherence and long-term work participation. Some of the effect of sense of coherence was mediated by mental functioning. The total effect of sense of coherence was strongest for patients with musculo-skeletal diagnoses (work participation: 1.11 (1.05, 1.17), days working without social security benefits: 1.05 (0.01, 109)). CONCLUSION: Improving coping resources may be beneficial to facilitate long-term work participation after injury or illness, especially for individuals with musculoskeletal diagnoses.

Body awareness and cognitive behavioral therapy for multisite musculoskeletal pain: patients` experiences with group rehabilitation.

BACKGROUND: An extended group program called Mind and Body (MB), based on body awareness exercises and cognitive behavioral therapy (CBT), was offered to a subgroup of patients who had completed their traditional outpatient multidisciplinary rehabilitation and were motivated for further treatment. PURPOSE: To explore how patients with multisite musculoskeletal pain experienced participation in the MB program with respect to usefulness, meaningfulness, behavioral changes, and transferability to daily life and work. METHOD: The study is rooted in the phenomenological tradition. Individual, semi-structured interviews were performed with eight patients aged 29-56 years. The data were analyzed using systematic text condensation. RESULTS: Two main themes emerged: 1) New knowledge provided increased body awareness, new ways of thinking, and acceptance of one's own situation. This theme reflected how new knowledge and MB coping strategies were useful in the process of changing problematic thoughts, increasing body awareness, and facilitating acceptance; and 2) Implementing new habits and strategies in daily life revealed how demanding it was to alter behavior, a process that unfolded over time. CONCLUSION: A combination of body awareness exercises and cognitive coping strategies was described as helpful in further improving function and coping with pain and stress in daily life and work.

Cytokine Patterns as Predictors of Antibiotic Treatment Effect in Chronic Low Back Pain with Modic Changes: Subgroup Analyses of a Randomized Trial (AIM Study).

Objective: Randomized trials testing the effect of antibiotics for chronic low back pain (LBP) with vertebral bone marrow changes on MRI (Modic changes) report inconsistent results. A proposed explanation is subgroups with low grade discitis where antibiotics are effective, but there is currently no method to identify such subgroups. The objective of the present study was to evaluate whether distinct patterns of serum cytokine levels predict any treatment effect of oral amoxicillin at one-year follow-up in patients with chronic low back pain and Modic changes at the level of a previous lumbar disc herniation. Design: We used data from an overpowered, randomized, placebo-controlled trial (the AIM study) that tested 100 days of oral 750 mg amoxicillin vs placebo three times daily in hospital outpatients with chronic (>6 months) LBP with pain intensity ≥5 on a 0-10 numerical rating scale and Modic changes type 1 (oedema type) or 2 (fatty type). We measured serum levels of 40 inflammatory cytokines at baseline and analysed six predefined potential predictors of treatment effect based on cytokine patterns in 78 randomized patients; three analyses with recursive partitioning, one based on cluster analysis and two based on principal component analyses. The primary outcome was the Roland-Morris Disability Questionnaire score at one-year follow-up in the intention to treat population. The methodology and overall results of the AIM study were published previously. Results: The 78 patients were 25-62 years old and 47 (60%) were women. None of the three recursive partitioning analyses resulted in any suggested subgroups. Of all main analyses, the largest effect estimate (mean difference between antibiotic and placebo groups) was seen in a subgroup not predefined as of main interest (Cluster category 3+4; -2.0, 95% CI: -5.2-1.3, RMDQ points; p-value for interaction 0.54). Conclusion: Patterns of inflammatory serum cytokine levels did not predict treatment effect of amoxicillin in patients with chronic LBP and Modic changes. Clinical Trial Registration Number: ClinicalTrials.gov (identifier: NCT02323412).

Long-Term Change and Predictors of Change in Physical and Mental Function after Rehabilitation: A Multi-Centre Study.

OBJECTIVE: To investigate changes and predictors of change in physical and mental function over a 3-year period after rehabilitation. DESIGN: Prospective cohort. PARTICIPANTS: Patients, across diseases, living in western Norway, accepted for somatic specialized interprofessional rehabilitation (n = 984). METHODS: Physical and mental function were assessed at admittance (baseline), and after 1 and 3 years using the Medical Outcome Study Short Form 36 (SF-36). Associations between changes in SF-36 component summary scores and sense of coherence, pain, disease group (musculoskeletal, neoplasm, cardiovascular, neurological, other), exercise habits and demographic variables were analysed using linear mixed modelling. RESULTS: In the total group, mean (standard deviation) physical component summary scores improved by 2.9 (8.4) and 3.4 (9.3) points at 1 and 3 years, respectively. Mental component summary scores improved by 2.1 (9.7) and 1.6 (10.8) points. Improvement in physical component summary was significantly greater for patients with higher sense of coherence (b = 0.09, p = 0.001) and for the neoplasm disease group (b = 2.13, p = 0.046). Improvement in mental component summary was significantly greater for patients with low sense of coherence (b = -0.13, p = < 0.001) and higher level of education (b = 3.02, p = 0.0302). Interaction with age (physical component summary: b = 0.22, p = 0.039/mental component summary b = 0.51, p = 0.006) indicated larger effect at 1 year than at 3 years. CONCLUSION: Physical and mental function improved in the total study group over the 3-year period. Sense of coherence at baseline was associated with improved physical and mental function, suggesting that coping resources are important in rehabilitation.

Minimal important change was on the lower spectrum of previous estimates and responsiveness was sufficient for core outcomes in chronic low back pain.

OBJECTIVES: The objective of this study was to estimate the minimal important change (MIC) and responsiveness of core patient reported outcome measures for chronic low back pain (LBP) and Modic changes. STUDY DESIGN AND SETTING: In the Antibiotics in Modic changes (AIM) trial we measured disability (RMDQ, ODI), LBP intensity (NRS) and health-related quality of life (EQ5D) electronically at baseline, three- and 12-month follow-up. MICs were estimated using Receiver Operating Curve (ROC) curve and Predictive modeling analyses against the global perceived effect. Credibility of the estimates was assessed by a standardized set of criteria. Responsiveness was assessed by a construct and criterion approach according to COSMIN guidelines. RESULTS: The MIC estimates of RMDQ, ODI and NRS scores varied between a 15-40% reduction, depending on including "slightly improved" in the definition of MIC or not. The MIC estimates for EQ5D were lower. The credibility of the estimates was moderate. For responsiveness, five out of six hypotheses were confirmed and AUC was >0.7 for all PROMs. CONCLUSION: When evaluated in a clinical trial of patients with chronic LBP and Modic changes, MIC thresholds for all PROMs were on the lower spectrum of previous estimates, varying depending on the definition of MIC. Responsiveness was sufficient.

Correlation between gene expression and MRI STIR signals in patients with chronic low back pain and Modic changes indicates immune involvement.

Disability and distress caused by chronic low back pain (LBP) lacking clear pathoanatomical explanations cause huge problems both for patients and society. A subgroup of patients has Modic changes (MC), identifiable by MRI as vertebral bone marrow lesions. The cause of such changes and their relationship to pain are not yet understood. We explored the pathobiology of these lesions using profiling of gene expression in blood, coupled with an edema-sensitive MRI technique known as short tau inversion recovery (STIR) imaging. STIR images and total RNA from blood were collected from 96 patients with chronic LBP and MC type I, the most inflammatory MC state. We found the expression of 37 genes significantly associated with STIR signal volume, ten genes with edema abundancy (a constructed combination of STIR signal volume, height, and intensity), and one gene with expression levels significantly associated with maximum STIR signal intensity. Gene sets related to interferon signaling, mitochondrial metabolism and defense response to virus were identified as significantly enriched among the upregulated genes in all three analyses. Our results point to inflammation and immunological defense as important players in MC biology in patients with chronic LBP.

The effect of infliximab in patients with chronic low back pain and Modic changes (the BackToBasic study): study protocol of a randomized, double blind, placebo-controlled, multicenter trial.

BACKGROUND: Low back pain is common and a significant number of patients experience chronic low back pain. Current treatment options offer small to moderate effects. Patients with vertebral bone marrow lesions visualized as Modic changes on magnetic resonance imaging may represent a subgroup within the low back pain population. There is evidence for inflammatory mediators being involved in development of Modic changes; hence, suppression of inflammation could be a treatment strategy for these patients. This study examines the effect of anti-inflammatory treatment with the TNF-α inhibitor infliximab in patients with chronic low back pain and Modic changes. METHODS/DESIGN: The BackToBasic trial is a multicenter, double blind, randomized controlled trial conducted at six hospitals in Norway, comparing intravenous infusions with infliximab with placebo. One hundred twenty-six patients aged 18-65 with chronic low back pain and type 1 Modic changes will be recruited from secondary care outpatients' clinics. The primary outcome is back pain-specific disability at day 154 (5 months). The study is designed to detect a difference in change of 10 (SD 18) in the Oswestry Disability Index at day 154/ 5 months. The study also aims to refine MRI-assessment, investigate safety and cost-effectiveness and explore the underlying biological mechanisms of Modic changes. DISCUSSION: Finding treatments that target underlying mechanisms could pose new treatment options for patients with low back pain. Suppression of inflammation could be a treatment strategy for patients with low back pain and Modic changes. This paper presents the design of the BackToBasic study, where we will assess the effect of an anti-inflammatory treatment versus placebo in patients with chronic low back pain and type 1 Modic changes. The study is registered at ClinicalTrials.gov under the identifier NCT03704363 . The EudraCT Number: 2017-004861-29.

Clinical effect modifiers of antibiotic treatment in patients with chronic low back pain and Modic changes - secondary analyses of a randomised, placebo-controlled trial (the AIM study).

BACKGROUND: Randomised trials on antibiotic treatment for patients with chronic low back pain and vertebral endplate changes visible on MRI (Modic changes) have shown mixed results. A possible explanation might be a real treatment effect in subgroups of the study populations. The purpose of the present study was to explore potential clinical effect modifiers of 3-months oral amoxicillin treatment in patients with chronic low back pain and type I or II Modic changes at the level of a previous lumbar disc herniation. METHODS: We performed analyses of effect modifiers on data from AIM, a double-blind parallel-group multicentre trial. One hundred eighty patients with chronic low back pain, previous disc herniation, Modic change type I (n = 118) or type II (n = 62) were randomised to 3-months oral treatment with 750 mg amoxicillin (n = 89) or placebo (n = 91) three times daily. The primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (possible values 0-24) at 1-year follow-up in the intention-to-treat population. The predefined minimal clinically important between-group mean difference was 4 RMDQ points (not reached in the primary analysis of AIM). Predefined baseline characteristics were analysed as potential effect modifiers, four primary (type I Modic changes, previous disc surgery, positive pain provocation test, high CRP) and five exploratory (disturbed sleep, constant low back pain, short duration of low back pain, younger age, and male) using ANCOVA with interaction terms. RESULTS: None of the four primary potential effect modifiers had strong evidence of modifying the treatment effect. In patients younger than 40 years the difference in mean RMDQ score between the treatment groups was - 4.0 (95%CI, - 6.9 to - 1.2), compared to - 0.5 (95%CI, - 2.3 to 1.3) in patients 40 years or older, both in favour of amoxicillin treatment (exploratory analysis). CONCLUSIONS: We did not find evidence for convincing clinical effect modifiers of antibiotic treatment in patients with chronic low back pain and Modic changes. Our results for younger age in these explorative analyses should not affect clinical treatment decisions without confirmation in future studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT02323412 , First registered 23 December 2014.

Association of Modic change types and their short tau inversion recovery signals with clinical characteristics- a cross sectional study of chronic low back pain patients in the AIM-study.

BACKGROUND: Modic Changes (MCs, magnetic resonance imaging (MRI) signal changes in the vertebral bone marrow extending from the vertebral endplate) may represent a subgroup of nonspecific chronic low back pain that could benefit from a specific management. The primary aim was to compare clinical characteristics between patients with type 1 versus type 2 MCs. The secondary aim was to explore associations between clinical characteristics and MC related short tau inversion recovery (STIR) signals. METHODS: This cross-sectional study used baseline data prospectively collected between 2015 and 2017 on the 180 patients included in the AIM-study (Antibiotics In Modic changes), a randomized controlled trial in a Norwegian hospital out-patient setting of patients with chronic low back pain, a lumbar disc herniation within the last 2 years, low back pain intensity score ≥ 5 (on a 0-10 scale) and current type 1 or type 2 MCs at the previously herniated lumbar disc level. We used prespecified clinical characteristics including self-report measures, physiologic measures and functional measures from clinical history and examination. The diagnostic accuracy of various clinical characteristics to discriminate between patients with type 1 MCs (with or without additional type 2 MCs) and patents with type 2 MCs only (not type 1) were assessed by calculating the area under the receiver-operating curve. We assessed the correlations of clinical characteristics with details of MC related STIR signal increase. RESULTS: No clinical characteristic differed between patients with type 1 (n = 118) versus type 2 (but not type 1) (n = 62) MCs. The clinical characteristics showed no/minor differences or no/weak correlations with MC related STIR signal increase. Patients with a positive Springing test (at any lumbar level) had slightly less volume of STIR signal increase than those with a negative test (mean difference 1.3 on a 0-48 scale, 95% CI 0.3 to 2.3). CONCLUSION: Clinical characteristics were similar for patients with type 1 MCs and patients with type 2 MCs, and showed no clinically relevant correlations with MC related STIR signal increase. TRIAL REGISTRATION: ClinicalTrials.gov NCT02323412, First registered 23 December 2014.

Effect of Early Interdisciplinary Rehabilitation for Trauma Patients: A Systematic Review.

OBJECTIVE: To perform a systematic review to assess the current scientific evidence concerning the effect of EIR for trauma patients with or without an associated traumatic brain injury. DATA SOURCE: We performed a systematic search of several electronic (Ovid MEDLINE, Embase, Cochrane Library Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health, and SveMed+) and 2 clinical trial registers (clinicaltrials.gov and International Clinical Trials Registry Platform). In addition, we handsearched reference lists from relevant studies. DATA EXTRACTION: Two review authors independently identified studies that were eligible for inclusion. The primary outcome measures were functional-related outcomes and return to work. The secondary outcome measures were length of stay in hospital, number of days on respirator, complication rate, physical and mental health measures, quality of life, and socioeconomic costs. DATA SYNTHESIS: Four studies with a total number of 409 subjects, all with traumatic brain-associated injuries, were included in this review. The included trials varied considerably in study design, inclusion and exclusion criteria, and had small numbers of participants. All studies were judged to have at least 1 high risk of bias. We found the quality of evidence, for both our primary and secondary outcomes, low. CONCLUSIONS: No studies that matched our inclusion criteria for EIR for trauma patients without traumatic brain injuries could be found. For traumatic brain injuries, there are a limited number of studies demonstrating that EIR has a positive effect on functional outcomes and socioeconomic costs. This review highlights the need for further research in trauma care regarding early phase interdisciplinary rehabilitation.

Symptom severity and quality of life in patients with concurrent neck pain and dizziness.

Purpose: There is little knowledge on how neck pain impacts dizzy patients, and if different diagnoses of dizziness associate with neck pain. The aim was to examine differences in dizziness severity, quality of life and demographics in dizzy patients with and without neck pain. Additionally, we examined if neck pain was associated with a non-vestibular or vestibular diagnosis.Methods: We included 236 consecutive patients referred to an otorhinolaryngological university clinic for vertigo and balance problems. The patients were divided in two groups: Patients with and without neck pain. Patient-reported outcomes measures were the Dizziness Handicap Inventory, RAND-12, neck pain and symptom duration.Results: A total of 59% of the patients reported neck pain. Patients with neck pain reported poorer quality of life (p < .001) and worse handicap due to dizziness (p < .001). There were no associations between reported neck pain and dizziness of non-vestibular or vestibular origin (p = .29).Conclusion: Neck pain is a common complaint among dizzy patients. Patients with concurrent dizziness and neck pain should warrant attention due to poorer general and dizziness-related quality of life. This finding appears unrelated to whether or not they receive a peripheral vestibular diagnosis.IMPLICATION FOR REHABILITATIONNeck pain is common in patients with dizziness and associated with higher dizziness handicap and lower quality of life.Neck pain should be addressed specifically in patients assessed for dizziness, irrespective of diagnosis.Further research is needed to better understand the interactions between neck pain and dizziness.

Neck pain associated with clinical symptoms in dizzy patients-A cross-sectional study.

OBJECTIVE: Many patients suffer from concurrent neck pain and dizziness. The aim of this study was to describe the clinical symptoms and physical findings in patients with concurrent neck pain and dizziness and to examine whether they differ from patients with dizziness alone. METHODS: Consecutive patients with dizziness and neck pain were recruited from an ear-nose-throat department and a spine clinic. They were divided into three groups: patients with dizziness only (n = 100), patients with dizziness as their primary complaint and additional neck pain (n = 138) and finally, patients with neck pain as their primary complaint accompanied by additional dizziness (n = 55). The patients filled in questionnaires regarding their symptom quality, time-course, triggers of dizziness and the Vertigo Symptom Scale Short Form. The physical examination included Cervical Range of Motion, American College of Rheumatology (ACR) Tender Points, Cervical Pressure Pain Thresholds and Global Physiotherapy Examination 52-Flexibility. RESULTS: Both neck pain groups were more likely to have a gradual onset of dizziness symptoms, more light-headedness, visual disturbances, autonomic/anxiety symptoms, decreased cervical range of motion, decreased neck and shoulder flexibility and increased number of ACR tender points compared with patients with dizziness alone. The group having dizziness as their primary complaint and also reporting neck pain had the highest symptom severity and tended to report rocking vertigo and increased neck tenderness. The group with neck pain as their primary complaint was more likely to report headache. CONCLUSION: Neck pain is associated with certain dizziness characteristics, increased severity of dizziness and increased physical impairment when compared with dizzy patients without neck pain.

Efficacy of antibiotic treatment in patients with chronic low back pain and Modic changes (the AIM study): double blind, randomised, placebo controlled, multicentre trial.

OBJECTIVE: To assess the efficacy of three months of antibiotic treatment compared with placebo in patients with chronic low back pain, previous disc herniation, and vertebral endplate changes (Modic changes). DESIGN: Double blind, parallel group, placebo controlled, multicentre trial. SETTING: Hospital outpatient clinics at six hospitals in Norway. PARTICIPANTS: 180 patients with chronic low back pain, previous disc herniation, and type 1 (n=118) or type 2 (n=62) Modic changes enrolled from June 2015 to September 2017. INTERVENTIONS: Patients were randomised to three months of oral treatment with either 750 mg amoxicillin or placebo three times daily. The allocation sequence was concealed by using a computer generated number on the prescription. MAIN OUTCOME MEASURES: The primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (range 0-24) at one year follow-up in the intention to treat population. The minimal clinically important between group difference in mean RMDQ score was predefined as 4. RESULTS: In the primary analysis of the total cohort at one year, the difference in the mean RMDQ score between the amoxicillin group and the placebo group was -1.6 (95% confidence interval -3.1 to 0.0, P=0.04). In the secondary analysis, the difference in the mean RMDQ score between the groups was -2.3 (-4.2 to-0.4, P=0.02) for patients with type 1 Modic changes and -0.1 (-2.7 to 2.6, P=0.95) for patients with type 2 Modic changes. Fifty patients (56%) in the amoxicillin group experienced at least one drug related adverse event compared with 31 (34%) in the placebo group. CONCLUSIONS: In this study on patients with chronic low back pain and Modic changes at the level of a previous disc herniation, three months of treatment with amoxicillin did not provide a clinically important benefit compared with placebo. Secondary analyses and sensitivity analyses supported this finding. Therefore, our results do not support the use of antibiotic treatment for chronic low back pain and Modic changes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02323412.

Predictors for Psychological Distress 2 Months After Mild Traumatic Brain Injury.

Objective: To predict psychological distress at 2 months for patients with mild traumatic brain injury. Method: A prospective cohort study of 162 patients with mild traumatic brain injury (MTBI) admitted consecutively to an outpatient clinic at Haukeland University Hospital, Norway. Demographic data were obtained from Statistics Norway and injury characteristics were obtained from the hospital records. Sick leave data from the last year before the injury were obtained from The Norwegian Labor and Welfare Service. Self-report questionnaires were used to obtain history about earlier disease and symptom profiles. The Hospital Anxiety and Depression Scale (HAD) detecting states of depression and anxiety were used as the dependent variable in a stepwise linear regression. Pre-injury factors and injury-related factors were examined as potential predictors for HAD. Results: In the first steps we observed a significant association between HAD at 2 months and education, whiplash associated disorder (WAD), and earlier sick listed with a psychiatric diagnosis. In the final step there was an association only between HAD and self-reported anxiety and WAD. There were no associations between HAD and injury-characteristics like severity at Glasgow Coma Scale or intracranial injury. Conclusion: Patients with low education, earlier psychiatric diagnosis, self-reported earlier anxiety and WAD were more likely to develop a psychological distress after a MTBI. These findings should be taken into consideration when treating patients with MTBI.

Cognitive functional therapy in patients with non-specific chronic low back pain-a randomized controlled trial 3-year follow-up.

OBJECTIVES: This randomized controlled trial investigated the efficacy of cognitive functional therapy (CFT) compared with manual therapy and exercise (MT-EX) for people with non-specific chronic low back pain (NSCLBP) at 3-year follow-up. METHODS: Hundred and twenty-one patients were randomized to CFT (n = 62) or MT-EX (n = 59). Three-year data were available for 30 (48.4%) participants in the CFT group, and 33 (55.9%) participants in the MT-EX group. The primary outcomes were disability (Oswestry disability Index [ODI]) and pain intensity (numerical rating scale) and secondary outcomes were anxiety/depression (Hopkins Symptoms Checklist) and pain-related fear (Fear-Avoidance Belief Questionnaire). A full intention to treat analysis was conducted using linear mixed models. RESULTS: Significantly greater reductions in disability were observed for the CFT group, with ODI scores at 3 years 6.6 points lower in the CFT than the MT-EX group (95%CI:-10.1 to -3.1, p < 0.001, standardized effect size = 0.70). There was no significant difference in pain intensity between the groups at 3 years (0.6 points 95%CI:-1.4-0.3, p = 0.195). Significantly greater reductions were also observed for the CFT group for Hopkins Symptoms Checklist and Fear-Avoidance Belief Questionnaire (Work). CONCLUSIONS: CFT is more effective at reducing disability, depression/anxiety and pain-related fear, but not pain, at 3-year follow-up than MT-EX. SIGNIFICANCE: Cognitive functional therapy (CFT) was more effective than manual therapy and exercise (MT-EX) in reducing disability at 3-year follow-up, in people with non-specific chronic low back pain. The sustained reduction in disability without concomitant reductions in pain intensity in the CFT group suggests a de-coupling of the pain-disability relationship. CFT resulted in long-lasting reductions in anxiety and depression, and pain-related fear regarding work compared to MT-EX. The findings support the long-term benefits of a individualized behaviourally orientated intervention that targets pain beliefs, functional restoration and lifestyle factors.

Modic changes-Their associations with low back pain and activity limitation: A systematic literature review and meta-analysis.

BACKGROUND: Previous systematic reviews have reported positive associations between Modic changes (MCs) and low back pain (LBP), but due to their narrow scope and new primary studies, there is a need for a comprehensive systematic review. Our objectives were to investigate if MCs are associated with non-specific LBP and/or activity limitation and if such associations are modified by other factors. METHODS: A protocol for this review was registered at PROSPERO prior to commencing the work (PROSPERO record: CRD42015017350). The MEDLINE, CINAHL and EMBASE databases were searched for relevant studies from first record to June 15th 2016. Prospective or retrospective cross-sectional cohort studies and case-control studies including people of all ages from general, working and clinical study populations were eligible for inclusion. Risk of bias assessment and data extraction for associations and potential modifiers were completed independently by pairs of reviewers. Meta-analysis was performed for homogeneous studies and presented as odds ratios (OR) with 95% CI. RESULTS: In all, 5210 citations were identified and 31 studies were included. One study had low risk of bias. Fifteen studies (48%) reported statistically significant positive associations between MCs and LBP and one study found a statistically significant negative association. Meta-analysis performed for studies using concordant pain with provocative discography as the clinical outcome resulted in an OR of 4.01 (1.52-10.61). One of seven studies reported a statistically significant positive association between MCs and activity limitation. Lumbar disc level and disc degeneration were found to modify the association between MCs and LBP. CONCLUSIONS: The results from this comprehensive systematic review indicate that the associations between MCs and LBP-related outcomes are inconsistent. The high risk of bias and the heterogeneity in terms of study samples, clinical outcomes and prevalence estimates of MCs and LBP may explain these findings. It is likely that new studies with low risk of bias will affect the direction and strength of these associations.

Measuring pressure pain threshold in the cervical region of dizzy patients-The reliability of a pressure algometer.

OBJECTIVES: A tool for measuring neck pain in patients with dizziness is needed to further investigate the relationship between the two symptoms. The objective of this study was to examine the reliability and validity of a hand-held pressure algometer in measuring pressure pain threshold (PPT) in different cervical regions of dizzy patients. METHODS: PPT was measured at two bilateral standardized sites of the neck by a trained physiotherapist in 50 patients with dizziness. Intraclass correlation coefficients (ICC) were calculated for intrarater and test-retest reliability. Concurrent validity was assessed by measuring the association between PPT and the American College of Rheumatology (ACR) tender points at each site and with the numeric pain rating scale (NPRS). RESULTS: Almost perfect intrarater (ICC = 0.815-0.940) and within-session test-retest (ICC = 0.854-0.906) reliability was found between the measures. On each site, a low PPT predicted a positive ACR tender point at each site (OR = 0.864-0.922). Last, we found a statistical inverse relationship between the PPT and the NPRS (R = -0.52 to -0.66). CONCLUSION: The study shows that a pressure algometer is a reliable tool for measuring PPT in the neck of dizzy patients. Further, the PPT correlates significantly with other subjective measures of pain indicating that it may be a useful tool for further research.

Antibiotic treatment In patients with chronic low back pain and Modic changes (the AIM study): study protocol for a randomised controlled trial.

BACKGROUND: A previous randomised controlled trial (RCT) of patients with chronic low back pain (LBP) and vertebral bone marrow (Modic) changes (MCs) on magnetic resonance imaging (MRI), reported that a 3-month, high-dose course of antibiotics had a better effect than placebo at 12 months' follow-up. The present study examines the effects of antibiotic treatment in chronic LBP patients with MCs at the level of a lumbar disc herniation, similar to the previous study. It also aims to assess the cost-effectiveness of the treatment, refine the MRI assessment of MCs, and further evaluate the impact of the treatment and the pathogenesis of MCs by studying genetic variability and the gene and protein expression of inflammatory biomarkers. METHODS/DESIGN: A double-blinded RCT is conducted at six hospitals in Norway, comparing orally administered amoxicillin 750 mg, or placebo three times a day, over a period of 100 days in patients with chronic LBP and type I or II MCs at the level of a MRI-confirmed lumbar disc herniation within the preceding 2 years. The inclusion will be stopped when at least 80 patients are included in each of the two MC type groups. In each MC type group, the study is designed to detect (ß = 0.1, α = 0.05) a mean difference of 4 (standard deviation 5) in the Roland Morris Disability Questionnaire score between the two treatment groups (amoxicillin or placebo) at 1-year follow-up. The study includes cost-effectiveness measures. Blood samples are assessed for security measures and for possible inflammatory mediators and biomarkers at different time points. MCs are evaluated on MRI at baseline and after 12 months. A blinded intention-to-treat analysis of treatment effects will be performed in the total sample and in each MC type group. DISCUSSION: To ensure the appropriate use of antibiotic treatment, its effect in chronic LBP patients with MCs should be re-assessed. This study will investigate the effects and cost-effectiveness of amoxicillin in patients with chronic LBP and MCs at the level of a disc herniation. The study may also help to refine imaging and characterise the biomarkers of MCs. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02323412 . Registered on 21 November 2014.

Virtual Reality Training for Upper Extremity in Subacute Stroke (VIRTUES): A multicenter RCT.

OBJECTIVE: To compare the effectiveness of upper extremity virtual reality rehabilitation training (VR) to time-matched conventional training (CT) in the subacute phase after stroke. METHODS: In this randomized, controlled, single-blind phase III multicenter trial, 120 participants with upper extremity motor impairment within 12 weeks after stroke were consecutively included at 5 rehabilitation institutions. Participants were randomized to either VR or CT as an adjunct to standard rehabilitation and stratified according to mild to moderate or severe hand paresis, defined as ≥20 degrees wrist and 10 degrees finger extension or less, respectively. The training comprised a minimum of sixteen 60-minute sessions over 4 weeks. The primary outcome measure was the Action Research Arm Test (ARAT); secondary outcome measures were the Box and Blocks Test and Functional Independence Measure. Patients were assessed at baseline, after intervention, and at the 3-month follow-up. RESULTS: Mean time from stroke onset for the VR group was 35 (SD 21) days and for the CT group was 34 (SD 19) days. There were no between-group differences for any of the outcome measures. Improvement of upper extremity motor function assessed with ARAT was similar at the postintervention (p = 0.714) and follow-up (p = 0.777) assessments. Patients in VR improved 12 (SD 11) points from baseline to the postintervention assessment and 17 (SD 13) points from baseline to follow-up, while patients in CT improved 13 (SD 10) and 17 (SD 13) points, respectively. Improvement was also similar for our subgroup analysis with mild to moderate and severe upper extremity paresis. CONCLUSIONS: Additional upper extremity VR training was not superior but equally as effective as additional CT in the subacute phase after stroke. VR may constitute a motivating training alternative as a supplement to standard rehabilitation. CLINICALTRIALSGOV IDENTIFIER: NCT02079103. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with upper extremity motor impairment after stroke, compared to conventional training, VR training did not lead to significant differences in upper extremity function improvement.