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.

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.

Multidisciplinary outpatient treatment in patients with mild traumatic brain injury: A randomised controlled intervention study.

OBJECTIVE: To evaluate the efficacy of a multidisciplinary outpatient follow-up programme compared to follow-up by a general practitioner for patients being at-risk or sick-listed with persistent post-concussion symptoms two months after a mild traumatic brain injury. DESIGN: Randomised controlled trial. PATIENTS: One hundred fifty-one patients, 16-56 years. METHODS: Multidisciplinary outpatient rehabilitation with individual contacts and a psycho-educational group intervention at two outpatient rehabilitation clinics compared to follow-up by a general practitioner after the multidisciplinary examination. Primary outcome was sustainable return-to-work first year post-injury. Secondary outcomes were post-concussion symptoms, disability, the patient's impressions of change and psychological distress. RESULTS: Days to sustainable return-to-work was 90 in the intervention and 71 in the control group (p = 0.375). The number of post-concussion symptoms were fewer in the intervention (6) compared to the control group (8) at 12 months (p = 0.041). No group differences were observed for disability (p = 0.193), patients impression of change (p = 0.285) or psychological distress (p = 0.716). CONCLUSION: The multidisciplinary outpatient follow-up programme focusing on better understanding and reassurance of favourable outcome for mild traumatic brain injury did not improve return-to-work, but may have reduced the development of post-concussion symptoms. Additional studies should focus on which factors exhibit a direct impact on return-to-work.

Is upper limb virtual reality training more intensive than conventional training for patients in the subacute phase after stroke? An analysis of treatment intensity and content.

BACKGROUND: Virtual reality (VR) training is thought to improve upper limb (UL) motor function after stroke when utilizing intensive training with many repetitions. The purpose of this study was to compare intensity and content of a VR training intervention to a conventional task-oriented intervention (CT). METHODS: A random sample of 50 video recordings was analyzed of patients with a broad range of UL motor impairments (mean age 61y, 22 women). Patients took part in the VIRTUES trial and were randomized to either VR or CT and stratified according to severity of paresis. A standardized scoring form was used to analyze intensity, i.e. active use of the affected UL expressed in % of total time, total active time and total duration of a training session in minutes, content of training and feedback. Two raters collected data independently. Linear regression models as well as descriptive and graphical methods were used. RESULTS: Patients in the VR group spent significantly more time actively practicing with an activity rate of 77.6 (8.9) % than patients in the CT 67.3 (13.9) %, (p = .003). This difference was attributed to the subgroup of patients with initially severe paresis (n = 22). While in VR severely impaired patients spent 80.7 % (4.4 %) of the session time actively; they reached 60.6 (12.1) % in CT. VR and CT also differed in terms of tasks and feedback provided. CONCLUSION: Our results indicate that patients with severely impaired UL motor function spent more time actively in VR training, which may influence recovery. The upcoming results of the VIRTUES trial will show whether this is correlated with an increased effect of VR compared to CT. TRIAL REGISTRATION: ClinicalTrials.gov NCT02079103 , February 27, 2014.

Self-Reported and Tested Function in Health Care Workers with Musculoskeletal Disorders on Full, Partial or Not on Sick Leave.

PURPOSE: The aim of this study was to describe self-reported and physically tested function in health care workers with musculoskeletal disorders (MSDs) and to examine how function was associated with work participation. METHODS: A cross-sectional study was conducted. 250 health care workers attended an evaluation where self-reported and physical function were measured. Differences between groups (full sick leave, partial sick leave, not on sick leave/working) were analyzed for categorical data (Chi square exact test) and continuous variables (Kruskal-Wallis and Mann-Whitney U tests). Logistic regression analysis was performed to examine which factors were associated with being on sick leave. RESULTS: Participants on full sick leave had statistically significant poorer function compared to those working and the group on partial sick leave. Logistic regression showed that a reduced level of the physical dimension of SF-12 and a high lift test were significantly related to full sick leave (OR 0.86, p < 0.001) (OR 0.79, p = 0.002). The physical dimension of SF-12 was the only variable that was associated to partial sick leave (OR 0.91, p = 0.005). CONCLUSION: Health care workers on full sick leave due to MSDs have reduced function on self-reported and physically tested function, compared to those working despite MSDs, as well as when compared to those on partial sick leave. More knowledge about work ability in occupational sub-groups is needed.

Striving for a life worth living: stroke survivors' experiences of home rehabilitation.

BACKGROUND: For mild-to-moderate stroke survivors, early supported discharge from hospital, followed by home rehabilitation is preferred over conventional care. How this mode of service contributes to recovery from stroke survivors' perspective needs further investigation. AIM: The aim of this study was to explore mild-to-moderate stroke survivors' experiences with home rehabilitation after early supported discharge from hospital. METHODS: A qualitative interpretive interview design was used in the context of a randomised controlled trial. A purposive sample of eight participants (45-80 years) was followed by an ambulant team, and a specific healthcare team provided home rehabilitation. Data were analysed using interpretive description, systematic text condensation and coping theory. FINDINGS: A crucial determinant for the participants' hopes for a life worth living was the mutual confidence expressed in encounters with healthcare professionals and the participants' ability to make sense of their now-altered body. The professional caretakers' communication qualities and their ability to attend to individual needs were important. Help in processing the emotional reactions caused by a changed body and in socialising was requested by participants. Professional caretakers providing home rehabilitation should strive for a more flexible- and individually tailored service and should seek increased cooperation among stakeholders. CONCLUSION: The focus on therapeutic communicative qualities, bodily changes, emotional processes, social concerns and long-term follow-up should be increased in order to achieve a more beneficial experience for stroke survivors.

Early supported discharge after stroke in Bergen (ESD Stroke Bergen): three and six months results of a randomised controlled trial comparing two early supported discharge schemes with treatment as usual.

BACKGROUND: Stroke causes lasting disability and the burden of stroke is expected to increase substantially during the next decades. Optimal rehabilitation is therefore mandatory. Early supported discharge (ESD) has previously shown beneficial, but all major studies were carried out more than ten years ago. We wanted to implement and study the results of ESD in our community today with comparisons between ESD and treatment as usual, as well as between two different ESD models. METHODS: Patients with acute stroke were included during a three year period (2008-11) in a randomised controlled study comparing two different ESD models to treatment as usual. The two ESD models differed by the location of treatment: either in a day unit or in the patients' homes. Patients in the ESD groups were followed by a multi-disciplinary ambulatory team in the stroke unit and discharged home as early as possible. The ESD models also comprised treatment by a multi-disciplinary community health team for up to five weeks and follow-up controls after 3 and 6 months. Primary outcome was modified Rankin Scale (mRS) at six months. RESULTS: Three-hundred-and-six patients were included. mRS scores and change scores were non-significantly better in the two ESD groups at 3 and 6 months. Within-group improvement from baseline to 3 months was significant in the ESD 1 (p = 0.042) and ESD 2 (p = 0.001) groups, but not in the controls. More patients in the pooled ESD groups were independent at 3 (p = 0.086) and 6 months (p = 0.122) compared to controls and there also was a significant difference in 3 month change score between them (p = 0.049). There were no differences between the two ESD groups. Length of stay in the stroke unit was 11 days in all groups. CONCLUSIONS: Patients in the ESD groups tended to be more independent than controls at 3 and 6 months, but no clear statistically significant differences were found. The added effect of supported discharge and improved follow-up seems to be rather modest. The improved stroke treatment of today may necessitate larger patient samples to demonstrate additional benefit of ESD. CLINICAL TRIAL REGISTRATION: Unique identifier: NCT00771771.

Missing a follow-up after mild traumatic brain injury--does it matter?

OBJECTIVE: This study sought to identify potential differing clinical characteristics between patients with a mild traumatic brain injury (MTBI) who attended a planned follow-up session and not. This study investigated whether clinical characteristics and attendance for a planned follow-up service 2-months after injury could be related to return-to-work (RTW) 1-year later. METHOD: Prospective cohort study of 343 patients with MTBI admitted consecutively to the Department of Neurosurgery in 2009-2011. Demographic and clinical data were obtained from the hospital files and data about sick leave from The Norwegian Labour and Welfare Service. Patients were categorized into two groups according to their attendance. RESULTS: One hundred and sixty-one (67%) patients attended (AG) and 80 (33%) did not (NAG) attend their follow-up appointments. The AG had significantly more frequently intracranial pathology on CT scan, had consumed less alcohol and were older. Logistic regression showed that follow-up attendance (OR = 16.89) and sick leave before injury (OR = 9.70) are unfavourably related to RTW at 12-months. Skull fracture and cause of injury had no influence of the outcome. CONCLUSION: Not attending the follow-up has a favourable outcome after MBTI, indicating that these patients have a reduced need for medical and rehabilitation support for their brain injury.

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.

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.

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.

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).

Is modified constraint-induced movement therapy more effective than bimanual training in improving arm motor function in the subacute phase post stroke? A randomized controlled trial.

OBJECTIVE: To compare the effect of modified constraint-induced movement therapy (mCIMT) to bimanual task-related training for patients in the subacute phase post stroke. DESIGN: A single-blinded randomized controlled trial. SETTINGS: Inpatient and outpatient rehabilitation clinics and the patient's home. SUBJECTS: Thirty patients in the subacute phase post stroke (2-16 weeks) were randomized to modified constraint-induced movement therapy with an emphasis on unimanual tasks, or bimanual task-related training, emphasizing bimanual tasks. All trained with a therapist 4 hours a week for four weeks, followed by a 2-3 hours daily self-training program. Patients in the modified constraint-induced movement therapy group were supposed to wear a restraining mitt on the unaffected hand for 4 hours a day for four weeks. MAIN MEASURES: Blinded assessments at pre and post treatment and after three months with Action Research Arm Test as a primary outcome measure, Nine-Hole Peg Test and Motor Activity Log. RESULTS: Power calculations suggested an inclusion of 60 patients, but due to recruitment difficulties the trial was stopped after an interim analysis at 30 patients. There was no difference in change (P > 0.05) between the groups on any of the measures, neither at post treatment nor at follow-up assessments. From pre-intervention to follow-up assessment the modified constraint-induced movement therapy group obtained a mean change score of 17.77 (14.66) on Action Research Arm Test, the bimanual group 15.47 (13.59). CONCLUSION: Bimanual training was as effective as modified constraint-induced movement therapy in improving arm motor function. Wearing a mitt seems unnecessary for most patients in the subacute phase post stroke when focused affected arm training is provided.

Predictors of outcome after surgery with disc prosthesis and rehabilitation in patients with chronic low back pain and degenerative disc: 2-year follow-up.

PURPOSE: A prospective study to evaluate whether certain baseline characteristics can predict outcome in patients treated with disc prosthesis or multidisciplinary rehabilitation. METHODS: Secondary analysis of 154 patients with chronic low back pain (LBP) for at least 1 year and degenerative discs originally recruited for a randomized trial. Outcome measures were Oswestry Disability Index (ODI) dichotomized to < or ≥15 points improvement and whether subjects were working at 2-year follow-up. A multiple logistic regression analysis was used. RESULTS: In patients treated with disc prosthesis, long duration of LBP and high Fear-Avoidance Beliefs for work (FABQ-W) predicted worse ODI outcome [odds ratio (OR) = 1.9, 95% confidence interval (CI) 1.2-3.2 and OR = 1.7, CI 1.2-2.4 for every 5 years or 5 points]. Modic type I or II predicted better ODI outcome (OR = 5.3, CI 1.1-25.3). In patients treated with rehabilitation, a high ODI, low emotional distress (HSCL-25), and no daily narcotics predicted better outcome for ODI (OR = 2.5, CI 1.4-4.5 for every 5 ODI points, OR = 2.1, CI 1.1-5.1 for every 0.5 HSCL points and OR = 23.6, CI 2.1-266.8 for no daily narcotics). Low FABQ-W and working at baseline predicted working at 2-year follow-up after both treatments (OR = 1.3, CI 1.0-1.5 for every 5 points and OR = 4.1, CI 1.2-13.2, respectively). CONCLUSIONS: Shorter duration of LBP, Modic type I or II changes and low FABQ-W were the best predictors of success after treatment with disc prosthesis, while high ODI, low distress and not using narcotics daily predicted better outcome of rehabilitation. Low FABQ-W and working predicted working at follow-up.

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.

Recovery of upper extremity motor function post stroke with regard to eligibility for constraint-induced movement therapy.

PURPOSE: To examine eligibility for modalities such as constraint-induced movement therapy (CIMT) and modified CIMT (mCIMT) in the subacute phase after stroke and to define the share of patients who should be offered this treatment. METHODS: A prospective, repeated-measures design was used. A total of 100 consecutive patients with arm paresis 1 to 2 weeks post stroke were screened. Eligible for CIMT were patients who were cognitively intact, medically stable, and able to extend the wrist and 3 fingers 10° as a lower limit. The active range of motion was registered, and motor function was assessed by the Action Research Arm Test (ARAT) and the Nine Hole Peg Test at 1 to 2 weeks, 4 weeks, and 3 months post stroke. RESULTS: From 100 patients, 54 were excluded from motor assessment, mostly due to cognitive impairments. Of the remaining 46 patients, 21 (46%) were eligible according to motor function of the hand at 1 to 2 weeks post stroke, whereas in the other patients motor function was either too good or too poor. The share of patients eligible declined to 31% after 4 weeks and 15% after 3 months. Within 3 months, 60% reached reasonable dexterity, expressed by an ARAT score ≯ 51, all receiving standard rehabilitation. CONCLUSION: Results indicate that eligibility for CIMT or mCIMT should not be considered before 4 weeks post stroke because much improvement in arm function was shown to occur during the first month post stroke with standard rehabilitation.

[Long-lasting low back pain and MRI changes in the intervertebral discs]. / Langvarige korsryggssmerter og MR-forandringer i ryggvirvlene.

BACKGROUND: Although low back pain is usually temporary, some patients do not recover and need treatment. Therefore, it is important to uncover causal and contributing factors. Here we give an overview of recent research on MRI findings and genetic factors that may be important for development of long-lasting low back pain. MATERIAL AND METHODS: A non-systematic search in PubMed and EMBASE was performed. The relevant research articles identified, as well as the authors' knowledge of the field formed the basis for this review. RESULTS: It is generally accepted that low back pain often stems from intervertebral discs, facet joints and lumbar multifundi muscles. However, it is also known that many patients with pronounced disc degeneration have so-called Modic changes, i.e. MRI changes in bone marrow close to the vertebral endplates. Several recent studies have shown an association between such changes and pain. It has also been demonstrated that patients with Modic changes and low back pain often have concomitant inflammation and growth of nociceptive nerve fibers into the endplates. To which extent this occurs, may be partly based on genetics. INTERPRETATIONS: Genetic factors may contribute to low back pain. New knowledge about genetic factors and Modic changes can create a basis for better diagnostics and more specific treatment of patients with long-lasting low back pain.