Longitudinal changes of serum cytokines in patients with chronic low back pain and Modic changes.

OBJECTIVES: To explore serum cytokine levels over time in patients with chronic low back pain (cLBP) and Modic changes (MCs), difference in change between treatment groups in the Antibiotics in Modic Changes (AIM) study and associations between change in cytokines and low back pain. METHODS: Serum concentrations of 39 cytokines were measured at baseline and 1 year from 73 participants in the AIM study; 30 randomized to placebo, 43 to Amoxicillin. Low back pain intensity was measured by numeric rating scale. Change in cytokine levels over time were assessed by paired t-tests. Difference in change in cytokine levels between treatment groups and associations between changes in LBP and cytokine levels were assessed by linear regression models. Networks of cytokine changes in each treatment groups were explored by Pearson's correlations. RESULTS: Five cytokines changed from baseline to 1 year, (mean change, log transformed values with CI) C-X-C motif chemokine ligand (CXCL) 10 (IP-10) (0.11 (0.01-0.20)), CXCL13 (0.61 (0.00-0.12)), C-C motif chemokine ligand (CCL)26 (0.05 (0.01-0.1)), granulocyte macrophage-colony stimulating factor (GM-CSF) (-0.12 (-0.23 to 0.00)) and CXCL11 (0.12 (0.03-0.22)). Treatment group only influenced change in CCL21 (ß 0.07 (0.01-0.12)), and IL-6 (ß -0.17 (-0.30 to -0.03)). Change in CXCL13 (ß 2.43 (0.49-4.38)), CCL27 (ß 3.07 (0.46-5.69)), IL-8 (ß 1.83 (0.08-3.58)) and CCL19 (ß 3.10 (0.86-5.43)) were associated with change in LBP. The correlation networks of cytokine changes demonstrate small differences between treatment groups. CONCLUSIONS: Cytokine levels are relatively stable over time in our sample, with little difference between treatment groups. Some cytokines may be associated with LBP intensity. The differences between the correlation networks suggest that long-term Amoxicillin-treatment may have longstanding effects to be further explored.

Evaluation of the EQ-5D-3L and 5L versions in low back pain patients.

BACKGROUND: The EuroQol EQ-5D is one of the most widely researched and applied patient-reported outcome measures worldwide. The original EQ-5D-3L and more recent EQ-5D-5L include three and five response categories respectively. Evidence from healthy and sick populations shows that the additional two response categories improve measurement properties but there has not been a concurrent comparison of the two versions in patients with low back pain (LBP). METHODS: LBP patients taking part in a multicenter randomized controlled trial of lumbar total disc replacement and conservative treatment completed the EQ-5D-3L and 5L in an eight-year follow-up questionnaire. The 3L and 5L were assessed for aspects of data quality including missing data, floor and ceiling effects, response consistency, and based on a priori hypotheses, associations with the Oswestry Disability Index (ODI), Pain-Visual Analogue Scales and Hopkins Symptom Checklist (HSCL-25). RESULTS: At the eight-year follow-up, 151 (87%) patients were available and 146 completed both the 3L and 5L. Levels of missing data were the same for the two versions. Compared to the EQ-5D-5L, the 3L had significantly higher floor (pain discomfort) and ceiling effects (mobility, self-care, pain/discomfort, anxiety/depression). For these patients the EQ-5D-5L described 73 health states compared to 28 for the 3L. Shannon's indices showed the 5L outperformed the 3L in tests of classification efficiency. Correlations with the ODI, Pain-VAS and HSCL-25 were largely as hypothesized, the 5L having slightly higher correlations than the 3L. CONCLUSION: The EQ-5D assesses important aspect of health in LBP patients and the 5L improves upon the 3L in this respect. The EQ-5D-5L is recommended in preference to the 3L version, however, further testing in other back pain populations together with additional measurement properties, including responsiveness to change, is recommended. TRIAL REGISTRATION: retrospectively registered: https://clinicaltrials.gov/ct2/show/NCT01704677 .

Development and validation of a prediction model for incident hand osteoarthritis in the HUNT study.

OBJECTIVE: To develop and externally validate prediction models for incident hand osteoarthritis (OA) in a large population-based cohort of middle aged and older men and women. DESIGN: We included 17,153 men and 18,682 women from a population-based cohort, aged 35-70 years at baseline (1995-1997). Incident hand OA were obtained from diagnostic codes in the Norwegian National Patient Register (1995-2018). We studied whether a range of self-reported and clinically measured predictors could predict hand OA, using the Area Under the receiver-operating Curve (AUC) from logistic regression. External validation of an existing prediction model for male hand OA was tested on discrimination in a sample of men. Bootstrapping was used to avoid overfitting. RESULTS: The model for men showed modest discriminatory ability (AUC = 0.67, 95% CI 0.62-0.71). Adding a genetic risk score did not improve prediction. Similar discrimination was observed in the model for women (AUC = 0.62, 95% CI 0.59-0.64). Prediction was not improved by adding a genetic risk score or hormonal and reproductive factors. Applying external validation, similar results were observed among men in HUNT (The Nord-Trøndelag Health Study) as in the developmental sample (AUC = 0.62, 95% CI 0.57-0.65). CONCLUSION: We developed prediction models for incident hand OA in men and women. For women, the model included body mass index (BMI), heavy physical work, high physical activity and perceived poor health. The model showed moderate discrimination. For men, we have shown that a prediction model including BMI, education and information on sleep can predict incident hand OA in several populations with moderate discriminative ability.

The causal role of smoking on the risk of headache. A Mendelian randomization analysis in the HUNT study.

BACKGROUND AND PURPOSE: Headache has been associated with various lifestyle and psychosocial factors, one of which is smoking. The aim of the present study was to investigate whether the association between smoking intensity and headache is likely to be causal. METHOD: A total of 58 316 participants from the Nord-Trøndelag Health (HUNT) study with information on headache status were genotyped for the rs1051730 C>T single-nucleotide polymorphism (SNP). The SNP was used as an instrument for smoking intensity in a Mendelian randomization analysis. The association between rs1051730 T alleles and headache was estimated by odds ratios with 95% confidence intervals. Additionally, the association between the SNP and migraine or non-migrainous headache versus no headache was investigated. All analyses were adjusted for age and sex. RESULTS: There was no strong evidence that the rs1051730 T allele was associated with headache in ever smokers (odds ratio 0.99, 95% confidence interval 0.95-1.02). Similarly, there was no association between the rs1051730 T allele and migraine or non-migrainous headache versus no headache. CONCLUSION: The findings from this study do not support that there is a strong causal relationship between smoking intensity and any type of headache. Larger Mendelian randomization studies are required to examine whether higher smoking quantity can lead to a moderate increase in the risk of headache subtypes.

Age of menarche is associated with knee joint replacement due to primary osteoarthritis (The HUNT Study and the Norwegian Arthroplasty Register).

OBJECTIVE: To investigate whether parity, age at menarche, menopausal status, age at menopause, use of oral contraceptives (OC) or use of hormone replacement therapy (HRT) were associated with total knee replacement (TKR) or total hip replacement (THR) due to primary osteoarthritis. METHOD: In a prospective cohort study of 30,289 women from the second and third surveys of the Nord-Trøndelag Health Study, data were linked to the Norwegian Arthroplasty Register (NAR) in order to identify TKR or THR due to primary osteoarthritis. Cox proportional hazards models were used to estimate the hazard ratios (HRs). RESULTS: We observed 430 TKRs and 675 THRs during a mean follow-up time of 8.3 years. Increasing age at menarche was inversely associated with the risk of TKR (P-trend < 0.001). Past users and users of systemic HRT were at higher risk of TKR compared to never users (HR 1.42 (95% confidence interval (CI) 1.06-1.90) and HR 1.40 (95% CI 1.03-1.90), respectively). No association was found between parity, age at menarche, menopausal status, age at menopause, oral contraceptive use or HRT use and THR. CONCLUSION: We found that increasing age at menarche reduced the risk of TKR. Past users and users of systemic HRT were at higher risk of TKR compared to never users. Parity did not increase the risk of THR or TKR.

The causal role of smoking on the risk of hip or knee replacement due to primary osteoarthritis: a Mendelian randomisation analysis of the HUNT study.

OBJECTIVE: Smoking has been associated with a reduced risk of hip and knee osteoarthritis (OA) and subsequent joint replacement. The aim of the present study was to assess whether the observed association is likely to be causal. METHOD: 55,745 participants of a population-based cohort were genotyped for the rs1051730 C > T single-nucleotide polymorphism (SNP), a proxy for smoking quantity among smokers. A Mendelian randomization analysis was performed using rs1051730 as an instrument to evaluate the causal role of smoking on the risk of hip or knee replacement (combined as total joint replacement (TJR)). Association between rs1051730 T alleles and TJR was estimated by hazard ratios (HRs) and 95% confidence intervals (CIs). All analyses were adjusted for age and sex. RESULTS: Smoking quantity (no. of cigarettes) was inversely associated with TJR (HR 0.97, 95% CI 0.97-0.98). In the Mendelian randomization analysis, rs1051730 T alleles were associated with reduced risk of TJR among current smokers (HR 0.84, 95% CI 0.76-0.98, per T allele), however we found no evidence of association among former (HR 0.97, 95% CI 0.88-1.07) and never smokers (HR 0.97, 95% CI 0.89-1.06). Neither adjusting for body mass index (BMI), cardiovascular disease (CVD) nor accounting for the competing risk of mortality substantially changed the results. CONCLUSION: This study suggests that smoking may be causally associated with the reduced risk of TJR. Our findings add support to the inverse association found in previous observational studies. More research is needed to further elucidate the underlying mechanisms of this causal association.

Evaluation of individualized quality of life and illness perceptions in low back pain. A patient education cluster randomized controlled trial.

OBJECTIVE: To evaluate the effect of a cognitive patient education intervention compared with usual care on secondary outcomes of individual quality of life and psychological outcomes of illness perceptions and pain catastrophizing in patients with low back pain. METHODS: A pragmatic cluster randomized controlled trial in which 16 general practitioners (GPs) and 20 physiotherapists (PTs) in primary care were randomly assigned to provide either a cognitive patient education intervention or usual treatment. Patients were followed up at 4 weeks and 12 months after treatment. Linear mixed models were used with group, time, type of clinician and interaction effects of group*time as fixed effects. RESULTS: A total of 203 patients provided data at baseline, 86% responded at 4 weeks and 74% at 12 months. For all the outcome measures there was a statistically significant effect of time (p<0.001) and type of clinician (p<0.05) during the follow-up year. There was a significant interaction effect of group×time on illness perceptions (p=0.003), however not for the other outcome measures. CONCLUSION: The cognitive patient education intervention initiated a faster improvement in illness perceptions but not in the other outcomes. PRACTICE IMPLICATIONS: A patient education intervention can be beneficial to improve illness perceptions, however more research is needed.

The predictive validity of the Örebro Musculoskeletal Pain Questionnaire and the clinicians' prognostic assessment following manual therapy treatment of patients with LBP and neck pain.

The purpose of this study was to compare the predictive ability of the standardised screening tool Örebro Musculoskeletal Pain Questionnaire (ÖMPQ) and the clinicians' prognostic assessment in identifying patients with low back pain (LBP) and neck pain at risk for persistent pain and disability at eight weeks follow-up. Patients seeking care for LBP or neck pain were recruited by 19 manual therapists in Norway. Patients completed the ÖMPQ and the low back- or neck specific Oswestry Disability Index/Neck Disability Index at baseline and 8 weeks after first consultation. The manual therapists filled in their assessment of patient's prognosis immediately after the first consultation, blinded for patient's answers to the questionnaire. A total of 157 patients (81with neck pain and 76 with LBP) were included. The best odds for predicting the outcome for LBP patients was found for the clinicians' assessment of prognosis (LR+ = 2.1 and LR- = 0.55), whereas the likelihood ratios were similar for the two tools in the neck group. For LBP patients, both the clinicians' assessment and the ÖMPQ contributed significantly in the separate regression models (p = 0.02 and p = 0.002, resp), whereas none of the tools where significant contributors for neck patients (p = 0.67 and 0.07). Neither of the two methods showed high precision in their predictions of follow-up at eight weeks. However, for LBP patients, the ÖMPQ and the clinicians' prognostic assessment contributed significantly in the prediction of functional outcome 8 weeks after the initial assessment of manual therapist, whereas the prediction for neck patients was unsure.

Efficacy of patient education and supervised exercise vs patient education alone in patients with hip osteoarthritis: a single blind randomized clinical trial.

OBJECTIVE: To compare the efficacy of patient education and supervised exercise with that of patient education alone for the management of pain in patients with hip osteoarthritis (OA). DESIGN: Single blind randomized clinical trial. SETTING: Recruitment of patients from hospitals, primary health care and advertisement, Oslo, Norway. PARTICIPANTS: 109 patients with radiographic and symptomatic hip OA with mild to moderate symptoms. INTERVENTIONS: Patient education (PE). Patient education and supervised exercise (PE+SE). PRIMARY OUTCOME MEASURE: The pain subscale of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC pain). RESULTS: No significant between group differences were found for WOMAC pain over the 16-month follow-up. Significant improvements were found for the secondary outcome WOMAC physical function (P=0.011) in the group receiving PE+SE compared to the group receiving PE only. No significant differences were found for WOMAC stiffness, the SF-36 subscales or the activity scale. The effect sizes (95% confidence interval) for WOMAC pain were -0.26 (0.11, -0.64), -0.35 (0.07, -0.77), and -0.30 (0.15, -0.75), and for WOMAC physical function -0.29 (0.09, -0.67), -0.48 (-0.06, -0.91), and -0.47 (-0.02, -0.93) at 4, 10 and 16 months, respectively, in favor of the group receiving both PE and SE. All patients attended the three-session PE program, and 75% performed ≥16 sessions of the 12-week SE program. CONCLUSION: The study could not demonstrate a significant difference in pain reduction over time between PE+SE vs PE alone. Adding SE to PE may improve physical function, but the magnitude of possible benefit is unknown as the 95% confidence intervals around the mean difference were wide. TRIAL REGISTRATION: Clinical Trials NCT00319423.

Systematic review of back schools, brief education, and fear-avoidance training for chronic low back pain.

BACKGROUND: Seven previous systematic reviews (SRs) have evaluated back schools, and one has evaluated brief education, with the latest SR including studies until November 2004. The effectiveness of fear-avoidance training has not been assessed. PURPOSE: To assess the effectiveness of back schools, brief education, and fear-avoidance training for chronic low back pain (CLBP). STUDY DESIGN: A SR. METHODS: We searched the MEDLINE database of randomized controlled trials (RCT) until August 2006 for relevant trials reported in English. Assessment of effectiveness was based on pain, disability, and sick leave. RCTs that reported back schools, or brief education as the main intervention, were included. For fear-avoidance training, evaluation of domain-specific outcome was required. Two reviewers independently reviewed the studies. RESULTS: Eight RCTs including 1,002 patients evaluated back schools, three studies were of high quality. We found conflicting evidence for back schools compared with waiting list, placebo, usual care, and exercises, and a cognitive behavioral back school. Twelve trials including 3,583 patients evaluated brief education. Seven trials, six of high quality, evaluated brief education in the clinical setting. We found strong evidence of effectiveness on sick leave and short-term disability compared with usual care. We found conflicting or limited evidence for back book or Internet discussion (five trials, two of high quality) compared with waiting list, no intervention, massage, yoga, or exercises. Three RCTs of high quality, including 364 patients, evaluated fear-avoidance training. We found moderate evidence that there is no difference between rehabilitation including fear-avoidance training and spinal fusion. CONCLUSIONS: Consistent recommendations are given for brief education in the clinical setting, and fear-avoidance training should be considered as an alternative to spinal fusion, and back schools may be considered in the occupational setting. The discordance between reviews can be attributed differences in inclusion criteria and application of evidence rules.

[Is exercise therapy and manipulation effective in low back pain?]. / Har treningsterapi og manipulasjon effekt ved korsryggssmerter?

We evaluated the effectiveness of exercises and manipulation on pain, disability and sick leave in a systematic review of randomized controlled trials including patients with low back pain. Low back pain is commonly a self-limiting illness and most patients are free of symptoms within 14 days. On the basis of 11 studies, no additional benefits from exercises and manipulation were found in patients with acute complaints (0-4 weeks); thus, our results do not support guidelines that prescribe manipulation in the acute stage. One study found reduced disability and sick leave in the subacute stage (4-12 weeks) when patients were told that it was safe to move and this strategy was reinforced by a graded exercise program and visits to the workplace. Seven studies evaluated manipulation; the effectiveness was no better than other treatments or placebo. Based on seven studies in patients with chronic low back pain (> 12 weeks), there is strong evidence that exercises reduce disability and pain, but their effectiveness on sick leave is not documented. Four studies compared different exercise regimens, but found no evidence in favour of one particular method. The effectiveness of manipulation in patients with chronic pain is poorly documented.

Intra- and interobserver reproducibility of Cybex EDI 320 measuring spinal mobility.

The purpose of the present study was to conduct intra- and interobserver reproducibility tests of the measurement of spinal movement using an electronic digital inclinometer (Cybex EDI 320). Sixteen healthy subjects with no history of back pain were tested. Their mean age was 28.5 years (range 24-34). After palpation of reference points and a standard warming-up procedure, three repetitions of maximal ventral, dorsal, and lateral flexion were performed for measurements of lumbar and thoracolumbar movements. Intra- and interobserver reproducibility were conducted with 2-5 days interval. The coefficient of variance in the intraobserver test for ventral and lateral flexion varied between 4.3 and 10.1%, in the two interobserver tests between 3.4 and 13.8%. However, the coefficient of variance in intra- and interobserver tests for dorsiflexion varied between 18.1 and 27.6%.