Recurrent headache and interpersonal violence in adolescence: the roles of psychological distress, loneliness and family cohesion: the HUNT study

Background: Recurrent headache is the most common and disabling pain condition in adolescence. Co-occurrence of psychosocial adversity is associated with increased risk of chronification and functional impairment. Exposure to interpersonal violence seems to constitute an important etiological factor. Thus, knowledge of the multiple pathways linking interpersonal violence to recurrent headache could help guide preventive and clinical interventions. In the present study we explored a hypothetical causal model where the link between exposure to interpersonal violence and recurrent headache is mediated in parallel through loneliness and psychological distress. Higher level of family cohesion and male sex is hypothesized to buffer the adverse effect of exposure to interpersonal violence on headache. Methods: The model was assessed using data from the cross-sectional, population-based Young-HUNT 3 study of Norwegian adolescents, conducted from 2006–2008. A cohort of 10 464 adolescents were invited. The response rate was 73% (7620), age ranged from 12 and 20 years, and 50% (3832) were girls. The study comprised self-report measures of exposure to interpersonal violence, loneliness, psychological distress and family cohesion, in addition to a validated interview on headache, meeting the International Classification of Headache Disorders criteria. Recurrent headache was defined as headache recurring at least monthly during the past year, and sub-classified into monthly and weekly headache, which served as separate outcomes. Results: In Conditional Process Analysis, loneliness and psychological distress consistently posed as parallel mediating mechanisms, indirectly linking exposure to interpersonal violence to recurrent headache. We found no substantial moderating effect of family cohesion or sex. Conclusions: Loneliness and psychological distress seem to play crucial roles in the relationship between exposure to interpersonal violence and recurrent headache. To facilitate coping and recovery, it may be helpful to account for these factors in preventive and clinical interventions. Trauma-informed, social relationship-based interventions may represent a major opportunity to alter trajectories of recurrent headache. Keywords: Interpersonal violence; Sexual abuse; Bullying; Loneliness; Social isolation; Psychological distress; Family cohesion; Social support; Recurrent headache

Does the risk of chronic low back pain depend on age at menarche or menopause? A population-based cross-sectional and cohort study: the Trøndelag Health Study

Objective In most population-based studies of low back pain (LBP), women have a higher risk than men, possibly reflecting hormonal influences. The aim of this study was to explore associations between age at menarche and menopause and risk of chronic LBP. Design Population-based cross-sectional and cohort study designs. Setting The HUNT2 and HUNT3 medical surveys of the entire population of Nord-Trøndelag County in Norway. Main outcome measure Prevalence or risk of chronic LBP, defined as LBP persisting at least 3 months continuously during last year. Participants Associations between age at menarche and prevalence of chronic LBP were examined in cross-sectional data from HUNT2, comprising 27 697 women aged 20–69 years, with 7300 women reporting LBP. The corresponding cohort data included 11 659 women without LBP at baseline in HUNT2, with 2353 women reporting LBP at follow-up 11 years later in HUNT3. Cross-sectional data on age at menopause or premenopausal status included 11 332 women aged 40–69 years, with 3439 women reporting chronic LBP. Corresponding cohort data included 7893 women without LBP at baseline, of whom 1100 developed LBP. Methods Associations between age at menarche or menopause and risk of chronic LBP were examined by generalised linear modelling. Results A U-shaped association was indicated between age at menarche and risk of chronic LBP, both in the cross-sectional and cohort studies. Age at menarche ≤11 years was associated with an increased risk of chronic LBP, with a relative risk of 1.32 (95% CI 1.15 to 1.52), compared with age 14 years at menarche, after relevant adjustments. Corresponding cross-sectional crude absolute risks were 32% and 25%, respectively. No association was established between age at menopause and risk of LBP. Being premenopausal had no influence on risk. Conclusions In contrast to results for age at menopause, the association with age at menarche suggests that hormonal factors affect the risk of LBP.publishedVersio

Anterior surgical treatment for cervical degenerative radiculopathy: a prediction model for non-success

Purpose By using data from the Norwegian Registry for Spine Surgery, we wanted to develop and validate prediction models for non-success in patients operated with anterior surgical techniques for cervical degenerative radiculopathy (CDR). Methods This is a multicentre longitudinal study of 2022 patients undergoing CDR surgery and followed for 12 months to fnd prognostic models for non-success in neck disability and arm pain using multivariable logistic regression analysis. Model performance was evaluated by area under the receiver operating characteristic curve (AUC) and a calibration test. Internal validation by bootstrapping re-sampling with 1000 repetitions was applied to correct for over-optimism. The clinical usefulness of the neck disability model was explored by developing a risk matrix for individual case examples. Results Thirty-eight percent of patients experienced non-success in neck disability and 35% in arm pain. Loss to follow-up was 35% for both groups. Predictors for non-success in neck disability were high physical demands in work, low level of education, pending litigation, previous neck surgery, long duration of arm pain, medium-to-high baseline disability score and presence of anxiety/depression. AUC was 0.78 (95% CI, 0.75, 0.82). For the arm pain model, all predictors for non-success in neck disability, except for anxiety/depression, were found to be signifcant in addition to foreign mother tongue, smoking and medium-to-high baseline arm pain. AUC was 0.68 (95% CI, 0.64, 0.72). Conclusion The neck disability model showed high discriminative performance, whereas the arm pain model was shown to be acceptable. Based upon the models, individualized risk estimates can be made and applied in shared decision-making with patients referred for surgical assessment

Shift work, low-grade inflammation, and chronic pain: a 7-year prospective study

Objectives - We investigated prospective associations of shift work with chronic pain and C‐reactive protein (CRP), an indicator of inflammation. Furthermore, we elucidated CRP as a possible mediator and/or moderator of effects of shift work on pain. Methods - Data from a 7 years follow‐up study were analyzed (N = 2323). Shift work and chronic pain of “neck/shoulder”, “arm/hand”, “upper back”, “low back”, “hip/leg/feet”, and “other regions” were measured by questionnaires. “Chronic widespread pain”, “number of chronic pain sites”, and “any chronic pain” were computed. CRP was measured in serum samples. Logistic and Poisson regressions were conducted. Mediation was assessed by casual mediation analyses and moderation by the Relative Excess Risk due to Interaction (RERI). Results - Shift work was not associated with any chronic pain variable and no mediation was detected. CRP was associated with low back pain, hip/leg pain, and “number of pain sites”, and also with the combination of shift work and CRP of 1–2.99 mg/L (compared to: no shiftwork and CRP  Conclusions - We found no evidence of shift work in general affecting CRP or chronic pain. However, shift work and elevated CRP combined may influence chronic pain

The rates of lumbar spinal stenosis surgery in Norwegian public hospitals: a threefold increase from 1999 to 2013

Accepted manuscript version of the following article: Grøvle, L., Fjeld, O.R., Haugen, A.J., Helgeland, J., Småstuen, M.C., Solberg, T., ... Grotle, M. (2018). The rates of lumbar spinal stenosis surgery in Norwegian public hospitals: a threefold increase from 1999 to 2013. Spine. Published version available at https://doi.org/10.1097/BRS.0000000000002858.Study Design: Retrospective administrative database study. Objective: To assess temporal and regional trends, and length of hospital stay, in lumbar spinal stenosis (LSS) surgery in Norwegian public hospitals from 1999 to 2013. Summary of Background Data: Studies from several countries have reported increasing rates of LSS surgery over the last decades. No such data have been presented from Norway. Methods: A database consisting of discharges from all Norwegian public hospitals was established. Inclusion criteria were discharges including a surgical procedure of lumbar spinal decompression and/or fusion in combination with an ICD-10 diagnosis of Spinal Stenosis (M48.0) or Other Spondylosis with Radiculopathy (M47.2), and a patient age of 18 years or older. Discharges with diagnoses indicating deformity, i.e. spondylolisthesis or scoliosis were not included. Results: During the 15-year period, 19 543 discharges were identified. The annual rate of decompressions increased from 10.7 to 36.2 and fusions increased from 2.5 to 4.4 per 100 000 people of the general Norwegian population. The proportion of fusion surgery decreased from 19.3% to 10.9%. Among individuals older than 65 years, the annual rate of surgery per 10000, including both decompressions and fusions, more than quadrupled from 40.2 to 170.3. The regional variation was modest, differing with a factor of 1.4 between the region with the highest and the lowest surgical rates. The mean length of hospital stay decreased from 11.0 (SD 8.0) days in 1999 to 5.0 (4.6) days in 2013, but patients who received fusion surgery stayed on average 3.6 days longer than those who received decompression only. Conclusions: The rate of LSS surgery more than tripled in Norway from 1999 to 2013. The mean length of hospital stay was reduced from 11 to 5 days. Conclusions: Level of Evidence: 4</p

Premonitory symptoms in migraine : A cross-sectional study in 2714 persons

Aim To describe the frequency and number of premonitory symptoms (PS) in migraine, the co-occurrence of different PS, and their association with migraine-related factors. Methods In this cross-sectional study, a validated questionnaire was sent to Finnish migraine families between 2002 and 2013 to obtain data on 14 predefined PS, migraine diagnoses, demographic factors, and migraine characteristics. The estimated response rate was 80%. Results Out of 2714 persons, 2223 were diagnosed with migraine. Among these, 77% reported PS, with a mean number of 3.0 symptoms compared to 30% (p Conclusion PS are experienced by a majority of migraineurs. More severe migraine is associated with a higher burden of PS. Since the material was not entirely representative of the general population of migraineurs, caution should be exercised in generalizing the results.Peer reviewe

Apparent diffusion coefficient values in Modic changes – interobserver reproducibility and relation to Modic type

Background Modic Changes (MCs) in the vertebral bone marrow were related to back pain in some studies but have uncertain clinical relevance. Diffusion weighted MRI with apparent diffusion coefficient (ADC)-measurements can add information on bone marrow lesions. However, few have studied ADC measurements in MCs. Further studies require reproducible and valid measurements. We expect valid ADC values to be higher in MC type 1 (oedema type) vs type 3 (sclerotic type) vs type 2 (fatty type). Accordingly, the purpose of this study was to evaluate ADC values in MCs for interobserver reproducibility and relation to MC type. Methods We used ADC maps (b 50, 400, 800 s/mm2) from 1.5 T lumbar spine MRI of 90 chronic low back pain patients with MCs in the AIM (Antibiotics In Modic changes)-study. Two radiologists independently measured ADC in fixed-sized regions of interests. Variables were MC-ADC (ADC in MC), MC-ADC% (0% = vertebral body, 100% = cerebrospinal fluid) and MC-ADC-ratio (MC-ADC divided by vertebral body ADC). We calculated mean difference between observers ± limits of agreement (LoA) at separate endplates. The relation between ADC variables and MC type was assessed using linear mixed-effects models and by calculating the area under the receiver operating characteristic curve (AUC). Results The 90 patients (mean age 44 years; 54 women) had 224 MCs Th12-S1 comprising type 1 (n = 111), type 2 (n = 91) and type 3 MC groups (n = 22). All ADC variables had higher predicted mean for type 1 vs 3 vs 2 (p  50% of their mean value was less frequent for MC-ADC (9% of MCs) vs MC-ADC% and MC-ADC-ratio (17–20%). Conclusions The MC-ADC variable (highest mean ADC in the MC) had best interobserver reproducibility, discriminated between MC type groups, and may be used in further research. ADC values differed between MC types as expected from previously reported MC histology.publishedVersio

Long-Term Use of Amoxicillin Is Associated with Changes in Gene Expression and DNA Methylation in Patients with Low Back Pain and Modic Changes

Long-term antibiotics are prescribed for a variety of medical conditions, recently including low back pain with Modic changes. The molecular impact of such treatment is unknown. We conducted longitudinal transcriptome and epigenome analyses in patients (n = 100) receiving amoxicillin treatment or placebo for 100 days in the Antibiotics in Modic Changes (AIM) study. Gene expression and DNA methylation were investigated at a genome-wide level at screening, after 100 days of treatment, and at one-year follow-up. We identified intra-individual longitudinal changes in gene expression and DNA methylation in patients receiving amoxicillin, while few changes were observed in patients receiving placebo. After 100 days of amoxicillin treatment, 28 genes were significantly differentially expressed, including the downregulation of 19 immunoglobulin genes. At one-year follow-up, the expression levels were still not completely restored. The significant changes in DNA methylation (n = 4548 CpGs) were mainly increased methylation levels between 100 days and one-year follow-up. Hence, the effects on gene expression occurred predominantly during treatment, while the effects on DNA methylation occurred after treatment. In conclusion, unrecognized side effects of long-term amoxicillin treatment were revealed, as alterations were observed in both gene expression and DNA methylation that lasted long after the end of treatment.publishedVersio

Cost–utility analysis of antibiotic treatment in patients with chronic low back pain and Modic changes: results from a randomised, placebo-controlled trial in Norway (the AIM study)

Objective To evaluate the cost–utility of 100 days of antibiotics in patients with chronic low back pain (LBP) and type I or II Modic changes included in the Antibiotic treatment In patients with chronic low back pain and Modic changes (AIM) study. Design A cost–utility analysis from a societal and healthcare perspective alongside a double-blinded, parallel group, placebo, multicentre trial. Setting Hospital outpatient clinics at six hospitals in Norway. The main results from the AIM study showed a small effect in back-related disability in favour of the antibiotics group, and slightly larger in those with type I Modic changes, but this effect was below the pre-defined threshold for clinically relevant effect. Participants 180 patients with chronic LBP, previous disc herniation and Modic changes type I (n=118) or type II (n=62) were randomised to antibiotic treatment (n=89) or placebo-control (n=91). Interventions Oral treatment with either 750 mg amoxicillin or placebo three times daily for 100 days. Main outcome measures Quality-adjusted life years (QALYs) by EuroQoL-5D over 12 months and costs for healthcare and productivity loss measured in Euro (€1=NOK 10), in the intention-to-treat population. Cost–utility was expressed in incremental cost-effectiveness ratio (ICER). Results Mean (SD) total cost was €21 046 (20 105) in the amoxicillin group and €19 076 (19 356) in the placebo group, mean difference €1970 (95% CI; −3835 to 7774). Cost per QALY gained was €24 625. In those with type I Modic changes, the amoxicillin group had higher healthcare consumption than the placebo group, resulting in €39 425 per QALY gained. Given these ICERs and a willingness-to-pay threshold of €27 500 (NOK 275 000), the probability of amoxicillin being cost-effective was 51%. Even when the willingness-to-pay threshold increased to €55 000, the probability of amoxicillin being cost-effective was never higher than 53%. Conclusions Amoxicillin treatment showed no evidence of being cost-effective for people with chronic LBP and Modic changes during 1-year follow-up.publishedVersio