Gene Expression Correlates with Disability and Pain Intensity in Patients with Chronic Low Back Pain and Modic Changes in a Sex-Specific Manner.

Chronic low back pain (cLBP) lacks clear physiological explanations, and the treatment options are of limited effect. We aimed to elucidate the underlying biology of cLBP in a subgroup of patients with Modic changes type I (suggestive of inflammatory vertebral bone marrow lesions) by correlating gene expression in blood with patient-reported outcomes on disability and pain intensity and explore sex differences. Patients were included from the placebo group of a clinical study on patients with cLBP and Modic changes.

Efficacy of a Tumor Necrosis Factor Inhibitor in Chronic Low-Back Pain With Modic Type 1 Changes: A Randomized Controlled Trial.

Objective: The efficacy of tumor necrosis factor inhibitors for treating chronic low-back pain with Modic changes is uncertain. This study investigated the superiority of infliximab over placebo in patients with Modic type 1 changes.

Methods: In this multicenter, randomized, triple-blind, placebo-controlled trial, patients aged 18 to 65 years with moderate to severe chronic low-back pain and Modic type 1 changes were enrolled from five Norwegian public hospitals between January 2019 and October 2022.

Impact of CYP2D6*2, CYP2D6*35, rs5758550, and related haplotypes on risperidone clearance in vivo.

Purpose: The CYP2D6 gene exhibits significant polymorphism, contributing to variability in responses to drugs metabolized by CYP2D6. While CYP2D6*2 and CYP2D6*35 are presently designated as alleles encoding normal metabolism, this classification is based on moderate level evidence. Additionally, the role of the formerly called "enhancer" single nucleotide polymorphism (SNP) rs5758550 is unclear.

Bacterial growth in patients with low back pain and Modic changes: protocol of a multicentre, case-control biopsy study.

Introduction: Bacterial infection and Modic changes (MCs) as causes of low back pain (LBP) are debated. Results diverged between two randomised controlled trials examining the effect of amoxicillin with and without clavulanic acid versus placebo on patients with chronic LBP (cLBP) and MCs. Previous biopsy studies have been criticised with regard to methods, few patients and controls, and insufficient measures to minimise perioperative contamination.

Longitudinal Relationship Between Reduced Modic Change Edema and Disability and Pain in Patients With Chronic Low Back Pain.

Study Design: Secondary analyses of a randomized trial [Antibiotics In Modic changes (MCs) study].

Objective: To assess whether or not reduced MC edema over time is related to reduced disability and pain in patients with chronic low back pain (LBP).

Summary Of Background Data: It is not clear whether or not reduced MC edema implies improved clinical outcomes.

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 ( = 100) receiving amoxicillin treatment or placebo for 100 days in the Antibiotics in Modic Changes (AIM) study.

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.

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.

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.

Impact of the novel CYP2C:TG haplotype and CYP2B6 variants on sertraline exposure in a large patient population.

Sertraline is a commonly used SSRI antidepressant drug, metabolized by CYP2C19 and CYP2B6, that exhibits a substantial interindividual variation in clinical response, of which only a part can be attributed to known genetic variants. In the current study we have examined the role of a newly discovered ultrarapid CYP2C:TG haplotype and CYP2B6 variants in order to identify the possible missing heritability for such variation in sertraline response in a large patient population (n = 840). Compared to the reference group (CYP2C19*1/*1, n = 160), sertraline exposure was increased by 128% in CYP2C19 PMs (n = 29, p < 0.

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.

Macrophage migration inhibitory factor: a potential biomarker for chronic low back pain in patients with Modic changes.

Background: Low back pain (LBP) is a leading cause of disability worldwide, but the aetiology remains poorly understood. Finding relevant biomarkers may lead to better understanding of disease mechanisms. Patients with vertebral endplate bone marrow lesions visualised on MRI as Modic changes (MCs) have been proposed as a distinct LBP phenotype, and inflammatory mediators may be involved in the development of MCs.

Impact of educational level and employment status on short-term and long-term pain relief from supervised exercise therapy and education: an observational study of 22 588 patients with knee and hip osteoarthritis.

Objectives: To investigate the impact of educational level and employment status on change in pain intensity after treatment among patients with knee and hip osteoarthritis (OA).

Design: A prospective cohort study.

Setting And Participants: We analysed 22 588 patients participating in the Good Life with osteoArthritis in Denmark (GLA:D).

A Novel CYP2C-Haplotype Associated With Ultrarapid Metabolism of Escitalopram.

Escitalopram is one of the most commonly used antidepressant drugs but exhibits a substantial interindividual variation in clinical response. A key factor underlying response differences is the polymorphic nature of the CYP2C19 gene encoding the major enzyme responsible for escitalopram metabolism. Although pre-emptive CYP2C19 genotyping may improve escitalopram treatment outcome by dose individualization, much of the interindividual variability cannot be assigned to the currently known CYP2C19 gene variants.

Oedema on STIR modified the effect of amoxicillin as treatment for chronic low back pain with Modic changes-subgroup analysis of a randomized trial.

Objective: To evaluate potential MRI-defined effect modifiers of amoxicillin treatment in patients with chronic low back pain and type 1 or 2 Modic changes (MCs) at the level of a previous lumbar disc herniation (index level).

Methods: In a prospective trial (AIM), 180 patients (25-64 years; mean age 45; 105 women) were randomised to receive amoxicillin or placebo for 3 months. Primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (0-24 scale) at 1 year.

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.

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.

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.

The Influence of Combined CYP2D6 and CYP2C19 Genotypes on Venlafaxine and O-Desmethylvenlafaxine Concentrations in a Large Patient Cohort.

Purpose: The antidepressant venlafaxine is largely O-desmethylated by CYP2D6, whereas CYP2C19 mediates an alternative metabolic route of venlafaxine through N-desmethylation. The aim of this study was to investigate the combined effect of genotype-predicted CYP2D6 and CYP2C19 phenotypes on serum concentrations of venlafaxine and metabolites in a large patient population.

Methods: Patients were retrospectively included from a therapeutic drug monitoring service at Diakonhjemmet Hospital in Oslo (Norway) between January 01, 2007, and December 31, 2017.

Impact of CYP2C19 genotype on sertraline exposure in 1200 Scandinavian patients.

Sertraline is an (SSRI-)antidepressant metabolized by the polymorphic CYP2C19 enzyme. The aim of this study was to investigate the impact of CYP2C19 genotype on the serum concentrations of sertraline in a large patient population. Second, the proportions of patients in the various CYP2C19 genotype-defined subgroups obtaining serum concentrations outside the therapeutic range of sertraline were assessed.

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.