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. In this study, we minimise contamination risk, include a control group and optimise statistical power. The main aim is to compare bacterial growth between patients with and without MCs. METHODS AND ANALYSIS: This multicentre, case-control study examines disc and vertebral body biopsies of patients with cLBP. Cases have MCs at the level of tissue sampling, controls do not. Previously operated patients are included as a subgroup. Tissue is sampled before antibiotic prophylaxis with separate instruments. We will apply microbiological methods and histology on biopsies, and predefine criteria for significant bacterial growth, possible contamination and no growth. Microbiologists, surgeons and pathologist are blinded to allocation of case or control. Primary analysis assesses significant growth in MC1 versus controls and MC2 versus controls separately. Bacterial disc growth in previously operated patients, patients with large MCs and growth from the vertebral body in the fusion group are all considered exploratory analyses. ETHICS AND DISSEMINATION: The Regional Committees for Medical and Health Research Ethics in Norway (REC South East, reference number 2015/697) has approved the study. Study participation requires written informed consent. The study is registered at ClinicalTrials.gov (NCT03406624). Results will be disseminated in peer-reviewed journals, scientific conferences and patient fora. TRIAL REGISTRATION NUMBER: NCT03406624.

Correction: Clinical improvement after surgery for degenerative cervical myelopathy; A comparison of Patient-Reported Outcome Measures during 12-month follow-up.

[This corrects the article DOI: 10.1371/journal.pone.0264954.].

Childhood trauma and the use of opioids and other prescription analgesics in adolescence and young adulthood: The HUNT Study.

ABSTRACT: Opioid and nonopioid analgesics are commonly prescribed to young people to alleviate pain. Even short-term prescriptions increase the risk of persistent use and future misuse of potent analgesics, such as opioids. Childhood trauma exposure has been found to be related to pain conditions and to using more prescription analgesics. This large, prospective cohort study aimed to investigate the association of a broad range of childhood trauma exposures with prescription rates for opioid and nonopioid analgesics in adolescence and young adulthood. Self-reported data on childhood trauma exposures from adolescents (aged 13-19 years) who participated in the Young-HUNT3 Study (2006-2008, n = 8199) were linked to data from the Norwegian Prescription Database (NorPD, 2004-2021). We found that exposure to childhood trauma was consistently associated with higher prescription rates for opioids throughout adolescence and young adulthood. The highest incidence rate ratio (IRR) in adolescence was observed for sexual abuse (IRR 1.63, confidence interval [CI] 1.19-2.23). In young adulthood, the highest IRR was observed for physical violence (2.66, CI 2.27-3.12). The same overall pattern was observed for nonopioid analgesics. The more frequent prescriptions of opioid and nonopioid analgesics to participants exposed to childhood trauma suggests a higher symptom load of pain causing them to seek professional help with pain relief. Receiving potent analgesics is not without risk, and the likelihood of misuse may be elevated among trauma-exposed individuals. A trauma-informed approach to pain could be vital for guiding clinicians to the most effective and least harmful treatment for each patient.

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. PATIENTS AND METHODS: Linear regression was conducted separately in 2 subgroups with MC edema at baseline on short tau inversion recovery (STIR) or T1/T2-weighted magnetic resonance imaging, respectively. Independent variable: reduced edema (yes/no) at 1 year on STIR or T1/T2-series, respectively. Dependent variable: 1-year score on the Roland-Morris Disability Questionnaire (RMDQ), Oswestry Disability Index (ODI), or 0 to 10 numeric rating scale for LBP intensity, adjusted for the baseline score, age, smoking, body mass index, physical workload, and baseline edema on STIR (STIR analysis only). Post hoc, we, in addition, adjusted all analyses for baseline edema on STIR, treatment group (amoxicillin/placebo), and prior disc surgery-or for disc degeneration. RESULTS: Among patients with MC edema on STIR at baseline (n = 162), reduced edema on STIR was not significantly related to the RMDQ ( B : -1.0, 95% CI: -2.8, 0.8; P = 0.27), ODI ( B :-1.4, 95% CI: -5.4, 2.6; P = 0.50), or LBP intensity scores ( B : -0.05, 95% CI: -0.8, 0.7; P = 0.90) after 1 year. Among patients with MC edema on T1/T2-series at baseline (n = 116), reduced edema on T1/T2 ( i.e ., reduced volume of the type 1 part of MCs) was not significantly related to RMDQ ( B: -1.7, 95% CI: -3.8, 0.3; P = 0.10) or ODI score ( B : -2.3, 95% CI: -7.1, 2.5; P = 0.34) but was significantly related to LBP intensity at 1 year ( B : -0.9, 95% CI: -1.8, -0.04; P = 0.04; correlation coefficient: 0.24). The post hoc analyses supported these results. CONCLUSION: Reduced MC edema over 1 year was not significantly associated with pain-related disability but was (on T1/T2-series) significantly but weakly related to reduced LBP intensity. LEVEL OF EVIDENCE: Level 3.

Problematic alcohol use in young adults exposed to childhood trauma: The Trøndelag Health (HUNT) Study.

Problematic alcohol use (PAU) severely impacts the health, functioning, and long-term prospects of young people. Prior research indicates that childhood trauma exposure may be an important risk factor for PAU, but few longitudinal studies have looked at how specific trauma types influence this risk. The aim of this study was to investigate the association between childhood trauma exposure and PAU in a large, population-based cohort of young people. The study sample included 1,913 adolescents who participated in the Trøndelag Health Study (HUNT) between 2006 and 2008 (age range: 12-20) and completed follow-up 10 years later as young adults (age range: 22-32). The results revealed an increased risk of PAU in young adults exposed to childhood trauma, especially direct physical violence, OR = 2.38, [95% CI 1.56, 3.64]. Young adults who had witnessed violence, OR = 1.55, [95% CI 1.11, 2.17], or experienced an accident, disaster, or other traumatic event, OR = 1.60, [95% CI 1.19, 2.15], also had higher odds of PAU compared to those without such experiences. These associations remained consistent after adjusting for symptoms of headaches and pain as well as posttraumatic and general psychological distress as reported by the participants in adolescence. Future prevention efforts targeting PAU among adolescents and young adults should address violence and other trauma exposure as potential drivers of problematic drinking.

Killing pain? A prospective population-based study on trauma exposure in childhood as predictor for frequent use of over-the-counter analgesics in young adulthood. The HUNT study.

Frequent and increasing use of over-the-counter analgesics (OTCA) is a public health concern. Pain conditions and psychological distress are related to frequent OTCA use, and as exposure to potentially traumatic events (PTE) in childhood appears to increase risk of experiencing such symptoms, we aimed to assess childhood PTEs and related symptoms in adolescence as predictors for frequent OTCA use in young adulthood. Prospective population survey data were used (n = 2947, 59.1% female, 10-13 years follow-up). Exposure to PTEs, symptoms of post-traumatic stress, anxiety and depression, musculoskeletal pain and headache were assessed in adolescence (13-19 years). Use of OTCA was assessed in young adulthood (22-32 years) and use of OTCA to treat musculoskeletal pain and headache served as separate outcomes in ordinal logistic regression analyses. Overall, exposure to childhood PTEs, particularly direct interpersonal violence, was significantly and consistently related to more frequent use of OTCA to treat musculoskeletal pain and headaches in young adulthood. Adjusting for psychological symptoms and pain attenuated associations, indicating that these symptoms are of importance for the relationship between traumatic events and OTCA use. These findings emphasize the need to address symptomatology and underlying causes at an early age.

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.

Musculoskeletal pain is not clearly associated with the risk of anterior cruciate ligament reconstruction in adolescents.

Objectives: The purpose of this study was to investigate whether self-reported musculoskeletal pain (MSP) was associated with a future anterior cruciate ligament reconstruction (ACLR). Methods: In this population-based prospective cohort study, we included 8087 participants from the adolescent part of the Trøndelag Health Study (Young-HUNT) in Norway. The exposure was self-reported MSP from the Young-HUNT3 study (2006-2008), which was categorised into two MSP load groups (high MSP and low MSP) based on frequency and number of pain sites. The outcome was ACLRs recorded in the Norwegian Knee Ligament Register between 2006 and 2019. Logistic regression was used to investigate association between MSP load and ACLR, given as ORs with 95% CIs. All tests were two-sided and p values of ≤0.05 were considered statistically significant. Results: 8087 adolescents were included. We identified a total of 99 ACLRs, with 6 ACLRs (0.9%) in adolescents who reported high MSP load and 93 ACLRs (1.3%) among those who reported low MSP load. Adolescents reporting high MSP load had 23% lower odds of an ACLR (OR 0.77, 95% CI 0.31 to 1.91) compared with adolescents with low MSP load. However, the CIs were very wide. Conclusion: Self-reported high MSP load in adolescents was not associated with increased risk of future ACLR. Although the number of participants was high, the relatively few cases of ACLR mean that we cannot be conclusive about the presence or absence of an association.

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).

"I've kept going" - a multisite repeated cross-sectional study of healthcare workers' pride in personal performance during the COVID-19 pandemic.

BACKGROUND: For healthcare workers, working through a pandemic may include both challenges, such as coping with increased demands and a lack of control, and rewards, such as experiencing a sense of achievement and meaningfulness. In this study, we explore the accomplishments healthcare workers themselves are proud of achieving at work, in order to elucidate the positive aspects of working through a pandemic. METHODS: In June 2020 (T1), December 2020 (T2), and May 2021 (T3), healthcare workers (n = 1,996) at four Norwegian hospitals participated in a web-based survey assessing job strain, psychological health, and support during the pandemic. The survey included the open-ended question "During the past two weeks, what have you been feeling proud of achieving at work?". Responses (1,046) to this item were analyzed using conventional content analysis, which resulted in 13 subthemes under 6 themes. RESULTS: For some, pride was found in their professional identity and dedication to their work. Others took pride in specific achievements, such as juggling their own needs (e.g., health, private life) with those of the workplace, contributing to cohesion and collaboration, their ability to learn and adjust, in being a useful resource at work, and in their efforts towards developing the organization and workplace. IMPLICATIONS: The current findings shed light on what healthcare workers feel proud of achieving in their day-to-day work. Assessment of these factors provides insight on both positive and negative aspects of working clinically during a pandemic, and highlights specific targets for building sustainable and rewarding work environments for healthcare workers.

Exposure to traumatic events and use of over-the-counter analgesics in adolescents: cross-sectional findings from the Young-HUNT study.

OBJECTIVE: Frequent and increasing use of over-the-counter analgesics (OTCA) among adolescents is a public health concern. Prior research indicates that adolescents exposed to traumatic events may be at increased risk of suffering from headaches and musculoskeletal pain. In this study, we assessed the association between trauma exposure and use of OTCA for headaches and musculoskeletal pain. DESIGN: A cross-sectional population study among adolescents, self-reported data on trauma exposure, pain and use of OTCA. SETTING AND PARTICIPANTS: All 10 608 adolescents aged 13-19 years in a region of Norway were invited in this school-based survey, participation rate was 76%. OUTCOME MEASURE: Frequency of OTCA use for headache and musculoskeletal pain served as separate outcomes in ordinal logistic regression analyses. RESULTS: Trauma exposure was significantly and consistently related to higher frequency use of OTCA for headache and musculoskeletal pain, of which associations for bullying (OR 1.79, 95% CI 1.50 to 2.12, and OR 2.12, 95% CI 1.70 to 2.66), physical violence (OR 1.49, 95% CI 1.25 to 1.78 and OR 1.83, 95% CI 1.45 to 2.32) and sexual abuse (OR 1.83, 95% CI 1.55 to 2.18 and OR 1.53, 95% CI 1.18 to 1.90) were particularly strong. A dose-response relationship was found between interpersonal violence and OTCA use for headache (OR 1.46, 95% CI 1.29 to 1.66 for one type and OR 1.81, 95% CI 1.53 to 2.14 for two or more types) and musculoskeletal pain (OR 1.61, 95% CI 1.91 to 3.00 for one type and OR 2.39, 95% CI 1.91 to 3.00 for two or more types). The associations remained significant after adjustment for pain, although an attenuation in strength was observed. CONCLUSION: Trauma exposed adolescents use OTCA for headaches and musculoskeletal pain more frequently than those not exposed. The higher frequency of pain conditions among trauma exposed only partially explained their more frequent OTCA use, indicating an increased risk relating to features beyond frequency of pain.

Cluster headache polygenetic risk and known functional variants of CYP3A4 are not associated with treatment response.

BACKGROUND AND PURPOSE: The response to cluster headache treatments has a high interindividual variation. To date, treatment response has only been assessed by a candidate gene approach and no investigations into metabolic pathways have been performed. Our aim was to investigate the association between the polygenetic risk of cluster headache and treatment response to first-line cluster headache treatments as well as known functional variants of CYP3A4 and the response to verapamil. Further, it was aimed to replicate previous single nucleotide polymorphisms found to be associated with treatment response in cluster headache and/or migraine. METHODS: In, 508 cluster headache patients diagnosed according to the International Classification of Headache Disorders were genotyped and participated in a semi-structured interview to evaluate treatment response. Polygenetic risk scores were calculated by the effect retrieved from a meta-analysis of the latest two genome-wide association studies on cluster headache. RESULTS: Inferior treatment response to oxygen, triptans and verapamil is associated with chronicity of cluster headache were confirmed but no evidence was found that a response could be predicted by a high genetic risk of cluster headache. Likewise, verapamil response was not associated with functional variants of CYP3A4. No support of the genetic variants previously reported to be associated with treatment response to triptans or verapamil was found. CONCLUSION: The clinically relevant variation in treatment response for cluster headache was not influenced by genetic factors in the present study.

Menopausal hormone therapy, oral contraceptives and risk of chronic low back pain: the HUNT Study.

BACKGROUND: There are indications that use of menopausal hormone therapy (MHT) and oral contraceptives (OC) increases the risk of low back pain (LBP), with higher oestrogen levels involved in the underlying mechanisms. The purpose of the present study was to investigate associations between use of systemic MHT or OC and risk of chronic LBP in a large population-based data set. METHODS: Data were obtained from two surveys in the Trøndelag Health Study in Norway, HUNT2 (1995-1997) and HUNT3 (2006-2008). A cross-sectional study of association between use of systemic MHT and prevalence of chronic LBP comprised 12,974 women aged 40-69 years in HUNT2, with 4007 women reporting chronic LBP. A cohort study involving MHT comprised 6007 women without chronic LBP at baseline in HUNT2, and after 11 years 1245 women reported chronic LBP at follow-up in HUNT3. The cross-sectional study of association with use of OC included 23,593 women aged 20-69 years in HUNT2, with 6085 women reporting chronic LBP. The corresponding cohort study included 10,586 women without chronic LBP at baseline in HUNT2, of whom 2084 women reported chronic LBP in HUNT3. Risk of chronic LBP was examined in both study designs in generalised linear models with adjustment for potential confounders. RESULTS: In the cohort study, current users of systemic MHT at baseline showed a greater risk of chronic LBP (relative risk (RR) 1.30; 95% CI: 1.14-1.49; compared with never users). The risk increased according to duration of MHT use (P for linear trend = 0.003). Known users of systemic MHT based exclusively on oestrogen experienced the highest risk (RR 1.49; 95% CI: 1.16-1.91), but an increased risk was also seen among known users of oestrogen-progestin combination MHT (RR 1.35; 95% CI: 1.16-1.57). A slight increase in risk of chronic LBP was found in the cohort study among former users of OC (RR 1.17; 95% CI: 1.06-1.30; compared with never users). CONCLUSIONS: Long-lasting use of systemic MHT, in particular therapy based on oestrogen only, is associated with greater risk of chronic LBP. Having been a user of OC most likely entails a minor increase in risk.

Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity.

BACKGROUND: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. METHODS: A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. RESULTS: Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20-1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01-1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59-0.67) to 0.65 (95% CI, 0.62-0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (ß=-4.82×10-3 per year [95% CI, -6.49×10-3 to -3.14×10-3]; P=1.82×10-8), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86-0.98]; P=0.0041). CONCLUSIONS: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH.

Amoxicillin Did Not Reduce Modic Change Edema in Patients With Chronic Low Back Pain: Subgroup Analyses of a Randomised Trial (the AIM Study).

STUDY DESIGN: Exploratory subgroup analyses of a randomised trial [Antibiotics in Modic changes (AIM) study]. OBJECTIVE: The aim was to assess the effect of amoxicillin versus placebo in reducing Modic change (MC) edema in patients with chronic low back pain. SUMMARY OF BACKGROUND DATA: The AIM study showed a small, clinically insignificant effect of amoxicillin on pain-related disability in patients with chronic low back pain and MC type 1 (edema type) on magnetic resonance imaging (MRI). MATERIALS AND METHODS: A total of 180 patients were randomised to receive 100 days of amoxicillin or placebo. MC edema was assessed on MRI at baseline and one-year follow-up. Per-protocol analyses were conducted in subgroups with MC edema on short tau inversion recovery (STIR) or T1/T2-weighted MRI at baseline. MC edema reductions (yes/no) in STIR and T1/T2 series were analyzed separately. The effect of amoxicillin in reducing MC edema was analyzed using logistic regression adjusted for prior disk surgery. To assess the effect of amoxicillin versus placebo within the group with the most abundant MC edema on STIR at baseline ("STIR3" group), we added age, STIR3 (yes/no), and STIR3×treatment group (interaction term) as independent variables and compared the marginal means (probabilities of edema reduction). RESULTS: Compared to placebo, amoxicillin did not reduce MC edema on STIR (volume/intensity) in the total sample with edema on STIR at baseline (odds ratio 1.0, 95% CI: 0.5, 2.0; n=141) or within the STIR3 group (probability of edema reduction 0.69, 95% CI: 0.47, 0.92 with amoxicillin and 0.61, 95% CI: 0.43, 0.80 with placebo; n=41). Compared with placebo, amoxicillin did not reduce MC edema in T1/T2 series (volume of the type 1 part of MCs) (odds ratio: 1.0, 95% CI: 0.5, 2.3, n=104). Edema declined in >50% of patients in both treatment groups. CONCLUSIONS: From baseline to one-year follow-up, amoxicillin did not reduce MC edema compared with placebo. LEVEL OF EVIDENCE: 2.

Differential response to prolonged amoxicillin treatment: long-term resilience of the microbiome versus long-lasting perturbations in the gut resistome.

The collateral impact of antibiotics on the microbiome has attained increasing attention. However, the ecological consequences of long-term antibiotic exposure on the gut microbiome, including antibiotic resistance, are still limited. Here, we investigated long-term exposure effects to amoxicillin on the human gut microbiome and resistome. Fecal samples were collected from 20 patients receiving 3-months of amoxicillin or placebo treatment as part of a Norwegian multicenter clinical trial on chronic low back pain (AIM study). Samples were collected at baseline, last day of treatment, and 9 months after antibiotic cessation. The abundance and diversity of microbial and resistome composition were characterized using whole shotgun and functional metagenomic sequencing data. While the microbiome profiles of placebo subjects were stable over time, discernible changes in diversity and overall microbiome composition were observed after amoxicillin treatment. In particular, health-associated short-chain fatty acid producing species significantly decreased in proportion. However, these changes were short-lived as the microbiome showed overall recovery 9 months post-treatment. On the other hand, exposure to long-term amoxicillin was associated with an increase in total antimicrobial resistance gene load and diversity of antimicrobial resistance genes, with persistent changes even at 9 months post-treatment. Additionally, beta-lactam resistance was the most affected antibiotic class, suggesting a targeted response to amoxicillin, although changes at the gene level varied across individuals. Overall, our results suggest that the impact of prolonged amoxicillin exposure was more explicit and long-lasting in the fecal resistome than in microbiome composition. Such information is relevant for designing rational administration guidelines for antibiotic therapies.

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 find 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 significant 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.

Killing pain?: a population-based registry study of the use of prescription analgesics, anxiolytics, and hypnotics among all children, adolescents and young adults in Norway from 2004 to 2019.

The ongoing opioid epidemic has been a global concern for years, increasingly due to its heavy toll on young people's lives and prospects. Few studies have investigated trends in use of the wider range of drugs prescribed to alleviate pain, psychological distress and insomnia in children, adolescents and young adults. Our aim was to study dispensation as a proxy for use of prescription analgesics, anxiolytics and hypnotics across age groups (0-29 years) and sex over the last 15 years in a large, representative general population. The study used data from a nationwide prescription database, which included information on all drugs dispensed from any pharmacy in Norway from 2004 through 2019. Age-specific trends revealed that the prevalence of use among children and adolescents up to age 14 was consistently low, with the exception of a substantial increase in use of melatonin from age 5. From age 15-29, adolescents and young adults used more prescription drugs with increasing age at all time points, especially analgesics and drugs with higher potential for misuse. Time trends also revealed that children from age 5 were increasingly dispensed melatonin over time, while adolescents from age 15 were increasingly dispensed analgesics, including opioids, gabapentinoids and paracetamol. In contrast, use of benzodiazepines and z-hypnotics slightly declined in young adults over time. Although trends were similar for both sexes, females used more prescription drugs than their male peers overall. The upsurge in use of prescription analgesics, anxiolytics and hypnotics among young people is alarming.Trial registration The study is part of the overarching Killing Pain project. The rationale behind the Killing Pain research was pre-registered through ClinicalTrials.gov on April 7, 2020. Registration number NCT04336605; https://clinicaltrials.gov/ct2/show/record/NCT04336605 .