Prevalence and Risk Factors of Multi-type Post-COVID Pain in a Cohort of Previously Hospitalized COVID-19 Survivors: A Danish Cross-Sectional Survey.

This population-based study investigated the prevalence of de novo, multi-type, post-COVID pain and its associated risk factors in previously hospitalized COVID-19 survivors. The nationwide, cross-sectional study included a cohort of Danish residents previously hospitalized due to SARS-CoV-2 infection between March 2020 and December 2021. Demographic data, pre-existing medical comorbidities, previous pain-related symptoms, medication use for pain management, pain intensity (4-point scale), and development of de novo, multi-type, post-COVID pain were collected by a self-reported survey distributed via e-Boks (a secured national digital mail system used in Denmark to provide public information to residents). The sample comprised 4,712 previously hospitalized COVID-19 survivors (48.6% women, mean age: 60.1±15.6 years). At the time of the study (21±6 months after hospitalization), 18.0% (847) reported the presence of de novo, multi-type, post-COVID pain, and 38.6% of any pain. A multivariate analysis revealed that female sex (OR 1.711, 95%CI 1.444-2.023), higher body mass index (OR 1.032, 95%CI 1.019-1.045), intensive care unit admission (OR 1.597, 95%CI 1.324-1.926), previous history of whiplash (OR 2.471, 95%CI 1.004-6.081), anxiety (OR 3.626, 95%CI 1.335-9.708), and younger age (OR 0.982, 95%CI 0.976-0.987) were factors associated with development of de novo, multi-type, post-COVID pain. High income (OR 0.635, 95%CI 0.494-0.817) and high educational level (OR 0.774, 95%CI 0.609-0.984) were protective factors. In conclusion, multi-type pain as a de novo post-COVID symptom was present in 18.0% of previously hospitalized COVID-19 survivors more than one year after hospital discharge and as such can be considered as adding to the global burden of chronic pain. PERSPECTIVE: The study investigates the prevalence of de novo, multi-type, post-COVID pain in previously hospitalized COVID-19 survivors. This article presents potential risk factors associated with developing new pain symptoms. The results will contribute to understanding the possibility of predicting post-infectious pain from COVID-19 for future analysis.

Walking performance in individuals with lumbar spinal stenosis- possible outcome measures and assessment of known-group validity.

BACKGROUND CONTEXT: One of the primary goals of treatments received by individuals with lumbar spinal stenosis with neurogenic claudication is to improve walking ability. Thus, a thorough and valid assessment of walking ability in patients with lumbar spinal stenosis is needed. Duration of continuous walking and steps per day could be relevant when evaluating walking ability in daily living. PURPOSE: To describe and evaluate a method for estimating continuous walking periods in daily living and to evaluate the known-group validity of steps per day in individuals with lumbar spinal stenosis. STUDY DESIGN: This is a cross-sectional observational study. PATIENT SAMPLE: The study contains three study groups: individuals with lumbar spinal stenosis, individuals with low back pain, and a background population from the Lolland-Falster Health Study (LOFUS). OUTCOME MEASURES: Participants in all three study groups wore an accelerometer on the thigh for seven days. METHODS: Accelerometer data were processed to summarize the continuous walking periods according to their length: the number of short (4-9 seconds), moderate (10-89 seconds), and extended (≥90 seconds) continuous walking periods per day, and the number of steps per day. Results from the three groups were compared using negative binomial regression with lumbar spinal stenosis as the reference level. RESULTS: Continuous walking periods of moderate length were observed 1.48 (95% CI 1.27, 1.72) times more often in individuals from the background population than in individuals with LSS. Continuous walking periods of extended length were observed 1.53 (95% CI 1.13, 2.06) times more often by individuals with low back pain and 1.60 (95% CI 1.29, 1.99) times more often by individuals from the background population. The number of steps per day was 1.22 (95% CI 1.03, 1.46) times larger in individuals with LBP and 1.35 (95% CI 1.20, 1.53) times larger in individuals from background population. CONCLUSIONS: The impact of neurogenic claudication on walking ability in daily living seems possible to describe by continuous walking periods along with steps per day. The results support known-group validity of steps per day. This is the next step toward a clinically relevant and comprehensive assessment of walking in daily living in individuals with lumbar spinal stenosis.

Tip of the iceberg: unveiling the impact on back disorders from cumulative physical job exposure and evaluating bias from the healthy worker effect using a nationwide longitudinal cohort study.

PURPOSE: Longitudinal studies across various sectors with physically demanding jobs are notably absent in back disorder risk research. This study aimed to investigate the relationship between cumulative physical job exposure (PJE) and hospital-diagnosed back disorders among individuals in Denmark. To assess the healthy worker effect, we compared the cumulative risk estimate with results from a naive cross-sectional model ignoring PJE history. METHODS: A nationwide longitudinal cohort study was conducted using Danish registers, encompassing individuals born between 1975 and 1978 and working in 1996. Cumulative PJE was measured with a 10-year look-back period for each year 2006-2017. PJE consisted of lower-body occupational exposures, including the total weight lifted, stand/sit ratio, and the frequency of lifting more than 20 kg per day from a job exposure matrix. Odds ratio for back disorders was estimated for each year and all years combined. RESULTS: The results unveiled a significant 31% increase in the risk of hospital-diagnosed back disorders after 4 years of cumulative PJE. The lowest risk (7%) was observed for incident back disorders with 1 year of exposure, suggesting a healthy worker effect. Nevertheless, this risk is still significantly elevated. This cumulative estimate is fourfold the estimate from the 2006 naive cross section model. CONCLUSION: Our study clearly demonstrates an 31% increase in the risk of hospital-diagnosed back disorders with just 4 years of PJE over a 10-year period. Further, we find that cross-sectional studies strongly underestimate the risk of back disorders due to the healthy worker effect.

Interest in mHealth Among Patients With Low Back Pain: Cross-Sectional Study.

BACKGROUND: Digitally supported self-management tailored to an individual's need, in addition to usual care, may reduce pain-related disability compared to usual care alone, and patients with low back pain (LBP) using mobile health (mHealth) solutions express positive experiences. Hence, implementing mHealth solutions designed to support self-management is desirable from a clinical and patient perspective. Easily accessible mHealth solutions that can support the self-management of patients with LBP are available, but interest may be subgroup specific. Understanding the characteristics and preferences of patients with LBP labeled as interested may help to reach relevant LBP patient groups and inform the development and implementation of effective interventions with mHealth for patients with LBP. OBJECTIVE: This study aims to explore the proportion of patients with LBP labeled as interested in testing an mHealth solution designed to support self-management in addition to usual care and to assess how these patients differ from those who were labeled as not interested. METHODS: This exploratory cross-sectional study analyzed demographic and patient-reported outcomes from the SpineData registry, a Danish registry of patients with LBP in an outpatient setting. Between February and December 2019, the SpineData registry was used to assess the preliminary eligibility of patients for a clinical trial (selfBACK). Patients were labeled as interested or uninterested depending on if they responded to an invitation to be tested for eligibility for the trial Outcomes were selected from the International Classification of Functioning core set of LBP using a clinical approach. Associations were assessed in a backward selection process, and the proportion of variance explained was assessed with pseudo-R2 statistic. RESULTS: This study included 843 patients, with 181 (21%) individuals labeled as interested in participating in the selfBACK trial. Notably, the cohort labeled as interested differed from their uninterested counterparts in two key aspects: age (36-65 years: 116/181, 64.1% vs 347/662, 52.4%; P=.003) and smoking status (smokers: 22/181, 12.5% vs 174/662, 26.6%; P<.001). Those aged 36-65 years had higher odds of being labeled as interested compared to individuals aged 18-35 years (odds ratio [OR] 0.43, 95% CI 0.26-0.71) and those 65 years or older (OR 0.77, 95% CI 0.53-1.15). Nevertheless, age accounted for only a modest proportion of variance (R2=0.014). Smokers demonstrated lower odds of being labeled as interested (OR 0.39, 95% CI 0.24-0.64), with smoking status explaining a similarly small proportion of variance (R2=0.019). Collectively, age and smoking status accounted for 3.3% of the variance. CONCLUSIONS: Our investigation revealed that 181 (21%) individuals with LBP invited to participate in the mHealth solution trial for self-management expressed interest. Generally, the characteristics of those labeled as interested and uninterested were comparable. Of note, patients aged 36-65 years had a higher frequency of being labeled as interested compared to their younger and older counterparts.

Assessing Work Functioning in Patients with Persistent Low Back Pain: Exploring the Structural Validity of the Work Rehabilitation Questionnaire.

PURPOSE: Assessing work functioning in patients with persistent low back pain (LBP) is important for understanding their ability to engage in work-related activities. This study aims to evaluate the item characteristics, factor structure, and internal consistency of the Work Rehabilitation Questionnaire (WORQ) in patients with persistent LBP. METHODS: Four hundred and twenty-five individuals with LBP completed the WORQ. Item characteristics, exploratory factor analysis (EFA), and consistency were performed to identify the underlying factors. RESULTS: Missing responses were < 2% for each item. The analysis revealed three factors: psychological wellbeing, physical functioning, and cognitive ability. The factors demonstrated strong internal consistency, with Cronbach's alpha values ranging from 0.88 to 0.93 and McDonald's Omega from 0.92 to 0.96. Fifteen items did not fit into any identified factors, suggesting their potential value in screening functioning levels beyond the factors. CONCLUSIONS: The WORQ is a valid instrument for evaluating work limitations in individuals with persistent LBP. Further research should assess its responsiveness to changes from interventions that target workability. Advancing this knowledge has the potential to promote work rehabilitation and improve the quality of life for patients with persistent LBP.

Long-term prognosis at 1.5 years after infection with wild-type strain of SARS-CoV-2 and Alpha, Delta, as well as Omicron variants.

OBJECTIVES: Knowledge is limited on how changing SARS-CoV-2 variants may translate into different characteristics and affect the prognosis of patients with long COVID, especially following Omicron variants. We compared long-term prognosis of patients in a Danish Post-COVID Clinic infected with wild-type strain, Alpha, Delta, or Omicron variants as well as the pre-Omicron compared to the Omicron period. METHODS: At enrollment, a Post-COVID symptom Questionnaire (PCQ), and standard health scores, were registered and repeated four times until 1.5 years after infection. PCQ was the primary outcome to assess the severity of long COVID, and Delta PCQ to assess failure to improve. RESULTS: A total of 806 patients were enrolled. Patients infected with Omicron and Delta variants presented with more severe long COVID (median PCQ 43 in Delta vs 38 in wild-type, P = 0.003) and health scores (EuroQol five-dimension five-level-index was 0.70 in Omicron vs 0.76 in wild-type, P = 0.009 and 0.78 pre-Omicron, P = 0.006). At 1.5 years after infection, patients had no clinically meaningful decline in severity of long COVID, and 57% (245/429) of patients failed to improve 1.5 years after infection, with no differences between variants. CONCLUSION: More than half of patients referred to a Post-COVID Clinic failed to improve in long COVID severity 1.5 years after infection regardless of variants of SARS-CoV-2.

Examination of autoantibodies to type I interferon in patients suffering from long COVID.

Long COVID (LC) is an emerging global health concern. The underlying mechanism and pathophysiology remain unclear. Presence of neutralizing autoantibodies against type 1 interferons (IFN) has been established as a predictor of critical COVID-19. We hypothesized that persistent autoimmune activity with autoantibodies against type 1 IFN may contribute to symptoms in patients with LC. Plasma samples and clinical information were obtained from a Danish LC cohort consisting of adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Information on symptoms and quality of life was derived from an LC-specific questionnaire and the EQ-5D-5L questionnaire. Detection of type 1 IFN autoantibodies in plasma were performed by ELISA. Samples collected between June, 2020, and September, 2021, from 279 patients were analyzed and compared to a control group of 94 individuals with prior mild SARS-CoV-2 infection who did not develop LC symptoms. In total, five LC patients (1.8%) and 3 (3.2%) of the controls had detectable circulating type 1 IFN autoantibodies. Collectively, prevalence of autoantibodies against type 1 IFN subtypes in our LC cohort were primarily driven by men and did not exceed the prevalence in controls. Thus, in our cohort, anti-type I IFN autoantibodies are unlikely to drive LC symptoms.

Complement Proteins L-Ficolin and M-Ficolin Are Increased in Patients With Axial Spondyloarthritis and Decrease After Tumor Necrosis Factor Inhibitor Treatment.

OBJECTIVE: We have previously reported elevated levels of the complement lectin pathway proteins L-ficolin and H-ficolin in patients with axial spondyloarthritis (axSpA) compared with healthy controls. The aim of the present study was to investigate these biomarkers in a cross-sectional cohort of patients suffering from low back pain (LBP). Further, we aimed to investigate changes in lectin pathway protein levels after initiation of adalimumab (ADA; a tumor necrosis factor inhibitor) in a longitudinal cohort of patients with axSpA. METHODS: Lectin pathway protein levels (mannan-binding lectin [MBL], collectin liver 1, H-ficolin, L-ficolin, M-ficolin, MBL-associated serine protease [MASP]-1, MASP-2, MASP-3, MBL-associated protein 19 [MAp19], and MAp44) in EDTA plasma were determined in 2 well-characterized cohorts: (1) a clinical cross-sectional cohort of patients with LBP, including patients with axSpA (n = 23), patients with unspecific LBP (uLBP) with ≥ 1 SpA features (n = 55), and patients with uLBP without SpA features or magnetic resonance imaging findings suggestive of axSpA (n = 64); and (2) a randomized double-blinded, placebo-controlled trial cohort of patients with axSpA (n = 49) initiating ADA therapy. Lectin pathway protein levels were determined using immunoassays. RESULTS: Plasma levels of L-ficolin and M-ficolin were significantly increased in the cross-sectional cohort of newly diagnosed patients with axSpA compared with clinically relevant controls with uLBP (all P < 0.05). Both L-ficolin and M-ficolin decreased significantly after ADA therapy (P < 0.05). CONCLUSION: L-ficolin and M-ficolin levels are elevated in newly diagnosed patients with axSpA compared with clinically relevant controls. Both L-ficolin and M-ficolin levels decrease significantly after initiating ADA therapy. These findings provide new insights into the inflammatory processes in axSpA and support the involvement of complement in axSpA pathogenesis.

Exploring usual care for patients with low back pain in primary care: a cross-sectional study of general practitioners, physiotherapists and chiropractors.

OBJECTIVES: To explore the elements and composition of care provided by general practitioners (GPs), physiotherapists (PTs) and chiropractors (DCs) to patients with low back pain (LBP). DESIGN: Observational study. SETTING: Primary care setting, Denmark. PARTICIPANTS: Primary care clinicians (GPs, PTs and DCs) in the Region of Southern Denmark were invited to register consecutive adult patient visits with LBP as the primary complaint. PRIMARY OUTCOME MEASURES: Clinicians reported care elements provided to patients with LBP. Elements varied due to professional differences (eg, prescriptive rights). Data were descriptively analysed, on group and individual levels, for frequency and combination of care elements, and practice patterns were explored with latent class analysis. RESULTS: The clinicians (33 GPs, 67 PTs and 43 DCs with a median experience of 15 years and 59% were females) registered 3500 patient visits. On average, the visits involved patients aged 51 years, and 51% were with females. The frequencies of common care elements across professions were information (42%-56% of visits between professions) and advice (56%-81%), while other common elements for GPs were pain medication (40%) and referrals to PTs (36%), for PTs, use of exercises (81%) and for DCs, use of manual therapy (96%). Substantial variation was observed within professions and distinct practice patterns, with different focuses of attention to information and advice versus exercise and manual therapy, were identified for PTs and DCs. CONCLUSIONS: These data indicate substantial variation in the care elements provided by GPs, PTs and DCs to LBP patients. The compositions of care and practice patterns identified challenge the understanding of usual care as a uniform concept and professions as homogeneous groups. Strategic use of particular care elements in different parts of treatment courses is indicated. Longitudinal data and qualitative enquiry are needed to assess if or how care is tailored to individual patients.

Content of clinicians' communication with patients suffering from spinal pain in assessment situations in a specialized spine center: A qualitative study evaluating psychologically informed pain assessments before and after clinicians' participation in an Acceptance and Commitment Therapy course.

INTRODUCTION: Assessment is an important part of chronic pain rehabilitation and should be conducted in line with the current biopsychosocial conceptualization of pain to capture the subjectivity and context of pain. However, pain assessment is commonly conducted from a biomedical framework. A course in Acceptance and Commitment Therapy (ACT) was provided to spinal pain clinicians as a framework to promote more person-centered and psychosocially focused assessments and related psychologically informed practices. The purpose of this qualitative study was to explore the verbal content of clinicians' communication with patients experiencing spinal pain in assessment situations before and after clinicians participated in an ACT course. METHODS: Pain assessments of patients with chronic low back pain conducted by six spinal pain clinicians from different professions were audio-recorded and transcribed. This was done before and after participation in an eight-day ACT course with four following supervisions. A thematic analysis was carried out by two authors across all material, and a comparison of the applied number of codes pre-course and post-course was carried out as an indicator of change. RESULTS: Data consisted of transcripts from the six clinicians across 23 different patients (12 before course participation). Through analysis, 11 codes were developed, which were clustered in three overarching themes: Psychological domains, Communication Techniques, and Intervention Elements. Overall, there was an increase in the application of many of the codes in the transcripts from pre-course to post-course, however with large differences across codes. Increases were primary related to the discussion of life values and value-based action and quality of life as well as the employment of mirroring, challenging beliefs and assumptions, and addressing coping and pacing. CONCLUSIONS: While not the case for all factors, the present findings indicate an increase in including psychological factors and employing interpersonal communication skills after a course in ACT. However, it remains unknown due to the design if the changes reported in this study reflect a clinically valuable change and whether they are due to the ACT training itself. Future research will improve our understanding of the effectiveness of this type of intervention in assessment practices.

Surgical trends and regional variation in Danish patients diagnosed with lumbar spinal stenosis between 2002 and 2018: a retrospective registry-based study of 83,783 patients.

BACKGROUND: Lumbar spinal stenosis (LSS) is the most common reason for spine surgery in older people. However, surgery rates vary widely both internationally and nationally. This study compared patient and sociodemographic characteristics, geographical location and comorbidity between surgically and non-surgically treated Danish patients diagnosed with LSS from 2002 to 2018 and described variations over time. METHODS: Diagnostic ICD-10 codes identifying patients with LSS and surgical procedure codes for decompression with or without fusion were retrieved from the Danish National Patient Register. Patients ≥ 18 years who had been admitted to private or public hospitals in Denmark between 2002 and 2018 were included. Data on age, sex, income, retirement status, geographical region and comorbidity were extracted. A multivariable logistic regression model was used to calculate the relative risk for surgically versus non-surgically treated LSS patients using the total population and subsequently divided into three time periods. Variations over time were displayed graphically. RESULTS: A total of 83,783 unique patients with an LSS diagnosis were identified, and of these, 38,362 (46%) underwent decompression surgery. Compared to those who did not receive surgery, the surgically treated patients were more likely to be aged 65-74 years, were less likely to have comorbidities, had higher income and were more likely to reside in the northern part of Denmark. Patients aged 65-74 years remained more likely to receive surgery over time, although the difference between age groups eventually diminished, as older patients (aged ≥ 75) were increasingly more likely to undergo surgery. Large variations and differences in the relative risk of surgery were observed within and between the geographical regions. The likelihood of receiving surgery varied up to threefold between regions. CONCLUSION: Danish patients with LSS who receive surgery differ in a number of respects from those not receiving surgery. Patients aged 65 to 74 years were more likely to receive surgery than other age groups, and LSS surgical patients were healthier, more often retired and had higher incomes than those not undergoing surgery. There were considerable variations in the relative risk of surgery between and within geographical regions.

Economic burden of osteoarthritis - multi-country estimates of direct and indirect costs from the BISCUITS study.

Data from 'BISCUITS', a large Nordic cohort study linking several registries, were used to estimate differences in average direct and indirect costs between patients with osteoarthritis and controls (matched 1:1 based on birth year and sex) from the general population in Sweden, Norway, Finland and Denmark for 2017. Patients ≥18 years with ≥1 diagnosis of osteoarthritis (ICD-10: M15-M19) recorded in specialty or primary care (the latter available for a subset of patients in Sweden and for all patients in Finland) during 2011-2017 were included. Patients with a cancer diagnosis (ICD-10: C00-C43/C45-C97) were excluded. Productivity loss (sick leave and disability pension) and associated indirect costs were estimated among working-age adults (18-66 years). In 2017, average annual incremental direct costs among adults with osteoarthritis (n=1,157,236) in specialty care relative to controls ranged between €1,259 and €1,693 (p<0.001) per patient across all countries. Total average annual incremental costs were €3,224-€4,969 (p<0.001) per patient. Healthcare cost differences were mainly explained by osteoarthritis patients having more surgeries. However, among patients with both primary and secondary care data, primary care costs exceeded the costs of surgery. Primary care constituted 41 and 29 % of the difference in direct costs in Sweden and Finland, respectively. From a societal perspective, the total economic burden of osteoarthritis is substantial, and the incremental cost was estimated to €1.1-€1.3 billion yearly for patients in specialty care across the Nordic countries. When including patients in primary care, incremental costs rose to €3 billion in Sweden and €1.8 billion in Finland. Given the large economic impact, finding cost-effective and safe therapeutic strategies for these patients will be important.

Demographic and clinical characteristics of patients with low back pain in primary and secondary care settings in Southern Denmark.

OBJECTIVE: To describe and compare the demographic and clinical characteristics of patients with acute or chronic low back pain across all health care settings treating this condition.Design and setting: Concurrent prospective survey registration of all consecutive consultations regarding low back pain at general practitioners, chiropractors, physiotherapists, and the secondary care spine centre in Southern Denmark. SUBJECTS: Patients ≥16 years of age with low back pain. MAIN OUTCOME MEASURE: Demographic characteristics, symptoms, and clinical findings were registered and descriptively analysed. Pearson's chi-square tested differences between the populations in the four settings. Multiple logistic regression assessed the odds of consulting specific settings, and t-test assessed differences between patients attending for a first and later consultation. RESULTS: Thirty-six general practitioners, 44 chiropractors, 74 physiotherapists, and 35 secondary care Spine Centre personnel provided information on 5645 consultations, including 1462 first-visit consultations. The patients differed significantly across the settings. Patients at the Spine Centre had the most severe symptoms and signs and were most often on sick leave. Compared to the other populations, the chiropractor population was younger, whereas the physiotherapist population was older, more often females, and had prolonged symptoms. In general practice, first-time consultations were with milder cases while patients who attended for a second or later consultation had the worst symptoms, findings, and risk of sick leave compared to the other primary care settings. CONCLUSION: The demographic and clinical characteristics of patients with low back pain differ considerably across the health care settings treating them.KEY POINTSThe study describes the symptoms and clinical findings of patients with low back pain consulting the Danish health care system in all its settings.Patients with chiropractors were youngest, while those with physiotherapists were the oldest and most frequently female.First consultations in general practice were generally with the least symptomatic patients while those returning for a subsequent consultation had more severe disease including more sick leave compared to patients in the other primary care settings.Our findings call for caution when generalizing between health care settings for patients with low back pain.

Myopathy as a cause of Long COVID fatigue: Evidence from quantitative and single fiber EMG and muscle histopathology.

OBJECTIVE: To describe neurophysiological abnormalities in Long COVID and correlate quantitative electromyography (qEMG) and single fiber EMG (sfEMG) results to clinical scores and histopathology. METHODS: 84 patients with non-improving musculoskeletal Long COVID symptoms were examined with qEMG and sfEMG. Muscle biopsies were taken in a subgroup. RESULTS: Mean motor unit potential (MUP) duration was decreased in ≥ 1 muscles in 52 % of the patients. Mean jitter was increased in 17 % of the patients in tibialis anterior and 25 % in extensor digitorum communis. Increased jitter was seen with or without myopathic qEMG. Low quality of life score correlated with higher jitter values but not with qEMG measures. In addition to our previously published mitochondrial changes, inflammation, and capillary injury, we show now in muscle biopsies damage of terminal nerves and motor endplate with abundant basal lamina material. At the endplate, axons were present but no vesicle containing terminals. The post-synaptic cleft in areas appeared atrophic with short clefts and coarse crests. CONCLUSIONS: Myopathic changes are common in Long COVID. sfEMG abnormality is less common but may correlate with clinical scores. sfEMG changes may be due to motor endplate pathology. SIGNIFICANCE: These findings may indicate a muscle pathophysiology behind fatigue in Long COVID.

High-dose coenzyme Q10 therapy versus placebo in patients with post COVID-19 condition: a randomized, phase 2, crossover trial.

Background: Post COVID-19 condition (PCC) is defined as symptoms lasting more than 12 weeks after developing COVID-19. Evidence of mitochondrial dysfunction has been reported in peripheral blood mononuclear cells obtained from patients with COVID-19. We hypothesized that PCC is caused by prolonged mitochondrial dysfunction. Given that coenzyme Q10 (CoQ10) can improve mitochondrial function, we examined whether high-dose CoQ10 can reduce the number and/or severity of PCC-related symptoms. Methods: In this placebo-controlled, double-blind, 2 × 2 crossover interventional trial, participants were recruited from two centres at Aarhus University Hospital and Gødstrup Hospital, Denmark. They were randomly assigned to receive either oral capsules of CoQ10 in a dose of 500 mg/day or placebo for 6 weeks, with crossover treatment after a 4-week washout period. The ED-5Q and a PCC-symptom specific questionnaire were completed by the participants at 5 visits during the 20-week study period. The primary endpoint was the change in the number and/or severity of PCC-related symptoms after the 6-week intervention compared to placebo. Participants who completed the two-dosing period were included in the primary analysis, while all participants receiving one dose were included in safety assessment. Findings: From May 25th, 2021, to September 22nd, 2021, 121 participants underwent randomization, and 119 completed both dosing periods - 59 and 60 in group A and B, respectively. At baseline, the mean PCC-related symptom score was 43.06 (95% CI: 40.18; 45.94), and the mean EQ-5D health index was 0.66 (95% CI: 0.64; 0.68). The difference between CoQ10 and placebo was not significant with respect to either the change in EQ-5D health index (with a mean difference of 0.01; 95% CI: -0.02; 0.04; p = 0.45) or the change in PCC-related symptom score (with a mean difference of -1.18; 95% CI: -3.54; 1.17; p = 0.32). Interpretation: Based on self-reported data, CoQ10 treatment does not appear to significantly reduce the number or severity of PCC-related symptoms when compared to placebo. However, we observed a significant spontaneous improvement on both scores regardless of treatment during 20 weeks observation. Funding: Placebo and CoQ10 capsules were provided by Pharma Nord, and the trial was supported by grants from the Novo Nordisk Foundation (NNF21OC0066984). This trial is registered with EudraCT, 2020-005961-16 and ClinicalTrials.gov, NCT04960215. The trial is completed.

Burden of disease and management of osteoarthritis and chronic low back pain: healthcare utilization and sick leave in Sweden, Norway, Finland and Denmark (BISCUITS): study design and patient characteristics of a real world data study.

OBJECTIVES: Osteoarthritis (OA) and chronic low back pain (CLBP) are common musculoskeletal disorders with substantial patient and societal burden. Nordic administrative registers offer a unique opportunity to study the impact of these conditions in the real-world setting. The Burden of Disease and Management of Osteoarthritis and Chronic Low Back Pain: Health Care Utilization and Sick Leave in Sweden, Norway, Finland and Denmark (BISCUITS) study was designed to study disease prevalence and the societal and economic burden in broad OA and CLBP populations. METHODS: Patients in Sweden, Norway, Finland and Denmark with diagnoses of OA or CLBP (low back pain record plus ≥2 pain relief prescriptions to indicate chronicity) were identified in specialty care, in primary care (Sweden and Finland) and in a quality-of-care register (Sweden). Matched controls were identified for the specialty care cohort. Longitudinal data were extracted on prevalence, treatment patterns, patient-reported outcomes, social and economic burden. RESULTS: Almost 1.4 million patients with OA and 0.4 million with CLBP were identified in specialty care, corresponding to a prevalence in the Nordic countries of 6.3 and 1.9%, respectively. The prevalence increased to 11-14% for OA and almost 6% for CLBP when adding patients identified in primary care. OA patients had a higher Elixhauser comorbidity index (0.66 vs. 0.46) and were using opioids (44.7 vs. 10.2%) or long-term nonsteroidal anti-inflammatory drug (NSAIDs) (20.9 vs. 4.5%) more than four times as often as compared to controls. The differences were even larger for CLBP patients compared to their controls (comorbidity index 0.89 vs. 0.39, opioid use 77.7 vs. 9.4%, and long-term NSAID use 37.2 vs. 4.8%). CONCLUSIONS: The BISCUITS study offers an unprecedented, longitudinal healthcare data source to quantify the real-world burden of more than 1.8 million patients with OA or CLBP across four countries. In subsequent papers we aim to explore among others additional outcomes and subgroups of patients, primarily those patients who may benefit most from better healthcare management.

Psychiatric disorders, diagnosed in psychiatric clinics, in patients with back pain: A cohort study.

Aims: The aim of this study was to evaluate whether patients with a non-specific back pain disorder are more likely to be diagnosed with a psychiatric disorder than patients with a specific back pain disorder (such as a herniated disc or inflammatory back disorder). Methods: This was a retrospective cohort study using Danish registries. Results: Our study population included 24,518 patients younger than 61 years and 12,274 patients older than 61 years. In both subpopulations, 60% had a non-specific back pain diagnosis (BPD). In the younger subpopulation, 2.1% of the patients with a non-specific BPD and 1.3% of the patients with a specific BPD had a psychiatric diagnosis within one year of their BPD. In the older subpopulation, 0.6% of patients had a psychiatric diagnosis in both BPD groups. The most frequent psychiatric diagnoses were stress-related disorders. In the younger subpopulation, patients with non-specific back pain had a higher risk of being diagnosed with a psychiatric disorder than patients with specific back pain (adjusted odds ratio 1.56, 95% confidence interval 1.25-1.94). The type of BPD had no effect on the risk of having a psychiatric diagnosis among older patients. Conclusions: Patients with a non-specific back pain disorder younger than 61 years were more likely to be diagnosed with a psychiatric disorder than patients with a specific back pain disorder. We recommend that spine specialists pay special attention to patients younger than 61 years with a back pain disorder to prevent them from developing a psychiatric disorder.

Biopsychosocial Rehabilitation for Inflammatory Arthritis and Osteoarthritis Patients: A Systematic Review and Meta-Analysis of Randomized Trials.

OBJECTIVE: To assess the benefits and harms associated with biopsychosocial rehabilitation in patients with inflammatory arthritis and osteoarthritis (OA). METHODS: We performed a systematic review and meta-analysis. Data were collected through electronic searches of Cochrane CENTRAL, MEDLINE, Embase, PsycInfo, and CINAHL databases up to March 2019. Trials examining the effect of biopsychosocial rehabilitation in adults with inflammatory arthritis and/or OA were considered eligible, excluding rehabilitation adjunct to surgery. The primary outcome for benefit was pain and total withdrawals for harm. RESULTS: Of the 27 trials meeting the eligibility criteria, 22 trials (3,750 participants) reported sufficient data to be included in the quantitative synthesis. For patient-reported outcome measures, biopsychosocial rehabilitation was slightly superior to control for pain relief (standardized mean difference [SMD] -0.19 [95% confidence interval (95% CI) -0.31, -0.07]), had a small effect on patient global assessment score (SMD -0.13 [95% CI -0.26, -0.00]), with no apparent effect on health-related quality of life, fatigue, self-reported disability/physical function, mental well-being, and reduction in pain intensity ≥30%. Clinician-measured outcomes displayed a small effect on observed disability/physical function (SMD -0.34 [95% CI -0.57, -0.10]), a large effect on physician global assessment score (SMD -0.72 [95% CI -1.18, -0.26]), and no effect on inflammation. No difference in harms existed in terms of the number of withdrawals, adverse events, or serious adverse events. CONCLUSION: Biopsychosocial rehabilitation produces a significant but clinically small beneficial effect on patient-reported pain among patients with inflammatory arthritis and OA, with no difference in harm. Methodologic weaknesses were observed in the included trials, suggesting low-to-moderate confidence in the estimates of effect.

Characteristics of a Danish Post-COVID Cohort Referred for Examination due to Persistent Symptoms Six Months after Mild Acute COVID-19.

BACKGROUND: Post-COVID Clinics were recommended for patients with persistent symptoms following COVID-19, but no specific tests were suggested for evaluation. This study aimed to present a post-COVID clinic patient cohort and evaluate the use of a post-COVID symptom questionnaire (PCQ) score. METHODS: Patients were referred from a population of approximately 1 million citizens. PCQ and standardized health scales were registered. Descriptive analyses were performed to assess the prevalence of symptoms, and correlation analyses was undertaken to asses convergent and discriminant trends between PCQ scores and health scales. RESULTS: Of 547 patients, 447 accepted inclusion. The median age was 47 years and 12% of the patients were hospitalized. At a median of 6.3 (IQR 4.4-9.9) months after the onset of symptoms, 82% of the patients reported both physical exhaustion and concentration difficulties. Functional disability and extreme fatigue were reported as moderate to severe by 33% and 62% of the patients, respectively. The PCQ score correlated significantly with each of the standardized health scales. CONCLUSION: Patients referred to a Post-COVID Clinic were previously generally healthy. At the time of diagnosis, they reported multiple symptoms with severely affected health. The PCQ score could be used as valid measure of Post-COVID severity.

Mental Fatigue, Activities of Daily Living, Sick Leave and Functional Status among Patients with Long COVID: A Cross-Sectional Study.

Studies suggest that persistent symptoms after COVID-19 (long COVID) influence functioning and activities of daily living (ADL). However, it is still uncertain how and to what extent. This study aimed to describe patient-reported mental fatigue, ADL problems, ADL ability, sick leave and functional status among patients with long COVID. In this cross-sectional study, 448 patients, ≥18 years old and referred to occupational therapy at a Danish Post-COVID-19 Clinic, were included. Mental fatigue was measured by the Mental Fatigue Scale, ADL problems and ability were measured by the Canadian Occupational Performance Measure, sick leave was self-reported and functional status was evaluated by the Post-COVID-19 Functional Status Scale. Mean age was 46.8 years, 73% of the patients were female, and 75% suffered from moderate to severe mental fatigue. The majority reported difficulties performing productive and leisure activities. The median performance and satisfaction scores were 4.8 and 3, respectively. In total, 56% of the patients were on sick leave, and 94% were referred to rehabilitation. A decrease in functional status was found between pre-COVID-19 and assessment. Conclusively, the patients were highly affected in their everyday life and had distinct rehabilitation needs. Future research is needed to address causalities and rehabilitation for this patient group.