Intervertebral Disc Disorders Research Articles

Current trends in the medical treatment of neuropathic low back pain: a Swedish registry-based study of 1.7 million people

BackgroundLow back pain, a common problem worldwide, causes more global disability than any other condition and is associated with high costs to society. This observational registry-based study describes the current trends in the medical treatment of neuropathic low back pain in the Swedish region of Västra Götaland, which has a population of 1.7 million. The study aims to; (1) identify the prevalence of neuropathic low back pain within the study population; (2) to explore the patterns of medical treatment utilization, including the prevalence and distribution of opioids (OG) and analgesics specified for neuropathic low back pain (NG) and (3) to evaluate the long-term trends and changes in medical treatment practice for neuropathic low back pain over the study period.MethodsThis study includes a descriptive analysis of aggregated data extracted from the Swedish primary care registry VEGA and the pharmaceutical prescription registry Digitalis between the years 2017 and 2021. The data were stratified by year, age, gender, pharmaceutical code (ATC), and sub-diagnoses and presented as the prevalence of unique patients retrieving prescribed medication within six months before or after a registered diagnosis of neuropathic low back pain. The pharmaceutical codes were furthermore grouped into two groups depending on their mechanism of action; opioid group (OG) and neuropathic group (NG).ResultsIn all four diagnosis groups, more patients used opioid analgesics than neuropathic analgesics. The greatest difference between the opioid group and neuropathic group was in the lumbar spinal stenosis diagnosis group (67.1% vs. 40.6%), followed by the lumbar root canal stenosis diagnosis (65.9% vs. 44.2%), the nerve root and plexus compressions in intervertebral disc disorders diagnosis (57.5% vs. 40.8%), and lumbago with sciatica diagnosis (38.4% vs. 22.7%).ConclusionsThe trends suggest a general increase in the prescription rate and therefore patients’ use of neuropathic analgesics for neuropathic pain associated with the studied diagnoses. However, opioid treatment remains the most common. The results indicate that the treatment for neuropathic low back pain needs to be improved.

Causal associations between sarcopenia-related traits and intervertebral disc degeneration: a two-sample mendelian randomization analysis.

Sarcopenia (SP) and intervertebral disc degeneration (IVDD) have a higher incidence in the elderly population. Previous studies have indicated a potential association between SP and IVDD. The objective of this study is to elucidate the potential causal relationship between sarcopenia-related traits and IVDD through Two-sample Mendelian randomization (MR) analysis. We utilized a genome-wide association study conducted on the European population to collect aggregated data on sarcopenia and IVDD. Inverse variance weighting was primarily employed, supplemented by MR Egger, weighted median, simple model, and weighted model methods. Additionally, sensitivity analysis was performed to assess the robustness of the findings. Appendicular lean mass is positively associated with "Other intervertebral disc disorders" (OIDD) and "Prolapsed or slipped disc" (POSD) (OIDD: p = 0.002, OR = 1.120; POSD: p < 0.001, OR = 1.003), while grip strength (GS) is positively associated with POSD (left: p = 0.004, OR = 1.008; right: p < 0.001, OR = 1.010). It is worth mentioning that walking pace has significant causal relationship with "Low back pain" (LBP), "Lower back pain or/and sciatica" (LBPOAS), "Sciatica with lumbago" (SWL) and OIDD (LBP: p < 0.001, OR = 0.204; LBPOAS: p < 0.001, OR = 0.278; SWL: p = 0.003, OR = 0.249; OIDD: p < 0.001, OR = 0.256). The present study revealed the causal relationship between SP-related traits and IVDD and recommended to prevent and treat sarcopenia as a means of preventing IVDD in clinic practice.

Bio‐Functional Hydrogel Microspheres for Musculoskeletal Regeneration

AbstractThe worldwide prevalence of musculoskeletal disorders is expected to rise due to an accelerating aging population and increasing associated factors. Despite the high rate of disability induction, clinical options for the treatment of musculoskeletal disorders remain limited. Hydrogel microspheres (HMSs), which are colloidal particles with crosslinked polymer networks at the nanometer scale, are characterized by excellent biocompatibility, easy‐to‐tune structures (e.g., stiffness, porosity, and composition), and high encapsulation efficiency of therapeutic agents (e.g., drugs and cells). At present, multiple techniques are utilized for the fabrication of HMSs and encapsulation of therapeutic agents. The HMSs can be produced and used in different states to match specific utilizations. These desirable properties, along with their injectability, bestow HMSs with mutifunctionalities that can be utilized for a variety of biomedical applications (e.g., delivery of biologics, tissue regeneration, and bio‐lubrication), and thus enable them to be promising tools for tackling a variety of clinical diseases. Herein, the focus is the fabrication and application of therapeutic HMSs for i) bone disorders, ii) cartilage and osteochondral disorders, iii) intervertebral disc (IVD) disorders, and iv) neurovascular disorders, with the aim of overviewing the recent progress to summarize key contributions and findings and highlight the limitations and opportunities in this field.

Causal association of leisure sedentary behavior and cervical spondylosis, sciatica, intervertebral disk disorders, and low back pain: a Mendelian randomization study.

Some studies suggest sedentary behavior is a risk factor for musculoskeletal disorders. This study aimed to investigate the potential causal association between leisure sedentary behavior (LSB) (including television (TV) viewing, computer use, and driving) and the incidence of sciatica, intervertebral disk degeneration (IVDD), low back pain (LBP), and cervical spondylosis (CS). We obtained the data of LSB, CS, IVDD, LBP, sciatica and proposed mediators from the gene-wide association studies (GWAS). The causal effects were examined by Inverse Variance Weighted (IVW) test, MR-Egger, weighted median, weighted mode and simple mode. And sensitivity analysis was performed using MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) and MR-Egger intercept test. Multivariable MR (MVMR) was conducted to investigate the independent factor of other LSB; while two-step MR analysis was used to explore the potential mediators including Body mass index (BMI), smoking initiation, type 2 diabetes mellitus (T2DM), major depressive disorder (MDD), schizophrenia, bipolar disorder between the causal association of LSB and these diseases based on previous studies. Genetically associated TV viewing was positively associated with the risk of CS (OR = 1.61, 95%CI = 1.25 to 2.07, p = 0.002), IVDD (OR = 2.10, 95%CI = 1.77 to 2.48, p = 3.79 × 10-18), LBP (OR = 1.84, 95%CI = 1.53 to 2.21, p = 1.04 × 10-10) and sciatica (OR = 1.82, 95% CI = 1.45 to 2.27, p = 1.42 × 10-7). While computer use was associated with a reduced risk of IVDD (OR = 0.66, 95%CI = 0.55 to 0.79, p = 8.06 × 10-6), LBP (OR = 0.49, 95%CI = 0.40 to 0.59, p = 2.68 × 10-13) and sciatica (OR = 0.58, 95%CI = 0.46 to 0.75, p = 1.98 × 10-5). Sensitivity analysis validated the robustness of MR outcomes. MVMR analysis showed that the causal effect of TV viewing on IVDD (OR = 1.59, 95%CI = 1.13 to 2.25, p = 0.008), LBP (OR = 2.15, 95%CI = 1.50 to 3.08, p = 3.38 × 10-5), and sciatica (OR = 1.61, 95%CI = 1.03 to 2.52, p = 0.037) was independent of other LSB. Furthermore, two-step MR analysis indicated that BMI, smoking initiation, T2DM may mediate the causal effect of TV viewing on these diseases. This study provides empirical evidence supporting a positive causal association between TV viewing and sciatica, IVDD and LBP, which were potentially mediated by BMI, smoking initiation and T2DM.

Combining adhesive and nonadhesive injectable hydrogels for intervertebral disc repair in an ovine discectomy model.

Intervertebral disc (IVD) disorders (e.g., herniation) directly contribute to back pain, which is a leading cause of global disability. Next-generation treatments for IVD herniation need advanced preclinical testing to evaluate their ability to repair large defects, prevent reherniation, and limit progressive degeneration. This study tested whether experimental, injectable, and nonbioactive biomaterials could slow IVD degeneration in an ovine discectomy model. Ten skeletally mature sheep (4-5.5 years) experienced partial discectomy injury with cruciate-style annulus fibrosus (AF) defects and 0.1 g nucleus pulposus (NP) removal in the L1-L2, L2-L3, and L3-L4 lumbar IVDs. L4-L5 IVDs were Intact controls. IVD injury levels received: (1) no treatment (Injury), (2) poly (ethylene glycol) diacrylate (PEGDA), (3) genipin-crosslinked fibrin (FibGen), (4) carboxymethylcellulose-methylcellulose (C-MC), or (5) C-MC and FibGen (FibGen + C-MC). Animals healed for 12 weeks, then IVDs were assessed using computed tomography (CT), magnetic resonance (MR) imaging, and histopathology. All repaired IVDs retained ~90% of their preoperative disc height and showed minor degenerative changes by Pfirrmann grading. All repairs had similar disc height loss and Pfirrmann grade as Injury IVDs. Adhesive AF sealants (i.e., PEGDA and FibGen) did not herniate, although repair caused local endplate (EP) changes and inflammation. NP repair biomaterials (i.e., C-MC) and combination repair (i.e., FibGen + C-MC) exhibited lower levels of degeneration, less EP damage, and less severe inflammation; however, C-MC showed signs of herniation via biomaterial expulsion. All repair IVDs were noninferior to Injury IVDs by IVD height loss and Pfirrmann grade. C-MC and FibGen + C-MC IVDs had the best outcomes, and may be appropriate for enhancement with bioactive factors (e.g., cells, growth factors, and miRNAs). Such bioactive factors appear to be necessary to prevent injury-induced IVD degeneration. Application of AF sealants alone (i.e., PEGDA and FibGen) resulted in EP damage and inflammation, particularly for PEGDA IVDs, suggesting further material refinements are needed.

Multi-Trait Exome-Wide Association Study of Back Pain-Related Phenotypes.

Back pain (BP) is a major contributor to disability worldwide, with heritability estimated at 40-60%. However, less than half of the heritability is explained by common genetic variants identified by genome-wide association studies. More powerful methods and rare and ultra-rare variant analysis may offer additional insight. This study utilized exome sequencing data from the UK Biobank to perform a multi-trait gene-based association analysis of three BP-related phenotypes: chronic back pain, dorsalgia, and intervertebral disc disorder. We identified the SLC13A1 gene as a contributor to chronic back pain via loss-of-function (LoF) and missense variants. This gene has been previously detected in two studies. A multi-trait approach uncovered the novel FSCN3 gene and its impact on back pain through LoF variants. This gene deserves attention because it is only the second gene shown to have an effect on back pain due to LoF variants and represents a promising drug target for back pain therapy.

Analysis of Conservative Treatment Trends for Lumbar Disc Herniation with Radiculopathy in Korea: A Population-Based Cross-Sectional Study.

This study aimed to analyze the trends in conservative treatment and associated medical costs for lumbar intervertebral disc disorders with radiculopathy in Korea. This population-based cross-sectional study included patients aged ≥ 20 years with at least one "intervertebral disc disorder with radiculopathy" claim (Korean Standard Classification of Diseases (KCD)-7 code: M511) who sought treatment from tertiary, general, or Korean Medicine hospitals or clinics between 2010 and 2019 and whose data were extracted from the Korean Health Insurance Review and Assessment Service National Patients Sample database. Intervention frequency, ratio, and medical costs, including medication, were analyzed. The number of patients with lumbar intervertebral disc disorders and radiculopathy undergoing conservative treatment increased by >30%, and medical costs increased from USD 3,342,907 to USD 5,600,456 during the 10-year period. The non-surgical treatments mainly used were medication and physiotherapy, and the most commonly prescribed medication was non-opioid analgesics. Meanwhile, the number of patients who used nerve plexus and root and ganglion nerve blocks showed the most significant increase. In conclusion, the number of patients with radiculopathy who received nerve blocks, particularly nerve plexus and root and ganglion nerve blocks, and related expenditure increased, implying a gradual shift in medical decisions from systemic pain reduction to specific and targeted pain treatments. Future studies and clinical practice guidelines may require further inspection of real-world practice to advise optimal treatment choices for an effective treatment plan.

Causal effects of body mass index, education, and lifestyle behaviors on intervertebral disc disorders: Mendelian randomization study.

This study aimed to investigate the causal risk factors for intervertebral disc disorders (IVDD) to help establish prevention strategies for IVDD-related diseases. We performed two-sample Mendelian randomization analyses to investigate the causal effects of body mass index (BMI), education, and lifestyle behaviors (sedentary behavior, smoking, and sleeping) on thoracic/thoracolumbar/lumbosacral IVDD (TTL-IVDD) and cervical IVDD. The inverse-variance weighted (IVW) method was conducted as the primary model to pool effect sizes using odds ratio and 95% confidence interval. The strength of causal evidence was evaluated from the effect size and different Mendelian randomization methods (MR-Egger/weighted median/weighted mode method, Cochran's Q test, leave-one-out analysis, MR Steiger, MR-PRESSO and radial IVW analyses). We found strong evidence for the causal associations between IVDD and BMI (TTL-IVDD, 1.27 [1.18, 1.37], p = 2.40 × 10-10 ; cervical IVDD, 1.24 [1.12, 1.37, p = 6.58 × 10-5 ), educational attainment (TTL-IVDD, 0.57 [0.51, 0.64], p = 9.64 × 10-21 ; cervical IVDD, 0.58 [0.49, 0.68], p = 1.78 × 10-10 ), leisure television watching (TTL-IVDD, 1.54 [1.29, 1.84], p = 7.80 × 10-6 ; cervical IVDD, 1.65 [1.29, 2.11], p = 0.0001), smoking initiation (TTL-IVDD, 1.37 [1.25, 1.50], p = 1.78 × 10-10 ; cervical IVDD, 1.32 [1.16, 1.51], p = 6.49 × 10-5 ), short sleep (TTL-IVDD, 1.28 [1.09, 1.49], p = 0.0027; cervical IVDD, 1.53 [1.21, 1.94], p = 0.0008), or frequent insomnia (TTL-IVDD, 1.20 [1.11, 1.30], p = 1.54 × 10-5 ; cervical IVDD, 1.37 [1.20, 1.57], p = 7.80 × 10-6 ). This study provided genetic evidence that increased BMI, low educational attainment, sedentary behavior by leisure television watching, smoking initiation, short sleep, and frequent insomnia were causal risk factors for IVDD. More efforts should be directed toward increasing public awareness of these modifiable risk factors and mobilizing individuals to adopt healthy lifestyles.

Global prevalence of hospital admissions for low back pain: a systematic review with meta-analysis

ObjectivesTo determine the proportion of low back pain presentations that are admitted to hospital from the emergency department (ED), the proportion of hospital admissions due to a primary diagnosis of...

Potential causal association between leisure sedentary behaviors, physical activity and musculoskeletal health: A Mendelian randomization study.

Increasing evidence shows that leisure sedentary behaviors (LSB) and physical activity (PA) are associated with various musculoskeletal disorders. However, the causality between LSB/PA and musculoskeletal health remained unknown. In this study, we aimed to evaluate the causal relationships between LSB/PA and lower back pain (LBP), intervertebral disc disorder (IVDD), rheumatoid arthritis (RA), and bone mineral density (BMD) by using a two-sample Mendelian randomization method. The exposure data were obtained from large-scale genome-wide association studies (GWAS), including the PA dataset (self-reported PA, n = 377,234; accelerometer-assessed PA, n = 91,084) and LSB dataset (n = 422,218). The outcome data were derived from the FinnGen LBP dataset (n = 248,528), FinnGen IVDD dataset (n = 256,896), BMD GWAS dataset (n = 56,284), and RA GWAS dataset (n = 58,284). The causal relationships were estimated with inverse variance weighted (IVW), MR-Egger, and weighted median methods. Sensitivity analyses were performed with Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis to estimate the robustness of our findings. Genetically predicted leisure television watching increased the risk of LBP (OR = 1.68, 95% CI 1.41 to 2.01; P = 8.23×10-9) and IVDD (OR = 1.62, 95% CI 1.37 to 1.91; P = 2.13 × 10-8). In addition, this study revealed a potential causal relationship between computer use and a reduced risk of IVDD (OR = 0.60, 95% CI 0.42 to 0.86; P = 0.005) and RA (OR = 0.28, 95% CI 0.13 to 0.60; P = 0.001). Our results suggest that leisure television watching is a risk factor for LBP and IVDD, whereas leisure computer use may act as a protective factor against IVDD and RA. These findings emphasized the importance of distinguishing between different sedentary behaviors in musculoskeletal disease studies.

Effect of Disease Severity on Comorbid Conditions in Atopic Dermatitis: Nationwide Registry-Based Investigation in Finnish Adults

The majority of registry studies on atopic dermatitis include only patients and diagnoses from specialized healthcare. The aim of this retrospective, real-world cohort study was to evaluate the effect of atopic dermatitis severity on comorbidities and total morbidity, with comprehensive data from both primary and specialty healthcare registries covering the entire Finnish adult population. In total, 124,038 patients were identified (median age 46 years; 68% female) and stratified by disease severity. All regression analyses (median follow-up 7.0 years) were adjusted at a minimum for age, sex, obesity, and educational level. Compared with mild atopic dermatitis, severe atopic dermatitis was significantly associated with multiple morbidities, including neurotic, stress-related and somatoform disorders, abscesses, erysipelas/cellulitis, impetigo, herpes zoster, extragenital herpes, bacterial conjunctivitis, septicaemia, lymphomas, alopecia areata, urticaria, other dermatitis, contact allergy, osteoporosis, and intervertebral disc disorders (p < 0.001). In addition, there were significant associations with alcohol dependence, depression, condylomas, rosacea, migraine, sleep apnoea, hypertension, enthesopathies, atherosclerosis, and drug-induced cataract (p < 0.05). Odds ratios were modest and mostly were between 1.10 and 2.75. Furthermore, patients with severe atopic dermatitis had lower incidences of prostate cancer, cystitis, and anogenital herpes than patients with mild atopic dermatitis (p < 0.05). These results suggest that severe atopic dermatitis results in significant overall morbidity.

SLC26A1 is a major determinant of sulfate homeostasis in humans.

Sulfate plays a pivotal role in numerous physiological processes in the human body, including bone and cartilage health. A role of the anion transporter SLC26A1 (Sat1) for sulfate reabsorption in the kidney is supported by the observation of hyposulfatemia and hypersulfaturia in Slc26a1-knockout mice. The impact of SLC26A1 on sulfate homeostasis in humans remains to be defined. By combining clinical genetics, functional expression assays, and population exome analysis, we identify SLC26A1 as a sulfate transporter in humans and experimentally validate several loss-of-function alleles. Whole-exome sequencing from a patient presenting with painful perichondritis, hyposulfatemia, and renal sulfate wasting revealed a homozygous mutation in SLC26A1, which has not been previously described to the best of our knowledge. Whole-exome data analysis of more than 5,000 individuals confirmed that rare, putatively damaging SCL26A1 variants were significantly associated with lower plasma sulfate at the population level. Functional expression assays confirmed a substantial reduction in sulfate transport for the SLC26A1 mutation of our patient, which we consider to be novel, as well as for the additional variants detected in the population study. In conclusion, combined evidence from 3 complementary approaches supports SLC26A1 activity as a major determinant of sulfate homeostasis in humans. In view of recent evidence linking sulfate homeostasis with back pain and intervertebral disc disorder, our study identifies SLC26A1 as a potential target for modulation of musculoskeletal health.

Characteristics of Work-Related Musculoskeletal Disorders in Korea.

This study aimed to analyze trends for work-related musculoskeletal disorders (WMSDs) from 1996 to 2020 in Korea and to investigate characteristics of WMSDs, including WMSD approval rates, distribution by WMSD names, and the effects of industry type and size, and workers’ age and gender on WMSD occurrence. The data included those obtained from the official yearbooks for industrial accidents published by the Ministry of Employment and Labor and those obtained personally from the Korea Workers’ Compensation & Welfare Service. The results showed that although the incidence of WMSDs differed by year, approximately 9500 cases of WMSDs occurred in 2019 and 2020, the incidence rate of WMSDs was approximately 5.0 per 10,000 workers, and the proportions of WMSDs among industrial accidents were almost 9%. Low back pain was the leading cause of WMSDs; WMSDs occupied 9.5−71.5% of total occupational diseases by year and occurred most frequently in the manufacturing industry, followed by construction, transportation/warehouse and communication, and mining industries, and nearly 60% of WMSDs occurred in small business with <50 workers. Among chronic WMSDs, rotator cuff syndrome in the shoulder ranked first, intervertebral disc disorders second, and rotator cuff and tendon injuries third. By body parts, the shoulder was most susceptible to chronic WMSDs, followed by the low back, leg, and elbow/lower arm. The chi-square test and logistic regression analysis showed that industry type and size and workers’ gender and age were significantly associated with WMSD approval. It can be concluded that the WMSD preventive efforts should focus on low back pain and rotator cuff syndrome by WMSD name, manufacturing by industry, small business by industry size, men by gender, and aged workers by age.

Chuna manual therapy in patients with functional dyspepsia: A protocol for systematic review and meta-analysis

Functional dyspepsia (FD) is a functional gastrointestinal disease that occurs without any explanatory organic disease, involving discomforts in upper abdomen such as bloating or pain after eating food. Although there is a standard treatment for FD, the disease often recurs or develops into a chronic condition, resulting in poor quality of life for the patients and high socioeconomic burden. Chuna therapy is a manual treatment commonly used in traditional Korean medicine (TKM) for musculoskeletal diseases such as intervertebral disc disorders and spinal stenosis. Recent studies have shown that Chuna therapy can be applied for the treatment of FD and is helpful in symptom improvement; however, high-quality evidence is still lacking. Therefore, this systematic review protocol intends to analyze the efficacy and safety of Chuna manual therapy for FD. We will search 11 electronic databases, including the Embase and MEDLINE, from their inception to June 2022. Two reviewers will independently screen the relevant studies and determine their compatibility with the search eligibility of this review. The primary outcome is the total clinical effective rate, and other variables such as dyspepsia-related symptom score, quality of life score, and adverse events will be analyzed. We will evaluate the quality of the evidence and interpret the overall findings using the Cochrane risk-of-bias tool for randomized trials and the Grading of Recommendations Assessment, Development, and Evaluation tool. To reduce the heterogeneity of the included studies, subgroup analysis according to the subdivisions of FD will be conducted and operational methods of Chuna therapy will be recorded in detail. This protocol describes the systematic review to establish scientific evidence of Chuna manual therapy in FD patients. We will categorize various types of Chuna therapy for providing guidelines that can be applied reproducibly in clinical practice.

Genome-wide association meta-analysis of knee and hip osteoarthritis uncovers genetic differences between patients treated with joint replacement and patients without joint replacement

ObjectivesOsteoarthritis is a common and severe, multifactorial disease with a well-established genetic component. However, little is known about how genetics affect disease progression, and thereby the need for joint placement....

Noncoding rare variants in PANX3 are associated with chronic back pain.

Back pain is the leading cause of years lived with disability worldwide, yet surprisingly, little is known regarding the biology underlying this condition. The impact of genetics is known for chronic back pain: its heritability is estimated to be at least 40%. Large genome-wide association studies have shown that common variation may account for up to 35% of chronic back pain heritability; rare variants may explain a portion of the heritability not explained by common variants. In this study, we performed the first gene-based association analysis of chronic back pain using UK Biobank imputed data including rare variants with moderate imputation quality. We discovered 2 genes, SOX5 and PANX3 , influencing chronic back pain. The SOX5 gene is a well-known back pain gene. The PANX3 gene has not previously been described as having a role in chronic back pain. We showed that the association of PANX3 with chronic back pain is driven by rare noncoding intronic polymorphisms. This result was replicated in an independent sample from UK Biobank and validated using a similar phenotype, dorsalgia, from FinnGen Biobank. We also found that the PANX3 gene is associated with intervertebral disk disorders. We can speculate that a possible mechanism of action of PANX3 on back pain is due to its effect on the intervertebral disks.

Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology

Back pain is a common and debilitating disorder with largely unknown underlying biology. Here we report a genome-wide association study of back pain using diagnoses assigned in clinical practice; dorsalgia (119,100 cases, 909,847 controls) and intervertebral disc disorder (IDD) (58,854 cases, 922,958 controls). We identify 41 variants at 33 loci. The most significant association (ORIDD = 0.92, P = 1.6 × 10−39; ORdorsalgia = 0.92, P = 7.2 × 10−15) is with a 3’UTR variant (rs1871452-T) in CHST3, encoding a sulfotransferase enzyme expressed in intervertebral discs. The largest effects on IDD are conferred by rare (MAF = 0.07 − 0.32%) loss-of-function (LoF) variants in SLC13A1, encoding a sodium-sulfate co-transporter (LoF burden OR = 1.44, P = 3.1 × 10−11); variants that also associate with reduced serum sulfate. Genes implicated by this study are involved in cartilage and bone biology, as well as neurological and inflammatory processes.

Hemoglobin and adult height loss among Japanese workers: A retrospective study.

Height loss starting in middle age is reported to be associated with increased all-cause and cardiovascular mortality later in life. However, the mechanisms underlying this association are unclear. Hypoxia and oxidative stress, which are known causes of cardiovascular disease, could be reduced by hemoglobin. Therefore, hemoglobin could be inversely associated with height loss. However, high body mass index (BMI) is a known risk factor for intervertebral disc disorder, a known cause of height loss in adults. High BMI might confound the association between hemoglobin and height loss. Therefore, we performed analyses stratified by BMI status. To clarify the association between hemoglobin and height loss, we conducted a retrospective study of Japanese workers (6,471 men and 3,180 women) aged 40–74 years. Height loss was defined as being in the highest quintile of height decrease per year. In men overall and men with BMI <25 kg/m2, hemoglobin was significantly inversely associated with height loss; but no association was observed for men with high BMI (BMI ≥25 kg/m2) and for women. For men, after adjusting for known cardiovascular risk factors, adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for height loss with each 1 standard deviation (SD) increase in hemoglobin (1.0 g/dL for men and 0.8g/dL for women) were 0.89 (0.83, 0.95) for men overall, 0.82 (0.75, 0.89) for men who do not have high BMI, and 1.01 (0.92, 1.12) for men with high BMI. For women, the corresponding values were 0.97 (0.89, 1.06), 0.98 (0.89, 1.09), and 0.93 (0.75, 1.15) respectively. Hemoglobin is significantly inversely associated with height loss in men who do not have high BMI, but not in men with high BMI or women. These results help clarify the mechanisms underlying height loss, which has been reported to be associated with a higher risk of mortality in adults.

The association between depression and chronic lower back pain from disc degeneration and herniation of the lumbar spine.

Chronic lower back pain induced by lumbar disc degeneration or herniation exerts a great impact on patients' daily lives. Depression and anxiety often exist among patients with lower back pain. Some studies mentioned about mechanisms, such as inflammatory biomarkers, which are commonly seen in herniated intervertebral disc (HIVD) and major depressive disorder (MDD). Method: Our study used a large database from the National Health Insurance to explore the incidence rate of MDD in patients with HIVD and correlated risk factors. A total of 41,874 patients with HIVD were included in this work. The control group was matched by using propensity scores. Results: The results showed a temporal association between prior HIVD and subsequent MDD after adjusting for potential confounding factors. Patients with HIVD were at high risk of developing MDD (hazard ratio, HR: 9.00, 95% confidence interval, CI: 7.196-11.257) even after adjusting for demographic characteristics and comorbidities (HR: 8.47, 95% CI: 6.84-10.49, p < 0.0001). Conclusions: The combination of HIVD and MDD represents an important health problem that is associated with higher disability rates, socioeconomic disadvantage, and greater utilization of health care resources. Early detection and combined treatment of depressive symptoms may benefit patients with HIVD.

Health problems among Swedish ambulance personnel: long-term risks compared to other professions in Sweden – a longitudinal register study

Objectives. This study aimed to investigate whether Swedish ambulance personnel differ in the extent of suffering from health problems compared to other occupational groups. Methods. Two cohorts of ambulance personnel from 2001 and 2008, with 1778 and 2753 individuals, respectively, were followed regarding assignment of diagnostic coding (International Classification of Diseases codes) until 2016. These two cohorts represent all who were employed as ambulance personnel by public employers during these years. Two comparison groups were added: other healthcare workers and other professions. All data were retrieved from national registers. The χ 2 test was were used for statistical calculation. Results. Swedish ambulance personnel are at a significantly higher risk of being affected by ‘Paroxysmal tachycardia, atrial fibrillation and flutter, other cardiac arrhythmias’, by ‘Other intervertebral disc disorders’ and by ‘Arthropathies’, when compared to both comparison groups in both cohorts. Almost similar results were seen for ‘Gonarthrosis’ and for ‘Dorsopathies’. Conclusions. Swedish ambulance personnel run the risk of being affected by certain diseases and injuries to a greater extent compared to other professions.