SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2.

We show that SARS-CoV-2 spike protein interacts with both cellular heparan sulfate and angiotensin-converting enzyme 2 (ACE2) through its receptor-binding domain (RBD). Docking studies suggest a heparin/heparan sulfate-binding site adjacent to the ACE2-binding site. Both ACE2 and heparin can bind independently to spike protein in vitro, and a ternary complex can be generated using heparin as a scaffold. Electron micrographs of spike protein suggests that heparin enhances the open conformation of the RBD that binds ACE2. On cells, spike protein binding depends on both heparan sulfate and ACE2. Unfractionated heparin, non-anticoagulant heparin, heparin lyases, and lung heparan sulfate potently block spike protein binding and/or infection by pseudotyped virus and authentic SARS-CoV-2 virus. We suggest a model in which viral attachment and infection involves heparan sulfate-dependent enhancement of binding to ACE2. Manipulation of heparan sulfate or inhibition of viral adhesion by exogenous heparin presents new therapeutic opportunities.

Clofazimine broadly inhibits coronaviruses including SARS-CoV-2.

The COVID-19 pandemic is the third outbreak this century of a zoonotic disease caused by a coronavirus, following the emergence of severe acute respiratory syndrome (SARS) in 20031 and Middle East respiratory syndrome (MERS) in 20122. Treatment options for coronaviruses are limited. Here we show that clofazimine-an anti-leprosy drug with a favourable safety profile3-possesses inhibitory activity against several coronaviruses, and can antagonize the replication of SARS-CoV-2 and MERS-CoV in a range of in vitro systems. We found that this molecule, which has been approved by the US Food and Drug Administration, inhibits cell fusion mediated by the viral spike glycoprotein, as well as activity of the viral helicase. Prophylactic or therapeutic administration of clofazimine in a hamster model of SARS-CoV-2 pathogenesis led to reduced viral loads in the lung and viral shedding in faeces, and also alleviated the inflammation associated with viral infection. Combinations of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted viral shedding from the upper respiratory tract. Clofazimine, which is orally bioavailable and comparatively cheap to manufacture, is an attractive clinical candidate for the treatment of outpatients and-when combined with remdesivir-in therapy for hospitalized patients with COVID-19, particularly in contexts in which costs are an important factor or specialized medical facilities are limited. Our data provide evidence that clofazimine may have a role in the control of the current pandemic of COVID-19 and-possibly more importantly-in dealing with coronavirus diseases that may emerge in the future.

Noninvasive detection of any-stage cancer using free glycosaminoglycans.

Cancer mortality is exacerbated by late-stage diagnosis. Liquid biopsies based on genomic biomarkers can noninvasively diagnose cancers. However, validation studies have reported ~10% sensitivity to detect stage I cancer in a screening population and specific types, such as brain or genitourinary tumors, remain undetectable. We investigated urine and plasma free glycosaminoglycan profiles (GAGomes) as tumor metabolism biomarkers for multi-cancer early detection (MCED) of 14 cancer types using 2,064 samples from 1,260 cancer or healthy subjects. We observed widespread cancer-specific changes in biofluidic GAGomes recapitulated in an in vivo cancer progression model. We developed three machine learning models based on urine (Nurine = 220 cancer vs. 360 healthy) and plasma (Nplasma = 517 vs. 425) GAGomes that can detect any cancer with an area under the receiver operating characteristic curve of 0.83-0.93 with up to 62% sensitivity to stage I disease at 95% specificity. Undetected patients had a 39 to 50% lower risk of death. GAGomes predicted the putative cancer location with 89% accuracy. In a validation study on a screening-like population requiring ≥ 99% specificity, combined GAGomes predicted any cancer type with poor prognosis within 18 months with 43% sensitivity (21% in stage I; N = 121 and 49 cases). Overall, GAGomes appeared to be powerful MCED metabolic biomarkers, potentially doubling the number of stage I cancers detectable using genomic biomarkers.

The importance of a healthy lifestyle despite chronic pain: Prospective cohort with 11-year register follow-up.

The purpose of the study was to investigate to which extent a healthy lifestyle in female healthcare workers with chronic pain contributes to reducing the risk of disability pension. We conducted a prospective cohort study with an 11-year registry follow-up. Overall, 2386 Danish female healthcare workers with chronic pain completed a questionnaire about work and lifestyle (leisure-time physical activity, smoking, and body mass index (BMI)). Data on disability benefit payments were obtained from the Danish Register for Evaluation of Marginalization. Two models (minimally and fully adjusted for different potential confounders) were tested using the Cox proportional hazards model. During the follow-up period, 17.9% of the healthcare workers obtained disability pension. Low levels of leisure time physical activity (reference: moderate level) increased the risk of disability pension in the minimally (Hazard Ratio: 1.38 (95% CI: 1.14-1.69)) and fully adjusted models (Hazard Ratio: 1.27 (95% CI: 1.04-1.56)). Being highly physically active, as opposed to being moderately active, did not confer additional protection. Additionally, a positive association was observed between smoking and disability pension in the minimally adjusted model (Hazard Ratio: 1.27 (95% CI: 1.05-1.54)). BMI was not an influential factor. In female healthcare workers with chronic pain, at least moderate levels of physical activity is a protective factor for disability pension. Effective promotion strategies should be designed for both workplace and non-workplace settings.

Fatal drug overdoses in individuals treated pharmacologically for chronic pain: a nationwide register-based study.

INTRODUCTION: Chronic pain patients may be at an increased risk for drug overdoses as a result of comorbid psychiatric disorders and treatment with risk-increasing prescription medications, such as opioids. We aimed to characterise fatal drug overdoses and investigate factors associated with the deaths among individuals who had been treated pharmacologically for chronic pain. METHODS: We included all individuals who received analgesics reimbursed for chronic pain in Norway during 2010-9 (n=569 047). Among this population, we identified all individuals with drug overdoses as cause of death (cases). Extracting data from national registries on diagnoses, filled prescriptions, and socioeconomic variables, we used a nested case-control design to compare the cases with age- and sex-matched controls from the study population. RESULTS: Overall, 623 (0.11%) individuals in the study population died of an overdose. Most, 66.8%, had overdosed accidentally, and 61.9% as a result of pharmaceutically available opioids. Compared with the controls (n=62 245), overdoses overall were associated strongly with substance use disorders (adjusted odds ratio 7.78 [95% confidence interval 6.20-9.77]), use of combinations of opioids, benzodiazepines and related drugs and gabapentinoids (4.60 [3.62-5.85]), previous poisoning with pharmaceuticals (2.78 [2.20-3.51]), and with living alone the last year of life (2.11 [1.75-2.54]). Intentional overdoses had a stronger association with previous poisonings with pharmaceuticals whereas accidental overdoses were strongly associated with substance use disorders. CONCLUSIONS: This study shows the need for better identification of overdose and suicide risk in individuals treated for chronic pain. Extra caution is needed when treating complex comorbid disorders, especially with overdose risk-increasing medications.

Change in self-reported somatic symptoms among patients in opioid maintenance treatment from baseline to 1-year follow-up.

BACKGROUND: High somatic comorbidity is common among patients in treatment for opioid use disorder (OUD). The present study aims to investigate changes in self-reported somatic health conditions and somatic symptoms among patients entering opioid maintenance treatment (OMT) programs. METHODS: We used data from the Norwegian Cohort of Patients in OMT and Other Drug Treatment (NorComt) study. Of 283 patients who entered OMT, 176 were included for analysis at a 1-year follow-up. Participants provided self-reported data during structured interviews on somatic conditions, somatic symptoms, substance use severity measures, and mental distress. A multivariable linear regression analysis identified factors associated with changes in the burden of somatic symptoms. RESULTS: Patients entering OMT reported a high prevalence of somatic conditions at the beginning of treatment, with 3 of 5 patients reporting at least one. The most prevalent condition was hepatitis C, followed by asthma and high blood pressure. Patients reported experiencing a high number of somatic symptoms. The intensity of these symptoms varied across a wide spectrum, with oral health complaints and reduced memory perceived as the most problematic. Overall, for the entire sample, there was no significant change in somatic symptoms from baseline to 1 year. Further analysis indicated that those who reported a higher burden of somatic symptoms at baseline had the greatest improvement at the 1-year follow-up. A higher number of somatic conditions and higher mental distress at baseline was associated with improvements in somatic symptoms burden at follow-up. CONCLUSIONS: Patients in OMT report a range of somatic conditions and somatic symptoms. Given the wide range of symptoms reported by patients in OMT, including some at high intensity levels, healthcare providers should take into consideration the somatic healthcare needs of individuals in OMT populations. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov no. NCT05182918. Registered 10/01/2022 (the study was retrospectively registered).

Workplace sexual and gender-based harassment in Denmark: a comparison of the self-labelling and behavioural list method.

AIM: Knowledge about the prevalence of sexual and gender-based harassment is hampered by disagreements about definitions and measurement methods. The two most common measurement methods are the self-labelling (a single question about exposure to sexual harassment) and the behavioural list method (an inventory of sexually harassing behaviours). The aim of this paper was to compare the self-labelling and the behavioural list methods for measuring sexual harassment and assess the association with depressive symptoms. METHODS: The study is based on a convenience sample of 1686 individuals employed in 29 workplaces in Denmark. Survey data were collected from November 2020 until June 2021 and there were 1000 participants with full data on key variables. We used a linear mixed-effects model to examine the relationship between sexual harassment and depressive symptoms. RESULTS: In total, 2.5% self-labelled as being sexually harassed, while 19.0% reported exposure to at least one type of sexual and gender-based harassment using the behavioural list method. Both groups reported higher levels of depressive symptoms compared with non-exposed employees. The most common types of behaviours were: that someone spoke derogatorily about women/men (11.6%); being belittled because of one's gender or sexuality (4.7%); and unwanted comments about one's body, clothes or lifestyle (4.5%). CONCLUSIONS: The behavioural list method yielded a higher prevalence of sexual and gender-based harassment compared with the self-labelling method. Self-labelling and reporting at least one type of sexual and gender-based harassment was associated with depressive symptoms.

Evaluation of heroin-assisted treatment in Norway: protocol for a mixed methods study.

BACKGROUND: Opioid agonist treatment (OAT) for patients with opioid use disorder (OUD) has a convincing evidence base, although variable retention rates suggest that it may not be beneficial for all. One of the options to include more patients is the introduction of heroin-assisted treatment (HAT), which involves the prescribing of pharmaceutical heroin in a clinical supervised setting. Clinical trials suggest that HAT positively affects illicit drug use, criminal behavior, quality of life, and health. The results are less clear for longer-term outcomes such as mortality, level of function and social integration. This protocol describes a longitudinal evaluation of the introduction of HAT into the OAT services in Norway over a 5-year period. The main aim of the project is to study the individual, organizational and societal effects of implementing HAT in the specialized healthcare services for OUD. METHODS: The project adopts a multidisciplinary approach, where the primary cohort for analysis will consist of approximately 250 patients in Norway, observed during the period of 2022-2026. Cohorts for comparative analysis will include all HAT-patients in Denmark from 2010 to 2022 (N = 500) and all Norwegian patients in conventional OAT (N = 8300). Data comes from individual in-depth and semi-structured interviews, self-report questionnaires, clinical records, and national registries, collected at several time points throughout patients' courses of treatment. Qualitative analyses will use a flexible inductive thematic approach. Quantitative analyses will employ a wide array of methods including bi-variate parametric and non-parametric tests, and various forms of multivariate modeling. DISCUSSION: The project's primary strength lies in its comprehensive and longitudinal approach. It has the potential to reveal new insights on whether pharmaceutical heroin should be an integral part of integrated conventional OAT services to individually tailor treatments for patients with OUD. This could affect considerations about drug treatment even beyond HAT-specific topics, where an expanded understanding of why some do not succeed with conventional OAT will strengthen the knowledge base for drug treatment in general. Results will be disseminated to the scientific community, clinicians, and policy makers. TRIAL REGISTRATION: The study was approved by the Norwegian Regional Committee for Medical and Health Research Ethics (REK), ref.nr.:195733.

Change in substance use among patients in opioid maintenance treatment: baseline to 1-year follow-up.

BACKGROUND: Individuals with opioid use disorder (OUD) often have concurrent use of non-opioid substances. When patients enter opioid maintenance treatment (OMT), less is known about outcomes regarding the use of other types of drugs. Here we aimed to investigate changes in substance use among patients entering outpatient OMT, from treatment initiation to 1-year follow-up. METHODS: We used data from the prospective Norwegian Cohort of Patient in OMT and Other Drug Treatment Study (NorComt). Among 283 patients who entered OMT at participating facilities across Norway, 179 were assessed at follow-up. Of these patients, 131 were in a non-controlled environment, and were included in the present analysis. The main outcome was change in substance use. Logistic regression analysis was applied to identify factors associated with abstinence from all substances (other than agonist medication) at follow-up. RESULTS: Along with opioid use, most patients reported polysubstance use prior to entering treatment. No significant differences were found in baseline characteristics between the included and non-included groups when examining attrition. At the 1-year follow-up, reduced substance use was reported. While in treatment, around two-thirds of patients continued using other drugs to varying degrees. At follow-up, about one-third of patients reported abstinence from all drugs, apart from the agonist medication. Factors related to abstinence included a goal of abstinence at baseline (OR = 5.26; 95% CI 1.14-19.55; p = 0.013) and increasing age (OR = 1.05; 95% CI 1.00-1.09; p = 0.034). CONCLUSIONS: The majority of patients entering OMT used other substances in addition to opioids. About one-third of patients reported abstinence at the 1-year follow up. Although the majority of patients continued co-use of other drugs while in treatment, for most substances, less than 10% reported daily use at follow-up, with the exception of cannabis which was used daily/almost daily by about 2 in 10. Higher age and treatment goal at the start of OMT were important factors related to reducing concomitant substance use during treatment. These findings suggest that many patients entering OMT are in need of treatment and support related to the use of other substances, to further improve prognosis. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov no. NCT05182918. Registered 10/01/2022 (the study was retrospectively registered).

Systematic Review of Workplace Interventions to Support Young Workers' Safety, Work Environment and Health.

PURPOSE: This systematic review investigates the effectiveness of workplace interventions to support young workers' work environment, safety and health. METHODS: A systematic search was conducted in bibliographic databases including PubMed, Web of Science Core Collection and PsycInfo for English or Scandinavian articles published from 2007 to 2022. The PICO strategy guided the assessment of study relevance and the bibliographical search for randomized controlled trials (RCTs) and non-RCTs in which (1) participants were young workers (mean age: 15-29), (2) interventions were initiated and/or carried out at the workplace, (3) a comparison group was included, and (4) an outcome measure related to work environment, safety and health was reported. We categorized each included study using the intervention classification framework. The quality assessment and evidence synthesis adhered to the guidelines developed by the Institute for Work & Health (Toronto, Canada). RESULTS: A total of 33 high and medium quality studies showed a moderate level of evidence for no benefit of 'Mental training' on stress. We found limited evidence of a positive effect of the following intervention types: 'Attitude and belief' on mental health problems, 'Behavior based' on anxiety, and 'Multifaceted' on hand eczema. We found limited evidence for no benefit of the following intervention types: 'Mental training' on mental health problems, and 'Physiological modifications' on musculoskeletal disorders. The remaining intervention types showed mixed or insufficient evidence. CONCLUSIONS: Except for a moderate level of evidence for no benefit of 'Mental training' on stress, the evidence synthesis recommends, that there is not enough evidence from the scientific literature to guide current practices. The results emphasizes a strong need for high quality interventions specifically aiming at increasing or maintaining young workers' work environment, safety and health. Included studies focused mainly on individual measures, highlighting the need for studies investigating possible preventive measures at the group or organizational level.

[Mental disorders and symptoms with persistent opioid use for chronic non-cancer pain ­ a registry study]. / Psykiske lidelser og plager ved vedvarende opioidbruk for langvarige ikke-kreftrelaterte smerter ­ en registerstudie.

Background: Knowledge of mental disorders among patients with persistent opioid use for the treatment of chronic non-cancer pain is essential, as mental disorders and symptoms can exacerbate or perpetuate pain and impact on the ability of patients to manage their illness. We have studied the prevalence of mental disorders and symptoms, including substance use disorders, in patients with persistent opioid use in 2019. Material and method: Persons ≥ 18 years with persistent opioid use and persons ≥ 18 years with at least one registered mental disorder in the specialist healthcare service in 2019 were included. Data were retrieved from national health registries in Norway. Patients who received opioids reimbursed for the treatment of chronic pain were compared with those who received opioids without reimbursement. Results: The prevalence of mental disorders and symptoms was 34 % among 14 403 persons who received reimbursed opioids, and 42 % among 38 001 persons who received opioids without reimbursement. This is equivalent to a two to threefold increase in prevalence compared to the general population. There was a particularly higher prevalence of anxiety disorders and substance use disorders. The prevalence of mental disorders and symptoms was highest in the age group 18-44 years (49-55 %). Interpretation: Among patients with persistent opioid use, a large proportion had mental disorders and symptoms, which are known risk factors for developing problematic opioid use and opioid use disorder.

Genome-wide screens uncover KDM2B as a modifier of protein binding to heparan sulfate.

Heparan sulfate (HS) proteoglycans bind extracellular proteins that participate in cell signaling, attachment and endocytosis. These interactions depend on the arrangement of sulfated sugars in the HS chains generated by well-characterized biosynthetic enzymes; however, the regulation of these enzymes is largely unknown. We conducted genome-wide CRISPR-Cas9 screens with a small-molecule ligand that binds to HS. Screening of A375 melanoma cells uncovered additional genes and pathways impacting HS formation. The top hit was the epigenetic factor KDM2B, a histone demethylase. KDM2B inactivation suppressed multiple HS sulfotransferases and upregulated the sulfatase SULF1. These changes differentially affected the interaction of HS-binding proteins. KDM2B-deficient cells displayed decreased growth rates, which was rescued by SULF1 inactivation. In addition, KDM2B deficiency altered the expression of many extracellular matrix genes. Thus, KDM2B controls proliferation of A375 cells through the regulation of HS structure and serves as a master regulator of the extracellular matrix.

Do different job demands interact as predictors of long-term sickness absence? A register-based follow-up on 55 467 Danish workers.

OBJECTIVES: To assess interactions between combinations of quantitative demands, emotional demands, unclear and contradictory demands, and violence/threats of violence in the prospective association with risk of long-term sickness absence (LTSA). METHODS: We included 55 467 employees from the 2012, 2014 and 2016 waves of the Work Environment and Health in Denmark (WEHD) survey. We measured the four independent variables in the WEHD survey and assessed risk of LTSA in a national register during 12 months of follow-up. Using Cox proportional hazards models, adjusted for age, sex, educational attainment and job group, we estimated risk of LTSA and assessed deviation from additivity using relative excess risk due to interaction (RERI). RESULTS: For combinations of high emotional demands and high quantitative demands (HR 1.50; 95% CI 1.33 to 1.70; RERI 0.06; 95% CI -0.15 o 0.26) and high emotional demands and violence/threats of violence (HR 1.76; 95% CI 1.53 to 2.02; RERI 0.12; 95% CI -0.43 to 0.66) we found no indications of deviations from additive effects in predicting LTSA. For combinations of violence/threats of violence and high quantitative demands (HR 1.90; 95% CI 1.64 to 2.20; RERI 0.36; 95% CI 0.01 to 0.71) and unclear and contradictory demands and high quantitative demands (HR 1.46; 95% CI 1.31 to 1.62; RERI 0.23; 95% CI 0.04 to 0.42) the results indicated an excess risk of LTSA above additivity (ie, superadditivity). CONCLUSIONS: Participants reporting high quantitative demands combined with either violence/threats of violence or unclear and contradictory demands showed a higher risk of LTSA than expected, indicating superadditivity. Results have implications for preventing negative health effects related to adverse psychosocial working conditions.

Effects of consecutive workdays and days off on low back pain, fatigue and stress: prospective cohort study among warehouse and construction workers.

OBJECTIVES: Limited knowledge exists about day-to-day changes in physical and mental symptoms in warehouse and construction workers. This study investigated the associations between consecutive workdays and days off with low back pain (LBP) intensity, bodily fatigue and mental stress. METHODS: Participants (n=224) received daily questions for 21 days about LBP, fatigue, stress (outcome, 0-10 scales), and workdays and days off (exposure). We tested associations between 1-3 workdays (n=148) and 1-2 days off (n=158) with LBP intensity, bodily fatigue and mental stress after work and the following morning using linear mixed models with repeated measures controlling for relevant confounders. RESULTS: Consecutive workdays led to progressively increased LBP intensity, with three workdays increasing LBP intensity by 1.76 (95% CI 1.48 to 2.03) points. Bodily fatigue and mental stress increased after one workday (2.06 (95% CI 1.80 to 2.32) and 0.97 (95% CI 0.77 to 1.17) points, respectively) and remained stable for three workdays. After 1 day off, bodily fatigue and mental stress decreased -1.82 (95% CI -2.03 to -1.61) and -0.88 (95% CI -1.05 to -0.71) points, respectively, without decreasing further. In contrast, LBP intensity decreased progressively -1.09 (95% CI -1.27 to -0.91) and -1.45 (95% CI -1.67 to -1.24) points after 1 and 2 days off, respectively. CONCLUSIONS: Workdays and days off affected the outcome variables differently. LBP intensity progressively increased with consecutive workdays, while workers needed 2 days off to recover. This study provides valuable knowledge about how to organise the workweek to prevent LBP, fatigue and stress, potentially reducing labour market withdrawal.

Shared decision making and associated factors among patients with psychotic disorders: a cross-sectional study.

BACKGROUND: Shared decision making is a process where patients and clinicians collaborate to make treatment choices based on the patients' preferences and best available evidence. The implementation of shared decision making remains limited for patients with psychotic disorders despite being recommended at policy level, being advocated as ethical right and wanted by the patient's. A barrier to implementation that is often mentioned is reduced decision-making capacity among patients. The challenges of implementing shared decision making highlights a need for more knowledge on shared decision making for these patients. Moreover, the association between patient-related characteristics and shared decision making is unclear, and further research have been suggested. More knowledge of factors associated with involvement in shared decision making can enhance understanding and help to empower patients in the decision-making process. The current study examined the extent of reported shared decision making among patients with a psychotic disorder in mental health care and factors associated with shared decision making. METHODS: This study included 305 participants with a psychotic disorder from 39 clinical inpatient and outpatient sites across Norway. Shared decision making was assessed using the CollaboRATE survey. A linear mixed model was estimated to assess characteristics associated with shared decision making scores. RESULTS: The CollaboRATE mean score was 6.3 (ranging from 0 to 9), the top score was 14.1% and increased global satisfaction with services was significantly associated with a higher level of shared decision making (regression coefficient 0.27, 95% confidence interval (0.23; 0.32), p < 0.001). CONCLUSIONS: The low top score shows that few patients felt that they received the highest possible quality of shared decision making, indicating that many patients found room for improvement. This suggests that services for patients with psychotic disorders should be designed to give them a greater role in decision making. Shared decision making might play a key role in mental health care, ensuring that patients with psychotic disorders are satisfied with the services provided. TRIAL REGISTRATION: NCT03271242, date of registration: 5 Sept. 2017.

Acts of offensive behaviour and risk of disability pension in Danish female eldercare workers: prospective cohort with 11-year register follow-up.

OBJECTIVES: To investigate whether acts of offensive behaviour (threats, violence, workplace bullying and sexual harassment) in the workplace and type of perpetrator (internal or external to the workplace) of the offensive behaviours predicted risk of disability pension in Danish eldercare workers. METHODS: We merged survey responses from 8731 female eldercare workers with a national register on social transfer payments (Danish Register for Evaluation of Marginalisation (DREAM)), including all types of disability benefits. Using Cox proportional hazards models, we investigated the prospective association between self-reported exposures at baseline and the risk of receiving disability pension (any type of disability benefit payment) during 11 years of follow-up, while adjusting for potential confounders. RESULTS: Self-reported exposure to threats (hazard ratio (HR) 1.14; 95% confidence interval (CI) 1.00-1.32), violence (HR 1.16; 95% CI 1.00-1.35) and bullying (HR 1.44; 95% CI 1.22-1.71) predicted increased risk of disability pension during follow-up, when adjusted for age and educational attainment. When further adjusted for psychosocial working conditions only bullying remained a statistically significant (HR 1.39; 95% CI 1.16-1.67) predictor of disability pension. The results indicated no elevated risk for participants reporting sexual harassment. Moreover, we observed stronger associations between self-reported exposure to threats, violence and workplace bullying and risk of disability pension when the perpetrator was internal to the workplace (i.e. colleagues, managers and/or subordinates), than when the perpetrator was reported to be external to the workplace (i.e. service users, and/or relatives of service users). CONCLUSIONS: Results indicate that prevention of work-related exposure to threats, violence and workplace bullying may contribute to reduce involuntary early retirement in female eldercare workers.

Exploring exposure to multiple psychosocial work factors: prospective associations with depression and sickness absence.

BACKGROUND: Most studies on the psychosocial working environment have focused on evaluating the isolated effect of individual psychosocial work factors or looked at effects through a lens of theories such as job strain or effort-reward imbalance. However, to fathom the intricate nature of workers' experience of occupational strain, there is a need to investigate the combined and cumulative effects of multiple exposures to psychosocial work factors on workers' health. METHODS: In this prospective cohort study, we created an additive index (range 0-4) on number of baseline exposures to quantitative demands, emotional demands, role conflicts, and workplace bullying. Via logistic regression and Cox regression, we estimated the association between the additive index of psychosocial work factors and depressive disorder and long-term sickness absence (LTSA). We assessed the onset of depressive disorder using the Major Depression Inventory at 6-month follow-up and the onset of LTSA using a national register during 12-month follow-up. RESULTS: For onset of depressive disorder, high exposure to any one [odds ratio (OR) 2.98], two (OR 3.14), three (OR 6.44) and all four (OR 9.62) adverse psychosocial work factors predicted a statistically significant increased risk. For onset of LTSA, high exposure to any one [hazard ratio (HR) 1.13], two (HR 1.67), three (HR 2.31) and all four (HR 4.04) psychosocial work factors predicted an increased risk. The two latter associations were statistically significant. Trend tests indicated an exposure-response relationship for both outcomes. CONCLUSIONS: Workers reporting exposure to multiple adverse psychosocial work factors had a higher risk of developing depressive disorder and LTSA.

Effects of Acute Exercise on Affect, Anxiety, and Self-Esteem in Poly-Substance Dependent Inpatients.

INTRODUCTION: Negative affect and anxiety frequently precede the onset of drug use in those with substance use disorder (SUD). Low self-esteem may increase the risk of relapse. We examined the short-term effects of exercise on affect, anxiety, and self-esteem in inpatients with poly-SUD. METHODS: This is a multicenter randomized control trial (RCT) with a crossover design. Thirty-eight inpatients (37.3 ± 6.4 years; 84% male) from three clinics participated in 45 min of soccer, circuit training, and control condition (psychoeducation) in a random order. Positive and negative affect (PANAS), state anxiety (single item), and self-esteem (Rosenberg SE-scale) were measured immediately before, immediately after, 1-h, 2-h, and 4-h post-exercise. Heart rate and ratings of perceived exertion were taken. Effects were assessed using linear mixed effects models. RESULTS: Compared to the control condition, there were significant post-exercise improvements in positive affect (ß = 2.99, CI = 0.39: 5.58), self-esteem (ß = 1.84, CI = 0.49: 3.20), and anxiety (ß = -0.69, CI = -1.34: -0.04) after circuit training (shown) and soccer. Effects persisted 4-h post-exercise. Reductions in negative affect were observed 2-h (circuit training: ß = -3.39, CI = -6.35: -1.51) and 4-h (soccer: ß = -3.71, CI = -6.03: -1.39) post-exercise, respectively. CONCLUSION: Moderately strenuous exercise undertaken in naturalistic settings may improve mental health symptoms in poly-SUD inpatients for up to 4-h post-exercise.

Analgesics and ASH medications in workers increase the risk of disability pension and mortality: prospective cohort.

BACKGROUND: Relying on medication for musculoskeletal and mental disorders are common, but may have long-term consequences. This study investigates whether use of analgesics and anxiolytic/sedative/hypnotic (ASH) medication increases the risk of disability pension and mortality. METHODS: After completing a survey in 2005, 7773 female eldercare workers were followed for 11 years in a national register. We estimated hazard ratios (HRs) for disability pension and mortality from using analgesics and ASH. RESULTS: During follow-up, 10.3% obtained disability pension and 2.4% died. For use of analgesics, a frequency-response association for the risk of disability pension existed with HR's (95% confidence interval) of 1.30 (1.07-1.57), 2.00 (1.62-2.46) and 3.47 (2.69-4.47) for monthly, weekly and daily use, respectively. For ASH, an increased risk of disability pension also existed (HR's between 1.51 and 1.64). For mortality risk, only daily use of analgesics and ASH remained significant. Population attributable fractions of analgesics and ASH, respectively, were 30% and 3% for disability pension and 5% and 3% for mortality. CONCLUSIONS: Frequent use of analgesics and ASH medication in workers increase the risk of disability pension and early death. Better management of musculoskeletal and mental health conditions, without excessive medication use, is necessary.

Cause-Specific Mortality among Patients in Treatment for Opioid Use Disorder in Multiple Settings: A Prospective Comparative Cohort Study.

INTRODUCTION: Among people receiving current or previous opioid maintenance treatment (OMT), the leading cause of premature death is an opioid overdose. However, other causes of mortality remain high in this group. An understanding of causes of deaths across multiple settings can be useful in informing more comprehensive prevention responses. The aim of this study was to describe all non-overdose causes of death in three national cohorts (Czechia, Denmark, and Norway) among OMT patients and to explore associations of non-overdose mortality with age and gender. METHODS: This prospective comparative cohort study used national mortality registry databases for OMT patients from Czechia (2000-2019), Denmark (2000-2018), and Norway (2010-2019). Crude mortality rates and age-standardized mortality rates (ASMRs) were calculated as deaths per 1,000 person years for cause-specific mortality. RESULTS: In total, 29,486 patients were included, with 5,322 deaths recorded (18%). We found variations in causes of death among the cohorts and within gender and age groups. The leading non-overdose causes of death were accidents in Czechia and Denmark, and neoplasms in Norway. Cardiovascular deaths were highest in Czechia, particularly for women in OMT (ASMR 3.59 vs. 1.24 in Norway and 1.87 in Denmark). CONCLUSION: This study found high rates of preventable death among both genders and all age groups. Different demographic structures, variations in risk exposure, as well as variations in coding practices can explain the differences. The findings support increased efforts towards screening and preventative health initiatives among OMT patients specific to the demographic characteristics in different settings.