| 1. |
- Björkenstam, Emma, et al.
(författare)
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Mental disorders and suicidal behavior in refugees and Swedish-born individuals : is the association affected by work disability?
- 2020
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Ingår i: Social Psychiatry and Psychiatric Epidemiology. - : Springer Nature. - 0933-7954 .- 1433-9285. ; 55:8, s. 1061-1071
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAmong potential pathways to suicidal behavior in individuals with mental disorders (MD), work disability (WD) may play an important role. We examined the role of WD in the relationship between MD and suicidal behavior in Swedish-born individuals and refugees.MethodsThe study cohort consisted of 4,195,058 individuals aged 16–64, residing in Sweden in 2004–2005, whereof 163,160 refugees were followed during 2006–2013 with respect to suicidal behavior. Risk estimates were calculated as hazard ratios (HR) with 95% confidence intervals (CI). The reference groups comprised individuals with neither MD nor WD. WD factors (sickness absence (SA) and disability pension (DP)) were explored as potential modifiers and mediators.ResultsIn both Swedish-born and refugees, SA and DP were associated with an elevated risk of suicide attempt regardless of MD. In refugees, HRs for suicide attempt in long-term SA ranged from 2.96 (95% CI: 2.14–4.09) (no MD) to 6.23 (95% CI: 3.21–12.08) (MD). Similar associations were observed in Swedish-born. Elevated suicide attempt risks were also observed in DP. In Swedish-born individuals, there was a synergy effect between MD, and SA and DP regarding suicidal behavior. Both SA and DP were found to mediate the studied associations in Swedish-born, but not in refugees.ConclusionThere is an effect modification and a mediating effect between mental disorders and WD for subsequent suicidal behavior in Swedish-born individuals. Also for refugees without MD, WD is a risk factor for subsequent suicidal behavior. Particularly for Swedish-born individuals with MD, information on WD is vital in a clinical suicide risk assessment.
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| 2. |
- Clark, Alice, et al.
(författare)
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Sleep Impairment and Prognosis of Acute Myocardial Infarction : A Prospective Cohort Study
- 2014
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Ingår i: Sleep. - : Oxford University Press (OUP). - 0161-8105 .- 1550-9109. ; 37:5, s. 851-U215
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Tidskriftsartikel (refereegranskat)abstract
- Study Objectives: Impaired sleep is an established risk factor for the development of cardiovascular disease, whereas less is known about how impaired sleep affects cardiovascular prognosis. The aim of this study is to determine how different aspects of impaired sleep affect the risk of case fatality and subsequent cardiovascular events following first-time acute myocardial infarction (AMI). Design: Prospective cohort study. Setting: The Stockholm Heart Epidemiology Program, Sweden. Participants: There were 2,246 first-time AMI cases. Measurements and Results: Sleep impairment was assessed by the Karolina Sleep Questionnaire, which covers various indices of impaired sleep: disturbed sleep, impaired awakening, daytime sleepiness, and nightmares. Case fatality, defined as death within 28 days of initial AMI, and new cardiovascular events within up to 10 y of follow-up were identified through national registries. In women, disturbed sleep showed a consistently higher risk of long-term cardiovascular events: AMI (hazard ratio [HR] = 1.69; 95% confidence interval [CI] 0.95-3.00), stroke (HR = 2.61; 95% CI: 1.19-5.76), and heart failure (HR = 2.43; 95% CI: 1.18-4.97), whereas no clear effect of impaired sleep on case fatality was found in women. In men, a strong effect on case fatality (odds ratio = 3.27; 95% CI: 1.76-6.06) was observed in regard to impaired awakening; however, no consistent effect of impaired sleep was seen on long-term cardiovascular prognosis. Conclusion: Results suggest sex-specific effects of impaired sleep that differ by short-and long-term prognosis. Sleep complaints are frequent, easily recognizable, and potentially manageable. Evaluation of sleep complaints may, even if they represent prognostic markers rather than risk factors, provide additional information in clinical risk assessment that could benefit secondary cardiovascular prevention.
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| 3. |
- Clark, Alice, et al.
(författare)
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Workplace discrimination as risk factor for long-term sickness absence : Longitudinal analyses of onset and changes in workplace adversity
- 2021
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:8
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Tidskriftsartikel (refereegranskat)abstract
- Workplace discrimination may affect the health of the exposed employees, but it is not known whether workplace discrimination is also associated with an increased risk of long-term sickness absence. The aim of this study was to examine the longitudinal associations of changes in and onset of workplace discrimination with the risk of long-term sickness absence. Data on workplace discrimination were obtained from 29,597 employees participating in survey waves 2004, 2006, 2008 and/or 2010 of the Finnish Public Sector Study. Four-year changes in long-term sickness absence (>= 10 days of medically certified absence with a mental or non-mental diagnosis) were assessed. This covered successive study waves in analyses of onset of workplace discrimination as well as fixed effect analyses of change in workplace discrimination (concurrent i.e. during the exposure year and 1-year lagged i.e. within one year following exposure), by using each employee as his/her own control. The risk of long-term sickness absence due to mental disorders was greater for employees with vs. without onset of workplace discrimination throughout the 4-year period, reaching a peak at the year when the onset of discrimination was reported (adjusted risk ratio 2.13; 95% confidence interval (CI) 1.80-2.52). The fixed effects analyses showed that workplace discrimination was associated with higher odds of concurrent, but not 1-year lagged, long-term sickness absence due to mental disorders (adjusted odds ratio 1.61; 95% CI 1.33-1.96 and adjusted odds ratio 1.02; 95% CI 0.83-1.25, respectively). Long-term sickness absence due to non-mental conditions was not associated with workplace discrimination. In conclusion, these findings suggest that workplace discrimination is associated with an elevated risk of long-term sickness absence due to mental disorders. Supporting an acute effect, the excess risk was confined to the year when workplace discrimination occurred.
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| 4. |
- Granholm, Anders, et al.
(författare)
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Dexamethasone 12 mg versus 6 mg for patients with COVID-19 and severe hypoxaemia: a pre-planned, secondary Bayesian analysis of the COVID STEROID 2 trial
- 2022
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Ingår i: Intensive Care Medicine. - : SPRINGER. - 0342-4642 .- 1432-1238. ; 48:1, s. 45-55
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Tidskriftsartikel (refereegranskat)abstract
- Purpose We compared dexamethasone 12 versus 6 mg daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia in the international, randomised, blinded COVID STEROID 2 trial. In the primary, conventional analyses, the predefined statistical significance thresholds were not reached. We conducted a pre-planned Bayesian analysis to facilitate probabilistic interpretation. Methods We analysed outcome data within 90 days in the intention-to-treat population (data available in 967 to 982 patients) using Bayesian models with various sensitivity analyses. Results are presented as median posterior probabilities with 95% credible intervals (CrIs) and probabilities of different effect sizes with 12 mg dexamethasone. Results The adjusted mean difference on days alive without life support at day 28 (primary outcome) was 1.3 days (95% CrI -0.3 to 2.9; 94.2% probability of benefit). Adjusted relative risks and probabilities of benefit on serious adverse reactions was 0.85 (0.63 to 1.16; 84.1%) and on mortality 0.87 (0.73 to 1.03; 94.8%) at day 28 and 0.88 (0.75 to 1.02; 95.1%) at day 90. Probabilities of benefit on days alive without life support and days alive out of hospital at day 90 were 85 and 95.7%, respectively. Results were largely consistent across sensitivity analyses, with relatively low probabilities of clinically important harm with 12 mg on all outcomes in all analyses. Conclusion We found high probabilities of benefit and low probabilities of clinically important harm with dexamethasone 12 mg versus 6 mg daily in patients with COVID-19 and severe hypoxaemia on all outcomes up to 90 days.
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| 5. |
- Granholm, Anders, et al.
(författare)
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Empirical meropenem versus piperacillin/tazobactam for adult patients with sepsis (EMPRESS) trial : Protocol
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Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Piperacillin/tazobactam may be associated with less favourable outcomes than carbapenems in patients with severe bacterial infections, but the certainty of evidence is low. Methods: The Empirical Meropenem versus Piperacillin/Tazobactam for Adult Patients with Sepsis (EMPRESS) trial is an investigator-initiated, international, parallel-group, randomised, open-label, adaptive clinical trial with an integrated feasibility phase. We will randomise adult, critically ill patients with sepsis to empirical treatment with meropenem or piperacillin/tazobactam for up to 30 days. The primary outcome is 30-day all-cause mortality. The secondary outcomes are serious adverse reactions within 30 days; isolation precautions due to resistant bacteria within 30 days; days alive without life support and days alive and out of hospital within 30 and 90 days; 90- and 180-day all-cause mortality and 180-day health-related quality of life. EMPRESS will use Bayesian statistical models with weak to somewhat sceptical neutral priors. Adaptive analyses will be conducted after follow-up of the primary outcome for the first 400 participants concludes and after every 300 subsequent participants, with adaptive stopping for superiority/inferiority and practical equivalence (absolute risk difference <2.5%-points) and response-adaptive randomisation. The expected sample sizes in scenarios with no, small or large differences are 5189, 5859 and 2570 participants, with maximum 14,000 participants and ≥99% probability of conclusiveness across all scenarios. Conclusions: EMPRESS will compare the effects of empirical meropenem against piperacillin/tazobactam in adult, critically ill patients with sepsis. Due to the pragmatic, adaptive design with high probability of conclusiveness, the trial results are expected to directly inform clinical practice.
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| 6. |
- Granholm, Anders, et al.
(författare)
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Higher vs Lower Doses of Dexamethasone in Patients with COVID-19 and Severe Hypoxia (COVID STEROID 2) trial: Protocol for a secondary Bayesian analysis
- 2021
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Ingår i: Acta Anaesthesiologica Scandinavica. - : WILEY. - 0001-5172 .- 1399-6576. ; 65:5, s. 702-710
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Tidskriftsartikel (refereegranskat)abstract
- Background Coronavirus disease 2019 (COVID-19) can lead to severe hypoxic respiratory failure and death. Corticosteroids decrease mortality in severely or critically ill patients with COVID-19. However, the optimal dose remains unresolved. The ongoing randomised COVID STEROID 2 trial investigates the effects of higher vs lower doses of dexamethasone (12 vs 6 mg intravenously daily for up to 10 days) in 1,000 adult patients with COVID-19 and severe hypoxia. Methods This protocol outlines the rationale and statistical methods for a secondary, pre-planned Bayesian analysis of the primary outcome (days alive without life support at day 28) and all secondary outcomes registered up to day 90. We will use hurdle-negative binomial models to estimate the mean number of days alive without life support in each group and present results as mean differences and incidence rate ratios with 95% credibility intervals (CrIs). Additional count outcomes will be analysed similarly and binary outcomes will be analysed using logistic regression models with results presented as probabilities, relative risks and risk differences with 95% CrIs. We will present probabilities of any benefit/harm, clinically important benefit/harm and probabilities of effects smaller than pre-defined clinically minimally important differences for all outcomes analysed. Analyses will be adjusted for stratification variables and conducted using weakly informative priors supplemented by sensitivity analyses using sceptic priors. Discussion This secondary, pre-planned Bayesian analysis will supplement the primary, conventional analysis and may help clinicians, researchers and policymakers interpret the results of the COVID STEROID 2 trial while avoiding arbitrarily dichotomised interpretations of the results. Trial registration ClinicalTrials.gov: NCT04509973; EudraCT: 2020-003363-25.
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| 7. |
- Granholm, Anders, et al.
(författare)
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Long-term outcomes of dexamethasone 12 mg versus 6 mg in patients with COVID-19 and severe hypoxaemia
- 2022
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Ingår i: Intensive Care Medicine. - : SPRINGER. - 0342-4642 .- 1432-1238. ; 48, s. 580-589
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Tidskriftsartikel (refereegranskat)abstract
- Purpose We assessed long-term outcomes of dexamethasone 12 mg versus 6 mg given daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia. Methods We assessed 180-day mortality and health-related quality of life (HRQoL) using EuroQoL (EQ)-5D-5L index values and EQ visual analogue scale (VAS) in the international, stratified, blinded COVID STEROID 2 trial, which randomised 1000 adults with confirmed COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 26 hospitals in Europe and India. In the HRQoL analyses, higher values indicated better outcomes, and deceased patients were given a score of zero. Results We obtained vital status at 180 days for 963 of 982 patients (98.1%) in the intention-to-treat population, EQ-5D-5L index value data for 922 (93.9%) and EQ VAS data for 924 (94.1%). At 180 days, 164 of 486 patients (33.7%) had died in the 12 mg group versus 184 of 477 (38.6%) in the 6 mg group [adjusted risk difference - 4.3%; 99% confidence interval (CI) - 11.7-3.0; relative risk 0.89; 0.72-1.09; P = 0.13]. The adjusted mean differences between the 12 mg and the 6 mg groups in EQ-5D-5L index values were 0.06 (99% CI - 0.01 to 0.12; P = 0.10) and in EQ VAS scores 4 (- 3 to 10; P = 0.22). Conclusion Among patients with COVID-19 and severe hypoxaemia, dexamethasone 12 mg compared with 6 mg did not result in statistically significant improvements in mortality or HRQoL at 180 days, but the results were most compatible with benefit from the higher dose.
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| 8. |
- Grynderup, Matias Brødsgaard, et al.
(författare)
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The associations between workplace bullying, salivary cortisol, and long-term sickness absence : a longitudinal study
- 2017
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 17:1, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Workplace stressors, such as bullying, are strongly related to subsequent long-term sickness absence, but little is known of the possible physiological mechanisms linking workplace stressors and sickness absence. The primary aim of this study was to investigate to what extent cortisol levels were associated with subsequent sickness absence and if cortisol mediated the association between workplace bullying and sickness absence. We additionally investigated possible bidirectional associations between bullying, cortisol, and long-term sickness absence.METHODS: Participants came from two Danish cohort studies, the "Psychosocial RIsk factors for Stress and MEntal disease" (PRISME) cohort and the "Workplace Bullying and Harassment" (WBH) cohort (n = 5418). Information about exposure to workplace bullying and morning and evening salivary cortisol was collected at three time points with approximately two years in between. After each data collection, all participants were followed for two years in registers, and cases with long-term sickness absence lasting 30 or more consecutive days were identified. The association between cortisol levels and subsequent sickness absence was assessed by logistic regression, while the extent to which the association between bullying and sickness absence was mediated by cortisol was quantified through natural direct and indirect effects.RESULTS: High evening cortisol was associated with a decreased risk of sickness absence (OR = 0.82, 95% CI = 0.68-0.99), but we did not find that high morning cortisol levels (OR = 0.98, 95% CI = 0.81-1.18) or high morning-to-evening slope (OR = 0.99, 95% CI = 0.82-1.18) were associated with subsequent sickness absence. We also tested for reverse causation and found that long-term sickness absence, but not salivary cortisol, was a strong risk factor for subsequent workplace bullying. There was no indication that cortisol mediated the association between workplace bullying and sickness absence.CONCLUSION: We found no straightforward and simple association between cortisol and long-term sickness absence. Furthermore, the association between workplace bullying and long-term sickness absence was not mediated by cortisol.
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| 9. |
- Hulvej Rod, Naja, et al.
(författare)
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Sleep Disturbances and Cause-Specific Mortality : Results From the GAZEL Cohort Study
- 2011
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 173:3, s. 300-309
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Tidskriftsartikel (refereegranskat)abstract
- Poor sleep is an increasing problem in modern society, but most previous studies on the association between sleep and mortality rates have addressed only duration, not quality, of sleep. The authors prospectively examined the effects of sleep disturbances on mortality rates and on important risk factors for mortality, such as body mass index, hypertension, and diabetes. A total of 16,989 participants in the GAZEL cohort study were asked validated questions on sleep disturbances in 1990 and were followed up until 2009, with <1% loss to follow-up. Body mass index, hypertension, and diabetes were measured annually through self-reporting. During follow-up, a total of 1,045 men and women died. Sleep disturbances were associated with a higher overall mortality risk in men (P = 0.005) but not in women (P = 0.33). This effect was most pronounced for men <45 years of age (≥3 symptoms vs. none: hazard ratio = 2.03, 95% confidence interval: 1.24, 3.33). There were no clear associations between sleep disturbances and cardiovascular mortality rates, although men and women with sleep disturbances were more likely to develop hypertension and diabetes (P < 0.001). Compared with people with no sleep disturbances, men who reported ≥3 types of sleep disturbance had an almost 5 times' higher risk of committing suicide (hazard ratio = 4.99, 95% confidence interval: 1.59, 15.7). Future strategies to prevent premature deaths may benefit from assessment of sleep disturbances, especially in younger individuals.
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| 10. |
- Jakobsen, Janus Christian, et al.
(författare)
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Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest: a statistical analysis plan.
- 2020
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- To date, targeted temperature management (TTM) is the only neuroprotective intervention after resuscitation from cardiac arrest that is recommended by guidelines. The evidence on the effects of TTM is unclear.The Targeted Hypothermia Versus Targeted Normothermia After Out-of-hospital Cardiac Arrest (TTM2) trial is an international, multicentre, parallel group, investigator-initiated, randomised, superiority trial in which TTM with a target temperature of 33°C after cardiac arrest will be compared with a strategy to maintain normothermia and active treatment of fever (≥37.8°C). Prognosticators, outcome assessors, the steering group, the trial coordinating team, and trial statisticians will be blinded to treatment allocation. The primary outcome will be all-cause mortality at 180days after randomisation. We estimate a 55% mortality in the targeted normothermia group. To detect an absolute risk reduction of 7.5% with an alpha of 0.05 and 90% power, 1900 participants will be enrolled. The secondary neurological outcome will be poor functional outcome (modified Rankin scale 4-6) at 180days after cardiac arrest. In this paper, a detailed statistical analysis plan is presented, including a comprehensive description of the statistical analyses, handling of missing data, and assessments of underlying statistical assumptions. Final analyses will be conducted independently by two qualified statisticians following the present plan.This SAP, which was prepared before completion of enrolment, should increase the validity of the TTM trial by mitigation of analysis-bias.
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| 11. |
- Jørgensen, Caroline Kamp, et al.
(författare)
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Centre for Statistical and Methodological Excellence (CESAME) : A Consortium Initiative for Improving Methodology in Randomised Clinical Trials
- 2023
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Ingår i: Health Services Insights. - 1178-6329. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- When conducting randomised clinical trials, the choice of methodology and statistical analyses will influence the results. If the planned methodology is not of optimal quality and predefined in detail, there is a risk of biased trial results and interpretation. Even though clinical trial methodology is already at a very high standard, there are many trials that deliver biased results due to the implementation of inadequate methodology, poor data quality and erroneous or biased analyses. To increase the internal and external validity of randomised clinical trial results, several international institutions within clinical intervention research have formed The Centre for Statistical and Methodological Excellence (CESAME). Based on international consensus, the CESAME initiative will develop recommendations for the proper methodological planning, conduct and analysis of clinical intervention research. CESAME aims to increase the validity of randomised clinical trial results which will ultimately benefit patients worldwide across medical specialities. The work of CESAME will be performed within 3 closely interconnected pillars: (1) planning randomised clinical trials; (2) conducting randomised clinical trials; and (3) analysing randomised clinical trials.
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| 12. |
- Lai, Eric T. C., et al.
(författare)
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Understanding pathways to inequalities in child mental health : a counterfactual mediation analysis in two national birth cohorts in the UK and Denmark
- 2020
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- Objectives We assessed social inequalities in child mental health problems (MHPs) and how they are mediated by perinatal factors, childhood illness and maternal mental health in two national birth cohorts.Design Longitudinal cohort studySetting We used data from the UK Millennium Cohort Study and the Danish National Birth Cohort.Primary and secondary outcome measures We applied causal mediation analysis to longitudinal cohort data. Socioeconomic conditions (SECs) at birth were measured by maternal education. Our outcome was child MHPs measured by the Strength and Difficulty Questionnaire at age 11. We estimated natural direct, indirect and total effects (TEs) of SECs on MHPs. We calculated the proportion mediated (PM) via three blocks of mediators—perinatal factors (smoking/alcohol use during pregnancy, birth weight and gestational age), childhood illness and maternal mental health.Results At age 11 years, 9% of children in the UK and 3.8% in Denmark had MHPs. Compared with high SECs, children in low SECs had a higher risk of MHPs (relative risk (RR)=4.3, 95% CI 3.3 to 5.5 in the UK, n=13 112; and RR=6.2, 95% CI 4.9 to 7.8 in Denmark, n=35 764). In the UK, perinatal factors mediated 10.2% (95% CI 4.5 to 15.9) of the TE, and adding maternal mental health tripled the PM to 32.2% (95% CI 25.4 to 39.1). In Denmark, perinatal factors mediated 16.5% (95% CI 11.9 to 21.1) of the TE, and including maternal mental health increased the PM to 16.9% (95% CI 11.2 to 22.6). Adding childhood illness made little difference in either country.Conclusion Social inequalities in child mental health are partially explained by perinatal factors in the UK and Denmark. Maternal mental health partially explained inequalities in the UK but not in Denmark.
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| 13. |
- Madelung, Ann Brinch, et al.
(författare)
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World Health Organization-defined classification of myeloproliferative neoplasms: Morphological reproducibility and clinical correlations-The Danish experience
- 2013
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Ingår i: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 88:12, s. 1012-1016
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Tidskriftsartikel (refereegranskat)abstract
- We examined inter-and intraobserver reproducibility and concordance between histological diagnosis and independently collected clinical findings in a large series of patients with the major subtypes of myeloproliferative neoplasms (MPNs) and controls. Seven hematopathologists reviewed 272 bone marrow biopsies including 43 controls. Diagnoses were determined according to the 2008 criteria of the World Health Organization (WHO). The participants were blinded to all clinical data except patient age. After initial evaluation all hematopathologists participated in a 3-day meeting with a leading clinician chaired by an expert hematopathologists. In cases with lack of consensus on fiber grading (n=57), a new evaluation was performed. In cases with discordance on morphological diagnosis (n=129), an additional nonblinded evaluation taking clinical data into consideration was carried out. For remaining cases with a lack of concordance between morphological diagnosis and clinical diagnosis (n=33), a similar nonblinded evaluation was performed. Consensus on final histological diagnosis and concordance with clinical diagnosis were determined. Blinded histological evaluation resulted in a 53% consensus rate. After re-evaluation of fiber content, consensus was reached in 60% of cases. Adding clinical data increased the histological consensus to 83%. For cases with a histological consensus, we found a concordance of 71% with the clinician's diagnoses. This is the first study to present a larger cohort of MPN patients mimicking the diagnostic challenges that hematopathologists face in their daily practice. The results support the postulates of the WHO that both morphological and clinical findings are essential for a valid diagnosis Am. J. Hematol. 88: 1012-1016, 2013. (C) 2013 Wiley Periodicals, Inc.
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| 14. |
- Magnusson Hanson, Linda L., et al.
(författare)
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Multicohort study of change in job strain, poor mental health and incident cardiometabolic disease
- 2019
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Ingår i: Occupational and Environmental Medicine. - : BMJ Publishing Group Ltd. - 1351-0711 .- 1470-7926. ; 76, s. 785-792
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Several recent large-scale studies have indicated a prospective association between job strain and coronary heart disease, stroke and diabetes. Job strain is also associated with poorer mental health, a risk factor for cardiometabolic disease. This study investigates the prospective relationships between change in job strain, poor mental health and cardiometabolic disease, and whether poor mental health is a potential mediator of the relationship between job strain and cardiometabolic disease. Methods: We used data from five cohort studies from Australia, Finland, Sweden and UK, including 47 757 men and women. Data on job strain across two measurements 1-5 years apart (time 1 (T1)-time 2 (T2)) were used to define increase or decrease in job strain. Poor mental health (symptoms in the top 25% of the distribution of the scales) at T2 was considered a potential mediator in relation to incident cardiometabolic disease, including cardiovascular disease and diabetes, following T2 for a mean of 5-18 years. Results: An increase in job strain was associated with poor mental health (HR 1.56, 95% CI 1.38 to 1.76), and a decrease in job strain was associated with lower risk in women (HR 0.70, 95% CI 0.60-0.84). However, no clear association was observed between poor mental health and incident cardiometabolic disease (HR 1.08, 95% CI 0.96-1.23), nor between increase (HR 1.01, 95% CI 0.90-1.14) and decrease (HR 1.08, 95% CI 0.96-1.22) in job strain and cardiometabolic disease. Conclusions: The results did not support that change in job strain is a risk factor for cardiometabolic disease and yielded no support for poor mental health as a mediator.
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| 15. |
- Mortensen, Camilla Bekker, et al.
(författare)
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Long-term outcomes with haloperidol versus placebo in acutely admitted adult ICU patients with delirium
- 2024
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Ingår i: Intensive Care Medicine. - 0342-4642. ; 50:1, s. 103-113
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: We assessed long-term outcomes in acutely admitted adult patients with delirium treated in intensive care unit (ICU) with haloperidol versus placebo. Methods: We conducted pre-planned analyses of 1-year outcomes in the Agents Intervening against Delirium in the ICU (AID-ICU) trial, including mortality and health-related quality of life (HRQoL) assessed by Euroqol (EQ) 5-dimension 5-level questionnaire (EQ-5D-5L) index values and EQ visual analogue scale (EQ VAS) (deceased patients were assigned the numeric value zero). Outcomes were analysed using logistic and linear regressions with bootstrapping and G-computation, all with adjustment for the stratification variables (site and delirium motor subtype) and multiple imputations for missing HRQoL values. Results: At 1-year follow-up, we obtained vital status for 96.2% and HRQoL data for 83.3% of the 1000 randomised patients. One-year mortality was 224/501 (44.7%) in the haloperidol group versus 251/486 (51.6%) in the placebo group, with an adjusted absolute risk difference of − 6.4%-points (95% confidence interval [CI] − 12.8%-points to − 0.2%-points; P = 0.045). These results were largely consistent across the secondary analyses. For HRQoL, the adjusted mean differences were 0.04 (95% CI − 0.03 to 0.11; P = 0.091) for EQ-5D-5L-5L index values, and 3.3 (95% CI − 9.3 to 17.5; P = 0.142) for EQ VAS. Conclusions: In acutely admitted adult ICU patients with delirium, haloperidol treatment reduced mortality at 1-year follow-up, but did not statistically significantly improve HRQoL.
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| 16. |
- Mortensen, Camilla B., et al.
(författare)
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Mortality and HRQoL in ICU patients with delirium : Protocol for 1-year follow-up of AID-ICU trial
- 2020
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 64:10, s. 1519-1525
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Tidskriftsartikel (refereegranskat)abstract
- Background: Intensive care unit (ICU)-acquired delirium is frequent and associated with poor short- and long-term outcomes for patients in ICUs. It therefore constitutes a major healthcare problem. Despite limited evidence, haloperidol is the most frequently used pharmacological intervention against ICU-acquired delirium. Agents intervening against Delirium in the ICU (AID-ICU) is an international, multicentre, randomised, blinded, placebo-controlled trial investigates benefits and harms of treatment with haloperidol in patients with ICU-acquired delirium. The current pre-planned one-year follow-up study of the AID-ICU trial population aims to explore the effects of haloperidol on one-year mortality and health related quality of life (HRQoL). Methods : The AID-ICU trial will include 1000 participants. One-year mortality will be obtained from the trial sites; we will validate the vital status of Danish participants using the Danish National Health Data Registers. Mortality will be analysed by Cox-regression and visualized by Kaplan-Meier curves tested for significance using the log-rank test. We will obtain HRQoL data using the EQ-5D instrument. HRQoL analysis will be performed using a general linear model adjusted for stratification variables. Deceased participants will be designated the worst possible value. Results: We expect to publish results of this study in 2022. Conclusion: We expect that this one-year follow-up study of participants with ICU-acquired delirium allocated to haloperidol vs. placebo will provide important information on the long-term consequences of delirium including the effects of haloperidol. We expect that our results will improve the care of this vulnerable patient group.
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| 17. |
- Mortensen, Jesper, et al.
(författare)
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Weekly hours of informal caregiving and paid work, and the risk of cardiovascular disease
- 2018
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Ingår i: European Journal of Public Health. - : Oxford University Press (OUP). - 1101-1262 .- 1464-360X. ; 28:4, s. 743-747
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Tidskriftsartikel (refereegranskat)abstract
- Background: Little is known on the association between weekly hours of informal caregiving and risk of cardiovascular disease (CVD). The objective was to investigate the individual and joint effects of weekly hours of informal caregiving and paid work on the risk of CVD. Methods: Pooled analysis with 1396 informal caregivers in gainful employment, from the Swedish Longitudinal Occupational Survey of Health and the Whitehall II study. Informal caregiving was defined as care for an aged or disabled relative. The outcome was CVD during 10years follow-up. Analyzes were adjusted for age, sex, children, marital status and occupational grade. Results: There were 59 cases of CVD. Providing care >20 h weekly were associated with a higher risk of CVD compared to those providing care 1-8 h weekly (hazard ratio = 2.63, 95%CI: 1.20; 5.76), irrespectively of weekly work hours. In sensitivity analyzes, we found this risk to be markedly higher among long-term caregivers (6.17, 95%CI: 1.73; 22.1) compared to short-term caregivers (0.89, 95%CI: 0.10; 8.08). Caregivers working >= 55 h weekly were at higher risk of CVD (2.23, 95%CI: 1.14; 4.35) compared to those working 35-40 h weekly. Those providing care >8 h and working <= 40 h weekly had a higher risk of CVD compared to those providing care 1-8 h and working <= 40 h (3.23, 95%CI: 1.25; 8.37). Conclusion: A high number of weekly hours of informal caregiving as opposed to few weekly hours is associated with a higher risk of CVD, irrespectively of weekly work hours. The excess risk seemed to be driven by those providing care over long periods of time.
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| 18. |
- Munch, Marie W., et al.
(författare)
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Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia The COVID STEROID 2 Randomized Trial
- 2021
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Ingår i: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 326:18, s. 1807-1817
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Tidskriftsartikel (refereegranskat)abstract
- Question What is the effect of 12 mg vs 6 mg of dexamethasone on the number of days alive without life support at 28 days in patients with COVID-19 and severe hypoxemia? Findings In this randomized trial that included 1000 patients with COVID-19 and severe hypoxemia, treatment with 12 mg/d of dexamethasone resulted in 22.0 days alive without life support at 28 days compared with 20.5 days in those receiving 6 mg/d of dexamethasone. This difference was not statistically significant. Meaning Compared with 6 mg of dexamethasone, 12 mg of dexamethasone did not statistically significantly reduce the number of days alive without life support at 28 days. This multicenter randomized clinical trial compares the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. IMPORTANCE A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. OBJECTIVE To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. DESIGN, SETTING, AND PARTICIPANTS A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. INTERVENTIONS Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and >= 1 serious adverse reactions at 28 days). RESULTS Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). CONCLUSIONS AND RELEVANCE Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference.
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| 19. |
- Munch, Marie Warrer, et al.
(författare)
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Higher vs lower doses of dexamethasone in patients with COVID-19 and severe hypoxia (COVID STEROID 2) trial : Protocol and statistical analysis plan
- 2021
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Ingår i: Acta Anaesthesiologica Scandinavica. - : WILEY. - 0001-5172 .- 1399-6576. ; 65:6, s. 834-845
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Tidskriftsartikel (refereegranskat)abstract
- Background The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of deaths and overburdened healthcare systems worldwide. Systemic low-dose corticosteroids have proven clinical benefit in patients with severe COVID-19. Higher doses of corticosteroids are used in other inflammatory lung diseases and may offer additional clinical benefits in COVID-19. At present, the balance between benefits and harms of higher vs. lower doses of corticosteroids for patients with COVID-19 is unclear. Methods The COVID STEROID 2 trial is an investigator-initiated, international, parallel-grouped, blinded, centrally randomised and stratified clinical trial assessing higher (12 mg) vs. lower (6 mg) doses of dexamethasone for adults with COVID-19 and severe hypoxia. We plan to enrol 1,000 patients in Denmark, Sweden, Switzerland and India. The primary outcome is days alive without life support (invasive mechanical ventilation, circulatory support or renal replacement therapy) at day 28. Secondary outcomes include serious adverse reactions at day 28; all-cause mortality at day 28, 90 and 180; days alive without life support at day 90; days alive and out of hospital at day 90; and health-related quality of life at day 180. The primary outcome will be analysed using the Kryger Jensen and Lange test adjusted for stratification variables and reported as adjusted mean differences and median differences. The full statistical analysis plan is outlined in this protocol. Discussion The COVID STEROID 2 trial will provide evidence on the optimal dosing of systemic corticosteroids for COVID-19 patients with severe hypoxia with important implications for patients, their relatives and society.
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| 20. |
- Pingel, Ronnie, 1978-
(författare)
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Some Aspects of Propensity Score-based Estimators for Causal Inference
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis consists of four papers that are related to commonly used propensity score-based estimators for average causal effects.The first paper starts with the observation that researchers often have access to data containing lots of covariates that are correlated. We therefore study the effect of correlation on the asymptotic variance of an inverse probability weighting and a matching estimator. Under the assumptions of normally distributed covariates, constant causal effect, and potential outcomes and a logit that are linear in the parameters we show that the correlation influences the asymptotic efficiency of the estimators differently, both with regard to direction and magnitude. Further, the strength of the confounding towards the outcome and the treatment plays an important role.The second paper extends the first paper in that the estimators are studied under the more realistic setting of using the estimated propensity score. We also relax several assumptions made in the first paper, and include the doubly robust estimator. Again, the results show that the correlation may increase or decrease the variances of the estimators, but we also observe that several aspects influence how correlation affects the variance of the estimators, such as the choice of estimator, the strength of the confounding towards the outcome and the treatment, and whether constant or non-constant causal effect is present.The third paper concerns estimation of the asymptotic variance of a propensity score matching estimator. Simulations show that large gains can be made for the mean squared error by properly selecting smoothing parameters of the variance estimator and that a residual-based local linear estimator may be a more efficient estimator for the asymptotic variance. The specification of the variance estimator is shown to be crucial when evaluating the effect of right heart catheterisation, i.e. we show either a negative effect on survival or no significant effect depending on the choice of smoothing parameters. In the fourth paper, we provide an analytic expression for the covariance matrix of logistic regression with normally distributed regressors. This paper is related to the other papers in that logistic regression is commonly used to estimate the propensity score.
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| 21. |
- Xu, Tianwei, et al.
(författare)
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Characteristics of Workplace Psychosocial Resources and Risk of Diabetes : A Prospective Cohort Study
- 2022
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 45:1, s. 59-66
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVETo examine whether characteristics of workplace psychosocial resources are associated with the risk of type 2 diabetes among employees.RESEARCH DESIGN AND METHODSParticipants were 49,835 employees (77% women, aged 40–65 years, and diabetes free at baseline) from the Finnish Public Sector cohort study. Characteristics of horizontal (culture of collaboration and support from colleagues) and vertical (leadership quality and organizational procedural justice) psychosocial resources were self-reported. Incident type 2 diabetes (n = 2,148) was ascertained through linkage to electronic health records from national registers. We used latent class modeling to assess the clustering of resource characteristics. Cox proportional hazards models were used to examine the relationship between the identified clusters and risk of type 2 diabetes during 10.9 years of follow-up, adjusting for age, sex, marital status, educational level, type of employment contract, comorbidity, and diagnosed mental disorders.RESULTSWe identified four patterns of workplace psychosocial resources: unfavorable, favorable vertical, favorable horizontal, and favorable vertical and horizontal. Compared with unfavorable, favorable vertical (hazard ratio 0.87 [95% CI 0.78; 0.97]), favorable horizontal (0.77 [0.67; 0.88]), and favorable vertical and horizontal (0.77 [0.68; 0.86]) resources were associated with a lower risk of type 2 diabetes, with the strongest associations seen in employees at age ≥55 years (Pinteraction = 0.03). These associations were robust to multivariable adjustments and were not explained by reverse causation.CONCLUSIONSA favorable culture of collaboration, support from colleagues, leadership quality, and organizational procedural justice are associated with a lower risk of employees developing type 2 diabetes than in those without such favorable workplace psychosocial resources.
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| 22. |
- Xu, Tianwei, et al.
(författare)
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Workplace bullying and violence as risk factors for type 2 diabetes : a multicohort study and meta-analysis
- 2018
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 61:1, s. 75-83
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: The aim of this multicohort study was to examine whether employees exposed to social stressors at work, such as workplace bullying and violence, have an increased risk of type 2 diabetes.METHODS: The study included 45,905 men and women (40-65 years of age and free of diabetes at baseline) from four studies in Sweden, Denmark and Finland. Workplace bullying and violence were self-reported at baseline. Incident diabetes was ascertained through national health and medication records and death registers. Marginal structural Cox models adjusted for age, sex, country of birth, marital status and educational level were used for the analyses.RESULTS: Nine per cent of the population reported being bullied at work and 12% were exposed to workplace violence or threats of violence. Bullied participants had a 1.46 (95% CI 1.23, 1.74) times higher risk of developing diabetes compared with non-bullied participants. Exposure to violence or threats of violence was also associated with a higher risk of diabetes (HR 1.26 [95% CI 1.02, 1.56]). The risk estimates attenuated slightly when taking BMI into account, especially for bullying. The results were similar for men and women, and were consistent across cohorts.CONCLUSIONS/INTERPRETATION: We found a higher risk of incident type 2 diabetes among employees exposed to bullying or violence in the workplace. Further research is needed to determine whether policies to reduce bullying and violence at work may reduce the incidence of type 2 diabetes in working populations. Research on the mechanisms is also highly warranted.
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| 23. |
- Xu, Tianwei, et al.
(författare)
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Workplace bullying and workplace violence as risk factors for cardiovascular disease : a multi-cohort study
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:14, s. 1124-1134
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Tidskriftsartikel (refereegranskat)abstract
- AimsTo assess the associations between bullying and violence at work and cardiovascular disease (CVD).Methods and resultsParticipants were 79 201 working men and women, aged 18–65 years and free of CVD and were sourced from three cohort studies from Sweden and Denmark. Exposure to workplace bullying and violence was measured at baseline using self-reports. Participants were linked to nationwide health and death registers to ascertain incident CVD, including coronary heart disease and cerebrovascular disease. Study-specific results were estimated by marginal structural Cox regression and were combined using fixed-effect meta-analysis. Nine percent reported being bullied at work and 13% recorded exposure to workplace violence during the past year. We recorded 3229 incident CVD cases with a mean follow-up of 12.4 years (765 in the first 4 years). After adjustment for age, sex, country of birth, marital status, and educational level, being bullied at work vs. not was associated with a hazard ratio (HR) of 1.59 [95% confidence interval (CI) 1.28–1.98] for CVD. Experiencing workplace violence vs. not was associated with a HR of 1.25 (95% CI 1.12–1.40) for CVD. The population attributable risk was 5.0% for workplace bullying and 3.1% for workplace violence. The excess risk remained similar in analyses with different follow-up lengths, cardiovascular risk stratifications, and after additional adjustments. Dose–response relations were observed for both workplace bullying and violence (Ptrend < 0.001). There was only negligible heterogeneity in study-specific estimates.ConclusionBullying and violence are common at workplaces and those exposed to these stressors are at higher risk of CVD.
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| 24. |
- Xu, Tianwei, et al.
(författare)
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Workplace psychosocial resources and risk of cardiovascular disease among employees: a multi-cohort study of 135 669 participants
- 2022
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Ingår i: Scandinavian Journal of Work, Environment and Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 48:8, s. 621-631
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Tidskriftsartikel (refereegranskat)abstract
- Objective In terms of prevention, it is important to determine effects on cardiovascular disease (CVD) when some workplace psychosocial resources are high while others are low. The aim of the study was to assess the prospective relationship between clustering of workplace psychosocial resources and risk of CVD among employees.Methods We pooled data from three cohort studies of 135 669 employees (65% women, age 18–65 years and free of CVD) from Denmark, Finland and Sweden. Baseline horizontal resources (culture of collaboration and support from colleagues) and vertical resources (leadership quality and procedural justice) were measured using standard questionnaire items. Incident CVD, including coronary heart and cerebrovascular disease, was ascertained using linked electronic health records. We used latent class analysis to assess clustering (latent classes) of workplace psychosocial resources. Cox proportional hazard models were used to examine the association between these clusters and risk of CVD, adjusting for demographic and employment-related factors and pre-existing physical and mental disorders.Results We identified five clusters of workplace psychosocial resources from low on both vertical and horizontal resources (13%) to generally high resources (28%). High horizontal resources were combined with either intermediate [hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.74–0.95] or high (HR 0.88, 95% CI 0.78–1.00) vertical resources were associated with lower risks of CVD compared to those with generally low resources. The association was most prominent for cerebrovascular disease (eg, general high resources: HR 0.80, 95% CI 0.67–0.96).Conclusions Individuals with high levels of workplace psychosocial resources across horizontal and vertical dimensions have a lower risk of CVD, particularly cerebrovascular disease.
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