Predictors of Symptom Reduction and Remission Among People with Anxiety: Secondary Analyses from a Randomized Controlled Trial.

Despite the substantial disease burden of anxiety disorders, only limited or conflicting data on prognostic factors is available. Most studies include patients in the secondary healthcare sector thus, the generalizability of findings is limited. The present study examines predictors of symptom reduction and remission in patients with anxiety disorders in a primary care setting. 214 patients with anxiety disorders, recruited as part of the Collabri Flex trial, were included in secondary analyses. Data on potential predictors of anxiety symptoms at 6-month follow-up was collected at baseline, including patient characteristics related to demography, illness, comorbidity, functional level, life quality, and self-efficacy. The outcomes were symptom reduction and remission. Univariate and multivariate linear and logistic regression analyses were conducted to assess the associations between predictor variables and the outcome, and machine-learning methods were also applied. In multiple linear regression analysis, anxiety severity at baseline (ß = -6.05, 95% CI = -7.54,-4.56, p < 0.001) and general psychological problems and symptoms of psychopathology (SCL-90-R score) (ß = 2.19, 95% CI = 0.24,4.14, p = 0.028) were significantly associated with symptom change at 6 months. Moreover, self-efficacy was associated with the outcome, however no longer significant in the multiple regression model. In multiple logistic regression analysis, anxiety severity at baseline (OR = 0.54, 95% CI = -1.13,-0.12, p = 0.018) was significantly associated with remission at 6 months. There was no predictive performance of the machine-learning models. Our study contributes with information that could be valuable knowledge for managing anxiety disorders in primary care.

The effects of collaborative care versus consultation liaison for anxiety disorders and depression in Denmark: two randomised controlled trials.

BACKGROUND: Collaborative care (CC) and consultation liaison (CL) are two conceptual models aiming to improve mental healthcare in primary care. The effects of these models have not been compared in a Danish setting. AIMS: To examine the effects of CC versus CL for persons with anxiety and depression in Danish general practices (trial registration: NCT03113175 and NCT03113201). METHOD: Two randomised parallel superiority trials for anxiety disorders and depression were carried out in 2018-2019. In the CC-group, care managers collaborated with general practitioners (GPs) to provide evidence-based treatment according to structured treatment plans. They followed up and provided psychoeducation and/or cognitive-behavioural therapy. The GPs initiated pharmacological treatment if indicated, and a psychiatrist provided supervision. In the CL-group, the intervention consisted of the GP's usual treatment. However, the psychiatrist and care manager could be consulted. Primary outcomes were depression symptoms (Beck Depression Inventory-II, BDI-II) in the depression trial and anxiety symptoms (Beck Anxiety Inventory, BAI) in the anxiety trial at 6-month follow-up. RESULTS: In total, 302 participants with anxiety disorders and 389 participants with depression were included. A significant difference in BDI-II score was found in the depression trial, with larger symptom reductions in the CC-group (CC: 12.7, 95% CI 11.4-14.0; CL: 17.5, 95% CI 16.2-18.9; Cohen's d = -0.50, P ≤ 0.001). There was a significant difference in BAI in the anxiety trial (CC: 14.9, 95% CI 13.5-16.3; CL: 17.9, 95% CI 16.5-19.3; Cohen's d = -0.34, P ≤ 0.001), with larger symptom reductions in the CC-group. CONCLUSIONS: Collaborative care was an effective model to improve outcomes for persons with depression and anxiety disorders.

Predictors of return to work for people on sick leave with depression, anxiety and stress: secondary analysis from a randomized controlled trial.

PURPOSE: Knowledge about predictors of return to work (RTW) in people on sick leave with common mental disorders (CMDs) may inform the development of effective vocational rehabilitation interventions for this target group. In this study, we investigated predictors of RTW at 6 and 12 months in people on sick leave with depression, anxiety disorders or stress-related disorders. METHODS: We have performed a secondary analysis, utilizing data from two RCTs that evaluated the efficacy of an integrated health care and vocational rehabilitation intervention. Data were obtained from mental health assessments, questionnaires and registers. Using Cox regression analysis, the relationship between baseline variables and RTW was analysed at 6 and 12 months after randomization within the group of CMD as a whole and within the subgroups of depression, anxiety and stress-related disorders. RESULTS: Symptom burden and employment status at baseline predicted RTW in the CMD group (n = 1245) and in the three diagnostic subgroups at both time points. RTW self-efficacy predicted RTW in the depression group but not in the anxiety or stress subgroups. CONCLUSION: Many predictors of RTW were similar over time and, to some extent, across the CMD subgroups. Findings highlight the need not only to take health-related and psychological factors into account when developing vocational rehabilitation interventions but also to consider workplace strategies and options for support.

Predictors of Return to Work for People with Anxiety or Depression Participating in a Randomized Trial Investigating the Effect of a Supported Employment Intervention.

Purpose Common mental disorders have a severe impact on society and individuals; rates of unemployment and disability pensions are high. Knowing which factors facilitate or hinder people's return to work is important when designing effective vocational rehabilitation interventions. Methods We conducted secondary analyses on data from 289 participants with depression or anxiety included in the Individual Placement and Support modified for people with mood and anxiety disorders (IPS-MA) trial. Associations of baseline characteristics and employment or education after 24 months were tested in univariate logistic regression analyses, variables with a p-value below 0.1 were included in multivariate analyses. Results In the univariate analyses, self-reported level of functioning (p = 0.032), higher age (p = 0.070), and higher level of readiness to change (p = 0.001) were associated with the outcome and included in the multivariate analysis. Only age (p = 0.030) and readiness to change (p = 0.003) remained significantly associated with return to work or education after 24 months in the multivariate analysis. Conclusion Higher age and lower readiness to change were associated with a lower chance of having returned to work or education. Factors modifying the effect of higher age should be identified, just as vocational rehabilitation should focus on improving factors related to people's readiness to change.

Integrated Mental Healthcare and Vocational Rehabilitation for People on Sick Leave with Anxiety or Depression: 24-Month Follow-up of the Randomized IBBIS Trial.

Integration of vocational rehabilitation and mental healthcare has shown some effect on work participation at 1-year follow-up after sick leave with depression and anxiety. We aimed to study the effect on work and health outcomes at 2-year follow-up, why we performed a randomized trial was conducted to study the effectiveness of integrated intervention (INT) compared to service as usual (SAU) and best practice mental healthcare (MHC). We included 631 participants, and at 24-month follow-up, we detected no differences in effect between INT and SAU. Compared to MHC, INT showed faster return-to-work (RTW) rates (p = 0.044) and a higher number of weeks in work (p = 0.024). No symptom differences were observed between the groups at 24 months. In conclusion, compared to SAU, INT was associated with a slightly higher work rate reaching borderline statistical significance at 12-month follow-up and lower stress levels at 6-month follow-up. The disappearance of relative effect between 12 and 24 months may be explained by the fact that the intervention lasted less than 12 months or by delayed spontaneous remission in the SAU group after 12 months. Despite the lack of effect at long-term follow-up, INT still performed slightly better than SAU overall. Moderate implementation difficulties, may partly explain the absence of the hypothesized effect. Integrated intervention, as implemented in this trial, showed some positive effects on mid-term vocational status and short-term stress symptom levels. However, these effects were not sustained beyond the duration of the intervention.

Integrating vocational rehabilitation and mental healthcare to improve the return-to-work process for people on sick leave with depression or anxiety: results from a three-arm, parallel randomised trial.

OBJECTIVE: The aim of this study was to investigate an integrated mental healthcare and vocational rehabilitation intervention to improve and hasten the process of return-to-work of people on sick leave with anxiety and depression. METHODS: In this three-arm, randomised trial, participants were assigned to (1) integrated intervention (INT), (2) improved mental healthcare (MHC) or (3) service as usual (SAU). The primary outcome was time to return-to-work measured at 12-month follow-up. The secondary outcomes were time to return-to-work measured at 6-month follow-up; levels of anxiety, depression, stress symptoms, and social and occupational functioning at 6 months; and return-to-work measured as proportion in work at 12 months. RESULTS: 631 individuals were randomised. INT yielded a higher proportion in work compared with both MHC (56.2% vs 43.7%, p=0.012) and SAU (56.2% vs 45%, p=0.029) at 12-month follow-up. We found no differences in return-to-work in terms of sick leave duration at either 6-month or 12-month follow-up, with the latter being the primary outcome. No differences in anxiety, depression or functioning between INT, MHC and SAU were identified, but INT and MHC showed lower scores on Cohen's Perceived Stress Scale compared with SAU at 12-month follow-up. CONCLUSIONS: Although INT did not hasten the process of return-to-work, it yielded better outcome with regard to proportion in work compared with MHC and SAU. The findings suggest that INT compared with SAU is associated with a few, minor health benefits. Overall, INT yielded slightly better vocational and health outcomes, but the clinical significance of the health advantage is questionable. TRIAL REGISTRATION NUMBER: NCT02872051.

Predictors of work and education among people with severe mental illness who participated in the Danish individual placement and support study: findings from a randomized clinical trial.

PURPOSE: People with severe mental illness experience disproportionately high rates of unemployment. Nonetheless, a substantial amount of research has demonstrated vocational benefits of the Individual Placement and Support (IPS) model and IPS supplemented with cognitive remediation (IPSE). The present study sought to examine demographic and clinical predictors of employment or education among people with severe mental illness and to investigate if IPS or IPSE can compensate for risk factors for unemployment. METHODS: Seven hundred twenty participants were randomly assigned to IPS, IPSE or Service as Usual. During the 18-month follow-up period participants in the two experimental groups obtained significantly more work or education. A series of univariate and multiple logistic regression analyses were conducted to assess the predictive power of demographic and clinical factors for the total population and for the three groups individually. RESULTS: The strongest predictor for vocational recovery, besides treatment allocation, was previous work history (OR = 1.78; 95% CI = 1.28-2.47). Men had a lower probability for vocational recovery compared to women (OR = 0.71; 95% CI = 0.50-0.99) and higher age was also negatively associated with work or education (OR = 0.79; 95% CI = 0.67-0.93). Moreover, vocational recovery was predicted by higher readiness for change, measured on the readiness for change scale (OR = 1.42; 95% CI = 1.19-1.70). Participation in IPS or IPSE could not compensate for negative risk factors such as low cognitive function or negative symptoms. CONCLUSIONS: In a multiple logistic regression analysis age, previous work history and motivation for change were statistically significant predictors of obtaining work or education among people with severe mental illness who participated in the Danish IPS trial.

Vocational Outcomes of the Individual Placement and Support Model in Subgroups of Diagnoses, Substance Abuse, and Forensic Conditions: A Systematic Review and Analysis of Pooled Original Data.

PURPOSE: To investigate the effect of Individual Placement and Support (IPS) according to diagnoses of schizophrenia, bipolar disorder, major depression, substance use disorders, or forensic psychiatric conditions. METHODS: A systematic search of the literature was conducted in June 2017 and repeated in December 2020. The systematic review included 13 studies. Analyses of pooled original data were based on the six studies providing data (n = 1594). No studies on forensic psychiatric conditions were eligible. Hours and weeks worked were analyzed using linear regression. Employment, and time to employment was analyzed using logistic regression, and cox-regression, respectively. RESULTS: The effects on hours and weeks in employment after 18 months were comparable for participants with schizophrenia, and bipolar disorder but only statistically significant for participants with schizophrenia compared to services as usual (SAU) (EMD 109.1 h (95% CI 60.5-157.7), 6.1 weeks (95% CI 3.9-8.4)). The effect was also significant for participants with any drug use disorder (121.2 h (95% CI 23.6-218.7), 6.8 weeks (95% CI 1.8-11.8)). Participants with schizophrenia, bipolar disorder, and any drug use disorder had higher odds of being competitively employed (OR 2.1 (95% CI 1.6-2.7); 2.4 (95% CI 1.3-4.4); 3.0 (95% CI 1.5-5.8)) and returned to work faster than SAU (HR 2.1 (95% CI 1.6-2.6); 1.8 (95% CI 1.1-3.1); 3.0 (95% CI 1.6-5.7)). No statistically significant effects were found regarding depression. CONCLUSIONS: IPS was effective regarding schizophrenia, bipolar disorder, and substance use disorder; however, the effect on hours, and weeks worked was not statistically significant regarding bipolar disorder. For people with depression the impact of IPS remains inconclusive. Non-significant results may be due to lack of power. TRIAL REGISTRATION: PROSPERO protocol nr. CRD42017060524.

Collaborative care for depression and anxiety disorders: results and lessons learned from the Danish cluster-randomized Collabri trials.

BACKGROUND: Meta-analyses suggest that collaborative care (CC) improves symptoms of depression and anxiety. In CC, a care manager collaborates with a general practitioner (GP) to provide evidence-based care. Most CC research is from the US, focusing on depression. As research results may not transfer to other settings, we developed and tested a Danish CC-model (the Collabri-model) for depression, panic disorder, generalized anxiety disorder, and social anxiety disorder in general practice. METHODS: Four cluster-randomized superiority trials evaluated the effects of CC. The overall aim was to explore if CC significantly improved depression and anxiety symptoms compared to treatment-as-usual at 6-months' follow-up. The Collabri-model was founded on a multi-professional collaboration between a team of mental-health specialists (psychiatrists and care managers) and GPs. In collaboration with GPs, care managers provided treatment according to a structured plan, including regular reassessments and follow-up. Treatment modalities (cognitive behavioral therapy, psychoeducation, and medication) were offered based on stepped care algorithms. Face-to-face meetings between GPs and care managers took place regularly, and a psychiatrist provided supervision. The control group received treatment-as-usual. Primary outcomes were symptoms of depression (BDI-II) and anxiety (BAI) at 6-months' follow-up. The incremental cost-effectiveness ratio (ICER) was estimated based on 6-months' follow-up. RESULTS: Despite various attempts to improve inclusion rates, the necessary number of participants was not recruited. Seven hundred thirty-one participants were included: 325 in the depression trial and 406 in the anxiety trials. The Collabri-model was implemented, demonstrating good fidelity to core model elements. In favor of CC, we found a statistically significant difference between depression scores at 6-months' follow-up in the depression trial. The difference was not significant at 15-months' follow-up. The anxiety trials were pooled for data analysis due to inadequate sample sizes. At 6- and 15-months' follow-up, there was a difference in anxiety symptoms favoring CC. These differences were not statistically significant. The ICER was 58,280 Euro per QALY. CONCLUSIONS: At 6 months, a significant difference between groups was found in the depression trial, but not in the pooled anxiety trial. However, these results should be cautiously interpreted as there is a risk of selection bias and lacking statistical power. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02678624 and NCT02678845 . Retrospectively registered on 7 February 2016.

Dimensions and subtypes of oppositionality and their relation to comorbidity and psychosocial characteristics.

The symptoms of oppositional defiant disorder (ODD), or oppositionality, seem to constitute a three-dimensional structure of angry/irritable, vindictiveness and argumentative behavior dimensions. Also, subjects with oppositionality are characterized by different comorbidity and longitudinal trajectories, suggesting that they could be divided into subtypes. This study is the first to examine the dimensions and subtypes of oppositionality in Nordic children. Study participants included 3435 children aged 7-10 years from the Danish National Birth Cohort. Information was collected using the Development and Well-Being Assessment (DAWBA) online version. A three-factor ODD model was identified. The angry/irritable dimension was associated with emotional problems and disorders, fewer social skills and fewer personal positive attributes. The argumentative behavior dimension was associated with hyperactivity/conduct problems, reduced social skills and positive attributes. The vindictiveness dimension was associated with externalizing, internalizing and prosocial problems. Four ODD subtypes were identified. The subtypes with many or mainly angry/irritable symptoms were characterized by comorbid psychopathology, increased functional impairment and psychosocial problems. Children with ODD had fewer positive attributes, more friendship/school problems and higher functional impairment than children with emotional disorders and control group children. Oppositionality consists of three dimensions differently associated with comorbidity and psychosocial characteristics, and the same pattern is seen for the four ODD subtypes identified in this study. Children with ODD experience more adversities and functional impairment than children with emotional disorders. Our results indicate that treatment of children with ODD would improve from extended knowledge on individual ODD dimensions and subtypes and the related child psychosocial characteristics.

Do Exercisers With Musculoskeletal Injuries Report Symptoms of Depression and Stress?

CONTEXT: Sports injuries in athletes can lead to negative emotional responses in terms of anger, anxiety, confusion, and sadness. Severe injuries can be understood as a stressful life event with increased levels of psychological distress, but injury assessment and rehabilitation typically focus on somatic symptoms. OBJECTIVE: The primary aim of this study was to estimate the prevalence of depression and emotional stress and to measure self-rated health in regular exercisers presenting to a sports medicine clinic with musculoskeletal injury. The secondary aim was to identify psychosocial factors associated with depression in injured exercisers and the potential need for psychological counseling. DESIGN: A cross-sectional survey study. SETTING: A sports medicine clinic for injuries of the foot, knee, or shoulder. PARTICIPANTS: Regular exercisers with present injuries (N = 694) and exercisers without injuries (N = 494). Regular exercisers were defined as those undertaking moderate exercise at least once a week. INTERVENTION: A questionnaire survey completed on paper by patients in a sports medicine clinic and a web-based version completed by online sports communities. MAIN OUTCOME MEASURES: Participants completed the Major Depression Inventory, Perceived Stress Scale, health-related quality of life, and questions on sociodemographics, exercise habits, and injury history. RESULTS: Symptoms of depression were reported by 12% of injured exercisers and 5% of noninjured controls (P < .001). Clinical stress was found in 30% of injured exercisers and 22% of controls (P = .002), and the EQ-5D-5L Visual Analog Scale score was lower for injured (69 [SD = 19]) than noninjured exercisers (87 [SD = 13], P < .001). Injured exercisers with symptoms of depression reported high stress levels and impaired daily functioning, were younger, and were more likely to have over 10 days injury-related work absence. CONCLUSIONS: The authors recommend psychological assessment of exercisers attending a sports medicine clinic for musculoskeletal injury and a supplemental clinical psychological interview for suspected depression or stress-related psychopathology.

Genetically determined high activities of the TNF-alpha, IL23/IL17, and NFkB pathways were associated with increased risk of ankylosing spondylitis.

BACKGROUND: Ankylosing spondylitis (AS) results from the combined effects of susceptibility genes and environmental factors. Polymorphisms in genes regulating inflammation may explain part of the heritability of AS. METHODS: Using a candidate gene approach in this case-control study, 51 mainly functional single nucleotide polymorphisms (SNPs) in genes regulating inflammation were assessed in 709 patients with AS and 795 controls. Data on the patients with AS were obtained from the DANBIO registry where patients from all of Denmark are monitored in routine care during treatment with conventional and biologic disease modifying anti-rheumatic drugs (bDMARDs). The results were analyzed using logistic regression (adjusted for age and sex). RESULTS: Nine polymorphisms were associated with risk of AS (p < 0.05). The polymorphisms were in genes regulating a: the TNF-α pathway (TNF -308 G > A (rs1800629), and - 238 G > A (rs361525); TNFRSF1A -609 G > T (rs4149570), and PTPN22 1858 G > A (rs2476601)), b: the IL23/IL17 pathway (IL23R G > A (rs11209026), and IL18-137 G > C (rs187238)), or c: the NFkB pathway (TLR1 743 T > C (rs4833095), TLR4 T > C (rs1554973), and LY96-1625 C > G (rs11465996)). After Bonferroni correction the homozygous variant genotype of TLR1 743 T > C (rs4833095) (odds ratios (OR): 2.59, 95% confidence interval (CI): 1.48-4.51, p = 0.04), and TNFRSF1A -609 G > T (rs4149570) (OR: 1.79, 95% CI: 1.31-2.41, p = 0.01) were associated with increased risk of AS and the combined homozygous and heterozygous variant genotypes of TNF -308 G > A (rs1800629) (OR: 0.56, 95% CI: 0.44-0.72, p = 0.0002) were associated with reduced risk of AS. CONCLUSION: We replicated associations between AS and the polymorphisms in TNF (rs1800629), TNFRSF1A (rs4149570), and IL23R (rs11209026). Furthermore, we identified novel risk loci in TNF (rs361525), IL18 (rs187238), TLR1 (rs4833095), TLR4 (rs1554973), and LY96 (rs11465996) that need validation in independent cohorts. The results suggest that genetically determined high activity of the TNF-α, IL23/IL17, and NFkB pathways increase risk of AS.

Physical Health, Medication, and Healthcare Utilization among 70-Year-Old People with Schizophrenia: A Nationwide Danish Register Study.

OBJECTIVES: In light of the excess early mortality in schizophrenia, mainly due to physical illnesses, we investigated medical comorbidity, use of medication, and healthcare utilization among individuals with schizophrenia who survived into older ages to uncover potential factors contributing to their longevity. DESIGN: A nationwide register-based case-control study comparing 70-year-olds with and without schizophrenia. SETTING: Cases were drawn from the Danish Psychiatric Central Register. Age- and sex-matched controls were drawn from the general population via the Civil Registration System. PARTICIPANTS: All Danish inhabitants who were diagnosed and registered with early onset schizophrenia in 1970-1979 and still alive at age 70 years. Controls alive at age 70 years. MEASUREMENTS: Chronic medical comorbidity, medications, and inpatient and outpatient healthcare utilization extracted from Danish healthcare registers. RESULTS: Older adults with schizophrenia did not differ from controls with regard to registered chronic medical illnesses, but were significantly less likely to receive medication for cardiovascular diseases (OR: 0.65; 99.29% CI: 0.50, 0.83) and more likely to be treated with analgesics (OR: 1.46; 99.29% CI: 1.04, 2.05). Overall, hospital admissions and number of days hospitalized were equal to controls, but with significantly fewer general medical outpatient contacts (RR: 0.37; 98.75% CI: 0.24, 0.55). CONCLUSIONS: Because the literature suggests that excess mortality continues into old age, it is possible that medical diseases were under-registered and/or under-treated. Focus on adequate medical treatment, in particular for cardiovascular disease, is needed. Future integration of psychiatric and general medical healthcare, especially outpatient care, might further optimize health outcomes for older adults with schizophrenia.

The Danish Ibbis Trials for Sickness Absentees with Common Mental Disorders: A Phase 4 Prospective Study Comparing Randomized Trial and Real-World Data.

Introduction: In two randomized controlled trials (RCT) we tested the efficacy of a novel integrated vocational rehabilitation and mental healthcare intervention, coined INT, for sickness absentees with common mental disorders. The aim was to improve vocational outcomes compared to Service As Usual (SAU). Contrary to expectations, the delivered intervention caused worse outcomes within some diagnostic groups and some benefits in others. In this phase 4 study, we examined the effectiveness of the intervention in real-world practice. Method: In this prospective intervention study, we allocated adult sickness absentees with either depression, anxiety, or adjustment disorder to receive INT in a real-world setting in a Danish Municipality. We compared the vocational outcomes of this group to a matched group who received INT as a part of the RCTs, after randomization to the intervention group herein. Primary outcome was return to work at any point within 12 months. Results: In the real-world group, 151 participants received INT during 2019. From the randomized trials, 302 matched participants who received INT between 2016-2018 were included. On the primary outcome - return to work within 12 months - the real-word group fared worse (48.3 vs 64.6 %, OR 0.54 [95%CI: 0.37-0.79], p = 0.001). Across most other vocational outcomes, a similar pattern of statistically significant poorer outcomes in the real-world group was observed: Lower number of weeks in work and lower proportion in work at 12 months (42.3% vs. 58.3% (p = 0.002)). Discussion: The real-word group showed significantly worse vocational outcomes. Like in many other studies of complex interventions, implementation was difficult in the original randomized trials and perhaps even more difficult in the less structured real-world setting. Since the intervention was less effective for some groups compared to SAU in the original trial, this negative effect may be even more pronounced in a real-world setting.

Real-Time Identification of Pancreatic Cancer Cases Using Artificial Intelligence Developed on Danish Nationwide Registry Data.

PURPOSE: Pancreatic cancer is expected to be the second leading cause of cancer-related deaths worldwide within few years. Most patients are not diagnosed in time for curative-intent treatment. Accelerating the time of diagnosis is a key component of reducing pancreatic cancer mortality. We developed and tested a dynamic algorithm aiming at proactively identifying patients with a substantially elevated risk of having undiagnosed pancreatic cancer. METHODS: Machine learning methodology was applied to a live stream of nationwide Danish registry data. A hybrid case-control and prospective cohort design relying on incidence density sampling was used. Three models with minimal tuning were tested. All performance evaluation metrics were based on out-of-sample, out-of-time data in a monthly walk-forward strategy to avoid any temporal biases or inflation of performance metrics. Outcome was a diagnosis of pancreatic cancer. RESULTS: Subgroups identified had a 10.1% risk of being diagnosed with pancreatic cancer within 1 year, corresponding to a number needed to screen of 9.9. When considering competing, potentially computed tomography-detectable GI cancers, this number is reduced to 5.7. The time of diagnosis can be accelerated by up to 142 days. CONCLUSION: Currently available nationwide live data and computational resources are sufficient for real-time identification of individuals with at least 10.1% risk of having undiagnosed pancreatic cancer and 17.7% risk of any GI cancer in the Danish population. For prospective identification of high-risk patients, the area under the curve is not a useful indication of the positive predictive values achieved. Viable design solutions are demonstrated, which address the main shortfalls of the existing cancer prediction efforts in relation to temporal biases, leaks, and performance metric inflation. Efficacy evaluations with resection rates and mortality as end points are needed.

30-Month Follow-Up of Individual Placement and Support (IPS) and Cognitive Remediation for People with Severe Mental Illness: Results from a Randomized Clinical Trial.

Background: The individual placement and support (IPS) model for persons with severe mental illness has proven to be more effective than traditional vocational approaches in improving competitive work over 18 months. In this study, the longer-term effects of IPS over 30 months were investigated in a Danish setting. Method: In a randomized clinical trial, we compared the effects of IPS, IPS enhanced with cognitive remediation and work-related social skills training (IPSE), and service as usual (SAU). At three locations in Denmark, 720 patients with serious mental illnesses were randomly assigned to the three groups. Competitive employment, education, and hospital admissions were tracked for 30 months using Danish national registers. Results: The beneficial effects of IPS on competitive employment and education at the 18-month follow-up were sustained over the 30-month follow-up period. Participants receiving IPS or IPSE were more likely to obtain competitive employment or education than those who received service as usual (IPS 65%, IPSE 65%, SAU 53%, p = 0.006), and they worked on average more weeks competitively (IPS 25 weeks, IPSE 21 weeks, SAU 17 weeks; IPS vs. SAU p = 0.004 and IPSE vs. SAU p = 0.007). Moreover, participants in the two IPS groups had fewer outpatient visits during the 30-month follow-up. However, this was only statistically significant when comparing IPSE with SAU p = 0.017. Conclusion: In conclusion, IPS and IPS enhanced with cognitive remediation and work-related skills training demonstrated that the vocational effects of the interventions are retrained over 30 months in a Danish context.

Integrated mental healthcare and vocational rehabilitation for people on sick leave with stress-related disorders: 24-month follow-up of the randomized IBBIS trial.

OBJECTIVES: Integrating vocational rehabilitation and mental healthcare has shown effects on vocational outcomes during sick leave with common mental disorders. In a previous paper, we showed that a Danish integrated healthcare and vocational rehabilitation intervention (INT) had a surprisingly negative impact on vocational outcomes compared to service as usual (SAU) at 6- and 12-month follow-up. That was also the case with a mental healthcare intervention (MHC) tested in the same study. This article reports the 24-month follow-up results of that same study. METHOD: A randomized, parallel-group, three-arm, multi-centre superiority trial was conducted to test the effectiveness of INT and MHC compared to SAU. RESULTS: In total, 631 persons were randomized. Contrary to our hypothesis, SAU showed faster return to work than both INT [hazard rate (HR) 1.39, P=0.0027] and MHC (HR 1.30, P=0.013) at 24-month follow-up. Overall, no differences were observed regarding mental health and functional level. Compared to SAU, we observed some health benefits of MHC, but not INT, at 6-month follow-up but not thereafter, and lower rates of employment at all follow-ups. Since implementation problems might explain the results of INT, we cannot conclude that INT is no better that SAU. The MHC intervention was implemented with good fidelity and did not improve return to work. CONCLUSION: This trial does not support the hypothesis that INT lead to faster return to work. However, implementation failure may explain the negative results.

Trends in pancreatic cancer incidence, characteristics, and outcomes in Denmark 1980-2019: A nationwide cohort study.

OBJECTIVE: To describe time-trends in incidence, characteristics, treatments, and survival in pancreatic cancer patients in Denmark during 1980-2019. DESIGN: A nationwide population-based cohort study of all Danish patients diagnosed with exocrine pancreatic cancer during the study period. Data was obtained from individual-level cross linkage between Danish healthcare registries. We present descriptive characteristics and survival estimates, which was obtained using the Kaplan-Meier estimator and Cox proportional hazards regression models. RESULTS: During the study period, 32,107 patients were diagnosed with pancreatic cancer. In the most recent period, the age-standardized incidence rate was 17.7 per 100,000 person-years. Throughout the study period, between 18.4% and 27.5% of patients had no tumor staging performed, and approximately half of the patient were only offered best supportive care. The proportion of patients treated with surgery doubled during the study period, and the use of adjuvant and neoadjuvant oncological therapy increased substantially. Median survival after surgical resection also increased to 25.8 months in the most recent time period. CONCLUSION: Pancreatic cancer incidence is increasing in Denmark, and this increase is projected to continue. The proportion of patients offered curative-intent treatment increased, which translates into an increase in overall survival. All numbers are comparable to best international standards.

Integrating vocational rehabilitation and mental healthcare to improve the return-to-work process for people on sick leave with stress-related disorders: results from a randomized trial.

OBJECTIVE: Stress-related disorders are common, associated with substantial individual suffering, and place a large economic burden on society. While treatment appears to be able to reduce symptoms, evidence of interventions to improve vocational outcomes is flimsy. Lack of integration of vocational rehabilitation and healthcare services has been suspected to be a major potential barrier in return-to-work (RTW) processes; therefore, we aimed to test the effectiveness of such integration. METHODS: We randomized participants who were on sick leave for ≥ 4 weeks with a stress-related disorder. They were allocated to (i) service as usual (SAU), (ii) improved mental healthcare (MHC), or (iii) integrated interventions (INT). The primary outcome was RTW rates measured at 12 months. Secondary outcome were RTW rates measured at 6 months, proportion in work at 12 months, and levels of stress, anxiety, depression, and functioning at 6 months. RESULTS: We included 666 participants. On the primary outcome and almost all other vocational outcomes, SAU was superior to both INT and MHC. MHC and INT did not differ on any vocational outcome. On several symptom scales, MHC showed lower values than SAU, whilst INT did not differ from the two other groups. CONCLUSION: Both the INT and the MHC intervention lowered RTW rates compared with SAU, and thereby yielded a worse outcome. However, the MHC group showed a tendency towards having lower symptom levels compared with those in the SAU group; accordingly, the SAU group is not unequivocally superior. MHC and INT showed no general differences.

Splenectomy and risk of COVID-19 infection, hospitalisation, and death.

OBJECTIVES: Splenectomy is a common surgical procedure, and splenectomized patients have shown to be severely more affected by certain infections than patients with a preserved splenic function. We investigated the risk of COVID-19 infection and subsequent hospitalisation and death in splenectomized patients. METHODS: We conducted a case-control study of all individuals with a microbiologically verified COVID-19 infection in Denmark through December 31, 2020. To each case, we matched three controls on age, sex, and region of residence. We examined the association between previous splenectomy and the risk of COVID-19 infection, hospitalisation, and death using a logistic regression model. RESULTS: We identified 165,623 individuals with a positive COVID-19 test and 493,300 matched controls. Mean age was 38 years. 130 and 422 splenectomies were performed in the COVID-19 positive individuals and controls, respectively. Splenectomized patients did not have a higher risk of COVID-19 infection than non-splenectomized patients (adjusted OR: 0.89; 95% CI: 0.73-1.08). Among COVID-19 positive individuals, splenectomized patients may have an increased risk of hospitalisation or death (adjusted OR for combined endpoint: 1.44; 95% CI: 0.79-2.61). CONCLUSIONS: Splenectomized patients are not at an increased risk of COVID-19 infection, but they may have a higher risk of hospitalisation or death among COVID-19 positive individuals. This may be attributed to higher comorbidity levels.