Mental illness and cardiovascular health: observational and polygenic score analyses in a population-based cohort study.

BACKGROUND: Individuals with serious mental illness have a markedly shorter life expectancy. A major contributor to premature death is cardiovascular disease (CVD). We investigated associations of (genetic liability for) depressive disorder, bipolar disorder and schizophrenia with a range of CVD traits and examined to what degree these were driven by important confounders. METHODS: We included participants of the Dutch Lifelines cohort (N = 147 337) with information on self-reported lifetime diagnosis of depressive disorder, bipolar disorder, or schizophrenia and CVD traits. Employing linear mixed-effects models, we examined associations between mental illness diagnoses and CVD, correcting for psychotropic medication, demographic and lifestyle factors. In a subsample (N = 73 965), we repeated these analyses using polygenic scores (PGSs) for the three mental illnesses. RESULTS: There was strong evidence that depressive disorder diagnosis is associated with increased arrhythmia and atherosclerosis risk and lower heart rate variability, even after confounder adjustment. Positive associations were also found for the depression PGSs with arrhythmia and atherosclerosis. Bipolar disorder was associated with a higher risk of nearly all CVD traits, though most diminished after adjustment. The bipolar disorder PGSs did not show any associations. While the schizophrenia PGSs was associated with increased arrhythmia risk and lower heart rate variability, schizophrenia diagnosis was not. All mental illness diagnoses were associated with lower blood pressure and a lower risk of hypertension. CONCLUSIONS: Our study shows widespread associations of (genetic liability to) mental illness (primarily depressive disorder) with CVD, even after confounder adjustment. Future research should focus on clarifying potential causal pathways between mental illness and CVD.

Fly-scan-oriented motion analyses and upgraded beamline integration architecture for the High-Dynamic Double-Crystal Monochromator at Sirius/LNLS.

The High-Dynamic Double-Crystal Monochromator (HD-DCM) is a mechatronic system with unique control-based architecture and deep paradigm changes as compared with traditional beamline monochromators. Aiming at unprecedented inter-crystal positioning stability in vertical-bounce double-crystal monochromators (DCMs) of the order of 10 nrad RMS (1 Hz to 2.5 kHz), and not only in fixed-energy but also in fly-scan operation, it has been developed according to a `first-time right' predictive design approach for hard X-ray beamlines at Sirius, the fourth-generation light source at the Brazilian Synchrotron Light Laboratory (LNLS/CNPEM). This work explores some of the challenges that emerge with this new technology and presents the latest commissioning results that demonstrate the unparallel performances of the HD-DCM at the undulator-based EMA (Extreme Methods of Analysis) beamline at Sirius. With the enabled fast spectroscopy fly-scan possibilities, a new energy-tuning evaluation method, based on wave-propagation simulations, becomes part of a motion-oriented analysis that is carried out to derive the multi-axis non-linear positioning problem, covering not only energy selection and fixed exit in the HD-DCM but also the emission spectrum of an adjustable-phase undulator (APU). The HD-DCM control scheme and its flexible operation modes are described in detail as well. Furthermore, a new integration topology between the HD-DCM and EMA's APU, coming already close to ultimate motion levels, is described and validated.

Cost-effectiveness of on-demand removal of syndesmotic screws.

PURPOSE: Syndesmotic screw removal following acute syndesmotic injury is a commonly performed procedure. However, recent studies suggest that the removal does not result in improved patient reported outcome, while the procedure has proved not to be without complications. The aim of this study was to present a health-economic evaluation of on-demand removal (ODR) compared to routine removal (RR) of the syndesmotic screw. METHODS: Data were collected from the RODEO trial, a randomized controlled non-inferiority trial comparing functional outcome of ODR with RR. Economic evaluation resulted in total costs, costs (in Euro) per quality adjusted life year (QALY) and costs per point improvement on the Olerud Molander Ankle Score (OMAS). This included both direct and indirect costs. RESULTS: Total costs for ODR were significantly lower with a mean difference of 3160 euro compared to RR (p < 0.001). The difference in QALY was not significant. The difference in OMAS at 12 months was 1.79 with an incremental cost-effectiveness ratio (ICER) of €-1763 (p = 0.512). The ICER was well below the willingness to pay. Although unit costs might vary between hospitals and countries, these results provide relevant data of cost-effectiveness. CONCLUSION: The clinical effectiveness of both ODR and RR can be considered equal. The costs are lower for patients treated with ODR, which leads to the conclusion that ODR is cost-effective.

Longitudinal associations between alcohol use, smoking, genetic risk scoring and symptoms of depression in the general population: a prospective 6-year cohort study.

BACKGROUND: Alcohol consumption, smoking and mood disorders are leading contributors to the global burden of disease and are highly comorbid. Yet, their interrelationships have remained elusive. The aim of this study was to examine the multi-cross-sectional and longitudinal associations between (change in) smoking and alcohol use and (change in) number of depressive symptoms. METHODS: In this prospective, longitudinal study, 6646 adults from the general population were included with follow-up measurements after 3 and 6 years. Linear mixed-effects models were used to test multi-cross-sectional and longitudinal associations, with smoking behaviour, alcohol use and genetic risk scores for smoking and alcohol use as independent variables and depressive symptoms as dependent variables. RESULTS: In the multi-cross-sectional analysis, smoking status and number of cigarettes per day were positively associated with depressive symptoms (p < 0.001). Moderate drinking was associated with less symptoms of depression compared to non-use (p = 0.011). Longitudinally, decreases in the numbers of cigarettes per day and alcoholic drinks per week as well as alcohol cessation were associated with a reduction of depressive symptoms (p = 0.001-0.028). Results of genetic risk score analyses aligned with these findings. CONCLUSIONS: While cross-sectionally smoking and moderate alcohol use show opposing associations with depressive symptoms, decreases in smoking behaviour as well as alcohol consumption are associated with improvements in depressive symptoms over time. Although we cannot infer causality, these results open avenues to further investigate interventions targeting smoking and alcohol behaviours in people suffering from depressive symptoms.

Pediatric medulloblastoma express immune checkpoint B7-H3.

PURPOSE: Medulloblastomas (MB) are highly malignant brain tumors that predominantly occur in young infants. Immunotherapy to boost the immune system is emerging as a novel promising approach, but is often hampered by inhibitory immune checkpoints. In the present study, we have studied immune checkpoint B7-H3 expression in a tissue cohort of human pediatric MB. METHODS: Expression of B7-H3 was detected by immunohistochemistry and classified via B7-H3 staining intensity and percentage of B7-H3 positive tumor cells. Subsequently, B7-H3 protein expression was distinguished in MB molecular subtypes and correlated to immune cell infiltrates, patient characteristics, and survival. RESULTS: B7-H3 protein expression was found in 23 out of 24 (96%) human pediatric MB cases and in 17 out of 24 (71%) MB cases > 25% of tumor cells had any level of B7-H3 expression. B7-H3 protein expression was more frequent on Group-4 MB as compared with other molecular subtypes (p = 0.02). Tumors with high B7-H3 expression showed less influx of γδT cells (p = 0.002) and CD3+ T cells (p = 0.041). CONCLUSION: Immune checkpoint B7-H3 is differentially expressed by the large majority of pediatric MB. This further warrants the development of novel B7-H3-directed (immuno)therapeutic methods for children with incurable, metastatic, or chemo-resistant MB.

Validation of Central Pressure Estimation in Patients with an Aortic Aneurysm Before and After Endovascular Repair.

PURPOSE: The aim of this study was to investigate if non-invasive central pressure estimations are accurate in patients with an abdominal aortic aneurysm, before and after endovascular repair. Secondary evaluation was if measurement-accuracy was dependent on anatomical characteristics. METHODS: Procedural invasive and non-invasive pressure-measurements were performed simultaneously both before and after endovascular repair in 20 patients with an infrarenal abdominal aortic aneurysm. Invasive catheter measurements were performed in the abdominal aorta. A tonometric device was used to perform non-invasive pressure-wave-analysis at the radial artery. A generalized transfer-function was used to generate an ascending aortic waveform for both measurements, allowing for direct comparison. RESULTS: Pre-treatment the mean differences between methods were - 5.5 mmHg (p = .904), - 11.8 (p < .001), and - 7.2 mmHg (p = .124) for central systolic, diastolic, and mean pressure, respectively. The accuracy was dependent of aneurysm sac volume and intraluminal thrombus volume. Post-treatment limits of agreement were smaller for all pressure parameters compared to pre-treatment. The mean differences were 6.5 mmHg (p = .007), - 6.4 (p < .020), and 1.6 mmHg (p = .370) for central systolic, diastolic, and mean pressure, respectively. CONCLUSION: In untreated AAA's the accuracy of non-invasive central pressure estimation was acceptable (mean difference between 5 and 10 mmHg) when compared to invasive pressures, but dependent of AAA characteristics. After EVAR the accuracy of central pressure estimation improved (reduction of 75% of the mean difference between pre and post measurements) TRIAL REGISTRATION NUMBER: NCT03469388; 3-5-2018.

Correction to: Routine versus on demand removal of the syndesmotic screw; a protocol for an international randomised controlled trial (RODEO-trial).

An amendment to this paper has been published and can be accessed via the original article.

[Implementation of a stop-smoking support program for patients and employees in a psychiatric hospital: First results]. / Implementatie van een stoppen-met-rokenprogramma in een psychiatrisch ziekenhuis: eerste resultaten.

BACKGROUND: In contrast to several other countries, smoking is not an integral part of treatment during admission to a psychiatric hospital in The Netherlands.
AIM: Implementation of a smoking cessation program for patients and employees of a psychiatric ward of an academic medical center in The Netherlands.
METHOD: Prospective, mixed-method study of implementation of a smoking cessation program for patients and employees of a psychiatric academic hospital in Amsterdam. The program consisted of 7 weekly group meetings by certified smoking cessation coaches. Nicotine replacement therapy was provided for free, if necessary.
RESULTS: During 14 months, 65 individuals were seeking help to stop smoking: 39 patients and 26 employees. Of these, 29 patients and 16 employees participated in group meetings with an average of 2.6 times per person. There were 20 individuals who visited the group meetings or received individual coaching at least 3 times (6 patients and 14 employees). Fifty-five percent of these individuals reported to be smoke-free at 3 months after joining the first meeting. Employees were much more likely to quit than patients. From interviews with 20 participants, it was noticed that combining patients and employees in one group was perceived as a barrier due to a gap in processing speed.
CONCLUSION: On the psychiatric ward of an academic hospital in The Netherlands, there was a positive experience with providing smoking cessation treatment. A small number of employees and patients participated in a smoking cessation program and quitting smoking was reached by only a few patients. Supporting smoking cessation in a psychiatric hospital asks for intensive screening, diagnosing, treatment and smoke-free policies.

[Smoke-free psychiatric hospitals and the role of aggression: a systematic review]. / Is er een risico op toename van agressie bij een rookvrije ggz? Een literatuurstudie.

AIM: To provide an overview of the literature on transitions towards smoke-free psychiatric hospitals and the risk of aggression.
METHOD: A systematic search was made in medline, Embase and Psycinfo. Studies were included if they reported data on: a smoke-free intervention in a psychiatric hospital or ward, the number of aggressive incidents, and seclusions or prn drugs.
RESULTS: A total of 17 studies matched the inclusion/exclusion criteria; 5 reported a decrease in the number of aggressive incidents after implementation of a smoke-free ward, 7 showed an increase in the number of incidents, and 5 studies reported no differences. Heterogeneity between the studies was high with respect to the definition and implementation of the intervention, the definition and measurement of aggression, study design, length of follow-up, and the sample size.
CONCLUSION: These findings suggest that, after changing the policy towards a smoke-free psychiatric hospital, the risk of aggression is limited. However, several precautions related to the preparation and implementation of this transition seem to be essential. The results support further investment in the implementation of smoke-free psychiatric hospitals in the Netherlands, while maintaining safety.

Functional outcome of implant removal following fracture fixation below the level of the knee: a prospective cohort study.

AIMS: The aim of this study was to evaluate the functional outcome in patients undergoing implant removal (IR) after fracture fixation below the level of the knee. PATIENTS AND METHODS: All adult patients (18 to 75 years) undergoing IR after fracture fixation below the level of the knee between November 2014 and September 2016 were included as part of the WIFI (Wound Infections Following Implant Removal Below the Knee) trial, performed in 17 teaching hospitals and two university hospitals in The Netherlands. In this multicentre prospective cohort, the primary outcome was the difference in functional status before and after IR, measured by the Lower Extremity Functional Scale (LEFS), with a minimal clinically important difference of nine points. RESULTS: A total of 179 patients were included with a median age of 50 years (interquartile range (IQR) 37 to 60), of whom 71 patients (39.7%) were male. With a median score of 60 before IR (IQR 45 to 72) and 66 after IR (IQR 51 to 76) on the LEFS, there was a statistically significant improvement in functional outcome (p < 0 .001). A total of 31 surgical site infections (17.3%) occurred. CONCLUSION: Although IR led to a statistically significant improvement of functional outcome, the minimal clinically important difference was not reached. In conclusion, this study shows that IR does not result in a clinically relevant improvement in functional outcome. These results, in combination with the high complication rate, highlight the importance of carefully reviewing the indication for IR. Cite this article: Bone Joint J 2019;101-B:447-453.

New ecosystems in the deep subsurface follow the flow of water driven by geological activity.

Eukarya have been discovered in the deep subsurface at several locations in South Africa, but how organisms reach the subsurface remains unknown. We studied river-subsurface fissure water systems and identified Eukarya from a river that are genetically identical for 18S rDNA. To further confirm that these are identical species one metazoan species recovered from the overlying river interbred successfully with specimen recovered from an underlying mine at -1.4 km. In situ seismic simulation experiments were carried out and show seismic activity to be a major force increasing the hydraulic conductivity in faults allowing organisms to create ecosystems in the deep subsurface. As seismic activity is a non-selective force we recovered specimen of algae and Insecta that defy any obvious other explanation at a depth of -3.4 km. Our results show there is a steady flow of surface organisms to the deep subsurface where some survive and adapt and others perish. As seismic activity is also present on other planets and moons in our solar system the mechanism elucidated here may be relevant for future search and selection of landing sites in planetary exploration.

Non- or Minimally Displaced Distal Radial Fractures in Adult Patients: Three Weeks versus Five Weeks of Cast Immobilization-A Randomized Controlled Trial.

Background Patients with non- or minimally displaced distal radial fractures, that do not need repositioning, are mostly treated by a short-arm cast for a period of 4 to 6 weeks. A shorter period of immobilization may lead to a better functional outcome. Purpose We conducted a randomized controlled trial to evaluate whether the duration of cast immobilization for patients with non- or minimally displaced distal radial fractures can be safely shortened toward 3 weeks. Materials and Methods The primary outcomes were patient-reported outcomes measured by the Patient-Related Wrist Evaluation (PRWE) and Quick Disability of Arm, Shoulder and Hand (QuickDASH) score after 1-year follow-up. Secondary outcome measures were: PRWE and QuickDASH earlier in follow-up, pain (Visual Analog Scale), and complications like secondary displacement. Results Seventy-two patients (male/female, 23/49; median age, 55 years) were included and randomized. Sixty-five patients completed the 1-year follow-up. After 1-year follow up, patients in the 3 weeks immobilization group had significantly better PRWE (5.0 vs. 8.8 points, p = 0.045) and QuickDASH scores (0.0 vs. 12.5, p = 0.026). Secondary displacement occurred once in each group. Pain did not differ between groups ( p = 0.46). Conclusion Shortening the period of immobilization in adult patients with a non- or minimally displaced distal radial fractures seems to lead to equal patient-reported outcomes for both the cast immobilization groups. Also, there are no negative side effects of a shorter period of cast immobilization. Therefore, we recommend a period of 3 weeks of immobilization in patients with distal radial fractures that do not need repositioning.

Routine versus on demand removal of the syndesmotic screw; a protocol for an international randomised controlled trial (RODEO-trial).

BACKGROUND: Syndesmotic injuries are common and their incidence is rising. In case of surgical fixation of the syndesmosis a metal syndesmotic screw is used most often. It is however unclear whether this screw needs to be removed routinely after the syndesmosis has healed. Traditionally the screw is removed after six to 12 weeks as it is thought to hamper ankle functional and to be a source of pain. Some studies however suggest this is only the case in a minority of patients. We therefore aim to investigate the effect of retaining the syndesmotic screw on functional outcome. DESIGN: This is a pragmatic international multicentre randomised controlled trial in patients with an acute syndesmotic injury for which a metallic syndesmotic screw was placed. Patients will be randomised to either routine removal of the syndesmotic screw or removal on demand. Primary outcome is functional recovery at 12 months measured with the Olerud-Molander Score. Secondary outcomes are quality of life, pain and costs. In total 194 patients will be needed to demonstrate non-inferiority between the two interventions at 80% power and a significance level of 0.025 including 15% loss to follow-up. DISCUSSION: If removal on demand of the syndesmotic screw is non-inferior to routine removal in terms of functional outcome, this will offer a strong argument to adopt this as standard practice of care. This means that patients will not have to undergo a secondary procedure, leading to less complications and subsequent lower costs. TRIAL REGISTRATION: This study was registered at the Netherlands Trial Register (NTR5965), Clinicaltrials.gov ( NCT02896998 ) on July 15th 2016.

Satisfaction of psychotic patients with care and its value to predict outcomes.

BACKGROUND: A key indicator of quality of treatment from the patient's perspective is expressed by satisfaction with care. Our aim was to (i) explore satisfaction and its relation to clinical outcome measures; and (ii) explore the predictive value of satisfaction for the course of outcomes over three years. METHODS: Data of 654 patients with a non-affective psychosis included in a naturalistic longitudinal cohort study were analyzed. We included 506 males and 148 females with a mean age of 30.47 (SD 7.24) from The Netherlands. Satisfaction was measured with the self-rating Client Satisfaction Questionnaire-8. A wide range of interviewer-rated (e.g., Positive and Negative Symptom Scale) and self-rated (e.g., World Health Organization Quality of Life); outcomes of low, intermediate and high satisfied patients were compared using ANOVA, Chi2 or Kruskal-Wallis tests. The predictive value of satisfaction level on clinical outcomes after three years was tested using regression models. RESULTS: Satisfaction levels were low (19.4%), intermediate (48.9%) or high (31.7%). High satisfied patients showed significantly better interviewer-rated outcomes, e.g., less severe psychotic symptoms, and self-rated outcomes, e.g., better quality of life, compared to patients with intermediate or low satisfaction. Higher levels of satisfaction with care at baseline predicted a reduction of positive symptoms three years later (B=-.09, P-value=.013). CONCLUSIONS: Satisfaction of patients with psychosis is a valuable monitoring measure since high satisfied patients show more favorable outcomes ranging from psychopathological symptoms to quality of life. Further research into explanations of lower levels of satisfaction is commendable in order to improve outcomes.