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The objective of this population-based register study was (1) to investigate the association between young adults diagnosed with attention-deficit/hyperactivity disorder (ADHD) and subsequent labour market marginalisation (LMM) in two comparison groups, i.e. matched young adults from the general population without ADHD and unaffected siblings to persons with ADHD and (2) to assess the role of comorbid disorders.
This study included all young adults in Sweden, aged 19–29 years, with an incident diagnosis of ADHD 2006–2011 (n = 9718). Crude and multivariate sex-stratified hazard ratios (HRs) with 95% confidence intervals (CIs) were measured 5 years after the diagnosis of ADHD for the risk of disability pension, long-term sickness absence (SA) (>90 days), long-term unemployment (>180 days) and a combined measure of all three in young adults with ADHD compared to their siblings without ADHD and a matched comparison group.
In the adjusted analyses young adults with ADHD had a 10-fold higher risk of disability pension (HR = 10.2; CI 9.3–11.2), a nearly three-fold higher risk of long-term SA (HR = 2.7; CI 2.5–2.8) and a 70% higher risk of long-term unemployment (HR = 1.7; CI 1.6–1.8) compared to the matched comparison group. The risk estimates were lower compared to siblings for disability pension (HR = 9.0; CI 6.6–12.3) and long-term SA (HR = 2.5; CI 2.1–3.1) but higher in the long-term unemployed (HR = 1.9; CI 1.6–2.1). Comorbid disorders explained about one-third of the association between ADHD and disability pension, but less regarding SA and long-term unemployment.
Young adults with ADHD have a high risk for different measures of LMM and comorbidities explain only a small proportion of this relationship.
Augmented reality is a novel technology with potential to overlay aspects or objects from the home environment into hospital-based training, which may increase relevance and motivation for hospital-based rehabilitation. Consultation with people with lived experience and clinician stakeholders is an important step when exploring possibilities for use of new technology in the hospital environment.
This study sought to understand the need and acceptability of augmented reality from the perspectives of health professionals and stroke survivors during inpatient stroke rehabilitation.
This qualitative descriptive study included stroke survivors (n = 4) and health professionals (n = 10) from a large metropolitan hospital. Data collection was undertaken via focus groups which were transcribed verbatim and analysed using qualitative content analysis.
Inductive content analysis revealed three themes: everything is computerised these days; the possibilities are endless…but what about?; and bringing the outside into the hospital. Participants were open to the use of augmented reality for stroke rehabilitation; however there was uncertainty with pragmatic concerns and stroke survivors describing possible applications in building confidence and self-efficacy, and sharing experiences to enhance caregivers understanding.
This research identified that there is potential acceptability for augmented reality in stroke rehabilitation. The needs identified by the participants may inform development of current and future technology.
The Repugnant Conclusion is an implication of some approaches to population ethics. It states, in Derek Parfit's original formulation,
For any possible population of at least ten billion people, all with a very high quality of life, there must be some much larger imaginable population whose existence, if other things are equal, would be better, even though its members have lives that are barely worth living. (Parfit 1984: 388)
Discontentment is growing such that governments, and notably that of China, are increasingly providing subsidies to companies outside their jurisdiction, ‘buying their way’ into other countries’ markets and undermining fair competition therein as they do so. In response, the European Union recently published a proposal to tackle such foreign subsidization in its own market. This article asks whether foreign subsidies can instead be addressed under the existing rules of the World Trade Organization, and, if not, whether those rules allow States to take matters into their own hands and act unilaterally. The authors shed light on these issues and provide preliminary guidance on how to design a response to foreign subsidization which is consistent with international trade law.
This paper describes a small unmanned aerial vehicle (UAV)-based synthetic aperture radar (SAR) system using low-cost radar (5–6 GHz), position (GNSS/RTK) and attitude (IMU) sensors for the generation of high-resolution images. Measurements using straight as well as highly curved flight trajectories and varying flight speeds are presented, showing range and cross-range lobe-widths close to the theoretical limits. An analysis of the improvements obtained by the use of attitude angles (roll, pitch, and yaw), to correct for the relative offsets in antenna positions as the UAV moves, is included. A capability to generate SAR images onboard with the back-projection algorithm has been implemented using a GPU accelerated single-board computer. Generated images are transmitted to ground using a Wi-Fi data link.
Childhood maltreatment (CM) is a known risk factor for adolescent pregnancy. Sleep disturbances and psychological distress, both common negative sequelae of CM, often co-occur during pregnancy, although directionality remains unclear. Furthermore, little is known about how CM affects sleep–distress associations during pregnancy. In pregnant adolescents, we examined: (a) whether there are significant predictive associations from CM to sleep quality and distress and (b) bidirectional influences of distress and sleep quality. Healthy pregnant adolescents (n = 204) were recruited before or during the 2nd trimester. CM was assessed at enrollment; sleep quality and distress were assessed in the 2nd and 3rd trimesters. Hypotheses were tested using path analysis. Findings revealed that CM was associated with worse 2nd trimester sleep quality and distress (β = .19, p < .05 for sleep; β = .30, p < .001 for distress). Higher levels of 2nd trimester distress were associated with lower 3rd trimester sleep quality (β = .19, p < .05). Findings provide novel information about (a) associations from CM to prenatal mood and sleep in pregnant adolescents, and (b) sleep–distress directionality over the course of pregnancy. These results have implications for better understanding the ways in which CM potentially exerts influences later in life, and for targeting interventions to address physical and mental health during pregnancy.
The Montreal Cognitive Assessment (MoCA) is routinely used during the early assessment of people after stroke to indicate cognitive effects and inform clinical decision-making.
The purpose of this study was to examine the relationship between cognition in the first week post-stroke and personal and instrumental activities of daily skills at 1 month and 3 months post-stroke.
A prospective cohort study consecutively recruited people admitted to the acute stroke ward. Acute cognitive status was measured using the MoCA within 1 week post-stroke onset. Functional outcomes were measured using the Functional Independence Measure (FIM) and the Australian Modified Lawton’s Instrumental Activities of Daily Living Scale (Lawton’s) at 1 month and 3 months post-stroke.
Fifty participants with predominantly mild stroke (n = 47) and mean age of 69.8 achieved a mean MoCA score of 23.1. Controlling for age, the MoCA was associated with the overall FIM score at 1 month (P = 0.02). It was nearing significance for the Lawton’s at 1 month (P = 0.06) but was not associated with either outcome at 3 months. A score of less than 23 on the MoCA was indicative of lower scores on both outcomes.
A low MoCA score within 1 week of stroke may indicate need for support or rehabilitation due to early impacts on personal activities of daily living, but is not associated with poor functional outcomes at 3 months.
Driving and stopping driving present challenging issues for older people living with memory problems and the family members supporting them. Changes to driving status impact the individual stopping driving and their family members. CarFreeMe is an existing, effective driving cessation program for older people that may be applicable to older people living with dementia. The purpose of this study was to adapt the program and explore feasibility and key stakeholder perspectives.
The Medical Research Council guidelines for conducting research into complex interventions guided the development, acceptability and feasibility piloting. A multidisciplinary approach was taken, and key stakeholders were involved throughout the process. This included an adaptation process, followed by expert reference group feedback and case series pilot study.
The background research indicated that some key changes were required to meet the needs of people living with dementia. Aspects of the content, language, format and activities were adapted and an additional module was created for family members – whose involvement was identified as important. A more personalized, flexible approach was recommended. The expert reference group [psychologists (n = 2), occupational therapists (n = 3) and dementia behavior consultants (n = 2)] indicated the program was appropriate and needed, and made recommendations for feasibility. Pilot testing with three families indicated acceptability.
A driving cessation program adapted for use with people living with dementia and their families required some changes to meet the needs and situations based on feedback from key stakeholders. Future studies will evaluate implementation outcomes across a range of settings.
In this paper, we analyze Fourier coefficients of automorphic forms on a finite cover G of an adelic split simply-laced group. Let
be a minimal or next-to-minimal automorphic representation of G. We prove that any
$\eta \in \pi $
is completely determined by its Whittaker coefficients with respect to (possibly degenerate) characters of the unipotent radical of a fixed Borel subgroup, analogously to the Piatetski-Shapiro–Shalika formula for cusp forms on
. We also derive explicit formulas expressing the form, as well as all its maximal parabolic Fourier coefficient, in terms of these Whittaker coefficients. A consequence of our results is the nonexistence of cusp forms in the minimal and next-to-minimal automorphic spectrum. We provide detailed examples for G of type
with a view toward applications to scattering amplitudes in string theory.
The Levelling-Down Objection is a standard objection to monistic egalitarian theories where equality is the only thing that has intrinsic value. Most egalitarians, however, are value pluralists; they hold that, in addition to equality being intrinsically valuable, the egalitarian currency in which we are equal or unequal is also intrinsically valuable. In this paper, I argue that the Levelling-Down Objection still minimizes the weight that the intrinsic badness of inequality could have in the overall intrinsic evaluation of outcomes, given a certain way of measuring the badness of inequality, namely, the Additive Individual-Complaints Measure.
To determine the efficacy of QTP in patients with bipolar I disorder with mixed symptoms.
Data from 2 phase III studies (D1447C00126 and D1447C00127) were pooled. Unlike previous analyses of these studies, mixed events were analyzed separately. Patients received QTP (400-800 mg/d)+Li/DVP to achieve ≥12 weeks of clinical stability followed by double-blind treatment with QTP (400-800 mg/d)+Li/DVP or PBO+Li/DVP for up to 104 weeks. Primary endpoint was time to first mood event post-randomization.
1326 patients were included in the ITT population. Relative to PBO, QTP significantly increased time to recurrence of mixed events (P< 0.0001). 445 ITT patients had a most recent mixed episode at study entry. In these patients, mood events were reported by fewer patients on QTP+Li/DVP (21.0%) than on PBO+Li/DVP (53.9%). These events included mixed (6.4% vs 22.1%), pure manic (5.0% vs 13.3%), and pure depressed events (9.6% vs 18.6%). Time to recurrence of mood events was significantly longer for patients on QTP+Li/DVP than for those on PBO+Li/DVP for mixed (HR, 0.23, 95% CI, 0.13-0.42, P< 0.0001), pure manic (HR, 0.30, 95% CI, 0.15-0.60, P=0.0007), and pure depressed events (HR, 0.38, 95% CI, 0.22-0.64, P=0.0003). No new safety concerns were noted.
In stable patients with bipolar I disorder, QTP+Li/DVP significantly increased: a) time to recurrence of mood events compared with PBO in patients with mixed symptoms at study entry; and b) time to occurrence of mixed mood events in patients with any mood episode at study entry.
Supported by funding from AstraZeneca Pharmaceuticals.
Combined data are presented from 2 long-term studies (D1447C00126; D1447C00127) of QTP in combination with Li or DVP in the prevention of mood events in bipolar I disorder. Data from Li and DVP treatment groups are analyzed separately to determine the added benefit of QTP.
Patients received QTP (400-800 mg/d)+Li/DVP to achieve ≥12 weeks of clinical stability followed by double-blind treatment with QTP (400-800 mg/d)+Li/DVP or PBO+Li/DVP for up to 104 weeks. Li or DVP treatment was openly assigned at the discretion of the investigator. Primary endpoint was time to first mood event post-randomization.
1326 patients were included in the ITT population. In both Li and DVP groups, the risk of recurrence of any mood event was significantly reduced following treatment with QTP relative to placebo (HR, 0.32, 95% CI, 0.24-0.44 and HR, 0.28, 95% CI, 0.21-0.37; for Li and DVP, respectively; P< 0.0001 for both). This trend was repeated for risk of recurrence of mania and depression events (P< 0.0001 vs placebo). Comparison of QTP+Li versus QTP+DVP groups revealed no differences in the risk of recurrence of mood, mania, or depression events. Safety data were generally consistent with the recognized safety profiles of QTP, Li, and DVP.
In stable patients with bipolar I disorder, treatment with QTP, in combination with either Li or DVP, resulted in similar significant increases in the time to recurrence of a mood event (mania or depression) compared with placebo, regardless of Li or DVP co-treatment.
Supported funding from AstraZeneca Pharmaceuticals.
Evaluate the effects of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with major depressive disorder (MDD) according to disease severity.
Pooled data (quetiapine XR 50, 150 and 300mg/day doses combined) from four 6- or 8-week placebo-controlled quetiapine XR monotherapy studies (D1448C00001, D1448C00002, D1448C00003, D1448C00004) were analysed. Key inclusion criterion for all 4 studies: HAM-D total score ≥22. Primary endpoint: change from randomisation in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. A post-hoc analysis assessed change from randomisation in MADRS total score and MADRS response (≥ 50% reduction in MADRS total score) at endpoint (Week 6 or Week 8) in 6 severity cohorts (defined by a MADRS total score at randomisation ≥24, ≥26, ≥28, ≥30, ≥32 or ≥34).
1752 patients (comprising the l’ all patients’ group) were evaluated (MADRS score ≥24 at randomisation, n=1601; ≥26, n=1467; ≥28, n=1269; ≥30, n=1038; ≥32, n=745; ≥34, n=500). Quetiapine XR significantly reduced mean MADRS total score at endpoint in lrsquo;all patients’ (p< 0.001 vs placebo) and in all 6 severity cohorts (≥24, ≥26, ≥28, ≥30 and ≥32, p< 0.001 vs placebo; ≥34, p< 0.01 vs placebo). MADRS response rates were significantly higher in the quetiapine XR group vs placebo in the ‘all patients’ group (p< 0.001 vs placebo) and in all 6 severity cohorts (≥24, ≥26, ≥28, ≥30 and ≥32, p< 0.001 vs placebo; ≥34, p=0.001 vs placebo).
Quetiapine XR monotherapy significantly improved depressive symptoms in patients with MDD irrespective of disease severity, including the most severe levels of depression.
Depression symptoms in bipolar disorder have debilitating effects on functioning and quality of life (QoL).
To assess effects of 8 weeks of quetiapine monotherapy on functioning and QoL in patients with bipolar depression (BPD).
To evaluate functioning and QoL using patient-reported outcomes.
Data from 4 trials (BOLDER I and II; EMBOLDEN I and II) of quetiapine (300 and 600 mg/day) in BPD were combined (n = 2593). The Sheehan Disability Scale (SDS) measured functioning (BOLDER II; EMBOLDEN I and II) and the QoL Enjoyment and Satisfaction Questionnaire (Q-LES-Q)-Short Form measured QoL (BOLDER I and II; EMBOLDEN II).
Quetiapine improved overall functioning (mean change [SE] in SDS total score: -7.23 [0.49], -7.49 [0.49], with quetiapine 300 mg/day and quetiapine 600 mg/day, respectively vs placebo (-5.91 [0.54]); P < 0.01 for both). Both doses improved functioning in SDS domains of work/school, social life, and family life/home responsibilities vs placebo (P < 0.05). Quetiapine 600 mg/day reduced days missed from work/school and productivity losses vs placebo (P < 0.01). QoL was improved with both quetiapine doses vs placebo (P < 0.001; least squares mean changes (SE) in Q-LES-Q total score from baseline to Day 57: 9.69 (0.51), 9.95 (0.50), and 6.81 (0.54) with quetiapine 300 mg/day, quetiapine 600 mg/day, and placebo, respectively). Tolerability was consistent with the known safety profile of quetiapine.
Quetiapine treatment (300 and 600 mg/day) for 8 weeks significantly improved functioning and QoL vs placebo in patients with BPD.
Supported by funding from AstraZeneca Pharmaceuticals LP.
Data from two, identically designed, placebo-controlled, randomised, double-blind clinical trials (D1444C00132+D1444C00133) for once-daily extended-release quetiapine fumarate (QTP-XR) were pooled and analysed.
Evaluate dose response, efficacy and safety for QTP-XR in schizophrenia.
Post-hoc analysis of data from patients receiving QTP-XR 400, 600, 800 mg/day or placebo. Endpoints: least squares means (LSM) change from baseline to Day 42 in PANSS total and positive and negative subscale scores. No corrections for multiplicity were performed. Adverse events (AEs) were recorded.
914 patients were included; PANSS scores were assessed in the MITT population (n = 889). LSM change from baseline in PANSS total score diverged significantly from placebo at: Day 14 for QTP-XR 800 mg/day (-15.3 vs -12.1 for placebo; p = 0.018); Day 21 for 600 mg/day (-17.3 vs -14.2; p = 0.039); Day 42 for 400 mg/day (-19.2 vs -15.4; p = 0.033).
Jonckheere-Terpstra analysis of change in PANSS total score at Day 42 showed a significant QTP-XR dose response (p = 0.0196; p < 0.001 with placebo). PANSS positive scores diverged by Day 21 for both QTP-XR 800 (-5.7 vs -4.8; p = 0.049) and 600 mg/day (-5.8 vs -4.8; p = 0.046). PANSS negative scores diverged by Day 21 (-4.0 vs -3.2; p = 0.040) and 42 (-4.8 vs -3.6; p = 0.009) for QTP-XR 800 and 600 mg/day, respectively. AEs occurred in 59.4%, 66.5%, 62.1% and 56.2% of patients in the QTP-XR 800, 600, 400 mg/day and placebo groups, respectively. Most common AEs were somnolence, dry mouth, sedation, insomnia, dizziness, headache, constipation and nausea.
QTP-XR was generally well tolerated and demonstrated efficacy that increased with dose in schizophrenia.
Quetiapine extended release (XR) was developed to provide convenient, once-daily dosing and rapid dose escalation when compared to the immediate-release (IR) formulation.
To review preclinical and clinical study data on the efficacy and safety of quetiapine XR in bipolar depression and major depressive disorder (MDD).
Review of published studies and presentations at scientific congresses.
Quetiapine fumarate demonstrates a broad spectrum of efficacy in psychotic and mood disorders. In pharmacologic studies, quetiapine and its major active metabolite, norquetiapine, have actions on 5-HT2A receptors and D2 receptors, considered to explain efficacy in psychosis and mania. Norquetiapine, unlike quetiapine and other atypical antipsychotics at relevant doses, has affinity for the norepinephrine transporter in-vitro and demonstrates binding in-vivo, which may contribute to antidepressant efficacy. Quetiapine XR as monotherapy (300 mg/day) was significantly more effective than placebo in a study of patients with acute bipolar depression, with onset of effect as early as 1 week. In large, placebo-controlled studies, quetiapine XR as monotherapy (50-300 mg/day), or adjunct therapy (150-300 mg/day) to antidepressants, has demonstrated efficacy against depressive and comorbid symptoms in MDD, with rapid onset of effect. The safety profile of quetiapine XR in these studies was broadly consistent with quetiapine IR. Sedation intensity during initial dose escalation was significantly lower with quetiapine XR than IR in 1 study in patients with bipolar depression.
Quetiapine XR is effective in bipolar depression and MDD and has a safety profile consistent with quetiapine IR.
Depression is associated with various inflammatory-related physical conditions, such cardiovascular and neurodegenerative diseases. Yet, little is known about the association between depression and autoimmune diseases.
Objectives and Aims
To examine the association between depression and risk of autoimmune disease, investigating the temporal and dose-response nature of these relationships.
A prospective study including approximately 1.1 million people is conducted using linked Danish registries. We have identified 145,217 participants with depression between 1995 and 2012. Survival analyses are used to estimate the relative risk of autoimmune disease among those with, compared to without, depression. Analyses are adjusted for covariates.
Preliminary analyses indicate an association between depression and an increased risk of several autoimmune diseases, with a potential dose-response correlation. Final results are still in progress.
Depression seems to be associated with increased risk of the onset of a range of autoimmune diseases. As such, depression may play a role in the etiology of certain autoimmune conditions.