Burden of Medication Overuse in Migraine: A Cross-sectional, Population-Based Study in Five European Countries Using the 2020 National Health and Wellness Survey (NHWS).

INTRODUCTION: Overuse of medication to treat migraine attacks can lead to development of a new type of headache or significant worsening of pre-existing headache, known as medication overuse headache. However, data concerning the burden of medication overuse (MO) in migraine are limited. This study aimed to assess the humanistic burden of MO in individuals with migraine from five European countries. METHODS: Data are from the 2020 National Health and Wellness Survey-a cross-sectional, population-based survey conducted in France, Germany, Italy, Spain, and the UK. Data were included from adults (≥ 18 years) with a self-reported diagnosis of migraine and at least one migraine attack and one headache in the past 30 days. MO was defined as (i) use of simple analgesics/over-the-counter medications on ≥ 15 days/month; or (ii) use of migraine medication, including combination analgesics, on ≥ 10 days/month. Humanistic burden of MO was assessed using the 12-Item Short-Form Health Survey (SF-12v2), EuroQol 5-Dimensions 5-Levels (EQ-5D), Short-Form 6-Dimensions (SF-6D), and Migraine Disability Assessment (MIDAS). The association of MO with humanistic burden was evaluated using generalized linear models adjusted for potential confounders in the full migraine population and in subgroups defined by headache frequency (monthly headache days [MHDs] 1-3, 4-7, 8-14, or ≥ 15). RESULTS: Among individuals with migraine, humanistic burden (SF-12v2, SF-6D, EQ-5D, and MIDAS) was higher in individuals who reported MO (n = 431) versus no MO (n = 3554), even after adjustment for confounding variables (p < 0.001 for all measures). MIDAS and EQ-5D scores were higher in individuals with MO than without, at all levels of headache frequency. For SF-12v2 and SF-6D, differences between groups with/without MO were seen only at lower levels of headache frequency (MHD 1-3 and 4-7). CONCLUSION: Among people with migraine, those who report MO face a greater humanistic burden than those without MO, irrespective of headache frequency.

Effectiveness and Safety of Vortioxetine for Major Depressive Disorder in Real-World Clinical Practice: Results from the Single-Arm RELIEVE China Study.

Background: Major depressive disorder (MDD) affects >163 million people worldwide and is a leading cause of disability in China. Functional impairment occurs alongside cognitive symptoms, anxiety, and depression, reducing quality of life and productivity in patients with MDD. Purpose: The multimodal antidepressant vortioxetine has demonstrated efficacy in relieving depressive and functional symptoms of MDD in randomized controlled trials (RCTs). The RELIEVE China study aimed to investigate the real-world effectiveness of vortioxetine in China. Patients and Methods: This was an observational, prospective cohort study in patients with MDD initiating treatment with vortioxetine at physician's discretion in China. Participants were followed up for 24 weeks and assessed at 3 time points: baseline, week 8, and week 24. The primary objective was to assess the change from baseline to weeks 8 and 24 in functional impairment as measured by Sheehan Disability Scale (SDS) total score. Additional assessments included SDS subdomains, measures of depression severity, anxiety, and cognition. The safety and tolerability of vortioxetine were also examined. Results: In total, 859 patients were included in the analysis. A consistent and significant improvement in functional impairment was observed during the study, with baseline mean SDS total score (16.7 points) decreasing by 5.42 (SE, 0.22) and 8.71 (SE, 0.226) points at week 8 and week 24, respectively (P<0.0001). Improvements in other functioning, cognitive, and anxiety assessments were also observed (all P<0.0001). A total of 74.7% of patients had responded, and 63.9% had reached remission at week 24. The tolerability profile of vortioxetine in this real-world population was consistent with the established tolerability profile for this drug. Conclusion: This study demonstrated the short- and long-term effectiveness and tolerability of vortioxetine for patients with MDD in a real-world setting in China. These findings are consistent with the efficacy and safety profile observed during RCTs.

Health-Related Quality of Life Over 6 Months in Patients With Major Depressive Disorder Who Started Antidepressant Monotherapy.

OBJECTIVES: Major depressive disorder (MDD) is increasing worldwide and is associated with impaired quality of life (QOL). This study aimed to assess the QOL and its association with cognitive symptoms in patients with MDD who started antidepressant monotherapy. METHODS: Data from the PERFORM (Prospective Epidemiological Research on Functioning Outcomes Related to Major Depressive Disorder) study were analyzed. A descriptive epidemiological analysis on EQ-5D-5L utility score, the level of each dimension, and the EuroQoL visual analog scale value was conducted at 4 visits during 6 months' follow-up. The association between cognitive complaints and changes in QOL measures was analyzed using multivariate linear regression analysis. RESULTS: The median EQ-5D-5L utility score improved from 0.67 at baseline to 0.82 at month 6. Although the proportion of patients reporting level 1 (no problem) in every dimension of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression increased over time, less than half of the patients achieved level 1 in pain/discomfort and depression/anxiety, which were closely related to depression and usual activities at month 6. Patients with no cognitive complaints or no history of MDD at baseline showed greater improvement in EQ-5D-5L utility scores and EuroQoL visual analog scale value for measuring QOL than those with these characteristics. CONCLUSIONS: Treatment over 6 months improved QOL in patients with MDD although there remained room for improvement in dimensions of usual activities, pain/discomfort, and depression/anxiety. Cognitive complaints or history of MDD at baseline predicted less improvement in QOL at 6 months. Any history of MDD might delay improvement in QOL after treatment.

Effectiveness of Vortioxetine in Patients With Major Depressive Disorder in Real-World Clinical Practice: Results of the RELIEVE Study.

Background: Randomized controlled clinical trials have shown vortioxetine to be efficacious and well tolerated for the treatment of major depressive disorder (MDD). The Real-Life Effectiveness of Vortioxetine in Depression (RELIEVE) study was undertaken to demonstrate the effectiveness and safety of vortioxetine for the treatment of MDD in routine clinical practice. Methods: RELIEVE was a 24-week, observational, prospective cohort study in outpatients with MDD initiating treatment with vortioxetine at their physician's discretion in routine care settings in Canada, France, Italy, and the USA (NCT03555136). The primary study outcome was patient functioning assessed by the Sheehan Disability Scale (SDS). Secondary outcomes included depression severity [9-item Patient Health Questionnaire (PHQ-9)], cognitive symptoms [5-item Perceived Deficits Questionnaire-Depression (PDQ-D-5)], and cognitive performance [Digit Symbol Substitution Test (DSST)]. Mixed models of repeated measures were used to assess change from baseline at week 24, adjusted for relevant confounders. Results: A total of 737 patients were eligible for inclusion in the full analysis set. Most patients (73.7%) reported at least one comorbid medical condition, 56.0% had comorbid anxiety and 24.4% had comorbid generalized anxiety disorder. Improvement in least-squares (LS) mean SDS score from baseline to week 24 was 8.7 points. LS mean PHQ-9, PDQ-D-5 and DSST scores improved by 7.4, 4.6, and 6.2 points, respectively. Adverse events were observed in 21.2% of patients [most commonly, nausea (8.2% of patients)]. Conclusions: These results demonstrate the effectiveness and tolerability of vortioxetine for the treatment of MDD in a large and heterogeneous patient population representative of that encountered in routine clinical practice.

Characterizing mood disorders in the AFFECT study: a large, longitudinal, and phenotypically rich genetic cohort in the US.

There has recently been marked progress in identifying genetic risk factors for major depression (MD) and bipolar disorder (BD); however, few systematic efforts have been made to elucidate heterogeneity that exists within and across these diagnostic taxa. The Affective disorders, Environment, and Cognitive Trait (AFFECT) study presents an opportunity to identify and associate the structure of cognition and symptom-level domains across the mood disorder spectrum in a prospective study from a diverse US population.Participants were recruited from the 23andMe, Inc research participant database and through social media; self-reported diagnosis of MD or BD by a medical professional and medication status data were used to enrich for mood-disorder cases. Remote assessments were used to acquire an extensive range of phenotypes, including mood state, transdiagnostic symptom severity, task-based measures of cognition, environmental exposures, personality traits. In this paper we describe the study design, and the demographic and clinical characteristics of the cohort. In addition we report genetic ancestry, SNP heritability, and genetic correlations with other large cohorts of mood disorders.A total of 48,467 participants were enrolled: 14,768 with MD, 9864 with BD, and 23,835 controls. Upon enrollment, 47% of participants with MD and 27% with BD indicated being in an active mood episode. Cases reported early ages of onset (mean = 13.2 and 14.3 years for MD and BD, respectively), and high levels of recurrence (78.6% and 84.9% with >5 episodes), psychotherapy, and psychotropic medication use. SNP heritability on the liability scale for the ascertained MD participants (0.19-0.21) was consistent with the high level of disease severity in this cohort, while BD heritability estimates (0.16-0.22) were comparable to reports in other large scale genomic studies of mood disorders. Genetic correlations between the AFFECT cohort and other large-scale cohorts were high for MD but not for BD. By incorporating transdiagnostic symptom assessments, repeated measures, and genomic data, the AFFECT study represents a unique resource for dissecting the structure of mood disorders across multiple levels of analysis. In addition, the fully remote nature of the study provides valuable insights for future virtual and decentralized clinical trials within mood disorders.

Prediction of residual cognitive disturbances by early response of depressive symptoms to antidepressant treatments in patients with major depressive disorder.

BACKGROUND: Patients with major depressive disorder (MDD) frequently retain cognitive disturbances after recovery from mood symptoms. We investigated the relationship between early response of mood symptoms and/or remission, and residual cognitive disturbances after 6 months of antidepressant treatment. METHODS: 518 patients with MDD were followed up for 6 months after antidepressant treatment initiation (first-line or switch from a previous drug). Subjective and objective cognitive disturbances were assessed by the Perceived Deficits Questionnaire - Depression (PDQ-D) and digit symbol substitution test (DSST), respectively. Depressive symptoms, as well as remission and early response to treatment, were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS). Multivariable linear and logistic regression models were used to adjust for confounders. RESULTS: Early response of depressive mood (≥50% reduction in MADRS score at month 1) was related with fewer residual subjective cognitive symptoms, as evaluated by the PDQ-D at month 6 (p<0.001). Likewise, early remission status at month 2 was inversely associated with PDQ-D scores at month 6 (p<0.001). Among patients with baseline DSST scores of ≥1 standard deviation below the norm, early response/remission was associated with better performance on the DSST at month 6 (p<0.05). LIMITATIONS: The cohort may not be representative of the general MDD patient population, and the possible influence of concomitant medications was not evaluated. CONCLUSIONS: These findings suggest that early improvements in depressive symptoms predict better cognitive outcomes in patients with MDD. Grouping of patients by mood and cognition status in early stages of antidepressant treatments may facilitate efforts to improve long-term functional outcomes.

Relationship of Subjective Cognitive Impairment with Psychosocial Function and Relapse of Depressive Symptoms in Patients with Major Depressive Disorder: Analysis of Longitudinal Data from PERFORM-J.

BACKGROUND: Accumulating evidence suggests the presence of cognitive impairment in patients with major depressive disorder (MDD), which affects their psychosocial function and quality of life (QoL). PERFORM-J (Prospective Epidemiological Research on Functioning Outcomes Related to MDD in Japan) is an observational, multicenter study to assess longitudinal changes in depressive symptoms, psychomotor speed, subjective cognitive function, and psychosocial function. METHODS: Five hundred and eighteen Japanese outpatients with MDD initiating new antidepressant monotherapy (first-line or switch from previous drug) as part of their routine medical care participated in this study. Assessments at baseline and over the 6-month observation period included physician-rated depression severity (Montgomery-Åsberg Depression Rating Scale), psychomotor speed (Digit Symbol Substitution Test; DSST), subjective cognition (Perceived Deficits Questionnaire-Depression), psychosocial function (Sheehan Disability Scale), and QoL (EuroQol-5 Dimension-5 Level). RESULTS: Antidepressant treatment for 6 months improved depressive symptoms and subjective cognitive impairment (cognitive complaints), whereas psychomotor speed remained impaired (ie, DSST total score was >1 standard deviation below the norm) in 35.6% of patients at 6 months. Impairment of subjective cognition, but not psychomotor speed at month 2 was associated with poor psychosocial function and QoL at 6 months. There was a trend for higher relapse rates at 6 months in patients with greater subjective cognitive impairment at 2 months. CONCLUSION: These findings highlight the importance of evaluating cognitive difficulties to predict long-term outcomes in patients with MDD. Early intervention for cognitive complaints may decrease the relapse rate, which warrants further study.

Impact of Cognitive Symptoms on Health-Related Quality of Life and Work Productivity in Chinese Patients with Major Depressive Disorder: Results from the PROACT Study.

PURPOSE: This post hoc analysis was undertaken to further explore the association of cognitive symptoms with health-related quality of life (HRQoL) and work productivity at the time of treatment initiation in Chinese patients with major depressive disorder (MDD) in the Prospective Research Observation to Assess Cognition in Treated patients with MDD (PROACT) study. PATIENTS AND METHODS: This was an epidemiological, non-interventional, prospective cohort study in adult outpatients with moderate-to-severe MDD initiating antidepressant monotherapy (first or second line). Crude and adjusted analyses of covariance were performed to assess the association of perceived cognitive symptoms (20-item Perceived Deficits Questionnaire-Depression [PDQ-D] total score) or observed cognitive performance (Digit Symbol Substitution Test [DSST] score) with HRQoL (EuroQoL 5-Dimensions Questionnaire index) and work productivity (Work Productivity and Activity Impairment [WPAI] or Sheehan Disability Scale [SDS] absenteeism and presenteeism scores). Adjusted analyses included depression severity, age, sex, residential area (urban/rural), and educational level. RESULTS: Of 1008 patients enrolled in the PROACT study, 986 were included in this analysis. Severity of perceived cognitive symptoms (ie, higher PDQ-D total score) was significantly associated with worse HRQoL (P<0.001) and higher levels of absenteeism (P=0.020 for the WPAI and P=0.002 for the SDS) and presenteeism (P<0.001 for both scales). The association of perceived cognitive symptoms with HRQoL and presenteeism was independent of depression severity. The association between observed cognitive performance (DSST score) and HRQoL was less robust. No association was seen between observed cognitive performance and levels of absenteeism or presenteeism assessed by either scale. CONCLUSION: Results of this real-world study illustrate the impact of cognitive symptoms on HRQoL and work productivity in Chinese patients with MDD, and highlight the importance of assessing and targeting cognitive symptoms in order to improve functional outcomes when treating patients with MDD.

Patient-reported depression severity and cognitive symptoms as determinants of functioning in patients with major depressive disorder: a secondary analysis of the 2-year prospective PERFORM study.

PURPOSE: To investigate the temporal interrelationship between depression severity, cognitive symptoms, and functioning in patients with major depressive disorder (MDD) in the PERFORM study (NCT01427439). PATIENTS AND METHODS: PERFORM was a 2-year, multicenter, prospective, noninterventional cohort study in outpatients with MDD who were either initiating antidepressant monotherapy or undergoing their first switch of antidepressant. Patients were enrolled by a general practitioner or psychiatrist. Structural equation model (SEM) analysis was used to explore temporal associations between patient-reported depression severity (9-item Patient Health Questionnaire score), cognitive symptoms (5-item Perceived Deficits Questionnaire score), and functional impairment (Sheehan Disability Scale total score). Standardized regression coefficients (SRCs) were used to evaluate the relationship between each outcome and scores from the most recent prior visit over the 2 years of follow-up. RESULTS: Between February 25, 2011, and February 19, 2015, 1,159 eligible patients with MDD completed the baseline and ≥1 follow-up visit at 194 sites in five European countries (France, Germany, Spain, Sweden, and the UK). Overall, 1,090 patients had assessments for ≥1 outcome measure at two consecutive visits. Severity of cognitive symptoms at baseline and Months 2 and 18 predicted functional impairment at Months 2, 6, and 24, respectively (SRC: 0.18, 0.15, and 0.22; P<0.001). Depression severity at Months 2, 6, and 12 predicted functional impairment at Months 6, 12, and 18, respectively (SRC: 0.17, 0.25, and 0.22; P<0.001). Severity of cognitive symptoms at baseline and Month 18 predicted depression severity at Months 2 and 24, respectively (SRC: 0.19 and 0.22; P<0.001). Functional impairment did not significantly predict the severity of depression or cognitive symptoms, and depression severity did not significantly predict the severity of cognitive symptoms at any time point. CONCLUSION: Patient-reported severity of cognitive symptoms appears to be an independent and significant determinant of subsequent functional impairment and depression severity in patients with MDD.

Relationship of cognitive impairment with depressive symptoms and psychosocial function in patients with major depressive disorder: Cross-sectional analysis of baseline data from PERFORM-J.

BACKGROUND: Evidence is accumulating for the presence of cognitive impairment in patients with major depressive disorder (MDD). The Prospective Epidemiological Research on Functioning Outcomes Related to Major Depressive Disorder in Japan (PERFORM-J) study is a 6-month, non-interventional, prospective, multicenter, epidemiological study. Using baseline data, the relationship between cognitive symptoms and psychosocial function was analyzed in Japanese patients with MDD. METHODS: A total of 518 Japanese outpatients (aged 18-65 years) with MDD initiating new antidepressant monotherapy (first-line or switch from a previous drug) participated. Assessment measures were: physician-rated Montgomery-Asberg Depression Rating Scale (MADRS) (depression severity); Digit Symbol Substitution Test (DSST) (objective cognition); and patient-rated Perceived Deficits Questionnaire - Depression (PDQ-D) (subjective cognition); Sheehan Disability Scale (SDS); Work Productivity and Activity Impairment questionnaire (WPAI) (psychosocial function); and EuroQol-5 Dimension-5 Level (quality of life). RESULTS: Over half of patients exhibited a greater than 1 standard deviation decline below norm in objective cognition, as measured by the DSST. Severity of depressive symptoms correlated positively with subjective (PDQ-D), but not objective (DSST) cognition. Depression severity and subjective cognition were significantly associated with psychosocial function, as measured by the SDS and WPAI (except the absenteeism items). Conversely, the association between objective cognition and psychosocial function was not significant. LIMITATIONS: Only outpatients were recruited. Occupations and job-related stress levels were not taken into account. CONCLUSIONS: Japanese patients with MDD presented a high incidence of cognitive impairment. The relationships between cognitive and psychosocial function in these patients suggest a need for therapeutics targeting cognitive impairment of MDD.

Agitation in patients with dementia: a systematic review of epidemiology and association with severity and course.

OBJECTIVES: More than 90% of individuals with Alzheimer's disease (AD) experience behavioral and neuropsychiatric symptoms (NPS), such as agitation. However, little is known regarding the specific burden of agitation for Alzheimer's patients. DESIGN: A global systematic literature review was conducted in MEDLINE and Embase for studies of clinical, humanistic, and economic burden of agitation in AD/dementia published from 2006-2016. References of identified papers and related literature reviews were examined. Studies meeting predetermined inclusion criteria for burden of agitation/NPS were summarized. RESULTS: Eighty papers met the inclusion criteria for burden of agitation in dementia. Wide ranges of agitation prevalence were reported, but few papers provided information on incidence. The association of agitation with AD severity was presented in multiple studies; a few suggested positive association of agitation with mortality. CONCLUSIONS: High prevalence of agitation is consistent with earlier reports, but several gaps in understanding of agitation in AD need further exploration.

Long-term follow-up on health-related quality of life in major depressive disorder: a 2-year European cohort study.

BACKGROUND: Major depressive disorder (MDD) is associated with significant impairments in health-related quality of life (HRQoL) and everyday functioning. This cohort study investigated the long-term development of HRQoL in patients with MDD and its association with patient characteristics, including depressive symptom severity and cognitive symptoms. METHODS: The Prospective Epidemiological Research on Functioning Outcomes Related to Major depressive disorder (PERFORM) study was a longitudinal cohort study conducted in 1,159 outpatients aged 18-65 years with MDD in France, Germany, Spain, Sweden, and the UK. The patients were either initiating antidepressant monotherapy or undergoing their first switch of antidepressant. HRQoL was assessed using the Medical Outcomes Study Short-Form 12-item Health Survey (SF-12) up to month 12 and the EuroQol Five Dimensions questionnaire up to month 24 (UK only). Depressive symptom severity was assessed up to month 24 by the patient-reported Patient Health Questionnaire and cognitive symptoms by the Perceived Deficit Questionnaire. Multivariate analyses were performed to identify patient characteristics associated with HRQoL. RESULTS: Mental HRQoL was severely impaired at baseline versus normative data (mean [SD] SF-12 mental component summary [MCS], 26.5 [9.2]); mean (SD) physical component summary (PCS) total score was 45.2 (12.1). SF-12 MCS improved over 12 months of follow-up (38.7 [11.6] at month 12), while SF-12 PCS remained stable (45.3 [11.1]). At each assessment time point, there was a clear pattern of lower SF-12 MCS and PCS total score in patients experiencing greater cognitive problems. The mean EuroQol Five Dimensions questionnaire utility index score generally decreased (i.e., worsened) with increasing severity of cognitive and depressive symptoms at all time points up to 24 months. Multivariate analyses identified both depression severity and cognitive symptoms as strongly and significantly associated with poor HRQoL. CONCLUSION: These findings highlight the importance of recognizing and managing residual symptoms in patients with MDD, including the cognitive symptoms, to restore long-term psychosocial functioning.

Characteristics of patients with depression initiating or switching antidepressant treatment: baseline analyses of the PERFORM cohort study.

BACKGROUND: Patients who require a switch in their antidepressant therapy may have different clinical profiles and treatment needs compared with patients initiating or maintaining a first-line antidepressant therapy. METHODS: The Prospective Epidemiological Research on Functioning Outcomes Related to Major depressive disorder (MDD) (PERFORM) study was a 2-year observational cohort study in outpatients with MDD in five European countries. Enrolled patients were either initiating or undergoing the first switch to an antidepressant monotherapy. Baseline data on patients' clinical status, functioning, productivity, quality of life and medical-resource use were compared in a cross-sectional baseline analysis. RESULTS: A total of 1402 patients were enrolled, of whom 1159 (82.7%) provided analysable baseline data. The majority (78.7%) of the analysable population were initiating antidepressant treatment and most (83.6%) were enrolled and followed up by general practitioners. Compared with patients initiating antidepressants, those switching antidepressants (21.3%) tended to have more severe depressive symptoms, greater anxiety, worse health-related quality of life, greater functional impairment, greater medical-resource use and had a different medical history. Limitations included an over-representation of switches due to lack of efficacy among patients who were switching treatment, as patients were selected based on presence of depressive symptoms. CONCLUSIONS: Patients with MDD who are switching treatment for the first time have a different profile and different depression-associated health needs compared with those initiating treatment. Therapeutic management should therefore be adapted for patients who switch. TRIAL REGISTRATION: ClinicalTrials.gov NCT01427439 ; Retrospectively registered 26 August 2011.

Functional impairment in patients with major depressive disorder: the 2-year PERFORM study.

BACKGROUND: The Prospective Epidemiological Research on Functioning Outcomes Related to Major depressive disorder (PERFORM) study describes the course of depressive symptoms, perceived cognitive symptoms, and functional impairment over 2 years in outpatients with major depressive disorder (MDD) and investigates the patient-related factors associated with functional impairment. METHODS: This was a 2-year observational study in 1,159 outpatients with MDD aged 18-65 years who were either initiating antidepressant monotherapy or undergoing their first switch of antidepressant. Functional impairment was assessed by the Sheehan Disability Scale and the Work Productivity and Activity Impairment questionnaire. Patients assessed depression severity using the nine-item Patient Health Questionnaire and severity of perceived cognitive symptoms using the five-item Perceived Deficit Questionnaire. To investigate which patient-related factors were associated with functional impairment, univariate analyses of variance were performed to identify relevant factors that were then included in multivariate analyses of covariance at baseline, month 2, months 6 and 12 combined, and months 18 and 24 combined. RESULTS: The greatest improvement in depressive symptoms, perceived cognitive symptoms, and functional impairment was seen immediately (within 2 months) following initiation or switch of antidepressant therapy, followed by more gradual improvement and long-term stabilization. Improvement in perceived cognitive symptoms was less marked than improvement in depressive symptoms during the acute treatment phase. Functional impairment in patients with MDD was not only associated with severity of depressive symptoms but also independently associated with severity of perceived cognitive symptoms when adjusted for depression severity throughout the 2 years of follow-up. CONCLUSION: These findings highlight the burden of functional impairment in MDD and the importance of recognizing and managing cognitive symptoms in daily practice.

A tolerability burden index in schizophrenia: incorporating patient perspective in clinical trial adverse event reporting.

Background: Adverse event (AE) reporting in clinical trials does not fully capture the patient-level perspective and comparing tolerability across treatments or among studies is difficult. Objective: This study was designed to develop a treatment tolerability index algorithm that combines AE reporting with physician- and patient-level AE information into a global burden score to allow comparison of the overall tolerability of antipsychotic medications used in treating schizophrenia. Study design: Data from a 4-arm, placebo-controlled clinical trial were used in the proposed tolerability index algorithm. For each patient, AEs were adjusted by frequency, severity, duration, and patient-experienced importance, and average tolerability-related burden scores were calculated. Setting: Algorithm development analyses. Patients: This study analyzed data from a previously completed clinical trial that evaluated a potential antipsychotic medication; no patients were involved in the current study. Intervention: No interventions were administered in this study; the analyses described used data derived from a previously completed clinical trial in which patients received bifeprunox, risperidone, or placebo. Main outcome measure: Burden scores and tolerability index scores were compared for patients who did or did not discontinue treatment because of AEs. Results: The number of AEs varied widely among patients. Burden scores were significantly worse for patients who discontinued treatment because of AEs. Mean tolerability index scores, adjusted based on AE frequency, severity-adjusted duration, and patient-experienced impact, were poorer for active medications than placebo, and increased with dose. Conclusion: The treatment tolerability index will allow comparison of AE burden and tolerability between treatments using existing clinical trial information. This suggests that scoring is possible, is clinically relevant, and allows standardized comparison of antipsychotic tolerability.

Mental health associations with eczema, asthma and hay fever in children: a cross-sectional survey.

OBJECTIVE: This study aimed to examine the association of eczema, asthma and hay fever with mental health in a general child population and to assess the influence of parental socioeconomic position on these associations. METHODS: We conducted a cross-sectional health survey of children aged 3, 6, 11 and 15 years in the City of Copenhagen, Denmark. Individual questionnaire data on eczema, asthma, and hay fever and mental health problems assessed using the Strengths and Difficulties Questionnaire (SDQ) was linked to register data on demographics and parental socioeconomic position. 9215 (47.9%) children were included in the analyses. RESULTS: Linear regression analyses showed that children with current eczema symptoms had higher SDQ scores (mean difference, 95% CI) of emotional problems (0.26, 0.12 to 0.39), conduct problems (0.19, 0.09 to 0.29) and hyperactivity problems (0.32, 0.16 to 0.48); children with current asthma symptoms had higher SDQ scores of emotional problems (0.45, 0.32 to 0.58), conduct problems (0.28, 0.18 to 0.38) and hyperactivity problems (0.52, 0.35 to 0.69); and children with current hay fever symptoms had higher SDQ scores of emotional problems (0.57, 0.42 to 0.72), conduct problems (0.22, 0.11 to 0.33), hyperactivity problems (0.44, 0.26 to 0.61) and peer problems (0.14, 0.01 to 0.26), compared with children without current symptoms of the relevant disease. For most associations, parental socioeconomic position did not modify the effect. CONCLUSIONS: Children with eczema, asthma or hay fever had more emotional, conduct and hyperactivity problems, but not peer problems, compared with children without these diseases. Atopic diseases added equally to the burden of mental health problems independent of socioeconomic position.

Health service use among children with and without eczema, asthma, and hay fever.

BACKGROUND: Atopic diseases, for example, eczema, asthma, and hay fever, are among the most common chronic diseases of childhood. Knowledge on health service use among children with atopic disease is limited. This study aimed to investigate the total use and costs of health services for children with and without eczema, asthma, and hay fever in a Danish general population. METHODS: We conducted a health survey with four complete birth cohorts from the City of Copenhagen. Individual questionnaire data on eczema, asthma, and hay fever for children aged 3, 6, 11, and 15 years were linked to register information on use and costs of health services and prescribed medication and parental education. In total 9,720 children participated (50.5%). RESULTS: We found increased health service use (number of additional consultations per year [95% confidence interval]) among children with current eczema symptoms (1.77 [1.29-2.26]), current asthma symptoms (2.53 [2.08-2.98]), and current hay fever symptoms (1.21 [0.74-1.67]), compared with children without these symptoms. We also found increased use of prescribed medication and most subtypes of health services. Current asthma symptoms and current eczema symptoms, but not current hay fever symptoms, increased the health service costs with at least €300 per year per child. CONCLUSION: Children with eczema, asthma, and hay fever used health services and prescribed medication more than children without these diseases.

Association between parental socioeconomic position and prevalence of asthma, atopic eczema and hay fever in children.

AIM: To determine the prevalence of asthma, atopic eczema and hay fever among children in different age groups and examine the associations with parental socioeconomic position. METHODS: A cross-sectional health survey of four complete birth-cohorts in the municipality of Copenhagen was conducted. Children aged 11 and 15 years and parents of children aged 3 and 6 years completed questionnaires on symptoms and diseases. Data were linked to national registers on demographics and socioeconomic position measured as education, employment and income. In total, 9720 children/parents responded (50.5%). RESULTS: The prevalence of asthma and hay fever increased with increasing age; asthma: from 3.2% among children aged 3 years to 15.4% among children aged 15 years; hay fever: from 3.1% among children aged 3 years to 21.3% among children aged 15 years. The prevalence of atopic eczema did not vary with age and ranged between 15.5% and 17.8%. Odds Ratios for children of parents with the lowest vs. the highest educational level were 1.50 (95% CI = 1.17-1.91) for asthma; 1.68 (95% CI = 1.35-2.10) for hay fever; and 0.75 (95% CI = 0.64-0.89) for atopic eczema. Unemployment was significantly associated with a decreased risk of atopic eczema and eczema symptoms. There was no independent association between household income and any of the outcomes. CONCLUSIONS: The prevalence of asthma and hay fever, but not atopic eczema, increased with increasing age. Atopic eczema was associated with high parental educational level, whereas asthma and hay fever were associated with low educational level. No association with household income was found.

Recent temporal trends in sleep duration, domain-specific sedentary behaviour and physical activity. A survey among 25-79-year-old Danish adults.

BACKGROUND: Prevalence of sedentary behaviour is high in many countries, but little is known about temporal trends in sitting time. OBJECTIVE: To examine temporal changes in sleep and domain-specific sedentary behaviour and moderate to vigorous leisure time physical activity (MVPA). METHODS: Two cross-sectional population-based surveys of 25-79-year-old inhabitants were conducted in The Capital Region of Denmark in 2007 (N = 69.800, response rate 52.3%) and 2010 (N = 77.517, response rate 54.8%). Information on sedentary behaviour and physical activity was obtained from self-report questionnaire and sociodemographic information from central registers. Data were weighted for survey design and for non-response and were analysed by multiple regression analyses. RESULTS: In 2007, the entire survey population reported a mean daily sleeping duration of 7.4 hours, leisure time sitting of 3.4 hours per day, occupational sitting of 4.4 hours per day, MVPA of 0.87 hours per day and a total 24-hour energy expenditure of 40.12 METs per day. In 2010, duration of sleep was unaltered (p = 0.1), sedentary leisure time and sedentary work time had increased by 12.6 minutes (p < 0.0001) and 13.2 minutes (p < 0.0001) per day, respectively. Time spent on MVPA had increased by 2.9 minutes per day (p < 0.0001). The 24-hour energy expenditure had decreased by 0.41 METs (p < 0.0001). CONCLUSIONS: Adult Danish men and women spend an increased amount of time sitting down at work and during leisure time, but also on leisure time MVPA. As duration of sleep is unaltered findings suggest that low intensity physical activity may be displaced in everyday life.

Social disparities in children's exposure to second hand smoke at home: a repeated cross-sectional survey.

BACKGROUND: Exposure to second hand smoke (SHS) is an important preventable cause of morbidity and mortality in children. We hypothesised that there has been a growth in social inequality in children's exposure to SHS at home over time. The purpose of this study was to investigate temporal change in smoking in homes including children, focusing on the socioeconomic differences. METHODS: Data is from a repeated cross-sectional survey, 'Health Profiles of the Capital Region of Denmark' conducted in 2007 and 2010, in 29 municipalities. The response rate was 52.3%, in both surveys. Our study included persons aged 25 to 64, living with children ≤15 years of age; N=9,289 in 2007 and 12,696 in 2010. Analyses were weighted for size of municipality and for non-response, which was higher among men and among persons who were younger, had a lower income, were living alone, were unemployed, and/or were of an ethnicity other than Danish. Regression analyses were used to investigate smoking in homes including children across parent/adult education levels, focusing on temporal changes. RESULTS: There were significant large socioeconomic differences in both 2007 and 2010. In 2010 it was more than 11 times more likely for a child to be exposed to SHS at home if the parent had very low education than if they were highly educated (p<0.001). Smoking in a home with children decreased from 16.2% in 2007 to 10.9% in 2010. The odds of a temporal decrease in domestic smoking did not differ significantly across parent education levels (p=0.40). CONCLUSIONS: Marked social inequalities in children's exposure to SHS and a significant temporal decrease in exposure, independent of the education level of the parent/adult, were found in repeated large cross-sectional population-based studies. Social disparities have persisted over time, but not increased. Both clinical and population policy interventions will be needed in order to control child SHS exposure. We call for legislative protection of children from tobacco smoke inside their home as a supplement to parental education and support for smoking cessation.