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Individual patient data (IPD) meta-analyses are increasingly common in the literature. In the context of estimating the diagnostic accuracy of ordinal or semi-continuous scale tests, sensitivity and specificity are often reported for a given threshold or a small set of thresholds, and a meta-analysis is conducted via a bivariate approach to account for their correlation. When IPD are available, sensitivity and specificity can be pooled for every possible threshold. Our objective was to compare the bivariate approach, which can be applied separately at every threshold, to two multivariate methods: the ordinal multivariate random-effects model and the Poisson correlated gamma-frailty model. Our comparison was empirical, using IPD from 13 studies that evaluated the diagnostic accuracy of the 9-item Patient Health Questionnaire depression screening tool, and included simulations. The empirical comparison showed that the implementation of the two multivariate methods is more laborious in terms of computational time and sensitivity to user-supplied values compared to the bivariate approach. Simulations showed that ignoring the within-study correlation of sensitivity and specificity across thresholds did not worsen inferences with the bivariate approach compared to the Poisson model. The ordinal approach was not suitable for simulations because the model was highly sensitive to user-supplied starting values. We tentatively recommend the bivariate approach rather than more complex multivariate methods for IPD diagnostic accuracy meta-analyses of ordinal scale tests, although the limited type of diagnostic data considered in the simulation study restricts the generalization of our findings.

[This corrects the article DOI: 10.1186/s41512-016-0001-y.].

Women have a consistently higher prevalence of major depressive disorder (MDD) than men. Hypotheses implicating hypothalamic-pituitary -adrenal, -gonadal, and -thyroid axes, immune response, genetic factors, and neurotransmitters have emerged to explain this difference. However, more evidence for these hypotheses is needed and new explanations must be explored. Here, we investigated sex differences in MDD markers using multiplex immunoassay measurements of 171 serum molecules in individuals

Item does not contain fulltext, Background: In recent years, researchers have used various techniques to elucidate the heterogeneity in depressive symptoms. This study seeks to resolve the extent to which variations in depression reflect qualitative differences between symptom categories and/or quantitative differences in severity. Methods: Data were used from the Netherlands Mental Health Survey and Incidence Study-2, a nationally representative face-to-face survey of the adult general population. In a subsample of respondents with a lifetime key symptom of depression at baseline and who participated in the first two waves (n=1388), symptom profiles at baseline were based on symptoms reported during their worst lifetime depressive episode. Depressive symptoms and DSM-IV diagnoses were assessed with the Composite International Diagnostic Interview 3.0. Three latent variable techniques (latent class analysis, factor analysis, factor mixture modelling) were used to identify the best subtyping model. Results: A latent class analysis, adjusted for local dependence between weight change and appetite change, described the data best and resulted in four distinct depressive subtypes: severe depression with anxiety (28.0%), moderate depression with anxiety (29.3%), moderate depression without anxiety (23.6%) and mild depression (19.0%). These classes showed corresponding clinical correlates at baseline and corresponding course and outcome indicators at follow-up (i.e., class severity was linked to lifetime mental disorders at baseline, and service use for mental health problems and current disability at follow-up). Limitations: Although the sample was representative of the population on most parameters, the findings are not generalisable to the most severely affected depressed patients. Conclusions: Depression could best be described in terms of both qualitative differences between symptom categories and quantitative differences in severity. In particular anxiety was a distinguishing feature within moderat

Women have a consistently higher prevalence of major depressive disorder (MDD) than men. Hypotheses implicating hypothalamic-pituitary -adrenal, -gonadal, and -thyroid axes, immune response, genetic factors, and neurotransmitters have emerged to explain this difference. However, more evidence for these hypotheses is needed and new explanations must be explored. Here, we investigated sex differences in MDD markers using multiplex immunoassay measurements of 171 serum molecules in individuals enrolled in the Netherlands Study of Depression and Anxiety (N-MDD = 231; N-control = 365). We found 28 sex-dependent markers of MDD, as quantified by a significant interaction between sex and log(2-)transformed analyte concentration in a logistic regression with diagnosis (MDD/control) as the outcome variable (p < 0.05; q < 0.30). Among these were a number of male-specific associations between MDD and elevated levels of proteins involved in immune response, including C-reactive protein, trefoil factor 3, cystatin-C, fetuin-A, beta 2-microglobulin, CD5L, FASLG receptor, and tumor necrosis factor receptor 2. Furthermore, only male MDD could be classified with an accuracy greater than chance using the measured serum analytes (area under the ROC curve = 0.63). These findings may have consequences for the generalization of inflammatory hypotheses of depression to males and females and have important implications for the development of diagnostic biomarker tests for MDD. More studies are needed to validate these results, investigate a broader range of biological pathways, and integrate this data with brain imaging, genetic, and other relevant data.

This longitudinal study examines to what extent different depressive and anxiety disorders and clinical characteristics are associated with subsequent weight change, while controlling for baseline weight, sociodemographics, health status, psychotropic medication use and (un)healthy lifestyle factors. Data are from a sample of 2447 respondents aged 18-65 years of the Netherlands Study of Depression and Anxiety (NESDA). Baseline depressive disorders and anxiety disorders were determined with the Composite International Diagnostic Interview (CIDI). Weight at baseline and after 2 years was measured and analyzed as continuous change score (mean change in weight 1. kg) and in categories of significant weight loss (<1. S.D. weight change equaling <4. kg), weight maintenance and weight gain (>1. S.D., >6. kg). After full adjustment for covariates baseline comorbid anxiety and depressive disorder and baseline Major Depressive Disorder (MDD) were associated with significant 2-year weight gain. Both current and remitted MDD at baseline and a baseline dysthymia, but none of the anxiety disorders, were associated with significant weight loss. This longitudinal study confirms a U-curved link between depression and weight change over 2 years. Furthermore, a dose-response effect of depression severity on 2-year weight gain was found.

Background The nosological status of generalized anxiety disorder (GAD) versus dysthymic disorder (DD) has been questioned. The aim of this study was to examine qualitative differences within (co-morbid) GAD and DD symptomatology. Method Latent class analysis was applied to anxious and depressive symptomatology of respondents from three population-based studies (2007 Australian National Survey of Mental Health and Wellbeing; National Comorbidity Survey Replication; and Netherlands Mental Health Survey and Incidence Study-2; together known as the Triple study) and respondents from a multi-site naturalistic cohort [Netherlands Study of Depression and Anxiety (NESDA)]. Sociodemographics and clinical characteristics of each class were examined. Results A three-class (Triple study) and two-class (NESDA) model best fitted the data, reflecting mainly different levels of severity of symptoms. In the Triple study, no division into a predominantly GAD or DD co-morbidity subtype emerged. Likewise, in spite of the presence of pure GAD and DD cases in the NESDA sample, latent class analysis did not identify specific anxiety or depressive profiles in the NESDA study. Next, sociodemographics and clinical characteristics of each class were examined. Classes only differed in levels of severity. Conclusions The absence of qualitative differences in anxious or depressive symptomatology in empirically derived classes questions the differentiation between GAD and DD. Copyright © Cambridge University Press 2013.

Item does not contain fulltext, BACKGROUND: Whether course trajectories of depressive and anxiety disorders are different, remains an important question for clinical practice and informs future psychiatric nosology. This longitudinal study compares depressive and anxiety disorders in terms of diagnostic and symptom course trajectories, and examines clinical prognostic factors. METHODS: Data are from 1209 depressive and/or anxiety patients residing in primary and specialized care settings, participating in the Netherlands Study of Depression and Anxiety. Diagnostic and Life Chart Interviews provided 2-year course information. RESULTS: Course was more favorable for pure depression (n=267, median episode duration = 6 months, 24.5% chronic) than for pure anxiety (n=487, median duration = 16 months, 41.9% chronic). Worst course was observed in the comorbid depression-anxiety group (n=455, median duration > 24 months, 56.8% chronic). Independent predictors of poor diagnostic and symptom trajectory outcomes were severity and duration of index episode, comorbid depression-anxiety, earlier onset age and older age. With only these factors a reasonable discriminative ability (C-statistic 0.72-0.77) was reached in predicting 2-year prognosis. LIMITATION: Depression and anxiety cases concern prevalent - not incident - cases. This, however, reflects the actual patient population in primary and specialized care settings. CONCLUSIONS: Their differential course trajectory justifies separate consideration of pure depression, pure anxiety and comorbid anxiety-depression in clinical practice and psychiatric nosology.

OBJECTIVE: To determine the prevalence, impact, and stability of different subtypes of headache in a 30 year prospective follow-up study of a general population sample. DESIGN: Prospective cohort study. SETTING: Canton of Zurich, Switzerland. PARTICIPANTS: 591 people aged 19-20 from a cohort of 4547 residents of Zurich, Switzerland, interviewed seven times across 30 years of follow-up. MAIN OUTCOME MEASURES: Prevalence of headache; stability of the predominant subtype of headache over time; and age of onset, severity, impact, family history, use of healthcare services, and drugs for headache subtypes. RESULTS: The average one year prevalences of subtypes of headache were 0.9% (female:male ratio of 2.8) for migraine with aura, 10.9% (female:male ratio of 2.2) for migraine without aura, and 11.5% (female:male ratio of 1.2) for tension-type headache. Cumulative 30 year prevalences of headache subtypes were 3.0% for migraine with aura, 36.0% for migraine without aura, and 29.3% for tension-type headache. Despite the high prevalence of migraine without aura, most cases were transient and only about 20% continued to have migraine for more than half of the follow-up period. 69% of participants with migraine and 58% of those with tension-type headache manifested the same predominant subtype over time. However, the prospective stability of the predominant headache subtypes was quite low, with substantial crossover among the subtypes and no specific ordinal pattern of progression. A gradient of severity of clinical correlates and service use was present across headache subtypes; the greatest effect was for migraine with aura followed by migraine without aura, and then tension-type headache and unclassified headaches. CONCLUSIONS: These findings highlight the importance of prospective follow-up of people with headache. The substantial longitudinal overlap among subtypes of headache shows the developmental heterogeneity of headache syndromes. Studies of the causes of headache t

Child maltreatment is generally referred to under the global categories of physical, sexual, emotional/psychological abuse and neglect. The Concerted Action on the Prevention of Child Abuse in Europe (CAPCAE) reports on the specific forms of harm and injury, actions and persons believed responsible in eight European countries. The most common actions across all participating countries responsible for harm were those of violent parenting or absent parenting. A review of prevention strategies found that few programmes focused on specific behaviours or included measures to indicate whether their actions were successful in preventing further harm to children. It is recommended that fathers need to be targeted in prevention as well as mothers and that specific data collection of actual harms, actions, persons responsible and outcomes needs to be implemented as a priority in all European countries. Such specificity avoids a focus on risk which is unacceptable in some countries, over inclusive of parents and resource intensive

Child maltreatment is generally referred to under the global categories of physical, sexual, emotional/psychological abuse and neglect. The Concerted Action on the Prevention of Child Abuse in Europe (CAPCAE) reports on the specific forms of harm and injury, actions and persons believed responsible in eight European countries. The most common actions across all participating countries responsible for harm were those of violent parenting or absent parenting. A review of prevention strategies found that few programmes focused on specific behaviours or included measures to indicate whether their actions were successful in preventing further harm to children. It is recommended that fathers need to be targeted in prevention as well as mothers and that specific data collection of actual harms, actions, persons responsible and outcomes needs to be implemented as a priority in all European countries. Such specificity avoids a focus on risk which is unacceptable in some countries, over inclusive of parents and resource intensive.

Item does not contain fulltext, Minor histocompatibility antigens can induce cytotoxic T cells that play an important role in the graft-versus-leukemia and graft-versus-host-disease (GvHD) activity after stem cell transplantation. Minor histocompatibility antigens (mHags) with expression limited to the hematopoietic system may have a prominent role in the graft-versus-leukemia reaction. Earlier in vitro studies demonstrated that cytotoxic T cells specific for the minor histocompatibility antigen HA-1 only lysed cells of hematopoietic origin. Despite this limited expression, an HA-1 mismatch is associated with GvHD. Yet, the hematopoietic-restricted HA-1 membrane expression motivated us to develop an ex vivo HA-1-specific protocol for cellular immunotherapy of relapsed leukemia. To ensure the feasibility and safety of such cellular therapy, broad HA-1 RNA analysis is indispensable. Here we demonstrate the hematopoietic-restricted expression at the HA-1 gene transcriptional level with high RNA expression in normal and in malignant hematopoietic cells and background expression levels in nonhematopoietic cells. In tissues that showed low HA-1 RNA expression, hematopoietic cells were present as demonstrated by CD45 RNA expression analyzed in parallel. Thus, the mHag HA-1 can function as an excellent target antigen for immunotherapy of hematological malignancies with no or low risk of GvHD.

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