Reference values for mental health assessment instruments: objectives and methods of the Leiden Routine Outcome Monitoring Study

Rationale, aims and objectives: Routine outcome monitoring (ROM) was developed to establish the outcome of psychotherapeutic and pharmacological treatments through repeated assessments before, during and after treatment. Although standardization of psychiatric assessments and their reference values are essential for patient care, for various ROM instruments reference values are not available. The aim of the Leiden ROM Study is to generate reference values for 22 ROM instruments, covering generic and specific mood, anxiety and somatoform (MAS) disorders, for the general population. This article describes the extensive process of recruitment, as well as baseline characteristics of patient versus non‐patient groups. Method: Cross‐sectional study in randomly selected participants aged 18–65 years from the Dutch population, included through general practitioners. Results: Extensive demographic, psychosocial, mental health, and biological data from 1302 participants, recruited via general practitioners, were collected during a two‐hour standardized assessment including observer‐rated and self‐report scales. These data will be compared with corresponding data from 7840 patients with psychopathology who were referred to secondary care. On‐going quality control and calibration ensured maintenance of high quality during data collection. Conclusions: This reference group study for mental health assessments is the first study of this size carried out in the Netherlands. The results of this study are expected to be of value to secondary psychiatric care because they allow the indication of progress in health, treatment effect and possible termination of treatment. Additionally, the reference values can be used by primary care physicians as decision threshold for referral to specialized mental health care and vice versa.     

Women and firesetting: A qualitative analysis of context, meaning, and development

Objectives. To explore subjective experiences of women in secure services of their firesetting behaviour, its personal meaning and the factors that contributed to its development. Design. An interview-based study using Interpretative Phenomenological Analysis. Methods. Interviews were carried out with nine women, in medium secure services, with histories of firesetting. Results. Three overarching but interlinked themes emerged, reflecting a narrative progression from the context of life experiences that preceded firesetting (including subthemes: distressing experiences and isolation from support), through the experience and meaning of the firesetting act (influencing others and getting help, achievement and control, and not thought through), to the individual's current position regarding past actions. Conclusions. The clinical implications of the findings are considered in the context of the existing male-orientated firesetting knowledge base and emerging models of service delivery to women in secure settings.     

Functional characterization of NF-kappaB inhibitor-like protein 1 (NFkappaBIL1), a candidate susceptibility gene for rheumatoid arthritis

Several studies have implicated the NF-kappaB inhibitor-like protein 1 (NFkBIL1) gene located in the class III region of the major histocompatibility complex (MHC) as a possible susceptibility locus for rheumatoid arthritis (RA). Based on limited homology, it has been suggested to be a member of the inhibitor of NF-kappaB (IkappaB) family of proteins, but a role in mRNA processing has also been proposed. We have investigated the expression of NFkBIL1 in RA synovial tissue and characterized its function. Real-time PCR showed the two NFkBIL1 mRNA splice variants are expressed in a tissue-specific manner. Dual immunofluorescent staining of human RA synovium with polyclonal anti-NFkBIL1 antibodies and anti-CD68, anti-CD3 or anti-factor VIII showed that NFkBIL1 was expressed in the rheumatoid synovial lining and sub-lining layers and co-localized in CD68+ and CD3+, but not Factor VIII+ cells. Confocal microscopy of cultured synovial fibroblasts revealed expression in speckled nuclear and homogenous cytoplasmic distributions, suggesting shuttling between the cytoplasmic and nuclear compartments. Functional tests showed that NFkBIL1 isoforms were incapable of associating with NF-kappaB and did not inhibit it, thus disproving the hypothesis that NFkBIL1 functions as an IkappaB. Affinity purification of endogenous NFkBIL1 proteins and co-immunoprecipitation experiments showed that NFkBIL1 can associate with mRNA and with three protein partners, identified by mass spectrometry as leukophysin, translation elongation factor 1 alpha and CTP synthase I. These data support a potential role for NFkBL1 in the pathogenesis of RA and indicates that it may be involved in mRNA processing or the regulation of translation.     

Tdap booster to adolescents with juvenile idiopathic arthritis on and off anti-TNF agents is safe and immunogenic

Introduction: The response to vaccines in juvenile idiopathic arthritis (JIA) patients on and off anti-tumor necrosis factor (anti-TNF) agents remains highly discussed. There are no published studies on the immune response following a Tdap booster dose in JIA patients so far.ObjectiveTo evaluate the immune response and safety after a Tdap booster in JIA patients and in healthy adolescents.MethodsNineteen adolescents with JIA according to the ILAR criteria on anti-TNF medication, 19 adolescents with JIA off anti-TNF medication, and 27 healthy adolescents (control group) were compared after a Tdap booster. Adverse events and disease activity were evaluated. Lymphocyte immunophenotyping was performed by flow cytometry. Tetanus, diphtheria and pertussis toxin antibodies were assessed by ELISA; whole blood was stimulated with whole-cell pertussis, and supernatants were assessed for cytokines by xMAP.ResultsThe three groups showed a similar frequency of adverse events. There was no disease reactivation after the Tdap booster. Tetanus, diphtheria and pertussis antibodies showed a significant response when D0 and D14 concentrations were compared in both JIA groups and controls. Over time, a different pattern of response to the Tdap booster was observed among the groups for tetanus antibodies (p = 0.005) but not for diphtheria and pertussis antibodies. In contrast to the protection attained for tetanus and diphtheria, in the three groups, not all individuals showed pertussis seroconversion at either D14 or D28. In addition, the seroconversion of three subjects with JIA on anti-TNF medication was not maintained at D28. JIA patients off anti-TNF showed a higher percentage of naive CD8 + T cells (p = 0.007) and central memory CD8 + cells (p = 0.003) and a lower percentage of effector CD8 + T cells (p = 0.003) and NK cell numbers (p = 0.018) than the control group. The JIA group off anti-TNF medication had fewer B lymphocytes than both the JIA group on anti-TNF medication and the control group (p = 0.016). Cellular immunity to Bordetella pertussis showed that IFNγ levels were significantly lower in both JIA groups than in the control group (p = 0.003), IL10 levels were higher in the JIA off anti-TNF group (p = 0.009), IL17A and IL5 levels were lower in the JIA on anti-TNF group than in the control group (p = 0.018 and p = 0.016, respectively); however, an increase in IFNγ (p = 0.008), IL17A (p = 0.030) and TNFα (p = 0.041) levels was observed at D14 in both patient groups. Both JIA groups showed higher levels of IL21 than the control group (p = 0.023).ConclusionWe conclude that individuals with JIA on or off anti-TNF agents showed a good response to a booster dose for the three antigens studied in the absence of major adverse events and without the reactivation of the disease.     

Monosodium glutamate and treadmill exercise: Anxiety-like behavior and spreading depression features in young adult rats

Objectives: The route of administration is an important factor in determining the action of some drugs. We previously demonstrated that subcutaneous monosodium glutamate (MSG) accelerated cortical spreading depression (CSD) in the rat and that treadmill exercise attenuated this effect. This study evaluated whether other routes of administration exert the same action by testing orogastric (gavage) and topical cortical MSG administration in treadmill-exercised and sedentary rats. Additionally, in the orogastric treatment we tested anxiety-like behavior.

Methods: Exercised and sedentary rats received per gavage water or MSG (1 or 2 g/kg) daily from postnatal (P) day 7 to 27. Behavioral tests (open field and elevated plus-maze) occurred at P53?±?3. At P56?±?3, we analyzed CSD parameters (velocity, amplitude, and duration of the negative potential change). Other three groups of rats received an MSG solution (25, 50 or 75?mg/ml) topically to the intact dura mater during CSD recording.

Results: MSG-gavage increased anxiety-like behavior and the CSD velocities compared with water-treated controls (P?<?0.05). Exercise decelerated CSD. In contrast to gavage, which accelerated CSD, topical MSG dose-dependently and reversibly impaired CSD propagation, reduced CSD amplitude and increased CSD duration (P?<?0.05).

Conclusions: The exercise-dependent attenuation of the effects of MSG confirms our previous results in rats treated subcutaneously with MSG. CSD results suggest two distinct mechanisms for gavage and topical MSG administration. Additionally, data suggest that exercise can help protect the developing and adult brain against the deleterious actions of MSG.     

Axial STIR MRI: a faster method for confirming femoral head reduction in DDH

Purpose  Non-concentric reduction of the femoral head within the acetabulum is detrimental to its delicate cartilaginous structure and may result in a growth disturbance. Successful relocation of the dislocated femoral head depends on subtle clinical findings and radiography. The combination of a dislocated femoral head and a severely dysplastic acetabulum can result in a clinical examination that is unhelpful in confirming reduction under anaesthesia. In cases where uncertainty existed regarding head reduction in a spica cast, we performed axial short inversion time inversion recovery (STIR) and axial proton density magnetic resonance imaging (MRI) scans. We retrospectively reviewed the efficiency and accuracy of MRI in confirming femoral head location after closed reduction and spica application in eight children. Methods  One hundred and fifty-three cases of developmental dysplasia were treated with examination under anaesthesia and spica application in our unit over a 3-year period. Eight cases where MRI scanning was performed were identified. Before application of the spica cast, we used radiographic screening to assess the stability of the reduction. Absence of the ossific nucleus within the femoral head made confirmation of the location with the image intensifier unreliable. To confirm concentric femoral head location after closed reduction and spica application, we performed an MRI scan in the immediate post-anaesthesia period. Results  All scans were performed within 30 min of application of the spica, and the average time for each scan was 5 min. All eight children who had MRI post-application of the spica had concentric reduction of the femoral head. MRI allowed three-dimensional appreciation of the acetabulum and femoral head. Use of the axial STIR images allows accurate assessment of the cartilaginous ossific nucleus. All patients were discharged the same afternoon and followed up as outpatients. No patient in our group required contrast arthrography. Conclusion  While not indicated in all cases of femoral head dislocation, MRI is useful to confirm concentric reduction of the femoral head in a dysplastic acetabulum when examination under anaesthesia and radiographic screening have been uncertain. In our series, 1 in 20 cases needed MRI. This is a reliable, non-invasive method confirming definite reduction of the femoral head prior to discharge in all of our patients. In this initial series, all patients had axial and coronal STIR and proton density MRI. We now only use axial STIR images because they provide adequate information regarding the position of the femoral head relative to the acetabulum.     

Socio-demographic variations in perspectives on cardiovascular disease and associated risk factors.

Coronary heart disease (CHD) rates in Ireland are very high but little is known about attitudes to the disease. Qualitative attitudinal data were collected in focus group settings from 74 individuals across socio-demographic categories in order to assess knowledge of and attitudes to CHD and associated risk factors. Focus group questions were derived from group deconstruction of constructs from the Health Belief Model, Theory of Planned Behaviour, Protection Motivation Theory and Social Learning Theory. Participants were drawn from the personnel lists of local government and a health authority hospital. Eight types of groups were constructed according to the various permutations of the three variables: age, gender and occupational group. Analyses revealed good knowledge levels about risk factors among participants. However, participants exhibited mixed loci of control and low motivation to change behaviours. Men generally were less motivated to change than women; older men thought it too late and younger ones too soon. Though white and blue collar groups' views were similar, the discussion in white collar groups was more varied. Participants were sceptical about apparently contradictory medical advice which undermined motivation to change. The data complement earlier work and suggest preventative initiatives should be more focused.