Predictive value of nonspecific bronchial responsiveness in occupational asthma

BACKGROUND: The diagnosis of occupational asthma (OA) can be challenging and needs a stepwise approach. However, the predictive value of the methacholine challenge has never been addressed specifically in this context. OBJECTIVE: We sought to evaluate the sensitivity, specificity, and positive and negative predictive values of the methacholine challenge in OA. METHODS: A Canadian database was used to review 1012 cases of workers referred for a suspicion of OA between 1983 and 2011 and having had a specific inhalation challenge. We calculated the sensitivity, specificity, and positive and negative predictive values of methacholine challenges at baseline of the specific inhalation challenge, at the workplace, and outside work. RESULTS: At baseline, the methacholine challenge showed an overall sensitivity of 80.2% and a specificity of 47.1%, with positive and negative predictive values of 36.5% and 86.3%, respectively. Among the 430 subjects who were still working, the baseline measures displayed a sensitivity of 95.4%, a specificity of 40.1%, and positive and negative predictive values of 41.1% and 95.2%, respectively. Among the 582 subjects tested outside work, the baseline measures demonstrated a sensitivity and specificity of 66.7% and 52%, respectively, and positive and negative predictive values of 31.9% and 82.2%, respectively. When considering all subjects tested by a methacholine challenge at least once while at work (479), the sensitivity, specificity, and positive and negative predictive values were 98.1%, 39.1%, and 44.0% and 97.7%, respectively. CONCLUSION: A negative methacholine challenge in a patient still exposed to the causative agent at work makes the diagnosis of OA very unlikely

La cécité à la répétition : les visages et les expressions faciales

La cécité à la répétition (Kanwisher, 1986, 1987) est définie comme une incapacité de voir ou de se rappeler le deuxième de deux éléments similaires ou identiques présentés visuellement, d'une façon séquentielle rapide dans une même séquence. Plusieurs mécanismes ont été proposés pour expliquer ce phénomène. Nous proposons d'utiliser les visages et les expressions faciales pour savoir si ce phénomène est relié à l'attention. Nous allons d'abord tenter de répéter certains résultats antérieurs afin de nous assurer que les techniques requises pour la présentation rapide de visages sont adéquates pour ce genre d'étude. Dans la première expérience, il est plus facile pour les participants de se rappeler les images répétées. Alors que les mots répétés ou non (Expérience 2) n'affectent aucunement le rappel immédiat de ces derniers. Finalement, la cécité à la répétition fut observée pour les phrases avec répétition (Expérience 3). Les résultats inattendus et les problèmes techniques lors de notre expérimentation sont les facteurs qui pour l'instant limitent l'étude de la cécité à la répétition avec des visages comme stimuli

Reducing behavior problems in children born after an unintended pregnancy:the generation R study

Objectives: To examine differences in behavior problems between children from intended versus unintended pregnancies, and to estimate how much the difference in problem behavior would be reduced if postnatal depression was eliminated and social support was increased within 6 months after birth. Methods: Data from the Generation R Study were used, a population-based birth cohort in Rotterdam, the Netherlands (N = 9621). Differences in child internalizing and externalizing behavior at ages 1.5, 3, 6, 9 and 13 years between pregnancy intention groups were estimated using linear regression. Associations of postnatal depression and social support with internalizing and externalizing problems were also estimated using linear regression. Child behavior outcomes where compared before and after modelling a situation in which none of the mothers experienced a postnatal depression and all mother experienced high social support. Results: Most pregnancies (72.9%) were planned, 14.8% were unplanned and wanted, 10.8% were unplanned with initially ambivalent feelings and 1.5% with prolonged ambivalent feelings. Children from unplanned pregnancies had more internalizing and externalizing problems at all ages as compared to children from a planned pregnancy, especially when ambivalent feelings were present. Hypothetically eliminating on postnatal depression reduced the differences in internalizing and externalizing problems by 0.02 to 0.16 standard deviation. Hypothetically increasing social support did not significantly reduce the difference in internalizing and externalizing problems. Conclusions: Children from an unplanned pregnancy have more behavior problems, in particular when mothers had prolonged ambivalent feelings. Eliminating postnatal depression may help to reduce the inequality in child behavior related to pregnancy intention.</p

Reducing behavior problems in children born after an unintended pregnancy:the generation R study

Objectives: To examine differences in behavior problems between children from intended versus unintended pregnancies, and to estimate how much the difference in problem behavior would be reduced if postnatal depression was eliminated and social support was increased within 6 months after birth. Methods: Data from the Generation R Study were used, a population-based birth cohort in Rotterdam, the Netherlands (N = 9621). Differences in child internalizing and externalizing behavior at ages 1.5, 3, 6, 9 and 13 years between pregnancy intention groups were estimated using linear regression. Associations of postnatal depression and social support with internalizing and externalizing problems were also estimated using linear regression. Child behavior outcomes where compared before and after modelling a situation in which none of the mothers experienced a postnatal depression and all mother experienced high social support. Results: Most pregnancies (72.9%) were planned, 14.8% were unplanned and wanted, 10.8% were unplanned with initially ambivalent feelings and 1.5% with prolonged ambivalent feelings. Children from unplanned pregnancies had more internalizing and externalizing problems at all ages as compared to children from a planned pregnancy, especially when ambivalent feelings were present. Hypothetically eliminating on postnatal depression reduced the differences in internalizing and externalizing problems by 0.02 to 0.16 standard deviation. Hypothetically increasing social support did not significantly reduce the difference in internalizing and externalizing problems. Conclusions: Children from an unplanned pregnancy have more behavior problems, in particular when mothers had prolonged ambivalent feelings. Eliminating postnatal depression may help to reduce the inequality in child behavior related to pregnancy intention.</p

Molecular adaptations of the blood–brain barrier promote stress resilience vs. depression

Preclinical and clinical studies suggest that inflammation and vascular dysfunction contribute to the pathogenesis of major depressive disorder (MDD). Chronic social stress alters blood–brain barrier (BBB) integrity through loss of tight junction protein claudin-5 (cldn5) in male mice, promoting passage of circulating proinflammatory cytokines and depression-like behaviors. This effect is prominent within the nucleus accumbens, a brain region associated with mood regulation; however, the mechanisms involved are unclear. Moreover, compensatory responses leading to proper behavioral strategies and active resilience are unknown. Here we identify active molecular changes within the BBB associated with stress resilience that might serve a protective role for the neurovasculature. We also confirm the relevance of such changes to human depression and antidepressant treatment. We show that permissive epigenetic regulation of cldn5 expression and low endothelium expression of repressive cldn5-related transcription factor foxo1 are associated with stress resilience. Regionand endothelial cell-specific whole transcriptomic analyses revealed molecular signatures associated with stress vulnerability vs. resilience. We identified proinflammatory TNFα/NFκB signaling and hdac1 as mediators of stress susceptibility. Pharmacological inhibition of stress-induced increase in hdac1 activity rescued cldn5 expression in the NAc and promoted resilience. Importantly, we confirmed changes in HDAC1 expression in the NAc of depressed patients without antidepressant treatment in line with CLDN5 loss. Conversely, many of these deleterious CLDN5-related molecular changes were reduced in postmortem NAc from antidepressanttreated subjects. These findings reinforce the importance of considering stress-induced neurovascular pathology in depression and provide therapeutic targets to treat this mood disorder and promote resilience

The effects of a multisite aerobic exercise intervention on asthma morbidity in sedentary adults with asthma: the Ex-asthma study randomised controlled trial protocol

Objective: Aerobic exercise can improve cardiovascular fitness and does not seem to be detrimental to patients with asthma, though its role in changing asthma control and inflammatory profiles is unclear. The main hypothesis of the current randomised controlled trial is that aerobic exercise will be superior to usual care in improving asthma control. Key secondary outcomes are asthma quality of life and inflammatory profiles. Design: A total of 104 sedentary adults with physician-diagnosed asthma will be recruited. Eligible participants will undergo a series of baseline assessments including: the asthma control questionnaire; the asthma quality-of-life questionnaire and the inflammatory profile (assessed from both the blood and sputum samples). On completion of the assessments, participants will be randomised (1:1 allocation) to either 12-weeks of usual care or usual care plus aerobic exercise. Aerobic exercise will consist of three supervised training sessions per week. Each session will consist of taking a short-acting bronchodilator, 10 min of warm-up, 40 min of aerobic exercise (50–75% of heart rate reserve for weeks 1–4, then 70–85% for weeks 5–12) and a 10 min cool-down. Within 1 week of completion, participants will be reassessed (same battery as at baseline). Analyses will assess the difference between the two intervention arms on postintervention levels of asthma control, quality of life and inflammation, adjusting for age, baseline inhaled corticosteroid prescription, body weight change and pretreatment dependent variable level. Missing data will be handled using standard multiple imputation techniques. Ethics and dissemination: The study has been approved by all relevant research ethics boards. Written consent will be obtained from all participants who will be able to withdraw at any time. Results: The result will be disseminated to three groups of stakeholder groups: (1) the scientific and professional community; (2) the research participants and (3) the general public. Registration Details: ClinicalTrials.gov Identifier NCT0095334

Psychiatric disorders among patients under investigation for occupational asthma: Prevalence and impact on employment status and health service use

Contexte : L’asthme professionnel (AP) est un important problème de santé au travail qui a un impact tant sur le secteur de l’emploi que sur les ressources en santé et l’individu lui-même. Entre 10 % et 30 % des asthmatiques qui le sont devenus à l’âge adulte mentionnent que leur asthme s’aggrave au travail et qu’il est souvent difficile à diagnostiquer et à traiter. La majorité (environ 70 %) des patients référés pour une évaluation relative à l’AP ne reçoivent pas un diagnostic d’AP, et jusqu’à 30 % d’entre eux ne reçoivent aucun diagnostic final de trouble médical (c. à d. biologique). Néanmoins, ces patients restent symptomatiques et incapables de travailler. Bien que plusieurs diagnostics différentiels soient considérés (p. ex. la rhinite, la bronchite à éosinophiles et l’hyperventilation), les troubles psychiatriques (dont beaucoup s’accompagnent d’affections somatiques pouvant ressembler à l’asthme, notamment le trouble panique et l’hypocondrie) ne font que rarement, sinon jamais l’objet d’une évaluation. Cela laisse entendre qu’un nombre important de patients ne reçoivent ni un diagnostic ni un traitement approprié pouvant les aider à retrouver un niveau de fonctionnement normal et à retourner au travail. Le fait de ne pas détecter la morbidité psychiatrique chez ces patients peut également avoir d’importantes répercussions sur l’utilisation des services de santé. Faute d’être diagnostiqués et traités, les patients atteints de troubles psychiatriques sont susceptibles de demeurer symptomatiques, ce qui augmente le risque qu’ils aient recours aux services de santé, notamment les services d’urgence et les consultations médicales, au prix de coûts élevés pour eux comme pour la société. Objectifs : L’objectif principal de cette étude était d’évaluer les taux de troubles psychiatriques (y compris l’hypocondrie et les troubles d’humeur et d’anxiété) et le niveau de détresse psychologique chez les patients soumis à une évaluation relative à l’AP. L’objectif secondaire de cette étude consistait à déterminer l’impact de la morbidité psychiatrique sur la situation d’emploi, l’utilisation des services de santé et la qualité de vie au terme d’un suivi de 12 à 18 mois. Méthodologie : Au total, 219 patients consécutifs (59 % de sexe masculin, âge moyen de 42 ans [± 11,1]) ont passé une entrevue sur leur situation sociodémographique et leurs antécédents médicaux le jour de leur évaluation relative à l’AP, qui comprenait un test spirométrique et un test de provocation spécifique par inhalation. Le questionnaire d’évaluation des troubles mentaux dans les soins primaires (PRIME-MD) a servi à évaluer les troubles d’humeur et d’anxiété, et l’Indice d’hypocondrie de Whiteley (IHW) a servi à évaluer les niveaux d’hypocondrie clinique. Les patients ont également rempli une batterie de questionnaires autoadministrés visant à établir leur niveau de détresse psychologique, y compris l’Inventaire de dépression de Beck-II (IDB-II), l’Inventaire d’anxiété de Beck (IAB) et l’Indice de sensibilité à l’anxiété (ASI). On a ensuite repris contact avec les patients 12 à 18 mois plus tard pour évaluer leur situation d’emploi, leur utilisation des services de santé et leur qualité de vie. Résultats : Des données ont pu être obtenues pour 196 patients, dont 152 (78 %) répondaient aux critères d’au moins un trouble diagnosticable. Les diagnostics finaux ont révélé ce qui suit : 26 % (n = 50) des patients souffraient d’AP, 25 % (n = 48) souffraient d’asthme exacerbé ou non au travail, 14 % (n = 28) souffraient d’un autre trouble inflammatoire, 13 % (n = 26) souffraient d’un trouble non inflammatoire, et 22 % (n = 44) n’avaient aucun trouble diagnosticable. Au total, 34 % (n = 67) des patients de l’échantillon répondaient aux critères d’un trouble psychiatrique actuel ; des troubles d’humeur et d’anxiété touchaient respectivement 29 % (n = 56) et 24 % (n = 47) des patients, et les scores de 6 % (n = 12) des patients à l’IHW étaient indicatifs d’hypocondrie. Les niveaux de dépression, d’anxiété et de sensibilité à l’anxiété se situaient dans la fourchette normale et ne différaient pas d’un groupe de diagnostic à l’autre. Fait intéressant, alors que les taux globaux de troubles psychiatriques étaient seulement légèrement plus élevés chez les patients non diagnostiqués (45 %) que chez les patients diagnostiqués (31 %) (F = 3,12 ; p = 0,079), les taux d’hypocondrie étaient nettement plus élevés chez les patients non diagnostiqués (14 %) que chez les patients diagnostiqués (4 %) (F = 5,71 ; p = 0,018). En outre, le fait de satisfaire aux critères de l’hypocondrie augmentait considérablement, soit par un facteur de près de 4, la probabilité de ne pas recevoir un diagnostic final (RRA ajusté = 3,92 ; IC de 95 % = [1,18 ; 13,05] ; p = 0,026). Selon les données de suivi après 12 à 18 mois, ajustées en fonction des covariables (inclusion faite des groupes de diagnostic), les patients atteints d’un trouble psychiatrique au départ affichaient des résultats nettement moins bons que ceux dont ce n’était pas le cas ; ils étaient notamment beaucoup moins susceptibles d’avoir un emploi (de travailler) (44 % vs 64 % ; F = 7,02 ; p = 0,009) et ils présentaient un taux plus élevé de visites à l’urgence au cours de la période de suivi (35 % vs 19 % ; F = 4,19 ; p = 0,042). Toujours après ajustement des données en fonction des covariables, il n’y avait aucun lien potentiel entre l’état de santé mental des participants et leur score au Questionnaire sur la qualité de vie des asthmatiques au moment du suivi. Conclusions et répercussions cliniques : Les taux de troubles d’humeur ou d’anxiété étaient anormalement élevés (2 à 4 fois plus élevés que les taux observés dans la population générale) chez les patients qui se présentaient pour une évaluation relative à l’AP. Bien que les taux globaux de troubles psychiatriques et les niveaux de détresse psychologique aient été comparables chez les patients appelés ou non à recevoir un diagnostic d’AP ou d’un autre trouble diagnosticable, l’hypocondrie était plus fréquente chez les patients qui ne recevaient pas un diagnostic de trouble effectif, ce qui suppose qu’elle peut expliquer un nombre important de cas « non diagnosticables » d’AP présumé. Les données de suivi indiquaient que, quel que soit le groupe de diagnostic, les patients atteints d’un trouble psychiatrique au départ affichaient de moins bons résultats après 12 à 18 mois, notamment en ce qu’ils étaient moins susceptibles d’avoir un emploi et en ce qu’ils faisaient un usage plus marqué de certains services de santé (visites à l’urgence). Les résultats de cette étude suggèrent globalement que l’évaluation (et le traitement) des troubles psychiatriques dans cette population exigent davantage d’efforts. Abstract Background: Occupational asthma (OA) is a significant occupational health problem impacting the employment sector, health care resources, and the individual. From 10 to 30% of all adult-onset asthmatics mention that their asthma worsens at work, and is often difficult to diagnose and treat. The majority of patients referred for evaluation of OA (approximately 70%) do not receive a diagnosis of OA, and as many as 30% of them will fail to receive a final diagnosis of any medical (i.e., biological) disorder. However, these patients will remain symptomatic and unable to work. Though several differential diagnoses are considered (e.g., rhinitis, eosinophilic bronchitis, hyperventilation syndrome), psychiatric disorders (many of which present with somatic complaints that may mimic asthma such as panic disorder and hypochondriasis) are rarely, if ever, assessed. This suggests that a significant number of patients will not be diagnosed or offered appropriate treatment that may help them return to a normal level of functioning, including returning to the workforce. Failing to detect psychiatric morbidity in these patients may also have important implications for health service use. Left undetected and untreated, patients with psychiatric disorders are likely to continue being symptomatic, increasing their risk for health service use such as emergency department and physician visits, at a high cost to both them personally and the society. Objectives: The primary objective of this study was to assess rates of psychiatric disorders (including mood and anxiety disorders, and hypochondriasis) and levels of psychological distress among patients under investigation for OA. The secondary objective of this study was to determine the impact of psychiatric morbidity on employment status, health service use and quality of life at 12-18 month follow-up. Methods: A total of 219 consecutive patients (59% male, mean age 42 ± 11.1 years) underwent a sociodemographic and medical history interview on the day of their OA evaluation, which included spirometry and specific inhalation challenge testing. The Primary Care Evaluation of Mental Disorders (PRIME-MD) was used to assess mood and anxiety disorders, and patients completed the Whiteley Hypochondriasis Index (WI) to assess clinical levels of hypochondriasis. Patients also completed a battery of self-report questionnaires assessing levels of psychological distress including the Beck Depression (BDI-II) and Beck Anxiety (BAI) Inventories, and the Anxiety Sensitvity Index (ASI). Patients were re-contacted approximately 12-18 months later to assess employment status, health service use, and quality of life. Results: Data were available for 196 patients, of which 152 (78%) met criteria for at least one diagnosable disorder. Final diagnostic results revealed that 26% (n=50) of patients had OA, 25% (n=48) had asthma or work-exacerbated asthma, 14% (n=28) had another inflammatory disorder, 13% (n=26) had a non-inflammatory disorder, and 22% (n=44) did not have a diagnosable disorder. A total of 34% (n=67) of the sample met criteria for a current psychiatric disorder; mood and anxiety disorders affected 29% (n=56) and 24% (n=47) of the sample respectively, and 6% (n=12) had scores on the WI suggestive of hypochondriasis. Levels of depression, anxiety and anxiety sensitivity were in the normal range and did not differ according to diagnostic group. Interestingly, while overall rates of psychiatric disorders were only marginally more common among patients without (45%) relative to those with (31%) a diagnosis (F=3.12, p=0.079), rates of hypochondriasis were significantly more common among patients without (14%) relative to those with (4%) a diagnosis (F=5.71, p=0.018). Moreover, meeting criteria for hypochondriasis significantly increased the likelihood of not receiving a final diagnosis by nearly 4-fold (adjusted OR=3.92, 95% CI=[1.18;13.05], p=0.026). Follow-up results indicated that after adjustment for covariates (including diagnostic group), patients with versus without a psychiatric disorder at baseline had significantly worse 12-18 month outcomes, including being significantly less likely to be employed (working) (44% vs. 64%, F=7.02, p=0.009), and having higher rates of emergency visits over the course of the follow-up (35% vs. 19%, F=4.19, p=.042). There was no prospective association between the psychiatric status of the participants and their score on the Asthma Quality of Life Questionnaire, at follow-up, after adjustment for covariates. Conclusions and clinical implications: Rates of mood or anxiety disorders were disproportionately high (2-4 times greater than rates observed in the general population) in patients presenting for evaluation of OA. Though overall rates of psychiatric disorders and levels of psychological distress were comparable among patients with and without eventual diagnoses of OA or other diagnosable disorders, hypochondriasis was more common among patients not receiving a diagnosable disorder, suggesting that it may underlie a significant proportion of ‘un-diagnosable’ cases of suspected OA. Follow-up results indicate that irrespective of the diagnostic group, patients with a psychiatric disorder at baseline have less favorable 12-18 month outcomes, including being less likely to be employed and having greater use of certain health services (emergency visits). Overall, the results of this study suggest that greater efforts should be made to assess (and treat) psychiatric disorders in this population