Identification of Preschool Children with Mental Health Problems in Primary Care: Systematic Review and Meta-analysis.

OBJECTIVE: Primary care practitioners determine access to care for many preschool children with mental health (MH) problems. This study examined rates of mental health (MH) problem identification in preschoolers within primary healthcare settings, related service use, and MH status at follow-up. The findings may inform evidence-based policy and practice development for preschool MH. METHOD: For this systematic review, MEDLINE®, EMBASE®, PsycInfo®, and ERIC ® were searched from inception to March 7, 2018 for reports in which a screening measure was used to identify MH problems in children aged 24-72 months, seen in primary and community health care settings. Meta-analyses, using random effects models to provide pooled estimates, were used when three or more studies examined identification rates. Findings on service use and persistence of disorders are summarized. RESULTS: Thirty-five publications representing 21 studies met the inclusion criteria. MH problems were identified in 17.6% of preschoolers (95% Confidence Interval (CI): 11.1-24.1), Q = 4.9, p > 0.1 by primary/community healthcare practitioners. Psychiatric diagnoses were identified in 18.4% of preschoolers (95% CI: 12.3 - 24.4), Q= 1.6, p > 0.1. Based on three studies, parents of 67-72% of identified children received advice and 26-42% received specialist referrals. In the subset of studies examining persistence of MH disorders, 25-67% of identified children had MH disorders after one to three years. CONCLUSION: While the identification rate by primary/community practitioners is similar to the diagnostic rate, these may not consistently be the same children. Substantial variability in management and outcomes indicate need for more rigorous evaluation of primary care services for this population.

OBJECTIF: Les praticiens des soins primaires déterminent l'accès aux soins pour de nombreux enfants d'âge préscolaire souffrant de problèmes de santé mentale (SM). La présente étude a examiné les taux d'identification des problèmes de SM chez les enfants d'âge préscolaire dans le contexte de soins primaires, de l'utilisation des services connexes et de l'état de la SM au suivi. Les résultats peuvent éclairer l'élaboration des politiques et des pratiques fondées sur des données probantes pour la SM préscolaire. MÉTHODE: La recherche pour cette revue systématique a été menée dans MEDLINE®, EMBASE®, PsycInfo®, et ERIC ® du début au 7 mars 2018, et ciblait des études utilisant une mesure de dépistage pour identifier les problèmes de santé mentale chez les 24 à 72 mois, vus dans les soins primaires et communautaires. Les méta-analyses, utilisant des modèles à effets aléatoires pour produire des estimations regroupées, ont été utilisées quand trois ou plusieurs études examinaient les taux d'identification. Les résultats de l'utilisation des services et de la persistance des troubles sont résumés. RÉSULTATS: Trente-cinq publications représentant 21 études satisfaisaient aux critères d'inclusion. Des problèmes de SM ont été identifiés chez 17,6% des enfants d'âge préscolaire (intervalle de confiance IC à 95%: 11,1 à 24,1; Q = 4,9, p > 0,1) par des praticiens des soins primaires/communautaires. Des diagnostics psychiatriques ont été posés chez 18,4 % des enfants d'âge préscolaire (IC à 95%: 12,3 à 24,4; Q = 1,6; p > 0,1). Selon trois études, les parents de 67 à 72% des enfants identifiés recevaient des conseils, 26 à 42 % étaient adressés à des spécialistes. Dans le sous-ensemble des études qui examinaient la persistance des troubles de SM, 25% à 67% des enfants identifiés avaient des troubles de SM d'ici 1 à 3 ans. CONCLUSION: Même si le taux d'identification par les praticiens des soins primaires /communautaires est semblable au taux de diagnostics, il ne s'agit peut-être pas constamment des mêmes enfants. La variabilité substantielle de la prise en charge et des résultats indique le besoin d'une évaluation plus rigoureuse des services de soins primaires pour cette population.

Deficiency of S100B confers resistance to experimental diabetes in mice.

The calcium binding protein S100B has been implicated in diabetic neuronal and vascular complications but has not been examined in the development of diabetes. S100B knock out (S100B KO) and wild-type (WT) mice were injected with 40 mg/kg body weight streptozotocin (STZ) for 5 days. Blood and pancreatic tissue samples were obtained to examine islet structure and function, the profile of glucose and insulin and expression of glucose transporter 2 (Glut2), S100B and its receptor, the receptor for advanced glycation end products (RAGE). Primary islet ß-cells cultures from WT mice were used to test the apoptotic potential of S100B. S100B KO mice were resistant to STZ induced-diabetes with lower urine volume, food and water intake compared to WT mice. S100B increased in the WT islet following diabetes but did not co-localize with beta or peri-islet Schwann cells but with CD3 + T lymphocytes. S100B KO mice exhibited enhanced glucose tolerance, insulin sensitivity, prevented ß-cell destruction and functional impairment in response to STZ treatment. S100B deficiency was associated with decreased Glut2 and RAGE. In primary ß-cell cultures from WT mice, S100B induced reactive oxygen species (ROS) and RAGE-dependent apoptosis. In the STZ diabetic animal model, abrogation of S100B enhances insulin sensitivity and reduces pancreatic islet, and ß-cell destruction. S100B may be a promising target for pharmacological interventions aimed at repressing diabetes.

Using the Delphi technique to improve clinical outcomes through the development of quality indicators in renal cell carcinoma.

PURPOSE: Optimal quality of care is needed for ideal outcomes. In renal cell carcinoma (RCC), there is a lack of information defining optimal care. This is particularly important in RCC, with increased complexity of care and a need for coordination among providers. The goal of this study was to identify quality indicators (QIs) and measures of quality care across the RCC disease spectrum. MATERIALS AND METHODS: A modified Delphi technique was used to select QIs that are relevant and practical to RCC care. This technique involved an expert panel of 13 urologic and medical oncologists who participated in two e-mail questionnaires and an in-person meeting to review and prioritize potential QIs. These potential QIs were identified from a systematic literature review or were suggested by panel members. RESULTS: From 233 literature citations, 34 possible QIs were identified; 24 additional potential QIs were suggested. A final set of 23 QIs was established. These are distributed across the RCC disease spectrum as follows (number of QIs in parentheses): screening (n=1), diagnosis/prognosis (n=3), surgical for localized disease (n=6), surgery for advanced disease (n=3), systemic therapy (n=6), and follow-up (n=2). In addition, two QIs related to survival outcomes (overall and progression-free survival) were selected. CONCLUSION: A systematic, consensus-based approach was used to determine relevant QIs in RCC care. These 23 QIs will provide a means of evaluating the quality of RCC care in an effort to improve outcomes in patients. The next step will be to establish a means of measuring each QI based on defined or yet-to-be-defined benchmarks.

S100B: role in cardiac remodeling and function following myocardial infarction in diabetes.

AIM: S100B plays a role in cardiac remodeling following myocardial infarction (MI) and in diabetic vascular complications but not examined in diabetic myocardium. We thus examined the effects of targeted deletion of S100B gene on post-MI hearts. MAIN METHODS: Coronary artery ligation or sham was performed 15 weeks after streptozotocin (STZ) or vehicle injection in wild-type (WT) and S100B knock-out (BKO) mice. Left ventricular (LV) structural and functional remodeling was studied 35 days after induction of MI. KEY FINDINGS: In diabetes, post-MI remodeling exhibited an attenuated increase in LV mass, dilation, and myocyte hypertrophy in association with increased apoptosis and fibrosis and reduced matrix metalloproteinase-2 (MMP-2) activity. Despite reduced LV dilation, impairment of cardiac function was similar to non-diabetic controls. Both diabetes and MI alone induced myocardial S100B and its canonical receptor for advanced glycation end product (RAGE) expression. By contrast, in post-MI diabetic myocardium, S100B expression was attenuated. Diabetic BKO, following MI demonstrated increased ventricular dilation compared to WT, in association with greater impairment of cardiac function, GLUT4 expression and systemic AGE levels. SIGNIFICANCE: These data suggest that S100B expression may serve to modulate cardiac metabolism and adverse consequences of AGE in diabetic post-MI remodeling and function.

S100B: a multifunctional role in cardiovascular pathophysiology.

S100B, a calcium-binding protein of the EF-hand type exerts both intracellular and extracellular functions. S100B is induced in the myocardium of human subjects and an experimental rat model following myocardial infarction. Forced expression of S100B in neonatal rat myocyte cultures, and high level expression of S100B in transgenic mice hearts and aortic smooth muscle cells inhibit cardiac hypertrophy and the associated phenotype, arterial smooth muscle proliferation, respectively, but demonstrate increased apoptosis following α(1)-adrenergic stimulation or myocardial infarction. Knocking out S100B, augmented hypertrophy, decreased apoptosis and preserved cardiac function following myocardial infarction. S100B induces apoptosis by an extracellular mechanism by interacting with the receptor for advanced glycation end products and activating ERK1/2 and p53 signaling. The intracellular, and extracellular, roles of S100B are attractive therapeutic targets for the treatment of both cardiac and vascular disease.

Intracellular and Extracellular Effects of S100B in the Cardiovascular Response to Disease.

S100B, a calcium-binding protein of the EF-hand type, exerts both intracellular and extracellular functions. S100B is induced in the myocardium of human subjects and an experimental rat model following myocardial infarction. Forced expression of S100B in neonatal rat myocyte cultures and high level expression of S100B in transgenic mice hearts inhibit cardiac hypertrophy and the associated phenotype but augments myocyte apoptosis following myocardial infarction. By contrast, knocking out S100B, augments hypertrophy, decreases apoptosis and preserves cardiac function following myocardial infarction. Expression of S100B in aortic smooth muscle cells inhibits cell proliferation and the vascular response to adrenergic stimulation. S100B induces apoptosis by an extracellular mechanism via interaction with the receptor for advanced glycation end products and activating ERK1/2 and p53 signaling. The intracellular and extracellular roles of S100B are attractive therapeutic targets for the treatment of both cardiac and vascular diseases.

Static strain stimulates expression of matrix metalloproteinase-2 and VEGF in microvascular endothelium via JNK- and ERK-dependent pathways.

VEGF and MMP protein production are both required for exercise-induced capillary growth in skeletal muscle. The underlying process by which muscle activity initiates an angiogenic response is not established, but it is known that mechanical forces such as muscle stretch are involved. We hypothesized that stretch of skeletal muscle microvascular endothelial cells induces production of MMP-2 and VEGF through a common signal pathway. Endothelial cells were grown on Bioflex plates and exposed to 10% static stretch for up to 24 h. MMP-2 protein level was measured by gelatin zymography and VEGF, MMP-2, and MT1-MMP mRNA levels were quantified by real-time quantitative PCR. ERK1/2 and JNK phosphorylation and VEGF protein levels were assessed by Western blotting. Effects of mitogen-activated protein kinases (MAPKs) (ERK1/2, JNK) and reactive oxygen species (ROS) on stretch-induced expression of MMP-2 and VEGF were tested using pharmacological inhibitors. Stretching of endothelial cells for 24 h caused significant increases in MMP-2 protein and mRNA level, but no change in MT1-MMP mRNA. While MMP-2 protein production was enhanced by H(2)O(2) in unstretched cells, ROS inhibition during stretch did not diminish MMP-2 mRNA or protein production. Inhibition of JNK suppressed stretch-induced MMP-2 protein and mRNA, but inhibition of ERK had no effect. In contrast, inhibition of ERK but not JNK attenuated the stretch-induced increase in VEGF mRNA. Our results demonstrate that differential regulation of MMP-2 and VEGF by MAPK signal pathways contribute to stretch-induced activation of microvascular endothelial cells.