'I have anxiety, but I have values and preferences' Experiences of users with generalized anxiety disorder: A qualitative study.

To understand the experience and perceptions of people diagnosed with generalized anxiety disorder, along the whole process and their role through the decision-making process for their treatment. A qualitative study through focus groups composed of people diagnosed with generalized anxiety disorder was carried out. Content analysis was carried out to explore the most representative issues. Five thematic categories were identified: onset of the disorder, symptoms and course; daily life with the disorder; coping with the disorder; demand of healthcare for anxiety, and treatment options and decision-making. Most of the patients reported physical symptoms of anxiety. The majority of participants perceived little social support from their environment and occupational interferences. Coping seems to differ among participant that have recovered or not recovered. The involvement of users with generalized anxiety disorder was scarce, and pharmacological treatment was always the first option offered. There is scarce orientation to elicit preferences and values of patients across the process of care for people with generalized anxiety disorder. The consequence is a biased predisposition of the healthcare system to provide pharmacological treatment as the first option and ignore the perspective of patients on how to cope with their illness.

¿En qué medida las guías de práctica clínica responden a las necesidades y preferencias de los usuarios diagnosticados de trastorno obsesivo compulsivo? / To What Extent do Clinical Practice Guidelines Respond to the Needs and Preferences of Patients Diagnosed with Obsessive-Compulsive Disorder?

RESUMEN Introducción: Para facilitar la toma de decisiones clínicas, están proliferando las guías de práctica clínica (GPC). Sin embargo, actualmente se carece de GPC para el trastorno obsesivo compulsivo (TOC) en las que se incluyan los requerimientos y las expectativas de los usuarios. Objetivos: El objetivo del presente trabajo es conocer si las recomendaciones de la guía «Obsessive-compulsive disorder: core interventions in the treatment of obsessive-compulsive disorder and body dysmorphic disorder¼ del National Institute for Clinical Excellence (NICE) se corresponden con las necesidades y preferencias de un grupo de usuarios diagnosticados de TOC. Métodos: Para ello, se conformaron 2 grupos focales con un total de 12 pacientes, a los que se preguntó sobre el impacto del TOC en sus vidas, su experiencia con los servicios de salud mental, la satisfacción con los tratamientos recibidos y los recursos personales de afrontamiento. Las preferencias y necesidades de los usuarios se compararon con las recomendaciones de la guía y, para facilitar su accesibilidad, se agruparon en 4 grandes áreas temáticas: información, accesibilidad, abordaje terapéutico y relación terapéutica. Resultados: Se observó una alta correspondencia entre las recomendaciones y las preferencias de los usuarios; por ejemplo, respecto a las intervenciones psicológicas de alta intensidad. La escasez de intervenciones psicológicas de baja intensidad antes de acudir al servicio de salud mental o la dificultad para acceder a los profesionales son algunas de las experiencias narradas que discreparon con las recomendaciones de la guía y de las necesidades expresadas por este grupo de usuarios. Conclusiones: Hay coincidencia entre las recomendaciones y las preferencias y necesidades de los usuarios; sin embargo, los servicios sanitarios responden a ellas parcialmente.

ABSTRACT Introduction: The number of Clinical Practice Guidelines (CPG) to help in making clinical decisions is increasing. However, there is currently a lack of CPG for Obsessive-Compulsive Disorder that take into account the requirements and expectations of the patients. Objective: The aim of the present study was to determine whether recommendations of the NICE guideline, "Obsessive-compulsive disorder: core interventions in the treatment of obsessive-compulsive disorder and body dysmorphic disorder" agrees with the needs and preferences of patients diagnosed with OCD in the mental health service. Material and method: Two focal groups were formed with a total of 12 participants. They were asked about the impact of the disorder in their lives, their experiences with the mental health services, their satisfaction with treatments, and about their psychological resources. Preferences and needs were compared with the recommendations of the guidelines, and to facilitate their analysis, they were classified into four topics: information, accessibility, treatments, and therapeutic relationship. Results: The results showed a high agreement between recommendations and patients preferences, particularly as regards high-intensity psychological interventions. Some discrepancies included the lack of prior low-intensity psychological interventions in mental health service, and the difficulty of rapid access the professionals. Conclusions: There is significant concordance between recommendations and patients preferences and demands, which are only partially responded to by the health services.

To What Extent do Clinical Practice Guidelines Respond to the Needs and Preferences of Patients Diagnosed with Obsessive-Compulsive Disorder? / ¿En qué medida las guías de práctica clínica responden a las necesidades y preferencias de los usuarios diagnosticados de trastorno obsesivo compulsivo?

INTRODUCTION: The number of Clinical Practice Guidelines (CPG) to help in making clinical decisions is increasing. However, there is currently a lack of CPG for Obsessive-Compulsive Disorder that take into account the requirements and expectations of the patients. OBJECTIVE: The aim of the present study was to determine whether recommendations of the NICE guideline, "Obsessive-compulsive disorder: core interventions in the treatment of obsessive-compulsive disorder and body dysmorphic disorder" agrees with the needs and preferences of patients diagnosed with OCD in the mental health service. MATERIAL AND METHOD: Two focal groups were formed with a total of 12 participants. They were asked about the impact of the disorder in their lives, their experiences with the mental health services, their satisfaction with treatments, and about their psychological resources. Preferences and needs were compared with the recommendations of the guidelines, and to facilitate their analysis, they were classified into four topics: information, accessibility, treatments, and therapeutic relationship. RESULTS: The results showed a high agreement between recommendations and patients preferences, particularly as regards high-intensity psychological interventions. Some discrepancies included the lack of prior low-intensity psychological interventions in mental health service, and the difficulty of rapid access the professionals. CONCLUSIONS: There is significant concordance between recommendations and patients preferences and demands, which are only partially responded to by the health services.

Outcomes for Children with Chronic Conditions Associated with Parent- and Provider-reported Measures of the Medical Home.

PURPOSE: Assess relationships between having a patient-centered medical home (PCMH) and health care utilization among low-income children with chronic conditions using parent and practice perspectives. METHODS: We analyzed data from 240 publicly insured children with chronic conditions. Parents completed surveys assessing PCMH access and their child's primary care practice completed the Medical Home Index (MHI) self-assessment. Multivariate negative binomial analyses were conducted to investigate relationships between PCMH and service use. RESULTS: Parent-report of a usual source of care was associated with lower rates of emergency care (ED) encounters and hospitalizations. Practice report of higher organizational capacity (e.g., communication, staff education) was associated with lower rates of ED visits and hospitalizations. Parent report of a PCMH was positively associated with practice MHI score. CONCLUSIONS: Among low-income children with chronic conditions, having a usual source of care and higher quality organizational capacity were associated with lower rates of ED visits and hospitalizations.

The interaction of caveolin 3 protein with the potassium inward rectifier channel Kir2.1: physiology and pathology related to long qt syndrome 9 (LQT9).

Mutations in CAV3 cause LQT syndrome 9 (LQT9). A previously reported LQT9 patient had prominent U waves on ECG, a feature that has been correlated with Kir2.1 loss of function. Our objective was to determine whether caveolin 3 (Cav3) associates with Kir2.1 and whether LQT9-associated CAV3 mutations affect the biophysical properties of Kir2.1. Kir2.1 current (IK1) density was measured using the whole-cell voltage clamp technique. WT-Cav3 did not affect IK1. However, F97C-Cav3 and T78M-Cav3 decreased IK1 density significantly by ∼60%, and P104L-Cav3 decreased IK1 density significantly by ∼30% at -60 mV. Immunostained rat heart cryosections and HEK293 cells cotransfected with Kir2.1 and WT-Cav3 both demonstrated colocalization of Kir2.1 and WT-Cav3 by confocal imaging. Cav3 coimmunoprecipitated with Kir2.1 in human ventricular myocytes and in heterologous expression systems. Additionally, FRET efficiency was highly specific, with a molecular distance of 5.6 ± 0.4 nm, indicating close protein location. Colocalization experiments found that Cav3 and Kir2.1 accumulated in the Golgi compartment. On-cell Western blot analysis showed decreased Kir2.1 cell surface expression by 60% when expressed with F97C-Cav3 and by 20% when expressed with P104L-Cav3 compared with WT-Cav3. This is the first report of an association between Cav3 and Kir2.1. The Cav3 mutations F97C-Cav3, P104L-Cav3, and T78M-Cav3 decreased IK1 density significantly. This effect was related to a reduced cell surface expression of Kir2.1. Kir2.1 loss of function is additive to the increase described previously in late INa, prolonging repolarization and leading to arrhythmia generation in Cav3-mediated LQT9.

Dynamic changes in sarcoplasmic reticulum structure in ventricular myocytes.

The fidelity of excitation-contraction (EC) coupling in ventricular myocytes is remarkable, with each action potential evoking a [Ca²âº](i) transient. The prevalent model is that the consistency in EC coupling in ventricular myocytes is due to the formation of fixed, tight junctions between the sarcoplasmic reticulum (SR) and the sarcolemma where Ca²âº release is activated. Here, we tested the hypothesis that the SR is a structurally inert organelle in ventricular myocytes. Our data suggest that rather than being static, the SR undergoes frequent dynamic structural changes. SR boutons expressing functional ryanodine receptors moved throughout the cell, approaching or moving away from the sarcolemma of ventricular myocytes. These changes in SR structure occurred in the absence of changes in [Ca²âº](i) during EC coupling. Microtubules and the molecular motors dynein and kinesin 1(Kif5b) were important regulators of SR motility. These findings support a model in which the SR is a motile organelle capable of molecular motor protein-driven structural changes.

An entirely specific type I A-kinase anchoring protein that can sequester two molecules of protein kinase A at mitochondria.

A-kinase anchoring proteins (AKAPs) tether the cAMP-dependent protein kinase (PKA) to intracellular sites where they preferentially phosphorylate target substrates. Most AKAPs exhibit nanomolar affinity for the regulatory (RII) subunit of the type II PKA holoenzyme, whereas dual-specificity anchoring proteins also bind the type I (RI) regulatory subunit of PKA with 10-100-fold lower affinity. A range of cellular, biochemical, biophysical, and genetic approaches comprehensively establish that sphingosine kinase interacting protein (SKIP) is a truly type I-specific AKAP. Mapping studies located anchoring sites between residues 925-949 and 1,140-1,175 of SKIP that bind RI with dissociation constants of 73 and 774 nM, respectively. Molecular modeling and site-directed mutagenesis approaches identify Phe 929 and Tyr 1,151 as RI-selective binding determinants in each anchoring site. SKIP complexes exist in different states of RI-occupancy as single-molecule pull-down photobleaching experiments show that 41 ± 10% of SKIP sequesters two YFP-RI dimers, whereas 59 ± 10% of the anchoring protein binds a single YFP-RI dimer. Imaging, proteomic analysis, and subcellular fractionation experiments reveal that SKIP is enriched at the inner mitochondrial membrane where it associates with a prominent PKA substrate, the coiled-coil helix protein ChChd3.

Protein kinase A-dependent biophysical phenotype for V227F-KCNJ2 mutation in catecholaminergic polymorphic ventricular tachycardia.

BACKGROUND: KCNJ2 encodes Kir2.1, a pore-forming subunit of the cardiac inward rectifier current, I(K1). KCNJ2 mutations are associated with Andersen-Tawil syndrome and catecholaminergic polymorphic ventricular tachycardia. The aim of this study was to characterize the biophysical and cellular phenotype of a KCNJ2 missense mutation, V227F, found in a patient with catecholaminergic polymorphic ventricular tachycardia. METHODS AND RESULTS: Kir2.1-wild-type (WT) and V227F channels were expressed individually and together in Cos-1 cells to measure I(K1) by voltage clamp. Unlike typical Andersen-Tawil syndrome-associated KCNJ2 mutations, which show dominant negative loss of function, Kir2.1WT+V227F coexpression yielded I(K1) indistinguishable from Kir2.1-WT under basal conditions. To simulate catecholamine activity, a protein kinase A (PKA)-stimulating cocktail composed of forskolin and 3-isobutyl-1-methylxanthine was used to increase PKA activity. This PKA-simulated catecholaminergic stimulation caused marked reduction of outward I(K1) compared with Kir2.1-WT. PKA-induced reduction in I(K1) was eliminated by mutating the phosphorylation site at serine 425 (S425N). CONCLUSIONS: Heteromeric Kir2.1-V227F and WT channels showed an unusual latent loss of function biophysical phenotype that depended on PKA-dependent Kir2.1 phosphorylation. This biophysical phenotype, distinct from typical Andersen-Tawil syndrome mutations, suggests a specific mechanism for PKA-dependent I(K1) dysfunction for this KCNJ2 mutation, which correlates with adrenergic conditions underlying the clinical arrhythmia.