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1.
Community Ment Health J ; 60(3): 562-571, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-37982974

RESUMEN

Mobile crisis teams (MCTs) deploy clinicians to assist individuals in acute crisis in the community. Little is known about the extent to which these teams provide evidence-based practices (EBPs) for suicide prevention nor the barriers they face. We surveyed 120 MCT clinicians across the United States about their: (1) use of suicide risk screening and assessment tools; (2) strategies used to address suicide risk (both EBPs and non-EBPs); and (3) perceived barriers to high-quality MCT services. Nearly all clinicians reported use of validated suicide screening tools and generic "safety planning." However, a sizeable minority also reported use of non-EBPs. Open-ended responses suggested many client/family-, clinician-, and systems-level barriers to MCT use of EBPs for suicide prevention. We identified several targets for future implementation efforts, including the need for de-implementation strategies to reduce use of ineffective and potentially harmful practices, and unique aspects of MCTs that require tailored implementation supports.


Asunto(s)
Prevención del Suicidio , Suicidio , Humanos , Estados Unidos , Práctica Clínica Basada en la Evidencia , Encuestas y Cuestionarios , Accesibilidad a los Servicios de Salud
2.
Diabetes Obes Metab ; 23(7): 1614-1623, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33729664

RESUMEN

AIM: To investigate the mechanisms underlying improvements in blood pressure (BP) and congestive heart failure outcomes following treatment with dapagliflozin, a sodium-glucose co-transporter-2 inhibitor. RESEARCH DESIGN AND METHODS: A total of 52 patients with type 2 diabetes (T2D) with an HbA1c of less than 8% participated in this prospective, double-blind and placebo-controlled study. Patients were randomized (1:1) to either dapagliflozin 10 mg daily or placebo for 12 weeks. Half the patients were also monitored for 6 h following their first dose for acute effects on BP. Blood and urine samples were collected and levels of angiotensinogen, angiotensin II, renin, aldosterone, endothelin-1, atrial natriuretic peptide (ANP), brain natriuretic peptide, cyclic adenosine monophosphate, cyclic guanosine monophosphate (cGMP) and neprilysin were measured. The expression of angiotensin-converting enzyme, guanylate cyclase and phosphodiesterase 5 (PDE5) was measured in circulating mononuclear cells (MNC). RESULTS: A total of 24 and 23 patients receiving dapagliflozin and placebo, respectively, completed the 12-week study. Systolic BP decreased significantly, compared with placebo, both after single-dose (by 7 ± 3 mmHg) and 12-week (by 7 ± 2 mmHg) treatment with dapagliflozin. Dapagliflozin suppressed angiotensin II and angiotensinogen (by 10.5 ± 2.1 and 1.45 ± 0.42 µg/mL, respectively) and increased ANP and cGMP (by 34 ± 11 and 29 ± 11 pmol/mL, respectively) compared with the placebo group. cGMP levels also increased acutely following a single dose of dapagliflozin. Dapagliflozin also suppressed PDE5 expression by 26% ± 11% in MNC. There were no changes observed in the other vasoactive mediators investigated. CONCLUSIONS: Dapagliflozin administration in T2D resulted in both acute and chronic reduction in systolic BP, a reduction in vasoconstrictors and an increase in vasodilators. These changes may potentially contribute to its antihypertensive effects and its benefits in congestive cardiac failure.


Asunto(s)
Diabetes Mellitus Tipo 2 , Compuestos de Bencidrilo , Glucemia , Presión Sanguínea , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Método Doble Ciego , Glucósidos/uso terapéutico , Humanos , Estudios Prospectivos
3.
Subst Use Misuse ; 56(8): 1095-1107, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33870829

RESUMEN

BACKGROUND: In the context of the opioid epidemic and growing awareness of addiction as a public health concern, there are efforts to inform the public, patients, families, and policy makers about the factors that contribute to addiction and facilitate recovery. Several theoretical models provide useful frameworks for this discussion, but each of them has limitations. OBJECTIVES: This paper presents an accessible yet comprehensive theoretical model that integrates empirical evidence about addiction etiology and recovery using the nature-nurture paradigm. RESULTS: The model presents substance use along a continuum, and identifies risk and protective factors in multiple domains that have been identified by research. The domains on the nature side of the model include genetic and biological factors, comorbid psychiatric and medical disorders, physiological reinforcement of substance use, and changes to neural mechanisms. The domains on the nurture side of the model include sociocultural factors, environmental factors, personality, emotions, cognitions, psychological reinforcement of substance use, and cognitive and behavioral changes. The progression from increased or decreased substance use to addiction or recovery is mediated by changes in neural mechanisms and cognitive and behavioral changes, which have feedback loops with the physiological and psychological reinforcement.Conclusions/Importance: This model is a useful heuristic, consistent with a public health framework, for discussing addiction and recovery with patients, their families, and the public. This integrated model of nature and nurture factors has the potential to inform clinical practice, consultation, research, prevention programs, educational programs, and public policy.


Asunto(s)
Conducta Adictiva , Trastornos Relacionados con Sustancias , Analgésicos Opioides , Emociones , Humanos , Refuerzo en Psicología
4.
Diabetes Obes Metab ; 22(10): 1742-1752, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32424935

RESUMEN

AIM: To investigate the effects of liraglutide treatment on glycaemic control and adipose tissue metabolism in overweight and obese people with type 1 diabetes (T1DM). RESEARCH DESIGN AND METHODS: A total of 84 adult overweight and obese patients with T1DM, with no detectable C-peptide, were randomized (1:1) to either placebo or 1.8 mg/d liraglutide for 6 months. Blood samples were collected at 0, 12 and 26 weeks. Subcutaneous adipose tissue biopsies, a high-calorie high-fat meal challenge test, continuous glucose monitoring, dual-energy X-ray absorptiometry and MRI were performed before and at the end of treatment. RESULTS: In all, 37 and 27 patients who received liraglutide and placebo, respectively, completed the study. Glycated haemoglobin fell by 0.41 ± 0.18% (4.5±1.4 mmol/mol) from baseline after liraglutide treatment (P = 0.001), and by 0.29 ± 0.19% (3.1±2.0 mmol/mol) compared to placebo (P = 0.1). There was no increase in hypoglycaemia, while the time spent in normal glycaemia increased (P = 0.015) and time spent in hyperglycaemia decreased (P = 0.019). Body weight fell significantly in the liraglutide group, mostly in the form of fat mass loss (including visceral fat), with no change in lean mass. Systolic blood pressure (SBP) also fell after liraglutide treatment. Liraglutide also caused a significant increase in the expression of adipose tissue triglyceride lipase, carnitine palmitoyl transferase-1, peroxisome proliferator-activated receptor (PPAR)α, PPARδ, uncoupling protein-2 and type 2 iodothyronine deiodinase in the adipose tissue. CONCLUSIONS: Liraglutide improves glycaemia, reduces adiposity and SBP. Liraglutide also stimulates mechanisms involved with an increase in lipid oxidation and thermogenesis, while conserving lean body mass.


Asunto(s)
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Adulto , Glucemia , Automonitorización de la Glucosa Sanguínea , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Método Doble Ciego , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/uso terapéutico , Liraglutida/uso terapéutico , Obesidad/complicaciones , Sobrepeso/complicaciones , Sobrepeso/tratamiento farmacológico , Resultado del Tratamiento , Pérdida de Peso
5.
Diabetes Obes Metab ; 20(8): 2029-2033, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29652095

RESUMEN

The aim of this study was to determine if weight loss following Roux-en-Y gastric bypass (RYGB) surgery in morbidly obese patients is associated with a decrease in plasma concentrations of neprilysin, mediators of the renin angiotensin system (RAS), catecholamines and endothelin-1, and also with an increase in the concentrations of vasodilators. Fasting blood samples were obtained from 15 patients with morbid obesity and diabetes prior to and 6 months after RYGB surgery. Circulating levels of neprilysin, vasoconstrictors, vasodilators, and the mRNA expression of related genes in circulating mononuclear cells (MNC) were measured. Six months after RYGB surgery the concentrations of neprilysin, angiotensinogen, angiotensin II, renin and endothelin-1 fell significantly by 27 ±16%, 22 ±10%, 22 ±8%, 35 ±13% and 17 ±6% (P < .05 for all), respectively, while ANP concentrations increased significantly by 24 ±13%. There was no significant change in aldosterone, BNP, cAMP or cGMP concentrations, or angiotensin converting enzyme (ACE) expression. These changes may contribute to the reduction of congestive cardiac failure and blood pressure risks after RYGB surgery.


Asunto(s)
Cirugía Bariátrica/efectos adversos , Endotelina-1/sangre , Insuficiencia Cardíaca/prevención & control , Hipertensión/prevención & control , Neprilisina/sangre , Obesidad Mórbida/cirugía , Sistema Renina-Angiotensina , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/epidemiología , Angiopatías Diabéticas/prevención & control , Cardiomiopatías Diabéticas/epidemiología , Cardiomiopatías Diabéticas/prevención & control , Femenino , Hemoglobina Glucada/análisis , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/etiología , Humanos , Hipertensión/complicaciones , Hipertensión/epidemiología , Hipertensión/etiología , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Obesidad Mórbida/complicaciones , Obesidad Mórbida/metabolismo , Obesidad Mórbida/fisiopatología , Periodo Posoperatorio , Estudios Prospectivos , Riesgo , Pérdida de Peso
6.
Cogn Behav Pract ; 25(4): 460-472, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31787833

RESUMEN

This article presents a pragmatic approach to assessing and managing suicide risk in children and adolescents. We first present general recommendations for conducting risk assessments with children and adolescents, followed by an algorithm for designating risk. Risk assessment and designation should be based on both distal (i.e., a prior history of self-harm behaviors) and proximal (i.e., suicide ideation, plans, intent, and preparations) predictors of suicide attempt. We then discuss safety planning as an easy-to-implement approach for intervening and managing suicide risk when working with children and adolescents. We end with a case example illustrating the implementation of risk assessment, risk designation, and safety planning with an adolescent client and her mother.

7.
Diabetes Obes Metab ; 19(5): 729-733, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-27891769

RESUMEN

In view of the known vasodilatory effects of glucagon-like peptide-1 and exenatide, we investigated the effects of exenatide on vasoactive factors. We analysed blood samples and mononuclear cells (MNCs) from a previous study, collected after a single dose and 12 weeks of exenatide or placebo treatment in a series of 24 patients with type 2 diabetes mellitus. After exenatide treatment, plasma concentrations of atrial natriuretic peptide, cyclic guanyl monophosphate (cGMP) and cyclic adenyl monophosphate increased significantly at 12 weeks. Plasma cGMP and adenylate cyclase expression in MNCs increased significantly after a single dose. Angiotensinogen concentration fell significantly 2 hours after a single dose and at 12 weeks, while renin and angiotensin II levels fell significantly only after a single dose and not after 12 weeks of treatment. Exenatide also suppressed the plasma concentration of transforming growth factor-ß and the expression of P311 in MNCs at 12 weeks. Thus, exenatide induces an increase in a series of vasodilators, while suppressing the renin-angiotensin system. These changes may contribute to the overall vasodilatory effect of exenatide.


Asunto(s)
Antihipertensivos/uso terapéutico , Factor Natriurético Atrial/agonistas , Regulación de la Expresión Génica/efectos de los fármacos , Péptido 1 Similar al Glucagón/agonistas , Leucocitos Mononucleares/efectos de los fármacos , Proteínas del Tejido Nervioso/antagonistas & inhibidores , Proteínas Oncogénicas/antagonistas & inhibidores , Péptidos/uso terapéutico , Ponzoñas/uso terapéutico , Adenilil Ciclasas/química , Adenilil Ciclasas/genética , Adenilil Ciclasas/metabolismo , Angiotensinógeno/antagonistas & inhibidores , Angiotensinógeno/sangre , Fármacos Antiobesidad/uso terapéutico , Factor Natriurético Atrial/sangre , Presión Sanguínea/efectos de los fármacos , AMP Cíclico/agonistas , AMP Cíclico/sangre , GMP Cíclico/agonistas , GMP Cíclico/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/inmunología , Diabetes Mellitus Tipo 2/metabolismo , Exenatida , Péptido 1 Similar al Glucagón/metabolismo , Humanos , Hipoglucemiantes/uso terapéutico , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Obesidad/sangre , Obesidad/tratamiento farmacológico , Obesidad/inmunología , Obesidad/metabolismo , Proteínas Oncogénicas/genética , Proteínas Oncogénicas/metabolismo , Sistema Renina-Angiotensina/efectos de los fármacos , Reproducibilidad de los Resultados , Método Simple Ciego , Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Factor de Crecimiento Transformador beta/sangre
8.
Diabetes Obes Metab ; 19(9): 1306-1311, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28304146

RESUMEN

In view of the occurrence of diabetic ketoacidosis associated with the use of sodium-glucose transport protein-2 inhibitors in patients with type 1 diabetes (T1DM) and the relative absence of this complication in patients treated with liraglutide in spite of reductions in insulin doses, we investigated the effect of liraglutide on ketogenesis. Twenty-six patients with inadequately controlled T1DM were randomly divided into 2 groups of 13 patients each. After an overnight fast, patients were injected, subcutaneously, with either liraglutide 1.8 mg or with placebo. They were maintained on their basal insulin infusion and were followed up in our clinical research unit for 5 hours. The patients injected with placebo maintained their glucose and glucagon concentrations without an increase, but there was a significant increase in free fatty acids (FFA), acetoacetate and ß-hydoxybutyrate concentrations. In contrast, liraglutide significantly reduced the increase in FFA, and totally prevented the increase in acetoacetate and ß-hydroxybutyrate concentrations while suppressing glucagon and ghrelin concentrations. Thus, a single dose of liraglutide is acutely inhibitory to ketogenesis.


Asunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Glucagón/antagonistas & inhibidores , Hipoglucemiantes/uso terapéutico , Cuerpos Cetónicos/antagonistas & inhibidores , Lipólisis/efectos de los fármacos , Liraglutida/uso terapéutico , Adulto , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/metabolismo , Método Doble Ciego , Resistencia a Medicamentos , Quimioterapia Combinada , Ácidos Grasos no Esterificados/antagonistas & inhibidores , Ácidos Grasos no Esterificados/sangre , Femenino , Ghrelina/antagonistas & inhibidores , Ghrelina/sangre , Glucagón/sangre , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Humanos , Hipoglucemiantes/administración & dosificación , Inyecciones Subcutáneas , Insulina/administración & dosificación , Insulina/uso terapéutico , Sistemas de Infusión de Insulina , Cuerpos Cetónicos/biosíntesis , Cuerpos Cetónicos/sangre , Liraglutida/administración & dosificación , Masculino , Persona de Mediana Edad
9.
J Appl Meas ; 18(3): 247-267, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29579738

RESUMEN

This study explored optimization of item-attribute matrices with the linear logistic test model (Fischer, 1973), with optimal models explaining more variance in item difficulty due to identified item attributes. Data were 8th-grade mathematics test item responses of two TIMSS 2007 booklets. The study investigated three categories of attributes (content, cognitive process, and comprehensive cognitive process) at two grain levels (larger, smaller) and also compared results with random attribute matrices. The proposed attributes accounted for most of the variance in item difficulty for two assessment booklets (81% and 65%). The variance explained by the content attributes was very small (13% to 31%), less than variance explained by the comprehensive cognitive process attributes which explained much more variance than the content and cognitive process attributes. The variances explained by the grain level were similar to each other. However, the attributes did not predict the item difficulties of two assessment booklets equally.


Asunto(s)
Evaluación Educacional/métodos , Evaluación Educacional/normas , Modelos Estadísticos , Psicometría/métodos , Psicometría/normas , Humanos , Matemática , Folletos
10.
Clin Endocrinol (Oxf) ; 85(5): 772-780, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27292585

RESUMEN

CONTEXT: As the syndrome of hypogonadotropic hypogonadism (HH) is associated with anaemia and the administration of testosterone restores haematocrit to normal, we investigated the potential underlying mechanisms. DESIGN: Randomized, double-blind, placebo-controlled trial. METHODS: We measured basal serum concentrations of erythropoietin, iron, iron binding capacity, transferrin (saturated and unsaturated), ferritin and hepcidin and the expression of ferroportin and transferrin receptor (TR) in peripheral blood mononuclear cells (MNC) of 94 men with type 2 diabetes. Forty-four men had HH (defined as subnormal free testosterone along with low or normal LH concentrations) while 50 were eugonadal. Men with HH were randomized to testosterone or placebo treatment every 2 weeks for 15 weeks. Blood samples were collected at baseline, 3 and 15 weeks after starting treatment. Twenty men in testosterone group and 14 men in placebo group completed the study. RESULTS: Haematocrit levels were lower in men with HH (41·1 ± 3·9% vs 43·8 ± 3·4%, P = 0·001). There were no differences in plasma concentrations of hepcidin, ferritin, erythropoietin, transferrin or iron, or in the expression of ferroportin or TR in MNC among HH and eugonadal men. Haematocrit increased to 45·3 ± 4·5%, hepcidin decreased by 28 ± 7% and erythropoietin increased by 21 ± 7% after testosterone therapy (P < 0·05). There was no significant change in ferritin concentrations, but transferrin concentration increased while transferrin saturation and iron concentrations decreased (P < 0·05). Ferroportin and TR mRNA expression in MNC increased by 70 ± 13% and 43 ± 10%, respectively (P < 0·01), after testosterone therapy. CONCLUSIONS: The increase in haematocrit following testosterone therapy is associated with an increase in erythropoietin, the suppression of hepcidin, and an increase in the expression of ferroportin and TR.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Ferritinas/efectos de los fármacos , Hepcidinas/efectos de los fármacos , Hipogonadismo/tratamiento farmacológico , Hierro/metabolismo , Testosterona/farmacología , Adulto , Anciano , Proteínas de Transporte de Catión/biosíntesis , Proteínas de Transporte de Catión/sangre , Diabetes Mellitus Tipo 2/sangre , Método Doble Ciego , Eritropoyetina/sangre , Ferritinas/sangre , Hematócrito , Hepcidinas/sangre , Humanos , Hipogonadismo/sangre , Hierro/sangre , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , Receptores de Transferrina/biosíntesis , Receptores de Transferrina/sangre
11.
Nat Rev Cancer ; 7(9): 713-22, 2007 09.
Artículo en Inglés | MEDLINE | ID: mdl-17721435

RESUMEN

Oestrogen receptor-alpha (ERalpha)-regulated transcription in breast cancer cells involves protein co-factors that contribute to the regulation of chromatin structure. These include co-factors with the potential to regulate histone modifications such as acetylation or methylation, and therefore the transcriptional state of target genes. Although much of the information regarding the interaction of specific co-factors with ER has been generated by studying specific promoter regions, we now have an improved understanding of the nature of these interactions and are better placed to relate these with ER activity and potentially with the activity of breast cancer drugs, including tamoxifen.


Asunto(s)
Cromatina/metabolismo , Receptor alfa de Estrógeno/fisiología , Transcripción Genética , Secuencia de Aminoácidos , Proteínas Portadoras/farmacología , Inmunoprecipitación de Cromatina , Corticosterona , Receptor alfa de Estrógeno/química , Humanos , Modelos Biológicos , Proteínas Nucleares/farmacología , Co-Represor 1 de Receptor Nuclear , Proteínas Represoras/farmacología , Tamoxifeno/farmacología , Activación Transcripcional , Factor Trefoil-1 , Proteínas Supresoras de Tumor/farmacología , Factores de Transcripción p300-CBP/farmacología
12.
Am J Physiol Endocrinol Metab ; 308(3): E185-91, 2015 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-25406260

RESUMEN

This study was conducted to investigate whether a high-fat/high-carbohydrate (HFHC) meal induces an increase in plasma concentrations of glucagon, dipeptidyl peptidase-IV (DPP-IV), and CD26 expression in mononuclear cells (MNC) while reducing insulin, C-peptide, proinsulin, GIP, and GLP-1 concentrations. Ten healthy normal subjects were given either a 910-calorie HFHC meal or an American Heart Association (AHA) meal rich in fruit and fiber during the first visit and the other meal during the second visit in crossover design. Blood samples were collected at baseline and at 15, 30, 45, 60, 75, 90, 120, 180, and 300 min following the meal. There was a significantly greater increase in glucose concentrations and lower increase in postprandial insulin, C-peptide, and proinsulin concentrations and lower insulin/glucose ratios following the HFHC meal. HFHC meal intake induced marked increases in plasma glucagon and DPP-IV concentrations and an increase in CD26 mRNA expression in MNC compared with the AHA meal. In addition, the HFHC meal induced a reduction in GIP and peak GLP-1 secretion compared with the AHA meal. This was associated with a significantly greater increase in oxidative stress and proinflammatory mediators including, ROS generation, TNFα, and IL-1ß mRNA expression and plasma concentrations of TBARS, FFA, and LPS. We conclude that the proinflammatory HFHC meals result in lower insulin, C-peptide, proinsulin, and GIP secretion in association with higher plasma glucagon and DPP-IV concentrations and CD26 expression in MNC compared with the AHA meal.


Asunto(s)
Dieta Alta en Grasa , Fibras de la Dieta/administración & dosificación , Frutas , Glucagón/sangre , Incretinas/sangre , Insulina/metabolismo , Adulto , Grasas de la Dieta/administración & dosificación , Regulación hacia Abajo/efectos de los fármacos , Femenino , Humanos , Insulina/sangre , Secreción de Insulina , Masculino , Comidas , Persona de Mediana Edad , Regulación hacia Arriba/efectos de los fármacos , Adulto Joven
13.
Subst Use Misuse ; 50(14): 1765-77, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26642782

RESUMEN

BACKGROUND: The correlates of alcohol misuse among female Veterans are not well understood. The present study explored associations among alcohol misuse, demographic/military-related characteristics, interpersonal violence exposure, and posttraumatic stress disorder (PTSD) and depression symptom severity. METHOD: Participants were 369 female Veteran patients of the VA New England Healthcare System. Participants completed a paper-and-pencil mail survey that included validated assessments of alcohol misuse, interpersonal violence, and psychological distress. RESULTS: Younger age, adulthood physical abuse, military sexual trauma, past-year psychological aggression by an intimate partner, and PTSD and depression symptom severity showed significant univariate associations with alcohol misuse (as indicated by unsafe drinking levels, presence or incipience of an alcohol use disorder, intrapersonal alcohol-related concerns, and/or interpersonal alcohol-related concerns). A couple of these associations remained significant when examined in logistic regression models. CONCLUSIONS: Findings suggest that female Veterans who are at risk for alcohol use disorders and/or are experiencing alcohol-related problems may benefit from screening and intervention efforts that take into account interpersonal violence exposures and mental health symptoms on a case-by-case basis. Results also suggest the importance of future research examining correlates and risk factors for substance misuse among female Veterans.


Asunto(s)
Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/psicología , Intoxicación Alcohólica/epidemiología , Intoxicación Alcohólica/psicología , Veteranos/psicología , Adulto , Distribución por Edad , Depresión/epidemiología , Depresión/psicología , Femenino , Encuestas Epidemiológicas , Humanos , Relaciones Interpersonales , Modelos Logísticos , Salud Mental , Persona de Mediana Edad , New England/epidemiología , Escalas de Valoración Psiquiátrica , Factores de Riesgo , Delitos Sexuales/psicología , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/psicología , Estados Unidos , United States Department of Veterans Affairs , Violencia/psicología
14.
Int J Radiat Oncol Biol Phys ; 118(5): 1472-1480, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37981040

RESUMEN

PURPOSE: Bladder cancer is predominantly a disease of older individuals. Concurrent chemotherapy and radiation is a bladder-sparing strategy for management of muscle-invasive bladder cancer; however, many patients are not candidates for chemotherapy due to comorbidities or impaired performance status. We conducted a study in a chemotherapy-ineligible patient population with the objectives of evaluating the safety, efficacy, and quality-of-life effect of the combination of nivolumab and radiation therapy in patients with localized/locally advanced urothelial cancer. METHODS AND MATERIALS: Eligible patients had muscle-invasive bladder cancer and were not candidates for standard chemoradiation strategy due to at least one of the following: performance status of 2, creatinine clearance ≤60 mL/min, cardiac disease, neuropathy, and intolerance to previous treatment. Creatinine clearance ≥40 mL/min, normal marrow, and liver function were required. The primary endpoint was progression-free survival at 12 months. Nivolumab was started within 3 days of radiation therapy and administered at a dose of 240 mg intravenously every 2 weeks for a maximum of 6 months. Radiation therapy was per standard of care for bladder cancer. Imaging and cystoscopy and biopsy evaluation were required at months 3, 6, and 12 and then annually until progression. RESULTS: Twenty patients were enrolled, with a median age of 78.5 years (range, 58-95 years); 80% of patients were >70 years of age, and 8 (40%) were >80 years of age. Median creatinine clearance was 52 mL/min. Nine patients (48%) were progression free at 12 months. Median progression-free survival was 11.4 months (90% CI, 7.5-23.7 months), and median overall survival was 15.6 months (90% CI, 9.1-26.1 months). CONCLUSIONS: Concurrent nivolumab and radiation therapy is tolerable but demonstrated limited efficacy in an older population with multiple comorbidities. Immune correlates demonstrated that patients with baseline programmed cell death ligand 1 combined prognostic score ≥5% had numerically longer progression-free survival.


Asunto(s)
Nivolumab , Neoplasias de la Vejiga Urinaria , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Niño , Nivolumab/uso terapéutico , Nivolumab/efectos adversos , Creatinina/uso terapéutico , Neoplasias de la Vejiga Urinaria/radioterapia , Supervivencia sin Progresión , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Músculos/patología
15.
Contemp Clin Trials ; 140: 107492, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38484793

RESUMEN

BACKGROUND: The Safety Planning Intervention with follow-up services (SPI+) is a promising suicide prevention intervention, yet many Emergency Departments (EDs) lack the resources for adequate implementation. Comprehensive strategies addressing structural and organizational barriers are needed to optimize SPI+ implementation and scale-up. This protocol describes a test of one strategy in which ED staff connect at-risk patients to expert clinicians from a Suicide Prevention Consultation Center (SPCC) via telehealth. METHOD: This stepped wedge, cluster-randomized trial compares the effectiveness, implementation, cost, and cost offsets of SPI+ delivered by SPCC clinicians versus ED-based clinicians (enhanced usual care; EUC). Eight EDs will start with EUC and cross over to the SPCC phase. Blocks of two EDs will be randomly assigned to start dates 3 months apart. Approximately 13,320 adults discharged following a suicide-related ED visit will be included; EUC and SPCC samples will comprise patients from before and after SPCC crossover, respectively. Effectiveness data sources are electronic health records, administrative claims, and the National Death Index. Primary effectiveness outcomes are presence of suicidal behavior and number/type of mental healthcare visits and secondary outcomes include number/type of suicide-related acute services 6-months post-discharge. We will use the same data sources to assess cost offsets to gauge SPCC scalability and sustainability. We will examine preliminary implementation outcomes (reach, adoption, fidelity, acceptability, and feasibility) through patient, clinician, and health-system leader interviews and surveys. CONCLUSION: If the SPCC demonstrates clinical effectiveness and health system cost reduction, it may be a scalable model for evidence-based suicide prevention in the ED.


Asunto(s)
Servicio de Urgencia en Hospital , Prevención del Suicidio , Telemedicina , Adulto , Femenino , Humanos , Masculino , Servicio de Urgencia en Hospital/organización & administración , Proyectos de Investigación , Telemedicina/organización & administración , Ensayos Clínicos Controlados Aleatorios como Asunto
16.
Am J Physiol Endocrinol Metab ; 304(8): E810-8, 2013 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-23403945

RESUMEN

The purpose of this study was to determine whether an insulin infusion exerts an anti-inflammatory effect and whether the infusion of small amounts of glucose results in oxidative and inflammatory stress in patients with type 1 diabetes. Ten patients with type 1 diabetes were infused with either 2 U/h of insulin with 100 ml 5% dextrose/h to or just dextrose (100 ml/h) or physiological saline (100 ml/h) for 4 h after an overnight fast on three separate days. Blood samples were collected at 0, 2, 4, and 6 h. Insulin with glucose infusion led to the maintenance of euglycemia and a significant suppression of reactive oxygen species (ROS) generation, p47(phox) expression, Toll-like receptor (TLR)-4, TLR-2, TLR-1, CD14, high-mobility group-B1 (HMGB1), p38 mitogen-activated protein (MAP) kinase, c-Jun NH2-terminal kinase (JNK)-1, and platelet/endothelial cell adhesion molecule expression and a fall in serum concentrations of C-reactive protein, HMGB1, and rapid upon activation T cell expressed and secreted. Glucose infusion led to an increase in plasma glucose concentration from 115 (fasting) to 215 (at 4 and 6 h) mg/dl and to an increase in ROS generation, the expression of TLR-4, TLR-2, TLR-1, HMGB1, p38 MAP kinase, and JNK-1, and plasma concentrations of HMGB1. While insulin reduces indexes of oxidative and inflammatory stress in patients with type 1 diabetes, even small amounts of glucose (20 g over 4 h) induce oxidative and inflammatory stress. These effects are reflected in TLR, p38 MAP kinase, and HMGB1 expression. The induction of significant oxidative and inflammatory stress by small amounts of glucose in patients with type 1 diabetes may have important pathophysiological and therapeutic implications.


Asunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Glucosa/administración & dosificación , Proteína HMGB1/metabolismo , Inflamación/tratamiento farmacológico , Insulina/administración & dosificación , Receptores Toll-Like/metabolismo , Adulto , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Estudios Cruzados , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/inmunología , Ácidos Grasos no Esterificados/sangre , Femenino , Expresión Génica/efectos de los fármacos , Expresión Génica/inmunología , Proteína HMGB1/genética , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/sangre , Inflamación/sangre , Inflamación/inmunología , Infusiones Intravenosas , Insulina/sangre , Proteínas Quinasas JNK Activadas por Mitógenos/genética , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Receptores de Lipopolisacáridos/genética , Receptores de Lipopolisacáridos/metabolismo , Masculino , Persona de Mediana Edad , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/inmunología , Receptor Toll-Like 1/genética , Receptor Toll-Like 1/metabolismo , Receptor Toll-Like 2/genética , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Receptores Toll-Like/genética , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
17.
Curr Cardiol Rep ; 15(4): 351, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23420447

RESUMEN

Hybrid coronary revascularization combines the benefits of both percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in the treatment of multivessel coronary artery disease (CAD) by combining the benefits of the LIMA-to-LAD graft and drug eluting stent (DES) to non-LAD regions. Through this approach, a patient receives the long-term benefit of the LIMA graft and avoids the morbidity of a full sternotomy and saphenous vein grafts. Available data related to outcomes following hybrid revascularization is limited to small studies. In this review we seek to provide an overview of hybrid revascularization in the era of modern drug eluting stent technology, discuss appropriate patient selection, and comment on future trial design. Additionally, we review the recent literature pertaining to the hybrid approach.


Asunto(s)
Puente de Arteria Coronaria/métodos , Enfermedad Coronaria/terapia , Intervención Coronaria Percutánea/métodos , Stents Liberadores de Fármacos , Humanos , Selección de Paciente , Intervención Coronaria Percutánea/instrumentación
18.
BMJ Open ; 13(12): e074116, 2023 12 12.
Artículo en Inglés | MEDLINE | ID: mdl-38086585

RESUMEN

INTRODUCTION: Brief interventions that reduce suicide risk following youth's experience with acute care due to suicidality are needed. METHODS AND ANALYSIS: The study will use a three-arm randomised controlled trial designed to test the effectiveness of the Safety Planning Intervention with structured follow-up (SPI+) and the Collaborative Assessment and Management of Suicidality (CAMS) compared with enhanced usual care. The primary outcomes measure will be suicidal events, defined as death by suicide, attempted suicide, preparatory acts toward imminent suicidal behaviour or suicidal ideation resulting in a change in emergency evaluation or inpatient admission. Secondary measures will be the number of suicide attempts and severity of suicidal ideation. The experimental interventions, SPI+ and CAMS, consist of up to eight sessions over approximately 8 weeks that are designed to manage (SPI+) or treat (CAMS) patient-identified 'drivers' of suicidal thoughts and behaviours. Mechanisms and moderators of change will be evaluated to understand treatment impacts. ETHICS AND DISSEMINATION: This study has been approved by the Seattle Children's Institutional Review Board and is monitored by external agencies including the University of Washington Institute for Translational Health Sciences, and a National Institute of Mental Health (NIMH)-appointed Data Safety and Monitoring Board. Trial results will help establish evidence towards safe and effective treatment strategies for youth transitioning from acute to outpatient care due to a suicidal crisis. The data will be shared with the NIMH Data Archives and disseminated through publications and conferences. TRIAL REGISTRATION NUMBER: NCT05078970.


Asunto(s)
Ideación Suicida , Intento de Suicidio , Niño , Humanos , Adolescente , Resultado del Tratamiento , Atención Ambulatoria , Hospitalización , Ensayos Clínicos Controlados Aleatorios como Asunto
19.
Am J Physiol Heart Circ Physiol ; 303(4): H486-95, 2012 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-22730385

RESUMEN

The congestive heart failure (CHF) syndrome with soft tissue wasting, or cachexia, has its pathophysiologic origins rooted in neurohormonal activation. Mechanical cardiocirculatory assistance reveals the potential for reverse remodeling and recovery from CHF, which has been attributed to device-based hemodynamic unloading whereas the influence of hormonal withdrawal remains uncertain. This study addresses the signaling pathways induced by chronic aldosteronism in normal heart and skeletal muscle at organ, cellular/subcellular, and molecular levels, together with their potential for recovery (Recov) after its withdrawal. Eight-week-old male Sprague-Dawley rats were examined at 4 wk of aldosterone/salt treatment (ALDOST) and following 4-wk Recov. Compared with untreated, age-/sex-/strain-matched controls, ALDOST was accompanied by 1) a failure to gain weight, reduced muscle mass with atrophy, and a heterogeneity in cardiomyocyte size across the ventricles, including hypertrophy and atrophy at sites of microscopic scarring; 2) increased cardiomyocyte and mitochondrial free Ca(2+), coupled to oxidative stress with increased H(2)O(2) production and 8-isoprostane content, and increased opening potential of the mitochondrial permeability transition pore; 3) differentially expressed genes reflecting proinflammatory myocardial and catabolic muscle phenotypes; and 4) reversal to or toward recovery of these responses with 4-wk Recov. Aldosteronism in rats is accompanied by cachexia and leads to an adverse remodeling of the heart and skeletal muscle at organ, cellular/subcellular, and molecular levels. However, evidence presented herein implicates that these tissues retain their inherent potential for recovery after complete hormone withdrawal.


Asunto(s)
Caquexia/etiología , Insuficiencia Cardíaca/etiología , Hiperaldosteronismo/complicaciones , Músculo Esquelético/patología , Miocardio/patología , Remodelación Ventricular , Animales , Caquexia/genética , Caquexia/metabolismo , Caquexia/patología , Caquexia/fisiopatología , Calcio/metabolismo , Cardiomegalia/etiología , Cardiomegalia/patología , Cardiomegalia/fisiopatología , Dinoprost/análogos & derivados , Dinoprost/metabolismo , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/patología , Insuficiencia Cardíaca/fisiopatología , Peróxido de Hidrógeno/metabolismo , Hiperaldosteronismo/genética , Hiperaldosteronismo/metabolismo , Masculino , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/patología , Proteínas de Transporte de Membrana Mitocondrial/metabolismo , Poro de Transición de la Permeabilidad Mitocondrial , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatología , Atrofia Muscular/etiología , Atrofia Muscular/patología , Atrofia Muscular/fisiopatología , Miocardio/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Necrosis , Ratas , Ratas Sprague-Dawley , Recuperación de la Función , Factores de Tiempo
20.
Psychiatr Serv ; 73(8): 910-917, 2022 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-34911351

RESUMEN

Over the past decade, police involvement in behavioral health crisis response has generated concern and controversy. Despite the salience and timeliness of this topic, the literature on service user experiences of interactions with officers is small and studies of youths and young adults are nonexistent. The authors aimed to investigate youths' and young adults' experiences of police involvement in involuntary psychiatric hold initiation and transport. In-depth interviews were conducted with 40 participants (ages 16-27) who had experienced an involuntary hold; the 28 participants who reported police involvement are the focus of this analysis. Data were inductively coded, and codes were grouped into larger themes. A majority of participants reported negative experiences; major themes characterizing negative encounters were the framing of distress as criminal or of intervention as disciplinary rather than therapeutic, perceived aggression and callousness from police officers, and poor communication. The authors also characterized the positive experiences of officer involvement reported by a minority of participants and youths' perspectives on the degree of control officers could exert over initiation and transport decisions. Findings help center the voices of youths and young adults with mental health challenges and raise important questions about contemporary policies regarding police involvement in crisis response and, more broadly, about coercive responses to distress or emotional crisis.


Asunto(s)
Coerción , Policia , Adolescente , Adulto , Humanos , Adulto Joven
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