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1.
Community Ment Health J ; 60(3): 562-571, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-37982974

RESUMO

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.


Assuntos
Prevenção do Suicídio , Suicídio , Humanos , Estados Unidos , Prática Clínica Baseada em Evidências , Inquéritos e Questionários , Acessibilidade aos Serviços de Saúde
2.
Diabetes Obes Metab ; 23(7): 1614-1623, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33729664

RESUMO

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.


Assuntos
Diabetes Mellitus Tipo 2 , Compostos Benzidrílicos , Glicemia , Pressão Sanguínea , Diabetes Mellitus Tipo 2/tratamento farmacológico , Método Duplo-Cego , Glucosídeos/uso terapêutico , Humanos , Estudos Prospectivos
3.
Subst Use Misuse ; 56(8): 1095-1107, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33870829

RESUMO

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.


Assuntos
Comportamento Aditivo , Transtornos Relacionados ao Uso de Substâncias , Analgésicos Opioides , Emoções , Humanos , Reforço Psicológico
4.
Diabetes Obes Metab ; 22(10): 1742-1752, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32424935

RESUMO

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.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Adulto , Glicemia , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Método Duplo-Cego , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/uso terapêutico , Liraglutida/uso terapêutico , Obesidade/complicações , Sobrepeso/complicações , Sobrepeso/tratamento farmacológico , Resultado do Tratamento , Redução de Peso
5.
Diabetes Obes Metab ; 20(8): 2029-2033, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29652095

RESUMO

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.


Assuntos
Cirurgia Bariátrica/efeitos adversos , Endotelina-1/sangue , Insuficiência Cardíaca/prevenção & controle , Hipertensão/prevenção & controle , Neprilisina/sangue , Obesidade Mórbida/cirurgia , Sistema Renina-Angiotensina , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/prevenção & controle , Cardiomiopatias Diabéticas/epidemiologia , Cardiomiopatias Diabéticas/prevenção & controle , Feminino , Hemoglobinas Glicadas/análise , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologia , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Hipertensão/etiologia , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Obesidade Mórbida/metabolismo , Obesidade Mórbida/fisiopatologia , Período Pós-Operatório , Estudos Prospectivos , Risco , Redução de Peso
6.
Cogn Behav Pract ; 25(4): 460-472, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31787833

RESUMO

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.
Artigo em Inglês | MEDLINE | ID: mdl-27891769

RESUMO

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.


Assuntos
Anti-Hipertensivos/uso terapêutico , Fator Natriurético Atrial/agonistas , Regulação da Expressão Gênica/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/agonistas , Leucócitos Mononucleares/efeitos dos fármacos , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas Oncogênicas/antagonistas & inibidores , Peptídeos/uso terapêutico , Peçonhas/uso terapêutico , Adenilil Ciclases/química , Adenilil Ciclases/genética , Adenilil Ciclases/metabolismo , Angiotensinogênio/antagonistas & inibidores , Angiotensinogênio/sangue , Fármacos Antiobesidade/uso terapêutico , Fator Natriurético Atrial/sangue , Pressão Sanguínea/efeitos dos fármacos , AMP Cíclico/agonistas , AMP Cíclico/sangue , GMP Cíclico/agonistas , GMP Cíclico/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/metabolismo , Exenatida , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Obesidade/sangue , Obesidade/tratamento farmacológico , Obesidade/imunologia , Obesidade/metabolismo , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Reprodutibilidade dos Testes , Método Simples-Cego , Fator de Crescimento Transformador beta/antagonistas & inibidores , Fator de Crescimento Transformador beta/sangue
8.
Diabetes Obes Metab ; 19(9): 1306-1311, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28304146

RESUMO

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.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Glucagon/antagonistas & inibidores , Hipoglicemiantes/uso terapêutico , Corpos Cetônicos/antagonistas & inibidores , Lipólise/efeitos dos fármacos , Liraglutida/uso terapêutico , Adulto , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/metabolismo , Método Duplo-Cego , Resistência a Medicamentos , Quimioterapia Combinada , Ácidos Graxos não Esterificados/antagonistas & inibidores , Ácidos Graxos não Esterificados/sangue , Feminino , Grelina/antagonistas & inibidores , Grelina/sangue , Glucagon/sangue , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Injeções Subcutâneas , Insulina/administração & dosagem , Insulina/uso terapêutico , Sistemas de Infusão de Insulina , Corpos Cetônicos/biossíntese , Corpos Cetônicos/sangue , Liraglutida/administração & dosagem , Masculino , Pessoa de Meia-Idade
9.
J Appl Meas ; 18(3): 247-267, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29579738

RESUMO

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.


Assuntos
Avaliação Educacional/métodos , Avaliação Educacional/normas , Modelos Estatísticos , Psicometria/métodos , Psicometria/normas , Humanos , Matemática , Folhetos
10.
Clin Endocrinol (Oxf) ; 85(5): 772-780, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27292585

RESUMO

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.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Ferritinas/efeitos dos fármacos , Hepcidinas/efeitos dos fármacos , Hipogonadismo/tratamento farmacológico , Ferro/metabolismo , Testosterona/farmacologia , Adulto , Idoso , Proteínas de Transporte de Cátions/biossíntese , Proteínas de Transporte de Cátions/sangue , Diabetes Mellitus Tipo 2/sangue , Método Duplo-Cego , Eritropoetina/sangue , Ferritinas/sangue , Hematócrito , Hepcidinas/sangue , Humanos , Hipogonadismo/sangue , Ferro/sangue , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Receptores da Transferrina/biossíntese , Receptores da Transferrina/sangue
11.
Nat Rev Cancer ; 7(9): 713-22, 2007 09.
Artigo em Inglês | MEDLINE | ID: mdl-17721435

RESUMO

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.


Assuntos
Cromatina/metabolismo , Receptor alfa de Estrogênio/fisiologia , Transcrição Gênica , Sequência de Aminoácidos , Proteínas de Transporte/farmacologia , Imunoprecipitação da Cromatina , Corticosterona , Receptor alfa de Estrogênio/química , Humanos , Modelos Biológicos , Proteínas Nucleares/farmacologia , Correpressor 1 de Receptor Nuclear , Proteínas Repressoras/farmacologia , Tamoxifeno/farmacologia , Ativação Transcricional , Fator Trefoil-1 , Proteínas Supressoras de Tumor/farmacologia , Fatores de Transcrição de p300-CBP/farmacologia
12.
Am J Physiol Endocrinol Metab ; 308(3): E185-91, 2015 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-25406260

RESUMO

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.


Assuntos
Dieta Hiperlipídica , Fibras na Dieta/administração & dosagem , Frutas , Glucagon/sangue , Incretinas/sangue , Insulina/metabolismo , Adulto , Gorduras na Dieta/administração & dosagem , Regulação para Baixo/efeitos dos fármacos , Feminino , Humanos , Insulina/sangue , Secreção de Insulina , Masculino , Refeições , Pessoa de Meia-Idade , Regulação para Cima/efeitos dos fármacos , Adulto Jovem
13.
Subst Use Misuse ; 50(14): 1765-77, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26642782

RESUMO

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.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/psicologia , Intoxicação Alcoólica/epidemiologia , Intoxicação Alcoólica/psicologia , Veteranos/psicologia , Adulto , Distribuição por Idade , Depressão/epidemiologia , Depressão/psicologia , Feminino , Inquéritos Epidemiológicos , Humanos , Relações Interpessoais , Modelos Logísticos , Saúde Mental , Pessoa de Meia-Idade , New England/epidemiologia , Escalas de Graduação Psiquiátrica , Fatores de Risco , Delitos Sexuais/psicologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Estados Unidos , United States Department of Veterans Affairs , Violência/psicologia
14.
Int J Radiat Oncol Biol Phys ; 118(5): 1472-1480, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37981040

RESUMO

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.


Assuntos
Nivolumabe , Neoplasias da Bexiga Urinária , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Nivolumabe/uso terapêutico , Nivolumabe/efeitos adversos , Creatinina/uso terapêutico , Neoplasias da Bexiga Urinária/radioterapia , Intervalo Livre de Progressão , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Músculos/patologia
15.
Contemp Clin Trials ; 140: 107492, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38484793

RESUMO

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.


Assuntos
Serviço Hospitalar de Emergência , Prevenção do Suicídio , Telemedicina , Adulto , Feminino , Humanos , Masculino , Serviço Hospitalar de Emergência/organização & administração , Projetos de Pesquisa , Telemedicina/organização & administração , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Am J Physiol Endocrinol Metab ; 304(8): E810-8, 2013 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-23403945

RESUMO

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.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Glucose/administração & dosagem , Proteína HMGB1/metabolismo , Inflamação/tratamento farmacológico , Insulina/administração & dosagem , Receptores Toll-Like/metabolismo , Adulto , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Estudos Cross-Over , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/imunologia , Ácidos Graxos não Esterificados/sangue , Feminino , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/imunologia , Proteína HMGB1/genética , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/sangue , Inflamação/sangue , Inflamação/imunologia , Infusões Intravenosas , Insulina/sangue , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Receptores de Lipopolissacarídeos/genética , Receptores de Lipopolissacarídeos/metabolismo , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Receptor 1 Toll-Like/genética , Receptor 1 Toll-Like/metabolismo , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Receptores Toll-Like/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
17.
Curr Cardiol Rep ; 15(4): 351, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23420447

RESUMO

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.


Assuntos
Ponte de Artéria Coronária/métodos , Doença das Coronárias/terapia , Intervenção Coronária Percutânea/métodos , Stents Farmacológicos , Humanos , Seleção de Pacientes , Intervenção Coronária Percutânea/instrumentação
18.
BMJ Open ; 13(12): e074116, 2023 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-38086585

RESUMO

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.


Assuntos
Ideação Suicida , Tentativa de Suicídio , Criança , Humanos , Adolescente , Resultado do Tratamento , Assistência Ambulatorial , Hospitalização , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Am J Physiol Heart Circ Physiol ; 303(4): H486-95, 2012 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-22730385

RESUMO

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.


Assuntos
Caquexia/etiologia , Insuficiência Cardíaca/etiologia , Hiperaldosteronismo/complicações , Músculo Esquelético/patologia , Miocárdio/patologia , Remodelação Ventricular , Animais , Caquexia/genética , Caquexia/metabolismo , Caquexia/patologia , Caquexia/fisiopatologia , Cálcio/metabolismo , Cardiomegalia/etiologia , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Dinoprosta/análogos & derivados , Dinoprosta/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Peróxido de Hidrogênio/metabolismo , Hiperaldosteronismo/genética , Hiperaldosteronismo/metabolismo , Masculino , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/patologia , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Poro de Transição de Permeabilidade Mitocondrial , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Atrofia Muscular/etiologia , Atrofia Muscular/patologia , Atrofia Muscular/fisiopatologia , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Necrose , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Fatores de Tempo
20.
Psychiatr Serv ; 73(8): 910-917, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34911351

RESUMO

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.


Assuntos
Coerção , Polícia , Adolescente , Adulto , Humanos , Adulto Jovem
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