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1.
JMIR Form Res ; 8: e45659, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38289663

RESUMO

BACKGROUND: Diabetes distress among adolescents with type 1 diabetes has been associated with suboptimal diabetes outcomes, including lower quality of life, increased diabetes self-management challenges, and suboptimal glycemic outcomes. OBJECTIVE: This study examined the feasibility and acceptability of a scalable self-led mindfulness-based intervention to reduce diabetes distress in adolescents with type 1 diabetes. METHODS: Adolescents (N=25) aged between 14 and 18 years diagnosed with type 1 diabetes completed a baseline assessment. Participants were randomized to receive a 10-week self-guided mindfulness-based stress reduction workbook program (e-book or paper option) immediately (n=15) or after a 10-week wait (n=10). During the intervention period, participants completed weekly assignments and feedback surveys. At 10 weeks and 20 weeks, follow-up assessments were completed. RESULTS: Findings indicated that participants did not find the original intervention feasible or acceptable. Adolescents reported barriers to completing the weekly material, such as that they forgot or that the material was not sufficiently related to their diabetes management. Adolescents also reported that a digital format rather than a workbook or e-book may be more acceptable. Results from weekly surveys provided the foundation for recommendations for future iterations of the mindfulness-based intervention for adolescents with type 1 diabetes. CONCLUSIONS: Participant feedback informed recommendations for self-led mindfulness programs for youth with type 1 diabetes. Adolescents indicated that a shorter, digital mindfulness-based intervention focused on diabetes-specific behaviors may be more helpful. TRIAL REGISTRATION: ClinicalTrials.gov NCT05115175; https://clinicaltrials.gov/study/NCT05115175.

2.
Circ Heart Fail ; 16(11): e010633, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37869881

RESUMO

BACKGROUND: Heart failure with preserved ejection fraction is associated with significant functional limitations, yet treatments for improving exercise performance have been elusive. We sought to explore the association between prespecified patient characteristics and changes in 6-minute walk distance that constitute a clinically significant response to dapagliflozin. METHODS: We performed a responder analysis to understand patient characteristics associated with clinically meaningful improvement in 6-minute walk test (6MWT) distance ≥15 m among patients randomized to 12 weeks of dapagliflozin versus placebo in the double-blind PRESERVED-HF trial (Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients With Preserved Ejection Fraction Heart Failure). RESULTS: A total of 289 randomized patients had 6MWT distance completed at baseline and 12 weeks. Patients randomized to dapagliflozin improved walking distance by ≥15 m more frequently than those on placebo (n=64, 44% versus n=48, 34%). After adjusting for baseline covariates, patients randomized to dapagliflozin were more likely to experience a clinically meaningful improvement in 6MWT distance compared with those that received placebo (adjusted odds ratio, 1.66 [95% CI, 1.00-2.75]; P=0.05). Dapagliflozin-treated patients were also less likely to have a ≥15 m reduction in 6MWT distance compared with placebo-treated patients (adjusted odds ratio, 0.56 [95% CI, 0.33-0.94]; P=0.03). These results were consistent across all prespecified subgroups (all P values for interaction were not significant). CONCLUSIONS: Compared with those on placebo, patients with heart failure with preserved ejection fraction randomized to dapagliflozin were more likely to experience a clinically meaningful improvement and less likely to experience a deterioration in physical function over 12 weeks as measured by 6MWT distance. Beneficial response to dapagliflozin was consistent across prespecified subgroups. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03030235.


Assuntos
Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Volume Sistólico/fisiologia , Compostos Benzidrílicos/efeitos adversos , Caminhada , Função Ventricular Esquerda
4.
JAMA Cardiol ; 8(5): 419-428, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36870047

RESUMO

Importance: Adding a sodium-glucose cotransporter-2 inhibitor (SGLT2-I) to standard-of-care treatment in patients with heart failure with preserved ejection fraction (HFpEF) reduces the risk of a composite outcome of worsening heart failure or cardiovascular mortality, but the cost-effectiveness in US patients with HFpEF is uncertain. Objective: To evaluate the lifetime cost-effectiveness of standard therapy plus an SGLT2-I compared with standard therapy in individuals with HFpEF. Design, Setting, and Participants: In this economic evaluation conducted from September 8, 2021, to December 12, 2022, a state-transition Markov model simulated monthly health outcomes and direct medical costs. Input parameters including hospitalization rates, mortality rates, costs, and utilities were extracted from HFpEF trials, published literature, and publicly available data sets. The base-case annual cost of SGLT2-I was $4506. A simulated cohort with similar characteristics as participants of the Empagliflozin in Heart Failure With a Preserved Ejection Fraction (EMPEROR-Preserved) and Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction (DELIVER) trials was used. Exposures: Standard of care plus SGLT2-I vs standard of care. Main Outcomes and Measures: The model simulated hospitalizations, urgent care visits, and cardiovascular and noncardiovascular death. Future medical costs and benefits were discounted by 3% per year. Main outcomes were quality-adjusted life-years (QALYs), direct medical costs (2022 US dollars), and incremental cost-effectiveness ratio (ICER) of SGLT2-I therapy from a US health care sector perspective. The ICER of SGLT2-I therapy was evaluated according to the American College of Cardiology/American Heart Association value framework (high value: <$50 000; intermediate value: $50 000 to <$150 000; and low value: ≥$150 000). Results: The simulated cohort had a mean (SD) age of 71.7 (9.5) years and 6828 of 12 251 participants (55.7%) were male. Standard of care plus SGLT2-I increased quality-adjusted survival by 0.19 QALYs at an increased cost of $26 300 compared with standard of care. The resulting ICER was $141 200 per QALY gained, with 59.1% of 1000 probabilistic iterations indicating intermediate value and 40.9% indicating low value. The ICER was most sensitive to SGLT2-I costs and effect of SGLT2-I therapy on cardiovascular death (eg, increasing to $373 400 per QALY gained if SGLT2-I therapy was assumed to have no effect on mortality). Conclusions and Relevance: Results of this economic evaluation suggest that at 2022 drug prices, adding an SGLT2-I to standard of care was of intermediate or low economic value compared with standard of care in US adults with HFpEF. Efforts to expand access to SGLT2-I for individuals with HFpEF should be coupled with efforts to lower the cost of SGLT2-I therapy.


Assuntos
Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Idoso , Feminino , Humanos , Masculino , Análise Custo-Benefício , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Volume Sistólico , Estados Unidos
5.
Hypertension ; 80(6): 1199-1208, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36883454

RESUMO

BACKGROUND: Team-based care (TBC), a team of ≥2 healthcare professionals working collaboratively toward a shared clinical goal, is a recommended strategy to manage blood pressure (BP). However, the most effective and cost-effective TBC strategy is unknown. METHODS: A meta-analysis of clinical trials in US adults (aged ≥20 years) with uncontrolled hypertension (≥140/90 mm Hg) was performed to estimate the systolic BP reduction for TBC strategies versus usual care at 12 months. TBC strategies were stratified by the inclusion of a nonphysician team member who could titrate antihypertensive medications. The validated BP Control Model-Cardiovascular Disease Policy Model was used to project the expected BP reductions out to 10 years and simulate cardiovascular disease events, direct healthcare costs, quality-adjusted life years, and cost-effectiveness of TBC with physician and nonphysician titration. RESULTS: Among 19 studies comprising 5993 participants, the 12-month systolic BP change versus usual care was -5.0 (95% CI, -7.9 to -2.2) mm Hg for TBC with physician titration and -10.5 (-16.2 to -4.8) mm Hg for TBC with nonphysician titration. Relative to usual care at 10 years, TBC with nonphysician titration was estimated to cost $95 (95% uncertainty interval, -$563 to $664) more per patient and gain 0.022 (0.003-0.042) quality-adjusted life years, costing $4400/quality-adjusted life year gained. TBC with physician titration was estimated to cost more and gain fewer quality-adjusted life years than TBC with nonphysician titration. CONCLUSIONS: TBC with nonphysician titration yields superior hypertension outcomes compared with other strategies and is a cost-effective way to reduce hypertension-related morbidity and mortality in the United States.


Assuntos
Doenças Cardiovasculares , Hipertensão , Hipotensão , Adulto , Humanos , Análise Custo-Benefício , Doenças Cardiovasculares/tratamento farmacológico , Hipertensão/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/fisiologia , Hipotensão/tratamento farmacológico
6.
J Am Coll Cardiol ; 79(16): 1623-1635, 2022 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-35450580

RESUMO

Despite the high prevalence of nutrition disorders in patients with heart failure (HF), major HF guidelines lack specific nutrition recommendations. Because of the lack of standardized definitions and assessment tools to quantify nutritional status, nutrition disorders are often missed in patients with HF. Additionally, a wide range of dietary interventions and overall dietary patterns have been studied in this population. The resulting evidence of benefit is, however, conflicting, making it challenging to determine which strategies are the most beneficial. In this document, we review the available nutritional status assessment tools for patients with HF. In addition, we appraise the current evidence for dietary interventions in HF, including sodium restriction, obesity, malnutrition, dietary patterns, and specific macronutrient and micronutrient supplementation. Furthermore, we discuss the feasibility and challenges associated with the implementation of multimodal nutrition interventions and delineate potential solutions to facilitate addressing nutrition in patients with HF.


Assuntos
Insuficiência Cardíaca , Desnutrição , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/terapia , Humanos , Desnutrição/prevenção & controle , Avaliação Nutricional , Estado Nutricional , Obesidade/complicações
7.
Am J Hypertens ; 35(6): 533-542, 2022 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-35040867

RESUMO

BACKGROUND: The PRedicting Out-of-OFfice Blood Pressure (PROOF-BP) algorithm accurately predicted out-of-office blood pressure (BP) among adults with suspected high BP in the United Kingdom and Canada. We tested the accuracy of PROOF-BP in a diverse US population and evaluated a newly developed US-specific algorithm (PROOF-BP-US). METHODS: Adults with ≥2 office BP readings and ≥10 awake BP readings on 24-hour ambulatory BP monitoring from 4 pooled US studies were included. We compared mean awake BP with predicted out-of-office BP using PROOF-BP and PROOF-BP-US. Our primary outcomes were hypertensive out-of-office systolic BP (SBP) ≥130 mm Hg and diastolic BP (DBP) ≥80 mm Hg. RESULTS: We included 3,058 adults, mean (SD) age was 52.0 (11.9) years, 38% were male, and 54% were Black. The area under the receiver-operator characteristic (AUROC) curve (95% confidence interval) for hypertensive out-of-office SBP was 0.81 (0.79-0.82) and DBP was 0.76 (0.74-0.78) for PROOF-BP. For PROOF-BP-US, the AUROC curve for hypertensive out-of-office SBP was 0.82 (0.81-0.83) and for DBP was 0.81 (0.79-0.83). The optimal predicted out-of-office BP ranges for out-of-office BP measurement referral were 120-134/75-84 mm Hg for PROOF-BP and 125-134/75-84 mm Hg for PROOF-BP-US. The 2017 American College of Cardiology/American Heart Association BP guideline (referral range 130-159/80-99 mm Hg) would refer 93.1% of adults not taking antihypertensive medications with office BP ≥130/80 mm Hg in the National Health and Nutrition Examination Survey for out-of-office BP measurement, compared with 53.1% using PROOF-BP and 46.8% using PROOF-BP-US. CONCLUSIONS: PROOF-BP and PROOF-BP-US accurately predicted out-of-office hypertension in a diverse sample of US adults.


Assuntos
Hipertensão , Adulto , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/fisiologia , Determinação da Pressão Arterial , Monitorização Ambulatorial da Pressão Arterial , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Estados Unidos/epidemiologia
8.
Health Psychol ; 41(1): 13-22, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34843266

RESUMO

OBJECTIVE: The development of habit (i.e., behavioral automaticity, the extent to which a behavior is performed with decreased thresholds for time, attention [effort], conscious awareness, and goal dependence), for goal-directed health behaviors facilitates health behavior engagement in daily life. However, there is a paucity of research examining automaticity for Type 1 diabetes self-management in adolescence. This study examined if greater perceived automaticity for diabetes self-management was associated with increased daily self-management, decreased daily self-regulation failures in glucose checking, and more optimal daily glycemic levels in adolescents with Type 1 diabetes. METHOD: Adolescents aged 13-17 and diagnosed with Type 1 diabetes (n = 79) completed the Self-Report Behavioral Automaticity Index, a measure of automaticity of diabetes self-management (i.e., automaticity of glucose checking, carbohydrate counting, and insulin dosing), and a measure of perceived self-management at baseline. One to 3 months later, a subsample of teens (n = 42) also completed a daily diary for a 7-day period including perceptions of daily self-management, daily self-regulation failures in glucose checking, and daily glucose levels. RESULTS: Greater overall automaticity of diabetes self-management was associated with greater baseline and daily self-management, fewer daily self-regulation failures in glucose checking, and lower average daily mean blood glucose levels but not more optimal daily variations in blood glucose levels. CONCLUSIONS: Greater automaticity for diabetes self-management may support more optimal daily diabetes self-management in adolescence. Further research is needed to clarify the benefits and mechanisms of automaticity and explore possible interventions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Assuntos
Diabetes Mellitus Tipo 1 , Autogestão , Adolescente , Glicemia , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/terapia , Hábitos , Comportamentos Relacionados com a Saúde , Humanos , Motivação
9.
J Health Psychol ; 27(6): 1354-1364, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34772288

RESUMO

We examined the prospective associations of COVID-19 fears and behavior, and daily physical activity and dysregulated eating. Adolescents (N = 31) aged 11-17 completed selected subscales of the Fear of Illness and Virus Evaluation and completed a 7-day health behavior diary. Greater fear of contamination was associated with lower daily physical activity. In contrast, greater COVID-19 precautionary behavior was associated with greater daily physical activity. COVID-19 fears and precautionary behaviors have differential associations with health promoting behavior engagement. Future studies should explore the mechanisms underlying these links to guide adaptation of health behavior interventions for this unique cohort.


Assuntos
COVID-19 , Adolescente , Saúde do Adolescente , Medo , Comportamentos Relacionados com a Saúde , Humanos , Pandemias
10.
Mol Psychiatry ; 27(2): 1120-1135, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34650207

RESUMO

Despite evidence implicating microglia in the etiology and pathophysiology of major depression, there is paucity of information regarding the contribution of microglia-dependent molecular pathways to antidepressant procedures. In this study, we investigated the role of microglia in a mouse model of depression (chronic unpredictable stress-CUS) and its reversal by electroconvulsive stimulation (ECS), by examining the effects of microglia depletion with the colony stimulating factor-1 antagonist PLX5622. Microglia depletion did not change basal behavioral measures or the responsiveness to CUS, but it completely abrogated the therapeutic effects of ECS on depressive-like behavior and neurogenesis impairment. Treatment with the microglia inhibitor minocycline concurrently with ECS also diminished the antidepressant and pro-neurogenesis effects of ECS. Hippocampal RNA-Seq analysis revealed that ECS significantly increased the expression of genes related to neurogenesis and dopamine signaling, while reducing the expression of several immune checkpoint genes, particularly lymphocyte-activating gene-3 (Lag3), which was the only microglial transcript significantly altered by ECS. None of these molecular changes occurred in microglia-depleted mice. Immunohistochemical analyses showed that ECS reversed the CUS-induced changes in microglial morphology and elevation in microglial LAG3 receptor expression. Consistently, either acute or chronic systemic administration of a LAG3 monoclonal antibody, which readily penetrated into the brain parenchyma and was found to serve as a direct checkpoint blocker in BV2 microglia cultures, rapidly rescued the CUS-induced microglial alterations, depressive-like symptoms, and neurogenesis impairment. These findings suggest that brain microglial LAG3 represents a promising target for novel antidepressant therapeutics.


Assuntos
Transtorno Depressivo Maior , Microglia , Animais , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Hipocampo/metabolismo , Camundongos , Microglia/metabolismo , Neurogênese/fisiologia
11.
Am Heart J Plus ; 13: 100099, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38560071

RESUMO

Background: Abnormal diurnal patterns of blood pressure (BP) on ambulatory BP monitoring (ABPM), defined by reduced BP dipping or elevated nighttime BP, are associated with increased risk for adverse cardiovascular events. Psychological stress is associated with abnormal diurnal patterns of BP. Exposure to an acute stressor (e.g., mental stress task) normally increases urinary sodium excretion. However, some individuals have sodium retention after stress provocation, revealing substantial between-person variability in the degree of stress-induced sodium excretion. Prior research suggests urinary sodium excretion that does not occur during the daytime may shift toward the nighttime, accompanied by an increase in nighttime BP. Associations between psychological stress and the diurnal patterns of sodium excretion and BP are not yet fully understood. Design: The study is conducted in both the laboratory and naturalistic environment with a multi-racial/ethnic sample of 211 healthy adults. In the laboratory, change in urinary sodium excretion in response to mental stress tasks is examined with pre-/post-stress assessments of sodium excretion. Changes in angiotensin-II, catecholamines, BP, heart rate, endothelin-1, and cortisol are also assessed. In the 24-hour naturalistic environment, the diurnal patterns of sodium excretion and systolic BP are assessed as daytime-to-nighttime ratio of sodium excretion and ABPM, respectively. Ecological momentary assessments of perceived stress are also collected. Summary: The SABRE study investigates previously unexplored associations between stress-induced urinary excretion in the laboratory, diurnal patterns of sodium excretion and BP in the naturalistic environment, and ecological stress. It has high potential to advance our understanding of the role of psychological stress in hypertension.

12.
Biol Conserv ; 257: 109038, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34580547

RESUMO

The COVID-19 pandemic has disrupted the timing and substance of conservation research, management, and public engagement in protected areas around the world. This disruption is evident in US national parks, which play a key role in protecting natural and cultural resources and providing outdoor experiences for the public. Collectively, US national parks protect 34 million ha, host more than 300 million visits annually, and serve as one of the world's largest informal education organizations. The pandemic has altered park conditions and operations in a variety of ways. Shifts in operational conditions related to safety issues, reduced staffing, and decreased park revenues have forced managers to make difficult trade-offs among competing priorities. Long-term research and monitoring of the health of ecosystems and wildlife populations have been interrupted. Time-sensitive management practices, such as control of invasive plants and restoration of degraded habitat, have been delayed. And public engagement has largely shifted from in-person experiences to virtual engagement through social media and other online interactions. These changes pose challenges for accomplishing important science, management, and public engagement goals, but they also create opportunities for developing more flexible monitoring programs and inclusive methods of public engagement. The COVID-19 pandemic reinforces the need for strategic science, management planning, flexible operations, and online public engagement to help managers address rapid and unpredictable challenges.

13.
Am J Hypertens ; 34(11): 1181-1188, 2021 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-34270687

RESUMO

BACKGROUND: The 2017 American College of Cardiology/American Heart Association blood pressure (BP) guideline recommends ambulatory BP monitoring to exclude white coat hypertension (WCH) among adults with office systolic BP (SBP)/diastolic BP (DBP) of 130-159/80-99 mm Hg, and masked hypertension (MHT) among adults with office SBP/DBP of 120-129/75-79 mm Hg after a 3-month trial of lifestyle modification. We estimated the proportion of individuals with ideal lifestyle factors among those who meet these office BP criteria. METHODS: We analyzed data from participants not taking antihypertensive medication in the Coronary Artery Risk Development in Young Adults (CARDIA) and Jackson Heart Study (JHS) who met the office BP criteria for screening for WCH (CARDIA n = 490, JHS n = 873) and MHT (CARDIA n = 486, JHS n = 614). We estimated the prevalence of lifestyle factors including ideal body mass index (BMI), physical activity, diet, and alcohol use among participants who met office BP criteria for WCH or MHT screening. RESULTS: Among participants who met office BP criteria for WCH screening, 15.5% in CARDIA and 3.6% in JHS had 3 or more ideal lifestyle factors. Among participants who met office BP criteria for MHT screening, 22.6% in CARDIA and 4.7% in JHS had 3 or more ideal lifestyle factors. Ideal BMI, diet, and physical activity were present in less than half of participants in each sample. CONCLUSIONS: Few participants who met office BP criteria for the screening of WCH or MHT had ideal lifestyle factors.


Assuntos
Hipertensão , Hipertensão Mascarada , Hipertensão do Jaleco Branco , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/fisiologia , Monitorização Ambulatorial da Pressão Arterial , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Estilo de Vida , Hipertensão Mascarada/diagnóstico , Hipertensão do Jaleco Branco/diagnóstico , Adulto Jovem
14.
Circulation ; 143(24): 2384-2394, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33855861

RESUMO

BACKGROUND: In LABBPS (Los Angeles Barbershop Blood Pressure Study), pharmacist-led hypertension care in Los Angeles County Black-owned barbershops significantly improved blood pressure control in non-Hispanic Black men with uncontrolled hypertension at baseline. In this analysis, 10-year health outcomes and health care costs of 1 year of the LABBPS intervention versus control are projected. METHODS: A discrete event simulation of hypertension care processes projected blood pressure, medication-related adverse events, fatal and nonfatal cardiovascular disease events, and noncardiovascular disease death in LABBPS participants. Program costs, total direct health care costs (2019 US dollars), and quality-adjusted life-years (QALYs) were estimated for the LABBPS intervention and control arms from a health care sector perspective over a 10-year horizon. Future costs and QALYs were discounted 3% annually. High and intermediate cost-effectiveness thresholds were defined as <$50 000 and <$150 000 per QALY gained, respectively. RESULTS: At 10 years, the intervention was projected to cost an average of $2356 (95% uncertainty interval, -$264 to $4611) more per participant than the control arm and gain 0.06 (95% uncertainty interval, 0.01-0.10) QALYs. The LABBPS intervention was highly cost-effective, with a mean cost of $42 717 per QALY gained (58% probability of being highly and 96% of being at least intermediately cost-effective). Exclusive use of generic drugs improved the cost-effectiveness to $17 162 per QALY gained. The LABBPS intervention would be only intermediately cost-effective if pharmacists were less likely to intensify antihypertensive medications when systolic blood pressure was ≥150 mm Hg or if pharmacist weekly time driving to barbershops increased. CONCLUSIONS: Hypertension care delivered by clinical pharmacists in Black barbershops is a highly cost-effective way to improve blood pressure control in Black men.


Assuntos
Anti-Hipertensivos/economia , Análise Custo-Benefício , Adulto , Negro ou Afro-Americano , Idoso , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Barbearia , Pressão Sanguínea/efeitos dos fármacos , Esquema de Medicação , Medicamentos Genéricos/economia , Medicamentos Genéricos/uso terapêutico , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Farmacêuticos/psicologia , Anos de Vida Ajustados por Qualidade de Vida
15.
J Virol ; 95(10)2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33658340

RESUMO

HIV-1 infection persists in humans despite expression of antiviral type 1 interferons (IFN). Even exogenous administration of IFNα only marginally reduces HIV-1 abundance, raising the hypothesis that people living with HIV-1 (PLWH) are refractory to type 1 IFN. We demonstrated type 1 IFN refractoriness in CD4+ and CD8+ T cells isolated from HIV-1 infected persons by detecting diminished STAT1 phosphorylation (pSTAT1) and interferon-stimulated gene (ISG) induction upon type 1 IFN stimulation compared to healthy controls. Importantly, HIV-1 infected people who were virologically suppressed with antiretrovirals also showed type 1 IFN refractoriness. We found that USP18 levels were elevated in people with refractory pSTAT1 and ISG induction and confirmed this finding ex vivo in CD4+ T cells from another cohort of HIV-HCV coinfected persons who received exogenous pegylated interferon-α2b in a clinical trial. We used a cell culture model to recapitulate type 1 IFN refractoriness in uninfected CD4+ T cells that were conditioned with media from HIV-1 inoculated PBMCs, inhibiting de novo infection with antiretroviral agents. In this model, RNA interference against USP18 partly restored type 1 IFN responses in CD4+ T cells. We found evidence of type 1 IFN refractoriness in PLWH irrespective of virologic suppression that was associated with upregulated USP18, a process that might be therapeutically targeted to improve endogenous control of infection.ImportancePeople living with HIV-1 (PLWH) have elevated constitutive expression of type 1 interferons (IFN). However, it is unclear whether this impacts downstream innate immune responses. We identified refractory responses to type 1 IFN stimulation in T cells from PLWH, independent of antiretroviral treatment. Type 1 IFN refractoriness was linked to elevated USP18 levels in the same cells. Moreover, we found that USP18 levels predicted the anti-HIV-1 effect of type 1 IFN-based therapy on PLWH. In vitro, we demonstrated that refractory type 1 IFN responses were transferrable to HIV-1 uninfected target CD4+ T cells, and this phenomenon was mediated by type 1 IFN from HIV-1 infected cells. Type 1 IFN responses were partially restored by USP18 knockdown. Our findings illuminate a new mechanism by which HIV-1 contributes to innate immune dysfunction in PLWH, through the continuous production of type 1 IFN that induces a refractory state of responsiveness.

16.
J Card Fail ; 27(4): 435-444, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33238139

RESUMO

BACKGROUND: Independent associations between cardiovascular risk factor exposures during midlife and later life development of heart failure (HF) with preserved ejection fraction (HFpEF) versus reduced EF (HFrEF) have not been previously studied. METHODS: We pooled data from 4 US cohort studies (Atherosclerosis Risk in Communities, Cardiovascular Health, Health , Aging and Body Composition, and Multi-Ethnic Study of Atherosclerosis) and imputed annual risk factor trajectories for body mass index, systolic and diastolic blood pressure, low-density lipoprotein and high-density lipoprotein cholesterol, and glucose starting from age 40 years. Time-weighted average exposures to each risk factor during midlife and later life were calculated and analyzed for associations with the development of HFpEF or HFrEF. RESULTS: A total of 23,861 participants were included (mean age at first in-person visit, 61.8 ±1 0.2 years; 56.6% female). During a median follow-up of 12 years, there were 3666 incident HF events, of which 51% had EF measured, including 934 with HFpEF and 739 with HFrEF. A high midlife systolic blood pressure and low midlife high-density lipoprotein cholesterol were associated with HFrEF, and a high midlife body mass index, systolic blood pressure, pulse pressure, and glucose were associated with HFpEF. After adjusting for later life exposures, only midlife pulse pressure remained independently associated with HFpEF. CONCLUSIONS: Midlife exposure to cardiovascular risk factors are differentially associated with HFrEF and HFpEF later in life. Having a higher pulse pressure during midlife is associated with a greater risk for HFpEF but not HFrEF, independent of later life exposures.


Assuntos
Doenças Cardiovasculares , Insuficiência Cardíaca , Adulto , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Feminino , Fatores de Risco de Doenças Cardíacas , Insuficiência Cardíaca/epidemiologia , Humanos , Masculino , Prognóstico , Fatores de Risco , Volume Sistólico
17.
Hypertension ; 76(6): 1953-1961, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33131312

RESUMO

Almost 1 in 5 US adults with hypertension has apparent treatment resistant hypertension (aTRH). Identifying modifiable risk factors for incident aTRH may guide interventions to reduce the need for additional antihypertensive medication. We evaluated the association between cardiovascular health and incident aTRH among participants with hypertension and controlled blood pressure (BP) at baseline in the Jackson Heart Study (N=800) and the Reasons for Geographic and Racial Differences in Stroke study (N=2316). Body mass index, smoking, physical activity, diet, BP, cholesterol and glucose, categorized as ideal, intermediate, or poor according to the American Heart Association's Life's Simple 7 were assessed at baseline and used to define cardiovascular health. Incident aTRH was defined by uncontrolled BP, systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg, while taking ≥3 classes of antihypertensive medication or controlled BP, systolic BP <130 mm Hg and diastolic BP <80 mm Hg, while taking ≥4 classes of antihypertensive medication at a follow-up visit. Over a median 9 years of follow-up, 605 (19.4%) participants developed aTRH. Incident aTRH developed among 25.8%, 18.2%, and 15.7% of participants with 0 to 1, 2, and 3 to 5 ideal Life's Simple 7 components, respectively. No participants had 6 or 7 ideal Life's Simple 7 components at baseline. The multivariable adjusted hazard ratios (95% CIs) for incident aTRH associated with 2 and 3 to 5 versus 0 to 1 ideal components were 0.75 (0.61-0.92) and 0.67 (0.54-0.82), respectively. These findings suggest optimizing cardiovascular health may reduce the pill burden and high cardiovascular risk associated with aTRH among individuals with hypertension.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Sistema Cardiovascular/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Idoso , American Heart Association , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/fisiopatologia , Resistência a Medicamentos , Exercício Físico/fisiologia , Feminino , Inquéritos Epidemiológicos/métodos , Inquéritos Epidemiológicos/estatística & dados numéricos , Humanos , Hipertensão/fisiopatologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Estados Unidos
18.
Hypertension ; 76(4): 1169-1175, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32903103

RESUMO

The 2017 American College of Cardiology/American Heart Association blood pressure (BP) Hypertension Clinical Practice Guidelines recommends ambulatory BP monitoring to detect masked hypertension. Data on the short-term reproducibility of masked hypertension are scarce. The IDH study (Improving the Detection of Hypertension) enrolled 408 adults not taking antihypertensive medication from 2011 to 2013. Office BP and 24-hour ambulatory BP monitoring were performed on 2 occasions, a median of 29 days apart. After excluding participants with office hypertension (mean systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg), the analytical sample included 254 participants. Using the κ statistic, we evaluated the reproducibility of masked awake hypertension (awake systolic/diastolic BP ≥130/80 mm Hg) defined by the 2017 BP guideline thresholds, as well as masked 24-hour (24-hour systolic/diastolic BP ≥125/75 mm Hg), masked asleep (asleep systolic/diastolic BP ≥110/65 mm Hg), and any masked hypertension (high awake, 24-hour, and asleep BP). The mean (SD) age of participants was 38.0 (12.3) years and 65.7% were female. Based on the first and second ambulatory BP recordings, 24.0% and 26.4% of participants, respectively, had masked awake hypertension. The κ statistic (95% CI) was 0.50 (0.38-0.62) for masked awake, 0.57 (0.46-0.69) for masked 24-hour, 0.57 (0.47-0.68) for masked asleep, and 0.58 (0.47-0.68) for any masked hypertension. Clinicians should consider the moderate short-term reproducibility of masked hypertension when interpreting the results from a single ambulatory BP recording.


Assuntos
Pressão Sanguínea/fisiologia , Hipertensão Mascarada/diagnóstico , Adulto , Monitorização Ambulatorial da Pressão Arterial , Feminino , Humanos , Masculino , Hipertensão Mascarada/fisiopatologia , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
19.
Hypertension ; 76(4): 1090-1096, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32829666

RESUMO

Guidelines recommend using out-of-office blood pressure (BP) measurements to confirm the diagnoses of hypertension and in the titration of antihypertensive medication. The prevalence of out-of-office BP phenotypes for an office systolic/diastolic BP goal <140/90 mm Hg has been reported. However, the prevalence of these phenotypes when targeting an office systolic/diastolic BP goal <120/80 is unknown. The SPRINT (Systolic Blood Pressure Intervention Trial) Ambulatory BP Ancillary study evaluated out-of-office BP using ambulatory BP monitoring in 897 participants 27 months after randomization to intensive versus standard BP targets (office systolic BP <120 versus <140 mm Hg). We used office and daytime BP to assess the proportion of participants with white-coat effect (standard target: office BP ≥140/90 mm Hg and daytime BP <135/85 mm Hg versus intensive target: office BP ≥120/80 mm Hg and daytime BP <120/80 mm Hg) and masked uncontrolled hypertension (standard target: office BP <140/90 mm Hg and daytime BP ≥135/85 mm Hg versus intensive target: office BP <120/80 mm Hg and daytime BP ≥120/80 mm Hg) in each treatment arm. The prevalence of white-coat effect and masked uncontrolled hypertension was 9% and 34%, in both treatment groups. Among participants with uncontrolled office BP, white-coat effect was present in 20% and 23% in the intensive and standard groups, respectively. Among participants with controlled office BP, masked uncontrolled hypertension was present in 62% and 56% in the intensive and standard groups, respectively. In conclusion, a more intensive BP target resulted in a similar proportion of patients with white-coat effect and masked uncontrolled hypertension compared with a standard target.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão Mascarada/tratamento farmacológico , Hipertensão do Jaleco Branco/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/fisiologia , Monitorização Ambulatorial da Pressão Arterial , Feminino , Humanos , Masculino , Hipertensão Mascarada/diagnóstico , Hipertensão Mascarada/fisiopatologia , Pessoa de Meia-Idade , Hipertensão do Jaleco Branco/diagnóstico , Hipertensão do Jaleco Branco/fisiopatologia
20.
Am J Cardiol ; 127: 58-63, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32416964

RESUMO

Salt taste sensitivity can change after heart failure (HF) hospitalization, however the relation between changes in salt taste sensitivity with HF symptoms, biomarkers, and outcomes is unknown. We assessed salt taste sensitivity over 12 weeks following HF hospitalization using a validated, point-of-care salt taste test. Subjects were divided into 2 groups: increase or no increase in salt taste sensitivity. HF biomarkers and outcomes were compared using 2-sample t tests and log-transformed t tests for non-normally distributed parameters. Baseline characteristics generally did not differ for subjects with an increase in salt taste sensitivity over 12 weeks compared with those without an increase in salt taste sensitivity. The total number of 12-week hospital days was 60 versus 121 days, with an average number of hospital days of 5.45 [3.88] versus 11.00 [6.74] (p = 0.03) among those hospitalized in the groups with an increase versus no increase in salt taste sensitivity, respectively. In conclusion, changes in salt taste sensitivity occurred in some but not all subjects in a 12-week period following HF hospitalization. Subjects with increased salt taste sensitivity over this time period were rehospitalized for fewer days. Improved salt taste sensitivity may represent a novel prognostic factor in postdischarge patients with HF.


Assuntos
Insuficiência Cardíaca/diagnóstico , Hospitalização , Cloreto de Sódio na Dieta/farmacologia , Percepção Gustatória/fisiologia , Paladar/fisiologia , Idoso , Feminino , Seguimentos , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Prognóstico , Método Simples-Cego , Paladar/efeitos dos fármacos , Percepção Gustatória/efeitos dos fármacos
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