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AIMS: Traditional atherosclerotic cardiovascular disease (ASCVD) risk factors fail to address the full spectrum of the complex interplay of atherosclerotic and atherothrombotic factors integral to ASCVD events. This study sought to examine the association between atherothrombotic biomarkers and ASCVD events. METHODS AND RESULTS: The association between atherothrombotic biomarkers and 877 ASCVD events with and without adjustment for traditional risk factors was evaluated via Cox proportional hazards models and factor analysis in 5789 Multi-Ethnic Study of Atherosclerosis participants over a median follow-up of 14.7 years. Factor analysis accounted for multidimensional relationship and shared variance among study biomarkers, which identified two new variables: a thrombotic factor (Factor 1), principally defined by shared variance in fibrinogen, plasmin-antiplasmin complex, factor VIII, D-dimer, and lipoprotein(a), and a fibrinolytic factor (Factor 2), principally defined by shared variance of plasminogen and oxidized phospholipids on plasminogen. In a model including both factors, the thrombotic factor was associated with the higher risk of ASCVD events [hazard ratio (HR) 1.57, 95% confidence interval (CI) 1.45, 1.70], while the fibrinolytic factor was associated with the lower risk of ASCVD events (HR 0.76, 95% CI 0.70, 0.82), with estimated ASCVD free survival highest for low atherothrombotic Factor 1 and high atherothrombotic Factor 2. CONCLUSION: Two atherothrombotic factors, one representative of thrombotic propensity and the other representative of fibrinolytic propensity, were significantly and complementarily associated with incident ASCVD events, remained significantly associated with incident ASCVD after controlling for traditional risk factors, and have promise for identifying patients at high ASCVD event risk specifically due to their atherothrombotic profile.
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Aterosclerose , Doenças Cardiovasculares , Aterosclerose/complicações , Doenças Cardiovasculares/etiologia , Etnicidade , Humanos , Lipoproteína(a) , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de RiscoRESUMO
Importance: Discussions about goals of care are important for high-quality palliative care yet are often lacking for hospitalized older patients with serious illness. Objective: To evaluate a communication-priming intervention to promote goals-of-care discussions between clinicians and hospitalized older patients with serious illness. Design, Setting, and Participants: A pragmatic, randomized clinical trial of a clinician-facing communication-priming intervention vs usual care was conducted at 3 US hospitals within 1 health care system, including a university, county, and community hospital. Eligible hospitalized patients were aged 55 years or older with any of the chronic illnesses used by the Dartmouth Atlas project to study end-of-life care or were aged 80 years or older. Patients with documented goals-of-care discussions or a palliative care consultation between hospital admission and eligibility screening were excluded. Randomization occurred between April 2020 and March 2021 and was stratified by study site and history of dementia. Intervention: Physicians and advance practice clinicians who were treating the patients randomized to the intervention received a 1-page, patient-specific intervention (Jumpstart Guide) to prompt and guide goals-of-care discussions. Main Outcomes and Measures: The primary outcome was the proportion of patients with electronic health record-documented goals-of-care discussions within 30 days. There was also an evaluation of whether the effect of the intervention varied by age, sex, history of dementia, minoritized race or ethnicity, or study site. Results: Of 3918 patients screened, 2512 were enrolled (mean age, 71.7 [SD, 10.8] years and 42% were women) and randomized (1255 to the intervention group and 1257 to the usual care group). The patients were American Indian or Alaska Native (1.8%), Asian (12%), Black (13%), Hispanic (6%), Native Hawaiian or Pacific Islander (0.5%), non-Hispanic (93%), and White (70%). The proportion of patients with electronic health record-documented goals-of-care discussions within 30 days was 34.5% (433 of 1255 patients) in the intervention group vs 30.4% (382 of 1257 patients) in the usual care group (hospital- and dementia-adjusted difference, 4.1% [95% CI, 0.4% to 7.8%]). The analyses of the treatment effect modifiers suggested that the intervention had a larger effect size among patients with minoritized race or ethnicity. Among 803 patients with minoritized race or ethnicity, the hospital- and dementia-adjusted proportion with goals-of-care discussions was 10.2% (95% CI, 4.0% to 16.5%) higher in the intervention group than in the usual care group. Among 1641 non-Hispanic White patients, the adjusted proportion with goals-of-care discussions was 1.6% (95% CI, -3.0% to 6.2%) higher in the intervention group than in the usual care group. There was no evidence of differential treatment effects of the intervention on the primary outcome by age, sex, history of dementia, or study site. Conclusions and Relevance: Among hospitalized older adults with serious illness, a pragmatic clinician-facing communication-priming intervention significantly improved documentation of goals-of-care discussions in the electronic health record, with a greater effect size in racially or ethnically minoritized patients. Trial Registration: ClinicalTrials.gov Identifier: NCT04281784.
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Demência , Assistência Terminal , Humanos , Feminino , Idoso , Masculino , Comunicação , Hospitalização , Demência/terapia , Planejamento de Assistência ao PacienteRESUMO
Systolic and diastolic blood pressures provide information about cardiovascular disease (CVD) but are only extremes of the pressure waveform during the cardiac cycle. We developed summaries of the pressure decay, called PTC1 and PTC2, that are related to arterial compliance and to an existing proprietary summary that has been shown to predict CVD. We derived the summaries from a Windkessel model (consisting of a decaying exponential plus a dampened cosine, with an intercept so they are independent of calibration with blood pressure, unlike the proprietary measures), and we estimated them using nonlinear least squares with standard, free software. Among 6,228 adults from the Multi-Ethnic Study of Atherosclerosis, initially free of CVD in 2000-2002, mean PTC2 was 94 (standard deviation, 46) milliseconds. During median 15-year follow-up, there were 911 CVD events (including 609 incidents of coronary heart disease and 270 strokes). One-standard-deviation higher PTC2 was associated with 17% (95% confidence interval: 10, 24) lower CVD risk, after adjustment for traditional risk factors. Results were similar for PTC1. PTC1 and PTC2 are relatively straightforward to compute and add information beyond traditional risk factors for prediction of CVD. Our work enables others to replicate and extend our results with waveforms from any suitable device.
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Aterosclerose/fisiopatologia , Determinação da Pressão Arterial/métodos , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/etiologia , Indicadores Básicos de Saúde , Adulto , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/complicações , Doenças Cardiovasculares/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Medição de Risco/métodos , Fatores de RiscoRESUMO
Importance: Patients with chronic illness frequently use Physician Orders for Life-Sustaining Treatment (POLST) to document treatment limitations. Objectives: To evaluate the association between POLST order for medical interventions and intensive care unit (ICU) admission for patients hospitalized near the end of life. Design, Setting, and Participants: Retrospective cohort study of patients with POLSTs and with chronic illness who died between January 1, 2010, and December 31, 2017, and were hospitalized 6 months or less before death in a 2-hospital academic health care system. Exposures: POLST order for medical interventions ("comfort measures only" vs "limited additional interventions" vs "full treatment"), age, race/ethnicity, education, days from POLST completion to admission, histories of cancer or dementia, and admission for traumatic injury. Main Outcomes and Measures: The primary outcome was the association between POLST order and ICU admission during the last hospitalization of life; the secondary outcome was receipt of a composite of 4 life-sustaining treatments: mechanical ventilation, vasopressors, dialysis, and cardiopulmonary resuscitation. For evaluating factors associated with POLST-discordant care, the outcome was ICU admission contrary to POLST order for medical interventions during the last hospitalization of life. Results: Among 1818 decedents (mean age, 70.8 [SD, 14.7] years; 41% women), 401 (22%) had POLST orders for comfort measures only, 761 (42%) had orders for limited additional interventions, and 656 (36%) had orders for full treatment. ICU admissions occurred in 31% (95% CI, 26%-35%) of patients with comfort-only orders, 46% (95% CI, 42%-49%) with limited-interventions orders, and 62% (95% CI, 58%-66%) with full-treatment orders. One or more life-sustaining treatments were delivered to 14% (95% CI, 11%-17%) of patients with comfort-only orders and to 20% (95% CI, 17%-23%) of patients with limited-interventions orders. Compared with patients with full-treatment POLSTs, those with comfort-only and limited-interventions orders were significantly less likely to receive ICU admission (comfort only: 123/401 [31%] vs 406/656 [62%], aRR, 0.53 [95% CI, 0.45-0.62]; limited interventions: 349/761 [46%] vs 406/656 [62%], aRR, 0.79 [95% CI, 0.71-0.87]). Across patients with comfort-only and limited-interventions POLSTs, 38% (95% CI, 35%-40%) received POLST-discordant care. Patients with cancer were significantly less likely to receive POLST-discordant care than those without cancer (comfort only: 41/181 [23%] vs 80/220 [36%], aRR, 0.60 [95% CI, 0.43-0.85]; limited interventions: 100/321 [31%] vs 215/440 [49%], aRR, 0.63 [95% CI, 0.51-0.78]). Patients with dementia and comfort-only orders were significantly less likely to receive POLST-discordant care than those without dementia (23/111 [21%] vs 98/290 [34%], aRR, 0.44 [95% CI, 0.29-0.67]). Patients admitted for traumatic injury were significantly more likely to receive POLST-discordant care (comfort only: 29/64 [45%] vs 92/337 [27%], aRR, 1.52 [95% CI, 1.08-2.14]; limited interventions: 51/91 [56%] vs 264/670 [39%], aRR, 1.36 [95% CI, 1.09-1.68]). In patients with limited-interventions orders, older age was significantly associated with less POLST-discordant care (aRR, 0.93 per 10 years [95% CI, 0.88-1.00]). Conclusions and Relevance: Among patients with POLSTs and with chronic life-limiting illness who were hospitalized within 6 months of death, treatment-limiting POLSTs were significantly associated with lower rates of ICU admission compared with full-treatment POLSTs. However, 38% of patients with treatment-limiting POLSTs received intensive care that was potentially discordant with their POLST.
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Diretivas Antecipadas , Cuidados Críticos , Cuidados para Prolongar a Vida , Planejamento Antecipado de Cuidados , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doença Crônica/terapia , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Médicos , Ordens quanto à Conduta (Ética Médica) , Estudos Retrospectivos , Assistência TerminalRESUMO
OBJECTIVES: To develop an enhanced understanding of factors that influence providers' views about end-of-life care, we examined the contributions of provider, hospital, and country to variability in agreement with consensus statements about end-of-life care. DESIGN AND SETTING: Data were drawn from a survey of providers' views on principles of end-of-life care obtained during the consensus process for the Worldwide End-of-Life Practice for Patients in ICUs study. SUBJECTS: Participants in Worldwide End-of-Life Practice for Patients in ICUs included physicians, nurses, and other providers. Our sample included 1,068 providers from 178 hospitals and 31 countries. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We examined views on cardiopulmonary resuscitation and withholding/withdrawing life-sustaining treatments, using a three-level linear mixed model of responses from providers within hospitals within countries. Of 1,068 providers from 178 hospitals and 31 countries, 1% strongly disagreed, 7% disagreed, 11% were neutral, 44% agreed, and 36% strongly agreed with declining to offer cardiopulmonary resuscitation when not indicated. Of the total variability in those responses, 98%, 0%, and 2% were explained by differences among providers, hospitals, and countries, respectively. After accounting for provider characteristics and hospital size, the variance partition was similar. Results were similar for withholding/withdrawing life-sustaining treatments. CONCLUSIONS: Variability in agreement with consensus statements about end-of-life care is related primarily to differences among providers. Acknowledging the primary source of variability may facilitate efforts to achieve consensus and improve decision-making for critically ill patients and their family members at the end of life.
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Atitude do Pessoal de Saúde , Consenso , Assistência Terminal , Adulto , Reanimação Cardiopulmonar , Feminino , Hospitais , Humanos , Internacionalidade , Masculino , Pessoa de Meia-Idade , Suspensão de TratamentoRESUMO
Arterial dysfunction has been linked to decline in cardiac function and increased risk of cardiovascular disease events. We calculated the value of arterial function, measured at baseline (2000-2002), in predicting time to first coronary heart disease (CHD) event (median follow-up, 10.2 years) among participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Measures included the following: C1 and C2, derived from diastolic pulse contour analysis from the radial artery blood pressure waveform obtained by tonometry (n = 6,336); carotid distensibility and Young's elastic modulus at the carotid artery, derived from carotid artery ultrasonography (n = 6,531 and 6,528); and aortic distensibility, measured using cardiac magnetic resonance imaging (n = 3,677). After adjustment, the hazard ratio for a CHD event per standard-deviation increment in arterial function was 0.97 (95% confidence interval (CI): 0.86, 1.10) for C1, 0.73 (95% CI: 0.63, 0.86) for C2, 0.98 (95% CI: 0.86, 1.11) for carotid distensibility, 0.99 (95% CI: 0.90, 1.09) for Young's modulus, and 0.90 (95% CI: 0.74, 1.10) for aortic distensibility. We examined the area under the receiver operating characteristic curve for the model with full adjustment plus the addition of each measure individually. C2 provided additional discrimination for the prediction of CHD (area under the curve = 0.736 vs. 0.743; P = 0.04). Lower C2 was associated with a higher risk of future CHD events.
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Doenças da Aorta/diagnóstico por imagem , Pressão Arterial/fisiologia , Artérias Carótidas/diagnóstico por imagem , Doença das Coronárias/epidemiologia , Rigidez Vascular/fisiologia , Idoso , Idoso de 80 Anos ou mais , Glicemia/análise , Índice de Massa Corporal , Proteína C-Reativa/análise , Calcinose/diagnóstico por imagem , Colesterol/sangue , Doença das Coronárias/patologia , Doença das Coronárias/fisiopatologia , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Fatores de Risco , Ultrassonografia , Estados Unidos/epidemiologiaRESUMO
RATIONALE: Lung clearance index (LCI), measured by multiple breath washout (MBW), is a noninvasive measure of ventilation inhomogeneity that holds promise as an objective physiologic endpoint for clinical trials in infants and preschool children with cystic fibrosis (CF). OBJECTIVES: To study the feasibility of using LCI to assess treatment effect outcomes in CF trials of infants and preschoolers. METHODS: The Infant Study of Inhaled Saline trial was a multicenter, randomized, controlled trial of hypertonic (7%) versus isotonic (0.9%) saline inhaled twice daily for 48 weeks in children with CF under 6 years of age. LCI measurements were performed in a single-center pilot substudy at baseline and 48 weeks using a respiratory mass spectrometer and sulfur hexafluoride as the tracer gas. LCI measurements were standardized using published normative data (zLCI) to account for height-related changes in LCI during early childhood. A generalized estimating equation model with an interaction between treatment group and test occasion was used to estimate a treatment effect. MEASUREMENTS AND MAIN RESULTS: A total of 27 participants were randomized; 25 participants, aged (median [range]) 2.6 (0.34-4.95) years, had acceptable baseline and follow-up LCI measures. On average, LCI decreased in the hypertonic saline group (n = 12) by 1.19 z-scores units (95% confidence interval [CI] = -2.46 to 0.06), and remained stable in the isotonic saline group (n = 13) at 0.81 (95% CI = -0.40 to 2.02). A significant treatment effect was observed for zLCI (2.01; 95% CI = 0.26 to 3.76; P = 0.025). CONCLUSIONS: MBW testing is feasible in an interventional study in infants and preschool children with CF. These pilot findings support the development of MBW and LCI as an objective outcome measure in interventional trials in young children with CF, and provide estimates for sample size calculations for future studies.
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Testes Respiratórios/métodos , Fibrose Cística/terapia , Solução Salina Hipertônica/administração & dosagem , Administração por Inalação , Pré-Escolar , Ensaios Clínicos como Assunto , Fibrose Cística/diagnóstico , Estudos de Viabilidade , Feminino , Humanos , Lactente , Masculino , Projetos Piloto , Resultado do TratamentoRESUMO
BACKGROUND: Left ventricular mass (LVM) and hypertrophy (LVH) are important parameters, but their use is surrounded by controversies. We compare LVM by echocardiography and cardiac magnetic resonance (CMR), investigating reproducibility aspects and the effect of echocardiography image quality. We also compare indexing methods within and between imaging modalities for classification of LVH and cardiovascular risk. METHODS: Multi-Ethnic Study of Atherosclerosis enrolled 880 participants in Baltimore city, 146 had echocardiograms and CMR on the same day. LVM was then assessed using standard techniques. Echocardiography image quality was rated (good/limited) according to the parasternal view. LVH was defined after indexing LVM to body surface area, height(1.7) , height(2.7) , or by the predicted LVM from a reference group. Participants were classified for cardiovascular risk according to Framingham score. Pearson's correlation, Bland-Altman plots, percent agreement, and kappa coefficient assessed agreement within and between modalities. RESULTS: Left ventricular mass by echocardiography (140 ± 40 g) and by CMR were correlated (r = 0.8, P < 0.001) regardless of the echocardiography image quality. The reproducibility profile had strong correlations and agreement for both modalities. Image quality groups had similar characteristics; those with good images compared to CMR slightly superiorly. The prevalence of LVH tended to be higher with higher cardiovascular risk. The agreement for LVH between imaging modalities ranged from 77% to 98% and the kappa coefficient from 0.10 to 0.76. CONCLUSIONS: Echocardiography has a reliable performance for LVM assessment and classification of LVH, with limited influence of image quality. Echocardiography and CMR differ in the assessment of LVH, and additional differences rise from the indexing methods.
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Ecocardiografia/estatística & dados numéricos , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Hipertrofia Ventricular Esquerda/diagnóstico , Hipertrofia Ventricular Esquerda/etnologia , Imagem Cinética por Ressonância Magnética/estatística & dados numéricos , Idoso , Baltimore/etnologia , Humanos , Tamanho do Órgão , Prevalência , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Adult congenital heart disease (ACHD) can negatively impact quality of life (QOL). Strengthening resilience may improve this and other psychosocial outcomes important for living a meaningful life. OBJECTIVES: The purpose of this study was to describe resilience and key psychosocial health outcomes in ACHD and evaluate the associations between resilience and these outcomes. METHODS: We conducted a prospective cohort study of outpatients with moderate or complex ACHD between May 2021 and June 2022. Participants completed surveys at baseline and 3 months, evaluating resilience (Connor-Davidson Resilience Scale-10), health-related QOL (EQ5D-3L, linear analog scale), health status (Euroqol visual analog scale), self-competence (Perceived Competence Scale), and psychological symptom burden (Hospital Anxiety and Depression Scale) and distress (Kessler-6). RESULTS: The mean participant age (N = 138) was 41 ± 14 years, 51% were female, and 83% self-identified as non-Hispanic White. ACHD was moderate for 75%; 57% were physiologic class B. Mean baseline resilience score (Connor-Davidson Resilience Scale-10) was 29.20 ± 7.54. Participants had relatively good health-related QOL, health status, and self-competence, and low psychological symptom burden and distress. Higher baseline resilience was associated with better values of all outcomes at 3 months (eg, 1 point higher resilience was associated with 0.92 higher linear analog scale; 95% CI: 0.52-1.32) with or without adjustment for demographics. After further adjusting for the baseline psychosocial measure, only the association between resilience and QOL measures at 3 months remained statistically significant. CONCLUSIONS: Resilience is positively associated with health-related QOL for outpatients with moderate or complex ACHD, though relationships are small in magnitude. Study findings can guide the application of resilience-building interventions to the ACHD population.
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BACKGROUND: Adults with congenital heart disease (ACHD) are at risk for lower quality of life (QOL) and psychological health. Behavioral interventions to meet their psychosocial needs are lacking. The aim of this study is to evaluate the feasibility of implementing the Promoting Resilience in Stress Management (PRISM) intervention in ACHD and its efficacy in increasing resilience in this population. METHODS: We designed a phase II randomized controlled clinical trial of patients with moderate or complex ACHD, physiological stages C or D. Enrolled participants will be randomized to receive PRISM or usual care. PRISM is a manualized, skills-based behavioral intervention comprised of four one-on-one sessions targeting resilience resources (stress-management, goal-setting, cognitive reframing, meaning making), an optional session on advance care planning, and a facilitated family meeting. Participants in both groups will complete study questionnaires at enrollment and 3-months later. The primary aim is to describe feasibility, namely the proportions of patients who a) enroll in the study among those eligible, and b) complete the PRISM intervention among those randomized to that arm. We will also evaluate PRISM's efficacy by using linear regression models to compare changes in mean resilience scores between assigned groups. In exploratory analyses, we will evaluate effects on QOL, psychological distress, perceived competence for health care management, and comfort with advance care planning. DISCUSSION: This study will provide rigorous evidence to determine the feasibility and efficacy of a brief intervention to promote resilience and psychosocial health in ACHD. Findings may guide the development of a future multi-site effectiveness study. CLINICAL TRIAL REGISTRATION: NCT04738474.
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PURPOSE: Suboptimal communication with clinicians, fragmented care and failure to align with patients' preferences are determinants of post intensive care unit (ICU) burden in family members. Our aim was to evaluate the impact of a nurse facilitator on family psychological burden. METHODS: We carried out a randomised controlled trial in five ICUs in France comparing standard communication by ICU clinicians to additional communication and support by nurse facilitators. We included patients > 18 years, with expected ICU length of stay > 2 days, chronic life-limiting illness, and their family members. Facilitators were trained to help families to secure care in line with patient's goals, beginning in ICU and continuing for 3 months. Assessments were made at baseline and 1, 3 and 6 months post-randomisation. Primary outcome was the evolution of family symptoms of depression over 6 months using a linear mixed effects model on the depression subscale of the Hospital Anxiety and Depression Scale (HADS). Secondary outcomes included HADS-Anxiety, Impact of Event Scale-6, goal-concordant care and experience of serious illness (QUAL-E). RESULTS: 385 patients and family members were enrolled. Follow-up at 1-, 3- and 6-month was completed by 284 (74%), 264 (68.6%) and 260 (67.5%) family members respectively. The intervention was associated with significantly more formal meetings between the ICU team and the family (1 [1-3] vs 2 [1-4]; p < 0.001). There was no significant difference between the intervention and control groups in evolution of symptoms of depression over 6 months (p = 0.91), nor in symptoms of depression at 6 months [0.53 95% CI (- 0.48; 1.55)]. There were no significant differences in secondary outcomes. CONCLUSION: This study does not support the use of facilitators for family members of ICU patients.
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Comunicação , Estado Terminal , Família , Unidades de Terapia Intensiva , Relações Profissional-Família , Humanos , Masculino , Feminino , Estado Terminal/psicologia , Estado Terminal/terapia , Pessoa de Meia-Idade , Família/psicologia , Unidades de Terapia Intensiva/organização & administração , Idoso , França , Adulto , Depressão/psicologiaRESUMO
This study aimed to describe lung function in a cohort of children with cystic fibrosis (CF) who underwent infant pulmonary function tests (IPFTs) and preschool spirometry. Children performed up to four IPFTs (raised volume rapid thoracic compression technique) over 1 yr and five preschool spirometry tests over up to 2 yrs during participation in prospective, multicentre studies of infant and preschool lung function. All lung function data were reviewed centrally for measurement acceptability. 45 children had 252 acceptable measurements (137 IPFTs and 115 preschool spirometries) at ages 0.3-6.5 yrs. The median number of measurements per participant was 6 (range 3-9). Recent Pseudomonas aeruginosa infection was associated with 5.1% (95% CI 0.01-9.9%) lower forced expiratory volume in 0.5 s (FEV(0.5)) and 16.4% (95% CI 7.0-24.9%) lower forced expiratory flow at 25-25% of forced vital capacity (FEF(25-75%)), after adjustment for length, test type and centre. Recent cough was associated with 5.7% (95% CI 1.1-10.1%) lower FEV(0.5) and 10.1% (95% CI 0.6-18.7%) lower FEF(25-75%). Even after accounting for infection status, cough, sex, length, test type and centre, there was significant inter-individual variability in lung function (p<0.01 for each of FEV(0.5), FEF(25-75%) and forced vital capacity). Recent P. aeruginosa infection and cough are associated with lower lung function in children with CF. Significant inter-individual variability in lung function remains to be explained.
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Fibrose Cística/fisiopatologia , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Estudos Prospectivos , Testes de Função RespiratóriaRESUMO
The optimal strategy for monitoring cystic fibrosis lung disease in infancy remains unclear. Our objective was to describe longitudinal associations between infant pulmonary function tests, chest radiograph scores and other characteristics. Cystic fibrosis patients aged ≤24 months were enrolled in a 10-centre study evaluating infant pulmonary function tests four times over a year. Chest radiographs â¼1 year apart were scored using the Wisconsin and Brasfield systems. Associations of infant pulmonary function tests with clinical characteristics were evaluated with mixed effects models. The 100 participants contributed 246 acceptable flow/volume (forced expiratory volume in 0.5 s (FEV0.5) and forced expiratory flow at 75% of the forced vital capacity (FEF75%)), 303 functional residual capacity measurements and 171 chest radiographs. Both Brasfield and Wisconsin chest radiograph scores worsened significantly over the 1-year interval. Worse Wisconsin chest radiograph scores and Staphylococcus aureus were both associated with hyperinflation (significantly increased functional residual capacity), but not with diminished FEV0.5 or FEF75%. Parent-reported cough was associated with significantly diminished forced expiratory flow at 75% but not with hyperinflation. In this infant cohort in whom we previously reported worsening in average lung function, chest radiograph scores also worsened over a year. The significant associations detected between both Wisconsin chest radiograph score and S. aureus and hyperinflation, as well as between cough and diminished flows, reinforce the ability of infant pulmonary function tests and chest radiographs to detect early cystic fibrosis lung disease.
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Fibrose Cística/diagnóstico por imagem , Fibrose Cística/fisiopatologia , Pulmão/fisiopatologia , Tosse , Fibrose Cística/complicações , Feminino , Volume Expiratório Forçado , Capacidade Residual Funcional , Humanos , Lactente , Estudos Longitudinais , Pulmão/diagnóstico por imagem , Pulmão/microbiologia , Masculino , Radiografia Torácica , Reprodutibilidade dos Testes , Testes de Função Respiratória , Infecções Estafilocócicas/diagnóstico , Staphylococcus aureus , Estados UnidosRESUMO
We investigated inter-arm systolic blood pressure (sIAD) difference, reproducibility, and incident cardiovascular disease (CVD). We hypothesized that higher sIAD values have low prevalence and nonpersistence over years, but that CVD risk is higher starting from the time of first high absolute sIAD. In Multi-Ethnic Study of Atherosclerosis participants (n = 6725, 53% female, 45-84 years old), Doppler systolic blood pressure (SBP) measurements were made in both arms (10-minute interval) thrice over 9.5 years. Proportional hazards for CVD (coronary heart disease, heart failure, stroke, peripheral arterial disease (PAD)) over 16.4 years were tested according to time-varying absolute inter-arm difference with covariates: (1) age, gender, race, and clinic; (2) model 1 plus height, heart rate, BP, antihypertensives, BMI, smoking status, lipids, lipid lowering medication, and diabetes. High sIAD was not persistent across exams. Maximum absolute sIAD ≥ 15 mmHg was found at least once in 815 persons. Maximum absolute sIAD had a graded relationship with incident stroke or PAD: 6.2% events; model 2 hazard ratio per 10 mmHg 1.34 (95% CI, 1.15-1.56) and this risk was approximately doubled for maximum absolute sIAD ≥ 15 mmHg vs 0-4 mmHg. Total CVD risk (18.4% events) was increased only for maximum absolute sIAD ≥25 mmHg. Associations with incident CVD did not differ for higher SBP in left vs right arm. A higher maximum absolute sIAD at any exam was associated with greater risk for stroke and PAD especially for values ≥ 15 mmHg, and ≥25 mmHg for other CVD. Measuring SBP between arms may help identify individuals at risk for CVD.
Assuntos
Aterosclerose , Doenças Cardiovasculares , Hipertensão , Acidente Vascular Cerebral , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Pressão Sanguínea/fisiologia , Reprodutibilidade dos Testes , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Aterosclerose/complicações , Fatores de Risco , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/complicaçõesRESUMO
BACKGROUND: There is limited literature on differences in arterial compliance, as assessed from arterial pressure waveforms, with age, sex, and race/ethnicity. PTC1 and PTC2 are indices of arterial compliance, which are derived from a Windkessel model of the waveform, relatively easy to obtain, and associated with cardiovascular disease. METHOD: PTC1 and PTC2 were computed from radial artery waveforms from participants of the Multi-Ethnic Study of Atherosclerosis at baseline and again 10 years later. We evaluated the association of PTC1, PTC2, and 10-year change in PTC1 and PTC2 with age, sex, and race/ethnicity. RESULTS: Among 6245 participants in 2000-2002 (meanâ±âSD of age was 62â±â10 years; 52% female; 38% White, 12% Chinese, 27% Black, and 23% Hispanic/Latino), meansâ±âSDs for PTC1 and PTC2 were 394â±â334 and 94â±â46âms. After adjustment for cardiovascular disease risk factors, mean PTC2 was 1.1âms (95% confidence interval: 1.0, 1.2) lower (arterial stiffness was greater) per year older age, was 22âms (19, 24) lower for females, and varied by race/ethnicity ( P â<â0.001; e.g., 5âms lower for Blacks compared with Whites), although the differences were smaller at older ages ( P â<â0.001 for age-sex, P â<â0.001 for age-race/ethnicity interactions). Among 3701 participants with repeat measurements in 2010-2012, arteries had stiffened (meanâ±âSD 10-year decrease in PTC2: 13â±â46âms) consistent with cross-sectional age-trend and tended to stiffen less for females and Blacks consistent with cross-sectional age-interactions. CONCLUSION: Differences in arterial compliance by age, sex, and race/ethnicity lend support to identify and act on societal factors that may drive health disparities.
Assuntos
Doenças Cardiovasculares , Etnicidade , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Doenças Cardiovasculares/etiologia , Artéria Radial , Estudos Transversais , Fatores de RiscoRESUMO
CONTEXT: Goals-of-care discussions are important for patient-centered care among hospitalized patients with serious illness. However, there are little data on the occurrence, predictors, and timing of these discussions. OBJECTIVES: To examine the occurrence, predictors, and timing of electronic health record (EHR)-documented goals-of-care discussions for hospitalized patients. METHODS: This retrospective cohort study used natural language processing (NLP) to examine EHR-documented goals-of-care discussions for adults with chronic life-limiting illness or age ≥80 hospitalized 2015-2019. The primary outcome was NLP-identified documentation of a goals-of-care discussion during the index hospitalization. We used multivariable logistic regression to evaluate associations with baseline characteristics. RESULTS: Of 16,262 consecutive, eligible patients without missing data, 5,918 (36.4%) had a documented goals-of-care discussion during hospitalization; approximately 57% of these discussions occurred within 24 hours of admission. In multivariable analysis, documented goals-of-care discussions were more common for women (OR=1.26, 95%CI 1.18-1.36), older patients (OR=1.04 per year, 95%CI 1.03-1.04), and patients with more comorbidities (OR=1.11 per Deyo-Charlson point, 95%CI 1.10-1.13), cancer (OR=1.88, 95%CI 1.72-2.06), dementia (OR=2.60, 95%CI 2.29-2.94), higher acute illness severity (OR=1.12 per National Early Warning Score point, 95%CI 1.11-1.14), or prior advance care planning documents (OR=1.18, 95%CI 1.08-1.30). Documentation of these discussions was less common for racially or ethnically minoritized patients (OR=0.823, 95%CI 0.75-0.90). CONCLUSION: Among hospitalized patients with serious illness, documented goals-of-care discussions identified by NLP were more common among patients with older age and increased burden of acute or chronic illness, and less common among racially or ethnically minoritized patients. This suggests important disparities in goals-of-care discussions.
Assuntos
Planejamento Antecipado de Cuidados , Assistência Terminal , Adulto , Humanos , Feminino , Estudos Retrospectivos , Objetivos , Doença CrônicaRESUMO
Importance: Family members of patients with severe acute brain injury (SABI) are at risk for poor psychological outcomes. Objective: To explore the utility of the early use of a palliative care needs checklist in identifying care needs of patients with SABI and family members who are at risk of poor psychological outcomes. Design, Setting, and Participants: This prospective cohort study included patients with SABI in an intensive care unit (ICU) for 2 days or more and a Glasgow Coma Scale score of 12 or lower and their family members. This single-center study was conducted at an academic hospital in Seattle, Washington, from January 2018 to June 2021. Data were analyzed from July 2021 to July 2022. Exposure: At enrollment, a 4-item palliative care needs checklist was completed separately by clinicians and family members. Main Outcomes and Measures: A single family member for each enrolled patient completed questionnaires assessing symptoms of depression and anxiety, perception of goal-concordant care, and satisfaction in the ICU. Six months later, family members assessed their psychological symptoms, decisional regret, patient functional outcome, and patient quality of life (QOL). Results: A total of 209 patient-family member pairs (family member mean [SD] age, 51 [16] years; 133 women [64%]; 18 Asian [9%], 21 Black [10%], 20 [10%] Hispanic, and 153 White [73%] participants) were included. Patients had experienced stroke (126 [60%]), traumatic brain injury (62 [30%]), and hypoxic-ischemic encephalopathy (21 [10%]). At least 1 need was identified for 185 patients or their families (88%) by family members and 110 (53%) by clinicians (κ = -0.007; 52% agreement). Symptoms of at least moderate anxiety or depression were present in 50% of family members at enrollment (87 with anxiety and 94 with depression) and 20% at follow-up (33 with anxiety and 29 with depression). After adjustment for patient age, diagnosis, and disease severity and family race and ethnicity, clinician identification of any need was associated with greater goal discordance (203 participants; relative risk = 1.7 [95% CI, 1.2 to 2.5]) and family decisional regret (144 participants; difference in means, 17 [95% CI, 5 to 29] points). Family member identification of any need was associated with greater symptoms of depression at follow-up (150 participants; difference in means of Patient Health Questionnaire-2, 0.8 [95% CI, 0.2 to 1.3] points) and worse perceived patient QOL (78 participants; difference in means, -17.1 [95% CI, -33.6 to -0.5] points). Conclusions and Relevance: In this prospective cohort study of patients with SABI and their families, palliative care needs were common, although agreement on needs was poor between clinicians and family members. A palliative care needs checklist completed by clinicians and family members may improve communication and promote timely, targeted management of needs.
Assuntos
Lesões Encefálicas , Cuidados Paliativos , Humanos , Feminino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Prospectivos , Lesões Encefálicas/epidemiologia , Lesões Encefálicas/terapia , Avaliação de Resultados em Cuidados de Saúde , Família/psicologiaRESUMO
Despite the prognostic value of arterial stiffness (AS) and pulsatile hemodynamics (PH) for cardiovascular morbidity and mortality, epigenetic modifications that contribute to AS/PH remain unknown. To gain a better understanding of the link between epigenetics (DNA methylation) and AS/PH, we examined the relationship of eight measures of AS/PH with CpG sites and co-methylated regions using multi-ancestry participants from Trans-Omics for Precision Medicine (TOPMed) Multi-Ethnic Study of Atherosclerosis (MESA) with sample sizes ranging from 438 to 874. Epigenome-wide association analysis identified one genome-wide significant CpG (cg20711926-CYP1B1) associated with aortic augmentation index (AIx). Follow-up analyses, including gene set enrichment analysis, expression quantitative trait methylation analysis, and functional enrichment analysis on differentially methylated positions and regions, further prioritized three CpGs and their annotated genes (cg23800023-ETS1, cg08426368-TGFB3, and cg17350632-HLA-DPB1) for AIx. Among these, ETS1 and TGFB3 have been previously prioritized as candidate genes. Furthermore, both ETS1 and HLA-DPB1 have significant tissue correlations between Whole Blood and Aorta in GTEx, which suggests ETS1 and HLA-DPB1 could be potential biomarkers in understanding pathophysiology of AS/PH. Overall, our findings support the possible role of epigenetic regulation via DNA methylation of specific genes associated with AIx as well as identifying potential targets for regulation of AS/PH.
RESUMO
Despite the prognostic value of arterial stiffness (AS) and pulsatile hemodynamics (PH) for cardiovascular morbidity and mortality, epigenetic modifications that contribute to AS/PH remain unknown. To gain a better understanding of the link between epigenetics (DNA methylation) and AS/PH, we examined the relationship of eight measures of AS/PH with CpG sites and co-methylated regions using multi-ancestry participants from Trans-Omics for Precision Medicine (TOPMed) Multi-Ethnic Study of Atherosclerosis (MESA) with sample sizes ranging from 438 to 874. Epigenome-wide association analysis identified one genome-wide significant CpG (cg20711926-CYP1B1) associated with aortic augmentation index (AIx). Follow-up analyses, including gene set enrichment analysis, expression quantitative trait methylation analysis, and functional enrichment analysis on differentially methylated positions and regions, further prioritized three CpGs and their annotated genes (cg23800023-ETS1, cg08426368-TGFB3, and cg17350632-HLA-DPB1) for AIx. Among these, ETS1 and TGFB3 have been previously prioritized as candidate genes. Furthermore, both ETS1 and HLA-DPB1 have significant tissue correlations between Whole Blood and Aorta in GTEx, which suggests ETS1 and HLA-DPB1 could be potential biomarkers in understanding pathophysiology of AS/PH. Overall, our findings support the possible role of epigenetic regulation via DNA methylation of specific genes associated with AIx as well as identifying potential targets for regulation of AS/PH.