RESUMEN
Introduction: Autonomic dysfunction has been implicated as a consequence of traumatic brain injury (TBI). Heart rate variability (HRV) may be a viable measure of autonomic dysfunction that could enhance rehabilitative interventions for individuals with TBI. This pilot study sought to assess the feasibility and validity of using the Zeriscope™ platform system in a real-world clinical setting to measure HRV in active-duty service members with TBI who were participating in an intensive outpatient program. Methods: Twenty-five service members with a history of mild, moderate, or severe TBI were recruited from a military treatment facility. A baseline assessment was conducted in the cardiology clinic where point validity data were obtained by comparing a 5-min recording of a standard 12-lead electrocardiogram (ECG) output against the Zeriscope platform data. Results: Compared with the ECG device, the Zeriscope device had a concordance coefficient (rc) of 0.16, falling below the standard deemed to represent acceptable accuracy in HR measurement (i.e., 0.80). Follow-up analyses excluding outliers did not significantly improve the concordance coefficient to an acceptable standard for the total participant sample. System Usability Survey responses showed that participants rated the Zeriscope system as easy to use and something that most people would learn to use quickly. Conclusions: This study demonstrated promise in ambulatory HRV measurement in a representative military TBI sample. Future research should include further refinement of such ambulatory devices to meet the specifications required for use in a military active-duty TBI population.
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Lesiones Traumáticas del Encéfalo , Personal Militar , Dispositivos Electrónicos Vestibles , Lesiones Traumáticas del Encéfalo/diagnóstico , Frecuencia Cardíaca , Humanos , Monitoreo Fisiológico , Proyectos PilotoRESUMEN
Blockade of the programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint augments antitumor immunity and induces durable responses in patients with solid cancers, but data on clinical efficacy in leukemias are sparse. Chronic lymphocytic leukemia (CLL) is associated with a tumor-supportive microenvironment and a dysfunctional immune system, as shown by "exhausted" T cells, defective immunologic synapse formation, and immunosuppressive myeloid cells. These defects involve aberrant expression of PD-L1 and are closely mirrored in the Eµ-TCL1 mouse model for CLL. In this study, we treated mice after adoptive transfer of Eµ-TCL1 CLL with PD-L1-blocking antibodies, which prevented CLL development and was accompanied by a reactivation of immune effector functions. This included restoration of mature macrophages and major histocompatibility complex class II-expressing dendritic cells and prevention of aberrant and exhaustion-like T-cell phenotypes. In addition, PD-L1 blockade restored CD8 T-cell cytotoxicity and immune synapse formation and normalized T-cell cytokines and proliferation ex vivo and in vivo. Our data demonstrate that early PD-L1 blockade effectively corrects leukemia-induced immune dysfunction and thus prevents CLL development in mice. Targeting PD-L1/PD-1 interactions should therefore be further explored in clinical studies with CLL patients, ideally in combination with novel compounds to help eliminate CLL.
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Anticuerpos/farmacología , Antígeno B7-H1/antagonistas & inhibidores , Transformación Celular Neoplásica/efectos de los fármacos , Enfermedades del Sistema Inmune/prevención & control , Leucemia Linfocítica Crónica de Células B/inmunología , Leucemia Linfocítica Crónica de Células B/prevención & control , Animales , Antígeno B7-H1/inmunología , Antígeno B7-H1/fisiología , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/inmunología , Transformación Celular Neoplásica/inmunología , Células Cultivadas , Células Dendríticas/efectos de los fármacos , Células Dendríticas/fisiología , Modelos Animales de Enfermedad , Femenino , Inflamación/prevención & control , Leucemia Linfocítica Crónica de Células B/patología , Ratones , Ratones Endogámicos C57BLRESUMEN
T-cell defects, immune suppression, and poor antitumor immune responses are hallmarks of chronic lymphocytic leukemia (CLL), and PD-1/PD-L1 inhibitory signaling has emerged as a major immunosuppressive mechanism. However, the effect of different microenvironments and the confounding influence of aging are poorly understood. The current study uses the Eµ-TCL1 mouse model, which replicates human T-cell defects, as a preclinical platform to longitudinally examine patterns of T-cell dysfunction alongside developing CLL and in different microenvironments, with a focus on PD-1/PD-L1 interactions. The development of CLL was significantly associated with changes in T-cell phenotype across all organs and function. Although partly mirrored in aging wild-type mice, CLL-specific T-cell changes were identified. Murine CLL cells highly expressed PD-L1 and PD-L2 in all organs, with high PD-L1 expression in the spleen. CD3(+)CD8(+) T cells from leukemic and aging healthy mice highly expressed PD-1, identifying aging as a confounder, but adoptive transfer experiments demonstrated CLL-specific PD-1 induction. Direct comparisons of PD-1 expression and function between aging CLL mice and controls identified PD-1(+) T cells in CLL as a heterogeneous population with variable effector function. This is highly relevant for therapeutic targeting of CD8(+) T cells, showing the potential of reprogramming and selective subset expansion to restore antitumor immunity.
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Envejecimiento/inmunología , Antígeno B7-H1/fisiología , Linfocitos T CD8-positivos/inmunología , Leucemia Linfocítica Crónica de Células B/inmunología , Receptor de Muerte Celular Programada 1/fisiología , Envejecimiento/genética , Animales , Diferenciación Celular/genética , Diferenciación Celular/inmunología , Células Cultivadas , Modelos Animales de Enfermedad , Cadenas mu de Inmunoglobulina/genética , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/patología , Ratones , Ratones Transgénicos , Proteínas Proto-Oncogénicas/genética , Transducción de Señal/inmunologíaRESUMEN
Importance: The COVID-19 pandemic has led to an unprecedented shift in ambulatory cardiovascular care from in-person to remote visits. Objective: To understand whether the transition to remote visits is associated with disparities in patient use of care, diagnostic test ordering, and medication prescribing. Design, Setting, and Participants: This cross-sectional study used electronic health records data for all ambulatory cardiology visits at an urban, multisite health system in Los Angeles County, California, during 2 periods: April 1, 2019, to December 31, 2019 (pre-COVID) and April 1 to December 31, 2020 (COVID-era). Statistical analysis was performed from January to February 2021. Exposure: In-person or remote ambulatory cardiology clinic visit at one of 31 during the pre-COVID period or COVID-era period. Main Outcomes and Measures: Comparison of patient characteristics and frequencies of medication ordering and cardiology-specific testing across 4 visit types (pre-COVID in-person (reference), COVID-era in-person, COVID-era video, COVID-era telephone). Results: This study analyzed data from 87â¯182 pre-COVID in-person, 74â¯498 COVID-era in-person, 4720 COVID-era video, and 10â¯381 COVID-era telephone visits. Across visits, 79â¯572 patients were female (45.0%), 127â¯080 patients were non-Hispanic White (71.9%), and the mean (SD) age was 68.1 (17.0) years. Patients accessing COVID-era remote visits were more likely to be Asian, Black, or Hispanic individuals (24â¯934 pre-COVID in-person visits [28.6%] vs 19â¯742 COVID-era in-person visits [26.5%] vs 3633 COVID-era video visits [30.4%] vs 1435 COVID-era telephone visits [35.0%]; P < .001 for all comparisons), have private insurance (34â¯063 pre-COVID in-person visits [39.1%] vs 25â¯474 COVID-era in-person visits [34.2%] vs 2562 COVID-era video visits [54.3%] vs 4264 COVID-era telephone visits [41.1%]; P < .001 for COVID-era in-person vs video and COVID-era in-person vs telephone), and have cardiovascular comorbidities (eg, hypertension: 37â¯166 pre-COVID in-person visits [42.6%] vs 31â¯359 COVID-era in-person visits [42.1%] vs 2006 COVID-era video visits [42.5%] vs 5181 COVID-era telephone visits [49.9%]; P < .001 for COVID-era in-person vs telephone; and heart failure: 14â¯319 pre-COVID in-person visits [16.4%] vs 10â¯488 COVID-era in-person visits [14.1%] vs 1172 COVID-era video visits [24.8%] vs 2674 COVID-era telephone visits [25.8%]; P < .001 for COVID-era in-person vs video and COVID-era in-person vs telephone). After adjusting for patient and visit characteristics and in comparison with pre-COVID in-person visits, during video and telephone visits, clinicians had lower odds of ordering any medication (COVID-era in-person: odds ratio [OR], 0.62 [95% CI, 0.60-0.64], COVID-era video: OR, 0.22 [95% CI, 0.20-0.24]; COVID-era telephone: OR, 0.14 [95% CI, 0.13-0.15]) or tests, such as electrocardiograms (COVID-era in-person: OR, 0.60 [95% CI, 0.58-0.62]; COVID-era video: OR, 0.03 [95% CI, 0.02-0.04]; COVID-era telephone: OR, 0.02 [95% CI, 0.01-0.03]) or echocardiograms (COVID-era in-person: OR, 1.21 [95% CI, 1.18-1.24]; COVID-era video: OR, 0.47 [95% CI, 0.42-0.52]; COVID-era telephone: OR, 0.28 [95% CI, 0.25-0.31]). Conclusions and Relevance: Patients who were Asian, Black, or Hispanic, had private insurance, and had at least one of several cardiovascular comorbidities used remote cardiovascular care more frequently in the COVID-era period. Clinician ordering of diagnostic testing and medications consistently decreased when comparing pre-COVID vs COVID-era and in-person vs remote visits. Further studies are needed to clarify whether these decreases represent a reduction in the overuse of tests and medications vs an underuse of indicated testing and prescribing.
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Atención Ambulatoria , COVID-19 , Cardiología/métodos , Pandemias , Aceptación de la Atención de Salud , Pautas de la Práctica en Medicina , Telemedicina/métodos , Anciano , Anciano de 80 o más Años , Instituciones de Atención Ambulatoria , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/terapia , Estudios Transversales , Etnicidad , Femenino , Disparidades en Atención de Salud , Humanos , Seguro de Salud , Masculino , Persona de Mediana Edad , SARS-CoV-2RESUMEN
BACKGROUND: An unprecedented shift to remote heart failure outpatient care occurred during the coronavirus disease 2019 (COVID-19) pandemic. Given challenges inherent to remote care, we studied whether remote visits (video or telephone) were associated with different patient usage, clinician practice patterns, and outcomes. METHODS: We included all ambulatory cardiology visits for heart failure at a multisite health system from April 1, 2019, to December 31, 2019 (pre-COVID) or April 1, 2020, to December 31, 2020 (COVID era), resulting in 10 591 pre-COVID in-person, 7775 COVID-era in-person, 1009 COVID-era video, and 2322 COVID-era telephone visits. We used multivariable logistic and Cox proportional hazards regressions with propensity weighting and patient clustering to study ordering practices and outcomes. RESULTS: Compared with in-person visits, video visits were used more often by younger (mean 64.7 years [SD 14.5] versus 74.2 [14.1]), male (68.3% versus 61.4%), and privately insured (45.9% versus 28.9%) individuals (P<0.05 for all). Remote visits were more frequently used by non-White patients (35.8% video, 37.0% telephone versus 33.2% in-person). During remote visits, clinicians were less likely to order diagnostic testing (odds ratio, 0.20 [0.18-0.22] video versus in-person, 0.18 [0.17-0.19] telephone versus in-person) or prescribe ß-blockers (0.82 [0.68-0.99], 0.35 [0.26-0.47]), mineralocorticoid receptor antagonists (0.69 [0.50-0.96], 0.48 [0.35-0.66]), or loop diuretics (0.67 [0.53-0.85], 0.45 [0.37-0.55]). During telephone visits, clinicians were less likely to prescribe ACE (angiotensin-converting enzyme) inhibitor/ARB (angiotensin receptor blockers)/ARNIs (angiotensin receptor-neprilysin inhibitors; 0.54 [0.40-0.72]). Telephone visits but not video visits were associated with higher rates of 90-day mortality (1.82 [1.14-2.90]) and nonsignificant trends towards higher rates of 90-day heart failure emergency department visits (1.34 [0.97-1.86]) and hospitalizations (1.36 [0.98-1.89]). CONCLUSIONS: Remote visits for heart failure care were associated with reduced diagnostic testing and guideline-directed medical therapy prescription. Telephone but not video visits were associated with increased 90-day mortality.
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COVID-19 , Cardiólogos/tendencias , Insuficiencia Cardíaca/terapia , Pautas de la Práctica en Medicina/tendencias , Telemedicina/tendencias , Anciano , Anciano de 80 o más Años , Técnicas y Procedimientos Diagnósticos/tendencias , Prescripciones de Medicamentos , Utilización de Medicamentos/tendencias , Servicio de Urgencia en Hospital/tendencias , Femenino , Adhesión a Directriz/tendencias , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Hospitalización/tendencias , Humanos , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Teléfono/tendencias , Factores de Tiempo , Resultado del Tratamiento , Comunicación por Videoconferencia/tendenciasAsunto(s)
Países Desarrollados/economía , Países en Desarrollo/economía , Agricultura/economía , Agricultura/estadística & datos numéricos , Américas/epidemiología , Región del Caribe/epidemiología , Clima , Comercio/economía , Comercio/historia , Comercio/estadística & datos numéricos , Países Desarrollados/historia , Países Desarrollados/estadística & datos numéricos , Países en Desarrollo/historia , Países en Desarrollo/estadística & datos numéricos , Emigración e Inmigración/historia , Emigración e Inmigración/estadística & datos numéricos , Geografía , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Política , Densidad de PoblaciónRESUMEN
OBJECTIVE: To determine the prevalence of, and patient characteristics associated with, antiplatelet therapy in a cohort of primary care patients with Type 1 or Type 2 diabetes. METHODS: Subjects participating in a randomized trial of a decision support system were interviewed at home and medication usage verified by a research assistant. Eligibility for antiplatelet therapy was determined by American Diabetes Association criteria and clinical contraindications. The association between antiplatelet use and patient characteristics was examined using bivariate and multivariate logistic regression. RESULTS: The mean age of subjects was 64 years (range 31-93). The prevalence of antiplatelet use was 54% overall; 45% for subjects without known CVD vs. 78% for those with CVD; 46% for women vs. 63% for men; and 45% for younger subjects (age < 65) vs. 62% for senior citizens. After controlling for race/ethnicity, income, education, marital status, insurance status and prescription coverage, the following were associated with the use of antiplatelet therapy: presence of known CVD (OR 3.4 [2.2, 5.1]), male sex (OR 2.0 [1.4, 2.8]), and age > or = 65 (OR 1.9 [1.3, 2.7]). The prevalence of antiplatelet therapy for younger women without CVD was 32.8% compared to a prevalence of 90.3% for older men with CVD. CONCLUSION: Despite clinical practice guidelines recommending antiplatelet therapy for patients with diabetes, there are still many eligible patients not receiving this beneficial therapy, particularly patients under 65, women, and patients without known CVD. Effective methods to increase antiplatelet use should be considered at the national, community, practice and provider level.