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1.
Cancers (Basel) ; 16(4)2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38398114

RESUMEN

Neuroblastoma is the most common extracranial solid tumour in children, comprising close to 10% of childhood cancer-related deaths. We have demonstrated that activation of NTRK1 by TP53 repression of PTPN6 expression is significantly associated with favourable survival in neuroblastoma. The molecular mechanisms by which this activation elicits cell molecular changes need to be determined. This is critical to identify dependable biomarkers for the early detection and prognosis of tumours, and for the development of personalised treatment. In this investigation we have identified and validated a gene signature for the prognosis of neuroblastoma using genes differentially expressed upon activation of the NTRK1-PTPN6-TP53 module. A random survival forest model was used to construct a gene signature, which was then assessed across validation datasets using Kaplan-Meier analysis and ROC curves. The analysis demonstrated that high BASP1, CD9, DLG2, FNBP1, FRMD3, IL11RA, ISGF10, IQCE, KCNQ3, and TOX2, and low BSG/CD147, CCDC125, GABRB3, GNB2L1/RACK1 HAPLN4, HEBP2, and HSD17B12 expression was significantly associated with favourable patient event-free survival (EFS). The gene signature was associated with favourable tumour histology and NTRK1-PTPN6-TP53 module activation. Importantly, all genes were significantly associated with favourable EFS in an independent manner. Six of the signature genes, BSG/CD147, GNB2L1/RACK1, TXNDC5, FNPB1, B3GAT1, and IGSF10, play a role in cell differentiation. Our findings strongly suggest that the identified gene signature is a potential prognostic biomarker and therapeutic target for neuroblastoma patients and that it is associated with neuroblastoma cell differentiation through the activation of the NTRK1-PTPN6-TP53 module.

2.
Transl Androl Urol ; 12(10): 1607-1613, 2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37969781

RESUMEN

Background: Malignant priapism, a rare disease with only about 500 reported cases to date, consists of persistent erection secondary to invasion or metastasis of a primary neoplasm. While treatment guidelines for priapism in non-malignant cases have been established, there is currently no guideline for treating malignant priapism. Herein, we describe three cases of malignant priapism and suggest a step-by-step approach for clinical management. Case Description: This study reports three cases of malignant priapism resulting from advanced genitourinary cancers. All patients experienced a sub-acute progression of penile pain and ultimately underwent palliative penectomy, resulting in sustained symptom relief. Conclusions: Treatment of malignant priapism needs to be individualized to the needs of the patient. No matter the primary or secondary nature of the disease, current data suggest that malignant priapism is associated with poor outcomes and emphasis should be put on palliative care. Similar to previous cases, our cases died shortly after the diagnosis of malignant priapism. Conventional procedures such as shunting may not necessarily provide symptom relief in these patients. Although new radiation techniques have shown favorable outcomes, penectomy should be considered the last resort in clinical management. Revisions to the existing management guidelines for priapism are necessary to address its occurrence in malignant contexts.

3.
Cureus ; 15(7): e42725, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37654920

RESUMEN

Introduction and objective The purpose of this study is to better characterize at which point during the course of diagnosis and treatment of locally advanced prostate cancer the internet is utilized and to evaluate the search trends over time. Methods Monthly Google Trends data were collected from 2004 to 2021 for prostate cancer-specific terms. Temporal trends were analyzed by comparing average search volume indexes (aSVI) and analysis with joinpoint software of six-month percent change (6mPC). Chloropleths were created for geographic pattern comparisons. Results Search terms associated with interventions demonstrated the highest aSVI with terms such as "prostate biopsy" (aSVI: 33.59), "prostatectomy" (aSVI: 31.6), and "prostate radiation" (aSVI: 16.45). Terms associated with treatment side effects increased at a high rate with "radiation side effects" (21.4 6mPC, p<0.05) and "prostatectomy side effects" (14.4 6mPC, p<0.05). Prostate-specific antigen (PSA)-related search terms demonstrated a strong positive trend on joinpoint analysis with search terms "What is PSA?" (8.9 6mPC, p<0.05), and "What is normal PSA?" (15.1, p<0.05). Geographic patterns demonstrated higher search volumes in regard to screening and diagnostic terms in the northeast, while the southern regions demonstrated relatively higher search volumes for treatment and interventions. Conclusions The internet continues to be a growing part of the dynamics of prostate cancer management with more men utilizing the internet each year to help understand their diagnosis. Specifically, we found that the internet is used more for searches pertaining to PSA, procedures, and interventions affecting the quality of life.

4.
Urol Pract ; 10(6): 605-610, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37498314

RESUMEN

INTRODUCTION: In 2014, the AUA published guidelines regarding the evaluation of cryptorchidism. This multi-institutional study aims to determine if these guidelines reduced the age of referral and the utilization of ultrasound in boys with cryptorchidism. We hypothesize that delayed referral continues, and utilization of ultrasound remains unchanged. METHODS: A retrospective review of boys referred for the evaluation of cryptorchidism was performed at 4 academic institutions, collecting data for 1 year prior (2013) and 2 nonconsecutive years following guideline creation (2015 and 2019). Across these time frames, we compared median ages at evaluation and surgery, and rates of patient comorbidities, orchiopexy, and preevaluation ultrasound. RESULTS: A total of 3,293 patients were included. The median age at initial pediatric urology evaluation in all cohorts was 39 months (IQR: 14-92 months). Following publication of the AUA Guidelines, there was no difference (P = .08) in the median age at first evaluation by a pediatric urologist between 2013 and 2015, and an increase (P = .03) between 2013 and 2019. Overall, 21.2% of patients received an ultrasound evaluation prior to referral, with no significant difference between 2013 and 2015 (P = .9) or 2019 (P = .5) cohorts. CONCLUSIONS: Our data suggest that, despite publication of the AUA Guidelines on evaluation and treatment of cryptorchidism, there has been no reduction in the age of urological evaluation or the utilization of imaging in boys with undescended testis. Finding alternative avenues to disseminate these evidence-based recommendations to referring providers and exploring barriers to guideline adherence is necessary to improve care for patients with cryptorchidism.


Asunto(s)
Criptorquidismo , Masculino , Humanos , Niño , Lactante , Preescolar , Criptorquidismo/diagnóstico , Derivación y Consulta , Orquidopexia/métodos , Estudios Retrospectivos , Ultrasonografía
5.
J Interv Card Electrophysiol ; 66(7): 1659-1668, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36735111

RESUMEN

BACKGROUND: Remote monitoring (RM) can facilitate early detection of subclinical and symptomatic atrial fibrillation (AF), providing an opportunity to evaluate the need for stroke prevention therapies. We aimed to characterize the burden of RM AF alerts and its impact on anticoagulation of patients with device-detected AF. METHODS: Consecutive patients with a cardiac implantable electronic device, at least one AF episode, undergoing RM were included and assigned an estimated minimum CHA2DS2-VASc score based on age and device type. RM was provided via automated software system, providing rapid alert processing by device specialists and systematic, recurrent prompts for anticoagulation. RESULTS: From 7651 individual, 389,188 AF episodes were identified, 3120 (40.8%) permanent pacemakers, 2260 (29.5%) implantable loop recorders (ILRs), 987 (12.9%) implantable cardioverter defibrillators, 968 (12.7%) cardiac resynchronization therapy (CRT) defibrillators, and 316 (4.1%) CRT pacemakers. ILRs transmitted 48.8% of all AF episodes. At twelve-months, 3404 (44.5%) AF < 6 min, 1367 (17.9%) 6 min-6 h, 1206 (15.8%) 6-24 h, and 1674 (21.9%) ≥ 24 h. A minimum CHA2DS2-VASc score of 2 was assigned to 1704 (63.1%) of the patients with an AF episode of ≥ 6 h, 531 (31.2%) who were not anticoagulated at 12-months, and 1031 (61.6%) patients with an AF episode duration of ≥ 24 h, 290 (28.1%) were not anticoagulated. CONCLUSIONS: Despite being intensively managed via RM software system incorporating cues for anticoagulation, a substantial proportion of patients with increased stroke risk remained unanticoagulated after a device-detected AF episode of significant duration. These data highlight the need for improved clinical response pathways and an integrated care approach to RM. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry: ACTRN12620001232921.


Asunto(s)
Fibrilación Atrial , Desfibriladores Implantables , Marcapaso Artificial , Humanos , Anticoagulantes , Fibrilación Atrial/diagnóstico , Australia , Factores de Riesgo
6.
BMJ ; 375: n2496, 2021 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-34654718
8.
Ann Clin Biochem ; 58(6): 632-637, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34467779

RESUMEN

BACKGROUND: The growing number of laboratory investigation requests is placing an increased burden upon NHS resources. Around a quarter of all tests are unnecessary repeats, and almost a third have no impact on patient management. Doctors recognise that tests should only be performed when clinically indicated, but a culture persists of undertaking unnecessary repeat investigations. METHODS: A cohort study was undertaken at a district general hospital to observe the impact of introducing educational interventions in the form of a poster and a series of educational lectures, encouraging clinicians to consider whether an investigation was clinically indicated. Data was collected from nine different sites across the hospital run by different medical teams regarding the number of tests undertaken and the impact on patient care. RESULTS: Data from over 13,000 tests and over 2000 patients was analysed from nine different sites across the hospital. There was a significant reduction (33%, p = 0.0001) in the number of blood tests performed. This reduction in testing saved £7006 over the course of 1 month, in addition to other benefits. There was a reduction in testing in eight out of the nine sites in which the study was undertaken, demonstrating good generalisability of results. There was no significant increase in length of admission or mortality. CONCLUSION: Educational interventions to doctors have a significant and safe impact in reducing the number of unnecessary investigations, providing cost saving benefits to the NHS.


Asunto(s)
Hospitales , Estudios de Cohortes , Pruebas Hematológicas , Humanos
9.
JACC Clin Electrophysiol ; 7(2): 226-234, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33602404

RESUMEN

OBJECTIVES: This study sought to determine the remote monitoring (RM) alert burden in a multicenter cohort of patients with a cardiac implantable electronic device (CIED). BACKGROUND: RM of CIEDs allows timely recognition of patient and device events requiring intervention. Most RM involves burdensome manual workflow occurring exclusively on weekdays during office hours. Automated software may reduce such a burden, streamlining real-time alert responses. METHODS: We retrospectively analyzed 26,713 consecutive patients with a CIED undergoing managed RM utilizing PaceMate software between November 2018 and November 2019. Alerts were analyzed according to type, acuity (red indicates urgent, and yellow indicates nonurgent) and CIED category. RESULTS: In total, 12,473 (46.7%) patients had a permanent pacemaker (PPM), 9,208 (34.5%) had an implantable cardioverter-defibrillator (ICD), and 5,032 (18.8%) had an implantable loop recorder (ILR). Overall, 82,797 of the 205,804 RM transmissions were alerts, with the remainder being scheduled transmissions. A total of 14,638 (54.8%) patients transmitted at least 1 alert. Permanent pacemakers were responsible for 25,700 (31.0%) alerts, ICDs for 15,643 (18.9%) alerts, and ILRs for 41,454 (50.1%) alerts, with 3,935 (4.8%) red alerts and 78,862 (95.2%) yellow alerts. ICDs transmitted 2,073 (52.7%) red alerts; 5,024 (32.1%) ICD alerts were for ventricular tachyarrhythmias and antitachycardia pacing/shock delivery. CONCLUSIONS: In an RM cohort of 26,713 patients with CIEDs, 54.8% of patients transmitted at least 1 alert during a 12-month period, totaling over 82,000 alerts. ILRs were overrepresented, and ICDs were underrepresented, in these alerts. The enormity of the number of transmissions and the growing ILR alert burden highlight the need for new management pathways for RM.


Asunto(s)
Desfibriladores Implantables , Marcapaso Artificial , Taquicardia Ventricular , Humanos , Monitoreo Fisiológico , Estudios Retrospectivos
10.
JACC Clin Electrophysiol ; 7(5): 630-641, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33640353

RESUMEN

OBJECTIVES: This study sought to evaluate the effect of weight loss on the atrial substrate for atrial fibrillation (AF). BACKGROUND: Whether weight loss can reverse the atrial substrate of obesity is not known. METHODS: Thirty sheep had sustained obesity induced by ad libitum calorie-dense diet over 72 weeks. Animals were randomized to 3 groups: sustained obesity and 15% and 30% weight loss. The animals randomized to weight loss underwent weight reduction by reducing the quantity of hay over 32 weeks. Eight lean animals served as controls. All were subjected to the following: dual-energy x-ray absorptiometry, echocardiogram, cardiac magnetic resonance, electrophysiological study, and histological and molecular analyses (fatty infiltration, fibrosis, transforming growth factor ß1, and connexin 43). RESULTS: Sustained obesity was associated with increased left atrium (LA) pressure (p < 0.001), inflammation (p < 0.001), atrial transforming growth factor ß1 protein (p < 0.001), endothelin-B receptor expression (p = 0.04), atrial fibrosis (p = 0.01), epicardial fat infiltration (p < 0.001), electrophysiological abnormalities, and AF burden (p = 0.04). Connexin 43 expression was decreased in the obese group (p = 0.03). In this obese ovine model, 30% weight reduction was associated with reduction in total body fat (p < 0.001), LA pressure (p = 0.007), inflammation (p < 0.001), endothelin-B receptor expression (p = 0.01), atrial fibrosis (p = 0.01), increase in atrial effective refractory period (cycle length: 400 and 300 ms; p < 0.001), improved conduction velocity (cycle length: 400 and 300 ms; p = 0.01), decreased conduction heterogeneity (p < 0.001), and decreased AF inducibility (p = 0.03). Weight loss was associated with a nonsignificant reduction in epicardial fat infiltration in posterior LA (p = 0.34). CONCLUSIONS: Weight loss in an obese ovine model is associated with structural and electrophysiological reverse remodeling and a reduced propensity for AF. This provides evidence for the direct role of obesity in AF substrate and the role of weight reduction in patients with AF.


Asunto(s)
Fibrilación Atrial , Obesidad , Pérdida de Peso , Animales , Tejido Adiposo , Atrios Cardíacos/diagnóstico por imagen , Obesidad/complicaciones , Ovinos
11.
J Am Heart Assoc ; 9(24): e017861, 2020 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-33280488

RESUMEN

Background The physiology underlying "brain fog" in the absence of orthostatic stress in postural tachycardia syndrome (POTS) remains poorly understood. Methods and Results We evaluated cognitive and hemodynamic responses (cardiovascular and cerebral: heart rate, blood pressure, end-tidal carbon dioxide, and cerebral blood flow velocity (CBFv) in the middle cerebral artery at baseline, after initial cognitive testing, and after (30-minutes duration) prolonged cognitive stress test (PCST) whilst seated; as well as after 5-minute standing in consecutively enrolled participants with POTS (n=22) and healthy controls (n=18). Symptom severity was quantified with orthostatic hypotensive questionnaire at baseline and end of study. Subjects in POTS and control groups were frequency age- and sex-matched (29±11 versus 28±13 years; 86 versus 72% women, respectively; both P≥0.4). The CBFv decreased in both groups (condition, P=0.04) following PCST, but a greater reduction in CBFv was observed in the POTS versus control group (-7.8% versus -1.8%; interaction, P=0.038). Notably, the reduced CBFv following PCST in the POTS group was similar to that seen during orthostatic stress (60.0±14.9 versus 60.4±14.8 cm/s). Further, PCST resulted in greater slowing in psychomotor speed (6.1% versus 1.4%, interaction, P=0.027) and a greater increase in symptom scores at study completion (interaction, P<0.001) in the patients with POTS, including increased difficulty with concentration. All other physiologic responses (blood pressure and end-tidal carbon dioxide) did not differ between groups after PCST (all P>0.05). Conclusions Reduced CBFv and cognitive dysfunction were evident in patients with POTS following prolonged cognitive stress even in the absence of orthostatic stress.


Asunto(s)
Disfunción Cognitiva/fisiopatología , Arteria Cerebral Media/fisiopatología , Síndrome de Taquicardia Postural Ortostática/fisiopatología , Síndrome de Taquicardia Postural Ortostática/psicología , Adolescente , Adulto , Presión Sanguínea/fisiología , Dióxido de Carbono/fisiología , Estudios de Casos y Controles , Circulación Cerebrovascular/fisiología , Femenino , Frecuencia Cardíaca/fisiología , Hemodinámica/fisiología , Humanos , Masculino , Arteria Cerebral Media/diagnóstico por imagen , Pruebas Neuropsicológicas/normas , Intolerancia Ortostática/fisiopatología , Índice de Severidad de la Enfermedad , Ultrasonografía Doppler Transcraneal/métodos , Adulto Joven
12.
Clin Cancer Res ; 26(13): 3443-3454, 2020 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-32220887

RESUMEN

PURPOSE: Immune dysregulation is described in multiple myeloma. While preclinical models suggest a role for altered T-cell immunity in disease progression, the contribution of immune dysfunction to clinical outcomes remains unclear. We aimed to characterize marrow-infiltrating T cells in newly diagnosed patients and explore associations with outcomes of first-line therapy. EXPERIMENTAL DESIGN: We undertook detailed characterization of T cells from bone marrow (BM) samples, focusing on immune checkpoints and features of immune dysfunction, correlating with clinical features and progression-free survival. RESULTS: We found that patients with multiple myeloma had greater abundance of BM regulatory T cells (Tregs) which, in turn, expressed higher levels of the activation marker CD25 compared with healthy donors. Patients with higher frequencies of Tregs had shorter PFS and a distinct Treg immune checkpoint profile (increased PD-1, LAG-3) compared with patients with lower frequencies of Tregs. Analysis of CD4 and CD8 effectors revealed that low CD4effector (CD4eff):Treg ratio and increased frequency of PD-1-expressing CD4eff cells were independent predictors of early relapse over and above conventional risk factors, such as genetic risk and depth of response. Ex vivo functional analysis and RNA sequencing revealed that CD4 and CD8 cells from patients with greater abundance of CD4effPD-1+ cells displayed transcriptional and secretory features of dysfunction. CONCLUSIONS: BM-infiltrating T-cell subsets, specifically Tregs and PD-1-expressing CD4 effectors, negatively influence clinical outcomes in newly diagnosed patients. Pending confirmation in larger cohorts and further mechanistic work, these immune parameters may inform new risk models, and present potential targets for immunotherapeutic strategies.


Asunto(s)
Médula Ósea/patología , Linfocitos Infiltrantes de Tumor/inmunología , Mieloma Múltiple/etiología , Mieloma Múltiple/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Linfocitos T Reguladores/inmunología , Biomarcadores de Tumor , Estudios de Casos y Controles , Citocinas/metabolismo , Femenino , Humanos , Activación de Linfocitos/inmunología , Recuento de Linfocitos , Linfocitos Infiltrantes de Tumor/metabolismo , Linfocitos Infiltrantes de Tumor/patología , Masculino , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/mortalidad , Pronóstico , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Subgrupos de Linfocitos T/patología , Linfocitos T Reguladores/metabolismo , Linfocitos T Reguladores/patología
14.
JACC Clin Electrophysiol ; 5(10): 1101-1114, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31648734

RESUMEN

Education has long been recognized as an important component of chronic condition management. Whereas education has been evaluated in atrial fibrillation (AF) populations as part of multifaceted interventions, it has never been tested as a single entity. The aim of this review is to describe the rationale for and role of education as part of comprehensive AF management. The development and use of educational material as part of the intervention of a randomized controlled trial, the HELP-AF (Home-Based Education and Learning Program in AF) study, will be described. This study was designed to determine the impact of a home-based structured educational program on outcomes in individuals with AF. An educational resource was developed to facilitate delivery of 4 key messages targeted at empowering individuals to self-manage their condition. The key messages focused on strategies for managing future AF episodes, the role of pharmacotherapy in the treatment of AF, the appropriate use of medicines to manage stroke risk and the role of cardiovascular risk factor management in AF. To support structured educational visiting, an educational booklet titled Living Well With Atrial Fibrillation (AF) was developed by a multidisciplinary team and was further refined following input from expert clinicians and patient interviews. Using a structured educational visiting approach, education was delivered by trained clinicians within the patient's home.


Asunto(s)
Fibrilación Atrial/terapia , Folletos , Educación del Paciente como Asunto/métodos , Automanejo , Materiales de Enseñanza , Antiarrítmicos/uso terapéutico , Anticoagulantes/uso terapéutico , Manejo de la Enfermedad , Alfabetización en Salud , Visita Domiciliaria , Humanos , Conocimiento de la Medicación por el Paciente , Atención Dirigida al Paciente , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control
15.
Can J Cardiol ; 35(7): 846-854, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31292083

RESUMEN

BACKGROUND: Atrial fibrillation (AF) is a growing global epidemic, with its prevalence expected to significantly rise over coming decades. AF poses a substantial burden on health care systems, largely due to hospitalizations. Home-based clinical characterization has demonstrated improved outcomes in cardiac populations, but its impact on AF remains poorly defined. To test this hypothesis in AF, we developed the Home-Based Education and Learning Program for Patients With Atrial Fibrillation (HELP-AF) study. METHODS: The HELP-AF study is a prospective multicentre randomized controlled trial that will recruit 620 patients presenting to hospital emergency departments (EDs) with symptomatic AF (ANZCTR Registration: ACTRN12611000607976). Patients will be randomized to either the HELP-AF intervention or usual care. The intervention consists of 2 home visits by a nurse or pharmacist trained in the structured educational visiting (SEV) method. Patients in the control group will receive usual discharge follow-up care. RESULTS: The primary endpoints are total unplanned hospital admissions and quality of life. Secondary endpoints include AF symptom severity and burden score; time to first hospital admission; total unplanned days in hospital; total AF-related hospital admissions (including atrial flutter); total cardiac and noncardiac hospital admissions; total AF- or atrial flutter-related; cardiac- and noncardiac-related ED presentations; and all-cause mortality. An economic evaluation will also be performed. Clinical endpoints will be adjudicated by independent blinded assessors. Follow-up will be at 24 months. CONCLUSIONS: This study will assess the efficacy of a home-based structured patient-centred educational intervention in patients with AF.


Asunto(s)
Fibrilación Atrial/terapia , Servicio de Urgencia en Hospital , Servicios de Atención a Domicilio Provisto por Hospital , Educación del Paciente como Asunto , Humanos , Estudios Multicéntricos como Asunto , Admisión del Paciente , Estudios Prospectivos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto
16.
JACC Clin Electrophysiol ; 5(6): 692-701, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-31221356

RESUMEN

OBJECTIVES: This study sought to determine night-to-night variability in the severity of sleep-disordered breathing (SDB) and the dynamic intraindividual relationship to daily risk of incident atrial fibrillation (AF) by using simultaneous long-term day-by-day SDB and AF monitoring. BACKGROUND: Night-to-night variability in SDB severity may result in a dynamic exposure to SDB related conditions impacting the timing and extent of cardiovascular responses. METHODS: This study was an observational cohort study. Daily data for AF burden and average respiratory disturbance index (RDI) were extracted from pacemakers capable of monitoring nightly SDB and daily AF burden in 72 patients. Nightly RDI values were grouped into quartiles of severity within each patient. AF burdens of >5 min, >1 h, and >12 h were the outcome variables. RESULTS: A total of 32% of patients had a mean RDI of ≥20/h, indicative of overall severe SDB. There was significant night-to-night variation in RDI reflected by an absolute SD of ±6.3 events/h (range 2 to 14 events/h) within any given patient. Within each patient, the nights with the highest RDI (in their highest quartile) conferred a 1.7-fold (1.2 to 2.2; p < 0.001), 2.3-fold (1.6 to 3.5; p < 0.001), and 10.2-fold (3.5 to 29.9; p < 0.001) increase risk of having at least 5 min, 1 h, and 12 h, respectively, of AF during the same day compared with the best sleep nights (in their lowest quartiles). CONCLUSIONS: There is considerable night-to-night variability in SDB severity which cannot be detected by 1 single overnight sleep study. SDB burden may be a better metric with which to assess the extent of dynamic SDB related cardiovascular responses such as daily AF risk than the categorical diagnosis of SDB. (Night-to-Night Variability in Severity of Sleep Apnea and Daily Dynamic Atrial Fibrillation Risk [VARIOSA-AF]; ACTRN 12618000757213).


Asunto(s)
Fibrilación Atrial/epidemiología , Dispositivos de Terapia de Resincronización Cardíaca , Monitoreo Fisiológico , Síndromes de la Apnea del Sueño/fisiopatología , Estudios de Cohortes , Humanos , Incidencia , Modelos Logísticos , Índice de Severidad de la Enfermedad , Síndromes de la Apnea del Sueño/epidemiología
17.
Heart Lung Circ ; 28(4): e43-e46, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29885787

RESUMEN

INTRODUCTION: Recent registry data suggests oral anticoagulation (OAC) usage remains suboptimal in atrial fibrillation (AF) patients. The aim of our study was to determine if rates of appropriate use of OAC in individuals with AF differs between the emergency department (ED) and cardiac outpatient clinic (CO). METHODS: This was a retrospective study of consecutive AF patients over a 12-month period. Data from clinical records, discharge summaries and outpatient letters were independently reviewed by two investigators. Appropriateness of OAC was assessed according to the CHA2DS2-VASc score. RESULTS: Of 455 unique ED presentations with AF as a primary diagnosis, 115 patients who were treated and discharged from the ED were included. These were compared to 259 consecutively managed AF patients from the CO. Inappropriate OAC was significantly higher in the ED compared to the CO group (65 vs. 18%, p<0.001). Treatment in the ED was a significant multivariate predictor of inappropriate OAC (odds ratio 8.2 [4.8-17.7], p<0.001). CONCLUSIONS: This patient level data highlights that significant opportunity exists to improve disparities in the use of guideline adherent therapy in the ED compared to CO. There is an urgent need for protocol-driven treatment in the ED or streamlined early follow-up in a specialised AF clinic to address this treatment gap.


Asunto(s)
Anticoagulantes/administración & dosificación , Fibrilación Atrial/tratamiento farmacológico , Servicio de Urgencia en Hospital/tendencias , Pacientes Ambulatorios , Mejoramiento de la Calidad , Accidente Cerebrovascular/prevención & control , Terapia Trombolítica/métodos , Administración Oral , Anciano , Fibrilación Atrial/complicaciones , Australia/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología
18.
J Infect Dis ; 219(1): 89-100, 2019 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-30107546

RESUMEN

Objective: Immune activation is associated with morbidity and mortality during human immunodeficiency virus (HIV) infection, despite receipt of antiretroviral therapy (ART). We investigated whether microbial translocation drives immune activation in HIV-infected Ugandan children. Methods: Nineteen markers of immune activation and inflammation were measured over 96 weeks in HIV-infected Ugandan children in the CHAPAS-3 Trial and HIV-uninfected age-matched controls. Microbial translocation was assessed using molecular techniques, including next-generation sequencing. Results: Of 249 children included, 142 were infected with HIV; of these, 120 were ART naive, with a median age of 2.8 years (interquartile range [IQR], 1.7-4.0 years) and a median baseline CD4+ T-cell percentage of 20% (IQR, 14%-24%), and 22 were ART experienced, with a median age of 6.5 years (IQR, 5.9-9.2 years) and a median baseline CD4+ T-cell percentage of 35% (IQR, 31%-39%). The control group comprised 107 children without HIV infection. The median increase in the CD4+ T-cell percentage was 17 percentage points (IQR, 12-22 percentage points) at week 96 among ART-naive children, and the viral load was <100 copies/mL in 76% of ART-naive children and 91% of ART-experienced children. Immune activation decreased with ART use. Children could be divided on the basis of immune activation markers into the following 3 clusters: in cluster 1, the majority of children were HIV uninfected; cluster 2 comprised a mix of HIV-uninfected children and HIV-infected ART-naive or ART-experienced children; and in cluster 3, the majority were ART naive. Immune activation was low in cluster 1, decreased in cluster 3, and persisted in cluster 2. Blood microbial DNA levels were negative or very low across groups, with no difference between clusters except for Enterobacteriaceae organisms (the level was higher in cluster 1; P < .0001). Conclusion: Immune activation decreased with ART use, with marker clustering indicating different activation patterns according to HIV and ART status. Levels of bacterial DNA in blood were low regardless of HIV status, ART status, and immune activation status. Microbial translocation did not drive immune activation in this setting. Clinical Trials Registration: ISRCTN69078957.


Asunto(s)
Traslocación Bacteriana/inmunología , Biomarcadores/sangre , Infecciones por VIH/inmunología , Traslocación Bacteriana/genética , Recuento de Linfocito CD4 , Niño , Preescolar , ADN Bacteriano/sangre , ADN Ribosómico , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/microbiología , Humanos , Lactante , Inflamación , Masculino , Uganda , Carga Viral
20.
Int J Cardiol ; 272: 155-161, 2018 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-30057161

RESUMEN

BACKGROUND: Sleep-disordered breathing (SDB) is highly prevalent in patients with atrial fibrillation (AF) and its treatment can improve rhythm control. Polysomnography (PSG) is the gold standard for the diagnosis of SDB but its high cost and limited availability constrain its role as a standard SDB screening tool. We sought to assess the diagnostic utility of overnight oximetry in predicting SDB in AF patients. METHODS: We analyzed prospectively collected data on 439 patients with documented AF (62% paroxysmal AF) who underwent PSG. Overnight oximetry was used to determine the oxygen desaturation index (ODI, number of desaturation/h) by a novel automated computer algorithm. ODI was validated against PSG derived apnea-hypopnea index (AHI). RESULTS: The sample consisted of 69% men with a mean age of 59.9 ±â€¯11.3 years and body mass index of 30 ±â€¯5 kg/m2. The median AHI was 9.5 [3.6-21.0]/h and the prevalence of moderate (AHI 15-29/h) and severe SDB (AHI ≥ 30/h) was 17.3% and 16.6% respectively. The ODI was able to detect moderate-to-severe SDB (AHI ≥ 15/h; area under the receiver-operating-characteristic curve (AUC): 0.951, 95% CI: 0.929-0.972) and severe SDB (AHI ≥ 30/h; 0.932, 95% CI: 0.895-0.968) with high diagnostic accuracy. An ODI cut-off of 4.1/h resulted in a 91% sensitivity and 83% specificity in discriminating between patients with and without AHI ≥ 15/h. An ODI of 7.6/h yielded a sensitivity and specificity for AHI ≥ 30/h of 89% and 83%, respectively. CONCLUSIONS: ODI derived from a simple and low-cost overnight oximetry can be used as an accessible and reliable screening tool, particularly to rule out SDB.


Asunto(s)
Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Oximetría/normas , Síndromes de la Apnea del Sueño/diagnóstico , Síndromes de la Apnea del Sueño/epidemiología , Anciano , Fibrilación Atrial/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oximetría/métodos , Polisomnografía/métodos , Polisomnografía/normas , Estudios Prospectivos , Reproducibilidad de los Resultados , Síndromes de la Apnea del Sueño/fisiopatología
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