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1.
Can Fam Physician ; 63(1): 45-50, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28115442

RESUMEN

OBJECTIVE: To determine if comorbidities and high-risk medications affect the frequency of family physician visits among older patients. DESIGN: Retrospective chart review. SETTING: Academic family health team at Sunnybrook Health Sciences Centre in Toronto, Ont. PARTICIPANTS: Among patients aged 65 years and older who were registered patients of the family health team between July 1, 2013, and June 30, 2014, the 5% who visited their family physicians most frequently and the 5% who visited their family physicians least frequently were selected for the study (N = 265). MAIN OUTCOME MEASURES: Predictors of frequent visits to family physicians. RESULTS: The significant predictors of being a high-frequency user were female sex (odds ratio [OR] = 2.20, P = .03), age older than 85 years (OR = 5.35, P = .001), and higher total number of medications (OR = 1.49, P < .001). Age-adjusted Charlson comorbidity index score, number of Beers criteria medications, and Anticholinergic Risk Scale score were not significant predictors (P > .05). CONCLUSION: Female sex, age older than 85, and higher total number of medications were independent significant predictors of higher frequency of family physician visits among older patients. Validated tools, such as the Charlson comorbidity index, Beers criteria, and Anticholinergic Risk Scale, did not independently predict the frequency of visits, indicating that predicting frequency of visits is likely complex.


Asunto(s)
Comorbilidad , Medicina Familiar y Comunitaria/organización & administración , Prescripción Inadecuada/estadística & datos numéricos , Visita a Consultorio Médico/estadística & datos numéricos , Atención Primaria de Salud/organización & administración , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Modelos Logísticos , Masculino , Oportunidad Relativa , Ontario , Estudios Retrospectivos , Factores de Riesgo
2.
Proc Natl Acad Sci U S A ; 108(42): 17544-9, 2011 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-21976486

RESUMEN

Cells sense and respond to changes in oxygen concentration through gene regulatory processes that are fundamental to survival. Surprisingly, little is known about how anemia affects hypoxia signaling. Because nitric oxide synthases (NOSs) figure prominently in the cellular responses to acute hypoxia, we defined the effects of NOS deficiency in acute anemia. In contrast to endothelial NOS or inducible NOS deficiency, neuronal NOS (nNOS)(-/-) mice demonstrated increased mortality during anemia. Unlike wild-type (WT) animals, anemia did not increase cardiac output (CO) or reduce systemic vascular resistance (SVR) in nNOS(-/-) mice. At the cellular level, anemia increased expression of HIF-1α protein and HIF-responsive mRNA levels (EPO, VEGF, GLUT1, PDK1) in the brain of WT, but not nNOS(-/-) mice, despite comparable reductions in tissue PO(2). Paradoxically, nNOS(-/-) mice survived longer during hypoxia, retained the ability to regulate CO and SVR, and increased brain HIF-α protein levels and HIF-responsive mRNA transcripts. Real-time imaging of transgenic animals expressing a reporter HIF-α(ODD)-luciferase chimeric protein confirmed that nNOS was essential for anemia-mediated increases in HIF-α protein stability in vivo. S-nitrosylation effects the functional interaction between HIF and pVHL. We found that anemia led to nNOS-dependent S-nitrosylation of pVHL in vivo and, of interest, led to decreased expression of GSNO reductase. These findings identify nNOS effects on the HIF/pVHL signaling pathway as critically important in the physiological responses to anemia in vivo and provide essential mechanistic insight into the differences between anemia and hypoxia.


Asunto(s)
Anemia/fisiopatología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Óxido Nítrico Sintasa de Tipo I/metabolismo , Adaptación Fisiológica , Anemia/genética , Animales , Encéfalo/irrigación sanguínea , Encéfalo/metabolismo , Gasto Cardíaco , Células Endoteliales de la Vena Umbilical Humana , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Óxido Nítrico Sintasa de Tipo I/deficiencia , Óxido Nítrico Sintasa de Tipo I/genética , Oxígeno/sangre , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transducción de Señal , Resistencia Vascular , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/metabolismo
4.
Can J Anaesth ; 57(8): 779-91, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20512540

RESUMEN

PURPOSE: Clinical studies demonstrate that anemia increases the risk of morbidity and mortality. Tissue hypoxia is an attractive but incompletely characterized candidate mechanism of anemia-induced organ injury. Physiological responses that optimize tissue oxygen delivery (nitric oxide synthase-NOS) and promote cellular adaptation to tissue hypoxia (hypoxia inducible factor-HIF) may reduce the risk of hypoxic organ injury and thereby improve survival during anemia. The presence of vascular diseases would likely impair the efficacy of these physiological mechanisms, increasing the risk of anemia-induced organ injury. In all cases, biological signals that indicate the activation of these adaptive mechanisms could provide an early and treatable warning signal of impending anemia-induced organ injury. Thus, we review the evidence for tissue hypoxia during acute hemodilutional anemia and also explore the novel hypothesis that methemoglobin, a measurable byproduct of increased NOS-derived nitric oxide (NO), may serve as a biomarker for "anemic stress". SOURCE: Published peer-reviewed studies provided the main source of information. Data from experimental studies were reassessed to derive the relationship between hemodilution (reduced hemoglobin concentration) and increased methemoglobin levels. PRINCIPAL FINDINGS: Active physiological mechanisms (sympathetic nervous system) are required to maintain optimal tissue oxygen delivery during hemodilutional anemia. Despite these responses, tissue hypoxia occurs during acute hemodilution, as demonstrated by a decrease in tissue PO(2) and an increase in hypoxic cellular responses (NOS, HIF). Optimal tissue oxygen delivery may be compromised further when cardiovascular responses are impaired. The positive correlation between decreased hemoglobin concentration (Hb) and an increase in methemoglobin levels in acutely anemic animals supports the hypothesis that anemia-induced increases in tissue NOS activity could promote methemoglobin formation. Methemoglobin may be a measurable byproduct of NO-mediated Hb oxidation. CONCLUSIONS: Evidence continues to demonstrate that anemia increases morbidity and mortality, possibly via hypoxic mechanisms. A potential strategy for assessing "anemic stress" was derived from experimental data based on a readily measurable biomarker, methemoglobin. New methods for measuring real-time hemoglobin and methemoglobin levels in patients may provide the basis to translate this idea into clinical practice. Further mechanistic studies are required to determine if the impact of reduced tissue oxygen delivery and activation of hypoxic cellular mechanism can be linked to measurable changes in biomarkers and clinical outcomes in acutely anemic patients.


Asunto(s)
Anemia/epidemiología , Anemia/etiología , Hemodilución/efectos adversos , Anemia/mortalidad , Animales , Biomarcadores , Humanos , Hipoxia/metabolismo , Enfermedades Renales/epidemiología , Enfermedades Renales/etiología , Metahemoglobina/metabolismo , Isquemia Miocárdica/epidemiología , Isquemia Miocárdica/etiología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo I/metabolismo , Consumo de Oxígeno/fisiología , Ratas , Ratas Sprague-Dawley , Medición de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Sistema Nervioso Simpático/fisiopatología
5.
Anesthesiology ; 111(5): 988-1000, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19809291

RESUMEN

BACKGROUND: Perioperative beta-blockade and anemia are independent predictors of increased stroke and mortality by undefined mechanisms. This study investigated the effect of beta-blockade on cerebral tissue oxygen delivery in an experimental model of blood loss and fluid resuscitation (hemodilution). METHODS: Anesthetized rats were treated with metoprolol (3 mg x kg) or saline before undergoing hemodilution with pentastarch (1:1 blood volume exchange, 30 ml x kg). Outcomes included cardiac output, cerebral blood flow, and brain (PBrO2) and kidney (PKO2) tissue oxygen tension. Hypoxia inducible factor-1alpha (HIF-1alpha) protein levels were assessed by Western blot. Systemic catecholamines, erythropoietin, and angiotensin II levels were measured. RESULTS: Hemodilution increased heart rate, stroke volume, cardiac output (60%), and cerebral blood flow (50%), thereby maintaining PBrO2 despite an approximately 50% reduction in blood oxygen content (P < 0.05 for all). By contrast, PKO2 decreased (50%) under the same conditions (P < 0.05). Beta-blockade reduced baseline heart rate (20%) and abolished the compensatory increase in cardiac output after hemodilution (P < 0.05). This attenuated the cerebral blood flow response and reduced PBrO2 (50%), without further decreasing PKO2. Cerebral HIF-1alpha protein levels were increased in beta-blocked hemodiluted rats relative to hemodiluted controls (P < 0.05). Systemic catecholamine and erythropoietin levels increased comparably after hemodilution in both groups, whereas angiotensin II levels increased only after beta-blockade and hemodilution. CONCLUSIONS: Cerebral tissue oxygen tension is preferentially maintained during hemodilution, relative to the kidney, despite elevated systemic catecholamines. Acute beta-blockade impaired the compensatory cardiac output response to hemodilution, resulting in a reduction in cerebral tissue oxygen tension and increased expression of HIF-1alpha.


Asunto(s)
Antagonistas Adrenérgicos beta/farmacología , Encéfalo/efectos de los fármacos , Hemodilución , Metoprolol/farmacología , Oxígeno/metabolismo , Angiotensina II/sangre , Animales , Encéfalo/metabolismo , Gasto Cardíaco/efectos de los fármacos , Catecolaminas/sangre , Circulación Cerebrovascular/efectos de los fármacos , Eritropoyetina/sangre , Subunidad alfa del Factor 1 Inducible por Hipoxia/análisis , Masculino , Metoprolol/efectos adversos , Ratas , Ratas Sprague-Dawley , Accidente Cerebrovascular/etiología
6.
Circ Cardiovasc Qual Outcomes ; 11(11): e004683, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30354285

RESUMEN

BACKGROUND: Chest pain is one of the most common reasons for emergency department (ED) visits in developed countries. Whether higher volume EDs have better outcomes, specifically for patients with chest pain, is unknown and pertinent. METHODS AND RESULTS: We conducted a study using population-based data on 498 291 patients ≥40 years old, presenting to ED in Ontario, Canada from 2008 to 2014, with chest pain and were discharged after assessment. We evaluated processes of care after discharge from ED. The primary outcome was a composite of all-cause death or hospitalization for acute coronary syndrome. Hierarchical logistic regression models adjusting for potential confounding variables were used to evaluate the association of annual ED chest pain volume and outcome. We also determined if there was a volume threshold above which an increased ED volume was not associated with a lower adverse outcome. The mean age of our patients was 59 years, 46.7% were men, and 20% had diabetes mellitus. Patients discharged from higher volume EDs had higher rates of cardiologist consultations, cardiac medication use, and cardiac testing within 30 days of ED assessment. Higher ED volume was associated with significantly lower adjusted odds ratio for mortality or acute coronary syndrome (odds ratio, 0.87; 95% CI, 0.82-0.92 per each unit increase in the log of volume) at 30 days and at 1 year (odds ratio, 0.92; 95% CI, 0.88-0.92). Once the annual ED chest pain volume reached 1400 cases (95% CI, 910-1900), an increase of annual chest pain volume of 100 was associated with relative decrease in the odds of the composite outcome at 30 days of <1%. CONCLUSIONS: Evaluations of chest pain in EDs with higher chest pain volume had lower rates of death or hospitalizations for acute coronary syndrome. There was a volume threshold above which an increase in volume was no longer associated with reduced outcomes.


Asunto(s)
Síndrome Coronario Agudo/diagnóstico , Dolor en el Pecho/diagnóstico , Infarto del Miocardio/diagnóstico , Anciano , Servicio de Urgencia en Hospital , Femenino , Hospitalización , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Ontario/epidemiología , Dimensión del Dolor , Alta del Paciente
7.
J Clin Epidemiol ; 67(6): 622-8, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24508144

RESUMEN

OBJECTIVES: A P-value <0.05 is one metric used to evaluate the results of a randomized controlled trial (RCT). We wondered how often statistically significant results in RCTs may be lost with small changes in the numbers of outcomes. STUDY DESIGN AND SETTING: A review of RCTs in high-impact medical journals that reported a statistically significant result for at least one dichotomous or time-to-event outcome in the abstract. In the group with the smallest number of events, we changed the status of patients without an event to an event until the P-value exceeded 0.05. We labeled this number the Fragility Index; smaller numbers indicated a more fragile result. RESULTS: The 399 eligible trials had a median sample size of 682 patients (range: 15-112,604) and a median of 112 events (range: 8-5,142); 53% reported a P-value <0.01. The median Fragility Index was 8 (range: 0-109); 25% had a Fragility Index of 3 or less. In 53% of trials, the Fragility Index was less than the number of patients lost to follow-up. CONCLUSION: The statistically significant results of many RCTs hinge on small numbers of events. The Fragility Index complements the P-value and helps identify less robust results.


Asunto(s)
Interpretación Estadística de Datos , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Perdida de Seguimiento , Tamaño de la Muestra
8.
BMJ ; 342: d1569, 2011 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-21444636

RESUMEN

OBJECTIVE: To investigate the impact of industry funding on reporting of subgroup analyses in randomised controlled trials. DESIGN: Systematic review. DATA SOURCES: Medline. STUDY SELECTION: Randomised controlled trials published in 118 core clinical journals (defined by the National Library of Medicine) in 2007. 1140 study reports in a 1:1 ratio by high (five general medicine journals with largest number of total citations in 2007) versus lower impact journals, were randomly sampled. Two reviewers, independently and in duplicate, used standardised, piloted forms to screen study reports for eligibility and to extract data. They also used explicit criteria to determine whether a randomised controlled trial reported subgroup analyses. Logistic regression was used to examine the association of prespecified study characteristics with reporting versus not reporting of subgroup analyses. RESULTS: 469 randomised controlled trials were included, of which 207 (44%) reported subgroup analyses. High impact journals (adjusted odds ratio 2.64, 95% confidence interval 1.62 to 4.33), non-surgical (versus surgical) trials (2.10, 1.26 to 3.50), and larger sample size (3.38, 1.64 to 6.99) were associated with more frequent reporting of subgroup analyses. The strength of association between trial funding and reporting of subgroups differed in trials with and without statistically significant primary outcomes (interaction P=0.02). In trials without statistically significant results for the primary outcome, industry funded trials were more likely to report subgroup analyses (2.29, 1.30 to 4.72) than non-industry funded trials. This was not true for trials with a statistically significant primary outcome (0.79, 0.46 to 1.36). Industry funded trials were associated with less frequent prespecification of subgroup hypotheses (31.3% v 38.0%, adjusted odds ratio 0.49, 0.26 to 0.94), and less use of the interaction test for analyses of subgroup effects (41.4% v 49.1%, 0.52, 0.28 to 0.97) than non-industry funded trials. CONCLUSION: Industry funded randomised controlled trials, in the absence of statistically significant primary outcomes, are more likely to report subgroup analyses than non-industry funded trials. Industry funded trials less frequently prespecify subgroup hypotheses and less frequently test for interaction than non-industry funded trials. Subgroup analyses from industry funded trials with negative results for the primary outcome should be viewed with caution.


Asunto(s)
Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Proyectos de Investigación , Recolección de Datos/métodos , Análisis de Regresión
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