RESUMEN
BACKGROUND: Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. METHODS: In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. FINDINGS: Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88-1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90-1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41-0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22-3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31-0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64-0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37-3·91], p=0·771) was similar. INTERPRETATION: In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status. FUNDING: National Institute of Neurological Disorders and Stroke.
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Hemorragia Cerebral Intraventricular/terapia , Drenaje/métodos , Fibrinolíticos/uso terapéutico , Cloruro de Sodio/uso terapéutico , Accidente Cerebrovascular/terapia , Irrigación Terapéutica/métodos , Activador de Tejido Plasminógeno/uso terapéutico , Anciano , Hemorragia Cerebral Intraventricular/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: In the treatment of severe intraventricular hemorrhage (IVH), thrombolytic use and clot size are known to influence clot lysis rates. We evaluated the effect of other variables on IVH clot lysis rates among patients treated with recombinant tissue-type plasminogen activator or placebo. METHODS: One hundred patients with IVH and intracerebral hemorrhage volume <30 mL requiring emergency external ventricular drainage from 2 multicenter trials were treated with intraventricular administration of recombinant tissue-type plasminogen activator (n=78; 53 males, 25 females) or placebo (n=22; 7 males, 15 females). IVH volume was quantified daily by head CT. A segmented linear regression using an optimized spline knot for each patient was fit. Random effects linear regression was used to estimate the effect of prespecified patient characteristics on clot lysis rates over the first 6 days. RESULTS: Stability IVH volumes were larger in males (N=60; 54 ± 5 mL) than females (N=40; 36 ± 5 mL; P=0.01). Intraventricular thrombolytic treatment was associated with an increase in clot lysis rate of 14.6% of stability IVH volume/day before the spline knot compared with the placebo group (P<0.001). After adjustment for thrombolytic, higher baseline serum plasminogen and lower baseline platelet count were independently associated with an increase in clot lysis of 1.28%/day per 10-g/dL increase (P<0.001) and 0.70% /day per 10×10(3)/uL decrease (P<0.001) before the knot, respectively. CONCLUSIONS: Although thrombolysis remains the major determinant of IVH clot lysis rate, higher baseline serum plasminogen and lower platelet count also predict faster clot lysis. Further studies are needed to confirm whether plasminogen availability and thrombus structure impact IVH clot removal. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique identifier: NCT00650858.
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Hemorragia Cerebral/sangre , Hemorragia Cerebral/tratamiento farmacológico , Fibrinolíticos/uso terapéutico , Plasminógeno/metabolismo , Activador de Tejido Plasminógeno/uso terapéutico , Anciano , Anciano de 80 o más Años , Femenino , Fibrinolíticos/administración & dosificación , Humanos , Infusiones Intraventriculares , Modelos Lineales , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Valor Predictivo de las Pruebas , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/uso terapéutico , Caracteres Sexuales , Factores de Tiempo , Activador de Tejido Plasminógeno/administración & dosificaciónRESUMEN
BACKGROUND AND PURPOSE: Patients with intracerebral hemorrhage and intraventricular hemorrhage have a reported mortality of 50% to 80%. We evaluated a clot lytic treatment strategy for these patients in terms of mortality, ventricular infection, and bleeding safety events, and for its effect on the rate of intraventricular clot lysis. METHODS: Forty-eight patients were enrolled at 14 centers and randomized to treatment with 3 mg recombinant tissue-type plasminogen activator (rtPA) or placebo. Demographic characteristics, severity factors, safety outcomes (mortality, infection, bleeding), and clot resolution rates were compared in the 2 groups. RESULTS: Severity factors, including admission Glasgow Coma Scale, intracerebral hemorrhage volume, intraventricular hemorrhage volume, and blood pressure were evenly distributed, as were adverse events, except for an increased frequency of respiratory system events in the placebo-treated group. Neither intracranial pressure nor cerebral perfusion pressure differed substantially between treatment groups on presentation, with external ventricular device closure, or during the active treatment phase. Frequency of death and ventriculitis was substantially lower than expected and bleeding events remained below the prespecified threshold for mortality (18% rtPA; 23% placebo), ventriculitis (8% rtPA; 9% placebo), symptomatic bleeding (23% rtPA; 5% placebo, which approached statistical significance; P=0.1). The median duration of dosing was 7.5 days for rtPA and 12 days for placebo. There was a significant beneficial effect of rtPA on rate of clot resolution. CONCLUSIONS: Low-dose rtPA for the treatment of intracerebral hemorrhage with intraventricular hemorrhage has an acceptable safety profile compared to placebo and historical controls. Data from a well-designed phase III clinical trial, such as CLEAR III, will be needed to fully evaluate this treatment.
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Coagulación Sanguínea/fisiología , Hemorragia Cerebral/tratamiento farmacológico , Terapia Trombolítica/métodos , Trombosis/tratamiento farmacológico , Activador de Tejido Plasminógeno/administración & dosificación , Hemorragia Cerebral/fisiopatología , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Placebos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Trastornos Respiratorios/inducido químicamente , Trombosis/fisiopatología , Activador de Tejido Plasminógeno/efectos adversos , Resultado del Tratamiento , Regulación hacia Arriba/fisiologíaRESUMEN
PURPOSE: To evaluate change from baseline to 12 months follow-up in study and nonstudy (fellow) eye visual fields from the Ischemic Optic Neuropathy Decompression Trial (IONDT). DESIGN: Randomized controlled trial and observational study. PARTICIPANTS: The IONDT enrolled patients >or=50 years with acute nonarteritic ischemic optic neuropathy (NAION). Randomized patients (n = 258) had visual acuity
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Neuropatía Óptica Isquémica/fisiopatología , Campos Visuales/fisiología , Enfermedad Aguda , Anciano , Descompresión Quirúrgica , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Neuropatía Óptica Isquémica/cirugía , Factores de Tiempo , Agudeza Visual/fisiología , Pruebas del Campo VisualRESUMEN
PURPOSE: To determine the role of vision and visual attention factors in automobile crash involvement. METHODS: Drivers aged 65 to 84 years were identified during the baseline interview (1993-1995) of the Salisbury Eye Evaluation (SEE) Study. Crash involvement through December 1997 was determined from Maryland State motor vehicle records. Vision tests at baseline included distance acuity at normal and low luminance, contrast sensitivity, glare sensitivity, stereoacuity, and visual fields. Visual attention was evaluated with the Useful Field of View Test (UFOV; Visual Awareness, Chicago, IL). Survival analysis was used to determine the relative risk of a crash as a function of demographic variables, miles driven, vision, and visual attention. RESULTS: One hundred twenty (6.7%) of the 1801 drivers were involved in a crash during the observation interval. Glare sensitivity and binocular field loss were significant predictors of crash involvement (P < 0.05). For those with moderate or better vision (<3 letters for glare sensitivity and <20 points missed for binocular visual fields) increased glare sensitivity or reduced visual fields were, paradoxically, associated with a reduction in crash risk, whereas for those with poorer levels of vision, increased glare sensitivity or reduced visual fields were associated with increased crash risk. Worse UFOV score was associated with increased crash risk. CONCLUSIONS: Glare sensitivity, visual field loss, and UFOV were significant predictors of crash involvement. Acuity, contrast sensitivity, and stereoacuity were not associated with crashes. These results suggest that current vision screening for drivers' licensure, based primarily on visual acuity, may miss important aspects of visual impairment.
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Accidentes de Tránsito , Conducción de Automóvil , Trastornos de la Visión/fisiopatología , Personas con Daño Visual , Anciano , Anciano de 80 o más Años , Cognición/fisiología , Sensibilidad de Contraste/fisiología , Femenino , Deslumbramiento , Humanos , Masculino , Estudios Prospectivos , Factores de Riesgo , Selección Visual , Agudeza Visual/fisiología , Campos Visuales/fisiologíaRESUMEN
BACKGROUND: Craniotomy, according to the results from trials, does not improve functional outcome after intracerebral haemorrhage. Whether minimally invasive catheter evacuation followed by thrombolysis for clot removal is safe and can achieve a good functional outcome is not known. We investigated the safety and efficacy of alteplase, a recombinant tissue plasminogen activator, in combination with minimally invasive surgery (MIS) in patients with intracerebral haemorrhage. METHODS: MISTIE was an open-label, phase 2 trial that was done in 26 hospitals in the USA, Canada, the UK, and Germany. We used a computer-generated allocation sequence with a block size of four to centrally randomise patients aged 18-80 years with a non-traumatic (spontaneous) intracerebral haemorrhage of 20 mL or higher to standard medical care or image-guided MIS plus alteplase (0·3 mg or 1·0 mg every 8 h for up to nine doses) to remove clots using surgical aspiration followed by alteplase clot irrigation. Primary outcomes were all safety outcomes: 30 day mortality, 7 day procedure-related mortality, 72 h symptomatic bleeding, and 30 day brain infections. This trial is registered with ClinicalTrials.gov, number NCT00224770. FINDINGS: Between Feb 2, 2006, and April 8, 2013, 96 patients were randomly allocated and completed follow-up: 54 (56%) in the MIS plus alteplase group and 42 (44%) in the standard medical care group. The primary outcomes did not differ between the standard medical care and MIS plus alteplase groups: 30 day mortality (four [9·5%, 95% CI 2·7-22.6] vs eight [14·8%, 6·6-27·1], p=0·542), 7 day mortality (zero [0%, 0-8·4] vs one [1·9%, 0·1-9·9], p=0·562), symptomatic bleeding (one [2·4%, 0·1-12·6] vs five [9·3%, 3·1-20·3], p=0·226), and brain bacterial infections (one [2·4%, 0·1-12·6] vs zero [0%, 0-6·6], p=0·438). Asymptomatic haemorrhages were more common in the MIS plus alteplase group than in the standard medical care group (12 [22·2%; 95% CI 12·0-35·6] vs three [7·1%; 1·5-19·5]; p=0·051). INTERPRETATION: MIS plus alteplase seems to be safe in patients with intracerebral haemorrhage, but increased asymptomatic bleeding is a major cautionary finding. These results, if replicable, could lead to the addition of surgical management as a therapeutic strategy for intracerebral haemorrhage. FUNDING: National Institute of Neurological Disorders and Stroke, Genentech, and Codman.
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Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/cirugía , Fibrinolíticos/farmacología , Evaluación de Resultado en la Atención de Salud , Hemorragia Posoperatoria/etiología , Trombectomía/métodos , Activador de Tejido Plasminógeno/farmacología , Anciano , Hemorragia Cerebral/mortalidad , Terapia Combinada , Femenino , Fibrinolíticos/administración & dosificación , Fibrinolíticos/efectos adversos , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos , Cirugía Asistida por Computador , Trombectomía/efectos adversos , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/efectos adversosRESUMEN
OBJECTIVE: Animal models and clinical studies suggest that intraventricular thrombolysis improves clot resolution and clinical outcomes among patients with intraventricular hemorrhage. However, this intervention may increase the rates of rebleeding and infection. To assess the safety and efficacy of intraventricular thrombolysis, we conducted a pilot, randomized, double-blind, controlled, multicenter study. METHODS: Patients with intraventricular hemorrhage requiring ventriculostomy were randomized to receive intraventricular injections of normal saline solution or urokinase (25000 international units) at 12-hour intervals. Injections continued until ventricular drainage was discontinued according to prespecified clinical criteria. Head computed tomographic scans were obtained daily, for quantitative determinations of intraventricular hemorrhage volumes. The rate of clot resolution was estimated for each group. RESULTS: Twelve subjects were enrolled (urokinase, seven patients; placebo, five patients). Commercial withdrawal of urokinase precluded additional enrollment. The urokinase and placebo groups were similar with respect to age (49.6 versus 55.2 yr, P = 0.43) and presenting Glasgow Coma Scale scores (7.14 versus 8.00, P = 0.72). Randomization to the urokinase treatment arm (P = 0.02) and female sex (P = 0.008) favorably affected the clot resolution rate. The sex-adjusted clot half-life for the urokinase-treated group was reduced 44.6%, compared with the value for the placebo group (4.69 versus 8.48 d). CONCLUSION: Intraventricular thrombolysis with urokinase speeds the resolution of intraventricular blood clots, compared with treatment with ventricular drainage alone.
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Hemorragia Cerebral/tratamiento farmacológico , Ventrículos Cerebrales , Embolia Intracraneal/tratamiento farmacológico , Terapia Trombolítica/métodos , Activador de Plasminógeno de Tipo Uroquinasa/administración & dosificación , Adulto , Anciano , Volumen Sanguíneo/efectos de los fármacos , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/diagnóstico por imagen , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Inyecciones Intraventriculares , Embolia Intracraneal/diagnóstico , Embolia Intracraneal/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Tomografía Computarizada por Rayos X , Activador de Plasminógeno de Tipo Uroquinasa/efectos adversos , VentriculostomíaRESUMEN
A cohort of 4729 junior college students in an urban and a rural area in Taiwan was followed up for a period of 20 months. Students' characteristics, including riding exposures, as well as human, vehicular, and environmental factors were collected using one initial and three follow-up questionnaires. The Anderson-Gill (AG) multiplicative intensity model was used to determine the risk of a motorcycle crash over time while also allowing for the modeling of multiple events. The average response rate for the four assessments was 92%. The adjusted relative hazard (RH) for students living in the rural as opposed to the urban area for crashes was 1.67 at the beginning of the study but decreased to 0.66 by the end. Past motorcycle crash history, number of riding days, average riding distance, risk-taking level, alcohol consumption, and traffic violations were all significantly associated with an increased risk of being involved in a crash. Conversely, increasing age, riding experience, and automobile licensure were related to a decreased risk of crashing. Furthermore, helmet use was not independently related to the risk of crashing. In conclusion, a high-risk group predisposed to involvement in a motorcycle crash, including both non-injury and injury-related crashes, can be identified using selected risk factors for crash prevention among young riders.
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Accidentes de Tránsito/prevención & control , Motocicletas , Estudiantes , Accidentes de Tránsito/estadística & datos numéricos , Adolescente , Adulto , Análisis Factorial , Femenino , Humanos , Estudios Longitudinales , Masculino , Análisis Multivariante , Análisis de Regresión , Factores de Riesgo , Asunción de Riesgos , Población Rural , Estudiantes/estadística & datos numéricos , Taiwán/epidemiología , Población UrbanaRESUMEN
BACKGROUND: In adults, intraventricular thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) facilitates resolution of intraventricular haemorrhage (IVH), reduces intracranial pressure, decreases duration of cerebrospinal fluid diversion, and may ameliorate direct neural injury. We hypothesize that patients with small parenchymal haematoma volumes (<30 cc) and relatively large IVH causing acute obstructive hydrocephalus would have improved clinical outcomes when given injections of low-dose rtPA to accelerate lysis and evacuation of IVH compared with placebo. METHODS: The Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage III trial is an investigator-initiated, phase III, randomized, multicenter, double-blind, placebo-controlled study comparing the use of external ventricular drainage (EVD) combined with intraventricular injection of rtPA to EVD plus intraventricular injection of normal saline (placebo) for the treatment of IVH. Patients with known symptom onset within 24 h of the computed tomography scan confirmed IVH and third or fourth ventricle obstruction, with or without supratentorial intracerebral haemorrhage volume <30 cc, who require EVD are screened with a computed tomography scan at least six hours after EVD placement and, if necessary, at consecutive 12-h intervals until stabilization of any intracranial bleeding has been established. Patients who meet clinical and imaging criteria (no ongoing coagulopathy and no suspicion of aneurysm, arteriovenous malformation, or any other vascular anomaly) will be randomized to either intraventricular rtPA or placebo. RESULTS: The primary outcome measure is dichotomized modified Rankin Scale 0-3 vs. 4-6 at 180 days. Clinical secondary outcomes include additional modified Rankin Scale dichotomizations at 180 days (0-4 vs. 5-6), ordinal modified Rankin Scale (0-6), mortality and safety events at 30 days, mortality at 180 days, functional status measures, type and intensity of intensive care unit management, rate and extent of ventricular blood clot removal, and quality of life measures.
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Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/etiología , Ventrículos Cerebrales/efectos de los fármacos , Accidente Cerebrovascular/complicaciones , Activador de Tejido Plasminógeno/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Terapia Trombolítica/métodos , Tomógrafos Computarizados por Rayos X , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Recent reports suggest that when thrombolytic agents are administered within the clot, lysis rate accelerates at the expense of increased risk of worsening edema. To test this hypothesis, we report on the volumetric analysis of (1) the intraparenchymal hematoma and, (2) perihematomal edema in a cohort of ICH patients treated with intraclot rtPA. METHODS: A convenience sample of highly selected ICH patients underwent frameless stereotactic aspiration and thrombolysis (FAST) of the clot. Two milligrams of rtPA were administered every 12 h until ICH volume < or =10 cc, or catheter fenestrations were no longer in continuity with the clot. ICH and perihematomal edema volumes were calculated from CT scans. Using random effects linear regression we estimated the rate of hematoma and edema volume resolution as well as their relationship during the first 8 days of lytic therapy. RESULTS: Fifteen patients were treated, mean age: 60.7 years, median time from ictus to FAST: 1 (range 0-3) day. Using a random effects model that considered volume resolution over the first 8 days following lytic therapy we found that the both percentage hematoma and percentage perihematoma edema resolution per day were quadratic with respect to time. Percentage residual hematoma volume on day K = 97.7% - [24.36%*K] + [1.89%*K (2)]; P < 0.001 for both terms. Percentage residual edema on day K = 97.4% - [13.94%*K] + [1.30%*K (2)]; P < 0.001 for K and P = 0.01 for K (2). Examination of each patient's volume data suggests that there exists a strong direct relationship between perihematoma edema volume and same day hematoma volume. CONCLUSIONS: In this cohort of ICH patients treated using FAST, volumetric analysis of ICH and perihematomal edema seems to suggest that local use of rtPA does not exacerbate brain edema formation. Furthermore, there seems to be a strong association between reduction in ICH volume and reduction in edema volume, as would be expected following the concept of "hemotoxicity" postulated by some investigators.
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Edema Encefálico/tratamiento farmacológico , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/cirugía , Trombectomía/métodos , Terapia Trombolítica , Adulto , Anciano de 80 o más Años , Edema Encefálico/diagnóstico por imagen , Hemorragia Cerebral/diagnóstico por imagen , Niño , Terapia Combinada , Femenino , Hematoma/diagnóstico por imagen , Hematoma/tratamiento farmacológico , Hematoma/cirugía , Humanos , Masculino , Persona de Mediana Edad , Técnicas Estereotáxicas , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
BACKGROUND: The existence of race and gender differences in the provision of cardiovascular health care has been increasingly recognized. However, few studies have examined whether these differences exist in the emergency department (ED) setting. OBJECTIVES: To evaluate race, gender, and insurance differences in the receipt of early, noninvasive diagnostic tests among persons presenting to an ED with a complaint of chest pain. METHODS: Data were drawn from the U.S. National Hospital Ambulatory Health Care Survey of EDs. Visits made during 1995-2000 by persons aged 30 years or older with chest pain as a reason for the visit were included. Factors affecting the likelihood of ordering electrocardiography, cardiac monitoring, oxygen saturation measurement using pulse oximetry, and chest radiography were analyzed using multivariate probit analysis. RESULTS: A total of 7,068 persons aged 30 years or older presented to an ED with a primary complaint of chest pain during the six-year period, corresponding to more than 32 million such visits nationally. The adjusted probability of ordering a test was highest for non-African American patients for all tests considered. African American men had the lowest probabilities (74.3% and 62% for electrocardiography and chest radiography, respectively), compared with 81.1% and 70.3%, respectively, among non-African American men. Only 37.5% of African American women received cardiac monitoring, compared with 54.5% of non-African American men. Similarly, African American women were significantly less likely than non-African American men to have their oxygen saturation measured. Patients who were uninsured or self-pay, as well as patients with "other" insurance, also had a lower probability than insured persons of having these tests ordered. CONCLUSIONS: This study documents race, gender, and insurance differences in the provision of electrocardiography and chest radiography testing as well as cardiac rhythm and oxygen saturation monitoring in patients presenting with chest pain. These observed differences should catalyze further study into the underlying causes of disparities in cardiac care at an earlier point of patient contact with the health care system.
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Población Negra , Dolor en el Pecho/diagnóstico , Servicio de Urgencia en Hospital/estadística & datos numéricos , Calidad de la Atención de Salud , Población Blanca , Adulto , Dolor en el Pecho/diagnóstico por imagen , Dolor en el Pecho/fisiopatología , Electrocardiografía , Femenino , Humanos , Seguro de Salud , Masculino , Persona de Mediana Edad , Oximetría , Probabilidad , Radiografía , Estudios Retrospectivos , Factores Sexuales , Estados UnidosRESUMEN
PURPOSE: Anterior thalamic nucleus (AN) deep brain stimulation (DBS) is effective in raising EEG and clonic seizure threshold in experimental models. Little is known about the specific properties of DBS that afford its anticonvulsant effect. We sought to test the hypothesis that experimental seizures and the anticonvulsant action of AN DBS alter the underlying regional neurochemistry of AN, specifically with facilitation of the serotonergic system to local electrical stimulation. METHODS: Halothane-anesthetized adult Sprague-Dawley male rats underwent stereotactically guided bilateral placement of bipolar stimulating steel electrodes and dialysis probes-guide cannulae in AN and posterior thalamus (PT), and placement of four epidural EEG screw electrodes 48 h before experiments. Both stimulated (AN DBS) and nonstimulated (NO DBS) animals (n=7 per group) were infused with i.v. pentylenetetrazol (PTZ, 5.5 mg/kg/min). Simultaneous thalamic and cortical EEG were recorded, and microdialysis samples were collected from AN and PT in 20-min epochs. AN stimulation was delivered (150 microA; 0.1-ms pulse duration) 40 min before and continued during PTZ infusion. RESULTS: Bilateral AN stimulation delayed the onset of EEG seizures compared with controls: 82+/-8 vs. 58+/-5 min (p=0.02). PTZ infusion alone, or together with stimulation, resulted in a steady increase in norepinephrine (NE), but not dopamine, at AN and PT sites (p<0.001). Although extracellular serotonin was measured at very low levels, the metabolite, 5-hydroxyindoleacetic acid (5-HIAA) increased selectively in AN after stimulation and during preconvulsant infusion of PTZ (p<0.001), returning to baseline after the first generalized seizure. CONCLUSIONS: These data suggest that PTZ and DBS together enhance the nonselective release of NE in thalamic nuclei while specifically stimulating AN-localized serotonin. Low serotonin levels at baseline and during STIM alone or PTZ infusion may indicate efficient reuptake systems for serotonin, with 5-HIAA serving as a surrogate marker for serotonergic activity. Modulation of the AN-specific serotonergic activity may be critical in altering PTZ seizure threshold and be an important neurotransmitter system underlying the efficacy of AN DBS.
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Encéfalo/metabolismo , Catecolaminas/metabolismo , Estimulación Encefálica Profunda/métodos , Convulsiones/inducido químicamente , Convulsiones/terapia , Tálamo/cirugía , Animales , Encéfalo/fisiología , Cromatografía Líquida de Alta Presión , Modelos Animales de Enfermedad , Electrodos Implantados , Electroencefalografía , Ácido Glutámico/metabolismo , Masculino , Microdiálisis , Pentilenotetrazol , Distribución Aleatoria , Ratas , Convulsiones/metabolismo , Técnicas Estereotáxicas , Tálamo/metabolismo , Distribución Tisular , Ácido gamma-Aminobutírico/metabolismoRESUMEN
INTRODUCTION: To test the feasibility and safety of a minimally invasive technique, we report our experience in treating spontaneous intracerebral hemorrhage (ICH) patients by using frameless stereotactic clot aspiration-thrombolysis and its effects on their 30-day survival. We compared the observed cohort mortality with its predicted 30-day ICH mortality, by using previously validated methods. METHODS: Selection criteria were diagnosis of hypertensive ICH > or =35 cc, reduced level of consciousness, and no brainstem compression. Frameless stereotactic puncture/clot aspiration followed by intraclot external catheter placement was performed. Two milligrams of recombinant tissue plasminogen activator (rtPA) was administered q12 hours until ICH volume < or =10 cc, or the catheter fenestrations were no longer in continuity with the clot. RESULTS: Fifteen patients were treated, mean age was 60.7 years. Hemorrhage locations included basal ganglia (13), thalamic (1), and lobar (1); mean systolic blood pressure; and admission ICH volumes were 229.3 mmHg and 59.1 cc, respectively. Median time from ictus to clot aspiration/thrombolysis was 1 (range 0-3) day. Mean hematoma volume was reduced to 17% of pretreatment size. Complications were ventriculitis (6.6%) and clot enlargement (13.3%). Two patients were dead at 30 days. Median Glasgow Coma Scale (GCS) scores were 10.5 (4-15) at admission and 11.0 (3-15) at discharge. By using the most conservative estimate for analysis, probability of observing two or fewer deaths among 15 patients with an overall probability of dying calculated at 0.33 was p = 0.079. CONCLUSIONS: In this selected cohort of patients with ICH, stereotactic aspiration and thrombolytic washout seemed to be feasible and to have a trend towards improved 30-day survival, when using their predicted mortality data as "historical control." Complications did not exceed expected incidence rates. Based on the experience presented here as well as previous similar reports, a larger, randomized study addressing dose escalation, patient selection, and best therapeutic window is needed.
Asunto(s)
Hemorragia Cerebral/terapia , Trombosis Intracraneal/terapia , Terapia Trombolítica/métodos , Biopsia con Aguja Fina , Femenino , Fibrinolíticos/uso terapéutico , Humanos , Hipertensión Intracraneal/complicaciones , Masculino , Persona de Mediana Edad , Proteínas Recombinantes , Técnicas Estereotáxicas , Activador de Tejido Plasminógeno/uso terapéutico , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
BACKGROUND: Practicing primary care physicians often encounter the difficult clinical situation of evaluating the older driver. We wanted to investigate the relation between self-reported driving behavior, neuropsychological measures, and crash risk to inform the development of a test battery that could predict unsafe driving behavior and was feasible for use by primary care physicians. METHODS: This study was a prospective follow-up of 107 drivers aged 65 years and older recruited from a primary care setting in 1995. Tests of attention, visual information processing, spatial orientation, and general mental status were administered at baseline. At baseline and after 2 years of follow-up, patients were asked about their driving history using the driving questionnaire. Risk for reported crashes in the follow-up period was assessed in relation to baseline driving history and measures of cognition. RESULTS: Baseline self-reports of driving habits and attitudes were associated with an increased risk of reporting a crash after 2 years of follow-up (relative risk ratio = 5.31; 95% confidence interval [CI], 0.63, 44.63). In addition, baseline tests of attention, visual information processing, and spatial orientation were associated with an increased risk of reporting motor vehicle crash at follow-up. For example, respondents with poor performance on the Trail Making Test-part A, were almost four times more likely to report a crash at follow-up (risk ratio = 3.15; 95% CI, 0.76, 13.07). CONCLUSION: Although our conclusions are tempered by small sample size, this preliminary study suggests that brief cognitive tests and simple questions about driving habits warrant further investigation as indicators of crash risk with potential utility for assessing older drivers in primary care.
Asunto(s)
Accidentes de Tránsito/estadística & datos numéricos , Conducción de Automóvil , Trastornos del Conocimiento/complicaciones , Pruebas Neuropsicológicas , Anciano , Conducción de Automóvil/psicología , Trastornos del Conocimiento/fisiopatología , Trastornos del Conocimiento/psicología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Oportunidad Relativa , Atención Primaria de Salud , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Análisis y Desempeño de Tareas , Estados Unidos , Pruebas de VisiónRESUMEN
BACKGROUND: Evaluation of the older driver is a difficult task for primary care physicians. We investigated the physician-perceived barriers to assessing older drivers in primary care practice. METHODS: Twenty family physicians whose patients had completed a clinical questionnaire and neuropsychological tests participated in one of 2 focus groups. Physicians were asked about barriers to assessing older drivers in primary care and the usefulness of neuropsychological tests for assessing driving ability. RESULTS: A number of themes emerged related to barriers in the assessment of the older driver. Major themes included concerns about being liable for the results of driving related screening and about patients reacting unfavorably to a driving assessment including cognitive tests. Physicians uniformly agreed that a protocol to guide driving assessment would be useful. CONCLUSIONS: Physicians encounter a number of barriers to assessing older drivers but recognize the importance of driving within the context of geriatric functional assessment.