Randomised clinical trial: a phase 1, dose-ranging study of the anti-matrix metalloproteinase-9 monoclonal antibody GS-5745 versus placebo for ulcerative colitis.

BACKGROUND: Matrix metalloproteinase-9 is a proteolytic enzyme whose expression is increased in ulcerative colitis. AIM: To evaluate the safety and efficacy of GS-5745, a fully humanised anti-matrix metalloproteinase-9 monoclonal antibody, in moderately-to-severely active ulcerative colitis. METHODS: We randomised 74 patients with ulcerative colitis to treatment with single or multiple ascending intravenous or subcutaneous doses of GS-5745 or placebo. Multiple-dose cohorts received either IV infusions (0.3, 1.0, 2.5 or 5.0 mg/kg GS-5745 or placebo) every 2 weeks (three total IV infusions) or five weekly SC injections (150 mg GS-5745 or placebo). The primary outcomes were the safety, tolerability and pharmacokinetics of escalating single and multiple doses of GS-5745. Exploratory analyses in the multiple-dose cohorts included clinical response (≥3 points or 30% decrease from baseline in Mayo Clinic score and ≥1 point decrease in the rectal bleeding subscore or a rectal bleeding subscore ≤1) and clinical remission (a complete Mayo Clinic score ≤2 with no subscore >1) at Day 36. Biological effects associated with a clinical response to GS-5745 were explored using histological and molecular approaches. RESULTS: Twenty-three of the 42 patients (55%) receiving multiple doses of GS-5745 had adverse events, compared with 5/8 patients (63%) receiving placebo. GS-5745 showed target-mediated drug disposition, approximately dose-proportional increases in maximum plasma concentration and more than dose-proportional increases in the area under the plasma drug concentration-time curve. Clinical response occurred in 18/42 patients (43%) receiving GS-5745 compared with 1/8 patients (13%) receiving placebo. Clinical remission occurred in 6/42 patients (14%) receiving GS-5745 and 0/8 (0%) receiving placebo. Patients with a clinical response to GS-5745 had reductions in matrix metalloproteinase-9 tissue levels (mean 48.9% decrease from baseline compared with a mean 18.5% increase in nonresponders, P = 0.008) significant improvements in histopathology scores (confirmed with three separate histological disease activity indices), as well as changes in colonic gene expression that were consistent with reduced inflammation. CONCLUSION: This phase 1 trial provides preliminary evidence for the safety and therapeutic potential of GS-5745 in the treatment of ulcerative colitis.

Probing fundamental film parameters of immobilized enzymes--towards enhanced biosensor performance. Part I--QCM-D mass and rheological measurements.

Enzyme immobilization is an ever-growing research-area for both analytical and industrial applications. Of critical importance in this area are the effects of immobilization procedures upon the functionality of the immobilized biomolecules. Both beneficial and detrimental effects can be conferred through the selection and tuning of the immobilization procedure. Quartz-crystal microbalance with dissipation (QCM-D) has been previously used to great effect in tracking alterations to thin films of biomolecules immobilized onto quartz transducers. In this study, we investigate the ability of QCM-D to track and monitor film parameters of a monolayer of laccase immobilized on a series of self-assembled monolayers (SAMs), differing in lateral density of binding residues on the SAM and height of the SAM from the quartz surface. Both mass gains and rheological parameters for these varying surfaces were measured and trends later compared to the apparent enzyme kinetics of the immobilized laccase films, assessed electroanalytically (Paper II in this two part study). For covalent attachment of proteins, both shear and viscosity were increased relative to physically adsorbed proteins. An increase in lateral density of protein-binding surface of the SAM components was shown to increase the shear/viscosity of the resultant film while an increase in distance from the electrode (through incorporation of lysine linkers) was shown to decrease the shear/viscosity while simultaneously increasing the wet mass gain of the films. Shear and viscosity may be indicative of both enzyme denaturation and increased lateral protein packing within the film structure hence it is assumed that less distortion occurs with the inclusion of linkers which allow for more optimal protein immobilization.

Probing fundamental film parameters of immobilized enzymes--towards enhanced biosensor performance. Part II-Electroanalytical estimation of immobilized enzyme performance.

The method of immobilization of a protein has a great influence on the overall conformation, and hence, functioning of the protein. Thus, a greater understanding of the events undergone by the protein during immobilization is key to manipulating the immobilization method to produce a strategy that influences the advantages of immobilization while minimizing their disadvantages in biosensor design. In this, the second paper of a two-part series, we have assessed the kinetic parameters of thin-film laccase monolayers, covalently attached to SAMs differing in spacer-arm length and lateral density of spacer arms. This was achieved using chronoamperometry and an electroactive product (p-benzoquinone), which was modeled in a non-linear regressional fashion to extract the relevant parameters. Finally, comparisons between the kinetic parameters presented in this paper and the rheological parameters of laccase monolayers immobilized in the same manner (Part I of this two paper series) were performed. Improvements in the maximal enzyme-catalysed current, i(max), the apparent Michaelis-Menten constant, K(m) and the apparent biosensor sensitivity were noted for most of the surfaces with increasing linker length. Decreasing the lateral density of the spacer-arms brought about a general improvement in these parameters, which is attributed to the decrease in multiple points of immobilization undergone by functional proteins. Finally, comparisons between rheological data and kinetics data showed that the degree of viscosity exhibited by protein films has a negative influence on attached protein layers, while enhanced protein hydration levels (assessed piezoelectrically from data obtained in Paper 1) has a positive effect on those surfaces comprising rigidly bound protein layers.

Critical assessment of the Quartz Crystal Microbalance with Dissipation as an analytical tool for biosensor development and fundamental studies: Metallophthalocyanine-glucose oxidase biocomposite sensors.

One of the challenges in electrochemical biosensor design is gaining a fundamental knowledge of the processes underlying immobilisation of the molecules onto the electrode surface. This is of particular importance in biocomposite sensors where concerns have arisen as to the nature of the interaction between the biological and synthetic molecules immobilised. We examined the use of the Quartz Crystal Microbalance with Dissipation (QCM-D) as a tool for fundamental analyses of a model sensor constructed by the immobilisation of cobalt(II) phthalocyanine (TCACoPc) and glucose oxidase (GOx) onto a gold-quartz electrode (electrode surface) for the enhanced detection of glucose. The model sensor was constructed in aqueous phase and covalently linked the gold surface to the TCACoPc, and the TCACoPc to the GOx, using the QCM-D. The aqueous metallophthalocyanine (MPc) formed a multi-layer over the surface of the electrode, which could be removed to leave a monolayer with a mass loading that compared favourably to the theoretical value expected. Analysis of frequency and dissipation plots indicated covalent attachment of glucose oxidase onto the metallophthalocyanine layer. The amount of GOx bound using the model system compared favourably to calculations derived from the maximal amperometric functioning of the electrochemical sensor (examined in previously-published literature, Mashazi, P.N., Ozoemena, K.I., Nyokong, T., 2006. Electrochim. Acta 52, 177-186), but not to theoretical values derived from dimensions of GOx as established by crystallography. The strength of the binding of the GOx film with the TCACoPc layer was tested by using 2% SDS as a denaturant/surfactant, and the GOx film was not found to be significantly affected by exposure to this. This paper thus showed that QCM-D can be used in order to model essential processes and interactions that dictate the functional parameters of a biosensor.

Electrochemical monitoring of the biodegradation of 2,4-dimethylaniline.

2,4-Dimethylaniline is a recalcitrant degradant of the pesticide amitraz and is also an industrial pollutant which is genotoxic, teratogenic and carcinogenic. The biological degradation of 2,4-dimethylaniline was examined and monitored by cyclic voltammetry. Pseudomonas species isolated from cattle dip tanks initially metabolized 2,4-dimethylaniline by oxidative deamination, following a degradation pathway via a 3-methylcatechol intermediate. The bacteria were capable of utilizing 2,4-dimethylaniline as a nitrogen source and, following deamination, as a carbon source. The formation of the metabolite, 3-methylcatechol, was monitored and confirmed by voltammetric monitoring.

Propofol administrado por gastroenterologos para sedación en endoscopia digestiva / Gastroenterology administered propofol for gastrointestinal endoscopy desation

Los narcóticos y las benzodiazepinas han sido ampliamente utilizados durante años por endoscopistas para sedación en endoscopia gastrointestinal. El propofol es un agente hipnótico de acción rápida y efecto corto que ha sido utilizado para tales fines siempre bajo la indicación de Anestesiólogos. Se presenta la experiencia con el uso de Propofol para procedimientos diagnósticos y terapéuticos en endoscopia gastrointestinal administrado por personal de enfermería bajo indicación y supervisión de edoscopistas. Entre octubre del 2002 y Marzo Del 2004 se realizaron 4200 procedimientos de endoscopia digestiva utilizando propofol para sedación sin la participación de anestesiólogo: 2085 endoscopias digestivas superiores diagnósticas, 1537 colonoscopias diagnósticas, 230 CPRE terapéuticas, 57 USE y 391 procedimientos terapéuticos diversos. El nivel de tolerancia al procedimiento y el grado de satisfacción por la sedación fue registrado como bueno o excelente en el 98 por ciento de los casos. El tiempo de recuperación post procedimiento hasta el reestablecimiento de todas las funciones neuropsicomotoras fue de 15 minutos. El 93 por ciento de los pacientes pudo recordar con claridad los detalles de la entrevista post- endoscopia. La tasa de complicaciones ventilatorias fue de 0,15 por ciento: 5 pacientes presentaron desaturación de P02 por debajo de 85 por ciento ameritando ventilación manual con máscara entre 1 y 4 minutos sin consecuencias. Un paciente presentó paro respiratorio durante la inducción para CPRE con 30 mg de propofol ameritando intubación endotraqueal y el procedimiento debió realizarse bajo anestesia general. No hubo perforaciones por colonoscopias. El uso de propofol administrado por personal de enfermeria bajo indicación de endoscopistas gastrointestinales es una modalidad segura, eficiente, de alto rendimiento en la rotación y alto nivel de aceptación por parte de los pacientes.

Impacto del ultrasonido endoscópico en la evaluación de las lesiones subepiteliales del tracto digestivo: experiencia en el Hospital de Clínicas Caracas / Impact of the endoscopic ultrasound in the digestive tract subepitelial lesions evaluation: experience in the Clinicas Caracas Hospital

EL Ultrasonido Endoscópico (USE) es el método de mayor valor y el que con mas frecuencia se emplea en la evaluación de las lesiones subepiteliales del tracto digestivo, como lo han demostrado grandes estudios multicéntricos. El propósito de este estudio es demostrar el impacto en nuestro centro de la endosonografía para el estudio de las lesiones subepiteliales. Para ello se realizó un estudio retrospectivo donde se incluyeron todos los pacientes que acudieron a la unidad de Exploraciones Digestivas del Hospital de Clínicas Caracas, entre junio de 1999 y mayo de de 2004, con diagnóstico endoscópico de lesiones subepileliales en el tracto gastrointestinal. Los datos se registraron en una tabla de elaborada al efecto, en la que se registraron edad, sexo, motivo del estudio, descripción endoscópica y hallazgos endosonográficos, así como conducta asumida (impacto) de acuerdo a los hallazgos. Se obtuvo un total 152 pacientes, en los que predominó el sexo femenino, con edades comprendidas entre 19 y 85 años. Las patologías mas frecuentes fueron leiomioma 21 por ciento, tumores asociados a tejido linfoide (MALTomas) 15 por ciento y 13 por ciento que comprendía lesiones poco comunes, con un impacto en la conducta terapéutica asumida en el 96 por ciento de todos los pacientes. Concluimos que el USE es un método seguro, de mínima invasión y nos permite decidir la conducta a seguir en la mayoría de los pacientes con lesiones subepiteliales

Usos no hemostaticos de los clips endoscópicos / Non haemostatic uses of the endoscopic clips

Los clips endoscópicos son de gran utilidad en tratamiento de sangramiento digestivo. En el presente reporte se describe el uso de los clips endoscópicos en situaciones y patologías no hemorrágicas. En 30 pacientes los clips endoscópicos fueron utilizados con fines no hemostáticos. En 16 pacientes se realizó fijación endoscópica de sondas de alimentación nasoyeyunal. En 10 pacientes se colocaron clips como marcas radiológicas para asistir la colocación de prótesis metálicas autoexpansibles. Dos pacientes con perforaciones quirúrgicas fueron tratados endoscopicamente con estos dispositivos y en 2 pacientes se colocaron clips para localizar campo de radioterapia externa (un caso de linfoma duodenal y un caso de adenocarcinoma superficial de unión esófago gástrica resecado endoscópicamente). En los dieciséis pacientes a los que se les realizó fijación de sonda nasoyeyunal el procedimiento fue eficiente y sin complicaciones. El marcaje radiológico permitió localizar con precisión los límites de lesiones malignas y diez prótesis metálicas autoexpansibles fueron colocadas adecuadamente. En dos pacientes se logró localizar con facilidad el campo de radioterapia externa. Dos casos de perforaciones quirúrgicas fueron manejados exitosamente. No hubo complicaciones relacionadas con la colocación de los clips. Conclusión: Los clips endoscópicos son útiles y seguros en algunas situaciones y patologías no hemorrágicas. Sin embargo estas situaciones e indicaciones deben ser individualmente evaluadas en ausencia de estudios clínicos controlados

Endocinch: tres años de experiencia y modificación de la técnica original / Endocinch: three years of experience and the original technique modification

La gastroplicatura endoscópica intraluminal (Endocinch) es uno de los procedimientos endoscópicos actualmente disponibles para control sintomático de reflujo gastroesofágico. Se presenta los resultados de tres años de experiencia en Venezuela. Entre mayo de 2001 y Mayo de 2004 se realizaron 81 procedimientos de Endocinch en 73 pacientes con enfermedad por reflujo gastroesofágico. Todos los pacientes incluidos en el estudio se encontraban en tratamiento con al menos 1 dosis diaria de inhibidores de bomba de protones. Sesenta y ocho pacientes presentaban hernia hiatal de 3.5 cms en promedio. El 50 por ciento de los pacientes tenían diagnóstico endoscópico de esofagitis grado B. El 41 por ciento de los pacientes presentaba síntomas respiratorios en relación a reflujo. Hasta la fecha el seguimiento promedio es de 24 meses. Se utilizó gastroplicatura de configuración triangular (tres puntos por plicatura) y otras modificaciones de la técnica original en 77 de los 81 procedimientos. 58 por ciento de los pacientes se encuentra sin medicación, incluyendo tres pacientes con antecedente de cirugía antireflujo. El 10 por ciento recibe tratamiento a demanda con inhibidores de bomba de protones (entre 1 y dos dosis por semana). Del resto de los 23 pacientes cuatro no presentaron mejoría después del procedimiento (5 por ciento) aún cuando a tres de ellos se les realizó segunda sesión y 19 refirieron reaparición de los síntomas en los primeros seis meses. De este último grupo dos fueron sometidos a cirugía y cinco recibieron segunda sesión de Endocinch con buenos resultados. Actualmente 17 pacientes reciben medicación diaria. De 30 pacientes con episodios de regurgitación noctura que interrumpía el sueño se observó desaparición del síntoma en el 90 por ciento. No hubo compliaciones mayores. En tres años de experiencia La gastroplicatura endoscópica intraluminal es eficicente para el control sintomático de reflujo gastroesofágico en el 68% de los casos y luce un procedi...

Experiencia en ultrasonido endoscópico en pediatría:Hospital de Clínicas Caracas: informe preliminar / Endoscopic ultrasound experience in pediatric: Hospital of Clinical Caracas: preliminary inform

El Ultrasonido Endoscópico (USE) es considerado de gran utilidad para investigar anormalidades estructurales de esófago, páncreas y enfermedades del sistema digestivo, en pacientes pediátricos como en adultos. Sin embargo es poco indicado a pesar de tener un gran potencial y ser posible su realización. Con el propósito de dar a conocer el USE en pediatría se presenta a continuación la experiencia obtenida en nuestra institución, se incluyeron en el estudio de forma retrospectiva los USE realizados a pacientes, desde enero del 2001 hasta marzo del 2003. Se encontró que es un recurso más en la evaluación de estos pacientes

Sleep. 2: pathophysiology of obstructive sleep apnoea/hypopnoea syndrome.

The pathogenesis of airway obstruction in patients with obstructive sleep apnoea/hypopnoea syndrome is reviewed. The primary defect is probably an anatomically small or collapsible pharyngeal airway, in combination with a sleep induced fall in upper airway muscle activity.

Genioglossal activation in patients with obstructive sleep apnea versus control subjects. Mechanisms of muscle control.

Pharyngeal dilator muscle activation (GGEMG) during wakefulness is greater in patients with obstructive sleep apnea (OSA) than in healthy control subjects, representing a neuromuscular compensatory mechanism for a more collapsible airway. As previous work from our laboratory has demonstrated a close relationship between GGEMG and epiglottic pressure, we examined the relationship between genioglossal activity and epiglottic pressure in patients with apnea and in control subjects across a wide range of epiglottic pressures during basal breathing, negative-pressure (iron-lung) ventilation, heliox breathing, and inspiratory resistive loading. GGEMG was greater in the patients with apnea under all conditions (p < 0.05 for all comparisons), including tonic, phasic, and peak phasic GGEMG. In addition, patients with apnea generated a greater peak epiglottic pressure on a breath-by-breath basis. Although the relationship between GGEMG and epiglottic negative pressure was tight across all conditions in both groups (all R values > = 0.69), there were no significant differences in the slope of this relationship between the two groups (all p values > 0.30) under any condition. Thus, the increased GGEMG seen in the patient with apnea during wakefulness appears to be a product of an increased tonic activation of the muscle, combined with increased negative-pressure generation during inspiration.

Genioglossal inspiratory activation: central respiratory vs mechanoreceptive influences.

Upper airway dilator muscles are phasically activated during respiration. We assessed the interaction between central respiratory drive and local (mechanoreceptive) influences upon genioglossal (GG) activity throughout inspiration. GG(EMG) and airway mechanics were measured in 16 awake subjects during baseline spontaneous breathing, increased central respiratory drive (inspiratory resistive loading; IRL), and decreased respiratory drive (hypocapnic negative pressure ventilation), both prior to and following dense upper airway topical anesthesia. Negative epiglottic pressure (P(epi)) was significantly correlated with GG(EMG) across inspiration (i.e. within breaths). Both passive ventilation and IRL led to significant decreases in the sensitivity of the relationship between GG(EMG) and P(epi) (slope GG(EMG) vs P(epi)), but yielded no change in the relationship (correlation) between GG(EMG) and P(epi). During negative pressure ventilation, pharyngeal resistance increased modestly, but significantly. Anesthesia in all conditions led to decrements in phasic GG(EMG), increases in pharyngeal resistance, and decrease in the relationship between P(epi) and GG(EMG). We conclude that both central output to the GG and local reflex mediated activation are important in maintaining upper airway patency.

Upper-airway collapsibility: measurements and sleep effects.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by repetitive pharyngeal collapse during sleep. Several techniques have been proposed to assess the collapsibility of the upper airway in awake humans, but sleep-wake comparisons have rarely been attempted and there are few studies comparing OSA patients to control subjects. We sought to compare two collapsibility measurement techniques between normal and apneic subjects, and between wakefulness and sleep. DESIGN: We conducted three studies. First, we examined whether collapsibility assessed by negative pressure pulses (NPPs) during wakefulness reflected values during sleep in 21 normal subjects. Second, we determined in these normal subjects whether collapsibility during sleep assessed by NPPs was predictive of collapsibility measured by inspiratory resistive loading (IRL). Finally, we compared upper-airway collapsibility between apnea patients (n = 22) and normal volunteers (n = 38) during wakefulness by NPPs. SETTING: Clinical and research laboratories at the Brigham and Women's Hospital. PARTICIPANTS: Two populations of normal subjects (n = 21 and n = 38) and OSA patients (n = 22). MEASUREMENTS AND RESULTS: Collapsibility during wakefulness, as measured by NPPs, correlated significantly with collapsibility during sleep (r = 0.62; p = 0.003). There was also a significant correlation between the two measures of collapsibility (IRL and NPP) during sleep (r = 0.53; p = 0.04). Both measures revealed a significant increase in pharyngeal collapsibility during sleep as compared to wakefulness. Finally, apnea patients had significantly greater pharyngeal collapsibility than control subjects during wakefulness (p = 0.017). CONCLUSIONS: These data suggest that upper-airway collapsibility measured during wakefulness does provide useful physiologic information about pharyngeal mechanics during sleep and demonstrates clear differences between individuals with and without sleep apnea.

Recurrence of symptomatic ventricular arrhythmias in patients with implantable cardioverter defibrillator after the first device therapy: implications for antiarrhythmic therapy and driving restrictions. CARE Group.

OBJECTIVES: The purpose of this study was to investigate whether clinical or electrophysiologic characteristics could predict initial and subsequent implantable cardioverter defibrillator (ICD) therapy. BACKGROUND: Identification of markers to predict subsequent ICD therapy and symptoms after the first event could affect patient management. METHODS: We analyzed baseline and follow-up data on 125 ICD patients followed for 408+/-321 days. Medications and ICD programming were not changed after first ICD therapy. RESULTS: Implantable cardioverter defibrillator therapy occurred in 58 patients (46%). Clinical features were as follows: mean left ventricular ejection fraction (LVEF) 29%+/-15%; coronary artery disease 84%; presenting arrhythmia with sustained monomorphic ventricular tachycardia (SMVT) in 68%. In a multivariate analysis the relative risk for ICD therapy in patients presenting with SMVT versus cardiac arrest (CA) was 2.57 (range, 1.32 to 5.01), and for patients with LVEF < or =25%, 1.95 (1.11 to 3.45), respectively (p < 0.05). Implantable cardioverter defibrillator therapy was not predicted by any other variable. Forty-six patients had second ICD therapy. Mean time to second ICD therapy was only 66+/-93 days compared with 138+/-168 days for first ICD therapy (p < 0.05). No predictor for second ICD therapy was found. Regarding symptoms, impaired consciousness during initial ICD therapy was predicted only by SMVT cycle length <250 ms at electrophysiologic testing. In contrast, symptoms were similar between first and second ICD therapy (p = 0.0001). Of note, ventricular tachycardia cycle length preceding first and second ICD therapy was similar (r = 0.76, p = 0.001). CONCLUSIONS: First ICD therapy tends to occur in patients presenting with SMVT and LVEF < or =25%. Subsequent therapy occurs sooner and is unpredictable, suggesting that antiarrhythmic drug therapy should be considered after the first symptomatic ICD therapy. Symptoms during first ICD therapy predict subsequent symptoms, and patients presenting with SMVT and asymptomatic first ICD therapy are at very low risk for future syncopal ICD therapy.

Increased prevalence of obstructive sleep apnea syndrome in obese women with polycystic ovary syndrome.

Obstructive Sleep Apnea (OSA) is considerably more common in men than women. Preliminary data suggest that androgens may play a role in the male predominance of apnea. Polycystic Ovary Syndrome (PCOS) is characterized by menstrual disturbances, androgen excess, and frequently obesity. These features suggest that women with PCOS may be at increased risk for OSA. To determine whether obese women with PCOS have an increased prevalence of sleep apnea compared with age and weight-matched reproductively normal women, we performed overnight polysomnography for determination of the apnea-hypopnea index (AHI) in 18 obese women with PCOS and age and weight-matched control women. Additional measurements included waist, hip, and neck circumferences, serum total testosterone, unbound testosterone, and DHEAS. Women with PCOS had a higher AHI than controls (22.5 +/- 6.0, vs. 6.7 +/- 1.0, P = 0.008). Women with PCOS were also more likely to suffer from symptomatic OSA syndrome (44.4% vs. 5.5%, P = 0.008). AHI correlated with waist-hip ratio (r = 0.51, P < 0.03), serum testosterone (r = 0.52, P < 0.03) and unbound testosterone (r = 0.50, P < 0.05) in women with PCOS. We conclude that obese women with PCOS are at increased risk of OSA when compared with matched reproductively normal women. Women with PCOS should be carefully questioned regarding symptoms of sleep apnea.

Managing patients with acute, nonvariceal gastrointestinal hemorrhage: development and effectiveness of a clinical care pathway.

OBJECTIVES: To develop a clinical care pathway for the management of patients with acute upper or lower nonvariceal GI hemorrhage (GIH) who do not require immediate surgical intervention. To test the effectiveness and safety of the pathway in improving the efficiency of care for patients with acute GIH. METHODS: A multidisciplinary team developed the evidence-based GIH clinical care pathway by consensus techniques. In a quasiexperimental design, pathway outcomes were measured prospectively during the first 8 months of pathway implementation, and compared to similar time periods in the 2 prior yr. Effectiveness measures were the number of patients <65 yr of age admitted for GIH and the hospital length of stay for all patients. Thirty-day safety outcomes were the rates of recurrent GIH, mortality, and readmission to hospital for any reason. RESULTS: Of 368 patients studied after pathway implementation, 81 (22%) were managed as outpatients. The number of admissions for pathway patients <65 yr of age was significantly lower compared to 691 prepathway patients (p < 0.002). Mean length of stay (+/- 95% CI) for pathway inpatients was 3.5 (3.1, 3.9) days, compared to 5.3 (4.9, 5.7) and 4.6 (4.2, 5) days in the 2 prepathway yr, respectively (p < 0.001). Multivariable regression controlling for admission vital signs, comorbid conditions, age, and the etiology of GIH confirmed that admission after pathway implementation was an independent predictor of a reduced length of hospital stay. There were no significant between-year differences in the 30-day rates of recurrent GIH, mortality, or hospital readmission. CONCLUSION: A multidisciplinary clinical care pathway may improve the efficiency of caring for patients with acute upper or lower nonvariceal GIH. Decreasing the number of admissions for GIH and reducing the hospital length of stay can be achieved without increasing the number of adverse outcomes.

Late occurrence of heart block after radiofrequency catheter ablation of the septal region: clinical follow-up and outcome.

INTRODUCTION: There are few data regarding the occurrence of delayed heart block at least 24 hours after radiofrequency catheter ablation (RFCA) of AV nodal reentry or posteroseptal accessory pathways (APs). We investigated the late occurrence of heart block in this population, the clinical outcome, and whether findings at electrophysiologic study could have predicted its development. METHODS AND RESULTS: Two of 418 patients with AV nodal reentry undergoing RFCA using a posterior approach and 1 of 54 patients with RFCA of a posteroseptal AP developed late heart block. Anterograde and retrograde AV nodal conduction before and after RFCA were normal. Patients received 12, 15, and 32 RFCA lesions, respectively, using a mean maximum power of 44 W. The RFCA sites were the posterior septum for posteroseptal AP and the posterior and mid-septum for patients with AV nodal reentry, with no His electrogram ever recorded at the ablation site. During RFCA, junctional tachycardia occurred with 1:1 VA conduction in the patient with a posteroseptal AP, but occasional intermittent single retrograde blocked complexes were present in both patients with AV nodal reentry. No rapid junctional tachycardia or >1 consecutive retrograde blocked complex was ever observed during RFCA. Persistent high-degree AV block with junctional escape developed 2 days after RFCA in the posteroseptal AP patient. A permanent pacemaker was implanted, and normal conduction was noted 16 days after RFCA. Both patients with AV nodal reentry complained of fatigue, mainly on exertion, 3 to 4 days after RFCA, and ECG-documented exercise-induced variable AV block was obtained. Because heart block resolved in our initial patient, a prolonged monitoring period was allowed. Symptoms disappeared at 13 and 8 days, and a follow-up treadmill test showed normal PR interval and no heart block. No recurrence of heart block has been seen in any of these three patients. CONCLUSION: Late unexpected heart block after RFCA of AV nodal reentry and posteroseptal AP is rare, often resolves uneventfully in 1 to 2 weeks, and no specific electrophysiologic findings predicted its occurrence. Prolonged clinical observation is preferable to immediate pacemaker implantation in such patients.