RESUMEN
O objetivo é analisar as evidências científicas disponíveis atualmente sobre a eficácia e a segurança da nadroparina em pacientes com tromboembolia pulmonar de repetição, visando à redução da reincidência dos eventos tromboembólicos, sangramentos e demais eventos adversos. A tromboembolia pulmonar (TEP) e a trombose venosa profunda (TVP) constituem o tromboembolismo venoso (TEV), doença silenciosa potencialmente fatal. Ambas constituem processos patológicos freqüentes que podem afetar tanto pessoas sãs quanto aquelas que se submeteram a processos cirúrgicos ou médicos invasivos. Podem se manifestar de modo isolado ou em conjunto e, em regra, os sintomas são inespecíficos; muitas vezes, a primeira manifestação já leva ao óbito. Ou então, manifestam-se de forma aguda fazendo com que o doente procure atenção médica. A embolia pulmonar comumente tem início súbito, apresentando-se com dispnéia, dor pleural, tosse, hemoptise ou choque, na ausência de outras causas. Em regra, os sintomas ocorrem de forma aguda e levam o paciente a procurar atendimento médico. Podem ser classificados em três grupos: dispnéia isolada; dor pleurítica e hemoptise; e colapso circulatório. A gravidade depende da magnitude da embolia e da condição cardiorrespiratória prévia. Nadroparina é uma heparina de baixo peso molecular com propriedades anticoagulantes, registrada na Agência Nacional de Vigilância Sanitária (ANVISA) com o nome comercial de Fraxiparina®, na forma farmacêutica de solução injetável para uso subcutâneo e com apresentação de seringas preenchidas com 0,3 mL de solução equivalente a 2850 UI anti-Xa em cartuchos contendo 10 seringas ou 0,6 mL de solução equivalente a 5700 UI anti-Xa em cartuchos contendo 5 seringas.A Fraxiparina® é indicada para profilaxia de doenças tromboembólicas, tais como \r\naquelas associadas à cirurgia em geral ou ortopédica e em pacientes clínicos de alto risco (insuficiência respiratória e/ou infecção respiratória e/ou insuficiência cardíaca) hospitalizados em unidade de tratamento intensivo; tratamento de doenças tromboembólicas; prevenção de coagulação durante a hemodiálise; \r\ntratamento de angina instável e infarto do miocárdio não-Q. O presente relatório demonstrou que não existem evidências científicas robustas a respeito da tecnologia avaliada para o tratamento de TEP. Uma parcela da \r\nliteratura sobre a condição clínica traz os resultados das HBPM de forma agrupada, nesses casos, em regra, o comparador é HNF. Os membros da CONITEC presentes na 19ª reunião do plenário realizada nos dias 04/09/2013 e 05/09/2013 apreciaram a proposta de incorporação da nadroparina em pacientes com\r\ntromboembolia pulmonar de repetição e, decidiram, por unanimidade, pela não incorporação do medicamento.
Asunto(s)
Humanos , Nadroparina , Embolia Pulmonar/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Brasil , Análisis Costo-Beneficio , Garantía de la Calidad de Atención de Salud , Evaluación de la Tecnología Biomédica , Sistema Único de SaludRESUMEN
Objetivo: realizar una valoración clínica preliminar del uso de nadroparina cálcica inyectable, en el tratamiento y profilaxis de la enfermedad tromboembólica venosa.Métodos: mediante la revisión de historias clínica, se realizó una valoración preliminar de la tolerancia, efecto y complicaciones del uso de la nadroparina cálcica inyectable de 5 700 UI anti-Xa (0,6 mL), en pacientes con trombosis venosa profunda de los miembros, y de la nadroparina cálcica de 2 850 UI anti Xa (0,3 mL) de forma profiláctica, en pacientes que se encontraban bajo tratamiento anticoagulante oral e iban a ser sometidos a algún tipo de proceder invasivo.Resultados: todos los pacientes tuvieron una evolución satisfactoria. Mejoría de los síntomas y signos de trombosis, buena tolerancia al medicamento en todos los casos y no presentaron complicaciones hemorrágicas ni retrombosis.Conclusión: tanto la nadroparina cálcica inyectable de 2 850 UI anti-Xa (0,3 mL), como la de 5 700 UI anti-Xa (0,6 mL) resultaron efectivas, tolerables y prácticamente inocuas en el tratamiento y profilaxis de la enfermedad tromboembólica venosa(AU)
Objective: to make a preliminary clinical assessment of Nadroparin calcium injection for the treatment and prophylaxis of thrombotic venous disease.Methods: through review of medical histories, a preliminary assessment was made in terms of tolerance and effect of, and complication from the use of 5 700 UI anti-Xa (0,6 mL) Nadroparin calcium injection in patients with deep venous thrombosis in limbs, and of 2 850 UI anti-Xa (0,3 mL) Nadroparin calcium, as prophylactic method, in patients under low oral anticoagulant treatment who were going to undergo some sort of invasive procedure.Results: all the patients recovered satisfactorily. Symptoms and signs improved, there was good tolerance to the drug in all the cases, and neither hemorrhage nor repeated thrombosis occurred.Conclusions: the two forms of the drug, that is, 2 850 UI anti-Xa (0,3 mL) Nadroparin calcium injection as well as 5 700 UI anti-Xa (0,6 mL) Nadroparin calcium were effective, tolerable and practically harmless in the treatment and the prophylaxis of thrombotic venous disease(AU)
Asunto(s)
Humanos , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/prevención & control , Heparina de Bajo-Peso-Molecular/uso terapéutico , Nadroparina/uso terapéuticoRESUMEN
Objetivo. Evaluar críticamente la información sobre la farmacología básica y clínica de la nadroparina cálcica. Fuente de datos. Se hizo una búsqueda en la literatura científica de octubre de 1985 a septiembre de 2010, en las bases de datos electrónicas: Pubmed, Cochrane, MDConsult,Scielo y Medscape, y en el Instituto Nacional de Vigilancia de Medicamentos y Alimentos (INVIMA).Selección de estudios. Se incluyeron los estudios publicados en inglés, español o francés, realizados en humanos y animales de experimentación, en los que se revisarala farmacología básica y clínica de la nadroparina cálcica. Extracción y síntesis de datos. Se revisaron 792 resúmenes y se seleccionaron 60artículos que cumplieron los criterios de inclusión, de acuerdo con un método se resolvieron todas las discrepancias por discusión y consenso.Conclusión. En algunos estudios la nadroparina cálcica ha mostrado una eficacia igual o superior a la de la heparina no fraccionada y la de un placebo. Sin embargo, la información evaluada no es lo suficientemente sólida para considerar superior lanadroparina frente a las otras heparinas de bajo peso molecular. La literatura científica muestra que, en general, el tratamiento con estas últimas es más seguro y costo-efectivo que con heparina no fraccionada. No existen pruebas suficientes, fuertes y concluyentes para calificar la nadroparina cálcica como superior aotras heparinas de bajo peso molecular en el tratamiento antitrombótico. Las de bajo peso molecular han demostrado una reducción significativaen la angiogénesis tumoral y un aumento en la supervivencia de pacientes con enfermedades oncológicas. Sin embargo, se requieren más investigaciones para caracterizar y comprender mejor este nuevo hallazgo...
Objective: To evaluate critically the evidence on the basic and clinical pharmacology of nadroparin calcium.Data source: We conducted a literature review from October 1985 to September 2010 in the electronic databases: Pubmed, Cochrane,MD Cosult, Medscape, Scielo and Instituto Nacional de Vigilancia de Medicamentos y Alimentos (INVIMA).Study selection: Studies published in English, Spanish or French made in humans and animals for experimentation which reviewed the basic and clinical pharmacology of nadroparin calcium wereincluded. Data extraction and synthesis: 792 abstracts were reviewed by authors and 60 papers were selected that met inclusion criteria according to a standardized method All discrepancies were resolved by discussion and consensus. Conclusion: Some studies have shown that the efficacy of nadroparin calcium is equal or superior to unfractionated heparin (UFH) and placebo, however, the strength of assessed evidencehas been insufficient for considering nadroparin calcium superior to other low molecular weight heparins (LMWH). Literature shows that LMWHstherapy is more cost-effective and safer than UFH therapy in general. It does not exist enough, strong and conclusive evidence for considering antithrombotic nadroparin calcium therapy greater to other LMWHs. LMWHs have shown a significantreduction in tumor angiogenesis and increased survival in oncology patients. To conduct further research is necessary to characterize and understand better this new finding...
Asunto(s)
Anticoagulantes , Heparina , Nadroparina , Tromboembolia VenosaRESUMEN
Hereditary angioedema is caused by a C1-inhibitor deficiency. It is a life-threatening disease. Its management includes treating acute attacks, short-term prophylaxis, and long-term prophylaxis. We report our experience with nadroparin for the short-term prophylaxis and treatment of angioedema attacks. We indicated treatment with nadroparin 0.3-0.6 mL SC 20 min after the onset of prodromes, then every 8-12 h for 1 day; short-term prophylaxis with 0.3-0.6 mL 1 h before a triggering event and then every 12-24 h for 1 more day. For children, treatment included 0.3 mL SC 20 min after the onset of prodromes, then every 12-24 h for 1 day; short-term prophylaxis was 0.3 mL 1 h before a triggering event and 1 more dose after 24 h. For the treatment, a complete response was considered when nadroparin totally stopped an acute attack within 2 h after injection. Partial response was considered if after 2 h analgesics and/or other therapy were required. Failure was established if after 4 h no response was obtained and fresh frozen plasma and other in-patient measures were required. For short-term prophylaxis, only complete responses and failures were considered. We included 29 adults and 5 children. Functional C1-inhibitor and C4 levels rose after nadroparin. We recorded 256 treatments (89.8% complete responses, 8.2% partial responses, and 1.9% failures), and 102 short-term prophylactic regimens (90.2% complete responses, and 9.8% failures). We found 38 mild adverse events without severe hemorrhagic episodes. If our results are reproduced subsequently, nadroparin may be an alternative for the treatment and short-term prophylaxis of angioedema attacks.
Asunto(s)
Angioedemas Hereditarios/tratamiento farmacológico , Nadroparina/uso terapéutico , Adolescente , Adulto , Anciano , Angioedemas Hereditarios/sangre , Anticoagulantes/uso terapéutico , Niño , Proteína Inhibidora del Complemento C1/metabolismo , Complemento C4/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Nadroparina/efectos adversos , Adulto JovenRESUMEN
Tipo de estudio: ensayo clínico, unicéntrico, prospectivo, doble longitudinal, descriptivo, analítico, realizado en la Unidad de Cuidados Coronarios del hospital Luis Vernaza de Guayaquil, en pacientes con síndrome coronario agudo. Objetivo: determinar cual de las dos heparinas es superior, tanto en mejoría clínica como en costos y efectos secundarios. Resultados: se estudió un total de 34 pacientes; 14 con heparina sódica (grupo A) y 14 con nadroparina cálcica (grupo B), aparte de la aspirina y demás medicación antianginosa a criterio médico. La edad de presentación más frecuente en varones fue entre los 50 y 59 años, y en mujeres entre los 70 y 79 años; el grupo A tuvo una estancia hospitalaria de 29,35 días (ET 4,39) y en el grupo B de 21,24 días (ET 3,53) p= 0,160; los gastos en el grupo B fueron el doble que en el grupo A; el grupo A tuvo sangrados leves en un 2,9%, anginas recurrentes 11,76%, infarto recurrente 2,9%, trombocitopenia 2,9%. El grupo B tuvo sangrados leves en el 8,8%, infarto recurrente en el 2,9% y angina recurrente en el 14,7%. Conclusiones: absoluta paridad entre las dos estrategias terapéuticas; la única diferencia radica en los costos.
Type of study: clinic test, unicentric, prospective, double longitudinal, analytic and descriptive, performed in the Coronary Unit Care of Luis Vernaza Hospital of Guayaquil, with patient with acute coronary syndrome. Objective: To establish which of two heparin is superior, as much in clinic provement as in fees and secondary effects. Results: In the study was with 34 patients; 14 with sodic heparine (group A) and 14 with nadroparine calcium (group B), besides aspirin and any antiangina drugs of medical criteria. The age more frequently in men was between 50 to 59 years, and women between 70 to 79 years; Group A had a hospital stay of 29,35 days (ET 4,39) and group B de 21,24 days (ET 3,53) p= 0,160; the expenses in the group B was double than group A; Group A had mild bleeding in 2,9 %, recurrent angina 11,76%, recurrent heart attack 2,9 %, thrombocytopenia 2,9%. Group B had mild bleeding in 8,8%, recurrent heart attack in 2,9% and recurrent angina in 14,7%. Conclusion: Absolute similarity between two therapeutic strategies; the only difference is in fees.
Asunto(s)
Masculino , Adulto , Femenino , Persona de Mediana Edad , Síndrome Coronario Agudo , Cuidados Críticos , Heparina , Nadroparina , Anticoagulantes , FibrinolíticosRESUMEN
The low-molecular weight heparin nadroparin calcium is used clinically for the prevention and treatment of venous and arterial thrombosis. The antifactor Xa and antifactor IIa assays were validated by investigating the parameters of range, linearity (r2 = 0.9905 and r2 = 0.9914, respectively) precision, accuracy, and robustness. The 2 methods incorporated a chromogenic endpoint and detection at 405 nm, yielding good results with detection limits of 0.004 and 0.01 IU/mL and quantitation limits of 0.01 and 0.03 IU/mL, respectively, for the antifactor Xa and antifactor IIa assays. Nadroparin calcium pharmaceutical products were evaluated by the antifactor Xa assay and the antifactor IIa assay, giving potencies between 93.86 and 109.88%, with an antifactor Xa/antifactor IIa ratio between 3.2 and 3.7. The results demonstrated the validity of the assays that are useful methodologies for the routine quality control of nadroparin in pharmaceutical formulations.
Asunto(s)
Técnicas de Química Analítica/métodos , Química Farmacéutica/métodos , Factor Xa/análisis , Nadroparina/análisis , Protrombina/análisis , Animales , Calibración , Bovinos , Factor Xa/química , Humanos , Nadroparina/química , Protrombina/química , Control de Calidad , Reproducibilidad de los Resultados , Trombosis/prevención & control , Factores de Tiempo , Trombosis de la Vena/prevención & controlRESUMEN
BACKGROUND: Several clinical practice guidelines (CPG) on antithrombotic prophylaxis in surgical patients help to decide about the prophylaxis strategy based on the patient risk of deep venous thrombosis (DVT). However, the physician risk estimates of DVT could have little inter-observer reproducibility, which could lead to different individual prophylaxis practices. METHODS: Physicians were asked to evaluate DVT risk in eight clinical vignettes, describing actual patients cared for in our hospital. The vignettes included all possible levels of DVT risk. RESULTS: The degree of prophylaxis strategies accuracy was 63% (95% CI 523-75%). Overall agreement was 0.32 (z = 7.61, p < 0.001) and for each level of risk kappa was 0.38 (z = 6.50, p < 0.001); 0.1 (z = 1.65, p < 0.049) and 0.5 (z = 8.45, p < 0.001) for small, moderate and high risk group respectively CONCLUSIONS: Our results showed that there is poor agreement when physicians have to evaluate the risk for postoperative DVT, and in the cases of low and moderate risks of DVT there is the smallest agreement. In addition, the data also showed that the overall accuracy of DVT prophylaxis strategy was only moderate and the risk evaluation did not correlate to the selection of the strategy. The issue of inter-observers variability should be taken into account when CPG performance are analysed, especially when considering the risk-evaluation to choose the appropriate actions.
Asunto(s)
Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Guías de Práctica Clínica como Asunto , Medición de Riesgo/estadística & datos numéricos , Trombosis de la Vena/epidemiología , Trombosis de la Vena/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Argentina/epidemiología , Vendajes/estadística & datos numéricos , Toma de Decisiones , Ambulación Precoz/estadística & datos numéricos , Femenino , Heparina/uso terapéutico , Hospitales Universitarios/normas , Humanos , Masculino , Auditoría Médica , Persona de Mediana Edad , Nadroparina/uso terapéutico , Variaciones Dependientes del Observador , Complicaciones Posoperatorias/clasificación , Premedicación/estadística & datos numéricos , Trombosis de la Vena/etiologíaRESUMEN
Objetivo: Determinar la seguridad de una Heparina de Bajo Peso Molecular (HBPM) Nadroparina Cálcica en Cirugía Ortopédica Mayhor, mediante un estudio clínico experimental con 70 pacientes hosp;italizados para cirugía de cadera en el Servicio de Ortopedia y Traumatología del Hospital Nacional Guillermo Almenara Irigoyen -IPSS, entre mayo y setiembre de 1996. Pacientes: Se asignaron al azar en el grupo/profilaxis 35 pacientes que recibieron Nadroparina Cálcica 03 ml desde 2 horas antes de la operación y 35 pacientes en el grupo-control que siguieron el esquema convencional sin usar anticoagulantes. Resultados: El volumen de sangrado intra y post-operatorio, sangrado mayhor operatorio no mostraron diferencias estadísticamente significativas entre los 2 grupos, tampoco se presentó sangrado extra-operatorio, ni reacciones adversar al fármaco. El porcentaje de fallecimiento en el grupo control fue de 8.6 por ciento y cero en el grupo p;rofilaxis. Conclusión: La profilaxis del Tromboedmbolismo Venoso en Cirugía Cadera con Nadroparina Cálcica, mostró seguridad, tolerancia y facilidad de manejo sin necesidad de monitoreo laboratorial
Asunto(s)
Humanos , Nadroparina , Heparina de Bajo-Peso-Molecular , Cadera/cirugíaRESUMEN
Objetivo.- Determinar la seguridad de una heparina de bajo peso molecular (HBPM) nadroparina cálcica en Cirugía Ortopédica Mayor, mediante un estudio clínico experimental aleotorizado con 70 paciedntes hospitalizados para cirugía de cadera en el Servicio de Ortopedia y Traumatología del Hospital Nacional Guillermo Almenara Irigoyen, IPSS, entred diciembdrfe 1996 y marzo de 1997. Pacientes.- Se asignaron en el grupo-p;rofilaxis 35 pacientes que recivbierffon 0.3 ml de nadroparina cálcica desde 12 horas antes de la operación y 35 pacientes en el grupo control que siguieron el esquema convencional sin usar anticoagulantes. Resultados.- El volumen de sangrado intra y p;ost operatorio, así como el sangrado mayor operatorio no mostgraron diferencias estadísticamente significativas entre los dos grupos, tampoco se presentó sangrado extra operatorio, ni reacciones adversas al fármaco. El porcentaje de fallecidos en el grupo control fue de 8.6 por ciento y cero en el grupo profilaxis. Conclusión.- La profilaxis de tromboembolismo venoso (TEV) en Cirugía de Cadera con nadroparina cálcica, mostró seguridad, tolerancia y facilidad de manejo sin necesidad de monitoreo laboratorial
Asunto(s)
Humanos , Tromboflebitis/prevención & control , Nadroparina/uso terapéutico , Cadera/cirugía , CaderaRESUMEN
BACKGROUND: Low molecular weight heparin can be administered by the subcutaneous route and has a stable and prolonged antithrombotic effect. These features have prompted clinical essays about its use as an alternative to unfractionated heparin in the treatment of unstable angina. AIM: To compare the clinical effects of low molecular weight heparin and unfractionated conventional heparin in patients with unstable angina or non Q infarction. PATIENTS AND METHODS: Seventy patients (47 male) admitted to the hospital with the diagnosis of unstable angina or non Q acute myocardial infarction were randomly assigned to receive unfractionated intravenous heparin or subcutaneous low molecular weight heparin bid. All received aspirin p.o. and i.v. nitroglycerin. The incidence of recurrent angina, acute myocardial infarction or a need for emergency surgical revascularization during hospital stay were assessed in both groups. RESULTS: Compared to patients with low molecular weight heparin, patients receiving unfractionated heparin had a higher incidence of recurrent resting angina (23 and 47.5% respectively, p < 0.04) and higher need for emergency surgical revascularization (3.3 and 17.5% respectively, p < 0.06). Patients treated with unfractionated conventional heparin had a 3 times higher risk of having an adverse cardiovascular event than patients receiving low molecular weight heparin (O.R. 0.33, confidence intervals 0.11-0.58). CONCLUSIONS: Low molecular weight heparin is superior to unfractionated conventional heparin in the treatment of unstable angina and non Q acute myocardial infarction.
Asunto(s)
Angina Inestable/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Heparina/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Nadroparina/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Heparina/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Nadroparina/administración & dosificación , RecurrenciaRESUMEN
Unfractionated heparin (UFH) exerts its anticoagulant properties by increasing the inactivation of thrombin and activated factor X by antithrombin III. Apart from this main action release of tissue factor pathway inhibitor (TFPI) from endothelial cells could also be important for the antithrombotic activity of heparins. Four different heparin preparations were injected subcutaneously into 5 healthy volunteers 1 week apart: (1) UFH 2,500 IU fix dose (FixUFH), (2) 1 mg/kg body weight of low molecular weight heparin (LMWH), (3) the combined LMWH-adjusted dose plus UFH 2,500 IU fix dose (ComHep) and (4) UFH 2,500 IU/10 kg body weight (UFHvar). Plasma samples were drawn before and 1, 2, 4, 6, 12 and 24 h afterwards. FixUFH did not affect the concentration of total and free TFPI. Total TFPI increased in the 1st hour after LMWH injection from 74 to 124 ng/ml (p < 0.01), after ComHep from 82 to 144 ng/ml (p < 0.01), and after UFHvar from 91 to 113 ng/ml (p < 0.05). All observed elevations were significant at the peak value (+/- 2 h, p < 0.01 compared with baselines). The increase of free TFPI produced by UFHvar (74.5 and 70.5 ng/ml) was significantly higher than with LMWH (42.8 and 38.0 ng/ml) at 2 and 4 h (p < 0.001 and p < 0.01, respectively). UFHvar and ComHep but not LMWH produced a statistically significant increase of free TFPI compared with FixUFH at 2, 4 and 6 h (p < 0. 01). We concluded that at comparable therapeutic doses, subcutaneous UFHvar released more free TFPI than LMWH and ComHep. A synergism between LMWH and low dose of UFH was found in 4-, 6- and 12-hour blood samples.
Asunto(s)
Anticoagulantes/uso terapéutico , Fibrinolíticos/uso terapéutico , Heparina de Bajo-Peso-Molecular/uso terapéutico , Heparina/uso terapéutico , Lipoproteínas/metabolismo , Adulto , Análisis de Varianza , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Femenino , Humanos , Inyecciones Subcutáneas , Masculino , Nadroparina/uso terapéutico , Valores de ReferenciaRESUMEN
Envenomation by the Bothrops lanceolatus, a snake found only in Martinique, leads to swelling and pain, and occasionally to systemic signs and/or coagulopathy. Severe thromboses at some distance from the site of the bite may appear within 48 hr. Uncertainties as to the actual development of thrombotic complications in patients appearing to be suffering from moderate poisoning and as to the availability and the toxicity of a monospecific antivenom (AVS) initially led us to reserve antivenom for the most severe cases, and to use anticoagulants to prevent thromboses in all patients. This approach was modified after we observed serious thromboses in patients with moderate poisoning. Of 50 adult snake bite cases hospitalized between June 1991 and August 1994, 11 developed serious thrombotic complications at 36 /+- 27 hr (mean +/- SD) (range 12-96) following envenomation, despite early preventive anticoagulant therapy. Those included pulmonary embolism (two cases), cerebral infarction (six cases), myocardial infarction (one case), and cerebral and myocardial infarctions (two cases). Sixteen patients were not treated with AVS: 10 of these recovered without complications and six developed systemic thrombosis causing permanent disability in three cases. Thirty were treated with an intravenous infusion of 2-6 vials of AVS given 2-48 hr after the bite. Of these, three died of cerebral infarction that developed before the initiation of serotherapy. All others recovered. Among patients treated with AVS, three presented with mild anaphylactic reactions, while one developed serum sickness that responded to steroids. These data indicate that preventive anticoagulant therapy is of limited efficacy in Martinique.(ABSTRACT TRUNCATED AT 250 WORDS)