How and when to use clozapine.

OBJECTIVE: Clozapine is the only approved strategy for treatment-resistant schizophrenia, although it is highly underutilized. We aim to generate practical and actionable evidence-based recommendations for the use of this drug considering prescription barriers. METHOD: Narrative review. RESULTS: A consistent body of evidence supports the efficacy of clozapine reducing morbidity and mortality in schizophrenia. The main obstacles to its use are the lack of experience by prescribers and perceived treatment burden. Systematic screening of eligibility, utilization of available resources for consultation, developing a professional network with other stakeholders, as well as optimizing how clozapine is presented to patients is discussed. Furthermore, specific evidence-based recommendations for initiation, maintenance, and safety monitoring with clozapine are provided. CONCLUSION: Clozapine prescription is one of the areas in psychiatry with the greatest mismatch between efficacy and utilization in clinical practice. Although multiple barriers to the use of clozapine exist, some of these may be overcome by updates of routine clinical practice.

Vivax malaria in a blood donor in Spain, relapse or a new infection in a malaria non-endemic country?

Malaria is a vectorborne disease caused by protozoan of the genus Plasmodium, which can also be transmitted by the transfusion of infected red blood cells. One year after return from a travel to Honduras, a Spanish traveller developed vivax malaria. Prior to the onset of symptoms, the donor made a donation that tested non-reactive using an immunological test for malaria. Samples from the donor taken before donation and tested by serological and molecular methods were negative but positive at the time of hospital admission. The possible sources of the donors' infection, imported versus locally acquired, are discussed.

New graphic AUC-based method to estimate overall survival benefit: pomalidomide reanalysis.

WHAT IS KNOWN AND OBJECTIVE: Difference in median survival is an erratic measure and sometimes does not provide a good assessment of survival benefit. The aim of this study was to reanalyse the overall survival benefit of pomalidomide from pivotal clinical trial using a new area under curve (AUC)-based method. COMMENT: In the pivotal trial, pomalidomide plus low-dose dexamethasone showed a significant survival benefit over high-dose dexamethasone, with a difference between medians of 4.6 months. The new AUC method applied to the survival curves, obtained an overall survival benefit of 2.6 months for the pomalidomide treatment. This average difference in OS was calculated for the 61.5% of patients for whom the time to event is reliable enough. WHAT IS NEW AND CONCLUSION: This 2-month differential would have major clinical and pharmacoeconomic implications, on both cost-effectiveness studies and on the willingness of the healthcare systems to pay for this treatment.

Direct and indirect comparison of the efficacy and safety of adalimumab, etanercept, infliximab and golimumab in psoriatic arthritis.

WHAT IS KNOWN AND OBJECTIVE: Psoriatic arthritis is an autoimmune disease characterized by chronic inflammation of the skin and joints. Anti-TNF drugs reduce the severity of the disease in the long term. This study compares the efficacy and safety of adalimumab, etanercept, infliximab and golimumab in patients with psoriatic arthritis. METHODS: Direct comparison was based on a literature search of drug comparison studies, whereas indirect treatment comparison was based on phase III clinical trials with biological agents, involving similar populations and durations, and with the same outcome. ACR50 was taken as primary outcome for comparison, whereas ACR20 and ACR70 were used as secondary outcomes. Indirect comparisons were made using infliximab as the reference drug and the Bucher method. In calculating δ (the maximum acceptable difference as a clinical criterion of equivalence), use was made of half of the absolute risk reduction obtained in the meta-analysis of the clinical trials included in the indirect comparison (ARR 32%; δ: 16%). The four anti-TNF drugs were also compared in relation to the secondary outcomes and adverse effects. RESULTS AND DISCUSSION: Reported direct and indirect comparisons of the four drugs did not include golimumab, and did not yield conclusive results. Four clinical trials - one for each drug studied - were identified. The estimated differences for the primary outcome, ACR50, between infliximab and the other drugs were adalimumab (ARR 4%, 95% CI -9·5 to 17·5), etanercept (ARR 4%, 95% CI -10·5 to 18·5) and golimumab (ARR 9%, 95% CI -5·4 to 23·4). Likewise, there were no relevant differences between the drugs in relation to the secondary efficacy outcomes, except for etanercept, which was less effective in ACR70 response. For adverse reactions, there were also no significant differences except for injection site, reactions which were more frequent with etanercept, with a mean difference of 26% relative to infliximab. WHAT IS NEW AND CONCLUSION: No significant differences were found in ACR50 responses to the four drugs after 24 weeks. Injection-site reactions were more common with etanercept, but this was insufficient to invalidate the inference that clinically the four drugs can be regarded as clinically equivalent for the treatment of psoriatic arthritis.

Controlled Ovarian Stimulation Initiated at Different Phases of the Menstrual Cycle for Fertility Preservation in Oncological Patients: a Retrospective Study.

The purpose of this study is to compare conventional start in early follicular phase (EFP) with late follicular phase (LFP) and luteal phase (LP) in controlled ovarian stimulation (COS) for fertility preservation (FP) to assess differences in clinical outcomes. Retrospective study of the first cycles of COS for FP in oncological patients between 2012 and 2020 in a tertiary hospital. Two-hundred forty-eight cycles were classified into 3 groups: 176 cycles in EFP, 8 cycles in LFP, and 52 cycles in LP. Comparing LFP to EFP, there were no differences in number of oocytes (10.0 [6.3-16.0] vs 12.0 [8.0-18.0]; p = 0.253) or number of metaphase II (MII) obtained (7.0 [2.3-13.3] vs 9.0 [6.0-13.0]; p = 0.229). Total number of days needed was higher in LFP (14.5 [12.5-16.0] vs 3.0 vs 10.0 [8.3-11.0 p = 0.000) but without significant differences in number of days of usage of gonadotropins (11.5 [8.3-12.8] vs 10.0 [8.3-11.0] p = 0.308). No differences were found between LP and EFP in number of oocytes (14.5 [9.0-20.0] p = 0.151) or MII (11.5 [7.0-16.0] p = 0.084). Number of days of gonadotropins (11.0 [10.0-12.0] p = 0.00) and total dosing (3000.0 [2475.0-3600.0] p = 0.013) were significantly higher in LP. FORT and FOI were similar in all groups. COS with a random start in fertility preservation has similar outcomes to EFP start. Therefore, we can initiate COS at any phase of the menstrual cycle with optimal results. However, LP may need more days of stimulation.

[Ovarian cryopreservation in girls with cancer: new challenges]. / Criopreservación ovárica en niñas con cáncer: nuevos retos.

BACKGROUND: Ovarian cortex cryopreservation (OCC) for future autotransplant represents a treatment alternative for those paediatric cancer survivors affected of ovarian failure and fertility disorders. METHODS: Patients with high gonadotoxic risk are included in the Oncology Paediatric Fertility Preservation Programme: those receiving pelvic radiotherapy, bone marrow transplantation, high doses of cranial radiotherapy or alquilating agents, or those with bilateral ovarian pathology. Prior to the oncological treatment, the ovarian tissue is harvested laparoscopically. At the same time, other invasive procedures are done. Once malignancy is ruled out of the specimen and the presence of primordial follicles is confirmed, the multidisciplinary team of oncologist, paediatric surgeon and fertility specialist coordinate the processing and delivery of the ovarian cortex to the Comunidad Valenciana Tissue Bank. RESULTS: From July 2008 to May 2010 eight patients have been included in the programme, aged between 8-18 years old and with diagnosis of: Hodgkin's lymphoma (n= 2), Acute Myeloblastic and Lymphoblastic leukaemia (n= 2), pelvic Ewing's sarcoma, bilateral ovarian Teratoma and Meduloblastoma. Five patients underwent non gonadotoxic chemotherapy before OCC. Six additional procedures were done using the same anaesthetic event. Partial oophorectomy was performed in half the cases, total oophorectomy in the rest of them, and an ovarian pexia was once associated. All taken samples were found to be valid. CONCLUSIONS: OCC of selected patients was performed safely, with neither postoperative complications nor delay of the oncological treatment. Therefore, the first national experience in this procedure has been satisfactorily achieved.

“Displasia ósea florida: signos imagenológicos reportados en artículos odontológicos publicados entre el 2012 y 2021” / Florid bone dysplasia: imaging signs reported in dental articles published between 2012 and 2021

Introducción: Identificar los signos imagenológicos característicos de la displasia ósea florida reportados en artículos publicados en revistas odontológicas indexadas en la principal fuente de información de salud (Medline) entre el año 2012 al 2021. Materiales y métodos: Se llevó a cabo un estudio observacional, transversal y retrospectivo evaluando las principales revistas odontológicas encontradas en publicaciones entre los años 2012 al 2021 mediante la búsqueda electrónica en la base de datos de Medline vía PubMed, usando los términos (cemento-osseus displasia) AND (radiology), luego se procedió a depurar la muestra siguiendo los criterios de selección estipulados. Resultados: Se evaluó un total de 7 artículos que cumplieron con los criterios de selección en donde se recopiló la información de 363 casos de displasia ósea florida. Encontrándose en promedio esta lesión a los 51.88 años según la edad con predominio en el sexo femenino, en promedio 49.51 frente a 2.34 para el masculino. Según la ubicación de la lesión, los artículos muestran que es más frecuente en mandíbula con un promedio de 28 casos, seguido de ambos maxilares con 23.29 casos y muy raro en la maxila con 0.57 casos. Imagenológicamente los artículos describen lesiones radiolúcidas o hipodensas en promedio 2.29 casos, mixtas 36.57 casos y radiopacas o hiperdensas en promedio 20.29 casos. Conclusiones: De acuerdo a lo descrito en la literatura, la displasia ósea florida suele presentarse con mayor frecuencia en mujeres adultas, a partir de la quinta década de vida, disminuyendo su incidencia de la sexta década en adelante. Su localización más frecuente es en la mandíbula, en segundo lugar, en ambos maxilares y muy raramente solo en la maxila. Imagenológicamente se presentan con mayor incidencia con un patrón mixto. (AU)

Introduction: Identify the characteristic imaging signs of florid bone dysplasia reported in articles published in dental journals indexed in the main source of health information (Medline) between 2012 and 2021. Materials and methods: An observational, cross-sectional and retrospective study was carried out evaluating the main dental journals found in publications between the years 2012 and 2021 through the electronic search in the Medline database via PubMed. Using the terms (cemento-osseus dysplasia) AND (radiology), we then proceeded to refine the sample following the stipulated selection criteria. Results: A total of 7 articles that met the selection criteria were evaluated, where information from 363 cases of florid bone dysplasia was collected. Finding this lesion on average at 51.88 years according to age, with a predominance in the female sex, on average 49.51 compared to 2.34 for the male. Depending on the location of the lesion, the articles show that it is more frequent in the mandible with an average of 28 cases, followed by both maxillae with 23.29 cases and very rare in the maxilla with 0.57 cases. Imagingly, the articles describe radiolucent or hypodense lesions in an average of 2.29 cases, mixed 36.57 cases, and radiopaque or hyperdense lesions in an average of 20.29 cases. Conclusions: According to what has been described in the literature, florid bone dysplasia tends to occur more frequently in adult women, starting in the fifth decade of life, decreasing its incidence from the sixth decade onwards. Its most frequent location is in the mandible, secondly, in both jaws and very rarely only in the maxilla. Imaging, they present with a higher incidence with a mixed pattern. (AU)

Evaluación de los comparadores empleados en los estudios pivotales de nuevos medicamentos e indicaciones / Assessment of comparators used in pivotal studies of new medicines and indications

Objetivo: En algunos casos, los estudios pivotales para aprobar nuevos medicamentos no emplean el comparador más adecuado. El objetivo es cuantificar este problema analizando los Informes de Posicionamiento Terapéutico (IPT) publicados por el Ministerio de Sanidad español.Métodos: El comparador se clasificó en seis categorías según la adecuación del tratamiento, es decir, si coincidía con el estándar de tratamiento al ser autorizado: A-“inicialmente adecuado”, B-“sin comparador por causa ética”, C-“sin comparador excluyendo los clasificados en B”, D-“inadecuado” y E-“parcialmente subóptimo” (cuando era estándar solo para parte de los pacientes).La variable principal fue la proporción de nuevos fármacos/indicaciones con comparación suficiente (categorías A, B y C) o deficiente (el resto). La información sobre comparadores y tratamiento estándar se extrajo del IPT. Resultados: Se analizaron aleatoriamente 186 IPT con nuevos medicamentos/indicaciones, publicados entre 2013 y 2022. La comparación se consideró suficiente en un 73,7% (IC95 66,9-79,5) de los casos. El 26,3% restante (IC95 20,5-33,1) presentaba comparaciones deficientes en el ensayo pivotal, ya fuera por comparador inadecuado (11,3%), parcialmente subóptimo (5,4%) o ausencia de un estudio comparativo (9,7%). No hubo diferencias en relación con el año de aprobación.Conclusiones: Aproximadamente uno de cada cuatro nuevos medicamentos o indicaciones carece de una comparación suficiente en el momento de empezar a ser utilizado en la práctica clínica. La proporción no mejora a lo largo de los últimos 10 años. Las agencias reguladoras deben ser más exigentes en la selección del comparador para los ensayos clínicos pivotales, por cuestiones éticas y sanitarias. (AU)

Objective: Pivotal studies to approve new medicines often do not use the most appropriate comparator. The objective is to quantify this problem by analysing the Therapeutic Positioning Reports (IPT for its acronym in Spanish) published by the Spanish Health Ministry.Methods: The comparator was classified into six categories, based on the appropriateness of the treatment, i.e. whether it matched the standard of treatment when authorised: A-«initially adequate» (at the start of the study), B-«no comparator for ethical reasons», C-«no comparator -excluding B-«, D-«inadequate» and E-«partially suboptimal» (when it was standard for part of the included patients but not for all of them).The primary endpoint was the proportion of new drugs/indications with sufficient (categories A, B and C) or poor comparator (the rest). Information on comparators and standard treatment was extracted from the IPT. Results: We randomly analysed 186 IPTs with new drugs or indications, published between 2013 and March 2022. Comparability was assessed as sufficient in 73.7% (95%CI 66.9-79.5) of cases. The remaining 26.3% (95%CI 20.5-33.1) had poor comparisons in the pivotal trial, either due to inadequate comparator (11.3%), partially suboptimal (5.4%) or absence of a comparative study excluding ethical justification (9.7%). Conclusions: Approximately one in four new medicines or indications lacks sufficient comparability at the time of entry into clinical practice. The proportion has not improved over the last 10 years. Regulatory agencies need to be more stringent in comparator selection for pivotal clinical trials, for ethical and health reasons. (AU)

Protocolo de optimización de uso de medicamentos biológicos en enfermedades inflamatorias inmunomediadas / Protocol for optimization of the use of biological drugs in immune-mediated inflammatory diseases

Objetivo: La artritis reumatoide (AR), espondilitis anquilosante, psoriasis (Ps), artritis psoriásica (APs) están mediadas por factor de necrosis tumoral (TNF). El objetivo es el diseño multidisciplinar de un protocolo personalizado de agentes biológicos en enfermedades reumáticas y dermatológicas. Métodos: Se seleccionaron pacientes con AR, APs, espondiloartritis y Ps que recibían etanercept o adalimumab durante al menos 6 meses ininterrumpidamente. La monitorización terapéutica consideró criterios bioquímicos y criterios clínicos. Rangos terapéuticos óptimos de adalimumab: 5-8 μg/mL para AR y APs, 3.2-7 μg/mL para Ps y 4.6-12 μg/mL para espondiloartritis. Rangos óptimos de etanercept fueron: 2-3 μg/mL para AR y espondiloartritis, y 2-7 μg/mL para Ps y APs. Resultados: Se realizaron propuestas de optimización del tratamiento en pacientes con adecuada respuesta clínica y niveles de fármaco biológico superiores al rango terapéutico óptimo. Si la propuesta de optimización fue aceptada por facultativo, se valoró percepción de la enfermedad del paciente al primer y tercer mes. Los pacientes con niveles plasmáticos de fármaco inferiores al rango terapéutico óptimo, ausencia de anticuerpos anti-fármaco y adecuada respuesta clínica fueron propuestos a optimización de tratamiento mediante discontinuación o espaciamiento de administración. Los pacientes con niveles plasmáticos de fármaco inferiores al rango óptimo y anticuerpos anti-fármaco fueron propuestos a cambio de tratamiento o discontinuación, si se pudiera alcanzar control de enfermedad. Conclusiones: Este protocolo permite la personalización terapéutica de etanercept y adalimumab para enfermedades inflamatorias inmunomediadas en áreas de dermatología y reumatología. La implantación del protocolo podría mejorar la eficacia, seguridad, conveniencia y eficiencia de etanercept y adalimumab. (AU)

Objective: Rheumatoid arthritis (RA), ankylosing spondylitis, psoriasis (Ps), psoriatic arthritis (PAs) are mediated by tumor necrosis factor (TNF). The objective is the multidisciplinary design of a personalized protocol of biological agents in rheumatic and dermatological diseases. Methods: Patients with RA, PAs, spondyloarthritis and Ps receiving etanercept or adalimumab for at least 6 months uninterruptedly were selected. Therapeutic monitoring considered biochemical criteria and clinical criteria. Optimal therapeutic ranges of adalimumab were: 5-8 μg/mL for RA and APs, 3.2-7 μg/mL for Ps and 4.6-12 μg/mL for spondyloarthritis. Optimal ranges of etanercept were: 2-3 μg/mL for RA and spondyloarthritis, and 2-7 μg/mL for Ps and APs. Results: Proposals were elaborated to optimize treatment in patients with adequate clinical response and levels of biological drug higher than the optimal therapeutic range. If the optimization proposal was accepted by the physician, the patient’s perception of disease was evaluated at the first and third months. Patients with plasma drug levels below the optimal therapeutic range, absence of anti-drug antibodies and adequate clinical response were proposed for treatment optimization by discontinuation or spacing of administration. Patients with plasma drug levels below the optimal range and anti-drug antibodies were proposed in exchange for treatment or discontinuation -if disease control could be achieved-. Conclusions: This protocol allows the therapeutic personalization of etanercept and adalimumab for immune-mediated inflammatory diseases in areas of dermatology and rheumatology. Implementation of the protocol could improve the efficacy, safety, convenience and efficiency of etanercept and adalimumab. (AU)

Infections of implantable cardioverter-defibrillators: frequency, predisposing factors and clinical significance.

The prognosis for patients with ventricular arrhythmias has improved dramatically with the aid of implantable cardioverter-defibrillators (ICDs). Although infection is a serious complication that frequently causes dysfunction and loss of ICDs, the frequency, predisposing risk-factors, and clinical and microbiological features are only partially understood. This study describes a retrospective review of 423 procedures in 278 patients with ICD primary implants and replacements performed at a tertiary-care hospital. Generators were placed in either a pectoral (68%) or abdominal (32%) site, and electrodes were placed transvenously in 97% of the patients. Most (95%) interventions were performed in a one-stage procedure. Infection developed with ten (2.4%) implanted devices. Four cases occurred within 30 days of surgery ('early infections') and six occurred > 1 month after surgery ('late infections'). In univariate analysis, factors associated with the development of an early infection were: two-stage surgery, a sub-costal approach, and abdominal generator placement. In patients with late infections, a significant association was found with trauma or decubitus ulcer in the generator area. Infection presented with local signs without systemic complications. Seven of the ten patients required complete removal of the system.

Marjolin's ulcer arising from a laparostomy scar.

Marjolin's ulcer is the malignant transformation of a scar, usually as a squamous cell carcinoma. An uncommon presentation form is from a laparostomy scar. A 49-year-old patient that had a laparostomy during the treatment of a necrohemorrhagic pancreatitis in 1987 complained 13 years later of a 20-cm ulcer on the laparostomy scar. A resection of the abdominal wall including the ulcer and a segmental transverse colectomy were performed because of infiltration by an invasive squamous cell carcinoma. Ten months later, axillary lymphadenectomy was performed because of lymph node metastasis. Currently, the patient is free of disease. Lymph node infiltration is frequent in squamous cell carcinoma on Marjolin's ulcer and survival is not good. Prophylaxis of this disease includes meticulous care of wounds, with early skin grafts when required and treatment of infections.

[Anticholinesterases in the treatment of Alzheimer's disease]. / Anticolinesterásicos en el tratamiento de la enfermedad de Alzheimer.

INTRODUCTION: Among the numerous pathophysiological theories that attempt to explain the development of Alzheimer's disease (AD) there are two facts that stand out above the rest: on the one hand, the formation of neurofibrillary tangles inside cells and, on the other, the extra-cellular deposition of beta-amyloid protein. These two mechanisms lead to neurodegeneration and the death of cells by means of a process called 'apoptosis' or 'programmed cell death'. In the early stages of this neurodegenerative process it is more pronounced in cholinergic-type brain centres. This led to the formulation of the so-called cholinergic theory of Alzheimer, which provides the rationale behind the use of the drugs that are currently available to treat this disease, namely, acetylcholine esterase (AChE) inhibitors (rivastigmine, donepezil and galanthamine). DEVELOPMENT AND CONCLUSIONS: We review the possible pharmacological approaches that could help to prevent or delay cell death, and which act on the mechanisms involved in the production of neurofibrillary tangles or the deposition of beta-amyloid protein. We also review the main characteristics of cholinergic neurotransmission, which will help us to understand the therapeutic approaches that have been applied in an attempt to enhance deficient cholinergic neurotransmission. One of the most notable of these is the amount of attention recently being paid to the enzyme AChE, which increases the bioavailability of the neurotransmitter in the cholinergic synapses by preventing the hydrolysis of acetylcholine; these are the only drugs currently available for the symptomatic treatment of this disease.

[Cutaneous alternariosis and its diagnosis in an inmunocompromised patient]. / Alternariosis cutánea en paciente inmunocomprometido. Su diagnóstico.

In this paper, a cutaneous alternariosis is described. This is a strange opportunist infection with less than 100 cases. The patient was not VIH although inmunocompromised due to several factors: Malabsorption Syndrome, megaloblastic anemia secondary to gastrectomy and distal pancreatomy with gastrodigiunostomia due to gastric adenocarcinoma four years ago; splenectomied in the same operation, long treatment with hydantoin, and corticosteroids. The patient was managed in the internal medicine unit due to a problematic respiratory infection with cardiac rhythm disorder and progressive debility in lower limbs, together with cutaneous lesions in which "alternaria sp" was isolated by culture. After beginning treatment with oral itraconazole, his evolution was excellent. The main interest consists in the rareness and the original presentation of the cutaneous alternariosis in this case.

Respiratory disorders and quality of sleep in patients on the waiting list for lung transplantation.

BACKGROUND: The purpose of this study was to assess the quality of sleep and extent of respiratory disorders in patients awaiting lung transplantation as compared with a control group. METHODS: From September 2003 to November 2003, 17 clinically stable patients on the waiting list for lung transplantation and 14 healthy controls (with similar age, gender, and body mass index) were studied. Diagnostic polysomnography (PSG) was carried out for all subjects. RESULTS: Seventeen patients were included, 15 men and 2 women, aged 51 +/- 14 years. The indication for lung transplantation was emphysema in 7 cases, pulmonary fibrosis in 6, and "other" in 4. Patients awaiting lung transplantation had the following respiratory values: mean FEV1, 1105 mL (34% of predicted); PaO2, 54 mm Hg; and PaCO2, 44 mm Hg. Significant differences were found among the waiting-list patients in terms of predominance of light sleep, wakeful periods, and phase changes per sleep-hour, as compared with the control group. The recording of the respiratory events showed an apnea-hypopnea index of 6.13, sleeping time with SaO2 <90% of 1.80%, and a mean number of significant desaturations (<4%) of 6.38. There were no statistically significant differences with respect to the control group. CONCLUSIONS: Poor quality of sleep was observed in patients awaiting lung transplantation as compared with a healthy control group. There was no evidence of more respiratory events or significant desaturations in these patients, probably due to the provision of supplementary oxygen therapy during the PSG.

Chronic alcoholism decreases polyunsaturated fatty acid levels in human plasma, erythrocytes, and platelets--influence of chronic liver disease.

The effect of chronic ethanol ingestion on fatty acid composition of plasma, erythrocyte and platelet phospholipids and on plasma 6-keto-PGF1alpha was studied. Two groups of alcoholic subjects, one of them with chronic liver disease, were studied and compared to a control group of healthy subjects. Linoleic acid was not affected by alcoholism but its larger metabolites arachidonic acid (20:4n6) and docosatetraenoic acid (22:4n6) tended to be lower in erythrocytes and platelets of both groups of alcoholic patients; the decrease was more marked in the presence of chronic liver disease. Docosahexaenoic acid (22:6n3) was markedly decreased in plasma, erythrocytes and platelets obtained from alcoholic patients with chronic liver disease. Plasma levels of 6-keto-PGF1alpha, a metabolite of prostacyclin (PGI2), remained unchanged. We conclude that chronic ethanol ingestion induces important changes in long-chain polyunsaturated fatty acids, mainly in platelets, and that these changes are exacerbated when patients suffer from chronic liver disease.

Therapeutic decision tree for patients with sustained ventricular tachyarrhythmias or aborted cardiac arrest: a critical review of the Antiarrhythmics Versus Implantable Defibrillator trial and the Canadian Implantable Defibrillator Study.

Antiarrhythmic drugs, mainly amiodarone and sotalol, radiofrequency catheter ablation, and the implantable cardioverter defibrillator (ICD) are the 3 therapeutic options in patients with sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Idiopathic VT, incessant VT, frequently recurring, hemodynamically stable VT, and VT based on bundle branch reentry, are candidates for radiofrequency catheter ablation. Patients with high-risk ventricular tachyarrhythmias should receive ICDs as initial therapy. Two studies, the Antiarrhythmics Versus Implantable Defibrillator trial (AVID) and the Canadian Implantable Defibrillator Study (CIDS) have tried to approach the problem of these high-risk ventricular tachyarrhythmias. Although at 3 years, the ICD in AVID demonstrated a significant relative risk reduction over amiodarone of 31.5%, CIDS could not duplicate this finding. At 3 years, the relative risk reduction conferred by the ICD over amiodarone in CIDS was only 13.7%. A careful analysis of both studies suggests that CIDS was insufficiently powered to demonstrate statistically significant benefits similar to those shown by AVID, and furthermore, seemed to include an undetermined number of low-risk VT patients. The problem in the CIDS trial in this regard was the recruitment of patients in whom the inclusion criteria were met by the arrhythmias induced during the electrophysiology stimulation study, but which did not exist in real life. In addition CIDS included 14% of patients with (1) undocumented syncope and inducible monomorphic sustained VT; or (2) long runs of spontaneous nonsustained VT. Under these circumstances, the therapeutic implications of AVID remain unchallenged.

Current role and future perspectives for radiofrequency catheter ablation of postmyocardial infarction ventricular tachycardia.

The most common substrate for ventricular tachycardia (VT) is a postmyocardial infarction (MI) scar. Radiofrequency catheter ablation (RFCA) in post-MI VT faces clinical, electrophysiologic, anatomic, and methodologic difficulties not found in many other human tachycardias. The pathophysiologic understanding of post-MI VT is incomplete; this influences the process of selecting RFCA target sites, which is time consuming, demands catheter stability, and has low sensitivity and predictive value for VT interruption by RF current. Improving and simplifying the methodology of RFCA in post-MI VT is badly needed. We review the pathophysiology of post-MI VT from the data reported on endocardial, epicardial, and intramural ventricular mapping obtained either intraoperatively or in a Langendorff perfused set-up in hearts from transplanted patients. From these studies we conclude that (1) some post-MI VT cases are not amenable to RFCA (reentry around the scar, VT having a subepicardial or deep intramural substrate, or a wide, extensive, subendocardial intrascar area of slow conduction); and (2) searching for the endocardial exit is advantageous for selecting the RFCA targets. We also comment on a new self-reference mapping catheter that allows the recording of high gain, noise-free, unfiltered and filtered unipolar signals as well as unipolar pacing. Among the unresolved issues in these patients is the meaning of fast nonclinical VT induced after successful RFCA of the clinical VT, which may explain why a substantial number of these patients still receive an implantable cardioverter-defibrillator.

Amiodarone and "primary" prevention of sudden death: critical review of a decade of clinical trials.

Several trials have evaluated the role of amiodarone in decreasing mortality in patients at high risk of developing sudden death. Current evidence does not support the prophylactic use of amiodarone in myocardial infarction (MI) survivors with a depressed left ventricular function and/or frequent or complex ventricular ectopy. Some postinfarction trials (e.g., the Spanish Study of Sudden Death [SSSD]) found mortality rates in controls much lower than the expected figures. Other postinfarction trials--the European Amiodarone Myocardial Infarction Arrhythmia Trial (EMIAT) and the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial (CAMIAT)--despite observing a 2-year mortality rate of about 15% as expected, could not demonstrate a significant reduction in mortality. Amiodarone decreases the risk of sudden death in postinfarction patients by about 35%. In patients with a history of heart failure and left ventricular dysfunction, evidence is not sufficiently strong to use amiodarone for prevention of sudden death. The 2 major trials on such patients, Group for the Study of Survival in Heart Failure in Argentina (Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina or GESICA) and the Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure (STAT-CHF), arrived at conflicting results. Meta-analyses have been performed to overcome the small sample size of these trials, with the aim of assessing the benefit of amiodarone on total mortality. Differences among the recruited populations make it difficult to extract clinically applicable conclusions from these overviews. Even accepting that amiodarone might decrease total mortality by 10%, it is difficult to identify the patients for whom such a beneficial effect applies. A practical consequence of amiodarone trials is that this drug can be used rather safely in patients with left ventricular dysfunction of any etiology as, in contrast to some class I agents, it does not increase mortality. Therefore, amiodarone is the drug of choice when antiarrhythmic drug treatment is indicated in patients with left ventricular dysfunction.