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1.
Toxicol Sci ; 183(1): 14-35, 2021 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-34109416

RESUMO

Originally developed to inform the acute toxicity of chemicals on fish, the zebrafish embryotoxicity test (ZET) has also been proposed for assessing the prenatal developmental toxicity of chemicals, potentially replacing mammalian studies. Although extensively evaluated in primary studies, a comprehensive review summarizing the available evidence for the ZET's capacity is lacking. Therefore, we conducted a systematic review of how well the presence or absence of exposure-related findings in the ZET predicts prenatal development toxicity in studies with rats and rabbits. A two-tiered systematic review of the developmental toxicity literature was performed, a review of the ZET literature was followed by one of the mammalian literature. Data were extracted using DistillerSR, and study validity was assessed with an amended SYRCLE's risk-of-bias tool. Extracted data were analyzed for each species and substance, which provided the basis for comparing the 2 test methods. Although limited by the number of 24 included chemicals, our results suggest that the ZET has potential to identify chemicals that are mammalian prenatal developmental toxicants, with a tendency for overprediction. Furthermore, our analysis confirmed the need for further standardization of the ZET. In addition, we identified contextual and methodological challenges in the application of systematic review approaches to toxicological questions. One key to overcoming these challenges is a transition to more comprehensive and transparent planning, conduct and reporting of toxicological studies. The first step toward bringing about this change is to create broad awareness in the toxicological community of the need for and benefits of more evidence-based approaches.


Assuntos
Testes de Toxicidade , Peixe-Zebra , Animais , Feminino , Gravidez , Coelhos , Ratos
2.
Sci Rep ; 11(1): 6403, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33737635

RESUMO

Drug-induced liver injury (DILI) causes one in three market withdrawals due to adverse drug reactions, causing preventable human suffering and massive financial loss. We applied evidence-based methods to investigate the role of preclinical studies in predicting human DILI using two anti-diabetic drugs from the same class, but with different toxicological profiles: troglitazone (withdrawn from US market due to DILI) and rosiglitazone (remains on US market). Evidence Stream 1: A systematic literature review of in vivo studies on rosiglitazone or troglitazone was conducted (PROSPERO registration CRD42018112353). Evidence Stream 2: in vitro data on troglitazone and rosiglitazone were retrieved from the US EPA ToxCast database. Evidence Stream 3: troglitazone- and rosiglitazone-related DILI cases were retrieved from WHO Vigibase. All three evidence stream analyses were conducted according to evidence-based methodologies and performed according to pre-registered protocols. Evidence Stream 1: 9288 references were identified, with 42 studies included in analysis. No reported biomarker for either drug indicated a strong hazard signal in either preclinical animal or human studies. All included studies had substantial limitations, resulting in "low" or "very low" certainty in findings. Evidence Stream 2: Troglitazone was active in twice as many in vitro assays (129) as rosiglitazone (60), indicating a strong signal for more off-target effects. Evidence Stream 3: We observed a fivefold difference in both all adverse events and liver-related adverse events reported, and an eightfold difference in fatalities for troglitazone, compared to rosiglitazone. In summary, published animal and human trials failed to predict troglitazone's potential to cause severe liver injury in a wider patient population, while in vitro data showed marked differences in the two drugs' off-target activities, offering a new paradigm for reducing drug attrition in late development and in the market. This investigation concludes that death and disability due to adverse drug reactions may be prevented if mechanistic information is deployed at early stages of drug development by pharmaceutical companies and is considered by regulators as a part of regulatory submissions.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Diabetes Mellitus/tratamento farmacológico , Rosiglitazona/efeitos adversos , Troglitazona/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/patologia , Diabetes Mellitus/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Humanos , Hipoglicemiantes , Fígado/efeitos dos fármacos , Fígado/patologia , Rosiglitazona/uso terapêutico , Troglitazona/uso terapêutico
3.
Med Ref Serv Q ; 39(1): 90-99, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32069203

RESUMO

This column describes a project funded by the Big Data to Knowledge initiative to develop online learning modules for researchers, clinicians, and informationists/librarians on aspects of next-generation sequencing projects. The modules describe a framework for next-generation sequencing projects, with particular emphasis placed on experimental design, ethical considerations, data storage, and data sharing. The author outlines how the modules were developed and summarizes their contents.


Assuntos
Big Data , Biologia Computacional/educação , Instrução por Computador/tendências , Bases de Dados Genéticas , Sequenciamento de Nucleotídeos em Larga Escala , Humanos
4.
J Cardiovasc Pharmacol Ther ; 24(4): 359-364, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30614246

RESUMO

AIMS: There are limited data on aspirin (ASA) desensitization for patients with coronary disease. We present our experience with a rapid nurse-led oral desensitization regimen in patients with aspirin sensitivity undergoing coronary angiography. METHODS: This single-center retrospective observational study includes patients with a history of ASA sensitivity undergoing coronary angiography with intent to perform percutaneous coronary intervention (PCI). RESULTS: Between January 2012 and January 2017, 24 patients undergoing coronary angiography for stable coronary disease (7 cases) or acute coronary syndromes (non-ST-segment myocardial infarction [NSTEMI; 8 cases], STEMI [9 cases]) underwent aspirin desensitization having reported previous reactions to aspirin. At initial presentation, previous sensitivity reactions were reported as: mucocutaneous reactions in 17 patients (urticaria in 3 [13%], nonurticarial rash in 6 [25%], angio-oedema in 8 [33%]), respiratory sensitivity in 4 (17%), and systemic anaphylactoid reactions in 3 (13%). Seventeen (71%) patients underwent PCI. Desensitization was acutely successful in 22 (92%) patients and unsuccessful in 2 (8%) patients who both had a single short-lived episode of acute bronchospasm treated successfully with nebulized salbutamol. Fifteen successfully desensitized patients completed 12 months of aspirin; no patient had recurrent hypersensitivity reaction. Aspirin was stopped prior to 12 months in 7 patients (replaced by warfarin [1 case], no antiplatelet or single antiplatelet clinically indicated and clopidogrel chosen [4 cases], patient choice without evidence of recurrent hypersensitivity [1 case], and death due to cardiogenic shock following STEMI [1 case]). CONCLUSION: A rapid aspirin desensitization protocol is safe and effective across a broad spectrum of hypersensitivity reactions and clinical presentations.


Assuntos
Síndrome Coronariana Aguda/terapia , Aspirina/administração & dosagem , Dessensibilização Imunológica , Hipersensibilidade a Drogas/prevenção & controle , Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/administração & dosagem , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Síndrome Coronariana Aguda/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Aspirina/efeitos adversos , Aspirina/imunologia , Dessensibilização Imunológica/efeitos adversos , Dessensibilização Imunológica/enfermagem , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico por imagem , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/imunologia , Estudos Retrospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Fatores de Tempo , Resultado do Tratamento
5.
Coron Artery Dis ; 29(7): 564-572, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29944476

RESUMO

BACKGROUND: The PRAMI and CvLPRIT trials support preventive percutaneous coronary intervention (PCI) for multivessel coronary disease found during ST-segment elevation myocardial infarction (STEMI). We assess our real-world experience of the management of multivessel disease identified during primary PCI (PPCI) in a large UK regional centre. PATIENTS AND METHODS: All STEMI patients who underwent culprit-only PPCI during the study period (August 2011 to August 2013) were retrospectively assessed for eligibility to each trial. The two resulting groups were designated as the 'observational' cohorts. Primary outcomes were then determined and compared with the culprit-only revascularisation cohorts from the respective published randomized controlled trials (RCTs). RESULTS: A total of 1143 consecutive cases were presented during the study period. Of these, 343 would have been suitable for inclusion to PRAMI and were included in the 'observational PRAMI' cohort; 196 patients were included in the 'observational CvLPRIT' cohort.The 'observational PRAMI' cohort experienced fewer primary outcome events (13.1 vs. 22.9%), cardiac deaths (0.6 vs. 4.3%) and nonfatal myocardial infarctions (3.5 vs. 8.7%) than the culprit-only PCI PRAMI cohort (n=231); there were significantly more diabetics (P=0.022) and anterior STEMI initial presentations in the culprit-only PCI PRAMI cohort. Primary outcomes were comparable to those of the preventive PCI PRAMI cohort.The 'observational CvLPRIT' cohort showed no significant difference in primary outcomes over 12 months (16.8 vs. 21.2%), but significantly lower all-cause mortality (2 vs. 6.9%) than the culprit-only PCI CvPLRIT cohort (n=146). The 30-day event rates were similar to the preventive PCI arm; the 12-month events were better than the nonpreventive, but not as good as the preventive RCT cohorts. CONCLUSION: Outcomes from culprit-only primary PCI for multivessel disease in patients selected by the RCT criteria from an all-comers population representing real-life experience are better than those published in the two main RCTs. The RCTs may have selected a high-risk population for study exaggerating the benefits of preventive PCI.


Assuntos
Doença da Artéria Coronariana/terapia , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Inglaterra , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Fatores de Tempo , Resultado do Tratamento
6.
Schizophr Res ; 185: 58-66, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28038920

RESUMO

Clozapine is the only medication indicated for treating refractory schizophrenia, due to its superior efficacy among all antipsychotic agents, but its mechanism of action is poorly understood. To date, no studies of human postmortem brain have characterized the gene expression response to clozapine. Therefore, we addressed this question by analyzing expression data extracted from published microarray studies involving brains of patients on antipsychotic therapy. We first performed a systematic review and identified four microarray studies of postmortem brains from antipsychotic-treated patients, then extracted the expression data. We then performed generalized linear model analysis on each study separately, and identified the genes differentially expressed in response to clozapine compared to other atypical antipsychotic medications, as well as their associated canonical pathways. We also found a number of genes common to all four studies that we analyzed: GCLM, ZNF652, and GYPC. In addition, pathway analysis highlighted the following processes in all four studies: clathrin-mediated endocytosis, SAPK/JNK signaling, 3-phosphoinositide synthesis, and paxillin signaling. Our analysis yielded the first comprehensive compendium of genes and pathways differentially expressed upon clozapine treatment in the human brain, which may provide insight into the mechanism and unique efficacy of clozapine, as well as the pathophysiology of schizophrenia.


Assuntos
Antipsicóticos/uso terapêutico , Encéfalo/efeitos dos fármacos , Clozapina/uso terapêutico , Expressão Gênica/efeitos dos fármacos , Esquizofrenia , Transdução de Sinais/efeitos dos fármacos , Autopsia , Encéfalo/fisiopatologia , Bases de Dados Bibliográficas/estatística & dados numéricos , Feminino , Humanos , Masculino , Esquizofrenia/tratamento farmacológico , Esquizofrenia/patologia , Esquizofrenia/fisiopatologia , Transdução de Sinais/genética
8.
Environ Int ; 92-93: 630-46, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27039952

RESUMO

Assessments of methodological and reporting quality are critical to adequately judging the credibility of a study's conclusions and to gauging its potential reproducibility. To aid those seeking to assess the methodological or reporting quality of studies relevant to toxicology, we conducted a scoping review of the available guidance with respect to four types of studies: in vivo and in vitro, (quantitative) structure-activity relationships ([Q]SARs), physico-chemical, and human observational studies. Our aims were to identify the available guidance in this diverse literature, briefly summarize each document, and distill the common elements of these documents for each study type. In general, we found considerable guidance for in vivo and human studies, but only one paper addressed in vitro studies exclusively. The guidance for (Q)SAR studies and physico-chemical studies was scant but authoritative. There was substantial overlap across guidance documents in the proposed criteria for both methodological and reporting quality. Some guidance documents address toxicology research directly, whereas others address preclinical research generally or clinical research and therefore may not be fully applicable to the toxicology context without some translation. Another challenge is the degree to which assessments of methodological quality in toxicology should focus on risk of bias - as in clinical medicine and healthcare - or be broadened to include other quality measures, such as confirming the identity of test substances prior to exposure. Our review is intended primarily for those in toxicology and risk assessment seeking an entry point into the extensive and diverse literature on methodological and reporting quality applicable to their work.


Assuntos
Exposição Ambiental , Poluentes Ambientais/toxicidade , Viés , Humanos , Reprodutibilidade dos Testes , Projetos de Pesquisa
9.
Heart ; 96(19): 1557-63, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20736208

RESUMO

BACKGROUND: Strategies to reduce DTB (door-to-balloon) time have been previously described. However, there is no well-established data-monitoring system that can be used for prompt feedback. The aims of this study were to use statistical process control (SPC) methodology to measure current processes, to provide real-time feedback on the impact of a change in service delivery and to identify individual outliers for specific investigation. METHODS: A prospective study was conducted in a tertiary centre in North England. Data were collected for 841 consecutive STEMI patients from the local district undergoing PPCI. The impact on median DTB time after changes in protocols were prospectively determined. RESULTS: Median DTB times fell significantly as a result of changes in protocol. The upper control limit (UCL) decreased from 209 to 86 min and narrower control limits indicated improved performance. The main outliers included patients presenting to the Accident and Emergency department and patients who developed STEMI while being treated in non-cardiology wards for other reasons (18.3% of the study population). CONCLUSIONS: SPC provides a statistically robust mechanism for assessing the effect of process redesign interventions, and in this context provides a clear visual representation of DTB times for individual patients. Identification of significant outliers allows investigation of any variation with a special cause. It allows a unit to identify when a system of service delivery, albeit stable, is inadequate and needs redesign and can monitor the impact of changes in protocol.


Assuntos
Angioplastia Coronária com Balão/estatística & dados numéricos , Serviços Médicos de Emergência/organização & administração , Infarto do Miocárdio/terapia , Idoso , Protocolos Clínicos , Interpretação Estatística de Dados , Inglaterra , Medicina Baseada em Evidências , Retroalimentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo
10.
BMJ ; 336(7650): 931-4, 2008 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-18367500

RESUMO

OBJECTIVE: To use funnel plots and cumulative funnel plots to compare in-hospital outcome data for operators undertaking percutaneous coronary interventions with predicted results derived from a validated risk score to allow for early detection of variation in performance. DESIGN: Analysis of prospectively collected data. SETTING: Tertiary centre NHS hospital in the north east of England. PARTICIPANTS: Five cardiologists carrying out percutaneous coronary interventions between January 2003 and December 2006. MAIN OUTCOME MEASURES: In-hospital major adverse cardiovascular and cerebrovascular events (in-hospital death, Q wave myocardial infarction, emergency coronary artery bypass graft surgery, and cerebrovascular accident) analysed against the logistic north west quality improvement programme predicted risk, for each operator. Results are displayed as funnel plots summarising overall performance for each operator and cumulative funnel plots for an individual operator's performance on a case series basis. RESULTS: The funnel plots for 5198 patients undergoing percutaneous coronary interventions showed an average observed rate for major adverse cardiovascular and cerebrovascular events of 1.96% overall. This was below the predicted risk of 2.06% by the logistic north west quality improvement programme risk score. Rates of in-hospital major adverse cardiovascular and cerebrovascular events for all operators were within the 3sigma upper control limit of 2.75% and 2sigma upper warning limit of 2.49%. CONCLUSION: The overall in-hospital major adverse cardiovascular and cerebrovascular events rates were under the predicted event rate. In-hospital rates after percutaneous coronary intervention procedure can be monitored successfully using funnel and cumulative funnel plots with 3sigma control limits to display and publish each operator's outcomes. The upper warning limit (2sigma control limit) could be used for internal monitoring. The main advantage of these charts is their transparency, as they show observed and predicted events separately. By this approach individual operators can monitor their own performance, using the predicted risk for their patients but in a way that is compatible with benchmarking to colleagues, encapsulated by the funnel plot. This methodology is applicable regardless of variations in individual operator case volume and case mix.


Assuntos
Angioplastia Coronária com Balão/normas , Cardiologia/normas , Competência Clínica/normas , Angioplastia Coronária com Balão/estatística & dados numéricos , Cardiologia/estatística & dados numéricos , Doenças Cardiovasculares/etiologia , Transtornos Cerebrovasculares/etiologia , Humanos , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Fatores de Risco
11.
Catheter Cardiovasc Interv ; 71(2): 138-45, 2008 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-18231990

RESUMO

BACKGROUND: Rescue angioplasty (rPCI) for failed fibrinolysis is associated with a low mortality if successful, but a high mortality if it fails. The latter may reflect a high-risk group or harm in some patients. Predictors of success or failure of rPCI may aid selection of patients to be treated. METHODS: Unselected patients referred for rPCI from March 1994 to March 2005 were studied to determine the predictors of a failed procedure and 1-year mortality. RESULTS: Of 440 patients undergoing emergency coronary angiography for failed fibrinolysis (1-year mortality 18%), 101 had thrombolysis in myocardial infarction flow grade (TFG) 3 in the infarct-related vessel. rPCI was attempted in 318 of 339 patients with 75 years, shock, and final TFG < 3 were independent predictors of 1-year mortality. CONCLUSIONS: Cardiogenic shock is an independent predictor of a failed rPCI. Age group >75 years and shock were the only independent clinical predictors of 1-year mortality. These clinical variables may help in selecting patients for either a strategy of rescue angioplasty after failed fibrinolysis, or in selecting specific patients who might do better with a policy of primary angioplasty.


Assuntos
Angioplastia Coronária com Balão , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/terapia , Terapia Trombolítica , Idoso , Comorbidade , Angiografia Coronária , Feminino , Humanos , Balão Intra-Aórtico , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/epidemiologia , Seleção de Pacientes , Radiografia Intervencionista , Retratamento , Choque Cardiogênico/mortalidade , Análise de Sobrevida , Fatores de Tempo , Falha de Tratamento
12.
Catheter Cardiovasc Interv ; 70(5): 691-700, 2007 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-17932899

RESUMO

UNLABELLED: The impact of chronic coronary obstructions on resting blood flow in stable cardiac patients and the response to percutaneous coronary intervention (PCI) using the TIMI frame count method has not been well documented. We studied the impact of coronary artery stenosis severity on the corrected TIMI frame count (cTFC) in chronically stenosed coronary arteries. We prospectively and quantitatively determined the impact of stenting on the cTFC during elective PCI. METHODS: In substudy 1, analysis was performed to obtain the mean cTFC for arteries with <50% stenosis (Group A), 51-75% stenosis (Group B), 76-85% stenosis (Group C1), 86-95% stenosis (Group C2) and 96-99% stenosis (Group C3). In substudy 2, the cTFC and quantitative coronary angiography were performed pre- and post-PCI. RESULTS: In substudy 1, the cTFC increased exponentially beyond a diameter stenosis of 75% (P < 0.01). However there was no significant difference in the cTFC for coronary arteries with <75% stenosis. In substudy 2, the overall pre- and poststenting cTFC was 17.1 +/- 11.7 and 7.8 +/- 2.7 (P < 0.01) and the TFC index [calculated by dividing the mean cTFC for the relevant artery by the mean cTFC for the corresponding coronary artery in a previously derived control group in our laboratory] was 1.6 +/- 1 and 0.7 +/- 0.2 (P = < 0.01), respectively. CONCLUSION: We have demonstrated that there was a significant increase in the cTFC when the coronary artery stenosis was more than 75% reflecting significant flow abnormalities at this degree of stenosis in chronically diseased coronary arteries. Following stenting there is a significant improvement in the cTFC, which is better than the cTFC for arteries with normal flow, suggesting early hyperaemia.


Assuntos
Cateterismo Cardíaco , Circulação Coronária , Estenose Coronária/fisiopatologia , Estenose Coronária/terapia , Stents , Idoso , Análise de Variância , Velocidade do Fluxo Sanguíneo , Doença Crônica , Angiografia Coronária , Estenose Coronária/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estatísticas não Paramétricas , Resultado do Tratamento
13.
Acute Card Care ; 9(4): 231-8, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17851976

RESUMO

UNLABELLED: The TIMI frame count (TFC) is a useful measure of coronary flow. To be widely applicable, the effect of different catheter sizes and the use of intracoronary glyceryl trinitrate (ICGTN) must be determined when films are acquired at lower acquisition rates (12.5 frames/s, f/s). METHODS: We compared 6F versus 5F diagnostic catheters (n = 44), 6F versus 7F diagnostic catheters (n = 45) and 6F diagnostic versus 7F guide catheters (n = 44). In the nitrate angiography group (n = 141), coronary angiography was performed before and after 200 micrograms of ICGTN. In the nitrate percutaneous coronary intervention (PCI) group (n = 48), coronary angiography was performed before and after 200 micrograms of ICGTN after the completion of the elective PCI procedure. RESULTS: The mean difference in the uncorrected TFC using 6F and 5F was 0.02 (95 % CI -0.5, 0.6; P = 0.9); using 6F and 7F diagnostic catheters it was 0.3 (95% CI -0.49, 1.1; p = 0.4); and using 6F diagnostic and 7F guide catheters it was 0.4 (95% CI -2.6, 3.4; P = 0.7) respectively. In the nitrate angiography group, the uncorrected TFC before and after ICGTN was 13.1+/-6.2 and 15+/-7.5 (equivalent to 31.4+/-14.9 and 36+/-2 at 30 f/s), with a mean difference of 1.9 (95% CI 1.3, 2.5; P = or <0.0001). In the nitrate PCI group, the uncorrected TFC before and after ICGTN administration was 9.2+/-3.7 and 10.3+/-4.2 (equivalent to 22.6+/-9.6 and 25.2+/-11 at 30 f/s) respectively with a mean difference between the two injections of 1.2 (95% CI -0.4, 1.9; P = 0.003). CONCLUSION: We have demonstrated that the catheter sizes did not significantly affect the TFC when angiography was performed at 12.5f/s. The use of ICGTN significantly increased the TFC in both normal and diseased coronary arteries. This effect was also observed when ICGTN was administered into the culprit vessels after the completion of the elective PCI procedure. This effect must be considered when investigating the impact of specific treatments or drugs on coronary flow.


Assuntos
Angioplastia Coronária com Balão/instrumentação , Cateterismo Cardíaco/instrumentação , Angiografia Coronária/instrumentação , Circulação Coronária/fisiologia , Nitroglicerina , Vasodilatadores , Idoso , Circulação Coronária/efeitos dos fármacos , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
14.
J Invasive Cardiol ; 19(8): 339-46, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17712202

RESUMO

UNLABELLED: The intra-aortic balloon pump (IABP) is the most commonly used temporary cardiac assist device. The precise role and the mechanism of any benefit in high-risk patients undergoing percutaneous coronary intervention (PCI) have not been fully determined. We hypothesized that the use of an IABP following PCI in high-risk non-shocked patients would immediately increase coronary blood flow, tissue perfusion and hence preserve left ventricular function. METHODS: Predefined high-risk, but non-shocked, patients were randomized to either an IABP or no IABP following PCI. Angiography was performed pre-PCI, immediately post-PCI and 10 minutes after the completion of the procedure. TIMI flow grade (TFG), TIMI frame count (TFC) and myocardial blush grade (MBG) were measured. Echocardiographic wall motion index (WMI) was measured on days 1 and 30 following PCI. RESULTS: Of 33 patients, 17 received IABP and 16 did not. At final angiography, the TFG was 2.8 +/- 0.7 and 2.9 +/- 0.3 (p = 0.6), the TFC was 19.9 +/- 23 and 16.9 +/- 16.9 (p = 0.7), and the MBG was 2.5 +/- 0.9 and 2.5 +/- 0.7 (p = 0.9) in the IABP and the no-IABP arms. The WMI on day 1 was 1.7 +/- 0.4 and 1.7 +/- 0.4 (p = 0.7), and on day 30, it was 1.5 +/- 0.4 and 1.5 +/- 0.4 (p = 0.9). There was no difference in the total sum of ST-segment elevation prior to PCI (12.6 +/- 7.7 vs. 13.5 +/- 7.9; p = 0.8), nor in the summed ST change in subsequent electrocardiograms (ECGs) to 48 hours in both of the groups. CONCLUSION: Whether an IABP is of any benefit in non-shocked, but high-risk, patients undergoing PCI remains to be established, but any potential benefit does not appear to be associated with early improvement in coronary flow. Whether the insertion of an IABP improves coronary flow beyond 10 minutes is not known. However, the IABP did not significantly affect subsequent left ventricular wall motion index or ECG ST-segment resolution in this study.


Assuntos
Angioplastia Coronária com Balão , Circulação Coronária , Doença das Coronárias/fisiopatologia , Doença das Coronárias/terapia , Balão Intra-Aórtico , Adulto , Idoso , Angiografia Coronária , Doença das Coronárias/complicações , Doença das Coronárias/diagnóstico , Ecocardiografia , Feminino , Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco
15.
J Invasive Cardiol ; 19(5): 217-23, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17476036

RESUMO

BACKGROUND: Trials of rescue angioplasty (rPCI) following failed fibrinolysis have excluded patients with cardiogenic shock and the benefit of rPCI in this setting is unknown. We compared the clinical, angiographic characteristics, 30-day and 1-year outcomes of cardiogenic shock patients undergoing rPCI with those undergoing primary percutaneous coronary intervention (PPCI). METHODS: Of the 171 patients undergoing PCI for cardiogenic shock between 1994 and 2005 at our institution, the indication was for PPCI in 65 and rPCI in 59 patients. Clinical, procedural, 30- day and 1-year mortality data were compared. RESULTS: There were no differences between the cohorts with regard to clinical and pre-PCI angiographic variables, except that patients who underwent rPCI were more likely to be interhospital transfers (64% vs. 43%; p = 0.02) and had a longer door-to-balloon time (median 298 [IQR 395 to 180] minutes in the rPCI group vs. 131 [IQR 215 to 90] minutes in the PPCI group; p <0.01). Glycoprotein IIb/IIIa inhibitors were used less often (20% vs. 42%; p = 0.01), but use of stents was similar in both groups. Patients undergoing rPCI had a lower rate of final TIMI 3 flow grade (56% vs. 74%; p = 0.04) and a higher 1-year mortality (71% vs. 49%; p = 0.01). In the patients with final TIMI flow 3, 1-year mortality was higher in the rPCI group (61% vs. 37%; p = 0.04). In patients with successful procedures (survived procedure, no emergency CABG, TIMI 3 flow), 1-year mortality was higher in the rPCI group (59% vs. 33%; p = 0.02). One-year mortality was 85% in both groups if the procedure was unsuccessful. One-year mortality in patients >70 years old with cardiogenic shock undergoing rPCI was 100% (n = 15) and 70% (n = 14) with PPCI. Rescue angioplasty, anterior myocardial infarction, multivessel disease and postprocedure TIMI flow grade <3 were found to be independent predictors of mortality at 30 days. CONCLUSIONS: In the setting of cardiogenic shock, rPCI patients were treated later than those undergoing PPCI. They had a lower final TIMI 3 flow and higher 1-year mortality. Even patients with a successful rPCI procedure had a higher 1-year mortality than those with a successful PPCI. Rescue angioplasty in the setting of cardiogenic shock was found be an independent predictor of mortality. Rescue angioplasty in elderly patients in cardiogenic shock (>75 years) may be a futile treatment. Efforts should be made to improve reperfusion and survival in these patients, possibly by either adopting PPCI for all patients presenting with ST-elevation acute myocardial infarction or, if this is not logistically possible, adopting PPCI for selected high-risk patients or early referral for rPCI in high-risk groups receiving fibrinolysis.


Assuntos
Angioplastia Coronária com Balão/mortalidade , Mortalidade Hospitalar/tendências , Choque Cardiogênico/mortalidade , Choque Cardiogênico/terapia , Terapia Trombolítica/métodos , Idoso , Angioplastia Coronária com Balão/métodos , Cateterismo Cardíaco/métodos , Estudos de Coortes , Angiografia Coronária/métodos , Tratamento de Emergência/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Probabilidade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/etiologia , Estatísticas não Paramétricas , Análise de Sobrevida , Terapia Trombolítica/mortalidade , Fatores de Tempo
16.
Am Heart J ; 153(5): 763-71, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17452151

RESUMO

BACKGROUND: Early (30 days) and midterm (6 months) clinical outcomes in trials comparing rescue angioplasty (rescue percutaneous coronary intervention [rPCI]) with conservative treatment of failed fibrinolysis complicating ST-segment elevation myocardial infarction have shown variable results. Whether early rPCI confers late (up to 3 years) clinical benefits is not known. METHODS: The MERLIN trial compared rPCI and a conservative strategy in patients with failed fibrinolysis complicating ST-segment elevation myocardial infarction. Three hundred seven patients with electrocardiographic evidence of failure to reperfuse at 60 minutes were included. Patients in cardiogenic shock were excluded. Thirty-day and 1-year results have been reported. Results of 3 years of follow-up are presented. RESULTS: Three-year mortality in the conservative arm and rPCI, respectively, was 16.9% versus 17.6% (P = .9, relative difference [RD] -0.8, 95% CI [-9.3 to 7.8]). Death rates were similar (3.9% vs 3.2%) between 1- and 3-year follow-up, respectively. The incidence of the composite secondary end point of death, reinfarction, stroke, unplanned revascularization, or heart failure was significantly higher in the conservative arm (64.3% vs 49%, P = .01, RD 15.3, 95% CI [4.2-26]). There was no significant difference in the rate of reinfarction (0.7% vs 0.7%) or heart failure (1.3% vs 2.7%) between 1 and 3 years between the conservative and rPCI arms, respectively. The incidence of subsequent unplanned revascularization at 3 years was significantly higher in the conservative arm (33.8% vs 14.4%, P < .01, RD 19.4, 95% CI [10-28.7]), most of which occurred within 1 year; the rates between 1 and 3 years were 3.9% in the conservative arm versus 2% in the rPCI arm. There was a trend toward fewer strokes in the conservative arm at 3 years (conservative arm 2.6% vs rPCI 6.5%, P = .1, RD -3.9%, 95% CI [-9.4 to 0.8]), with similar stroke rates (1.3% vs 1.3%) between 1- and 3-year follow-up. CONCLUSIONS: Rescue angioplasty did not confer a late survival advantage at 3 years. The composite end point occurred less often in the rPCI arm mainly because of fewer unplanned revascularization procedures in the early phase of follow-up. The highest risk of clinical events in patients with failed reperfusion is in the first year, beyond which the rate of clinical events is low.


Assuntos
Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/terapia , Revascularização Miocárdica/estatística & dados numéricos , Terapia Trombolítica/estatística & dados numéricos , Comorbidade , Feminino , Seguimentos , Insuficiência Cardíaca/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Stents , Acidente Vascular Cerebral/epidemiologia , Análise de Sobrevida , Fatores de Tempo , Falha de Tratamento , Reino Unido/epidemiologia
17.
Eur J Radiol ; 61(2): 342-50, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17101256

RESUMO

UNLABELLED: A new generation of intravascular contrast agents, the non-ionic monomers have safety profiles that are superior to those of older ionic compounds. There are, however, significant differences between these agents. AIM: The aim of this study was to determine the incidence of early (<24h) and late (>24h to 7 days) reactions to two non-ionic contrast agents currently used during cardiac catheterisation: iopamidol 340 (Niopam Bracco UK Ltd.) and iomeprol 350 (Iomeron Bracco UK Ltd.). METHODS: This was a prospective, randomised, double blinded trial. One thousand nine hundred and eighty-five patients undergoing cardiac catheterisation received one of the following contrast agents on a weekly basis: iopamidol 340 (Niopam) and iomeprol 350 (Iomeron). Reactions that were possibly related to the contrast agents were recorded on predefined data collection forms during the first 24h of the procedure (early reaction) and after 24h to 7 days (late reaction) by means of a questionnaire. RESULTS: The baseline characteristics were matched in both the groups. There was no significant difference in the incidence of heat sensation experienced between the two groups (p=0.1). Early non-heat reactions occurred in 2.7% of patients receiving iopamidol 340 (Niopam) and 4% of those receiving iomeprol 350 (Iomeron) (p=0.1). Significant electrocardiographic changes were recorded in 1.7% of patients who received iopamidol 340 (Niopam), and 1% of those who received iomeprol 350 (Iomeron) (p=0.2). Bradycardia occurred more frequently in the iopamidol 350 group (0.8%) compared to the iomeprol 350 group (0.1%) p=0.02. Late reactions occurred in 16.2% of those receiving iopamidol 340 (Niopam) and 21.7% of those receiving iomeprol 350 (Iomeron) (p=0.02). A total of 23 (3.7%) patients in the iopamidol group and 39 (6.2%) patients in the iomeprol group reported nausea, p=0.01. CONCLUSIONS: The incidence of early adverse reactions was similar with the two non-ionic contrast agents. Although bradycardia was slightly more frequent using iopamidol 340, nausea was reported more commonly 24h after the procedure in patients receiving Iomeron 350 (Iomeron). We conclude that there were only minor clinical differences between these agents; both are safe and well tolerated.


Assuntos
Bradicardia/induzido quimicamente , Cateterismo Cardíaco/efeitos adversos , Meios de Contraste/efeitos adversos , Iopamidol/análogos & derivados , Iopamidol/efeitos adversos , Náusea/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste/administração & dosagem , Método Duplo-Cego , Eletrocardiografia , Feminino , Temperatura Alta , Humanos , Injeções Intravenosas , Iopamidol/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo
18.
Catheter Cardiovasc Interv ; 67(6): 879-86, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16652368

RESUMO

UNLABELLED: We determined the effectiveness of the Rescue device in restoring flow and achieving optimal tissue perfusion during percutaneous coronary intervention (PCI) in thrombus-laden coronary arteries. METHODS: A total of 30 patients with an acute coronary syndrome underwent PCI using the Rescue device. RESULTS: The mean age was 65.5 +/- 9.8 years. Although the Rescue device could not be passed across the lesion in 6 (20%) cases, debris was aspirated in 26 (87%). The uncorrected TIMI frame count improved following the use of the Rescue device and improved further at the completion of PCI (92.2 +/- 23.9 pre-PCI vs. 38.7 +/- 31.3 post-Rescue vs. 21.96 +/- 24 post-PCI, P < 0.0001). The thrombus score improved from 4 +/- 0 to 2.2 +/- 1.29 to 0.86 +/- 1.4 (P < 0.0001). TIMI flow grade (TFG) 3 was restored in 60% of cases following the Rescue device and in 87% after PCI. Myocardial blush grade 3 occurred in only 13% of patients following the Rescue device and 37% of patients after PCI. CONCLUSION: These data suggest that the Rescue device can aspirate considerable amounts of debris in the majority of patients and significantly improves the angiographic epicardial coronary blood flow. How effective such a device is in improving tissue perfusion and, thereby, clinical outcomes for patients remains to be seen.


Assuntos
Angioplastia Coronária com Balão , Aterectomia Coronária , Circulação Coronária , Trombose Coronária/terapia , Infarto do Miocárdio/terapia , Reperfusão Miocárdica , Idoso , Aterectomia Coronária/métodos , Angiografia Coronária , Trombose Coronária/diagnóstico por imagem , Trombose Coronária/fisiopatologia , Embolia/prevenção & controle , Feminino , Humanos , Masculino , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Stents , Resultado do Tratamento , Grau de Desobstrução Vascular
19.
Am Heart J ; 151(4): 863.e1-6, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16569550

RESUMO

UNLABELLED: Antiarrhythmic agents enhance maintenance of sinus rhythm (SR) after direct current cardioversion (DCC) for atrial fibrillation but there are few comparative trials. BACKGROUND: The aims of the study were (1) to establish whether patients successfully cardioverted to SR are more likely to stay in SR over 6 months if taking amiodarone or sotalol, and if so, to establish whether one agent is better than the other; (2) to establish whether taking amiodarone or sotalol is better at achieving chemical cardioversion within the 6 weeks before DCC; and (3) to establish whether DCC is more likely to be successful on a drug. METHODS: Randomized, prospective, nonblinded, controlled study of treatment with either amiodarone (n = 27), sotalol (n = 36), or no antiarrhythmic agent (n = 31). RESULTS: Chemical cardioversion occurred in 7 patients in the amiodarone group (A), 7 patients in the sotalol group (S), but none in the no-antiarrhythmic group (N). A total of 33 (92%) patients in the sotalol group, 22 (81%) patients in the amiodarone group, and 23 (74%) patients in the no-antiarrhythmic group were in SR after cardioversion. Of the original cohort of patients, 17 (63%) patients in the amiodarone group remained in SR at 6-month follow-up, compared with 14 (39%) in the sotalol group and 5 (16%) in the no-antiarrhythmic group (A vs N, P < .0002, P < .0006B [after Bonferroni correction]; A vs S, P = .05, P = .15B; and S vs N, P = .03, P = .09B). CONCLUSIONS: Amiodarone and sotalol achieved chemical cardioversion before planned electrical cardioversion in 26% and 19% of patients, respectively. After successful cardioversion, amiodarone appears better than sotalol at maintaining SR at 6 months.


Assuntos
Amiodarona/uso terapêutico , Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Cardioversão Elétrica , Sotalol/uso terapêutico , Idoso , Amiodarona/administração & dosagem , Antiarrítmicos/administração & dosagem , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sotalol/administração & dosagem , Resultado do Tratamento
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