Looking beyond borders: integrating best practices in benefit-risk analysis into the field of food and nutrition.

An integrated benefit-risk analysis aims to give guidance in decision situations where benefits do not clearly prevail over risks, and explicit weighing of benefits and risks is thus indicated. The BEPRARIBEAN project aims to advance benefit-risk analysis in the area of food and nutrition by learning from other fields. This paper constitutes the final stage of the project, in which commonalities and differences in benefit-risk analysis are identified between the Food and Nutrition field and other fields, namely Medicines, Food Microbiology, Environmental Health, Economics and Marketing-Finance, and Consumer Perception. From this, ways forward are characterized for benefit-risk analysis in Food and Nutrition. Integrated benefit-risk analysis in Food and Nutrition may advance in the following ways: Increased engagement and communication between assessors, managers, and stakeholders; more pragmatic problem-oriented framing of assessment; accepting some risk; pre- and post-market analysis; explicit communication of the assessment purpose, input and output; more human (dose-response) data and more efficient use of human data; segmenting populations based on physiology; explicit consideration of value judgments in assessment; integration of multiple benefits and risks from multiple domains; explicit recognition of the impact of consumer beliefs, opinions, views, perceptions, and attitudes on behaviour; and segmenting populations based on behaviour; the opportunities proposed here do not provide ultimate solutions; rather, they define a collection of issues to be taken account of in developing methods, tools, practices and policies, as well as refining the regulatory context, for benefit-risk analysis in Food and Nutrition and other fields. Thus, these opportunities will now need to be explored further and incorporated into benefit-risk practice and policy. If accepted, incorporation of these opportunities will also involve a paradigm shift in Food and Nutrition benefit-risk analysis towards conceiving the analysis as a process of creating shared knowledge among all stakeholders.

State of the art in benefit-risk analysis: introduction.

Risk-taking is normal in everyday life if there are associated (perceived) benefits. Benefit-Risk Analysis (BRA) compares the risk of a situation to its related benefits and addresses the acceptability of the risk. Over the past years BRA in relation to food and food ingredients has gained attention. Food, and even the same food ingredient, may confer both beneficial and adverse effects. Measures directed at food safety may lead to suboptimal or insufficient levels of ingredients from a benefit perspective. In BRA, benefits and risks of food (ingredients) are assessed in one go and may conditionally be expressed into one currency. This allows the comparison of adverse and beneficial effects to be qualitative and quantitative. A BRA should help policy-makers to make more informed and balanced benefit-risk management decisions. Not allowing food benefits to occur in order to guarantee food safety is a risk management decision much the same as accepting some risk in order to achieve more benefits. BRA in food and nutrition is making progress, but difficulties remain. The field may benefit from looking across its borders to learn from other research areas. The BEPRARIBEAN project (Best Practices for Risk-Benefit Analysis: experience from out of food into food; http://en.opasnet.org/w/Bepraribean) aims to do so, by working together with Medicines, Food Microbiology, Environmental Health, Economics & Marketing-Finance and Consumer Perception. All perspectives are reviewed and subsequently integrated to identify opportunities for further development of BRA for food and food ingredients. Interesting issues that emerge are the varying degrees of risk that are deemed acceptable within the areas and the trend towards more open and participatory BRA processes. A set of 6 'state of the art' papers covering the above areas and a paper integrating the separate (re)views are published in this volume.

State of the art in benefit-risk analysis: food microbiology.

Over the past years benefit-risk analysis (BRA) in relation to foods and food ingredients has gained much attention; in Europe and worldwide. BRA relating to food microbiology is however a relatively new field of research. Microbiological risk assessment is well defined but assessment of microbial benefits and the weighing of benefits and risk has not been systematically addressed. In this paper the state of the art in benefit-risk analysis in food microbiology is presented, with a brief overview of microbiological food safety practices. The quality and safety of foods is commonly best preserved by delaying the growth of spoilage bacteria and contamination by bacterial pathogens. However, microorganisms in food can be both harmful and beneficial. Many microorganisms are integral to various food production processes e.g. the production of beer, wine and various dairy products. Moreover, the use of some microorganisms in the production of fermented foods are often claimed to have beneficial effects on food nutrition and consumer health. Furthermore, food safety interventions leading to reduced public exposure to foodborne pathogens can be regarded as benefits. The BRA approach integrates an independent assessment of both risks and benefits and weighs the two using a common currency. Recently, a number of initiatives have been launched in the field of food and nutrition to address the formulation of the benefit-risk assessment approach. BRA has recently been advocated by EFSA for the public health management of food and food ingredients; as beneficial and adverse chemicals can often be found within the same foods and even the same ingredients. These recent developments in the scoping of BRA could be very relevant for food microbiological issues. BRA could become a valuable methodology to support evaluations and decision making regarding microbiological food safety and public health, supplementing other presently available policy making and administrative tools for microbiological food safety management.

State of the art in benefit-risk analysis: food and nutrition.

Benefit-risk assessment in food and nutrition is relatively new. It weighs the beneficial and adverse effects that a food (component) may have, in order to facilitate more informed management decisions regarding public health issues. It is rooted in the recognition that good food and nutrition can improve health and that some risk may be acceptable if benefit is expected to outweigh it. This paper presents an overview of current concepts and practices in benefit-risk analysis for food and nutrition. It aims to facilitate scientists and policy makers in performing, interpreting and evaluating benefit-risk assessments. Historically, the assessments of risks and benefits have been separate processes. Risk assessment is mainly addressed by toxicology, as demanded by regulation. It traditionally assumes that a maximum safe dose can be determined from experimental studies (usually in animals) and that applying appropriate uncertainty factors then defines the 'safe' intake for human populations. There is a minor role for other research traditions in risk assessment, such as epidemiology, which quantifies associations between determinants and health effects in humans. These effects can be both adverse and beneficial. Benefit assessment is newly developing in regulatory terms, but has been the subject of research for a long time within nutrition and epidemiology. The exact scope is yet to be defined. Reductions in risk can be termed benefits, but also states rising above 'the average health' are explored as benefits. In nutrition, current interest is in 'optimal' intake; from a population perspective, but also from a more individualised perspective. In current approaches to combine benefit and risk assessment, benefit assessment mirrors the traditional risk assessment paradigm of hazard identification, hazard characterization, exposure assessment and risk characterization. Benefit-risk comparison can be qualitative and quantitative. In a quantitative comparison, benefits and risks are expressed in a common currency, for which the input may be deterministic or (increasingly more) probabilistic. A tiered approach is advocated, as this allows for transparency, an early stop in the analysis and interim interaction with the decision-maker. A general problem in the disciplines underlying benefit-risk assessment is that good dose-response data, i.e. at relevant intake levels and suitable for the target population, are scarce. It is concluded that, provided it is clearly explained, benefit-risk assessment is a valuable approach to systematically show current knowledge and its gaps and to transparently provide the best possible science-based answer to complicated questions with a large potential impact on public health.

State of the art in benefit-risk analysis: economics and marketing-finance.

All market participants (e.g., investors, producers, consumers) accept a certain level of risk as necessary to achieve certain benefits. There are many types of risk including price, production, financial, institutional, and individual human risks. All these risks should be effectively managed in order to derive the utmost of benefits and avoid disruption and/or catastrophic economic consequences for the food industry. The identification, analysis, determination, and understanding of the benefit-risk trade-offs of market participants in the food markets may help policy makers, financial analysts and marketers to make well-informed and effective corporate investment strategies in order to deal with highly uncertain and risky situations. In this paper, we discuss the role that benefits and risks play in the formation of the decision-making process of market-participants, who are engaged in the upstream and downstream stages of the food supply chain. In addition, we review the most common approaches (expected utility model and psychometrics) for measuring benefit-risk trade-offs in the economics and marketing-finance literature, and different factors that may affect the economic behaviour in the light of benefit-risk analyses. Building on the findings of our review, we introduce a conceptual framework to study the benefit-risk behaviour of market participants. Specifically, we suggest the decoupling of benefits and risks into the separate components of utilitarian benefits, hedonic benefits, and risk attitude and risk perception, respectively. Predicting and explaining how market participants in the food industry form their overall attitude in light of benefit-risk trade-offs may be critical for policy-makers and managers who need to understand the drivers of the economic behaviour of market participants with respect to production, marketing and consumption of food products.

State of the art in benefit-risk analysis: environmental health.

Environmental health assessment covers a broad area: virtually all systematic analysis to support decision making on issues relevant to environment and health. Consequently, various different approaches have been developed and applied for different needs within the broad field. In this paper we explore the plurality of approaches and attempt to reveal the state-of-the-art in environmental health assessment by characterizing and explicating the similarities and differences between them. A diverse, yet concise, set of approaches to environmental health assessment is analyzed in terms of nine attributes: purpose, problem owner, question, answer, process, use, interaction, performance and establishment. The conclusions of the analysis underline the multitude and complexity of issues in environmental health assessment as well as the variety of perspectives taken to address them. In response to the challenges, a tendency towards developing and applying more inclusive, pragmatic and integrative approaches can be identified. The most interesting aspects of environmental health assessment are found among these emerging approaches: (a) increasing engagement between assessment and management as well as stakeholders, (b) strive for framing assessments according to specific practical policy needs, (c) integration of multiple benefits and risks, as well as (d) explicit incorporation of both scientific facts and value statements in assessment. However, such approaches are yet to become established, and many contemporary mainstream environmental health assessment practices can still be characterized as relatively traditional risk assessment.

State of the art in benefit-risk analysis: medicines.

Benefit-risk assessment in medicine has been a valuable tool in the regulation of medicines since the 1960s. Benefit-risk assessment takes place in multiple stages during a medicine's life-cycle and can be conducted in a variety of ways, using methods ranging from qualitative to quantitative. Each benefit-risk assessment method is subject to its own specific strengths and limitations. Despite its widespread and long-time use, benefit-risk assessment in medicine is subject to debate and suffers from a number of limitations and is currently still under development. This state of the art review paper will discuss the various aspects and approaches to benefit-risk assessment in medicine in a chronological pathway. The review will discuss all types of benefit-risk assessment a medicinal product will undergo during its lifecycle, from Phase I clinical trials to post-marketing surveillance and health technology assessment for inclusion in public formularies. The benefit-risk profile of a drug is dynamic and differs for different indications and patient groups. In the end of this review we conclude benefit-risk analysis in medicine is a developed practice that is subject to continuous improvement and modernisation. Improvement not only in methodology, but also in cooperation between organizations can improve benefit-risk assessment.

State of the art in benefit-risk analysis: consumer perception.

Benefit and risk perception with respect to food consumption, have been a part of human daily life from beginning of time. In today's society the food chain is long with many different types of actors and low degree of transparency. Making informed food choices where knowledge of benefits and risks is part of the decision making process are therefore complicated for consumers. Thus, to understand how consumers perceive benefits and risks of foods, their importance in relation to quality evaluations are aspects that need to be addressed. The objective of this paper is to discuss state of the art in understanding consumer perceptions of benefits and risks of foods in order to improve understanding of consumer behaviour in the food domain. Risks may be associated with both acute and long term consequences, some of which may have serious effects. Perceived risks are connected to morbidity and mortality along two dimensions relating to unknown risk, and to which extent the risk is dreaded by the consumer. Unfamiliar, uncertain, unknown, uncontrollable, and severe consequences are some factors associated with risk perception. Novel food processing techniques, for instance, score high on several of these parameters and are consequently regarded with suspicion and perceived as risky by consumers. On a daily basis, benefits of foods and food consumption are more important in most consumers' minds than risks. Benefits are often associated with food's ability to assuage hunger, and to provide pleasure through eating and socialising. In addition, two main categories of benefits that are important for acceptance of product innovations are health and environmental benefits. Benefit and risk perception of foods seem to be inversely correlated, so when something is perceived as being highly beneficial, it is correspondingly perceived as having low risk. However, slightly different paths are used in the formation of these perceptions; benefit perception is based on heuristics and experience, while risk perception is to a larger extent the result of cognitive information processing. Consumers are particularly conservative when it comes to perception and acceptance of foods compared to other products. Benefit-risk evaluations tend to be skewed towards acceptance of all that is traditional and well-known (benefits), and rejection or suspicion towards anything that is novel or highly processed (risks) regardless of actual risk. Knowledge of how consumers perceive benefits and risks of foods, may contribute to understanding benefit-risk perception in other areas related to personal, societal or environmental perspectives.

Prospective evaluation of patient tolerability, satisfaction with patient information, and complications in endoscopic ultrasonography.

BACKGROUND AND STUDY AIMS: Prospective data are lacking on the safety of endoscopic ultrasonography (EUS) and on patient satisfaction with the procedure. We prospectively recorded complications related to EUS in order to establish morbidity and mortality. In addition the levels of patient satisfaction were evaluated, with regard to the tolerability of the procedure (pain, discomfort, and anxiety levels) and the provision of information. PATIENTS AND METHODS: 3324 consecutive patients who underwent EUS were studied with regard to complications. During the study period 300 patients were interviewed and followed up in detail as part of the evaluation of patient satisfaction. RESULTS: Ten patients (0.3 %) suffered from a complication related to the EUS procedure, and two patients died (0.06 %). There were no significant differences between the complication rates for EUS-guided fine-needle aspiration (EUS-FNA) and for EUS, but both fatal cases related to EUS-FNA/EUS-guided intervention. Nine of the ten patients with complications (90 %) had a diagnosis of malignancy, and esophageal perforation accounted for half of all complications. Although the majority of patients with nonlethal complications were managed well on conservative regimens, only one case, of self-limiting acute pancreatitis, could be classified as a mild complication. With regard to patient tolerability, only minor incidents occurred during the EUS procedure (tracheal suction 5 %, vomiting 0.3 %, aspiration 0.3 %) and no intervention was necessary. During the procedure, 80 % of the patients had no or only slight pain and more than 95 % experienced only slight or no anxiety, whereas more than half of the patients experienced moderate to severe discomfort. More than 90 % of the patients were satisfied or very satisfied with the information provided to them before and after the EUS, and the same number of patients were ready without hesitation to undergo an additional EUS examination if necessary. CONCLUSIONS: EUS, EUS-FNA and EUS-guided intervention are safe techniques, but severe and lethal complications do occur. The EUS procedures can be performed with a high level of patient satisfaction and with low levels of pain, discomfort and anxiety.

[Main clinical and surgical determinants of in-hospital mortality after surgical revascularization of left main coronary artery stenosis: 2 year retrospective study (1998-1999)]. / Les facteurs cliniques et opératoires associés à la mortalité hospitalière après chirurgie d'une sténose du tronc commun de l'artère coronaire gauche. Analyse rétrospective de janvier 1998 à décembre 1999.

UNLABELLED: Stenosis of left main coronary artery (LMCA) is a common finding on coronary angiographies (7 to 10%). Mortality is very high for conservative therapy in comparison with surgery, which provides very good long-term outcome and is accepted as the standard therapy of this condition. Over the last few years, percutaneous coronary intervention (PCI) has become a new alternative in selected patients. AIM OF THE STUDY: To assess in hospital mortality in subjects referred to our surgical unit for coronary artery bypass grafting (CABG) and to identify the main clinical and surgical determinants of in-hospital mortality. METHODS: Two year retrospective analysis (1998-1999) of in-hospital mortality and morbidity of patients having left main stenosis referred for CABG. RESULTS: Among a group of 1443 patients operated for coronary heart disease, LMCA stenosis was found in 330 patients (22.9%). The mean age was 63 +/- 8.6 years. Elective surgery was done in 173 patients (52.4%), and acute operation (i.e. urgent, emergent or desperate) in 157 patients (47.6%). The total in-hospital mortality was 4.2% (14/330). Elective surgery in-hospital mortality was 1.7% (3/173) and urgent surgery in-hospital mortality was 7% (11/157). The main risk factors of in-hospital mortality were age > 68 years, low ejection fraction (LVEF<0.4), history of myocardial infarction, gender (female) and urgency of the operation. CONCLUSION: The proportion of patients undergoing CABG for left main stenosis is relatively high in our center and their mortality is quite low especially for elective operations. As the mortality of patients treated by PCI for LMCA stenosis is similar to surgery in high-risk patients, we postulate that this approach can be a real alternative treatment for such patients. Because of its potential benefit, combined revascularisation is also an alternative that should be considered in some cases. Furthermore, as a new generation of coated stents has emerged in the treatment of restenosis after PCI, we hypothesize that this method can in the near future be accepted as equivalent to surgery. However several randomized clinical trials must first be conduced prove this point.

[Effect of primary coronary angioplasty on long-term prognosis in patients with diabetes mellitus]. / Vliv prímé koronární angioplastiky na dlouhodobou prognózu nemocných s diabetes mellitus.

OBJECTIVES: To investigate feasibility and safety of primary PCI in diabetic patients. BACKGROUND: Diabetic patients with acute myocardial infarction (AMI) have been shown to be at high risk for adverse clinical outcomes. Limited data is available on long term prognosis of diabetics treated with primary PCI. METHODS: Retrospective analysis of consecutive 67 diabetic patients and 211 non diabetic patients treated with primary PCI from 1/1995 to 12/1999, follow up for 38 +/- 12 months. RESULTS: The baseline characteristics were comparable in both groups. The mean age was 62 years in diabetic patients and 59 years in non diabetic patients. Hypertension (50% vs. 36%, p = 0.05), contraindications to thrombolytic treatment (13.4% vs. 5.7%, p = 0.037), cardiogenic shock (16.4% vs. 7.1%, p = 0.023), multivessel disease (34% vs. 23%, p = 0.07) and longer time delay to treatment (240 vs. 180 min., p = 0.05) were more often present in diabetic group. 47% of diabetic and 42% of nondiabetic patients received stents. The TIMI 2 or 3 flow rates were reached in 91% of diabetic patients and in 90% of nondiabetic patients, but TIMI 2 flow was found more often in diabetics (9% vs. 2.4%, p = 0.016). Higher rate of bleeding complications leading to significant change in the blood count (7.5% vs. 1.4%, p = 0.01) and higher 30 day mortality (11.9% vs. 5.2%, p = 0.05) was observed in diabetic group. However when the shock patients were excluded from the analysis, the 30 day mortality was different insignificantly in both groups (4.5% vs. 2.4%, p = 0.36). During follow up of 259 acute phase survivors 24 patients died. There was a trend to higher total long term mortality (22.3% vs. 13.2%, p = 0.07) and higher rate of nonfatal reinfarction (13.4% vs. 6.2%, p = 0.05) in diabetic group. CONCLUSIONS: Primary PCI is safe and effective treatment of diabetic patients presenting with AMI. The higher rate of slow flow in infarct related artery after PCI observed in diabetics can be one of reasons for higher 30 day mortality in this group. Mean ischemic time in diabetics is behind the 4 hour border, where the possible benefit from reperfusion decreases. The main reason for higher mortality in our diabetic group was the higher rate of cardiogenic shock. Higher risk of bleeding complications at puncture site in diabetic patients can be explained by the lower quality of vessel wall.

[Pharmacologic therapy of acute coronary syndromes]. / Farmakologická lécba akutních koronárních syndromu.

Acute coronary syndromes (ACS) are caused by neoinclusive thrombosis of the coronary artery. Arterial atherothrombosis usually results from a cracked atheroma plate and includes platelet and plasmatic component of coagulation. The aim of pharmacological treatment is to influence activated platelets and plasma procoagulant activity. Several clinical studies have demonstrated the benefits of antithrombotic treatment by acetylsalicylic acid, clopidogrel and by blockers of platelet receptors IIb/IIIa. In ACS anticoagulant therapy the non-fractionated heparin are replace ed by low-molecular heparins. The new standard in ACS therapy should become a combination of the acetylsalicylic acid, enoxaparine and clopidogrel. Blockers of platelet receptors IIb/IIIa should be given namely to patients indicated for the early invasive treatment.

[Comparison of the morphology of atherosclerotic plaques in patients with stable angina pectoris and acute coronary syndrome using intravascular ultrasonography]. / Srovnání morfologie aterosklerotických plátu u nemocných se stabilní anginou pectoris a akutním koronárním syndromem pri vysetrení intravaskulárním ultrazvukem.

The article summarises present knowledge on the differences in the structure of atherosclerotic plaques in patients with stable angina pectoris and in those with acute coronary syndrome during intravascular ultrasound examination. Authors describe differences in the pathologic anatomy and also in the clinics. The review includes pictures of the typical structural features and references of papers with similar topics.

[Long-term prognosis in patients with acute myocardial infarct and treatment with direct coronary angioplasty]. / Dlouhodobá prognóza nemocných s akutním infarktem myokardu pri lécbe prímou koronární angioplastikou.

BACKGROUND: Primary coronary angioplasty (PTCA) has a beneficial effect on the immediate prognosis for patients with acute myocardial infarction. Number of information about effects of direct PTCA on the long-term prognosis are less numerous. The aim of the work was to establish the long-term prognosis for not-selected patients treated by direct PTCA. METHODS AND RESULTS: The studied group consisted of 279 patients with acute myocardial infarction treated by direct PTCA in years 1995 to 1999 for the period of 38 +/- 12 months. Part of them were out-door patients of our clinic. The necessary data of the other patients were obtained by a questionnaire and by a telephone contact. 45 (16%) patients were lost from the follow up. The mortality rate of the study group was compared with data in the central register of Czech Republic. Positive angiographic effect of the direct PTCA (residual stenosis < 50% + flow TIMI 3) was achieved in 90% of patients. 30-day mortality was 6.8%, after excluding patients with cardiogenic shock it decreased to 3.2%. 6 patients (2.2%) had non-fatal infarction within 30 days after the first attack. From 259 patients who survived the acute infarction phase 24 died during the next period of follow up, 18 (7%) patients had a relapse of non-fatal infarction. PTCA of the infarcted artery was done in 15% of patients, PTCA of another artery in 9% of patients. The aorthocoronary bypass was indicated in 6% of patients. Almost half of relapses occurred during the first year after the hospitalisation. The risk factors of the death during the follow up were the age > 70 years, ejection fraction < 35%, impairment of 3 or more coronary artery branches, i.m. in the history, duration of ischemia > 4 hours, and diabetes mellitus. The total mortality was 11.4% in the first year, 1.4% in the second and 3.3% in the third year of the follow up. CONCLUSIONS: The beneficial prognostic effect of the direct PTCA on patients with acute infarction carries through the whole period of follow up. Prognosis of the risk patients remains critical. Next revascularization of the infarcted artery was in our cohort of patients necessary in 21% of patients.

[Long-term treatment with statins in patients with ischemic heart disease after coronary angioplasty]. / Dlouhodobá lécba statiny u pacientu s ischemickou chorobou srdecní po koronární angioplastice.

UNLABELLED: Long-term statin therapy is the corner-stone in management of patients with coronary artery disease. PURPOSE OF STUDY: The aim of our study was to analyze the state of the statin therapy at patients undergoing percutaneous coronary intervention (PCI) and to determine predictors of long-term statin treatment. METHODS: We performed a retrospective study in 520 patients who underwent percutaneous coronary angioplasty in 2nd Dept. of Internal Medicine, 1st School of Medicine, Charles University, Prague during the year 2000. Data were collected from hospital records and from a mailed questionnaire. RESULTS: The response rate was 61.9% and the average response time was 11.6 +/- 3.5 months after PCI. Long-term statin therapy was prescribed in 52.5%. In patients with hypercholesterolemia 67.1% were treated in comparison with 32.3% treated patients without this diagnosis (p < 0.0001). Patients aged 70 years and older were treated significantly less frequently then younger individuals (30.6% vs. 61.3%, p < 0.0001). Patients with a history of prior revascularization procedure were treated significantly more often then patients undergoing the first procedure (64.8% vs. 49.8%, p < 0.05). Multivariate logistic regression analysis was applied to detect significant predictors of long-term statin therapy. Only hypercholesterolemia and statin prescription at discharge were identified as independent positive predictors, whereas age > or = 70 years and male gender had negative predictive value. CONCLUSION: By course of evidence-based medicine, patients who underwent PCI in our study are undertreated by statins. Statin treatment should be initiated in all patients treated by PCI with increased cardiovascular risk. Patients at defined risk for undertreatment are mainly older patients and men. The prescription of statin therapy at the time of hospital discharge appears to be a very effective tool to improve long-term statin therapy.

[Comparison of the occurrence of positive and negative vascular remodeling in patients with stable vs unstable angina pectoris]. / Srovnání výskytu pozitivní a negativní cévní remodelace u nemocných se stabilní vs. nestabilní anginou pectoris.

BACKGROUND: The vascular remodelling refers to the increase or decrease in EEM (external elastica membrane) area that occurs during development of atherosclerosis. The positive remodeling, which was thought only as a compensatory factor during atheroma development, was also found as a one of the main features of unstable plaque. The intravascular ultrasound is very good tool to measure different type of arterial remodelling. These findings correlate with histologic post-mortem specimen with excellent results. AIM OF THE STUDY: To correlate the remodelling index from patients suffered from stable angina pectoris (SAP) and from patients suffered from unstable angina (UA). METHOD: We performed IVUS in 51 patients. In the group of patients with unstable angina were included patients with worsening angina symptoms in last six weeks or with angina in rest. We used IVUS--endosonics In-Vision with 30 MHz probe Awanar with mechanical pull-back. We studied the occurrence of positive remodelling, negative remodeling (an index that describes remodeling is expressed as: lesion EEM CSA/reference EEM CSA. If the lesion EEM area is greater than the reference EEM area, positive remodelling has occurred, and the index will be > 1.0. If the lesion EEM area is smaller than the reference EEM area, negative remodelling has occurred, and the index will be < 1.0). RESULTS: We performed the intravascular ultrasound in 51 patients, 22 patients (43.1%) with unstable angina (UA) and in 29 patients (56.9%) stable angina (SAP). The positive remodelling was found in 14 patients (63.6%) in UA group vs. 5 patients (17.2%) in group with SAP, p < 0.05. The negative remodelling was found in 6 patients (27.3%) in UA group vs. 23 patients (79.3%) in SAP group, p < 0.05. CONCLUSION: Positive remodelling is more often found in patients with UA vs. in patients with SAP. Positive arterial remodelling is therefore one of the features of unstable atherosclerotic plaque.

[Idiopathic aneurysm of the pulmonary artery]. / Idiopatické aneuryzma arterie pulmonalis.

Aneurysm of pulmonary artery (PAA) is relatively rare clinical finding and appears mostly in association with significant cardiovascular or pulmonary abnormalities and is frequently caused by pulmonary hypertension. Its diagnosis is not difficult. However, guidelines for the treatment were not yet established. Patients with PAA are at risk for sudden death by a rupture of aneurysm. Therefore, surgical correction (graft replacement) is the method of choice. Nevertheless, it seems that certain group of patients with asymptomatic idiopathic aneurysm of pulmonary artery without presence of any serious cardiovascular or pulmonary abnormality can profit from conservative approach. We refer a 62-years old man with idiopathic PAA, in whom we did not indicate surgical correction. However, the long-term follow-up is necessary.

[Effect of delaying reperfusion therapy with PTCA on long term prognosis in patients with acute myocardial infarct]. / Vliv délky zpozdení reperfuzní lécby prímou PTCA na dlouhodobou prognózu nemocných s akutním infarktem myokardu.

BACKGROUND: The benefit of thrombolysis in patients with acute myocardial infarction (AMI) strongly depends on the time from onset of symptoms to the initiation of treatment. For AMI patients treated with PTCA this time seems to be important only to a certain time level. The aim of this study was to assess the influence of time to treatment of AMI with coronary angioplasty on short term and long term prognosis. METHODS: We followed 339 consecutive AMI patients treated with coronary angioplasty from 1995 to 1999 in a cardiac care unit. Patients were divided to five groups according to time to treatment. RESULTS: Time to treatment < 90 min. was achieved in 35 (10.5%); 91-210 min. in 105 (31%); 211-330 min. in 72 (21%); 331-690 min. in 74; > 691 min. in 53 (15.5%) patients. Ischemic time (time from symptom onset to reperfusion) in the groups was < 2 h.; 2-4 h.; 4-6 h; 6-12 h; > 12 h. respectively. The ejection fraction of left ventricle 3-5 days after AMI was 50%, 51%, 45%, 40%, 46% and the 30 day mortality was 5.7%, 2.9%, 11.1%, 10.8%, 11.3% in the groups respectively, showing no significant differences between the groups. However the higher rate of TIMI 3 flow was achieved in patients with time to treatment shorter than 3.5 h. compared to patients treated later (93.6% vs. 83.9%, p = 0.007). The lower 30 day mortality (3.6% vs. 11.1%, p = 0.012), lower 3 year mortality (8.6% vs. 19.1%, p = 0.003), lover frequency of heart failure during hospitalisation (11.4% vs. 28.1%, p < 0.001) as well as lower maximal level of released kreatinkinase (32 +/- 29 vs. 44 +/- 39 mukat/l, p = 0.005) was observed in patients treated within 3.5 h. from symptoms onset compared to patients treated later. CONCLUSION: The success rate of primary PTCA to achieve normal flow in infarct related artery is high, but decreases when treatment is started later than 3.5 h. from AMI onset. The short term and long term mortality as well as incidence of heart failure during acute phase is lowest when the intervention was started within 3.5 h. from symptoms onset. Initiation of intervention after 3.5 h. resulted in significant mortality increase, but further delay of treatment had minimal impact on patients prognosis. Great effort needs to be paid to start the primary PTCA within 3.5 h. from AMI onset in as many patients as possible. From our data we can indirectly conclude: patients without a chance for reperfusion with thrombolytic therapy within 4 h. from symptoms onset should be considered candidates for PTCA regardless the time of transportation. In patients with chance to reperfuse infarct related artery within 4 h. from symptoms onset with thrombolytic treatment (thrombolysis needs to be started before 2.5-3rd h.) while having low probability to start PTCA within 3.5 h., the thrombolysis should be given first and PTCA performed later if needed.

[Video-assisted myocardial revascularization and left-sided minithoracotomy using the Symmetry automatic connector]. / Videoasistovaná revaskularizace myokardu z levostranné minitorakotomie s pouzitím automatického konektoru Symmetry.

OBJECTIVE: Introduction of the new method of videoassisted multiple direct revascularization of the heart muscle from left-sided minithoracotomy (LAST--Left Anterior Small Thoracotomy) using an automatic connector of central anastomoses Symmetry (St. Jude Medical ATG, Inc., St. Paul, MN) in patients indicated for re-operation of bypasses of the coronary arteries or with pathological conditions of the sternum and for the cosmetic effect of submammary incisions in women. METHOD: From September 2001 to the end of February 2002 15 patients with affections of three arteries had an operation from a LAST approach with videoscopic construction of central anastomoses by means of a Symmetry connector with portal entries and the use of extracorporeal circulation introduced from the groin without cardioplegic arrest. Nine men and six women were operated with a mean age of 68.7 years and a mean ejection fraction (EF) of 58.2%. In seven instances reoperation of aortocoronary bypasses was involved; two patients with multiple myelomas (morbus Kahler) had a brittle and cavernously altered sternum, all six women wanted a small skin incision below the breast. The criterion for ruling out the mentioned procedure was marked atherosclerotic affection of the ascendent aorta, affection of the arteries in the aortoiliac area and affection of one or two coronary arteries suitable for miniinvasive revascularization without extracorporeal circulation. Fourteen patients had an angiographic check up examination of the patency of grafts before they were discharged. RESULTS: The total number of distal anastomoses per patient was 3.13 +/- 0.6, the median period of extracorporeal circulation was 112 +/- 34 minutes and the mean time of operation 186 +/- 52 minutes. Blood losses were on average 425 ml/24 h without necessity of revision on account of haemorrhage. Eleven (73%) patients were subjected to an ultra fast track protocol with extubation on the operating table. The mean time spent in the postoperative department was 8.6 hours and the total hospitalization period 5.5 days. None of the operated patients died. Peroperative ischaemia of the heart muscle was not observed, in one instance the authors observed a newly developed atrial fibrillation. During an angiographic check-up the authors detected 6 (13.6%) stenoses and occlusions in 44 checked bridged vessels. CONCLUSION: The alternative approach reduces the risk of cardiac injury during reoperation and the danger of impaired healing of the sternotomical wound in patients with pathological conditions of the sternum, with contamination of the surrounding tissue (e.g. in tracheostomy) or malignant disease. The cosmetic effect of the submammary incision, the small inguinal incision and endoscopic saphenous vein harvesting should be considered in elective direct revascularization of the heart muscle in women. Bridging of the coronary arteries with optical assistance from minithoracotomy and with an automatic connector of central anastomoses seems to be a safe alternative of standard sternotomy only with methodological but not anatomical or functional restriction.

[Direct percutaneous transluminal coronary angioplasty in patients with acute myocardial infarct treated at the Cardiac Center of the General Medical School Hospital in Prague: a 1-year retrospective study]. / Prímá perkutánní transluminální koronární angioplastika u pacientu s akutním infarktem myokardu v Kardiocentru Vseobecné fakultní nemocnice Praha: jednorocní retrospektivní studie.

UNLABELLED: Direct percutaneous transluminal coronary angioplasty (d-PTCA) in patients with acute myocardial infarctions (AIM) has become an alternative of thrombolytic treatment. If the involved department has adequate experience the success rate of the procedure is high and the immediate and long-term results are better than those of thrombolysis. Moreover contrary to thrombolytic treatment successful percutaneous coronary intervention in AIM is more beneficial for patients also later than 6 hours after the development of infarction pain. In the Cardiocentre of the General Faculty Hospital (GFH) patients with AIM are constantly attended, i.e. those indicated for reperfusion therapy are treated solely by the d-PTCA method. OBJECTIVE AND METHOD: Retrospective analysis of d-PTCA in AIM made during the annual period from Jan. 1 2000 to Dec. 31 2000. Into the observation study patients were included with clinical and/or ECG signs of AIM when the period from the onset of pain to the beginning of intervention did not exceed 12 hours. All patients were given before the procedures 500 mg of acetylsalicylic acid and 10,000 u. heparin. Cardiac catheterization was implemented by the percutaneous Seldinger technique via the a. femoralis l.dx., in exceptional cases from the left femoral artery. An approach via the a. radialis and/or a. brachialis was not used in any of the patients. From the investigation patients were excluded who had before the percutaneous coronary intervention (PCI) a thrombolytic preparation (so-called rescue-PTCA). RESULTS: During the mentioned period in the Cardiocentre of the GFH a total of 673 PTCA were performed, incl. 127 (18.9%) d-PTCA in patients with AIM. In the mentioned group of 127 patients subjected to intervention were 87 (68.5%) men and 40 (31.5%) women. The mean age of the men was 59.1 +/- 12 years and the mean age of the women 68.2 +/- 12 years. As to the main risk factors of coronary atherosclerosis arterial hypertension was present in 48%, smoking in 42%, diabetes in 23% and hyperlipoproteinaemia in 31% of the treated patients. More than one third of the patients had a history of myocardial infarction (38%). The infarcted artery was the r. interventricularis anterior (LAD) in 51 (40.2%), the right coronary artery (RCA) in 54 (42.5%), the r. circumflex (LCX) in 16 (12.6%), the left main coronary artery in 2 (1.6%) and the bypass in 4 (3.1%). Multiple coronary affections were recorded in 80 (63%) patients, affections of one artery in 47 (37%). Primary procedural success (flow TIMI 3/2) was achieved in 121 patients (95.3%). Normal flow through the infarcted artery TIMI 3 was achieved in 118/127 (85.8%) patients. In 91 (71.7%) into the infarcted artery a coronary stent was implanted, during hospitalization no subacute stenosis of the stent developed. The mean period between the onset of infarction pain--injection was 4.4 +/- 2.3 hours. The mean period of the entire procedures was 48 +/- 14.5 minutes. As contrast material only non-ionic contrast substances were used (Iomeron 350) with a mean consumption of 150 ml per patient. The mean skiascopic time was 13.6 +/- 1.8 min. A total of 9 (7.1%) patients were treated with GP IIb/IIIa receptor blockers (abciximab). The total hospitalization mortality of the intervened group was 7.1% (9 patients). In a sub-group of 9 patients who at the onset of the procedure were in cardiogenic shock 3 (33%) died. The hospitalization mortality of the sub-group of patients with AIM without cardiogenic shock, treated with d-PTCA was 5.1% (6/118). During hospitalization the authors did not observe any intracranial haemorrhage. DISCUSSION: The group of subjects with AIM subjected to catheterization who are treated by d-PTCA is relatively numerous in our department. According to a number of clinical studies successful d-PTCA in AIM gives better short-term and long-term results as compared with thrombolytic therapy. The primary success rate of d-PTCA was high and the hospital mortality was low and comparable with contemporary data in the literature. CONCLUSION: Direct PTCA is effective treatment in patients with acute myocardial infarction. The authors results confirm the high procedural success rate and acceptable hospital mortality. These favourable results of an invasive approach to treatment of AIM must be compared in future with bolus thrombolytic treatment by new types of thrombolytic preparations in combination with anti-platelet treatment with blockers of platelet glycoprotein receptors IIb/IIIa with/or without subsequent percutaneous coronary intervention.