Short-term Risk Of Death Research Articles

Prognostic relevance of pericardial effusion in patients with malignant diseases

TO THE EDITOR: Malignancy is a common cause of pericardial effusion, and malignant pericardial effusion is a serious manifestation in advanced malignancies [1]. Malignancy-related pericardial effusion is associated with significantly decreased patient survival [1]. Slight malignant pericardial effusions are frequently asymptomatic; however, symptomatic patients often present with cardiac tamponade, which can rapidly lead to cardiovascular collapse or death [2]. Therefore, early diagnosis and timely treatment may decrease a patient's short-term risk of death. We evaluated both the etiology and prognosis of pericardial involvement in several malignancies. We retrospectively reviewed the records of 215 patients (126 males and 89 females) with pericardial effusion and malignant diseases, including solid tumors and hematological malignancies, from January 1991 to December 2010. In all cases, the clinical diagnosis was confirmed by pathological examination of the primary tumor site. All patients underwent pericardiocentesis, and pericardial fluid analyses were performed for cytology. We analyzed the incidence of the etiology of malignancies and overall survival according to the results of the pericardial fluid analysis. Overall survival was calculated from the day of initial diagnosis to the date of patient's death from any other cause or to the latest follow-up date. Among 215 patients, 113 (52.6%) showed pericardial involvement in their malignant diseases. The etiological diagnosis and pericardial fluid analysis results are summarized in Table 1. Pericardial involvement of malignancy was most frequent in breast carcinoma (85.0%), followed by lung adenocarcinoma (61.9%), gastric adenocarcinoma (58.8%), thymic carcinoma (33.3%), and esophageal squamous cell carcinoma (17.6%). In a survival analysis using the Cox proportional hazards model, the pericardial involvement group showed significantly poorer survival rates than the non-pericardial involvement group (hazard ratio, 2.157; 95% confidence interval, 1.327-3.507; P=0.002). The median survival time was significantly longer in patients with no evidence of pericardial involvement in their malignant diseases than in those with pericardial involvement in malignancy (118.2 months vs. 34.8 months; P=0.001) (Fig. 1). Fig. 1 Overall survival according to pericardial involvement in the malignant disease. The pericardial involvement group had a significantly poorer survival rate than the non-pericardial involvement group (Pa, pericardial involvement group vs. non-pericardial ... Table 1 Etiological diagnosis and frequency of pericardial involvement in malignant diseases. In studies, the most common cause of malignant pericardial effusion was lung cancer (34-76%), followed by breast cancer (10-17%) [1, 3, 4]. However, in the present study, ductal cell carcinoma of the breast had the highest incidence of pericardial involvement. Because our study population included only patients with advanced-stage breast cancer, the incidence of their pericardial involvement is not representative of all patients with breast cancer. Several treatment modalities, including both medical and surgical modalities, have been proposed for malignant pericardial effusion [5]. Timely management of pericardial effusion is important to improving the clinical outcome. In conclusion, patients with pericardial involvement in their malignant diseases had a relatively poorer prognosis than those without pericardial involvement in malignant diseases. Cautious morphologic analyses of pericardial fluid are recommended before application of palliative or therapeutic pericardiocentesis, especially in patients with lung or breast carcinoma.

The evolution of and challenges in defining the clinical endpoint in tuberculosis treatment trials with non-inferiority designs

Background The first clinical trial to evaluate an effective drug for the treatment of tuberculosis (TB) conducted in 1946 by the Medical Research Council (MRC) under the direction of Bradford Hill is also widely regarded as the first properly conducted randomised clinical trial in any disease area. This new treatment was shown to significantly reduce the short term risk of death in patients with TB. As treatment improved, death became an increasingly uncommon outcome and change in clinical symptoms, radiographic appearance and bacteriological response were the commonly reported endpoints. Eventually, bacteriological failure and relapse became the primary endpoints of interest. Patients lost to follow-up were excluded from the primary analysis, as were patients not completing treatment or changing treatment for adverse events in what would today be regarded as a per protocol (PP) analysis. In recent years the first phase III trials for new TB regimens for several decades have been initiated. Due to the high efficacy of the standard regimen in trial settings, these trials are designed as non-inferiority trials. Guidelines recommend both an intention-to-treat (ITT) and a PP analysis for non-inferiority trials. Classifying all patients with missing endpoints as unfavourable, as is recommended by the US FDA for other infectious diseases, is not appropriate in the context where losses to follow-up in the 12-18 months after treatment (when signs and symptoms have usually ceased) could easily exceed the true bacteriological unfavourable outcome (approximately 5%). Objective In this paper, we will discuss the complexities in (1) defining the composition of the clinical endpoint used in a TB treatment trial with a non-inferiority design and (2) performing the appropriate analyses. The relative roles of bacteriology and clinical signs and symptoms as well as the classification of patients with missing endpoints are important issues which can radically affect the overall trial results.

Carotid Stenting at the Crossroads

STROKE IS A MAJOR CAUSE OF DEATH AND DISABILITY. Approximately 10% to 15% of ischemic strokes are attributable to atherosclerosis of the internal carotid arteries, and there is great interest in surgical and endovascular approaches to stroke prevention. Carotid artery surgery or endarterectomy (CEA) has been the traditional intervention, and carotid angioplasty with stenting (CAS) is the newer percutaneous procedure. Both procedures increase the short-term risk of death or stroke due to the intervention in exchange for a lower long-term risk of stroke. Therefore, the magnitude and balance of the risks and benefits for these procedures are crucial considerations. Patients with symptomatic disease (ie, those who have had a stroke or transient ischemic attack in the past 6-12 months in the distribution of a carotid artery with 50% stenosis) benefit from CEA, which reduces the absolute risk of stroke by 8% per year. Asymptomatic patients (those with carotid occlusive disease without neurological symptoms) have a more modest benefit from CEA (absolute stroke reduction of 0.8%-1% per year). Carotid artery surgery or endarterectomy is considered beneficial only if it can be performed with a 30-day risk of death or stroke of 6% or less among symptomatic patients and 3% or less among those who are asymptomatic. Carotid angioplasty with stenting was originally approved by the US Food and Drug Administration (FDA) in 2004 for patients who were at too high a risk for CEA because of comorbidity or anatomical factors. In October 2004, because of uncertainty about efficacy, Medicare restricted reimbursement for CAS to high-risk symptomatic patients enrolled in postapproval studies. In March 2005, Medicare expanded coverage to allow treatment of high-risk symptomatic patients with carotid stenosis greater than 70% outside of trials using FDAapproved stents and embolic protection devices. The Centers for Medicare & Medicaid Services (CMS) also covers CAS for symptomatic patients with 50% to 70% carotid stenosis and asymptomatic patients with greater than 80% carotid stenosis if the procedure is performed in a postapproval or randomized controlled trial (RCT). Since then, CAS use has increased substantially, with large geographic variations in utilization. The Carotid Revascularization Endarterectomy vs Stenting Trial (CREST) compared CAS with CEA for patients with symptomatic and asymptomatic carotid disease. However, debate persists regarding interpretation of the study findings; CAS was equivalent to CEA for the primary composite end point of periprocedural death, stroke, or myocardial infarction or subsequent ipsilateral stroke. Carotid angioplasty with stenting was associated with worse outcomes than CEA for the combined outcome of periprocedural death or stroke or subsequent stroke, the end point used in trials comparing CEA with medical therapy. In May 2011, based on the CREST results, the FDA expanded the indication for CAS to all patients with carotid disease, not just those at high surgical risk. Against this backdrop, the outcomes and use of CAS in real-world practice is of great importance. In this issue of JAMA, Nallamothu and colleagues examine the relationship between operator experience and 30-day mortality rates following CAS using national Medicare administrative data from 24 701 procedures performed by 2339 physicians between 2005 and 2007. The authors found that patients treated by lowest-volume operators ( 6 CAS procedures per year) had an increased odds of death compared with patients treated by high-volume operators ( 24 procedures per year). Low-volume operators were much less likely to use an embolic protection device, an intervention associated with improved outcomes. They also demonstrated a “learning curve” at the individual physician level among the 1792 “later adopters” who started performing CAS after the 2005 CMS cov-

Incidence, Correlates, and Consequences of Acute Kidney Injury in Patients With Pulmonary Arterial Hypertension Hospitalized With Acute Right-Side Heart Failure

Background Though much is known about the prognostic influence of acute kidney injury (AKI) in left-side heart failure, much less is known about AKI in patients with pulmonary arterial hypertension (PAH). Methods and Results We identified consecutive patients with PAH who were hospitalized at Stanford Hospital for acute right-side heart failure. AKI was diagnosed according to the criteria of the Acute Kidney Injury Network. From June 1999 to June 2009, 105 patients with PAH were hospitalized for acute right-side heart failure (184 hospitalizations). AKI occurred in 43 hospitalizations (23%) in 34 patients (32%). The odds of developing AKI were higher among patients with chronic kidney disease (odds ratio [OR] 3.9, 95% confidence interval [CI] 1.8–8.5), high central venous pressure (OR 1.8, 95% CI 1.1–2.4, per 5 mm Hg), and tachycardia on admission (OR 4.3, 95% CI 2.1–8.8). AKI was strongly associated with 30-day mortality after acute right-side heart failure hospitalization (OR 5.3, 95% CI 2.2–13.2). Conclusions AKI is relatively common in patients with PAH and associated with a short-term risk of death.

Mortality in patients with meticillin-resistant Staphylococcus aureus bacteraemia, England 2004–2005

A population-based study was undertaken to determine the short term risk of death in English patients diagnosed with meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia. All patients with an MRSA-positive blood culture taken in 2004 and 2005 in England identified through routine surveillance were matched to the national registry of deaths. The study found an overall case fatality (all-cause) within 7 days of MRSA-positive blood culture diagnosis of 20%, rising to 38% within 30 days. Risk of death was highest on the day subsequent to the blood specimen being drawn (4%). Seven-day case fatality rates in women were 16% higher than for men (odds ratio: 1.16; 95% confidence interval: 1.04-1.29), although no significant difference was discernable by day 30. Risk of death increased with rising age, with 28% (425/1513) of patients aged ≥85 years dying within 7 days and 57% (859/1513) within 30 days. A seasonal pattern in case fatality rates was evident, highest in the winter and lowest in the summer. The age-standardised mortality ratios within the first week were 180 and 225 times as high for men and women, respectively, as for the general population. This declined rapidly after 10 weeks to approximately 9 for both sexes. An estimated 5.53 deaths per 100,000 population followed MRSA bacteraemia in 2004 and 2005, although no inference on causality or attributable mortality could be made through this study. The stable, elevated risk of death observable after 10 weeks compared with that in the general population gave an indication of the background risk of death unrelated to MRSA infection.

Abstract 4954: Risk Factors for Death or Transplant in Chronic Symptomatic Heart Failure in Children: Subanalysis of Pediatric Carvedilol Study

The Pediatric Carvedilol Study trial offers a unique opportunity to investigate patient characteristics and risk factors associated with death or transplant in a population of children with moderate heart failure symptoms. The database from the Pediatric Carvedilol Study trial includes 157 children enrolled with symptomatic heart failure (NYHA II–IV) and ejection fraction (EF)<40%. For this analysis, the patients were divided into by outcome into 2 groups: those who died or underwent heart transplant during the study period (D/HTx) and those who did not (non-D/HTx). Baseline variables were compared using standard parametric and non-parametric testing. Multivariate analysis was performed using logistic regression Results: Of the 157 children, the median age at enrollment was 3 yrs (0.2–17.8yrs). Fifty-two percent were male, and 116/157 (74%) had a left ventricle (LV) as the systemic ventricle. All pts except 3 were NYHA/Ross class II-III, with a median EF of 25.7%, median BNP of 111, and median LVEDD z-score of 6.04. Overall incidence of D/HTx in the enrolled patients over the study period was 30/157 (19%), with 12 deaths and 18 transplants. Risk factors for D/HTx were older age (8.1yrs vs 2.1 yrs, p< 0.006), higher BNP levels at enrollment (250 vs 80, p<0.003) and worse AVV regurgitation (p<0.012), but not diagnosis of congenital heart disease, ventricular morphology, or qualitative assessment of systemic ventricular dysfunction. In the subgroup of patients with a systemic LV, the D/HTx group had a significantly larger EDD z-score (7.7 vs 5.8, p=0.05), but no difference in ejection fraction (25.9 vs 25.6, p=0.8) compared to the non D/HTx. In a multi-variate model after adjusting for age, LV EDD z-score and BNP at enrollment were significantly related to risk for D/HTx. For this pediatric population with chronic symptomatic heart failure, risk factors for death or transplant included older age, higher BNP, and AVVR. In the subgroup of patients with a systemic left ventricle, larger LV EDD z-score, but not lower EF, was significantly related to short term risk for death or transplant.

A Low Protein Diet Increases the Hypoxic Tolerance in Drosophila

Dietary restriction is well known to increase the life span of a variety of organisms from yeast to mammals, but the relationships between nutrition and the hypoxic tolerance have not yet been considered. Hypoxia is a major cause of cell death in myocardial infarction and stroke. Here we forced hypoxia-related death by exposing one-day-old male Drosophila to chronic hypoxia (5% O2) and analysed their survival. Chronic hypoxia reduced the average life span from 33.6 days to 6.3 days when flies were fed on a rich diet. A demographic analysis indicated that chronic hypoxia increased the slope of the mortality trajectory and not the short-term risk of death. Dietary restriction produced by food dilution, by yeast restriction, or by amino acid restriction partially reversed the deleterious action of hypoxia. It increased the life span of hypoxic flies up to seven days, which represented about 25% of the life time of an hypoxic fly. Maximum survival of hypoxic flies required only dietary sucrose, and it was insensitive to drugs such as rapamycin and resveratrol, which increase longevity of normoxic animals. The results thus uncover a new link between protein nutrition, nutrient signalling, and resistance to hypoxic stresses.

A simple prediction rule identified patients with pulmonary embolism at low risk of short term death

A simple prediction rule identified patients with pulmonary embolism at low risk of short term death

Decompensated heart failure and cachexia: Is it time to legalize anabolics?

Heart failure is the leading cause of hospitalization in the western world with an annual cost estimated at $30 billions in the USA. Hospitalized patients with the syndrome are at 35– 50% short-term risk for death or rehospitalization [1] .C urrent medical and ICD therapy reduced the incidence of sudden cardiac death. However, these improvements in patient management will increase the percentage of patients progressing to advanced heart failure, a condition characterized by severe symptoms and lengthy hospitalizations. In these patients, it is very difficult to start life saving therapies, like ACEinhibitorsandbeta-blockersbecauseoftheinstabilityand theseverehemodynamicabnormalities.Manyofthesepatients are cachectic and inotrope dependent. Clinical management is more difficult in the presence of cardiac cachexia. Cachexia is present in 12–16% of outpatients with chronic heart failure [2] but the incidence increases in patients with end stage heart failure [3]. Although it is a syndrome associated with significant morbidity and mortality, there is currently no causal therapy for cachexia [2,4–7]. Over the past few years, cardiac cachexia has been brought into focus by a number of studies, fuelling an interest in defining optimal patient management strategies. Cachexia is characterized by muscle wasting and loss of fat and bone mass [8]. The pathophysiological mechanisms which lead to tissue wasting have not been clarified. However, it has been suggested that apoptosis and fibrosis [9,10], catabolic/anabolic imbalance, cytokines and other proinflammatory mediators, the ubiquitin system [11], natriuretic peptides [12], catecholamines [13], renin–angiotensin system [14], insulin resistance and abnormalities in the GH anabolic pathway, are all implicated in the pathogenesis of tissue wasting and cachexia [15]. Recently, Bocchi et al. [16], investigated the effects of high doses of recombinant human growth hormone (GH) in 6 patients with cardiac cachexia and decompensated advanced CHF (5 dobutamine-dependent). Inotropic therapy is associated with increased mortality and should be used only in selected patients with acute heart failure or in the so called inotrope-dependent patients ( 5 out of 6 in this study). Inotropic therapy has been used as a bridge to oral lifesaving therapies but not always with success. In the study of Bocchi et al. [16] ,G H improved impressively functional class and hemodynamics. Moreover, allowed discontinuation of inotropes infusion, permitted the

Controversies in cardiology

HomeCirculationVol. 112, No. 8Controversies in cardiology Free AccessArticle CommentaryPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessArticle CommentaryPDF/EPUBControversies in cardiology Originally published23 Aug 2005https://doi.org/10.1161/circ.112.8.ivCirculation. 2005;112:ivThere are several areas of therapeutics where current practice differs between the United States and Europe. In the case of nesiritide, the use of this drug is undoubtedly controversial. This recombinant human brain natriuretic peptide is given to tens of thousands of patients in the United States every week at a cost of about $500 for each dose, and many physicians there are extremely enthusiastic about this new treatment for acute decompensated heart failure (ADHF).Aggressive marketing by the manufacturer, Scios Inc, has been suggested as one reason for its increasing use1 while many cardiologists in Europe are far less enthusiastic and have questioned whether nesiritide offers any improvement over current optimal management. Also the European Agency for the Evaluation of Medicinal Products has still not approved nesiritide and awaits the results of a trial involving 1900 patients before it will even consider doing so. In the UK, the assessment of nesiritide by the National Institute for Clinical Excellence is going at a snail’s pace and will not make any recommendations until August 2007.One recent meta-analysis published in March this year has suggested that nesiritide significantly increases the risk of worsening renal function in patients with ADHF,2 and another published a month later concluded that nesiritide may be associated with an increased risk of death after treatment for ADHF.3Scios Inc have stated in a letter to physicians and patient advocates dated 6 May 2005 that they remain confident in the safety profile of nesiritide and the benefits it offers to patients with acute decompensated heart failure. Differences of opinion on either side of the Atlantic appear set to continue.In the case of rosuvastatin, Europe and the US again seem at variance. Concerns were expressed in correspondence in a UK journal4 that rosuvastatin has an as yet unproven safety record, but family doctors and specialists are keen to prescribe it, even to individuals with no previous experience with lipid-lowering drugs, and to some who have predisposing risk factors for a potentially lethal side-effect. This was followed in June 2005 by new research that suggested that this drug, which has not been used in end-point trials, caused more kidney and muscle problems than rival medications although the rate of these complications was low.5The US Food and Drug Administration has contended that rosuvastatin’s risks are no greater than its competitors and rejected consumer efforts to remove the drug from sale, but did order a label warning that serious muscle problems and kidney damage could occur, especially among Asians.Manufacturer AstraZeneca strongly disagreed with the conclusions of the Circulation study and said the higher reports of side-effects may have been the result of heightened awareness of the problems following the withdrawal of cerivastatin in 2001. But in the UK, the Medicines and Healthcare Product Regulatory Agency issued advice as long ago as May 2004 that all patients start on 10 mg daily, and that the40- dose is contraindicated in patients with predisposing risk factors for muscle toxicity.Future issues of Circulation: European perspectives in cardiology will follow forthcoming developments and look at other variations in practice.References1 Topol EJ. Nesiritide—;not verified. N Engl J Med. 2005; 353 (2): 113–;6.CrossrefMedlineGoogle Scholar2 Sackner-Bernstein JD, Skopicki HA, Aaronson KD. Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure. Circulation. 2005; 111 (12): 1487–91.LinkGoogle Scholar3 Sackner-Bernstein JD, Kowalski M, Fox M, Aaronson K. Short-term risk of death after treatment with nesiritide for decompensated heart failure: a pooled analysis of randomized controlled trials. JAMA. 2005; 293 (15): 1900–5.CrossrefMedlineGoogle Scholar4 Florentinus SR, Heerdink ER, Klungel OH, de Boer A. Should rosuvastatin be withdrawn from the market?. Lancet. 2004; 364 (9445): 1577.CrossrefGoogle Scholar5 Alsheikh-Ali AA, Ambrose MS, Kuvin JT, Karas RH. The safety of rosuvastatin as used in common clinical practice: a postmarketing analysis. Circulation. 2005; 111 (23): 3051–7.LinkGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails August 23, 2005Vol 112, Issue 8 Advertisement Article InformationMetrics https://doi.org/10.1161/circ.112.8.iv Originally publishedAugust 23, 2005 PDF download Advertisement

Short-term Risk of Death After Treatment With Nesiritide for Decompensated Heart Failure: A Pooled Analysis of Randomized Controlled Trials

ContextNesiritide improves symptoms in patients with acutely decompensated heart failure compared with placebo and appears to be safer than dobutamine. Its short-term safety relative to standard diuretic and vasodilator therapies is less clear.ObjectiveTo investigate the safety of nesiritide relative to noninotrope-based control therapies, primarily consisting of diuretics or vasodilators.Data SourcesPrimary reports of completed clinical trials as of December 2004 were obtained from the US Food and Drug Administration (FDA), the study sponsor (Scios Inc), a PubMed literature search using the terms nesiritide, clinical trials, and humans, and a manual search of annual meetings of 3 heart associations.Study SelectionOf 12 randomized controlled trials evaluating nesiritide, 3 met all inclusion criteria: randomized double-blind study of patients with acutely decompensated heart failure, therapy administered as single infusion (≥6 hours), inotrope not mandated as control, and reported 30-day mortality.Data ExtractionData were extracted from FDA and sponsor documents and corroborated with published articles when available. Thirty-day survival was assessed by meta-analysis using a fixed-effects model and time-dependent risk by Kaplan-Meier analysis with Cox proportional hazards regression modeling. Where deaths were described within a range of days after treatment, an extreme assumption was made favoring nesiritide over control therapy, an approach relevant to the time-dependent analyses.Data SynthesisIn the 3 trials, 485 patients were randomized to nesiritide and 377 to control therapy. Death within 30 days tended to occur more often among patients randomized to nesiritide therapy (35 [7.2%] of 485 vs 15 [4.0%] of 377 patients; risk ratio from meta-analysis, 1.74; 95% confidence interval [CI], 0.97-3.12; P = .059; and hazard ratio after adjusting for study, 1.80; 95% CI, 0.98-3.31; P = .057).ConclusionsCompared with noninotrope-based control therapy, nesiritide may be associated with an increased risk of death after treatment for acutely decompensated heart failure. The possibility of an increased risk of death should be investigated in a large-scale, adequately powered, controlled trial before routine use of nesiritide for acutely decompensated heart failure.

Short-term Risk of Death After Treatment With Nesiritide for Decompensated Heart Failure

Nesiritide improves symptoms in patients with acutely decompensated heart failure compared with placebo and appears to be safer than dobutamine. Its short-term safety relative to standard diuretic and vasodilator therapies is less clear. To investigate the safety of nesiritide relative to noninotrope-based control therapies, primarily consisting of diuretics or vasodilators. Primary reports of completed clinical trials as of December 2004 were obtained from the US Food and Drug Administration (FDA), the study sponsor (Scios Inc), a PubMed literature search using the terms nesiritide, clinical trials, and humans, and a manual search of annual meetings of 3 heart associations. Of 12 randomized controlled trials evaluating nesiritide, 3 met all inclusion criteria: randomized double-blind study of patients with acutely decompensated heart failure, therapy administered as single infusion (> or =6 hours), inotrope not mandated as control, and reported 30-day mortality. Data were extracted from FDA and sponsor documents and corroborated with published articles when available. Thirty-day survival was assessed by meta-analysis using a fixed-effects model and time-dependent risk by Kaplan-Meier analysis with Cox proportional hazards regression modeling. Where deaths were described within a range of days after treatment, an extreme assumption was made favoring nesiritide over control therapy, an approach relevant to the time-dependent analyses. In the 3 trials, 485 patients were randomized to nesiritide and 377 to control therapy. Death within 30 days tended to occur more often among patients randomized to nesiritide therapy (35 [7.2%] of 485 vs 15 [4.0%] of 377 patients; risk ratio from meta-analysis, 1.74; 95% confidence interval [CI], 0.97-3.12; P = .059; and hazard ratio after adjusting for study, 1.80; 95% CI, 0.98-3.31; P = .057). Compared with noninotrope-based control therapy, nesiritide may be associated with an increased risk of death after treatment for acutely decompensated heart failure. The possibility of an increased risk of death should be investigated in a large-scale, adequately powered, controlled trial before routine use of nesiritide for acutely decompensated heart failure.

Platelet glycoprotein IIb/IIIa inhibitors during percutaneous coronary interventions: a pharmacological and clinical review

One of the most significant advances of the last decade has been the development of platelet glycoprotein (GP) IIb/IIIa receptor inhibitors. A large series of randomised, controlled clinical trials of these agents have shown a significant reduction in ischaemic events, not only in acute coronary syndrome patients, but also in patients who undergo elective percutaneous coronary interventions. Even though the use of oral antiplatelet and antithrombotic therapies in addition to percutaneous coronary interventions have had a significant impact in clinical outcomes after acute coronary syndromes, the use of GP IIb/IIIa inhibitors provide additional protection against recurrent ischaemia and has been identified as the pivotal mediator of platelet aggregation, making it a logical target for the control of platelet response to vascular injury. A series of key trials performed over the last few years with GP IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention, have shown a reduction in the risk of short-term death and non-fatal myocardial infarction. The pharmacology and molecular basis of GP IIb/IIIa receptor inhibition and the use of these agents in patients undergoing percutaneous coronary intervention (during acute coronary syndromes and in elective procedures) and their safety issues will be reviewed. A special emphasis has been made on the role of these agents in diabetic patients and their beneficial effect in reducing peri-procedural creatine kinase myocardial band fraction elevation and associated complications.

Prognostic value of isolated troponin elevation across the spectrum of chest pain syndromes

The risk of death or recurrent myocardial infarction (MI) in patients with chest pain and baseline isolated troponin elevation is unclear. To determine the early and short-term risk of death or MI associated with isolated troponin elevation across a spectrum of chest pain syndromes, we used baseline creatine kinase (CK)-MB and troponin data from the Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network (PARAGON) B troponin substudy, the Global Utilization of Strategies To Open Occluded Coronary Arteries (GUSTO) IIa troponin substudy, and the Chest Pain Evaluation by Creatine Kinase-MB, Myoglobin, and Troponin I (CHECKMATE) study. Patients were grouped into 1 of 4 categories based on marker status (troponin-positive/CK-MB-positive, troponin-positive/CK-MB-negative, troponin-negative/CK-MB-positive, or troponin-negative/CK-MB-negative). The adjusted odds of death or MI occurring at 24 hours and 30 days was assessed by baseline marker status using multivariable logistic regression, with the group negative for both markers used as the reference. Patients who were positive for both markers had the highest odds of the 24-hour and 30-day end point. The adjusted odds of the 30-day end point for patients with isolated troponin elevation were 1.3 (95% confidence interval 0.7 to 2.3) and 4.8 (95% confidence interval 1.4 to 16.0) for high- and low-risk patients, respectively. The risk for 24-hour and 30-day death or MI with isolated positive CK-MB results was lower than with isolated positive troponin results, and it was not significantly greater than if the 2 markers were negative. For patients with high- and low-risk chest pain, baseline troponin elevation without CK-MB elevation was associated with increased risk for early and short-term adverse outcomes. This suggests that these patients should be admitted to the hospital and monitored in either an intensive care or step-down unit.

Short and long term mortality associated with foodborne bacterial gastrointestinal infections: registry based study

Objectives: To determine the excess mortality associated with infections with Salmonella, Campylobacter, Yersinia enterocolitica, and Shigella and to examine the effect of pre-existing illness.Design: Registry based, matched cohort study.Setting: Denmark.Participants:...

Cardiac markers clarified

Infection Control/Laboratory Manager St. Mary’s Regional Medical Center Enid, Okla. Clinical director’s note:The information in question came from the AHA-ACC guidelines (Guidelines for the Management of Patients with Unstable Angina and Non ST-segment Elevation Myocardial Infarction, Table 6, Short-term Risk of Death or Nonfatal MI in Patients with Unstable Angina, pg. 979). Institution laboratories must carefully review their reference ranges to ensure that they’re in line with AHA-ACC recommendations.

Acute myocardial infarction in the elderly with diabetes

Objective: Diabetes mellitus (DM) has been associated with an elevated, short-term risk of death after myocardial infarction (MI). Among the studies of DM, however, few studies have included elderly subjects. The purpose of the present investigation was to determine if non-insulin-treated DM (NIRxDM) and insulin-treated DM (IRxDM) were associated with specific comorbid conditions, clinical findings on arrival, and MI characteristics, as well as a higher 30-day mortality rate in elderly patients with acute MI. Design: The study design was a retrospective medical record review and secondary data analysis of previously collected data from the Cooperative Cardiovascular Project. Setting: Study setting was Connecticut from June 1, 1992, through February 28, 1993. Patients: Subjects included the entire Medicare population (n = 2050), aged 65 years or older who were hospitalized for acute MI. Outcome Measures: Mortality rate at 30 days after MI was measured. Results: A history of DM was observed in 29% of the study population. DM status was associated with previous comorbid conditions, poorer functional status, higher body mass index, heart failure on arrival, non-Q-wave MI, and development of atrial fibrillation and oliguria during hospitalization. Patients with DM were less likely to have chest pain on arrival to the hospital. Diabetic status was not a significant predictor of short-term mortality; at 30 days after MI, 17% (n = 242) of the subjects without DM, 19% (n = 71) of those with NIRxDM, and 18% (n = 39) of the subjects with IRxDM died (P =.460). After adjustment for other prognostic factors, it was noted that MI characteristics present on hospital arrival predicted mortality at 30 days in both patients with NIRxDM and patients with IRxDM. Conclusions: The slightly, but not significantly, increased mortality risk in patients with DM should not minimize the importance of monitoring DM in the acute MI setting. Hospitalization for MI provides an opportunity to provide aggressive lipid and blood pressure management, optimize blood glucose, control heart failure, and institute other secondary preventive interventions in the elderly population with DM. (Heart Lung® 2002;31:327-39.)

Late sustained monomorphic ventricular tachycardia increases the short-term risk of death in patients with myocardial infarction

Late sustained monomorphic ventricular tachycardia increases the short-term risk of death in patients with myocardial infarction

Assessment of deaths attributable to air pollution: should we use risk estimates based on time series or on cohort studies?

Epidemiologic studies are crucial to the estimation of numbers of deaths attributable to air pollution. In this paper, the authors present a framework for distinguishing estimates of attributable cases based on time-series studies from those based on cohort studies, the latter being 5-10 times larger. The authors distinguish four categories of death associated with air pollution: A) air pollution increases both the risk of underlying diseases leading to frailty and the short term risk of death among the frail; B) air pollution increases the risk of chronic diseases leading to frailty but is unrelated to timing of death; C) air pollution is unrelated to risk of chronic diseases but short term exposure increases mortality among persons who are frail; and D) neither underlying chronic disease nor the event of death is related to air pollution exposure. Time-series approaches capture deaths from categories A and C, whereas cohort studies assess cases from categories A, B, and C. In addition, years of life lost can only be derived from cohort studies, where time to death is the outcome, while in time-series studies, death is a once-only event (no dimension in time). The authors conclude that time-series analyses underestimate cases of death attributable to air pollution and that assessment of the impact of air pollution on mortality should be based on cohort studies.

Biochemical markers of cardiac damage: From traditional enzymes to cardiac-specific proteins

Measurement of cardiac markers in blood has been the mainstay for diagnosis of acute myocardial infarction for nearly 50 years. The field has evolved from measurement of enzyme activity to mass concentrations of proteins using automated non-isotopic immunoassays. With changing clinical practices, cardiac markers are now needed to detect the presence of minor myocardial infarction in patients with unstable angina. Outcome studies have shown that patients with increased troponin are at high short-term risk for death and AMI. Recent developments involve the use of cardiac markers to select the most appropriate therapy for patients with acute coronary syndromes. The success of new cardiac markers such as troponin is due to their high cardiac specificity and the existence of assays with low detection limits. Traditional enzymes such as CK and CK-MB are thought to be released only in situations of irreversible myocardial necrosis. In the case of cardiac troponin, clinical observations and animal studies suggest that cytosolic free troponin may be released in reversible ischemia in addition to irreversible cell damage. The IFCC S-SCM has recommended use of two cut-off concentrations for cardiac troponin to differentiate normal from minor myocardial injury and AMI. A low cut-off may detect reversible ischemic events in some cases.