Asymptomatic thrombophilia--a family affair.
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Family Health↗
Biomedical subjects
R J Goldberg
Publications and source records attributed to R J Goldberg.
Predictors of major bleeding in acute coronary syndromes: the Global Registry of Acute Coronary Events (GRACE).
AIMS: There have been no large observational studies attempting to identify predictors of major bleeding in patients with acute coronary syndromes (ACS), particularly from a multinational perspective. The objective of our study was thus to develop a prediction rule for the identification of patients with ACS at higher risk of major bleeding. METHODS AND RESULTS: Data from 24045 patients from the Global Registry of Acute Coronary Events (GRACE) were analysed. Factors associated with major bleeding were identified using logistic regression analysis. Predictive models were developed for the overall patient population and for subgroups of patients with ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina. The overall incidence of major bleeding was 3.9% (4.8% in patients with STEMI, 4.7% in patients with NSTEMI and 2.3% in patients with unstable angina). Advanced age, female sex, history of bleeding, and renal insufficiency were independently associated with a higher risk of bleeding (P<0.01). The association remained after adjustment for hospital therapies and performance of invasive procedures. After adjustment for a variety of potential confounders, major bleeding was significantly associated with an increased risk of hospital death (adjusted odds ratio 1.64, 95% confidence interval 1.18, 2.28). CONCLUSIONS: In routine clinical practice, major bleeding is a relatively frequent non-cardiac complication of contemporary therapy for ACS and it is associated with a poor hospital prognosis. Simple baseline demographic and clinical characteristics identify patients at increased risk of major bleeding.
Adult↗
Creatinine clearance and adverse hospital outcomes in patients with acute coronary syndromes: findings from the global registry of acute coronary events (GRACE).
OBJECTIVE: To determine whether creatinine clearance at the time of hospital admission is an independent predictor of hospital mortality and adverse outcomes in patients with acute coronary syndromes (ACS). DESIGN: A prospective multicentre observational study, GRACE (global registry of acute coronary events), of patients with the full spectrum of ACS. SETTING: Ninety four hospitals of varying size and capability in 14 countries across four continents. PATIENTS: 11 774 patients hospitalised with ACS, including ST and non-ST segment elevation acute myocardial infarction and unstable angina. MAIN OUTCOME MEASURES: Demographic and clinical characteristics, medication use, and in-hospital outcomes were compared for patients with creatinine clearance rates of > 60 ml/min (normal and minimally impaired renal function), 30-60 ml/min (moderate renal dysfunction), and < 30 ml/min (severe renal dysfunction). RESULTS: Patients with moderate or severe renal dysfunction were older, were more likely to be women, and presented to participating hospitals with more comorbidities than those with normal or minimally impaired renal function. In comparison with patients with normal or minimally impaired renal function, patients with moderate renal dysfunction were twice as likely to die (odds ratio 2.09, 95% confidence interval 1.55 to 2.81) and those with severe renal dysfunction almost four times more likely to die (odds ratio 3.71, 95% confidence interval 2.57 to 5.37) after adjustment for other potentially confounding variables. The risk of major bleeding episodes increased as renal function worsened. CONCLUSION: In patients with ACS, creatinine clearance is an important independent predictor of hospital death and major bleeding. These data reinforce the importance of increased surveillance efforts and use of targeted intervention strategies in patients with acute coronary disease complicated by renal dysfunction.
Adult↗
Prevalence and quality of warfarin use for patients with atrial fibrillation in the long-term care setting.
BACKGROUND: Evidence-based clinical practice guidelines recommend the use of warfarin sodium for stroke prevention in most patients with atrial fibrillation (AF) who do not have risk factors for hemorrhagic complications, irrespective of age. METHODS: The medical records of all residents of a convenience sample of long-term care facilities in Connecticut (n = 21) were reviewed. The percentages of all patients with AF (AF patients) and ideal candidates for warfarin therapy (ie, AF patients with no risk factors for hemorrhage) who received warfarin were determined; for patients receiving warfarin, the percentage of days spent in the therapeutic range of international normalized ratio (INR) values (2.0-3.0) was also assessed. The relationship between receipt of warfarin and the presence of stroke and bleeding risk factors was assessed in multivariate models. RESULTS: Atrial fibrillation was present in 429 (17%) of the 2587 long-term care residents. Overall, 42% of AF patients were receiving warfarin. However, only 44 (53%) of 83 ideal candidates were receiving this therapy. In residents who received warfarin therapy, the therapeutic range of INR values was maintained only 51% of the time. The odds of receiving warfarin in the study sample decreased with increasing number of risk factors for bleeding and increased (nonsignificant trend) with increasing number of stroke risk factors present. CONCLUSIONS: Atrial fibrillation is very common among residents of long-term care facilities. Even among apparently ideal candidates, warfarin therapy is underused for stroke prevention in patients with AF. Prescribing decisions and monitoring related to warfarin therapy in the long-term care setting warrant improvement.
Aged↗
Age and the utilization of cardiac catheterization following uncomplicated first acute myocardial infarction treated with thrombolytic therapy (The Second National Registry of Myocardial Infarction [NRMI-2]).
Considerable data indicates that patients <50 years of age have lower morbidity and mortality after acute myocardial infarction (AMI) than older patients. It has been demonstrated that use of routine cardiac catheterization and revascularization in younger patients with AMI and successful thrombolysis does not confer benefit compared with a more conservative approach. Despite this, it has been our impression that cardiac catheterization is frequently employed in younger patients with AMI. Patients with uncomplicated initial AMI treated with thrombolytic therapy in the Second National Registry of Myocardial Infarction (NRMI-2) between June 1994 and April 1998 were identified. Patients were categorized into 4 age strata for purposes of analysis. A total of 61,232 cases met our inclusion criteria. Cardiac catheterization was performed during hospitalization in 78% of patients after an uncomplicated initial AMI. Age was inversely associated with receipt of cardiac catheterization: 85% of those < or =49 years old underwent catheterization compared with 63% of those > or =70 years old. Regression analysis revealed that use of catheterization was 2.9 times greater (95% confidence intervals 2.7 to 3.2) in patients < or =49 years old compared with those > or =70 years old. Geographic location and payor status also strongly influenced utilization of this procedure. In conclusion, routine coronary angiography after uncomplicated AMI is extensively utilized in all age groups, particularly in those <50 years of age. The efficacy and cost effectiveness of this strategy in these patients has not yet been determined in clinical trials.
Age Factors↗
Temporal trends (1986-1997) in cholesterol level assessment and management practices in patients with acute myocardial infarction: a population-based perspective.
BACKGROUND: Elevated serum cholesterol levels are associated with increased risk for acute myocardial infarction (AMI) and adverse patient outcomes. It is unclear what proportion of patients have their serum cholesterol levels measured during hospitalization for AMI and are given hypolipidemic therapy. OBJECTIVE: To examine decade-long trends in measurement of serum cholesterol levels during hospitalization for AMI and use of hypolipidemic therapy. METHODS: Observational study of 5204 residents of the Worcester, Mass, metropolitan area hospitalized with validated AMI in all greater Worcester hospitals in seven 1-year periods from 1986 through 1997. RESULTS: Increases in the measurement of serum cholesterol levels during hospitalization for AMI were observed between 1986 and 1991, followed by a progressive decrease; only 24% of patients with AMI in 1997 underwent cholesterol level testing. Younger age, male sex, and absence of a history of cardiovascular disease were associated with an increased likelihood measurement of serum cholesterol levels. Although the relative use of hypolipidemic therapy increased significantly over time (0.4% in 1986 vs 10.7% in 1997), the absolute rate of use remained low. In patients with elevated serum cholesterol levels (>/=6.2 mmol/L [>/=240 mg/dL]), 1.9% received hypolipidemic therapy in 1986 and 36.6% in 1997. CONCLUSIONS: These findings suggest recent declines in the assessment of total cholesterol levels in patients hospitalized with AMI. Although the use of hypolipidemic therapy during hospitalization for AMI has increased over time, considerable room for improvement remains.
Age Distribution↗
Outcomes and early revascularization for patients > or = 65 years of age with cardiogenic shock.
Hospital survival of patients with acute myocardial infarction (AMI) complicated by cardiogenic shock has improved during recent years. It is unclear whether this mortality benefit also applies to elderly patients with cardiogenic shock. Elderly residents (age > or = 65 years) of the Worcester, Massachusetts metropolitan area (1990 census population = 437,000) hospitalized with confirmed AMI and cardiogenic shock in all metropolitan Worcester, Massachusetts hospitals between 1986 and 1997 constituted the sample of interest. We examined the use of coronary reperfusion strategies, adjunctive therapy, and hospital mortality in a cohort of 166 cardiogenic patients treated early in the reperfusion era (1986 to 1991) compared with 144 patients with AMI treated approximately 1 decade later (1993 to 1997). There was a significant increase in the use of an early revascularization strategy over time (2% vs 16%, p <0.001). Marked increases in use of antiplatelet therapy, beta blockers, and angiotensin-converting enzyme inhibitors were also observed over the decade-long experience. In-hospital case fatality declined significantly over time, from 80% (1986 to 1991) to 69% (1993 to 1997) in elderly patients who developed cardiogenic shock (p = 0.03). After adjusting for differences in potentially confounding prognostic characteristics between patients hospitalized in the 2 study periods, an even more pronounced reduction in hospital mortality (42%) was observed for the most recently hospitalized cohort. The most powerful predictor of in-hospital survival was use of an early revascularization approach to treatment. Thus, hospital mortality has declined for patients > or = 65 years of age with AMI complicated by cardiogenic shock, and this decline has occurred in the setting of broader use of early revascularization and adjunctive medical therapy for this high-risk population.
Adrenergic beta-Antagonists↗
Inhibition of extracellular signal-regulated kinase 1/2 phosphorylation and induction of apoptosis by sulindac metabolites.
Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and sulindac is associated with a decreased mortality from colorectal cancer. Sulindac causes regression of precancerous adenomatous polyps and inhibits the growth of cultured colon cell lines. Whereas induction of apoptotic cell death is thought to account for the growth inhibitory effect of sulindac, less is known about its biochemical mechanism(s) of action. Sulindac is metabolized in vivo to sulfide and sulfone derivatives. Both the sulfide and sulfone metabolites of sulindac as well as more potent cyclic GMP-dependent phosphodiesterase inhibitors were shown to cause inhibition of extracellular signal-regulated kinase (ERK)1/2 phosphorylation at doses (40-600 microM) and times (1-5 days) consistent with the induction of apoptosis by the drugs. Treatment of HCT116 human colon cancer cells with the specific mitogen-activated protein kinase kinase, U0126 (5-50 microM) resulted in a time- and dose-dependent inhibition of ERK1/2 phosphorylation, and induction of apoptosis. U0126 treatment (20 microM) increased basal apoptosis, and potentiated the apoptotic effect of sulindac sulfide and sulindac sulfone. These results suggest that the inhibition of ERK1/2 phosphorylation is responsible for at least part of the induction of programmed cell death by sulindac metabolites. Inhibition of ERK1/2 activity may, therefore, be a useful biochemical target for the development of chemopreventive and chemotherapeutic drugs for human colon cancer.
3',5'-Cyclic-GMP Phosphodiesterases↗
Sex differences in 2-year mortality after hospital discharge for myocardial infarction.
BACKGROUND: An interaction between sex and age is thought to affect hospital mortality after myocardial infarction; younger, but not older, women have been shown to have higher mortality rates than men. It is currently unknown whether findings are similar after hospital discharge. OBJECTIVE: To determine whether an interaction between sex and age affects 2-year mortality after myocardial infarction. DESIGN: Community-based prospective cohort study. SETTING: 16 community hospitals serving the Worcester, Massachusetts, metropolitan area. PATIENTS: 6826 patients who survived hospitalization for acute myocardial infarction during ten 1-year periods between 1975 and 1995. MEASUREMENTS: Mortality 2 years after hospital discharge. RESULTS: The overall 2-year mortality rate was higher in women (28.9%) than in men (19.6%). When patients were examined by age group, however, only women younger than 60 years of age had a higher mortality rate than men of similar age. The sex difference decreased with increasing age; among the oldest patients, women had a lower mortality rate than men (P = 0.009 for the interaction between sex and age). This relationship was not affected by adjustment for demographic characteristics and medical history, clinical characteristics, and hospital and discharge treatments; the hazard of 2-year death for women compared with men increased 15.4% (95% CI, 4.3% to 27.6%) for every 10-year decrease in age. In absolute terms, after adjustment for demographic characteristics and medical history, among patients younger than 60 years of age women were at greater risk than men (risk difference, 1.8 percentage points). At older ages, however, women were at lower risk than men. CONCLUSIONS: Younger, but not older, women who survive hospitalization for myocardial infarction have a higher long-term mortality rate than men. This provides additional evidence that younger women with myocardial infarction are at greater risk for death than men.
Adult↗
Twenty-two year (1975 to 1997) trends in the incidence, in-hospital and long-term case fatality rates from initial Q-wave and non-Q-wave myocardial infarction: a multi-hospital, community-wide perspective.
OBJECTIVES: The goal of this study was to examine long-term trends in the incidence, in-hospital and long-term mortality patterns in patients with an initial non-Q-wave myocardial infarction (NQWMI) as compared with those with an initial Q-wave myocardial infarction (QWMI). BACKGROUND: Limited data are available describing trends in the incidence and mortality from an initial QWMI and NQWMI from a multi-hospital community-wide perspective. METHODS: Our study was an observational study of 5,832 metropolitan Worcester, Massachusetts residents (1990 census = 437,000) hospitalized with validated initial acute MI in all greater Worcester hospitals during 11 annual periods between 1975 and 1997. RESULTS: The incidence of QWMI progressively decreased between 1975/78 (incidence rate = 171/100,000 population) and 1997 (101/100,000 population). In contrast, the incidence of NQWMI progressively increased between 1975/78 (62/100,000 population) and 1997 (131/100,000 population). Hospital death rates were 19.5% for patients with QWMI and 12.5% for those with NQWMI. After controlling for various covariates, patients with QWMI remained at significantly increased risk for hospital mortality (adjusted odds ratio = 1.63; 95% confidence interval: 1.35, 1.97). While the hospital mortality of QWMI has progressively declined over time (1975/78 = 24%; 1997 = 14%), the in-hospital mortality for NQWMI has remained the same (1975/78 = 12%; 1997 = 12%). These trends remained after adjusting for potentially confounding prognostic factors. The multivariable adjusted two-year mortality after hospital discharge declined over time for patients with QWMI and NQWMI. CONCLUSIONS: Despite impressive declines in the incidence, in-hospital and long-term mortality associated with QWMI, NQWMI is increasing in frequency and has the same in-hospital mortality now as it did 22 years ago.
Aged↗
Circulating monocyte-platelet aggregates are an early marker of acute myocardial infarction.
OBJECTIVES: We investigated whether elevated levels of circulating monocyte-platelet aggregates (MPA) can be used to identify patients with acute myocardial infarction (AMI). BACKGROUND: Commonly used blood markers of AMI reflect myocardial cell death, but do not reflect the earlier pathophysiologic processes of plaque rupture, platelet activation and resultant thrombus formation. Circulating MPA form after platelet activation. METHODS: In a single center between October 1998 and November 1999, we measured circulating MPA in a blinded fashion by whole blood flow cytometry in 211 consecutive patients who presented to the emergency department (ED) with chest pain and were admitted to rule out AMI. Acute myocardial infarction was diagnosed by a CK-MB fraction greater than three times control. RESULTS: Patients with AMI (n = 61), as compared with those without AMI (n = 150), had significantly higher numbers of circulating MPA (11.6 +/- 11.4 vs. 6.4 +/- 3.6, mean +/- SD, p < 0.0001). After controlling for age, the adjusted odds of developing AMI for patients in the 2nd, 3rd and 4th quartiles of MPA, in comparison with patients in the lowest quartile (odds ratio = 1.0), were 2.1 (95% confidence interval [CI]: 0.7, 6.8), 4.4 (95% CI: 1.5, 13.1) and 10.8 (95% CI: 3.6, 32.0), respectively. The number of circulating MPA in patients with AMI presenting within 4 h of symptom onset (14.4) was significantly greater than those presenting after 4 h (9.4) and after 8 h (7.0), (p < 0.001). Of the 61 patients with AMI, 35 (57%) had a normal creatine kinase isoenzyme ratio at the time of presentation to the ED, but had high levels of circulating MPA (13.3). CONCLUSIONS: Circulating MPA are an early marker of AMI.
Creatine Kinase↗
Recent magnitude of and temporal trends (1994-1997) in the incidence and hospital death rates of cardiogenic shock complicating acute myocardial infarction: the second national registry of myocardial infarction.
BACKGROUND: Limited recent data are available to describe the magnitude of, and temporal trends in, the incidence and case-fatality rates associated with cardiogenic shock complicating acute myocardial infarction. The purpose of this study was to examine recent (1994-1997) trends in the incidence of, and hospital death rates from, cardiogenic shock complicating acute myocardial infarction from a large, multihospital national perspective. METHODS: An observational study was performed of 426,253 patients hospitalized with acute myocardial infarction in 1662 hospitals throughout the United States between 1994 and 1997. RESULTS: The incidence rates of cardiogenic shock averaged 6.2%. There was evidence for a slight decline in these rates between 1994 (6.6%) and 1997 (6.0%). Results of a multivariable regression analysis controlling for factors that might affect the risk of development of cardiogenic shock indicated that patients hospitalized in more recent years were at significantly lower risk for shock. Patients with shock had a markedly increased risk for dying during hospitalization compared with patients not having shock (74% vs 10%). Significant, albeit small, absolute differences were observed in the risk of dying after cardiogenic shock over time (76% dying in 1997, 72% dying in 1994). These improving trends were magnified, however, after potentially confounding prognostic factors were controlled: patients having shock in 1997 were at approximately one fifth lower risk of dying (odds ratio 0.79, 95% confidence interval 0.71-0.87) than those hospitalized in 1994. CONCLUSIONS: Our findings indicate a slight decline in the incidence rates of cardiogenic shock and improving trends in the hospital survival of patients with shock. Despite these trends, it remains of considerable importance to prevent this clinical syndrome, given its high lethality.
Aged↗
The use of intra-aortic balloon counterpulsation in patients with cardiogenic shock complicating acute myocardial infarction: data from the National Registry of Myocardial Infarction 2.
BACKGROUND: Cardiogenic shock complicating acute myocardial infarction (AMI) remains the leading cause of death in patients hospitalized with AMI. Although several studies have demonstrated the importance of establishing and maintaining a patent infarct-related artery, it remains unclear as to whether intra-aortic balloon counterpulsation (IABP) provides incremental benefit to reperfusion therapy. The purpose of this study was to determine whether IABP use is associated with lower in-hospital mortality rates in patients with AMI complicated by cardiogenic shock in a large AMI registry. METHODS: We evaluated patients participating in the National Registry of Myocardial Infarction 2 who had cardiogenic shock at initial examination or in whom cardiogenic shock developed during hospitalization (n = 23,180). RESULTS: The mean age of patients in the study was 72 years, 54% were men, and the majority were white. The overall mortality rate in all patients who had cardiogenic shock or in whom cardiogenic shock developed was 70%. IABP was used in 7268 (31%) patients. IABP use was associated with a significant reduction in mortality rates in patients who received thrombolytic therapy (67% vs 49%) but was not associated with any benefit in patients treated with primary angioplasty (45% vs 47%). In a multivariate model, the use of IABP in conjunction with thrombolytic therapy decreased the odds of death by 18% (odds ratio, 0.82; 95% confidence interval, 0.72 to 0.93). CONCLUSIONS: Patients with AMI complicated by cardiogenic shock may have substantial benefit from IABP when used in combination with thrombolytic therapy.
Aged↗
Decade-long trends (1986 to 1997) in the medical treatment of patients with acute myocardial infarction: A community-wide perspective.
BACKGROUND: Although there are an increasing number and variety of medications available for the treatment of patients with acute myocardial infarction (AMI), few data are available describing recent, and changes over time in, use of different cardiac medications in patients with AMI from a more generalizable, community-wide perspective. Moreover, it is unclear whether the demographic and clinical profile of patients receiving these agents is similar or varies according to the type of agent prescribed. METHODS AND RESULTS: The purpose of this study was to examine recent patterns and changes over a decade-long period (1986 to 1997) in the use of cardiac medications during the acute hospitalization and at the time of hospital discharge in metropolitan Worcester, Mass, residents (1990 census estimate, 437,000) hospitalized with confirmed AMI. There was a marked increase in the use of angiotensin-converting enzyme inhibitors, aspirin, beta-blockers, lipid-lowering agents, and thrombolytic therapy between 1986 and 1997. The use of calcium antagonists, lidocaine, and other antiarrhythmic agents declined over this period. Similar trends were observed in the use of these agents in hospital survivors at the time of hospital discharge. Patient age, presence of comorbidities, and AMI-associated characteristics influenced the use of these therapies; sex differences in the use of several of these medications were also noted. CONCLUSIONS: The results of this population-based observational study provide insights into changing prescribing patterns in the hospital treatment of patients with AMI. Despite encouraging increases in the use of several of these agents, considerable opportunities for increased utilization remain.
Acute Disease↗
Depression in the workplace: costs and barriers to treatment.
Surveys estimate that 1.8 to 3.6 percent of workers in the U.S. labor force suffer from major depression. Depression has a significant impact on vocational functioning. Seventeen to 21 percent of the workforce experiences short-term disability during any given year, and 37 to 48 percent of workers with depression experience short-term disability. Studies indicate that treating workplace depression provides favorable cost offsets for employers, although a number of methodological issues have influenced the interpretation of these findings. In addition to disability costs, cost analyses need to include lost wages and indirect costs to employers, such as the costs of hiring and training new employees. In general, employers are not aware of the extent of the indirect costs of untreated depression. They have mistaken assumptions about the availability of effective treatment, and they are unaware of how often depression contributes to worker disability. The workers' compensation system and the courts have been slow to recognize depression as a work-related disability, and as a result employers have few incentives to treat and prevent workplace depression.
Major Depressive Disorder↗
Treating dementia: do conventional neuroleptics still have a role?
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Aged↗
Depression in the workplace: economics and interventions.
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Depressive Disorder↗
Decade-long trends and factors associated with time to hospital presentation in patients with acute myocardial infarction: the Worcester Heart Attack study.
BACKGROUND: Duration of prehospital delay in patients with acute myocardial infarction (AMI) is receiving increasing attention given the time-dependent benefits associated with prompt use of coronary reperfusion strategies. OBJECTIVE: To examine trends (1986-1997) in time to hospital presentation and factors associated with prolonged delay in a community-wide study of patients with AMI. METHODS: Longitudinal study of 3837 residents of the Worcester, Mass, metropolitan area hospitalized with AMI in 7 one-year periods between 1986 and 1997 in whom information about prehospital delay was available. RESULTS: The mean, median, and distribution of delay times exhibited either inconsistent or no changes over time. In 1986, the mean and median prehospital delay times were 4.1 and 2.2 hours, respectively; these times were 4.3 and 2.0 hours, respectively, in patients hospitalized in 1997. Overall, with no significant differences noted over time, approximately 44% of patients with AMI presented to area-wide hospitals in less than 2 hours after the onset of acute coronary symptoms. Increasing age, history of angina or diabetes, onset of symptoms in the afternoon or evening, and hospitalization in the most recent study year (1997) were significantly associated with delays of more than 2 hours in seeking hospital care after controlling for a variety of factors that might affect delay. CONCLUSIONS: The results of this population-based study suggest that a large proportion of patients with AMI continue to exhibit prolonged delay. The characteristics of many of these individuals can be identified in advance for targeted educational efforts. Arch Intern Med. 2000;160:3217-3223.
Aged↗