Pulmonary embolism mortality in the United States, 1979-1998: an analysis using multiple-cause mortality data

Background Pulmonary thromboembolism (PTE) is a common clinical problem that is associated with substantial morbidity and mortality. Estimates of PTE mortality and predictions of PTE trends have varied widely. These estimates play a role in the planning of national health strategies. The analysis of pulmonary embolism mortality trends and comorbidities may elucidate how well we treat and prevent the disease as well as identify additional risk factors. Methods We analyzed PTE (International Classification of Diseases, Ninth Revision code 415.1) as reported on death certificates in the Multiple-Cause Mortality Files compiled by the National Center for Health Statistics from 1979 to 1998. Results Of all the 42 932 973 decedents, 572 773 (1.3%) had PTE listed on their death certificates and 194 389 of these (33.9%) had PTE as the underlying cause of death. The age-adjusted rate of deaths with PTE decreased from 191 per million in 1979 to 94 per million in 1998 overall, decreasing 56% for men and 46% for women. During the study period, the age-adjusted mortality rates for blacks were consistently 50% higher than those for whites, and those for whites were 50% higher than those for people of other races (Asian, American Indian, etc). Within racial strata, mortality rates were consistently 20% to 30% higher among men than among women. Conditions that were of higher likelihood in persons who died with PTE included thrombophlebitis, fractures, trauma, postoperative complications, certain cancers, and the inflammatory bowel diseases. Conclusions Mortality with PTE in the United States has decreased during the 20-year period. The mortality rates between men and women and between racial groups vary substantially. These findings may be useful in better directing preventive therapy efforts

Clinical Manifestations of Acute Pulmonary Embolism: Henry Ford Hospital Experience, A Five-Year Review

Clinical findings of 112 patients with angiographically proven pulmonary embolism over a five-year period were analyzed. Recent immobilization, chronic heart disease, deep venous thrombosis, malignancy, and recent surgery were the most frequent predisposing factors. Only 5% had no identifiable risk factors. Presenting syndromes were circulatory collapse (25%), pulmonary infarction (59%), and uncomplicated pulmonary embolism (18%). Dyspnea and pleuritic chest pain were the predominant symptoms. The combination of dyspnea, pleuritic chest pain, and hemoptysis occurred in 23% of the patients. The most frequent signs were tachypnea, tachycardia, and rales. Most of the patients demonstrated arterial oxygen tension (PaO2) between 50 and 70 mm Hg, and 9% had a PaO2 greater than 80 mm Hg. The most common chest x-ray findings were infiltration and consolidation, pleural effusion, and atelectasis. The most common electrocardiographic abnormalities were nonspecific ST and T-wave changes in 42% of patients. Lung scans were most frequently interpreted as indeterminate probability. A continuing reassessment of the features of pulmonary embolism may assist in selecting patients for confirmatory diagnostic studies

Filgrastim in Patients With Pneumonia and Severe Sepsis or Septic Shock

Evaluate the safety of filgrastim(recombinant methionyl human granulocyte colony-stimulating factor)administration, combined with standard therapy, in patients withpneumonia and either septic shock or severe sepsis who were receivingmechanical ventilation. Multicenter, double-blind, randomized, placebo-controlled study. ICU, multicenter. Eighteen patients with pneumonia and hypotension, or in the absence ofshock, two or more end-organ dysfunctions, were enrolled and treated. Baseline acute physiology and chronic health evaluation II scores andmedian age for the filgrastim (n = 12) and placebo (n = 6) groupswere 25.0 and 49.5 years and 31.5 and 56.5 years, respectively. Filgrastim (300 μg) or placebo wasadministered IV daily for up to 5 days. Study end points included safety; biologicalresponse, including endogenous cytokine levels, endotoxin levels, andneutrophil counts; and mortality. Cytokine and endotoxin levels werehighly variable in both groups. By day 29, 3 of 12 filgrastim-treatedpatients and 4 of 6 placebo-treated patients had died. There were nodifferences in types and occurrences of adverse events, including ARDS, or in outcome between the two groups. Three of four placebo-treatedpatients had persistent bacterial growth on bronchoscopy repeated after48 h compared with 2 of 10 filgrastim-treated patients. Filgrastim appeared to be well tolerated inthis population of patients with pneumonia and severe sepsis or septicshock. Larger studies to determine the benefit of filgrastim inpatients with pneumonia and sepsis or organ dysfunction arewarranted

The Alliance AMBUSH Trial: Rationale and Design

Unlike medulloblastoma (MB) in children, robust prospective trials have not taken place for older patients due to the low incidence of MB in adults and adolescent and young adults (AYA). Current MB treatment paradigms for older patients have been extrapolated from the pediatric experience even though questions exist about the applicability of these approaches. Clinical and molecular classification of MB now provides better prognostication and is being incorporated in pediatric therapeutic trials. It has been established that genomic alterations leading to activation of the sonic hedgehog (SHH) pathway occur in approximately 60% of MB in patients over the age of 16 years. Within this cohort, protein patched homolog (PTCH) and smoothened (SMO) mutations are commonly found. Among patients whose tumors harbor the SHH molecular signature, it is estimated that over 80% of patients could respond to SHH pathway inhibitors. Given the advances in the understanding of molecular subgroups and the lack of robust clinical data for adult/AYA MB, the Alliance for Clinical Trial in Oncology group developed the AMBUSH trial: Comprehensive Management of AYA and Adult Patients with Medulloblastoma or Pineal Embryonal Tumors with a Randomized Placebo Controlled Phase II Focusing on Sonic Hedgehog Pathway Inhibition in SHH Subgroup Patients (Adult & Adolescent MedulloBlastoma Using Sonic Hedgehog Trial). This trial will enroll patients 18 years of age or older with MB (any molecular subgroup and risk stratification) or pineal embryonal tumor. Patients will be assigned to one of three cohorts: (1) average risk non-SHH-MB, (2) average risk SHH-MB, and (3) high risk MB or pineal embryonal tumors. All patients will receive protocol-directed comprehensive treatment with radiation therapy and chemotherapy. Patients with SHH-MB in cohort 1 will be randomized to a smoothened inhibitor or placebo as maintenance therapy for one year

Challenges in the diagnosis of acute pulmonary embolism

The state of the art of diagnostic evaluation of hemodynamically stable patients with suspected acute pulmonary embolism was reviewed. Diagnostic evaluation should begin with clinical assessment using a validated prediction rule in combination with measurement of D-dimer when appropriate. Imaging should follow only when necessary. Although with 4-slice computed tomography (CT) and 16-slice CT, the sensitivity for detection of pulmonary embolism was increased by combining CT angiography with CT venography, it is not known whether CT venography increases the sensitivity of 64-slice CT angiography. Methods to reduce the radiation exposure of CT venography include imaging only the proximal leg veins (excluding the pelvis) and obtaining discontinuous images. Compression ultrasound can be used instead. In young women, radiation of the breasts produces the greatest risk of radiation-induced cancer. It may be that scintigraphy is the imaging test of choice in such patients, but this pathway should be tested prospectively. A patient-specific approach to the diagnosis of pulmonary embolism can be taken safely in hemodynamically stable patients to increase efficiency and decrease cost and exposure to radiation

Comparison of 1.5 and 3.0 T for contrast-enhanced pulmonary magnetic resonance angiography

OBJECTIVE: In a recent multi-center trial of gadolinium contrast-enhanced magnetic resonance angiography (Gd-MRA) for diagnosis of acute pulmonary embolism (PE), two centers utilized a common MRI platform though at different field strengths (1.5T and 3T) and realized a signal-to-noise gain with the 3T platform. This retrospective analysis investigates this gain in signal-to-noise of pulmonary vascular targets. METHODS: Thirty consecutive pulmonary MRA examinations acquired on a 1.5T system at one institution were compared to 30 consecutive pulmonary MRA examinations acquired on a 3T system at a different institution. Both systems were from the same MRI manufacturer and both used the same Gd-MRA pulse sequence, although there were some protocol adjustments made due to field strength differences. Region-of-interests were manually defined on the main pulmonary artery, 4 pulmonary veins, thoracic aorta, and background lung for objective measurement of signal-to-noise, contrast-to-noise, and bolus timing bias between centers. RESULTS: The 3T pulmonary MRA protocol achieved higher spatial resolution yet maintained significantly higher signal-to-noise ratio (≥ 13%, p = 0.03) in the main pulmonary vessels relative to 1.5T. There was no evidence of operator bias in bolus timing or patient hemodynamic differences between groups. CONCLUSION: Relative to 1.5T, higher spatial resolution Gd-MRA can be achieved at 3T with a sustained or greater signal-to-noise ratio of enhanced vasculature