Inter-rater reliability of a classification system for hospital adverse drug event reports.

Hospital pharmacovigilance systems frequently classify adverse drug event (ADE) reports on various axes such as severity and type of outcome in an attempt to better detect changes in the frequency of certain types of ADEs. The aim of this study was to measure the inter-observer reliability of an ADE classification system. Two pharmacists and two internal medicine physicians reviewed 150 pharmacist-generated ADE reports and used a structured form to classify reports on four domains: the presence or absence of process measures leading to ADE; the individual who initiated the process that potentially leads to ADE; the severity of ADE; and whether the ADE was related to dose. There was wide variation in inter-observer reliability of different elements in a classification system for ADEs. Agreement on specific processes associated with ADEs ranged from poor to moderate, which limits the ability to target accurately processes to improve drug utilization.

Outcome of medical versus invasive treatment strategies for non-high-risk ischemic heart disease.

The purpose of this study was to evaluate the outcomes of medical management compared with invasive management for patients with mild or moderate ischemia (non-high-risk) on stress tomographic myocardial perfusion scintigraphy. Of the 1,352 non-high-risk patients, 116 (9%) subsequently were referred for coronary angiography within the first 30 days after the scan; 99 (85%) of this group also underwent early revascularization procedures. The remaining 1,236 patients (91%) with non-high-risk ischemia did not undergo early invasive management. Unadjusted actuarial 3-year rate of cardiac death or nonfatal infarction was significantly better estimated survival in the medically managed group (2%) compared with the invasively managed group (22%), p = 0.0001. Subsequent coronary revascularization procedures during 3-year follow-up were less frequent in the medically managed group (4%) than in the invasively managed group (42%), p = 0.0001. A multivariable analysis identified invasive management strategy (p = 0.0001) as the only correlate of cardiac events during follow-up. In summary, this study showed that patients with non-high-risk ischemia on stress perfusion imaging can be treated safely with a conservative medical management strategy.

Coronary angiographic rates after stress single-photon emission computed tomographic scintigraphy.

BACKGROUND: There is speculation that coronary angiography may be overused for the assessment of coronary artery disease. Because of its proved ability to differentiate high- and low-risk subsets of patients with coronary artery disease, myocardial perfusion scintigraphy should be an effective strategy in patient selection for angiography. This retrospective clinical study analyzed the relation between scintigraphic findings and subsequent angiography. METHODS AND RESULTS: Coronary angiographic rates were determined by following up on all stress single-photon emission computed tomographic (SPECT) myocardial perfusion studies performed in a cardiology practice nuclear laboratory during a 26-month interval. All patients were followed up for at least 3 months; mean follow-up was 8.9 months. Subsequent angiography was determined from catheterization laboratory logs, medical records, and telephone contact. Scintigraphic studies were graded according to presence or absence of reversible perfusion defects, affected coronary territories, and lung uptake of 201Tl. Scans were categorized high risk if more than two of the following three criteria were met: reversibility of left anterior descending or multivessel distributions or abnormal lung uptake of thallium. Of 4162 studies, 60% had reversible perfusion defects. Of such studies, 32% were followed up by angiography versus 3.5% without reversible defects. Among studies with reversible defects, the subsequent angiography rate was 60% for those showing high-risk reversibility, compared with 9% for all other studies demonstrating reversibility. Multivariate logistic regression identified high-risk reversibility (odds ratio 20.96) and any reversibility (odds ratio 8.22) as the strongest predictors of angiography. Other correlates of lesser statistical significance were angina and absence of prior infarction or coronary bypass. CONCLUSION: In this large retrospective study, the results of SPECT scintigraphy overpowered all other clinical and treadmill characteristics in determining the likelihood of subsequent coronary angiography. Only rarely were patients categorized as relatively low risk by scintigraphy referred for angiography. As such, SPECT scintigraphy as used in a private practice, self-referral environment appears to be effective in stratifying potential candidates for coronary angiography.

Comparison of stress echocardiography and stress myocardial perfusion scintigraphy for diagnosing coronary artery disease and assessing its severity.

The cumulative published literature dealing with the most frequently utilized noninvasive cardiac stress imaging modalities (radionuclide myocardial perfusion scintigraphy and echocardiography) was reviewed to gain insight on their comparative diagnostic accuracies. To be included, studies had to be performed in conjunction with exercise or a commonly used intravenous pharmacologic stress agent (dipyridamole, adenosine or dobutamine) and had to report temporally related coronary angiography findings. A total of > 75 studies were included, involving > 7,000 patients. Exercise single-photon emitted computed tomographic (SPECT) scintigraphy was more sensitive than exercise echocardiography for detecting coronary artery disease (CAD), localizing it to the proper coronary artery distribution and correctly identifying the presence of multivessel CAD. Adenosine, dipyridamole, and dobutamine provided similar diagnostic accuracy when performed in conjunction with SPECT scintigraphy, and all were more accurate than dobutamine echocardiography. Clinical specificity was similarly high with adenosine SPECT, dipyridamole echocardiography, and exercise echocardiography, and lower with exercise SPECT. Normalcy rate was high for exercise SPECT and similar to clinical specificity for echocardiography.

Four- versus 6-minute infusion protocol for adenosine thallium-201 single photon emission computed tomography imaging.

Intravenous adenosine infusion results in immediate maximal coronary arteriolar vasodilatation. Side effects occur in most patients who receive adenosine. For these reasons, a shorter infusion for pharmacologic stress thallium-201 testing may improve patient tolerability without compromising diagnostic accuracy. In a retrospective, unblinded evaluation, we compared side effects and accuracy of a standard 6-minute adenosine infusion single photon emission computed tomography (SPECT) study with a 4-minute protocol in 730 and 621 patients, respectively. Adenosine was infused at 140 micrograms/kg/minute in both groups; thallium-201 was injected at the 3-minute mark of the 4-minute protocol and at the 4-minute mark of the 6-minute protocol. Angiographic follow-up (mean 8 days) after thallium-201 testing was available in 233 (32%) of the patients in the 6-minute protocol and in 174 (28%) of the patients in the 4-minute protocol (p not significant (NS). Side effects occurred in 90% of the patients in the 6-minute protocol and in 91% of the patients in the 4-minute protocol (p = NS). Premature termination of the infusion was required in 4% of the patients in the 6-minute protocol and 2% of the patients in the 4-minute protocol (p = 0.02). Second- or third-degree atrioventricular block was noted in 4.5% and 3.0% of the 6- and 4-minute groups, respectively (p = NS). The duration of symptoms averaged 2.9 +/- 4.4 minutes in the patients in the 6-min protocol and 2.1 +/- 1.6 minutes in the patients in the 4-minute protocol (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine thallium-201 is superior to exercise thallium-201 for detecting coronary artery disease in patients with left bundle branch block.

OBJECTIVES: We sought to assess the comparative diagnostic accuracy of adenosine versus exercise in conjunction with thallium-201 scintigraphy for the detection and localization of coronary artery disease in patients with left bundle branch block on the rest electrocardiogram (ECG). BACKGROUND: Patients with left bundle branch block on the rest ECG frequently have artifactual reversible septal perfusion defects on exercise thallium-201 scintigraphy. Adenosine thallium scintigraphy is a theoretically attractive alternative in these patients. METHODS: One hundred seventy-three consecutive patients with left bundle branch block were evaluated with either exercise thallium (n = 56) or adenosine thallium (n = 117) scintigraphy. The tomographic thallium images were interpreted visually with adjunctive quantitative analysis. Follow-up cardiac catheterization was performed in 31 of the 56 patients in the exercise thallium group and 42 of the 117 patients in the adenosine thallium group. RESULTS: Minor subjective side effects were noted in most patients in the adenosine thallium group (86%); atrioventricular block occurred in seven patients (6%). The overall predictive accuracy was 93% in the adenosine thallium group and 68% in the exercise thallium group (p = 0.01). The combined specificity for the detection of disease in the coronary arteries subtending the septum (the left anterior descending and right coronary arteries) was only 42% with exercise thallium scintigraphy versus 82% with adenosine thallium scintigraphy (p < 0.0002). CONCLUSIONS: Adenosine thallium imaging 1) was superior to exercise thallium imaging in the detection of coronary artery disease in patients with left bundle branch block; 2) obviated septal artifacts, thereby markedly improving the specificity in the left anterior descending and right coronary arteries; and 3) was safe in patients with left bundle branch block.

Safety and diagnostic accuracy of adenosine thallium-201 scintigraphy in patients unable to exercise and those with left bundle branch block.

Three hundred forty consecutive patients (mean age 69 +/- 9 years) were evaluated with adenosine tomographic thallium-201 scintigraphy for suspected coronary artery disease. Minor side effects occurred in 91% of patients. Out of 28 patients (8%) with potentially serious side effects, 28 had significant atrioventricular (AV) block (second-degree, 24 patients; third-degree, four patients; syncope occurred in two patients). Acute bronchospasm and severe refractory angina pectoris occurred in one patient each. All side effects were transient and without sequelae. One hundred twenty-one patients underwent coronary angiography within 9 days of adenosine thallium imaging. The predictive accuracies of adenosine thallium imaging for identifying and localizing ischemia to a specific coronary distribution were: left anterior descending = 88%, left circumflex = 84%, right coronary = 88%. The predictive accuracy of adenosine thallium imaging in patients with left bundle branch block was 91%, and was higher than the 71% predictive accuracy noted in 39 patients who underwent exercise thallium testing (p = 0.04). It is concluded that adenosine thallium-201 myocardial scintigraphy was (1) highly accurate for the detection and localization of significant coronary artery disease; (2) it was more accurate at detecting ischemia in patients with left bundle branch block than exercise thallium testing, and (3) subjective side effects were common and were of no diagnostic importance; transient AV block occurred occasionally.

Effects of environmental toxicants on metabolic activity of natural microbial communities.

Two methods of measuring microbial activity were used to study the effects of toxicants on natural microbial communities. The methods were compared for suitability for toxicity testing, sensitivity, and adaptability to field applications. This study included measurements of the incorporation of C-labeled acetate into microbial lipids and microbial glucosidase activity. Activities were measured per unit biomass, determined as lipid phosphate. The effects of various organic and inorganic toxicants on various natural microbial communities were studied. Both methods were useful in detecting toxicity, and their comparative sensitivities varied with the system studied. In one system, the methods showed approximately the same sensitivities in testing the effects of metals, but the acetate incorporation method was more sensitive in detecting the toxicity of organic compounds. The incorporation method was used to study the effects of a point source of pollution on the microbiota of a receiving stream. Toxic doses were found to be two orders of magnitude higher in sediments than in water taken from the same site, indicating chelation or adsorption of the toxicant by the sediment. The microbiota taken from below a point source outfall was 2 to 100 times more resistant to the toxicants tested than was that taken from above the outfall. Downstream filtrates in most cases had an inhibitory effect on the natural microbiota taken from above the pollution source. The microbial methods were compared with commonly used bioassay methods, using higher organisms, and were found to be similar in ability to detect comparative toxicities of compounds, but were less sensitive than methods which use standard media because of the influences of environmental factors.