Early noninvasive detection of failed epicardial reperfusion after fibrinolytic therapy.

Available noninvasive techniques for identifying patients with failed epicardial reperfusion after fibrinolytic therapy are limited by poor accuracy. It is unknown whether combining multiple noninvasive predictors would improve diagnostic accuracy and facilitate identification of candidates for rescue percutaneous coronary intervention. In the Thrombolysis In Myocardial Infarction (TIMI) 14 trial, we evaluated the ability of ST-segment resolution (n = 606), chest pain resolution (n = 859), and the ratio of 60-minute/baseline serum myoglobin (n = 308) to identify patients with angiographic evidence of failed reperfusion 90 minutes after fibrinolysis. Three criteria were prospectively defined: <50% ST resolution at 90 minutes, presence of chest pain at the time of angiography, and myoglobin ratio <4. Patients who met any individual criterion were more likely to have less than TIMI 3 flow and an occluded infarct-related artery (TIMI 0/1 flow) than those who did not meet the criterion (p <0.005 for each). When the 3 criteria were used together (n = 169), patients who satisfied 0 (n = 29), 1 (n = 68), 2 (n = 51), or 3 (n = 21) of the criteria had a 17%, 24%, 35%, and 76% probability of failing to achieve TIMI 3 flow (p <0.0001 for trend), a 0%, 6%, 18%, and 57% probability of an occluded infarct-related artery (p <0.0001 for trend), and a 0%, 1.5%, 2.0%, and 9.5% rate of 30-day mortality (p = 0.05 for trend), respectively. Use of the criteria in combination increased positive predictive values without decreasing negative predictive values. In conclusion, ST-segment resolution, chest pain resolution, and early washout of serum myoglobin can be used in combination to aid in the early noninvasive identification of candidates for rescue percutaneous coronary intervention.

Myoglobin levels at 12 hours identify patients at low risk for 30-day mortality after thrombolysis in acute myocardial infarction: a Thrombolysis in Myocardial Infarction 10B substudy.

OBJECTIVE: We sought to identify, by use of serum cardiac markers, patients at low risk for 30-day mortality after ST-segment elevation myocardial infarction. BACKGROUND: Baseline cardiac markers are currently used to identify patients at increased risk for short-term events. We hypothesized that serum markers measured after treatment could identify patients at low risk for 30-day mortality. METHODS: A total of 839 patients from the Thrombolysis in Myocardial Infarction (TIMI) 10B study had myoglobin, cardiac-specific troponin-I, creatine kinase (CK)-MB measurements at the following time points; baseline, 90 minutes, and 3 and 12 hours after thrombolysis. By use of receiver operating characteristic analysis, thresholds were derived to predict 30-day mortality with at least 95% negative predictive value. RESULTS: Ninety minutes after thrombolysis myoglobin was superior to troponin-I or CK-MB in identifying patients at low risk for mortality. The 30-day mortality for 12-hour myoglobin < or = 239 ng/mL was 1.4% compared with 9.1% for levels > 239 ng/mL (P < .001). For 12-hour troponin-I (threshold 81.5 ng/mL), mortality was 1.9% versus 6.6% (P = .001) if above threshold; similarly for CK-MB at 12 hours (threshold 191 ng/mL) it was 3.3% versus 7.9% (P = .02). Multivariate analysis of baseline and posttreatment cardiac markers, age, sex, infarct artery location, and 90-minute TIMI flow grade identified only 12-hour myoglobin among the cardiac markers as independently predicting a low 30-day mortality (odds ratio 0.11, 95% confidence interval 0.02-0.50, P < .004). CONCLUSION: Serum cardiac markers can identify greater than two thirds of patients at low risk for 30-day mortality. A low 12-hour myoglobin level (< or = 239 ng/mL in this substudy) identifies such patients at low risk and could potentially assist in early risk stratification and triage after ST-segment elevation myocardial infarction.

Monoclonal gammopathy of undetermined significance and exposure to breast implants.

BACKGROUND: Animal studies and uncontrolled case series in humans have suggested a possible association between breast implant exposure and monoclonal gammopathy. OBJECTIVE: To assess whether there is an increased risk of monoclonal gammopathy in women with silicone breast implants, we conducted a retrospective study of women exposed to breast implants and matched nonexposed women nested within a prospective cohort study (the Nurses' Health Study). METHODS: We used serum protein electrophoresis and immunoglobulin subtype by immunofixation to test 288 women exposed to breast implants and 288 age-matched, nonexposed women who previously had provided a blood sample (1989-1990) for monoclonal proteins. RESULTS: Among the women exposed to breast implants, 5 had monoclonal gammopathy of undetermined significance (MGUS) compared with 4 women among those not exposed (odds ratio, 1.25; 95% confidence interval, 0.27-6.39). The distribution of isotypes was similar across exposure groups. The exposed women with MGUS tended to be older than the nonexposed women (mean age, 60.4 years vs 52.5 years, respectively; P =.03). None of the 9 women with MGUS had reported multiple myeloma or other hematologic malignancies up through 1996. CONCLUSIONS: We find little evidence to support a substantial increased risk of MGUS in women exposed to breast implants. Larger studies are needed to determine if a more modest relationship exists.

Cardiac troponin I for stratification of early outcomes and the efficacy of enoxaparin in unstable angina: a TIMI-11B substudy.

OBJECTIVES: We sought to evaluate cardiac troponin I (cTnI) for predicting early clinical outcomes and the efficacy of enoxaparin among patients with non-ST segment elevation acute coronary syndrome (ACS) and negative creatine kinase, MB fraction (CK-MB) levels. BACKGROUND: Cardiac TnI identifies patients with unstable angina who are at higher risk of death or myocardial infarction (MI) by 30 days. The utility of cTnI for predicting very early clinical events, including recurrent ischemia, and the efficacy of enoxaparin are not yet established. METHODS: At baseline and 12 h to 24 h after enrollment in the Thrombolysis in Myocardial Infarction (TIMI)-11B trial, samples were collected for cTnI determination. RESULTS: Among 359 patients with negative serial CK-MB values, 50.1% had a cTnI result > or =0.1 ng/ml within the first 24 h. Patients with elevated cTnI were at higher risk of death or MI at 48 h (3.9 vs. 0%, p = 0.01) and 14 days (13.9 vs. 2.2%, p<0.0001). Elevated cTnI also correlated with higher risk of recurrent ischemia requiring urgent revascularization by 48 h (10.0 vs. 1.7%, p = 0.001) and 14 days (20.6 vs. 5.6%, p< or =0.0001). Enoxaparin had a greater benefit among patients with elevated vs. normal cTnI (p = 0.03), achieving a 47% reduction in the risk of death, MI or urgent revascularization by 14 days in cTnI-positive patients (p = 0.007). CONCLUSIONS: Elevation of cTnI among patients with non-ST segment elevation ACS and negative levels of CK-MB identifies those at higher risk for very early adverse outcomes, including severe recurrent ischemia. Treatment with enoxaparin reduces the risk associated with elevated cTnI.

Differences in TDx fetal lung maturity assay values between twin and singleton gestations.

OBJECTIVE: The purpose of this study was to quantify differences in indexes of pulmonary maturity between singleton and twin gestations by means of the TDx fetal lung maturity assay. STUDY DESIGN: We identified records of a total of 830 singleton and twin pregnancies not complicated by diabetes and delivered between 28 and 37 weeks' gestation from December 1994 through August 1995. Among these, 170 (20%) had TDx fetal lung maturity measurements performed within 72 hours of delivery. Linear regression was used to assess differences in TDx fetal lung maturity assay values between singleton gestations (n = 143 gestations) and twin gestations (n = 27 gestations) while controlling for potential confounding factors. RESULTS: Twin gestations were no more likely than singleton gestations to undergo TDx fetal lung maturity screening (odds ratio, 1.3; 95% confidence interval, 0.8-2.2). Pregnancy complications and corticosteroid treatment were similar in the two groups. After 31 weeks' gestation the twin gestations had significantly higher TDx fetal lung maturity values. Linear regression with controls for gestational age indicated that twin gestations on average had a TDx fetal lung maturity value that was 22.0 mg/g (95% confidence interval, 9.8-34.6 mg/g) higher than that of gestational age-matched singleton gestations. CONCLUSION: Beyond 31 weeks' gestation twin pregnancies appeared to have a TDx fetal lung maturity value that was 22 mg/g higher than that of singleton pregnancies. If the underlying incidences of respiratory distress syndrome are similar between twin and singleton gestations, then the potential exists for false-positive prediction of adequate lung maturity values among twin gestations.

Clinical efficacy of three assays for cardiac troponin I for risk stratification in acute coronary syndromes: a Thrombolysis In Myocardial Infarction (TIMI) 11B Substudy.

BACKGROUND: Significant analytic variability exists between the multiple assays for cardiac troponin I (cTnI) approved for clinical use. Until adequate cTnI standardization is possible, an evidence-based approach evaluating each assay at specific thresholds appears warranted. METHODS: We examined the efficacy of three cTnI assays for predicting death, myocardial infarction (MI), or the composite of death, MI, or urgent revascularization at 43 days among patients with non-ST-elevation acute coronary syndromes enrolled in the Thrombolysis In Myocardial Infarction (TIMI) 11B study. RESULTS: Six hundred eighty-one patients with serum samples obtained at baseline and/or 12-24 h had cTnI determined using all three assays. Baseline cTnI was > or = 0.1 microg/L for 368, 395, and 418 patients with the Bayer Immuno 1(TM), ACS:180, and Dimension RxL assays, respectively. Correlation coefficients for the RxL with the ACS:180 and Bayer Immuno 1 results were 0.89 (P = 0.0001) and 0.87 (P = 0.0001), with a coefficient of 0.92 (P = 0.0001) for the ACS:180 and Bayer Immuno 1 assays. Patients with cTnI > or = 0.1 microg/L were at increased risk fo death or MI by 43 days (relative risk, 2.2-3.0; P <0.0006), regardless of the assay used. This prognostic capacity persisted among those with creatine kinase MB isoenzyme concentrations within the reference interval. Moreover, cTnI was the strongest multivariate predictor of death, MI, or urgent revascularization with adjusted odds ratios of 2.1-2.9 (P <0. 0006). CONCLUSION: This study demonstrates the prognostic efficacy of three independently developed cTnI assays at a threshold of 0.1 microg/L for the prediction of adverse clinical outcomes among patients with non-ST-elevation acute coronary syndromes.

Appropriateness of prostate-specific antigen testing.

We established criteria for appropriate use of the prostate-specific antigen (PSA) assay and used them to evaluate PSA test utilization at 1 tertiary care institution. During a 6-month period, 2,330 PSA results were reported for outpatients and 95 for inpatients. We reviewed medical records for a random sample of 338 outpatient results (14.51%) and all 95 inpatient results, of which 21% (71/338) of outpatient and 17% (16/95) of inpatient results were inappropriate according to our test utilization criteria. Among outpatients, 52% of tests were done for screening and 19% for monitoring for cancer recurrence. For inpatients, workup for cancer (53/95 [56%]) was the most frequent indication for testing and screening the second (24/95 [25%]). Of tests failing the criteria, 66 (76%) of 87 resulted from excessively frequent and age-inappropriate screening. We assessed the potential effect on clinical outcome if these tests were not performed. Of the 87 tests considered inappropriate, only 1 test result influenced clinical management for patients younger than 75 years. By instituting simple limits on age and frequency, we estimate that 74% (64/87) of the inappropriate tests could have been eliminated.

Comparison of disaturated phosphatidylcholine and fetal lung maturity surfactant/albumin ratio in diabetic and nondiabetic pregnancies.

We studied fetal lung maturity (FLM) by the amniotic fluid surfactant/albumin (FLM S/A) ratio and the disaturated phosphatidylcholine (DSPC) amniotic fluid levels at different gestational ages in diabetic (179 women with type 1 diabetes mellitus antedating pregnancy; infants delivered within 72 hours after amniotic fluid testing for DSPC level and FLM S/A ratio) and nondiabetic pregnancies (2 independent nondiabetic groups, 300 for FLM S/A ratio and 1,231 for DSPC level). The degree of maternal glycemia during gestation was estimated by serial measurements of hemoglobin A1. Multiple regression analyses, including gestational age (GAs) and diabetic status as independent variables and FLM S/A ratio and DSPC level as dependent variables, revealed significant effect from diabetic status and GA for FLM S/A ratio and a significant effect from GA but not from diabetic status for DSPC level. Glucose levels were controlled adequately throughout gestation as reflected by mean total glycated hemoglobin levels. Amniotic fluid levels of DSPC, the major surface tension-lowering component of pulmonary surfactant, are not significantly different between diabetic and nondiabetic pregnancies at different GAs.

Improving response to critical laboratory results with automation: results of a randomized controlled trial.

OBJECTIVE: To evaluate the effect of an automatic alerting system on the time until treatment is ordered for patients with critical laboratory results. DESIGN: Prospective randomized controlled trial. INTERVENTION: A computer system to detect critical conditions and automatically notify the responsible physician via the hospital's paging system. PATIENTS: Medical and surgical inpatients at a large academic medical center. One two-month study period for each service. MAIN OUTCOMES: Interval from when a critical result was available for review until an appropriate treatment was ordered. Secondary outcomes were the time until the critical condition resolved and the frequency of adverse events. METHODS: The alerting system looked for 12 conditions involving laboratory results and medications. For intervention patients, the covering physician was automatically notified about the presence of the results. For control patients, no automatic notification was made. Chart review was performed to determine the outcomes. RESULTS: After exclusions, 192 alerting situations (94 interventions, 98 controls) were analyzed. The intervention group had a 38 percent shorter median time interval (1.0 hours vs. 1.6 hours, P = 0.003; mean, 4.1 vs. 4.6 hours, P = 0.003) until an appropriate treatment was ordered. The time until the alerting condition resolved was less in the intervention group (median, 8.4 hours vs. 8.9 hours, P = 0.11; mean, 14.4 hours vs. 20.2 hours, P = 0.11), although these results did not achieve statistical significance. The impact of the intervention was more pronounced for alerts that did not meet the laboratory's critical reporting criteria. There was no significant difference between the two groups in the number of adverse events. CONCLUSION: An automatic alerting system reduced the time until an appropriate treatment was ordered for patients who had critical laboratory results. Information technologies that facilitate the transmission of important patient data can potentially improve the quality of care.

Intrinsic limitations to unilateral parathyroid exploration.

OBJECTIVE: To evaluate a method of limited parathyroid exploration for primary hyperparathyroidism. SUMMARY BACKGROUND DATA: Although preoperative localization of parathyroid adenomas has become sensitive enough for clinical practice, it has not achieved success as the basis for limited parathyroid exploration, because multiglandular disease is routinely underdiagnosed. The rapid intraoperative parathyroid hormone assay is sensitive for multiglandular disease, because hormone levels will not fall within 10 minutes of adenoma removal if additional abnormal tissue is present. A combination technique in which the exploration is limited according to the localization studies and the success is confirmed with the parathyroid hormone assay has promise for producing a high rate of curative limited parathyroid explorations. METHODS: Forty-eight consecutive patients with primary hyperparathyroidism and indications for surgery underwent preoperative localization. After tests, 45 patients underwent unilateral parathyroid exploration and confirmation of the success of unilateral exploration during surgery using the rapid parathyroid hormone assay. The intraoperative management of these patients and their follow-up to 3 months was recorded. RESULTS: Thirty-two of the 48 patients (67%) had successful unilateral exploration as gauged by a marked drop in parathyroid hormone levels during the procedure and by 3-month clinical follow-up. Of the 16 patients who ultimately underwent bilateral exploration, 7 had parathyroid hormone levels that did not fall after adenoma removal. Of these seven, five were found to have a second adenoma and two had slow metabolism of hormone with no additional abnormal tissue found. In 5 of the 16 patients, bilateral exploration was performed for erroneous localization. Four additional patients underwent bilateral exploration for improved exposure or negative results on localization tests. CONCLUSIONS: These results show that unilateral parathyroid exploration is limited by the intrinsic 15% rate of multiglandular primary hyperparathyroidism, combined with the imperfections of preoperative localizing techniques. Although an 85% rate of unilateral exploration can theoretically be obtained for unselected cases, the other vagaries of the technique make a 70% rate a more reasonable expectation.

Myoglobin, creatine-kinase-MB and cardiac troponin-I 60-minute ratios predict infarct-related artery patency after thrombolysis for acute myocardial infarction: results from the Thrombolysis in Myocardial Infarction study (TIMI) 10B.

OBJECTIVES: We examined the diagnostic performance of serum myoglobin, creatine-kinase-MB (CK-MB) and cardiac troponin-I (cTnI) for predicting the infarct-related artery (IRA) patency in patients receiving TNK-tissue plasminogen activator (TNK-tPA) therapy for acute myocardial infarction (AMI) in the Thrombolysis in Myocardial Infarction (TIMI) 10B trial. BACKGROUND: A reliable noninvasive serum marker of IRA patency is desired to permit early identification of patients with a patent IRA after thrombolysis. METHODS: We measured myoglobin, CK-MB and cTnI concentrations in sera obtained just before thrombolysis (T0) and 60 min later (T60) in 442 patients given TNK-tPA and who underwent coronary angiography at 60 min. RESULTS: Angiography at 60 min showed a patent IRA (TIMI flow grade 2, 3) in 344 and occluded IRA (TIMI flow grade 0, 1) in 98 patients. The median serum T60 concentration, the ratio of the T60 and T0 serum concentration (60-min ratio) and the slope of increase over 60 min for each serum marker were significantly higher in patients with patent arteries compared with patients with occluded arteries. The area under the receiver-operating characteristic (ROC) curve for diagnosis of occlusion was 0.71, 0.70 and 0.71 for the 60-min ratio of myoglobin, cTnI and CKMB, respectively. The 60-min ratios of > or =4.0 for myoglobin, > or =3.3 for CK-MB and > or =2.0 for cTnI yielded a probability of patency of 90%, 88% and 87%, respectively. CONCLUSIONS: The diagnostic performance of serum myoglobin, CK-MB and cardiac troponin-I (cTnI) 60-min ratios was similar. The probability of a patent IRA was very high (90%) in patients with 60-min myoglobin ratio > or =4.0, and early invasive interventions to establish IRA patency may not be necessary in this group. Serum marker determinations at baseline and 60-min after thrombolysis may permit rapid triage of patients receiving thrombolytic therapy by ruling out IRA occlusion.

A randomized trial of a computer-based intervention to reduce utilization of redundant laboratory tests.

PURPOSE: To determine the impact of giving physicians computerized reminders about apparently redundant clinical laboratory tests. SUBJECTS AND METHODS: We performed a prospective randomized controlled trial that included all inpatients at a large teaching hospital during a 15-week period. The intervention consisted of computerized reminders at the time a test was ordered that appeared to be redundant. Main outcome measures were the proportions of clinical laboratory orders that were canceled and the proportion of the tests that were actually performed. RESULTS: During the study period, there were 939 apparently redundant laboratory tests among the 77,609 study tests that were ordered among the intervention (n = 5,700 patients) and control (n = 5,886 patients) groups. In the intervention group, 69% (300 of 437) of tests were canceled in response to reminders. Of 137 overrides, 41% appeared to be justified based on chart review. In the control group, 51% of ordered redundant tests were performed, whereas in the intervention group only 27% of ordered redundant tests were performed (P <0.001). However, the estimated annual savings in laboratory charges was only $35,000. This occurred because only 44% of redundant tests performed had computer orders, because only half the computer orders were screened for redundancy, and because almost one-third of the reminders were overridden. CONCLUSIONS: Reminders about orders for apparently redundant laboratory tests were effective when delivered. However, the overall effect was limited because many tests were performed without corresponding computer orders, and many orders were not screened for redundancy.

Evaluating the appropriateness of digoxin level monitoring.

BACKGROUND: Digoxin level determinations can be useful clinically in patients receiving digoxin therapy but are sometimes misused. METHODS: Explicit appropriateness criteria were adapted from previously published criteria and revised using local expert opinion. They were then used to evaluate the appropriateness of random samples of inpatient and outpatient serum digoxin levels. Overall agreement between reviewers regarding appropriateness was good (K = 0.65). Patients in the study included 162 inpatients in whom 224 digoxin levels were measured and 117 outpatients in whom 130 digoxin levels were measured during a 6-month period. The main outcome measure was the proportion of digoxin levels with an appropriate indication. RESULTS: Among inpatient levels, only 16% (95% confidence intervals [CI], 11%-20%) were appropriate. Of the 189 digoxin levels considered inappropriate, only 26 (14%) had a result of 2.3 nmol/L or more (> or =1.8 ng/ mL). None of these levels resulted in an important change in therapy, and no patient had a toxic reaction to the therapy. Among inappropriate levels, daily routine monitoring accounted for 78%. Of the 130 outpatient levels, 52% (95% CI, 44%-61%) were appropriate. Of 62 inappropriate levels, only 4 (6%) had a result of 2.3 nmol/L or more (> or =1.8 ng/mL). One result led to a change in therapy, but none of the patients were believed to experience a toxic reaction. Among the inappropriate levels, 87% of patients underwent early routine monitoring before a steady state was achieved. CONCLUSIONS: A high proportion of digoxin levels were inappropriate, particularly among inpatients. In both groups, the primary reason tests were judged inappropriate was early routine monitoring. Few inappropriate tests resulted in important data. Interventions to improve the use of digoxin levels could potentially save substantial resources without missing important clinical results.

The role of cardiac troponin-I (cTnI) in risk stratification of patients with unstable coronary artery disease.

In patients with chest pain at rest but no ST-segment elevation on the electrocardiogram, the diagnoses of unstable angina and non-Q-wave myocardial infarction (MI) are usually considered together because they cannot be differentiated clinically or angiographically. Since the extent of myocardial necrosis is an important determinant of the risk of death, it is important to identify serum markers with which to predict prognosis, in order to initiate appropriate medical treatment and/or invasive procedures in these patients. Cardiac troponin-I (cTnI), one of the subunits of the troponin regulatory complex, binds to actin and inhibits interactions between actin and myosin. The presence of elevated cTnI in serum is a significant prognostic indicator in patients with unstable angina and non-Q wave MI. Its independent prognostic potential persists even after adjustment for independent baseline variables known to be significantly associated with an increased risk of cardiac events. The use of cTnI in the triage of patients with unstable coronary disease may identify those at greater risk for adverse cardiac events.

What proportion of common diagnostic tests appear redundant?

PURPOSE: To identify ancillary tests for which there are criteria defining the earliest interval at which a repeat test might be indicated, to determine how often each test is repeated earlier than these intervals and, if repeated, provides useful information. SUBJECTS AND METHODS: We performed a retrospective cohort study of 6,007 adults discharged from a large teaching hospital during a 3-month period in 1991. We measured the proportion of commonly performed diagnostic tests that were redundant, and their associated charges. RESULTS: Of the 6,007 patients discharged, 5,289 (88%) had at least one of 12 target tests performed. Overall, 78,798 of the target tests were performed during the study period, of which 22,237 (28%) were repeated earlier than test-specific predefined intervals. This percentage varied substantially by test (range, 2% to 62%). To assess how many early repeats were justified, we performed chart reviews in a random sample stratified by test. For two tests, nearly all the initial results in the sample were abnormal, and all repeats were considered justified. Of early repeats following a normal initial result for the remaining 10 tests, chart review found no clinical indication for 92%, and a weighted mean of 40% appeared redundant. Overall, 8.6% of these 10 tests appeared redundant; if these were not performed, the annual charge reductions would be $930,000 at our hospital, although the impact on costs would be much smaller. CONCLUSIONS: For some tests, an important proportion are repeated too early to provide useful clinical information. Most such tests might be eliminated using computerized reminder systems.

How promptly are inpatients treated for critical laboratory results?

OBJECTIVE: The purpose of the study is to determine how frequently critical laboratory results (CLRs) occur and how rapidly they are acted upon. A CLR was defined as a result that met either the critical reporting criteria used by the laboratory at Brigham and Women's Hospital or other, more complex criteria. DESIGN: This is a retrospective cohort study in a large academic tertiary-care hospital. MEASUREMENTS: The proportion of chemistry and hematology results obtained in a 13-day period that met the hospital laboratory's critical reporting criteria were calculated. The charts of a stratified random sample of patients with CLRs due to sodium, potassium, and glucose were reviewed to determine the time interval until an appropriate treatment was ordered and the time interval until the critical condition was resolved. RESULTS: In 13 days, 1938 of 201,037 laboratory results (0.96%, or 0.44 per patient-day) met the hospital's critical reporting criteria. In the chart review, 222 CLRs were included in the stratified random sample, and 99 of these met the inclusion criteria. Among these 99 CLRs, the median time interval until an appropriate treatment was ordered was 2.5 hours. This interval was 1.8 hours when the CLR met the laboratory's criteria and a phone call was made, and 2.8 hours when the CLR met more complex criteria not requiring a phone call (p = 0.07). For 27 (27%) of the CLRs, an appropriate treatment was ordered only after five or more hours. The median time until the condition resolved was 14.3 hours: 12.0 hours for CLRs that met the hospital's criteria and 20.9 hours for the CLRs that met the more complex criteria (p = 0.006). CONCLUSION: Although CLRs meeting the hospital's criteria were reported promptly by the laboratory, treatment delays were still common. Results that did not meet the hospital's critical criteria but still represented serious clinical situations were more often associated with treatment delays. Difficulty communicating critical results directly to the responsible caregiver is the likely cause of some delays in treatment. New communications methods, including computer-based technologies, should be explored and tested for their potential to reduce treatment delays and improve clinical care.