Breast magnetic resonance imaging: are those who need it getting it?

BACKGROUND: Indications for breast magnetic resonance imaging (mri), a very sensitive but less-specific tool for breast investigation, remain controversial, and accessibility is limited. The purposes of our study were to determine the proportion of breast mri exams performed for various clinical indications, to assess the wait times for breast mri, and to create a list of evidence-based indications for breast mri. METHODS: The indications for breast mri exams performed in September 2013 at our academic centre were audited. A multidisciplinary meeting held in May 2014 established a list of evidence-based indications for breast mri, after which, in September 2014 and 2015, breast mri exams were re-audited for clinical indications, and pending requests were calculated. RESULTS: In September 2013, surveillance of women with a prior diagnosis of breast cancer represented 21% of breast mri exams (24 of 113), with preoperative staging representing 18% of exams (20 of 113) and high-risk screening representing 12% (13 of 113). Of pending mri requests, 230 were within the recommended delay period, and 457 exceeded the recommended delay. After elaboration of evidence-based guidelines, repeat audits in September 2014 and September 2015 showed that mri performed for women with a prior breast cancer diagnosis represented 23% (33 of 141) and 7% (10 of 143) of exams respectively, with preoperative staging having declined to 9% (13 of 141) and 11% (16 of 143) of exams, and high-risk screening having increased to 36% (51 of 141) and 46% (66 of 143) of exams. Overall, wait times were improved for all breast mri indications. CONCLUSIONS: Through multidisciplinary discussion, we actualized a list of breast mri indications, prioritized requests more adequately, and improved wait times.

Recommendations on breast cancer screening and prevention in the context of implementing risk stratification: impending changes to current policies.

In recent years, risk stratification has sparked interest as an innovative approach to disease screening and prevention. The approach effectively personalizes individual risk, opening the way to screening and prevention interventions that are adapted to subpopulations. The international perspective project, which is developing risk stratification for breast cancer, aims to support the integration of its screening approach into clinical practice through comprehensive tool-building. Policies and guidelines for risk stratification-unlike those for population screening programs, which are currently well regulated-are still under development. Indeed, the development of guidelines for risk stratification reflects the translational aspects of perspective. Here, we describe the risk stratification process that was devised in the context of perspective, and we then explain the consensus-based method used to develop recommendations for breast cancer screening and prevention in a risk-stratification approach. Lastly, we discuss how the recommendations might affect current screening policies.

The role of community pharmacists in the prevention and management of osteoporosis and the risk of falls: results of a cross-sectional study and qualitative interviews.

UNLABELLED: In a mailed survey and qualitative interviews, it was observed that community pharmacists and public health authorities believe that pharmacists should play a significant role in the prevention and management of osteoporosis and the risk of falls. However, pharmacists acknowledge a wide gap between their ideal and actual levels of involvement. INTRODUCTION: The aim of this study was to explore perceptions of community pharmacists and public health authorities regarding the role of pharmacists in providing services in relation to osteoporosis and risk of falls and the barriers to providing them. METHODS: Using a modified five-step version of Dillman's tailored design method, a questionnaire was mailed to a random sample of 1,250 community pharmacists practicing in Montreal (Quebec, Canada) and surrounding areas. A similar questionnaire was sent to public health officers in these regions. Additionally, telephone interviews were conducted with regional and ministry level public health officers. RESULTS: Of the 1,250 pharmacists contacted, 28 were ineligible. In all, 571 of 1,222 (46.7 %) eligible community pharmacists and all the public health officers returned the questionnaire. Six public health officers (five regional and one at ministry level) were interviewed. Most pharmacists believed they should be involved in screening for osteoporosis (46.6 %) and risk of falls (50.3 %); however, fewer reported actually being involved in such services (17.4 % and 19.2 %, respectively). In their view, the main barriers to providing these services in current practice were lack of time (78.8 %), lack of clinical tools (65.4 %), and lack of coordination with other healthcare professionals (54.5 %). Public health authorities also thought community pharmacists should play a significant role in providing osteoporosis and fall risk services. However, few community pharmacist-mediated activities are in place in the participating regions. CONCLUSIONS: Although community pharmacists and public health authorities believe pharmacists should play a significant role with regard to osteoporosis and the risk of falls, they acknowledge a wide gap between the ideal and actual levels of pharmacist involvement.

Effectiveness of interventions to improve the detection and treatment of osteoporosis in primary care settings: a systematic review and meta-analysis.

This study aims to evaluate the effectiveness of primary care interventions to improve the detection and treatment of osteoporosis. Eight electronic databases and six gray literature sources were searched. Randomized controlled trials, controlled clinical trials, quasi-randomized trials, controlled before-after studies, and interrupted time series written in English or French from 1985 to 2009 were considered. Eligible studies had to include patients at risk (women ≥ 65 years, men ≥ 70 years, and men/women ≥ 50 years with at least one major risk factor for osteoporosis) or at high risk (men/women using oral glucocorticoids or with previous fragility fractures) for osteoporosis and fractures. Outcomes included bone mineral density (BMD) testing, osteoporosis treatment initiation, and fractures. Data were pooled using a random effects model when applicable. Thirteen studies were included. The majority were multifaceted and involved patient educational material, physician notification, and/or physician education. Absolute differences in the incidence of BMD testing ranged from 22% to 51% for high-risk patients only and from 4% to 18% for both at-risk and high-risk patients. Absolute differences in the incidence of osteoporosis treatment initiation ranged from 18% to 29% for high-risk patients only and from 2% to 4% for at-risk and high-risk patients. Pooling the results of six trials showed an increased incidence of osteoporosis treatment initiation (risk difference (RD) = 20%; 95% CI: 7-33%) and of BMD testing and/or osteoporosis treatment initiation (RD = 40%; 95% CI: 32-48%) for high-risk patients following intervention. Multifaceted interventions targeting high-risk patients and their primary care providers may improve the management of osteoporosis, but improvements are often clinically modest.

Impact of a primary care physician workshop on osteoporosis medical practices.

SUMMARY: Attendance at a fragility-fractures-prevention workshop by primary care physicians was associated with higher rates of osteoporosis screening and treatment initiation in elderly female patients and higher rates of treatment initiation in high-risk male and female patients. However, osteoporosis management remained sub-optimal, particularly in men. INTRODUCTION: Rates of osteoporosis-related medical practices of primary care physicians exposed to a fragility-fractures-prevention workshop were compared with those of unexposed physicians. METHODS: In a cluster cohort study, 26 physicians exposed to a workshop were matched with 260 unexposed physicians by sex and year of graduation. For each physician, rates of bone mineral density (BMD) testing and osteoporosis treatment initiation among his/her elderly patients 1 year following the workshop were computed. Rates were compared using multilevel logistic regression models controlling for potential patient- and physician-level confounders. RESULTS: Twenty-five exposed physicians (1,124 patients) and 209 unexposed physicians (9,663 patients) followed at least one eligible patient. In women, followed by exposed physicians, higher rates of BMD testing [8.5% versus 4.2%, adjusted OR (aOR) = 2.81, 95% CI 1.60-4.94] and treatment initiation with bone-specific drugs (BSDs; 4.8% vs. 2.4%, aOR = 1.95, 1.06-3.60) were observed. In men, no differences were detected. In patients on long-term glucocorticoid therapy or with a previous osteoporotic fracture, higher rates of treatment initiation with BSDs were observed in women (12.0% vs. 1.9%, aOR = 7.38, 1.55-35.26), and men were more likely to initiate calcium/vitamin D (5.3% vs. 0.8%, aOR = 7.14, 1.16-44.06). CONCLUSIONS: Attendance at a primary care physician workshop was associated with higher rates of osteoporosis medical practices for elderly women and high-risk men and women. However, osteoporosis detection and treatment remained sub-optimal, particularly in men.

Better adherence to antihypertensive agents and risk reduction of chronic heart failure.

AIMS: Antihypertensive (AH) agents have been shown to reduce the risk of major cardiovascular events including chronic heart failure (CHF). However, the impact of changes in patterns of AH agents use on CHF is unknown. Our objective was to estimate to which different patterns of AH agent use is associated with the occurrence of CHF in a population-based study. METHOD AND RESULTS: A cohort of 82 320 patients was reconstructed using the Régie de l'assurance maladie du Québec's databases. Patients were eligible if they were between 45 to 85 years of age, had no indication of cardiovascular disease and were newly treated with AH therapy between 1999 and 2004. A nested case-control design was used to study the occurrence of CHF. Every case of CHF was matched for age and duration of follow-up to a maximum of 15 randomly selected controls. Adherence level was reported as a medication possession ratio. Conditional logistic regression models were used to estimate the rate ratio (RR) of CHF adjusting for different covariables. The mean patient age was 65 years, 37% were male, 8% had diabetes, 19% had dyslipidaemia and mean time of follow-up at 2.7 years. High adherence level (95%) to AH therapy compared with lower adherence level (60%) was associated with an additional reduction of CHF events (RR: 0.89; 0.80-0.99). Risk factors for CHF were being on social assistance, diabetes, dyslipidaemia, higher chronic disease score and developing a cardiovascular condition during follow-up. CONCLUSION: Our study suggests that a better adherence is associated with a significant risk reduction of CHF. Adherence to AH therapy needs to be improved to optimize benefits.

The upgraded arecibo observatory.

Arecibo Observatory's giant spherical reflector antenna has undergone a massive upgrading over the past 3 years. The surface of the reflector has been replaced with aluminum panels to obtain an accuracy of 3.2 mm r.m.s. over the reflector surface. The superstructure has been stabilized and modified to permit operation at S-band frequencies. A high-power S-band radar transmitter has been added to the existing UHF system. These additions and improvements provide the observatory with new and promising research capabilities in the fields of radio and radar astronomy.

Effect of storage media, temperature, and time on preservation of Cryptosporidium parvum oocysts for PCR analysis.

The effect of storage media, temperature, and time on suitability of oocysts for use in subsequent molecular studies was examined. Cryptosporidium parvum oocysts were stored for 3, 6, 9, or 12 months in sterile dH(2)O, 70 or 95% ethanol, (room temperature [RT], 4, -20, and -70 degrees C), 10% formalin (RT and 4 degrees C), PBS, TE buffer, antibiotic-antimycotic (A-A) solution (4, -20 and -70 degrees C), 2% sulphuric acid, 2.5% potassium dichromate (4 degrees C), and gDNA from 10(4) oocysts was extracted in triplicate and subjected to PCR. To determine the effect of storage media on PCR sensitivity, gDNA from 10(4), 10(2), and 10(0) oocysts stored for 15 months in the media listed above at RT or 4 degrees C was also extracted in triplicate and subjected to PCR. At RT, ethanol was suitable for up to 15 months, while gDNA from oocysts stored in dH(2)O amplified inconsistently after 3 months. At 4 degrees C, all tested media except dH(2)O and formalin were suitable for storage of 10(4) oocysts up to 15 months, but only 70% ethanol, A-A solution, 2% sulphuric acid and 2.5% potassium dichromate supported amplification of gDNA from fewer than 100 oocysts. At -20 degrees C, 95% ethanol, PBS, or TE were suitable for up to 9 months, while 70% ethanol and A-A solution were effective up to 12 months, and gDNA from oocysts stored in dH(2)O was inconsistently amplified after 6 months. Storage at -70 degrees C for up to 12 months was effective regardless of media type. Oocysts stored in formalin at RT or 4 degrees C could not be amplified by PCR despite washing prior to gDNA extraction. To maintain gDNA quality suitable for PCR, it is recommended that coccidian oocysts be stored at -70 degrees C in dH(2)O, ethanol, PBS, TE or A-A solution, at 4 degrees C in A-A or ethanol, or at RT in ethanol where refrigerated storage is unavailable.

Electrocardiographic and ventriculographic recovery patterns in Q wave myocardial infarction.

To further define the capacity for recovery after acute phase electrical and mechanical injury in patients with Q wave myocardial infarction who were treated with standard measures, 120 lead body surface potential maps and radionuclide angiograms were recorded at day 5 before discharge and month 6 after infarction in 23 patients with a first infarction (12 anterior and 11 inferior by standard 12 lead electrocardiographic criteria). In addition to assessment of spatial changes in electrocardiographic and wall motion patterns, five quantitative variables were evaluated: minimal Q zone integral, sigma Q wave integral, maximal ST integral, left ventricular ejection fraction and left ventricular wall motion abnormality score. From day 5 to month 6 after infarction, the only change in the inferior infarction group was a gain in sigma Q wave (-91 +/- 40 mu V X s X 10(2) to -68 +/- 24 mu V X s X 10(2); p less than 0.05). In contrast, all variables improved over the same time period in the anterior infarction group: Q zone minimum, -34 +/- 20 to -24 +/- 13 mu V X s (p less than 0.05); sigma Q wave, -160 +/- 122 X 10(2) to -120 +/- 90 mu V X s X 10(2) (p less than 0.05); ST maximum, 44 +/- 19 to 18 +/- 9 mu V X s (p less than 0.01); ejection fraction, 54 +/- 7 to 63 +/- 17% (p less than 0.05); and wall motion score, 6 +/- 3 to 3 +/- 3 (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

The relationship of mast cells and their secreted products to the volume of fibrosis in posttransplant hearts.

A series of 96 posttransplant endomyocardial biopsies taken from 11 patients was subjected to quantitative analysis of mast cells and fibrosis. Ultrastructural analysis showed that mast cell numbers were increased and there was obvious degranulation in some posttransplant hearts. Activated mast cells and their secreted products, which contain heparin and histamine, are toxic to the hearts and may contribute to interstitial and perimyocytic fibrosis. The numbers of mast cells and granules were correlated with volume of fibrosis (r = 0.63, P less than 0.025; r = 0.73, P less than 0.01). There were differences between the release of mast cell granule contents seen in the posttransplant hearts and the rapid and massive reaction of anaphylactic degranulation of mast cells. Some mast cells progressively lost their dense granule contents, displaying a variety of piecemeal degranulation that indicates a slow degranulation process. These events occurred from the first week; they lasted from weeks to months. The fibrosis developed quickly in the cases with more mast cells and degranulation. The cases with fewer mast cells and granules showed only mild increases in the volume of fibrosis. Mast cells appeared as early as the first posttransplantation week. Patients with greater numbers of mast cells underwent more severe rejection episodes. This study demonstrated that mast cells play an early and important role in the perimyocytic and interstitial fibrosis of posttransplant hearts. Mast cells may also be important in the inflammatory process of rejection reaction. The severity of fibrosis appears related to the density of mast cells and their granules.

Non-Q-wave acute myocardial infarction: body surface potential map and ventriculographic patterns.

Day 5 body surface map and radionuclide angiographic patterns were compared among 56 patients with first non-Q-wave or Q-wave acute myocardial infarction (AMI). Three radionuclide angiographic patterns were recognized in patients with non-Q infarction: no wall motion abnormalities (n = 8), single-segment wall motion abnormalities (n = 10) and multiple-segment wall motion abnormalities (n = 9). In contrast, only 2 radionuclide angiographic patterns were identified in patients with Q-wave infarction: multiple-segment wall motion abnormalities (n = 25) and single-segment wall motion abnormalities (n = 4). The Q-wave distributions of 14 of 18 patients with non-Q infarction with 0 or 1 wall motion abnormalities were normal; 2 patients had "missed" anterior; 1 patient had inferior; and 1 had posterior AMI patterns. Of 9 patients with non-Q infarction who had multiple-segment wall motion abnormalities, 8 had infarct Q waves on the posterior torso. Q-wave patterns in patients with anterior (n = 17) and inferior (n = 12) Q-wave infarctions were typical and homogeneous for each group. Quantitative analysis of minimum Q-zone integral, sigma Q-wave integrals, ST-integral maximum, wall motion abnormality score and ejection fraction revealed no differences between patients with non-Q-wave and those with inferior Q-wave infarction. In contrast, patients with anterior AMI had significantly more abnormal values of all variables than either of the other groups. Overall, the data support the concept of non-Q-wave AMI as a distinct, if heterogeneous, pathophysiologic entity.(ABSTRACT TRUNCATED AT 250 WORDS)

Health-related quality of life with coronary heart disease prevention and treatment.

Estimating the net benefits of dyslipidemia treatment is limited by the lack of comprehensive and standardized information on the preference for dyslipidemia and coronary heart disease. In a hospital-based study, we measured the health-related quality of life (HRQOL) of healthy participants without dyslipidemia (n = 307) and with dyslipidemia (n = 251) and patients with coronary heart disease (n = 320). Compared to the healthy participants without dyslipidemia, those with dyslipidemia reported lower adjusted mean scores on the Rating Scale (-2.8 points, P = 0.02) and the SF-36 General Health Scale (-3.3 points, P = 0.02). No differences were observed on the Time Trade-off and the Standard Gamble Scales. Coronary patients reported lower scores on all preference scales and most SF-36 scales. The causes of the small but real reduction in HRQOL reported by dyslipidemic individuals should be identified in order to optimize the net benefits of lipid therapy.

Indirect measurement of infarct size. Correlative variability of enzyme, radionuclear angiographic, and body-surface-map variables in 34 patients during the acute phase of first myocardial infarction.

To gain a correlative perspective of indirect indications of the size of a myocardial infarct, we measured several body-surface electrocardiographic variables and several enzyme and radionuclear angiographic indicators of an infarct's size in 34 patients during the acute phase of first infarction. We found that bivariate correlations ranged widely, from an r value of 0.05 to an r value of 0.92, but were significantly (p less than 0.001) higher when variables from the same technique were correlated (mean r, 0.60 +/- 0.27), as opposed to correlations of variables from different techniques (mean r, 0.27 +/- 0.18). Trivariate comparisons among techniques produced significantly (p less than 0.001) higher r values, but the highest, an r value of 0.76 (total wall motion abnormality score; peak lactic dehydrogenase level; ST-segment integral maximum), indicated that even in this best case, only about 60 percent of the variation of one variable was dependent on or due to the two other variables. These data demonstrate that multiple indirect quantitative indicators of myocardial injury can vary widely in their correlations within the same population of infarcts, and much remains unknown in their relationships during the acute phase. Caution should be exercised, therefore, in their clinical application to predict an infarct's size in individual patients with acute myocardial infarction.

Male infertility associated with round-headed acrosomeless spermatozoa.

The properties of spermatozoa with round head syndrome in four unrelated patients are reported. The findings were as follows: (1) Electron microscopy demonstrated that all spermatozoa lacked an acrosome and postacrosomal sheath. (2) Acrosin activity was only 1% to 6% of that found in sperm obtained from fertile donors. (3) Phospholipase A2 activity was not significantly different from that of spermatozoa from donors of unknown fertility. (4) Electrophoresis of whole sperm extracts revealed deficiencies in major protein bands. (5) The round-headed spermatozoa failed to bind or penetrate the vitellus in the egg penetration test. (6) The rates of chemically induced nuclear chromatin decondensation of round-headed spermatozoa suggest that the acrosome content is not involved in this process.

Exposure to ionizing radiation increases responsiveness to neural secretory stimuli in the ferret jejunum in vitro.

Experiments were designed to determine the effects of ionizing radiation on jejunal epithelial function in the ferret in vitro. Basal and stimulated electrolyte transport were determined in Ussing chambers at 0.5, 2, 24 and 48 h post-irradiation. Tissue histamine and 5-hydroxytryptamine levels were measured. Myeloperoxidase activity was also measured as an index of inflammation. Basal short circuit current was reduced at 2 h post-irradiation, but was elevated at 48 h. Basal conductance was significantly increased by 24 and 48 h. Responsiveness to electrical field stimulation was depressed at 0.5 h, and was greater than control by 24 and 48 h post-irradiation. Similarly, short circuit current responses to prostaglandin E2 were depressed at 0.5 h and elevated at 24 h. No significant change was observed in the response to carbachol post-irradiation, indicating that alterations in responsiveness were not likely at the level of the enterocyte. Changes in responsiveness to electrical field stimulation correlated significantly with increases in mucosal mast cell numbers. Myeloperoxidase activity, indicative of neutrophil infiltration, did not increase post-irradiation, nor was there histological evidence of an inflammatory cell infiltrate. There were no changes in tissue histamine or 5-hydroxytryptamine. Histology also revealed little microscopic morphological change from shams in tissue from irradiated ferrets. The results of this study demonstrate effects of irradiation on electrolyte transport in the ferret jejunum. The enhanced neurally evoked electrolyte transport observed at 24-48 h post-irradiation was not correlated with the development of inflammation, but was correlated with changes in mast cell numbers.

The measurement of rectal and testis temperature in conscious mice, with observations on the effect of direct heating.

The application of Newton's law of cooling to freshly killed mice was found not to measure accurately their rectal or testis temperature. Improvements in the fitting process gave satisfactory results for rectal temperature only. A diffusion model was applied to testis cooling but was of no avail. Finally a satisfactory correction factor was determined empirically. This method was applied to conscious mice whose hindquarters were immersed in a stirred oilbath at 34 to 42 degrees C for 1 h, and to controls. It was found that both rectal and testis temperatures increased with bath temperature, producing a graph with a slope of only 0.5, indicating a regulatory capacity. Conscious mice, but not anaesthetised, can maintain a testis temperature of 39 degrees C in a bath at 42 degrees C.

Conventional and chained standard gambles in the assessment of coronary heart disease prevention and treatment. Canadian Collaborative Cardiac Assessment Group.

The authors compared the abilities of descriptive and valuational health-related quality-of-life measures to discriminate healthy participants (n=39) from those on diets for dyslipidemia (n=35) and angina patients (n=30). On the rating scale, the time tradeoff, and the General Health Perception subscale of the SF-36 Health Survey, the participants with dyslipidemia or angina reported lower mean scores than the healthy participants. No differences were detected between these groups on conventional or chained standard gamble (SG) scales. The distribution of the conventional and the chained SG scores was very skewed, with the vast majority of scores being equal or very close to the maximum score. It is concluded that in this study the discriminant ability of the chained SG was comparable to that of the conventional SG and inferior to descriptive and non-risky valuational scaling techniques. This may be explained by the distortion of probabilities, by a misunderstanding of the SG chained assessment, and by a strong certainty effect.

Effectiveness of a non-amalgamated ambulance service on out-of-hospital sudden cardiac death.

Many Canadian communities rely on non-amalgamated ambulance services to respond to out-of-hospital sudden cardiac arrest victims. These pre-hospital care systems lack a central coordinating and dispatching facility, a publicized, easily-accessible telephone number (911) and vehicles equipped with monitor-defibrillators, and are generally staffed by personnel trained only in basic cardiac life support. To receive definitive care, the victim of a cardiac arrest in these communities must be successfully transported to a hospital. In the study area, 114 victims of out-of-hospital sudden death were identified in a community served by a non-amalgamated ambulance service over a 12-month period for an annual incidence rate of 6.1/10,000. The mean age was 64 +/- 11.5 years with the majority (78%) of arrests occurring in the home. The collapse to CPR time was 10.2 +/- 6.7 minutes and the ambulance response time was 5.2 +/- 3.9 minutes. The estimated time from collapse to the victims receiving definitive care was 36.4 +/- 19.1 minutes. Overall, only 8 victims (8.8%) survived and were discharged from hospital. Based on the data presented, survival rate for cardiac arrest victims treated by a non-amalgamated ambulance system are inferior to those reported for pre-hospital care services capable of providing advanced cardiac life support at the scene. Whether all of the components of an established paramedic program are required to improve survival rates in individual communities remains undetermined.

Noninvasive testing in women presenting with chest pain: evidence for diagnostic uncertainty.

OBJECTIVE: To gain insight into the diagnostic utility of exercise stress testing in women. DESIGN: Observational prospective cohort study. SETTING: The Victoria General Hospital, Halifax, Nova Scotia. PARTICIPANTS: Consecutive women with chest pain referred by cardiologists or internists for exercise stress testing between May 30, 1992 and November 30, 1992 and followed prospectively to February 28, 1993. INTERVENTION: The proportion of patients subsequently referred for thallium scintigraphy and/or coronary angiography and their clinical profiles were determined. MAIN RESULTS: Of 183 patients studied, stress testing was positive in 48 (26.2%), negative in 48 (26.2%) and nondiagnostic in 87 (47.5%). Women with negative results were more likely to have had normal baseline electrocardiograms (ECGs) (P = 0.002) and least likely to have undergone prior angiography (P = 0.0003). Subsequent thallium scintigraphy and/or coronary angiography was undertaken in 33.3%, 18.8% and 27.6% with positive, negative and nondiagnostic index stress tests, respectively. None of chest pain, cardiac risk factors, previous cardiac investigations or baseline ECG discriminated 33 patients with negative or nondiagnostic stress results who had additional tests from 102 who did not. CONCLUSION: Exercise stress testing poorly screens women with chest pain for coronary artery disease (diagnostic in only 52.5%). Further study was undertaken in 27.6% with nondiagnostic tests and, surprisingly, in 18.8% with negative results. Why certain women with nondiagnostic, and so many with negative, stress tests were referred for further investigation was unclear. These results suggest diagnostic uncertainty when females presenting with chest pain are assessed.