Breakthrough zygomycosis after voriconazole administration among patients with hematologic malignancies who receive hematopoietic stem-cell transplants or intensive chemotherapy.

Zygomycosis is increasingly reported as a cause of life-threatening fungal infections. A higher proportion of cases reported over the last decades have been in cancer patients, with or without hematopoietic stem cell transplantation (HSCT). The new anti-fungal agent voriconazole is a recently identified risk factor for developing zygomycosis. We reviewed the clinical characteristics and outcomes of a large cohort of cancer patients who developed zygomycosis after exposure to voriconazole. Health care professionals at 13 large cancer centers provided clinical information on cancer patients with zygomycosis and prior exposure to voriconazole. Criteria for inclusion were 5 days or more of voriconazole use and diagnostic confirmation with tissue or histology. Fifty-eight cases were identified among patients with hematologic malignancies, 62% including patients who underwent a HSCT procedure. Fifty-six patients received voriconazole for primary or secondary prophylaxis against fungal infection. In addition to prior exposure to voriconazole, patients also had several of the previously established risk factors for zygomycosis. Amphotericin B was the most commonly prescribed anti-fungal therapy. Overall mortality was 73%. We conclude that zygomycosis after exposure to voriconazole is a recently described entity that is frequently fatal, despite treatment with currently available anti-fungal agents and surgery.

Low complication rate of corticosteroid-treated asthmatics undergoing surgical procedures.

OBJECTIVE: To determine the incidence of perioperative complications in asthmatic patients who received preoperative treatment with corticosteroids and whether these could be predicted using any study variables such as age, sex, severity of asthma, or surgery type. METHODS: Using a retrospective cohort design, we studied 71 asthmatic patients who underwent 89 surgical procedures; 86 of 89 patients received preoperative treatment with systemic corticosteroids. The main outcome measures evaluated were incidence of postoperative bronchospasm, infection, clinical evidence of adrenocortical insufficiency, and death. RESULTS: Three patients (4.5%) developed mild postoperative bronchospasm; five (5.6%) developed postoperative infections, two of which were wound infections (2.2%); there were no patients with evidence of adrenocortical insufficiency; there was one death related to a neurosurgical intraoperative complication. Incidence of infection was not statistically different from two comparison surgical groups. None of the complications was predicted using any of the study variables. CONCLUSION: Asthmatic patients who are treated preoperatively with corticosteroids can undergo surgical procedures with a low incidence of complications.

Idiopathic anaphylaxis. An attempt to estimate the incidence in the United States.

BACKGROUND: Idiopathic anaphylaxis has been described and classified, and increasing numbers of cases are being seen in the United States and abroad. Treatment regimens have been shown to be effective in prophylactic management. There is no available information about the number of cases in the United States. METHODS: We attempted to determine the number of cases of idiopathic anaphylaxis in the United States by mailing a questionnaire to all graduates (for the last 31 years) of the Northwestern University Allergy-Immunology Fellowship training program. RESULTS: Response to the questionnaire was 100%, and 633 cases were reported by this survey of 75 allergists. The current total number of identified cases of idiopathic anaphylaxis from all reports of cases in the United States is 1020. CONCLUSIONS: By extrapolation of the cases of idiopathic anaphylaxis reported by the allergists surveyed to the approximately 4000 allergists in the United States, the estimated number of cases in the United States is between 20,592 and 47,024. Idiopathic anaphylaxis is potentially fatal, represents a source of major medical health care costs, causes anxiety to patients and families, occurs in pediatric and adult populations, and is controlled by appropriate regimens. The estimated number of cases emphasizes the need for careful attention to idiopathic anaphylaxis by physicians.

An autopsy-based study of diagnostic errors in geriatric and nongeriatric adult patients.

One hundred sixty-two consecutive adult autopsies (87 of subjects over age 65 years and 75 of subjects aged 23 to 64 years) performed at a university hospital were studied retrospectively by six internists to determine (1) if diagnostic errors were quantitatively or qualitatively different between the two age groups; (2) if the underlying causes of error (divided into nine categories) were different or age related in any way between the two groups; and (3) any aspects of care that related age to clinical outcome. We found the frequency of major clinical/autopsy discrepancies to be similar to those in previous studies (35%), but in only 7% of cases were these likely to have affected therapy/outcome. Ther was no difference in the frequency of major discrepancies between age groups. There were significantly more "unexpected" minor discrepancies in the older patients, probably related to the multiplicity and complexity of their problems, but these would have affected therapy/outcome in only 1 (3%) of 37 cases. The most common causes of 136 clinical "errors" in 151 autopsies were, in order of frequency: a diagnostic "blind spot," a conscious decision not to pursue a clinical finding (not a real "error"), failure to account for a symptom or sign, atypical presentations, and inadequate follow-up of abnormal laboratory findings. There were no differences between the geriatric and adult groups in terms of frequency or cause of the errors. We conclude that (1) there is no difference in the diagnostic accuracy regarding cause of death between geriatric and nongeriatric patients in the acute hospital environment, and (2) closer attention to basic knowledge and clinical skills and a special focus on judgment and reasoning skills, utilizing autopsy findings among other things, will lead to even further improvement in clinical care at all ages.

Substance use disorder in hospitalized severely mentally ill psychiatric patients: prevalence, correlates, and subgroups.

The prevalence and demographic and clinical correlates of lifetime substance use disorders were examined in a cohort of 325 recently hospitalized psychiatric patients (53% schizophrenia or schizoaffective disorder). Alcohol use was the most common type of substance use disorder, followed by cannabis and cocaine use. Univariate analyses indicated that gender (male), age (younger), education (less), history of time in jail, conduct disorder symptoms, and antisocial personality disorder symptoms were predictive of substance use disorders. Lifetime cannabis use disorder was uniquely predicted by marital status (never married) and fewer psychiatric hospitalizations during the previous 6 months. Optimal classification tree analysis, an exploratory, nonlinear method of identifying patient subgroups, was successful in predicting 74 percent to 86 percent of the alcohol, cannabis, and cocaine use disorders. The implications of this method for identifying specific patient subgroups and service needs are discussed.

Prevalence of substance abuse in schizophrenia: demographic and clinical correlates.

Methodological issues involved in assessing the prevalence of substance abuse in schizophrenia are discussed, and previous research in this area is comprehensively reviewed. Many studies suffer from methodological shortcomings, including the lack of diagnostic rigor, adequate sample sizes, and simultaneous assessment of different types of substance abuse (e.g., stimulants, sedatives). In general, the evidence suggests that the prevalence of substance abuse in schizophrenia is comparable to that in the general population, with the possible exceptions of stimulant and hallucinogen abuse, which may be greater in patients with schizophrenia. Data are presented on the association of substance abuse with demographics, diagnosis, history of illness, and symptoms in 149 recently hospitalized DSM-III-R schizophrenic, schizophreniform, and schizoaffective disorder patients. Demographic characteristics were strong predictors of substance abuse, with gender, age, race, and socioeconomic status being most important. Stimulant abusers tended to have their first hospitalization at an earlier age and were more often diagnosed as having schizophrenia, but did not differ in their symptoms from nonabusers. A history of cannabis abuse was related to fewer symptoms and previous hospitalizations, suggesting that more socially competent patients were prone to cannabis use. The findings show that environmental factors may be important determinants of substance abuse among schizophrenic-spectrum patients and that clinical differences related to abuse vary with different types of drugs.

First-year residents' caring, medical knowledge, and clinical judgment in relation to laboratory utilization.

PURPOSE: To investigate first-year residents' levels of caring (concern for others' well-being), medical knowledge, and clinical judgment in relation to their levels of laboratory utilization. METHOD: Self-report questionnaires about caring, knowledge, and judgment were given in 1986-87 to 36 first-year residents in a three-year internal medicine residency program of the McGaw Medical Center of Northwestern University. Inpatient laboratory utilization data obtained from structured chart audits over a one-year period were used to construct comparable diagnosis- and severity-specific physician practice profiles, from which the residents received overall utilization scores for laboratory test charges. Statistical methods included Cronbach's alpha reliability coefficient and multiple regression analysis. RESULTS: The multiple regression analysis showed that medical knowledge was an independent predictor of increased laboratory utilization (standardized beta = .54, p < .04, partial R2 = .07); clinical judgment was an independent predictor of decreased utilization (standardized beta = -.53, p < .05, partial R2 = .06); and caring was unrelated to utilization (standardized beta = .15, ns, partial R2 = .01). CONCLUSION: The finding that clinical judgment was related to less laboratory utilization suggests that future research should investigate the decision-making concomitants of judgment to better understand its translation into resource utilization. It is possible that the relationship between medical knowledge and laboratory utilization is developmentally specific, and thus the knowledge of more experienced physicians, who would likely be more precise decision makers than first-year residents, may be related to decreased rather than increased utilization.

Human leucocyte antigens (HLA) and trimellitic anhydride (TMA) immunological lung disease.

Occupational immunological lung disease, due to low molecular weight, reactive chemicals such as trimellitic anhydride (TMA), is an emerging health problem. If there were a marker that was highly predictive of the ability of the immune system to recognize TMA as an allergen, better prevention strategies could be employed with at risk individuals. The purpose of this study is to evaluate whether human leucocyte antigen (HLA) class specificity is associated with the development of late respiratory systemic syndrome (LRSS) or asthma due to immunological sensitivity to trimellitic anhydride (TMA). This is a case control study of 17 individuals with LRSS, 12 with asthma and 22 TMA similarly exposed individuals who did not develop LRSS or asthma. Comparing the sensitized individuals (LRSS or asthma) with the non-sensitized individuals (controls), we found no difference in frequency of any HLA antigen. In summary, the lack of association of HLA antigens with LRSS or asthma due to TMA suggests that these will not be useful markers to identify at risk individuals.

Psychological androgyny and preference for intubation in a hypothetical case of end-stage lung disease.

Psychological androgyny theory (PAT) was employed as a model of the interpersonal (social) and task activities required of physicians for care of their patients. According to PAT, individuals with a large repertoire of task and social skills ("androgynous" individuals) should be optimally adaptable to contingencies reflecting varying combinations of task and social challenges. The authors examined the relationship between androgyny and preference for intubation on a patient management problem involving end-stage lung disease for 67 general internists and internal medicine housestaff from two hospitals. Results revealed a negative relationship between androgyny and preference for intubation, suggesting that androgynous and nonandrogynous physicians respond differently to complex and difficult decision-making tasks. Indirect evidence is offered to suggest that this response reflects a general tendency to utilize fewer health care resources. Discussion focuses on the need to improve the precision of measurement of these latent constructs.

Psychological androgyny and preference in loss-framed gambles of medical students: possible implications for resource utilization.

Physician decisions concerning allocation of health care resources to patients are highly variable and poorly understood. Psychological androgyny theory (PAT) has been employed as a model of the interpersonal and task activities required of physicians for care of their patients. Several studies have successfully predicted physician resource utilization using measures derived from PAT. Using a sample of 97 first-year medical students, the authors explored the relationship between PAT and risk preference in loss-framed gambles in order to elucidate the process whereby variables derived from PAT predict resource utilization. As hypothesized, students selecting the certain loss had significantly higher mean androgyny scores than did students selecting uncertainty. Research involving these constructs is integrated in the context of a theoretical "causal model," which highlights issues deserving of future research.

Relating patient satisfaction to waiting time perceptions and expectations: the disconfirmation paradigm.

OBJECTIVE: To determine the association of patient satisfaction with waiting time perceptions and expectations. METHODS: A random sample of patients seen at one community hospital ED during a one-year period was surveyed by telephone within two to four weeks of evaluation to determine perceived satisfaction and waiting time perceptions and expectations. RESULTS: In response to 3,641 attempted phone surveys, 1,574 patients had usable interviews. Consistent with a hypothesis derived using the disconfirmation paradigm (i.e., that satisfaction is a function of the magnitude and direction of the difference between perceived service and expected service), the patients were least satisfied when waiting times were longer than expected, were relatively satisfied when waiting times were perceived as equal to expectations, and were highly satisfied when waiting times were shorter than expected (p < 0.0001). Overall, the measure of effect strength (values from 0 to 1) of perceived waiting time vs expectation on the patient satisfaction score was 0.32, indicating moderate association. CONCLUSIONS: The current study supports the validity of the disconfirmation paradigm in relating patient satisfaction to waiting time perceptions and expectations. Furthermore, it emphasizes that achieving satisfaction in a service encounter necessitates that perceived performance meet or exceed patient expectations.

Statistical methodology: VIII. Using confirmatory factor analysis (CFA) in emergency medicine research.

How many underlying characteristics (or factors) does a set of survey questions measure? When subjects answer a set of self-report questions, is it more appropriate to analyze the questions individually, to pool responses to all of the questions to form one global score, or to combine subsets of related questions to define multiple underlying factors? Factor analysis is the statistical method of choice for answering such questions. When researchers have no idea beforehand about what factors may underlie a set of questions, they use exploratory factor analysis to infer the best explanatory model from observed data "after the fact." If, on the other hand, researchers have a hypothesis beforehand about the underlying factors, then they can use confirmatory factor analysis (CFA) to evaluate how well this model explains the observed data and to compare the model's goodness-of-fit with that of other competing models. This article describes the basic rules and building blocks of CFA: what it is, how it works, and how researchers can use it. The authors begin by placing CFA in the context of a common research application-namely, assessing quality of medical outcome using a patient satisfaction survey. They then explain, within this research context, how CFA is used to evaluate the explanatory power of a factor model and to decide which model or models best represent the data. The information that must be specified in the analysis to estimate a CFA model is highlighted, and the statistical assumptions and limitations of this analysis are noted. Analyzing the responses of 1,614 emergency medical patients to a commonly-used "patient satisfaction" questionnaire, the authors demonstrate how to: 1) compare competing factor-models to find the best-fitting model; 2) modify models to improve their goodness-of-fit; 3) test hypotheses about relationships among the underlying factors; 4) examine mean differences in "factor scores"; and 5) refine an existing instrument into a more streamlined form that has fewer questions and better conceptual and statistical precision than the original instrument. Finally, the role of CFA in developing new instruments is discussed.

Prospective evaluation of emergency medicine instruction for rotating first-postgraduate-year residents.

OBJECTIVE: To determine whether either bedside teaching alone (group A) or bedside teaching with written course materials (group B) improved written examination scores, satisfaction with the rotation, or clinical grades of rotating PGY1 residents. METHODS: A prospective, controlled educational trial was conducted. Sixty-five PGY1 residents from diverse specialties rotated in the ED for one month over a ten-month study period, and were included in the study. The PGY1 residents were assigned to group by month of rotation. All the PGY1 residents received unstructured bedside teaching by emergency medicine (EM) residents and faculty. In addition, group B received written course materials on day 1. RESULTS: Mean posttest scores were higher than mean pretest scores for the interns considered as a whole (p < 0.0001), but mean pretest, posttest, and clinical grades were comparable across instructional groups. Mean satisfaction ratings were higher for group A than for group B (p < 0.015). The interns specializing in EM achieved higher mean test scores (p < 0.013) and clinical grades (p < 0.003) than did the interns specializing in another medical specialty. CONCLUSION: Both instructional methods were associated with improved written test performance. Written course materials did not augment bedside teaching in terms of test scores, clinical grades, or satisfaction with the rotation. At a university-based, high-volume ED, bedside teaching offers educational benefit to rotating PGY1 residents that may not be augmented by written course materials.

Computers and connectivity in Illinois emergency departments.

UNLABELLED: Although the Internet has been described as "ubiquitous," little is known about the extent to which physicians have access to the Internet while providing clinical care. OBJECTIVE: To assess the extent of Internet connectivity within the clinical area of every ED within the state of Illinois. METHODS: This was a prospective observational study. Each Illinois ED listed in a published directory was called by telephone, and a responsible party was identified to provide information regarding the type and size of the ED, patient demographics, the types of personal computers (PCs) available in the ED (if any), the types of operating systems used, the availability of access to the World Wide Web (Web), and the highest speed at which an Internet connection could be established. Responses regarding the presence and types of PCs and the types of operating systems used were assessed using one-factor chi-square. Univariate and multivariate predictors of the type of PC used, the presence or absence of Web access, and the highest speed of Internet access were evaluated using optimal discriminant analysis and nonlinear classification tree analysis, respectively. RESULTS: One hundred ninety-eight of the 199 EDs in the state of Illinois (99.5%) completed the survey. Of the responding EDs, 50.5% had PCs, but only 17.6% had Web access. When Web access was available, it was most often available through a high-speed Internet connection that was faster than a dial-up modem. Most departments (68.1%) with PCs used the Windows 95 or Windows 98 operating systems. A majority (62.5%) used the Netscape browser exclusively. Larger EDs (more than six ED beds) in rural or suburban areas were more likely to have a PC compared with smaller EDs (six or fewer beds). Large EDs (more than 12 ED beds) in private tertiary care or academic hospitals were most likely to have Web access. CONCLUSIONS: Although half of Illinois EDs have PCs, only one in six has access to the Internet; thus, most emergency physicians do not have ready access to the Web from the site where they deliver clinical care.

A clinical and immunologic study to assess risk of TMA-induced lung disease as related to exposure.

The objective of this study was to determine whether there are trimellitic anhydride (TMA) exposure levels that are very unlikely to cause immunologically mediated respiratory disease. A 3-year clinical and immunologic survey study of 286 employees was conducted at a facility that manufactures TMA. Each employee was assigned an exposure classification from 1 (highest) to 5 (lowest). Of the 28 individuals in exposure class 1, 8 (29%) developed disease; of the 57 class 2 employees, 2 (4%) developed disease; of the 79 class 3 employees, 4 (5%) developed disease. Of the 98 class 4 employees and the 24 class 5 employees, none developed disease. Inasmuch as individuals in class 4 and 5 (TMA exposure < 0.002 mg/m3) are at low risk of developing disease due to TMA, it appears that they do not warrant routine inclusion in surveillance studies.

Study of employees with anhydride-induced respiratory disease after removal from exposure.

The purpose of this study was to determine clinical and immunologic status of hexahydrophthalic anhydride (HHPA) employees who have had immunologic respiratory disease and who have been removed from exposure for at least 1 year. In a retrospective study, 16 consecutive employees with HHPA-induced immunologic respiratory disease who had been removed from exposure for more than 1 year were evaluated. Eleven had asthma, allergic rhinitis, or both; five had hemorrhagic rhinitis. Respiratory symptoms were obtained by physician-administered questionnaire. Physical examination, spirometry, and chest film were obtained. Antibody against HHPA conjugated to human serum albumin (HHP-HSA) was determined by enzyme-linked immunosorbant assay. Symptoms, signs, and pulmonary functions were normalized in all employees. There was a decline in antibody titers for both IgE and IgG against HHP-HSA. There were no chest film findings attributable to HHPA. In this group, there appeared to be no evidence of permanent anatomic sequelae after removal from exposure for at least 1 year. Specific antibody was still present, but titers were lower at follow-up than at presentation for a substantial proportion of the sample.

Use of the Rand Structured Implicit Review Instrument for Quality of Care Assessment.

The Rand Structured Implicit Review Instrument is a 27-item instrument that rates process quality of care for patients with five common illnesses. This study reports on the use of this instrument for hospitalized patients with long lengths of stay. A total of 120 medical records were reviewed by multiple physician reviewers for patients discharged with congestive heart failure, acute myocardial infarction, and pneumonia. Mean inter-rater reliability was assessed for a subsample of six records by kappa score. A multiple regression analysis was used to estimate the relationship between process ratings for the quality of documentation, assessment, monitoring, and therapy and overall quality of care scores, controlled for physician judgments about patients' prognosis and selected patient characteristics. Each reviewer also evaluated the instrument. Mean kappa for trichotomized ratings of quality of care was 0.50. The majority of all quality of care ratings were in the good or very good range (77.5%). The full regression model, including process subscale quality ratings, prognostic items, and patient characteristics, accounted for 38% of the total variance in the quality of care ratings. Items measuring the quality of assessment (p < 0.0001), therapy (p < 0.02) and monitoring (p < 0.01) were significant. Physicians accepted the use of such a form moderately well. The Rand quality of care form shows consistency in rating overall quality of care and individual dimensions of quality. Achieving a high level of inter-rater reliability is difficult with implicit review. By focusing on specific areas of potentially deficient care, structured review instruments can improve clinical quality improvement efforts.

Comparing three preprocessing strategies for longitudinal data. An example in functional outcomes research.

Longitudinal monitoring of individual patient data is becoming routine in physician office practice. This study compares three different methods for evaluating clinical outcomes for individual patients: raw change score analysis versus normative and ipsative statistical analyses. Two discrete samples of intermittent claudication patients making vascular surgery office visits--drawn from interventional management versus stable, routinely followed control groups--were tested four times using both generic and disease-specific functional status measures. Results indicated that the ipsative method was most consistent with several different types of a priori hypotheses that are often evaluated in analysis of repeated measures data.

A path analysis of medical school and residency performance. Implications for housestaff selection.

The selection and subsequent performance of 212 internal medicine residents was examined by factor analysis and path analysis. A three-factor solution accounted for most of the variance among the nine selection variables. These three factors, labeled Board Scores, Faculty Evaluations, and Academic Distinction, were then combined with in-training residency performance evaluations and composite scores on the ABIM certifying examination to produce a comprehensive path model of house staff selection and performance. The Academic Distinction factor emerged as the strongest predictor of residency performance,; the Faculty Evaluations factor was also a significant component of the model. Standardized test scores correlated poorly with clinical performance. The data suggest that increased attention to the content of letters of reference could substantially improve their predictive validity. Other means of reporting subjective evaluations may also be needed to increase the stature of non-cognitive attributes in house staff selection decisions.

Statistical analysis for single-case designs. Evaluating outcome of imaginal exposure treatment of chronic PTSD.

A recently developed statistical method for single-case subject designs based on classical test theory was used to examine the efficacy of imaginal exposure treatment for posttraumatic stress disorder (PTSD) in four Vietnam veterans. The method was sensitive to intraindividual changes across different outcome measures even when relatively few data points were available. Two veterans clearly improved from exposure and maintained their gains at 3- and 15-month follow-ups. One veteran improved marginally, whereas one veteran's symptoms worsened. Changes in heart rate monitored over the first two imaginal exposures indicated that veterans with greater heart-rate habituation responded better to exposure than did veterans with less or no habituation. The results suggest that the statistical method illustrated here has some advantages over other methods (e.g., visual inspection, time-series analysis) for examining clinical interventions in single-case designs.