Effects of a rapid antigen test for group A streptococcal pharyngitis on physician prescribing and antibiotic costs.

Decision analysis and opinion survey suggest that introduction of rapid antigen detection tests should decrease the number of patients with negative test results for group A streptococcal pharyngitis treated by antibiotics. We reviewed all cases in which a test for group A streptococcal pharyngitis was performed during the last 7 months of culture diagnosis and the first 7 months of antigen test diagnosis at an inner city community health center, recording culture or antigen test results, whether antibiotics were prescribed, and patient status (as regular health center patients or patients referred to the center). Positive rates for culture and antigen-test periods were similar (10% and 12%), but 53% of patients with negative culture were treated, where only 32% of patients with negative antigen-test results received prescriptions. Significant reductions in the treatment of patients with negative test results were found in both patient-status subpopulations: health center patients, 43% to 29%; referred patients, 91% to 52%. Among health center patients reductions were consistent for both adult (30% to 21%) and child and adolescent (55% to 45%) age groups. For all patients with negative test results, direct costs of diagnostic reagents and antibiotic prescriptions fell from $3.58 per patient with culture to $3.45 with antigen testing; the $0.13 savings per patient was due to less treatment of referred patients. Thus, rapid antigen testing led to (1) significantly fewer patients with negative test results receiving antibiotic prescriptions; and, (2) savings in antibiotic costs offsetting reagent cost of antigen detection diagnosis.

Clinical and microbiological evidence for endemic pharyngitis among adults due to group C streptococci.

Group C beta-hemolytic streptococci cause rare epidemic outbreaks of pharyngitis, but their role in sporadic endemic pharyngitis has been uncertain. We addressed the question of whether non-group A beta-hemolytic streptococci are associated with endemic pharyngitis in two ways. First, we compared rates of isolation from throat swabs of group A, B, C, and G and ungrouped beta-hemolytic streptococci ("culture negative") in adult patients vs those rates in controls. Second, we collected in standardized form clinical indexes of patients with pharyngitis: signs and symptoms graded for severity, the examining physician's subjective estimate of the probability of streptococcal pharyngitis, a logistic regression score predicting streptococcal pharyngitis, and whether antibiotic therapy was prescribed. After collecting data and cultures on 1425 patients with sore throats and cultures on 284 controls, we found the following: group C streptococci were isolated significantly more frequently in patients with sore throats than in controls (6% vs 1.4%); four clinical signs and two symptoms distinguished group C-associated pharyngitis as more severe than culture-negative pharyngitis; and six clinical signs and one symptom distinguished group C-associated pharyngitis as less severe than group A pharyngitis. Physicians' subjective estimates, logistic regression scores, and antibiotic treatment all characterized group C-associated pharyngitis as more severe than culture-negative sore throats but less severe than group A pharyngitis. From these data we present the first definitive evidence that group C streptococci are associated with endemic pharyngitis, show that clinical presentation distinguishes a group of patients with group C-associated pharyngitis from populations with culture-negative sore throats and from those with group A pharyngitis. Physicians' response to that presentation merits consideration in the context of rapid group-specific diagnosis of streptococcal pharyngitis by group A antigen tests.

The "iron screen": modification of standard laboratory practice with data analysis.

Multivariate analysis was applied to iron deficiency anemia to generate an efficient sequence of diagnostic laboratory tests. A three step diagnostic system--serum ferritin level and mean corpuscular volume as a screen in all patients, followed by serum iron level and total iron binding capacity in some patients, and by erythrocyte sedimentation rate in a few patients--was constructed using a previously validated data reduction system. When compared to bone marrow iron stores, this system was found to have 96 per cent accuracy. In one year of clinical trial the "iron screen" classified 396 of 416 patients in a hospital setting. This sequential strategy shows how clinical laboratory data can be utilized to render diagnoses of defined probability.

Chronic obstructive airway disease. Impact of health education.

We conducted a controlled study of the impact of an education program on the health outcomes and perceptions of patients with varying degrees of airway obstruction in two communities. In one community, patients with chronic obstructive airway disease (COAD) were identified, assessed and offered an educational program. In the other community, patients were identified, assessed and advised of the findings only. Patients at both sites were given the same pretest and, one year later, the same posttest. These tests measured physical and social function, and health outcomes (eg, respiratory symptoms, exercise tolerance, mental health), plus patients' health perceptions. Posttest results showed a significant difference between groups on a health perception measure and locus of control, but no difference on health outcomes. We conclude that education programs for COAD are unlikely to improve patients' health status unless they are part of a comprehensive medical program that includes physical reconditioning.

Performance of a predictive model for streptococcal pharyngitis in children.

CONTEXT: Group A beta-hemolytic streptococcus (GABHS) pharyngitis is a common childhood illness. The clinical diagnosis is difficult to determine and laboratory tests have limitations; hence, the condition is generally overdiagnosed and overtreated. Several clinical pediatric-specific predictive models have been published but none have been prospectively studied. OBJECTIVE: To test the performance of a previously published predictive model for GABHS pharyngitis in children in different clinical settings and during different seasons. DESIGN: Prospective cohort study. SETTINGS: Pediatric emergency department and 2 pediatric outpatient clinics. PATIENTS: Children aged between 1 and 18 years with pharyngitis on initial examination at study sites between April 1, 1999, and March 31, 2000. INTERVENTIONS: Recording of clinical features during initial evaluation using a standardized form and recovery of GABHS from patients' throats using reference standard methods. MAIN OUTCOME MEASURES: Posttest probability for GABHS positive throat culture associated with the model's positive predictors (moderate to severe tonsillar swelling, cervical lymphadenopathy [moderate to severe tenderness and enlargement of cervical lymph nodes], scarletiniform rash, and the absence of coryza) and the models' negative predictors (absence of the above signs and the presence of coryza). RESULTS: Of 587 patients analyzed, 218 (37%) had a positive throat culture for GABHS. Forty-nine percent were boys. Mean +/- SD age was 6.7 +/- 3.9 years. There was no difference between the subsets within the sample. The posttest probability values for a positive throat culture associated with positive and negative predictors of the model were 79% and 12%, respectively. CONCLUSIONS: A pediatric predictive model for GABHS pharyngitis performed better than physicians' subjective estimates for a positive throat culture and was comparable with a rapid antigen detection test. The model performed consistently well in different populations and across seasons. It can be useful if reliable microbiological testing and/or follow-up are not attainable.

Fatal peritonitis following IUD-associated salpingitis.

Previous reports have implicated the Dalkon shield intrauterine device (IUD) in septic second trimester abortion and maternal death from sepsis. In the case reported here, Fusobacterium necrophorum, a rarely pathogenic vaginal anaerobe, gained access to the uterus in a woman wearing a Dalkon shield and caused acute parametritis, overwhelming peritonitis, systemic sepsis, and death. It is well known that IUDs can contribute to the development of serious pelvic infections, and in this case it is possible that the Dalkon shield was the cause of the ascending infection into the uterus.

Identification of species-specific, non-cross-reactive proteins of Borrelia burgdorferi.

The low specificity of diagnostic tests for Lyme disease is due to the fact that Borrelia burgdorferi possesses many antigenic proteins that are cross-reactive with other spirochetes and bacteria. The low sensitivity is a result of high (> or = 1:100) dilutions used for patient sera during testing to eliminate non-specific cross-reactivity. The present study was conducted to identify species-specific non-cross-reactive protein(s) of B. burgdorferi that might be used as antigen(s) in serologic tests. Whole-cell sonicates of B. burgdorferi were tested against pooled sera from patients with symptoms, signs, and serologic features diagnostic of Lyme disease (LD), rheumatoid arthritis, infectious mononucleosis, systemic lupus erythematosus, Rocky Mountain spotted fever, secondary syphilis, and from healthy individuals. Different LD pools were also tested against whole-cell sonicates of Treponema pallidum, Treponema phagedenis, Leptospira interrogans, and Escherichia coli. Comparison among patterns obtained by each serum pool revealed that IgM antibodies to species-specific 39-, 23-, and 22-kD proteins and IgG antibodies to 34- and 31-kD proteins were present only in the patients with LD and absent from patients with rheumatoid arthritis, infectious mononucleosis, systemic lupus erythematosus, Rocky Mountain spotted fever, secondary syphilis, and healthy individuals pools. These results suggest that 39-, 23-, and 22-kD proteins may be used in an IgM immunoassay for diagnosis of LD.

Rapid identification of motile Aeromonas.

The clinical relevance and taxonomy of motile Aeromonas species are areas of current controversy. Strains of motile Aeromonas isolates (n = 60) from various sources were identified to species level using the following tests (all incubated at 30 degrees and 37 degrees C): esculin hydrolysis; formation of gas from glucose; production of acetoin; production of acid from mannitol and arabinose; decarboxylation of lysine and ornithine, dihydrolation of arginine; and pyrazinamide hydrolysis in a semisolid medium. The tests' results were similar at incubation temperatures of 30 degrees and 37 degrees C. Of the strains, 59 (98%) of 60 were identified to species level by the full battery of tests: 25 as A. hydrophila, 18 as A. caviae, 14 as A. sobria, one as A. veronii, and one as A. schubertii. (The only A. veronii and A. schubertii isolates identified were ATCC strains). All (25 of 25) strains of A. hydrophila and 17 (94%) of 18 of A. caviae hydrolyzed pyrazinamide in less than 24 hr, whereas all strains of A. sobria showed no pyrazinamidase activity. Absence of pyrazinamidase was, thus, a convenient phenotypic marker for A. sobria. Four additional tests (esculin hydrolysis, acetoin production, lysine decarboxylation, and gas production from glucose) identified within 24 hr all examples of the three common species of Aeromonas. Recently proposed species did not contribute to our ability to discriminate among stool, other clinical, and environmental isolates of Aeromonas spp.

Evaluation of two ELISA's for detecting Chlamydia trachomatis from endocervical swabs.

Two enzyme immunoassays (EIAs) detecting Chlamydia trachomatis from endocervical swabs, Syva MicroTrak (MT) and Abbott Chlamydiazyme (CZ), were compared with a tissue culture (TC) standard. Initially, 8% (100 of 1250) of specimens were TC positive, yielding sensitivities of 94% (94 of 100) for MT and 79% (79 of 100) for CZ with identical 98% specificities (1129 of 1150 for MT and 1130 of 1150 for CZ). Discrepant specimens were retested by both EIAs and assayed for elementary bodies (EBs) by a fluorescent antibody test. After discrepancy analysis, 9.5% (118) of 1240 patients were either TC or EB positive, yielding sensitivities of 94.1% for MT (111 of 118) and 79.7% for CZ (94 of 118) with identical specificities of 100% (1122 of 1122). These results indicate that the MT is significantly more sensitive (p less than 0.05, McNemar test) than CZ in detecting C. trachomatis from endocervical swabs.

Kaposiform hemangioendothelioma of the thymus.

Kaposiform hemangioendothelioma is a rare pediatric neoplasm that presents most commonly in the soft tissues. We report the case of a 1-month-old infant who presented with stridor and was found to have a diffusely infiltrating tumor in the thymus that extended into the pericardium and up the carotid sheaths. Histologic examination revealed a vascular tumor infiltrating among the lobules of the lymphocyte-depleted thymus. The lesion had features of both a capillary hemangioma and Kaposi sarcoma. Immunoperoxidase studies on formalin-fixed, paraffin-embedded tissue demonstrated the neoplastic endothelial cells to be positive for vascular markers CD31 and CD34. Antibody to factor VIII-related antigen labeled feeding vessels, but failed to stain the lobules of tumor. Although these tumors have been treated in a fashion similar to capillary hemangiomas in the past, it may be important to differentiate Kaposiform hemangioendotheliomas because of their association with Kasabach-Merritt syndrome and recent success with more aggressive chemotherapy regimens.

Reference laboratory telephone service quality.

OBJECTIVES: To establish the rates with which reference laboratories resolve inquiries telephoned to them from primary laboratories and to identify reference laboratory practices associated with higher rates of inquiry resolution. DESIGN AND PARTICIPANTS: For 2 months, or until 50 contacts had occurred, 545 primary laboratories participating in the College of American Pathologists Q-Probes laboratory quality improvement program prospectively documented and characterized telephone inquiries they made to a reference laboratory of their choice. Participants also cataloged their own laboratory's demographic and practice characteristics and their reference laboratory's customer service characteristics. MAIN OUTCOME MEASURE: Rates with which reference laboratories resolved telephone inquiries. RESULTS: Participants characterized 11 031 (78.7%) of 14 017 telephone inquiries as resolved by the reference laboratories. Ranked according to inquiry resolution rates, primary laboratories in the 90th percentile characterized reference laboratories as resolving 100% of their inquiries; those in the 10th percentile characterized reference laboratories as resolving only 54.2% of their inquiries. The rate of resolved inquiries was significantly higher (P =.0047) for participants using reference laboratories with 24-hour customer service than it was for participants using reference laboratories with less than 24-hour service. Most primary laboratories (80.9%) chose to monitor 1 of 11 national reference laboratories; in this subset, median rates of inquiry resolution ranged from 90.2% to 55.0% (P <.0001), despite no significant variation in other measured customer service characteristics. CONCLUSIONS: Primary laboratories experience significant differences in the rates with which reference laboratories resolve telephone inquiries. The performance benchmark for reference laboratories is resolution of at least 90% of telephone inquiries from primary laboratory customers.

Blood culture contamination: a College of American Pathologists Q-Probes study involving 640 institutions and 497134 specimens from adult patients.

OBJECTIVE: To examine clinical and laboratory practices associated with contamination of blood culture specimens from adults. DESIGN AND SETTING: A College of American Pathologists Q-Probes quality improvement study involving prospective evaluation of adult blood culture contamination rates in 640 institutions. MAIN OUTCOME MEASURE: Proportion of contaminated blood cultures. RESULTS: A total of 497134 blood cultures were studied. The median adult inpatient blood culture contamination rate was 2.5% (central 80th percentile=0.9%-5.4%) by laboratory assessment. There was no significant difference in contamination rates between inpatient and outpatient cultures (P=.273). The median contamination rate by clinical assessment (2.1%) was significantly lower (P=.005), primarily because of a lower proportion of cultures with coagulase-negative Staphylococcus that were interpreted as contaminants when only one of multiple specimens was positive. Specimen collection variables associated with significantly lower contamination rates included use of a dedicated phlebotomy service (P=.039), use of tincture of iodine for skin disinfection (P=.036), and application of an antiseptic to the top of the collection device before inoculation (P=.018). Teaching institutions and high numbers of occupied beds were demographic factors associated with higher contamination rates for inpatients but not for outpatients. Culture parameters associated with higher contamination rates included microbial growth from a single specimen, isolation of certain microbial species (eg, coagulase-negative Staphylococcus), and longer time to detect growth in culture. Contamination rates were not significantly affected by the type of blood culture method used, specimen volume, or use of a double-needle collection procedure. CONCLUSIONS: There is wide variation in blood culture contamination rates among institutions. Three specimen collection factors and three culture variables were identified as having a significant effect on blood culture contamination.

Indications and immediate patient outcomes of pathology intraoperative consultations. College of American Pathologists/Centers for Disease Control and Prevention Outcomes Working Group Study.

OBJECTIVE: To evaluate the reasons (indications) for and immediate intraoperative surgical results (outcomes) associated with pathology intraoperative consultation. DESIGN: In 1992 and 1993, surgeons collaborated with pathologists in 472 voluntarily participating institutions from the United States (462), Canada (7), Australia (2), and New Zealand (1) in a study jointly sponsored by the College of American Pathologists and the Centers for Disease Control and Prevention. Pathologists selected 20 consecutive intraoperative consultations and assembled a cover letter, a checklist questionnaire, and a copy of the corresponding surgical pathology report, all of which were sent to the surgeon(s) for retrospective evaluation. PARTICIPANTS: The study was distributed to participants in the College of American Pathologists voluntary Q-Probes quality improvement and Surgical Pathology Performance Improvement programs and to Canadian and Australian hospitals with more than 200 beds. RESULTS: Evaluation of 9164 cases established the five most common indications for intraoperative consultation: (1) establish or confirm diagnosis to determine type or extent of operation (51%), (2) confirm adequacy of margins (16%), (3) confirm nature of tissue to direct sampling for immediate culture or other laboratory study (10%), (4) expedite obtaining diagnosis to inform family or patient (8%), and (5) confirm sufficient tissue submitted to secure diagnosis in permanent section (8%). The information provided by the intraoperative consultation resulted in changed surgical procedures that were either modified, terminated, or newly initiated in 47%, 30%, 6%, 9%, and 28% of cases, corresponding respectively to each of the above five common indications. Rarely cited reasons for intraoperative consultation were to expedite obtaining diagnosis for surgeon's knowledge (3%), to facilitate patient management, other professional communication or discharge planning prior to permanent section availability (3%), academic protocol (< 1%), and consultation not needed or no reason for request (< 1%). CONCLUSIONS: This multi-institutional, interdisciplinary database confirms that pathology intraoperative consultations, regardless of the initial indications, influence immediate patient care decisions, resulting in changed surgical procedures in an average of 39% of all operative cases.

Using routine documentation of medical care to observe physician behavior.

This observational study compared the utilization of pulmonary function tests (PFTs) for outpatients at community hospitals in New Hampshire in 1975 and 1980. It was hypothesized that if preliminary care physicians were shifting toward using PFTs for early detection of chronic obstructive airway disease (COAD), an increase in the number of tests ordered, a decrease in the mean age of patients tested, and an increase in the mean lung functions (FEV1/FVC) would be observed. For hospitals providing data for 1975 and 1980, 85% showed an increase in the number of outpatient tests ordered (p = 0.002), the mean age of outpatients tested decreased at 75% of the hospitals (p = 0.019), and the mean FEV1/FVC increased at 67% of the hospitals (p = 0.014). The hypotheses thus confirmed, it is concluded that New Hampshire physicians are using PFTs for early detection of COAD.

Environmental causes of cancer death.

People increasingly look to the forensic autopsy as a way of determining whether a particular cancer death was environmentally caused. The forensic pathologist must be diligent pursuing evidence that links potential environmental causes to cancer but must also educate the public providing reassurance that most cancers are not due to industrial pollution. Cigarette smoking and various life-style factors appear to account for more cancers than do man-made environmental contaminants. Assessing the possibility that a cancer death is due to a specific environmental agent requires extensive information. First, one must obtain an accurate history of lifetime occupational and environmental exposures. Second, one must analyze this information in view of epidemiologic data on the cancer risks associated with each exposure. Finally, one should seek to document through the autopsy that exposure to a potentially harmful agent actually occurred. The carefully done forensic autopsy can alert the public to dangerous conditions and can provide individuals a basis for recovery in court for damages due to harmful exposures.

Differential medium for mixed cultures of alpha-hemolytic streptococci from blood.

Alpha-hemolytic streptococci (AHS) were isolated from blood cultures from 100 patients, and species were identified by the Ruoff and Kunz scheme. When isolates were inoculated onto sheep blood agar, all 100 cultures appeared to be pure, with identifications based on colonial morphology and Gram stain. When isolates were subcultured onto mitis salivarius agar (MSA), mixtures of two species of AHS were detected in 10 cultures from patients (10%). These mixed cultures would have been reported as pure cultures of Streptococcus milleri (six cultures), Streptococcus salivarius (three cultures), Streptococcus sanguis I (one culture), with identifications based on biochemical profiles. Cultures on MSA demonstrated S. milleri (six cultures), Streptococcus mitis (five cultures), S. salivarius (three cultures), S. sanguis I (one culture), and S. sanguis II (five cultures). The inability to separate AHS species by colony morphology on sheep blood agar demands that a differential medium such as MSA be routinely used for subculture. Failure to use such a medium may account for some of the confusing biochemical profiles associated with AHS species identification.

Throat cultures and rapid tests for diagnosis of group A streptococcal pharyngitis.

This article reviews the use of diagnostic tests to guide management of adults with sore throats. Pharyngitis due to group A beta-hemolytic streptococci represents the major diagnostic concern in these patients. Organisms other than group A streptococci can cause pharyngitis, but their clinical importance and their diagnostic tests have not yet been established. For many years, physicians have used routine throat cultures to diagnose group A streptococcal pharyngitis. Rapid tests have recently been introduced that detect the group A streptococcal antigen on throat swab specimens. Because both tests have high sensitivity and specificity, the choice of tests may depend on test turnaround time. Rapid tests should improve management by decreasing both short-term morbidity and inappropriate use of antibiotics.

Reye's syndrome. A review from the forensic viewpoint.

Reye's syndrome, encephalopathy and fatty change in the liver and other viscera, typically occurs suddenly in infants and children recovering from a viral illness, particularly influenza or varicella. Its rapid clinical course may suggest a drug-related insult and the differential diagnosis includes a variety of toxins. There are grounds for suspicion that exogenous substances--including aspirin--may be cofactors with recent viral illness in the syndrome's pathogenesis. For these reasons, medical examiners may be called upon to rule the diagnosis in or out, to assess the possibility of direct toxic injury, or to document presence or absence of possible cofactors. With these tasks in mind, this review summarizes the diagnostic, pathologic, and laboratory findings of Reye's syndrome and considers the roles of viral infection, heritable predispositions, and exogenous toxins in its causation. It singles out salicylate treatment for special considerations as a possible cofactor, and concludes with a suggested approach to the forensic medical investigation of possible cases of Reye's syndrome.

Meningitis due to Neisseria mucosa: case report and review.

Neisseria mucosa is a species of gram-negative cocci that has a characteristic mucoid, adherent colonial morphology and includes pigmented and nonpigmented morphotypes. The ability of N. mucosa to reduce nitrates distinguishes it from other Neisseria species. N. mucosa is part of the normal human nasopharyngeal flora and infrequently causes human infections, including meningitis. We report a unique case of a patient with a cerebrospinal fluid shunt infection due to N. mucosa and review five other reports of cases of meningitis caused by this organism. Seven additional previously reported cases of presumed N. mucosa meningitis have been excluded from this review on the basis of the current criteria for identification of the organism. In the reports of established cases, female infants and children who often had predisposing conditions predominate. Although the outcome for such patients has been favorable, no clinical or laboratory findings are helpful in distinguishing meningitis due to N. mucosa from that due to other bacteria.