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Background: Paenibacillus thiaminolyticus is a cause of postinfectious hydrocephalus among Ugandan infants. To determine whether Paenibacillus spp is a pathogen in neonatal sepsis, meningitis, and postinfectious hydrocephalus, we aimed to complete three separate studies of Ugandan infants. The first study was on peripartum prevalence of Paenibacillus in mother-newborn pairs. The second study assessed Paenibacillus in blood and cerebrospinal fluid (CSF) from neonates with sepsis. The third study assessed Paenibacillus in CSF from infants with hydrocephalus., Methods: In this observational study, we recruited mother-newborn pairs with and without maternal fever (mother-newborn cohort), neonates (aged ≤28 days) with sepsis (sepsis cohort), and infants (aged ≤90 days) with hydrocephalus with and without a history of neonatal sepsis and meningitis (hydrocephalus cohort) from three hospitals in Uganda between Jan 13, 2016 and Oct 2, 2019. We collected maternal blood, vaginal swabs, and placental samples and the cord from the mother-newborn pairs, and blood and CSF from neonates and infants. Bacterial content of infant CSF was characterised by 16S rDNA sequencing. We analysed all samples using quantitative PCR (qPCR) targeting either the Paenibacillus genus or Paenibacillus thiaminolyticus spp. We collected cranial ultrasound and computed tomography images in the subset of participants represented in more than one cohort., Findings: No Paenibacillus spp were detected in vaginal, maternal blood, placental, or cord blood specimens from the mother-newborn cohort by qPCR. Paenibacillus spp was detected in 6% (37 of 631 neonates) in the sepsis cohort and, of these, 14% (5 of 37 neonates) developed postinfectious hydrocephalus. Paenibacillus was the most enriched bacterial genera in postinfectious hydrocephalus CSF (91 [44%] of 209 patients) from the hydrocephalus cohort, with 16S showing 94% accuracy when validated by qPCR. Imaging showed progression from Paenibacillus spp-related meningitis to postinfectious hydrocephalus over 1-3 months. Patients with postinfectious hydrocephalus with Paenibacillus spp infections were geographically clustered., Interpretation: Paenibacillus spp causes neonatal sepsis and meningitis in Uganda and is the dominant cause of subsequent postinfectious hydrocephalus. There was no evidence of transplacental transmission, and geographical evidence was consistent with an environmental source of neonatal infection. Further work is needed to identify routes of infection and optimise treatment of neonatal Paenibacillus spp infection to lessen the burden of morbidity and mortality., Funding: National Institutes of Health and Boston Children's Hospital Office of Faculty Development., Competing Interests: Declaration of interests KB is Principal Investigator on a Joint Global Health Trials grant from the UK Medical Research Council and has received travel grants and honoraria for speaking at Hot Topics in Neonatology. JEE has received honoraria for participation on the Data Safety Monitoring Board of AbbVie. BCW has received honoraria for participation on the Data Safety Monitoring Board for the Endoscopic versus Shunt Treatment of Hydrocephalus in Infants trial of the Hydrocephalus Clinical Research Network and is the Chairman of Neurokids. JNP has been employed by Genentech and N-Power Medicine; has held stocks and holds and is planning patents at Genentech and N-Power Medicine; has received honoraria for speaking at the International Human Microbiome Consortia meeting; and has received travel support from Genentech. All other authors declare no competing interests. The National Institutes of Health (NIH) Director's Pioneer Award 5DP1HD086071 and NIH Director's Transformative Award 1R01AI145057 has been given to SJS, and the Boston Children's Hospital Office of Faculty Development Career Development Award to SUM. No authors are employed by the NIH., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Over two million stillbirths and neonatal deaths occur in sub-Saharan Africa (sSA) annually. Despite multilateral efforts, reducing perinatal mortality has been slow. Although targeted pathologic investigation can often determine the cause of perinatal death, in resource-limited settings, stillbirths, early neonatal deaths, and placentas are rarely examined pathologically. However, the placenta is a key source of diagnostic information and is the main determinant of fetal growth and development in utero , influencing child health outcomes., Methods: In 2016, our collaborative intercontinental group began investigating infectious perinatal death and adverse child health outcomes in Uganda. We developed and initiated a 4-day combined didactic/practical curriculum to train health workers in placental collection, gross placental examination, and tissue sampling for histology. We also trained a local technician to perform immunohistochemistry staining., Results: Overall, we trained 12 health workers who performed gross placental assessment for > 1,000 placentas, obtaining > 5,000 formalin-fixed tissue samples for research diagnostic use. Median placental weights ranged from 425 to 456 g, and 33.3% of placentas were < 10th percentile in weight, corrected for gestational age. Acute chorioamnionitis (32.3%) and maternal vascular malperfusion (25.4%) were common diagnoses., Discussion: Through a targeted training program, we built capacity at a university-affiliated hospital in sSA to independently perform placental collection, gross pathologic examination, and placental tissue processing for histology and special stains. Our training model can be applied to other collaborative research endeavors in diverse resource-limited settings to improve research and clinical capacity and competency for diagnostics and management of stillbirth, neonatal death, and child health outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bebell, Ngonzi, Meier, Carreon, Birungi, Kerry, Atwine and Roberts.)

Objectives: To estimate the prevalence of cytomegalovirus (CMV) infections among newborn-mother pairs, neonates with sepsis, and infants with hydrocephalus in Uganda., Design and Methods: Three populations-newborn-mother pairs, neonates with sepsis, and infants (≤3 months) with nonpostinfectious (NPIH) or postinfectious (PIH) hydrocephalus-were evaluated for CMV infection at 3 medical centers in Uganda. Quantitative PCR (qPCR) was used to characterize the prevalence of CMV., Results: The overall CMV prevalence in 2498 samples across all groups was 9%. In newborn-mother pairs, there was a 3% prevalence of cord blood CMV positivity and 33% prevalence of maternal vaginal shedding. In neonates with clinical sepsis, there was a 2% CMV prevalence. Maternal HIV seropositivity (adjusted odds ratio [aOR] 25.20; 95% confidence interval [CI] 4.43-134.26; p = 0.0001), residence in eastern Uganda (aOR 11.06; 95% CI 2.30-76.18; p = 0.003), maternal age <25 years (aOR 4.54; 95% CI 1.40-19.29; p = 0.02), and increasing neonatal age (aOR 1.08 for each day older; 95% CI 1.00-1.16; p = 0.05), were associated risk factors for CMV in neonates with clinical sepsis. We found a 2-fold higher maternal vaginal shedding in eastern (45%) vs western (22%) Uganda during parturition (n = 22/49 vs 11/50, the Fisher exact test; p = 0.02). In infants with PIH, the prevalence in blood was 24% and in infants with NPIH, it was 20%. CMV was present in the cerebrospinal fluid (CSF) of 13% of infants with PIH compared with 0.5% of infants with NPIH (n = 26/205 vs 1/194, p < 0.0001)., Conclusions: Our findings highlight that congenital and postnatal CMV prevalence is substantial in this African setting, and the long-term consequences are uncharacterized., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The composition of the maternal vaginal microbiome influences the duration of pregnancy, onset of labor, and even neonatal outcomes. Maternal microbiome research in sub-Saharan Africa has focused on non-pregnant and postpartum composition of the vaginal microbiome. Here we aimed to illustrate the relationship between the vaginal microbiome of 99 laboring Ugandan women and intrapartum fever using routine microbiology and 16S ribosomal RNA gene sequencing from two hypervariable regions (V1-V2 and V3-V4). To describe the vaginal microbes associated with vaginal microbial communities, we pursued two approaches: hierarchical clustering methods and a novel Grades of Membership (GoM) modeling approach for vaginal microbiome characterization. Leveraging GoM models, we created a basis composed of a preassigned number of microbial topics whose linear combination optimally represents each patient yielding more comprehensive associations and characterization between maternal clinical features and the microbial communities. Using a random forest model, we showed that by including microbial topic models we improved upon clinical variables to predict maternal fever. Overall, we found a higher prevalence of Granulicatella, Streptococcus, Fusobacterium, Anaerococcus, Sneathia, Clostridium, Gemella, Mobiluncus, and Veillonella genera in febrile mothers, and higher prevalence of Lactobacillus genera (in particular L. crispatus and L. jensenii), Acinobacter, Aerococcus, and Prevotella species in afebrile mothers. By including clinical variables with microbial topics in this model, we observed young maternal age, fever reported earlier in the pregnancy, longer labor duration, and microbial communities with reduced Lactobacillus diversity were associated with intrapartum fever. These results better defined relationships between the presence or absence of intrapartum fever, demographics, peripartum course, and vaginal microbial topics, and expanded our understanding of the impact of the microbiome on maternal and potentially neonatal outcome risk., (© 2021. The Author(s).)

Context: Additional reviews of diagnostic surgical and cytology cases have been shown to detect diagnostic discrepancies., Objective: To develop, through a systematic review of the literature, recommendations for the review of pathology cases to detect or prevent interpretive diagnostic errors., Design: The College of American Pathologists Pathology and Laboratory Quality Center in association with the Association of Directors of Anatomic and Surgical Pathology convened an expert panel to develop an evidence-based guideline to help define the role of case reviews in surgical pathology and cytology. A literature search was conducted to gather data on the review of cases in surgical pathology and cytology., Results: The panel drafted 5 recommendations, with strong agreement from open comment period participants ranging from 87% to 93%. The recommendations are: (1) anatomic pathologists should develop procedures for the review of selected pathology cases to detect disagreements and potential interpretive errors; (2) anatomic pathologists should perform case reviews in a timely manner to avoid having a negative impact on patient care; (3) anatomic pathologists should have documented case review procedures that are relevant to their practice setting; (4) anatomic pathologists should continuously monitor and document the results of case reviews; and (5) if pathology case reviews show poor agreement within a defined case type, anatomic pathologists should take steps to improve agreement., Conclusions: Evidence exists that case reviews detect errors; therefore, the expert panel recommends that anatomic pathologists develop procedures for the review of pathology cases to detect disagreements and potential interpretive errors, in order to improve the quality of patient care.

Context: The anticoagulant warfarin has been identified as the second most frequent drug responsible for serious, disabling, and fatal adverse drug events in the United States, and its effect on blood coagulation is monitored by the laboratory test called international normalized ratio (INR)., Objective: To determine the presence of INR policies and procedures, INR practices, and completeness and timeliness of reporting critical INR results in participants' clinical laboratories., Design: Participants reviewed their INR policies and procedure requirements, identified their practices by using a questionnaire, and studied completeness of documentation and timeliness of reporting critical value INR results for outpatients and emergency department patients., Results: In 98 participating institutions, the 5 required policies and procedures were in place in 93% to 99% of clinical laboratories. Fifteen options for the allowable variations among duplicate results from different analyzers, 12 different timeliness goals for reporting critical values, and 18 unique critical value limits were used by participants. All required documentation elements were present in 94.8% of 192 reviewed INR validation reports. Critical value INR results were reported within the time frame established by the laboratory for 93.4% of 2604 results, but 1.0% of results were not reported. Although the median laboratories successfully communicated all critical results within their established time frames and had all the required validation elements based in their 2 most recent INR calculations, those participants at the lowest 10th percentile were successful in 80.0% and 85.7% of these requirements, respectively., Conclusions: Significant opportunities exist for adherence to INR procedural requirements and for practice patterns and timeliness goals for INR critical results' reporting.

Context: Hemolysis is an important clinical laboratory quality attribute that influences result reliability., Objective: To determine hemolysis identification and rejection practices occurring in clinical laboratories., Design: We used the College of American Pathologists Survey program to distribute a Q-Probes-type questionnaire about hemolysis practices to Chemistry Survey participants., Results: Of 3495 participants sent the questionnaire, 846 (24%) responded. In 71% of 772 laboratories, the hemolysis rate was less than 3.0%, whereas in 5%, it was 6.0% or greater. A visual scale, an instrument scale, and combination of visual and instrument scales were used to identify hemolysis in 48%, 11%, and 41% of laboratories, respectively. A picture of the hemolysis level was used as an aid to technologists' visual interpretation of hemolysis levels in 40% of laboratories. In 7.0% of laboratories, all hemolyzed specimens were rejected; in 4% of laboratories, no hemolyzed specimens were rejected; and in 88% of laboratories, some specimens were rejected depending on hemolysis levels. Participants used 69 different terms to describe hemolysis scales, with 21 terms used in more than 10 laboratories. Slight and moderate were the terms used most commonly. Of 16 different cutoffs used to reject hemolyzed specimens, moderate was the most common, occurring in 30% of laboratories. For whole blood electrolyte measurements performed in 86 laboratories, 57% did not evaluate the presence of hemolysis, but for those that did, the most common practice in 21 laboratories (24%) was centrifuging and visually determining the presence of hemolysis in all specimens., Conclusions: Hemolysis practices vary widely. Standard assessment and consistent reporting are the first steps in reducing interlaboratory variability among results.

Context: Hemolyzed specimens delay clinical laboratory results, proliferate unnecessary testing, complicate physician decisions, injure patients indirectly, and increase health care costs., Objective: To determine quality improvement practices when hemolysis occurs., Design: We used the College of American Pathologists (CAP) Survey Program to distribute a Q-Probes-type questionnaire about hemolysis practices to CAP Chemistry Survey participants., Results: Of 3495 participants sent the questionnaire, 846 (24%) responded. Although 85%, 69%, and 55% of participants had written hemolysis policies for potassium, lactate dehydrogenase, and glucose, respectively, only a few (46%, 40%, and 40%) had standardized hemolysis reports between their primary and secondary chemistry analyzers for these 3 analytes. Most participants (70%) had not attempted to validate the manufacturers' hemolysis data for these 3 analytes; however, essentially all who tried, succeeded. Forty-nine percent of participants had taken corrective action to reduce hemolysis during the past year and used, on average, 2.4 different actions, with collection and distribution of hemolysis data to administrative leadership (57%), troubleshooting outliers (55%), retraining phlebotomist (53%), and establishment of quality improvement teams among the laboratory and at problem locations (37%) being the most common actions. When asked to assess their progress in reducing hemolysis, 70% noted slow to no progress, and 2% gave up on improvement. Upon measuring potassium, lactate dehydrogenase, and glucose, approximately 60% of participants used the same specimen flag for hemolysis as for lipemia and icterus., Conclusions: Hemolysis decreases the quality and increases the cost of health care. Practices for measuring, reporting, and decreasing hemolysis rates need improvement.

Context: Many production systems employ standardized statistical monitors that measure defect rates and cycle times, as indices of performance quality. Clinical laboratory testing, a system that produces test results, is amenable to such monitoring., Objective: To demonstrate patterns in clinical laboratory testing defect rates and cycle time using 7 College of American Pathologists Q-Tracks program monitors., Design: Subscribers measured monthly rates of outpatient order-entry errors, identification band defects, and specimen rejections; median troponin order-to-report cycle times and rates of STAT test receipt-to-report turnaround time outliers; and critical values reporting event defects, and corrected reports. From these submissions Q-Tracks program staff produced quarterly and annual reports. These charted each subscriber's performance relative to other participating laboratories and aggregate and subgroup performance over time, dividing participants into best and median performers and performers with the most room to improve. Each monitor's patterns of change present percentile distributions of subscribers' performance in relation to monitoring durations and numbers of participating subscribers. Changes over time in defect frequencies and the cycle duration quantify effects on performance of monitor participation., Results: All monitors showed significant decreases in defect rates as the 7 monitors ran variously for 6, 6, 7, 11, 12, 13, and 13 years. The most striking decreases occurred among performers who initially had the most room to improve and among subscribers who participated the longest. All 7 monitors registered significant improvement. Participation effects improved between 0.85% and 5.1% per quarter of participation., Conclusions: Using statistical quality measures, collecting data monthly, and receiving reports quarterly and yearly, subscribers to a comparative monitoring program documented significant decreases in defect rates and shortening of a cycle time for 6 to 13 years in all 7 ongoing clinical laboratory quality monitors.

Context: The speed and accuracy of preliminary blood culture reports impacts patient management and outcomes., Objective: To evaluate the accuracy and timeliness of preliminary blood culture results among multiple laboratories., Design: Q-Probes participants collected turnaround time (TAT) data on preliminary Gram stains, compared accuracy of up to 100 preliminary to final culture Gram stain results, and described blood culture laboratory practices., Results: Sixty-four laboratories and 5031 blood cultures were evaluated. All participants used continuously monitoring blood culture systems. Median TAT from initial growth detection to notification of results was 45 minutes, with the longest component being preparation of Gram stains (median time = 25 minutes). Participants (N = 40) reporting a continuous schedule for processing blood cultures had significantly lower overall TAT (median= 37 minutes) compared with 15 participants with intermittent processing schedules (median= 124 minutes), P= .003. Time to complete Gram stain processing was lower (median time = 21 minutes) for 39 participants using continuous processing schedule compared with 14 others (median time= 67 minutes), P= .03. Goals for total TAT were used by 27 of 56 participants (48.2%). Having goals did not significantly affect TAT. A total of 4962 of 5021 Gram stain results (98.8%) agreed with final culture results. The highest discrepancy rates occurred among gram-positive bacilli (20 of 335; 6.0%) and mixed cultures (22 of 106; 20.8%)., Conclusions: This study provides benchmarks for assessing blood culture quality performance. Timeliness and accuracy of preliminary blood culture reports were excellent. However, nearly one-third of laboratories did not process blood cultures continuously. This significantly prolonged reporting results, which could affect patient outcomes.

Context: During the past 25 years, the College of American Pathologists' (CAP) Q-Probes program has been available as a subscription program to teach laboratorians how to improve the quality of clinical laboratory services., Objective: To determine the accomplishments of the CAP Q-Probes program., Design: We reviewed Q-Probes participant information, study data and conclusions, author information, and program accomplishments., Results: During this time 117 Q-Probes clinical pathology studies were conducted by 54 authors and coauthors, 42,899 laboratories enrolled from 24 countries, 98 peer-reviewed publications occurred and were cited more than 1600 times, and the studies were featured 59 times in CAP Today. The most frequent studies (19) focused on turnaround times for results or products at specific locations (emergency department, operating room, inpatients, outpatients), specific diseases (acute myocardial infarction, urinary tract), availability for specific events such as morning rounds or surgery, a specific result (positive blood cultures), and a method on how to use data for improvement (stat test outliers). Percentile ranking of study participants with better performance provided benchmarks for each study with attributes statistically defined that influenced improved performance. Other programs, such as an ongoing quality improvement program (Q-Tracks), a laboratory competency assessment program, a pathologist certification program, and an ongoing physician practice evaluation program (Evalumetrics), have been developed from Q-Probes studies., Conclusions: The CAP's Q-Probes program has made significant contributions to the medical literature and has developed a worldwide reputation for improving the quality of clinical pathology services worldwide.

Context: The Q-Tracks program, created in 1999, is a quality monitoring subscription service offered by the College of American Pathologists., Objective: To establish benchmarks in quality metrics, monitor changes in performance over time, and identify practice characteristics associated with better performance., Design: The Q-Tracks program provides ongoing study of multiple metrics offered in most laboratory disciplines. The design enables measuring the effects of process changes and comparisons with other participating laboratories. Each laboratory Q-Tracks monitor has a primary quality indicator and additional secondary indicators., Results: To date, 19 Q-Tracks monitors have been offered, with 12 currently active monitors. Q-Tracks are primarily conducted in hospital-based laboratories in the United States, Canada, and 21 other countries. Common to most Q-Tracks monitors is a demonstration of performance improvement by subscribers with long-term participation. This finding was seen in preanalytic, turnaround time, and postanalytic measures. Q-Tracks monitors contribute to the overall demonstration and improvement of laboratory and hospital quality because they address core quality measures for the College of American Pathologists Laboratory Accreditation Program and multiple Joint Commission National Patient Safety Goals., Conclusions: The Q-Tracks program has established multiple benchmarks in most disciplines of the laboratory and has demonstrated significant performance improvement in benchmarks and individual laboratories over time.

Context: The rate of surgical pathology report defects is an indicator of quality and it affects clinician satisfaction., Objective: To establish benchmarks for defect rates and defect fractions through a large, multi-institutional prospective application of standard taxonomy., Design: Participants in a 2011 Q-Probes study of the College of American Pathologists prospectively reviewed all surgical pathology reports that underwent changes to correct defects and reported details regarding the defects., Results: Seventy-three institutions reported 1688 report defects discovered in 360,218 accessioned cases, for an aggregate defect rate of 4.7 per 1000 cases. Median institutional defect rate was 5.7 per 1000 (10th to 90th percentile range, 13.5-0.9). Defect rates were higher in institutions with a pathology training program (8.5 versus 5.0 per 1000, P = .01) and when a set percentage of cases were reviewed after sign-out (median, 6.7 versus 3.8 per 1000, P = .10). Defect types were as follows: 14.6% misinterpretations, 13.3% misidentifications, 13.7% specimen defects, and 58.4% other report defects. Overall, defects were most often detected by pathologists (47.4%), followed by clinicians (22.0%). Misinterpretations and specimen defects were most often detected by pathologists (73.5% and 82.7% respectively, P < .001), while misidentifications were most often discovered by clinicians (44.6%, P < .001). Misidentification rates were lower when all malignancies were reviewed by a second pathologist before sign-out (0.0 versus 0.6 per 1000, P < .001), and specimen defect rates were lower when intradepartmental review of difficult cases was conducted after sign-out (0.0 versus 0.4 per 1000, P = .02)., Conclusion: This study provides benchmarking data on report defects and defect fractions using standardized taxonomy.

Rapid identification of pathogens directly from positive blood cultures can play a major role in reducing patient mortality rates. We evaluated the performance of the Verigene Gram-Positive Blood Culture (BC-GP) assay (Nanosphere Inc., Northbrook, IL) for detection of commonly isolated Gram-positive organisms as well as associated resistance markers from positive blood cultures. Positive blood cultures (VersaTREK; Trek Diagnostic Systems, Independence, OH) from 203 patients with Gram-positive organism infections were analyzed using the BC-GP assay within 12 h for the detection of 12 different organisms, including staphylococci, streptococci, and enterococci, as well as for the presence of 3 resistance markers (mecA, vanA, and vanB). Results were compared to those of routine laboratory methods for identification and susceptibility testing. For identification of organisms and detection of resistance markers in 178 monomicrobial positive blood cultures, the BC-GP assay showed 94% and 97% concordance, respectively, with routine methods. After 25 polymicrobial cultures were included, the results showed 92% and 96% agreement for identification and resistance markers, respectively, for a total of 203 positive cultures. In 6/25 polymicrobial cultures, at least 1 isolate was not detected. Concordance levels for detection of major pathogens such Staphylococcus aureus (n = 45) and enterococci (n = 19) were 98% and 95%, respectively. Agreement levels for detection of resistance markers such as mecA and vanA/B were 92% and 100%, respectively. The BC-GP assay is capable of providing rapid identification of Gram-positive cocci as well as detection of resistance markers directly from positive blood cultures at least 24 to 48 h earlier than conventional methods.

Context: Publicly available information concerning laboratory staffing benchmarks is scarce. One of the few publications on this topic summarized the findings of a Q-Probes study performed in 2004. This publication reports a similar survey with data collected in 2010., Objective: To assess the relationship between staffing levels in specified laboratory sections and test volumes in these sections and quantify management span of control., Design: The study defined 4 laboratory sections: anatomic pathology (including cytology), chemistry/hematology/immunology, microbiology, and transfusion medicine. It divided staff into 3 categories: management, nonmanagement (operational or bench staff), and doctoral (MD, PhD) supervisory staff. People in these categories were tabulated as full-time equivalents and exclusions specified. Tests were counted in uniform formats, specified for each laboratory section, according to Medicare rules for the bundling and unbundling of tests., Results: Ninety-eight participating institutions provided data that showed significant associations between test volumes and staffing for all 4 sections. There was wide variation in productivity based on volume. There was no relationship between testing volume per laboratory section and management span of control. Higher productivity in chemistry/hematology/immunology was associated with a higher fraction of tests coming from nonacute care patients. In both the 2004 and 2010 studies, productivity was inseparably linked to test volume., Conclusions: Higher test volume was associated with higher productivity ratios in chemistry/hematology/immunology and transfusion medicine sections. The impact of various testing services on productivity is section-specific.

Context: Accurate specimen labeling is a major patient-safety initiative by the Joint Commission and the College of American Pathologists. Inadequate specimen labels have led to patient injury from wrong patient diagnosis, wrong side treatment, and delay in diagnosis., Objectives: To quantify the rates of mislabeled cases, specimens, blocks, and slides and to identify the sources of error and the ways in which errors are detected., Design: In this voluntary-subscription Q-Probes study, participants prospectively reviewed surgical pathology cases for 8 weeks or until 30 errors (mislabeled cases, specimens, blocks, and slides) were identified. Information collected on each labeling error included the work location where the defect occurred, what was mislabeled, the number of items affected, the point of detection, and the consequences of the mislabeling error, along with institutional demographics and practice. The rates of mislabeled cases, specimens, blocks, and slides were tested for association with institutional demographics and practice variables., Results: Of the 136 institutions providing information on a total of 1811 mislabeling occurrences, the overall mislabeling rates per 1000 were 1.1 cases, 1.0 specimen, 1.7 blocks, and 1.1 slides. Of all mislabeling events, 27.1% were cases, 19.8% specimens, 25.5% blocks, and 27.7% slides. The work locations at which the errors occurred were 20.9% before accessioning, 12.4% at accessioning, 21.7% at block labeling, 10.2% during gross pathology, and 30.4% at tissue cutting. Errors were typically detected in the first or second steps immediately following the error. Lower mislabeled slide rates were associated with continuous individual case accessioning and use of formal checks at accessioning. Routinely including a statement in the gross description that the specimen is labeled with the patient's name and is properly identified was also associated with lower rates of specimen mislabeling. The errors were corrected before reports were issued 96.7% of the time; for 3.2% of errors, a corrected report was issued. In 1.3% of error occurrences, participants gauged that patient care was affected., Conclusions: This study quantified mislabeling rates across 136 institutions of cases (0.11%), specimens (0.1%), blocks (0.17%), and slides (0.11%). Errors in labeling appear nearly equally throughout the system of accessioning, gross pathology processing, and tissue cutting. Errors are typically detected in the immediate steps after the errors occurred, reinforcing the need for quality checks throughout the system.

Objectives: To determine the normative distribution of time elapsed for blood bank personnel to fill nonscheduled operating room (OR) blood component orders in hospital communities throughout the United States, and to examine hospital blood bank practices associated with faster blood component delivery times., Design: Participants in the College of American Pathologists Q-Probes laboratory quality improvement program collected data prospectively on the times elapsed for blood bank personnel to fill nonscheduled emergent orders from hospital ORs for red blood cell (RBC) products, fresh frozen plasma (FFP), and platelets (PLTs). Participants also completed questionnaires describing their hospitals' and blood banks' laboratory and transfusion practices., Setting and Participants: Four hundred sixty-six public and private institutions located in 48 states in the United States (n = 444), Canada (n = 9), Australia (n = 8), the United Kingdom (n = 4), and Spain (n = 1)., Main Outcome Measures: The median time elapsed between requests for blood components by OR personnel and the retrieval of those components by blood component transport personnel, and the median time elapsed between requests for blood components by OR personnel and the arrival of those components in ORs., Results: Participants submitted data on 12 647 units of RBCs, FFP, and PLTs. The median aggregate request-to-retrieval turnaround times (TATs) for RBCs, FFP, and PLTs ranged from 30 to 35 minutes, and the median aggregate request-to-arrival TATs for RBCs, FFP, and PLTs ranged from 33 to 39 minutes. Most of the TAT was consumed by events occurring prior to, rather than after release of components from blood banks. Shorter prerelease TATs were associated with having surgical schedules that listed patients' names and procedures available to blood bank personnel prior to surgeries, and having adequate clotted specimens in the blood bank and completed type-and-screen procedures performed before requests for blood components were submitted to blood banks. Among the fastest-performing 10% of participants (90th percentile and above), request-to-retrieval TATs ranged from 12 to 24 minutes for the 3 blood components, whereas among the slowest-performing 10% of participants (10th percentile and below), request-to-retrieval TATs ranged from 63 to 115 minutes for the 3 components. Median TATs ranged from 33 to 37 minutes for the 3 components. Institutions with TATs in the fastest-performing 25th percentile more frequently stored cross-matched RBCs in the OR daily, stocked PLTs for unexpected surgical use, stored PLTs in or near the OR, and had laboratory rather than nonlaboratory personnel deliver components to the OR than did those institutions with TATs in the slowest-performing 25th percentile., Conclusions: Hospital blood bank personnel can deliver blood components to the OR in slightly longer than 30 minutes, measured from the time that those units are requested by OR personnel. Practices aimed at saving time before components are released from blood banks will be more efficient in reducing overall TAT than those practices aimed at saving time after components are released from blood banks. Specific practices associated with shorter blood delivery TATs included providing blood bank personnel with access to the names of surgical patients potentially requiring blood components, having pretransfusion testing completed on those patients prior to surgery, having ample blood products on hand, and having laboratory personnel control blood product delivery.

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.

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.

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.

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.

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.

After oral surgery, a 32-year-old man developed a brain abscess. Actinomycosis was suspected due to history, clinical findings, response to penicillin therapy, and demonstration of "sulfur granules" in the surgical specimen, but anaerobic cultures were negative for Actinomyces. Aerobic cultures yielded Streptococcus sanguis and Pseudomonas cepacia. Coccoid organisms demonstrated histologically reacted positively with periodic acid-Schiff, Gomori's methenamine silver, and Brown and Brenn stains, were Ziehl-Neelsen-negative, and did not include branching filaments. Fluorescent antibody assay for Actinomyces israelii was also negative. Electron microscopy revealed cell wall morphology and pattern of cell division characteristic of gram-positive cocci. These findings led to a final diagnosis of botromycosis due to S. sanguis. This third report of cerebral botryomycosis emphasizes the differential diagnosis with actinomycosis, the association with intermittently treated jaw disease, and identification of the causative agent by histologic, immunologic, and electron microscopic methods.

We compared a fluorescent monoclonal antibody and a DNA probe for identification of Neisseria gonorrhoeae (GC) from primary genital cultures of presumptive GC and selected bacterial isolates other than GC. The monoclonal antibody was sensitive (94%) and specific (100%) enough to identify GC in selective primary genital culture. The DNA probe was sensitive (95%) but not adequately specific (65%) to function as a confirmatory test.

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.

Molecular laboratory techniques were used to study the epidemiology of an outbreak of nosocomial Legionnaires' disease. All patient isolates were Legionella pneumophila serogroup 1 and showed identical plasmid profiles and reactions with serogroup-specific monoclonal antibodies. L pneumophila was also cultured from four of five cooling tower water samples; however, the isolate from only one tower was serogroup 1 of the same subtype as patient isolates. Since the cases were temporally clustered and epidemiologically associated with exposure to cooling tower aerosols, the single cooling tower implicated by molecular analysis was the most likely source of the outbreak. Chlorination of cooling tower ponds has eradicated the epidemic strain. Since potable water also harbored the infecting organism and was the probable source for cooling tower contamination, decontamination of the hospital water system was also undertaken. Superchlorination of hot water holding tanks to 17 ppm on a weekly basis has effectively eradicated L pneumophila from the potable water system and appears to be a reasonable, simple, and relatively inexpensive alternative to previously described methods of control.

In the laboratory diagnosis of pharyngitis, results from latex agglutination tests (LAT) performed directly on throat swabs are often compared with the isolation of group A beta-hemolytic streptococci (GABHS) from simultaneously obtained swabs cultivated on a variety of media under different atmospheric conditions. In this study, results of an LAT, Directigen, were compared with those of two different media: sheep blood agar (SBA) and group A selective strep agar (ssA). Specimens inoculated on SBA were incubated in three different atmospheres: air, 3 to 5% CO2, and anaerobically. Those inoculated on ssA were incubated in 3 to 5% CO2 only. Isolation of GABHS was confirmed by coagglutination. The standard for true positivity was the isolation of GABHS from at least one of the simultaneous cultures. Comparisons were made with samples from 693 adult patients. GABHS was isolated on at least one of the three cultures in 143 patients, demonstrating an isolation rate of 20.6%. LAT exhibited a sensitivity of 95.1%. SBA incubated in air, in CO2, or anaerobically had sensitivities of 86.2, 85.9, and 93.7%, respectively. The ssA detected 99.3% of the positive specimens. Single SBA culture proved to be inferior to LAT and therefore was a poor standard for measuring LAT performance. Single ssA cultures demonstrated the greatest sensitivity in GABHS detection and therefore could serve as a standard for measuring LAT performance.