Evaluation of a microarray-based assay for rapid identification of Gram-positive organisms and resistance markers in positive blood cultures.

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.

Paenibacillus spp infection among infants with postinfectious hydrocephalus in Uganda: an observational case-control study.

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.

Discordant Streptococcus agalactiae (Group B streptococcus) gestational infection in monochorionic/diamniotic and dichorionic/diamniotic twins.

Infection due to Streptococcus agalactiae or Group B streptococcus may be acquired during parturition or gestation. Discordant twin gestational Group B streptococcus infections are rarely reported. We describe two cases of fatal discordant gestational Group B streptococcus infection in both a monochorionic/diamniotic pregnancy and in a dichorionic/diamniotic pregnancy. In both instances, cultures, examination of the placentae, and autopsy findings demonstrated infection by Group B streptococcus in only the presenting fetus. Despite the ubiquity of this organism, this is the first documented case of discordant gestational Group B streptococcus infection in monochorionic/diamniotic twins and only the third case documented in dichorionic/diamniotic twins.

Building Perinatal Pathology Research Capacity in Sub-Saharan Africa.

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.

Cytomegalovirus infections in infants in Uganda: Newborn-mother pairs, neonates with sepsis, and infants with hydrocephalus.

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.

Study of amended reports to evaluate and improve surgical pathology processes.

BACKGROUND: : Amended surgical pathology reports record defects in the process of transforming tissue specimens into diagnostic information. OBJECTIVE: : Systematic study of amended reports tests 2 hypotheses: (a) that tracking amendment frequencies and the distribution of amendment types reveals relevant aspects of quality in surgical pathology's daily transformation of specimens into diagnoses and (b) that such tracking measures the effect, or lack of effect, of efforts to improve surgical pathology processes. MATERIALS AND METHODS: : We applied a binary definition of altered reports as either amendments or addenda and a taxonomy of defects that caused amendments as misidentifications, specimen defects, misinterpretations, and report defects. During the introduction of a LEAN process improvement approach-the Henry Ford Productions System-we followed trends in amendment rates and defect fractions to (a) evaluate specific interventions, (b) sort case-by-case root causes of misidentifications, specimen defects, and misinterpretations, and (c) audit the ongoing accuracy of the classification of changed reports. LEAN is the management and production system of the Toyota Motor Corporation that promotes continuous improvement; it considers wasted resources expended for purposes other than creating value for end customers and targets such expenditures for elimination. RESULTS: : Introduction of real-time editing of amendments saw annual amendment rates increase from 4.8/1000 to 10.1/1000 and then decrease in an incremental manner to 5.6/1000 as Henry Ford Productions System-specific interventions were introduced. Before introduction of HFPS interventions, about a fifth of the amendments were due to misidentifications, a 10th were due to specimen defects, a quarter due to misinterpretation, and almost half were due to report defects. During the period of the initial application of HFPS, the fraction of amendments due to misidentifications decreased as those due to report defects increased, in a statistically linked manner. As HFPS interventions took hold, misidentifications fell from 16% to 9%, specimen defect rates remained variable, ranging between 2% and 11%, and misinterpretations fell from 18% to 3%. Reciprocally, report defects rose from 64% to 83% of all amendment-causing defects. A case-by-case study of misidentifications, specimen defects, and misinterpretations found that (a) intervention at the specimen collection level had disappointingly little effect on patient misidentifications; (b) standardization of specimen accession and gross examination reduced only specimen defects surrounding ancillary testing; but (c) a double review of breast and prostate cases was associated with drastically reduced misinterpretation defects. Finally, audit of both amendments and addenda demonstrated that 10% of the so-called addenda actually qualified as amendments. DISCUSSION: : Monitored by the consistent taxonomy, rates of amended reports first rose, then fell. Examining specific defect categories provided information for evaluating specific LEAN interventions. Tracking the downward trend of amendment rates seemed to document the overall success of surgical pathology quality improvement efforts. Process improvements modestly decreased fractions of misidentifications and markedly decreased misinterpretation fractions. Classification integrity requires real time, independent editing of both amendments (changed reports) and addenda (addition to reports).

Vaginal microbiome topic modeling of laboring Ugandan women with and without fever.

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.

Amended reports: development and validation of a taxonomy of defects.

Amended pathology reports produce rework, confusion, and distrust. To develop a reproducible amendment taxonomy we derived a classification from 141 amended reports, then validated it with 130 new cases before 4 observers independently reviewed 430 cases measuring agreement (k). Next, agreement in classifying 30 other amended reports in 7 institutions was measured. We further tracked amendment rates, defect categories, defect discoverers, and discovery mechanisms. In the 430-case validation set agreement was excellent (k = 0.8780 [range, 0.8416-0.9144]). Among the 7 institutions, agreement was good (k = 0.6235 [range, 0.3105-0.8975]). Amendment rates ranged from 2.6 to 4.8 per 1,000 reports. Misinterpretation fractions varied least (23%-29%). Misidentification fractions ranged more widely (20%-38%). Specimen defects were least frequent (4%-10%) and report defects most frequent (29%-48%). Misidentifications and report defects inversely correlated. Pathologists discovered most misinterpretations, and clinicians found most misidentifications. Conference review revealed 40% to 80% of misinterpretations. This taxonomy produced excellent reproducibility and good agreement across institutions.

Eosinophilic globules in 3 cases of glomeruloid hemangioma of the head and neck: a characteristic offering more evidence for thanatosomes with or without POEMS.

Glomeruloid hemangiomas (GHs) are glomeruli-like capillary tufts lined by endothelial cells that contain periodic acid-Schiff (PAS) positive eosinophilic globules (EGs). These hemangiomas are characteristic cutaneous manifestation of POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, and Skin changes). Hemangiomas histologically identical to GHs but not associated with POEMS have recently been designated as papillary hemangiomas. In this report, we present solitary head and neck GHs in 3 patients, 2 without POEMS, with particular attention to the characteristic EGs. We performed immunostains for hemoglobin A, kappa and lambda light chains, factor VIII-related antigen, CD31 and CD34, PAS stain after diastase digestion (PASD), and electron microscopic examinations on routinely fixed tissues containing EGs. Eosinophilic globules stained uniformly positive for PASD but only peripherally positive for hemoglobin and light chains on surfaces, with interiors negative for antigens. Factor VIII-related antigen and CD31 and CD34 confirmed cells containing EGs to be endothelial. Electron microscopic examination suggested that EGs are enlarged secondary lysosomes (thanatosomes). These features fail to support red blood cells or immunoglobulins as EG constituents. Glomeruloid hemangiomas may be vascular proliferations stimulated by endothelial cells' protein phagocytosis but not by phagocytosis of either hemoglobin-containing red blood cells or immunoglobulins. The vascular lesions in POEMS syndrome appear identical to papillary hemangioma in cases without the other syndromic manifestations.

What's to Be Done About Laboratory Quality? Process Indicators, Laboratory Stewardship, the Outcomes Problem, Risk Assessment, and Economic Value: Responding to Contemporary Global Challenges.

OBJECTIVES: For 50 years, structure, process, and outcomes measures have assessed health care quality. For clinical laboratories, structural quality has generally been assessed by inspection. For assessing process, quality indicators (QIs), statistical monitors of steps in the clinical laboratory total testing, have proliferated across the globe. Connections between structural and process laboratory measures and patient outcomes, however, have rarely been demonstrated. METHODS: To inform further development of clinical laboratory quality systems, we conducted a selective but worldwide review of publications on clinical laboratory quality assessment. RESULTS: Some QIs, like seven generic College of American Pathologists Q-Tracks monitors, have demonstrated significant process improvement; other measures have uncovered critical opportunities to improve test selection and result management. The College of Pathologists of Australasia Key Indicator Monitoring and Management System has deployed risk calculations, introduced from failure mode effects analysis, as surrogate measures for outcomes. Showing economic value from clinical laboratory testing quality is a challenge. CONCLUSIONS: Clinical laboratories should converge on fewer (7-14) rather than more (21-35) process monitors; monitors should cover all steps of the testing process under laboratory control and include especially high-risk specimen-quality QIs. Clinical laboratory stewardship, the combination of education interventions among clinician test orderers and report consumers with revision of test order formats and result reporting schemes, improves test ordering, but improving result reception is more difficult. Risk calculation reorders the importance of quality monitors by balancing three probabilities: defect frequency, weight of potential harm, and detection difficulty. The triple approach of (1) a more focused suite of generic consensus quality indicators, (2) more active clinical laboratory testing stewardship, and (3) integration of formal risk assessment, rather than competing with economic value, enhances it.

Frequency and outcome of cervical cancer prevention failures in the United States.

We measured the frequency and outcome of cervical cancer prevention failures that occurred in the Papanicolaou (Pap) and colposcopy testing phases involving 1,646,580 Pap tests in 4 American hospital systems between January 1, 1998, and December 31, 2004. We defined a screening failure as a 2-step or greater discordant Pap test result and follow-up biopsy diagnosis. A total of 5,278 failures were detected (0.321% of all Pap tests); 48% and 52% of failures occurred in the Pap test and colposcopy phases, respectively. Missed squamous cancers (1 in 187,786 Pap tests), glandular cancers (1 in 19,426 Pap tests), and high-grade lesions (1 in 6,870 Pap tests) constituted 4.1% of all failures. Unnecessary repeated tests or diagnostic delays occurred in 70.8% and 63.9% of failures involving high- and low-grade lesions, respectively. We conclude that cervical cancer prevention practices are remarkably successful in preventing squamous cancers, although a high frequency of failures results in low-impact negative outcomes.

Double slide viewing as a cytology quality improvement initiative.

Few studies have measured the effect of pre-sign out double viewing of cytology cases as a means to decrease error. Three Agency for Healthcare Research and Quality-funded project sites performed pre-sign out double viewing of 431 pulmonary cytology cases. Two-step or more differences in diagnosis were arbitrated as interpretive errors, and the effect of double viewing was measured by comparing the frequency of cytologic-histologic correlation-detected errors in the previous 2 years with the double-viewing period. The number of interpretive errors detected by double viewing for the 3 institutions was 2.7%, 0% and 1.9%, respectively. Double viewing did not lower the frequency of cytologic-histologic correlation false-negative errors. We conclude that double viewing detects errors in up to 1 of every 37 cases and that biases in the double-viewing process limit error detection.

Errors in thyroid gland fine-needle aspiration.

Scant published data exist on redesigning pathology practice based on error data. In this first step of an Agency for Healthcare Research and Quality patient safety project, we measured the performance metrics of thyroid gland fine-needle aspiration, performed root cause analysis to determine the causes of error, and proposed error-reduction initiatives to address specific errors. Eleven cytologists signed out 1,543 thyroid gland aspirates in 2 years, and surgical pathology follow-up was obtained in 364 patients. Of the 364 patients, 91 (25.0%) had a false-negative diagnosis and 36 (9.9%) a false-positive diagnosis. Root cause analysis showed that major sources of error were pre-analytic (poor specimen quality) and analytic (interpretation of unsatisfactory specimens as nonneoplastic and lack of diagnostic category standardization). We currently are evaluating the effectiveness of error reduction initiatives that target pre-analytic and analytic portions of the diagnostic pathway.

Use of a new method in reaching consensus on the cause of cytologic-histologic correlation discrepancy.

Pathologists exhibit very poor agreement in adjudicating the cause of cytologic-histologic correlation discrepancies, which contributes to problems in designing interventions to reduce discrepancy frequency. In this observational study, we developed a visual method of adjudicating discrepancy cause, termed the No-Blame Box method, which consisted of initially assessing specimen interpretability by separately evaluating specimen quality and the presence of tumor. Five pathologists blindly adjudicated the cause of discrepancy in pulmonary specimens from 40 patients. The kappa statistic of all pathologist pairs in adjudicating discrepancy cause using the No-Blame Box method ranged from 0.400 to 0.796, indicating acceptable to excellent agreement. Pathologists ranged in their assessment of specimen interpretability from 13% to 20%, and in no case did all 5 pathologists concur that a specimen was interpretable. Most discrepancies resulted from pathologists diagnosing noninterpretable samples. Pathologists who used the No-Blame Box showed significant agreement in the adjudication of discrepancy cause.

Interpretive Diagnostic Error Reduction in Surgical Pathology and Cytology: Guideline From the College of American Pathologists Pathology and Laboratory Quality Center and the Association of Directors of Anatomic and Surgical Pathology.

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.

Timeliness and accuracy of reporting preliminary blood culture results: a College of American Pathologists Q-probes study of 65 institutions.

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.

Clinical Laboratory Quality Practices When Hemolysis Occurs.

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.

Practices for Identifying and Rejecting Hemolyzed Specimens Are Highly Variable in Clinical Laboratories.

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.

Correlation of High Body Mass Index With More Advanced Localized Prostate Cancer at Radical Prostatectomy Is Not Reflected in PSA Level and PSA Density but Is Seen in PSA Mass.

OBJECTIVES: Prostate cancer screening algorithms and preoperative nomograms do not include patients' body mass index (BMI). We evaluated outcomes at radical prostatectomy (RP) adjusted to BMI. METHODS: Serum prostate-specific antigen (PSA) levels, PSA mass, PSA density (PSAD), and RP findings were analyzed with respect to BMI in 4,926 men who underwent RP between 2005 and 2014. RESULTS: In total, 1,001 (20.3%) men were normal weight, 2,547 (51.7%) were overweight, and 1,378 (28%) were obese. Median PSA levels (ng/mL) were normal weight, 5.0; overweight, 5.1; and obese, 5.2 (P = .094). Median PSA mass increased with increasing BMI: 15.9 vs 17.4 vs 19.4 µg (P < .001). Median PSAD was not significantly different: 0.11 vs 0.11 vs 0.11 ng/mL/g (P = .084). Median prostate weight increased with increasing BMI: 44 vs 45 vs 49 g (P < .001). Median prostatectomy tumor volume increased with increasing BMI: 3.9 vs 4.7 vs 5.9 cm(3) (P < .001). Overweight and obese patients had a higher Gleason score and more locally advanced cancer (P < .001). Frequency of positive surgical margins increased with higher BMIs (P < .001). Frequency of lymph node metastasis did not differ significantly (P = .088). CONCLUSIONS: While BMI correlates with tumor volume, Gleason score, and extent of disease at RP, there is no routinely measured clinical parameter reflecting this. Only PSA mass highlights this correlation. Thus, BMI and potentially PSA mass should be taken into account in predictive algorithms pertaining to prostate cancer and its surgical treatment.

Assessing Clinical Laboratory Quality: A College of American Pathologists Q-Probes Study of Prothrombin Time INR Structures, Processes, and Outcomes in 98 Laboratories.

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.