PLIN1 Haploinsufficiency Is Not Associated With Lipodystrophy.

Context: Monogenic partial lipodystrophy is a genetically heterogeneous disease where only variants with specific genetic mechanisms are causative. Three heterozygous protein extending frameshift variants in PLIN1 have been reported to cause a phenotype of partial lipodystrophy and insulin resistance. Objective: We investigated if null variants in PLIN1 cause lipodystrophy. Methods: As part of a targeted sequencing panel test, we sequenced PLIN1 in 2208 individuals. We also investigated the frequency of PLIN1 variants in the gnomAD database, and the type 2 diabetes knowledge portal. Results: We identified 6/2208 (1 in 368) individuals with a PLIN1 null variant. None of these individuals had clinical or biochemical evidence of overt lipodystrophy. Additionally, 14/17,000 (1 in 1214) individuals with PLIN1 null variants in the type 2 diabetes knowledge portal showed no association with biomarkers of lipodystrophy. PLIN1 null variants occur too frequently in gnomAD (126/138,632; 1 in 1100) to be a cause of rare overt monogenic partial lipodystrophy. Conclusions: Our study suggests that heterozygous variants that are predicted to result in PLIN1 haploinsufficiency are not a cause of familial partial lipodystrophy and should not be reported as disease-causing variants by diagnostic genetic testing laboratories. This finding is in keeping with other known monogenic causes of lipodystrophy, such as PPARG and LMNA, where only variants with specific genetic mechanisms cause lipodystrophy.

Development and initial validation of a project-based rubric to assess the systems-based practice competency of residents in the clinical chemistry rotation of a pathology residency.

CONTEXT: Systems-based practice (SBP) is 1 of 6 core competencies required in all resident training programs accredited by the Accreditation Council for Graduate Medical Education. Reliable methods of assessing resident competency in SBP have not been described in the medical literature. OBJECTIVE: To develop and validate an analytic grading rubric to assess pathology residents' analyses of SBP problems in clinical chemistry. DESIGN: Residents were assigned an SBP project based upon unmet clinical needs in the clinical chemistry laboratories. Using an iterative method, we created an analytic grading rubric based on critical thinking principles. Four faculty raters used the SBP project evaluation rubric to independently grade 11 residents' projects during their clinical chemistry rotations. Interrater reliability and Cronbach α were calculated to determine the reliability and validity of the rubric. Project mean scores and range were also assessed to determine whether the rubric differentiated resident critical thinking skills related to the SBP projects. RESULTS: Overall project scores ranged from 6.56 to 16.50 out of a possible 20 points. Cronbach α ranged from 0.91 to 0.96, indicating that the 4 rubric categories were internally consistent without significant overlap. Intraclass correlation coefficients ranged from 0.63 to 0.81, indicating moderate to strong interrater reliability. CONCLUSIONS: We report development and statistical analysis of a novel SBP project evaluation rubric. The results indicate the rubric can be used to reliably assess pathology residents' critical thinking skills in SBP.

Challenges and opportunities for medical directors in pathology and laboratory medicine: standardization, integration, and innovation.

Because the practice of pathology and laboratory medicine evolves rapidly, laboratory medical directors must constantly introduce new tests and services and continue to provide consistent, reliable results for existing tests. Innovations in laboratory medicine are frequently introduced, and the number of commercial vendors of test kits and reagents increases yearly. These innovations, however, may pose barriers to standardization and integration of laboratories and to interpretation of results generated by different laboratories. We propose a practical framework for medical directors to address the seemingly contradictory challenges of standardizing and integrating while simultaneously providing the flexibility to introduce innovations. We recommend initiating standardization first, then integration, while maintaining flexibility for innovation. As organizations strive to create effective processes to enhance value, the role of the laboratory medical director will become critical in resolving the natural tension between standardization/integration and innovation in laboratory medicine and pathology.

Continuous monitoring of stat and routine outlier turnaround times: two College of American Pathologists Q-Tracks monitors in 291 hospitals.

CONTEXT: The laboratory test turnaround times (TATs) that exceed the expectations of clinicians who order those tests, the so-called outlier test reporting rates, may be responsible for perceptions of inadequate laboratory service. OBJECTIVE: To monitor outlier test reporting rates for emergency department stat potassium results and routine inpatient morning blood tests. DESIGN: In 2 different monitors, each conducted for 2 years, laboratory personnel in institutions enrolled in the College of American Pathologists (CAP) Q-Tracks program tracked the percentages of emergency department stat potassium results and/or the percentages of morning rounds routine test results that were reported later than self-imposed reporting deadlines. SETTING: A total of 291 hospitals participating in 2 CAP Q-Tracks monitors. RESULTS: Participants monitored 225,140 stat emergency department potassium TATs, of which 33,402 (14.8%) were outliers, and 1,055040 routine morning test reporting times, of which 123,554 (11.7%) were outliers. For both monitors, there was a significant (P <.05) downward trend in the outlier rates as the number of quarters in which participants submitted data increased. CONCLUSION: Outlier reporting rates for emergency department stat potassium and routine morning test results decreased during the 2-year period of continuous monitoring. The CAP Q-Tracks program provides an effective vehicle by which providers of laboratory services may improve the timeliness with which they deliver the results of laboratory tests.

Biochemical markers of myocardial injury test turnaround time: a College of American Pathologists Q-Probes study of 7020 troponin and 4368 creatine kinase-MB determinations in 159 institutions.

CONTEXT: Rapid diagnosis of acute myocardial infarction in patients presenting to emergency departments (EDs) with chest pain may determine the types, and predict the outcomes of, the therapy those patients receive. The amount of time consumed in establishing diagnoses of acute myocardial infarction may depend in part on that consumed in the generation of the blood test results measuring myocardial injury. OBJECTIVE: To determine the normative rates of turnaround time (TAT) for biochemical markers of myocardial injury and to examine hospital and laboratory practices associated with faster TATs. DESIGN: Laboratory personnel in institutions enrolled in the College of American Pathologists Q-Probes Program measured the order-to-report TATs for serum creatine kinase-MB and/or serum troponin (I or T) for patients presenting to their hospital EDs with symptoms of acute myocardial infarction. Laboratory personnel also completed detailed questionnaires characterizing their laboratories' and hospitals' practices related to testing for biochemical markers of myocardial injury. ED physicians completed questionnaires indicating their satisfaction with testing for biochemical markers of myocardial injury in their hospitals. SETTING: A total of 159 hospitals, predominantly located in the United States, participating in the College of American Pathologists Q-Probes Program. RESULTS: Most (82%) laboratory participants indicated that they believed a reasonable order-to-report TATs for biochemical markers of myocardial injury to be 60 minutes or less. Most (75%) of the 1352 ED physicians who completed satisfaction questionnaires believed that the results of tests measuring myocardial injury should be reported back to them in 45 minutes or less, measured from the time that they ordered those tests. Participants submitted TAT data for 7020 troponin and 4368 creatine kinase-MB determinations. On average, they reported 90% of myocardial injury marker results in slightly more than 90 minutes measured from the time that those tests were ordered. Among the fastest performing 25% of participants (75th percentile and above), median order-to-report troponin and creatine kinase-MB TATs were equal to 50 and 48.3 minutes or less, respectively. Shorter troponin TATs were associated with performing cardiac marker studies in EDs or other peripheral laboratories compared to (1) performing tests in central hospital laboratories, and (2) having cardiac marker specimens obtained by laboratory rather than by nonlaboratory personnel. CONCLUSION: The TAT expectations of the ED physicians using the results of laboratory tests measuring myocardial injury exceed those of the laboratory personnel providing the results of those tests. The actual TATs of myocardial injury testing meet the expectations of neither the providers of those tests nor the users of those test results. Improving TAT performance will require that the providers and users of laboratory services work together to develop standards that meet the needs of the medical staff and that are reasonably achievable by laboratory personnel.

Specimen collection volumes for laboratory tests.

CONTEXT: Unnecessary tests, inefficient ordering practices, and collection of more blood than is required for testing contribute to iatrogenic anemia in hospitalized patients. Laboratories accredited by the College of American Pathologists are expected to review phlebotomy practices for specimen collection volumes periodically. OBJECTIVE: To report specimen collection, analytic, and discard volumes for routine laboratory tests and to identify practice variables associated with overcollection and blood wastage. DESIGN: Clinical laboratories participating in the College of American Pathologists Q-Probes laboratory improvement program recorded collection container size, laboratory-defined requested volume, manufacturer-defined analytic volume, and average discard volume for routine complete blood cell counts and electrolyte panels ordered for patients in intensive care units. Participants provided information about their specimen collection, processing, and analytic practices in a questionnaire. SETTING AND PARTICIPANTS: A total of 140 public and private institutions. MAIN OUTCOME MEASURES: Overcollections for routine collections and for situations in which a reduced volume of specimen is collected, and average discard volume per tube. RESULTS: Laboratories collected a median of 2.76 mL (or 8.5 times) more than their instrument's analytic volume for routine complete blood cell counts and 1.75 mL (or 12 times) more than their instrument's analytic volume for routine electrolyte panels. For clinical situations in which reduced collection volumes were necessary, overcollection for the same analytes was 0.5 mL (3 times) and 0.44 mL (4.2 times), respectively. The median discard volume was 2.8 mL/tube for complete blood cell counts and 2.0 mL/tube for electrolyte panels. Specimen collection container size was directly associated with overcollections and discard volumes. Instrument analytic volume was not a determinant of blood wastage. CONCLUSIONS: Most laboratories can decrease collection volumes without compromising the ability of the laboratory to report a reliable and timely result. Use of smaller collection tubes can help reduce blood wastage.

Testing for group a streptococci.

CONTEXT: Laboratory diagnosis of group A streptococcal pharyngitis in physician office and small-hospital laboratories. OBJECTIVE: To characterize laboratory practices for the diagnosis of group A streptococcal pharyngitis and to identify opportunities for improvement. DESIGN: Voluntary self-assessment questionnaire, used to assess the laboratory practices of 790 laboratories subscribing to the College of American Pathologists Excel Microbiology Proficiency Testing Program. RESULTS: We observed discrepancies between self-reported and recommended specimen collection and laboratory testing practices for some laboratories. The most notable discrepancies were failing to provide a written specimen-collection procedure (17.8%), sampling the tongue and oral mucosa (2%), failing to always perform back-up cultures when rapid antigen test results were negative (57.5%), and finalizing culture reports within 24 hours or less (34.0%). Additionally, among those respondents who used the bacitracin disk, 57.9% (277 respondents) applied the disk directly onto a primary plate. CONCLUSIONS: Opportunities exist to improve testing practices for the diagnosis of group A streptococcal pharyngitis for some physician office and small-hospital laboratories.

Accuracy of rapid strep testing in patients who have had recent streptococcal pharyngitis.

BACKGROUND: Some clinicians have questioned the accuracy of rapid diagnosis of group A streptococcal pharyngitis by commercial immunochemical antigen test kits in the setting of recent streptococcal pharyngitis, believing that the false-positive rate was increased because of presumed antigen persistence. METHODS: We studied 443 patients--211 cases--who had clinical pharyngitis diagnosed as group A beta-hemolytic streptococcus infection in the past 28 days and compared them with 232 control patients who had symptoms of pharyngitis but no recent diagnosis of streptococcal pharyngitis. Our aim was narrowly focused to compare the rapid strep test with the culture method we used in our clinical practice. RESULTS: We found that the rapid strep test in this setting showed no difference in specificity (0.96 vs 0.98); hence, the assertion that rapid antigen testing had higher false-positive rates in those with recent infection was not confirmed. We also found that in patients who had recent streptococcal pharyngitis, the rapid strep test appears to be more reliable (0.91 vs 0.70, P < .001) than in those patients who had not had recent streptococcal pharyngitis. CONCLUSIONS: The findings of this study indicate that the rapid strep test is both sensitive and specific in the setting of recent group A beta-hemolytic streptococcal pharyngitis, and its use might allow earlier treatment in this subgroup of patients.

Diurnal variation of serum iron, iron-binding capacity, transferrin saturation, and ferritin levels.

Serum iron levels vary throughout the day. Morning levels are generally assumed to be higher than afternoon or evening levels. We studied whether our practice of restricting serum iron collections to the morning was necessary. Serum iron, iron-binding capacity, transferrin saturation, and ferritin levels were determined on blood specimens obtained from 20 healthy adult volunteers at 8 AM, noon, and 4 PM (day 1) and 8 AM (day 2). Although statistically significant differences among mean values for the collection times were observed for iron, iron-binding capacity, and (log) ferritin, no consistent diurnal variation was seen. Morning iron levels were higher than afternoon levels for only half of the subjects. Between-day variation for all 4 analytes was similar to within-day variation. We conclude that the practice of restricting iron specimen collections to a specific time of day does not improve the reliability of the test result.

Outpatient phlebotomy success and reasons for specimen rejection.

OBJECTIVES: To determine the rate with which blood collection is successful on the initial phlebotomy encounter, the rate with which laboratory personnel judge specimens unsuitable for analysis, and the practice characteristics associated with fewer unsuccessful collections and fewer rejected specimens. DESIGN: Clinical laboratories participating in the College of American Pathologists Q-Probes laboratory improvement program prospectively characterized the outcome of outpatient phlebotomies for 3 months or until 20 unsuccessful phlebotomy encounters occurred. By questionnaire, participants provided information about test ordering, patient preparation, and specimen collection. SETTING AND PARTICIPANTS: Institutions in the United States (n = 202), Canada (n = 4), Australia (n = 3), and South Korea (n = 1). MAIN OUTCOME MEASURES: Percentage of successful encounters and percentage of unsuitable specimens. RESULTS: Of 833289 encounters, 829723 were successful. Phlebotomies were unsuccessful because patients were not fasting as directed (32.2%), phlebotomy orders were missing information (22.5%), patients specimens were difficult to draw (13.0%), patients left the collection area before specimens were collected (11.8%), patients were improperly prepared for reasons other than fasting (6.3%), patients presented at the wrong time (3.1%), or for other reasons (11.8%). Only 2153 specimens (0.3%) were unsuitable; these samples were hemolyzed (18.1%), of insufficient quantity (16.0%), clotted (13.4%), lost or not received in the laboratory (11.5%), inadequately labeled (5.8%), at variance with previous or expected results (4.8%), or unacceptable for other reasons (31.1%). Facilities staffed by laboratory-administered phlebotomists reported higher success rates than facilities staffed by nonlaboratory-administered phlebotomists (P =.002). CONCLUSIONS: Most outpatient phlebotomy encounters are successful and result in specimens suitable for laboratory analysis.