The Laboratory Stewardship Committee of the Cleveland Clinic is a multidisciplinary team of clinicians, pathologists, administrators, nurses and other caregivers.  The team has a commitment to work toward optimizing test utilization to promote best practices and the best possible patient care.  The goals include: working to decrease unnecessary phlebotomy, which in turn improves patient satisfaction and decreases the likelihood of iatrogenic anemia and the sequelae thereof; reduction of unnecessary daily and duplicate orders; the conscientious use of molecular testing; the promotion of best practices; the development of evidence-based guidelines for optimal testing; and, the reduction of health care costs through thoughtful and judicious use of healthcare resources.  

Ten ongoing interventions have been integrated into the Cleveland Clinic practice since 2011.  These interventions deter duplicate or largely unnecessary tests (e.g., unneeded repetitive daily orders), notify providers of duplicate and expensive tests, and provide guidance for the use of complex molecular genetic testing.  These interventions in 2018 stopped 49,071 unnecessary tests for a cost-savings of $875,876.  These interventions, in aggregate since 2011, have resulted in the cessation of 209,143 unnecessary tests, which has saved $5,935,942.

Learning Objectives:
1. List at least 5 criteria that are important for building an effective Laboratory Stewardship committee.
2. Support tools in conjunction with Computerized Physician/Provider Order Entry.
3. Compare and contrast three of the methods discussed that were used to address expensive and/or molecular tests.

Thyroid autoimmunity (TAI) tends to be more common in women consulting for fertility problems. However, any underlying causal mechanism connecting TAI to fertility aspects is yet to be established. Increased levels of anti-thyroid peroxidase abs (TPO-abs) have been defined as the most sensitive marker of TAI and are linked to the risk of (sub) clinical hypothyroidism. Therefore,  most studies investigating the prevalence of TAI in infertile women or any relation between TAI and pregnancy outcomes are based on the presence of TPO-abs  alone and do not consider the impact of thyroglobulin autoantibodies (Tg-abs). Assisted reproductive technology (ART) is often proposed as a treatment option for couples confronted with fertility problems. TAI has been linked to adverse pregnancy outcome with an increased risk of miscarriage and preterm delivery in spontaneous pregnancy as well as in pregnancy after ART. Since the late 1990s numerous studies have been published on the impact of TAI and pre-conception TSH thresholds on the outcome after ART. The outcome of these studies is often conflicting.   Therefore, todays guidelines on the management of TAI in the particular case of ART are based on limited evidence.

The present presentation we will give an overview on the association of TAI and female infertility. Underlying possible mechanisms that may connect TAI to fertility issues will be discussed. In addition, evidence on the impact of TAI, pre-conception TSH thresholds and possible benefit of levothyroxine treatment on outcome after ART will be reviewed.

Breast cancer is the most frequently occurring form of cancer in women.  Whilst 5-year survival rates for localized disease approach 99%, cases of advanced breast cancer have a much poorer prognosis, with 5-year survival of around 27%.  Therefore, new treatment modalities for this indication are clearly welcome.  The Novartis drug PIQRAYTM (alpelisib) is the first -selective PI3Kinase inhibitor to be approved by the FDA for treatment of cases of advanced Hormone Receptor +ve / HER2 -ve breast cancer that also harbour activating mutations in the PIK3CA gene.  There are present in about 40% of cases, and therefore, it is necessary to use a companion diagnostic (CDx) test to identify patients eligible for treatment.  The therascreen PIK3CA RGQ PCR Kit is a rapid and reliable test, able to detect the presence of any of the 11 clinically actionable PIK3CA mutations in DNA from both FFPE tumor tissue and plasma specimens.  Clinically validated during the SOLAR-1 clinical trial, this test is currently the only FDA-approved CDx for this indication.  Available in the USA since May 2019, the Kit supports the delivery of precision medicine to patients for whom few other treatment options may remain.

Thyroid function tests play a central role to assess thyroid function and are valuable companions for clinicians. The evolution of the tests is permanent and clinical laboratories are key players in defining decision limits and validating new methods. In addition, several standardization efforts are also underway and will have an impact on test performance.

However, thyroid function tests can be sensitive to different types of interference and therefore have an impact on the clinical decision. Such interference may be suspected in the event of clinical and / or biological discrepancies. Their identification is based on additional laboratory tests including a comparison of assay methods, dilution procedures, blocking reagent studies, and polyethylene glycol precipitation. Interdisciplinary exchanges with clinical teams are essential to identify these interferences and continue to improve the performance of our assays.

Applying machine learning methods to structured, expert-curated content from scientific literature is a powerful way to discover latent knowledge. Building on the QIAGEN Knowledge Base, we use this approach to infer new disease-gene associations, build network-based disease models, and interpret gene expression data in order to create actionable hypotheses.

Random drug testing is used as a preventive and detection tool for drug or alcohol use, and medication compliance in the monitoring of regulatory and treatment compliance monitoring. Urine screening is generally viewed as the preferred method for assessing substance use and may be supplemented with hair, blood or nail testing to assess for drug use over long periods. A positive drug test does not provide information about the levels of impairment but only that a drug or substance was used within the detection period and requires immediate attention. Selection of competent laboratories and Medical Review Officer support is essential to ensure accurate drug testing and evaluation.

Central to the diagnosis and management of patients with diabetes mellitus is the measurement of hemoglobin A1c (HbA1c).  Major studies have defined the therapeutic targets of HbA1c in order to reduce the risk of the complications arising from the disease.  Through the NGSP, proficiency testing (PT) has played an important role to uphold the standardization of HbA1c assays and support the reliability of results across the globe.  PT provides an objective assessment of method performance in the hands of the end-user such that HbA1c results continue to be traceable to the reference methods.  The analytical improvements over time have led to the international endorsement of HbA1c as a screening and diagnostic test for diabetes.

Learning objectives:
1. State the benefits of an accuracy-based proficiency testing scheme for HbA1c.
2. Understand the traceability of HbA1c assays to the NGSP and IFCC reference methods.

70,237 drug overdose deaths occurred in the United States in 2017 and opioids were involved in 47,600 of those deaths (67.8%).1 Ohio had the second highest rate of opioid overdose deaths in the U.S. in 2017, with 4,293 reported deaths (39.2 deaths per 100,000 persons) compared to the average national rate of 14.6 deaths per 100,000 persons.2
 
The states with the highest rates of death in 2017 due to drug overdose were West Virginia (57.8 per 100,000), Ohio (46.3 per 100,000), Pennsylvania (44.3 per 100,000), the District of Columbia (44.0 per 100,000), and Kentucky (37.2 per 100,000).1
 
The continual influx of newer synthetic opioids has proven a challenge to physicians, healthcare professionals, forensic scientists, and medical examiners in clinical and forensic settings. A brief overview of opioid pharmacology, history and regional trends will be presented as well as the details of how one synthetic opioid, new to Ohio in 2016, was discovered and dealt with by legislative means.
 
After attending this presentation, attendees will:

1. Recognize the nature of opioids as psychoactive substances
2. Understand how the rapid introduction of synthetic opioids in the illicit drug market makes identification difficult for clinical and forensic laboratories.
 

References:
 
1.Scholl L, Seth P, Kariisa M, Wilson N, Baldwin G. Drug and Opioid-Involved Overdose Deaths – United States, 2013-2017. Morb Mortal Wkly Rep. ePub: 21 December 2018.
 
2.National Institute on Drug Abuse (NIDA) Ohio Opioid Summary - March 2019

Burn patients are at risk for organ dysfunction secondary to “burn shock” and sepsis. The initial 24 hours following major burn injury presents with significant hypotension due to profound systemic inflammation. This severe hypotension is further exacerbated by excessive evaporative water loss directly from the burn wound. Following the acute resuscitation period, burn patients are also at high risk for infection with sepsis-related multi-organ dysfunction being the most frequent cause of burn-related deaths. Acute kidney injury (AKI) is reported to be the most common type of organ dysfunction in both “burn shock” and sepsis.

Traditional indicators of AKI include creatinine and urine output. Unfortunately, both biomarkers have known limitations—delaying recognition of AKI. The use of artificial intelligence (AI) and machine learning (ML) has been proposed to offset these limitations. Our study implemented the first AI/ML algorithm to quickly predict sepsis and AKI with and without novel renal injury biomarkers such as neutrophil gelatinase associated lipocalin (NGAL). For sepsis, our custom AI/ML technique exhibited clinical sensitivity and specificity superior to burn sepsis criteria recommended by the American Burn Association. For AKI, a separate AI/ML algorithm was developed and predicted AKI in burn patients nearly two days earlier than traditional techniques. This same AI/ML algorithm was then tested (generalization) in a mixed burned and non-burned trauma patient population. As in the burn-only cohort, the AI/ML algorithm enhanced the performance of traditional biomarkers.

Artificial intelligence and ML may enable early recognition of challenging diseases such as AKI and sepsis in high-risk populations. Interestingly, AI/ML could enhance the predictive performance of legacy disease biomarkers. More studies are needed to determine the clinical impact of early sepsis and AKI recognition by AI/ML in the severely burned population.

Learning Objectives:

1. Describe the current state of artificial intelligence (AI) / machine learning (ML) in society versus laboratory medicine.
2. Identify best practices for developing and validating a health-related AI/ML algorithm.
3. Describe the clinical value of AI/ML for burn-related sepsis and acute kidney injury.

Facioscapulohumeral muscular dystrophy (FSHD), one of the most common forms of progressive muscular dystrophies and is often conventionally diagnosed by Southern blot analysis. The accurate detection involves the identification of the D4Z4 microsatellite repeat contractions. High-throughput optical mapping of those repeats using the Bionano Saphyr® genome imaging platform provides multiple advantages and aids in the proper detection of the repeat contractions to improve molecular detection of FSHD. In addition to the repeat size and haplotype information, it gives a high resolution view of the repeat regions and has a higher sensitivity to mosaic alleles. The PerkinElmer Genomics laboratory recently analyzed known publicly available FSHD cell lines, clinical specimens, and control samples using the Saphyr platform and recently launched Bionano EnFocusTM FSHD analysis tool, and found expected repeat contractions in the FSHD-positive samples. Accuracy and precision studies demonstrate the robustness of this platform.
 
For Research Use Only. Not for use in diagnostic procedures.