Clinical Science: Clinical Laboratory & Diagnostics PDF

Clinical Science: Clinical Laboratory & Diagnostics Overview, Introduction & Behavioral Medicine Agnes Compagnone, DMSc, PA-C October 8, 2024  Course Section-Overview & Introduction (10-15 minutes) Behavioral Medicine (40-50...

Clinical Science: Clinical Laboratory & Diagnostics Overview, Introduction & Behavioral Medicine Agnes Compagnone, DMSc, PA-C October 8, 2024  Course Section-Overview & Introduction (10-15 minutes) Behavioral Medicine (40-50 minutes) WELCOME Break (5-10 minutes) Wrap-up/Q&A/Active learning exercises (10-20 minutes)  Context in training (What & Why: Diagnostics & Diagnostic Studies) Course Approach Section: Overview Expectations Teaching Style  DIAGNOSTICS “Diagnostics..…important tools that empower the health workforce in the identification of diseases or DEFINITION health conditions” World Health Organization (WHO) https://www.who.int/health-topics/diagnostics#tab=tab_1 WHAT & WHY… DIAGNOSTICS (TOOLS) DIAGNOSTIC STUDIES History Diagnostic tests Physical exam/vitals Radiological tests Screenings Imaging studies Imaging/radiology Laboratory tests Laboratory tests Laboratory studies Procedures Digital health applications Medical devices WHAT & WHY: DIAGNOSTIC STUDIES(DIAGNOSTICS) WHY-IMPORTANT CLINICAL DECISION MAKING Diagnosis Health conditions-similar symptoms Systematic approach Screening Formulate a differential diagnosis Monitoring Diagnose “rule in” or” rule out” Final diagnosis Management & treatment plans Clinical Decision Making (LO5)  Objectives will drive content & assessment Focus areas condense information Supplemental material integrated to enhance learning Approach Longitudinal approach supporting spiral curriculum Basic lab and diagnostic principles interwoven Emphasis-appropriately utilizing diagnostic studies tools to achieve best health outcomes Teaching Style Highly Value: experiential and collaborative learning Employ: active learning, reflection & group activities Enhance critical clinical reasoning, critical thinking, and non-cognitive skills Growth Mindset: continuous learning and improvement Student Experience: Important to me, have fun & enjoy! MY GOAL: Great Clinicians Great Clinicians "The good physician treats the disease; the great physician treats the patient who has the disease". William Osler A Little About Me Agnes Compagnone, DMSc, MPAS, PA-C Behavioral Medicine Clinical Science: Clinical Laboratory & Diagnostics Agnes Compagnone, DMSc, PA-C  Objectives 1. Discuss common laboratory and diagnostic studies in behavioral medicine. 2. Describe considerations for ordering laboratory and diagnostic studies in behavioral medicine. 3. Select appropriate laboratory and diagnostic studies for assessing common behavioral medicine conditions. 4. Interpret laboratory and diagnostic studies relevant to behavioral medicine. 5. Integrate behavioral medicine laboratory and diagnostic studies to formulate differential and final diagnoses. Overview Role of laboratory and diagnostic studies in Behavior medicine Define focus areas Highlight lab principles Review common behavioral health conditions and considerations for ordering associated lab & diagnostic studies Practice selecting & interpreting diagnostic studies  BEHAVIORAL MEDICINE IS Role of COMPLEX Screening Laboratory Monitoring & Patient management Substance abuse and addiction Diagnostic treatment Differential Diagnoses Studies Ruling in or out medical condition (organic cause) LAB BASICS Impact test considerations and interpretation Reference Ranges/Values CLINICAL PEARL* High & Low number values Define normal results Labs use different ranges and methodologies to define normal results* Common units of measure Mcg/dL = micrograms per deciliter Micromole/L = micromoles per liter Pg/mL = picograms per milliliter LAB BASICS Impact test considerations and interpretation *Recommend patients return to same Labs use different ranges and laboratories when comparing lab data, methodologies to define normal repeating labs, utilizing lab studies for results* treatment and monitoring purposes. LAB BASICS Impact test considerations and interpretation Negative, Positive, or Inconclusive Negative (normal) Didn’t find what assessing/rule out Positive (abnormal) Found what looking for/rule in Inconclusive (uncertain)/Invalid Unsure, not clearly negative or positive  LAB BASICS Sensitivity The probability that a patient with a disease/condition (or intake of an end-product assessing) will have a positive test result The ability of a diagnostic study/test to designate a person with a disease/condition (or intake of an end-product assessing) as positive Note: Higher sensitivity = fewer false positives Specificity The probability that a patient without the disease/condition (or intake of an end-product assessing) will have a negative test result The ability of diagnostic study/test to designate a person without the disease/disease (or intake of an end-product assessing) as negative. LAB BASICS SERUM Reduced variability: Results are Blood sample minus all blood less inconsistent between cell components samples Yellow fluid left in tube Increased sensitivity: Results are more sensitive Preferred methodology over blood when assessing Fewer false results: Results are substances via blood sample less likely to be false positives or negatives Less interference with other blood products/elements SERUM SAMPLES RED TOP Yellow TOP with coagulant agent  Clinical Conditions Anxiety Disorders Depression Bipolar disorder Areas of Substance Abuse Focus Laboratory Studies Substance Abuse-Urine Drug Testing (interpreting) Lithium Levels (interpreting) Vitamin B12/MMA (consideration/selecting) TSH/T4 (consideration/selecting)  Anxiety Disorders: Differential Diagnoses BACKGROUND INFORMATION Most common psychiatric disorders (APA) Often generate physical symptoms; see Primary Care Providers Symptoms vary; disorder dependent OVER 70+ Differential Diagnoses Anxiety Disorders: Differential Diagnoses Common Differential Diagnosis Medication induced Depression(other psychological/behavioral medicine disorders) Thyroid disorder/goiter Diabetes Hypercalcemia Alcohol & substance use Diagnostic Considerations: Anxiety Disorders Patient Presentation-Low index of suspicion of a contributing medical disorder* Complete blood count (CBC) Chemistry profile Thyroid stimulating hormone (TSH) Urinalysis (UA) ?Urine Drug Screen *Examples: To discuss during lecture Diagnostic Considerations: Anxiety Disorders *LOW INDEX OF SUSPICION (Examples) Patient history reveals symptoms associated with typical anxiety disorders(palms sweating, impending doom, feeling nervous, increased heart rate, trouble sleeping). No marked physical exam findings (signs) Younger age Family history of anxiety disorders Consider urine drug screening: consider in adolescent population, + family history(FH) of drug use/abuse, + prior history. Diagnostic Considerations: Anxiety Disorders Patient Presentation: Highly suspicious of contributing medical disorder Central Nervous System EEG (seizure), brain CT, lumbar puncture Infection/Sepsis Rapid Plasma Reagin (RPR) test, lumbar puncture, HIV test Primary Thyroid Disorder Thyroid panel Diagnostic Considerations: Depressive Disorders Patient Presentation: Low index of suspicion Patient Presentation: High index of suspicion of a contributing medical disorder of a contributing medical disorder Rapid plasma reagin (RPR) BACKGROUND HIV test INFORMATION Electrolytes, including calcium, Complete Chemistry Thyroid- phosphate, and magnesium levels blood count profile stimulating Liver function tests (LFTs) (CBC) hormone Blood alcohol level (TSH) Blood and urine toxicology screen Arterial blood gas (ABG) Urinalysis Vitamin B- Dexamethasone suppression test (UA) 12 (Cushing disease)Cosyntropin (ACTH) stimulation test (Addison disease) Diagnostic Considerations: Depressive Disorders HIGH INDEX OF SUSPICION…continued Must rule out medical conditions/organic causes associated with: Infection Medication induced Endocrine disorder Tumor Neurologic disorder Depressive Disorders: Differential Diagnosis HIGH INDEX OF SUSPICION…continued Central nervous system diseases (eg, Parkinson disease, dementia, multiple sclerosis, neoplastic lesions) Endocrine disorders (eg, hyperthyroidism, hypothyroidism) Drug-related conditions (eg, cocaine abuse, side effects of some CNS depressants) Infectious disease (eg, mononucleosis) BACKGROUND INFORMATION Sleep-related disorders Depression Disorders: Differential Diagnoses COMMON DIFFERENTIAL DIAGNOSIS Anemia Chronic Fatigue Syndrome (Myalgic Encephalomyelitis) Hypoglycemia Hypopituitarism (Panhypopituitarism) Medication induced BEHAVIORAL MEDICINE/PSYCH DISORDERS Dissociative Disorders Illness Anxiety Disorder Schizoaffective Disorder Schizophrenia Somatic Symptom Disorder KEY TAKEAWAYS: Anxiety & Depression Disorders No one lab or diagnostic study to diagnose Systematic process of ruling in or ruling out based on clinical suspicion Several differential diagnoses making it complex Use your clinical judgement to formulate index of suspicion Low Index of Suspicion for Anxiety and Depression Disorder Initial lab considerations include : CBC, Chem profile, UA, TSH(Thyroid functions) A urine drug screening should also be strongly considered if adolescent, + family history, + past patient history, or population aligns/support Vitamin B12 is also a common lab test ordered in initial assessments if patient older (>60 yo), has a history of gastric bypass or GI disorder. Substance Use/Abuse Drug Testing: Introduction DEFINITION: Biological sample to detect the absence or presence of a drug or its metabolites. ROLES: Confirm use, non-use, misuse or abuse; diagnostic, treatment, and monitoring for addiction. MOST COMMON SUBSTANCES TESTED: Amphetamines, cannabinoids(THC), cocaine, opioids, phencyclidines(PCP). Drug Testing: Introduction  Biological Testing Samples: urine, blood, serum, plasma, saliva/oral fluids, sweat, breath, hair, and nails. Most Common Sample: Urine Drug Testing: Why Urine: non-invasive Lab Basics high xenobiotic (foreign substance) concentration levels widely available and broad options Urine Drug Testing: Lab Basics Forms of Testing Immunoassay Chromatography Immunoassay “Presumptive” test Qualitative (doesn’t measure quantity) Identifies presence of drug class based on threshold Lacks specificity versus chromatography Chromatography “Definitive” test Gold standard due to specificity and sensitivity Urine Drug Testing: Lab Basics Urine Immunoassay (IA) Uses antibodies or enzymes to detect presence of selected drugs or metabolites Based on a pre-determined threshold cutoffs Lower specificity versus chromatography Commonly referred to as urine drug screening (UDS) WHAT & HOW TO SELECT?... Urine Drug Testing: Lab Basics URINE IMMUNOASSAY URINE IMMUNOASSAY Disadvantages Patient sensitivity BENEFITS CONVENIENT COST EFFECTIVE READILY Tampering abilities AVAILABLE False-results Negatively impact patient/provider relations NON-INVASIVE FAST RESULTS WHAT & HOW TO SELECT?... SUBSTANCE USE/ABUSE: DIAGNOSTIC STUDY CONSIDERATIONS Urine Immunoassay Chromatography Initial assessment Patient disputes results Screening Testing has major implications (eg, Highly suspicious legal, high profile, employment) Patient reports Suspect false results Clinical setting Intake of medications or foods that cross react Workplace, drug addiction, and rehabilitation settings Urine Immunoassay Drug Testing: False Results FALSE POSITIVES: positive test result with no presence of the identified xenobiotic (foreign chemical substance) Due to cross-reactivity of antibodies or enzymes from medication or foods with similar chemical compounds Common with opioids, amphetamines, cannabinoids, PCP and methadone. Rarely occur with cocaine Urine Immunoassay Drug Testing: Interpreting Common cross-reactivity agents leading to false positives Pseudoephedrine-amphetamines Dextromethorphan-PCP and opioids Diphenhydramine-PCP Ibuprofen (Advil®)/NSAIDS-THC/PCP Ranitidine(Zantac®)-amphetamines Proton Pump Inhibitors (Prilosec®)-THC Quinolones-amphetamines, opiates Foods: poppy seeds(opioids), cocoa tea (cocaine), tonic water(opioids due to quinine/cutting agent) Urine Immunoassay Drug Testing: Interpreting FALSE NEGATIVES: negative test Urine Specimen Validity Testing result with no presence of xenobiotic Non-detectable medications Characteristics of a valid urine specimen: Tampering is a common cause of false negatives Types of tampering: diluting, substituting or contaminating(ad To interpret results first you ensure urine specimen is validated Compare urine specimen with normal urine reference ranges Table Source: Federal Practitioner Urine Immunoassay Drug Testing: Interpreting Urine Specimen Validity Testing…continued Dilution, Substitution, Adulteration of Urine Specimen If urine specimen sample produces results out of physiological range, then >200mcg/ml Invalid what? Table Source: Federal Practitioner Urine Immunoassay Drug Testing: Interpreting Urine Specimen Validity Testing…continued If urine specimen Sample would be considered invalid (document) sample produces Ask the patient to provide another urine sample results out of physiological range, then what? Table Source: Federal Practitioner Bipolar Disorders: Lithium Levels Bipolar Disorder: Lithium Levels BACKGROUND INFORMATION LITHIUM Mood stabilizer drug First-line treatment Used in the treatment of manic and depressive phases of bipolar disorder FDA approved for treating bipolar I disorder Off-label (non-FDA approved): adjunct therapy to treat depressive disorder Lithium Level: Considerations & Interpretation SERUM REFERENCE RANGE Therapeutic levels of lithium is 0.8- 1.2mEg/L Target serum levels very depending on the indication of lithium treatment Levels should be assessed 8-12 hours of after dosing Most patients achieve steady state serum within 3-5 days Toxic level is >2mEq/L Photo Source: Psych Scene Hub Lithium Level: Considerations Clinical presentation and patient history determine frequency of measuring lithium levels Indication for lithium treatment dictates desired serum concentration Acute mania patients require high serum concentration levels Prophylaxis against relapse requires lower serum concentration levels Lithium Level: Considerations Elderly patients require closer monitoring for signs of lithium toxicity Renal function, alterations in renal function (dehydration), medications can cause toxicity(diuretics, NSAIDs, ACE inhibitors). Symptoms associated with lithium toxicity Graphic Source: RecapEM Lithium Level: Interpretation CLINICAL DECISION MAKING Lithium Level: Considerations & Interpretation TOXICITY Narrow therapeutic index Levels >2 mEq/L considered toxic Consider in acute & chronic ingestion context No antidote: hydration & discontinuing med Can result in: Nephritis Seizures Cardiac abnormalities Photo Source: Psych Scene Hub Lithium Level: Interpretation CLINICAL Always keep in mind the DECISION Patient patient MAKING in progress Maintain high level of Suspicion suspicion Employ a low threshold to Treatment treat patients you suspect have lithium toxicity Remember lab levels alone Remember do not predict toxicity & don’t dictate treatment KEY TAKEAWAYS: Lithium Levels & Toxicity Lithium Levels When initiating lithium treatments, therapy levels are frequently checked two times per week Levels should be checked 8-12 hours after dosing (newer research is trending to 12 hours) Lithium target serum concentrations vary depending on indication/condition treating and patient clinical presentation (eg, low levels for depression and elderly population, mid-range levels for maintenance/prophylaxis and higher levels for mania Once lithium target serum concentrations are stable (reach a steady state) levels can be monitored every 3 months first year, 6 months after unless risk factors/status changes Elderly (>60 yo) population requires closer monitoring and follow-up due to increased risk of lithium toxicity due to decreased renal function, co-morbidities & drug interactions KEY TAKEAWAYS: Lithium Levels & Toxicity Lithium Toxicity Lithium levels should be measured in symptomatic patients If suspect lithium toxicity check lithium concentration levels immediately, IV hydration, d/c lithium and re-check levels every 6-12 hours Additional labs that should be ordered in conjunction with lithium levels when suspect and/or treating lithium toxicity include UA, kidney function, and electrolyte levels initiating lithium treatments, therapy levels are frequently checked two times per week Consider lithium toxicity from acute and chronic ingestion perspectives Interactive Learning & Wrap Up Presented in class/lecture Practice Questions/Case #1 A 22-year-old female presents to an outpatient clinic to see you because she is having increased feelings of anxiousness and impending doom and difficulty sleeping. Her family history is positive for her mother having generalized anxiety disorder and diabetes. Her remaining history was non-contributory, her physical exam was without findings. You are her PCP, don’t suspect drug use, or an underlying medical condition or organic cause inducing these symptoms. A. What other baseline labs would you consider ordering for her initial assessment?  Practice Questions/Case #2 A 23 yo male presents to your outpatient clinic requesting a 5-panel urine drug screening to comply with graduate school requirements. Your clinic conducts urine drug screenings routinely utilizing on-site urine immunoassay tests. You follow clinical protocol, collect the urine sample and run the urine drug screening and a urinalysis (UA) two minutes after the patient voided. Your next step is to validate the urine. Using the below patient UA sample results and lab UA reference range table validate the patient urine sample. A. What are your findings? B. Is the specimen valid (provide rational for your answer)? C. What would be the most appropriate next step? Patient UA Results Lab UA reference ranges Characteristics Results Creatinine, mg/dl 300 Specific gravity 1.001 pH 6.0 Temperature (Degrees in 89 Fahrenheit) Practice Questions/Case #2 …continued The patient provided a second urine sample and the urine UA characteristics were all in normal reference range. The immunoassay the 5-panel urine drug screening was positive for opioids. The patient appears surprised and denies taking any prescription medications, illegal drugs, vitamins, herbs or supplements. D. What would be the most appropriate next step to confirm or rule out this disputable finding? F. What are some considerations that could have caused this result on the immunoassay UDT? Practice Questions/Case #3 A 68-year-old male patient with a history of hypertension (HTN) and bipolar disorder presented to an urgent complaining of nausea, vomiting, loose stools, and feeling very tired for 3 days that came on suddenly The patient reported no fever, chills, sweats, coughing, blood or mucus in stools, cough, rashes, swelling of hands or feet, chest pain, racing heart or recent travel. The patient appeared calm, in no acute distress, vital signs were within normal limits and the physical exam was non-contributory. Of note, the patient stated he started taking “a water pill, a diuretic” (patient didn’t know the name) for his high blood pressure two weeks ago in addition to Zestril (an ACE inhibitor). The patient confirmed he has been taking lithium for years (the same dose), and his lithium level was checked two weeks ago at the Quest lab in town. A. What condition(s) is high on your differential diagnosis? B. What findings in the above case increase your suspicion that the cause of the patient’s complaints might be related to increased lithium levels? C. What laboratory test(s) would you order in this case and any special instructions for the testing?