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HOW TO PASS THE TEST LECTURE 5 OF THE 6 PART MINI MED SCHOOL SERIES Presenter: Sergiy Shatenko DISCLOSURES I am a medical student This session is not intended to give you a diagnosis or replace you seeing your health professional OVERVIEW Statistics (I will try to make this as fun as possible) Screening tests Common blood tests QUIZ 1. How is a diagnostic test different from a screening test? 2. What does” Pap” stand for in Pap test? 3. What does hemoglobin A1C measure? LEVELS OF DISEASE PREVENTION Primary – health protection and prevention of disease onset (“An apple a day keeps the doctor away” lecture) Secondary prevention – early detection of disease to minimize morbidity and mortality (This lecture) Tertiary prevention – treatment and rehabilitation of disease to prevent progression and permanent disability DEFINITIONS Population – a collection of individuals who share a common trait Sample – selection of individuals from that population Sample size – contributes to the precision of the estimate Bias – trend in the collection, analysis, interpretation, publication, or review of data that can lead to conclusions that are systematically different form the truth ( Sampling bias, measurement bias, recall bias) Confounder – a variable that is related to both exposure and outcome that is not measured or is not distributed equally between groups BIAS IN SCREENING Lead-time bias – over-estimation of survival based on earlier detection with screening (Example: Huntington’s disease) Length-time bias – overestimation of survival time due to sampling of prevalent as opposed to incident cases (Example: Lung cancer) DEFINITIONS Incidence – number of new cases in a population in a period of time Prevalence – total number of cases in a population in a period of time INTERPRETING TEST RESULTS Medical test Disease Test result Present Absent Positive 24 14 Negative 6 56 30 70 38 62 INTERPRETING TEST RESULTS Sensitivity = true positive/(true positive + false negative) = 24/30 = 80% Specificity = true negative/(true negative + false positive) =56/70 =80% Disease Test result Present Absent Positive 24 14 Negative 6 56 30 70 38 62 WHAT IT ACTUALLY MEANS SnOut high sensitivity – if negative -> rule out SpIN High specificity – positive -> rule in What clinicians want to know when applying the test to their patients WHAT PATIENTS WANT TO KNOW Positive predictive value (PPV) = True positive/(True positive + False positive) = 24/(24+14) = 63% Negative predictive value (NPV) = True negative/(True negative + False negative) = 56/(56+6) = 90% Disease Test result Present Absent Positive 24 14 Negative 6 56 PPV AND NPV ARE DEPENDENT ON PREVALENCE Same test if the disease is 10 times less prevalent: PPV = 11% NVP = 99.2% Disease Test result Present Absent Positive 24 194 Negative 6 776 GOLD STANDARD TEST Best available test Not necessarily 100% sensitive and specific Used as a diagnostic test Sometimes not practical LIKELIHOOD RATIO (LR) Positive likelihood ratio = sensitivity/(1-specificity) (= 4 in our example) Determines whether a test usefully changes the probability that a condition exists Used in the context of pre-test probability Changes the post-test probability If LR >1, there is increased probability that the disease state exists LR = 1, does not change the probability LR <1, decreases the probability HOW A DIAGNOSIS IS MADE Pre - test probability LR test 1 Post - test probability Pre - test probability LR test 2 Post - test probability EXAMPLE OF LIKELIHOOD RATIO FOR MIGRAINE POUND criteria Pulsating duration of 4-72 hOurs Unilateral Nausea Disabling If 4 of the 5 criteria are met, the LR for migraine is 24 if 3 are met, the LR is 3.5 if 2 or fewer are met, the LR is 0.41 LIKELIHOOD RATIO FOR ACUTE CORONARY SYNDROME (HEART ATTACK) Radiation to both arms LR+ 2.6, LR- 0.93 Prior coronary artery disease LR+ 2.0, LR- 0.75 ST elevation on ECG LR + 5.7-53.9, LR – 0.1 SCREENING Purpose of screening : Take asymptomatic individuals and divide them into high risk versus low risk group High risk group goes on to more diagnostic investigations Tries to catch the disease at an earlier stage NOT TO DIAGNOSE TYPES OF SCREENING Mass screening – screening all members of the population for a disease (Example: Scoliosis) Selective screening – screening a specific subgroup of the population who are at risk (Example: Breast Cancer) Multiphasic screening – the use of multiple screening tests on the same occasion (Example: annual health check up) Opportunistic screening – screening of persons who come to a health practitioner for some other purpose (Example: screening for high blood pressure when a patient comes in for a flu shot) CRITERIA FOR SCREENING TEST Disease Should be serious Natural history must be understood Must have an asymptomatic stage that can be detected by a test Early detection and intervention must result in improved outcomes Goldilocks incidence (not too high, not too low) CRITERIA FOR SCREENING TEST Screening test High specificity and sensitivity Safe, rapid, relatively inexpensive Acceptable to providers and to populations CRITERIA FOR SCREENING TEST Diagnosis and treatment There is an available, effective, acceptable and safe treatment Early treatment should be more effective than later CRITERIA FOR SCREENING TEST Health Care system Adequate capacity for reporting, follow-up, and treatment of positive screens Cost effective Sustainable program Clear policy guidelines CERVICAL CANCER SCREENING The Pap test (Papanicolaou Test) 1 in 156 women will develop cervical cancer in their lifetime BC Cancer Agency screening guidelines Women 25-69 should be screened every 3 years (recently changed) WHAT ARE THEY LOOKING FOR? POSITIVE PAP TESTS BC Cervical cancer screening program report WHAT ARE THE NEXT STEPS? Retest in 6 months X4 for patients with ASCUS/LSIL Colposcopy and/or colposcopy guided biopsy for patients HSIL/AGC/ASC-H POST COLPOSCOPY PPV for Cervical intraepithelial neoplasia grade 3 or adenocarcinoma in situ is 4.6% Premalignant changes with high rate of progression PPV for invasive cancer 0.5% These numbers will change with the new screening guidelines PELVIC EXAMS IN WELL WOMEN American College of obstetricians and gynecologists recommend doing them yearly, however this is expert opinion only American College of physicians recommends against doing them Canadian Task Force on Preventive Health Care recommended adopting the American College of Physicians recommendation Kauffman RP, Griffin SJ, Lund JD, Tullar PE. Current recommendations for cervical cancer screening: do they render the annual pelvic examination obsolete? Med Princ Pract. 2013;22(4):313–22. - See more at: http://www.cfpc.ca/ProjectAssets/Templates/Resource.aspx?id=777&langType=4105&terms=pelvic+exam#sthash.nl3G86r8.dpuf BREAST CANCER SCREENING 1 in 9 women will develop breast cancer in their lifetime BC Cancer agency screening guidelines all women women 50 – 74: every two years 40 – 49 talk to your doctor about the benefits and limitations of screening 40 – 74 with a 1st degree relative with breast cancer: every year Younger then 40 if you have BRCA1 or BRCA2 mutation, or chest wall radiation or strong family history 75+ talk to your doctor about the benefits and limitations of screening WHAT ARE THEY LOOKING FOR Looking for asymmetry, architectural distortions, calcifications BREAST CANCER SCREENING Sensitivity 87.9% Specificity 93.1% With a prevalence of under 1% PPV of about 6.3% (2.5% in 40-49 and 13.5% in 70-79) WHAT ARE THE NEXT STEPS? Diagnostic mammogram Ultrasound Needle biopsy Open biopsy 6% of those who have a positive mammogram actually have breast cancer SELF BREAST EXAMS? Studies show that self-examinations don't save women's lives and that they can lead to unneeded tests, such as biopsies. The Canadian Cancer Society recommends that all women be familiar with how their breasts look and feel and to talk to their doctors about any changes Healthlink BC: https://www.healthlinkbc.ca/health-topics/hw3791 COLORECTAL CANCER SCREENING 4.4% of people will get colon cancer in their lifetime BC Cancer agency screening guidelines Men and women ages 50-74 should get screened using the FIT test Men and women ages 50-74 with a family history or personal history of adenomas should get colonoscopy screening WHAT ARE THEY LOOKING FOR? FIT test AKA Fecal immunochemical test Detects hemoglobin in the stool Colonoscopy COLON CANCER SCREENING 4.8% of those screened had positive result After a colonoscopy 4% PPV for colorectal cancer 60% PPV for adenoma TERMINOLOGY Epithelium Benign Malignant Glandular Adenoma Adenocarcinoma Transitional Transitional papilloma Transitional cell carcinoma Liver Adenoma Hepatocellular carcinoma Skin Papilloma Squamous cell carcinoma Nevus Melanoma Basal cell carcinoma Bone Osteoma Osteosarcoma Fat Lipoma Liposarcoma Cartillage Chondroma Chondrosarcoma Smooth muscle Leiomyoma Leiomyosarcoma “Striped” muscle Rhabdomyoma Rhabdomyosarcoma Vessels Angioma Angiosarcoma ADENOMAS ARE NOT MALIGNANT BY DEFINITION, WHAT’S THE BIG DEAL? Vast majority of colorectal carcinomas are adenocarcinomas These are often preceded by adenomas Adenomas can be identified and removed during colonoscopy PROSTATE CANCER SCREENING 1 in 6 males will develop prostate cancer Not a population screening test BC cancer agency recommendations Digital rectal exam (DRE) should be done annually in men 50-70 Digital rectal exam should be done if obstructive urinary symptoms are present PSA (Prostate specific antigen) recommended if suspicious DRE or suspicious urinary symptoms DIGITAL RECTAL EXAM WHAT THEY ARE LOOKING FOR? Digital rectal exam Feeling the prostate for any hard masses or irregularities Prostate specific antigen Blood test for a glycoprotein that the prostate releases Checking to see if the levels are above normal PROSTATE CANCER SCREENING DRE Sensitivity 59% Specificity 94% 24% Positive predictive value PSA (4.0 ng/mL) Sensitivity 21% Specificity 91% PPV 25% (40-60% if >10 ng/mL) Next steps? Biopsy MRI MOVEMBER FOUNDATION Prostate cancer Testicular cancer Men’s health and suicide prevention COMMON MEDICAL TESTS AND HOW THEY WORK Hemoglobin A1c CBC Iron Thyroid HEMOGLOBIN A1C Measure of the percentage of hemoglobin that has been altered by glucose (glycosylated) Indirect measurement of 3 month average blood glucose Life span of a red blood cell is 60-120 days Can now be used to diagnose diabetes (>6.5%) Advantages: provides an average, no need to fast Disadvantages: provides an average COMPLETE BLOOD COUNT (CBC) Most commonly ordered test WHAT DOES IT TELL YOU White blood cells Increased in: infection, immune reaction, drugs, bone marrow disease Decreased in: infection, drugs, bone marrow disease Hemoglobin Increased in: lung disease, heart disease, doping Decreased in: nutrient deficiency, liver/kidney disease, cancer Mean cell volume Helps differentiate the different types of anemia Platelets If low Increased bleeding risk Causes: medications, some infection, pregnancy, cancer IRON Ferritin – storage form of iron, a measure of iron reserves Iron in the blood Serum iron Total Iron Binding Capacity Transferrin saturation FERRITIN SERUM IRON AND TOTAL IRON BINDING CAPACITY THYROID Thyroid stimulating hormone Pituitary is the sensor Releases TSH to regulate thyroid function A CLINICAL SCENARIO A patient comes in complaining of fatigue Started slowly over the past few months Patient looks pale Diagnosis? Anemia 105