Statistics & Preventative Medicine

1. Statistics & Preventative Medicine Board Review Candice Sech, MD

2. Statistics • The difficulty with statistics comes with all of the jargon • I will go over the different definitions, with examples, to help you form a picture in your mind, and understand these different concepts • We will then go over how to interpret and approach questions likely seen on the boards

3. Sensitivity-Proportion of diseased population with positive test • Looks at patients with disease • Independent of prevalence of disease • Ex. The sensitivity of a CT scan in detecting disease X is 97% • Real words: 97 % of pts. with disease X will have a positive CT scan (ability to detect when disease present) • Formula: TP/TP + FN

4. Specificity-Proportion of pts. without disease with a negative test • Looks at patients without disease • Independent of prevalence of disease • Ex. The specificity of a CT scan in detecting disease X is 97% • Real words: 97% of pts. without disease X will have a negative CT scan (ability to detect when disease not present) • Formula: TN/TN + FP

5. Positive Predictive Value (PPV) • Looks at pts. with positive test • Ex. The PPV of test X for detecting disease Y is 12% • Real words: Of pts. with a positive test X, 12% actually have disease Y (true positive) • Formula: TP/TP + FP • Does reflect prevalence of disease

6. Negative Predictive Value (NPV) • Looks at pts. with negative test • Ex. The NPV of test X for detecting disease Y is 12% • Real words: Of pts. with a negative test X, 12% actually don’t have disease (True negative) • Formula: TN/TN + FN • Does reflect prevalence of disease

7. + disease - disease • Use “The table” + test TP FP - test FN TN

8. When prevalence of a disease drops the PPV falls & NPV rises • Real words: The less common a disease is, the more likely that a positive test represents a false positive • Ex. Pheo is very rare (low prevalence), if you did 24 hr. urine for metanephrines on everyone, almost all will be false positives • When prevalence of a disease increases, the PPV increases & NPV falls • Real words: The more common a disease is, the more likely that a positive test represents a true positive • Ex. DM is very common (high prevalence), if you tested everyone for DM, almost all will be true positives

9. P Value-significance of a finding • Usually P values <0.05 are considered “statistically significant” • Ex. The P value of high heels causing spurs on women’s feet is <0.05 • Real words: The likelihood that finding that high heels cause spurs on women’s feet by chance alone is less than 5% • Let’s say in the above example the P value was <0.5 • Real words: The likelihood that finding that high heels cause spurs on women’s feet by chance alone is less than 50% • That’s a pretty big likelihood that it’s chance alone, thus not statistically significant

10. Number needed to treat (NNT) • Know this, it will be on your boards • Real words: How many pts. do I need to treat with treatment X, to prevent one bad outcome • Formula: 1/(rate in placebo-rate in treatment group) –or- 1/(absolute risk reduction) • Ex. CHF plus drug X-10/50 that received drug died • CHF plus Placebo-20/50 that received placebo died, what is the NNT? • 1/(2/5-1/5) = 1/(.4 - .2) = 1/.2 = 5 • Real words: You must treat 5 pts. with CHF, with drug X, to prevent one bad outcome

11. 95% Confidence Intervals-essentially same as saying P<0.05 • If the values do not cross zero, it is considered significant • Ex. The 95% confidence interval is 0.5 to 1.9, that is considered significant • If they say the 95% confidence interval is -0.7 to 1.6 that is non-significant

12. Type 1 error-Concluding that there is a difference (reject null hypothesis) when there is no difference • Type 2 error-Concluding that there is no difference (accept null hypothesis) when one exists

13. They will not give you all of the numbers, and then let you just calculate sensitivity, etc. • They may give you some numbers, and then you figure out the rest, or put it into words, rather than numbers • This is why you need to understand the concepts, rather than just memorizing a bunch of formulas • Let’s go over an example……

14. Example 1: Incidence of cancer is 1/200 in a population. For test, sensitivity=99%, and frequency of abnormal tests in the population is 1.3%, what is the ratio of false positives to true positives? • If population isn’t given, assume 1 million • An incidence of 1/200, gives 5,000 people with cancer • Abnormal test frequency is 1.3%=13,000 abnl. Tests • Pts. Without cancer=1 million-5000=995,000 pts. • Number of NL tests=1million-13,000=987,000 tests • Now, fill in the table DZ No DZ 13,000 + test TP FP - test FN TN 987,000 5,000 995,000

15. Fill the rest in • Sensitivity=TP/(TP+FN)=.99=TP/5,000 • So TP=4,950 • All the others are filled in by subtraction DZ No DZ 13,000 8,050 4,950 + test 986,950 50 - test 987,000 5,000 995,000

16. Preventative Medicine • Not many concepts here, unfortunately, just rote memorization

17. Breast Cancer • Yearly breast exam after age 40 • Yearly mammogram after age 50 • Between age 40-50 use of mammograms is unclear, some say yearly, some q1-2 years, likely won’t have question with a pt. in this age range as screening length is controversial • Know-High incidence of false positive mammogram results between ages of 40 to 50 • Blood Pressure/Cholesterol • BP-every 2 years, and every clinical encounter • Chol.-Screening for total cholesterol in men 35-65 yrs. old and women 45-65 yrs. old is appropriate, but not mandatory

18. Prostate Cancer • ACP/ACS recommends PSA be done between ages of 50-69, frequency based on discussion of pluses and minuses with the pt. • No PSA recommended >70 yrs. old • Colon Cancer • DRE yearly for pts. >40 yrs. old • FOBT yearly over age of 50 • Sigmoidoscopy-ACS/ACP recommends q3-5 yrs, starting at age 50

19. Colonoscopy recommendations: • Colonoscopy q10 yrs. after age 50 for average risk pt. • If polyp is found, repeat in 3 yrs. • FH of colon cancer screening should begin at age 40, or 10 yrs. prior to age of the family member, the earlier date is respected • Follow-up exam in pts. with FH of colon cancer is q5 yrs. • Multiple family members with colon ca. (Lynch syndrome), screening begins at age 25, and q1-2 yrs • Colonoscopy is q1yr. after a hemicolectomy for colon cancer to verify the absence of recurrence

20. Pap Smear • Start at age 18, or when sexually active • If three negative results with annual exam, may continue q3 years (except HIV pts.) • If previous pap smears have been negative, patients >70 years old do not need further smears

21. Vaccinations • Attenuated live virus: MMR, oral polio, nasal influenza, yellow fever • Attenuated live bacteria: typhoid (two types) and BCG • The live vaccines may cause the actual disease in immunosuppressed patients (remember those with congenital immunodeficiences) • All except the attenuated live vaccines can be given in pregnancy • AIDS pts.: yearly influenza, hep. B, pneumococcal, HiB, childhood vaccines (MMR may be given to AIDS pts.) • Do NOT give AIDS pts. nasal influenza, oral polio, or smallpox

22. Strep. Pneumoniae vaccine -Persons older than 2 yrs. of age with asplenia, SS or an debilitating disease -Anyone older than 65 yrs. old -Repeat once in 5-6 yrs. 2)Influenza -Active within 2 weeks -Given q1yr. after the age of 50 and also yearly to high-risk patients, and their household contacts -Health care workers

23. 3) Varicella -All individual older than 12 mths. who aren’t immune -Hx. Of chicken pox is sufficient to assume immunity 4) Hepatitis A -Persons 2 yrs. of age or older who are at increased risk of infection by HAV, chronic liver disease, travelers 5) Hepatitis B -All those at risk, all adolescents

24. 6) Tetanus -Booster is recommended q10 yrs. -May be given at 5 years for “dirty” wound management 7) Typhoid -Oral recommended vs. parenteral 8) Yellow Fever -Based on travel 9) Smallpox -On demand -Contraindications: eczema or household contacts with people with exfoliative skin conditions -immunosuppression (HIV, steroids >20mg/day) -radiation therapy -pregnancy

25. Prophylaxis • Malaria • Depends on area (chloroquine resistant) • Malarone, Mefloquine (neuropsychological side effects), Chloroquine • Meningococcemia • Chemoprophylaxis with rifampin, ciprofloxacin, or ceftriaxone • Know: Healthcare workers do NOT receive chemoprophylaxis unless they had recent “intimate” oral contact with the case patient (ie, Intubation)

26. Travelers’ Diarrhea • Empiric self treatment v. prevention • Prevention & treatment: FQs, Bactrim, Azithromycin • Self treatment: • 1-2 stools/24 hrs.: none; loperamide • 3 stools/24 hrs.: Add single dose antibiotic • 6 stools/24 hrs. & fever or blood: Continue antibiotic x 3d • Iatrogenic Infections • Remove lines ASAP • WASH YOUR HANDS

27. Questions from Medstudy, 11th edition • In a 75 y/o man should you do a PSA? • When should PAP smears be initiated? • What are the live-virus vaccines? • Who should not receive a live-virus vaccine? • What patient groups should get the pneumococcal vaccine? • Is history of chicken pox sufficient to assume immunity and therefore no need to vaccinate? • Who should get Hepatitis A vaccine? • True or False: All healthcare workers exposed to a pt. who died of meningoccemia should be prophylaxed within 48 hrs. • What are the treatment options for travelers’ diarrhea? • What is the most effective way to prevent the spread of disease in the hospital? • You have invented a test that is 90% sensitive and 95% specific for screening of breast cancer. If you tested 100 women with known breast cancer, how many would the test pick up? • If a study shows new treatment for lung cancer improves survival by 60% and the P-value is 0.2, would you recommend this treatment?

28. 13) If a study shows a newer treatment for lung cancer improves survival by 5% and the 95% confidence interval for the study is 1.6 to 4.9. Would you consider this new treatment? 14) Regarding specificity and sensitivity, which is independent of the prevalence of the disease in a selected population? 15) In what case would the number of false positives be high despite a very high specificity and sensitivity? 16) How is the positive predictive value used in determining whether a screening program is feasible? 17) After what age are mammograms definitely of benefit as a screening test? 18) Are breast self-exams beneficial? • What is the general age group for which pap smears are recommended? 20) Which are the live vaccines, and which are the dead vaccines? What is their significance in a pt. who is immunocompromised?

29. PREVENTATIVE MEDICINE PEARLS/SCENARIOS: • DM pts. should be seen by an opthalmologist at the time of diagnosis • Daily ASA should be given to all pts. with increased risk for CAD (>2 risk factors) • Pts. s/p MI with PUD may take daily ASA, with a PPI • If a pt. has concerns re: developing ovarian cancer, has no FH of cancer, there is no screening test (CA 125 is not done to screen) • Screening CXR are NOT done in pts. with COPD, etc., unless pt. has symptoms • If pt. has grade II esophageal variaces, may begin Nadolol as primary prophylaxis • KNOW when antibiotic prophylaxis is given for heart lesions and for what procedures • The only substance known to prevent breast cancer in persons at increased risk is Tamoxifen • The most important risk factor for the development of colon cancer is age • A 55 year old man, with NO risk factors or symptoms for CAD, does not need a screening exercise treadmill test, just cholesterol panel

30. PREVENTATIVE MEDICINE PEARLS/SCENARIOS • Smoking is a risk factor for pancreatic cancer • A 35 yr. old pt. with Hep. C, genotype 1B, elevated LFTs should receive: Hep. B, Hep. A, pneumococcal, influenza vaccine • Cervical cancer screening with a PAP smear is primary prevention • A 48 yr. old pt. with DM, LDL-138, HDL-54, should be started on Simvistatin, LDL goal is 100, treatment started at LDL>130 • Pts. with 3 negative pap smears may have q3 paps thereafter • Pts. with HIV and 3 negative pap smears still have paps q1 yrs. • Hand washing is the most effective method of preventing nosocomial diarrhea in the US • Breast cancer is the most likely cause of death for a woman between the ages of 45 and 54 in the US • Annual BP measurement has the most evidence to support and is also recommended by the US Preventative Services Task Force

31. PREVENTATIVE MEDICINE PEARLS/SCENARIOS: • A 38 yr. old male with apathy, attitude problems, wide gait, slow reflexes, anemic, thrombocytopenia, leukopenia, with a high homocysteine level needs to be considered for B12 deficiency • Deficiency of Folate will increase blood homocysteine level but not methymalonic acid • A pt. on long term TPN, Chromium deficiency is associated with diabetes (glucose intolerance) • If a 74 yr. old woman in a NH develops influenza, and the NH residents haven’t been immunized yet, they should be given rimantidine plus the influenza vaccine (not effective for 2 weeks) • A 45 yr. old man presents for a vaccine, and has a 6 yr. old child that just developed chicken pox, he should get varicella immune globulin • Oral polio vaccine can not be given to an immunocomprimised pt. • Low molecular weight heparin starting 12 hrs. post-op is the best prophylaxis for DVT in a pt. going for hip replacement • Endocarditis prophylaxis is indicated in a pt. with bicuspid valve undergoing a dental cleaning

32. PREVENTATIVE MEDICINE PEARLS/SCENARIOS: • Pts. should be advised to eat at least 6 servings of fruits and/or vegetables daily • A 32 yr. old obese pt., with no PMH, wanting a pill to lose weight, should be told that a low calorie diet and exercise are the best ways to lose weight • The half-life of albumin is 3 weeks, and can be used to assess the degree of malnutrition • Riboflavin deficiency is associated with angular stomatitis, cheilosis, glossitis, seborrheic dermatitis, and anemia • A pt. with iron deficiency anemia needs to be considered for celiac disease, and may have an atrophic tongue • A 50 year old female presents to clinic, she only needs a TSH if she has symptoms of hypothyroidism, not screening TSH • Folic acid helps to prevent certain birth defects • A mammogram should be performed every 1-2 years in women after age 50 • In a 55 yr. old with a positive occult stool, both colonoscopy and BE WITH flex. Sig. are acceptable screening strategies

33. Resources used: MedStudy, 11th Edition Conrad Fischer’s Board Review for Internal Medicine-2005 Thank You!!!!