step 1 studying deck 2 Flashcards
what murmur radiates to the neck
aortic stenosis
calcium degeneration and impaired leaflet mobility
why don’t CCBs affect skeletal muscle
the skeletal muscle does not depend on extracellular calcium influx
skeletal muscle contraction only in reponse to acetylcholing
what is a side effect of antracyclines
antracyclines are chemo agents associated with severe cardiotoxicity (specifically dilate cardiomyopathy)
(daunorubicin, doxorubicin, epirubicin, idarubicin)
dilated cardiomyopathy is cumulative dose dependent and can present months after stopping the drug
doxorubicin associated cardiomyopathy is characterized by swelling of the sarcoplasmic reticulum as an early sign… later on you see a loss of cardiomyocytes (“myofibrillar dropout”)… symptoms are of biventricular CHF
prevention of doxorubicin cardiomyopathy= dexrazoxane (an iron chelating agent that decreases oxygen free radical formation)
what are some causes of restrictive cardiomyopathy
hemochromatosis amyloidosis sarcoidosis radiation therapy (chemo= dilated cardiomyopathy)
what are some causes of pericardial fibrosis
cardiac surgery
radiation therapy
viral infections of the pericardium
what are Janeway lesions
non tender, macular, red lesions to the palms and soles
due to micro-emboli to skin vessels
(septic embolization from IE valvular vegetations)
associated with IE (fever, SOB, new holosystolic murmur at the apex (mitral regurg)… here you can also see petechiae, splinter hemorrhages, roth spots, janeway lesions, and osler nodes (painful lesions to the fingers and toes due to immune complexes)
what vagal maneuvers can be used to acutely terminate paroxysmal supraventricular tachycardia (PSVT)
carotid sinus massage (increases baroreceptor firing)
valsalva
cold water immersion
carotid sinus:
afferent limb= from baroreceptors in sinus to the vagal nucleus and medullary centers via glossopharyngeal nerve (9)
efferent limb=parasympathetic impuses to the SA and AV nodes via the vagus nerve (10)
PNS slows conduction through the AV node and prolongs refractory period
what would cause excessive LA systolic pressure
mitral regurg
(mitral stenosis would increase LA pressure during diastole, not during systole, because there is obstruction to passive filling)
there is a characteristic upsloping “v wave” in the LA during catheterization
what does this patient have?
40 yo F with depression and HTN. found obtunded in apartment, hypotensive, and bradycardic…. IV glucagon is given and she improves
the patient overdosed on her beta blocker meds (causes a diffuse non selective blockade of beta receptors leading to depressed contractility, bradycardia, and varying AV block (end with low CO state)…. notice that depression was first in her pmh
glucagon is the drug of choice for beta blocker overdose
glucagon activates GPCR on cardiac myocytes and increases cAMP to increase intracellular calcium during muscle contraction and increase SA node firing (to increase HR and contractility in this patient independent of adrenergic receptors)
what is costosternal syndrome
aka costochondritis
aka anterior chest wall syndrome
due to repetitive activity/injury
what drugs have negative chronotropic effects
when used concomitantly, these can have additive negative affects on HR, AV node conduction, and myocardial contractility
ADRs= bradycardia, sinus arrest, hypotension
beta blockers (ex metoprolol, atenolol)
non dihydropyridine CCBs (verapamil, diltiazem)
cardiac glycosides (digoxin)
amiodarone and sotalol (class 3 antiarrhythmics)
cholinergic agonists (pilocarpine, rivastigmine)
what is the reflexive response to vasodilator medications
reflex tachycardia
example= beta blockers and non dihydropyridine CCBs both decrease HR, AV node conduction, and myocardial contractility
how do fibrates work
they reduce hepatic VLDL production
gemfibrozil
fenofibrate
they activate peroxisome proliferator-activated receptor alpha (PPAR alpha) leading to decreased hepatic VLDL production and increased LPL activity
theyre great for decreasing TGs
other options are fish oil with omega 3 FA to decrease VLDL production and inhibit apo B synthesis (to decrease TGs)
what does ezetimibe, cholestyramine, and PCSK9 inhibitors do
ezetimibe blocks cholesterol absorption
cholestyramine is a bile acid binding resin (increases fecal losses)
PCSK9i are monoclonal ab’s that reduce LDL receptor degredatikon in the liver
what keeps the PDA open
prostaglandin E2 from the placenta combined with right to left blood flow across the PDA
PDA= continuous murmurm tachycardia, widened pulse pressure in large PDAs (this 12 day old BP was 41/12), and respiratory distress
after birth the separation from the placenta and rapid drop in pulmonary vasc resistance normally closes the PDA (failure to close is common in premies)
untreated PDAs can cause pulmonary edema, heart failure, or eisenmenger syndrome
tx= in babies give NSAIDS to inhibit prostaglandin E2 (indomethacin, ibuprofen)
how can you recognize pulsus paradoxus in a question stem
korotkoff sounds are what is heard when you listen with a stethoscope while taking a manual blood pressure
this question stem says:
at 120 mmHg intermittent korotkoff sounds are heard only during respiration and at 100 mmHg korotkoff sounds are heard throughout the resp cycle
(the difference between the systolic pressure at which they sounds are heard and the pressure at which they are heard throughout all the phases of respiration= 20 mmHg…. and pulsus paradoxus is an exaggerated drop in systolic BP with inspiration >10 mmHg)
pulsus paradoxis= pericardial disease
(in tamponade the RV volume increases as normal but because the RV can’t expand, the right ventricle pushes the interventricular septum into the LV causing a lower end diastolic volume and lower stroke volume and drastic change in the systolic BP)
basically seen in severe obstructive lung diseases and pericardial issues
what is the cause of pulsus parvus el tardus
slow rising low amplitude pulse due to diminished stroke volume and prolonged LV ejection time
due to a fixed LVOT (ex= from aortic stenosis)
what does valsalva doe to preload
(straining phase)
decreases preload
blowing out against a closed glottis increases intrathoracic pressure which is exerted onto the pericardium which then compresses the IVC and SCV and less blood is returned to the heart
what does pheylephrine do
selective alpha 1 agonist
what makes pitting edema become hard and non pitting
due to progressive fibrosis and thickening of the overlying skin
a 23 yo F immigrant has SOB and as a child had bilateral knee swelling. she has a murmur over the apex
mitral regurg, radiates to the axilla
knee swelling as a child= ARF as a kid
ARF in other countries almost always have significant mitral valve disease (=MR in first few decades of life)
in older patients they typically have mitral stenosis and regurg (MS would only be heard in diastole)
involuntary head bobbing is a sign of what
wide pulse pressure
caused by aortic regurg
what does the graphs look like for a noncompetitve/irreversible inhibitor vs a recersible competitive inhibitor drug
noncompetative/irreversible= Vmax is decreased... graph has a similar shape but does not peak as high vertically (ex= phenoxybenzamine is an irreversible alpha 1 and alpha 2 antagonist... used to treat a pheo which over produces norepi, and thus the graph showed norepi and then drug A which ended up with this pattern meaning the drug was inhibiting norepi and the answer was phenoxybenzamine... even high doses of norepi cant overcome phenoxygbenzamine because its irreversible)
reversible competative inhibitor= same Vmax, but the Km is increased (thus the same shape but the graph is shifted to the right)
(ex= labetalol and phentolamine are reversible competitive antagonists of alpha 1 and beta receptors… high dose norepi can overcome these drug’s inhibition)
what is coarctation of the aorta associated with
can be associated with berry aneurysms at the circle of willis
these berry aneurysms are prone to rupture when associated with coarctation due to HTN
results in spontaneous intracranial subarachnoid hemorrhage
what is mitochondrial vacuolization
this is NOT mitochondrial swelling which is associated with reversible injury
this IS being able to see the vacuoles and phospholipid containing densities within the mitochondria which is associated with irreversible injury
(permanent inability for mitochondria to further make ATP via oxidative phosphorylation)
what are other signs of reversible cell injury besides mitochondrial swelling
- myofibril relaxation in cardiac myocytes (seen in the first 30 mins after a severe ischemia)… this is due to ATP depletion and lactate accumulation
- disaggregation of polysomes (seen in hypoxic/ischemic injury due to ATP depletion and detatchment of ribosomes from the rough ER)
- disaggregation of nuclear granules or clumping of nuclear chromatin (secondary to decreased pH intracellularly)
- TG droplet accumulation in liver, striated muscle, and kidney cells (injury causes decreased production of lipid acceptor proteins that incorporate TG into lipoproteins)
- glycogen loss (due to low ATP… also myocardial glycogen stores may be completely depleted within 30 mins of severe ischemia)
splinter hemorrhages in the nailbeds are associated with what
IE
look for a new onset murmur!
what parameter is the most similar between pulmonary circulation and systemic circulation and what is the exception
blood flow per minute must be closely matched between the two to maintain blood flow throughout the body
(otherwise the LV would soon empty completely or soon be overloaded)
exception= bronchial circuit
(oxygenates the pulmonary parenchyma and drains into the LA… sort of an independent right to left shunt… but this is only <5% of the total CO)
anaphylaxis does what to preload
drastically reduces preload/venous return to the heart
due to widespread venous and arteriolar dilation and increased capillary permeability
(afterwards the CO increases to try and maintain blood pressure)
what does prussian blue stain?
intracellular iron
golden cytoplasmic granules in macrophages turning blue with a prussian blue stain are consistent with hemosiderin laden macrophages (siderophages)
these was seen in a patient with HF due to LV dysfunction which caused repeated pulmonary edema… this disrupted the blood gas barrier over time and led to alveolar hemorrhage… the RBC were eventually phagocytosed by macrophages and the iron from hemoglobin was converted to hemosiderin (that were subsequently stained with prussian blue)
what do the presence of hemosiderin laden macrophages in pulmonary alveoli indicate
chronic elevation of pulmonary capillary hydrostatic pressures leading to extravasation of RBCs
commonly caused by left HF
what is the most common artery involved in atherosclerosis
large elastic arteries
ABDOMINAL AORTA #1 coronary arteries #2 popliteal arteries #3 internal carotids #4 circle of willis #5
also involved is aorta, carotid, and iliac arteries
also large to medium muscular arteries (coronary and popliteal arteries)
affecting what channel prolongs the QT interval
potassium
what syndrome prolongs QT interval and has sensorineural hearing loss
Jervell and lange nielsen syndrome
AR
predisposition to syncope and sudden cardiac death
due to mutation in the potassium channels
(KCNQ1 and KCNE1 genes) that encode for the alpha and beta subunits of vg K+ channels
what syndrome is caused by mutations in the cardiac calcium or sodium channels
brugada syndrome
AD
mutation in cardiac sodium or L type calcium channels
ekg= pseudo RBBB or STE in leads V1-V3
what problem is caused by a mutation to a membrane anchoring protein in the heart
dystrophin= structural membrane protein in the heart that stabilizes the plasma membrane of myocytes
Duchenne muscular dystrophy
x linked mut in dystrophin
present with progressive proximal muscle degeneration and weakness
also causes cardiomyopathy and conduction abnormalitis
how do you fix a hibernating myocardium (aka left ventricular systolic dysfunction due to reduced blood flow at rest)
thats when there is chronic myocardial ischemia and subsequent decreased contractility in that portion
fix this with coronary revascularization and restoration of blood flow
describe ischemic preconditioning
repetitive episodes of angina prior to an MI can delay the time to cell death during complete occlusion and provide a greater time for myocardial salvage with revascularization!
clinically, how does reperfusion injury manifest (heart)
arrhythmias
microvascular dysfunction with myocardial stunning
myocyte injury and death
what are some ADRs of non dihydropyridine blockers
constipation (v>d)
new onset second degree AV block
syncope
(diltiazem and verapamil)
used for
HTN
stable angina
atrial arrhythmias
block L type calcium channels (phase 0 of the pacemaker cell AP) thus slow down conduction through the SA and AV nodes (which cause AV block)
dont forget the negative HR and contractility effects
what is the suffix of the dihydropyridine CCBs
-dipine
mostly only vasodilator effects, practically none on cardiac
what is indapamide
a thiazide
lidocaine treats what kind of arrhythmias
ventricular (typically ischemic)
true or false
beta blockers can worsen AV block
true they can cause AV block too
not associated with constipation though
this patient also has COPD and is on oxygen (and you cant give nonspecific beta blockers to lung patients because it impairs bronchodilation via beta 2)
what is terazosin
-zosin (alpha 1 blockers)
it treats BPH and mild HTN
what are the diagnostic criteria for stable angina
- deep poorly localized chest pain or arm pain
- pain reproducible with exertion or emotional stess
- relieved within 5 mins of resting or with sublingual nitroglycerin
stable angina atherosclerosis must occlude at least 75% of the lumen to cause any symptoms
(asymptomatic less than 75%)
does an ulcerated atherosclerotic plaque with a partially obstructive thrombus describe stable or unstable angina
unstable angina (or sub-endocardial infarction)
what enzyme within an atherosclerotic plaque makes the plaque unstable
metalloproteinases
activated macrophages infiltrating the atheroma help break down collagen by secreting metalloproteinases
this ongoing inflammation destabilizes the plaque via the metalloproteinases and leads to plaque rupture
what is lysyl oxidase
a mediator that cross links lysine and hydroxylysine residues (with copper as a cofactor) which strengthens collagen fibers
what is procollagen peptidase
an enzyme that cleaves the ends of procollagen that comes from fibroblasts or smooth muscle cells to make tropocollagen
tropocollagin then aggregates to form collagen fibrils
what is prolyl hydroxylase
the enzyme that hydroxylates proline on procollagen into the stable collagin triple helix
(uses vitamin C as a cofactor)
what are the cyanosis patterns for a
PDA
coarctation of the aorta
right to left shut
TOF
PDA= clubbing and cyanosis without BP or HR changes means a large PDA complicated with eisenmenger syndrome
(also remember that it is basically children with symptoms of heart failure)… this kid had only clubbing and cyanosis of the toes because the PDA delivers unoxygenated blood distal to the left subclavian artery so the upper extremities still get oxygenated blood
Coarct= lower extremity cyanosis (but would see a difference in pulses from upper to lower extremities here)
right to left shunt= when severe will cause whole body cyanosis
TOF= whole body cyanosis
where is the pterion
the region of the skull where the frontal, parietal, temporal, and sphenoid bones all meet in one spit
the bone is thin there and overlies the middle meningeal artery (a BRANCH of the MAXILLARY ARTERY… which comes off the external carotid artery… enters the skull at the foramen spinosum and supplies the dura mater and periosteum)
lacerating the middle meningeal artery causes an epidural hematoma (emergency treatment needed to prevent cushing reflex-HTN/bradycardia/resp depression, brain herniation-uncal herniation with oculomotor nerve palsy, and death)
what causes restlessness and purposeless jerking movements 3 months after a sore throat
syndenham chorea (acquired chorea of childhood)
the neurologic manifestations of ARF!! (occurs 1-8 months s/p GAS infection)
due to ab’s that cross react with the basal ganglia
theyre at risk for chronic rheumatic heart disease
what is ebsteins anomaly
displacement of a malformed tricuspid valve into the right ventricle
presents soon after birth with cyanosis and HF from severe tricuspid regurg
what is the diagnosis of a rare vasc tumor assocated with arsenic or polyvinyl chloride exposure that stains for CD31 cell marker
liver angiosarcoma
a rare malignant vascular endothelial cancer associated with carcinogen exposure
due to:
arsenic (pesticides)
thorotrast (radioactive contrast medium)
polyvinyl chloride (plastic)
CD31= PECAM1 (platelet endothelial cell adhesion molecule) which is expressed on endothelial cells to function in WBC migration
thus the tumor came from vascular endothelial cells and liver angiosarcoma is a vascular endothelial cell cancer
what is the attributable risk percent in the exposed and how do you calculated it
ARP exposed= 100 x [(risk in the exposed - risk in unexposed)/risk in exposed]
basically attributable risk percent in the exposed measures the impact of a risk factor, its the excess risk you get by being in a population that is exposed to whatever it is that you’re measuring (like smoking)…
it is very similar to the relative risk equation
ARP exposed= 100 x [(RR-1)/RR] where the RR in this case is the risk in the exposed over the unexposed
in this case it said during a 10 year follow up smokers have a 5 x risk of esophageal cancer compared to non smokers (with RR= 5.0; 95% CI being 2.9-7.1)
thus:
ARP exposed= 100 x [(5-1)/5]= 100 x (4/5)= 100 x 0.8 = 80% of esophageal cancer is attributed to smoking
describe the difference between the mean, median, and mode (three measures of central tendency)
mean= average
median= middle number (doesn’t have to exist in the data set)
mode= most frequent number
describe the positive predictive value and what it depends on
Predictive values are performance measures of diagnostic tests and depend on the prevalence of a disease youre looking for
PPV= probablility that someone who tests positive actually has the disease
PPV= TP/(TP + FP)
(aka the true positive over all the positives)
true positives depends on the sensitivity and the false positives depends on the specificity
as a disease prevalence increases, the number of true positives also increases which increases PPV (you’ll be more likely to catch people with the disease if the disease is more prevalent)
similarly the NPV will increase as the disease prevalence decreases (you will catch more people without the disease if the disease is super rare)
What is a positive and negative likelihood ratio
they indicated how a positive or negative test will influence the pretest probability of having the disease (how likely it is you actually have the disease)
likelihood ratios >1 indicate that the test result is associated with the presence of the disease
likelihood ratios <1 mean the test is associated with the absence of the disease
these are based on the test’s sensitivity and specificity
what are the only things measured in sensitivity vs specificity
sensitivity= only measure people with the disease (but includes true positives and false negatives)
specificity= only measure people without the disease (true negatives and false positives)
these are not dependent on prevalence… these are fixed values and also do not vary with pretest probability
how does having a high pretest probability affect their negative predictive value
if the patient has a high pretest probability of an outcome (such as a patient testing for thyroid cancer who had significant radiation to her thyroid as a child)….
then she will have a low negative predictive value (meaning her NPV is not as strong as someone without risk factors)
the opposite is also true, meaning that someone with no risk factors (and thus a low pretest probability) will have a higher NPV (meaning that her negative predictive value is much stronger, indicating that it is much more likely that she is truly negative for the disease)
what is validity in terms of a study test
validity = the accuracy (that the test is actually measuring what it is supposed to be measuring)
what is the equation for prevalence
prevalence= (incidence) x (duration of disease)
give an example of selective survival bias
in case control study
when cases are chosen from the entire population of people with a disease as a opposed to people who are newly diagnosed
if this study was on cancer and you chose people who were not only newly diagnosed, you would end up with a higher proportion of people with more benign cancers and would liver longer (it makes sense because you could be recruiting people with breast cancer who had it for 5 years and maybe their case wasn’t a bad one… a bunch of these people would make it look like a population with breast cancer lived loner than the average person newly diagnosed)
How is effect modification different from confounding
effect modification= when the effect of an exposure on an outcome is modified by another variable (a variable that changes the observed outcome of a risk factor on disease)
confounding= a third variable that influence both the dependent and independent variables
you can distinguish between these two using stratified analysis (looking at the cohort as different subgroups)
with effect modification, the groups will have different measures of association where as with confounding, stratification will reveal no significant different between groups
This question stem mentions that theyre measuring risk of DVT in women who smoke vs dont smoke who are taking a new estrogen agonist drug… the RR of women who smoke is 1.70 p=0.01 and the RR of women who do not smoke is 0.96 p=0.68
the effect modification here is smoking on DVT (outcome) in women taking estrogen (exposure)… the difference in measures of association was evident when they showed that one group (the smokers) had a real significant association (p<0.05) and the non smokers had no significant difference (p>0.05)
if this was confounding then the difference would disappear in BOTH groups.
effect modification is not a bias and is not due to flaws in the design or analysis. it is a natural phenomenon that should be described, not corrected
describe a cross sectional study
also known as a prevalence study
its where there are simultaneous measurements of exposure and outcome
its a snapshot study that often measures using surveys
super easy to perform and are cheap!
what is the hawthorne effect
the observer effect
which is when study subjects change their behavior as a result of awareness that they are being studied
can seriously affect the validity of the study
common in studies of behavioral outcomes or outcomes influenced by behavior
must keep the subject unaware they are being studied (beware of ethical problems)
what is berkson’s bias
think: Dr. Berkman ~ berksons (hospital cause thats where he worked)
the selection bias created by choosing hospitalized patients as the control group
(the control group are more likely to encounter the exposure than the general population)
what is lead time bias
the apparent prolongation of survival that arises from a screening test that detects a disease earlier
there is no real effect on prognosis of the disease but it appears as if the patient is living longer because they were detected earlier
what is the pygmalion effect
describes the fact that the researcher’s beliefs in the efficacy of the treatment can affect the outcome
this is the classroom effect where teachers unconsciously facilitated the success of students they were told had higher IQs
what is a type 2 beta error
falsely saying there was no difference when there actually was
the probability of a type 2 beta error is determined by the power
(the power is how likely the study is to detect a difference if one actually exists…
power = 1 - beta)
the larger the sample size the greater the power
what is the equation for relative risk?
RR= risk to exposed/ risk to unexposed
RR= [a/(a+b)] / [c/(c+d)]
(helps to put it in standard format contingency table so that you recognize that RR= [outcome A/ total group with that exposure] / [outcome B/ total group with no exposure]
sometimes they dont give you the total and you have to add the outcomes together for the same exposure to get the denominator
what is the equation for odds ratio
this is the cross multiplying one within the middle of the table
OR= (a x d)/ (b x c)
the odds ration is used in case control studies because you cannot get a RR (you cannot determine the risk of an outcome because you hand picked the outcome in your case group)
what is the 68/95/99 rule
the 68/95/99 rule states that
68% of all observations lie within 1 SD of the mean
95% within 2 SD
and 99.7% within 3 SD
(this applies to a normal bell shaped distribution)
the actual numbers are a little different though
with 95% within 1.96 [z-score] SD
and 99% within 2.58 [z-score] SD
because you can only test a sample of the whole population, you end up getting some variability between means
(thus you need to account for standard error [SE]… basically it estimates how far the sample mean probably is from the true population mean)
SE= SD/ (square root of sample size)
so calculating the likely true range for the unknown population mean (the confidence interval) you would calculate
CI of the mean= mean +/- [z-score for confidence level] x [SE}
thus (for 95% CI):
CI= mean +/- 1.96 x (SD/ square root of n)
what happens to the sensitivity of a test if the cutoff point was shifted left
the cutoff point was changed to a lower value (shift to the left)
thus sensitivity of the test would increase because more people with the disease will be caught (more true positives… but probably not by much)
that being said there will be more false positives and a decreased specificity
how do you interpret a RR number
<1 is decreased risk of disease
=1 means null value
> 1 means increased risk of disease
thus the 95% CI for RR cannot cross 1
whereas the 95% CI for Absolute risk cannot cross 0
what is the difference in p values for CI’s that are 95% vs 99%
95% CI corresponds to a p value <0.05
99% CI corresponds to a p value < 0.01
what is the definition of health promotion
the process of enabling people to increase control over their health and determinants, and therby improving their health
aka improve diet
exercise regularly
dont smoke
lose weight if needed
its primary prevention
what is the difference between primary, secondary, and tertiary prevention
primary= before disease
secondary= after disease before symptoms
-case finding
tertiary= after symptoms to minimize progression or complications
how do you measure a patient’s “risk age”
a health risk assessment
which is a questionaire that uses demographics, medical info, lifestyle, and family history info to calculate the patient’s “risk age”
if the risk age>chronological age then they have a higher risk of death than the average person their age
what is the “stages of change” model
assessment of a patient’s readiness to change a problem behavior
precontemplative contemplation preparation action maintenance
mostly used for smoking
what should be maximized in a study to ensure that a difference will not be missed if one truly exists
1 - beta
(aka power)
beta= type 2 error (saying there is no difference when there really is)
theyre very similar but the question asked which should be MAXIMIZED and you would want to maximize the power (chance of detecting a true difference) and you would want to minimize a type 2 error
how do you measure the type 1 error in a study
with alpha
alpha is the max probability of making a type 1 error the researcher is willing to accept (type 1 error= finding a difference that does not exist)
generally alpha is compared to the p value
ex= if the alpha is set to 0.05 then there is a 5% chance of type 1 error and significance will be set at p value <0.05
what is detection bias
the fact that a risk factor itself can lease to extra diagnostic investigation and more probability that the disease is identified
ex- patients who smoke may have more imaging surveillance due to smoking which detects more cancer in general
which statistical method tests categorical (qualitative) variables vs quantitative (continuous) variables
categorical/qualitative= disease status blood type groups (this example patients are divided based on serum fibrinogen levels and again based on simvastatin exposure... the outcomes are not reported in mg/dL which would be quantitative but are categorized into high vs low which is a category)
- chi square test for independence/association (2 categorical variables)
- logistic regression (2 categorical variables or a categorical outcome)
quantitative/continuous= numerical values
body weight
glucose levels
- correlation coefficient (2 numerical variables)
- linear regression (2 numerical variables or a numerical outcome)
- t test and ANOVA (numerical outcome)
the FDA will only approve drug X if (drug X) + standard care decreases the rate of cancer recurrence at least 40% compared to standard therapy alone… recurrence rate on the standard therapy is 8% thus what is the max incidence of recurrent disease acceptable for the new drug + standard therapy?
so the drug/standard therapy combo must be 8% - (40% of 8%) = #
so 40% OF 8% is
0.40 x 8%= 3.2%
thus the maximum acceptable recurrance is
8% - 3.2% = 4.8%
is the maximum reoccurance rate acceptable if the drug will be approved is 4.8% recurrance
how do you calculate the relative risk reduction (RRR)
RRR= (absolute risk in the control - absolute risk in the treatment) / absolute risk control
this can overestimate the effectiveness of an intervention because RRR would be 50% if the drug reduced disease from 2% to 1% and likewise if the drug reduced disease from 50% to 25%
(2-1)/2= 50%
(50-25)/50= 50%
describe the difference between accuracy and precision
accuracy= validity
aka the test is measuring what it is supposed to (specifically the numbers… so if a new test measures 200 three times in a row but the gold standard measures 280 then it is not measuring what it is supposed to and has low accuracy)
*when the darts are near the center circle (aka close to the gold standard of measurement)
precision= reliability
(the test gives similar results with repeated measurements… the example above measured 200 three times in a row on the same sample and has great precision but all three numbers are way off from the actual value and thus has low accuracy)
*when the darts are clustered close to the other darts
describe the way the curves look in a negatively and positively skewed distribution
the “tail” is on the side of the skew
negative:
the hump on the right side because there are more outliers in the lower numbers which makes a “tail” in the negative direction
positive:
the hump on the left side because there are more outliers in the higher numbers which makes a “tail” in the positive direction
mode= tip of the hump mean= most towards the outliers median= in between (the better measure of central tendency)
what is an ecological study
when a study measures populations and not individuals
(they are kind of like a cross sectional studies but in populations instead of individuals)
useful for generating hypothesis but not for conclusions about the individuals within these populations (this would be an ecological fallacy)
what is a nested case control study
they start with a cohort study in which people are followed over time and the participants who develop an outcome of interest become the cases for a case control study
what is a qualitative study
one that focuses on discussion groups and interviews for narrative information that can be crucial for explaining the quantitative results
what is the major limitation of a cross sectional study
that the temporal relationship between exposure and outcome is not always clear
(its a snapshot in time and wont tell you if one thing likely caused the other)
what is a crossover study
when subjects are randomly allocated to a sequence of 2+ treatments given consecutively
(one group does A then B and the other group does B then A )
basically each group CROSSES OVER to the other treatment but in different orders
this allows patients to serve as their own controls
drawbacks= effects of one treatment may carry over and alter the response of the subsequent treatment
(to avoid this, a “washout phase” of no treatment is added between the treatments)
what is a case series study
a descriptive study that tracks patients with a known condition to document the natural history or response to treatment
how do you calculate cumulative incidence
CI= (new cases) / (total population at risk)
does not account for deaths or time in the denominator (whereas incidence RATE does consider time because it is reported as cases per year)
DOES account for those who already had the disease
Cumulative incidence= (new cases) / (total population - starting prevalence)
how do you calculate the rate of increase of a disease
increase in prevalence= (new cases - [deaths or cures])/ total population
how do you calculate the prevalence of disease
prevalence= ([existing prevalence + new cases] - death) / (population - total deaths)
a test has the specificity of 95%
if this test is used on 8 blood samples taken from patients who dont have the disease, what is the probability that all 8 tests come back negative?
each of the 8 blood samples is an independent event
each has a 95% chance of correctly testing negative (0.95)
thus the probability is
(0. 95) x (0.95) x (0.95) x (0.95) x (0.95) x (0.95) x (0.95) x (0.95)=
0. 95 ^ 8
on the other hand, the probability of at least 1 event turning out differently is 1-P
(P being all the events being the same)
so 1 - [0.95 ^8]
lung cancer has been the leading cause of cancer mortality since when
since the 1980’s
(female use of cigarettes peaked in the 1950’s and incidence of lung cancer increased 20-50 years later)
it started to decline slightly in 2000 do to decreased use
on a graph its starts low, peaks the highest, and rises rapidly starting 1980
what is the most common non skin cancer and the second cause of cancer death
breast cancer
the one that stays constantly pretty high on the graph, surpassed by lung cancer around 1980
mortality started to decrease in 1990’s due to adjuvant chemo and or radiation
what has caused the steady decline in colon cancer mortality
decreased since the 1950’s due to better surgery techniques and adjuvant chemotherapy
also protective against colon cancer:
colorectal cancer screening
menopausal hormone therapy in women
aspirin use
why has pancreatic cancer mortality rates slowly increased over time
incidence and mortality have increased in women and has become the 4th most common cause of cancer death in women
they follow the pattern of increased smoking in women but lung cancer kills way more
why has stomach cancer declined dramatically
incidence and mortality decreased drastically over the first half of the 20th century because of better refrigeration and food preservation (thus decreased salt intake), better sanitation, and more adequate housing (decreased h pylori infection rates)
what is the name for the time elapsed from exposure to manifestation of a disease
incubation period (for infectious disease) or latent period (for non-communicable chronic disease)
in the question stem, men who took supplements longer than 5 years had protection from stroke and men who took it less than 5 years didnt have protection (p value >0.05)… the explanation could be that there is a discrepancy because reduction of stroke with supplements is associated with a long latent period
(aka you need to take supplements for a long time to see an outcome effect)
latent period concept can be applied to disease pathogenesis and exposure to risk modifiers
how can you reduce the effect of selection bias on a study
you can adjust for the differences in baseline characteristics related to behaviors to reduce the effect of this bias
what explains why there is a significant difference between alcohol consumption and bladder cancer but when the subjects are broken up by smoker vs non smoker there is no longer a significant difference in EITHER group
confounding
what is the rare disease assumption
in a case control study for rare diseases you assume that the OR approximates the RR when the incidence is low (<10%)
dont forget that if 95% of the population falls within 2 SD and 5% falls outside of it, that the 5% is split between both sides on the extreme ends
so if youre asked to look for how many are above a certain number, remember that its half of that 5%!!!
what are other names for observer bias
detection bias
or
expectancy bias
important when outcomes are subjective
(the pathologists at the hospital are much more likely to diagnose the disease maybe because they know what the study is looking for or they have medical historys whereas outside pathologists may be blinded to the study objective or medical history)
the investigators evaluation is affected by preconceived expectations or prior knowledge leading to an overestimation of disease association or treatment effects
fix this by blinding the study
what is the equation for:
ARR
RRR
RR
ARR= control rate- treatment rate
(remember to use the rate of people, aka the number over the total, not the absolute number of people presented in the 2x2 table)
RRR= ARR/ control rate
RR= treatment rate/control rate
what is the equation for number needed to treat? (NNT)
NNT= 1/ARR
first there were 25 people with MI out of 1000 total in the control group
control event rate= 25/1000= 0.025
there were 10 out of 1000 people with MI in the experimental group
experimental event rate = 10/1000= 0.01
so the ARR was 0.025 - 0.01= 0.015
aka 1.5%
the NNT = 1/ 0.015 = 66.6 =~ 67
67 patients need to be treated with the experimental drug to prevent MI
the ideal NNT is 1 meaning that all patients would benefit…
Describe how to make a 2x2 table when given the information:
200 total people
50% have dementia
new test to catch dementia has a sensitivity of 90% and a specificity of 80 %
in the columns label the table dementia present and dementia absent
in the rows label test result positive and test result negative
in the total column place the numbers 100 under the bottom of each dementia present and absent
since the sensitivity was 90% the top left box will have 90 TP tests meaning that the bottom left box will have 10 FN
since the specificity is 80%, then the bottom right box will have 80 TN and in the top right will have 20 FP
add up the totals across the rows and use that information to calculate the NPV
NPV= TN/ (all negatives)
what is attrition bias
a type of selection bias that results from a loss of follow up with subjects
the remaining subjects are at a disproportionately different risk of outcome than the original population
attrition bias is not the loss of subjects at random between both the exposed and unexposed groups, it happens mainly to one group
what is a misclassification bias
either the outcome or exposures is not identified correctly
but they affect all groups the same
ex= when BPs are taken on all adult subjects with a child size BP cuff accidentally
what is the difference between determining a patient’s risk for a disease and the relative risk
risk= only the number of people with the exposure over the total with that outcome for what you are looking for
ex= 18 people with low beta carotene got alzheimers out of 45 people with low beta carotene… thus his risk of getting alzheimers with low beta carotene is 40%
(you do not take into account the people who got alzheimers with normal beta carotene levels because that would be relative risk)
be sure to read carefully which one they want
how do you calculate the power of a study
power = 1 - beta
beta is the type 2 error- aka not finding a difference that actually does exist
what does ANOVA stand for
Analysis of variance
used to find a significant difference between the means of 2+ groups
(the outcome must be measured as a quantitative number, not a categorical group
in what circumstance would be it be useful to do a multiple logistic regression to analyze data
when you want to predict the probability of a binary outcome
(aka presence or absence of cancer based on one or many independent variables that can be either numerical or categorical)
what is the pearson correlation coefficient used for
measure the strength and direction of a linear relationship between two numerical values
if you want to do a case control study to determine if exposure to chemicals increases the rate of AML, who do you pick as your cases and your controls
cases= children with AML
control= children without AML
cases and controls should be selected regardless of exposure to chemicals
(selecting subjects based on exposure status is inappropropriate because comparing the frequency of exposure between the groups is what determines whether the exposure was more prevalent among cases compared to controls)
aka if you’re fixing the outcome you can not fix the exposure otherwise its not really a study
how do you calculate the number needed to harm (NNH)
NNH= 1/ ARI
(absolute risk increase)
ARI= (adverse event rate in experimental group) - (adverse event rate in control group)
Describe he case fatality rate
the number of people with a disease who died divided by the total number of people who had that disease
what does the mutation in CF cause?
CF= AR disease with recurrent sinopulmonary infections, pancreatic insufficiency, and malabsorption
different mutations all affect the CF transmembrane conductance regulator gene (CFTR)
The most common CFTR mutation is delta F508 (70% of cases)= a 3 base pair deletion of phenylalanine at amino acid position 508
**this causes abnormal
post translational processing of the transmembrane protein
(improper folding and glycosylation which is seen by the ER who sends it for proteasomal degredation)
drugs like lumacaftor can partially correct the folding defect and increase the functional CFTR
what are the functions of the other less common mutations causing CF
- you can have decreased transcription/amount of normal CFTR (milder, dx in adults)
- mutation affecting chloride conduction through CFTR (defect in the formation of the channel)
- a truncated protein on the cell surface due to a premature termination (leads to recognition and degredation… common in ashkenazi jews)
- protein withdecreased response to cAMP and ATP (mut that reduce the ability of the channel to open)
BUT, again remember that delta F508 is the most common and impairs post translational processing of the transmembrane protein
describe what TB looks like on histology
a picture is used that has a brown clumpy string of circles that looks like a turd
histo= epithelioid macrophages and multinucleated giant cells (the turd)… these are the predominant cells of granulomas
granulomas are formed when macrophages cannot easily digest or remove foreign substances
interferon gamma (from mature TH1 cells) contributes most to the granulomas because interferon gamma activates macrophages to improve their myocobacteria killing ability
for most people the granulomas effectively controls TB infection
dont forget TB live in macrophage phagolysosomes
what do macrophages secrete and why
IL-12= tell helper T cells to become TH1 (because TH1 secretes interferon gamma which helps macrophages kill ingested mycobacteria)
TNF alpha= to recruit more monocytes and macrophages to help fight infection
what does C3a do
stimulates mast cell histamine release
histamine increases vasc permeability and vasodilation
what is an anaphylatoxin
a complement fragment or peptide
what does IL 4 do
tells T cells to become TH2, increases B cell growth, and promotes class switches to IgE
what does IL 5 do
promotes B cell growth/differentiation
promotes eosinophil growth/diff
simulates class switching to IgA
what do the leukotrienes do
C4, D4, E4= vasoconstriction, increased vasc permeability, and bronchospasm
what does platelet activating factor do
causes platelet aggregation
vasoconstriction
bronchoconstriction
and increased leukocyte adhesion to endothelium
at super low concentrations it can have the opposite effect (vasodilation and increased permeability)
what does thromboxane A2 do
its a powerful platelet aggregator and vasoconstrictor
describe how macrophages kill TB
macrophage immunity to TB is led by TH1 cells
without TH1 cells helping make granulomas the host couldn’t fight the infection
granuloma formation and maintenance requires:
interferon gamma
IL 12
TNF alpha
TB causes caseating granulomas
what kind of drugs are dexamethasone and betamethasone
corticosteroids
give to women in preterm labor (for premie babies born before 32 weeks) to increase surfactant production
this decreases the risk of respiratory distress syndrome and decreases mortality
works by accelerating the maturation of type 2 pneumocytes
what type of surfactant is made in the terminal saccular stage of lung development
DPPC (a type of lecithin)… aka dipalitoylphosphatidylcholine
surfactant is lipoprotein rich in phospholipids which helps create a lipid rich monolayer that separates alveolar gas from underlying aqueous fluid
prevents atelectasis and end expiratory collapse and increases compliance
until 33 weeks gestation, lecithin:sphingomyelin levels are about equal… after 33 weeks lecithin rises dramatically and a ratio of 2 indicates mature fetal lungs
you can test the markers because the fetus effluxes the lung fluid into the amniotic fluid
what impact does uncontrolled maternal hyperglycemia have on the baby
it causes high insulin levels in the baby
the high insulin inhibits the effects or cortisol on the maturation of surfactant proteins (their babies are at higher risk for resp distress)
even though steroids raise blood sugars, their benefit given to preterm mommas has benefits that far outweight the risks
why is magnesium sulfate given antenatally to women at risk for preterm delivery
it has been shown to decrease the risk for cerebral palsy (which results in permanent neurologic disability)
though lung function in premies is more important and the more common cause of death
what medications can be used to inhibit preterm labor (aka tocolysis)
Nifedipine (CCB- causes myometrial relaxation by inhibiting myosin light chain kinase mediated phosphorylation)
terbutaline (beta agonst that increases cAMP in myometrial cells in order to inhibit myosin light chain kinase and relax smooth muscle)
what is the most common mutation causing PAH and how does PAH present
mut= inactivating mutation of BMPR2 gene (which is pro-apoptotic)
PAH presents as SOB and exercise intolerance in women 20-40
How is PAH treated
lung transplant
vasodilators can improve symptoms until they can get a transplant
ex=
bosentan (endothelin receptor blocker) leads to vasodilation of the pulmonary arteries
endothelin is a potent vasoconstrictor that also causes endothelial proliferation (can slow progression of cor pulmonale)
what does clopidogrel do
it inhibits ADP-induced platelet aggregation
used for atherosclerotic ischemic disease to prevent clots in stents that are placed
what does enalapril do
its an ACEI
treats
CHF
HTN
DM nephropathy
what does etanercept do
it inhibits TNF activity by binding TNF and preventing its interaction with its own receptor
TNF is proinflammatory
blocking TNF is used to treat RA, psoriasis, and psoriatic arthritis
what is indomethacin
an NSAID (non specific COX inhibitor) that suppresses prostaglandin synthesis
used as an anti inflammatory and pain reliever
what is the neuromuscular treatment for obstructive sleep apnea
OSA= recurrent upper airway collapse during sleep due to a neuromuscular weakness of upper airway dilator muscles
tx= stimulation of the hypoglossal nerve (CN 12) using an implantable nerve stimulator causes the tongue to move forward slightly, increasing the diameter of the airway
loud snoring and gasping respirations indicates an oropharyngeal cause of OSA rather than diaphragm dysfunction
what is the culprit:
gram positive cocci in chains, beta hemolytic, and bacitracin resistant
gram pos cocci in chains= strep
(remember staph is clusters)
group A and B strep are beta hemolytic
but, strep pyogenes (GAS) is bacitracin sensitive
so the answer is strep agalactiae (GBS)
how does a group B strep infection threaten infants
if the mom is colonized it can be transmitted to the baby and cause:
neonatal septicemia
neonatal meningitis
pneumonia
Baby Brains get Beta hemolytic Bacitracin Blocking (resistant) group B strep during Belabored deliver
what is the treatment if a pregnant women is carrying group B strep
universal screening for colonization of the vaginal and rectum at 35-37 weeks gestation
positive culture or previously infected infant= treat with INTRAPARTUM (aka during labor) antibiotics prophylaxis
1st line tx= penicillin (or ampicillin)
this lasts for about 4 weeks
what groups of people are at high risk for TB
health care workers
immigrants from endemic countries
prison inmates
what does a CD8+ T cell do
its a cytotoxic T cell
TH1 cells release INF gamma and IL-2 which activate cytotoxic T cells
cytotoxic T cells kill infected host cells during viral infection
what do natural killer cells do
NK cells are part of the innate immune system and do not require host stimulation to function
they help kill malignant and virally infected cells
describe the histology of TB
its a purple empty circle surrounded by dark purple cells that almost form a full encaseating circle around the center
(“multiple nuclei peripherally shaped as a horshoe”)
this is a caseating granuloma and in the center is a Langhans giant cell (not the same thing as a langerhan cell which is an antigen presenting cell of the skin and mucosa)
Describe alpha 1 antitrypsin deficiency
alpha 1 antitrypsin is made in the liver and is meant to stop neutrophil elastase from degrading the alveolar walls (esp lower lungs)
deficiency of this protein means they get excessive degredation of their alveolar elastin
presents as early onset, lower lobe emphysema
what makes elastin in the lungs able to stretch and recoil
interchain cross links involving lysine
elastin is a fibrous CT protein that provides elasticity to skin, blood vessels and pulm alveoli
it is made as tropoelastin and contains proline and lysine
unlike collagen it has little hydroxylation
tropoelastin is secreted extracellularly where it interacts with the fibrillin microfibril scaffold
lysyl oxidase and copper alters the lysine and forms desmosine cross linkages which accounts for the rubber like properties of elastin
how is collagen made into the triple helix
procollagen is made and then it undergoes post translational hydroxylation and glycosylation
then disulfide bridges are formed between the C- terminals of the three collagens at the alpha chain to make the triple helix
What is Train of four (TOF) stimulation
stimulation test used during anesthesia to asses the degree of paralysis induced by agents that block the NMJ
a peripheral nerve is stimulated 4 x in quick succession and the muscular response is recorded… the height of each bar is the strength of each twitch (higher bars= more individual muscle fibers)
what is the difference in train of four stimulation between nondepolarizing NMJ blockers and depolarizing NMJ blockers
nondepolarizing= vecuronium
competitive inhibitor of post synaptic Ach receptors prevent activation and cause progressively decreasing twitches
(“fading pattern” because less Ach is released with each impulse)
depolarizing= succinylcholine
two phases of action.
phase 1. initially prevent repolarization and show equal reduction of all 4 twitches
(because presynaptic Ach receptor stimulation helps mobilize presynaptic Ach vesicles for release)
phase 2. persistent exposure to sux causes eventual desensitization and inactivation of Ach receptors (functionally similar to nondepolarizing blockers)… phase two seen in patients with the abnormal cholinesterases
cholinesterase inhibitors can reverse non-depolarizing NMJ blockers or depolarizing in phase 2 only
what does succinylcholine do
depolarizing NMJ blocker
(muscle relaxant)
used for rapid sequence intubation due to rapid onset (<1 min)
duration is typically <10 mins due to metabolism by cholinesterase
some patients are homozygous for an atypical plasma cholinesterase which breaks down sux super slow (these patients end up with paralysis for hours with sux and must be placed onto mechanical ventilated until it wears off)
what is dantrolene used for
malignant hyperthermia
and neuroleptic malignant syndrome (similar but to neuroleptics/antipsychotics)
dantrolene is a skeletal muscle relaxer
works by reducing the amount of calcium released by the SR
what kind of drugs are pancuronium and tubocurarine
non depolarizing NMJ blockers
these do not function in phases and their Train of Four responses are always a fading pattern
cholinesterase inhibitors (like neostigmine) reverse nondepolarizing blockers
what does major basic protein from eosinophils do
major basic protein is a potent anti-helminthic (worm) and anti-parasitic toxin capable of causing damage to epithelial and endothelial cells of the lungs in patients with atopic (extrinisc allergic) asthma
it attaches to and disrupts the outer membrane of helminths
what is in the granules of basophils
granules stain dark blue, are irregularly sized, and obscure the nucleus
they contain:
heparin
histamine
and SRS-A (slow reacting substance of anaphylaxis, a mixture of leukotrienes)
what is aspergillus fumigatus
a mold that is inhaled as spores and can cause disease in immunosuppressed or neutropenic patients
presents with cough and hemoptysis
(here in a patient with past TB infection, treated, and smoking history)… or can be asymptomatic
causes aspergilloma (mycetoma) which represents aspergillus colonization… it develops in old lung cavities (like ones from TB, emphysema, or sarcoidosis)… aspergillus colonizes the cavity and forms a “fungus ball” seen on xray as a radiopaque structure that shifts when the patient changes position
aspergillomas are not contagious
aspergillus can cause allergic bronchopulmonary aspergillosis (ABPA) in patients with asthma (presents with wheezing and migratory pulmonary infiltrates…dx with increased IgE titers and ab’s to aspergillus)
explain the pressure volume curve of the lung and chest wall complaince
lung volume is always positive, chest wall is almost always negative, they oppose one another equally at the functional residual capacity (FRC) resulting in an airway pressure of zero
at FRC, lung volume is zero, alveolar pressure is zero, and pleural pressure is -5 (always negative)
makes sense if you look at each graph seperately, those are the values where the graphs fluctuate around
the consequence of a constantly negative pleural pressure= puncturing the pleura only brings air inward into the intrapleural space and thus a pneumothorax will develop
the FRC is also thought of as the air left in the lungs after a passive exhale (aka the residual volume plus the expiratory reserve volume)
what is alpha 1 antitrypsin deficiency associated with
panacinar emphysema
liver cirrhosis
smoking dramatically increases the risk of panacinar emphysema by inducing inflammation (neutrophils and macrophages release neutrophil elastase= permanently inactivates A1AT via oxidation of methionine residues)
smokers get symptomatic around 35 whereas nonsmokers get symptoms at 50
an HIV patient with CD4 counts of 800 presents with focal lobar community acquired pneumonia. what is the bug that caused it?
normally you might assume its an AIDS related opportunistic pathogen like pneumocystis jiroveci (asociated with counts <200)
BUT
a normal adults CD4 count is 400-1400 and our patient’s is 800 (meaning that he is currently not immunocompromised)
that being said, the most common cause of community acquired pneumonia in an immunocompetent adult is strep pneumoniae (70%)
what is the most common cause of atypical pneumonia and who does it show up in
mycoplasma pneumoniae
school age children
military recruits
college students
(dont forget strep pneumoniae is the most common cause of CAP in adults)
what is the pattern of an obstructive lung disease on pulmonary function test
obstruction of air leaving the lungs bronchiectasis chronic bronchitis emphysema asthma
decreased FEV1/FVC ratio
