MRC Basic Science/Stats/Epi Flashcards
- ) What is a Case-Control Study? What Level of Evidence?
2. ) What stat is calculated?
- ) Group of patients compared RETROSPECTIVELY (ie. look at disease and see what risk factors they had) = Level 3
- ) Odds Ratio = probability event will occur/probability event will not occur
- ) What is a Cohort Study? What Level of Evidence?
2. ) What stat is calculated?
1.) Group of patients compared PROSPECTIVELY (ie. look at risk factors 1st and see who gets dz) = Level 2
2.) Relative Risk = risk in exposed/risk in unexposed
(RISK = INCIDENCE!)…only a cohort study can tell you incidence b/c it is going forward in time!
RR = 1: No association
RR > 1: positive association (risk in exposed > risk in unexposed) CANNOT INFER CAUSAL!! - can’t tell!
RR < 1: negative association (risk in exposed < risk in unexposed) CANNOT INFER PROTECTIVE!!
**If 95% CI crosses 1 = NOT SIGNIFICANT
1.) What type of study are:
Case-Control, Cohort, Case Series, and Case Report?
2.) What type of study is a RCT?
- ) Observational
2. ) Experimental
- ) What Level of Evidence is a RCT typically?
2. ) What can downgrade it?
- ) Level 1
- ) Poor f/u (<80%), heterogeneous results, no blinding, concerns about randomization. ANY OF THESE WOULD MAKE IT A LEVEL 2 STUDY!!
What is the difference b/t a systematic review and a meta-analysis?
Systematic review just looks at a bunch of studies.
Meta-analysis uses fancy STATS to combine the results!
FDA Phases of Research - what happens in each Phase I-IV?
I -> “First in Man” to determine safety
II -> Determine if device/drug is effective (MOST COMMON phase of failure)
III -> Confirm efficacy through large trials
IV -> Postmarketing surveillance
Does QI study require IRB?
NO! Not research!!
Name the studies that are Levels 1-5 of evidence?
o Level 1 – Randomized controlled trial or Meta-analysis
o Level 2 – Cohort study (PROSPECTIVE)
o Level 3 – Case-control study (RETROSPECTIVE)
o Level 4 – Case series, cross sectional
o Level 5 – Expert opinion
What types of Bias occurs BEFORE a study (3)?
o Selection – improper recruitment of subjects with different features
*Prevent this with randomization that is blinded
o Channeling – subjects unequally given treatment based on their features
o Chronology – use of historical controls
What types of Bias occurs DURING a study (5)?
o Detection – looking harder at one group than another
o Recall – relying on patients to remember events
o Interviewer – influence the interviewer has on responders
o Performance – procedures not performed in uniform way
o Hawthorne Effect – alteration of behavior of subjects based on knowledge they are being observed
What types of Bias occurs AFTER a study (3)?
o Citation – more likely to believe study in top journal
o Publication – positive results more likely to be published
o Conflict of Interest – researcher personal conflicts
What is the difference b/t incidence and prevalence?
Incidence = risk over time (looked at with cohort studies b/c they are PROSPECTIVE) Prevalence = proportion of existing cases in the population being looked at - at a single moment (snapshot)
What statistical tests are used to evaluate categorical data? And how do you know which one to use?
Chi-squared (most common to use)
Fischer exact -> use for SMALL groups (remember that exact count easier with small group!)
What statistical tests are used to evaluate continuous data? And how do you know which one to use?
T-test, ANOVA, Pearson correlation co-efficient, Regression, Mann-Whitney U test.
PARAMETRIC DATA: (bell curve, data normally distributed)
T-test (two groups)
ANOVA (3 or more) “OVA two!
NONPARAMETRIC DATA -> pick Mann-Whitney U test
Determine relationships -> Pearson correlation co-efficient
Predict outcomes from variables -> Regression
What is sensitivity?
How do you calculate sensitivity?
Sensitivity = ability of a test to detect dz
TP/TP+FN
SnOUT = negative result rules OUT a diagnosis if you have high sensitivity
What is specificity?
How do you calculate specificity?
Specificity = ability to detect health
TN/TN+FP
SpIN = positive result rules IN a diagnosis if you have high specificity
What is PPV?
How do you calculate PPV?
How likely you are to have dz w/ a positive result.
TP/TP+FP
What is NPV?
How do you calculate NPV?
How likely you are to not have dz w/ a negative result.
TN/TN+FN
What is a Type I error?
Alpha error = False positive error
Incorrectly rejected the null hypothesis -> said there was a difference and there IS NOT! (Cried wolf!) MORE DEVASTATING!
Only willing to except this 5% of the time
p < 0.05 is a marker of certainty -> which means the likelihood of the results happening by random chance is 5/100 when no association really exists. *NOTE: A HIGH P-VALUE DOES NOT MEAN IS STATISTICALLY INSIGNIFICANT, IT MEANS THAT THERE IS A HIGH DEGREE OF UNCERTAINTY!!
What is a Type II error?
Beta error = False negative
Incorrectly accepted the null hypothesis -> said there was no difference/association and there was - you missed it!
LESS devastating
Willing to accept this 20% of the time.
What is the Power of a study?
Probability of finding a significant association if it exists -> ability to find a true positive or true negative.
Calculated by 1-beta = 80% chance of doing a study that finds p < 0.05 if true association exists.
What test gives you detection of publication bias in meta-analysis?
Funnel plot
- ) What is the equation of Stress?
2. ) What is the equation of Strain?
- ) Stress = Force/Area
2. ) Strain = change in height/original height
What is the definition of Hooke’s Law?
Stress is proportional to strain in the elastic zone of the stress strain curve (initial linear part of curve)
What is the definition of the Yield Point?
Point at which when you go past adding more strain there is permanent deformation (move from the elastic/linear part of Stress/Strain curve to the plastic/nonlinear portion
What is Young’s Modulus?
The slope in the elastic zone - this is a unique characteristic of each material.
A higher Young’s Modulus can withstand greater force = more stiff.
Remember: Stiffness = slope = Youngs Modulus
The linear/elastic region of the stress/strain curve ends in “X” and the non-linear/plastic region ends in “Y”
X = Yield Point Y = Ultimate Strength
What is is Ultimate Strength?
Maximum stress the material can sustain. The highest point on the graph! (*NOTE: this is not the breaking point….that occurs at a lower stress b/c the material will deform/necking and cross-sectional area will decrease and then the material will fail under less stress)
What is necking?
Occurs after the Ultimate Strength - and is the reduction of cross-sectional area of the material, overall decrease stress
What is the breaking point = fracture point?
Failure of material that occurs after necking of the material
What is fatigue?
Failure of the material below the ultimate strength due to numerous loading cycles
What is the difference b/t stiffness, strength, and toughness of a material?
- Stiffness depends on the elastic properties = ability of an object to resist deformation. Young’s Modulus tells you stiffness (higher means more stiff!) - so higher slope means more stiff on graph and lower slope means more flexible!
- Strength depends on the plastic properties; highest area on curve occurs in plastic zone = ultimate strength.
- Toughness is amount of energy a material can absorb before failure = area under the stress/strain curve
What is the ductiliy of a material?
How is the represented on the stress/strain curve?
Amount of deformation a material undergoes before fracture.
Difference b/t the Yield Point and Fracture/Breaking Point.
Brittle material = small diff
Ductile material = big difference
What does viscoelastic mean?
Mechanical properties vary with external conditions. Biologic materials are typically viscoelastic
What is creep?
Deformation with time under a constant load.
Can cause failure under loads significantly below ultimate strength.
What is the difference b/t isotropic material and anisotropic material?
Isotropic -> behaves the same regardless of force
Anisotropic -> behaves differently depending on force (MOST biomaterials are this!!)
Which metal has the MOST bacterial adherence?
The LEAST?
MOST = Titanium alloy LEAST = Tantalum
What additional quality is seen on the Stress/Strain curve of ligaments that is not seen on curves for metals/biomaterialas?
Toe region at beginning of curve! In the toe region until the crimped fibers of the ligaments have straightened.
What is the equation for stiffness of a:
- ) Plate
- ) Cylindrical nail
- ) R^3
2. ) R^4
What is Wolff’s Law?
Remodeling of bone occurs in response to mechanical stress (this is what happen when the fracture callus remodels)
- ) What cell lineage do osteoblasts come from and what 3 key transcription factors contribute to their formation (versus other types of cells forming)?
- ) What other cells come from this same cell lineage and what factors make these cells form?
- ) What cell line are osteoclasts derived from?
- ) Mesenchymal progenitor cell. Runx2, Osx, Wnt/Beta-catenin
- ) Adipocytes: PPAR-gamma; Chondrocytes: Sox
- ) Hematopoietic/myeloid progenitor
- ) What is the function of Sclerostin (SOST)?
- ) What effect does PTH have on Sclerostin?
- ) What effect does Calcitonin have on Sclerostin?
1.) Released by osteocytes and inhibits Wnt pathway/osteoblasts-> inhibits bone formation (part of normal feedback mechanism).
When bone is not loaded -> SOST is released and you get less bone formation! (lack of stress = lack of bone….in accordance with Wolff’s law!)
2.) PTH increases Sclerostin (makes sense b/c PTH is secreted in response to low Ca and thus in line w/ osteoblast inhibition to make sure the Ca isn’t taken up from blood to make bone!)
3.) Calcitonin decreases Sclerostin
- ) How do osteoclasts bind to bone?
2. ) How is bone resorbed by osteoclast?
- ) Integrin on the surface of the osteoclast binds to Vibronectin on surface of the bone to create a sealing zone
- ) W/in sealing zone Howships lacunae is created and carbonic anhydrase creates an acidic area is created and cathepsin K enzyme digests organic matrix at the ruffled border
What 2 molecules produced by Osteoblasts regulate Osteoclasts?
- ) RANKL - activates osteoclasts
2. ) OPG - binds to RANKL so that it cannot interact with RANK; prevents osteoclast activity
What is the role of Calcitonin?
Released by the parafollicular (“C”) cells of the thyroid gland.
DIRECTLY BINDS osteoclasts to slow bone resorption -> reducing serum Ca
(opposes the effect of PTH - which is secreted by the Chief cells of the parathyroid gland)
What is the role of PTH?
- PTH is secreted by the Chief cells of the parathyroid gland in response to low Serum Ca
- Sustained PTH makes osteoblasts release RANKL to activate osteoclasts and get bone resorption to help increase Ca in serum. Also causes increased Ca re-absorption in kidneys
- Pulsed/Intermittent PTH gives net ANABOLIC effect and builds bone! (this is how Teraparatide = 1st 34 AA’s of PTH drug works! Only anabolic osteoporosis drug!)
- *Also remember that Vit D parallels PTH (“PDH”) and also causes increases in reabsorption of Ca in the kidneys and intestines
What collagen type is predominantly found in bone?
bONE = Type ONE
What is the most abundant noncollagenous matrix protein in bone?
What is another important fact about this protein?
Osteocalcin - most specific marker of mature osteoblasts
What is the Hueter-Volkmann Law?
Compressive force -> inhibit bone growth
Tensile force -> stimulates bone growth
What are the 3 main types of bone formation?
- ) Intramembranous -> flat bones, primary fx healing
- ) Enchondral -> long bones, physis, fracture callus (bone laid down on cartilagenous framework - converts a soft callus to hard callus)
- ) Appositional -> Periosteal bone enlargement (width)
What area of the physis do SH fx occur through?
Zone of Provisional Calcification (which is in the Zone of Hypertrophy)
What dz effects the reserve zone?
Diastrophic dwarfism
What dz effects the proliferative zone?
Gigantism
Achondroplasia
What dz effects the hypertrophic zone?
Muccopolysaccharidosis (Morquio, Hurler)
Rickets
(SH fxs!!)
In appositional bone growth what group of cells is responsible for this growth of width?
Groove of Ranvier = wedge-shaped zone of cells contiguous with the epiphysis at the periphery -> supplies chondrocytes to the periphery
What is the Perichondral Ring of La Croix?
Involved in appositional growth and is a dense fibrous tissue that supports the physis peripherally
(Picture in my mind like a crown supporting the outside of the physis around the bone!)
How do NSAIDs effect fracture healing molecularly?
Inhibition of COX-2 by NSAIDS causes repression of Runx2/Osx (which is critical for differentiation of osteoblasts)
(Remember that the 3 main stages of fx healing are -> INFLAMMATION, repair, remodeling)
Are the following items Osteoinductive, Osteoconductive, or Osteogenic?
- ) Autograft
- ) DBM
- ) CaPhosph and CaSulfate
- ) Allograft
- ) Autograft - all 3!
- ) DBM - osteoinductive and condutive
- ) CaPhosph and CaSulfate - osteoinductive and conductive
- ) Osteoinductive and osteoconductive
When does peak bone mass occur?
3rd Decade of life (b/t 16-25 yo)
What is the recommended intake of Ca and VitD for adults over 50 yo for osteoporosis prevention?
Ca 1200-1500 mg
Vit D 800-1,000 IU
What is an XR finding of Rickets?
Physeal cupping
- ) What is the inheritance of Familial Hypophosphatemic Rickets?
- ) What lab value helps to differentiate this from Nutritional Rickets?
- ) X-linked from mutated PHEX gene -> cannot absorb phosphate
- ) They will have NORMAL CALCIUM LEVELS!
- ) What are the 2 types of Vit D dependent rickets?
2. ) How do you tell the difference w/ the labs?
1.) Type I -> defect in 1 alpha-hydroxylase so cannot make active Vit D. (Autosomal recessive inheritance). Tx: just give physiologic dose Vit D
Type II -> defect in the receptor for 1,25-Vit D. Tx: give HIGH dose Vit D
2.) Look at Vit D levels. In Type 1 have low 1,25-OH; and Type 2 has HIGH levels!
What 5 medications should you be aware that might disrupt the Vit D pathway?
Prednisone PPI's Antiepileptics SSRIs Heprin
What score gives you the dx of osteoporosis?
What about osteopenia?
Osteoporosis: T score < -2.5 (T score to treat!)
Osteopenia T score b/t -1 and -2.5
Who should receive osteoporosis treatment?
- Have prior hip or vertebral fx
OR
* T score -2.5 or less at femoral neck or vertebrae
OR
* Osteopenia (T-score between -1 and -2.5) AND
* FRAX score suggestive of 10 yr risk of hip fx is 3% or more OR
* major osteoporosis fx risk 20% or more
What is the MoA of Bisphosphonates?
Binds to bone surface and gets taken up by osteoclasts -> apoptosis.
Non-Nitrogen containing -> ATP toxic/non-functional analog
Nitrogen containing -> inhibits farnesyl pyrophosphate synthease enzyme which inhibits protein prenylation and GTPase formation needed in cholesterol pathway.
What are examples of osteoporosis medications and how do they work?
- ) Bisphosphonates - bind to bone and are ingested by osteoclasts -> apoptosis.
- ) Estrogen based - ie Raloxifene -> reduces osteoclast activity
- ) Teriparatide -> activates adenyl cyclase -> pulsed administration has net anabolic effect (CONTRAINDICATED IN PTS w/ Paget’s or previous bone mets due to risk of secondary osteosarcoma)
- ) Denusomab -> Ab to RANKL (can be used in osteoporosis, MM, GCT, mets -> remember that the tumor cells secrete cytokines that make osteoblasts secrete more RANKL)
- ) What is the functional unit of a muscle?
2. ) What is it composed of?
1.) Sarcomere
2.) Thick filaments = myosin (longer/thicker word)
Thin filaments = actin
A band = myosin
I band = actin
What are the main sources of energy for muscles in:
- ) 0-10sec of activity
- ) 1-4 min
- ) 4+ min
- ) ATP & CP
- ) Glycogen & lactic acid
- ) Glycogen & fatty acids
When muscle is injured what is the common location of injury and what type of contraction typically causes injury?
- ) Myotendinous jxn
2. ) Eccentric contraction
What is the organization of nerve anatomy?
axon (surrounded in myelin), surrounded by endoneurium, grouped together into fascicles which are surrounded by perineurium, surrounded by epineurium
What are C type nerve fibers?
Pain
What is the rate of nerve regeneration?
1 mm/day
What is the return of function after a nerve injury (ie in what order do things come back?)
- ) Sympathetic activity
- ) Pain
- ) Temp
- ) Touch
- ) Proprioception
- ) Motor
What must be intact for full nerve recovery after injury?
Endoneurium
What type of collagen makes up majority of tendons?
Type I
What are the transitional tissues involved in tendon attachment to bone?
Tendon -> Fibrocartilage -> Mineralized Fibrocartilage -> Bone
What are the 2 types of ligament attachment to bone?
- Direct: ligament-fibrocartilage-mineralized fibrocartilage-bone
- Indirect (more common): ligament-mineralized fibrocartilage-periosteum-bone
- MCL attaches indirectly to bone via Sharpey’s fibers (made of Type I collagen)
- Indirect (more common): ligament-mineralized fibrocartilage-periosteum-bone
