Clinical sciences Flashcards
what is the p value and whats its sig value
Stat sig p value = 0.05 = probability that the null hypothesis is true/that you can reject the null hypothesis
if a trial estimate is 1.4 what does that mean
Estimate 1.4 = 40% more likely to be in remission (or 1.4x)
if a CI is described as (95% between 0.8 and 2) what does this mean
CI = estimate of precision (95% between 0.8 and 2) = 20% worsening of outcome and 100% improvement
when do you use
- chi squared
- t test
- mann whitney u test
Chi squared: categorical data
T test: continuous variable that’s normally distributed (and in 2 groups)
Mann Whitney U test: continuous variable that’s NOT normally distributed (and is in 2 groups)
case control study
- explain
- when do you use
- what bias?
for rare diseases. Start with the outcome. but get recall bias!
cohort study
- what for
what is it
what bias
Cohort: for common diseases. Start with the exposure/risk. Get channeling bias (if haven’t randomised ppl to a tx, there’s often a reason they ended up with that one)
type 1 error
- what is it
what causes it
Type 1: when we get a false positive
= incorrectly concluding that there’s a stat sig difference in a dataset
— (causes: failure to adjust for confounders, inadequate blinding, not performing an intention to treat analysis, poor randomisation)
type 2 error
what is it and what causes it
Type 2: when we get a false negative
= incorrectly conclusing that there’s no stat sig difference in a dataset
— (sample size is too small; classically inadequately powered study)
Aka boy who cried wolf: 1st time he cried wolf, village came running and he had made it up = false positive
but 2nd time, there is a wolf but village doesn’t believe him = false negative
sensitivity equation
= the number of pts with a positive test who have the disease divided by all pts with the disease
if high wont miss many ppl with the disease
= few false negatives aka good for ruling out diseases (like d-dimer in pe)
true positive = new test +ve & ref test +ve
Sensitive so it picks up lots of trash as +ve too
- False neg = new test -ve and ref test +ve
specificity equation and what is it
Specificity = true neg / (true neg + false positive)
= the number of pts who have a negative test and dont have the disease dividedby the number of patients who dont have the disease
= few false positives; so if its positive you probably have the disease = relatively diagnostic
- the test is specific to the disease, only positive when you have it
- true neg = both neg
= False +ve = new test +ve and ref test -ve
NNT equation & what is it
NNT = 1/absolute risk difference
- ARR = the event rate in the control arm - event rate in treatment arm
- aka 10% of control group relapsed vs 5% of treatment arm
- Absolute risk diff = 10-5 = 5% = 0.05
- so NNT = 1/0.05 = 20
endothelin what is used in primary pulmonary hypertension
endothelin antagonist
p53 is a what
tumour suppressor
positive and negative predictive values
Negative predictive value = chance of testing negative and not having the disease = true negs/all the people who tested negative
PPV: true positives/all who tested positive
complement deficiencies predispose to ? - c1 inh protein def? - C1q, C1rs, C2, C4 deficiency C3 deficiency C5 deficiency: C5-9 deficiency:
- C5-9 def predisposes to n.meningitidis infections
- C1q, C1rs, C2 and C4: immune complex disease (eg SLE, HSP)
NOTES
C1 inhibitor protein deficiency: hereditary angioedema
C1q, C1rs, C2, C4 deficiency (classical pathway components)
C3 deficiency: recurrent bacterial infections (esp encapsulated)
C5 deficiency: Leiner disease (recurrent diarrhoea, wasting and seborrhoeic dermatitis)
C5-9 deficiency:encodes the membrane attack complex (MAC)
relative risk equation
A total of 100 patients received the new drug whilst 100 patients received a placebo. Of the patients taking the experimental drug, 60 felt improved symptoms compared to 20 patients in the control group.
whats the RR of the drug improving migraine syms
Relative risk = EER/CER = ratio of a risk happening in the experimental group vs control group
EG 60/100 in expt group had improved symptoms, 20/100 in placebo group did - so 60/20 = 3
boy, brother & their male maternal cousin what is it most likely?
mitochondrial
HLA A3 B51 B27 (3) DQ2 DQ8 DR2 (2) DR3 (3) DR4 (2)
HLA-A3: haemochromatosis
HLA-B51: Behcet’s disease
HLA-B27
• ankylosing spondylitis
• reactive arthritis
• acute anterior uveitis
HLA-DQ2/DQ8: coeliac disease
HLA-DR2
• narcolepsy
• Goodpasture’s
HLA-DR3
• dermatitis herpetiformis
• Sjogren’s syndrome
• primary biliary cirrhosis
HLA-DR4
• type 1 diabetes mellitus
rheumatoid arthritis - esp DRB1 gene (DRB104:01 and DRB104:04 hence the association with DR4)
expressivity v penetrance
· Expressivity = extent to which a genotype shows its phenotypic expression in an individual
· Penetrance = proportion of a population of individuals who carry a disease-causing allele who express the related disease phenotype.
turner’s
- denoted as?
- features
- most common cardiac abn
· 45X0
· Short, webbed neck, shield chest, primary amenorrhoea, high arched palate, horseshoe kidney, high gonadotrophins
· Most common cardiac defect: bicuspid aortic valve (also ass w aortic root dilatation & coarctation of aorta)
NOTES
Features
• short stature
• shield chest, widely spaced nipples
• webbed neck
• bicuspid aortic valve (15%), coarctation of the aorta (5-10%)
• primary amenorrhoea
• cystic hygroma (often diagnosed prenatally)
• high-arched palate
• short fourth metacarpal
• multiple pigmented naevi
• lymphoedema in neonates (especially feet)
• gonadotrophin levels will be elevated
• Hypothyroidism
• horseshoe kidney (most common renal abn)
• increased incidence of autoimmune disease (especially autoimmune thyroiditis) and Crohn’s disease
fragile x
- inheritance
- type of disease
fts in males and females
Features in males • learning difficulties • large low set ears, long thin face, high arched palate • Macro-orchidism • hypotonia • autism is more common • mitral valve prolapse
Females (1 fragile chromosome and 1 normal): normal to mild
trinucleotide repeat
standard error of the mean equation
SEM = standard deviation / square root (number of patients)
So the SEM gets smaller as the sample size increases
breast feeding CI
- drugs
- other 2
Drugs to avoid: • abx: ciprofloxacin, tetracycline, chloramphenicol, sulphonamides • psych: lithium, benzodiazepines, clozapine • aspirin • carbimazole • methotrexate • sulfonylureas • cytotoxic drugs • Amiodarone
Other CI
• Galactosaemia (babies can’t metabolise galactose - so can’t BF as it has lots of lactose in - they need non-lactose formula)
• viral infection
X-linked recessive diseases (14)
• Androgen insensitivity syndrome • Becker muscular dystrophy • Colour blindness • Duchenne muscular dystrophy • Fabry's disease • G6PD deficiency • Haemophilia A,B • Hunter's disease • Lesch-Nyhan syndrome • Nephrogenic diabetes insipidus • Ocular albinism • Retinitis pigmentosa • Wiskott-Aldrich syndrome Chronic granulomatous disease: X-linked recessive in >70% (but some other patterns of inheritance)
key feature of a normal distribution (and any others)
KEY BITS
· Mean = mode = median
· standard deviation (SD) is a measure of how much dispersion exists from the mean
NOTES
Properties of the Normal distribution
• symmetrical i.e. Mean = mode = median
• 68.3% of values lie within 1 SD of the mean
• 95.4% of values lie within 2 SD of the mean
• 99.7% of values lie within 3 SD of the mean
• this is often reversed, so that within 1.96 SD of the mean lie 95% of the sample values
the range of the mean - (1.96 *SD) to the mean + (1.96 * SD) is called the 95% confidence interval
- Ie If a repeat sample of 100 observations are taken from the same group 95 of them would be expected to lie in that range
Standard deviation
- the standard deviation (SD) is a measure of how much dispersion exists from the mean - SD = square root (variance)
equations
- LV ejection fraction
- stroke volume
- CO
- systemic vascular resistance
- pulse pressure (2 factors that increase it)
· LV ejection fraction = (stroke volume / end diastolic LV volume) x100%
NOTES
Stroke volume = end diastolic LV volume - end systolic LV volume
Cardiac output = stroke volume x heart rate
Systemic vascular resistance = mean arterial pressure / cardiac output
Pulse pressure = Systolic Pressure - Diastolic Pressure
- Factors which increase pulse pressure
○ a less compliant aorta (this tends to occur with advancing age)
increased stroke volume
radial nerve
- continuation of what?
- damage at axilla > ?
- whats missing if damaged later on?
- sensory innervation of the hand - where?
- main motor effect
= Continuation of posterior cord of the brachial plexus (root values C5 to T1)
Patterns of damage:
· wrist drop
• sensory loss to small area between the dorsal aspect of the 1st and 2nd metacarpals
Axillary damage = as above + paralysis of triceps
Sensory to hand: back of hand from thumb > half way through ring finger (excl tips of index/middle/ring) + abit of the palmar aspect of the thumb
Extension (forearm, wrist, fingers, thumb)
what do you use these tests for
- chi squared
- t test
- mann whitney u
• Chi squared: categorical data
• T test: continuous variable that’s normally distributed (and in 2 groups)
Mann Whitney U test: continuous variable that’s NOT normally distributed (and is in 2 groups)
difference between type 1 and type 2 errors
• Type 1: when we get a false positive
= incorrectly concluding that there’s a stat sig difference in a dataset
○ — (causes: failure to adjust for confounders, inadequate blinding, not performing an intention to treat analysis, poor randomisation)
• Type 2: when we get a false negative
= incorrectly conclusing that there’s no stat sig difference in a dataset
○ — (sample size is too small; classically inadequately powered study)
Aka boy who cried wolf: 1st time he cried wolf, village came running and he had made it up = false positive
• but 2nd time, there is a wolf but village doesn’t believe him = false negative
whats the power of the study
how can you increase it
Power of the study = the probability of correctly rejecting the null hypothesis when it’s false
- The probability of detecting a stat sig difference
- Power = 1 - probability of a type 2 error
Power is increased with increased sample size
damage to this causes? - ulnar nerve radial nerve long thoracic nerve axillary nerve
Ulnar nerve damage > claw hand
Radial nerve damae > wrist drop
Long thoracic nerve damage > winged scapula
loss of shoulder abduction: deltoid muscle, axillary nerve (C5 + C6)
damage to lower trunk of BP causes?
damage to upper trunk?
Erb-Duchenne palsy (‘waiter’s tip’)
• damage of the upper trunk of the brachial plexus (C5,C6)
• may be secondary to shoulder dystocia during birth
• the arm hangs by the side and is internally rotated, elbow extended
Klumpke injury
• damage of the lower trunk of the brachial plexus (C8, T1)
• may be secondary to shoulder dystocia during birth. Also may be caused by a sudden upward jerk of the hand
associated with Horner’s syndrome
median nerve
- from what
- supplies what motor and what sensory in hand
(C6, C8, T1) LOAF muscles - Lateral two lumbricals - Opponens pollis - Abductor pollis brevis - Flexor pollis brevis
Features depend on the site of the lesion:
• wrist: paralysis of thenar muscles, opponens pollicis
• elbow: loss of pronation of forearm and weak wrist flexion
Palmar aspect of lateral 3½ fingers
ulnar nerve
- from what of BP
- motor stuff
- sensory stuff
c8 t1
intrinsic hand muscles. exc LOAF
wrist flexion
medial 1.5 fingers
PCR
- what do you need
- main adv?
reverse transcriptase PCR: whats diff
thermostable DNA polymerase (taq), 2 DNA oligonucleotide primers.
adv: very sensitive only need 1 strand of sample dna.
rev trans PCR: to amplify RNA. RNA converted to DNA by rev transcriptase.
leptin + ghrelin
- where is each from
what effects
Leptin:
• Secreted by adipose tissue
○ More adipose if obese = higher levels
• Stims release of MSH
• Plays key role in regulation of body wt
• High levels decrease appetite
NOTES
Leptin
• acts on satiety centres in the hypothalamus and decreases appetite
• stimulates the release of melanocyte-stimulating hormone (MSH) and corticotrophin-releasing hormone (CRH)
• Low levels of leptin stimulates the release of neuropeptide Y (NPY)
DETAILS
Ghrelin
• stimulates hunger
• produced mainly by the P/D1 cells lining the fundus of the stomach and epsilon cells of the pancreas
levels increase before meals and decrease after meals
homocystinuria
- inheritance
- pathology
- features
- Ix?
- Tx?
· AR
· deficiency of cystathionine beta synthase»_space; very high plasma and urine homocysteine
Features • often: fine, fair hair • MSK ○ Marfanoid body habitus: arachnodactyly etc ○ osteoporosis ○ kyphosis • neuro: may have learning diffs, seizures • ocular ○ downwards (inferonasal) dislocation of lens ○ severe myopia • increased risk of arterial and VTE • malar flush, livedo reticularis
Investigations
• high homocysteine levels in serum and urine
• cyanide-nitroprusside test (also positive in cystinuria)
Tx: vitamin B6 (pyridoxine)supplements.
incidence v prevalence
relationship?
- incidence = number of new cases per population in a given time period
- prevalence = total number of cases per population at a particular point in time.
- prevalence = incidence * duration of condition
median nerve
- damage at wrist?
- at elbow?
Damage at wrist
• ‘claw hand’ - hyperextension of the metacarpophalangeal joints and flexion at the distal and proximal interphalangeal joints of the 4th and 5th digits
• wasting and paralysis of intrinsic hand muscles (except lateral two lumbricals)
• wasting and paralysis of hypothenar muscles
• sensory loss to the medial 1 1/2 fingers (palmar and dorsal aspects)
Damage at elbow
• as above (however, ulnar paradox - clawing is more severe in distal lesions)
radial deviation of wrist
AD condition: if both parents are affected
- what are the chances of an unaffected child? affected heterozygote? affected homozygote?
- 25% chance of unaffected child
- 50% chance of affected heterozygous child
25% chance of affected homozygous child
- 50% chance of affected heterozygous child
mitosis v meiosis
diploid v haploid
mitosis: in somatic cells. results in 2 diploid daughter cells which are the same as the parent cell
meiosis: in gametes. results in 4 haploid daughter cells (each cell contains 1 homologue of each chr pair and so are genetically diff)
somatic cells: 22 pairs of autosomes + 1 pair of sex chrs
- normal chr complement = diploid cells
- gametes = 1 copy of each chr = haploid
case-control study
- describe
- outcome measure?
- 3 advs
- 1 disadv
- Observational and retrospective.
- Patients with a particular condition (cases) are identified and matched with controls. Data is then collected on past exposure to a possible causal agent for the condition.
- The usual outcome measure is the odds ratio.
- Inexpensive, produce quick results
- Useful for studying rare conditions
- Prone to confounding
cohort study
- describe
- usual outcome measure
• Observational and prospective.
• 2 (or more) are selected according to their exposure to a particular agent (e.g. medicine, toxin) and followed up to see how many develop a disease or other outcome.
The usual outcome measure is the relative risk.
digeorge syndrome
- cause
- inheritance
- what is it
- features
AD
CATCH22: · C - Cardiac abnormalities · A - Abnormal facies · T - Thymic aplasia · C - Cleft palate · H - Hypocalcaemia/ hypoparathyroidism · 22 - Caused by chromosome 22 deletion
Variable presentation:
· at risk of viral and fungal infections
· parathyroid gland hypoplasia → hypocalcaemic tetany
· thymus hypoplasia
· T-lymphocyte deficiency/dysfunction
DETAILS
= a primary immunodeficiency disorder
· caused by T-cell deficiency and dysfunction
· an example of a microdeletion syndrome (deletion of a section of chr 22)
general rules for AR v AD
AR conditions = metabolic (except inherited ataxias)
○ Friedrich’s ataxia, ataxia telangiectasia - AR
○ Hunter’s, G6PD are x-linked recessive
AD are structural (except hyperlipidaemia type 2, hypokalaemic periodic paralysis)
ADH
- where is it synth? secreted from?
- acts on?
- whats its aim and how does it do it
- what increases its secretion (4)
- decreases secretion (3)
- Synth in supraoptic nuclei of hypothal > released by post pit
- Function: conserves body water:
• Acts on collecting ducts»_space; promote water reabsorption by inserting aquaporin 2 channels
- Function: conserves body water:
Regulation Increases secretion • extracellular fluid osmolality increase • volume decrease • pressure decrease • angiotensin II
Decreases secretion
• extracellular fluid osmolality decrease
• volume increase
temperature decrease
actions of
- nucleus, ribosome, rough ER, smooth ER, golgi, lysosome, nucleolus, mitochondria
Nucleus: DNA maintenance, RNA transcription, RNA splicing
Ribosome: translates RNA into proteins
Rough ER: translate and fold new proteins
Smooth ER: synth steroids and lipids Golgi: packages molecules getting secreted Lysosome: breaks down large molecules Nucleolus: ribosome production Mitochondria: aerobic respiration
bohr effect?
haldane effect?
chloride shift?
Bohr effect = increasing acidity (or pCO2) means oxygen binds less well to Hb
Haldane effect = increase pO2 means CO2 binds less well to Hb
NOTES
Chloride shift
• CO2 diffuses into RBCs
• CO2 + H20 —- carbonic anhydrase -→ HCO3- + H+
• H+ combines with Hb
HCO3- diffuses out of cell,- Cl- replaces it
what does the adrenal medulla secrete
· Secretes virtually all adrenaline in the body
And a small amount of noradrenaline
screening programme criteria 10
- The condition should be an important public health problem
- There should be an acceptable treatment for patients with recognised disease
- Facilities for diagnosis and treatment should be available
- There should be a recognised latent or early symptomatic stage
- The natural history of the condition should be adequately understood (including its development from latent to declared disease)
- There should be a suitable test or examination
- The test or examination should be acceptable to the population
- There should be agreed policy on whom to treat
- The cost of case-finding (including diagnosis and subsequent treatment of patients) should be economically balanced in relation to the possible expenditure as a whole
- Case-finding should be a continuous process and not a ‘once and for all’ project
wilson and junger criteria
what do southern, northern and western blots do
- SNOW (South - NOrth - West)
- DROP (DNA - RNA - Protein)
Southern: detects DNA
Northern: detects RNA
Western: detects proteins
congenital
- toxoplasmosis
- CMV
- rubella
CMV most common congenital infection in UK
toxoplamosis: cerebral calcifications, chorioretinitis
Congenital CMV
- microcephaly, hepatosplenomegaly and sensorineural hearing loss. - Infected infants will typically be born premature or have a low birth weight
Congenital rubella
- triad of sensorineural deafness, microphthalmia and congenital heart disease.
pre-test probability: what is it? equivalent to what?
post-test prob: what is it, eqn
same for
- pre test and post test odds
Pre-test probability = prevalence of a condition
NOTES
DETAILS
Pre-test probability = The proportion of people with the target disorder in the population at risk at a specific time (point prevalence) or time interval (period prevalence)
Post-test probability
= The proportion of patients with that particular test result who have the target disorder
= post test odds / (1 + post-test odds)
Pre-test odds = The odds that the patient has the target disorder before the test is carried out
= pre-test probability / (1 - pre-test probability)
Post-test odds
= The odds that the patient has the target disorder after the test is carried out
= pre-test odds x likelihood ratio
where the likelihood ratio for a positive test result = sensitivity / (1 - specificity)
renin
- secreted by?
- what does it do?
- factors stimulating its secretion
- factors reducing its secretion
- secreted by juxtaglomerular cells
- hydrolyses angiotensinogen to produce angiotensin I
Factors stimulating renin secretion • hypotension causing reduced renal perfusion • hyponatraemia • sympathetic nerve stimulation • catecholamines • erect posture
Factors reducing renin secretion
drugs: beta-blockers, NSAIDs
adrenal cortex: layers and what they release?
Adrenal cortex (mnemonic GFR - ACD)
• zona glomerulosa (on outside): mineralocorticoids, mainly aldosterone
• zona fasciculata (middle): glucocorticoids, mainly cortisol
• zona reticularis (on inside): androgens, mainly dehydroepiandrosterone (DHEA)
angiotensin 2
- how is it made
- actions: 5
• angiotensin-converting enzyme (ACE) in the lungs converts angiotensin I → angiotensin II
• wide variety of actions:
• vasoconstriction of vascular smooth muscle»_space; raised BP
• vasoconstriction of efferent arteriole of the glomerulus → increased filtration fraction (FF) to preserve GFR.
○ Remember that FF = GFR / renal plasma flow
• stimulates thirst (via the hypothalamus)
• stimulates aldosterone and ADH release
increases proximal tubule Na+/H+ activity
aldosterone: released by?
in response to (3)
- causes?
Aldosterone
• released by zona glomerulosa in response to raised angiotensin II, potassium, and ACTH levels
• causes retention of Na+ in exchange for K+/H+ in distal tubule
relative risk
RR increase/decrease
EG if we look at a trial comparing the use of paracetamol for dysmenorrhoea compared to placebo we may get the following results
Total number of patients Experienced significant pain relief
Paracetamol 100 60
Placebo 80 20
RR = EER /CER
RR reduction/increase = (EER-CER) / CER
Experimental event rate, EER = 60 / 100 = 0.6
Control event rate, CER = 20 / 80 = 0.25
Therefore the relative risk ratio = EER / CER = 0.6 / 0.25 = 2.4
b cells
plasma cells
b cells: humoral immune response. hyperacute organ rejection
plasma cells: differentiate from b cells and produce lots of Ab specific to an antigen
helper t cells
cytotoxic t cells
both: cell mediated immune response. acute and chronic organ rejection. recognises antigens presented by mhc class 2 molecules
helpet: expresses cd4
cytotoxic: expresses cd8. induces apoptosis in virally infected and tumour cells. MHC class 1
levels of evidence 1a to IV
and grading recommendations A-C
Levels of evidence
• Ia - meta-analysis of randomised controlled trials
• Ib - at least one randomised controlled trial
• IIa - at least one well designed controlled trial which is not randomised
• IIb - at least one well designed experimental trial
• III - evidence from case, correlation and comparative studies
• IV - evidence from a panel of experts
Grading of recommendation
• Grade A - based on evidence from at least one randomised controlled trial (i.e. Ia or Ib)
• Grade B - based on evidence from non-randomised controlled trials (i.e. IIa, IIb or III)
Grade C - based on evidence from a panel of experts (i.e. IV)
Atrial natriuretic peptide sec by MAIN ACTION, OTHER ACTIONS antagonises? degraded by?
Basics
• secreted mainly from myocytes of right atrium and ventricle
○ secreted by both atria (right»_space; left)
• Sec in response to increased blood volume
• 28 amino acid peptide hormone, which acts via cGMP
• degraded by endopeptidases
MAIN ACTION: VASODILATION
Actions
• natriuretic, i.e. promotes excretion of sodium
• lowers BP
antagonises actions of angiotensin II, aldosterone
variance
what is it
relationship to standard deviation
Variance (measure of the spread of scores away from the mean) = square of standard deviation
vitamin K
- action
- how long does it take for effect
2 causes of deficiency
Acts as a cofactor in carboxylation of clotting factors 2, 7, 9 and 10
Notes
Details
a fat-soluble vitamin
Clinically, it is used to reverse the effects of warfarinisation
• takes up to 4 hours for there to be a change in the INR
Vitamin K deficiency
• fat-soluble: so levels may fall in conditions affecting fat absorption
Can also occur after prolonged use of broad-spectrum antibiotics by eliminating the gut flora
TH1 - involved in (2), secrete?
TH2 involved in (1), secrete?
Th1
• involved in the cell-mediated response and delayed (type IV) hypersensitivity
• secrete IFN-gamma, IL-2, IL-3
Th2
• involved in mediating humoral (antibody) immunity
• e.g. stimulating production of IgE in asthma
secrete IL-4, IL-5, IL-6, IL-10, IL-13
