stats and clinical sciences Flashcards
what is epidemiology
study of disease in population
it specifically look at the patterns, associations and effects of the disease in a defined population
what is incidence?
the number of individuals that develop a condition (new cases) during a defined period of time in a defined population
What is prevalence?
The total number of individuals in a defined population that have a condition at or during a specific period of time
prevalence = incidence x average duration
what is point prevalence?
the total number of individuals in a defined population that has a condition at specific time point
what is period prevalence?
the proportion of a population which have a condition during a defined period of time
what is lifetime prevalence?
the proportion of a population that will experience the condition at some point during their lifetime.
what is the crude birth rate
the number of live births / mid-yeah population
what is crude birth rate
The incidence of death from a specified condition or disease
what is sensitivity
the ability of a test to correctly identify those with a condition
what is specificity
the ability of a test to correctly identify those that do not have a condition
what is the positive predictive value ?
The probability that a subject with a positive test actually has the condition being tested for
What is number neaded to treat ?
the number of patients it is necessary to treat to stop an event or illness, i.e needing to treat 10 people with a statin to prevent one heart attack
what is a type one error?
Incorrectly rejecting the null hypothesis (saying a treatment or intervention works when it does not)
What is a type two error?
incorrectly accepting the null hypothesis (saying a treatment does not work when it does)
what are the different types of bias?
Information bias - results from systematic differences in the way data is obtained from the study groups - examples include observer bias, interviewer bias, recall bias, instrument bias
Reporter bias - occurs when people report particular events with an unconscious preference
selection bias - occurs when there is a systematic difference between the study participants verses those who did not participate or between those in the treatment group vs those in the control group
What is the difference between parametric and non-parametric?
arametric tests are those that make assumptions about the parameters of the population distribution from which the sample is drawn. This is often the assumption that the population data are normally distributed. Non-parametric tests are “distribution-free” and, as such, can be used for non-Normal variables.
What are the statistical tests used for parametric data?
Student’s t-test - paired or unpaired
Pearson’s product-moment coefficient - correlation
paired data refers to data obtained from a single group of patients, e.g. Measurement before and after an intervention. Unpaired data comes from two different groups of patients, e.g. Comparing response to different interventions in two groups
what are the statistical tests used for non-parametric tests?
Non-parametric tests:
Mann-Whitney U test
compares ordinal, interval, or ratio scales of unpaired data
Wilcoxon signed-rank test
compares two sets of observations on a single sample, e.g. a ‘before’ and ‘after’ test on the same population following an intervention
chi-squared test
used to compare proportions or percentages e.g. compares the percentage of patients who improved following two different interventions
Spearman, Kendall rank - correlation
What are the phases of the cardiac action potential?
Phase 0 - rapid depolarisation - rapid sodium influx, these channels automatically deactivate after a few ms
1 - early repolarisation - efflux of potassium
2 - plateau - slow influx of calcium
3 - final dépolarisation - efflux of potassium
3 - final dépolarisation - efflux of potassium
4 - restoration of ionic concentrations - resting potential is restored by Na+/K+ ATPase. There is slow entry of sodium into the cell decreasing the potential difference until the threshold potential is reached, triggering a new action potential
what is the conduction velocity in the different areas of the heart?
Atrial conduction - spreads along ordinary atrial myocardial fibres at 1m/sec
AV node conduction 0.05m/sec
Ventricular contraction - the Purkinje fibres are of large diameter and achieve velocities of 2-4 m/sec, the fastest conduction in the heart. This allows a rapid and coordinated contraction of the ventricles
What is the most important stimulator of the central chemoreceptors?
a decrease in pH.
Central chemoreceptors, located in the medulla oblongata of the brain, are primarily sensitive to changes in the pH of cerebrospinal fluid. They respond to changes in hydrogen ion concentration resulting from alterations in arterial CO2 tension
An increase in arterial pCO2 leads to an increase in hydrogen ions and this a decrease in pH. This stimulates central chemoreceptors leading to an increased rate and depth of respiration to eliminate excess CO2 and restore blood pH to normal
what controls respiration?
central regulatory centres
central and peripheral chemoreceptors
pulmonary receptors
where are the central respiratory regulatory centres?
medullary respiratory centre
apneustic centre (lower pons)
pneumotaxic centre (upper pons)
where are the central and peripheral chemoreceptors?
central: raised [H+] in ECF stimulates respiration
peripheral: carotid + aortic bodies, respond to raised pCO2 & [H+], lesser extent low pO2
What are the pulmonary receptors involved in respiratory control?
stretch receptors, lung distension causes slowing of respiratory rate (Hering-Bruer reflex)
irritant receptor, leading to bronchoconstriction
juxtacapillary receptors, stimulated by stretching of the microvasculature
What is the likelihood ratio for a positive test result?
How much the odds of the disease increase when a test is positive
how is absolute risk reduction calculated?
Absolute risk reduction = (Control event rate) - (Experimental event rate)
what are the two types of error when testing the null hypothesis?
Type I - the null hypothesis is rejected when its true
Type II - the null hypothesis is accepted when it is false
how is power defined in medical statistics?
Power = 1 - the probability of a type II error
how do you calculate a liklihood ratio for a positive test result ?
Likelihood ratio for a positive test result = sensitivity / (1 - specificity)
how do you calculate likelihood ratio for a negative test result?
likelihood ratios for a negative test result = 1-sensitivity/specificity
what is the power of a study?
the probability of detecting a statistically significant difference
what are the properties of 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
what are the levels of evidence?
Ia - evidence from meta-analysis of randomised controlled trials
Ib - evidence from at least one randomised controlled trial
IIa - evidence from at least one well-designed controlled trial which is not randomised
IIb - evidence from at least one well-designed experimental trial
III - evidence from case, correlation and comparative studies
IV - evidence from a panel of experts
how are recommendations graded?
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)
what are the functions of vitamin D?
increases plasma calcium and plasma phosphate
increases renal tubular reabsorption and gut absorption of calcium
increases osteoclastic activity
increases renal phosphate reabsorption
What kind of disorder is fragile X syndrome?
Fragile X syndrome is a trinucleotide repeat disorder.
what are the features of fragile X?
Features in males
learning difficulties
large low set ears, long thin face, high arched palate
macroorchidism
hypotonia
autism is more common
mitral valve prolapse
Features in females (who have one fragile chromosome and one normal X chromosome) range from normal to mild
How is fragile X diagnosed?
can be made antenatally by chorionic villus sampling or amniocentesis
analysis of the number of CGG repeats using restriction endonuclease digestion and Southern blot analysis
what are the subunits of trop and what do they bind to?
Subunits of troponin
troponin C: binds to calcium ions
troponin T: binds to tropomyosin, forming a troponin-tropomyosin complex
troponin I: binds to actin to hold the troponin-tropomyosin complex in place
which tract are pain and temp carried in?
spinothalamic tract
where does the spinothalamic tract decussate?
At the level it enters at
there fore a hemisection of the cord will result in contralateral loss of these functions.
which spinal tract are motor neurones carried in?
the corticospinal tract
what does the dorsal column medial lemniscus pathway carry?
fine touch, vibration and proprioception
what does the spinocerebellar tract carry?
cconeys proprioception
what are the features of Friedrich’s ataxia?
Autosomal recessive - trinucleotide repeat disorder - GAA repeat in the X25 gene on chromosome 9.
age 10-15 - gait ataxia, kyphoscoliosis
Neurological features
absent ankle jerks/extensor plantars
cerebellar ataxia
optic atrophy
spinocerebellar tract degeneration
Other features
hypertrophic obstructive cardiomyopathy (90%, most common cause of death)
diabetes mellitus (10-20%)
high-arched palate
how does a CN6 palsy present?
diplopia
could be a sign of brain mets
The sixth cranial nerve (CN6) innervates the lateral rectus muscle which is responsible for moving the eye laterally. CN6 arises from the pons which sits on the clivus. Hence, a tumour involving the clivus would compress the CN6 causing its palsy. his leads to restricted lateral gaze which results in horizontal diplopia as seen in this patient.
What does a CN4 palsy cause?
vertical diplopia
what does a CN3 palsy cause?
CN3 palsy causes ptosis and involves four extraocular muscles
when do you see a barrelled chest?
in conditions such as emphysema
What is the Cushing reflex ?
Cushing’s triad, compromised of widening pulse pressure, bradycardia and irregular breathing, is a late sign indicating impending brain herniation. Systolic hypertension occurs as a reflex to maintain cerebral perfusion pressure in the presence of raised intracranial pressure.
what is the cerebral perfusion pressure?
The cerebral perfusion pressure (CPP) is defined as being the net pressure gradient causing blood flow to the brain. The CPP is tightly autoregulated to maximise cerebral perfusion. A sharp rise in CPP may result in a rising ICP, a fall in CPP may result in cerebral ischaemia. It may be calculated by the following equation:
CPP= Mean arterial pressure - Intra cranial pressure
What is Niacin?
What are the consequences of Niacin deficiency?
Vitamin B 3
Niacin is a water soluble vitamin of the B complex group. It is a precursor to NAD+ and NADP+ and hence plays an essential metabolic role in cells.
Biosynthesis
Hartnup’s disease: hereditary disorder which reduces absorption of tryptophan
carcinoid syndrome: increased tryptophan metabolism to serotonin
Consequences of niacin deficiency:
pellagra: dermatitis, diarrhoea, dementia
What are the layers of the epidermis
Stratum corneum- Flat, dead, scale-like cells filled with keratin
Continually shed
Stratum lucidum- Clear layer - present in thick skin only
Stratum granulosum- Cells form links with neighbours
Stratum spinosum- Squamous cells begin keratin synthesis
Thickest layer of epidermis
Stratum germinativum The basement membrane - single layer of columnar epithelial cells
Gives rise to keratinocytes
Contains melanocytes
what are the risk factors for calcium oxalate renal stones?
Hypercalciuria
Hyperoxaluria
Hypocitraturia
they are radio opaque
what leads to cystine renal stones?
Inherited recessive disorder of transmembrane cystine transport leading to decreased absorption of cystine from intestine and renal tubule
Multiple stones may form
Relatively radiodense because they contain sulphur
What causes uric acid renal stones?
Uric acid is a product of purine metabolism
May precipitate when urinary pH low
May be caused by diseases with extensive tissue breakdown e.g. malignancy
More common in children with inborn errors of metabolism
Radiolucent
what causes calcium phosphate stones?
May occur in renal tubular acidosis, high urinary pH increases supersaturation of urine with calcium and phosphate
Renal tubular acidosis types 1 and 3 increase risk of stone formation (types 2 and 4 do not)
Radio-opaque stones (composition similar to bone)
what causes struvite renal stones?
Stones formed from magnesium, ammonium and phosphate
Occur as a result of urease producing bacteria (and are thus associated with chronic infections)
Under the alkaline conditions produced, the crystals can precipitate
Slightly radio-opaque
what is the usual outcome measures in a cohort study?
relative risk
what statistical test do you use for correlation?
Correlation
parametric (normally distributed): Pearson’s coefficient
non-parametric: Spearman’s coefficient
what is Tay-Sachs disease and how does it present?
It causes an accumulation of GM2 ganglioside within lysosomes. Typical presentation is by around 6 months of age. Key features include developmental delay/regression and a cherry-red spot on the macula.
what are the features of Fabry disease?
A. Features can be remembered with the mnemonic FABRY-C:
Febrile episodes
Angiokeratomas (in bathing trunk distribution), Alpha galactosidase A defect
Burning - peripheral neuropathy of hands/feet
Renal failure
Young (premature) death
Cardiovascular disease/corneal ‘whorl’ keratopathy (also occurs with amiodarone)
what kind of hormone is growth hormone?
an anabolic hormone
what is the source of growth hormone?
Anterior pituitary: Somatotrophs comprise 50% of the cells of the anterior pituitary gland
what is the function of growth hormone?
Postnatal growth and development
Numerous actions on protein, carbohydrate and fat metabolism (including increasing lipolysis and gluconeogenesis)
what is the mechanism of action of growth hormone?
Mechanism of action
acts on a transmembrane receptor for growth factor
binding of GH to the receptor leads to receptor dimerization
acts directly on tissues and also indirectly via insulin-like growth factor 1 (IGF-1), primarily secreted by the liver
what increases and decreases the secretion of growth hormone?
Increases secretion
growth hormone releasing hormone (GHRH): released in pulses by the hypothalamus
fasting
exercise
sleep (particularly delta sleep)
Decreases secretion
glucose
somatostatin (itself increased by somatomedins, circulating insulin-like growth factors, IGF-1 and IGF-2)
what are the most common form of CNS tumour?
- 60% = Glioma and metastatic disease
20% = Meningioma
10% = Pituitary lesions
what is endothelin?
Endothelin is a potent, long-acting vasoconstrictor and bronchoconstrictor.
when is Endothelia secreted from?
It is secreted initially as a prohormone by the vascular endothelium and later converted to ET-1 by the action of endothelin converting enzyme. It acts via interaction with a G-protein linked to phospholipase C leading to calcium release.
what promotes and inhibits the release of endothelin ?
Promotes release
angiotensin II
ADH
hypoxia
mechanical shearing forces
Inhibits release
nitric oxide
prostacyclin
what conditions are endothelin raised in?
primary pulmonary hypertension
myocardial infarction
heart failure
acute kidney injury
asthma
which part of an antibody do immune cells bind to?
Immune cells bind to the crystallising region (Fc) of immunoglobulins
what is IgG and what is its function?
monomer
Enhance phagocytosis of bacteria and viruses
* Fixes complement and passes to the fetal circulation
* Most abundant isotype in blood serum
what is IgA
monomer/dimer
IgA is the predominant immunoglobulin found in breast milk. It is also found in the secretions of digestive, respiratory and urogenital tracts and systems
* Provides localized protection on mucous membranes
* Most commonly produced immunoglobulin in the body (but blood serum concentrations lower than IgG.)
* Transported across the interior of the cell via transcytosis
what is IgM and what is its shape and function?
Pentamer
First immunoglobulins to be secreted in response to an infection
* Fixes complement but does not pass to the fetal circulation
* Anti-A, B blood antibodies (note how they cannot pass to the fetal circulation, which could of course result in haemolysis)
Pentamer when secreted
What is the shape of IgD and what is its function ?
Monomer
Role in immune system largely unknown
* Involved in activation of B cells
What is IgE and what is its function ?
monomer
Mediates type 1 hypersensitivity reactions
* Synthesised by plasma cells
* Binds to Fc receptors found on the surface of mast cells and basophils
* Provides immunity to parasites such as helminths
* Least abundant isotype in blood serum
how do you calculate the number needed to treat
1/absolute risk reduction
what conditions are associated with HLA-DR3
dermatitis herpetiformis
Sjogren’s syndrome
primary biliary cirrhosis
what conditions are associated with HLA A3
haemochromatosis
what condition is associated with Behet’s disease?
Behcet’s disease
what conditions are associated with HLA-B27?
ankylosing spondylitis
reactive arthritis
acute anterior uveitis
psoriatic arthritis
what conditions are associated with HLA-DQ2/DQ8
coeliac
what conditions are associated with HLA DR2
narcolepsy
Goodpasture’s
what conditions are associated with HLA-DR4?
type 1 diabetes mellitus*
rheumatoid arthritis - in particular the DRB1 gene (DRB104:01 and DRB104:04 hence the association with DR4)
what cancer is the general p53 associated with?
Common to many cancers, Li-Fraumeni syndrome
what cancer is APC gene associated with?
colorectal cancer
what cancer is BRAC1 and BRCA 2 associated with?
Breast and ovarian cancer
In men, there is an increased risk of breast cancer and prostate cancer
what cancer is associated with NF1 gene?
Neurofibromatosis
What cancer is the gene Rb associated with?
retinoblastoma
what cancer is the gene WT1 associated with?
wilms tumour
which cancer is associated with Multiple tumor suppressor 1 (MTS-1, p16) associated with
melanoma
what is the difference between tumour suppressor genes and oncogenes?
Tumour suppressor genes - loss of function results in an increased risk of cancer
Oncogenes - gain of function results in an increased risk of cancer
what are the histological features of diabetic nephropathy?
Diabetic nephropathy histological findings- Kimmelstiel-Wilson lesions, nodular glomerulosclerosis
what conditions are x-linked recessive?
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
how Is variance calculated ?
Variance is a measure of the spread of scores away from the mean.
Variance = square of standard deviation
therefore the standard deviation is the square root of variance
what is the function of vitamin K
Vitamin K is a fat-soluble vitamin which acts as a cofactor in the carboxylation of clotting factors (II, VII, IX, X).
what is turners syndrome?
Turner’s syndrome is a chromosomal disorder affecting around 1 in 2,500 females. It is caused by either the presence of only one sex chromosome (X) or a deletion of the short arm of one of the X chromosomes. Turner’s syndrome is denoted as 45,XO or 45,X.
what are the features of turners syndrome?
short stature
shield chest, widely spaced nipples
webbed neck
bicuspid aortic valve (15%), coarctation of the aorta (5-10%)
an increased risk of aortic dilatation and dissection are the most serious long-term health problems for women with Turner’s syndrome
regular monitoring in adult life for these complications is an important component of care
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 is much more common in Turner’s
horseshoe kidney: the most common renal abnormality in Turner’s syndrome
what are the examples of adenosine diphosphate (ADP) receptor inhibitors ?
Clopidogrel
Prasugrel
Ticagrelor
Ticlopidine
what is the mechanism of action of ADP receptor inhibitors ?
Adenosine diphosphate (ADP) is one of the main platelet activation factors, mediated by G-coupled receptors P2Y1 and P2Y12.
The main target of ADP receptor inhibition is the P2Y12 receptor, as it is the one which leads to sustained platelet aggregation and stabilisation of the platelet plaque.
why may ticagrelor cause dyspnoea ?
due to the impaired clearance of adenosine
what PPI can not be used with clopidogrel?
omeprazole and eso
