Epidemiology, Biochemistry and Molecular biology Flashcards
A term referring to systematic inaccuracy.
Bias refers to systematic inaccuracy due either to consistent over-recording or under-recording and is usually due to recorder bias which may be subconscious.
The proportion of those who do not have the disease that are correctly identified as negative.
Specificity
Sensitivity relates to the test’s ability to identify positive results. Where a test has a high sensitivity it is has few false negatives.
Specificity relates to the ability of the test to correctly identify negative results. A test with high specificity has few false positives. If a test with high specificity is positive, that person is likely to have the disease because of the low false positive rate.
Therefore, in order to detect genuine positives (to indicate disease), we need a test with high specificity rather than a high sensitivity.
A type 1 error.
False positive
Type 1 error is the incorrect rejection of the null hypothesis (that there is no difference between groups) and may also be interpreted as a ‘false positive’ observation, that is, you say that there is a difference when there is not.
Error is any random source of inaccuracy. For example an error collecting variable, leading to a less precise estimate.
A random source of inaccuracy.
Error
Bias refers to systematic inaccuracy due either to consistent over-recording or under-recording and is usually due to recorder bias which may be subconscious.
Error is any random source of inaccuracy. For example an error collecting variable, leading to a less precise estimate.
A type 2 error.
False negative
A type 1 error is a false positive and a type 2 error is a false negative.
Ability to exclude a true negative.
Specificity
The terms sensitivity and specificity can be applied to statistical tests as well as to clinical and biological tests. The probability of picking up a genuine positive result is the sensitivity of the test whereas the probability that the test can indicate a true negative result is the specificity of the test.
Which is the most abundant immunoglobulin in the plasma? (Please select 1 option) IgA IgD IgE IgG IgM
IgG
IgG makes up 70-80% of plasma immunoglobulin. IgG plays an important role in toxin neutralisation and bacterial opsonisation.
IgA appears selectively in seromucous secretions, tears, sweat and breast milk and fuctions by inhibiting the binding of organisms to mucosal surfaces and prevents them entering cells.
IgD is present only in small amounts in plasma and is possibly involved in the control of B cell activation.
IgE is found in minute amounts in plasma and binds to mast cells.
IgM is the first type of immunoglobulin formed after initial antigen contact.
A 38-year-old lady is admitted with cellulitis surrounding a traumatic wound.
She has never taken penicillin previously. She is placed on intravenous flucloxacillin and benzylpenicillin. Shortly after the second dose she becomes acutely short of breath and collapses.
She is resuscitated successfully after administration of intravenous adrenaline.
What type of reaction has this lady experienced?
(Please select 1 option)
Type I hypersensitivity
Type II hypersensitivity
Type III hypersensitivity
Type IV hypersensitivity
Type V hypersensitivity
Type I hypersensitivity
This lady has had an anaphylactic reaction.
This is a type I reaction and is mediated by the binding of the antigen and IgE on mast cells; other examples would include latex allergy, and non-anaphylactic type I reactions include asthma and allergic rhinitis.
Type II reactions involve antibody to cell-bound antigen causing cell destruction, for example, haemolysis following blood transfusion.
Type III reaction results from deposition of immune complexes in tissues, for example, acute post-streptoccoal glomerulonephritis.
Type IV reactions are caused by T lymphocytes which react with antigen producing a delayed hypersensitivity reaction, for example, Heaf test for in immunised individuals.
A 48-year-old lady presents complaining of restlessness, weight loss and tremor. On examination she is found to have warm, sweaty and shaky hands. She is in atrial fibrillation. Eye examination reveals exopthalmos and lid-lag. Thyroid examination demonstrates a smooth goitre. She also has pre-tibial myxoedema. Thyroid fucntion tests (TFTs) show a low level of TSH and elevated T3 and T4. What is the most likely diagnosis? (Please select 1 option) De Quervain’s thyroiditis Graves’ disease Hashimoto’s disease Multinodular goitre Toxic solitary adenoma
Graves’ disease
This ladies TFTs show hyperthyroidism.
Graves’ disease is the most common cause of thyrotoxicosis and occurs as a result of the development of antibodies raised against the thyroid-stimulating hormone (TSH) receptor.
De Quervain’s thyroiditis and Hashimoto’s disease are causes of hypothyroidism.
Both a toxic solitary adenoma and a multinodular goitre can cause hyperthyroidism (although most multinodular goitres are non-toxic) but do not cause the eye signs.
Which cells secrete antibodies? (Please select 1 option) B lymphocytes Memory cells Neutrophils Plasma cells T lymphocytes
Plasma cells
Antigen binding leads to B lymphocytes activation and the formation of antibody-secreting plasma cells.
Which immunoglobulin forms pentamers? (Please select 1 option) IgA IgD IgE IgG IgM
IgM
IgM molecules are pentameric structures formed from five basic monomer units.
IgA molecules are dimers.
This Kaplan-Meier curve provides information regarding the survival in months of two patient groups who received two different oncological therapies.
Which of the following can be concluded from this plot?
(Please select 1 option)
Significantly improved survival is seen in group 1 following five months of treatment
Survival probability is improved with treatment in group 1
Survival probability is improved with treatment in group 2
There is a significantly improved survival associated with therapy in group 1 versus group 2
There is no significant difference in survival between the two groups
Survival probability is improved with treatment in group 1
Kaplan-Meier curves represent the proportion of the study population still surviving (or free of disease, or reaching the designated study endpoint) at successive times.
One cannot infer information regarding statistical significance without an actual calculation and although there appears a clear difference between these two groups, group size may be small and hence the differences in survival may not necessarily be different.
The only thing that one may confidently state regarding the above graph is that survival was increased more in group 1 than group 2. It may or may not be statistically significant.
A 35-year-old shop worker presents with pain in her calves which develops after 50 yards of walking. The pain settles with rest.
On examination she has yellow discolouration of her palmar creases.
Her fasting lipid profile reveals:
Cholesterol 9.6 mmol/L (
Type III hyperlipidaemia
Remnant hyperlipidaemia (type III hyperlipidaemia) is associated with:
Hypercholesterolaemia, typically 8-12 mmol/L
Hypertriglyceridaemia, typically 5-20 mmol/L
Normal ApoB concentration
Palmar xanthomata - orange discoloration of skin creases
Tuberoeruptive xanthomata - elbows and knees
Early onset of cardiovascular disease
Early onset of peripheral vascular disease.
Remnant hyperlipidaemia is due to abnormal function of the ApoE receptor, which is normally required for clearance of chylomicron remnants and IDL from the circulation.
The receptor defect causes levels of chylomicron remnants and IDL to be higher than normal in the blood stream. The receptor defect is an autosomal recessive mutation or polymorphism.The genotype of the homozygous condition is apo E-2/E-2 and occurs with a frequency of 1:100.
Hypoalphalipoproteinaemia is a rare, familial condition and is associated with low HDL.
Chylomicronaemia is associated particularly with hypertriglyceridaemia and not with large elevations in cholesterol.
Familial hypercholesterolaemia is due to LDL-receptor deficiency, and is not associated with elevated triglyceride levels.
A researcher compared the mean scores for nausea on a rating scale between standard therapy and a new drug in the treatment of chemotherapy induced nausea. Which one of the following is the most appropriate statistical test? (Please select 1 option) Chi square test Life table analysis (log rank test) Paired t test Pearson correlation Unpaired t test
Unpaired t test This is the correct answerThis is the correct answer
The two sample unpaired t test is used to test the null hypothesis that the two populations corresponding to the two random samples are equal.
For a paired t test, the data are dependent, that is, there is a one-to-one correspondence between the values in the two samples; for example, the same subject measured before and after a process change, or the same subject measured at different times.
A clinical investigation examined the effectiveness of a new test for diagnosing pancreatic carcinoma. The sensitivity was reported as 70%.
Which one of the following statements is correct?
(Please select 1 option)
70% of people will be correctly classified as having or not having the disease
70% of people with a normal test result will not have the disease
70% of people with an abnormal test result will have the disease
70% of people with the disease will have a normal test result
70% of people with the disease will have an abnormal test result
70% of people with the disease will have an abnormal test result This is the correct answerThis is the correct answer
Sensitivity is the conditional probability that the test will be positive if the condition is present.
Specificity is the conditional probability that the test will be negative if the condition is absent.
Therefore, interpreting the data there is a 70% probability of the test being positive when tested in a group of patients with the disease.
A newborn is noted to have an umbilical hernia. Which of the following is associated with umbilical hernia? (Please select 1 option) Congenital hypoparathyroidism Down syndrome Infants of diabetic mothers Post-term delivery Turner's syndrome
Down syndrome
Umbilical hernias occur more frequently in infants of Afro-American descent, premature babies and females.
The vast majority of umbilical hernias are not related to any disease condition.
However, umbilical hernias can be associated with rare diseases, such as:
Mucopolysaccharide storage diseases
Beckwith-Wiedemann syndrome
Down syndrome, and
congenital hypothyroidism.
Which of the following is a polygenic disorder? (Please select 1 option) Ankylosing spondylitis Erythropoietic porphyria Fragile X syndrome Huntington's disease Pendred’s syndrome
Unlike the other conditions, no one specific genetic defect has been identified to account for ankylosing spondylitis.
Hungtindon’s chorea is an autosomal dominant condition.
Fragile X syndrome is due to a trinucleatide repeat at the FMR 1 gene on the X chromosome.
Erythropoietic porphyria is an autosomal recessive condition as is Pendred’s syndrome.
A publication assesses a new diagnostic test for thyroid cancer. Which of the following terms would reflect the number of cases of thyroid cancer correctly identified by this new test? (Please select 1 option) Accuracy Negative predictive value Positive predictive value Sensitivity Specificity
Sensitivitiy
The specificity of a test is the probability that a test will produce a true negative result when used on an unaffected population.
The sensitivity of a test is the probability that it will produce a true positive result when used on an affected population (as determined by a reference or “gold standard”).
The positive predictive value of a test is the probability that a person is affected when a positive test result is observed.
The negative predictive value of a test is the probability that a person is not affected when a negative test result is observed.
Accuracy is expressed through the above four parameters.
A new antiplatelet agent has been proven to reduce the risk of stroke in a year from 10% in patients treated with conventional treatment to 6% in patients treated with conventional treatment plus the new agent.
The cost of this new drug is £100 per month.
How much extra would a hospital need to spend over the course of a year to prevent one stroke?
(Please select 1 option)
£1,200
£6,000
£18,000
£30,000
£100,000
£30,000
The ‘absolute risk reduction’ is 10% − 6% = 4%.
The ‘number needed to treat’ to prevent a stroke therefore equals 100/4 = 25.
25 patients would need to be treated at a cost of £100/month for 12 months to prevent a stroke which gives the total cost as £30,000.
In a trial of a new drug the following results were obtained:
Improved Not improved
Treatment group 44 16
Placebo group 36 26
Which of the following statements regarding the statistical analysis or interpretation of the trial is true?
(Please select 1 option)
A Student’s t test could be used
Pearson’s co-efficient of linear regression would be an appropriate significance test
The data could be evaluated using the chi square test
The numbers are too small to draw any conclusions
The results so obviously show the benefit of treatment that statistical analysis is not required
The data could be evaluated using the chi square test
These data would be ideal for a chi square test. It is a 2 × 2 contingency table for which there is a special chi squared formula that gives a value that can be looked up in a table giving the p value.
The Student’s t test cannot be used as we are comparing proportions not means.
Pearson’s co-efficient cannot be calculated as there is no linear regression to plot.
Nothing is ever so obvious that no statistical analysis is needed.
Apoptosis is induced by which of the following? (Please select 1 option) Activation of caspases Antibodies DNA synthesis Necrosis The MAP kinase pathway
Activation of caspases
A key event in the initiation of apoptosis is the activation of a cascade of cysteine-aspartate specific proteases known as caspases.
A cohort study of 7,500 patients aimed to find out whether the use of olive oil in cooking has an impact on cardiovascular disease.
Approximately half the patients used olive oil in cooking and half used animal fat.
Which of these is a disadvantage of a cohort study?
(Please select 1 option)
It is not possible to measure the incidence/risk of a disease
They are not suitable when exposure to risk factors is rare
They are susceptible to recall bias; there is a differential ability of patients to remember exposure to a risk factor
They can only provide information about one outcome
When the outcome of interest is rare a very large sample size is needed
When the outcome of interest is rare a very large sample size is needed This is the correct answerThis is the correct answer
A cohort study takes a group of individuals and follows them for a period of time, the aim being to study whether the exposure to a particular aetiological factor has any effect on the incidence of disease.
As such they are relatively time consuming and expensive to perform. Advantages include being able to study exposure factors that are rare and being less susceptible to recall bias than case-control studies.
They are also able to measure the incidence/risk of a disease.
Results are usually expressed as the relative risk of developing the disease given exposure to the aetiological factor.
A trial is proposed to see whether excess alcohol use is a risk factor for osteoporosis.
It is decided to perform a case-control study rather than a cohort study.
Which of these is an advantage of a case-control study?
(Please select 1 option)
It can provide information on a wide range of outcomes
It is expensive to perform
It is possible to measure the incidence of a disease directly
It is possible to study diseases that are rare
The time sequence of events can be assessed
It is possible to study diseases that are rare
A case-control study compares the characteristics of a group of patients with the disease with a control group of patients who do not have the disease.
Advantages of case-control studies are that:
They are particularly suitable for rare diseases
A wide range of risk factors can be investigated
There is no loss to follow up
They are relatively cheap and quick to perform.
Results are usually quoted as an odds ratio.
In a double blind controlled trial assessing the impact of a new antihypertensive in the treatment of stroke versus conventional antihypertensive therapy in the secondary prevention of stroke, the authors report an absolute annual risk reduction in the incidence of stroke of 0.5%.
The cost of the new treatment is £100 more expensive per patient per year than conventional therapy.
What would be the cost of implementing the new therapy for each stroke prevented?
(Please select 1 option)
£2000
£4000
£10,000
£20,000
£50,000
£20,000
In this case, the annual incidence of stroke is reduced by 0.5% and treatment is £100 more than conventional therapy.
Thus for every 200 patients treated one less stroke would occur with the new drug versus the conventional therapy.
Number needed to treat (NNT) is therefore 200 per year to prevent one stroke.
Thus the annual cost of this treatment associated with preventing one stroke would be:
200 patients × £100 = £20,000.
An experienced group of surgeons report on a randomised placebo-controlled trial comparing a particular carotid surgery technique to a sham operation.
Their study concludes that ‘using this advanced surgical technique reduces the risk of stroke from 4.3% to 3.8% (p .
What has this study proved about the surgical procedure?
(Please select 1 option)
Acceptability
Effectiveness
Efficacy
Safety
Usefulness
Efficacy
This is an experienced group of vascular surgeons working in ideal conditions. Similar studies have been reported for carotid surgery but it has been difficult to prove their usefulness outside areas of expertise.
It is often difficult to generalise the findings in a study group to everyday practice.
Efficacy = the effect of something under ideal or laboratory conditions. Effectiveness = the effect of something in the real world.