Question 291#

Which one of the following best describes the Haldane effect?

A. Increase in pO₂ means CO₂ binds less well to Hb

Correct Answer A:

Respiratory physiology:

Chloride shift:

• CO₂ diffuses into RBCs
• CO₂ + H₂0 ---- carbonic anhydrase ---> HCO₃^- + H⁺
• H⁺ combines with Hb
• HCO₃^- diffuses out of cell,- Cl^- replaces it

Bohr effect:

• Increasing acidity (or pCO₂) means O₂ binds less well to Hb

Haldane effect:

• Increase pO₂ means CO₂ binds less well to Hb

Question 292#

Which one of the following processes is responsible for ketone production during diabetic ketoacidosis?

A. Glycogenolysis

Correct Answer E:

The low-insulin conditions seen in diabetic ketoacidosis stimulate the process of lipolysis and the production of the ketone bodies, beta-hydroxybutyrate and acetoacetate, which can be used as metabolic fuel.

Diabetic ketoacidosis:

The most common precipitating factors of diabetic ketoacidosis (DKA) are infection, missed insulin doses and myocardial infarction.

American Diabetes Association diagnostic criteria are as follows:

• Blood glucose >13.8 mmol/l
• PH < 7.30
• Serum bicarbonate <18 mmol/l
• Anion gap > 10
• Ketonaemia

Management:

• Fluid replacement: most patients with DKA are deplete around 5-8 litres. Isotonic saline is used initially
• Insulin: an intravenous infusion should be started at 0.1 unit/kg/hour. Once blood glucose is < 15 mmol/l an infusion of 5% dextrose should be started
• Correction of hypokalaemia

Complications of DKA and its treatment:

• Gastric stasis
• Cerebral oedema
• Thromboembolism
• Acute respiratory distress syndrome
• Acute renal failure

Question 293#

What is the main advantage of non-inferiority trials when testing a new drug?

A. Prevents ethical dilemmas

Correct Answer E:

Study design: new drugs:

When a new drug is launched there are a number of options available in terms of study design. One option is a placebo controlled trial. Whilst this may provide robust evidence it may be considered unethical if established treatments are available and it also does not provide a comparison with standard treatments.

If a drug is therefore to be compared to an existing treatment a statistician will need to decide whether the trial is intended to show superiority, equivalence or non-inferiority:

• Superiority: whilst this may seem the natural aim of a trial one problem is the large sample size needed to show a significant benefit over an existing treatment
• Equivalence: an equivalence margin is defined (-delta to +delta) on a specified outcome. If the confidence interval of the difference between the two drugs lies within the equivalence margin then the drugs may be assumed to have a similar effect
• Non-inferiority: similar to equivalence trials, but only the lower confidence interval needs to lie within the equivalence margin (i.e. -delta). Small sample sizes are needed for these trials. Once a drug has been shown to be non-inferior large studies may be performed to show superiority

It should be remembered that drug companies may not necessarily want to show superiority over an existing product. If it can be demonstrated that their product is equivalent or even non-inferior then they may compete on price or convenience. 

Question 294#

You are a ST1 doctor in general medicine. A 19-year-old female who has type 1 diabetes mellitus is admitted with her fourth episode of diabetic ketoacidosis in the past two months. You suspect she runs her sugars high to keep her weight down. She is generally non-compliant and often self-discharges after 24 hours.

What is the most appropriate response?

A. Take her on a tour of the ward showing her patients with amputated legs or those on dialysis as an incentive to get better control

Correct Answer B:

Managing young diabetic patients may be frustrating but needs to be approached in an empathetic manner. Taking time to explore why her control is so bad is the best response in this scenario. The GP should hopefully have a long term relationship with the patient and may be in a position to address these problems. 

Taking no action ignores the problem. Trying to scare her by showing her patients with complications is a poor option not least because it fails to respect the privacy of the other patients.

Telling her she is wasting NHS resources is uncaring and unprofessional. Telling her not to turn up at hospital again is indefensible from an ethical and medicolegal perspective.

Question 295#

A new blood test is developed to screen for prostate cancer. Trials have shown it has a sensitivity for detecting clinically significant prostate cancer of 80% but a specificity of 60%.

What is the likelihood ratio for a positive test result?

A. Cannot be calculated

Correct Answer B:

Likelihood ratio for a positive test result = sensitivity / (1 - specificity).

Likelihood ratio for a positive test result = sensitivity / (1 - specificity) = 0.8 / (1 - 0.6) = 2

Screening test statistics:

It would be unusual for a medical exam not to feature a question based around screening test statistics. The available data should be used to construct a contingency table as below:

TP = true positive; FP = false positive; TN = true negative; FN = false negative

The table below lists the main statistical terms used in relation to screening tests:

Positive and negative predictive values are prevalence dependent. Likelihood ratios are not prevalence dependent.