Question 181#

You are a ST1 doctor in medicine. A 67-year-old man has been investigated for anaemia and weight loss. Endoscopy shows a gastric tumour which is confirmed as an adenocarcinoma on biopsy. On discussing the diagnosis the patient states that he has had 'a good life' and doesn't want any treatment. Clinical examination is unremarkable. He is able to retain and understand the information you give to him, including the likely curative nature of surgery.

What is the most appropriate action?

A. Respect his wishes and book a follow-up appointment for four weeks

Correct Answer A: This question is ultimately about autonomy. By being able to understand and retain the information you give him the patient has demonstrated that he is competent to make decisions. It should be noted that the Mental Capacity Act 2005 states that 'a person is not to be treated as unable to make a decision merely because he makes an unwise decision'.

A CT head and bloods may exclude causes that would impair judgment but would you override his decision even if you noticed evidence of a cerebral metastases? As there is no evidence that this man is suffering from a mental illness referral to a psychiatrist would be inappropriate.

By speaking to the wife alone you are risking breaching confidentiality. Detaining him under the Mental Health Act simply because you disagree with his decision is clearly wrong.

Question 182#

A 54-year-old man is brought to the Emergency Department after being found collapsed in the street. He is known to have a history of alcoholic liver disease. Blood tests reveal the following:

• Calcium 1.62 mmol/l
• Albumin 33 g/l

Which one of the following is the most appropriate management of the calcium result?

A. 10ml of 10% calcium chloride over 10 minutes

Correct Answer C: Even after correction for the low albumin level this patient has significant hypocalcaemia which should be corrected. 

Hypocalcaemia: causes and management:
The clinical history combined with parathyroid hormone levels will reveal the cause of hypocalcaemia in the majority of cases.

Causes:

• Vitamin D deficiency (osteomalacia)
• Chronic renal failure
• Hypoparathyroidism (e.g. post thyroid/parathyroid surgery)
• Pseudohypoparathyroidism (target cells insensitive to PTH)
• Rhabdomyolysis (initial stages)
• Magnesium deficiency (due to end organ PTH resistance)

Acute pancreatitis may also cause hypocalcaemia. Contamination of blood samples with EDTA may also give falsely low calcium levels.

Management:

• Acute management of severe hypocalcaemia is with intravenous replacement. The preferred method is with intravenous calcium gluconate, 10ml of 10% solution over 10 minutes
• Intravenous calcium chloride is more likely to cause local irritation
• ECG monitoring is recommended
• Further management depends on the underlying cause

Question 183#

Which one of the following statements regarding leukotrienes is not true?

A. Secreted by leukocytes

Correct Answer D: 

Leukotrienes:
Function:

• Mediators of inflammation and allergic reactions
• Cause bronchoconstriction, mucous production
• Increase vascular permeability, attract leukocytes
• Leukotriene D4 has been identified as the SRS-A (slow reacting substance of anaphylaxis)

Production: 

• Secreted by leukocytes
• Formed from arachidonic acid by action of lipoxygenase
• It is thought that the NSAID induced bronchospasm in asthmatics is secondary to the express production of leukotrienes due to the inhibition of prostaglandin synthetase

Question 184#

A new antihypertensive is in phase III development. A study is designed where a margin is defined (- delta to +delta) on mean blood pressure reduction. If the confidence interval of the difference between the new drug and ramipril lies within this margin then the trial can be said to have produced a positive result.

What is this an example of?

A. Non-inferiority trial

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 185#

Which type of secondary messenger system does nitric oxide stimulate? 

A. Cyclic GMP

Correct Answer A:  

Second messengers:

Overview:

• Many different types
• Allow amplification of external stimulus

Cyclic AMP:

• e.g. adrenaline, noradrenaline, glucagon, LH, FSH, TSH, calcitonin, parathyroid hormone

Protein kinase activity:

• e.g. insulin, growth hormone, prolactin, oxytocin, erythropoietin, growth factors

Calcium and/or phosphoinositides:

• e.g. ADH, GnRH, TRH

Cyclic GMP:

• e.g. ANP, nitric oxide