Erythropoietin (EPO) is used to distinguish between primary and secondary polycythaemia. Secondary polycythaemia can be caused by tumours in the kidney that may secrete EPO or EPO-like proteins.

Over consumption of fluids, prolonged race duration and inadequate training all can predispose to acute hyponatraemia.
Mild symptoms include a decreased ability to think, headaches, nausea, and an increased risk of falls. Severe symptoms include confusion, seizures, and coma. Normal serum sodium levels are 135 – 145 mEq/liter (135 – 145 mmol/L). Hyponatremia is generally defined as a serum sodium level of less than 135 mEq/L and is considered severe when the level is below 120 mEq/L.
The correct treatment to give is hypertonic saline. Decompressive craniotomy would help alleviate raised intracranial pressure due to cerebral oedema however is not an appropriate first line treatment. Demeclocycline is used for SIADH and mannitol is more likely to be used in the context of traumatic brain injury.
Hyponatremia is corrected slowly, to lessen the risk of the development of central pontine myelinolysis (CPM), a severe neurological disease involving a breakdown of the myelin sheaths covering parts of nerve cells. During treatment of hyponatremia, the serum sodium (salt level in the blood) should not rise by more than 8 mmol/L over 24 hours.

Thyroid storm, also referred to as thyrotoxic crisis, is an acute, life-threatening, hypermetabolic state induced by excessive release of thyroid hormones (THs) in individuals with thyrotoxicosis.
Patients with thyroid storm should be treated in an ICU setting for close monitoring of vital signs and for access to invasive monitoring and inotropic support, if necessary.
– Supportive measures
If needed, immediately provide supplemental oxygen, ventilatory support, and intravenous fluids. Dextrose solutions are the preferred intravenous fluids to cope with continuously high metabolic demand.
– Correct electrolyte abnormalities.
– Treat cardiac arrhythmia, if necessary.
– Aggressively control hyperthermia by applying ice packs and cooling blankets and by administering acetaminophen (15 mg/kg orally or rectally every 4 hours).
– Antiadrenergic drugs.
– Thionamides: Correct the hyperthyroid state. Administer antithyroid medications to block further synthesis of thyroid hormones (THs).
High-dose propylthiouracil (PTU) or methimazole may be used for treatment of thyroid storm.
– Administer glucocorticoids to decrease peripheral conversion of T4 to T3. This may also be useful in preventing relative adrenal insufficiency due to hyperthyroidism and improving vasomotor symptoms.
– Bile acid sequestrants prevent reabsorption of free THs in the gut (released from conjugated TH metabolites secreted into bile through the enterohepatic circulation).
– Treat the underlying condition.

Tetracycline is not recommended in pregnancy because of the risk to fetal development (bones, teeth!). Metronidazole in pregnancy: currently not thought to be an increased risk in pregnancy; however this is not effective against chlamydia. Amoxicillin is shown to be an adequate treatment for chlamydia, so this is the correct answer.

An odds ratio (OR) is a measure of the association between an exposure and an outcome. The OR represents the odds that an outcome will occur given a particular exposure, compared to the odds of the outcome occurring in the absence of that exposure. Odds ratios are most commonly used in case-control studies, however they can also be used in cross-sectional and cohort study designs as well (with some modifications and/or assumptions). Where

a = Number of exposed cases

b = Number of exposed non-cases

c = Number of unexposed cases

d = Number of unexposed non-cases

OR=(a/c) / (b/d) = ad/bc

Herpes zoster oticus is a viral infection of the inner, middle, and external ear. It manifests as severe otalgia with associated cutaneous vesicular eruption, usually of the external canal and pinna. When associated with facial paralysis, the infection is called Ramsay Hunt syndrome.

Loss of vision after consumption of antifreeze is a characteristic presentation of methanol poisoning.

Pathophysiology of methanol toxicity:
When ingested, methanol is absorbed rapidly via the gastrointestinal tract in less than 10 minutes. Methanol is not protein-bound and is absorbed directly into the total body water compartment.
Metabolism occurs mainly in the liver through serial oxidation via alcohol dehydrogenase and aldehyde dehydrogenase but begins with alcohol dehydrogenase present in the gastric mucosa.
Alcohol dehydrogenase oxidizes methanol to formaldehyde, and aldehyde dehydrogenase subsequently oxidizes formaldehyde to formic acid.
Formic acid is the primary toxic metabolite that accounts for the associated anion gap metabolic acidosis and end-organ damage.

Clinical presentation:
Patients who present within the first 12 to 24 hours following ingestion may appear normal, and this is described as the latent period.
Nausea, vomiting, and abdominal pain subsequently ensue, followed by CNS depression and hyperventilation due to metabolic acidosis.
Ocular symptoms associated with retinal toxicity are often evident in the form of blurry vision, decreased visual acuity, photophobia, and “halo vision.”

Treatment:
Treatment options for methanol toxicity include supportive care, fomepizole (Antizole, 4-Methylpyrazole or 4MP), ethanol, dialysis, and folate.

Lead poisoning is characterised by abdominal pain, fatigue, constipation, peripheral neuropathy (mainly motor), and blue lines on gum margin in 20% of the adult patients (very rare in children).

For diagnosis, the level of lead in blood is usually considered with levels greater than 10 mcg/dL being significant. Furthermore, the blood film shows microcytic anaemia and basophilic stippling of red blood cells. Urinary coproporphyrin is increased (urinary porphobilinogen and uroporphyrin levels are normal to slightly increased). Raised serum and urine levels of delta-aminolaevulinic acid may also be seen, making it sometimes difficult to differentiate from acute intermittent porphyria.

Insulinoma is associated with LOW fasting glucose, HIGH insulin level, and HIGH C peptide. Insulin-abuse or overdose will cause HGH insulin levels and a LOW C peptide. If the C peptide is low, be suspicious.

Absolute risk reduction (ARR) – also called risk difference (RD) – is the most useful way of presenting research results to help your decision-making. In this example, the ARR is 8 per cent (20 per cent – 12 per cent = 8 per cent). This means that, if 100 children were treated, 8 would be prevented from developing bad outcomes. Another way of expressing this is the number needed to treat (NNT). If 8 children out of 100 benefit from treatment, the NNT for one child to benefit is about 13 (100 ÷ 8 = 12.5). CER = 20 / 400 = 1 / 20 = 0.05, EER = 10 / 400 = 0.025, ARR =CER – EER = 0.025

Arthrocentesis should usually be done when there is a suspicion of pseudogout or septic arthritis as in this case which leads to an early diagnosis and prompt treatment. Polarized microscopy demonstrates weakly positively birefringent rhomboid crystals which are blue when parallel to light and yellow when perpendicular to light. Elevated serum uric acid levels that cause gout are usually found after large consumption of alcohol or meat, or post surgery. Autoimmune diseases like SLE, RA etc require an autoimmune screen.

Rheumatoid Scleritis is a painful inflammatory condition of the sclera in patients with rheumatoid arthritis. It might be diffuse, nodular, or necrotizing in nature. This occurs mostly in the sixth decade of life and mostly when the rheumatoid disease is in remission. Sclera is the first ocular manifestation in a patient of rheumatoid arthritis. This inflammation might later spread to the adjacent ocular structures like the cornea, causing keratitis, the uveal tract causing uveitis and the lens causing cataracts.

Because Charcot-Marie-Tooth disease (type 1) is an autosomal dominant condition; therefore, there is a 50% chance that the children of this patient will be affected.

Obsessive-Compulsive Disorder (OCD) is a common, chronic and long-lasting disorder in which a person has uncontrollable, reoccurring thoughts (obsessions) and behaviours (compulsions) that he or she feels the urge to repeat over and over.
People with OCD may have symptoms of obsessions, compulsions, or both. These symptoms can interfere with all aspects of life, such as work, school, and personal relationships.

Obsessions are repeated thoughts, urges, or mental images that cause anxiety. Common symptoms include:
Fear of germs or contamination
Unwanted forbidden or taboo thoughts involving sex, religion, and harm
Aggressive thoughts towards others or self
Having things symmetrical or in a perfect order

Compulsions are repetitive behaviours that a person with OCD feels the urge to do in response to an obsessive thought. Common compulsions include:
-Excessive cleaning and/or handwashing
-Ordering and arranging things in a particular, precise way
-Repeatedly checking on things, such as repeatedly checking to see if the door is locked or that the oven is off
-Compulsive counting

Research also shows that a type of CBT called Exposure and Response Prevention (ERP) is effective in reducing compulsive behaviours in OCD, even in people who did not respond well to SRI medication. ERP has become the first-line psychotherapeutic treatment for OCD

Immune thrombocytopenic purpura (ITP) refers to thrombocytopaenia occurring in the absence of toxic exposure or other diseases associated with low platelets and involves IgG-type antibodies. It is characterised by normal or increased marrow megakaryocytes, shortened platelet survival, and the absence of splenomegaly. Autoimmune haemolytic anaemia (AIHA) occurs commonly in association with ITP. Leukemic transformation, however, does not occur in ITP.

In neonatal ITP, IgG antibodies are passively transferred across the placenta. The infant platelet count may be normal at birth but decreases within 12–24 hours. It is rarely severe enough to induce bleeding diathesis in the infant.

Bradycardia and miosis should be anticipated following the administration of anticholinesterases.

Anticholinesterase agents include the following medications:
– Pyridostigmine, neostigmine, and edrophonium which play a significant role in the diagnosis and the management of myasthenia gravis.
– Rivastigmine, galantamine and donepezil are cholinesterase inhibitors found to be significantly useful in the management of Alzheimer’s disease.

Mechanism of action and pharmacological effects:
Inhibition of cholinesterase increases the level and the duration of action of acetylcholine within the synaptic cleft.

Thus, cholinergic effects such as a reduction in heart rate (bradycardia), miosis (pupillary constriction), increased secretions, increased gastrointestinal motility and reduction in BP may occur with anticholinesterases.

Toxins such as organophosphates and carbamates also are primarily anticholinergic and cause the following typical SLUDGE symptoms:
– Salivation
– Lacrimation
– Urination
– Diaphoresis
– Gastrointestinal upset
– Emesis

This case presents with sensorimotor neuropathy secondary to his DM. The progression of the neuropathy, known dying-back neuropathy, is a distal axonopathy or axonal degeneration as where the sensorimotor loss begins distally and travels proximally.

CXR, blood, and urine tests should be carried out initially to exclude an underlying malignancy. If these are normal, a CT scan of abdomen and pelvis should be arranged as the patient’s age is >40 years. Antiphospholipid antibodies should also be checked for the first unprovoked DVT/PE. There is no history, however, to support an inherited thrombophilia.

The National Institute for Health and Care Excellence (NICE) published guidelines in 2012 for the investigation and management of DVT. If a patient is suspected of having DVT, a two-level DVT Wells score should be used:

DVT likely: 2 points or more
DVT unlikely: 1 point or less

This system of points is based on the following clinical features:
1. Active cancer (treatment ongoing, within six months, or palliative)—1
2. Paralysis, paresis, or recent plaster immobilisation of the lower extremities—1
3. Recently bedridden for three days or more, or major surgery within 12 weeks requiring general or regional anaesthesia—1
4. Localised tenderness along the distribution of the deep venous system—1
5. Entire leg swollen—1
6. Calf swelling at least three cms larger than the asymptomatic side—1
7. Pitting oedema confined to the symptomatic leg—1
8. Collateral superficial veins (non-varicose)—1
9. Previously documented DVT—1
10. An alternative diagnosis is at least as likely as DVT—2

If two points or more—DVT is ‘likely’
If one point or less—DVT is ‘unlikely’

Management

1. LMWH or fondaparinux should be given initially after a DVT is diagnosed.
2. A vitamin K antagonist such as warfarin should be given within 24 hours of the diagnosis.
3. LMWH or fondaparinux should be continued for at least five days or until the international normalised ratio (INR) is 2.0 or above for at least 24 hours. LMWH or fondaparinux is given at the same time as warfarin until the INR is in the therapeutic range.
4. Warfarin should be continued for at least three months. At three months, clinicians should assess the risks and benefits of extending the treatment.
5. Consider extending warfarin beyond three months for patients with unprovoked proximal DVT if their risk of VTE recurrence is high and there is no additional risk of major bleeding. This essentially means that if there is no obvious cause or provoking factor (surgery, trauma, significant immobility, etc.), it may be implied that the patient has a tendency to thrombose and should be given treatment longer than the normal of three months. In practice, most clinicians give six months of warfarin for patients with an unprovoked DVT/PE.
6. For patients with active cancer, LMWH should be used for six months.

As both malignancy and thrombophilia are obvious risk factors for DVT, therefore, all patients with unprovoked DVT/PE who are not already known to have cancer should undergo the following investigations:
1. Physical examination (guided by the patient’s full history)
2. Chest X-ray
3. Blood tests (full blood count, serum calcium, and liver function tests) and urinalysis
4. Testing for antiphospholipid antibodies
5. Testing for hereditary thrombophilia in patients who have had unprovoked DVT/PE and have a first-degree relative who has a history of DVT/PE.

Renal elimination of a drug has no role in altering the bioavailability of a drug.
The bioavailability of a drug is the proportion of the drug which reaches systemic circulation.
Mathematically, bioavailability is the AUCoral/AUCiv x 100%, where AUC = area under the concentration-time curve following a single (oral or iv) dose.

Other options are true:
By definition, the bioavailability of a drug given intravenously is 100%.
Drugs given orally that undergo high pre-systemic (first-pass) metabolism in the liver or gut wall have a low bioavailability e.g. lidocaine.
Bioavailability is also affected by the degree of absorption from the gut and this can change depending on gut motility and administration of other drugs.

This patient meets the diagnostic criteria for neutropenic sepsis, which is a relatively common complication of cancer therapy – usually chemotherapy occurring 7–14 days after. It is defined as a neutrophil count of <0.5 x 10^9/L in a patient undergoing anticancer treatment and who has either a temperature higher than 38°C or has other features consistent with clinically significant sepsis. Management approach is the same as mentioned in this case. However, if the patient still remains unwell, then an antifungal such as amphotericin B is started after risk-stratifying the patient and carrying out investigations (e.g. HRCT and Aspergillus PCR) to determine the likelihood of systemic fungal infection.

Relative risk reduction (RRR) tells you by how much the treatment reduced the risk of bad outcomes relative to the control group who did not have the treatment. In the previous example, the relative risk reduction of fever and rash in the group of the children on the intervention was 40 per cent (1 – 0.6 = 0.4 or 40 per cent). RRR = (EER -CER) / CER = (0.1 – 0.4) / 0.4 = -0.75 or 75% reduction.

Hypogammaglobulinemia is a complication of chronic lymphocytic leukaemia (CLL) that leads to recurrent infections.

CLL is a type of cancer caused by monoclonal proliferation of well-differentiated lymphocytes, typically B cells (99%). Onset of the disease is usually asymptomatic and later constitutes anorexia, weight loss, bleeding, and recurrent infections. Lymphadenopathy is more marked in CLL than in chronic myelogenous leukaemia (CML).

Investigations to diagnose CLL include blood film and immunophenotyping. Smudge cells (also known as smear cells) seen on the blood film point towards CLL. Complications of the disease include hypogammaglobulinemia leading to recurrent infections, autoimmune haemolytic anaemia in 10–15% of the patients, and transformation to high-grade lymphoma (Richter’s transformation).

Most new moms experience postpartum baby blues after childbirth, which commonly include mood swings, crying spells, anxiety and difficulty sleeping. Baby blues typically begin within the first two to three days after delivery, and may last for up to two weeks.

Postpartum depression may be mistaken for baby blues at first — but the signs and symptoms are more intense and last longer, and may eventually interfere with your ability to care for your baby and handle other daily tasks. Symptoms usually develop within the first few weeks after giving birth, but may begin earlier, during pregnancy or later, up to a year after birth.

The period prevalence of postpartum depression among women is a striking 21.9% the first year after birth, which makes it one of the most common medical complications of childbearing. Sertraline has been identified as an antidepressant of choice for breastfeeding women because infants are unlikely to develop quantifiable serum sertraline levels and very few adverse events associated with sertraline have been reported.

Women with a prior episode of postpartum psychosis have about a 30% risk of having another episode in the next pregnancy.

Hepatitis B full vaccine and Ig should be given to babies born to hepatitis B positive mothers. Hepatitis B vaccine alone or Ig alone is not sufficient to prevent the infection in the new-born baby.

Venesection should be done (essentially blood-letting) to decrease the too-high ferratin level. IV Desterrioxamine would have the opposite effect. ASA does not have to do with ferritin. You do not just watch this and recheck. And you do not want to make the patient anaemic.

This woman is receiving methotrexate, an immunosuppressant, to control her rheumatoid arthritis. In such immunocompromised patients, BNF suggests clarithromycin as first-line management.

Spironolactone is an aldosterone antagonist diuretic that is well-known to cause gynaecomastia because it increases testosterone clearance and oestradiol production. The patient’s primary complaint of gynaecomastia should immediately prompt discontinuation of spironolactone and replacement with Eplerenone, which lacks the antiandrogenic effects, and thus there is less risk of gynaecomastia.

Furosemide is a loop diuretic that is known to have significant ototoxicity side-effects although the mechanism is not fully known.

Autosomal recessive polycystic kidney disease (ARPKD) is less common than ADPKD (dominant form) but can already present with symptoms and be diagnosed on prenatal ultrasound.

Early morning waking is a highly suggestive feature of depression in this patient.

NICE use the DSM-IV criteria to grade depression:
1. Depressed mood most of the day, nearly every day
2. Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day
3. Significant weight loss or weight gain when not dieting or decrease or increase in appetite nearly every day
4. Insomnia or hypersomnia nearly every day
5. Psychomotor agitation or retardation nearly every day
6. Fatigue or loss of energy nearly every day
7. Feelings of worthlessness or excessive or inappropriate guilt nearly every day
8. Diminished ability to think or concentrate, or indecisiveness nearly every day
9. Recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide

Subthreshold depressive symptoms: Fewer than 5 symptoms
Mild depression: Few, if any, symptoms over the 5 required to make the diagnosis, and symptoms result in only minor functional impairment
Moderate depression: Symptoms or functional impairment are between ‘mild’ and ‘severe’
Severe depression: Most symptoms and the symptoms markedly interfere with functioning. Can occur with or without psychotic symptoms.

Treatment of depression:
Psychotherapy (in the form of cognitive behavioural therapy or interpersonal therapy) alone or in combination with medications such as:
– Selective serotonin reuptake inhibitors (SSRIs)
– Serotonin/norepinephrine reuptake inhibitors (SNRIs)
– Atypical antidepressants
– Serotonin-Dopamine Activity Modulators (SDAMs)
– Tricyclic antidepressants (TCAs)

There is also empirical support for the ability of CBT to prevent relapse.

Electroconvulsive therapy is a useful treatment option for patients with severe depression refractory to medication or those with psychotic symptoms. The only absolute contraindications is raised intracranial pressure.

Side-effects:
Headache
Nausea
Short term memory impairment
Memory loss of events before ECT
Cardiac arrhythmia
Long-term side-effects: Impaired memory