Ciprofloxacin is recommended for use as meningococcal chemoprophylaxis in all age groups and in pregnancy, and is the most appropriate for this patient.

However, rifampicin is the drug of choice for meningococcal chemoprophylaxis because it is licensed for chemoprophylaxis, but multiple doses are necessary and it is not readily available in community pharmacies. It also interacts with oral contraceptives.

Colonic mass movement describes the intense contraction that begins halfway along the transverse colon and pushes the intestinal contents in the proximal colon towards the rectum. It occurs shortly after a meal due to distension of the stomach and duodenum as part of the gastrocolic reflex and if faeces is present in the rectum, stimulates the urge to defecate. Distention of the rectum causes firing of afferent cholinergic parasympathetic fibres. The internal sphincter is made up of circular smooth muscle innervated by the autonomic fibres, and the more distal external sphincter is composed of striated muscle innervated by motor fibres from the pudendal nerve. During defaecation, relaxation of pelvic muscles straightens the rectum.

In foreign body aspiration, the foreign body is more likely to enter the right main bronchus because it is shorter, wider and more vertical than the left main bronchus. In a patient who is standing or sitting, the foreign body tends to become lodged in the posterobasal segment of the inferior lobe of the right lung.

Mannitol is the most widely used osmotic diuretic that is most commonly used to reduce cerebral oedema and intracranial pressure.
It is recommended to use mannitol for the reduction of CSF pressure/cerebral oedema in a dose of 0.25-2 g/kg as an intravenous infusion over 30-60 minutes. This can be repeated 1-2 times after 4-8 hours if needed.

Mannitol has several contraindications and some of them are listed below:
1. Anuria due to renal disease
2. Acute intracranial bleeding (except during craniotomy)
3. Severe cardiac failure
4. Severe dehydration
5. Severe pulmonary oedema or congestion
6. Known hypersensitivity to mannitol

Calcium resonium is an ion-exchange resin that exchanges sodium for potassium as it passes through the intestine, leading to excretion of potassium from the body. Salbutamol and insulin act to increase intracellular uptake of K+ via Na-K ATP pump. Sodium bicarbonate acts to correct acidosis and thus promotes intracellular uptake of K+. Calcium gluconate acts to protect the cardiac membrane and has no effect on serum K+ levels.

Short vessels called arteriovenous anastomoses (AVAs) link tiny arteries and veins. They have a large lumen diameter. The strong and muscular walls allow AVAs to completely clog the vascular lumen, preventing blood flow from artery to vein (acting like a sphincter). When the AVAs open, they create a low-resistance connection between arteries and veins, allowing blood to flow into the limbs’ superficial venous plexuses. There is no diffusion of solutes or fluid into the interstitium due to their strong muscle walls.

AVAs are densely innervated by adrenergic fibres from the hypothalamic temperature-regulation centre. High sympathetic output occurs at normal core temperatures, inducing vasoconstriction of the AVAs and blood flow through the capillary networks and deep plexuses. When the temperature rises, sympathetic output decreases, producing AVA vasodilation and blood shunting from the artery to the superficial venous plexus. Heat is lost to the environment as hot blood rushes near to the skin’s surface.
AVAs are a specialized anatomical adaptation that can only be found in large quantities in the fingers, palms, soles, lips, and pinna of the ear.

ALL affects children predominantly.

The CNS is commonly involved in ALL.

The Philadelphia chromosome is present in 25% of adult ALL and 5% of childhood ALL cases.

The cure rate in children is approximately 80% in children and 50% in adults.

ALL is classified into 3 groups using the French-American-British (FAB) classification:
ALL-L1: small uniform cells
ALL-L2: large varied cells
ALL-L3: large varied cells with vacuoles.

According to a 2018 audit conducted by the Royal College of Emergency Medicine (RCEM), the standard of care for children presenting to EDs with fractured limbs has deteriorated, with most patients waiting longer than ever before for pain relief. More than one-tenth of the children who came in with significant pain from a limb fracture received no pain relief at all.

For all patients, including children, the Agency for Health Care Policy and Research (AHCPR) in the United States recommends using the ABCs of pain management:
A – Ask about pain regularly. Assess pain systematically.
B – Believe the patient and family in their reports of pain and what relieves it.
C – Choose pain control options appropriate for the patient, family, and setting.
D – Deliver interventions in a timely, logical, coordinated fashion.
E – Empower patients and their families. Enable patients to control their course to the greatest extent possible.

The RCEM guidelines recommend assessing a child’s pain within 15 minutes of arrival. This is a fundamental requirement. For the assessment of pain in children, a variety of rating scales are available; which one is used depends on the child’s age and ability to use the scale. These are some of them:
Faces of Wong-Baker Scale for assessing pain
Scale of numerical evaluation
The behavioural scale is a scale that measures how people behave.

The RCEM has provided the following visual guide:
The RCEM has established the following guidelines for when patients in severe pain should receive appropriate analgesia:
100% within 60 minutes of arrival or triage, whichever is earliest
75% within 30 minutes of arrival or triage, whichever is earliest
50% within 20 minutes of arrival or triage, whichever is earliest

The rate of baroreceptor firing slows down when blood pressure falls too low. This causes an increase in sympathetic stimulation of the heart, resulting in an increase in cardiac output. It also causes vasoconstriction by activating alpha 1 receptors in smooth muscle, which causes sympathetic stimulation of peripheral vessels.

Alpha2 receptors can be found in both the brain and the peripheral nervous system. They control sympathetic outflow in the brain stem.

Beta1 receptors, which are found on the cell membrane of cardiac muscle cells, stimulate heart rate and myocardial contractility. The smooth muscle cell membrane contains beta2 receptors, which promote smooth muscle relaxation in the lungs causing bronchodilation, GI tract, and peripheral blood vessels.

Abciximab (ReoPro) is a glycoprotein IIb/IIIa receptor antagonist that is a chimeric monoclonal antibody. It is primarily used during and after coronary artery procedures such as angioplasty to inhibit platelet aggregation.

It’s approved for use as a supplement to heparin and aspirin in high-risk patients undergoing percutaneous transluminal coronary intervention to prevent ischaemic complications. Only one dose of abciximab should be given (to avoid additional risk of thrombocytopenia).

Before using, it is recommended that baseline prothrombin time, activated clotting time, activated partial thromboplastin time, platelet count, haemoglobin, and haematocrit be measured. 12 and 24 hours after starting treatment, haemoglobin and haematocrit should be measured again, as should platelet count 2-4 hours and 24 hours after starting treatment.
When used for high-risk patients undergoing angioplasty, the EPIC trial(link is external)found that abciximab reduced the risk of death, myocardial infarction, repeat angioplasty, bypass surgery, and balloon pump insertion.

The use of abciximab is contraindicated in the following situations:
Internal bleeding is present.
Within the last two months, you’ve had major surgery, intracranial surgery, or trauma.
Stroke in the previous two years
Intracranial tumour
Aneurysm or arteriovenous malformation
Haemorrhagic diathesis is a type of haemorrhagic diathesis.
Vasculitis
Retinopathy caused by hypertension

The following are some of the most common abciximab side effects:
Manifestations of bleeding
Bradycardia
Back ache
Pain in the chest
Vomiting and nausea
Pain at the puncture site
Thrombocytopenia

The mean incubation period for P. falciparum is 12 days.

WHO World Malaria Report 2019 states that an estimated 228 million cases of malaria occurred worldwide in 2018, and reports steadily decreasing the number of cases since 2010. In 2018, nineteen sub-Saharan African countries and India carried approximately 85% of the global malaria burden. The most prevalent and pathogenic malaria parasite, most commonly associated with severe illness and death, especially in the WHO African region, accounting for 99.7% malaria cases, is P. falciparum.

The vector for Plasmodium spp. is a female Anopheles mosquito that inoculates sporozoites contained in her salivary glands into the puncture wound when feeding. Sporozoites enter peripheral bloodstream and are uptake by hepatocytes, where they undergo an asexual pre-erythrocytic liver-stage as liver schizonts lasting up to 2 weeks before the onset of the blood stage.

Intravenous or intramuscular artesunate is the first-line treatment in all patients worldwide and should be used for at least 24 hours and until the oral medication is tolerated.

The measles virus is an enveloped virus classified in the genus
Morbillivirus.
Measles is highly contagious and spreads by aerosol. Initial replication takes place in the mucosal cells of the respiratory tract; measles virus then replicates in the local lymph nodes and spreads systemically. The virus circulates in the T and B cells and monocytes, until eventually the lungs, gut, bile duct, bladder, skin, and lymphatic organs are involved. After an incubation period of 7 to 10 days, there is an abrupt onset, with symptoms of sneezing, runny nose and cough, red eyes, and rapidly rising fever. About 2 to 3 days later, a maculopapular rash appears on the head and trunk. Koplik spots, lesions on the oral mucosa consisting of irregular red spots, with a bluish white speck in the centre, generally appear 2 to 3 days before the rash and are diagnostic.

Measles is easily diagnosed clinically, so few requests for laboratory identification are made. The virus is fragile and must be handled carefully. The specimens of choice are from the nasopharynx and urine, but the virus can only be recovered from these sources in the early stages of infection. The virus grows on PMK cells, causing the formation of distinctive spindle-shaped or multinucleated cells.

A single dose of IV benzodiazepine will terminate the seizure in 60 to 80 percent of patients who present with seizures.

Because benzodiazepines are lipid-soluble, they cross the blood-brain barrier quickly. This explains their quick onset of action.

As a first-line treatment, IV lorazepam should be given. If IV lorazepam is not available, IV diazepam can be used instead, and buccal midazolam can be used if intravenous access cannot be established quickly. Lorazepam can be administered via the rectal route, but it is less reliable and has a lower absorption rate and bioavailability.

Aspirin works by inhibiting cyclo-oxygenase in an irreversible manner, resulting in a decrease in prostaglandin and thromboxane production. As a result, platelet activation and aggregation are reduced.

The vagus nerve, ‘the wanderer’, contains motor fibres (to the palate and vocal cords), sensory components (posterior and floor of external acoustic meatus) and visceral afferent and efferent fibres.

Palatal weakness can cause nasal speech and nasal regurgitation of food. The palate moves asymmetrically when the patient says ‘ahh’. Recurrent nerve palsy results in hoarseness, loss of volume and ‘bovine cough’.

Fick’s law describes the rate of diffusion in a solution. Fick’s law states that:
Jx = -D A (ΔC / Δx)
Where:
Jx = The amount of substance transferred per unit time
D = Diffusion coefficient of that particular substance
A = Surface area over which diffusion occurs
ΔC = Concentration difference across the membrane
Δx = Distance over which diffusion occurs
The negative sign reflects movement down the concentration gradient

The Likelihood Ratio (LR) is the likelihood that a given test result would be expected in a patient with the target disorder compared to the likelihood that that same result would be expected in a patient without the target disorder.

The LR is used to assess how good a diagnostic test is and to help in selecting an appropriate diagnostic tests or sequence of tests. They have advantages over sensitivity and specificity because they are less likely to change with the prevalence of the disorder, they can be calculated for several levels of the symptom/sign or test, they can be used to combine the results of multiple diagnostic test and they can be used to calculate post-test probability for a target disorder.

A LR greater than 1 produces a post-test probability which is higher than the pre-test probability. An LR less than 1 produces a post-test probability which is lower than the pre-test probability. When the pre-test probability lies between 30 and 70 per cent, test results with a very high LR (say, above 10) rule in disease. An LR below 1 produces a post-test probability les than the pre-test probability. A very low LR (say, below 0.1) virtually rules out the chance that the patient has the disease.

A CT pulmonary angiogram is an angiogram of the blood vessels of the lungs. It is a diagnostic imaging test used to check for pulmonary embolism.

A pulmonary embolism is caused by a blood clot or thrombus that has become lodged in an artery in the lung and blocks blood flow to the lung. A patient with pulmonary embolism may feel an abrupt onset of pleuritic chest pain, shortness of breath, and hypoxia. Also, pulmonary embolism can result in alveolar dead space.

Dead space represents the volume of ventilated air that does not participate in gas exchange. The alveolar dead space is caused by ventilation/perfusion imbalances in the alveoli. It is defined as the sum of the volumes of alveoli that are ventilated but not perfused.

Aside from pulmonary embolism, smoking, bronchitis, emphysema, and asthma are among the other causes of alveolar dead space.

The other types of dead space are the following: Anatomical dead space is the portion of the airways that conducts gas to the alveoli. This is usually around 150 mL, and there is no possibility of gas exchange in these areas. Physiological dead space is the sum of anatomical and alveolar dead spaces.

Physiological dead space can account for up to 30% of the tidal volume.

Cushing’s syndrome is a group of symptoms and signs brought on by long-term exposure to high amounts of endogenous or exogenous glucocorticoids. Cushing’s syndrome affects about 10-15 persons per million, and it is more common in those who have had a history of obesity, hypertension, or diabetes.

Cushing’s syndrome has a wide range of clinical manifestations that are dependent on the degree of cortisol overproduction. The appearance might be vague and the diagnosis difficult to detect when cortisol levels are just somewhat elevated. On the other hand, in long-term cases of severely increased cortisol levels, the presentation might be colourful and the diagnosis simple.

Cushing’s syndrome has the following clinical features:
Obesity and weight growth in the true sense
Supraclavicular fat pads are fat pads that are located above the clavicle.
Buffalo hump
Fullness and plethora of the face (‘moon facies’)
Muscle atrophy and weakening at the proximal level
Diabetes mellitus, also known as impaired glucose tolerance
Hypertension
Skin thinning and bruising
Depression
Hirsutism
Acne
Osteoporosis
Amenorrhoea or oligomenorrhoea

Cortisol levels fluctuate throughout the day, with the greatest levels occurring around 0900 hours and the lowest occurring at 2400 hrs during sleep. The diurnal swing of cortisol levels is lost in Cushing’s syndrome, and levels are greater during the whole 24-hour period. In the morning, levels may be normal, but they may be high at night-time, when they are generally repressed. As a result, random cortisol testing is not an effective screening technique and is not advised.

The following are the two most common first-line screening tests:
Cortisol levels in the urine are measured every 24 hours.
A diagnosis of Cushing’s syndrome can be made if more than two collections measure cortisol excretion more than three times the upper limit of normal.
Physical stress (e.g., excessive exercise, trauma), mental stress (e.g., sadness), alcohol or drug misuse, complex diabetes, and pregnancy can all cause false positives.
Renal dysfunction, inadequate collection, and cyclical Cushing’s disease can all cause false negatives.
The overnight low-dose dexamethasone suppression test (LDDST) involves giving 1 mg of dexamethasone at 11 p.m. and measuring blood cortisol levels at 8 a.m. the next day.
Cushing’s syndrome is diagnosed when cortisol is not suppressed to less than 50 nmol/L.
It might be difficult to tell the difference between mild Cushing’s disease and normal cortisol production.
False positives can occur as a result of depression, severe systemic sickness, renal failure, prolonged alcohol misuse, old age, and the use of hepatic enzyme-inducing medicines, among other things.
False negatives are extremely uncommon in Cushing’s disease patients.

A characteristic biochemical picture might also be helpful in confirming the diagnosis of Cushing’s syndrome. The following are the primary characteristics:
Hypokalaemia
Alkalosis metabolique

Metronidazole and the other 5-nitroimidazole agents inhibit nucleic acid synthesis by forming toxic free radical metabolites in the bacterial cell that damage DNA.

Vancomycin inhibits cell wall peptidoglycan formation by binding the D-Ala-D-Ala portion of cell wall precursors.

Erythromycin inhibits protein synthesis and blocks translocation by binding to the 23S rRNA of the 50S ribosomal subunit.

Chloramphenicol blocks peptidyl transferase at 50S ribosomal subunit.

Gentamicin, an aminoglycoside antibiotic, acts by binding to the 30S subunit of the bacterial ribosome inhibiting the binding of aminoacyl-tRNA and thus preventing initiation of protein synthesis.

An overview of the different mechanisms of action of the various types of antimicrobial agents is shown below:
1. Inhibition of cell wall synthesis
– Penicillins
– Cephalosporins
– Vancomycin
2. Disruption of cell membrane function
– Polymyxins
– Nystatin
– Amphotericin B
3. Inhibition of protein synthesis
– Macrolides
– Aminoglycosides
– Tetracyclines
– Chloramphenicol
4. Inhibition of nucleic acid synthesis
– Quinolones
– Trimethoprim
– 5-nitroimidazoles
– Rifampicin
5. Anti-metabolic activity
– Sulphonamides
– Isoniazid

Listeria monocytogenes is a gram-positive bacteria that does not produce spores.

Staphylococcus aureus is a gram-positive bacteria, while Candida albicans is a gram-positive yeast with a single bud.

Among the choices, gram-negative bacteria include only Klebsiella pneumoniae and Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an oxidase-positive bacterium, while Klebsiella pneumoniae is an oxidase-negative bacterium.

P. aeruginosa can cause urinary tract infections (UTIs) and is spread through poor hygiene or contaminated medical equipment or devices, such as catheters that haven’t been fully sterilized.

Platelets are produced in the bone marrow by fragmentation of the cytoplasm of megakaryocytes, derived from the common myeloid progenitor cell. The time interval from differentiation of the human stem cell to the production of platelets averages 10 days. Thrombopoietin is the major regulator of platelet formation and 95% of this is produced by the liver. The normal platelet count is approximately 150 – 450 x 109/L and the normal platelet lifespan is 10 days. Under normal circumstances, about one-third of the marrow output of platelets may be trapped at any one time in the normal spleen.

On standing from a prone position, gravity causes blood to pool in veins in the legs. Central venous pressure (CVP) falls, causing a fall in stroke volume and cardiac output (due to Starling’s law) and thus a fall in blood pressure. Normally this fall in BP is rapidly corrected by the baroreceptor reflex which causes venoconstriction (partially restoring CVP), and an increase in heart rate and contractility, so restoring cardiac output and blood pressure. Impaired autonomic nervous activity in the elderly accounts for the greater likelihood of postural hypotension. Any symptoms of dizziness, blurred vision or syncope is due to a transient fall in cerebral perfusion that occurs before cardiac output and mean arterial pressure (MAP) can be corrected.

Atropine 500 mcg IV bolus should be administered if there are any adverse features or risk of asystole. If the reaction is not adequate, repeat the steps every 3 to 5 minutes up to a maximum dose of 3 mg. In the case of acute myocardial ischemia or myocardial infarction, atropine should be taken with caution since the increased heart rate may aggravate the ischemia or increase the size of the infarct.

5, 10, 15 /20, 25, 30 /35, 40, 45 /50, 60, 70
Sample size (n) = 12
Median = [(n+1)/2]th value
= (12+1)/2 = 6.5
= halfway between 6th and 7th value
= (30 +35)/2 = 32.5
The lower (first) quartile = halfway between 15 and 20
= 17.5
The upper (third) quartile = halfway between 45 and 50
= 47.5
The interquartile range is the difference between the upper quartile and lower quartile
= 47.5 – 17.5 = 30

Innate, or non-specific, immunity is the immune system we are born with.
There are three aspects of innate immunity:
1. Anatomical barriers, such as:
The cough reflex
Enzymes in tears and skin oils
Mucus – which traps bacteria and small particles
Skin
Stomach acid
2. Humoral barriers, such as:
The complement system
Interleukin-1
3. Cellular barriers, such as:
Neutrophils
Macrophages
Dendritic cells
Natural killer cells
Antibody production is part of the specific, or inducible immune response. T-lymphocytesare responsible for the cell mediated immune response which is part of specific, or inducible immunity.

Anaphylaxis is an example of a type I hypersensitivity reaction.

It is IgE mediated.

It requires a prior exposure to the antigen. The initial exposure sensitizes the body to the antigen and a second exposure to that antigen leads to an anaphylactic reaction.

Massive calcium influx into the cells leads to mast cell degranulation.

The Immunoglobulin antigen complex binds to Fc receptors on the surface of mast cells. The result is mast cell degranulation and release of histamine, proteoglycans and serum proteases from cytoplasmic granules.

Hepatitis D virus (HDV) is an RNA virus that was discovered in 1977 and is structurally unrelated to the hepatitis A (HAV), hepatitis B (HBV), and hepatitis C (HCV) viruses. HDV causes a unique infection that requires the assistance of HBV viral particles to replicate and infect hepatocytes. Its clinical course is varied and ranges from acute, self-limited infection to acute, fulminant liver failure. Chronic liver infection can lead to end-stage liver disease and associated complications (including accelerated fibrosis, liver decompensation, and hepatocellular carcinoma).

Macrolide antibiotics (e.g. clarithromycin and erythromycin) are cytochrome P450 enzyme inhibitors. They increase blood levels of theophylline leading to hypokalaemia, and potentially increasing the risk of Torsades de pointes when they are prescribed together.

Co-prescription with theophylline should be avoided.

Factors that enhance theophylline clearance include cigarette smoking, carbamazepine, phenobarbital, phenytoin, primidone, and rifampin.
Medications that inhibit clearance include ethanol, ciprofloxacin, erythromycin, verapamil, propranolol, ticlopidine, tacrine, allopurinol, and cimetidine.

Proton pump inhibitors (PPIs) have a variety of side effects, including:
Vomiting and nausea
Pain in the abdomen
Flatulence
Diarrhoea
Constipation
Headache

PPIs have been linked to a significant increase in the risk of focal tachyarrhythmias (link is external).
Low serum magnesium and sodium levels have been linked to long-term use of PPIs, according to the US Food and Drug Administration (link is external).

Long-term PPI use has also been linked to an increased risk of fracture, according to epidemiological evidence (link is external). Observational studies have discovered a slight link between hip, wrist, and spine fractures. However, there is no link between the two and an increased risk of pelvic fracture. For this reason, the MHRA recommends that patients at risk of osteoporosis who take PPIs maintain an adequate calcium and vitamin D intake.