Digoxin is a cardiac glycoside used in the treatment of atrial fibrillation and flutter, and congestive cardiac failure. It acts by inhibiting the membrane Na/K ATPase in cardiac myocytes. This raises intracellular sodium concentration and increases intracellular calcium availability indirectly via Na/Ca exchange. The increase in intracellular calcium levels causes an increases the force of myocardial contraction (positive inotrope), and slows the heart rate (negative chronotrope).

Following neuronal injury, as seen in traumatic brain injury, the axon undergoes anterograde degeneration. Degradation starts from the cell body (proximally) and progresses distally. The axon becomes fragmented and degenerates.

The brain shows no reactive changes to injury is incorrect. Following major injury such as stroke, the brain undergoes a process of liquefactive degeneration, which leaves cystic spaces within the brain.

Axonal regeneration does not occur to any significant extent within the central nervous system unlike what is seen in the peripheral nervous system.

Astrocytes undergo reactive gliosis, leaving behind a firm translucent tissue around sites of damage.

C-reactive protein(CRP) is synthesized in the liver in response to increased interleukin-6 (IL-6) secretion by macrophages and T-cells.
Some conditions that cause CRP levels to a rise include: bacterial infection, fungal infection, severe trauma, autoimmune disease, Organ tissue necrosis, malignancy and surgery.

It is useful in the clinical setting as a marker of inflammatory activity and can be used to monitor infections.

CRP levels start to rise 4-6 hours after an inflammatory trigger and reaches peak levels at 36-50 hours.

In the absence of a disease process, the normal plasma concentration is less than 5 mg/l.

CRP is useful for monitoring inflammatory conditions (e.g. rheumatoid arthritis and malignancy), can be used as a prognostic marker in acute pancreatitis, and serial measurement can be used to recognize the onset of nosocomial infections in the intensive care settling.

Absolute risk and relative risk are used to assess the strength of a relationship between a disease and a factor that may affect it.

Absolute risk (AR) is the risk of developing a disease over a time period:
AR = the number of events that occur in a group / number of people in that group

The absolute risk reduction (ARR) is the difference between the absolute risk in the control group (ARC) and the absolute risk in the treated group (ART).

ARR = ARC – ART

The control group is the warfarin group, therefore the ARC is 20/500 (0.04).
Treatment group is the ticagrelor group and ART = 30/300 (0.1).

ARR = 0.04 – 0.1 = -0.06. This shows that treatment with ticagrelor increases risk of developing stroke. This is also termed a relative risk increase.

Relative risk, or risk ratio, (RR) is used to compare the risk in the two different groups. It is the ratio of the absolute risks of the disease in the treatment group (ART) to the absolute risk of the disease in the control group (ARC):
RR=ART /ARC

Therefore RR = 0.1 / 0.04 = 2.5
RR < 1 means the intervention reduces the risk of the outcome being studied
RR = 1 means the treatment has no effect on the outcome being studied
RR > 1 means the intervention increased the risk of the outcome being studied
Since RR is 2.5, ticagrelor increases the risk of stroke.

SUMMARY
Absolute risk reduction is -0.06
Absolute risk in warfarin group = 0.04
Relative risk = 2.5
Ticagrelor has no effect on stroke is incorrect because RR is not =1

Extrapyramidal side effects are most common with piperazine phenothiazines (fluphenazine, prochlorperazine, and trifluoperazine) and butyrophenones (fluphenazine, prochlorperazine, and trifluoperazine) (benperidol and haloperidol). The most common causative antipsychotic drug is haloperidol.

Tardive dyskinesia (rhythmic, involuntary movements of the tongue, face, and jaw) is most commonly associated with long-term or high-dose treatment. It is the most serious form of extrapyramidal symptoms because withdrawal of the causative drug may make it irreversible, and treatment is usually ineffective.

Dystonia (abnormal facial and body movements) is more common in children and young adults, and it usually shows up after only a few doses. Procyclidine 5 mg IV or benzatropine 2 mg IV as a bolus can be used to treat acute dystonia.

An unpleasant feeling of restlessness characterises akathisia. The inability to initiate movement is known as akinesia.

Renal impairment causes increased cerebral sensitivity, so lower doses should be used.

In elderly patients with dementia-related psychosis who are treated with haloperidol, there is an increased risk of death. This appears to be due to a higher risk of heart attacks and infections like pneumonia.

The following are some of the antipsychotic drugs’ contraindications:
Reduced level of consciousness/coma
Depression of the central nervous system
Phaeochromocytoma

Digoxin is most useful for controlling the ventricular response in persistent and permanent atrial fibrillation and atrial flutter. Digoxin is usually only effective for controlling the ventricular rate at rest, and should therefore only be used as monotherapy in predominantly sedentary patients with non-paroxysmal atrial fibrillation. It is now rarely used for rapid control of heart rate, as even with intravenous administration, response may take many hours. Digoxin is reserved for patients with worsening or severe heart failure due to left ventricular systolic dysfunction refractory to combination therapy with first-line agents. Digoxin is contraindicated in supraventricular arrhythmias associated with accessory conduction pathways e.g. Wolff-Parkinson-White syndrome.

Phaeochromocytomas are catecholamine-secreting tumours which occur in about 0.1% of patients with hypertension. In about 90% of cases they arise from the adrenal medulla. The remaining 10%, which arise from extra-adrenal chromaffin tissue, are termed paragangliomas. Common presenting symptoms include one or more of headache, sweating, pallor and palpitations. Less commonly, patients describe anxiety, panic attacks and pyrexia. Hypertension, whether sustained or episodic, is present in at least 90% of patients. Left untreated phaeochromocytoma can occasionally lead to hypertensive crisis, encephalopathy, hyperglycaemia, pulmonary oedema, cardiac arrhythmias, or even death.

Klebsiella pneumoniae is among the most common Gram-negative bacteria encountered by physicians worldwide and accounts for 0.5-5.0% of all cases of pneumonia. This organism can cause extensive pulmonary necrosis and frequent cavitation.

It is one of the causes that could be suspected when there is cavitatory pneumonia with or without a bulging fissure sign. Often, there can be extensive lobar opacification with air bronchograms.

A helpful feature which may help to distinguish from pneumococcal pneumonia is that Klebsiella pneumoniae develops cavitation in 30-50% of cases (in comparison, cavitation is rare in pneumococcal pneumonia). This occurs early and progresses quickly.

Bumetanide is a loop diuretic that inhibits sodium, chloride, and potassium reabsorption by acting on the Na.K.2Cl co-transporter in the ascending loop of Henlé. This reduces the osmotic gradient that forces water out of the collecting duct system and prevents the formation of a hypertonic renal medulla. This has a strong diuretic effect on the body.

It’s primarily used in patients with heart failure who aren’t responding to high doses of furosemide. Bumetanide and furosemide differ primarily in terms of bioavailability and pharmacodynamic potency.

In the intestine, furosemide is only partially absorbed, with a bioavailability of 40-50 percent. Bumetanide, on the other hand, is almost completely absorbed in the intestine and has a bioavailability of about 80%. Bumetanide is 40 times more potent than furosemide, and one milligram is roughly equivalent to 40 milligrams of furosemide.

Bumetanide also lowers the concentration of neuronal chloride, making GABA’s action more depolarizing. In the neonatal period, it is being studied as an antiepileptic.

A boxplot is a vertical or horizontal rectangle used to display the interquartile range, with the ends of the rectangle corresponding to the upper and lower quartiles of the data values. The box contains 50% of the data values. A line drawn through the rectangle corresponds to the median value. Whiskers, starting at the ends of the rectangle usually indicate the minimum and maximum values, therefore the entire box and whisker plot represents the range. Any outliers can be plotted independent of the box and whisker plot.