Pacemaker spikes on the ECG indicate that pacemaker is functioning. The most probable cause for this presentation is the change of the position of the tip of the pacing wire. Increasing the voltage will solve the problem. If it works, repositioning of the pacing wire should be done.

Agitation, hypomania and suicidal intent within a few days after initiating corticosteroid therapy is highly suggestive of a diagnosis of corticosteroid-induced psychosis.

In some patients corticosteroid related psychosis has been diagnosed up to 12 weeks or more after commencing therapy.

Euphoria and hypomania are considered to be the most common psychiatric symptoms reported during short courses of steroids.
During long-term treatment, depressive symptoms were the most common.
Higher steroid doses appear to carry an increased risk for such adverse effects; however, there is no significant relationship between dose and time to onset, duration, and severity of symptoms.

Management: Reduction or cessation of corticosteroids is the mainstay of treatment for steroid psychosis. For those patients who cannot tolerate this reduction/cessation of steroids, mood stabilizers may be of some benefit.

When the aim of the randomized controlled trial (RCT) is to show that one treatment is superior to another, a statistical test is employed and the trial (test) is called a superiority trial (test).

Gastrin is released by G cells in the antrum of the stomach. It stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach and also aids in gastric motility. It is released in response to the following stimuli: vagal stimulation, antrum distention, hypercalcemia. It is inhibited by the following: presence of acid in stomach, SST, secretion, GIP, VIP, glucagon, calcitonin.

Asthma is a condition characterized by airway hyperresponsiveness, which results in reversible increases in bronchial smooth muscle tone, and variable amounts of inflammation of the bronchial mucosa.
During an acute asthma attack, the already inflamed airways narrow further due to bronchospasm, which leads to increased airway resistance. Because of the increased smooth muscle tone during an asthma attack, the airways also tend to close at abnormally high lung volumes, trapping air behind occluded or narrowed small airways. Thus the acute asthmatic will breathe at high lung volumes, his functional residual capacity will be elevated, and he will inspire close to total lung capacity. The accessory muscles of respiration are often used to maintain the lungs in a hyperinflated state.

During episodes of acute asthma, pulmonary function tests reveal an obstructive pattern. This includes a decrease in the rate of maximal expiratory air flow (a decrease in FEV1 and the FEV1/FVC ratio) due to the increased resistance, and a reduction in forced vital capacity (FVC) correlating with the level of hyperinflation of the lungs. Because these patients breathe at such high lung volumes (near the top of the pressure-volume curve, where lung compliance greatly decreases), they must exert significant effort to create an extremely negative pleural pressure, and consequently fatigue easily. Overinflation also reduces the curvature of the diaphragm, making it less efficient in generating further negative pleural pressure.

Normal pO2 but decreased oxygen saturation is characteristic of methemoglobinemia.

Methemoglobinemia is a rare condition in which the haemoglobin iron is in oxidized or ferric state (Fe3+) and cannot reversibly bind oxygen. Normally, the conversion of ferrous form of iron (Fe2+) to its ferric form (Fe3+) is regulated by NADH methaemoglobin reductase, which results in the reduction of methaemoglobin to haemoglobin. Disruption in the enzyme leads to increased methaemoglobin in the blood. There is tissue hypoxia as Fe3+ cannot bind oxygen, and hence the oxygen-haemoglobin dissociation curve is shifted to the left.

Methemoglobinemia can occur due to congenital or acquired causes. Congenital causes include haemoglobin variants such as HbM and HbH, and deficiency of NADH methaemoglobin reductase. Acquired causes are drugs (e.g. sulphonamides, nitrates, dapsone, sodium nitroprusside, and primaquine) and chemicals (such as aniline dyes).

The features of methemoglobinemia are cyanosis, dyspnoea, anxiety, headache, severe acidosis, arrhythmias, seizures, and loss of consciousness. Patients have normal pO2 but oxygen saturation is decreased. Moreover, presence of chocolate-brown coloured arterial blood (colour does not change with addition of O2) and brown urine also point towards the diagnosis of methemoglobinemia.

Hypersegmented neutrophils in the peripheral blood film is suggestive of megaloblastic changes in bone marrow.

He has a consequence of atherosclerotic disease (MI). The most probable diagnosis is cutaneous cholesterol emboli as it is more common after anticoagulation or thrombolytics, the skin involvement, eosinophilia and raised IgE. It is more common above 60 yrs. of age.

The best treatment for the patient in question would be methylene blue.
The most probable diagnosis in this patient is methemoglobinemia due to the ingestion of amyl nitrate.

Amyl nitrate promotes the formation of methaemoglobin, which avidly conserves oxygen and leads to decreased tissue oxygen saturations.

Treatment of choice includes methylene blue and vitamin C.

Adverse effects:
Benign side effects include green or blue discoloration of urine and patients should be forewarned.
Significant side effects are based on methylene blue, itself, being an oxidizing agent and an inhibitor of monoamine oxidase A (MAO-A).
As an oxidizing agent, methylene blue can actually precipitate methemoglobinemia or haemolysis in high doses or when ineffectively reduced.
Methylene blue administration in a patient taking a serotonergic agents may predispose to serotonin syndrome.

Note: Although methylene blue administration is controversial in the setting of G6PD-deficiency due to reduced levels of NADPH, it is not contraindicated and should be administered cautiously and judiciously.

Adult onset Still’s disease (AOSD) is an uncommon systemic inflammatory disease on the clinical spectrum of autoinflammatory disorders. Its presentation and clinical course may result in several well-differentiated phenotypes: from a systemic and highly symptomatic pattern to a chronic articular pattern. Overproduction of numerous pro-inflammatory cytokines is observed in AOSD. Anakinra, a human interleukin (IL)-1R antagonist, has recently been approved in the treatment of AOSD. Denosumab is a RANK ligand inhibitor used in the treatment of osteoporosis. Mepolizumab is used in the treatment of severe asthma with elevated eosinophils. There is some evidence to support the use of tocilizumab, an anti-IL6 monoclonal antibody in adult onset Still’s, but there is stronger data favouring the use of tocilizumab in the treatment of rheumatoid arthritis. Rituximab is usually reserved for patients who are unresponsive to anakinra.

With a bilirubin of 33, automatically the diagnosis from the choices listed is primary biliary cirrhosis or autoimmune hepatitis, not SLE, mono, or Primary Sjogren’s Syndrome. With autoimmune hepatitis, however, you would not expect such a high bilirubin and would expect very high AST/ALT, which here is just mildly elevated. This makes primary biliary cirrhosis the most likely answer. The classic presentation is itching in a middle-aged woman. The dry mouth is likely due to Sicca Syndrome, which occurs in 70% of cases of PBC, but with these liver function tests, PBC is most the likely answer.

Involvement of lymph nodes on both sides of the diaphragm accompanied by night sweats would be staged as IIIB according to the Ann Arbor staging system for Hodgkin lymphoma (HL).

HL is a malignant proliferation of lymphocytes characterised by the presence of distinctive giant cells known as Reed-Sternberg cells. It has a bimodal age distribution being most common in the third and seventh decades of life.

Staging of HL is done according to the Ann Arbor staging system:
Stage
I: Single lymph node region (I) or one extra lymphatic site (IE)

II: Two or more lymph node regions on same side of the diaphragm (II) or local extra lymphatic extension plus one or more lymph node regions on same side of the diaphragm (IIE)

III: Lymph node regions on both sides of the diaphragm (III) which may be accompanied by local extra lymphatic extension (IIIE)

IV: Diffuse involvement of one or more extra lymphatic organs or sites

Suffix
A: No B symptoms

B: Presence of at least one of the following: unexplained weight loss >10% baseline during 6 months before staging; recurrent unexplained fever >38°C; recurrent night sweats—poor prognosis.

The right and left lung anatomy are similar but asymmetrical. The right lung consists of three lobes: right upper lobe (RUL), right middle lobe (RML), and right lower lobe (RLL). The left lung consists of two lobes: right upper lobe (RUL) and right lower lobe (RLL). The right lobe is divided by an oblique and horizontal fissure, where the horizontal fissure divides the upper and middle lobe, and the oblique fissure divides the middle and lower lobes. In the left lobe there is only an oblique fissure that separates the upper and lower lobe.

The lobes further divide into segments which are associated with specific segmental bronchi. Segmental bronchi are the third-order branches off the second-order branches (lobar bronchi) that come off the main bronchus.

The right lung consists of ten segments. There are three segments in the RUL (apical, anterior and posterior), two in the RML (medial and lateral), and five in the RLL (superior, medial, anterior, lateral, and posterior). The oblique fissure separates the RUL from the RML, and the horizontal fissure separates the RLL from the RML and RUL.

There are eight to nine segments on the left depending on the division of the lobe. In general, there are four segments in the left upper lobe (anterior, apicoposterior, inferior and superior lingula) and four or five in the left lower lobe (lateral, anteromedial, superior and posterior). The medium sized airways offer the maximum airway resistance, not smaller ones.

The pons is above the level of decussation of the corticospinal tracts so a pontine lesion would cause a contralateral limb weakness.
The facial motor nucleus is located in the pons and supplies the ipsilateral facial muscles.
A right cerebral lesion would give left upper and lower limb weakness. It would also cause a left sided facial weakness.
A left cerebral lesion would give right upper and lower limb weakness with right facial weakness.
Finally, a cervical spinal cord lesion would not cause a facial weakness.

The patient is most likely to have Postpartum thyroiditis which goes through 2 phases; hypothyroid and a hyperthyroid phase.
The hyperthyroid phase of postpartum thyroiditis occurs between 2 and 10 months postpartum. Most commonly, it presents at 3 months. Symptoms more common in women with hyperthyroid postpartum thyroiditis include palpitations, fatigue, heat intolerance, and irritability/nervousness. The frequency of asymptomatic hyperthyroidism is 33%.
Untreated, the hyperthyroidism resolves spontaneously within 2–3 months. This phase is diagnosed by the combination of a low serum TSH concentration in the presence of thyroid peroxidase antibodies, in women who are TSH receptor antibody-negative. Free T4 levels are typically elevated but may be normal.
Treatment of hyperthyroidism, when necessary, is based on symptom severity and should be a joint decision of patient and physician. Beta-blockers such as propranolol are given to alleviate palpitations, irritability, and nervousness. The morbidity associated with treatment is the side effects of beta-blockade. The downside of withholding treatment is allowing the woman to remain symptomatic. Antithyroid medicines (thioureas) are not a potential treatment alternative, because the hyperthyroidism is caused by destructive thyroiditis resulting in the release of preformed thyroid hormone.

Narrow complex tachycardia with hypotension is a medical emergency. Immediate synchronized cardioversion is the ideal management.

The level of haemoglobin A1c (HbA1c), also known as glycated haemoglobin, determines how well a patient’s blood glucose level has been controlled over the previous 8–12 weeks. Recent studies have been made to correlate between HbA1c and average glucose level.
Using the following formula: Average blood glucose (mmol/l) = (1.98 x 1 HbA1c) – 4.29

From the given history and physical examination findings, this patient has Bell’s palsy. There is no evidence to suggest involvement of any other cranial nerves, which might raise suspicion of a cerebello-pontine angle space-occupying lesion. With her history of possible optic neuritis, there is a possibility that the lesion is in fact a manifestation of multiple sclerosis, although this should be differentiated by examination of an upper motor neuron lesion (with sparing of the forehead facial muscles because of bilateral innervation). In light of her diabetes and the limited evidence of benefit from corticosteroid use, the most sensible first management step for her would be meticulous eye care to avoid corneal ulceration, as a result of the difficulty she is having closing her left eye.

Anorexia nervosa is an eating disorder characterized by an abnormally low body weight, an intense fear of gaining weight and a distorted perception of weight. People with anorexia place a high value on controlling their weight and shape, using extreme efforts that tend to significantly interfere with their lives.

The minimum level of severity is based, for adults, on current body mass index (BMI) (see below) or for
children and adolescents, on BMI percentile. The ranges below are derived from World Health
Organization categories for thinness in adults; for children and adolescents, corresponding BMI percentiles
should be used. The level of severity may be increased to reflect clinical symptoms, the degree of
functional disability, and the need for supervision.
Mild: BMI > 17 kg/m2
Moderate: BMI 16-16.99 kg/m2
Severe: BMI 15-15.99 kg/m2
Extreme: BMI < 15 kg/m2 Anorexia nervosa is more common in women than in men, with a female-to-male ratio of 10-20:1 in developed countries. The prognosis of anorexia nervosa is guarded. Morbidity rates range from 10-20%, with only 50% of patients making a complete recovery. Of the remaining 50%, 20% remain emaciated and 25% remain thin. The main change in the diagnosis of Anorexia Nervosa was to remove the criterion of amenorrhea (loss of menstrual cycle). Removing this criterion means that boys and men with Anorexia will finally be able to receive an appropriate diagnosis.
Similarly, girls and women who continue to have their period despite other symptoms associated with Anorexia, such as weight loss and food restriction, will now be eligible for a diagnosis of Anorexia.

Blurring of vision and dry mouth are antimuscarinic side-effects that are more common with imipramine than other types of tricyclic antidepressants.

Tricyclic antidepressants (TCAs) are used less commonly now for depression due to their side-effects and toxicity in overdose. They are however used widely in the treatment of neuropathic pain, where smaller doses are typically required.

Mechanism of action: Tricyclic antidepressants impose their therapeutic effects by inhibiting presynaptic reuptake of norepinephrine and serotonin in the central nervous system (this, may give rise to seizures).

Common side-effects:
Drowsiness
Dry mouth
Blurred vision
Constipation
Urinary retention

Low-dose amitriptyline is commonly used in the management of neuropathic pain and the prophylaxis of headaches (both tension and migraine).
Lofepramine has a lower incidence of toxicity in overdose
Amitriptyline and dosulepin (dothiepin) are considered the most dangerous in overdose.

In acute angle closure glaucoma (AACG) there is a rise in IOP secondary to an impairment of aqueous outflow. Management options include reducing aqueous secretions with acetazolamide and inducing pupillary constriction with topical pilocarpine.

The type of significance test used depends on whether the data is parametric (can be measured, usually normally distributed) or non-parametric.
Parametric tests:
Student’s t-test – paired or unpaired*
Pearson’s product-moment coefficient – correlation

Non-parametric tests:
Mann-Whitney U test – unpaired data
Wilcoxon signed-rank test – compares two sets of observations on a single sample
chi-squared test – used to compare proportions or percentages
Spearman, Kendall rank – correlation.

The outcome measured is not normally distributed, i.e. it is non-parametric. This excludes the Student’s t-tests. We are not comparing percentages/proportions so the chi-squared test is excluded. The Mann–Whitney U test is a nonparametric test of the null hypothesis that it is equally likely that a randomly selected value from one sample will be less than or greater than a randomly selected value from a second sample.
This test can be used to investigate whether two independent samples were selected from populations having the same distribution.

Relative Risk = (Probability of event in exposed group) / (Probability of event in not exposed group)
Experimental event rate, EER = 10 / 200 = 0.05

Control event rate, CER = 12 / 600 = 0.02

Therefore the relative risk = EER / CER = 0.05 / 0.02 = 2.5

Temporal arteritis is a chronic large- and medium-sized vessel vasculitis that typically involves the temporal arteries. Classical symptoms include temporal headaches, jaw claudication, amaurosis fugax. Physical exam shows scalp tenderness, palpation of the temporal area may demonstrate an absent pulse, knot-like swelling, and vision loss. Lab results reveal an increased erythematous sedimentation rate and C-reactive protein. Temporal artery biopsy confirms the diagnosis. Management approach: high-dose systemic corticosteroids should be promptly administered even before the diagnosis is established. Temporal artery biopsy confirms the diagnosis. Inability to manage this or administer glucocorticoids might lead to development of blindness.

Nice guidelines for lung reduction surgery:

FEV1 > 20% predicted
PaCO2 < 7.3 kPa
TLco > 20% predicted
Upper lobe predominant emphysema

This patient has pCO2 of 7.4 so she is unsuitable for referral for lung reduction surgery.

The most likely diagnosis is chronic tophaceous gout, which is classically associated with chronic renal impairment or long term diuretic therapy. There is tophus formation due to urate crystal deposition in and around the joint. These tophi can also form in the bones and soft tissues. Renal manifestations with uric acid include nephrolithiasis and uric acid nephropathy. Whenever there is an acute on chronic attack of gout, the inciting cause must be established and in case of diuretic use, they should be immediately replaced with another medication. Allopurinol is never started during an acute episode. it is first allowed to settle before administration of allopurinol. Although dietary restriction must be observed in people with a propensity of gout, this scenario clearly presents diuretics as the cause.

Streptococcus pneumonia is the chief causative organism for lobar pneumonia in this age group patients. Typically patients present with rusty coloured sputum and a cough. Pneumocystis jiroveci is responsible for causing pneumocystis pneumonia among immunocompromised patients.

Giant Cell Arteritis (Temporal Arteritis) is the most probable diagnosis. GCA should always be considered in the differential diagnosis of a new-onset headache in patients 50 years of age or older with an elevated erythrocyte sedimentation rate. Temporal artery biopsy remains the criterion standard for diagnosis of this granulomatous vasculitis. High-dose corticosteroid therapy is the universally accepted treatment.

One of the options of Psoriasis treatment is vitamin D analogues i.e. calcipotriol. Acne is exacerbated by steroids. Erythema nodosum can be caused by various diseases and the treatment of the primary condition resolves the symptoms. Lipomas requires surgery, whereas Steven-Johnson syndrome requires use of steroids and eliminating the culprit drug, which is one of the most common causes.

Polymerase chain reaction (PCR) is a method widely used in molecular biology to make several copies of a specific DNA segment. Using PCR, copies of DNA sequences are exponentially amplified to generate thousands to millions of more copies of that particular DNA segment.The main advantage of PCR is its sensitivity: only one strand of sample DNA is needed to detect a particular DNA sequence. It now has many uses including prenatal diagnosis, detection of mutated oncogenes and diagnosis of infections. PCR is also extensively used in forensics.