A case-control study is designed to help determine if an exposure is associated with an outcome (i.e., disease or condition of interest). In theory, the case-control study can be described simply. Case-control studies have specific advantages compared to other study designs. They are comparatively quick, inexpensive, and easy. They are particularly appropriate for (1) investigating outbreaks, and (2) studying rare diseases or outcomes. Sudden infant death syndrome is a rare medical event, thus case-control study is the most suitable option.

Soluble guanylyl cyclase (GC-1) is the primary receptor of nitric oxide (NO) in smooth muscle cells and maintains vascular function by inducing vasorelaxation in nearby blood vessels. GC-1 converts guanosine 5′-triphosphate (GTP) into cyclic guanosine 3′,5′-monophosphate (cGMP), which acts as a second messenger to improve blood flow.

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.

All of the aforementioned listed tumours, except brain tumours, can metastasise to lungs and produce the typical CXR picture consisting of hilar lymphadenopathy with either diffuse multinodular shadows resembling miliary disease or multiple large well-defined masses (canon balls). Occasionally, cavitation or calcification may also be seen.

Most brain tumours, however, do not metastasise. Some, derived form neural elements, do so but in these cases, intraparenchymal metastases generally precede distant haematogenous spread.

Because of the patient’s history of chronic analgesic use of daily paracetamol intake, the most likely diagnosis of this case is Analgesic misuse headache. In these cases, the headache is only temporarily relieved by analgesics. Treatment involves gradual withdrawal of analgesics.

Spironolactone is an aldosterone antagonist which acts in the distal convoluted tubule. It is a potassium-sparing diuretic that prevents the body from absorbing too much salt and keeps the potassium levels from getting too low. Spironolactone is used to treat heart failure, high blood pressure (hypertension), or hypokalaemia (low potassium levels in the blood).

Pseudogout is a paroxysmal joint inflammation due to calcium pyrophosphate crystal deposition (calcium pyrophosphate dihydrate). Aetiology includes mostly idiopathic (primary form) and secondary form occurring as a result of joint trauma, familial chondrocalcinosis, hyperparathyroidism, hemochromatosis, gout, hypophosphatemia. Clinical presentation: Often asymptomatic.
Acute (pseudogout attack): monoarthritis (rarely oligoarthritis), mostly affecting the knees and other large joints (e.g., hips, wrists, and ankles). It may become chronic (can affect multiple joints). Osteoarthritis with CPPD (most common form of symptomatic CPPD): progressive joint degeneration with episodes of acute inflammatory arthritis typical of pseudogout attacks. Arthrocentesis should be performed, especially in acute cases. Polarized light microscopy: detection of rhomboid-shaped, positively birefringent CPPD crystals. Synovial fluid findings: 10,000-50,000 WBCs/μL with > 90% neutrophils. X-ray findings: cartilage calcification of the affected joint (chondrocalcinosis). Fibrocartilage (meniscus, annulus fibrosus of intervertebral disc) and hyaline cartilage (joint cartilage) may be affected.

The patient is most likely a case of haemophilia A which is the genetic deficiency of clotting factor VIII in blood.

Haemophilia is an X-linked recessive disorder of coagulation. Up to 30% of patients have no family history of the condition. Haemophilia A is more common than haemophilia B and accounts for 90% of the cases. In haemophilia B (Christmas disease), there is a deficiency of clotting factor IX.

Characteristic features of haemophilia include hemarthrosis, haematomas, and prolonged bleeding following trauma or surgery. Coagulation profile of a haemophiliac person shows prolonged bleeding time, activated partial thromboplastin time (APTT), thrombin time (TT), but a normal prothrombin time (PT).

Myotonic dystrophy is the most likely diagnosis here.
It is a multisystem disorder causing cognitive impairment, cataracts, cardiac problems and testicular atrophy, as well as affecting the muscles. Patients have muscle weakness, normally worse distally, and/or myotonia (which is worse in cold weather).
On examination, patients may also have frontal balding, a myopathic facies, bilateral ptosis, an ophthalmoplegia and wasting of facial muscles and other limb muscles. Myotonic dystrophy is associated with diabetes mellitus and pituitary dysfunction.
Diagnosis is normally based on clinical features with a characteristic electromyogram (EMG) of myotonic discharges. Creatine kinase is generally normal and muscle biopsy is non-specific.

This presentation could be due to either a meningitis or encephalitis, which are clinically not distinguishable from the given history. Encephalitis is mostly viral and in UK herpes simplex virus is the main cause. Advanced neuro imaging and EEG will help to differentiate them however from the given answers CSF analysis is the most appropriate, provided that intracranial pressure is not raised. CSF analysis will help to differentiate a pyogenic meningitis from other forms of meningitis and encephalitis.

Behçet disease is a rare vasculitic disorder that is characterized by a triple-symptom complex of recurrent oral aphthous ulcers, genital ulcers, and uveitis. The systemic manifestations can be variable. Ocular disease has the greatest morbidity, followed by vascular disease generally from active vasculitis. Cutaneous manifestations can occur in up 75% of patients with Behcet disease and can range from acneiform lesions, to nodules and erythema nodosum. GI manifestations can be severe. Differentiating Behçet disease from active inflammatory bowel disease can be clinically difficult. Herpes would have ideally responded to acyclovir. Sarcoidosis does not have genital and oral ulcerations.

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.

A variety of proteins compose the structure of microfibrils, the most prominent of which are the two fibrillins. Fibrillin-1 a scaffolding protein is encoded by FBN1 on human chromosome 15q21 and fibrillin-2 is encoded by FBN2 on 5q23. Mutations in FBN1 produce Marfan syndrome, a pleiotropic autosomal dominant connective tissue disorder with prominent manifestations in the skeleton, eye and cardiovascular system. A number of conditions related to Marfan syndrome are also due to FBN1 mutations.

Melanocytic naevi are skin tumours produced by melanocytes. They usually present in childhood but increase during puberty. The mnemonic A-B-C-D, is used by institutions to assess for suspicion of malignancy. The letters stand for asymmetry, border, colour, and diameter. If a mole starts changing in size, colour, shape or, especially, if the border of a mole develops ragged edges or becomes larger than a pencil eraser, it would be an appropriate time to consult with a physician. Other warning signs include if it begins to crust over, bleed, itch, or become inflamed.

Paget’s accelerates the remodelling process with old bone breaking down more quickly which disrupts the normal growth process. New bone development eventually adjusts to the faster pace and speeds up on its own. The pace is too fast for healthy bone growth, and the regrowth ends up softer and weaker than normal. The effect of this accelerated process causes bone pain, fractures, and deformities. Since osteosarcoma is a type of bone cancer linked to abnormal bone growth, this makes it a rare but possible complication of Paget’s disease although the chances of developing osteosarcoma are minimal. Fractures are painful and restrict movement whereas this patients pain is gradually developing. Pain associated with osteoarthritis is usually mild to moderate and worsens as the day progresses.

Rotterdam criteria for the diagnosis of polycystic ovary syndrome:
Two of the following three criteria are required:
1. Oligo/anovulation
2. Hyperandrogenism
– Clinical (hirsutism or less commonly male pattern alopecia) or
– Biochemical (raised FAI or free testosterone)
3. Polycystic ovaries on ultrasound
Other aetiologies must be excluded such as congenital adrenal hyperplasia, androgen-secreting tumours, Cushing syndrome, thyroid dysfunction and hyperprolactinaemia.
Cushing’s is excluded because there would have been marked obesity, hypertension and other related features.

The human cell has two type of DNA: Nuclear DNA and Mitochondrial DNA (MtDNA). A MtDNA copy is passed down entirely unchanged, through the maternal line. Males cannot pass their MtDNA to their offspring although they inherit a copy of it from their mother. Mitochondrial inheritance therefore has the following characteristics:
– Inheritance is only via the maternal line
– All children of affected males will not inherit the disease
– All children of affected females will inherit it

After renal transplant, asymptomatic patients can still have graft dysfunction as an early complication, with rising serum creatinine; therefore, urine and blood cultures should be ordered first. This should be followed by measuring the Tacrolimus levels, as this drug can be directly nephrotoxic. Next, a Doppler ultrasound of the transplant site should be ordered, to check for any obstructions or occlusions.

The clinical presentation is suggestive of congenital rubella syndrome. The classic triad of presenting symptoms includes sensorineural hearing loss, ocular abnormalities (cataract, infantile glaucoma, and pigmentary retinopathy) and congenital heart disease (patent ductus arteriosus and pulmonary artery stenosis). Other findings in congenital rubella syndrome include CNS abnormalities (mental retardation, behavioural disorders, encephalographic abnormalities, hypotonia, meningoencephalitis, and microcephaly), hepatosplenomegaly, and jaundice.

It should be noted that as a general rule 5-HT receptor agonists are used in the acute treatment of migraine whilst 5-HT receptor antagonists are used in prophylaxis. NICE produced guidelines in 2012 on the management of headache, including migraines. Prophylaxis should be given if patients are experiencing 2 or more attacks per month. Modern treatment is effective in about 60% of patients. NICE advises either topiramate or propranolol ‘according to the person’s preference, comorbidities and risk of adverse events’. Propranolol should be used in preference to topiramate in women of child bearing age as it may be teratogenic and it can reduce the effectiveness of hormonal contraceptives.

The diagnosis is inferior ST elevation myocardial infarction. As the right coronary artery supplies the SA and AV nodes and bundle of His, conduction abnormalities are more common with inferior MIs. The most immediate drug management is high dose Aspirin. Definite treatment is urgent cardiac revascularization.

Osteoarthritis (OA) is a disabling joint disease characterized by a noninflammatory degeneration of the joint complex (articular cartilage, subchondral bone, and synovium) that occurs with old age or from overuse. It mainly affects the weight-bearing and high-use joints, such as the hip, knee, hands, and vertebrae. Despite the widespread view that OA is a condition caused exclusively by degenerative “wear and tear” of the joints, newer research indicates a significant heterogeneity of causation, including pre-existing peculiarities of joint anatomy, genetics, local inflammation, mechanical forces, and biochemical processes that are affected by proinflammatory mediators and proteases. Major risk factors include advanced age, obesity, previous injuries, and asymmetrically stressed joints. In early-stage osteoarthritis, patients may complain of reduced range of motion, joint-stiffness, and pain that is aggravated with heavy use. As the disease advances, nagging pain may also occur during the night or at rest. Diagnosis is predominantly based on clinical and radiological findings. Classic radiographic features of OA do not necessarily correlate with clinical symptoms and appearance. RA involves proximal interphalangeal joints not distal. Gout occurs as a result of overproduction or underexcretion of uric acid and frequently involves first toe. Fibromyalgia is a disorder characterized by widespread musculoskeletal pain accompanied by fatigue, sleep, memory and mood issues.

The patient’s chronic renal failure causes decreased renal hydroxylation of vitamin D which leads to decreased calcium absorption in the gut. Simultaneously, there is also decreased renal excretion of phosphate, and this combination of factors results in increased PTH levels.

According to NICE guidelines (2013) all people who have had an acute MI treatment should be offered with ACE inhibitor, dual antiplatelet therapy (aspirin plus a second antiplatelet agent), a beta-blocker and a statin.

The key to this question is anti-smooth muscle antibodies. This is a finding of autoimmune hepatitis, which can be seen in type I diabetics. This also fits with her clinical picture. If you know these two facts, you should get every question correct regarding autoimmune hepatitis. Liver function testing is the best answer, then and should be elevated to indicate inflammation of the liver. Hepatic US, CK, thyroid function testing, short synacthen test are not helpful in the diagnosis of autoimmune hepatitis.

Classic Kallmann syndrome (KS) is due to isolated hypogonadotropic hypogonadism. Most patients have gonadotropin-releasing hormone (GnRH) deficiency, as suggested by their response to pulsatile GnRH therapy. The hypothalamic-pituitary function is otherwise normal in most patients, and hypothalamic-pituitary imaging reveals no space-occupying lesions. By definition, either anosmia or severe hyposmia is present in patients with Kallmann syndrome.

The combination of Insulinoma and Parathyroid diseases is suggestive of MEN 1 syndrome.
Multiple endocrine neoplasia type 1 (MEN1) is a rare hereditary tumour syndrome inherited in an autosomal dominant manner and characterized by a predisposition to a multitude of endocrine neoplasms primarily of parathyroid, entero-pancreatic, and anterior pituitary origin, as well as non-endocrine neoplasms.
Other endocrine tumours in MEN1 include foregut carcinoid tumours, adrenocortical tumours, and rarely pheochromocytoma. Nonendocrine manifestations include meningiomas and ependymomas, lipomas, angiofibromas, collagenomas, and leiomyomas.

Primary hyperparathyroidism (PHPT), due to parathyroid hyperplasia is the most frequent and usually the earliest expression of MEN-1, with a typical age of onset at 20–25 years.

Cataract is a condition characterized by clouding of the lens of the eye. This condition most frequently occurs due to age-related degenerative processes in the lens, but can also be associated with ocular trauma, metabolic disorders, side-effects of drugs, or congenital infections. The clouding causes distortion of light, as it passes through the lens, resulting in visual impairment and glare. Initially, a cataract presents discretely and may even go unnoticed, but the visual impairment worsens as the cataract grows larger.

Diagnosis is typically established on the basis of a thorough history and direct visualization of the cataract (by means of slit-lamp microscopy). Surgery is indicated with significant visual impairment and involves lens extraction and implantation of an artificial lens. Untreated cataracts eventually lead to complete blindness.

Pneumocystis Jiroveci. This causative organism is responsible for pneumonia in individuals that have a compromised immune system. Symptoms include cyanosis, dry cough and in some cases, diffuse bilateral alveolar shadows on CXR. Co-trimoxazole is normally the treatment for this.

CURB Pneumonia Severity Score estimates the mortality of community-acquired pneumonia to help determine inpatient vs. outpatient treatment.
Select Criteria:
Confusion (abbreviated Mental Test Score <=8) (1 point)
Urea (BUN > 19 mg/dL or 7 mmol/L) (1 point)
Respiratory Rate > 30 per minute (1 point)
Blood Pressure: diastolic < 60 or systolic < 90 mmHg (1 point) The CURB-65 scores range from 0 to 5. Clinical management decisions can be made based on the score:
Score Risk Disposition
0 or 1 – 1.5% mortality – Outpatient care
2 – 9.2% mortality – Inpatient vs. observation admission
≥ 3 – 22% mortality – Inpatient admission with consideration for ICU admission with score of 4 or 5