Indapamide is a mild thiazide-like diuretic with hypotensive effect, and compared to other thiazides, it is reported to also have less metabolic derangements. However, it may have beneficial hypo-calciuric effects that are often associated with thiazides, thus, in this case, we would recommend prescribing this to the patient.

Reactive arthritis, (formerly known as Reiter’s syndrome), is an autoimmune condition that occurs after a bacterial infection of the gastrointestinal or urinary tract. It is categorized as a seronegative spondylarthritis because of its association with HLA-B27. Reactive arthritis primarily affects young men and usually presents with musculoskeletal or extra‑articular symptoms. The characteristic triad consists of arthritis, conjunctivitis, and urethritis. The diagnosis is based on clinical features such as patient history and physical examination; there are no specific tests for reactive arthritis. Treatment is primarily symptomatic and consists of the administration of NSAIDs, as most patients recover spontaneously. extraarticular dermatologic manifestations include skin lesions of the glans resembling psoriasis (balanitis circinata); hyperkeratinisation of the palms and soles (keratoderma blenorrhagicum), oral ulcers.

The patient is displaying signs and symptoms of hyperviscosity syndrome, secondary to the Waldenström’s macroglobulinemia. Treatment of choice is plasmapheresis.

Waldenström’s macroglobulinemia (also called lymphoplasmacytic lymphoma) is an uncommon type of non-Hodgkin lymphoma seen in older people. It is a lymphoplasmacytoid malignancy characterised by the secretion of a monoclonal IgM paraprotein. Its features include monoclonal IgM paraproteinemia; hyperviscosity syndrome leading to bilateral central retinal vein occlusion (CRVO) and hence, visual disturbances; weight loss and lethargy; hepatosplenomegaly and lymphadenopathy; and cryoglobulinemia. It is not, however, associated with bone pain.

Here, the patient seems to be intolerant to standard metformin. In such cases, modified-release preparations is considered as the most appropriate next step.
There is some evidence that these produce fewer gastrointestinal side-effects in patients intolerant of standard-release metformin.

Metformin is a biguanide and reduces blood glucose levels by decreasing the production of glucose in the liver, decreasing intestinal absorption and increasing insulin sensitivity.
Metformin decreases both the basal and postprandial blood glucose.
Other uses: In Polycystic Ovarian Syndrome (PCOS), Metformin decreases insulin levels, which then decreases luteinizing hormone and androgen levels. Thus acting to normalize the menstruation cycle.

Note:
Metformin is contraindicated in patients with severe renal dysfunction, which is defined as a glomerular filtration rate (GFR) less than 30 ml/min/1.732m2.
Metformin overdose has been associated with hypoglycaemia and lactic acidosis, for this reason, it has a black box warning for lactic acidosis.

This patient has polycystic ovarian syndrome (PCOS). Medical management of PCOS is aimed at the treatment of metabolic derangements, anovulation, hirsutism, and menstrual irregularity.
First-line medical therapy usually consists of an oral contraceptive to induce regular menses. The contraceptive not only inhibits ovarian androgen production but also increases sex hormone-binding globulin (SHBG) production. The American College of Obstetricians and Gynaecologists (ACOG) recommends the use of combination low-dose hormonal contraceptive agents for long-term management of menstrual dysfunction.
If symptoms such as hirsutism are not sufficiently alleviated, an androgen-blocking agent may be added. Pregnancy should be excluded before therapy with oral contraceptives or androgen-blocking agents are started.
First-line treatment for ovulation induction when fertility is desired is clomiphene citrate. Second-line strategies may be equally effective in infertile women with clomiphene citrate–resistant PCOS.

NICE now recommends the three acetylcholinesterase inhibitors (donepezil, galantamine and rivastigmine) as options for managing mild to moderate Alzheimer’s disease. Memantine is reserved for patients with moderate to severe Alzheimer’s.

Hypocalcaemia occurs in patients with impaired function of the parathyroid glands. This is most common after thyroid or parathyroid surgery, but it can be idiopathic—mostly in young adults and less often as part of a genetic syndrome, such as autoimmune polyglandular syndrome type 1. Usually, the first and most useful test to perform in such cases is the measurement of the parathyroid hormone.

Troponin T is a 37 ku protein that binds to tropomyosin, thereby attaching the troponin complex to the thin filament.

The given clinical scenario is suggestive of myo-neuropathy and is most likely to be caused by colchicine toxicity.
It gives rise to subacute proximal muscle weakness and on occasions can lead to an acute necrotizing myopathy. Creatine phosphokinase may be normal or may be elevated.
Weakness resolves when the drug is discontinued but the neuropathic features remain.
Death is usually a result of respiratory depression and cardiovascular collapse.
Treatment is symptomatic and supportive, and the treatment for colchicine poisoning includes lavage and measures to prevent shock.

A prominent A wave is observed in the jugular venous pulse and this indicates the presence of established pulmonary hypertension. In addition the pulmonic component of the second heart sound (P2) may be increased and the P2 may demonstrate fixed or paradoxical splitting. The signs of right ventricular failure include a high-pitched systolic murmur of tricuspid regurgitation, hepatomegaly, a pulsatile liver, ascites, and peripheral oedema.

According to the history the patient has cardiogenic shock and pulmonary oedema. On-going ischaemia is indicated by persisting symptoms. So the most appropriate management is coronary angiography and rescue PCI. There are no indications for blood transfusion at this moment and it will aggravate the pulmonary oedema. Haemodialysis, beta blockers and furosemide cannot be given due to low blood pressure.

Diagnosis of multiple myeloma (MM) is based on the confirmation of (a) one major criterion and one minor criterion or (b) three minor criteria in an individual who has signs or symptoms of multiple myeloma.

Major criteria:
1. >30% plasma cells on bone marrow biopsy
2. Monoclonal band of paraprotein on electrophoresis: >35g/L for IgG, 20g/L for IgA, or >1g of light chains excreted in the urine per day

Minor criteria:
1. 10–30% plasma cells on bone marrow biopsy
2. Abnormal monoclonal band but levels less than listed above
3. Lytic bone lesions observed radiographically
4. Immunosuppression

Onycholysis is the separation of the distal edge of the nail from the vascular nailbed causing whiteness of the free edge. Causes include:
– Idiopathic
– Trauma, excessive manicuring
– Infection: especially fungal
– Skin disease: psoriasis, dermatitis
– Impaired peripheral circulation e.g. Raynaud’s
– Systemic disease: hyper/hypothyroidism, reactive arthritis, porphyria cutanea tarda
– Sometimes a reaction to detergents (e.g. washing dishes with bare hands, using detergent-based shampoos or soaps).
– Patients with hepatocellular dysfunction may develop hair-thinning or hair loss and nail changes such as clubbing, leukonychia (whitening), or onycholysis.

The question describes an alcohol abusing man with chronic epigastric discomfort, radiating into his back, worse with meals, and foul-smelling stools, weight loss, as well as chronic nausea. This is likely, thus chronic pancreatitis due to alcohol abuse. Hepatomegaly and peripheral neuropathy secondary to anaemia support the diagnosis of long term alcohol abuse. Bacterial overgrowth may present with diarrhoea and is a less likely diagnosis than pancreatitis. Celiac disease is a less likely diagnosis than pancreatitis, and you would also expect mention of diarrhoea. VIPoma would also likely present with diarrhoea. Cecal carcinoma would more than likely present with blood in the stool.

The patient is on stage IV according to the Ann Arbor staging system for Hodgkin lymphoma (HL). The disease has spread beyond the lymph nodes into the liver (involvement of extra lymphatic organ).

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

Atrioventricular septal defect (AVSD) also known as endocardial cushion defect is the most common cardiac abnormality in Down’s Syndrome.

This patient has complaints of diplopia in the right eye, when looking towards the right. Eyeball movements towards the right side are controlled by right lateral rectus muscle which is supplied by the abducent nerve.

The patient has acute promyelocytic leukaemia (APML) with associated disseminated intravascular coagulation (DIC). Although
the platelet count is high, platelet function is ineffective.

Patients may present, as in this case, with severe bleeding, and the most appropriate emergency treatment would be administration of fresh frozen plasma (FFP).

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.

A couple of papers written by the same authors indicate that children and adolescents taking an SSRI definitely experience discontinuation reactions that can be mild, moderate or severe when the medication is stopped suddenly or high doses are reduced substantially. Among the SSRIs paroxetine seems to be the worst offender and fluoxetine the least while sertraline and fluvoxamine tend to be intermediate. The rate of discontinuation syndrome varies with the particular SSRI involved. It is generally quoted as 25% but is higher for SSRIs with shorter half-lives. Paroxetine has been associated with more frequent discontinuation symptoms than the other SSRIs.

The use of fluoxetine with its long half-life appears safer in this respect than paroxetine and venlafaxine causing the most concerns.

Paroxetine has the shortest half-life with 21 hours of all listed SSRIs and as such it would be expected to have a higher incidence or severity (greater number of symptoms) and fluoxetine would have the least since it has a half life of 96 hours. Citalopram has a half-life of 35 hours while escitalopram has a half-life of 30 hours.

The most common symptoms reported are: dizziness, light-headedness, drowsiness, poor concentration, nausea, headache and fatigue.
Another common symptom in adults is paraesthesia described as burning, tingling, numbness or electric shock feelings usually in the upper half of the body or proximal lower limbs.

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.

It is proven that spironolactone has survival benefits and loop diuretics only give symptomatic relief. Beta blockers are however, known to improve exercise tolerance, left ventricular function and reduce symptoms. They also reduce the mortality associated with heart failure. So administration of beta blockers will reduce the time spent in hospital by improving symptoms.

Indications for surgery for the treatment of primary hyperparathyroidism:
1. Symptoms of hypercalcaemia such as thirst, frequent or excessive urination, or constipation
2. End-organ disease (renal stones, fragility fractures or osteoporosis)
3. An albumin-adjusted serum calcium level of 2.85 mmol/litre or above.

IgA nephropathy’s characteristic presentation is haematuria following a non-specific upper respiratory infection as was evident in this case. IgA nephropathy also usually occurs in children and young males, like this patient.

From the given answers, complete heart block with a narrow complex QRS complex is associated with the least risk of asystole. Transvenous pacing is indicated by the other given responses.

Pregnancies affected by T1DM are at increased risk for preterm delivery, preeclampsia, macrosomia, shoulder dystocia, intrauterine fetal demise, fetal growth restriction, cardiac and renal malformations, in addition to rare neural conditions such as sacral agenesis.
Successful management of pregnancy in a T1DM patient begins before conception. Research indicates that the implementation of preconception counselling, emphasizing strict glycaemic control before and throughout pregnancy, reduces the rate of perinatal mortality and malformations.
The 2008 bulletin from the National Institute for Health and Clinical Excellence recommends that preconception counselling be offered to all patients with diabetes. Physicians are advised to guide patients on achieving personalized glycaemic control goals, increasing the frequency of glucose monitoring, reducing their HbA1C levels, and recommend avoiding pregnancy if the said level is > 10%.
Other sources suggest deferring pregnancy until HbA1C levels are > 8%, as this margin is associated with better outcomes.

This patient has Klumpke’s paralysis due to damage to the T1 nerve root. This root eventually supplies the median and ulnar nerves. The ulnar nerve supplies all of the intrinsic hand muscles except for those of the thenar eminence and the first and second lumbricals, which are innervated by the median nerve.

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.

The following drugs should be used as normal during pregnancy:
short acting β2 -agonists
long acting β2- agonists
inhaled corticosteroids
oral and intravenous theophyllines

Use steroid tablets as normal when indicated during pregnancy for severe asthma. Steroid tablets should never be withheld because of pregnancy.
If leukotriene receptor antagonists are required to achieve adequate control of asthma then they should not be withheld during pregnancy.

Thioridazine has a quinidine-like action on the heart and is known to cause cardiac arrhythmias including prolonged PR and QT intervals and widening of QRS complexes. Intravenous magnesium sulphate is regarded as the treatment of choice for this arrhythmia.