Understanding Protein C Deficiency

Protein C deficiency is a genetic condition that increases the risk of developing blood clots. It is inherited in an autosomal codominant manner, meaning that a person only needs to inherit one copy of the mutated gene from either parent to develop the condition.

One of the main features of protein C deficiency is an increased risk of venous thromboembolism, which is the formation of blood clots in the veins. This can lead to serious complications such as deep vein thrombosis and pulmonary embolism.

Another feature of protein C deficiency is skin necrosis, which can occur when a person with the condition starts taking warfarin, a medication used to prevent blood clots. When warfarin is first started, the body’s production of protein C is temporarily reduced, which can lead to a procoagulant state and an increased risk of thrombosis. This can result in the death of skin tissue, particularly in the venules, leading to skin necrosis. To prevent this, concurrent administration of heparin may be necessary.

In summary, protein C deficiency is a genetic condition that increases the risk of blood clots, particularly in the veins. It can also lead to skin necrosis when warfarin is first started. Early diagnosis and appropriate management can help prevent serious complications.

The individual is experiencing chronic widespread pain, along with lethargy and difficulty concentrating. Palpation reveals multiple tender points. While immunological results align with a previous diagnosis of rheumatoid arthritis, there is no indication of a flare-up or the development of a new connective tissue disease or myositis. Chronic regional pain syndrome typically involves persistent burning pain in one limb following a minor injury, but this is not the case here. The symptoms are indicative of fibromyalgia, which is not a diagnosis of exclusion and can coexist with other conditions.

Fibromyalgia is a condition that causes widespread pain throughout the body, along with tender points at specific anatomical sites. It is more common in women and typically presents between the ages of 30 and 50. Other symptoms include lethargy, cognitive impairment (known as fibro fog), sleep disturbance, headaches, and dizziness. Diagnosis is made through clinical evaluation and the presence of tender points. Management of fibromyalgia is challenging and requires an individualized, multidisciplinary approach. Aerobic exercise is the most effective treatment, along with cognitive behavioral therapy and medication such as pregabalin, duloxetine, and amitriptyline. However, there is a lack of evidence and guidelines to guide treatment.

To improve this patient’s HbA1c, the addition of liraglutide is recommended as sulphonylureas and pioglitazone are contraindicated due to previous adverse reactions and heart failure, respectively. Liraglutide activates the GLP-1 receptor to increase insulin secretion, suppress glucagon secretion, and slow gastric emptying. However, it should only be continued if there is a reduction in HbA1c of at least 11 mmol/mol and a weight loss of at least 3% of initial body weight in 6 months. Increasing the dose of metformin is unlikely to achieve the target HbA1c, and insulin should be avoided due to previous hypoglycemic episodes.

When analyzing data from a right heart catheter, it is important to note that the saturation levels should gradually decrease as venous blood reaches the pulmonary capillary wedge saturation, which should be equivalent to arterial blood. Additionally, it is normal for oxygenation in the superior vena cava to be lower than in the inferior vena cava due to the brain’s high oxygen demands. In this study, there were no sudden increases in oxygen saturations, indicating no left to right shunt. However, the SVC saturation was significantly higher than the IVC, indicating anomalous pulmonary venous drainage of more highly oxygenated blood into the SVC.

Understanding Oxygen Saturation Levels in Cardiac Catheterisation

Cardiac catheterisation and oxygen saturation levels can be confusing, but with a few basic rules and logical deduction, it can be easily understood. Deoxygenated blood returns to the right side of the heart through the superior and inferior vena cava with an oxygen saturation level of around 70%. The right atrium, right ventricle, and pulmonary artery also have oxygen saturation levels of around 70%. The lungs oxygenate the blood to a level of around 98-100%, resulting in the left atrium, left ventricle, and aorta having oxygen saturation levels of 98-100%.

Different scenarios can affect oxygen saturation levels. For instance, in an atrial septal defect (ASD), the oxygenated blood in the left atrium mixes with the deoxygenated blood in the right atrium, resulting in intermediate levels of oxygenation from the right atrium onwards. In a ventricular septal defect (VSD), the oxygenated blood in the left ventricle mixes with the deoxygenated blood in the right ventricle, resulting in intermediate levels of oxygenation from the right ventricle onwards. In a patent ductus arteriosus (PDA), the higher pressure aorta connects with the lower pressure pulmonary artery, resulting in only the pulmonary artery having intermediate oxygenation levels.

Understanding the expected oxygen saturation levels in different scenarios can help in diagnosing and treating cardiac conditions. The table above shows the oxygen saturation levels that would be expected in different diagnoses, including VSD with Eisenmenger’s and ASD with Eisenmenger’s. By understanding these levels, healthcare professionals can provide better care for their patients.

Importance of Chest Radiograph Review and Smoking Cessation in Older Smokers

It is crucial to review the chest radiograph of an older patient who is a smoker to rule out the possibility of cancer. Additionally, it is important to assess the patient’s thoughts on smoking cessation and provide support in dealing with it.

Waiting for only one week after the radiograph may not be sufficient to detect any changes, while waiting for two weeks may miss the chance to detect changes in over half of the cases. Waiting for four weeks may still miss changes in a significant number of cases, as up to 73% of radiographs may show changes after six weeks. Therefore, it is necessary to review the chest radiograph at an appropriate time to ensure timely detection of any abnormalities.

Furthermore, given the patient’s age and smoking history, it is crucial to provide support for smoking cessation. Never is not an option, as the patient’s health is at risk. By providing support and resources for smoking cessation, the patient can improve their overall health and reduce the risk of developing cancer or other smoking-related illnesses.

Chemotherapy is a common treatment for cancer, but it can also cause severe side effects. One such drug is 5-fluorouracil (5-FU), which is metabolically activated to 5-fluoro-2’deoxyuridine-5-monophosphate (F-dUMP) and inhibits DNA synthesis. The breakdown of 5-FU is carried out by dihydropyrimidine dehydrogenase (DPD), and a pharmacogenetic disorder can cause a deficiency of this enzyme, leading to severe toxicity and potentially fatal outcomes. Rapid administration of 5-FU can also cause reactions, but it is unlikely to be the cause of severe symptoms. Similarly, a low dose of folinic acid, which is given concurrently with 5-FU, is unlikely to cause such symptoms. Therefore, understanding the genetic susceptibility to toxicity from 5-FU due to a deficiency of the catabolising enzyme is crucial in managing the side effects of chemotherapy.

The patient’s symptoms, including choreiform movements, rigidity, eye movement abnormalities, and cognitive problems, strongly suggest Huntington’s disease (HD). HD is a trinucleotide repeat disorder that affects the huntingtin gene on chromosome 4. Genetic anticipation is observed in HD, where successive generations tend to show an earlier onset of a more severe phenotype due to expansion of the repeat length. There is currently no cure for HD, and patients who are at risk but asymptomatic can choose to undergo predictive testing after undergoing genetic counseling. Other rare causes of adult-onset movement disorders, such as neuroacanthocytosis and genetic prion disease, should also be considered. Tests for Wilson’s disease are unlikely to be necessary due to the presence of an autosomal dominant mode of inheritance. A single gene test for HD is recommended over a next-generation gene chip for Parkinson’s disease, as the clinical features are not compatible with Parkinson’s.

Leptospirosis is commonly diagnosed through serology, but it may take up to 7 days for antibodies to appear. This patient’s occupational and social history puts her at risk for zoonotic infections, and her symptoms, including liver involvement, coagulopathy, and myalgia in the calves and lower back, suggest leptospirosis.

Culture testing for the organism is difficult, with the highest yield within the first 10 days of illness. As this patient has been symptomatic for at least 2 weeks, culture pick-up rates are now lower. Leptospires are shed in urine during and after the illness, but transmission is not through respiratory droplets, so normal social interactions are safe.

There is no vaccine for leptospirosis, so hand hygiene is important for those at occupational risk. Most cases are mild and self-resolve, but antibiotics such as doxycycline, azithromycin, or amoxicillin may be used. Rats are the most common source of transmission, but dogs, cattle, and pigs can also transmit the disease.

Leptospirosis: A Tropical Disease with Early and Late Phases

Leptospirosis is a disease caused by the bacterium Leptospira interrogans, which is commonly spread through contact with infected rat urine. While it is often associated with certain occupations such as sewage workers, farmers, and vets, it is more prevalent in tropical regions and should be considered in returning travelers. The disease has two phases: an early phase characterized by flu-like symptoms and fever, and a later immune phase that can lead to more severe symptoms such as acute kidney injury, hepatitis, and aseptic meningitis. Diagnosis can be made through serology, PCR, or culture, but treatment typically involves high-dose benzylpenicillin or doxycycline.

Management of Relapsed Hodgkin Lymphoma

Relapsed Hodgkin lymphoma that occurs within a year of initial treatment requires aggressive management. The established gold standard for such cases is salvage chemotherapy followed by BEAM conditioned autologous stem cell transplantation. However, if the relapse occurs after a year, repeating ABVD chemotherapy may be considered as an option. It is important to note that involved field radiation therapy (IFRT) has no role in the management of relapsed disease.

It is crucial to combine chemotherapy and ASCT for maximal disease clearing effect. Therefore, using either of these options alone is not recommended. It is essential to manage relapsed Hodgkin lymphoma promptly and effectively to improve the chances of a successful outcome.

In the case of P-wave systole, which is a unique situation that deviates from the standard cardiac arrest algorithm, external pacing may lead to the restoration of spontaneous circulation. Atropine is no longer administered for any rhythm associated with cardiac arrest, while amiodarone and defibrillation are included in the protocol for shockable rhythms. If hypovolemia is suspected as the underlying cause of cardiac arrest, an IV fluid bolus is recommended. However, in this particular scenario, external pacing is more likely to result in the return of spontaneous circulation.

The 2015 Resus Council guidelines for adult advanced life support outline the steps to be taken in the event of a cardiac arrest. Patients are divided into those with ‘shockable’ rhythms (ventricular fibrillation/pulseless ventricular tachycardia) and ‘non-shockable’ rhythms (asystole/pulseless-electrical activity). Key points include the ratio of chest compressions to ventilation (30:2), continuing chest compressions while a defibrillator is charged, and delivering drugs via IV access or the intraosseous route. Adrenaline and amiodarone are recommended for non-shockable rhythms and VF/pulseless VT, respectively. Thrombolytic drugs should be considered if a pulmonary embolus is suspected. Atropine is no longer recommended for routine use in asystole or PEA. Following successful resuscitation, oxygen should be titrated to achieve saturations of 94-98%. The ‘Hs’ and ‘Ts’ outline reversible causes of cardiac arrest, including hypoxia, hypovolaemia, and thrombosis.

In 2011, the National Institute for Clinical Excellence updated its guideline for managing hypertension, emphasizing the use of ambulatory blood pressure monitoring (ABPM) as the first line of diagnosis for those with elevated clinic readings. ABPM involves taking two measurements per hour during waking hours and using the average of at least 14 measurements to confirm hypertension.

Secondary causes of hypertension should be investigated in patients under 40 without traditional risk factors, those with other symptoms, and those with resistant hypertension. Hyperaldosteronism is the most common cause, and a trial of spironolactone may be used for both diagnosis and treatment.

Drug treatment for essential hypertension follows a stepwise approach, with ACE inhibitors recommended for those under 55 and calcium channel blockers for those over 55 or of black African or Caribbean origin. Combination therapy with ACE inhibitors and calcium channel blockers is recommended in step 2, followed by the addition of a thiazide-like diuretic in step 3. Further diuretics, beta-blockers, or alpha blockers may be considered in step 4, with expert advice sought. For more detailed information, see the provided link.

NICE released updated guidelines in 2019 for the management of hypertension, building on previous guidelines from 2011. These guidelines recommend classifying hypertension into stages and using ambulatory blood pressure monitoring (ABPM) and home blood pressure monitoring (HBPM) to confirm the diagnosis of hypertension. This is because some patients experience white coat hypertension, where their blood pressure rises in a clinical setting, leading to potential overdiagnosis of hypertension. ABPM and HBPM provide a more accurate assessment of a patient’s overall blood pressure and can help prevent overdiagnosis.

To diagnose hypertension, NICE recommends measuring blood pressure in both arms and repeating the measurements if there is a difference of more than 20 mmHg. If the difference remains, subsequent blood pressures should be recorded from the arm with the higher reading. NICE also recommends taking a second reading during the consultation if the first reading is above 140/90 mmHg. ABPM or HBPM should be offered to any patient with a blood pressure above this level.

If the blood pressure is above 180/120 mmHg, NICE recommends admitting the patient for specialist assessment if there are signs of retinal haemorrhage or papilloedema or life-threatening symptoms such as new-onset confusion, chest pain, signs of heart failure, or acute kidney injury. Referral is also recommended if a phaeochromocytoma is suspected. If none of these apply, urgent investigations for end-organ damage should be arranged. If target organ damage is identified, antihypertensive drug treatment may be started immediately. If no target organ damage is identified, clinic blood pressure measurement should be repeated within 7 days.

ABPM should involve at least 2 measurements per hour during the person’s usual waking hours, with the average value of at least 14 measurements used. If ABPM is not tolerated or declined, HBPM should be offered. For HBPM, two consecutive measurements need to be taken for each blood pressure recording, at least 1 minute apart and with the person seated. Blood pressure should be recorded twice daily, ideally in the morning and evening, for at least 4 days, ideally for 7 days. The measurements taken on the first day should be discarded, and the average value of all the remaining measurements used.

Interpreting the results, ABPM/HBPM above 135/85 mmHg (stage 1 hypertension) should be

Treatment options for lead poisoning

Lead poisoning is a condition that primarily affects children and adults with occupational exposure to heavy metals. The symptoms can range from abdominal pain and headaches to confusion and peripheral motor neuropathy. Diagnosis is confirmed through a plasma lead level test, and chelation therapy is the most appropriate intervention. The two chelating agents used for treatment are dimercaptosuccinic acid (DMSA) and calcium disodium edetate. After treatment, it is important to identify and prevent re-exposure to lead. Desferrioxamine is a chelating agent used for iron toxicity, while N-acetylcysteine is used for paracetamol overdose and hepatic encephalopathy. Plasma exchange is most useful in antibody-mediated conditions.

Diagnosis of Goodpasture’s Syndrome

This patient is likely suffering from Goodpasture’s syndrome, as indicated by the positive anti-GBM antibody. Although the presence of ANA and DS-DNA antibodies would suggest lupus nephritis, the short and acute nature of the symptoms is not typical of this condition. A renal biopsy would be necessary to confirm a diagnosis of lupus nephritis. Urinary tract infection is not a likely cause of the symptoms, and renal tuberculosis is also improbable.

The CT scan reveals widespread bleeding in the subarachnoid space, affecting the basal cisterns, sylvian fissures on both sides, and the inter-hemispheric fissure. This pattern is characteristic of subarachnoid hemorrhage, where blood enters the subarachnoid space.

Understanding Subarachnoid Haemorrhage

Subarachnoid haemorrhage (SAH) is a type of intracranial haemorrhage where blood is present in the subarachnoid space, which is located deep to the subarachnoid layer of the meninges. Spontaneous SAH is caused by various factors such as intracranial aneurysm, arteriovenous malformation, pituitary apoplexy, arterial dissection, mycotic aneurysms, and perimesencephalic. The most common symptom of SAH is a sudden-onset headache, which is severe and occipital. Other symptoms include nausea, vomiting, meningism, coma, seizures, and sudden death. SAH can be confirmed through a CT head scan or lumbar puncture. Treatment for SAH depends on the underlying cause, and most intracranial aneurysms are treated with a coil by interventional neuroradiologists. Complications of aneurysmal SAH include re-bleeding, vasospasm, hyponatraemia, seizures, hydrocephalus, and death. Predictive factors for SAH include conscious level on admission, age, and the amount of blood visible on CT head.

Understanding EPO and its Detection in Athletes

Erythropoietin (EPO) is a performance-enhancing drug that has become a major problem in high-level sports. It was first introduced in cycling in the late 1980s and works by increasing the red cell mass, which in turn increases the oxygen-carrying capacity of the blood. This should improve performance during intense exercise. However, EPO use comes with serious health risks, including hypertension, thrombosis, and even death.

EPO testing has been greatly refined, and levels can be detected in urine for several weeks after administration. Although blood sampling can also detect EPO, urine testing is preferred due to the risk of infection associated with blood sampling. Saliva testing is currently under development but is not as reliable as urine testing.

It is important to note that EPO use does not increase muscle bulk, but rather improves the oxygen-carrying capacity of the blood. While EPO may increase reticulocyte count, this alone is not diagnostic of EPO use, as high-altitude training can also increase red blood cell count.

In conclusion, EPO use is a serious issue in sports, and athletes should be aware of the health risks and the likelihood of detection through urine testing.

Treatment Options for Amaurosis Fugax

Amaurosis fugax is a medical condition characterized by temporary vision loss in one eye. The typical clinical presentation of this condition suggests that carotid endarterectomy is only necessary if there is more than 50% or 70% stenosis of the symptomatic carotid artery. It is important to note that the external carotid artery, which supplies the neck, face, and skull, is not responsible for the symptoms in this patient despite having 90% stenosis.

Aspirin is the most appropriate treatment for this patient. Warfarin is not indicated as the ECG showed sinus rhythm. It is important to consider the appropriate treatment options for amaurosis fugax to prevent further complications and improve the patient’s quality of life. Proper diagnosis and management of this condition can help prevent future vision loss and other related health issues.

Optimizing Treatment for a Patient with Type 2 Diabetes and Hypertension

Introduction:
This patient has type 2 diabetes and hypertension. While his blood pressure is relatively well controlled, his blood glucose levels need improvement to reduce the progression of retinopathy.

Gradual Transition to Insulin Therapy:
To achieve the target HbA1c of 53.0 mmol/mol (7.0%), a gradual transition to insulin therapy may be necessary.

Addition of Valsartan to Blood Pressure regimen:
Adding an ARB to an ACE inhibitor may not significantly improve blood pressure control and may increase the risk of hyperkalemia. Therefore, it should be avoided.

Addition of Amlodipine to Blood Pressure regimen:
The next step in further intensification of blood pressure control is adding a calcium antagonist such as amlodipine. However, only diltiazem has been shown to significantly impact proteinuria among the calcium antagonist class.

Laser Therapy:
While laser therapy can reduce the progression of retinopathy, there are currently no high-risk features identified on retinal photography.

Increasing Gliclazide Dose:
The dose-response curve for gliclazide above 160 mg is fairly flat, so increasing the sulfonylurea dose to 320 mg/day may not provide significant value.

According to DVLA guidance, determining whether someone with dementia is fit to drive is a challenging decision. If the individual exhibits impaired short-term memory, disorientation, or a lack of insight, it is likely that they are not fit to drive. Therefore, it is recommended to contact the DVLA, evaluate the risk factors, and seek further advice. Rather than immediately disqualifying the individual, a thorough assessment and decision with support from the DVLA is necessary. Factors that indicate an individual with dementia may not be safe to drive include significant short-term memory impairment, poor attention and concentration, and planning difficulties.

The DVLA has guidelines for individuals with neurological disorders who wish to drive cars or motorcycles. However, the rules for drivers of heavy goods vehicles are much stricter. For individuals with epilepsy or seizures, they must not drive and must inform the DVLA. If an individual has had a first unprovoked or isolated seizure, they must take six months off driving if there are no relevant structural abnormalities on brain imaging and no definite epileptiform activity on EEG. If these conditions are not met, the time off driving is increased to 12 months. Individuals with established epilepsy or those with multiple unprovoked seizures may qualify for a driving license if they have been free from any seizure for 12 months. If there have been no seizures for five years (with medication if necessary), a ’til 70 license is usually restored. Individuals should not drive while anti-epilepsy medication is being withdrawn and for six months after the last dose.

For individuals with syncope, a simple faint has no restriction on driving. A single episode that is explained and treated requires four weeks off driving. A single unexplained episode requires six months off driving, while two or more episodes require 12 months off. For individuals with other conditions such as stroke or TIA, they must take one month off driving. They may not need to inform the DVLA if there is no residual neurological deficit. If an individual has had multiple TIAs over a short period of time, they must take three months off driving and inform the DVLA. For individuals who have had a craniotomy, such as for meningioma, they must take one year off driving. If an individual has had a pituitary tumor, a craniotomy requires six months off driving, while trans-sphenoidal surgery allows driving when there is no debarring residual impairment likely to affect safe driving. Individuals with narcolepsy/cataplexy must cease driving on diagnosis but can restart once there is satisfactory control of symptoms. For individuals with chronic neurological disorders such as multiple sclerosis or motor neuron disease, they should inform the DVLA and complete the PK1 form (application for driving license holders’ state of health). If the tumor is a benign meningioma and there is no seizure history, the license can be reconsidered six months after surgery if the individual remains seizure-free.

The patient has been diagnosed with Hereditary Neuropathy with Liability to Pressure Palsy (HNPP), a neurological syndrome that causes mononeuropathy due to minor trauma to a peripheral nerve. This condition is most commonly seen in families with Dutch or German ancestry and is caused by a deletion in the peripheral myelin protein 22 gene on chromosome 17. It is an autosomal dominant condition that usually presents in the second or third decade of life.

The patient has previously experienced ulnar and radial nerve palsy, also known as Saturday night palsy. Nerve conduction studies in HNPP show slow conduction and small action potentials, indicating a demyelinating neuropathy. A nerve biopsy may also reveal a predominance of smaller fibers and localized thickening of the myelin sheath. Gene testing can confirm the diagnosis.

Management of HNPP is conservative and includes the use of wrist splints, ankle-foot orthoses, and protective padding.

Understanding Peripheral Neuropathy: Demyelinating vs. Axonal Pathology

Peripheral neuropathy is a condition that affects the nerves outside of the brain and spinal cord. It can be caused by a variety of factors, including alcohol, diabetes mellitus, vasculitis, vitamin B12 deficiency, and hereditary sensorimotor neuropathies. However, the pathology of peripheral neuropathy can be classified into two main types: demyelinating and axonal.

Demyelinating pathology is characterized by damage to the myelin sheath, which is the protective covering around nerve fibers. This type of neuropathy can be caused by conditions such as Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP), amiodarone, hereditary sensorimotor neuropathies (HSMN) type I, and paraprotein neuropathy.

On the other hand, axonal pathology is characterized by damage to the nerve fibers themselves. This type of neuropathy can be caused by factors such as alcohol, diabetes mellitus, vasculitis, vitamin B12 deficiency, and hereditary sensorimotor neuropathies (HSMN) type II.

It is important to note that some conditions, such as diabetes mellitus and vitamin B12 deficiency, can cause both demyelinating and axonal pathology. Understanding the type of pathology involved in peripheral neuropathy can help with diagnosis and treatment.

Decompensated Liver Disease: Causes, Signs, and Management

Decompensated liver disease is a condition where the liver is unable to function properly, leading to various complications. There are several causes of decompensation, including infections such as pneumonia and viral hepatitis, drugs like paracetamol and anaesthetic agents, toxins such as alcohol and Amanita phalloides mushroom, vascular disorders like Budd-Chiari syndrome and vena-occlusive disease, haemorrhage from upper gastrointestinal bleed, and constipation.

The signs of decompensated liver disease include asterixis, jaundice, hepatic encephalopathy, and constructional apraxia, which is a difficulty in drawing a clock face. To manage this condition, it is important to investigate and identify the underlying causes of decompensation. This may involve checking blood tests, reviewing the drug chart, performing a rectal examination for melaena and constipation, and conducting a septic screen.

To enhance nitrate clearance, phosphate enemas can be used to achieve a minimum of three loose stools per day. Lactulose can also be administered to enhance the binding of nitrate in the intestine. Proper management of decompensated liver disease can help prevent further complications and improve the patient’s quality of life.

Differentiating Causes of Bleeding: Acquired Haemophilia, Dysfibrinogenaemia, Chemotherapy-related Platelet Dysfunction, Vitamin K Deficiency, and Von Willebrand’s Disease

Bleeding can be caused by various factors, and it is important to differentiate the underlying cause to provide appropriate treatment. Acquired haemophilia is a condition where autoantibody inhibitors attack factor VIII, resulting in severe soft tissue haemorrhage even with minor injuries. This condition can be associated with autoimmune diseases and malignancies such as pancreatic, colon, breast cancers, and malignant melanoma. Dysfibrinogenaemia, on the other hand, can cause both bleeding and an increased risk for thrombosis. Congenital dysfibrinogenaemia can lead to major bleeding, chronic thromboembolic pulmonary hypertension, and renal amyloidosis.

Chemotherapy-related platelet dysfunction is another possible cause of bleeding, but a normal platelet count makes it less likely. Vitamin K deficiency, which leads to a lack of clotting factors II, VII, IX, and X, can increase the risk of bleeding and prolong the PT, but it does not present the same picture as acquired haemophilia. Lastly, acquired von Willebrand’s disease is more commonly seen in patients with hypothyroidism, and APTT may be in the normal range.

In summary, acquired haemophilia, dysfibrinogenaemia, chemotherapy-related platelet dysfunction, vitamin K deficiency, and acquired von Willebrand’s disease are some of the possible causes of bleeding. Proper evaluation and diagnosis are crucial in determining the appropriate treatment for each condition.

Differential Diagnosis for Progressive CNS Dysfunction in Late Childhood

subacute sclerosing panencephalitis (SSPE) is a rare condition that could explain the progressive CNS dysfunction in a patient with a history of measles in early life. SSPE typically presents with a decline in school proficiency, followed by myoclonic jerks, seizures, visual deterioration, pyramidal signs, rigidity, and unresponsiveness, ultimately leading to death within 1-3 years. Neurosarcoidosis, lipid storage disease, Schilder’s demyelinative disease, and ceroid lipofuscinosis are other potential differential diagnoses, but their clinical features do not match the patient’s presentation. It is important to consider SSPE in cases of progressive CNS dysfunction in late childhood, especially in patients with a history of measles.

Based on the symptoms presented, mixed acidosis observed on ABG, and ECG changes, it is likely that the patient has overdosed on Tricyclic Antidepressants (TCAs). TCA overdose can manifest in various ways, including cardiovascular effects such as tachycardia, prolonged QRS complexes, and cardiac arrhythmias, as well as central nervous system effects like altered mental status, seizures, and coma.

Intravenous magnesium is not recommended for this case of TCA overdose. Activated charcoal may only be appropriate if the patient’s Glasgow Coma Scale (GCS) is not reduced and they present within two hours of ingestion. Gastric lavage may be considered for potentially life-threatening TCA overdoses only if it can be administered within one hour of ingestion and the airway is protected. The main treatment for dysrhythmias or hypotension associated with TCA overdoses is sodium bicarbonate.

Tricyclic Overdose: Symptoms and Management

Tricyclic overdose is a common occurrence in emergency departments, with drugs like amitriptyline and dosulepin being particularly dangerous. Early symptoms include dry mouth, dilated pupils, agitation, sinus tachycardia, and blurred vision due to their anticholinergic properties. Severe poisoning can lead to arrhythmias, seizures, metabolic acidosis, and coma. ECG changes may include sinus tachycardia, widening of QRS, and prolongation of QT interval.

Management of tricyclic overdose involves IV bicarbonate as first-line therapy for hypotension or arrhythmias, especially if the QRS interval is wider than 100 msec or a ventricular arrhythmia is present. Other drugs for arrhythmias, such as class 1a and class Ic antiarrhythmics, should be avoided as they prolong depolarisation. Class III drugs like amiodarone should also be avoided as they prolong the QT interval. Intravenous lipid emulsion is increasingly used to bind free drug and reduce toxicity, while dialysis is ineffective in removing tricyclics. It is important to note that correction of acidosis is the first line in management of tricyclic-induced arrhythmias, and response to lignocaine may vary. Overall, prompt and appropriate management is crucial in treating tricyclic overdose.

Bilateral Optic Disc Drusens Diagnosis and Investigation

Bilateral optic disc drusens is the diagnosis for the condition being observed. The recommended investigation for this condition is an ultrasound of the orbits. This test will reveal the calcification of the drusens within the optic discs. Optic disc drusens are small, yellowish-white deposits that form within the optic nerve head. They are usually benign and do not cause any significant visual impairment. However, in some cases, they can lead to visual field defects or even optic nerve compression. Therefore, it is important to diagnose and monitor this condition to prevent any potential complications. An ultrasound of the orbits is the investigation of choice for this condition as it provides a non-invasive and accurate way to visualize the calcified drusens within the optic discs.

Cholestyramine: A Medication for Managing High Cholesterol

Cholestyramine is a medication used to manage high levels of cholesterol in the body. It works by reducing the reabsorption of bile acid in the small intestine, which leads to an increase in the conversion of cholesterol to bile acid. This medication is particularly effective in reducing LDL cholesterol levels. In addition to its use in managing hyperlipidaemia, cholestyramine is also sometimes used to treat diarrhoea following bowel resection in patients with Crohn’s disease.

However, cholestyramine is not without its adverse effects. Some patients may experience abdominal cramps and constipation while taking this medication. It can also decrease the absorption of fat-soluble vitamins, which can lead to deficiencies if not properly managed. Additionally, cholestyramine may increase the risk of developing cholesterol gallstones and raise the level of triglycerides in the blood. Therefore, it is important for patients to discuss the potential benefits and risks of cholestyramine with their healthcare provider before starting this medication.

HIVAN is characterized by collapsing FSGS and often presents as nephrotic syndrome. It is more likely to occur when the CD4 count is below 200. On the other hand, HIVICK is associated with immune complex deposition in the kidney, leading to membranoproliferative glomerulonephritis and typically presents with nephritic syndrome and low serum complement. Tenofovir toxicity can cause Fanconi syndrome or acute tubular necrosis (ATN). While lupus nephritis and hepatitis C can both present with nephrotic syndrome, a renal biopsy would reveal membranous or membranoproliferative patterns instead of FSGS.

HIV and Renal Involvement

Renal involvement is a common occurrence in HIV patients, which can be caused by the virus itself or as a result of treatment. The use of protease inhibitors like indinavir can lead to intratubular crystal obstruction. HIV-associated nephropathy (HIVAN) is responsible for up to 10% of end-stage renal failure cases in the United States. However, antiretroviral therapy has been found to alter the course of the disease. HIVAN is characterized by five key features, including massive proteinuria leading to nephrotic syndrome, normal or large kidneys, focal segmental glomerulosclerosis with focal or global capillary collapse on renal biopsy, elevated urea and creatinine, and normotension.

Overall, HIV patients should be monitored for renal involvement, and appropriate treatment should be administered to prevent further complications.

Importance of Continuous Chest Compressions in Cardiac Arrest

Current UK resuscitation guidelines highlight the significance of minimizing interruptions in chest compressions during a cardiac arrest. It is recommended to restart chest compressions immediately after each shock, before any other action is taken. The rhythm assessment and pulse check should be conducted after two minutes of continuous chest compressions. The guidelines also suggest a single shock strategy.

In advanced life support, adrenaline should be administered every 3-5 minutes, and amiodarone should be given after three shocks. Additionally, brief periods of echo (10 seconds) are now supported during an arrest situation, but it should be performed at the end of two minutes of compressions.

Therefore, the most appropriate immediate step in a cardiac arrest situation is to administer one shock and immediately restart chest compressions. This approach ensures that the patient receives continuous chest compressions, which is crucial for their survival.

Subacute thyroiditis is a condition characterized by malaise and neck pain, which can radiate to the ear or occiput. The thyroid gland may be tender and nodular, and ESR levels are often elevated. A Technetium-99m scan will show no uptake by the thyroid. Mild cases can be treated with NSAIDs, while more severe cases associated with hyperthyroidism require prednisolone at a dose of 30 mg/day. Carbimazole is not recommended. Toxic multinodular goitre presents with a nodular enlarged thyroid gland and a longer period of hyperthyroidism symptoms. Graves’ disease is associated with smooth thyroid enlargement and mild tenderness, with symptoms of thyrotoxicosis occurring over a longer period. Toxic solitary nodule is not associated with general thyroid tenderness, and symptoms of thyrotoxicosis develop gradually over weeks and months. Medullary carcinoma of the thyroid is a C-cell tumor that does not cause symptoms of thyrotoxicosis.

If a patient experiences optic neuritis and myelitis simultaneously, it may indicate a central neuroinflammatory condition. Miller-Fisher syndrome is unlikely if the patient has a full range of eye movements, and any ataxia observed is probably due to limb weakness. While multiple sclerosis may seem like a possible diagnosis for a patient with disseminated features, the location of the lesions (optic nerve and cervical cord) and the extensive involvement of the cord (beyond 3 vertebral levels) suggest neuromyelitis optic as a more likely cause.

Neuromyelitis optica (NMO) is a disorder of the central nervous system that can occur once or repeatedly. It was previously thought to be a variant of multiple sclerosis, but it is now recognized as a distinct disease, particularly common in Asian populations. The condition typically affects the optic nerves and cervical spine, and brain imaging is often normal. Vomiting is also a common symptom.

To diagnose NMO, a patient must have bilateral optic neuritis, myelitis, and two of the following three criteria: a spinal cord lesion involving three or more spinal levels, an initially normal MRI brain, or a positive serum antibody for aquaporin 4.

The management of NMO involves the use of immunosuppressants, such as the anti-CD20 agent rituximab.

If the patient has a blood pressure reading of 40/90 mmHg, their target blood pressure would be 130/80 mmHg if they have diabetes or a urinary ACR >70 mg/mmol. If they are monitoring their blood pressure at home, their target would be 135/85 mmHg.

Chronic kidney disease (CKD) patients often require more than two drugs to manage hypertension. The first-line treatment is ACE inhibitors, which are especially effective in proteinuric renal disease like diabetic nephropathy. However, these drugs can reduce filtration pressure, leading to a slight decrease in glomerular filtration pressure (GFR) and an increase in creatinine. NICE guidelines state that a decrease in eGFR of up to 25% or a rise in creatinine of up to 30% is acceptable, but any increase should prompt careful monitoring and exclusion of other causes. If the rise is greater than this, it may indicate underlying renovascular disease.

Furosemide is a useful anti-hypertensive drug for CKD patients, particularly when the GFR falls below 45 ml/min*. It also helps to lower serum potassium levels. However, high doses are usually required, and if the patient is at risk of dehydration (e.g. due to gastroenteritis), the drug should be temporarily stopped. The NKF K/DOQI guidelines suggest a lower cut-off of less than 30 ml/min.