Chemotherapeutic Agents for Acute Myeloid Leukemia (AML)

Remission induction therapy for AML patients with a favourable cytogenetic profile typically involves a combination of cytarabine and daunorubicin or idarubicin, known as the 7 plus 3 treatment. This involves a continuous infusion of cytarabine for seven days and daunorubicin or idarubicin on days 1-3. Infusion reactions such as nausea, vomiting, diarrhoea, alopecia, and stomatitis are monitored, and a bone marrow examination is performed after two weeks to determine the need for a second course of therapy. Complete clinical investigation profiling is performed after 4-5 weeks to assess remission.

Asparaginase, dexamethasone, and vincristine are not used for remission induction in AML but are used for the treatment of acute lymphocytic leukemia/lymphoblastic leukemia (ALL/LBL). Cyclophosphamide, doxorubicin, and vincristine are mainly used for small cell carcinoma of the lung.

Daunorubicin and idarubicin are not standalone drugs but are used in combination with cytarabine as part of the 7 plus 3 remission induction therapy for medically fit AML patients with favourable cytogenetics. Midostaurin, an FLT3 inhibitor, is only added as one of three agents for AML patients with FLT3 mutations and is not used as a standalone remission induction drug.

A blown right pupil is indicative of compression of the third cranial nerve, which is most commonly caused by an extradural bleed. However, as this option is not available, the process of transtentorial herniation would be the most appropriate answer. While intraventricular bleeds are more prevalent in premature neonates, deterioration due to hydrocephalus is a more gradual process.

Types of Traumatic Brain Injury

Traumatic brain injury can result in primary and secondary brain injury. Primary brain injury can be focal or diffuse. Diffuse axonal injury occurs due to mechanical shearing, which causes disruption and tearing of axons. intracranial haematomas can be extradural, subdural, or intracerebral, while contusions may occur adjacent to or contralateral to the side of impact. Secondary brain injury occurs when cerebral oedema, ischaemia, infection, tonsillar or tentorial herniation exacerbates the original injury. The normal cerebral auto regulatory processes are disrupted following trauma rendering the brain more susceptible to blood flow changes and hypoxia. The Cushings reflex often occurs late and is usually a pre-terminal event.

Extradural haematoma is bleeding into the space between the dura mater and the skull. It often results from acceleration-deceleration trauma or a blow to the side of the head. The majority of epidural haematomas occur in the temporal region where skull fractures cause a rupture of the middle meningeal artery. Subdural haematoma is bleeding into the outermost meningeal layer. It most commonly occurs around the frontal and parietal lobes. Risk factors include old age, alcoholism, and anticoagulation. Subarachnoid haemorrhage classically causes a sudden occipital headache. It usually occurs spontaneously in the context of a ruptured cerebral aneurysm but may be seen in association with other injuries when a patient has sustained a traumatic brain injury. Intracerebral haematoma is a collection of blood within the substance of the brain. Causes/risk factors include hypertension, vascular lesion, cerebral amyloid angiopathy, trauma, brain tumour, or infarct. Patients will present similarly to an ischaemic stroke or with a decrease in consciousness. CT imaging will show a hyperdensity within the substance of the brain. Treatment is often conservative under the care of stroke physicians, but large clots in patients with impaired consciousness may warrant surgical evacuation.

Anaphylaxis Management: Administering Adrenaline

Anaphylaxis is a severe and life-threatening hypersensitivity reaction that requires immediate management. The Resuscitation Council guidelines outline three essential criteria for recognizing anaphylaxis: sudden-onset, rapidly progressive symptoms, life-threatening Airway/Breathing/Circulation problems, and skin and mucosal changes.

The first step in anaphylaxis management is to administer adrenaline intramuscularly (im) at a dilution of 1:1000. The appropriate dosage for adrenaline administration varies based on the patient’s age. For a 4-year-old patient, the recommended dose is 150 micrograms im. However, adrenaline iv should only be administered by experienced specialists and is given at a dose of 50 micrograms in adults and 1 microgram/kg in children and titrated accordingly.

Adrenaline administration is only the first step in the treatment of anaphylaxis. It is crucial to follow the anaphylaxis algorithm, which includes establishing the airway and giving high-flow oxygen, iv fluid challenge, and chlorphenamine.

It is essential to note that administering an incorrect dose of adrenaline can be dangerous. For instance, administering 1 mg of adrenaline im is inappropriate for the management of anaphylaxis. Therefore, it is crucial to follow the Resuscitation Council guidelines and administer the appropriate dose of adrenaline based on the patient’s age.

The Fracture Risk Assessment tool (FRAX) was created by the World Health Organisation (WHO) to evaluate the risk of fractures in patients aged 40 to 90 years old, regardless of whether they have a bone mineral density (BMD) value. NICE recommends using FRAX or QFRACTURE to assess the risk of fragility fractures, with FRAX being the only option available in this case. While DEXA is used to measure BMD, FRAX should be used initially to determine the patient’s risk, and further investigation with a DEXA scan may be necessary based on the results. X-rays of the carpal bones or head of the humerus would not be appropriate, and a bone scan (bone scintigraphy) would not provide information on the patient’s risk of fracture. The source for this information is NICE 2012 guidelines on assessing the risk of fragility fracture in patients with osteoporosis.

Assessing the Risk of Osteoporosis

Osteoporosis is a concern due to the increased risk of fragility fractures. To determine which patients require further investigation, NICE produced guidelines in 2012 for assessing the risk of fragility fracture. Women aged 65 years and older and men aged 75 years and older should be assessed, while younger patients should be assessed in the presence of risk factors such as previous fragility fracture, history of falls, and low body mass index.

NICE recommends using a clinical prediction tool such as FRAX or QFracture to assess a patient’s 10-year risk of developing a fracture. FRAX estimates the 10-year risk of fragility fracture and is valid for patients aged 40-90 years. QFracture estimates the 10-year risk of fragility fracture and includes a larger group of risk factors.

If the FRAX assessment was done without a bone mineral density (BMD) measurement, the results will be categorised into low, intermediate, or high risk. If the FRAX assessment was done with a BMD measurement, the results will be categorised into reassurance, consider treatment, or strongly recommend treatment. Patients assessed using QFracture are not automatically categorised into low, intermediate, or high risk.

NICE recommends reassessing a patient’s risk if the original calculated risk was in the region of the intervention threshold for a proposed treatment and only after a minimum of 2 years or when there has been a change in the person’s risk factors.

Number Needed to Treat

Number needed to treat (NNT) is a statistical measure used in clinical trials to determine the average number of patients who need to be treated to prevent one additional bad outcome. It is the inverse of the absolute risk reduction (ARR), which is the difference between the event rate of the treatment group and the control group. In simpler terms, NNT is the number of patients that need to be treated with a new medication or intervention to prevent one additional negative outcome compared to a control group.

For example, if the NNT is 100, the ARR is 1%, meaning that one additional negative outcome can be prevented for every 100 patients treated. If the control group has an event rate of 3%, the treatment group’s event rate would be 2% (3% – 1%).

NNT is important for healthcare professionals and patients alike as it helps to determine the effectiveness of a treatment and the potential benefits and risks associated with it. By knowing the NNT, healthcare providers can make informed decisions about which treatments to recommend to their patients.

Total parenteral nutrition is the appropriate treatment for this patient with intractable vomiting and severe malnutrition. However, it should be administered via a central vein to avoid phlebitis. A peripherally inserted central catheter is the recommended method for delivering parenteral nutrition. Increasing oral intake and oral nutritional supplements are not suitable options for this patient due to their persistent vomiting. While a percutaneous endoscopic tube may be necessary for long-term feeding, it is not the best option at this stage as it is invasive and the patient’s condition may be reversible.

Nutrition Options for Surgical Patients

When it comes to providing nutrition for surgical patients, there are several options available. The easiest and most common option is oral intake, which can be supplemented with calorie-rich dietary supplements. However, this may not be suitable for all patients, especially those who have undergone certain procedures.

nasogastric feeding is another option, which involves administering feed through a fine bore nasogastric feeding tube. While this method may be safe for patients with impaired swallow, there is a risk of aspiration or misplaced tube. It is also usually contra-indicated following head injury due to the risks associated with tube insertion.

Naso jejunal feeding is a safer alternative as it avoids the risk of feed pooling in the stomach and aspiration. However, the insertion of the feeding tube is more technically complicated and is easiest if done intra-operatively. This method is safe to use following oesophagogastric surgery.

Feeding jejunostomy is a surgically sited feeding tube that may be used for long-term feeding. It has a low risk of aspiration and is thus safe for long-term feeding following upper GI surgery. However, there is a risk of tube displacement and peritubal leakage immediately following insertion, which carries a risk of peritonitis.

Percutaneous endoscopic gastrostomy is a combined endoscopic and percutaneous tube insertion method. However, it may not be technically possible in patients who cannot undergo successful endoscopy. Risks associated with this method include aspiration and leakage at the insertion site.

Finally, total parenteral nutrition is the definitive option for patients in whom enteral feeding is contra-indicated. However, individualised prescribing and monitoring are needed, and it should be administered via a central vein as it is strongly phlebitic. Long-term use is associated with fatty liver and deranged LFTs.

In summary, there are several nutrition options available for surgical patients, each with its own benefits and risks. The choice of method will depend on the patient’s individual needs and circumstances.

Common Antiemetic Receptors and their Corresponding Medications

Anti-nausea medications work by targeting specific receptors in the body. Here are some common antiemetic receptors and the medications that act on them:

Serotonin: Ondansetron is a medication that binds strongly to the serotonin HT3 receptor. This receptor is present both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone. Ondansetron is useful for treating nausea caused by gastrointestinal irritation, GI tumors, intestinal obstruction, and genitourinary or biliary stasis.

Acetylcholine: Acetylcholine is a neurotransmitter and not a receptor. It acts on muscarinic receptors.

Muscarinic: Hyoscine is an antimuscarinic medication used to treat nausea. Cyclizine and metoclopramide also have antimuscarinic activity.

Dopamine: Metoclopramide, domperidone, and prochlorperazine are dopamine receptor antagonists. Metoclopramide also acts on serotonin antagonists at high doses.

Nicotinic: Ondansetron does not act on nicotinic receptors.

Understanding Antiemetic Receptors and Medications

Mania is a state of elevated mood that persists and is accompanied by psychotic symptoms.

Bipolar disorder is characterized by highs that can be classified into two categories: mania and hypomania. Mania is the more severe form, and it is diagnosed based on two criteria: a prolonged time course (hypomania lasts less than 7-10 days) and the presence of psychotic symptoms. These symptoms can include mood congruent hallucinations or delusional beliefs related to the patient’s elevated mood and feelings of superiority. Delusions of grandeur, such as the belief of owning a kingdom, are common.

Symptoms of elevated mood include increased energy, reduced sleep, rapid or pressured speech, pressured thought, and a non-reactive affect or mood. These symptoms are seen in both hypomania and mania.

Understanding Bipolar Disorder

Bipolar disorder is a mental health condition that is characterized by alternating periods of mania/hypomania and depression. It typically develops in the late teen years and has a lifetime prevalence of 2%. There are two recognized types of bipolar disorder: type I, which involves mania and depression, and type II, which involves hypomania and depression.

Mania and hypomania both refer to abnormally elevated mood or irritability, but mania is more severe and can include psychotic symptoms for 7 days or more. Hypomania, on the other hand, involves decreased or increased function for 4 days or more. The presence of psychotic symptoms suggests mania.

Management of bipolar disorder may involve psychological interventions specifically designed for the condition, as well as medication. Lithium is the mood stabilizer of choice, but valproate can also be used. Antipsychotic therapy, such as olanzapine or haloperidol, may be used to manage mania/hypomania, while fluoxetine is the antidepressant of choice for depression. It is important to address any co-morbidities, as there is an increased risk of diabetes, cardiovascular disease, and COPD in individuals with bipolar disorder.

If symptoms suggest hypomania, routine referral to the community mental health team (CMHT) is recommended. However, if there are features of mania or severe depression, an urgent referral to the CMHT should be made. Understanding bipolar disorder and its management is crucial for healthcare professionals to provide appropriate care and support for individuals with this condition.

Developmental dysplasia of the hip is more likely to occur in females. Positive Barlow and Ortolani tests are indicative of DDH. High birth weight, breech presentation, and oligohydramnios are risk factors for DDH, while C-section birth is not a relevant factor.

Developmental dysplasia of the hip (DDH) is a condition that affects 1-3% of newborns and is more common in females, firstborn children, and those with a positive family history or breech presentation. It used to be called congenital dislocation of the hip (CDH). DDH is more often found in the left hip and can be bilateral in 20% of cases. Screening for DDH is recommended for infants with certain risk factors, and all infants are screened using the Barlow and Ortolani tests at the newborn and six-week baby check. Clinical examination includes testing for leg length symmetry, restricted hip abduction, and knee level when hips and knees are flexed. Ultrasound is used to confirm the diagnosis if clinically suspected, but x-ray is the first line investigation for infants over 4.5 months. Management includes the use of a Pavlik harness for children under 4-5 months and surgery for older children with unstable hips.

The quadruple test result shows a decrease in AFP, oestriol, and hCG, without change in inhibin A, indicating Edward’s syndrome. This condition is caused by trisomy 18 and can present with physical features such as micrognathia, low-set ears, rocker bottom feet, and overlapping fingers. The quadruple test is a screening test used to identify pregnancies with a higher risk of Down’s syndrome, Edwards’ syndrome, Patau’s syndrome, or neural tube defects. It is typically offered to patients who discover their pregnancy late and are no longer eligible for the combined test. ARPKD cannot be diagnosed with a quadruple test, but it can be detected prenatally with an ultrasound. Down’s syndrome would present with low AFP, low unconjugated oestriol, high hCG, and inhibin A, while neural tube defects would present with high AFP and normal oestriol, hCG, and inhibin A.

NICE updated guidelines on antenatal care in 2021, recommending the combined test for screening for Down’s syndrome between 11-13+6 weeks. The test includes nuchal translucency measurement, serum B-HCG, and pregnancy-associated plasma protein A (PAPP-A). The quadruple test is offered between 15-20 weeks for women who book later in pregnancy. Results are interpreted as either a ‘lower chance’ or ‘higher chance’ of chromosomal abnormalities. If a woman receives a ‘higher chance’ result, she may be offered a non-invasive prenatal screening test (NIPT) or a diagnostic test. NIPT analyzes cell-free fetal DNA in the mother’s blood and has high sensitivity and specificity for detecting chromosomal abnormalities. Private companies offer NIPT screening from 10 weeks gestation.