CDM revision Sem 2 Flashcards

Question

What are the risk factors for development of basal cell carcinoma?

Answer 1

Immunosuppression UV exposure Family history of skin ca

Answer 2

A diagnosis of pseudogout can be tricky to make. Pseudogout typically affects elderly women, and the joints that are normally affected are the wrists and knees. The associations are hyperparathyroidism, hypothyroidism, hypophosphataemia, haemochromatosis and Wilson's disease. On polarised light microscopy, psedogout presents with positively birefringent rhomboid crystals.

Answer 3

COX-2 inhibitors, also known as coxibs, such as celocoxib are a newer alternative to traditional NSAIDs like ibuprofen or naproxen. Coxibs selectively inhibit COX-2 which confers a lower risk of GI ulceration and so may be preferred in patients at high risk of GI ulceration. However, shortly after they were first released, the coxib rofecoxib was discontinued because it was found to increased the risk of cardiovascular events to a significantly higher extent than regular NSAIDs. This lead to a lack of uptake in coxib use, but more recent research has found that other coxibs, particularly moderate dose celocoxib, confers an equivalent cardiovascular risk to normal NSAIDs and are therefore safe to use in place of regular NSAIDs where necessary.

Answer 4

bullseye maculopathy-reduced visual acuity and colour vision annular lesions bilaterally around macular on fundoscope if suspected stop drug

Answer 5

This is a typical presentation of Turner's syndrome. She has a webbed neck and short stature which represent characteristic physical appearance. Infertility is usually how these patients present. Genotype is XO and majority of foetuses with this genetic make-up will spontaneously abort. As such, a live Turner's syndrome lady is most likely to be caused by mosaicism. Some cells are XO, some are normal (XX).

Answer 6

The normal state of genetic material in cells compromises two active sets of autosomes (the non-sex chromosomes) and one active X chromosome in the female, or in males who have multiple X chromosomes (Klinefelter's syndrome). The X chromosome that is “inactivated” becomes condensed, meaning it cannot be replicated (hence inactivated) and this creates the Barr Body - the condensed chromosome pushed against the nuclear membrane. They are rendered inactive in a process called lyonisation.

Answer 7

As she has booked in at 9 weeks, you can carry out chorionic villous sampling, which is undertaken at 10-14 weeks. It involves taking a small sample of cells called chorionic villi from theplacenta where it attaches to the wall of the uterus. Genetic analysis can then be carried out on these cells to determine the karyotype. If she had presented later, amniocentesis can be undertaken at 13-15 weeks; here, a sample of amniotic fluid, not placenta, is taken and tested. Ultrasound to determine the 'nuchal thickness' and blood tests such as beta hCG and PAPP-A are routinely used to screen for Down's syndrome, but do not involve obtaining a placental sample and are also screening tests, rather than being diagnostic.

Answer 8

Osteogenesis imperfecta is an autosomal dominant condition of collagen, resulting in bone material being more supple and so fractures occur more commonly. The type 1 procollagen compromises two chains encoded by COL1A1 gene and one chain encoded for by COL1A2. A mutation in either of these genes results in disruption of the whole fibril. It's mechanism of dominant inheritance is said to be the dominant negativeeffect. This is where the product of a defective gene (e.g. in this case, either COL1A1 or COL1A2) interferes with the action of the normal allele (e.g. here, whichever of COL1A1 or COL1A2 is not mutated). These usually need to form units called “multimers” - proteins that work together to form a complex structure.

Answer 9

Isoniazid more likely to cause hepatotoxicity than rifampicin

Answer 10

Give BCG vaccination According to NICE guidelines, BCG vaccination should be given to tuberculin skin test negative (mantoux negative) contacts of patients with confirmed pulmonary and laryngeal TB, who have not been previously vaccinated and are under the age of 35 or are over the age of 35 and work in healthcare. This patient had a negative test with only 1mm induration, a positive result would have been 5mm or more.

Answer 11

Ciprofloxacin This is associated with increased risk of Achilles tendinopathy and tendon rupture, although this is rare. It may also cause lowering of seizure threshold, prolongation of QT interval and Clostridium difficile colitis.

Answer 12

Campylobacter jejuni This is the most common cause of food poisoning in the UK, and is usually associated with eating contaminated or undercooked chicken. Summer BBQs are classically associated small outbreaks or groups of cases. Diarrhoea is often dysenteric (containing blood and mucus) due to bacterial invasion of the intestinal mucosa

Answer 13

DRABCDE approach If low risk can give oral antibiotics (quinolone + co-amoxiclav) ``` Features suggesting low risk: Hemodynamically stable Doesn't have acute leukemia No organ failure No soft tissue infection No indwelling lines ``` For most patients, they need empirical IV treatment with piperacillin and tazobactam (tazocin), with added coverage for MRSA or gram-negatives if thought at risk. A macrolide should also be added if diagnosed with pneumonia (to cover atypical organisms) May need 2-hourly assessments Daily measures of fever and baseline bloods until the patient is apyrexial and neutrophil count above 0.5x10^9 When the neutrophil count is normal, has been afebrile for 48 hours and blood tests have normalized, antibiotics can be stopped. Prophylaxis with a fluoroquinolone can be offered

Answer 14

Investigations Chest X-ray Sputum samples for culture and sensitivity testing (at least three needed - may need to consider lavage or sputum induction if cannot produce) Samples from non-pulmonary sites: may need biopsy and needle aspiration Samples are stained with Ziehl-Neelsen or Auramine staining for direct microscopy For culture, Lowenstein-Jensen (LJ) media is needed. PCR - GeneXpert, rapid results with additional drug sensitivity tested as well. Interferon-Gamma Release Assays (IGRAs) - cannot tell difference between latent or active TB, and not useful in very young or immunosuppressed patients. Results are obtained rapidly, however, and are not affected by prior BCG. Mantoux test - usually offered to contacts of infected patients. Positive in those who have had the BCG vaccine. Management

Answer 15

Severe pain whenever the left hip is hyperextended.

Answer 16

Vancomycin 32% Coagulase-negative staphylococci are the most common cause of endocarditis associated with hospital in-dwelling lines. Glycopeptides are first-line treatment

Answer 17

``` Live attenuated vaccines BCG MMR oral polio yellow fever oral typhoid ```

Answer 18

Within 5 days of admission: co-amoxiclav or cefuroxime More than 5 days after admission: piperacillin with tazobactam OR a broad-spectrum cephalosporin (e.g. ceftazidime) OR a quinolone (e.g. ciprofloxacin)

Answer 19

Organisms causing post splenectomy sepsis: Streptococcus pneumoniae Haemophilus influenzae Meningococci Important for meLess important Encapsulated organisms carry the greatest pathogenic risk following splenectomy. The effects of sepsis following splenectomy are variable. This may be the result of small isolated fragments of splenic tissue that retain some function following splenectomy. These may implant spontaneously following splenic rupture (in trauma) or be surgically implanted at the time of splenectomy. Management Key recommendations All those with hyposplenism or may become so (such as prior to an elective splenectomy) should receive pneumococcal, Haemophilus type b and meningococcal type C vaccines. These should be administered 2 weeks prior to splenectomy or two weeks following splenectomy. The vaccine schedule for meningococcal disease essentially consists of a dose of Men C and Hib at 2 weeks and then a dose of the MenACWY vaccine one month later. Those aged under 2 may require a booster at 2 years. A dose of pneumococcal polyvalent polysaccharide vaccine (PPV) is given at two weeks. A conjugated vaccine (PCV) is offered to young children. The PCV is more immunogenic but covers fewer serotypes. Boosting PPV is either guided by serological measurements (where available) or by routine boosting doses at 5 yearly intervals. Annual influenza vaccination is recommended in all cases Antibiotic prophylaxis is offered to all. The risk of post-splenectomy sepsis is greatest immediately following splenectomy and in those aged less than 16 years or greater than 50 years. Individuals with a poor response to pneumococcal vaccination are another high-risk group. High-risk individuals should be counselled to take penicillin or macrolide prophylaxis. Those at low risk may choose to discontinue therapy. All patients should be advised about taking antibiotics early in the case of intercurrent infections. Asplenic individuals travelling to malaria endemic areas are at high risk and should have both pharmacological and mechanical protection. Dosing Penicillin V 500mg BD or amoxicillin 250mg BD

Answer 20

Patients with an uncertain tetanus vaccination history should be given a booster vaccine + immunoglobulin, unless the wound is very minor and < 6 hours old Important for meLess important In this case, the most appropriate course of action is to give a tetanus booster and tetanus immunoglobulin. This man has an unknown vaccination, a tetanus prone wound (occurred whilst gardening) and it is more than 6 hours old. Metronidazole antibiotic is the treatment for tetanus rather than being used as a prophylactic agent. A tetanus booster alone is sufficient if a patient has a tetanus prone wound with a full vaccination history but the last dose being more than 10 years ago. Tetanus immunoglobulin can be used to treat proven cases of tetanus. In this case, as the vaccination history is not known a tetanus booster and immunoglobulin should be given. Simple wound cleaning can be used if a patient has had a full course of tetanus vaccines, with the last dose less than 10 years ago, irrespective of the severity of the wound. The vaccination history is not known in this case so wound cleaning only would not be appropriate

Answer 21

The BNF recommends flucloxacillin as first-line treatment for mild/moderate cellulitis. Clarithromycin, erythromycin (in pregnancy) or doxycyline is recommended in patients allergic to penicillin. NICE recommend that patients severe cellulitis should be offered co-amoxiclav, cefuroxime, clindamycin or ceftriaxone.

Answer 22

The combination of metronidazole and ethanol can cause a disulfiram-like reaction. Clinical features of this include head and neck flushing, nausea and vomiting, sweatiness, headache and palpitations. Cefoperazone, a cephalosporin, is also associated with a disulfiram-like reaction to alcohol.

Answer 23

Parvovirus B19 is the most likely infective cause of an aplastic anaemia crisis in patients with sickle cell disease Important for meLess important Erythema infectiosum is caused by parvovirus B19, a virus that reduces erythropoiesis for about a week. Those who already have a chronic haemolytic anaemia (e.g. sickle cell disease) are at high risk of aplastic anaemia.

Answer 24

Management intramuscular benzathine penicillin is the first-line management alternatives: doxycycline the Jarisch-Herxheimer reaction is sometimes seen following treatment fever, rash, tachycardia after the first dose of antibiotic in contrast to anaphylaxis, there is no wheeze or hypotension it is thought to be due to the release of endotoxins following bacterial death and typically occurs within a few hours of treatment No treatment is needed other than antipyretics if required

Answer 25

Necrotising fasciitis is a medical emergency that is difficult to recognise in the early stages. It can be classified according to the causative organism: type 1 is caused by mixed anaerobes and aerobes (often occurs post-surgery in diabetics). This is the most common type type 2 is caused by Streptococcus pyogenes Risk factors skin factors: recent trauma, burns or soft tissue infections diabetes mellitus the most common preexisting medical condition particularly if the patient is treated with SGLT-2 inhibitors intravenous drug use immunosuppression The most commonly affected site is the perineum (Fournier's gangrene). Features acute onset pain, swelling, erythema at the affected site often presents as rapidly worsening cellulitis with pain out of keeping with physical features extremely tender over infected tissue with hypoaesthesia to light touch skin necrosis and crepitus/gas gangrene are late signs fever and tachycardia may be absent or occur late in the presentation Management urgent surgical referral debridement intravenous antibiotics Prognosis average mortality of 20%

Answer 26

Hepatitis A Human Normal Immunoglobulin (HNIG) or hepatitis A vaccine may be used depending on the clinical situation Hepatitis B HBsAg positive source: if the person exposed is a known responder to HBV vaccine then a booster dose should be given. If they are in the process of being vaccinated or are a non-responder they need to have hepatitis B immune globulin (HBIG) and the vaccine unknown source: for known responders the green book advises considering a booster dose of HBV vaccine. For known non-responders HBIG + vaccine should be given whilst those in the process of being vaccinated should have an accelerated course of HBV vaccine Hepatitis C monthly PCR - if seroconversion then interferon +/- ribavirin HIV the risk of HIV transmission depends heavily on the incident (e.g. needle stick, type of sexual intercourse, human bite etc) and the current viral load of the patient please see the BHIVA link for charts which outline the risk depending on the incident. Generally, low-risk incidents such as human bites don't require post-exposure prophylaxis a combination of oral antiretrovirals (e.g. Tenofovir, emtricitabine, lopinavir and ritonavir) as soon as possible (i.e. Within 1-2 hours, but may be started up to 72 hours following exposure) for 4 weeks serological testing at 12 weeks following completion of post-exposure prophylaxis reduces risk of transmission by 80% Varicella zoster VZIG for IgG negative pregnant women/immunosuppressed

Answer 27

The table below summarises the characteristic cerebrospinal fluid (CSF) findings in meningitis: Bacterial Viral Tuberculous Fungal Appearance Cloudy Clear/cloudy Slight cloudy, fibrin web Cloudy Glucose Low (< 1/2 plasma) 60-80% of plasma glucose* Low (< 1/2 plasma) Low Protein High (> 1 g/l) Normal/raised High (> 1 g/l) High White cells 10 - 5,000 polymorphs/mm³ 15 - 1,000 lymphocytes/mm³ 30 - 300 lymphocytes/mm³ 20 - 200 lymphocytes/mm³ The Ziehl-Neelsen stain is only 20% sensitive in the detection of tuberculous meningitis and therefore PCR is sometimes used (sensitivity = 75%) *mumps is unusual in being associated with a low glucose level in a proportion of cases. A low glucose may also be seen in herpes encephalitis

Answer 28

Features of congenital syphilis blunted upper incisor teeth (Hutchinson's teeth), 'mulberry' molars rhagades (linear scars at the angle of the mouth) keratitis saber shins saddle nose deafness

Answer 29

Chlamydia is the most commonly diagnosed sexually transmitted infection. It can be asymptomatic and if left untreated can cause complications such as pelvic inflammatory disease and infertility. It is diagnosed using nucleic acid amplification tests (NAATs). Women can do a self swab and men can do a first pass urine sample. Gonorrhoea is also diagnosed using NAATs. Treatment of Chlamydia is with azithromycin or doxycycline. Chlamydia is the most prevalent sexually transmitted infection in the UK and is caused by Chlamydia trachomatis, an obligate intracellular pathogen. Approximately 1 in 10 young women in the UK have Chlamydia. The incubation period is around 7-21 days, although it should be remembered a large percentage of cases are asymptomatic Features asymptomatic in around 70% of women and 50% of men women: cervicitis (discharge, bleeding), dysuria men: urethral discharge, dysuria ``` Potential complications epididymitis pelvic inflammatory disease endometritis increased incidence of ectopic pregnancies infertility reactive arthritis perihepatitis (Fitz-Hugh-Curtis syndrome) ``` Investigation traditional cell culture is no longer widely used nuclear acid amplification tests (NAATs) are now the investigation of choice urine (first void urine sample), vulvovaginal swab or cervical swab may be tested using the NAAT technique for women: the vulvovaginal swab is first-line for men: the urine test is first-line Chlamydiatesting should be carried out two weeks after a possible exposure Screening in England the National Chlamydia Screening Programme is open to all men and women aged 15-24 years the 2009 SIGN guidelines support this approach, suggesting screening all sexually active patients aged 15-24 years relies heavily on opportunistic testing Management doxycycline (7 day course) if first-line this is now preferred to azithromycin due to concerns about Mycoplasma genitalium. This infection is often coexistant in patients with Chlamydia and there is evidence of rising levels of macrolide resistance, hence why doxycycline is preferred if doxycycline is contraindicated / not tolerated then either azithromycin (1g od for one day, then 500mg od for two days) should be used if pregnant then azithromycin, erythromycin or amoxicillin may be used. The SIGN guidelines suggest azithromycin 1g stat is the drug of choice 'following discussion of the balance of benefits and risks with the patient' patients diagnosed with Chlamydia should be offered a choice of provider for initial partner notification - either trained practice nurses with support from GUM, or referral to GUM for men with urethral symptoms: all contacts since, and in the four weeks prior to, the onset of symptoms for women and asymptomatic men all partners from the last six months or the most recent sexual partner should be contacted contacts of confirmed Chlamydia cases should be offered treatment prior to the results of their investigations being known (treat then test)

Answer 30

The clinical presentation raises a suspicion of meningitis. Streptococcus pneumoniae, Neisseria meningitidis, Mycobacterium tuberculosis and Cryptococcus neoformans are causative organisms of meningitis. The India ink stain on cerebrospinal fluid (CSF) analysis points towards Cryptococcus neoformans as the causative organism. Streptococcus pneumoniae would have a gram-positive stain while Neisseria meningitidis would have a gram-negative stain. Mycobacterium tuberculosis would have a Ziehl–Neelsen (acid-fast) stain. In toxoplasmosis, the head CT usually shows single or multiple ring enhancing lesions, and mass effect may be seen

Answer 31

Red man syndrome is associated with rapid intravenous infusion vancomycin. It is a common adverse reaction of intravenous vancomycin use and is a distinct entity from anaphylaxis due to vancomycin use. Typical symptoms include redness, pruritus and a burning sensation, predominantly in the upper body (face, neck and upper chest). Severe cases can be associated with hypotension and chest pain. The pathophysiology of red man syndrome is attributed to vancomycin-related activation of mast cells with release of histamine. The management of red man syndrome involves cessation of the infusion, and when symptoms have resolved, recommencement at a slower rate. In patients who are more symptomatic antihistamines can be administered, and may require intravenous fluids if the syndrome is associated with hypotension.

Answer 32

Methicillin-resistant Staphylococcus aureus (MRSA) was one of the first organisms which highlighted the dangers of hospital-acquired infections. Who should be screened for MRSA? all patients awaiting elective admissions (exceptions include day patients having terminations of pregnancy and ophthalmic surgery. Patients admitted to mental health trusts are also excluded) from 2011 all emergency admissions will be screened How should a patient be screened for MRSA? nasal swab and skin lesions or wounds the swab should be wiped around the inside rim of a patient's nose for 5 seconds the microbiology form must be labelled 'MRSA screen' Suppression of MRSA from a carrier once identified nose: mupirocin 2% in white soft paraffin, tds for 5 days skin: chlorhexidine gluconate, od for 5 days. Apply all over but particularly to the axilla, groin and perineum The following antibiotics are commonly used in the treatment of MRSA infections: vancomycin teicoplanin linezolid ``` Some strains may be sensitive to the antibiotics listed below but they should not generally be used alone because resistance may develop: rifampicin macrolides tetracyclines aminoglycosides clindamycin ``` Relatively new antibiotics such as linezolid, quinupristin/dalfopristin combinations and tigecycline have activity against MRSA but should be reserved for resistant cases

Answer 33

Condition Recommended treatment Exacerbations of chronic bronchitis Amoxicillin or tetracycline or clarithromycin Uncomplicated community-acquired pneumonia Amoxicillin (Doxycycline or clarithromycin in penicillin allergic, add flucloxacillin if staphylococci suspected e.g. In influenza) Pneumonia possibly caused by atypical pathogens Clarithromycin Hospital-acquired pneumonia Within 5 days of admission: co-amoxiclav or cefuroxime More than 5 days after admission: piperacillin with tazobactam OR a broad-spectrum cephalosporin (e.g. ceftazidime) OR a quinolone (e.g. ciprofloxacin) Urinary tract Condition Recommended treatment Lower urinary tract infection Trimethoprim or nitrofurantoin. Alternative: amoxicillin or cephalosporin Acute pyelonephritis Broad-spectrum cephalosporin or quinolone Acute prostatitis Quinolone or trimethoprim Skin Condition Recommended treatment Impetigo Topical hydrogen peroxide, oral flucloxacillin or erythromycin if widespread Cellulitis Flucloxacillin (clarithromycin, erythromycin or doxycycline if penicillin-allergic) Cellulitis (near the eyes or nose) Co-amoxiclav (clarithromycin, + metronidazole if penicillin-allergic) Erysipelas Flucloxacillin* (clarithromycin, erythromycin or doxycycline if penicillin-allergic) Animal or human bite Co-amoxiclav (doxycycline + metronidazole if penicillin-allergic) Mastitis during breast-feeding Flucloxacillin Ear, nose & throat Condition Recommended treatment Throat infections Phenoxymethylpenicillin (erythromycin alone if penicillin-allergic) Sinusitis Phenoxymethylpenicillin Otitis media Amoxicillin (erythromycin if penicillin-allergic) Otitis externa** Flucloxacillin (erythromycin if penicillin-allergic) Periapical or periodontal abscess Amoxicillin Gingivitis: acute necrotising ulcerative Metronidazole Genital system Condition Recommended treatment Gonorrhoea Intramuscular ceftriaxone Chlamydia Doxycycline or azithromycin Pelvic inflammatory disease Oral ofloxacin + oral metronidazole or intramuscular ceftriaxone + oral doxycycline + oral metronidazole Syphilis Benzathine benzylpenicillin or doxycycline or erythromycin Bacterial vaginosis Oral or topical metronidazole or topical clindamycin Gastrointestinal Condition Recommended treatment Clostridium difficile First episode: metronidazole Second or subsequent episode of infection: vancomycin Campylobacter enteritis Clarithromycin Salmonella (non-typhoid) Ciprofloxacin Shigellosis Ciprofloxacin

Answer 34

There are two strains of the herpes simplex virus (HSV) in humans: HSV-1 and HSV-2. Whilst it was previously thought HSV-1 accounted for oral lesions (cold sores) and HSV-2 for genital herpes it is now known there is considerable overlap Features painful genital ulceration may be associated with dysuria and pruritus the primary infection is often more severe than recurrent episodes systemic features such as headache, fever and malaise are more common in primary episodes tender inguinal lymphadenopathy urinary retention may occur Investigations nucleic acid amplification tests (NAAT) is the investigation of choice in genital herpes and are now considered superior to viral culture HSV serology may be useful in certain situations such as recurrent genital ulceration of unknown cause Management general measures include: saline bathing analgesia topical anaesthetic agents e.g. lidocaine oral aciclovir some patients with frequent exacerbations may benefit from longer-term aciclovir Pregnancy elective caesarean section at term is advised if a primary attack of herpes occurs during pregnancy at greater than 28 weeks gestation women with recurrent herpes who are pregnant should be treated with suppressive therapy and be advised that the risk of transmission to their baby is low Oral aciclovir 400 mg TDS (three times daily) until delivery is recommended in the RCOG guidelines for women who present with a primary herpes infection in their third trimester of pregnancy, especially if the woman is expected to deliver within 6 weeks.

Answer 35

Non-pregnant women local antibiotic guidelines should be followed if available CKS/2012 SIGN guidelines recommend trimethoprim or nitrofurantoin for 3 days send a urine culture if: aged > 65 years visible or non-visible haematuria Pregnant women if the pregnant woman is symptomatic: a urine culture should be sent in all cases should be treated with an antibiotic for first-line: nitrofurantoin (should be avoided near term) second-line: amoxicillin or cefalexin trimethoprim is teratogenic in the first trimester and should be avoided during pregnancy asymptomatic bacteriuria in pregnant women: a urine culture should be performed routinely at the first antenatal visit Clinical Knowledge Summaries recommend an immediate antibiotic prescription of either nitrofurantoin (should be avoided near term), amoxicillin or cefalexin. This should be a 7-day course the rationale of treating asymptomatic bacteriuria is the significant risk of progression to acute pyelonephritis a further urine culture should be sent following completion of treatment as a test of cure Men an immediate antibiotic prescription should be offered for 7 days as with non-pregnant women, trimethoprim or nitrofurantoin should be offered first-line unless prostatitis is suspected NICE Clinical Knowledge Summaries state: 'Referral to urology is not routinely required for men who have had one uncomplicated lower urinary tract infection (UTI).' Catherised patients do not treat asymptomatic bacteria in catheterised patients if the patient is symptomatic they should be treated with an antibiotic a 7-day, rather than a 3-day course should be given Acute pyelonephritis For patients with sign of acute pyelonephritis hospital admission should be considered local antibiotic guidelines should be followed if available the BNF currently recommends a broad-spectrum cephalosporin or a quinolone (for non-pregnant women) for 10-14 days

Answer 36

Patients with cystic fibrosis develop bronchiectasis early on during their life resulting in repeated hospital admissions with lower respiratory tract infections. The pathological process behind bronchiectasis results in sputum pooling within the larger airways with poor removal. Subsequently colonisation occurs with bacteria and occasionally fungi. The most common bacteria is the gram negative rod Pseudomonas aeruginosa and should always be taken into account if providing empirical treatment. If the patient is systemically well then antibiotic sensitivities should be sought from a culture sample before starting treatment. However, an anti-pseudomonal agent such as piperacillin with tazobactam or ciprofloxacin should be used as part of empirical treatment for sepsis in cystic fibrosis patients.

Answer 37

Fitz-Hugh-Curtis syndrome is a complication of pelvic inflammatory disease in which the liver capsule becomes inflamed causing right upper quadrant pain. This leads to scar tissue formation and peri-hepatic adhesions. It usually occurs in women who have either chlamydia or gonorrhoea. Treatment is through eradication of the responsible organism although laparoscopy is required in some patients to perform lysis of adhesions that have formed.

Answer 38

Leptospirosis is caused by the spirochaete Leptospira interrogans (serogroup L. icterohaemorrhagiae), classically being spread by contact with infected rat urine. Epidemiology leptospirosis is commonly seen in questions referring to sewage workers, farmers, vets or people who work in an abattoir however, on an international level, leptospirosis is far more common in the tropics so should be considered in the returning traveller Weil's disease should always be considered in high-risk patients with hepatorenal failure Features the early phase is due to bacteraemia and lasts around a week may be mild or subclinical fever flu-like symptoms subconjunctival suffusion (redness)/haemorrhage second immune phase may lead to more severe disease (Weil's disease) acute kidney injury (seen in 50% of patients) hepatitis: jaundice, hepatomegaly aseptic meningitis Investigation serology: antibodies to Leptospira develop after about 7 days PCR culture growth may take several weeks so limits usefulness in diagnosis blood and CSF samples are generally positive for the first 10 days urine cultures become positive during the second week of illness Management high-dose benzylpenicillin or doxycycline

Answer 39

Gastroenteritis may either occur whilst at home or whilst travelling abroad (travellers' diarrhoea) Travellers' diarrhoea may be defined as at least 3 loose to watery stools in 24 hours with or without one of more of abdominal cramps, fever, nausea, vomiting or blood in the stool. The most common cause is Escherichia coli. Another pattern of illness is 'acute food poisoning'. This describes the sudden onset of nausea, vomiting and diarrhoea after the ingestion of a toxin. Acute food poisoning is typically caused by Staphylococcus aureus, Bacillus cereus or Clostridium perfringens

Answer 40

Clostridium botulinum gram positive anaerobic bacillus 7 serotypes A-G produces botulinum toxin, a neurotoxin which irreversibly blocks the release of acetylcholine may result from eating contaminated food (e.g. tinned) or intravenous drug use neurotoxin often affects bulbar muscles and autonomic nervous system ``` Features patient usually fully conscious with no sensory disturbance flaccid paralysis diplopia ataxia bulbar palsy ``` Treatment botulism antitoxin and supportive care antitoxin is only effective if given early - once toxin has bound its actions cannot be reversed

Answer 41

Mycoplasma pneumoniae is a cause of atypical pneumonia which often affects younger patients. It is associated with a number of characteristic complications such as erythema multiforme and cold autoimmune haemolytic anaemia. Epidemics of Mycoplasma pneumoniae classically occur every 4 years. It is important to recognise atypical pneumonia as it may not respond to penicillins or cephalosporins due to it lacking a peptidoglycan cell wall. Features the disease typically has a prolonged and gradual onset flu-like symptoms classically precede a dry cough bilateral consolidation on x-ray complications may occur as below Complications cold agglutins (IgM): may cause an haemolytic anaemia, thrombocytopenia erythema multiforme, erythema nodosum meningoencephalitis, Guillain-Barre syndrome and other immune-mediated neurological diseases bullous myringitis: painful vesicles on the tympanic membrane pericarditis/myocarditis gastrointestinal: hepatitis, pancreatitis renal: acute glomerulonephritis Investigations diagnosis is generally by Mycoplasma serology positive cold agglutination test Management doxycycline or a macrolide (e.g. erythromycin/clarithromycin)

Answer 42

Antiretroviral therapy (ART) involves a combination of at least three drugs, typically two nucleoside reverse transcriptase inhibitors (NRTI) and either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). This combination both decreases viral replication but also reduces the risk of viral resistance emerging Following the 2015 BHIVA guidelines it is now recommended that patients start ART as soon as they have been diagnosed with HIV, rather than waiting until a particular CD4 count, as was previously advocated. Entry inhibitors maraviroc (binds to CCR5, preventing an interaction with gp41), enfuvirtide (binds to gp41, also known as a 'fusion inhibitor') prevent HIV-1 from entering and infecting immune cells Nucleoside analogue reverse transcriptase inhibitors (NRTI) examples: zidovudine (AZT), abacavir, emtricitabine, didanosine, lamivudine, stavudine, zalcitabine, tenofovir general NRTI side-effects: peripheral neuropathy tenofovir: used in BHIVAs two recommended regime NRTI. Adverse effects include renal impairment and ostesoporosis zidovudine: anaemia, myopathy, black nails didanosine: pancreatitis Non-nucleoside reverse transcriptase inhibitors (NNRTI) examples: nevirapine, efavirenz side-effects: P450 enzyme interaction (nevirapine induces), rashes Protease inhibitors (PI) examples: indinavir, nelfinavir, ritonavir, saquinavir side-effects: diabetes, hyperlipidaemia, buffalo hump, central obesity, P450 enzyme inhibition indinavir: renal stones, asymptomatic hyperbilirubinaemia ritonavir: a potent inhibitor of the P450 system Integrase inhibitors block the action of integrase, a viral enzyme that inserts the viral genome into the DNA of the host cell examples: raltegravir, elvitegravir, dolutegravir 'Navir tease a pro': HIV drugs that end with -navir are protease inhibitors e.g. ritonavir. Note that due to tolerability issues, ritonavir is now more commonly used to boost the levels of other HIV drugs 'It's grave/great you integrate': HIV drugs that end with -gravir are integrase inhibitors e.g. raltegravir

Answer 43

HIV seroconversion occurs from 3-12 weeks Important for meLess important Seroconversion, the period where an antibody response is created and is detectable, can occur between 3 to 12 weeks. Most people create antibodies between 4 and 6 weeks. However, even if patients take the ELISA test and receive a negative result, they are recommended to redo the test 3 months (after exposure) to confirm they are HIV free.

Answer 44

All patients with a CD4 count lower than 200/mm3 should receive prophylaxis against Pneumocystis jiroveci pneumonia Important for meLess important All patients with a CD4 count lower than 200 cells/mm³ should receive prophylaxis against Pneumocystis jirovecii pneumonia. Aciclovir is sometimes used as longterm herpes suppression treatment in patients with both HIV and HSV.

Answer 45

The BNF recommends flucloxacillin as first-line treatment for mild/moderate cellulitis. Clarithromycin, erythromycin (in pregnancy) or doxycyline is recommended in patients allergic to penicillin. NICE recommend that patients severe cellulitis should be offered co-amoxiclav, cefuroxime, clindamycin or ceftriaxone.

Answer 46

For patients with gonorrhoea, a combination of oral cefixime + oral azithromycin is used if the patient refuses IM ceftriaxone Important for meLess important NICE guidelines advise that patients with a positive gonorrhoea test should be referred to a sexual health clinic for management and follow up. The first-line treatment is a single dose of IM ceftriaxone.

Answer 47

Disseminated gonococcal infection (DGI) and gonococcal arthritis may also occur, with gonococcal infection being the most common cause of septic arthritis in young adults. The pathophysiology of DGI is not fully understood but is thought to be due to haematogenous spread from mucosal infection (e.g. Asymptomatic genital infection). Initially there may be a classic triad of symptoms: tenosynovitis, migratory polyarthritis and dermatitis. Later complications include septic arthritis, endocarditis and perihepatitis (Fitz-Hugh-Curtis syndrome) Key features of disseminated gonococcal infection tenosynovitis migratory polyarthritis dermatitis (lesions can be maculopapular or vesicular)

Answer 48

Influenza and pertussis

Answer 49

Type of viral haemorrhagic fever (also dengue fever, Lassa fever, Ebola). Basics zoonotic infection: spread by Aedes mosquitos incubation period = 2 - 14 days Features may cause mild flu-like illness lasting less than one week classic description involves sudden onset of high fever, rigors, nausea & vomiting. Bradycardia may develop. A brief remission is followed by jaundice, haematemesis, oliguria if severe jaundice, haematemesis may occur Councilman bodies (inclusion bodies) may be seen in the hepatocytes The pattern of disease is most consistent with yellow fever. Classically it will present in two phases where the patient experiences a brief remission in between. Yellow fever is mostly concentrated in Africa but it still persists in some rural areas of South America. It can present very quickly with non-specific symptoms and it has an incubation period of 2-14 days which is fitting with this patients history.

Answer 50

Screening for latent tuberculosis The Mantoux test is the main technique used to screen for latent tuberculosis. In recent years the interferon-gamma blood test has also been introduced. It is used in a number of specific situations such as: the Mantoux test is positive or equivocal people where a tuberculin test may be falsely negative (see below) Mantoux test 0.1 ml of 1:1,000 purified protein derivative (PPD) injected intradermally result read 2-3 days later Diameter of induration Positivity Interpretation < 6mm Negative - no significant hypersensitivity to tuberculin protein Previously unvaccinated individuals may be given the BCG 6 - 15mm Positive - hypersensitive to tuberculin protein Should not be given BCG. May be due to previous TB infection or BCG > 15mm Strongly positive - strongly hypersensitive to tuberculin protein Suggests tuberculosis infection. ``` False negative tests may be caused by: miliary TB sarcoidosis HIV lymphoma very young age (e.g. < 6 months) ```

Answer 51

Chest x-ray upper lobe cavitation is the classical finding of reactivated TB bilateral hilar lymphadenopathy Sputum smear 3 specimens are needed rapid and inexpensive test stained for the presence of acid-fast bacilli (Ziehl-Neelsen stain) all mycobacteria will stain positive (i.e. nontuberculous mycobacteria) the sensitivity is between 50-80% this is decreased in individuals with HIV to around 20-30% Sputum culture the gold standard investigation more sensitive than a sputum smear and nucleic acid amplification tests can assess drug sensitivities can take 1-3 weeks (if using liquid media, longer if solid media) Nucleic acid amplification tests (NAAT) allows rapid diagnosis (within 24-48 hours) more sensitive than smear but less sensitive than culture

Answer 52

Both the meningitis ACWY and tetanus, diphtheria and polio vaccines are given at 14 years (school year 9) so these options are incorrect.

Answer 53

Progressive multifocal leukoencephalopathy (PML) widespread demyelination due to infection of oligodendrocytes by JC virus (a polyoma DNA virus) symptoms, subacute onset : behavioural changes, speech, motor, visual impairment CT: single or multiple lesions, no mass effect, don't usually enhance. MRI is better - high-signal demyelinating white matter lesions are seen

Answer 54

Chronic hepatitis C may be defined as the persistence of HCV RNA in the blood for 6 months. Potential complications of chronic hepatitis C rheumatological problems: arthralgia, arthritis eye problems: Sjogren's syndrome cirrhosis (5-20% of those with chronic disease) hepatocellular cancer cryoglobulinaemia: typically type II (mixed monoclonal and polyclonal) porphyria cutanea tarda (PCT): it is increasingly recognised that PCT may develop in patients with hepatitis C, especially if there are other factors such as alcohol abuse membranoproliferative glomerulonephritis Management of chronic infection treatment depends on the viral genotype - this should be tested prior to treatment the management of hepatitis C has advanced rapidly in recent years resulting in clearance rates of around 95%. Interferon based treatments are no longer recommended the aim of treatment is sustained virological response (SVR), defined as undetectable serum HCV RNA six months after the end of therapy currently a combination of protease inhibitors (e.g. daclatasvir + sofosbuvir or sofosbuvir + simeprevir) with or without ribavirin are used Complications of treatment ribavirin - side-effects: haemolytic anaemia, cough. Women should not become pregnant within 6 months of stopping ribavirin as it is teratogenic interferon alpha - side-effects: flu-like symptoms, depression, fatigue, leukopenia, thrombocytopeni

Answer 55

Over 50% of renal transplant patients have a significant infection within the first 12 months of having a renal transplant. At the time of transplant the CMV-serological status of the donor and recipient are noted. The highest risk is seen in CMV-seronegative recipients who receive a kidney from a CMV-seropositive donor. These patients are usually given antiviral prophylaxis. Cytomegalovirus tend to be seen after four weeks as before this time the immune system has not been fully affected by the immunosuppressants.

Answer 56

Preoperatively Don't remove body hair routinely If hair needs removal, use electrical clippers with single use head (razors increase infection risk) Antibiotic prophylaxis if: - placement of prosthesis or valve - clean-contaminated surgery - contaminated surgery Use local formulary Aim to give single dose IV antibiotic on anaesthesia If a tourniquet is to be used, give prophylactic antibiotics earlier

Answer 57

mmunocompotent patients Most infections are asymptomatic. Symptomatic patients usually have a self-limiting infection, often having clinical features resembling infectious mononucleosis (fever, malaise, lymphadenopathy). Other less common manifestations include meningoencephalitis and myocarditis. Serology is the investigation of choice. No treatment is usually required unless the patient has a severe infection or is immunosuppressed. HIV/immunosuppressed patients Cerebral toxoplasmosis accounts for around 50% of cerebral lesions in patients with HIV constitutional symptoms, headache, confusion, drowsiness CT: usually single or multiple ring-enhancing lesions, mass effect may be seen management: pyrimethamine plus sulphadiazine for at least 6 weeks Immunosuppressed patients may also develop a chorioretinitis secondary to toxoplasmosis. Congenital toxoplasmosis ``` Congenital toxoplasmosis is due to transplacental spread from the mother. It causes a variety of effects to the unborn child including neurological damage cerebral calcification hydrocephalus chorioretinitis ophthalmic damage retinopathy cataracts ```

Answer 58

Streptococcus pneumoniae commonly causes reactivation of the herpes simplex virus resulting in 'cold sores' Discuss (4) Improve

Answer 59

Overdose of tricyclic antidepressants is a common presentation to emergency departments. Amitriptyline and dosulepin (dothiepin) are particularly dangerous in overdose. Early features relate to anticholinergic properties: dry mouth, dilated pupils, agitation, sinus tachycardia, blurred vision. ``` Features of severe poisoning include: arrhythmias seizures metabolic acidosis coma ``` ECG changes include: sinus tachycardia widening of QRS prolongation of QT interval Widening of QRS > 100ms is associated with an increased risk of seizures whilst QRS > 160ms is associated with ventricular arrhythmias Management IV bicarbonate first-line therapy for hypotension or arrhythmias indications include widening of the QRS interval >100 msec or a ventricular arrhythmia other drugs for arrhythmias + class 1a (e.g. Quinidine) and class Ic antiarrhythmics (e.g. Flecainide) are contraindicated as they prolong depolarisation class III drugs such as amiodarone should also be avoided as they prolong the QT interval response to lignocaine is variable and it should be emphasized that correction of acidosis is the first line in management of tricyclic induced arrhythmias intravenous lipid emulsion is increasingly used to bind free drug and reduce toxicity dialysis is ineffective in removing tricyclics

Answer 60

``` The following groups of patients are at an increased risk of developing hepatotoxicity following a paracetamol overdose: patients taking liver enzyme-inducing drugs (rifampicin, phenytoin, carbamazepine, chronic alcohol excess, St John's Wort) malnourished patients (e.g. anorexia nervosa) or patients who have not eaten for a few days ``` Interestingly, acute alcohol intake, as opposed to chronic alcohol excess, is not associated with an increased risk of developing hepatotoxicity and may actually be protective. Paracetamol overdose - high risk if chronic alcohol, HIV, anorexia or P450 inducers

Answer 61

An oculogyric crisis is a dystonic reaction to certain drugs or medical conditions Features restlessness, agitation involuntary upward deviation of the eyes Causes antipsychotics metoclopramide postencephalitic Parkinson's disease Management intravenous antimuscarinic: benztropine or procyclidine

Answer 62

Opioids are substances which bind to opioid receptors. This includes both naturally occurring opiates such as morphine and synthetic opioids such as buprenorphine and methadone. ``` Features of opioid misuse rhinorrhoea needle track marks pinpoint pupils drowsiness watering eyes yawning ``` Complications of opioid misuse viral infection secondary to sharing needles: HIV, hepatitis B & C bacterial infection secondary to injection: infective endocarditis, septic arthritis, septicaemia, necrotising fasciitis venous thromboembolism overdose may lead to respiratory depression and death psychological problems: craving social problems: crime, prostitution, homelessness

Answer 63

Emergency management of opioid overdose IV or IM naloxone: has a rapid onset and relatively short duration of action Harm reduction interventions may include needle exchange offering testing for HIV, hepatitis B & C Management of opioid dependence patients are usually managed by specialist drug dependence clinics although some GPs with a specialist interest offer similar services patients may be offered maintenance therapy or detoxification NICE recommend methadone or buprenorphine as the first-line treatment in opioid detoxification compliance is monitored using urinalysis detoxification should normally last up to 4 weeks in an inpatient/residential setting and up to 12 weeks in the community

Answer 64

Lysergic acid diethylamide (LSD) is the first synthetic hallucinogen which gained popularity in the 1960s to 1980s as a recreational drug. Its psychedelic effects usually involve heightening or distortion of sensory stimuli and enhancement of feelings and introspection. It is one of the most potent psychoactive compounds known. Epidemiology Its usage has declined in recent years but still persists. The Drug Abuse Warning Network (DAWN) estimated that in 2011, the incidence of LSD-related emergency department attendance in the U.S. is 1.5 per 100,000 population. Adolescents and young adults are the most frequent users. Patients with LSD toxicity typically present following acute panic reactions (known as bad trips), massive ingestions or unintentional ingestions. Psychoactive symptoms Variable subjective experiences Impaired judgements which can lead to injury Amplification of current mood which leads to euphoria or dysphoria Agitation, appearing withdrawn - especially in inexperienced users Drug-induced psychosis ``` Somatic symptoms Nausea Headache Palpitations Dry mouth Drowsiness Tremors ``` ``` Signs Tachycardia Hypertension Mydriasis Paresthesia Hyperreflexia Pyrexia ``` Manifestations such as tachycardia, hypertension, pupillary dilation, tremor, and hyperpyrexia can occur within minutes following oral administration of 0.5–2 µg/kg. ``` Massive overdoses can lead to the following complications: Respiratory arrest Coma Hyperthermia Autonomic dysfunction Bleeding disorders ``` Investigations: The diagnosis of LSD toxicity is mainly based on history and examination. Most urine drug screens do not pick up LSD. Management Management of the intoxicated patient is dependent on the specific behavioural manifestation elicited by the drug. Agitation, e.g. from a 'bad trip', should be first managed with supportive reassurance in a calm, stress-free environment. If ineffective, benzodiazepines are the medication of choice. LSD-induced psychosis may require antipsychotics. Massive ingestions of LSD should be treated with supportive care, including respiratory support and endotracheal intubation if needed. Hypertension, tachycardia, and hyperthermia should be treated symptomatically. Hypotension should be treated initially with fluids and subsequently with vasopressors if required. Because LSD is rapidly absorbed through the gastrointestinal tract, activated charcoal administration and gastric emptying are of little clinical value by the time a patient presents to the emergency department.

Answer 65

Contraindications chronic kidney disease: NICE recommend that the dose should be reviewed if the creatinine is > 130 µmol/l (or eGFR < 45 ml/min) and stopped if the creatinine is > 150 µmol/l (or eGFR < 30 ml/min) metformin may cause lactic acidosis if taken during a period where there is tissue hypoxia. Examples include a recent myocardial infarction, sepsis, acute kidney injury and severe dehydration iodine-containing x-ray contrast media: examples include peripheral arterial angiography, coronary angiography, intravenous pyelography (IVP); there is an increasing risk of provoking renal impairment due to contrast nephropathy; metformin should be discontinued on the day of the procedure and for 48 hours thereafter alcohol abuse is a relative contraindication Starting metformin metformin should be titrated up slowly to reduce the incidence of gastrointestinal side-effects if patients develop unacceptable side-effects then modified-release metformin should be considered

Answer 66

Salicylate overdose A key concept for the exam is to understand that salicylate overdose leads to a mixed respiratory alkalosis and metabolic acidosis. Early stimulation of the respiratory centre leads to a respiratory alkalosis whilst later the direct acid effects of salicylates (combined with acute renal failure) may lead to an acidosis. In children metabolic acidosis tends to predominate. ``` Features hyperventilation (centrally stimulates respiration) tinnitus lethargy sweating, pyrexia* nausea/vomiting hyperglycaemia and hypoglycaemia seizures coma ``` Treatment general (ABC, charcoal) urinary alkalinization with intravenous sodium bicarbonate - enhances elimination of aspirin in the urine haemodialysis Indications for haemodialysis in salicylate overdose serum concentration > 700mg/L metabolic acidosis resistant to treatment acute renal failure pulmonary oedema seizures coma *salicylates cause the uncoupling of oxidative phosphorylation leading to decreased adenosine triphosphate production, increased oxygen consumption and increased carbon dioxide and heat production

Answer 67

Lithium is a mood stabilising drug used most commonly prophylactically in bipolar disorder but also as an adjunct in refractory depression. It has a very narrow therapeutic range (0.4-1.0 mmol/L) and a long plasma half-life being excreted primarily by the kidneys. Lithium toxicity generally occurs following concentrations > 1.5 mmol/L. Toxicity may be precipitated by: dehydration renal failure drugs: diuretics (especially thiazides), ACE inhibitors/angiotensin II receptor blockers, NSAIDs and metronidazole. ``` Features of toxicity coarse tremor (a fine tremor is seen in therapeutic levels) hyperreflexia acute confusion polyuria seizure coma ``` Management mild-moderate toxicity may respond to volume resuscitation with normal saline haemodialysis may be needed in severe toxicity sodium bicarbonate is sometimes used but there is limited evidence to support this. By increasing the alkalinity of the urine it promotes lithium excretion

Answer 68

ParacetamolManagement * activated charcoal if ingested < 1 hour ago * N-acetylcysteine (NAC) * liver transplantation SalicylateManagement • urinary alkalinization with IV bicarbonate • haemodialysis Opioid/opiatesNaloxoneBenzodiazepinesFlumazenil The majority of overdoses are managed with supportive care only due to the risk of seizures with flumazenil. It is generally only used with severe or iatrogenic overdoses. Tricyclic antidepressantsManagement * IV bicarbonate may reduce the risk of seizures and arrhythmias in severe toxicity * arrhythmias: class 1a (e.g. Quinidine) and class Ic antiarrhythmics (e.g. Flecainide) are contraindicated as they prolong depolarisation. Class III drugs such as amiodarone should also be avoided as they prolong the QT interval. Response to lignocaine is variable and it should be emphasized that correction of acidosis is the first line in management of tricyclic induced arrhythmias * dialysis is ineffective in removing tricyclics LithiumManagement • mild-moderate toxicity may respond to volume resuscitation with normal saline • haemodialysis may be needed in severe toxicity • sodium bicarbonate is sometimes used but there is limited evidence to support this. By increasing the alkalinity of the urine it promotes lithium excretion WarfarinVitamin K, prothrombin complexHeparinProtamine sulphate Beta-blockersManagement * if bradycardic then atropine * in resistant cases glucagon may be used Ethylene glycolManagement has changed in recent times * ethanol has been used for many years * works by competing with ethylene glycol for the enzyme alcohol dehydrogenase * this limits the formation of toxic metabolites (e.g. Glycoaldehyde and glycolic acid) which are responsible for the haemodynamic/metabolic features of poisoning * fomepizole, an inhibitor of alcohol dehydrogenase, is now used first-line in preference to ethanol * haemodialysis also has a role in refractory cases Methanol poisoningManagement * fomepizole or ethanol * haemodialysis Organophosphate insecticidesManagement * atropine * the role of pralidoxime is still unclear - meta-analyses to date have failed to show any clear benefit DigoxinDigoxin-specific antibody fragments IronDesferrioxamine, a chelating agent LeadDimercaprol, calcium edetate Carbon monoxideManagement * 100% oxygen * hyperbaric oxygen CyanideHydroxocobalamin; also combination of amyl nitrite, sodium nitrite, and sodium thiosulfate

Answer 69

Ethanol reduces the calcium-dependent secretion of anti-diuretic hormone (ADH) by blocking channels in the neurohypophyseal nerve terminal. Nausea associated with hangovers is mainly due to vagal stimulation to the vomiting centre. Following a particular severe episode of alcohol excess people may experience tremors. These are due to increased glutamate production by neurones to compensate for the previous inhibition by ethanol. Nutritional support SIGN recommends alcoholic patients should receive oral thiamine if their 'diet may be deficient' Drugs used benzodiazepines for acute withdrawal disulfram: promotes abstinence - alcohol intake causes severe reaction due to inhibition of acetaldehyde dehydrogenase. Patients should be aware that even small amounts of alcohol (e.g. In perfumes, foods, mouthwashes) can produce severe symptoms. Contraindications include ischaemic heart disease and psychosis acamprosate: reduces craving, known to be a weak antagonist of NMDA receptors, improves abstinence in placebo controlled trials

Answer 70

``` Causes monoamine oxidase inhibitors SSRIs St John's Wort, often taken over the counter for depression, can interact with SSRIs to cause serotonin syndrome ecstasy amphetamines ``` Features neuromuscular excitation (e.g. hyperreflexia, myoclonus, rigidity) autonomic nervous system excitation (e.g. hyperthermia) altered mental state Management supportive including IV fluids benzodiazepines more severe cases are managed using serotonin antagonists such as cyproheptadine and chlorpromazine

Answer 71

``` Drug Side-effect ACE inhibitors Cough Hyperkalaemia Bendroflumethiazide Gout Hypokalaemia Hyponatraemia Impaired glucose tolerance Calcium channel blockers Headache Flushing Ankle oedema Beta-blockers Bronchospasm (especially in asthmatics) Fatigue Cold peripheries Doxazosin Postural hypotension ```

Answer 72

The tables below show the monitoring requirements of common drugs. It should be noted these are basic guidelines and do not relate to monitoring effectiveness of treatment (e.g. Checking lipids for patients taking a statin) Cardiovascular drugs Drug Main monitoring parameters Details of monitoring Statins LFT LFTs at baseline, 3 months and 12 months ACE inhibitors U&E U&E prior to treatment U&E after increasing dose U&E at least annually Amiodarone TFT, LFT TFT, LFT, U&E, CXR prior to treatment TFT, LFT every 6 months Rheumatology drugs Drug Main monitoring parameters Details of monitoring Methotrexate FBC, LFT, U&E The Committee on Safety of Medicines recommend 'FBC and renal and LFTs before starting treatment and repeated weekly until therapy stabilised, thereafter patients should be monitored every 2-3 months' Azathioprine FBC, LFT FBC, LFT before treatment FBC weekly for the first 4 weeks FBC, LFT every 3 months Neuropsychiatric drugs Drug Main monitoring parameters Details of monitoring Lithium Lithium level, TFT, U&E TFT, U&E prior to treatment Lithium levels weekly until stabilised then every 3 months TFT, U&E every 6 months Sodium valproate LFT LFT, FBC before treatment LFT 'periodically' during first 6 months Endocrine drugs Drug Main monitoring parameters Details of monitoring Glitazones LFT LFT before treatment LFT 'regularly' during treatment

Answer 73

Cocaine is an alkaloid derived from the coca plant. It is widely used as a recreational stimulant. The price of cocaine has fallen sharply in the past decade resulting in cocaine toxicity becoming a much more frequent clinical problem. This increase has made cocaine a favourite topic of question writers. Mechanism of action cocaine blocks the uptake of dopamine, noradrenaline and serotonin The use of cocaine is associated with a wide variety of adverse effects: ``` Cardiovascular effects myocardial infarction both tachycardia and bradycardia may occur hypertension QRS widening and QT prolongation aortic dissection ``` ``` Neurological effects seizures mydriasis hypertonia hyperreflexia ``` Psychiatric effects agitation psychosis hallucinations ``` Others ischaemic colitis is recognised in patients following cocaine ingestion. This should be considered if patients complain of abdominal pain or rectal bleeding hyperthermia metabolic acidosis rhabdomyolysis ``` Management of cocaine toxicity in general, benzodiazepines are generally first-line for most cocaine-related problems chest pain: benzodiazepines + glyceryl trinitrate. If myocardial infarction develops then primary percutaneous coronary intervention hypertension: benzodiazepines + sodium nitroprusside the use of beta-blockers in cocaine-induced cardiovascular problems is a controversial issue. The American Heart Association issued a statement in 2008 warning against the use of beta-blockers (due to the risk of unopposed alpha-mediated coronary vasospasm) but many cardiologists since have questioned whether this is valid. If a reasonable alternative is given in an exam it is probably wise to choose it

Answer 74

Mefloquine (brand name Lariam) is used for both the prophylaxis and treatment of certain types of malaria. There has long been a concern about the neuropsychiatric side-effects of mefloquine. A recent review has however led to 'strengthened warnings' about the potential risks. The following advice is therefore given: certain side-effects such nightmares or anxiety may be 'prodromal' of a more serious neuropsychiatric event suicide and deliberate self harm have been reported in patients taking mefloquine adverse reactions may continue for several months due to the long half-life or mefloquine mefloquine should not be used in patients with a history of anxiety, depression schizophrenia or other psychiatric disorders patients who experience neuropsychiatric sife-effects should stop mefloquine and seek medical advice

Answer 75

Clinical features of digoxin toxicity*: GIT: nausea, vomiting, anorexia, diarrhoea Visual: blurred vision, yellow/green discolouration, haloes CVS: palpitations, syncope, dyspnoea CNS: confusion, dizziness, delirium, fatigue Management Digibind correct arrhythmias monitor potassium

Answer 76

Acetylcysteine should be given if: there is a staggered overdose* or there is doubt over the time of paracetamol ingestion, regardless of the plasma paracetamol concentration; or the plasma paracetamol concentration is on or above a single treatment line joining points of 100 mg/L at 4 hours and 15 mg/L at 15 hours, regardless of risk factors of hepatotoxicity Acetylcysteine is now infused over 1 hour (rather than the previous 15 minutes) to reduce the number of adverse effects. Acetylcysteine commonly causes an anaphylactoid reaction (non-IgE mediated mast cell release). Anaphylactoid reactions to IV acetylcysteine are generally treated by stopping the infusion, then restarting at a slower rate. Acetylcysteine should be given if: there is a staggered overdose* or there is doubt over the time of paracetamol ingestion, regardless of the plasma paracetamol concentration; or the plasma paracetamol concentration is on or above a single treatment line joining points of 100 mg/L at 4 hours and 15 mg/L at 15 hours, regardless of risk factors of hepatotoxicity Acetylcysteine is now infused over 1 hour (rather than the previous 15 minutes) to reduce the number of adverse effects. Acetylcysteine commonly causes an anaphylactoid reaction (non-IgE mediated mast cell release). Anaphylactoid reactions to IV acetylcysteine are generally treated by stopping the infusion, then restarting at a slower rate.

Answer 77

Acetylcysteine should be given if: there is a staggered overdose* or there is doubt over the time of paracetamol ingestion, regardless of the plasma paracetamol concentration; or the plasma paracetamol concentration is on or above a single treatment line joining points of 100 mg/L at 4 hours and 15 mg/L at 15 hours, regardless of risk factors of hepatotoxicity Acetylcysteine is now infused over 1 hour (rather than the previous 15 minutes) to reduce the number of adverse effects. Acetylcysteine commonly causes an anaphylactoid reaction (non-IgE mediated mast cell release). Anaphylactoid reactions to IV acetylcysteine are generally treated by stopping the infusion, then restarting at a slower rate.

Answer 78

Adverse effects lower seizure threshold in patients with epilepsy tendon damage (including rupture) - the risk is increased in patients also taking steroids cartilage damage has been demonstrated in animal models and for this reason quinolones are generally avoided (but not necessarily contraindicated) in children lengthens QT interval Contraindications Quinolones should generally be avoided in women who are pregnant or breastfeeding avoid in G6PD

Answer 79

Cataracts steroids Corneal opacities amiodarone indomethacin Optic neuritis ethambutol amiodarone metronidazole Retinopathy chloroquine, quinine Sildenafil can cause both blue discolouration and non-arteritic anterior ischaemic neuropathy

Answer 80

One of the effects of organophosphate poisoning is inhibition of acetylcholinesterase leading to upregulation of nicotinic and muscarinic cholinergic neurotransmission. In warfare, sarin gas is a highly toxic synthetic organophosphorus compound that has similar effects. ``` Features can be predicted by the accumulation of acetylcholine (mnemonic = SLUD) Salivation Lacrimation Urination Defecation/diarrhoea cardiovascular: hypotension, bradycardia also: small pupils, muscle fasciculation ``` Management atropine the role of pralidoxime is still unclear - meta-analyses to date have failed to show any clear benefit

Answer 81

NICE recommends using a combination of CRP and disease activity (using a composite score such as DAS28) to assess response to treatment

Answer 82

``` DMARDs methotrexate is the most widely used DMARD. Monitoring of FBC & LFTs is essential due to the risk of myelosuppression and liver cirrhosis. Other important side-effects include pneumonitis sulfasalazine leflunomide hydroxychloroquine ``` TNF-inhibitors the current indication for a TNF-inhibitor is an inadequate response to at least two DMARDs including methotrexate etanercept: recombinant human protein, acts as a decoy receptor for TNF-α, subcutaneous administration, can cause demyelination, risks include reactivation of tuberculosis infliximab: monoclonal antibody, binds to TNF-α and prevents it from binding with TNF receptors, intravenous administration, risks include reactivation of tuberculosis adalimumab: monoclonal antibody, subcutaneous administration Rituximab anti-CD20 monoclonal antibody, results in B-cell depletion two 1g intravenous infusions are given two weeks apart infusion reactions are common Abatacept fusion protein that modulates a key signal required for activation of T lymphocytes leads to decreased T-cell proliferation and cytokine production given as an infusion not currently recommend by NICE

Answer 83

Polymyalgia rheumatica (PMR) is a relatively common condition seen in older people characterised by muscle stiffness and raised inflammatory markers. Whilst it appears to be closely related to temporal arteritis the underlying cause is not fully understood and it does not appear to be a vasculitic process. Features typically patient > 60 years old usually rapid onset (e.g. < 1 month) aching, morning stiffness in proximal limb muscles weakness is not considered a symptom of polymyalgia rheumatica also mild polyarthralgia, lethargy, depression, low-grade fever, anorexia, night sweats Investigations raised inflammatory markers e.g. ESR > 40 mm/hr note creatine kinase and EMG normal Treatment prednisolone e.g. 15mg/od patients typically respond dramatically to steroids, failure to do so should prompt consideration of an alternative diagnosis

Answer 84

Hydroxychloroquine is used in the management of rheumatoid arthritis and systemic/discoid lupus erythematosus. It is pharmacologically very similar to chloroquine which is used to treat certain types of malaria. Adverse effects bull's eye retinopathy - may result in severe and permanent visual loss recent data suggest that retinopathy caused by hydroxychloroquine is more common than previously thought and the most recent RCOphth guidelines (March 2018) suggest colour retinal photography and spectral domain optical coherence tomography scanning of the macula baseline ophthalmological examination and annual screening is generally recommened A contrast to many drugs used in rheumatology, hydroxychloroquine may be used if needed in pregnant women. Monitoring the BNF advises: 'Ask patient about visual symptoms and monitor visual acuity annually using the standard reading chart'

Answer 85

``` Medications that may worsen osteoporosis (other than glucocorticoids): SSRIs antiepileptics proton pump inhibitors glitazones long term heparin therapy aromatase inhibitors e.g. anastrozole ```

Answer 86

If a patient is diagnosed with osteoporosis or has a fragility fracture further investigations may be warranted. NOGG recommend testing for the following reasons: exclude diseases that mimic osteoporosis (e.g. osteomalacia, myeloma); identify the cause of osteoporosis and contributory factors; assess the risk of subsequent fractures; select the most appropriate form of treatment The following investigations are recommended by NOGG: History and physical examination Blood cell count, sedimentation rate or C-reactive protein, serum calcium, albumin, creatinine, phosphate, alkaline phosphatase and liver transaminases Thyroid function tests Bone densitometry ( DXA) Other procedures, if indicated Lateral radiographs of lumbar and thoracic spine/DXA-based vertebral imaging Protein immunoelectrophoresis and urinary Bence-Jones proteins 25OHD PTH Serum testosterone, SHBG, FSH, LH (in men), Serum prolactin 24 hour urinary cortisol/dexamethasone suppression test Endomysial and/or tissue transglutaminase antibodies (coeliac disease) Isotope bone scan Markers of bone turnover, when available Urinary calcium excretion ``` So from the first list we should order the following bloods as a minimum for all patients: full blood count urea and electrolytes liver function tests bone profile CRP thyroid function tests ```

Answer 87

Epidemiology has a bimodal age distribution - 15-25 yrs and 35-46 yrs ``` Features arthralgia elevated serum ferritin rash: salmon-pink, maculopapular pyrexia typically rises in the late afternoon/early evening in a daily pattern and accompanies a worsening of joint symptoms and rash lymphadenopathy rheumatoid factor (RF) and anti-nuclear antibody (ANA) negative ``` The diagnosis of Still's disease in adults can be challenging. The Yamaguchi criteria is the most widely used criteria and has a sensitivity of 93.5%. Management NSAIDs should be used first-line to manage fever, joint pain and serositis they should be trialled for at least a week before steroids are added. steroids may control symptoms but won't improve prognosis if symptoms persist, the use of methotrexate, IL-1 or anti-TNF therapy can be considered

Answer 88

It is important to perform a chest X-ray to look for TB prior to starting biologics for rheumatoid arthritis as they can cause reactivation

Answer 89

Interferons (IFN) are cytokines released by the body in response to viral infections and neoplasia. They are classified according to cellular origin and the type of receptor they bind to. IFN-alpha and IFN-beta bind to type 1 receptors whilst IFN-gamma binds only to type 2 receptors. Interferon-alpha produced by leucocytes antiviral action useful in hepatitis B & C, Kaposi's sarcoma, metastatic renal cell cancer, hairy cell leukaemia adverse effects include flu-like symptoms and depression Interferon-beta produced by fibroblasts antiviral action reduces the frequency of exacerbations in patients with relapsing-remitting MS Interferon-gamma predominately natural killer cells. Also by T helper cells weaker antiviral action, more of a role in immunomodulation particularly macrophage activation may be useful in chronic granulomatous disease and osteopetrosis

Answer 90

A wide variety of extra-articular complications occur in patients with rheumatoid arthritis (RA): respiratory: pulmonary fibrosis, pleural effusion, pulmonary nodules, bronchiolitis obliterans, methotrexate pneumonitis, pleurisy ocular: keratoconjunctivitis sicca (most common), episcleritis, scleritis, corneal ulceration, keratitis, steroid-induced cataracts, chloroquine retinopathy osteoporosis ischaemic heart disease: RA carries a similar risk to type 2 diabetes mellitus increased risk of infections depression Less common Felty's syndrome (RA + splenomegaly + low white cell count) amyloidosis

Answer 91

Denosumab is a relatively new treatment for osteoporosis. It is a human monoclonal antibody that prevents the development of osteoclasts by inhibiting RANKL. Remember that osteoblasts build bone, osteoclasts eat bone. It is given as a subcutaneous injection, at a dose of 60mg, every 6 months. A larger dose of denosumab (120mg) may also be given every 4 weeks for the prevention of skeletal-related events (i.e. pathological fractures) in adults with bone metastases from solid tumours. For example, you may have noticed some of your breast cancer patients have been prescribed denosumab. Where does it fit in the management of osteoporosis? Oral bisphosphonates are still given first-line, with oral alendronate being the first-line treatment. If alendronate is not tolerated then NICE recommend using an alternative bisphosphonate - either risedronate or etidronate. Following this the advice becomes more complicated with the next-line medications only being started if certain T score and other risk factor criteria being met. Raloxifene and strontium ranelate were recommended as next-line drugs in the NICE criteria but following recent safety concerns regarding strontium ranelate it is likely there will be an increasing role for denosumab. NICE published a technology appraisal looking at the role of denosumab in 2010. A link is provided. What are the known side-effects of denosumab? Denosumab is generally well tolerated. Dyspnoea and diarrhoea are generally considered the two most common side effects, occuring in around 1 in 10 patients. Other less common side effects include hypocalcaemia and upper respiratory tract infections. What does the Drug Safety Update add? Cases of atypical femoral fractures have been noted in patients taking denosumab. Doctors are advised to look out for patients complaining of unusual thigh, hip or groin pain.

Answer 92

Psoriatic arthropathy correlates poorly with cutaneous psoriasis and often precedes the development of skin lesions. Around 10-20% percent of patients with skin lesions develop an arthropathy with males and females being equally affected Types* rheumatoid-like polyarthritis: (30-40%, most common type) asymmetrical oligoarthritis: typically affects hands and feet (20-30%) sacroilitis DIP joint disease (10%) arthritis mutilans (severe deformity fingers/hand, 'telescoping fingers') Management should be managed by a rheumatologist treat as rheumatoid arthritis but better prognosis

Answer 93

Ehler-Danlos syndrome is an autosomal dominant connective tissue disorder that mostly affects type III collagen. This results in the tissue being more elastic than normal leading to joint hypermobility and increased elasticity of the skin. Features and complications elastic, fragile skin joint hypermobility: recurrent joint dislocation easy bruising aortic regurgitation, mitral valve prolapse and aortic dissection subarachnoid haemorrhage angioid retinal streaks Beighton score is a useful tool to assess hypermobility. Beighton score is positive if at least 5/9 in adults, or at least 6/9 in children. See https://www.ehlers-danlos.com/assessing-joint-hypermobility/ on how to carry out the Beighton score assessment

Answer 94

Pseudogout (or "false gout") is a form of arthritis that results from deposits of calcium pyrophosphate crystals. Risk factors Advanced age Injury or previous joint surgery Hyperparathyroidism Haemochromatosis Hypomagnesaemia Hypophosphataemia Presentation Inflammation and pain in one joint (usually monoarticular arthritis but may be oligoarticular)- commonly the wrist or shoulder that worsens over weeks Affected joints are acutely inflamed with swelling, effusion, warmth and tenderness Microscopy Findings Positively berefringent romboid shaped crystals made of calcium pyrophosphate Treatment Acute episodes of pseudogout are treated very similarly to those of gout. Treatment is usually with a course of NSAIDs. If NSAIDs are contraindicated, a course of colchicine may be used instead. Colchicine is problematic because it is very prone to causing significant GI disturbances, especially diarrhoea. If both NSAIDs and colchicine are contraindicated, a short course of oral steroids, or an intra-articular steroid injection may be used. Unlike gout, there is no effective prophylactic treatment for pseudogout.

Answer 95

This is the correct answer. Felty's syndrome is a triad of rheumatoid arthritis, splenomegaly, and neutropenia. Her splenomegaly explains her abdominal discomfort, and her productive cough and coarse crackles suggest a pneumonia, which could be brought on by her neutropenia. Note that splenomegaly can occur in rheumatoid arthritis without Felty’s syndrome, and DMARDs alone can increase susceptibility to infection.

Answer 96

60mg Prednisolone once daily

Answer 97

This is the correct answer. A young patient with a history of active hepatitis B presents with systemic upset, nodular and ulcerating skin lesions and mononeuritis multiplex. Skin biopsy will reveal a non-granulomatous necrotising vasculitis.

Answer 98

Dual positivity (to both p- and c-ANCA) should raise suspicion of a false positive result. Cause include: subacute bacterial endocarditis (and other chronic infections), haematological malignancy, inflammatory bowel disease, and drug induced vasculitis (including cocaine induced vasculitis).

Answer 99

Systemic sclerosis can present as limited systemic sclerosis (including CREST) or diffuse systemic sclerosis. The difference is in the skin involvement (limited systemic sclerosis involves skin up to the elbows and knees). The antibody present in the limited form is anti-centromere. The antibodies present in the diffuse form are scl70 and RNA polymerase 1/2/3. An acute hypertensive crisis is one of the commonest causes of death and is an emergency. These patients are often on a renal ward and may require dialysis due to their renal failure. The treatment is intensive BP control. ACE inhibitors are first line.

Answer 100

Acute gout is an acute crystal arthropathy, characterised by acute onset joint pain, redness and swelling. It is more common in men (4-5:1) and in older age (peak incidence at 80 years). 50% of patients present with podagra, a term referring to acute monoarthritis of the first metatarsophalangeal joint. Others commonly involved include the ankle and tarsal joint, though any can be involved. Predisposing factors can be hereditary or acquired. A positive family history of gout increases risk, as do some uncommon tubular disorders (including Lesch Nyan syndrome). Acquired risk factors can be considered in terms of increased urate input (diet, cell turnover and metabolic changes) or reduced urate output (chronic kidney disease, endocrine disorders, and medications). Drugs are a common risk factor for developing gout. The CANT LEAP mnemonic (ciclosporin, alcohol, nicotinic acid, thiazides, loops, ethambutol, aspirin, and pyrazinamide) is a useful aid to help remember some of the common culprits.

Answer 101

Common culprits include: hydralazine, isoniazid, penicillamine, procainamide, and minocycline. It is associated with a wide range of serological abnormalities including antinuclear antibodies (ANA), anti-neutrophil cytoplastic antibodies (ANCA), and classically anti-histone antibodies. Treatment is withdrawal of the offending agent. Patients commonly relapse on re-challenging with the causative drug.

Answer 102

Polyarteritis nodosa is a systemic necrotising vasculitis of small and medium size vessels. It is seen predominantly in young adults with a slight male predominance (2:1) and is associated with chronic viral hepatitis (in particular hepatitis B infection). It is characterised by prominent non-specific systemic upset with fever, weight loss, arthralgia/myalgia and fatigue. Particularly suggestive symptoms include cutaneous nodules (hence the name) and ulcers, and testicular pain. As with all vasculitis, a mononeuritis multiplex may be seen, as well as renal and GI microvascular ischaemia presenting as renal impairment and gut angina respectively. Unlike small vessel ANCA-associated vasculitis, pulmonary involvement is rare. On laboratory testing the inflammatory markers are raised, though no single test is particularly suggestive. Positive p-ANCA is seen in 20% of cases. Biopsy of lesions reveals a necrotising vasculitis without granulomas (in contrast to granulomatosis with polyangiitis, and giant cell arteritis which may be on the differential). Initial treatment of severe disease is with steroids and cyclophosphamide (rituximab may also be used). Diagnosis and treatment of underlying hepatitis B should also be considered.

Answer 103

Investigations for polymyositis and dermatomyositis The three most important initial tests to perform on all patients in whom you suspect a diagnosis of dermatomyositis or polymyositis are: Muscle-derived serum elevation. Creatinine kinase is the most sensitive indicator and the level usually parallels disease activity, particularly in polymyositis. EMG is performed next. It confirms the myopathic pattern of the disorder and excludes a primary neurogenic disorder. Typical neurogenic records include short duration and low amplitude polyphasic motor units on voluntary activation. Muscle biopsy is required next for definitive diagnosis. In polymyositis, muscle biopsy shows endomysial inflammatory infiltrates and in dermatomyositis, it shows perivascular, perimysial inflammatory infiltrate. Elevated serum enzymes in polymyositis and dermatomyositis Blood tests that are elevated include lactate dehydrogenase, aldolase, ALT and AST. The following is a mnemonic to help remember the elevated serum enzymes in both dermatomyositis (DM) and polymyositis (PM): DM and PM turn your muscles into CLAAA (clay) ``` Creatine kinase Lactate dehydrogenase Aldolase ALT AST Other manifestations of dermatomyositis ``` Dermatomyositis can manifest as a para-neoplastic syndrome associated with visceral carcinomas - particularly gastric, colorectal, genitourinary and lung cancers. Therefore, in both polymyositis and dermatomyositis it may be necessary to look for an underlying malignancy with further investigations. Other manifestations of polymyositis Polymyositis can also manifest as a para-neoplastic syndrome - particularly in association with lung cancer. Treatment of polymyositis and dermatomyositis Corticosteroids are the mainstay of treatment. They are started at high doses initially, creatanine kinase is then monitored to guide the rate of tapering the dose. Many patients need an additional immunosuppressant such as methotrexate or azathioprine as a steroid-sparing agent. Hydroxychloroquine occasionally helps with skin disease in dermatomyositis. As well as pharmacological therapy, physiotherapy is essential to rehabilitate patients. References

Answer 104

Lamotrigine

Answer 105

X-linked gammaglobinemia

Answer 106

2-Myasthenia gravis,graves 3-RA,SLE 4-Steven Johnsons, chronic tranplant rejection

Answer 107

- T helper 2 cells, and the newly recruited eosinophils and basophils secrete pro-inflammatory mediators, cytokines and chemokines,leucotrienes in the late phase which can trigger a second reaction.(6 to 12 hours of after initial symptoms) - Repeat exposure can lead to ongoing local inflammation seen in allergic rhinitis and allergic asthma(structural damage)

Answer 108

Background history of asthma or allergy

Answer 109

triptase-released from activated mast cells(1-2 hours to 4-6 hours after) check baseline after 24 to exclude mastocytosis

Answer 110

ABCDE approach 500 micrograms of IM adrenaline 1 in 2000 for anaphylaxis Other -establish airway, high flow o2,IV fluids Consider IV 10 mg chlorphenamine and 200mg hydrocortisone In cardiac arres 1 mg of 1 to 10000 adrenaline is given IV

Answer 111

Thumbprinting | Sign of a swollen bowel wall – usually due to inflammation in IBD

Answer 112

IFN-alpha can be used to treat chronic hepatitis C infections, Kaposiís sarcoma and hairy cell leukaemia. Interferons are important in certain treatments for viral infections - IFN-alpha can be obtained from multiple sources and limits viral replication. Note that there are other treatments that are designed to target cytokines, or utilise cytokines as treatment: Rheumatoid arthritis: Anti-TNF Renal cell carcinoma: Anti-IL12 Melanoma: Anti-IL12 Neutropenia: GM-CSF or G-CSF

Answer 113

Severe Combined Immunodeficiency (SCID) is one of the few primary immunodeficiencies that does not always follow an X-linked inheritance pattern. SCID can follow an X-linked inheritance, most commonly with a mutation in the X-linked common ? Chain which is used by several cytokine receptors. However, SCID can also result from mutations in autosomal genes, such as those encoding the recombinase genes RAG-1 and RAG-2 (which are required to produce immunoglobulin). SCID is a serious immunodeficiency that presents with both compromised T cell and humoral immunity. Therefore, recurrent infections are likely to lead to investigation and diagnosis.

Answer 114

Important to consider non-allergic causes as even with positive allergy tests if there are other causes present then treatment of allergies may be ineffective in controlling symptoms. Consider: Infection Usually self -resolving Environmental triggers Smoke, perfume, paint fumes, changes in weather / temperature, alcohol, spicy food, stress and cause not known. Medicines and recreational drugs ACE inhibitors, beta blockers, NSAIDs, cocaine Overuse of nasal decongestants Reduce swelling of the blood vessels If used for >5-7 days then rebound symptoms Hormone changes Pregnancy, puberty, HRT, OCP Hypothyroidism Structural nasal problems Deviated nasal septum; polpys

Answer 115

He had asked his GP about desensitisation therapy This is only indicated when triple therapy, as outlined above has failed and oral steroids are required. It is helpful in severe cases and reduces symptoms and need for other medication; some medication may still be required despite immunotherapy It requires considerable commitment (teatment will be for a minimum of three years, it can be by continuous sublingual therapy or winter courses of 4-6 injections, and treatment effect may wear off and treatment may need to be repeated).

Answer 116

Cytomegalovirus (CMV) is transmitted in leucocytes. As most blood products (except granulocyte transfusions) are now leucocyte depleted CMV negative products are rarely required. Irradiated blood products are depleted of T-lymphocytes and used to avoid transfusion-associated graft versus host disease (TA-GVHD) caused by engraftment of viable donor T lymphocytes. The table below shows the indications for CMV and irradiated blood: Situation CMV negative Irradiated Granulocyte transfusions ✓ ✓ Intra-uterine transfusions ✓ ✓ Neonates up to 28 days post expected date of delivery ✓ ✓ Pregnancy: Elective transfusions during pregnancy (not during labour or delivery) ✓ Bone marrow / stem cell transplants ✓ Immunocompromised (e.g. chemotherapy or congenital) ✓ Patients with/previous Hodgkins Disease ✓ HIV

Answer 117

Cytotoxic agents The tables below summarises the mechanism of action and major adverse effects of commonly used cytotoxic agents. Alkylating agents Cytotoxic Mechanism of action Adverse effects Cyclophosphamide Alkylating agent - causes cross-linking in DNA Haemorrhagic cystitis, myelosuppression, transitional cell carcinoma Cytotoxic antibiotics Cytotoxic Mechanism of action Adverse effects Bleomycin Degrades preformed DNA Lung fibrosis Anthracyclines (e.g doxorubicin) Stabilizes DNA-topoisomerase II complex inhibits DNA & RNA synthesis Cardiomyopathy Antimetabolites Cytotoxic Mechanism of action Adverse effects Methotrexate Inhibits dihydrofolate reductase and thymidylate synthesis Myelosuppression, mucositis, liver fibrosis, lung fibrosis Fluorouracil (5-FU) Pyrimidine analogue inducing cell cycle arrest and apoptosis by blocking thymidylate synthase (works during S phase) Myelosuppression, mucositis, dermatitis 6-mercaptopurine Purine analogue that is activated by HGPRTase, decreasing purine synthesis Myelosuppression Cytarabine Pyrimidine antagonist. Interferes with DNA synthesis specifically at the S-phase of the cell cycle and inhibits DNA polymerase Myelosuppression, ataxia Acts on microtubules Cytotoxic Mechanism of action Adverse effects Vincristine, vinblastine Inhibits formation of microtubules Vincristine: Peripheral neuropathy (reversible) , paralytic ileus Vinblastine: myelosuppression Docetaxel Prevents microtubule depolymerisation & disassembly, decreasing free tubulin Neutropaenia Topoisomerase Inhibitors Cytotoxic Mechanism of action Adverse effects Irinotecan Inhibits topoisomerase I which prevents relaxation of supercoiled DNA Myelosuppression Other cytotoxic drugs Cytotoxic Mechanism of action Adverse effects Cisplatin Causes cross-linking in DNA Ototoxicity, peripheral neuropathy, hypomagnesaemia Hydroxyurea (hydroxycarbamide) Inhibits ribonucleotide reductase, decreasing DNA synthesis Myelosuppression

Answer 118

Next question Tumour markers Tumour markers may be divided into: monoclonal antibodies against carbohydrate or glycoprotein tumour antigens tumour antigens enzymes (alkaline phosphatase, neurone specific enolase) hormones (e.g. calcitonin, ADH) It should be noted that tumour markers usually have a low specificity Monoclonal antibodies Tumour marker Association CA 125 Ovarian cancer CA 19-9 Pancreatic cancer CA 15-3 Breast cancer Tumour antigens Tumour marker Association Prostate specific antigen (PSA) Prostatic carcinoma Alpha-feto protein (AFP) Hepatocellular carcinoma, teratoma Carcinoembryonic antigen (CEA) Colorectal cancer S-100 Melanoma, schwannomas Bombesin Small cell lung carcinoma, gastric cancer, neuroblastoma

Answer 119

Although most lung cancer is linked to smoking, squamous cell lung cancer is the most strongly linked with smoking. This type of lung cancer is also more commonly found near large airways, unlike adenocarcinoma which is more commonly peripheral. Small cell lung cancers also tend to be found near the larger airways. They tend to be associated with para-neoplastic syndromes and often metastasise early. Large cell carcinoma is considered a diagnosis of exclusion. The history is not typical of carcinoid. Furthermore, carcinoid tumours of the lung are rare.

Answer 120

There are three main subtypes of non-small cell lung cancer: Squamous cell cancer typically central associated with parathyroid hormone-related protein (PTHrP) secretion → hypercalcaemia strongly associated with finger clubbing hypertrophic pulmonary osteoarthropathy (HPOA) Adenocarcinoma typically peripheral most common type of lung cancer in non-smokers, although the majority of patients who develop lung adenocarcinoma are smokers Large cell lung carcinoma typically peripheral anaplastic, poorly differentiated tumours with a poor prognosis may secrete β-hCG

Answer 121

Human papillomavirus (HPV) subtypes 16,18, 33 are the most significant risk factors for developing cervical cancer. Though it should be noted that the majority of healthy women will spontaneously clear HPV within 2 years without developing cervical cancer. Smoking is a risk factor for cervical cancer likely through inhibition of the immune system in clearing HPV infection. Combined oral contraceptives (COC) are implicated in an increase in cervical cancer (and breast cancer), but in the case of cervical cancer risk is increased when taking COC for more than 5 years.

Answer 122

Medullary thyroid cancer will cause a rise in calcitonin levels. Medullary thyroid cancer is the only thyroid cancer that will cause a rise in calcitonin, as it originates from the parafollicular cells, which produce calcitonin.

Answer 123

Supportive features: - **Triggers:** hot and crowded environment, skipped breakfast - **Pre-syncopal symptoms:** nausea and malaise, hot and clammy, looked pale - **During:** brief myoclonic jerks - **After:** fast recovery (10-15min), recognised friends, no prolonged post-ictal phase It would be worth getting a full set of observations, ECG and systemically examining this lady, but you would expect these to be normal. Given the clear history of vasovagal syncope with triggers, blood tests would not be necessary. You reassure this lady, give conservative advice about syncope triggers and send her home.

Answer 124

Supportive features: - **Before:** No warning or pre-syncopal symptoms - **During:** Lasted 1-2 minutes. Load groan noise represents tonic contraction of diaphragm, followed by tonic rigid fall. Description of symmetrical jerking clonic-type movements. Non respsonsive. - **After:** Description of post-ictal period: drowsy and confused, not recognising people around her. 1st clear memory is >1hour later, after already in hospital. This patient is presenting with her first seizure. You would take a full history including asking about drugs and alcohol, any childhood seizures and any family history. You would do a full neurological examination to look for any focal neurology. You would also need to take a full set of bloods to look for any cause. This would include electrolytes, glucose and lactate. You would need to ask for a 12 -lead ECG. New focal neurological deficit, head trauma, fevers and persistent headaches would all be reasons to request a CT head now but otherwise you could allow the neurology team to decide this at a later date. If all history, examination and investigations were normal, it would appear that this lady has had an unprovoked seizure and you would need to inform her that she can no longer drive and will need to discuss the timings of this with a neurologist at her first fit clinic (which you would refer her to). It would be worth checking with your senior if they thought this patient was suitable for discharge.

Answer 125

Supportive features: - **Before:** Onset **during** exertion. Sudden onset, with little warning. - **During:** Brief loss of consciousness, in keeping with syncope. - **After:** Rapid recovery after collapse, in keeping with syncope A thorough history would be key in this patient, including any family history of sudden cardiac death. Examination would look for any murmurs and signs of heart failure. A 12-lead ECG would obviously be essential. Lying and standing blood pressure would also be useful. A full set of bloods would be required to rule out causes such as electrolyte imbalances. NICE guidelines state (Transient loss of consciousness ('blackouts') in over 16s [CG109]): Refer urgently for cardiovascular assessment, with the referral reviewed and prioritised by an appropriate specialist within 24 hours, anyone with TLoC who also has any of the following. - An ECG abnormality (see recommendations 1.1.2.2 and 1.1.2.3). - Heart failure (history or physical signs). - TLoC during exertion. - Family history of sudden cardiac death in people aged younger than 40 years and/or an inherited cardiac condition. - New or unexplained breathlessness. - A heart murmur Consider referring within 24 hours for cardiovascular assessment, as above, anyone aged older than 65 years who has experienced TLoC without prodromal symptoms. This lady would qualify for urgent referral based on transient loss of consciousness during exertion..

Answer 126

Although this lady would need to be assessed by a neurologist, she does have features suggestive of a dissociative seizure / non-epileptic attack. Supportive features: - **Triggers:** busy and crowded environment - may be stressful - **Before:** felt short of breath and racing heart - ?adrenaline/stress feeling. Dissociative seizures can be, but are not always triggered by stress/panic. - **During:** retained consciousness - able to hear people around her. Consciousness can **not** be retained during a generalised seizure (but can be during a focal seizure). The feeling of 'dissociation' or 'watching from the outside' is a common sensation. Often has limb movements which can be hard for witnesses to differentiate from a seizure. - **After:** Able to recognise people around immediately. Feeling groggy or run-down afterwards, 2 days is generally too long for post-ictal. It is important to note that sufferers of dissociative attacks do not have control over these events and they are often extremely distressing for them. These are sometimes called non-epileptic attack disorder Management of this patient is very similar to the management of your patient with a likely epileptic seizure as this is the other differential. You would again take a full history including asking about drugs and alcohol, any childhood seizures and any family history. You would do a full neurological examination, take a set of bloods and request a 12 lead ECG. They are unlikely to require an urgent CT head but you should check for those red flags. Your working diagnosis may be incorrect. This patient also requires a referral to the first fit clinic. She needs to be informed that she cannot drive. We have not yet reached a firm diagnosis but even if these do turn out to be dissociative seizures, they are themselves a reason not to drive and she must inform the DVLA.

Answer 127

Chronic pain is pain that has lasted **longer than 3 months,** persisting beyond the expected healing time for an episode of tissue damage. This type of pain can become counter-productive, leading to loss of function and having a significant impact on the health, social and pyschological well-being of a patient. Chronic pain can have several causes: - **Nociceptive pain:** Noci (pain) -ceptive (perception). Usually due to an organic disease. Pain that is triggered by stimuli that damage or threaten tissues. The most common of these is musculoskeletal e.g. osteoarthritis. This also includes cancer pain, visceral pain etc. - **Neuropathic pain:** Neuro (nerves) -pathy (disease). Due to pathology or pathological response of sensory nervous system e.g. peripheral neuropathy, MS, post-herpetic pain etc. - **Nociplastic pain:** Noci (pain) **-**plastic (change/modulation). ****Caused by abnormal pain processing, even when no physical/organic damage has occurred to our tissues or nerves. This term was introduced by the IASP council in 2017. “pain that arises from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain.” A patient can experience more than one type of pain at once. In fact, chronic nociceptive or neuropathic pain can lead to neuromodulation and increased nociplastic pain.

Answer 128

Chronic pain is more prevalent in some demographic groups, due to a combination of biological, psychological and social factors: - Older age groups - Co-morbid disease: particularly depression and cardiovascular disease - Female gender - Socio-economic deprivation - Smokers - Alcohol dependence - Increased BMI

Answer 129

- **Central Sensitisation:** increased responsiveness of nociceptors in the central nervous system. It has been proposed that previous painful experiences increase this sensitisation process. This can lead to usually non-painful stimuli (e.g. gut peristalsis in IBS) being processed as painful. - **Reduced negative feedback:** Reduced negative inhibition via the descending pain pathways. Because of the close ties with the cortex and limbic system, it is suggested that states of depression/anxiety/stress inhibit this system, leading to reduced pain inhibition. - **Somatisation:** Slightly controversial. Manifestation of psychological distress as physical pain or symptoms (similar to stress being felt as a headache). Becomes pathological when prolonged and distressing. Ascending and descending pathways which drugs act?

Answer 130

**Yellow flags** are our risk factors for developing chronic pain: - Maladaptive health behaviours - Adopting 'passive' rather than 'active' coping strategies - Anxiety - Depression and social isolation - Lack of social support or 'over-protective' caregivers - Ongoing litigation related to original pain/injury source - Unresolved anger - Poor job satisfaction or extended sick leave Each person's reaction to pain is different. A person's health behaviours often contribute to their ability to cope with and recover from chronic pain. Example of **maladaptive health beliefs and behaviours** include: - The belief that feeling pain means harm is occurring - Fear-avoidance of activities due to fear of pain/re-injury - Catastrophic thinking - Reliance on passive coping strategies (e.g. drugs and rest) rather than active (e.g. physiotherpay) - Low expectations of recovery - Adopting "the sick role"

Answer 131

- What is chronic fatigue syndrome? Chronic Fatigue Syndrome (sometimes called Myalgic Encephalomyelitis/ME) causes long-standing fatigue. It is not always associated with chronic pain but raises similar symptom clusters and diagnostic challenges to conditions such as fibromyalgia . CFS is when the level of fatigue is disabling in it's frequency and severity. There are several different ways to classify chronic fatigue. NICE defines the fatigue as: - Present for >4 months - New or clear onset - Not explained by anything else (including severe obesity BMI >40) - Causes significant reduction in activity level - Classically post-exertional (typically delayed onset, and lasts >24 hours) The patient may be very fatigued by what can seem like 'trivial' physical/mental exertion, and would often have been within the patients activity tolerance prior to onset of the disease. CFS is also associated with **at least one of:** - Difficulty sleeping - Widespread muscle/joint pain - Cognitive impairment i.e. poor memory, word-finding difficulties, poor concentration - Ongoing flu-like symptoms: malaise, painful lymph nodes, sore throat, headaches - Dizziness/nausea/palpitations/orthostatic intolerance **Additionally,** the symptoms are not explained by an alternative diagnosis e.g. depression, arthritis, malignancy etc. Remember, fatigue is not the same as depression. You may have to clarify the symptoms during the history to elicit the patient's meaning. * *Fatigue:** Reduced energy, subjective feeling of tiredness or exhaustion. * *Depression:** Reduced motivation and enjoyment. May feel down/weepy/upset. May be associated with concomitant fatigue. CFS can be present at the same time as commonly associated conditions such as IBS, migraine and fibromyalgia.

Answer 132

CFS very often has a 'triggering event' such as infection with EBV, other viral infections, vaccination commonly at a time of stress/exertion. It is not known what causes CFS and may theories have been investigated. There has been suggested neuroinflammatory and neuroendocrine involvement, and research into this is ongoing. Up until this time, there is no diagnostic blood tests, antibody or imaging modality that can diagnose CFS so it remains based on clinical acumen and ruling out differential diagnoses. A patient presenting with fatigue should undergo routine 'Tired all the time' (TATT) work-up plus any additional investigations indicated by the specific features of the history. Suggested tests might include: - FBC - U&Es - LFTs - TFTs - CRP/ESR - HbA1c - IgA anti-tissue transglutaminse (anti-ttg) - coeliac disease can cause fatigue without GI symptoms Consider if suggestive history: - Bone panel/myeloma screen - Vitamin D - EBV/CMV - Lyme serology - HIV/Hepatitis

Answer 133

NICE has previously recommended CBT and graded exercise therapy for CFS, but this remains a very controversial topic. Therapies for CFS are considered as **coping therapies** not curative therapies. The basis of treatment often involves supporting a patient to understand the disease and to find adaptations to cope with it and maximise their quality of life and functioning. Patient often report their symptoms vary day to day. Some patients report a tendency to "over-exert" themselves when experiencing a "good day" leading to days-weeks of increased fatigue. Patients are taught **pacing** techniques as a coping strategy to avoid this 'boom-bust' cycle. The principles of pacing are avoiding over-exertion, tracking activity and symptoms and varying activities.

Answer 134

Complex regional pain syndrome (CRPS) is rarely encountered in clinical practice, but is good to at least be aware of. The syndrome typically affects a distal limb, after an injury such as a fracture, surgery or trauma. The area affected goes on to develop chronic severe and debilitating pain, in excess of what would be expected from the original injury. Symptoms usually start within 1 month of the injury. It is thought to originate fro damage to either 1 major nerve or to the small sensory and autonomic nerves in an area. Unlike fibromyalgia and CFS there are often visible clinical signs at the affected limb, due to damage to the autonomic control of vasodilation, sweating and temperature. Sensory-allodynia,hyperalgesia, temperature and colour changes edema,reduced motor function Diagnosis is clinical. Nerve conduction studies and MRI can sometimes show nerve damage, but a normal scan dose not rule out CRPS. The pain is often so severe that the limb is rendered non-functional. It is not uncommon for patients to request amputation of the affected limb. Unfortunately, this has not been found to be curative of the pain and often leads to the development of phantom limb syndrome.

Answer 135

- Lack of understanding on behalf of patient - Unclear or unempathetic explanation from clinician - Felt stigma surrounding a diagnosis - feeling of stigma from clinicians/society - Feeling of being accused of "making it up" or "saying it's all my head" - Feeling that symptoms are "just being put down to being depressed" - Feeling that pain/symptoms are not being validated as real/significant - Feeling that another diagnosis is being missed - Lack of cure/treatment Alternatively, diagnosis can be really positive experience for some patients. Many fibromyalgia patients have waited for over 5 years before receiving their diagnosis. Receiving a diagnosis can offer a patients an explanation for their symptoms after years of uncertainty and distress. Having a diagnosis can allow patients to explain their disease to family/friends and join support groups.

Answer 136

- Felt stigma surrounding a diagnosis - feeling of stigma from clinicians/society t is important to identify features in chronic pain which predispose, precipitate and perpetuate chronic pain. For example, a pain condition may cause pain at night and lead to poor sleep. Un-refreshing sleep and chronic tiredness, in turn, leads to increased pain perception. A part of management is to identity these self-perpetuating cycles and offer the patient support to break them, through a mixture medication, education, physiotherapy and CBT.

Answer 137

**Summary: mechanical stimulation inhibits pain signalling** TENs (transcutaneous electrical nerve stimulation) machines are used to manage both acute and chronic pain. They work via sticky pads on the skin that give small electrical currents, feeling like a 'buzz' or 'tingling sensation'. This acts to interrupting painful signals, thus the intensity of the pain is reduced. They are used for acute pain, such as labour pain. There is little evidence to support their use for chronic pain but some patients may choose to try them, particularly for focal pain such as chronic back pain.

Answer 138

Illness anxiety disorder and medically unexplained symptoms can appear superficially similar but are distinct conditions. They can certainly overlap and a patient can experience both simultaneously. Illness anxiety disorder is usually described as a cycle of recurrent anxiety surrounding fears of ill-health. This can lead to healthcare avoidance or recurrent presentations to health services despite reassurance. Someone with illness anxiety disorder may be experiencing organic physical symptom, medically unexplained symptoms or no symptoms at all. Hyper-vigilance of bodily functions and sensory sensitisation can lead a patient with illness anxiety to develop new physical symptoms. People with medically unexplained symptoms may not have any associated illness anxiety. People experiencing medically unexplained symptoms often are concerned about specific possible diseases but may react well to reassurance and explanation, without demonstrating a recurrent cycle of illness anxiety.

Answer 139

- Delay in reaching a diagnosis, patient acceptance and management. - Perpetuate patient and clinician belief in an underlying organic disease, making later acceptance of medically unexplained symptoms more challenging. - Repeated negative results lead to patient understanding of self as a "medical mystery" who needs prolonged and increasingly specialist investigations or care to unveil the diagnosis. - Precipitate or perpetuate illness anxiety, or put patients through stress of awaiting results which may reveal a serious diagnosis e.g. cancer, despite being extremely unlikely. - Dis-empower patients and lead to an increased external locus of control, increasing dependence on healthcare and clinicians. - Repeated scans can increase radiation exposure. - Iatrogenic harm through invasive investigations e.g. biopsies, surgery. - Unnecessary costs to the NHS.

Answer 140

Ectopic beats and sinus tachycardia can be common causes of palpitations that do not affect a patient's prognosis. **Ectopics** - can be atrial or ventricular. Feels like a 'missed beat' then a 'heavy squeeze'. - Atrial ectopics are common and does not affect prognosis. - Ventricular ectopics can be associated with increased caffeine intake or stress - reducing caffeine and stress often improves palpitations in these patients. Ventricular ectopics also tend to be more common with increased age. A heavy burden of ventricular ectopics (e.g. bigeminy) can indicative of electrolyte disturbances, underlying cardiac ischaemia or structural abnormalities and warrants further investigation. **Sinus tachycardia** - a racing heart beat, but the rhythm is regular. Can be a physiological response to underlying pathology such as sepsis or PE. Sinus tachycardia is also associated with anxiety as the increase in catecholamine levels lead to increased heart rates. When serious disease has been ruled out, NICE recommends treating palpitations with reassurance, lifestyle advice and managing any cardiac risk factors e.g. hypertension, hypercholesterolaemia. Palpitations are a scary experience for patients, sometimes a single episode of palpitations can lead to anxiety and fear - "My heart is giving up!". This, in turn, leads to increased vigilance of their heart beat and anxiety that leads to further tachycardia. Exploring anxiety and life stressors sensitively can help a patient to identify features that could be causing/contributing to their symptoms. Relaxation, mindfulness and coping strategies can be helpful in reducing palpitation frequency and severity.

Answer 141

**Irritable bowel syndrome** Irritable bowel syndrome (IBS) is one of the most well-recognised cause of functional abdominal pain. It is common and well-described, thought to affect 10-20% of the population. It is defined as a **functional bowel condition** as the **functioning** of the bowel has been impaired - causing altered bowel habit and pain. Several theories have been proposed, however, thus far no organic pathology has been identified and examination and investigations are generally normal. IBS diagnosis should be approached based on a patient **positively** having IBS symptoms, not simply as a diagnosis of exclusion once organic disease has been ruled out. IBS is characterised by at least 6+ months of either: - **A:** Abdominal pain (cramping) - often relieved by defecation - **B:** Bloating - **C:** Constipation (+/- diarrhoea) - altered bowel frequency or form, mucous may be present in stool IBS is also associated with lethargy, nausea, backache and bladder dysfunction. 1 in 10 patient report IBS onset can develop after an episode of gastroenteritis. Depression and anxiety are more common amoungst IBS patients. People with IBS tend to have a predominantly constipation-type, diarrhoea-type or mixed.

Answer 142

Functional dyspepsia is an issue with upper GI pain and delayed gastric emptying. Symptoms that are primarily **upper gastrointestinal.** Symptoms include: - Dyspepsia - Nausea - Early satiety - Bloating - Increased burping These symptoms clearly also raise some red flags for upper GI disease and many patients will be investigated with bloods, H Pylori testing and often endoscopy - looking for ulcers, inflammation, malignancy etc. You should screen for red flags and ALARM symptoms in any patient with dyspepsia. Functional dyspepsia is diagnosed once organic diseases that could also explain the symptoms have been ruled out. Up to 60% of people with recurrent dyspepsia will have functional dyspepsia, it has previously been called 'non-ulcer dyspepsia'. 1 in 3 people with functional dyspepsia also have IBS.

Answer 143

**Centrally-mediated (functional) abdominal pain syndrome:** >6 months of abdominal pain, with no explained organic cause. The Rome III criteria defines the pain as: - Pain is nearly continuous for at least 3 months - Not, or minimally, related to eating/defecation/menses - Impairs daily functioning - Not attributable to another medical condition Prevalence is thought to be around 2% in adults. More common in females and younger adults/adolescents. Increased prevalence in patients with life/social stressors, which can be a precipitating or perpetuating factor. Abdominal migraine is a functional abdominal pain condition, primarily found in children. - Paroxysmal episodes of central abdominal pain, lasting >1 hour. - Associated with: nausea, vomiting, loss of appetite and sometimes headache/photophobia. - Long symptom-free periods in between episodes. Children with abdominal migraines may go to develop headache migraines in adolescence/adulthood. Abdominal migraine is predominantly noted in in paediatrics, but you may by interested in this **[interesting case report](https://pubmed.ncbi.nlm.nih.gov/16420398/)** about a patient with recurrent abdominal pain and migraines whose pain attacks resolved when placed on migraine prophylaxis.

Answer 144

This is chronic pain, lasting >6months, in the lower abdomen or pelvic area. The pain is not purely associated with menstruation, intercourse or pregnancy. This is generally a gynecological term, referring to women, or anyone with a uterus/ovaries. These patients may be seen by gynaecology, general surgery and primary care. Male chronic pelvic pain syndrome also exists, with both organic and functional causes, but is not the focus of this tutorial. Approach to chronic pelvic pain takes on a similar approach to abdominal pain. There are important organic pathologies to consider and investigate for, but for many patients investigations are normal. These cases are considered as functional pelvic pain. Pelvic pain can be associated with abnormal uterine bleeding, urinary symptoms and constipation. Some organic pelvic conditions e.g. endometriosis can be challenging to diagnose, this can make differentiating functional and organic pelvic pain fairly challenging. Similarly to functional abdominal pain, the pain may be a result of central sensitisation, biopyschosocial factors and contributing organic pathology. Red flags for pelvic pain: - Post-coital bleeding - Post-menopausal bleeding - PR bleeding - New GI symptoms e.g. constipation, bloating, early satiety, especially age >50 - Pelvic mass - Unexpected weight loss

Answer 145

Pelvic pain with a significant cyclical element (worsening pre/during menstruation) may be due to endometriosis. This is an organic condition caused by endometrial tissue growth at extra-uterine sites, leading to dysmenorrhea, pelvic pain and sometimes subfertility. It can be difficult to differentiate endometriosis from functional pelvic pain due to the investigations required. Endometriosis poses a diagnostic challenge as the gold-standard for proven diagnosis is to perform a laparoscopy. There an average of 7.5 years between symptom onset and diagnosis. Laparoscopy is an invasive investigation which carries a **[2.4 in 1000](https://www.rcog.org.uk/globalassets/documents/guidelines/gtg_41.pdf)** risk of damage to bowel, bladder or blood vessel. There is also a risk of adhesions after an invasive surgery, which could in turn lead to worsening of chronic pelvic pain. The benefits and risks of undergoing laparoscopy to diagnose endometriosis should be explained to patients undergoing investigations. Laparoscopy is not 100% sensitive and patients should be aware that they may have a normal result, even with endometriosis. Similarly, some women with functional pelvic pain without endometriosis may have similar symptoms, and risk undergoing a potentially harmful and invasive investigation that will not lead to eventual benefit. **[1/2 to 1/3](https://www.rcog.org.uk/globalassets/documents/guidelines/gtg_41.pdf)** of diagnostic laparoscopies will be negative.

Answer 146

Need for rigorous clinical validation Ethical implications of ongoing monitoring (wearable devices etc) The need to educate and prepare augmented doctors Avoiding dehumanizing by technology – ambient clinical intelligence

Answer 147

It is the statutory duty of a doctor to report a death to the Coroner if the death occurred in that Coroner’s area and is of the sort that needs reporting to the Coroner Not attended by a doctor during final illness 2. Not seen by a doctor either after death or within 14 days prior to death 3. Cause of death unknown 4. Cause of death may be unnatural 5. Others - in custody - war pension

Answer 148

``` 1. Criminal Murder Manslaughter Infanticide Aiding Suicide Dangerous or Careless Driving Suspicious ``` 2. Suicide Accident - no matter what the time interval RTC’s domestic industrial 4. Industrial Disease (pneumoconiosis, asbestosis) ``` 5. Deaths associated with Medical or Surgical Treatment During a medical or surgical procedure operation/anaesthetic 24 hour rule admission to hospital Where treatment caused, contributed to or accelerated death “Negligence” 6. Miscellaneous Abortion Neglect Acute alcohol Drug abuse Children ```

Answer 149

Medico-legal (Coroner’s; Forensic) Consented (Hospital) ``` Can only happen with informed consent from next of kin Regulated by the Human Tissue Authority and covered by The Human Tissue Act 2004 Next of Kin has to understand What an autopsy entails Why an autopsy is being requested The limitations of the autopsy When to expect a result Next of kin must decide The extent of the autopsy The extent of tissue retention What will happen to any retained tissue ```

Answer 150

``` “a framework for regulating the storage and use of human organs and tissue from the living and deceased” Replaces Human tissue act 1961 Anatomy act 1984 Human organ transplants act 1989 ``` Informed Consent above all Anything which includes cells Penalties of up to 3 years in prison Human Tissue Authority ``` The human tissue authority Issue codes of practice Inform the public License activities Inspect premises ```

Answer 151

``` Clinical History External examination confirm identity Evisceration Record findings Organ dissection Further tests Report ```

CDM revision Sem 2 Flashcards

(176 cards)