Key points and some collections 2015

Clinical science AIP - porphobilinogen deAminase; PCT - uroporphyrinogen deCarboxylase Absolute risk reduction = (Control event rate) - (Experimental event rate) Adrenal cortex mnemonic: GFR – ACD Anaphylaxis = type I hypersensitivity reaction Anticipation in trinucleotide repeat disorders = earlier onset in successive generations Antidiuretic hormone (ADH) - site of action = collecting ducts Autosomal recessive conditions are 'metabolic' - exceptions: inherited ataxias Autosomal dominant conditions are 'structural' - exceptions: hyperlipidaemia type II, hypokalaemic periodic paralysis BNP - actions:  vasodilator  diuretic and natriuretic  suppresses both sympathetic tone and the renin-angiotensinaldosterone system Cohort studies - relative risk Combined B- and T-cell disorders: SCID WAS ataxic (SCID, Wiskott-Aldrich syndrome, ataxic telangiectasia) Correlation  parametric (normally distributed): Pearson's coefficient  non-parametric: Spearman's coefficient DiGeorge syndrome - a T-cell disorder Epidermis - layers - bottom layer = stratum germinativum which gives rise to keratinocytes and contains melanocytes Funnel plots - show publication bias in meta-analyses Hereditary angioedema - C1-INH deficiency Hereditary angioedema - C4 is the best screening test inbetween attacks Human genome - 25,000 protein-coding genes Hypokalaemia - U waves on ECG Klinefelter's? - a karyotype Methaemoglobinaemia = oxidation of Fe2+ in haemoglobin to Fe3+ Mitochondrial diseases follow a maternal inheritance pattern Molecular biology techniques  SNOW (South - NOrth - West)  DROP (DNA - RNA - Protein) NNT = / Absolute Risk Reduction Nitric oxide - vasodilation + inhibits platelet aggregation Obesity hormones  Leptin Lowers appetite  Ghrelin Gains appetite Odds - remember a ratio of the number of people who incur a particular outcome to the number of people who not incur the outcome NOT a ratio of the number of people who incur a particular outcome to the total number of people Osteomalacia  low: calcium, phosphate  raised: alkaline phosphatase Oxygen dissociation curve  shifts Left - Lower oxygen delivery - Lower acidity, temp, 2-3 DPG - also HbF, carboxy/methaemoglobin  shifts Right - Raised oxygen delivery - Raised acidity, temp, 2-3 DPG Power = - the probability of a type II error Prolactin - under continuous inhibition Pulmonary surfactant - main constituent is dipalmitoyl phosphatidylcholine (DPPC) Refeeding syndrome causes hypophosphataemia Relative risk = EER / CER Renal tubular acidosis causes a normal anion gap Rheumatoid arthritis - HLA DR4 Rheumatoid factor is an IgM antibody against IgG Rituximab - monoclonal antibody against CD20 SIADH - drug causes: carbamazepine, sulfonylureas, SSRIs, tricyclics Skewed distributions  alphabetical order: mean - median - mode  '>' for positive, ' 4.5 then higher-dose thiazide-like diuretic Inferior MI - right coronary artery lesion JVP: C wave - closure of the tricuspid valve Labetalol is first-line for pregnancy-induced hypertension Methadone is a common cause of QT prolongation Most common cause of endocarditis:   Streptococcus viridans Staphylococcus epidermidis if < months post valve surgery Myoglobin rises first following a myocardial infarction Patent ductus arteriosus - collapsing pulse Patients with established CVD should take atorvastatin 80mg on Prosthetic heart valves - mechanical valves last longer and tend to be given to younger patients Second heart sound (S2)     loud: hypertension soft: AS fixed split: ASD reversed split: LBBB Sudden death, unusual collapse in young person - ? HOCM Tachycardia with a rate of 150/min ?atrial flutter Turner's syndrome - most common cardiac defect is bicuspid aortic valve Ventricular tachycardia - verapamil is contraindicated Young man with AF, no TIA or risk factors, no treatment is now preferred to aspirin Cardiac action potential: phases Phase - efflux of potassium Congenital heart disease Pulmonary valve stenosis is cyanotic Drug adverse effects Amiodarone may cause hyperthyroidism Amiodarone may cause photosensitivity Amlodipine may cause flushing Amiodarone may cause thrombophlebitis Amiodarone may cause slate-grey appearance Spironolactone may cause precipitation of digoxin toxicity Drug indications Cholestyramine , uses include: treatment resistant diarrhoea in Crohn's disease Drug mechanism of action Amiodarone - blocks potassium channels Ticagrelor - antagonist of the P2Y12 adenosine diphosphate (ADP) receptor ECG: coronary territories Ischaemic changes in leads II, III, aVF - right coronary Tall R waves V1-2 - usually left circumflex, also right coronary ECG: pathological changes PR depression – pericarditis Right axis deviation - Wolff-Parkinson-White syndrome (left-sided accessory pathway) Features (cardiovascular disorders) Patent ductus arteriosus - collapsing pulse Heart sounds Reversed split S2 – LBBB Fourth heart sound - aortic stenosis Soft S2 - aortic stenosis Fixed split S2 - atrial septal defect Loud S2 - atrial septal defect Loud S1 - mitral stenosis Third heart sound - constrictive pericarditis Reversed split S2 - WPW type B Reversed split S2 - aortic stenosis Loud S1 - left-to-right shunts Loud S2 - hyperdynamic states Fourth heart sound – HOCM Hypertension levels Blood pressure target (< 80 years, clinic reading) - 140/90 mmHg Blood pressure target (> 80 years, clinic reading) - 150/90 mmHg Definition of stage hypertension (Clinic reading) - 160/100 mmHg Criteria for considering immediate treatment - 180/110 mmHg Definition of stage hypertension (ABPM/HBPM) - 150/95 mmHg Hypertension: next step Poorly controlled hypertension, already taking an ACE inhibitor, calcium channel blocker and a thiazide diuretic K+ > 4.5mmol/l - increase dose of thiazide diuretic Infective endocarditis Colorectal cancer - Streptococcus bovis Patients with no past medical history - Streptococcus viridians Prosthetic valves after two months - Streptococcus viridians JVP An absent Y descent in the JVP may be caused by cardiac tamponade A paradoxical rise in the JVP during inspiration may be caused by constrictive pericarditis Murmurs Atrial septal defect - ejection systolic murmur Graham-Steel murmur (pulmonary regurgitation) - early diastolic murmur, highpitched and 'blowing' in character Ventricular septal defect - holosystolic murmur, 'harsh' in character Mitral regurgitation - holosystolic murmur, high-pitched and 'blowing' in character Pulses Pulsus parodoxus - severe asthma Pulsus parodoxus - cardiac tamponade Slow-rising/plateau pulse - aortic stenosis Collapsing pulse - patent ductus arteriosus Bisferiens pulse - mixed aortic valve disease Collapsing pulse - hyperkinetic states Stereotypical histories (cardiovascular disorders) A 30-year-old man presents with recurrent palpitations and syncope A resting ECG shows T wave inversion in V1-3 and epsilon waves He has a family history of sudden death - arrhythmogenic right ventricular cardiomyopathy A patient develops acute heart failure days after a myocardial infarction A new pansystolic murmur is noted on examination - ventricular septal defect Clinical Hematology and Oncology Activated protein C resistance (Factor V Leiden) is the most common inherited thrombophilia Acute myeloid leukaemia - good prognosis: t(15;17) Acute myeloid leukaemia - poor prognosis: deletion of chromosome or Acute promyelocytic leukaemia - t(15;17) Anaplastic thyroid cancer - aggressive, difficult to treat and often causes pressure symptoms Antiphospholipid syndrome in pregnancy: aspirin + LMWH Antiphospholipid syndrome: (paradoxically) prolonged APTT + low platelets Burkitt's lymphoma - c-myc gene translocation Burkitt's lymphoma is a common cause of tumour lysis syndrome CLL - immunophenotyping is investigation of choice CLL - treatment: Fludarabine, Cyclophosphamide and Rituximab (FCR) CML - Philadelphia chromosome - t(9:22) Cancer patients with VTE - months of LMWH Cetuximab - monoclonal antibody against the epidermal growth factor receptor Chronic myeloid leukaemia - imatinib = tyrosine kinase inhibitor Cisplatin is associated with hypomagnesaemia Colorectal cancer screening - PPV of FOB = - 15% Cyclophosphamide - haemorrhagic cystitis - prevent with mesna Desmopressiin - induces release of von Willebrand's factor from endothelial cells Disproportionate microcytic anaemia - think beta-thalassaemia trait EBV: associated malignancies:    Burkitt's lymphoma Hodgkin's lymphoma nasopharyngeal carcinoma Factor V Leiden mutation results in activated protein C resistance Gastric adenocarcinoma - signet ring cells Gingival hyperplasia: phenytoin, ciclosporin, calcium channel blockers and AML HRT: adding a progestogen increases the risk of breast cancer Hereditary haemorrhagic telangiectasia - autosomal dominant Hodgkin's lymphoma - best prognosis = lymphocyte predominant Hodgkin's lymphoma - most common type = nodular sclerosing ITP - give oral prednisolone IgM paraproteinaemia - ?Waldenstrom's macroglobulinaemia Metastatic bone pain may respond to NSAIDs, bisphosphonates or radiotherapy Myelofibrosis - most common presenting symptom – lethargy Oesophageal adenocarcinoma is associated with GORD or Barrett's Paraneoplastic features of lung cancer   squamous cell: PTHrp, clubbing, HPOA small cell: ADH, ACTH, Lambert-Eaton syndrome Patients with Sjogren's syndrome have an increased risk of lymphoid malignancies Philadelphia translocation, t(9;22) - good prognosis in CML, poor prognosis in AML + ALL 10 Tall, long fingered, aortic pathology, pneumothoraces - Marfan's syndrome STI > arthritis, urethritis, conjunctivitis - reactive arthritis Stereotypical histories (musculoskeletal disorders) A 25-year-old man develops a painful and swollen knee associated with dysuria and conjunctivitis - reactive arthritis A 65-year-old woman presents with aching and morning stiffness in the proximal limb muscles She is having difficulty getting out of a chair - polymyalgia rheumatic A 25-year-old man is admitted to hospital following a pneumothorax On examination he is noted to be tall with arachnodactyly and pectus excavatum Marfan's syndrome Treatment of choice Paget's disease of the bone , treatment of choice: a bisphosphonate 53 Cardiology HOCM TTT 1) Amiodarone 2) Beta-blockers or verapamil for symptoms 3) Cardioverter defibrillator 4) Dual chamber pacemaker 5) Endocarditis prophylaxis Brugada syndrome ICD arrhythmogenic right ventricular dysplasia (ARVD) 1) drugs: sotalol is the most widely Contraindicated  nitrates  ACE inhibitors  inotropes changes may be more apparent following flecainide used antiarrhythmic 2) catheter ablation to prevent ventricular tachycardia Catecholaminergic polymorphic ventricular tachycardia (CPVT) MAT 3) ICD 1) beta-blockers 2) ICD calcium channel blockers Not useful Cardioversion Digoxin SVT 1) 2) 3) 4) Valsalva Maneuver Adenosine If asthmatic give verapamil Electrical cardioversin WPW Definitive treatment: radiofrequency ablation medical therapy: sotalol**, amiodarone, flecainide **sotalol should be avoided if there is coexistent atrial fibrillation may deteriorate into ventricular fibrillation AF Pharmacological cardioversion:  amiodarone if structural heart disease,  flecainide in those without structural heart disease  sotalol Agents used to control rate: 1) beta-blockers 2) calcium channel blockers 3) digoxin Atrial Flutter 1) similar to that of atrial fibrillation although mediction may be less effective 2) atrial flutter is more sensitive to cardioversion however so lower energy levels may be used 3) radiofrequency ablation of the tricuspid valve isthmus is curative for most patients 54 Peri-arrest rhythms Bradycardia If there is adverse signs 1) Atropine is the first line treatment in this situation 2) If this fails to work, or there is the potential risk of asystole then transvenous pacing is indicated If there is a delay in the provision of transvenous pacing the following interventions may be used: 1) atropine, up to maximum of 3mg 2) transcutaneous pacing 3) adrenaline infusion titrated to response peri-arrest tachycardias  If there is any adverse signs then synchronised DC shocks should be given 1) Broad-complex tachycardia Regular:  assume ventricular tachycardia (unless previously confirmed SVT with bundle branch block)  loading dose of amiodarone followed by 24 hour infusion Irregular: Polymorphic VT (e.g Torsade de pointes) - IV magnesium AF with bundle branch block treat as for narrow complex tachycardia 2) Narrow-complex tachycardia Regular:  vagal manoeuvres followed by IV adenosine  if above unsuccessful consider diagnosis of atrial flutter and control rate (e.g Beta-blockers) Irregular:  probable atrial fibrillation  if onset < 48 hr consider electrical or chemical cardioversion  If onset > 48 hr then rate control (e.g Beta-blocker or digoxin) and anticoagulation 55 Anticoagulation  The European Society of Cardiology published updated guidelines on the management of atrial fibrillation in 2012 They suggest using the CHA2DS2-VASc score to determine the most appropriate anticoagulation strategy This scoring system superceded the CHADS2 score  Risk factor Points C Congestive heart failure H Hypertension (or treated hypertension) A2 Age >= 75 years Age 65-74 years D Diabetes S2 Prior Stroke or TIA V Vascular disease (including ischaemic heart disease and peripheral arterial disease) S Sex (female) The table below shows a suggested anticoagulation strategy based on the score:    Score Anticoagulation No treatment Males: Consider anticoagulation Females: No treatment or more Offer anticoagulation Doctors have always thought carefully about the risk/benefit profile of starting someone on warfarin A history of falls, old age, alcohol excess and a history of previous bleeding are common things that make us consider whether warfarinisation is in the best interests of the patient NICE now recommend we formalise this risk assessment using the HASBLED scoring system 56 Risk factor Points H Uncontrolled Hypertension, , systolic BP > 160 mmHg A Abnormal renal function (dialysis or creatinine > 200) Or Abnormal liver function (cirrhosis, bilirubin > times normal, ALT/AST/ALP > times normal for any renal abnormalities S Stroke, history of B Bleeding, history of bleeding or tendency to bleed L Labile INRs (unstable/high INRs, time in therapeutic range < 60%) E Elderly (> 65 years) D Drugs Predisposing to Bleeding (Antiplatelet agents, NSAIDs) Or Alcohol Use (>8 drinks/week) for drugs 57 for any liver abnormalities for alcohol Transient ischemic attack  NICE issued updated guidelines relating to stroke and transient ischemic attack (TIA) in 2008 They advocated use of ABCD2 prognostic score for risk stratifying patient who've had suspected TIA: A Age >60 years point B Blood pressure at presentation >140/90 mmHg point C Clinical features Unilateral weakness points Speech disturbance without weakness point More than 60 minutes points 10-59 minutes point Present point D2 Duration of symptoms Diabetes This gives a total score ranging from to 7: 1) People who have had a suspected TIA who are at a higher risk of stroke (ABCD2 score ≥ 4) should have:  aspirin (300 mg daily) started immediately  specialist assessment and investigation within 24 hours of onset of symptoms  measures for secondary prevention introduced as soon as the diagnosis is confirmed, including discussion of individual risk factors 2) If the ABCD2 risk score is or below:  specialist assessment within week of symptom onset, including decision on brain imaging  if vascular territory or pathology is uncertain, refer for brain imaging 3) People with crescendo TIAs (2 or more episodes in a week)  Should be treated as being at high risk of stroke, even though they may have an ABCD2 score of or below 58 Antithrombotic therapy: (From passmedicine notes)  clopidogrel is recommended first-line (as for patients who've had a stroke)  aspirin + dipyridamole should be given to patients who cannot tolerate clopidogrel  These recommendations follow the 2012 Royal College of Physicians National clinical guideline for stroke  These guidelines may change following the CHANCE study (NEJM 2013;369:11) This study looked at giving high-risk TIA patients aspirin + clopidogrel for the first 90 days compared to aspirin alone 11.7% of aspirin only patients had a stroke over 90 days compared to 8.2% of dual antiplatelet patients  With regards to carotid artery endarterectomy:  recommend if patient has suffered stroke or TIA in the carotid territory and are not severely disabled should only be considered if carotid stenosis > 70% according ECST* criteria or > 50% according to NASCET** criteria Treatment of TIA: (From on examination)  Clopidogrel is the NICE approved treatment of choice for secondary prevention in stroke, but is not licensed for treatment of TIA  NICE TA210 recommends Aspirin and Dipyridamole  It is suggested that all patients are started on Aspirin 300mg, and that a choice is made on future antiplatelet therapy at TIA clinic, depending on symptoms, presence of infarction on CT scan, tolerability of drugs, co morbidities  Clopidogrel may be preferred in patients who cannot tolerate dipyridamole; those with multivascular disease (eg coronary or peripheral vascular disease); those with overt infarction on CT brain  There is no strong evidence regarding appropriate treatment of patient who suffers TIA / stroke whilst on anti-platelet therapy  These drugs reduce, but not eliminate, the risk of recurrent stroke/TIA  Some patients are resistant to anti-platelet effect of Clopidogrel so can consider changing - also consider cardiac investigations looking for embolic source/arrhythmia  There is evidence that early Aspirin is beneficial for 1-14 days, but no evidence for immediate initiation of other antiplatelet drugs 59 Dermatology Bacterial infections Disease Impetigo Causative organism TTT Staphylcoccus aureus Limited, localised disease: or 1) topical fusidic acid is first-line 2) topical retapamulin is used second-line if Streptococcus pyogenes fusidic acid has been ineffective or is not tolerated 3) MRSA: Topical mupirocin (Bactroban) should be used in this situation (Not susceptible to either fusidic acid or retapamulin) Extensive disease: Bullous impetigo / staphylococ cal scalded skin syndrome Cellulitis   Rarely Staphylococcus releases an exfoliating toxin which acts high up in the epidermis:  oral flucloxacillin oral erythromycin if penicillin allergic Both bullous impetigo and SSSS are treated with antistaphylococcal antibiotics (e.g flucloxacillin) and supportive care A) Toxin A:  Causes blistering at the site of infection (bullous impetigo) B) Toxin B  Spreads through the body causing more widespread blistering (staphylococcal scalded skin syndrome, SSSS)  Streptococcus 1) The BNF recommends flucloxacillin as pyogenes and Staphylc first-line treatment for mild/moderate occus aureus are the cellulitis commonest causative 2) Clarithromycin or clindamycin is organisms recommended in patients allergic to  Group penicillin B Streptococcus has a 3) Many local protocols now suggest the predilection for use of oral clindamycin in patients who diabetic patients have failed to respond to flucloxacillin 4) Severe cellulitis should be treated with intravenous benzylpenicillin + flucloxacillin 60 Ecthyma Erythrasma Folliculitis  Streptococcus or Staphylococcus aureus or occasionally both  Phenoxymethylpenicillin (penicillin V) & flucloxacillin (both 500mg 4time/day) 1014 days diphtheroid Corynebacterium minutissimum  Staphylococcus aureus 1) is with topical antiseptics, topical  Topical miconazole or antibacterial are usually effective Oral erythromycin may be used for more extensive infection antibiotics (e.g sodium fusidate) or 2) oral antibiotics (e.g flucloxacillin 500 mg or erythromycin 500 mg both four times daily for 2–4 weeks) Boils (furuncles) Staphylococcus 1) oral antibiotics (e.g erythromycin 500 mg four times daily for 10–14 days) 2) Occasionally need incision and drainage 3) Prophylaxis: Antiseptics such as povidone iodine or chlorhexidine (as soap) and using a bath oil can be useful in prophylaxis Erysipelas Streptococcus pyogenes   Leprosy ‫جذام‬ Mycobacterium leprae IV antibiotics such as benzylpenicillin and erythromycin In penicillin allergic patient a macrolide is the drug of choice WHO recommended triple therapy: 1) rifampicin, 2) dapsone and 3) clofazimine Lupus vulgaris The most common form of cutaneous TB 61 Viral Infections Herpes simplex virus Eczema herpeticum HSV-1 and HSV-2 Management: 1) gingivostomatitis: oral aciclovir, chlorhexidine mouthwash 2) cold sores: topical aciclovir although the evidence base for this is modest 3) Genital herpes: oral aciclovir Some patients with frequent exacerbations may benefit from longer term acyclovir   Severe primary infection of the skin by HSV or It is more commonly seen in children with atopic eczema    Treatment requires systemic anti-virals, for example, aciclovir Systemic antibiotics may be required if lesions are secondarily impetiginised If life threatening, children should be admitted for IV acyclovir Parvovirus B19 (erythrogen ic virus) Molluscum contagiosu m no treatment is recommend in the initial phase due to the benign nature of the condition ‫المليساء المعدية‬ 62 Genital warts condylomata accuminata HPV 6&11 1) Topical podophyllum or cryotherapy is commonly used as first-line treatments depending on the location and type of lesion:  Multiple, non-keratinised warts are generally best treated with topical agents  Solitary, keratinised warts respond better to cryotherapy 2) imiquimod is a topical cream which is generally used second line 3) genital warts:  are often resistant to treatment and recurrence is common  although the majority of anogenital infections with HPV clear without intervention within 1-2 years 63 Fungal infections Pityriasis versicolor Malassezia furfur 1) topical antifungal e.g terbinafine or selenium sulphide 2) extensive disease or failure to respond to (tinea versicolor) Tinea capitis (Scalp ringworm) Tinea corporis (Ringworm) topical treatment then consider oral itraconazole     most common cause is Trichophyton tonsurans in the UK and the USA may also be caused by Microsporum canis acquired from cats or dogs 1) Oral antifungals:  Terbinafine for Trichophyton Trichophyton rubrum and Trichophyton verrucosum (e.g From contact with cattle) oral fluconazole tonsurans infections and  Griseofulvin for Microsporum infections 2) Topical ketoconazole shampoo should be given for the first weeks to reduce transmission Tinea pedis (Athlete's foot) Fungal nail infections 1) dermatophytes: mainly Trichophyton rubrum, accounts for 90% of cases (Onychomyc 2) yeasts: such osis) as Candida 3) non-dermatophyte moulds A) Dermatophyte infection: 1) oral terbinafine is currently recommended first-line 2) Oral itraconazole as an alternative 3) fingernail infections → weeks - months therapy is needed Toenails infections → - months B) Candida infection: 1) mild disease should be treated with topical antifungals (e.g Amorolfine) 2) more severe infections should be treated with oral itraconazole for 12 weeks 64 Infestations Scabies the mite Sarcoptes scabiei 1) permethrin 5% is first-line 2) malathion 0.5% is second-line 3) pruritus persists for up to 4-6 weeks post eradication Crusted seen in patients with (Norwegian) suppressed immunity, especially HIV scabies 1) Ivermectin is the treatment of choice 2) isolation is essential 65 Acne rosacea unknown aetiology 1) topical metronidazole may be used for 2) 3) 4) 5) Acne vulgaris  colonisation by the anaerobic bacterium Propioni-bacterium acnes mild symptoms (i.e Limited number of papules and pustules, no plaques) more severe disease is treated with systemic antibiotics e.g Oxytetracycline recommend daily application of a highfactor sunscreen camouflage creams may help conceal redness laser therapy may be appropriate for patients with prominent telangiectasia A simple step-up management scheme often used in the treatment of acne is as follows: 1) single topical therapy (topical retinoids, benzyl peroxide) 2) combination topical therapy (topical antibiotic, benzoyl peroxide, topical retinoid) 3) Oral antibiotics: e.g Oxytetracycline, doxycycline  Improvement may not be seen for 3-4 months  Minocycline now considered less appropriate due to the possibility of irreversible pigmentation  Gram negative folliculitis may occur as a complication of long-term antibiotic use  high-dose oral trimethoprim is effective if this occurs 4) oral isotretinoin: only under specialist supervision 5) There is no role for dietary modification in patients with acne 66 Seborrhoeic dermatitis in adults Malassezia furfur Scalp disease management: 1) over the counter preparations containing zinc pyrithione ('Head & Shoulders') and tar ('Neutrogena T/Gel') are first-line 2) the preferred second-line agent is ketoconazole (Nizoral) 3) selenium sulphide and topical corticosteroid may also be useful Face and body management: 1) topical antifungals: e.g Ketoconazole 2) topical steroids: best used for short periods 3) difficult to treat - recurrences are common Infectious diseases Palatal petechiae: Infectious mononucleosis Palatal vesicles:  Dengue fever Koplik spots: measles 67 ... most things low  G's and C's raised: growth hormone, glucose, salivary glands, cortisol,cholesterol, carotinaemia Antipsychotics in the elderly - increased risk of stroke and VTE Atypical antipsychotics... Churg-Strauss + others 29 On examination learning points Endocrinology  Hyponatreamia with urine sodium