WEEK 11 Flashcards
What is allergic asthma?
Recurrent reversible airway obstruction with attacks of wheezing, shortness of breath & often a nocturnal dry cough
- airway inflammation, bronchial hyper-resposiveness
What is the pathogenesis of asthma?
activation of Th2 profile of cytokine production in genetically susceptible people
- it attracts eosinophils to mucosal surface
- IL-5 & GMCSF cause eosinophils to produce cysteinyl leukotrienes & release granule proteins
- IgE synthesis promoted & expression of IgE receptors on mast cells & eosinophils
What are important mediators in asthma?
- leukotriene B4 and cysteinyl- leukotrienes IL-4, 5 and 13, and tissue damaging eosinophil proteins
What is used to monitor the treatment of asthma?
Peak expiratory flow rate
- also FEV, O2 sats and arterial blood gases
What are the 5 main classes of drugs used to treat asthma?
- Beta 2 adrenoreceptor agonists
- Anti - inflammatories
- Cysteinyl leukotriene antagonists (LTRA)
- Methylxanthines
- Anti-IgE treatment
Give examples of Beta 2 adrenoreceptor agonsts.
SABA e.g. salbutamol (lasts 3-5 hrs)
LABA e.g. salmeterol (lasts 8-12 hrs)
Give examples of inflammatory mediators. What is their action ?
GLUCOCORTICOIDS e.g. beclometasone, budesonide
- they prevent progression of chronic asthma
- decrease: formation of cytokines, generation of vasodilators and activation of eosinophils
- in deteriorating asthma, oral (prednisolone) or IV (hydrocortisone) can be given
Give an example of a cysteinyl leukotriene antagonist. What is its MoA?
Montelukast
- antagonises only CysLT1 which decreases exercise induced asthma and decreases early and late allergen responses, relaxes airways in mild asthma and decreases acute reactions to aspirin
- is used mainly as an add on to ICS and LABAs
What are methylxanthines? What are they used for?
Theophylline and its derivatives
- theophylline = increases cyclic nucleotides in cell to relax smooth muscle
- uniphyllin orally in addition to steroids for COPD
- rarely it is used IV aminophylline in acute severe asthma
Give an example of an anti-IgE treatment drug.
Omalizumab
What is the steps/process for treating acute severe asthma?
IMMEDIATE TREATMENT (adults)
- O2 (sats kept at 94-98%)
- salbutamol or terbutaline plus ipratropium via nebuliser
- IV hydrocortisone or prednisolone tablets
IF NO IMPROVEMENT IN PT
- IV magnesium sulphate
- switch from nebulised to IV salbutamol or aminophylline
MONITOR BLOOD GASES and PT EXHAUSTION/ALERTNESS
What is ipratropium? What is it used for?
SAMA used for some COPD patients, especially the long acting (LAMA) version - tiotropium
- rarely used in asthma
- used for cough caused by irritant stimuli
- decreases augmentation of mucus secretion and may increase bronchial secretion clearance
- not selective for one muscarinic type
- used for bronchospasm precipitated by beta blockers
- not effective against allergen challenge
What does PICO stand for?
Patient
Intervention
Comparison
Outcome
What is the 3 points for the ‘anatomy’ of a good question?
- Define who the q is about
- Define which option you’re considering (drug treatment) and a possible comparison (placebo or stnd therapy)
- Define desired (or undesired) outcome
What are the 3 types of information resources? (HINT: put in order of importance/priority)
- Systematic Reviews and Meta-analyses
- cochrane reviews, 2ndary sources of info - Clinical practice guidelines
- NICE and SIGN - Original article containing primary research data (RCT)
What is hypothesis construction? What is the difference between a null and alternative hypothesis?
Is one set of data different from another?
NULL = 2 sets of data from same population and NOT different
ALTERNATIVE = 2 sets of data from different population and are different
What are the 2 types of quantitative data? Describe them.
DISCRETE - can only have certain numerical values
CONTINUOUS - don’t have discrete steps
What are the categorical variables? Describe them.
NORMAL (unordered categories)
- male/female, green/blue eyes, alive/dead
ORDINAL (ordered categories)
- objective: heavy, moderate or light drinkers, grade of breast cancer
- subjective: health status questionnaires
What is hypothesis testing? What is the P value? What does a P of 0.1 mean? What value of P means a null hypothesis can be rejected?
Assume null hypothesis and determine the probability that the null hypothesis is correct: P value
P of 0.1 = 10% chance null hypothesis is correct
If P<0.05 then null hypothesis can be rejected as there’s a statistically significant difference
What is a (i) type I (ii) type II error?
(i) Rejecting null hypothesis when it is true (false +ve)
- concluding there’s an effect when there isn’t
(ii) NOT rejecting null when it’s false (false -ve)
- concluding there’s no effect when there is
What is the power of a test?
Its ability to reject a null hypothesis when it is false
- the capacity to detect an effect if one present
What is the pathogenesis of AMI?
Atherosclerotic plaque destabilisation
- rupture or erosion
- platelet adherence and aggregation
- intracoronary coagulation
What are the 4 complications of an acute myocardial infarction?
- ARRHYTHMIA
- bradycardia = heart block
- tachycardia = AF, VT, VF - MYOCARDIAL DEATH
- pericarditis, VSD, free wall rupture, papillary muscle necrosis - LV THROMBUS and EMBOLISATION
- HEART FAILURE
- pump failure
- LV dilatation
- LV aneurysm
How do you know if someone is dead?
- Cessation of the CIRCULATION
- no pulses
- no cardiac activity (no heart sounds or electrical activity) - Cessation of RESPIRATION
- Cessation of CEREBRAL function
- fixed dilated pupils (don’t constrict in response to a light stimulus)
What is the pathology of myocardial infarction? (HINT: there’s 4 points)
- Myocyte death
- Coagulation
- Inflammation
- neutrophil recruitment
- monocyte recruitment and macrophage formation
- digestion and removal of debris - Granulation and scar formation
Why is the association of psychological factors to asthma important?
Asthma related deaths Near fatal asthma Brittle asthma Non-compliance A&E visits
What are the main psychological factors of significant importance with relation to asthma?
depression
anxiety
panic
denial
What is the prevalence of anxiety within asthma children/adolescents? What does the expression of fear allow for?
up to 33% meet the criteria for comorbid anxiety disorders
Allows for appropriate psychological formation
- provision of information, discussion of accuracy, planned intervention and treatment plan
How do you encourage the exploration of fears?
attentive listening
comforting guidance
quiet and accepting presence
What is breathlessness a symptom of? What is it seen/explained as?
Respiratory disease AND panic attacks
- seen as complex interplay between between emotional, psychological, physical and functional factors
Describe the association of asthma and avoidance of it as a disease.
12-20 % pts refuse to accept asthma diagnosis
- avoidance is good short term (3 days) but long term it leads to more anxiety and depression, reduces physical functioning and more discomfort
What are the illness representations within Leventhals “Common Sense Model”?
- IDENTITY: name, signs and symptoms
- CAUSE: internal or external
- CONSEQUENCES: physical, social, economic, emotional
- TIMELINE: acute, recurrent, chronic
- CURE/CONTROL
What does the process of finding a cause for an asthma attack help patients with?
To make sense of their illness experience to guide their future self-management
Why is self-management important?
Prevents exacerbations
Improves care
Is a cost effective investment for healthcare services
What is a confidence interval?
It describes the uncertainty of the point estimate (mean)
- a range of values in which we can be relatively sure that the true effect lies
Why is confidence intervals better than P values? (HINT: there’s 4 points)
- Gives range of possible effect sizes
- Embraces the value of no difference between treatments (not significantly different from control)
- Help interpret clinical trial data by placing upper and lower bounds on true effect size
- Statistically significant doesn’t mean clinically important - the size of the effect determines importance
What are the 3 ways to measure the effectiveness of interventions?
- Number needed to treat (NNT)
- Relative risk
- Odds Ratio
State the ARR and the NNT for the following:
10000 men NOT given thrombolytic treatment after heart attack - 1000 deaths after 6 weeks
10000 men given thrombolytic treatment after heart attack - 800 deaths after 6 weeks .
Treatment saves 200/10000 lives (=ARR)
ARR = 0.02
NNT = (1/ARR) 50
=> need to treat 50 people for 1 of them to avoid dying within 6 weeks
How is the (i) probability (ii) odds calculated?
(i) no. favourable outcomes/ total no. possible outcomes
ii) no. favourable outcomes (successes) / no. unfavourable outcomes (failures
What is the (i) RRR (ii) ARR?
(i) 1 - relative risk
ii) risk difference (divide by 100 if %
What is the NNT the reciprocal of?
ARR
What are the 5 key EBM concepts?
- Evidence pyramid
- Clinical research study designs (strengths and weaknesses)
- Asking Qs and finding answers
- Basic statistics (variable types, P values, CI)
- Effectiveness of interventions (NNT, RR, odds ratio, forest plots)
