Week 11 Flashcards
1
Q
Describe Asthma?
A
- Recurrent, reversible airway obstruction
- Attacks of wheezing, shortness of breath
- Often nocturnal dry cough
2
Q
What is the pathogenesis of asthma in genetically susceptible people?
A
Activation of the Th2 profile of cytokine production
3
Q
What happens when the Th2 are activated in asthma?
A
- Attracts inflammatory granulocytes (eosinophil) to mucosal surface
- IL-5 & GMCSF cause eosinophils to produce cysteinyl leukotrienes & release granule proteins
- IgE synthesis is promoted, as is expression of IgE receptors on mast cells and eosinophils
4
Q
What are the important mediators in the pathogenesis of asthma?
A
- Leukotriene B4 & cysteinyl-leukotrienes (C4 & D4)
- Interleukins IL-4, IL-5, IL-13
- Tissue damaging eosinophil proteins
5
Q
What does GMCSF mean?
A
Granulocyte macrophage colony stimulating factors
6
Q
What would the cross section of a bronchiole in severe asthma show?
A
- Dilated blood vessels
- Thickened BM
- Mucus plug with eosinophils & desquamated epithelial cells
- Infiltration of inflammatory cells (mononuclear, eosinophils etc)
- Oedema
7
Q
How is the treatment for asthma measured?
A
Measuring the Peak expiratory flow rate.
also forced expiratory volume, oxygen saturation & arterial blood gases
8
Q
What are the eliciting agents of the Immediate phase of allergic asthma and what cells do they stimulate?
A
- Allergen, Non-specfic stimulus
- Stimulates Mast cells, mononuclear cells
9
Q
What happens in the Immediate phase of allergic asthma?
A
Bronchospasm
10
Q
How is the Immediate phase of allergic asthma reversed/treated?
A
- Beta2-adrenoceptor agonists
- CysLT-receptor antagonists
- Theophylline
11
Q
What are the eliciting agents of the Late phase of allergic asthma?
A
Chemotaxins & chemokines from immediate phase allergic asthma
12
Q
What happens in the late phase of allergic asthma?
A
- Infiltration of cytokine-releasing Th2 cells & monocytes
- Activation of inflammatory cells (eosinophils)
13
Q
What is the result of late phase allergic asthma?
A
- Airway inflammation
- Airway hyper-reactivity
- Bronchospasm, wheezing, coughing
14
Q
How is the late phase of allergic asthma reversed/treated?
A
Glucocorticoids
15
Q
What are the 5 different types of treatment / preventative medicines for asthma?
A
- Beta2 adrenoceptor agonists (SABA, LABA)
- Anti-inflammatory agents
- Cysteinyl leukotriene antagonists (LTRA)
- Methylxanthines
- Anti-IgE treatment
16
Q
How do Beta-adrenoreceptor agonists work?
A
Dilate bronchi via smooth muscle B2 receptors
17
Q
What does Short acting (SABA) do?
ie. Salbutamol
A
- Given by inhalation
- Immediate effects & lasts 3-5hrs
- “Rescue remedy” treats wheeze in patients
18
Q
What does Long acting (LABA) do?
ie. Salmeterol
A
- Lasts 8-12hrs
- Prevents bronchospasm (at night/during exercise) in patients requiring long-term therapy
19
Q
What are the main drugs used for anti-inflammatory action in asthma?
A
Glucocorticoids (ICS)
20
Q
What do Glucocorticoids do and don’t do?
A
- Prevent progression on chronic asthma
- Don’t prevent immediate response to allergen
21
Q
What do Glucocorticoids decrease?
A
- Formation of cytokines (released by Th2 lymphoctyes)
- Vasodilators such as prostaglandins by inhibiting COX
- Activation of eosinophils
22
Q
What do you give in deteriorating asthma?
A
Oral (prednisolone) or IV (hydrocortisone)
23
Q
What is the main inhaled Glucocorticoid?
A
Beclometasone
24
Q
How do cysteinyl-leukotriene receptor antagonists work?
A
- Cloned cysteinyl-leukotriene receptors CysLT1 & CysLT2 are expressed on respiratory mucosa and infiltrating inflammatory cells
- Lukast drugs antagonize only CysLT1
25
Give an example of a Lukast drug?
Montelukast
26
What do Lukast drugs do?
- Decrease exercise-induced asthma and decrease early & late phase responses
- Relax airways in mild asthma
- Mainly used as add-on to ICS & LABAs
- Decrease acute reactions to aspirin
27
Give an example of a Methylxanthine?
Theophylline
28
What is Theophylline and what does it do?
- Cyclic nucleotide phosphodiesterase inhibitor
| - Increases cyclic nucleotides in the cell to relax smooth muscle
29
What drug used to treat COPD comes under the Methylxanthine family?
Uniphyllin
| oral sustained release formulations used in addition to steroids
30
What Methylxanthine drug is rarely used as an IV drug in acute severe asthma?
Aminophylline
31
What is the immediate treatment for acute severe asthma?
- Oxygen (maintain SpO2 at 94-98%)
- Salbutamol or terbutaline + ipratropium via nebuliser
- IV hydrocortisone or prednisolone tablets
32
What would you do if patient was still not improving with immediate treatment for acute severe asthma?
- IV magnesium sulphate
| - Switch nebulised to IV salbutamol or aminophylline
33
Describe Ipratropium?
- Its a SAMA for COPD
- Rarely used for asthma
- Used for cough by irritant stimuli
- Decreases augmentation of mucous secretion & increase clearance of bronchial secretions
- Not effective against allergen challenge
- Not selective for 1 muscarinic receptor type
- Used for bronchospasm precipitated by beta-blocker
34
What is Tiotropium?
LAMA version of Ipratropium
35
When constructing a clinical question what does PICO stand for?
- Patient/Population/Problem
- Intervention
- Comparison (if any)
- Outcome
36
What is the "Anatomy" of a good question?
1. Define precisely who the question is about
2. Define which option you are considering and possible comparison
3. Define the desired outcome
37
What do systematic reviews/meta-analyses come under in information resources?
Secondary sources of information vetted by independent researchers and clinicians
38
What are Clinical Practice Guidelines?
Reviews covering large disease groups & treatment strategies (NICE & SIGN guidelines)
39
What do you look at when trying to answer a clinical question?
1. Start with- Cochrane Reviews, NICE & SIGN guidelines
| 2. Then use- Medline (Ovid, PubMed), google Scholar
40
What is a "Null Hypothesis"?
Two sets of data are from the same population and not different
41
What is an "Alternative Hypothesis"?
Two sets of data are from different populations and are different
42
What is discrete quantitative data?
Can only have certain numerical values (number of children)
43
What is continuous quantitative data?
Do not have discrete steps (height & weight)
44
What are nominal (unordered) categorical variables?
- Male/female
- Green/blue eyes
- Alive/dead
45
What are ordinal (ordered) categorical variables?
- Objective: heavy, moderate or light drinkers, grade of breast cancer
- Subjective: health status questionnaires (good, average, terrible)
46
How do we test the hypothesis?
- Assume the null hypothesis
| - Determine the probability that the null hypothesis is correct (P Value)
47
What is the P value?
P value of 0.1 means there is a 0.1 probability/10% chance/1 in 10 chance that the null hypothesis is correct
48
What is the P value cut off that indicates the null hypothesis should be rejected?
If P < 0.05 then there is a statistically significant difference (1 in 20 chance)
49
What does a P value > 0.10 mean?
- Greater than 10%
- No evidence against the null hypothesis
- Data consistent with null hypothesis
- Not significant
50
What does a P value > 0.05 mean?
- Greater than 5%
- Weak evidence against null hypothesis in favour of alternative
- Not significant
51
What does a P valve < 0.05 mean?
- Less than 5%
- Moderate evidence against null hypothesis in favour of alternative
- Significant
52
What does a P value < 0.01 mean?
- Less than 1%
- Strong evidence against the null hypothesis in favour of alternative
- Highly significant
53
What does a P value < 0.001 mean?
- Less than 0.1%
- Very strong evidence against null hypothesis in favour of alternative
- Very highly significant
54
What is a Type I error?
- Rejecting the null hypothesis when it is true (false positive)
- Concluding there is an effect when there isn't
- P is small
55
What is a Type II error?
- Not rejecting the null hypothesis when it is false (false negative)
- Concluding there is no effect when there is
- P is large
56
What is the relationship between analyte concentration and null hypothesis?
No difference in analyse concentration between healthy and sick
57
What is the relationship between analyte concentration and alternative hypothesis?
Difference in analyte concentration between healthy and sick
58
What is the Power of a test?
- Its ability to reject the null hypothesis when it is false
| - Capacity to detect an effect if one is present
59
What is the treatment for an STEMI and anteroseptal transmural MI?
Primary Percutaneous Coronary Intervention (PPCI)
60
What is the pathogenesis of AMI (acute myocardial infarction)?
- Atherosclerotic plaque destabilisation
- Rupture/erosion
- Platelet adherence & aggregation
- Intracoronary coagulation
61
What are the characteristics of an Unstable Plaque?
- Few SMCs
- Thin fibrous cap
- Inflammatory cells
- Eroded endothelium
- Activated macrophages
62
What are the characteristics of a Stable Plaque?
- More SMCs
- Thick fibrous cap
- Lack of inflammatory cells
- Foam cells
- Intact endothelium
63
What is the drug treatment for a MI?
- Aspirin
- Ticagrelor
- Ramipril
- Bisoprolol
- Simvastatin
64
What can cariogenic shock be secondary to?
- Ventricular septal rupture
- Acute mitral valve regurgitation (papillary muscle necrosis)
- Acute LV rupture
65
What is a Bradycardia?
Heart block
66
What is a Tachycardia?
- Atrial fibrillation
- Ventricular tachycardia
- Ventricular fibrillation
67
What can be the cause of Myocardial death?
- Pericarditis
- VSD
- Free wall rupture
- Papillary muscle necrosis
68
What are the different heart failures?
- Pump failure
- LV dilatation
- LV aneurysm
69
How do you know if someone is dead?
- Cessation of the circulation (no pulses, no cardiac activity)
- Cessation of respiration
- Cessation of cerebral function (fixed dilated pupils)
70
What do you need to do after pronouncing someone is dead?
- Inform family
- Inform coroner/procurator before certification of death
- Leave all lines/tubes devices in place
71
Give some examples of deaths that should be reported to the coroner?
- Cause of death unknown
- Death was violent or unnatural
- Death was sudden
- Deads within 24hrs of hospital admission
- If there is a possibility that the person took their own life
72
What is the pathology of MI?
- Myocyte death
- Coagulation
- Inflammation (neutrophil recruitment, monocyte & macrophage formation, digestion & removal of debris)
- Granulation and scar formation
73
Describe asthma as a chronic condition and its statistics?
- 7-10% children, 5% adults
- Psychological and physical morbidity
- Societal costs
- Morbidity & mortality increasing
74
What is the SIGN 141 policy?
- British guidance on the management of asthma
| - Covers asthma control with different client groups and outlines helpful interventios
75
What are the different types of assessments for asthma?
- Royal College of Physicians of London 3 questions
| - Asthma Control Test (ACT)
76
Why are Psychological factors of asthma important?
- Impact on disease process due to adherence to treatment and taking in information
- Depression & anxiety
- Consistently reduced quality of life
77
What are the psychological factors in asthma control?
- Convincing evidence of association of psychological factors with asthma related deaths, near fatal asthma, brittle asthma, non-compliance and A&E visits
- Depression, anxiety, panic and denial
78
What are the 3 psychological emotions asthmatic patients can have?
- Depression
- Panic
- Denial
79
What are the psychological cognitive factors asthmatic patient can have?
- Reduced confidence
| - Beliefs around vulnerability
80
Define Anxiety?
State of intense apprehension, uncertainty, and fear resulting from the anticipation of a threatening event or situation, often to a degree that normal physical and psychological functioning is disrupted
81
What are the psychological cues of anxiety?
- Thoughts that something bad is going to happen
- Fear of losing control
- Sense of dread, impending doom
- Loss of confidence
82
What are the behavioural cues of anxiety?
- Fidgeting
- Hesitation
- Avoidance
- Shaking
83
What are the cognitive cues of anxiety?
- Difficulties with concentration and attention
| - Memory problems, forgetful
84
What is breathlessness a symptom of?
Both respiratory disease & panic attacks
85
List some models testing asthma control?
- Impairment Disability Triad (WHO)
- International classification of function- Interaction of concepts (WHO 2001)
- Biomedical model
- Biopsychosocial model (Engel, 1977)
- Leventhal's Self-regulation model/Common Sense Model
86
Describe the different elements of Illness representation in the Common Sense Model/Leventhal's self-regulation?
1. Identity- name, signs & symptoms
2. Cause- internal or external
3. Consequences- physical, recurrent, chronic
4. Time-line- acute, recurrent, chronic
5. Cure/Control
87
Why do asthmatic patients need to be able to self manage their illness?
- Fluctuating nature of asthma means patients need to acquire decision-making skills to respond appropriately to changes in symptom control
- Patients need to be aware of bodily changes and to respond accordingly
88
What is a confidence interval?
Gives estimated range of values which is likely to include an unknown population parameter, the estimated range being calculated from a given set of sample data
89
Why are confidence intervals better than hypothesis tests?
More informative than hypothesis tests since they provide range of plausible values for the unknown parameter
90
What is the point estimate?
- Usually the mean
- Indicates magnitude of the effect of the experimental intervention compared to the control intervention
- Confidence interval describes the uncertainty of this estimate
91
What does the confidence interval describe?
Describes the range of values within which we can be reasonably sure that the true affect actually lies
92
What does a narrow confidence interval tell you?
The level of confidence in result is higher
93
What does a wide confidence interval tell you?
The level of confidence in results is lower
94
Why are confidence intervals better than P values?
- Give a range of possible effect sizes
- Embrace the value of no difference between treatments
- Help interpret clinical trail data by placing upper an lower bounds on the true effect size
- Statistically significant does not mean clinically important, the size of the effect determines importance
95
What does SIR mean?
Standardised infection rate
96
What are the 3 ways you can measure the effectiveness of interventions?
1. Number needed to treat (NNT)
2. Relative risk (RR)
3. Odds ratio
97
What is the number needed to treat (NNT)?
Treatment specific and describes the difference between treatment and control in achieving a particular clinical outcome
98
Describe the NNT & ARR of this example:
100 people given an analgesic tablet- 70 have pain relieved
Same 100 given placebo- 20 had pain relieved.
- Analgestic is responsible for 70-20= 50 of the 100 people obtaining pain relief
- Absolute risk reduction (ARR) is 50/100
- NNT is the reciprocal of ARR ie. 100/50
- NNT is 2, meaning 2 people have to be treated for one to obtain effective pain relief!
99
What 7 elements are in a forest plot?
1. List of individual studies
2. Each square represents an individual study
3. Line of no effect
4. X-axis scale: logarithmic for ratios (odds, risk ratio). Linear for differences
5. Combined results for all the studies
6. Length of the horizontal line is the 95% confidence interval
7. Size of square is proportional to the study weight
100
What are the 5 key EBM concepts?
1. Evidence pyramid
2. Clinical research study designs (strengths & weaknesses)
3. Asking questions and finding answers
4. Basic statistics (variable types, P values & confidence intervals)
5. Effectiveness of interventions (NNT, RR, odds ratio & forest plots)
101
What is a Forest plot?
Graphical representation of a meta-analysis
102
What % of confidence interval do we use in medicine?
95%
103
What is the equation for the probability?
Number of favourable outcomes / Total number of possible outcomes
104
What is the equation for the odd?
Number of favourable outcomes (successes) / Number of unfavourable outcomes(failures)
