Transcript 3rd presentation

Faculty of Medicine of the University of Porto
Department of Biostatistics and Medical Informatics
2005/06
Drug Allergy Prevalence
in the Adult Population
Group 13
Table of contents

Introduction
– Aim
Participants and Methods
 Results and Discussion
 Limitations
 Website
 Manuscript

2
Introduction
Adverse reactions to drugs include all non
therapeutic consequences of the drug with
the exception of treatment failures,
intentional or accidental poisoning, and
drug abuse1.
World Health Organization
1 - Joint Task Force on Practice Parameters, the American Academy of Allergy, Asthma and Immunology, and the
Joint Council of Allergy, Asthma and Immunology. Executive summary of disease management of drug
hypersensitivity: a practice parameter. Ann Allergy Asthma Immunol. 1999 Dec;83(6 Pt 3):665-700.
3
Introduction

The terms "drug allergy“, "drug
hypersensitivity" and "drug reaction" are
often used interchangeably2.
– Drug reactions encompass all adverse events
related to drug administration, regardless of
etiology.
– Drug hypersensitivity is defined as an immunemediated response to a drug agent in a
sensitized patient.
– Drug allergy is restricted specifically to a
reaction mediated by IgE.
2 - Riedl MA, Casillas AM. Adverse drug reactions: types and treatment options. Am Fam Physician. 2003 Nov
1;68(9):1781-90.
4
Introduction
Adverse Drug Reactions
Type A (predictable)2,3
Overdosage
 Side effects
 Secondary effects
 Drug-drug interactions

Type B (unpredictable)2,3
Dose independent, not related
with the pharmacologic actions
of the drug, often serious and
can cause death4,5
 Drug hypersensitivity
 Pseudoallergic
 Idiosyncrasy
 Intolerance
2 - Riedl MA, Casillas AM. Adverse drug reactions: types and treatment options. Am Fam Physician. 2003 Nov 1;68(9):1781-90.
3 - Vervloet D, Durham S. Adverse reactions to drugs. BMJ. 1998 May 16;316(7143):1511-4.
5
4 - Gruchalla RS. Drug metabolism, danger signals, and drug-induced hypersensitivity. J Allergy Clin Immunol. 2001 Oct;108(4):475-88.
5 - Gruchalla R. Understanding drug allergies. J Allergy Clin Immunol. 2000 Jun;105(6 Pt 2):S637-44.
Introduction

Drug hypersensitivity reactions are thought
to represent 25% of adverse drug reactions1
1 - Joint Task Force on Practice Parameters, the American Academy of Allergy, Asthma and Immunology, and the
Joint Council of Allergy, Asthma and Immunology. Executive summary of disease management of drug
hypersensitivity: a practice parameter. Ann Allergy Asthma Immunol. 1999 Dec;83(6 Pt 3):665-700.
6
Introduction
Drug hypersensitivity is a common and
complicated problem in clinical practice3,6
Multiple mechanisms of drug-host interaction,
many of which are poorly understood2
Diagnosis of drug hypersensitivity is difficult2,6
Drug-allergic reactions are underdiagnosed6
2 - Riedl MA, Casillas AM. Adverse drug reactions: types and treatment options. Am Fam Physician. 2003 Nov 1;68(9):1781-90.
3 - Vervloet D, Durham S. Adverse reactions to drugs. BMJ. 1998 May 16;316(7143):1511-4.
6 - Demoly P, Kropf R, Bircher A, Pichler WJ. Drug hypersensitivity: questionnaire. EAACI interest group on drug hypersensitivity.
Allergy. 1999 Sep;54(9):999-1003.
7
Introduction




They are the most common iatrogenic illness,
complicating 5 to 15 % of therapeutic drug
courses.2
In the USA, more than 100,000 deaths are
attributed annually to serious adverse drug
reactions.2
3 to 6 % of all hospital admissions are because of
adverse drug reactions.2
6 to 15 % of hospitalized patients in USA
experience a serious adverse drug2 reaction, being
the 4th and 6th leading cause of death of that
patients5
2 - Riedl MA, Casillas AM. Adverse drug reactions: types and treatment options. Am Fam Physician. 2003 Nov 1;68(9):1781-90.
5 - Gruchalla R. Understanding drug allergies. J Allergy Clin Immunol. 2000 Jun;105(6 Pt 2):S637-44.
8
Introduction

The main drugs implicated are antibiotics
and non-steroidal anti-inflammatory drugs3
3 - Vervloet D, Durham S. Adverse reactions to drugs. BMJ. 1998 May 16;316(7143):1511-4.
9
Introduction

Clinical manifestations of drug allergy3:
Anaphylaxis
Urticaria, rhinitis, asthma
Pulmonary
Interstitial pneumonitis, asthma
Hepatic
Acute or chronic hepatitis
Haematological
Haemolytic anaemia,
neutropenia
Renal
Interstitial nephritis, nephrotic
syndrome
Cardiac
Eosinophilic myocarditis
Other
© Dermatology database of
Institute for Biomedical
Informatics, Faculty of
Medicine, Ljubljana, Slovenia
Serum sickness, drug fever
3– Vervloet D, Durham S. Adverse reactions to drugs. BMJ. 1998 May 16;316(7143):1511-4.
10
Introduction
Other studies
The prevalence of self-reported drug allergy
study in a Portuguese population was 7.8%7
 A French study of 2067 adults aged 20-67
years reported that 14.7% gave reliable
histories of systemic adverse drug reactions3

3– Vervloet D, Durham S. Adverse reactions to drugs. BMJ. 1998 May 16;316(7143):1511-4.
Gomes E, Cardoso MF, Praca F, Gomes L, Marino E, Demoly P. Self-reported drug allergy in a general adult Portuguese
population. Clin Exp Allergy. 2004 Oct;34(10):1597-601.
11
Aim
To determine the lifetime prevalence of drug
allergy in the adult population
12
Secondary Aims
Identify the drugs that are most frequently
associated to allergic reactions, (classifying
them using the same system of INFARMED
database – ATC system)
 Describe the different types of allergic
expression
 Relate the allergic reactions already
described with the presence of some
diseases

13
Study participants





Target population - all adult people (above 18
years old) living in Porto region
Available population - all adult people living in
Porto region with telephone in their household
Unit of Analysis – single person
Inclusion Criteria – be an adult, have phone in
their household, live in Porto and have capacities
to answer the questionnaire properly
Exclusion Criteria – see flowchart
14
Flowchart
15
Study design
Observational, cross-sectional and
descriptive study, executed via phone
interviews.
 Data collection method – Phone
interviews, filling up a questionnaire
previously designed
 Sample selection method – two stages
random digit dialling
 Frequency measurement – lifetime
prevalence

16
Random Digit Dialling8
Two Stages RDD Sampling Methods
 Was used relative to the telephone numbers
of Porto region.
 Software randomly selected digits of the type
22xxxxx and generated prefix numbers
 Software randomly selected two digits and
generated suffix numbers

8 - Groves RM, Biemer PP, Lyberg LE, Massey JT, Nicholls WLII, Waksberg J, editors. Telephone Survey Methodology.
New York: John Wiley & Sons, Inc; 2001.
17
Random Digit Dialling
18
Data collection methods
Telephone interview
 Questionnaire

19
Main variables description
Presence of drug allergies in a life time
period
 Reaction type (skin, respiratory, digestive,
others)
 Suspected drug
 Presence of allergic diseases
 Other diseases
 Age
 Sex

20
Statistical Analysis






Descriptive analysis for all the variables.
To determine prevalence proportions graphs and
tables were used.
Qui-square or Fisher’s tests to find associations
between the main nominal variables
Wald test was used to determine an approximated
confidence interval for the principal proportions of
nominal variables.
For all the statistical tests we used a significance
level of 5% (a=0,05), thus a confidence level of
95%
We used the SPSS® 13.0 software
21
Results & Discussion

All phone calls were made between the 2nd
March and 26th April;

The time-table included the period between
9 a.m. and 6.30 pm;

Response rate: 75%
22
Results
23
Sample characterization
24
Next to celebrate birthday?
Amongst the inquired that
were asked about if they
were the next to celebrate
birthday, only 40%
answered negatively.
This results may be due to
the fact that a significant
part of the inquired were old
people living alone.
25
Felt sick due to drug’s intake?
19.7% of the
inquired
mentioned
feeling sick after
taking a drug at
least once during
his/her life.
95% confidence interval: 13% - 26%
26
The interviwed was the next adult to have birthday * Felt sick throughout his/her life after taking a
drug Crosstabulation
The interviwed was the
next adult to have birthday
No
Yes
Total
Count
% within The interviwed
was the next adult to
have birthday
% within Felt s ick
throughout his /her life
after taking a drug
Count
% within The interviwed
was the next adult to
have birthday
% within Felt s ick
throughout his /her life
after taking a drug
Count
% within The interviwed
was the next adult to
have birthday
% within Felt s ick
throughout his /her life
after taking a drug
Felt sick throughout
his/her life after taking
a drug
No
Yes
11
3
Total
14
78,6%
21,4%
100,0%
37,9%
50,0%
40,0%
18
3
21
85,7%
14,3%
100,0%
62,1%
50,0%
60,0%
29
6
35
82,9%
17,1%
100,0%
100,0%
100,0%
100,0%
Chi-Square Tests
Pears on Chi-Square
Continuity Correctiona
Likelihood Ratio
Fisher's Exact Test
Linear-by-Linear
Ass ociation
N of Valid Cas es
Value
,302 b
,008
,297
,293
df
1
1
1
1
Asymp. Sig.
(2-s ided)
,583
,927
,586
Exact Sig.
(2-s ided)
Exact Sig.
(1-s ided)
,664
,456
,588
35
a. Computed only for a 2x2 table
b. 2 cells (50,0%) have expected count less than 5. The minimum expected count is
2,40.
We found no association between
being (or not) the next to celebrate
birthday and having felt sick due to
drug’s intake.
27
Reported allergies & Age groups
Chi-Square Tests
Pears on Chi-Square
Likelihood Ratio
Linear-by-Linear
Ass ociation
N of Valid Cases
Value
1,391 a
1,424
,315
3
3
Asymp. Sig.
(2-s ided)
,708
,700
1
,575
df
150
a. 2 cells (25,0%) have expected count les s than 5. The
minimum expected count is 1,20.
We found no association between the occurence of allergy and the
different age groups.
28
Medical confirmation of drug allergy
95% Confidence interval: 6% - 16%
29
Reported allergies & medical confirmation
30
Drug allergy confirmed by a doctor * Felt sick throughout his/her life after taking a drug
Crosstabulation
Drug allergy confirmed
by a doctor
No
Yes
Total
Count
% within Drug allergy
confirmed by a doctor
% within Felt s ick
throughout his /her life
after taking a drug
Count
% within Drug allergy
confirmed by a doctor
% within Felt s ick
throughout his /her life
after taking a drug
Count
% within Drug allergy
confirmed by a doctor
% within Felt s ick
throughout his /her life
after taking a drug
Felt sick throughout
his/her life after taking
a drug
No
Yes
115
19
Total
134
85,8%
14,2%
100,0%
95,0%
63,3%
88,7%
6
11
17
35,3%
64,7%
100,0%
5,0%
36,7%
11,3%
121
30
151
80,1%
19,9%
100,0%
100,0%
100,0%
100,0%
Chi-Square Tests
There is an association
between the group that have
felt sick due to drug’s intake
and the group that have
medical confirmation of drug
allergy
Pears on Chi-Square
Continuity Correctiona
Likelihood Ratio
Fisher's Exact Test
Linear-by-Linear
Ass ociation
N of Valid Cas es
Value
24,192b
21,122
19,093
24,032
df
1
1
1
1
Asymp. Sig.
(2-s ided)
,000
,000
,000
Exact Sig.
(2-s ided)
Exact Sig.
(1-s ided)
,000
,000
,000
151
a. Computed only for a 2x2 table
b. 1 cells (25,0%) have expected count less than 5. The minimum expected count is
3,38.
31
Allergic reactions confirmed by doctor
$group_confirmed Frequencies
Drug group
- confirmed
a
by doctor
Antiinfectious
CNS
Mus culoskeletal system
Total
Res ponses
N
Percent
6
75,0%
1
12,5%
1
12,5%
8
100,0%
Percent of
Cas es
75,0%
12,5%
12,5%
100,0%
a. Group
$subgroup_confirmed Frequencies
Drug s ubgroup
- confirmed
by
a
doctor
Antibacterial/penicillin
Gout medications
Psycodrugs / Ans iolitics ,
s edatifs and hipnotics
Total
Res ponses
N
Percent
6
75,0%
1
12,5%
Percent of
Cas es
75,0%
12,5%
1
12,5%
12,5%
8
100,0%
100,0%
a. Group
$principle_confirmed Frequencies
Chemical subs tancea
- confirmed by doctor
Total
a. Group
Penicillin
Amoxicillin
Allopurinol
Alprazolam
Res ponses
N
Percent
5
62,5%
1
12,5%
1
12,5%
1
12,5%
8
100,0%
Percent of
Cas es
62,5%
12,5%
12,5%
12,5%
100,0%
32
Thinks that is allergic to drugs?
95% Confidence interval: 11% - 24%
33
Do you think you're alergic to drugs * Felt sick throughout his/her life after taking a drug
Crosstabulation
Do you think you're
alergic to drugs
No
Yes
Total
Count
% within Do you think
you're alergic to drugs
% within Felt s ick
throughout his /her life
after taking a drug
Count
% within Do you think
you're alergic to drugs
% within Felt s ick
throughout his /her life
after taking a drug
Count
% within Do you think
you're alergic to drugs
% within Felt s ick
throughout his /her life
after taking a drug
Felt s ick throughout
his/her life after taking
a drug
No
Yes
104
13
Total
117
88,9%
11,1%
100,0%
92,0%
44,8%
82,4%
9
16
25
36,0%
64,0%
100,0%
8,0%
55,2%
17,6%
113
29
142
79,6%
20,4%
100,0%
100,0%
100,0%
100,0%
Chi-Square Tests
Pears on Chi-Square
Continuity Correctiona
Likelihood Ratio
Fisher's Exact Test
Linear-by-Linear
Ass ociation
N of Valid Cas es
Value
35,454b
32,274
29,464
35,204
df
1
1
1
1
Asymp. Sig.
(2-s ided)
,000
,000
,000
Exact Sig.
(2-s ided)
Exact Sig.
(1-s ided)
,000
,000
,000
142
There is an association
between the group that have
felt sick due to drug’s intake
and the group that thinks they
have allergy to drugs
a. Computed only for a 2x2 table
b. 0 cells (,0%) have expected count les s than 5. The minimum expected count is
5,11.
34
Drugs that people think they are allergic
$group_thinkallergic Frequencies
Drug group
- Thinksa
allergic
Antiinfectious
Blood
CNS
Anti-allergic
Mus culoskeletal system
Total
Res ponses
N
Percent
7
46,7%
2
13,3%
4
26,7%
1
6,7%
1
6,7%
15
100,0%
Percent of
Cas es
50,0%
14,3%
28,6%
7,1%
7,1%
107,1%
$subgroup_thinkallergic Frequencies
a. Group
drug
s ubgroup
- Thinksa
allergic
$principle_thinkallergic Frequencies
Chemical
s ubstance
- Thinksa
allergic
Total
Penicillin
Acetylsalicylic acid
Metamizol magnes ium
Paracetamol
Amoxicillin
Cetirizine
Maprotiline
Allopurinol
Alprazolam
Res ponses
N
Percent
6
40,0%
2
13,3%
1
6,7%
1
6,7%
1
6,7%
1
6,7%
1
6,7%
1
6,7%
1
6,7%
15
100,0%
Percent of
Cas es
42,9%
14,3%
7,1%
7,1%
7,1%
7,1%
7,1%
7,1%
7,1%
107,1%
Total
Antibacterial/penicillin
Anticoagulant/
Antithrombotics Anticoagulant
Analges ic/Antipiretic
Antihis taminics -Non
s edantig antihistaminics
PsycodrugsAntidepres sives
Gout medications
Psycodrugs / Ans iolitics ,
s edatifs and hipnotics
Res ponses
N
Percent
7
46,7%
Percent of
Cas es
50,0%
2
13,3%
14,3%
2
13,3%
14,3%
1
6,7%
7,1%
1
6,7%
7,1%
1
6,7%
7,1%
1
6,7%
7,1%
15
100,0%
107,1%
a. Group
a. Group
35
Analysis confirmation?
16,4% of the inquired did some test or analysis
to confirm drug allergy
23,3% of the people who have felt sick after
taking a drug did some test or analysis
36
Allergic diseases
37
Existence of allergy disease * Felt sick throughout his/her life after taking a drug
Crosstabulation
Allergy to drugs & Allergic diseases
Felt s ick throughout
his/her life after taking
a drug
No
Yes
100
22
Total
allergy inquired
No
Count answered they had an122
17,8Exis
%tence
ofof the
allergy disease
disease
Yes
Total
% within Exis tence of
allergy dis ease
% within Felt s ick
throughout his /her life
after taking a drug
Count
% within Exis tence of
allergy dis ease
% within Felt s ick
throughout his /her life
after taking a drug
Count
% within Exis tence of
allergy dis ease
% within Felt s ick
throughout his /her life
after taking a drug
82,0%
18,0%
100,0%
82,6%
78,6%
81,9%
21
6
27
77,8%
22,2%
100,0%
17,4%
21,4%
18,1%
121
28
149
81,2%
18,8%
100,0%
100,0%
100,0%
100,0%
Chi-Square Tests
Pears on Chi-Square
Continuity Correctiona
Likelihood Ratio
Fisher's Exact Test
Linear-by-Linear
Ass ociation
N of Valid Cas es
Value
,254 b
,054
,246
,253
df
1
1
1
1
Asymp. Sig.
(2-s ided)
,614
,817
,620
Exact Sig.
(2-s ided)
Exact Sig.
(1-s ided)
,594
,395
,615
149
However, we couldn’t establish an association
between the occurrence
b. 0 cells (,0%) have expected count les s than 5. The minimum expected count is 38
of allergic disease and having felt sick5,07.
due to drug’s intake.
a. Computed only for a 2x2 table
Other allergies?

21,7% stated they had other kinds of allergy
such as allergy to pollen, food, dust,
animals.
39
Allergic to how many drugs?

Majority of the inquired was allergic to one
or two drugs
40
Frequency of allergy symptoms according to
type of reaction
41
Looked for medical assistance?
67% of those who have felt sick after taking a drug stated that they
looked for medical assistance.
42
Need medical assistance?
43
Need medical treatment?
30% of those who have felt sick after taking a drug stated that they
needed medical treatment.
44
Need medical treatment?
45
Prevalences
95% Confidence interval: 13% - 26%
95% Confidence interval: 11% - 24%
95% Confidence interval: 6% - 16%
The prevalence of self-reported drug allergy study in a Portuguese population was
7.8%7 whereas a French study reported that 14.7% gave reliable histories of
systemic adverse reactions to one or more drugs3.
Whether these results reflect population differences or study bias we can’t precise
with the present data. The elaboration of studies in what matters to this theme seems
therefore appropriate and necessary.
3– Vervloet D, Durham S. Adverse reactions to drugs. BMJ. 1998 May 16;316(7143):1511-4.
7 - Gomes E, Cardoso MF, Praca F, Gomes L, Marino E, Demoly P. Self-reported drug allergy in a general adult Portuguese
population. Clin Exp Allergy. 2004 Oct;34(10):1597-601.
46
Main limitations
Telephone interviews may not be accurate
enough to determine whether a reaction
were really of hypersensitivity or not
 People living in Porto, without a telephone at
home are excluded
 Interviews were done in a restricted period of
time
 Very low household rate

47
Discussion - difficulties

Questionnaire problems:
– excessive extension;
– complexity of phrasal structure and lexicon;
– too many similar questions led to some confusion.

Cooperation of the inquired population:
– difficulties to understand what was being said (advanced
age);
– lack of time (active class);
– people were afraid.

Slanting of the inquired population due to the
impossibility of making phone calls during all day:
– phone calls made only in the morning and afternoon;
– many of the population inquired was of advanced age;
– active population excluded.
48
Discussion - difficulties

Difficulties to contact the resident:
– the person who answered the phone didn’t live in that domicile and
was incapable to inform about the best hour to further contacts;
– Most of the times, the person who was next to celebrate birthday
was impossible to reach;
Random Digit Dialling disadvantages:
 Lots of unfruitful phone calls:
– most of the numbers dialled were not valid (nonattributed/commercial);
– phone numbers were valid not residences;
– this lead to a waste of precious time;

Even when the first combination of prefix and suffix was a
residence, the many of next ones weren’t:
– we had to make dozens of phone calls with the same prefix to
obtain five residences.
49
Conclusions

Our results showed a prevalence of adverse
drug reactions in the adult population of
13%-26%.

However, only 6%-16% were confirmed as
an allergy by a doctor.
50

The drugs that were most frequently
associated to allergic reactions were mainly
the antiinfectious drugs, such as Penicillin.

The most frequent type of allergic
expression was cutaneous reaction.
51
Gantt chart

Microsoft Project
52
Website
53
Manuscript
54
References
1 - Joint Task Force on Practice Parameters, the American Academy of Allergy, Asthma and
Immunology, and the Joint Council of Allergy, Asthma and Immunology. Executive
summary of disease management of drug hypersensitivity: a practice parameter. Ann
Allergy Asthma Immunol. 1999 Dec;83(6 Pt 3):665-700.
2 - Riedl MA, Casillas AM. Adverse drug reactions: types and treatment options. Am Fam
Physician. 2003 Nov 1;68(9):1781-90.
3 - Vervloet D, Durham S. Adverse reactions to drugs. BMJ. 1998 May 16;316(7143):1511-4.
4 - Gruchalla RS. Drug metabolism, danger signals, and drug-induced hypersensitivity. J
Allergy Clin Immunol. 2001 Oct;108(4):475-88.
5 - Gruchalla R. Understanding drug allergies. J Allergy Clin Immunol. 2000 Jun;105(6 Pt
2):S637-44.
6 - Demoly P, Kropf R, Bircher A, Pichler WJ. Drug hypersensitivity: questionnaire. EAACI
interest group on drug hypersensitivity. Allergy. 1999 Sep;54(9):999-1003.
7 - Gomes E, Cardoso MF, Praca F, Gomes L, Marino E, Demoly P. Self-reported drug allergy
in a general adult Portuguese population. Clin Exp Allergy. 2004 Oct;34(10):1597-601.
8 - Groves RM, Biemer PP, Lyberg LE, Massey JT, Nicholls WLII, Waksberg J, editors.
Telephone Survey Methodology. New York: John Wiley & Sons, Inc; 2001.
55
The End