X3- Papers Exercises
Hein Stigum
How to answer the questions
Reading a paper in epidemiology is easier if you sort out some basic facts. Why was the study
done? What design was used (cross-sectional, cohort or case-control)?
Studies generally have one (or a few) outcome variable(s) (the “disease”) and many
explanatory variables (the “exposures”). How was the disease measured (prevalence,
incidence proportion or incidence rate)? How was the effect of exposure on disease (the
association) measured (RD, RR or OR)?
Paper 1
Children with chronic conditions and disabilities in the Nordic countries in 1984 and
1996.
Abstract
Data from two cross sectional studies of about 20 000 children aged 2-17 years in the Nordic countries were
analysed according to the prevalence of chronic conditions and their association with demographic and socioeconomic factors in 1984 and 1996. Chronic illness was defined as a condition of at least three months duration
and interfering with daily functioning during the last year. In 1984 the prevalence of chronic conditions was
8.3% and in 1996 15.7%, based on two operational definitions. The prevalence was highest in single parent
families (OR = 1.43, CI = 1.23 – 1.67), workers and student families (OR = 1.22, CI = 1.10 – 1.35) and in lowincome families (OR = 1.15, CI = 1.04 – 1.27). According to the 1996 survey, about 53% of all children with
chronic conditions were only mildly affected, about 40% were moderately affected and 7 percent were severely
affected by their disability. Ten percent of the children had more than one diagnosis when counting all degrees
and only 0,3% had more than one severe diagnosis.
Table 1. Chronic conditions among children 2-17 years of age according to the Nordic study 1984 and 1996.
Columns contain variable names with categories, number of subjects in each category, percent with chronic
conditions and p-value for differences between the categories (crude analysis). The two last columns contain
adjusted odds ratio with 95% confidence interval based on logistic regression.
Variable
N
Percent
ALL COUNTRIES
19373
11.9
SURVEY
1984
1996
9788
9585
8.3
15.7
P value
(chi-square test)
<0,001
Odds Ratio
Confidence
Interval
1.00
2.13
1.94-2.35
COUNTRY
Sweden
Iceland
Norway
Finland
Denmark
3995
3161
3549
4501
4167
10.4
14.6
11.6
13.3
10.2
<0.001
SEX
Boys
Girls
9810
9459
12.5
11.4
0,017
6552
7214
5502
11.2
11.4
13.6
<0,001
AGE
2-6 years
7-12 years
13-17 years
1 year increase
10 year increase
PARENTAL MARITAL
STATUS
Married/living together
Single parent
16849
2252
11.2
16.9
<0,001
LIVING AREA
Large town (>100 000)
Built-up area (3000 – 100 000)
Rural (<3000)
6209
6818
6150
12.0
12.1
11.6
0,588
PARENTAL EDUCATION
Both low / missing
Woman low, man high
Woman high, man low
Both high
5553
1688
2241
9891
12.9
12.4
10.4
11.7
0.008
PARENTAL OCCUPATION
White collar/self-empl/miss
Workers/students
14098
5275
11.2
13.8
<0,001
PARENTAL INCOME
High income
Low income / missing
10836
8510
10.9
13.2
<0,001
1.00
1.49
1.21
1.42
1.05
1.29-1.72
1.04-1.41
1.23-1.62
0.91-1.21
1.00
0.91
0.83-1.00
1.02
1.01-1.03
1.00
1.42
1.23-1.65
Dropped from
the model
1.00
1.18
0.95
1.00
0.99-1.42
0.80-1.13
0.87-1.14
1.00
1.22
1.11-1.36
1.00
1.15
1.04-1.27
1)
a) What is the objective (purpose) of this study?
b) What type of design is this? How many subjects are included?
c) What is the outcome (“disease”)? What type of frequency (disease occurrence)
measure is used?
d) What is the main exposure (or exposures)? What type of association measure is used?
Could others have been calculated?
e) Discuss sources of error.
f) Explain the main results in words.
a) Hva er hensikten med denne studien?
b) Hvilket design er brukt? Hvor mange personer er inkludert?
c) Hva er utfallsvariabelen (”sykdom”)? Og hva slags frekvensmål (sykdoms
forekomstmål) er brukt på denne?
d) Hva er hovedeksponeringen (eller eksponeringene)? Hva slags assosiasjonsmål er
brukt? Kunne andre assosiasjonsmål vært regnet ut?
e) Diskuter feilkilder.
f) Forklar hovedresultatet i ord.
Paper 2
Human Papilloma Virus and Cervix Cancer
The association between human papillomavirus (HPV) and cervix cancer was studied. 103 women with cervical
cancer were identified in two gynaecological hospitals. 234 age matched controls were randomly selected from a
population registry. All subjects were interviewed about their sexual history and smoking history. All women
were tested for presence of HPV. HPV DNA was detected in 34/221 (15.4%) of controls and in 89/98 (90.8%) of
cases. The association between cervical cancer and the independent variables are shown below. The table
provides crude odds ratios and adjusted odds ratios from logistic regression. 95% confidence intervals are given
for both measures. (There is a significant association is the confidence interval does not contain the «null value»)
Crude
Adjusted
Odds Confidence
Odds Confidence
Variable
Ratio intervall
Ratio intervall
HPV
neg
pos
Smoking history
never
ever
Number of partners
1-3
4-9
10+
Oral contraceptive use
never
ever
Parity
Null
1+
1.0
68.0 (28.2 - 164.4)
1.0
73.7 (27.7 - 196.4)
1.0
4.1
(2.3 - 7.3)
1.0
1.5
(0.5 - 4.8)
1.0
5.5
8.2
(2.5 - 12.0)
(3.7 - 17.9)
1.0
1.9
5.2
(0.6 - 6.2)
(1.4 - 19.4)
1.0
1.6
(0.8 - 3.3)
1.0
1.4
(0.5 - 3.8)
1.0
0.5
(0.4 - 0.8)
1.0
1.8
(0.7 - 4.9)
2)
a) What is the objective (purpose) of this study?
b) What type of design is this? How many subjects are included?
c) What is the outcome (“disease”)? What type of frequency (disease occurrence)
measure is used?
d) What is the main exposure (or exposures)? What type of association measure is used?
Could others have been calculated?
e) Discuss sources of error.
f) Explain the main results in words.
g)
h)
i)
j)
a)
b)
c)
d)
Comparing crude and adjusted, is there evidence of confounding for any of the variables?
Can we, based on the table, tell which variable is causing the confounding?
Can we, based on the table, assess if there is interaction in the data?
How could a possible interaction between HPV status and smoking history be investigated?
Hva er hensikten med denne studien?
Hvilket design er brukt? Hvor mange personer er inkludert?
Hva er utfallsvariabelen (”sykdom”)?. Og hva slags frekvensmål er brukt på denne?
Hva er hovedeksponeringen (eller eksponeringene)? Hva slags assosiasjonsmål er
brukt? Kunne andre assosiasjonsmål vært regnet ut?
e) Diskuter feilkilder.
f) Forklar hovedresultatet i ord.
Paper 3
Is delivery by caesarean a risk factor for food allergy?
Background: A delayed and abnormal bacterial colonisation of the new-born intestine due to
improved hygienic conditions in the western world, has been offered as an explanation for the increase
in allergic diseases in the western world. Children delivered by a caesarean section are reported to
have a delayed colonisation of the intestines. Further, the use of antibiotics may interfere with the
colonisation process. The aim of this study was to examine whether caesarean delivery and the use of
antibiotics increased the risk of developing food allergy.
Design and analyses: A population-based cohort of 3623 children born in Oslo, Norway was
followed from birth until the age of two with questionnaires. At birth and at 6 months intervals the
parents completed questionnaires. 2803 families (77.4%) responded to all questionnaires. Information
was obtained regarding mode of delivery, maternal use of antibiotics during pregnancy and in infants
during the first 6 months of life, pregnancy complications and a number of potential confounders.
Both repeatedly parentally reported food reactions (at 12, 18 and 24 months) and objectively
confirmed food reactions were chosen as outcome measures.
Results: Parentally reported reactions to eggs, fish or nuts, and confirmed reactions to milk or egg,
were 3 and 2 fold, respectively, more common among children delivered by a caesarean. This
association was not seen for parentally perceived reactions to milk, however. In multivariate analysis,
adjusting for maternal education, maternal age, maternal smoking habits, gestational age, birth-weight,
pregnancy complications and breastfeeding, caesarean delivery was significantly associated with
parentally perceived reactions to egg, fish or nuts (OR =2.8 p=0.01) and to confirmed food reactions
(OR 1.9 CI 0.7-5.1). The effect was strongest among allergic mothers. The risk for subsequently
reported allergy to egg, fish or nuts, for children delivered by a caesarean whose mothers were allergic
compared to vaginally delivered children whose mothers were not allergic was estimated to OR 8.7
Correspondingly, the risk increase for subsequent confirmed reactions to milk or egg was estimated to
OR 9.7. Both estimates were highly significant in spite of small numbers. Among mothers not reported
to be allergic the association was weaker and not significant in the multivariate analysis. Maternal or
infant use of antibiotics were not associated with an increased risk of confirmed food allergy (but
associated with parentally reported reactions to milk). Conclusion: The results of this study indicates
that children delivered by a caesarean section may be at increased risk of developing food allergy,
especially if the mother is allergic. The findings supports the theory that factors interfering with the
bacterial colonisation of the intestines may play a role in the development of food allergy.
Table 2. Children with repeatedly reported reactions to egg, fish or nuts in a population based cohort of 2803 children,
according to caesarean delivery, maternal and infant use of antibiotics, short term breastfeeding, maternal allergy and
older siblings, adjusted for pregnancy complications, socioeconomic factors and other potential confounding factors.
n
2803
All
Caesarean delivery
Yes
328
No
2475
Maternal antibiotics
Yes
272
No
2531
Child antibiotics first 6 mo
Yes
963
No
1796
Breastmilk
One month or less 122
Longer than 1 month2615
Maternal allergy
Yes
571
No
2227
Older siblings
Yes
1063
No
1740
%
1.1
p
Crude
OR
(CI)
Adjusted
OR
(CI)
0.003
2.7
0.9
3.1
1
(1.4-6.9) *
3.0
1
(1.3-7.1) *
0.6
1
(0.2-2.7)
0.7
1
(0.2-3.1)
1.18
1
(0.6-2.4)
1.1
1
(0.5-2.3)
1.54
1
(0.4-6.5)
1.5
1
(0.3-6.9)
2.168
1
(1-4.6)
2.1
1
0.538
0.7
1.1
0.655
1.2
1.1
0.555
1.6
1.1
0.036
1.9
0.9
(1-4.5) *
0.404
1.3
1.0
1.353 (0.7-2.8)
1
1.3
1
(0.6-2.8)
Adjusted for birthweight, gestational age, preeclampsi, pregnancy bleedings and other pregnancy complications, maternal age,
maternal education and maternal smoking. Missing values for gestational age included as separate category.
131children not included in the analysis due to missing values with regard to other variables than gestational age.
3)
a) What is the objective (purpose) of this study?
b) What type of design is this? How many subjects are included?
c) What is the outcome (“disease”)? What type of frequency (disease occurrence)
measure is used?
d) What is the main exposure (or exposures)? What type of association measure is used?
Could others have been calculated?
e) Discuss sources of error.
f) Explain the main results in words.
a)
b)
c)
d)
Hva er hensikten med denne studien?
Hvilket design er brukt? Hvor mange personer er inkludert?
Hva er utfallsvariabelen (”sykdom”)?. Og hva slags frekvensmål er brukt på denne?
Hva er hovedeksponeringen (eller eksponeringene)? Hva slags assosiasjonsmål er
brukt? Kunne andre assosiasjonsmål vært regnet ut?
e) Diskuter feilkilder.
f) Forklar hovedresultatet i ord.