EAL

CD: Gastrointestinal Outcomes (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine the occurrence of GI symptoms in adults with celiac disease treated with a gluten-free diet for several years.

Inclusion Criteria:

Middle-aged celiac disease patients (aged 45 - 64 years) in remission after 8 -12 years of treatment with gluten-free diet. Diagnosis confirmed through biopsy and response to gluten-free diet.

Exclusion Criteria:

Patients with concomitant dermatitis herpetiformis.

Description of Study Protocol:

Recruitment

Diagnosed at 6 Swedish hospitals between years 1984 - 1988. Controls recruited by mail from a list of participants of a local health survey.

Design

Cohort Study.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

Subjects completed GSRS.

Statistical Analysis

Results are given as mean and 96% confidence intervals. The data set was non-normally distributed and allowed for using a nonparametric method (Mann Whitney U test) to compare means. The significance level was set at p < 0.05 (double sided).

Data Collection Summary:

Timing of Measurements

Patients were seen at least every second year by a gastroenterologist and a dietitian or general practitioner.

Dependent Variables

Validated GI Symptom Rating Scale, comprising 5 syndromes: indigestion, diarrhea, constipation, abdominal pain, and reflux.
Repeat intestinal biopsies to ascertain remission
Serological tests to ascertain remission

Independent Variables

Strict gluten-free diet for several years. Not defined, compliance not monitored.

Control Variables

Description of Actual Data Sample:

Initial N: 51 adults with celiac disease (59% women), 182 controls (57% women)

Attrition (final N): See above

Age: All subjects aged 45-64

Ethnicity: Not mentioned

Other relevant demographics: Not mentioned

Anthropometrics: Groups were of similar age and gender

Location: Sweden

Summary of Results:

Mean (95% CI) GSRS Scores of Celiac Patients

Syndrome	Celiac Men	Celiac Women
Indigestion	1.90 (1.51 - 2.29)	2.92 (2.43 - 3.41), p < 0.01
Diarrhea	1.52 (1.13 - 1.91)	2.07 (1.54 - 2.60)
Constipation	1.54 (1.21 - 1.87)	2.67 (2.12 - 3.22), p < 0.01
Abdominal Pain	1.56 (1.27 - 1.85)	2.38 (1.97 - 2.79), p < 0.01
Reflux	1.38 (1.01 - 1.75)	1.68 (1.31 - 2.05)
Total GSRS Score	1.58 (1.31 - 1.85)	2.34 (2.03 - 2.65), p < 0.001

Other Findings

Subjects with celiac disease reported significantly more GI symptoms (2.0; 95% CI = 1.79-2.27) than the general population sample (1.7; 95% CI = 1.57 - 1.81), as assessed by the GI Symptom Rating Scale total score (p < 0.01).

This was particularly true for women with celiac disease who scored worse than female controls for all syndromes on the GI Symptom Rating Scale, notably for indigestion (p < 0.006), diarrhea (p < 0.04), constipation (p < 0.001), and abdominal pain (p < 0.002).

By contrast, the men with celiac disease reported no more symptoms than male controls.

The women with celiac disease showed generally more complaints than the men with celiac disease did, notably within indigestion, constipation, and abdominal pain, corresponding to a 2-fold higher rate of GI symptoms (60% vs 29%, p < 0.04).

There was no difference in the GSRS total score between celiac disease patients with an entirely normal mucosa (2.0; 95% CI = 1.72 - 2.28) and those showing borderline findings, such as a raised IEL count (2.2; 95% CI = 1.48 - 2.84), p = NS.

Author Conclusion:

The main new finding of the study is that celiac disease patients adhering to a strict gluten-free diet for 8 - 12 years are not symptom free. Adult celiac disease patients on a gluten-free diet for several years experienced significantly more GI symptoms than the general population sample. This may have some of its origin in the composition of the gluten-free diet. The symptoms were more pronounced in the women. This may raise questions of an association with their subjective health status, which has been shown to be lower than in men with celiac disease.

Funding Source:

Government:

Medical Research Council of Southeast Sweden

Reviewer Comments:

Valid GSRS. Gluten-free diet compliance not assessed. Did not examine dietary intake of fiber.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
3.	Were study groups comparable?		???
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	No
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	???
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		N/A
	4.1.	Were follow-up methods described and the same for all groups?	N/A
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	N/A
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	N/A
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		N/A
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	N/A
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		???
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	No
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		???
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	???
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	No
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes