EAL

CD: Gastrointestinal Outcomes (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To evaluate whether untreated adult celiac patients had an increased prevalence of reflux esophagitis, and if so, to assess whether a gluten-free diet exerted any beneficial effect on gastro-esophageal reflux disease (GORD) symptoms.

Inclusion Criteria:

Retrospective review of patients undergoing endoscopy from 1996 - 2001.

Exclusion Criteria:

Exclusion criteria included age < 18 years, age > 70 years, severe chronic liver disease, coronary heart disease, alcohol abuse, drug addiction, and use of corticosteroids, NSAIDs, antisecretory drugs, drugs affecting GI motility, or antibiotics in the past 4 weeks.

Description of Study Protocol:

Recruitment

Retrospective review of patients referred for endoscopy for duodenal biopsy or upper GI symptoms, from 1996 - 2001.

Design

Case-Control Study.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

Each patient given a questionnaire for evaluation of GORD symptoms prior to and 4-12 months after endoscopy.

Statistical Analysis

Significance of differences assessed by Fisher's exact test and ANOVA or Student's t test for unpaired observations, as appropriate. A p value of less than 0.05 was considered to be statistically significant.

Data Collection Summary:

Timing of Measurements

Patients completed questionnaire for evaluation of GORD symptoms prior to and 4-12 months after endoscopy. Patients re-evaluated for GORD symptoms at 4 month intervals up to 1 year.

Dependent Variables

GORD symptom questionnaire, about heartburn, regurgitation, retrosternal pain, dysphagia, belching. Not shown to be valid or reliable measure.
Endoscopy and severity of esophagitis assessed according to Los Angeles classification system
24 hour esophageal pH monitoring to detect acid pathological reflux

Independent Variables

Celiac patients treated with gluten-free diet, not monitored or defined.
Esophagitis patients in both groups treated with 8 week course of omeprazole

Control Variables

Description of Actual Data Sample:

Initial N: 205 celiac patients (153 females, 52 males) and 400 non-celiac controls (244 females, 156 males)

Attrition (final N): See above

Age: Celiac patients median age 32 years, controls median age 37 years

Ethnicity: Not mentioned

Other relevant demographics:

Anthropometrics: Controls were similar but not matched

Location: Italy

Summary of Results:

	Celiac Patients (n=205)	Non-Celiac Controls (n=400)
Epigastric Pain	67 (32.7%)	192 (48%)
Postprandial Fullness	85 (41.5%)	153 (38.2%)
Nausea	25 (12.2%)	34 (8.5%)
Belching	26 (12.7%)	45 (11.2%)
Dysphagia	4 (1.9%)	12 (3%)
Heartburn	77 (37.5%)	121 (30.2%)
Regurgitation	38 (18.5%)	54 (13.5%)

Other Findings

Esophagitis was present in 39/205 (19%, 95% confidence interval 13.8 - 25.0%) celiac patients and in 32/400 (8%, 95% confidence interval 5.5 - 11.1%) dyspeptic subjects (p < 0.0001).

At the 1 year follow up, GORD symptoms relapsed in 10/39 (25.6%, 95% confidence interval 13 - 42.1%) celiacs with esophagitis and in 23/32 (71.8%, 95% confidence interval 53.2 - 86.2%) non-celiac subjects with esophagitis (p < 0.0001).

Author Conclusion:

In conclusion, celiac patients have a high prevalence of endoscopic esophagitis which does not seem to be accounted for by alteration of the physical barrier to acidic reflux. That a gluten free diet significantly decreased the relapse rate of GORD symptoms suggests that celiac disease may represent a risk factor for development of reflux esophagitis. Based on our study, a thorough examination of the duodenum at endoscopy is warranted in subjects with reflux esophagitis.

Funding Source:

University/Hospital:

CIRANAD- Second University of Napoli (Italy); MIUR (Italy)

Reviewer Comments:

Gluten-free diet not defined nor monitored. Questionnaire not shown to be a valid and reliable measure.

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?	???
	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?	N/A
	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?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	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%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	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?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	Yes
	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.)	Yes
	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?	Yes
	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?		Yes
	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?	???
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	Yes
	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?	No
	7.5.	Was the measurement of effect at an appropriate level of precision?	???
	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)?	N/A
	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