CD: Gastrointestinal Outcomes (2006)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To identify the frequency and nature of gastrointestinal symptoms in a large cohort of patients with diagnosed celiac disease and to determine the effect of a gluten-free diet on these symptoms.
Inclusion Criteria:
Celiac disease diagnosed according to internationally accepted criteria.  All patients had an intestinal biopsy specimen compatible with celiac disease.  Histologic evidence based on duodenal or jejunal biopsy specimens was obtained for all subjects and was interpreted by a single experienced gastrointestinal pathologist.  62% of patients had follow-up biopsies to evaluate recovery of duodenal mucosa, those who did not had a dramatic, clinical response to gluten-free diet.
Exclusion Criteria:
Excluded if not included above.
Description of Study Protocol:

Recruitment

215 patients evaluated at University of Iowa from 1990 - 1997 as having biopsy-confirmed celiac disease, constituting all the patients diagnosed with celiac disease between 1984 - 1997. 

Design

Cohort study.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

Patients received follow-up survey after following gluten-free diet for at least 6 months.

Statistical Analysis

McNemar's chi-square test was used to compare paired categorical variables.  The sign test was used to examine trends in the frequency of symptoms over time.  A P value < 0.05 was considered significant.  An ANOVA test based on ranks was used to test for any significance of sex on outcomes of the gluten-free diet.

Data Collection Summary:

Timing of Measurements

Patients completed follow-up systematic telephone survey asking detailed questions regarding gastrointestinal symptoms before and after the institution of a gluten-free diet for at least 6 months.

Dependent Variables

  • Telephone survey carried out by trained, experienced, gastrointestinal nurses.  Detailed questions asked concerning the presence of gastrointestinal symptoms at time of diagnosis, the patient's perspective on how the gluten-free diet affected each of these symptoms, and the duration, frequency, severity and features of the patient's bowel movements at diagnosis and after 6 months of gluten-free diet

Independent Variables

  • Gluten-free diet.  All subjects received similar dietary instruction by the same dietitian who was experienced in celiac disease.  Patient adherence to diet completed through follow-up visits.

Control Variables

 

Description of Actual Data Sample:

Initial N: 215 patients, 160 female, 55 male.

Attrition (final N):  See above.

Age:  Age at diagnosis ranged from 1 - 90 years, median 48 years, mean age 55 years.  80% were adults at time of diagnosis. 

Ethnicity:  Not mentioned.

Other relevant demographics:  Not mentioned. 

Anthropometrics:

Location:  Iowa 

 

Summary of Results:

 

Before GFD After GFD

P-value

Diarrhea 163 (75%) 73 (34%) <0.001
Constipation 83 (39%) 64 (30%) <0.02
Abdominal Pain 171 (79%) 6 (3%) <0.001
Abdominal Bloating 157 (73%) 9 (4%) <0.001
Nausea or Vomiting

96 (44%)

19 (9%)

<0.01

Lactose Intolerance

85 (39%)

27 (13%)

<0.001

Other Findings

One patient openly acknowledged eating gluten-containing foods on a regular basis.  All others denied deliberately consuming gluten more than once a month.  Except for the one non-compliant patient, all subjects showed substantial improvement on follow-up biopsy if performed.  The non-compliant patient had persistently positive endomysial antibodies and villous atrophy. 

91% patients gained weight between time of diagnosis and 6 months after starting a gluten-free diet, and the weight gain ranged from 0.5 - 46 kg (mean 7.5 kg).

Although diarrhea was the most frequent symptom in untreated celiac disease (reported by 75%), steatorrhea occurred in only 1/5 of patients.

Other complaints were common, and most responded to gluten exclusion.  The benefit of gluten exclusion was equally apparent in men and women.

The prevalence and frequency of diarrhea dropped substantially (p < 0.001) after institution of gluten-free diet.  Diarrhea responded in most patients, usually within days, and the mean time to resolution was 4 weeks.

Constipation was reported in 38.6% of subjects before diagnosis.  Most of these patients reported resolution of the constipation within 6 months of adapting to a gluten-free diet (P < 0.02).

Many patients had alternating diarrhea and constipation ( chi-square = 0.002), both of which were responsive to the gluten-free diet.

Most patients had abdominal pain and bloating before diagnosis (79%), which resolved with the diet.  Postprandial pain decreased significantly after a gluten-free diet (P = 0.001).   Almost all subjects reported complete relief of bloating with the institution of gluten-free diet (P < 0.0001).

 

 

Author Conclusion:
Celiac disease causes a wide range of gastrointestinal symptoms.  Clinicians must have a high level of suspicion to detect the atypical forms of celiac disease.  With a gluten-free diet, patients have substantial and rapid improvement of symptoms, including symptoms other than the typical ones of diarrhea, steatorrhea, and weight loss.
Funding Source:
Government: NIH
Reviewer Comments:
Compliance monitored through dietitian follow-up.
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? ???
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
  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? Yes
  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.) N/A
  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? Yes
  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? No
  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? No
  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? 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? Yes
  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? Yes
  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? Yes
  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? Yes
  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)? Yes
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  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