H/A: Diarrhea/Malabsorption (2009)

Citation:
 
Study Design:
Class:
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Quality Rating:
Research Purpose:

To evaluate the effectiveness of open-label pancreatic enzyme supplementation therapy in acquired immunodeficiency syndrome patients with fat malabsorption.

Inclusion Criteria:

Consecutive patients with HIV infection and fat malabsorption.

Exclusion Criteria:

None specifically mentioned.

Description of Study Protocol:

Recruitment

From a total of 85 patients examined at the outpatient clinics of two tertiary care centers for pediatric HIV infection, between October 1997 and March 1998, all consecutive subjects with steatorrhea were recruited.  Twenty-four consecutive patients with HIV infection and fat malabsorption were recruited.

Design

Before-and-after study.

Intervention

  • All subjects with steatorrhea underwent a pre-study assessment within one week before the study started; they were put on a standard diet and steatorrhea determination and faecal pancreatic function tests were done after one week
  • Steatorrhea was then re-evaluated after two weeks without pancreatic enzyme therapy
  • Pancreatic supplementation treatment was started (Creon 10,000 at a dose of 1,000 units of lipase per gram of ingested dietary fat) and steatorrhea was evaluated after two weeks.

Statistical Analysis

  • Student's T-test for paired data was used to compare the steatocrit values recorded at the pre-study assessment, during the wash-out period, and during pancreatic enzyme treatment
  • Fisher's exact test was used to compare the frequency of cases showing normal steatocrit values with and without pancreatic supplementation therapy
  • The chi-squared test for trend was used to compare the frequency of cases showing cured, improved or unchanged fat malabsorption with and without pancreatic enzyme supplementation therapy
  • The response rate to treatment was calculated based on an intention-to-treat 24 patients
  • Spearman's correlation coefficient r was applied to determine the significance of the correlation between baseline steatocrit values and the modifications in steatocrit values during the different phases of the study.

 

Data Collection Summary:

Timing of Measurements

Faecal fat loss, faecal elastase-1 and chymotrypsin evaluated at study entry. Faecal fat loss also measured after two weeks without pancreatic enzyme treatment and after a further two weeks of treatment with pancreatic extracts. Complete blood count (CBC) and serum chemistry panels were assayed at both baseline and end of study.

Dependent Variables

  • Faecal fat loss was evaluated by steatocrit assay
  • Pancreatic function was investigated by two distinct non-invasive tests: the quantitative determinations of faecal elastase-1 concentration (determined by ELISA) and chymotrypsin activity in faecal specimens (photometric assay) 
  • Side effects were recorded
  • CBC and serum chemistry panels.

Independent Variables

  • Pancreatic extracts: Creon 10,000 at a dose of 1,000 units of lipase per gram of ingested dietary fat
  • Compliance, assessed through pill counts.

Control Variables

  • HIV class according to the Centers for Disease Control criteria
  • CD4 lymphocyte count
  • Patient's weight expressed as a weight Z-score
  • Presence of opportunistic infections
  • Drug treatment, including zidovudine, dideoxydanosine, cotrimoxazole and pentamidine
  • Presence of diarrhea (defined as three or more unformed or liquid stools per day).

 

Description of Actual Data Sample:

Initial N: 24 patients were recruited; 11 males, 13 females

Attrition (final N): 19 completed the study; treatment was withdrawn in five patients due to the onset of abdominal pain, which disappeared within 24 hours of drug withdrawal

Age: Median age, 9.1 years 

Ethnicity: Not mentioned

Other relevant demographics: None of the patients were receiving the highly active antiretroviral combination therapy

Location: Italy.

 

Summary of Results:

 

Variables

Baseline After two weeks without pancreatic enzyme therapy (T-1)

After two weeks of treatment with pancreatic extracts (T-2)

Steatocrit value

7.4±2.6 7.3±3.7 (NS vs. baseline) 3.9±2.1 (P<0.0001)

Number of cases with normal steatocrit values

0/19

0/19

8/19

Other Findings

Six patients (25%) had abnormally low elastase-1 and/or chymotrypsin faecal concentration.

In all patients, steatocrit values were elevated at both study entry and after two weeks without pancreatic enzyme therapy.

Five patients proved intolerant to pancreatic enzyme treatment because of the onset of abdominal pain, and therapy was discontinued.

In the 19 patients who finished the study, steatocrit values during pancreatic enzyme treatment were significantly lower than at entry (P<0.0001).

After two weeks of pancreatic enzyme therapy, in eight of 19 patients, steatocrit values were within the normal limit and the frequency of cases cured or improved on pancreatic enzyme therapy was significantly higher than that observed during the previous study period without enzyme treatment (P<0.01).

A positive significant correlation was found between steatocrit values at entry and the Centers for Disease Control class (P<0.0005); also, the decrease in steatocrit values during pancreatic enzyme therapy (difference between steatocrit value after two weeks of pancreatic enzyme therapy and steatocrit value at study entry) positively correlated with the Centers for Disease Control class (P<0.05).    

No variations were observed in blood count and serum chemistry panel before and after pancreatic enzyme supplementation.

Author Conclusion:

In summary, this pilot open-label study showed that:

  1. Pancreatic enzyme supplementation therapy is highly effective in reducing faecal fat loss in HIV-infected patients with nutrient malabsorption
  2. There is a direct correlation between the clinical condition of the patients and the severity of steatorrhea.

Further double-blind studies must verify these results, and, if they are confirmed, pancreatic enzymes may prove an effective intervention against nutrient malabsorption in AIDS.

Funding Source:
Government: Ministero della Sanita, Istituto Superiore della Sanita
University/Hospital: MURST 60% 1999
Reviewer Comments:

Compliance checked through pill counts. Authors note that oral pancreatic enzymes can produce abdominal pain, and 20% of the patients included in this study had to suspend treatment.

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? N/A
  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? 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.) 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? 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? 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.) 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? 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? 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? 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? N/A
  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? N/A
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