EAL

H/A: Diarrhea/Malabsorption (2009)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To evaluate the efficacy of calcium carbonate in the treatment of protease inhibitor-induced persistent diarrhea in HIV-infected patients.

Inclusion Criteria:

HIV infection
Patients who were receiving one or more protease inhibitors at the onset of diarrhea
Current protease inhibitor therapy
Presence of diarrhea for a minimum of two weeks
Diarrhea that met the study definition of persistent diarrhea
Patients taking other antidiarrheal medications were included in the study and were requested to continue with their previous regimen in addition to assigned study therapy
Patients with a history of calcium carbonate use for past episodes of diarrhea could be included in the study.

Exclusion Criteria:

Patients with known contraindications to calcium therapy (hypercalcemia, renal calculi, hyperparathyroidism, bone metastases, decalcifying tumors, vitamin D overdose)
Patients who were receiving daily calcium supplements.

Description of Study Protocol:

Recruitment

Patients were identified through the Ottawa Hospital General Campus Immunodeficiency Clinic. Study posters were displayed in all clinic rooms to encourage patient participation. Over a four-week period, during regularly scheduled appointments, clinic staff identified patients who were experiencing diarrhea of at least two weeks' duration according to the study definition of persistent diarrhea.

Design

Before-and-after study.

Intervention

Along with dietary advice, patients were asked to take oral calcium carbonate 500mg twice daily for two weeks.

Statistical Analysis

Data were analyzed using paired T-tests to test for differences in visual analog scales and National Cancer Institute of Canada scores between baseline and 14 days
Kolmogorov-Smirnoff test was used to compare the distributions of these data with a normal distribution since the sample size was small
Pearson correlation was used to explore the relationships between change in diarrhea and patient baseline factors such as CD4 count, viral load and age
Non-parametric tests (Kruskal-Wallis and Mann-Whitney) were used to explore the relationships between sex, dietary compliance, duration of diarrhea and concurrent antidiarrheal therapy.

Data Collection Summary:

Timing of Measurements

Patients were asked to complete a questionnaire to assess severity of diarrhea as well as history of protease inhibitor and antidiarrheal therapy at baseline and after 14 days of calcium therapy.

Dependent Variables

Questionnaires incorporated a Visual Analog Scale and the National Cancer Institute of Canada scale were used to assess the severity of diarrhea (based upon number of bowel movements, cramping, incontinence and impact on daily life).

Independent Variables

Along with dietary advice, patients were asked to take oral calcium carbonate 500mg twice daily for two weeks.

Description of Actual Data Sample:

Initial N: 17 subjects; 13 male, 4 female
Attrition (final N): 17
Age: Median 42 years (range 28 to 60 years).

Other Relevant Demographics

Median CD4 count: 313 cells per mm³ (range, 10 to 1,075)
Median viral load: Less than 50 copies per mL (range, less than 50 to 119,927)
Protease inhibitor regimens:
- 11.7% nelfinavir
- 5.9% ritonavir
- 5.9% indinavir
- 29.4% lopinavir / ritonavir
- 17.6% saquinavir / ritonavir
- 5.9% ritonavir / indinavir
- 23.5% nelfinavir / saquinavir.

Location

Canada.

Summary of Results:

Scale	Day Zero	Day 14	Statistical Significance of Group Difference
Visual Analog Scale (zero to10)	6.6±2.1	5.3±1.9	0.01
National Cancer Institute of Canada (zero to four)	1.9±0.8	1.2±0.9	0.005

Other Findings

76% of patients included in the study were receiving dual protease inhibitor therapy.

At day zero, the mean Visual Analog Scale ±SD was 6.6±2.1 and decreased to 5.3±1.9 (P=0.01) after 14 days.

At day zero, the mean National Cancer Institute of Canada score was 1.9±0.8 and decreased to 1.2±0.9 (P=0.005) after 14 days.

No baseline patient factors predicted change in National Cancer Institute of Canada or Visual Analog Score grade (age, sex, protease inhibitor regimen, CD4 count, viral load, compliance with dietary suggestions, duration of diarrhea or concurrent antidiarrheal therapy).

Author Conclusion:

Calcium carbonate is effective in reducing, albeit modestly, diarrhea in people with persistent symptoms who use any protease inhibitors as part of their retroviral therapy. Further study, including a placebo-controlled randomized study, is required to more exactly quantify the benefits of calcium carbonate therapy in this population.

Funding Source:

Industry:

University/Hospital:

Ottawa Hospital

Reviewer Comments:

Authors note the following limitations: Lack of placebo control may positively influence scores, and relatively small sample size. Questionnaire not shown to be valid or reliable. No power analysis completed. Did not control for effect of other antidiarrheal medications.

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?		???
	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?		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?		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?		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?		???
	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?	???
	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?	No
	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)?	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