EAL

ONC: Probiotics (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To evaluate the effects of the consumption of active bacteria in fermented milk in patients experiencing bowel discomfort for at least one year following radiation therapy (XRT).

Inclusion Criteria:

Primary diagnosis of carcinoma of prostate (T1-4 N0M0) OR urinary bladder (T2-4 N0M0)
Karnofsky performance score of >90
Chronic bowel discomfort
At least one year after completion of XRT
Informed consent

Exclusion Criteria:

Pre-existing GI problems with intestinal surgery
Colostomy
Previous chemotherapy or radiation therapy

Description of Study Protocol:

Recruitment: 40 patients in Sweden

Design: Patients were consecutively randomized to the intervention or control group. All patients were instructed to record bowel habits and daily medicinal usuage in a calendar for 5 weeks.

Blinding used: Double-blind method used, but no details provided.

Intervention: Consume Verum halsofil 300 ml two times a day or the same volume of a control preparation (containing Lactococcus lactis, Lactococcus diacetylactis, leuconostock, and Lactococcus cremoris). Verum halsofil is a fermented milk product that contains lactococcus lactis and Lactococcus cremoris.

Statistical Analysis: Descriptive statistics.

Data Collection Summary:

Timing of Measurements

Initial visit:

Physician visit
Instructed to self-record bowel habits daily (pain, frequency, consistency, and presence of blood or mucus) and medications
Stool specimen analyzed

Weekly:

Seen by nurse to check product compliance

5 weeks later (Final):

Physician visit, stool specimen analyzed

Dietitian visit (time not recorded) to instruct all patients to follow a low fat diet.

Dependent Variables

Number of bowel movements per day
Patient discomfort (beneficial or unchanged)
Presence of Lactococcus lactis L1A cremoris strain

Independent Variable

Verum halsofil 300 ml two times a day.

Control Variable

Norrlandsfil 300 ml two times per day.

Description of Actual Data Sample:

Initial N: 40 patients

Attrition: Unclear. One excluded secondary to lactose intolerance, two lost to bad compliance with recording information. But final n at 35 weeks only added up to 34?

Age/Ethnicity/Anthropometrics: Not provided

XRT regimen:

Daily dose of 1.8-2.2 Gy with total dose of 62-66 Gy; mean field size was 14x14 cm, 4 field technique; mean treatment time was 6.5 weeks.

Summary of Results:

Variables	Verum halsofil (intervention)Group	Norrlandsfil (control) group	Statistical Significance of Group Difference
No. of stools at Day 1 (range)	2.1 (0-6)	2.4 (1-5)	Not provided
No. of stools at Day 35 (range)	1.6 (1-3)	1.9 (1-6)	Not provided
Presence of L1A	9 of 20	1 of 19

Other Findings

Patient discomfort outcomes were based on a beneficial or unchanged self-assessment by the patient. On day 35 of the study, 12/18 patients taking Verum Halsofil and 12/16 in the control group reported the drink to be beneficial.

Author Conclusion:

"The present study indicates that an intake of fermented milk products containing at least L. lactis (L1A) and/or L. cremoris can decrease the chronic bowel discomfort following irradiation of pelvic malignancies."

A small decrease in the number of bowel movements and problems with mucus was observed (no data presented in this paper on mucus).

No changes in pain and presence of blood noted.

Both groups reported less chronic bowel discomfort at the end of the study.

Since the L1A strain was found in the control group, it was suggested that choice of control solution needs to better investigated.

Further studies are needed to investigate the role of fermented milk containing probiotics and need to be lactose-free based.

Funding Source:

University/Hospital:

Medical Faculty/University Hospital (Sweden)

Not-for-profit

Foundation associated with industry:

Reviewer Comments:

This study does not provide useable data to draw conclusions. Nice to have long-term side effects of radiation therapy evaluated.

Limitations:

Did not exclude people with lactose intolerance
Intervention and control medication had similar bacterial strains
No comparison between groups to assess statistical significance
Number of participants did not add up
No characteristics of study population (age, sex, Weight, etc.)
Did not explain when to take study medication
Missing detailed information on diet prescribed
Did not use the WHO criteria for grading diarrhea
? Placebo or treatment effect in the control group since 12/16 subjects reported the control to be beneficial

Study funded by The Swedish Cancer Society, Lions Cancer Research Foundation, and Medical Faculty, University Hospital in Umea Sweden.

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?	No
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
3.	Were study groups comparable?		No
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	No
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	No
	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.)	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?		No
	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%.)	No
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	No
	4.4.	Were reasons for withdrawals similar across groups?	???
	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.)	???
	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?	No
	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?	N/A
	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?	???
	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?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	No
	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?		No
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	No
	8.2.	Were correct statistical tests used and assumptions of test not violated?	No
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	No
	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)?	No
	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?	No
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	No
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