EAL

ONC: Hematopoietic Cell Transplant (2007)

Citation:

Cheney C, Lenssen P, Aker S, Cunningham B, Gauvreau J, Darbinian J, Barale K. Sex Differences in Nitrogen Balance Following Marrow Grafting for Leukemia. Journal of the American College of Nutrition.1987;6(3):223-230

PubMed ID: 3298377

Study Design:

Time Study

Class:

C - Click here for explanation of classification scheme.

Quality Rating:

NEUTRAL: See Quality Criteria Checklist below.

Research Purpose:

To assess the gender differences in nitrogen balance following allogeniec marrow transplantation for leukemia.

Inclusion Criteria:

Adult patients with leukemia undergoing allogeneic marrow transplantation at Fred Hutchinson Cancer Research Center

Exclusion Criteria:

Not described

Description of Study Protocol:

Recruitment - 40 consecutive adults with leukemia undergoing allogeneic marrow transplantation were recruited at Fred Hutchinson Cancer Research Center

Design - Patients were followed from day 1 to 14 post HSCT. PN was initiated after cyclophosphamide infusion but prior to marrow infusion and continuted through day 14. PN provided 0.24g nitrogen per kilogram ideal body weight (IBW) and 1.55-1.65 estimated BEE (using Harris Benedict equation). 25%-30% of calories were provided as lipid. Patients were also allowed to consume an oral diet ad libitum. Some patients were placed in laminar airflow isolation and all patients received physical therapy.

Nursing records were used to collect data on oral and PN intake.Twenty four hour collections of urine and mixed urine-stool were collected from the patients day 1 through day 14 posttransplant and analyzed for total nitrogen (N). Nitrogen balance was calculated as the difference between oral and parenteral N intake and calculated plus estimated N losses. This value was corrected for changes in BUN.

TSF, height and weight were collected at baseline. Weight was subsequently measured on a daily basis. Clinical condition was categorized as moderately or severely stressed according to the following criteria:

Severely stressed:
- Sepsis (2 consecutive positive blood cultures or 1 positive with source)
- Fever (>=38.5C for 4 or more days)
- Pneumonia
- aGVHD (III or greater)
- Liver dysfunction (bili >8mg/dl, SGOT >200 IU/dl, or Alk Phos >400 IU/dl)
- Renal failure requiring dialysis
- Steroids exceeding dose 2mg/kg daily

Blinding used (if applicable) - n/a

Intervention (if applicable) -n/a

Statistical Analysis

Repeated measures ANOVA (effects of sex, time (due to serial measures) and the sex-time interaction)
ANOVA using a regression model (comparison of weekly averages between sexes)
ANCOVA (adjust for the differences in energy intakes between sexes)
Linear multiple regression preceded analysis of covariance (test for parallelism)
Two sample t-test (two-sided)
Chi-square statistic/Fisher's Exact test
P <0.05 significant

Data Collection Summary:

Timing of Measurements:

Daily measures

Total nitrogen intake - calculated from nursing records of oral and PN consumption
Nitrogen loss - 24 hour collection or urine or urine/stool
Energy intake - calculated from nursing records of oral and PN consumption
Body weight

Baseline:

Height
Triceps skinfold
Arm circumference

Weekly:

Clinical condition (moderately or severely stressed)

Dependent Variables:

Mean nitrogen balance
Body composition

Independent Variables

Nitrogen intake
Calorie intake

Description of Actual Data Sample:

Initial N: 40 (21 males, 19 females)

Attrition (final N): 37 (19 males, 18 females)

Age: Males (mean) 30.5 +/- 9.7, Females (mean) 28.7 +/- 6.9

Ethnicity: Not reported

Anthropometrics

Baseline	Males (n=21)	Females (n=29)
Percent IBW	97.8±12.3	99.3±8.0
Arm muscle area <10th percentile	10 (47%)	4 (14%)
Arm fat area <10th percentile	2 (10%)	3 (10%)
Weight <95% IBW	0	1 (3%)
Weight > 115% IBW	2 (10%)	0

Location: Seattle, Washington

Summary of Results:

Nitrogen and Energy Intakes
	Week 1		Week 2
	Males	Females	Males	Females
Nitrogen (g/kg IBW)	0.213±0.03	0.218±0.03	0.198±0.04	0.210±0.05
Total Calories (% BEE)	1.55±0.18	1.66±0.26	1.48±0.21	1.56±0.34
Non-Protein Caloreis (Kcal/g N)	148±14	154±17	151±15	150±17

No significant difference in nitrogen or caloric intake

Nitrogen Balance
	Week 1		Week 2
	Males	Females	Males	Females
Total (n)	21	19	19	18
Nitrogen balance (g/day)	-6 ± 2.8	-3.3 ± 2.2	-9.2 ± 3.5	-5.6 ± 4.1
Mean difference (95% CI)	-2.7 (-4.43,-0.97, p<0.005)		-3.6 (-6.09, -1.11, p<0.01)
Moderate stress (n)	12	16	7	9
Nitrogen balance g/day	-5.5 ± 2.1	-3.1 ± 2.2	-5.4 ± 1.9	-3.2 ± 2.5
Mean difference (95% CI)	-2.4 (-4.17, -0.64, p <0.01)		-2.2 (-4.74, 0.34, p <0.05)
Severe stress (n)	9	3	12	9
Nitrogen g/day	-6.7 ± 3.6	-4.4 ±2.2	-11.4 ± 2.0	-8.1 ± 3.9
Mean difference (95% CI)	difference not examined		-3.3 (-6.19, -0.41, p <0.05)

Average daily nitrogen balance lower in men (p<0.001)
Males with lower week 1 nitrogen balance (p<0.005)
Males with lower week 2 nitrogen balance (p<0.01)
Stress significantly affected nitrogen balance in week 2 (p<0.001)
After adjustment for caloric intake:
- Week 1
  - Male: -5.4g
  - Female: : -3.4g
  - p<0.025
- Week 2
  - Male: -9.0g
  - Female: -5.9g
  - p<0.01

Other Findings

No difference in post-transplant complications or stress classification
There were no significant effects on nitrogen balance by the branched-chain content of the amino acid solution, the type of renal-toxic drug used, stature as a surrogate for total body nitrogen or the arm muscle area percentile admission.
Males in the study experienced more periods of fever than the females which could have affected nitrogen balance results

Author Conclusion:

Males experienced a greater negative nitrogen balance than females despite similar nitrogen and caloric intake. These findings suggest that males may have higher per kg nutrient needs during stress and may differ from females in their metabolic response to stress.

Funding Source:

Government:

NHLBI, National Cancer Institute,

Industry:

Kendal McGaw

Pharmaceutical/Dietary Supplement Company:

Reviewer Comments:

Small sample size
Inclusion/Exclusion/Recruitment criteria not discussed
"Moderately stressed" not defined
Study inadequately controlled
e.g. "some patients were placed in laminar air flow...and experienced restricted amubulation
" posttransplant immunosuppression....differed among patients"
Other treatments, planned or unplanned not discussed
No subsequent body composition measures to assess impact of negative nitrogen balance
No actual measure of energy needs to asses if intake was adequate

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
	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
	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
	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
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
	1.	Was the research question clearly stated?	Yes
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.1.	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
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
	1.3.	Were the target population and setting specified?	Yes
	2.	Was the selection of study subjects/patients free from bias?	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?	No
	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?	No
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
	3.	Were study groups comparable?	No
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)	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?	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.)	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?	No
	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?	No
	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
	3.5.	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
	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.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	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
	4.2.	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
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	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
	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.	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
	5.1.	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
	5.2.	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
	5.3.	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
	5.4.	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
	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?	No
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		No
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	N/A
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	N/A
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	No
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	No
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	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
	6.4.	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?	No
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	No
	6.6.	Were extra or unplanned treatments described?	No
	6.6.	Were extra or unplanned treatments described?	No
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	No
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	No
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	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?	No
7.	Were outcomes clearly defined and the measurements valid and reliable?		No
	7.1.	Were primary and secondary endpoints described and relevant to the question?	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?	No
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	No
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	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
	7.4.	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?	No
	7.5.	Was the measurement of effect at an appropriate level of precision?	No
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	No
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	No
	7.7.	Were the measurements conducted consistently across groups?	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.	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
	8.1.	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
	8.2.	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
	8.3.	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)?	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)?	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?	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?	N/A
	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.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	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.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes