This Academy member benefit temporarily has been made public to allow all practitioners access to content that may assist in patient care during the national pandemic response. Click here for information on joining the Academy. 

NC: Behavior Change Strategies (2007-2008)

Citation:

Milas NC, Nowalk MP, Akpele L, Castaldo L, Coyne T, Doroshenko L, Kigawa L, Korzec-Ramirez D, Scherch LK, Snetselaar L. Factors associated with adherence to the dietary protein intervention in the Modification of Diet in Renal Disease Study. J Am Diet Assoc. 1995 Nov; 95 (11): 1,295-1,300.

PubMed ID: 7594126
 
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

To determine the characteristics and behaviors associated with adherence to dietary protein interventions among participants with chronic renal disease in the modification of diet in renal disease (MDRD) study.

Inclusion Criteria:
Participants were categorized as consistent adherers and non-adherers on the basis of urinary urea nitrogen excretion and dietary protein intake data from self-reports.
Exclusion Criteria:

Patients were not on dialysis and had not had a kidney transplant.

Description of Study Protocol:

Recruitment

Participants were 840 adults with renal diseases of diverse etiology who were not on dialysis and had not had a kidney transplant from 15 clinical centers in the United States.

Design

The MDRD study was a multi-center, randomized clinical trial designed to test the effect of three levels of protein and phosphorus intake and two levels of blood pressure control on the progression of chronic renal disease. Participants were 840 adults with renal diseases of diverse etiology who were not on dialysis and had not had a kidney transplant. Participants were assigned to one of two studies on the basis of baseline glomerular filtration rate (GFR). In study A, 585 participants with GFRs of 25 to 55 ml per minute per 1.73m2 were randomly assigned to a usual-protein (1.3g/kg per day) or a low-protein diet group (0.58g/kg per day with, 0.35g protein high in essential amino acids) and a usual or low blood pressure group (mean arterial pressure <107 vs. <92 mm HG). In Study B, 255 participants with GFRs of 13 to 24 L per minute per 1.73m2 were randomly assigned to a low protein or very low protein (0.28g/kg per day) diet group, supplemented with ketoacid-amino acids, and a usual or low blood pressure group. Average follow-up was 26 months. Participants were categorized as consistent adherers and non-adherers on the basis of urinary urea nitrogen excretion and dietary protein intake data from self reports. Psychosocial and behavioral factors were compared between groups. 15 clinical centers in the United States participated. Demographic and physiological characteristics were measured at each visit. GFR was measured at two and four months and every four months thereafter. Data for physiologic variables are the means from the six adherence visits between visit one and 24 adjusted for baseline values. Energy and nutrient intakes (protein, phosphorus and other nutrients) from three-day food records were analyzed for each tri-annual adherence assessment visit. Dates were coded and entered by dietary data entry.

Blinding Used

Not clear. Randomization used but not blinded

Intervention

In the nutrition intervention program, participants were assigned randomly to a usual, low- or very-low-protein diet group. Each eating pattern also specified a phosphorus goal. Intervention strategies provided knowledge and skills, feedback, modeling and support to allow participants to build on their successes and move toward self-management. Participants were instructed to record, or "self-monitor", the protein content of all foods consumed on a daily basis throughout the program. Some participants also chose to self-monitor content of phosphorus or other nutrients in foods consumed. Each participant attended monthly follow-up visits that included nutrition intervention activities as well as data collection.

Statistical Analysis

For all analysis, adherers were compared with non-adherers in each diet group. All comparisons of continuous variables between adherence groups were performed using one-way analysis of variance and covariance, and for categorical data, using two analyses. All analysis used the Statistical package for social sciences (SPSS-X, version 4.0, 1993, SPSS, Chicago, ILL). Separate analysis for the usual -protein and low-protein diet groups in study A, and for the low- and very low-protein diet groups in study B, were performed for the following reasons. First, adherences to the usual-protein diet generally required increases in protein intake, whereas adherences to the low- and very-low-protein diets required decreases in protein intake. Second, the proportion of adherers and non-adherers differed significantly among the diet and study groups. Finally, because the two study groups differed in severity of kidney disease, it was possible that factors related to adherence might differ between them.

Data Collection Summary:

Timing of Measurements

Two, four and every four months and average follow up was 26 months.

Weight, body mass index, transferrin level, and mean arterial pressure were measured at each follow up visit. GFR was measured at two and four months and every four months thereafter. Data for physiologic variables are the means from the six adherence visits between visit one and 24, adjusted for baseline values.

Dependent Variables

  • EPI: Protein intake from three-day food records; weight; BMI; Transferrin level; GFR
  • MAP: Protein intake and dietary behaviors of adherers and non-adherers
  • Factor or component
    • Knowledge and skills
    • Attitude toward eating pattern
    • Effect of health on eating pattern
    • Social support
    • Effect of eating pattern on socialization
    • Overall dietary satisfaction
    • Perceived success
    • Usefulness of dietitan support
    • Usefulness of self-monitoring
  • Specific Nutrition Intervention Strategies: Reviewed weighing and measuring skills; provided guidelines for increasing energy; provided guidelines for protein modification; reviewed flow sheet of adherence or biochemistry data; chose not to discuss urinary marker of protein intake; provided feedback based on self-monitoring or food record; provided new or more low-protein food products; included a food tasting session; planned for increased telephone contact; conducted telephone calls
  • Low protein diet; very low protein diet; usual protein diet.

Independent Variables

  • Psychosocial factor and intervention components
  • Specific intervention strategies
  • Protein diets.
Description of Actual Data Sample:

Initial N

840 participants (Study A: 585; Study B: 255).

Attrition (Final N)

  • Usual protein diet, N=294 (Adherers, N=147; Non-adherers, N=27)
  • Low protein diet, study A, N=291 (Adherers, N=101; Non-adherers, N=83)
  • Low protein diet, study B, N=129 (Adherers, N=59; Non-adherers, N=19)
  • Very-low protein diet, N=125 (Adherers, N=31; Non-adherers, N=46)

Age

Data not shown.

Ethnicity

Data not shown.

Other Relevant Demographics

Age, gender, race, marital status, education, income and standard weight were determined at baseline visits (Data not shown).

Anthropometrics

BMI, weight.

Location

15 clinical centers in the United States.

Summary of Results:

Adherence ranges for EPI were established for each diet group on the basis of the dietary protein goal. The ranges were based on intra-individual variability of the urinary urea nitrogen level.

Modification of Diet in Renal Disease Study
Dietary protein and phosphorus goals and adherence ranges for proteina

Diet or Eating Pattern Group
Protein Goal (g/kgb per day)
Adherence Range of Protein
Phosphorus Goal
mg/kg per day
Percentage of Goal
g/kg per day
 
 
Usual protein
1.3
±25
0.98-1.62
16-20
Low proteinc
0.575
±30
0.40-0.75
5-10
Very low proteind
0.28
-20+50
0.22-0.42
4-9

aNo adherence ranges were established for phosphorus
bKilogram standard body weight
cMore than 0.35g/kg per day of high-biological value protein
d
Supplemented with 0.28g/kg per day ketoacid-amino acid mixture (Ross Laboratories, Columbus, Ohio)

Physiologic Characteristics of Adherers and Non-Adherers in the Modification of Diet in Renal Disease Studya

Characteristics
Usual Protein Diet, N =294b
Low Protein Diet, Study A, N=291
Low Protein Diet, Study B, N=129
Very-Low Protein Diet, N=125
Adherers, N=147
Non-adherers, N=27
Adherers, N=101
Non-adherers, N=83
Adherers, N=59
Non-adherers, N=19
Adherers, N=31
Non-adherers, N=46
cEPI (g/kgSBW)
1.16±0.12
0.92±0.09
0.67±0.06
0.89±0.15
0.67±0.06
0.87±0.09
0.37±0.05
0.55±0.11
Protein intake from three-day food records (g/kgSBW)
1.29±0.15
1.13±0.25
0.58±0.07
0.67±0.21
0.48±0.08
0.72±0.15
0.32±0.04
0.42±0.12
Weight
kg
83.7±16.6
77.2±14.3
73.6±13.2
81.7±14.9
73.1±12.5
75.5±13.0
71.2±13.3
74.8±13.6
dBMI (kg/m2)
28.3±4.5
25.5±3.6
25.3±3.2
28.1±4.4
25.2±8.2
25.9±2.7
22.8±3.0
26.4±4.5
Transferrin level (g/L)
2.75*±0.42
2.83±0.56
2.46±0.36**
2.67±0.32
2.56±0.34
2.59±0.42
2.50±0.41
2.57±0.40
eGFR (mL/min per 1.73m2
35.1±10.5
32.0±9.8
34.3±10.2
35.4±10.8
16.5±5.6
17.5±5.6
15.9±7.2
16.7±5.5
fMAP, mm HG
96.2±6.3
95.8±7.5
96±9.6
96.3±7.1
97.5±6.7
98.5±9.8
97±8.5
97±6.4

aAdherers were defined as being in range for estimated protein intake (EPI) from urine urea nitrogen excretion and protein intake from food records; non-adherers were out of range for EPI.
bFor each diet group, the percentages of adherers and non-adherers are given. The remaining participants were either not present for at least four adherence visits or were inconsistently adherent (41%, usual protein group; 37% low protein group study A; 40% low protein group study B; 39% very-low protein group)
cEPI= estimated protein intake from urine urea nitrogen excretion in 24-hour urine collections, SBW= standard body weight
dBMI= body mass index
eGFR= glomerular filtration rate
f
MAP= Mean arterial pressure
*P<0.05;** P<0.01
 
Reported mean protein intake and dietary behaviors of adherer and non-adherer in the modification of diet in renal disease study over 24-month perioda

Factor Component a,b
Usual Protein Diet
Low Protein Diet, Study A
Low Protein Diet, Study B
Very-Low Protein Diet
Adherers, N=147
Non-adherers
N=27
Adherers, N=101
Non-adherers, N=93
Adherers, N=59
Non-adherers, N=19
Adherers, N=31
Non-adherers, N=46
Knowledge and skills
Attitude lowered eating pattern
4.7±0.4***
4.6±0.5***
4.4±0.6
3.9±0.8
4.7±0.4***
4.6±0.6***
4.2±0.7
3.4±0.7
4.7±0.3**
4.7±0.3***
4.2±0.7
3.7±1.1
4.7±0.4**
4.5±0.5***
4.3±0.6
Effect of health on eating pattern
Social support
1.4±0.6***
4.6±0.6
1.9±0.8
4.4±0.8
1.3±0.4**
4.6±0.6**
1.5±0.7
4.3±0.7
1.5±0.6*
4.6±0.6**
1.9±1.0
4.2±0.8
1.4±0.4**
4.5±0.6*
1.7±0.6
4.0±0.8
Effect of eating pattern on socialization
Overall dietary satisfaction
1.3±0.5
3.9±0.7*
1.2±0.3
3.6±0.6
1.5±0.5**
3.6±0.7*
1.7±0.7
3.3±1.0
1.4±0.5*
3.7±0.7
1.7±0.5
3.4±0.9
1.7±0.9
3.1±0.8
1.8±0.7
3.0±0.7
Perceived success
Usefulness of self-monitoring
4.3±0.7***
4.8±0.4
3.5±1.0
5.0±0.2
4.5±0.5***
4.9±0.3**
3.5±1.1
4.7±0.6
4.6±0.5***
5.0±0***
3.6±1.2
4.4±1.1
4.4±0.5***
5.0±0*
3.5±1.0
4.9±0.3
Usefulness of self monitoring
4.8±0.4
5.0±0.2
4.9±0.3**
4.7±0.6
5.0±0***
4.4±1.1
5.0±0*
4.9±0.3

aOnly those ratings were significantly different between adherence groups in two or more diet groups appear in the table
b Rated on a five-point Likert scale: 1= lowest, 3= neutral, 5= highest
*P<0.05; **P<0.01; ***P<0.001

 

Reported mean protein intake and dietary behaviors of adherer and non-adherer in the modification of diet in renal disease study over 24-month perioda

Protein intake and dietary behaviorsa
Usual Protein Diet
Low Protein Diet, Study A
Low Protein Diet, Study B
Very-Low Protein Diet
Adherers, N=147
Non-adherers
N=27
Adherers, N=101
Non-adherers, N=83
Adherers, N=59
Non-adherers, N=19
Adherers, N=31
Non-adherers, N=46
Protein intake from self monitoring(g/kg/SBWb)
1.21±0.17
1.17±0.46
0.57±0.09***
0.63±0.10
0.55±0.12**
0.65±0.13
0.31±0.04**
0.38±0.11
Protein intake from self monitoring (grams per day)
89±17
86±29
41±9***
45±9
39±11*
46±10
21±4**
27±9
Self-monitoring frequency
3.8±2.2
2.8±2.2
4.2±2.3*
3.4±2.2
4.3±2.3
3.7±7.0
4.5±2.4*
3.2±2.2
percentage who self-monitored frequently (six-seven days per week)
28.8*
22.2
37.8*
23.0
47.5
22.2
51.6**
16.7
Use of special food
103±11.3
119±105
341±257***
194±200
231±156*
159±128
302±212
230-177
productsc
 
 
 
 
 
 
 
 

aOnly those nutrient intakes and dietary behaviors that were significantly different between adherence groups in two or more diet groups appear in the table. bSBW=standard body weight; cTotal ordered per participant over 24-month period; *P<0.05 for comparisons between adherence groups; ** P<0.01; P<0.001.

Specific intervention strategies used by dietitians among adherers and non-adherers in the Modification of Diet in Renal Disease Study over 24-month perioda

aOnly those activities that were conducted with significantly different frequencies between adherence groups in two or more diet groups appear in the table ; b telephone calls made per month to adherent and non-adherent groups

*P<0.05; **P<0.01; ***P<0.001

Other Findings

  • EPI and dietary protein intake for the cohorts and includes the proportion of participants in each diet group who were classified as adherers and non-adherers
  • 50% of participants adhered to the usual protein; 35% and 46% to the study A and B low-protein diets, respectively; and 25% to the very-low -protein diet
  • Adherers were in the range for EPI and diet. In contrast, EPI was out of range for non-adherers, despite reported dietary protein being in range.
  • Adherers in the low protein, study A group weighed less and had a lower body mass index than non-adherers, and transferrin values were lower among adherers in both study A groups
  • No significant differences between adherers and non-adherers were noted in race, marital status, education or gender (data not shown)
  • Intakes of energy, fat, vitamins, and minerals (including phosphorus) were similar between adherers and non-adherers (data not shown). Participant ratings of hunger or food tastes did not differ between adherers and non-adherers in any group (data not shown). In the usual-protein diet group only, adherers rated their appetite as better than non-adherers (data not shown).
  • EPI was discussed less often with non-adherers than adherers. Adherers in all diet and study groups indicated more favorable attitudes about their eating patterns and perceived themselves as more successful than non-adherers. This finding suggests that successful participants received praise and encouragement from the dietitians, which helped to maintain their motivation sustain adherence. Additionally, feelings of success like boosted participants' self-esteem and promoted confidence their ability to reach study goals.
  • More frequent telephone contacts were made with non-adherers. Dietitians made telephone calls to solve problems, reinforce strategies discussed during the visit, and provide contact between monthly visits.
  • Results of this study suggest that adherence to low-protein diet patterns requires social support and assistance for replacing energy lost by a decrease in protein intake. In addition, adherence does not seem to require ongoing provision of guidelines for reducing protein intake. Dietitians emphasized protein modification guidelines and weighing and measuring techniques with non-adherers rather than adherers. Both strategies were used to minimize under reporting of protein intake. The intervention program stressed maintaining energy intake and demonstrated in both adherent and non-adherent groups that adherence to reduced-protein eating patterns could be achieved while maintaining similar energy and nutrient intakes. Examination of mean measures of nutritional status indicates that adherers did not experience unfavorable changes in weight or transferrin level.
  • Participants were also able to be successful without feelings of hunger or alterations in food tastes. Adherent participants reported that the eating pattern did not interfere with their ability to socialize, which suggests that successful participants made adherence to the eating pattern a priority and were able to assert their own needs in a social setting.
  • Providing participants with protein-modified food products and recipes and samples of products was beneficial in promoting adherence. The incorporation of low-protein foods and the inclusion of favorite foods increases palatability of low-protein eating and ensures that energy needs are met.
  • Our study demonstrated that self-monitoring helped participants achieve varying levels of protein intake, which is of particular importance for persons with kidney disease because the protein prescription may need to change as the disease progresses. In all study groups, adherers self-monitored protein intake more frequently than non-adherers. The frequency of self-monitoring differed by as much as 1.3 days per week between adherent and non-adherent groups. As many as 51% of adherent participants self-monitored on average six to seven days per week throughout the two-year study period. The frequency of self-monitoring suggests that dietitians communicated the importance of the strategy and the expectation that it be continued and that adherent participants fulfilled that expectation.
  • Adherers in all three reduced-protein groups rated self-monitoring and dietitian support as significantly more useful than did non-adherers. Knowing that participants found value in self-monitoring should alleviate the concern expressed by some counselors that self-monitoring is burdensome to participants. Counselor should also heighten their expectations of what willing participants can do to achieve adherence. These findings also emphasize the important role of the nutrition professional as a counselor.
Author Conclusion:
  • The MDRD study nutrition intervention program was well received by participants, and the program has many components that could be adapted to clinical practice. Self-management strategies were used with great success, which provides an impetus to incorporate these strategies in practice.
  • Recording foods and their protein content enabled participants to monitor their own success and promoted self-efficacy. Self-monitoring can be easily incorporated into clinical settings. Nutrient counters are available at low cost. Alternatively, a nutrient counter can be generated using a variety of nutrient analysis software, so a nutrition professional can tailor the counter by including only those foods or nutrients of interest to the client. Nutrient analysis software programs provide nutrient data reports, assist in meal planning, and produce menus that can be given to participants for reinforcement and feedback.
  • Even though self-reported protein intake may overstate adherence, the information is valuable in helping counselors identify dietary and behavioral factors related to adherence. Accurate weighing and measuring techniques should be emphasized routinely to strengthen the agreement between reported protein intake and biochemical measures of adherence. Consistency promotes confidence and provides valuable feedback to reinforce importance of dietary modification. Additionally, feedback appears to heighten effectiveness of intervention efforts.
  • The ratio of dietitians to participants and the frequency of contact have important implications for adherence
  • Most clinicians see a need to expand nutrition counseling opportunities for patients. As competition for the health care dollar increases, contacts in groups and by mail, telephone, audiotapes, and videotapes may provide effective counseling options to supplement traditional methods.
  • These findings, suggest that the self-management approach used in the MDRD study promotes long-term dietary adherence. Self-management strategies, particularly self-monitoring and the provision of feedback and support, be incorporated into nutrition intervention programs.
Funding Source:
Reviewer Comments:
  • Demographic details data not shown
  • This is a well-designed study. These findings suggest that the self-management approach used in the MDRD study promotes long-term dietary adherence. Self-management strategies, particularly self-monitoring and the provision of feedback and support, be incorporated into nutrition intervention programs.
  • Subjects are on different protein diet. It is better to assess biological markers for proteinuria, creatinine.
  • It is also necessary to know whether the protein diets are based on plant proteins or animal proteins. More information on the correlation of GFR and MAP with protein diets and psychological factors is necessary. It is observed that self-management approach used in the MDRD study is promoting long-term dietary adherence.
  • Based on these assessments, if it is possible calculating relative risk and relative incidence of the progression of disease is necessary
  • However, overall the results are promising further research is required for qualitative assessment to implement in daily clinical setting.

 

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? ???
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? ???
  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) ???
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) ???
  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? ???
  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? ???
  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? ???
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? No
  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.) No
  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? ???
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? No
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? ???
  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? ???
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? ???
  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? ???
  8.1. Were statistical analyses adequately described and the results reported appropriately? ???
  8.2. Were correct statistical tests used and assumptions of test not violated? ???
  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
  8.5. 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? Yes
  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? ???
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