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![Page 1: The 2013 Canadian Critical Care Nutrition Clinical Practice Guidelines: What are the Latest Recommendations? Daren K. Heyland MD Professor of Medicine.](https://reader037.fdocuments.us/reader037/viewer/2022110100/56649e0e5503460f94af8f17/html5/thumbnails/1.jpg)
The 2013 Canadian Critical Care Nutrition The 2013 Canadian Critical Care Nutrition Clinical Practice Guidelines: Clinical Practice Guidelines:
What are the Latest Recommendations?What are the Latest Recommendations?
Daren K. Heyland MD
Professor of MedicineQueen’s University, Kingston, ON Canada
On behalf of the Canadian Critical Care Nutrition Clinical Practice Guidelines Committee
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Disclosures
I have received speaker honoraria and/or I have been paid from grants from the following companies:
– Nestlé
– Fresenius Kabi
– Baxter
– Abbott
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Learning Objectives
Better understand the process by which CPGs are developed
Become familiar with recent randomized nutrition trials in critically ill adult patients
Enteral Fish oilsPN and type of Lipids New Sections
Review the updated analyses and recommendations of the Canadian CPGs
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www.criticalcarenutrition.com
Orginally published in 2003
Summarizes 198 trials studying 21283 patients
34 topics 17 recommendations
2005 update2005 update20072007 updateupdate20092009 updateupdate2013 update 2013 update
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Guideline Development
Effect sizeConfidence Intervals
Validity Homogeneity
Adequacy of control groupBiological plausibility
GeneralizabilitySafety
FeasibilityCost
evidence integration of values+
practiceguidelines
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Language of Recommendations
CONDITIONS LANGUAGE OF RECOMENDATION
No reservations about endorsing intervention.
“ strongly recommend”
Evidence supportive but minor uncertainties about safety, feasibility, or costs of intervention.
“recommend”
Supportive evidence weak and/or major uncertainties about safety, feasibility, or costs of intervention.
“ should be considered”
Inadequate or conflicting evidence.
“ insufficient data”
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Inclusion Criteria
Updated to 2013• Randomized controlled trials• Critically ill patients (not elective surgery)• Clinical Outcomes• EMBASE, Medline, Cinhal, reference lists
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New Evidence
67 new RCTs across 27 topics!
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Topic 2009 2013 Total
Enteral vs Parenteral 12 2 14
Early vs. delayed 14 2 16
Indirect Calorimetry 1 1 2
Arginine containing 24 2 26
Fish Oils/Borage Oils 4 4 8
Protein/peptides 4 1 5
Fibre 6 2 8
Small Bowel vs. Feeding 11 4 15
Probiotics 11 12 23
New RCTs per Topic
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Topic 2009 2013 Total
Combination EN + PN 5 3 8
PN Branched Chain A Acids 5 1 6
Intensive insulin 22 3 25
PN Type of lipids 5 4 9
PN Glutamine 17 11 28
Antioxidants 16 8 24
PN Selenium 11 7 18
New RCTs per topic
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New Topic # RCTs
Intentional Underfeeding: Trophic vs Full Feeds 2
Intentional Underfeeding: Hypocaloric EN 1
Fish Oils only 1
Threshold of GRVs 2
Discarding GRVs 1
EN: ß Hydroxyl Methyl Butyrate (HMB) 1
Early Supplemental PN vs Late 1
PN + EN Glutamine 1
Optimal glucose control: CHO Restricted Formula + Insulin Therapy
1
Vitamin D 1
New Topics (n=10)
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Enteral Fish Oils*
*Product enhanced with fish oils +borage oils + antioxidants
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Enteral Fish Oils**Product enhanced with fish oils +borage oils + antioxidants
2009 RecommendationBased on 5 studies, we recommend the use of
enteral formula with fish oils, borage oils, and
antioxidants in patients with ALI/ARDS
New RCTs = 4New RCTs = 4
Rice 2011Grau-Carmona 2011Thiella 2011Elamin 2012+ Pontes Arruda 2011+ Stapleton 2011 (fish oil only)
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Timing of FeedingTiming of Feeding
SSUUPPPPLLEEMMEENNTT
““Early Early Full”Full”Fast ramp upFast ramp up
““Early Early Trophic”Trophic”(10 ml/hr)(10 ml/hr)
N-3 + GLA +N-3 + GLA +AntioxidantsAntioxidants(Module delivered (Module delivered as as bolusbolus bid) bid)
ControlControlStandard ENStandard EN(480 cal/ 20 g pro)(480 cal/ 20 g pro)
n = 250 n = 250
n = 250 n = 250
NIH NHLBI
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OMEGA: 60-Day MortalityOMEGA: 60-Day Mortality
P=0.05P=0.14P=0.14
Rice et al JAMA Oct 2011
bolus: dilute effect?50% pts underfed
(trophic)protein in placebo
include but analyze without
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11 Spanish ICUs 89 patients with diagnosis of Sepsis on admission Randomized to:
• Fish Oil/Borage Oil formula OR• Standard polymeric formula
Outcomes: new organ dysfunction
Grau-Carmona Clin Nutr 2011
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Clinical Outcomes
Grau-Carmona Clin Nutr 2011
Fish Oils: Trend towards lower SOFA scores (NS)
First multicentre study to use “usual care” in control group…….no effect on
mortality
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89 patients from 5 centres in US
Mechanically ventilated patients with Acute lung injury (ALI)
Randomized to (separate from EN):• BOLUS fish oils 7.5 mls q 6 hrs, 9.75g EPA & 6.75 gm DHA/day OR• placebo i.e. normal saline X 14 days
EN or PN as per MDs discretion
Stapleton CCM 2011
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Clinical Outcomes
Stapleton CCM 2011
Fish Oils ONLYBolus
Separate from EN
X aggregate with RCTs of fish oil,
borage oil
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Fish Oils: Effect on mortality (n = 6)
2009: RR 0.67, 95% CI 0.51, 0.97, p = 0.003
No effect , statistical heterogeneity!
INTERSEPT, Stapleton data not included
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Fish oils: effect on mortality removing bolus RCT (n =5)
Significant effect, no statistical heterogeneity!
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EN Fish oils with new RCTs
Effect on mortality disappears when bolus study is included• statistical heterogeneity present
Effect on mortality is significant when bolus study excluded Infections (2 RCTs): no effect Reduction in ICU LOS still significant (heterogeneity) Concerns of control group, negative results of large studies
2013 Recommendations
Fish Oils/borage oil: Downgraded recommendation to “should be considered”
Fish Oils alone: insufficient data
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Use of PN and type of lipids
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EN + PN
No change from 2009we recommend that PN not be started
not be started at the same time as EN.
Insufficient evidence in those who are
not tolerating EN (case by case)
NEJM 2011Lancet 2012
Early Supplemental PN vs. LateCombined EN + PN
Strongly recommend that early PN & high IV
glucose not be used in low risk, short ICU stay
Insufficient evidence in those who are not
tolerating EN (case by case)
large multicentreearly PN: worse infections, LOSearly PN: no diff mortalityhigh glucose loadinglow risk patients
used indirect calorimetryNo difference mortalityreduced infections day 4-28
+ Abrishami 2010+ Chen 2011
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Lipid Free PN?
Recommendation: • Based on 2 level 2 studies, in critically ill patients who are not
malnourished, are tolerating some EN, or when parenteral nutrition is indicated for short term use (< 10 days), withholding soy bean emulsions should be considered.
• There are insufficient data to make a recommendation about withholding lipids high in soybean oil in critically ill patients who are malnourished or those requiring PN for long term (> 10 days).
• Practitioners will have to weigh the safety and benefits of withholding lipids high in soybean oil on an individual case-by-case basis in these latter patient populations.
There are no new randomized controlled trials since the 2009 update and hence there are no changes to the recommendation.
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Vanek VW, et al. Nutr Clin Pract 2012; 27: 150.
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High LCT
ω-6
MCT/LCT
50:50
High MUFA
Ω-9
High PUFA
Ω-3Mixtures
Soybean Oil
(SO)SO + Coconut
Olive Oil
(OO) + SOFish Oil (FO)
SO, FO,
Coconut, OO
Intralipid®
Lipofundin®
(MCT/LCT)® ClinOleic®
Omegaven® SMOF®
Lipoplus®
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Study or Subgroup1.1.1 LCT + MCT vs LCT
Garnacho-MonteroIovinelliLindgrenNijveldtSubtotal (95% CI)
Total eventsHeterogeneity: Tau² = 0.00; Chi² = 0.94, df = 3 (P = 0.82); I² = 0%Test for overall effect: Z = 0.53 (P = 0.59)
1.1.2 Fish oil containing emulsions vs LCT or LCT + MCT
BarbosaFrieseckeGrecuWang 2009Subtotal (95% CI)
Total eventsHeterogeneity: Tau² = 0.00; Chi² = 0.89, df = 3 (P = 0.83); I² = 0%Test for overall effect: Z = 1.16 (P = 0.25)
1.1.3 Olive oil containing emulsions vs LCT or LCT + MCT
Garcia de LorenzoHuschakPontes-Arruda 2012UmperrezSubtotal (95% CI)
Total eventsHeterogeneity: Tau² = 0.00; Chi² = 2.14, df = 3 (P = 0.54); I² = 0%Test for overall effect: Z = 0.49 (P = 0.62)
Total (95% CI)
Total eventsHeterogeneity: Tau² = 0.00; Chi² = 4.19, df = 11 (P = 0.96); I² = 0%Test for overall effect: Z = 1.27 (P = 0.20)Test for subgroup differences: Chi² = 0.25, df = 2 (P = 0.88), I² = 0%
Events
8212
13
418
20
24
44
195
32
69
Total
3512151274
13832828
152
1118
10351
183
409
Events
11301
15
422
32
31
41
218
34
80
Total
371215
872
10822628
146
1115
10149
176
394
Weight
13.4%3.2%0.8%1.7%
19.1%
6.6%27.9%
2.8%0.9%
38.3%
6.7%1.9%
26.5%7.5%
42.7%
100.0%
M-H, Random, 95% CI
0.77 [0.35, 1.69]0.67 [0.13, 3.30]
3.00 [0.13, 68.26]1.33 [0.14, 12.37]0.84 [0.43, 1.61]
0.77 [0.25, 2.34]0.81 [0.47, 1.39]0.62 [0.11, 3.41]0.20 [0.01, 3.99]0.76 [0.48, 1.21]
1.00 [0.33, 3.02]3.33 [0.42, 26.72]
0.89 [0.51, 1.55]0.60 [0.21, 1.71]0.90 [0.58, 1.39]
0.83 [0.62, 1.11]
Omega-6 Reducing LCT or LCT+MCT Risk Ratio Risk RatioM-H, Random, 95% CI
0.01 0.1 1 10 100Favours omega-6 reducing Favours LCT or LCT+MCT
Manzanares W, et al. Int Care Med 2013 (in press)
Ω-6 Sparing Strategies were associated with a reduction in Mortality (RR= 0.83, 95 % CI 0.62, 1.11, P= 0.20, heterogeneity I2 =0%)
Ω-6 Sparing Strategies were associated with a reduction in Mortality (RR= 0.83, 95 % CI 0.62, 1.11, P= 0.20, heterogeneity I2 =0%)
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Study or Subgroup1.4.1 Fish oil containing emulsions vs LCT or LCT + MCT
GrecuFrieseckeBarbosaSubtotal (95% CI)
Heterogeneity: Tau² = 0.00; Chi² = 1.84, df = 2 (P = 0.40); I² = 0%Test for overall effect: Z = 1.63 (P = 0.10)
1.4.2 Olive oil containing emulsions vs LCT or LCT + MCT
HuschakGarcia de LorenzoSubtotal (95% CI)
Heterogeneity: Tau² = 0.00; Chi² = 0.65, df = 1 (P = 0.42); I² = 0%Test for overall effect: Z = 2.57 (P = 0.01)
Total (95% CI)
Heterogeneity: Tau² = 3.00; Chi² = 5.36, df = 4 (P = 0.25); I² = 25%Test for overall effect: Z = 1.72 (P = 0.09)Test for subgroup differences: Chi² = 2.87, df = 1 (P = 0.09), I² = 65.2%
Mean
2.8322.8
10
1311
SD
1.6222.914.4
8.911.93
Total
88313
104
181129
133
Mean
5.2320.5
11
20.413
SD
2.819
12.64
716.25
Total
7821099
151126
125
Weight
50.5%16.4%
6.4%73.3%
21.1%5.6%
26.7%
100.0%
IV, Random, 95% CI
-2.40 [-4.76, -0.04]2.30 [-4.12, 8.72]
-1.00 [-12.07, 10.07]-1.81 [-3.98, 0.36]
-7.40 [-12.83, -1.97]-2.00 [-13.91, 9.91]
-6.47 [-11.41, -1.53]
-2.57 [-5.51, 0.37]
Year
200320082010
20052005
Omega-6 Reducing LCT or LCT+MCT Mean Difference Mean DifferenceIV, Random, 95% CI
-100 -50 0 50 100Favours omega-6 reducing Favours LCT or LCT+MCT
Ω-6 Sparing Strategies were associated with a trend towards a reduction in
Ventilation Days(WMD -2.57, 95% CI -5.51, 0.37, P=0.09)
Ω-6 Sparing Strategies were associated with a trend towards a reduction in
Ventilation Days(WMD -2.57, 95% CI -5.51, 0.37, P=0.09)
Manzanares W, et al. Int Care Med 2013 (in press)
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Study or Subgroup1.3.1 LCT + MCT vs LCT
NijveldtGarnacho-MonteroSubtotal (95% CI)
Heterogeneity: Tau² = 7.57; Chi² = 4.59, df = 1 (P = 0.03); I² = 78%Test for overall effect: Z = 0.67 (P = 0.51)
1.3.2 Fish oil containing emulsions vs LCT or LCT + MCT
GrecuFrieseckeBarbosaSubtotal (95% CI)
Heterogeneity: Tau² = 35.46; Chi² = 8.97, df = 2 (P = 0.01); I² = 78%Test for overall effect: Z = 0.28 (P = 0.78)
1.3.3 Olive oil containing emulsions vs LCT or LCT + MCT
Garcia de LorenzoHuschakUmperrezSubtotal (95% CI)
Heterogeneity: Tau² = 21.46; Chi² = 4.90, df = 2 (P = 0.09); I² = 59%Test for overall effect: Z = 1.16 (P = 0.25)
Total (95% CI)
Heterogeneity: Tau² = 10.21; Chi² = 21.87, df = 7 (P = 0.003); I² = 68%Test for overall effect: Z = 1.53 (P = 0.13)Test for subgroup differences: Chi² = 0.46, df = 2 (P = 0.80), I² = 0%
Mean
13.816.6
3.322812
32.917.9
17
SD
2.96.1
1.4825
14.4
10.611.2
18
Total
123547
88313
104
11185180
231
Mean
17.415.8
9.282313
41.825.115.2
SD
37
3.0820
12.6
16.37
14
Total
83745
7821099
11154975
219
Weight
19.1%18.3%37.4%
19.4%10.2%
5.5%35.1%
5.2%11.2%11.2%27.6%
100.0%
IV, Random, 95% CI
-3.60 [-6.25, -0.95]0.80 [-2.23, 3.83]
-1.46 [-5.77, 2.85]
-5.96 [-8.46, -3.46]5.00 [-1.90, 11.90]
-1.00 [-12.06, 10.06]-1.13 [-8.96, 6.69]
-8.90 [-20.39, 2.59]-7.20 [-13.47, -0.93]
1.80 [-4.51, 8.11]-4.08 [-10.97, 2.81]
-2.31 [-5.28, 0.66]
Year
19982002
200320082010
200520052012
Omega-6 Reducing LCT or LCT+MCT Mean Difference Mean DifferenceIV, Random, 95% CI
-100 -50 0 50 100Favours omega-6 reducing Favours LCT or LCT+MCT
Ω-6 Reducing Strategies were associated with a trend towards a reduction in ICU
LOS (WMD -2.31, 95% CI -5.28, 0.66, P=0.13)
Ω-6 Reducing Strategies were associated with a trend towards a reduction in ICU
LOS (WMD -2.31, 95% CI -5.28, 0.66, P=0.13) Manzanares W, et al. Int Care Med 2013 (in press)
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FO containing lipid emulsions were associated with a trend towards a
reduction in mortality RR= 0.71, 95 %CI 0.49-1.04, P= 0.08
FO containing lipid emulsions were associated with a trend towards a
reduction in mortality RR= 0.71, 95 %CI 0.49-1.04, P= 0.08
0.71 (0.49,1.04)
P= 0.08
Manzanares W, et al. JPEN 2013, in press.
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FO containing emulsions showed a trend towards reduction in the duration
of MV days WMD -1.41, 95% CI -3.43, 0.61, P=0.17
FO containing emulsions showed a trend towards reduction in the duration
of MV days WMD -1.41, 95% CI -3.43, 0.61, P=0.17
P= 0.17
-1.41 (-3.43,0.61)
Manzanares W, et al. JPEN 2013, in press.
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Which Alternative Lipid Emulsion to Use?
• No head to head trials (and not likely to be)
• We analyzed our International Nutrition Survey database to evaluate effect of Alt Lipids on outcomes.
• Analyzed adjusted for key confounding variables.
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Edmunds, Heyland (in submission)
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Which Alternative Lipid Emulsion to Use?
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Which Alternative Lipid Emulsion to Use?
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Characteristic Lipid-free(n=70)
Soybean oil(n=223)
MCT oil(n=65)
Olive oil(n=74)
Fish oil(n=19)
pa
Age (yrs), mean±SD 64.8 ±16.6 63.5 ±15.9 61.9 ±16.9 64.0 ±16.4 66.2 ±18.3 0.81
Sex, n (%)MaleFemale
50 (71.4)20 (28.6)
135 (60.5)88 (39.5)
42 (64.6)23 (35.4)
45 (60.8)29 (39.2)
9 (47.4)10 (52.6)
0.31
Body mass index (kg/m2), mean±SD 26.1 ±9.8 28.4 ±8.0 23.8 ±3.3 25.6 ±4.7 27.4 ±6.4 <0.001
Admission category, n (%)MedicalEmergency surgicalElective Surgical
34 (48.6)23 (32.9)13 (18.6)
65 (29.1)118 (52.9)40 (17.9)
20 (30.8)31 (47.7)14 (21.5)
21 (28.4)35 (47.3)18 (24.3)
3 (15.8)15 (78.9)
1 (5.3)0.011
APACHE II score, mean±SD 23.8 ±9.5 22.4 ±7.9 22.7 ±9.3 21.1 ±8.0 24.3 ±6.8 0.30
Mean daily calories from PN, mean±SD 1036 ±428 1466 ±372 1287 ±313 1553 ±388 1517 ±385 <0.001
Mean daily calories from propofol, mean±SD 39 ±89 28 ±97 14 ±37 43 ±65 13 ±30 0.005
Mean daily total calories (PN + propofol), mean±SD 1084 ±472 1499 ±387 1306 ±326 1625 ±406 1532 ±398 <0.001
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Which Alternative Lipid Emulsion to Use?
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Edmunds, Heyland (in submission)
Soybean
Fish Oil
Olive Oil
Lipid FreeMCT
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PN Type of Lipids
2009 Recommendation
There are insufficient data to make a recommendation on the
type of lipids to be used in critically ill patients receiving
parenteral nutrition.
2013 Recommendation: IV lipids that reduce the load of omega-6 fatty acids/soybean
oil emulsions should be considered. There are
insufficient data on type of soybean reducing lipids
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New Topic RCTs Recommendation
Intentional Underfeeding: Hypocaloric EN
1 Insufficient data
Threshold of GRVs 1 Insufficient data (250-500ml)
Discarding GRVs 1 Insufficient data
EN: ß Hydroxyl Methyl Butyrate (HMB)
1 Insufficient data
Optimal glucose control: CHO Restricted Formula + Insulin Therapy
1 Insufficient data
Vitamin D 1 Insufficient data
Other Topics
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Summary• Many recent RCTs in area of critical care nutrition • Careful review of the articles is recommended• Recommendations downgraded
EN Fish Oils/borage oils
PN Glutamine
• Recommendations upgraded Probiotics
Type of PN lipids
• Recommendations do not changeCombined AOX
PN Selenium and others
• New RecommendationsPN + EN Glutamine: strongly recommended NOT to be used
Early PN vs Delayed PN: Strongly recommend NOT be used
Other: Trophic vs full feeds: should NOT be considered
Updated recommendations will have an impact on practices in ICU
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Acknowledgment
Co Chair Daren HeylandLeah GramlichJohn DroverBrian JurewitschCarmen Christman Chelsea CorbettJan Greenwood Michele McCallGwynne MacdonaldGuiseppe PagliarelloJim Kutsogiannis
John MuscedereKhursheed JeejeebhoyCourtney Somers-BalotaDominique GarrelAdam Rahman
William ManzanaresPaul WischmeyerRene StapletonTodd RiceAndrew Davies Emma Ridley
Canadian Clinical Practice Guidelines Committee
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