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Cochrane Database of Systematic Reviews

Nutritional supplementation for hip fracture aftercare in older people

Information

DOI:
https://doi.org/10.1002/14651858.CD001880.pub6Copy DOI
Database:
  1. Cochrane Database of Systematic Reviews
Version published:
  1. 30 November 2016see what's new
Type:
  1. Intervention
Stage:
  1. Review
Cochrane Editorial Group:
  1. Cochrane Bone, Joint and Muscle Trauma Group

Copyright:
  1. Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Authors

  • Alison Avenell

    Correspondence to: Health Services Research Unit, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK

    [email protected]

  • Toby O Smith

    Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, UK

  • James P Curtain

    Department of General Medicine, Addenbrookes NHS Trust, Cambridge University Hospital, Cambridge, UK

  • Jenson CS Mak

    Department of Aged Care and Rehabilitation, Gosford Hospital, Gosford, Australia

  • Phyo K Myint

    Division of Applied Health Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK

Contributions of authors

Alison Avenell, Toby Smith, Jenson Mak and James Curtain assessed and extracted data from trials for this version of the review. Alison Avenell and Toby Smith revised the analysis, performed the GRADE review, prepared the 'Summary of findings' tables and re‐interpreted the data for this version of the review. Alison Avenell wrote the first draft of this version of the review and all authors revised drafts. All authors are guarantors of this review.

Sources of support

Internal sources

  • University of Aberdeen, UK.

  • University of East Anglia, Norwich, UK.

  • Cambridge University Hospitals NHS Trust, UK.

  • Gosford Hospital, Gosford, Australia.

External sources

  • Chief Scientist Office of the Scottish Government Health Directorates, UK.

Declarations of interest

Alison Avenell: none known
Toby O Smith: none known
James P Curtain: none known
Jenson CS Mak: none known
Phyo K Myint: none known

Acknowledgements

For this version of the review, we are grateful for the helpful comments at editorial and external review from Helen Handoll and Jane Portlock. We also thank Lindsey Elstub and Joanne Elliott for their help on this version.

This project was supported by the National Institute for Health Research via Cochrane Infrastructure funding to the Cochrane Bone, Joint and Muscle Trauma Group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health.

Version history

Published

Title

Stage

Authors

Version

2016 Nov 30

Nutritional supplementation for hip fracture aftercare in older people

Review

Alison Avenell, Toby O Smith, James P Curtain, Jenson CS Mak, Phyo K Myint

https://doi.org/10.1002/14651858.CD001880.pub6

2010 Jan 20

Nutritional supplementation for hip fracture aftercare in older people

Review

Alison Avenell, Helen HG Handoll

https://doi.org/10.1002/14651858.CD001880.pub5

2006 Oct 18

Nutritional supplementation for hip fracture aftercare in older people

Review

Alison Avenell, Helen HG Handoll

https://doi.org/10.1002/14651858.CD001880.pub4

2005 Apr 20

Nutritional supplementation for hip fracture aftercare in older people

Review

Alison Avenell, Helen HG Handoll

https://doi.org/10.1002/14651858.CD001880.pub3

2004 Jan 26

Nutritional supplementation for hip fracture aftercare in the elderly

Review

Alison Avenell, Helen HG Handoll

https://doi.org/10.1002/14651858.CD001880.pub2

2000 Jun 27

Nutritional supplementation for hip fracture aftercare in the elderly

Review

Alison Avenell, Helen HG Handoll

https://doi.org/10.1002/14651858.CD001880

Differences between protocol and review

We made the following changes in this update (2016).

Types of interventions

In response to feedback from an external referee, we added clarification that the nutritional interventions covered in this review were aimed at improving recovery from hip fracture.

Risk of bias

In the protocol and previous versions of this review (Avenell 2010), we assessed methodological quality using a subject‐specific modification of the former generic evaluation tool developed by the Cochrane Bone, Muscle and Joint Trauma Group. In this update, we have changed to assessing the risk of bias of all included trials using the Cochrane 'Risk of bias' tool (Higgins 2011).

Outcomes

In this update to the review, we do not report on the following outcomes, which were listed under 'Other outcomes' in previous versions of this review (Avenell 2010):

  • changes in anthropometric indices, such as weight, skinfold thickness, and mid‐upper arm circumference

  • new fractures

  • changes in bone mineral density, assessed by techniques involving radiation, for example dual photon absorptiometry, dual energy X‐ray absorptiometry, quantitative computed tomography

  • changes in nutritional indicators measured in blood, such as albumin, transferrin, vitamin and mineral levels, haemoglobin

  • changes in functional markers of nutritional status, including delayed cutaneous hypersensitivity (a marker of immune function) and grip strength

GRADE assessment

We used the GRADE approach to assess the quality of evidence related to the each of the primary outcomes for all comparisons.

Keywords

MeSH

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Study flow diagram
Figures and Tables -
Figure 1

Study flow diagram

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
Figures and Tables -
Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies

Risk of bias summary: review authors' judgements about each risk of bias item for each included study
Figures and Tables -
Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study

Forest plot of comparison: 1 Multinutrient supplements (oral, nasogastric, intravenous) versus control, outcome: 1.1 Mortality by end of study
Figures and Tables -
Figure 4

Forest plot of comparison: 1 Multinutrient supplements (oral, nasogastric, intravenous) versus control, outcome: 1.1 Mortality by end of study

Forest plot of comparison: 1 Multinutrient supplements (oral, nasogastric, intravenous) versus control, outcome: 1.2 Participants with complications at end of study
Figures and Tables -
Figure 5

Forest plot of comparison: 1 Multinutrient supplements (oral, nasogastric, intravenous) versus control, outcome: 1.2 Participants with complications at end of study

Funnel plot of comparison: 1 Multinutrient supplements (oral, nasogastric, intravenous) versus control, outcome: 1.1 Mortality by end of study
Figures and Tables -
Figure 6

Funnel plot of comparison: 1 Multinutrient supplements (oral, nasogastric, intravenous) versus control, outcome: 1.1 Mortality by end of study

Funnel plot of comparison: 1 Multinutrient supplements (oral, nasogastric, intravenous) versus control, outcome: 1.2 Participants with complications at end of study
Figures and Tables -
Figure 7

Funnel plot of comparison: 1 Multinutrient supplements (oral, nasogastric, intravenous) versus control, outcome: 1.2 Participants with complications at end of study

Comparison 1 Multinutrient supplements (oral, nasogastric, intravenous) versus control, Outcome 1 Mortality by end of study.
Figures and Tables -
Analysis 1.1

Comparison 1 Multinutrient supplements (oral, nasogastric, intravenous) versus control, Outcome 1 Mortality by end of study.

Comparison 1 Multinutrient supplements (oral, nasogastric, intravenous) versus control, Outcome 2 Participants with complications at end of study.
Figures and Tables -
Analysis 1.2

Comparison 1 Multinutrient supplements (oral, nasogastric, intravenous) versus control, Outcome 2 Participants with complications at end of study.

Comparison 1 Multinutrient supplements (oral, nasogastric, intravenous) versus control, Outcome 3 Participants with complications at end of study: random‐effects model.
Figures and Tables -
Analysis 1.3

Comparison 1 Multinutrient supplements (oral, nasogastric, intravenous) versus control, Outcome 3 Participants with complications at end of study: random‐effects model.

Comparison 1 Multinutrient supplements (oral, nasogastric, intravenous) versus control, Outcome 4 Unfavourable outcome (death or complications) at end of study.
Figures and Tables -
Analysis 1.4

Comparison 1 Multinutrient supplements (oral, nasogastric, intravenous) versus control, Outcome 4 Unfavourable outcome (death or complications) at end of study.

Comparison 1 Multinutrient supplements (oral, nasogastric, intravenous) versus control, Outcome 5 Unfavourable outcome (death or complications) ‐ oral supplements extra analyses.
Figures and Tables -
Analysis 1.5

Comparison 1 Multinutrient supplements (oral, nasogastric, intravenous) versus control, Outcome 5 Unfavourable outcome (death or complications) ‐ oral supplements extra analyses.

Comparison 1 Multinutrient supplements (oral, nasogastric, intravenous) versus control, Outcome 6 Adverse effects (putatively related to treatment).
Figures and Tables -
Analysis 1.6

Comparison 1 Multinutrient supplements (oral, nasogastric, intravenous) versus control, Outcome 6 Adverse effects (putatively related to treatment).

Comparison 2 Multinutrient supplements (oral, nasogastric routes, intravenous) versus control (split by nutritional status), Outcome 1 Mortality by end of study.
Figures and Tables -
Analysis 2.1

Comparison 2 Multinutrient supplements (oral, nasogastric routes, intravenous) versus control (split by nutritional status), Outcome 1 Mortality by end of study.

Comparison 2 Multinutrient supplements (oral, nasogastric routes, intravenous) versus control (split by nutritional status), Outcome 2 Mortality by end of study ‐ oral supplements only.
Figures and Tables -
Analysis 2.2

Comparison 2 Multinutrient supplements (oral, nasogastric routes, intravenous) versus control (split by nutritional status), Outcome 2 Mortality by end of study ‐ oral supplements only.

Comparison 2 Multinutrient supplements (oral, nasogastric routes, intravenous) versus control (split by nutritional status), Outcome 3 Participants with complications at end of study.
Figures and Tables -
Analysis 2.3

Comparison 2 Multinutrient supplements (oral, nasogastric routes, intravenous) versus control (split by nutritional status), Outcome 3 Participants with complications at end of study.

Comparison 2 Multinutrient supplements (oral, nasogastric routes, intravenous) versus control (split by nutritional status), Outcome 4 Unfavourable outcome (death or complications) at end of study.
Figures and Tables -
Analysis 2.4

Comparison 2 Multinutrient supplements (oral, nasogastric routes, intravenous) versus control (split by nutritional status), Outcome 4 Unfavourable outcome (death or complications) at end of study.

Comparison 3 Multinutrient supplements (oral, nasogastric routes, intravenous) versus control (by allocation concealment), Outcome 1 Mortality by end of study by risk of bias for allocation concealment.
Figures and Tables -
Analysis 3.1

Comparison 3 Multinutrient supplements (oral, nasogastric routes, intravenous) versus control (by allocation concealment), Outcome 1 Mortality by end of study by risk of bias for allocation concealment.

Comparison 3 Multinutrient supplements (oral, nasogastric routes, intravenous) versus control (by allocation concealment), Outcome 2 Participants with complications at end of study by risk of bias for allocation concealment.
Figures and Tables -
Analysis 3.2

Comparison 3 Multinutrient supplements (oral, nasogastric routes, intravenous) versus control (by allocation concealment), Outcome 2 Participants with complications at end of study by risk of bias for allocation concealment.

Comparison 4 High protein‐containing supplements versus low protein‐ or non‐protein‐containing supplements, Outcome 1 Mortality by end of study.
Figures and Tables -
Analysis 4.1

Comparison 4 High protein‐containing supplements versus low protein‐ or non‐protein‐containing supplements, Outcome 1 Mortality by end of study.

Comparison 4 High protein‐containing supplements versus low protein‐ or non‐protein‐containing supplements, Outcome 2 Unfavourable outcome (death or complications) at end of study.
Figures and Tables -
Analysis 4.2

Comparison 4 High protein‐containing supplements versus low protein‐ or non‐protein‐containing supplements, Outcome 2 Unfavourable outcome (death or complications) at end of study.

Comparison 5 Thiamin (vitamin B1) and water soluble vitamins versus control, Outcome 1 Mortality by end of study.
Figures and Tables -
Analysis 5.1

Comparison 5 Thiamin (vitamin B1) and water soluble vitamins versus control, Outcome 1 Mortality by end of study.

Comparison 5 Thiamin (vitamin B1) and water soluble vitamins versus control, Outcome 2 Participants with complications at end of study.
Figures and Tables -
Analysis 5.2

Comparison 5 Thiamin (vitamin B1) and water soluble vitamins versus control, Outcome 2 Participants with complications at end of study.

Comparison 6 Vitamin D versus control or lower dose supplementation, Outcome 1 Participants with complications at end of study.
Figures and Tables -
Analysis 6.1

Comparison 6 Vitamin D versus control or lower dose supplementation, Outcome 1 Participants with complications at end of study.

Comparison 6 Vitamin D versus control or lower dose supplementation, Outcome 2 Mortality by end of study.
Figures and Tables -
Analysis 6.2

Comparison 6 Vitamin D versus control or lower dose supplementation, Outcome 2 Mortality by end of study.

Comparison 7 Iron supplementation versus control, Outcome 1 Mortality by end of study.
Figures and Tables -
Analysis 7.1

Comparison 7 Iron supplementation versus control, Outcome 1 Mortality by end of study.

Comparison 7 Iron supplementation versus control, Outcome 2 Participants with complications at end of study.
Figures and Tables -
Analysis 7.2

Comparison 7 Iron supplementation versus control, Outcome 2 Participants with complications at end of study.

Comparison 8 Taurine versus placebo, Outcome 1 Mortality by end of study.
Figures and Tables -
Analysis 8.1

Comparison 8 Taurine versus placebo, Outcome 1 Mortality by end of study.

Comparison 9 Dietetic assistants versus usual care, Outcome 1 Mortality by end of study.
Figures and Tables -
Analysis 9.1

Comparison 9 Dietetic assistants versus usual care, Outcome 1 Mortality by end of study.

Comparison 9 Dietetic assistants versus usual care, Outcome 2 Participants with complications at end of study.
Figures and Tables -
Analysis 9.2

Comparison 9 Dietetic assistants versus usual care, Outcome 2 Participants with complications at end of study.

Summary of findings for the main comparison. Multinutrient supplements (oral) versus control for hip fracture aftercare in older people

Multinutrient supplements (oral) versus control for hip fracture aftercare in older people

Patient or population: Older people undergoing hip fracture aftercare
Settings: Acute hospital
Intervention: Multinutrient supplements (oral route) in addition to standard care. (Typically, supplements were started either pre‐operatively or within 2 days postoperatively and continued for at least a month)

Comparison: Standard postoperative nutritional support and care in control groups

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Control

Multinutrient supplements (oral) versus control

Mortality by end of study

Follow‐up: 1‐12 months

Study population

RR 0.81
(0.49 to 1.31)

968
(15 studies)

⊕⊕⊝⊝
low3

The statistical test for subgroup differences between the results for the 5 trials targeting malnourished participants and those 10 trials not targeting malnourished participants did not confirm a difference between the two subgroups for mortality

72 per 10001

59 per 1000
(36 to 95)

High risk2

250 per 1000

203 per 1000
(123 to 328)

Participants with complications (e.g. pressure sore, chest infection) at end of study
Follow‐up: 1‐12 months

Study population

RR 0.71
(0.59 to 0.86)

727
(11 studies)

⊕⊕⊝⊝
low6

Only 2 trials targeting malnourished people reported these data

443 per 10004

315 per 1000
(262 to 381)

Moderate risk5

290 per 1000

206 per 1000
(171 to 250)

Unfavourable outcome 7 by end of study

Follow‐up: 1‐12 months

Study population

RR 0.67

(0.51 to 0.89)

334

(6 studies)

⊕⊝⊝⊝
very low8

Only 1 trial targeting malnourished people reported these data

500 per 10004

335 per 1000

(255 to 445)

Putative side effects of treatment (e.g. vomiting and diarrhoea)

Follow‐up: during supplementation period

Study population

RR 0.99

(0.47 to 2.05)

442

(6 studies)

⊕⊝⊝⊝
very low9

Three of the 6 trials reported no adverse effects

50 per 10004

50 per 1000

(24 to 103)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1. The control group risk is the median control group risk across the 9 studies that reported one or more deaths in the control group.
2. The high control group risk is based on the one‐year mortality rate derived from Bentler 2009 (26%) and Mariconda 2015 (24.7% for those over 80 years). Pooled estimate includes no effect and 95% confidence intervals encompass relative risk increase greater than 25%.
3. Downgraded 1 level for high risk of bias and 1 level for imprecision.
4. The control group risk is the median control group risk across studies.
5. Moderate control risk is derived from participants whilst in hospital in Mariconda 2015.
6. Downgraded 2 levels for very serious risk of bias.
7. Unfavourable outcome was defined as the number of trial participants who died plus the number of survivors with complications. Where these data were unavailable, we accepted a slightly different definition (mortality or survivors with a major complication or two or more minor complications) provided in 3 trials.
8. Downgraded 2 levels for serious risk of bias and 1 for indirectness reflecting the mixed definition of the outcome measure.
9. Downgraded 3 levels individually for risk of bias, inconsistency and imprecision.

Figures and Tables -
Summary of findings for the main comparison. Multinutrient supplements (oral) versus control for hip fracture aftercare in older people
Summary of findings 2. Multinutrient supplements (nasogastric) versus control for hip fracture aftercare in older people

Multinutrient supplements (nasogastric) versus control for hip fracture aftercare in older people7

Patient or population: Older people undergoing hip fracture aftercare
Settings: Acute hospitals
Intervention: Multinutrient supplements (nasogastric). (Started within 5 days of surgery and continued usually until oral intake was sufficient or hospital discharge.)1

Comparison: Standard postoperative nutritional support and care in control groups

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Control

Multinutrient supplements (nasogastric) versus control

Mortality by end of study
Follow‐up: 1‐12 months

Study Population

RR: 0.99

(0.50 to 1.97)

280

(3 studies)

⊕⊝⊝⊝
very low3

Only 1 trial targeting malnourished participants reported these data

156 per 10002

155 per 1000

(78 to 308)

Participants with complications (e.g. pressure sore, aspiration pneumonia) at end of study
Follow‐up: 6 months

Study Population

RR: 1.09

(0.73 to 1.64)

18

(1 study)

⊕⊝⊝⊝
very low5

For consistency we have presented 95% CI here but have used 99% CI for single trial data in the main text: 99% CI 0.64 to 1.86.6

800 per 10004

872 per 1000

(584 to 1000)

Unfavourable outcome

Follow‐up: 1‐12 months

See comment

See comment

Outcome not reported

Putative side effects of treatment (e.g. aspiration pneumonia)

Follow‐up: during supplementation period

See comment

See comment

Insufficient data to draw any conclusions. However, poor toleration of tube feeding was noted.1

There was no report of aspiration pneumonia (1 study; 140 participants). One study reported 18 (28% of 64) participants in the intervention group developed diarrhoea ‐ this was ascribed to antibiotics in 16 ‐ but did not report on the control group. One study (18 participants) reported 3 cases of "bloating" in the intervention group; it found no feed‐induced diarrhoea

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk Ratio.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change

the estimate.
Very low quality: We are very uncertain about the estimate.

1. Nasogatric feeding was poorly tolerated but varied between studies. One study reported only 26% of the intervention group tolerated tube feeding for the full two weeks; another reported 78% completed the course (until hospital discharge).
2. The control group risk is the median control group risk across studies.
3. Downgraded 2 levels for serious risk of bias and one for inconsistency reflecting considerable heterogeneity (I2 = 69%)
4. The control group risk is that of the control group in the sole study contributing data.
5. Downloaded 2 levels for serious risk of bias and one level for imprecision.
6. The choice of 99% CIs reflected the extra burden of proof we considered appropriate for individual trials, in view of their generally poor quality.

Figures and Tables -
Summary of findings 2. Multinutrient supplements (nasogastric) versus control for hip fracture aftercare in older people
Table 1. Length of hospital stay data used for significance testing

Study ID

Intervention
(n, mean days, SD)

Control
(n, mean days, SD)

Mean difference (99% confidence intervaI)

Multinutritional oral supplements

Anbar 2014

22

10.1

3.2

28

12.5

5.5

‐2.40 days (‐5.60 to 0.80)

Botella‐Carretero 2010

30

13.3

4.3

30

12.8

4.0

0.50 days (‐2.26 to 3.26)

Brown 1992b

5

27.00

10.00

5

48.00

37.00

‐21.00 days (‐65.15 to 23.15)

Bruce 2003

50

17.70

9.40

58

16.60

9.20

1.10 days (‐3.53 to 5.73)

Madigan 1994

18

16.00

8.00

12

15.00

11.00

1.00 day (‐8.51 to 10.51)

Myint 2013

61

26.2

8.2

60

29.9

11.2

‐3.70 days (‐8.30 to 0.90)

Nasogastric tube feeding

Sullivan 1998

8

38.20

36.90

7

23.70

20.00

14.50 days (‐24.34 to 53.34)

High protein supplements

Espaulella 2000

85

16.40

6.60

86

17.20

7.70

‐0.80 days (‐3.62 to 2.02)

Neumann 2004

18

23.20

5.52

20

28.00

11.63

‐4.80 days (‐12.29 to 2.69)

Iron supplementation versus control

Parker 2010

150

18.8

17.4

150

21.3

20.6

‐2.50 days (‐8.17 to 3.17)

Serrano‐Trenas 2011

99

13.5

7.1

97

13.1

6.9

0.40 days (‐2.18 to 2.98)

Vitamin B1

Day 1988

28

35.00

34.00

30

29.00

30.00

6.00 days (‐15.75 to 27.75)

Vitamin, mineral and amino acid supplementation versus control

Scivoletto 2010

49

15.4

6.8

47

17.9

7.3

‐2.50 days (‐6.21 to 1.21)

Semi‐essential amino acid

Van Stijn 2015

111

13

10

123

13

11

0.00 days (‐3.54 to 3.54)

SD: standard deviation

Figures and Tables -
Table 1. Length of hospital stay data used for significance testing
Comparison 1. Multinutrient supplements (oral, nasogastric, intravenous) versus control

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mortality by end of study Show forest plot

20

1385

Risk Ratio (M‐H, Fixed, 99% CI)

0.79 [0.55, 1.15]

1.1 Oral supplements

15

968

Risk Ratio (M‐H, Fixed, 99% CI)

0.81 [0.49, 1.32]

1.2 Nasogastric tube feeding

3

280

Risk Ratio (M‐H, Fixed, 99% CI)

0.99 [0.50, 1.97]

1.3 Nasogastric tube feeding and oral supplements

1

57

Risk Ratio (M‐H, Fixed, 99% CI)

0.74 [0.23, 2.35]

1.4 Intravenous feeding and oral supplements

1

80

Risk Ratio (M‐H, Fixed, 99% CI)

0.11 [0.01, 2.00]

2 Participants with complications at end of study Show forest plot

14

882

Risk Ratio (M‐H, Fixed, 99% CI)

0.69 [0.59, 0.81]

2.1 Oral supplements

11

727

Risk Ratio (M‐H, Fixed, 99% CI)

0.71 [0.59, 0.86]

2.2 Nasogastric tube feeding

1

18

Risk Ratio (M‐H, Fixed, 99% CI)

1.09 [0.73, 1.64]

2.3 Nasogastric tube feeding and oral supplements

1

57

Risk Ratio (M‐H, Fixed, 99% CI)

1.11 [0.75, 1.65]

2.4 Intravenous feeding and oral supplements

1

80

Risk Ratio (M‐H, Fixed, 99% CI)

0.21 [0.10, 0.46]

3 Participants with complications at end of study: random‐effects model Show forest plot

14

882

Risk Ratio (M‐H, Random, 99% CI)

0.70 [0.53, 0.91]

3.1 Oral supplements

11

727

Risk Ratio (M‐H, Random, 99% CI)

0.72 [0.58, 0.89]

3.2 Nasogastric tube feeding

1

18

Risk Ratio (M‐H, Random, 99% CI)

1.09 [0.73, 1.64]

3.3 Nasogastric tube feeding and oral supplements

1

57

Risk Ratio (M‐H, Random, 99% CI)

1.11 [0.75, 1.65]

3.4 Intravenous feeding and oral supplements

1

80

Risk Ratio (M‐H, Random, 99% CI)

0.21 [0.10, 0.46]

4 Unfavourable outcome (death or complications) at end of study Show forest plot

6

334

Risk Ratio (M‐H, Fixed, 99% CI)

0.67 [0.51, 0.89]

4.1 Oral supplements

6

334

Risk Ratio (M‐H, Fixed, 99% CI)

0.67 [0.51, 0.89]

4.2 Nasogastric tube feeding

0

0

Risk Ratio (M‐H, Fixed, 99% CI)

0.0 [0.0, 0.0]

4.3 Nasogastric tube feeding and oral supplements

0

0

Risk Ratio (M‐H, Fixed, 99% CI)

0.0 [0.0, 0.0]

4.4 Intravenous feeding and oral supplements

0

0

Risk Ratio (M‐H, Fixed, 99% CI)

0.0 [0.0, 0.0]

5 Unfavourable outcome (death or complications) ‐ oral supplements extra analyses Show forest plot

6

Risk Ratio (M‐H, Fixed, 99% CI)

Subtotals only

5.1 Oral supplements: worst case scenario

6

353

Risk Ratio (M‐H, Fixed, 99% CI)

0.81 [0.62, 1.04]

5.2 Oral supplements: Hankins 1996 acute hospital data

1

31

Risk Ratio (M‐H, Fixed, 99% CI)

0.96 [0.71, 1.31]

5.3 Oral supplements: Hankins 1996 post discharge

1

31

Risk Ratio (M‐H, Fixed, 99% CI)

1.10 [0.50, 2.41]

6 Adverse effects (putatively related to treatment) Show forest plot

8

Risk Ratio (M‐H, Fixed, 99% CI)

Subtotals only

6.1 Oral supplements (mainly diarrhoea or/and vomiting)

6

442

Risk Ratio (M‐H, Fixed, 99% CI)

0.99 [0.47, 2.05]

6.2 Nasogatric tube feeding

1

18

Risk Ratio (M‐H, Fixed, 99% CI)

8.56 [0.51, 144.86]

6.3 Intravenous feeding and oral supplements

1

57

Risk Ratio (M‐H, Fixed, 99% CI)

1.85 [0.49, 7.03]

6.4 Nasogastric tube feeding and oral supplements

0

0

Risk Ratio (M‐H, Fixed, 99% CI)

0.0 [0.0, 0.0]

Figures and Tables -
Comparison 1. Multinutrient supplements (oral, nasogastric, intravenous) versus control
Comparison 2. Multinutrient supplements (oral, nasogastric routes, intravenous) versus control (split by nutritional status)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mortality by end of study Show forest plot

20

1385

Risk Ratio (M‐H, Fixed, 99% CI)

0.79 [0.55, 1.15]

1.1 Malnourished targeted

6

388

Risk Ratio (M‐H, Fixed, 99% CI)

0.55 [0.27, 1.11]

1.2 Malnourished not targeted

14

997

Risk Ratio (M‐H, Fixed, 99% CI)

0.92 [0.59, 1.42]

2 Mortality by end of study ‐ oral supplements only Show forest plot

15

968

Risk Ratio (M‐H, Fixed, 99% CI)

0.81 [0.49, 1.32]

2.1 Malnourished targeted

5

266

Risk Ratio (M‐H, Fixed, 99% CI)

0.39 [0.13, 1.20]

2.2 Malnourished not targeted

10

702

Risk Ratio (M‐H, Fixed, 99% CI)

0.99 [0.56, 1.72]

3 Participants with complications at end of study Show forest plot

14

882

Risk Ratio (M‐H, Fixed, 99% CI)

0.69 [0.59, 0.81]

3.1 Malnourished targeted

2

150

Risk Ratio (M‐H, Fixed, 99% CI)

0.64 [0.46, 0.89]

3.2 Malnourished not targeted

12

732

Risk Ratio (M‐H, Fixed, 99% CI)

0.70 [0.59, 0.84]

4 Unfavourable outcome (death or complications) at end of study Show forest plot

6

334

Risk Ratio (M‐H, Fixed, 99% CI)

0.67 [0.51, 0.89]

4.1 Malnourished targeted

1

29

Risk Ratio (M‐H, Fixed, 99% CI)

0.47 [0.17, 1.31]

4.2 Malnourished not targeted

5

305

Risk Ratio (M‐H, Fixed, 99% CI)

0.70 [0.52, 0.93]

Figures and Tables -
Comparison 2. Multinutrient supplements (oral, nasogastric routes, intravenous) versus control (split by nutritional status)
Comparison 3. Multinutrient supplements (oral, nasogastric routes, intravenous) versus control (by allocation concealment)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mortality by end of study by risk of bias for allocation concealment Show forest plot

20

1385

Risk Ratio (M‐H, Fixed, 99% CI)

0.79 [0.55, 1.15]

1.1 Low risk of bias

10

682

Risk Ratio (M‐H, Fixed, 99% CI)

0.57 [0.32, 1.01]

1.2 Unclear risk of bias

7

462

Risk Ratio (M‐H, Fixed, 99% CI)

1.22 [0.65, 2.28]

1.3 High risk of bias

3

241

Risk Ratio (M‐H, Fixed, 99% CI)

0.78 [0.34, 1.79]

2 Participants with complications at end of study by risk of bias for allocation concealment Show forest plot

14

882

Risk Ratio (M‐H, Fixed, 99% CI)

0.69 [0.59, 0.81]

2.1 Low risk of bias

9

622

Risk Ratio (M‐H, Fixed, 99% CI)

0.78 [0.66, 0.92]

2.2 Unclear risk of bias

5

260

Risk Ratio (M‐H, Fixed, 99% CI)

0.38 [0.24, 0.61]

2.3 High risk of bias

0

0

Risk Ratio (M‐H, Fixed, 99% CI)

0.0 [0.0, 0.0]

Figures and Tables -
Comparison 3. Multinutrient supplements (oral, nasogastric routes, intravenous) versus control (by allocation concealment)
Comparison 4. High protein‐containing supplements versus low protein‐ or non‐protein‐containing supplements

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mortality by end of study Show forest plot

4

361

Risk Ratio (M‐H, Fixed, 99% CI)

1.42 [0.85, 2.37]

1.1 Protein‐containing supplement v non‐protein‐containing supplement

3

315

Risk Ratio (M‐H, Fixed, 99% CI)

1.38 [0.82, 2.34]

1.2 High protein‐containing supplement v low protein‐containing supplement

1

46

Risk Ratio (M‐H, Fixed, 99% CI)

2.18 [0.21, 22.42]

2 Unfavourable outcome (death or complications) at end of study Show forest plot

2

223

Risk Ratio (M‐H, Fixed, 99% CI)

0.78 [0.65, 0.95]

2.1 Protein‐containing supplement v non‐protein‐containing supplement

2

223

Risk Ratio (M‐H, Fixed, 99% CI)

0.78 [0.65, 0.95]

Figures and Tables -
Comparison 4. High protein‐containing supplements versus low protein‐ or non‐protein‐containing supplements
Comparison 5. Thiamin (vitamin B1) and water soluble vitamins versus control

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mortality by end of study Show forest plot

1

Risk Ratio (M‐H, Fixed, 99% CI)

Totals not selected

2 Participants with complications at end of study Show forest plot

1

Risk Ratio (M‐H, Fixed, 99% CI)

Totals not selected

Figures and Tables -
Comparison 5. Thiamin (vitamin B1) and water soluble vitamins versus control
Comparison 6. Vitamin D versus control or lower dose supplementation

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Participants with complications at end of study Show forest plot

1

Risk Ratio (M‐H, Fixed, 99% CI)

Totals not selected

2 Mortality by end of study Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Figures and Tables -
Comparison 6. Vitamin D versus control or lower dose supplementation
Comparison 7. Iron supplementation versus control

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mortality by end of study Show forest plot

3

566

Risk Ratio (M‐H, Fixed, 99% CI)

0.98 [0.65, 1.46]

2 Participants with complications at end of study Show forest plot

2

266

Risk Ratio (M‐H, Fixed, 99% CI)

1.23 [0.63, 2.42]

Figures and Tables -
Comparison 7. Iron supplementation versus control
Comparison 8. Taurine versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mortality by end of study Show forest plot

1

Risk Ratio (M‐H, Fixed, 99% CI)

Totals not selected

Figures and Tables -
Comparison 8. Taurine versus placebo
Comparison 9. Dietetic assistants versus usual care

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mortality by end of study Show forest plot

1

Risk Ratio (M‐H, Fixed, 99% CI)

Totals not selected

2 Participants with complications at end of study Show forest plot

1

Risk Ratio (M‐H, Fixed, 99% CI)

Totals not selected

Figures and Tables -
Comparison 9. Dietetic assistants versus usual care