Study reference

Study characteristics

Patient characteristics

Intervention (I)

Control (C)

Outcome measures and effect size

Comments

Avenell, 2010

Type of study: systematic review and meta-analysis of (quasi-) randomised controlled trials

Country: UK

Source of funding: University of Teeside, Middlesbrough

University of Aberdeen,

Chief Scientist Office of the Scottish Government Health Directorates

Literature search up to: July 2008

Inclusion criteria: (quasi-) randomised controlled trials of nutritional supplements post hip fracture; participants were older people (most participants >65 yr); interventions were started within the first month after hip fracture and given for up to one year.

Exclusion criteria: studies that examined the secondary prevention of osteoporotic fractures after hip fracture; studies that focused on younger people, people with multiple trauma or people with pathological fractures; studies with mixed populations if separate data were not available; studies evaluating intravenous fluid administration in the immediate post-operative period for hydration purposes.

N of included studies:

24

A: Bastow, 1983

B: Bean, 1994

C: Botella-Carretero, 2008

D: Brown, 1992

E: Bruce, 2003

F: Day, 1988

G: Delmi, 1990

H: Duncan, 2006

I: Eneroth, 2006

J: Espaulella, 2000

K: Gallagher, 1992

L: Hankins, 1996

M: Hartgrink, 1998

N: Hoikka, 1980

O: Houwing, 2003

P: Madigan, 1994

Q: Miller, 2006

R: Neumann, 2004

S: Schürch, 1998

T: Stableforth, 1998

U: Sullivan, 1998

V: Sullivan, 2004

W: Tidermark, 2004

X: Tkatch, 1992

Important patient characteristics at baseline:

N, mean age(yr)

A: 122, 68-92

B: 59, 70-85

C: 90, mean 84

D: 10, not given but “elderly”

E: 109, mean 84

F: 60, ≥60

G: 59, mean 82

H: 318, mean 84

I: 80, mean 81

J: 171, mean 82.6

K: 97, not given

L: 32, mean 86

M: 140, mean 83.6

N: 37, mean 74

O: 103, mean 81

P: 34, all over 60

Q: 51, mean 83

R: 46, mean 83

S: 82, men 80.7

T: 61, mean 81.8

U: 18, mean 75.6

V: 57, mean 79

W: 40, mean 84

X: 72, mean 82

Sex (%female/%male):

A: 100/0

B: 100/0

C: 79/21

D: 100/0

E: 100/0

F: 73/27

G: 90/10

H: 100/0

I: 79/21

J: 79/21

K: not given, male and female

L: 84/16

M: 87/13

N: 78/22

O: 82/18

P: 73/27

Q: 82/18

R: 72/28

S: 90/10

T: 100/0

U: 6/94

V: 32/68

W: 100/0

X: 87/13

Although 17 trials had comparability of the groups at baseline (item d) or only a small chance of confounding, details of the nutritional status of the groups were often missing. Related to this is the lack of information on anthropometric parameters.

Intervention:

A: 1 L Clinifeed Iso (4.2 MJ or 1000 kcal, 28 g protein, 270 mosmol/L) via fine bore nasogastric tube using peristaltic pump, and normal ward diet, with free access to snacks and drinks.

B: Cetornan (ornithine a-ketoglutarate) 20 g/d (0.293 MJ or 70 kcal, 2.73 g N), presumed orally

C: Four 10 g packets a day of Vegenat-med Proteina (Vegenat SA, Badajoz, Spain) each providing 9 g protein and 38 kcal, dissolved in water, milk or soup from diet.

OR

Two 200 ml bricks a day (Resource Hiperproteico, Novartis Medical Nutrition, Barcelona) providing total of 37.6 g protein and 500 kcal.

D: Participant offered oral nutritional supplement Fresubin (Fresenius) calculated to make up deficit between intake from normal hospital diet and requirement. Fresubin provides 4.2 kJ or 1 kcal/ml, as 15% protein energy, 30% fat energy and 55% carbohydrate energy

E: One 235 ml can of Sustagen Plus daily (Mead Johnston), providing 352 kcal or 1.47 MJ, 17.6 g protein, 11.8 g fat, 44.2 g carbohydrate, 376 mcg retinol equivalents, 1.2 mcg vitamin D, 2.4 mg vitamin E, 15 mg vitamin C, 0.4 mg thiamin, 0.5 mg riboflavin, 8.7 mg niacin, 0.6 mg vitamin B6, 0.9 mcg vitamin

B12, 71 mcg folate, 1.9 mg pantothenic acid, 14 mcg biotin, 259 mg sodium, 491 mg potassium, 371 mg chloride, 263 mg calcium, 261 mg phosphorus, 3.8 mg iron, 106 mg magnesium, 3.8 mg zinc, 41 mcg

iodine, 0.4 mg copper, 0.6 mg manganese, 19 mcg selenium, 19 mcg chromium, 47 mcg molybdenum;

chocolate and vanilla flavours. Dietitian carried out preliminary taste test and offered encouragement and strategies to help with compliance, e.g. ways to alter taste and timing of supplement.

F: Intravenous Parentrovite IVHP (containing 250 mg thiamine hydrochloride, 4 mg riboflavine, 50 mg

pyridoxine, 160 mg nicotinamide, 500 mg ascorbic acid, 1 g anhydrous dextrose)

G: 250 ml oral nutritional supplement (1.06 MJ or 254 kcal, 20.4 g protein, 29.5 g carbohydrate, 5.8 g lipid, 525 mg calcium, 750 IU vitamin A, 25 IU vitamin D3, nicotinamide, folate, calcium pantothenate, biotin, minerals; and vitamins E, B1, B2, B6, B12, C)

H: additional attention of dietetic assistant (previous NHS experience, given 14 day period of orientation and training), working closely with specialist dietitian. Asked to ensure participants met nutritional needs, including by: checking personal and cultural food preferences; co-ordinating appropriate meal orders with catering staff; ordering nutritional supplements; provision of feeding aids; assisting with food choice, portion size and positioning at mealtimes; sitting with, encouraging and feeding; collecting information to aid nutritional assessment by dietitian.

I: 1000 ml Vitrimix (Kabi Pharmacia AB, Sweden) intravenously (amino acids, fat, carbohydrate, electrolytes daily for 3 days (100 kcal, 53 g protein daily), then 7 days oral Fortimel 400 ml (400 kcal.day; Nutricia AB, Netherlands). Trace elements (Tracel, Kabi Pharmacia AB), water and fat soluble vitamins (Soluvit Novum and Vitalipid Novum, Kabi Pharmacia AB) were added to Vitrimix.

J: 200 ml oral supplement in 3 flavours (0.62 MJ or 149 kcal, 20 g protein, 1.5 g carbohydrate, 7 g fat, 800 mg calcium, 3 IU vitamin A, 1.7 mg thiamin, 2.02 mg riboflavin, 2.25 mg pyridioxine, 5.5 mcg vitamin B12, 122.25 mg vitamin C, 25 IU vitamin D3, 10 mg calcium pantothenate, 16.87 mg vitamin E, 0.45 mg biotin, 500 mcg folic acid, 22.5 mg nicotinamide), prepared by pharmaceutical company (Clinical Nutrition S.A., Spain)

K: Small-bore nasogastric tube providing 3.90 MJ or 933 kcal, 33 g protein each night; normal diet and snacks

L: Oral supplement of 250 ml Sustagen twice daily (total daily intake 22.5 g protein, 10 g fat, 60 g

carbohydrate, 1.712 MJ or 409 kcal energy, 500 mcg vitamin A, 6.6 mcg vitamin D, 50.8 mg vitamin C, 1.2 mg thiamin, 1.15 mg riboflavin, 13 mg niacin, 1.3 mcg vitamin B12, 825 mg calcium, 670 mg phosphorus, 8 mg iron, 66 mcg iodine, 1.2 g potassium, 370 mg sodium) plus standard hospital diet

M: Nasogastric tube feed of 1 L Nutrison Steriflo Energy-plus ( 340 mosmol/L, 6.28 MJ or 1500 kcal, 60 g protein, 184 g carbohydrate, 58 g fat, 800 mg sodium, 1350 mg potassium, 1250 mg chloride, 570 mg calcium, 570 mg phosphate, 200 mg magnesium, 10 mg iron, 10 mg zinc, 1.5 mg copper, 3 mg manganese, 1 mg fluoride, 50 mcg molybdenum, 43 mcg selenium, 33 mcg chromium, 0.1 mg iodide, 670 mcg retinol equivalents, 5 mcg vitamin D, 8.1 mg alpha tocopherol, 40 mcg vitamin K, 1 mg thiamin,

1.1 mg riboflavin, 26 mg niacin, 4 mg pantothenic acid, 1.3 mg vitamin B6, 130 mcg folic acid, 2 mcg

vitamin B12, 100 mcg biotin, 50 mg vitamin C, 200 mg choline) plus normal hospital diet. If participant removed tube, replaced a maximum of 3 times.

N: 1 mcg 1-alpha-hydroxycholecalciferol and 1 g calcium as calcium carbonate daily

O: 400 ml/day oral supplement (600 kcal or 2.51 MJ, 40 g protein, 6 mg arginine, 20 mg zinc, 500

mg vitamin C, 200 mg vitamin E as alpha-tocopherol, 4 mg carotenoids (Cubitan, NV Nutricia, The Netherlands)); and regular diet

P: 250 ml oral supplement prepared by dietitian from ProMod (protein powder) and Polyjoule (glucose polymer) providing 1.30 MJ or 310 kcal; 16 g protein, 41.4 g carbohydrate, 9.2 g fat, 0.19 mg riboflavin, 245 mg calcium, phosphorus 171 mg, and standard hospital diet.

OR

One multivitamin/mineral tablet daily (ELEVIT RDI, Roche) providing 750 mcg vitamin A, 1.1

mg thiamin, 1.7 mg riboflavin, 20 mg nicotinamide, 7 mg pantothenic acid, 1.9 mg pyridoxine, 2 mcg vitamin B12, 200 mcg biotin, 200 mcg folic acid, 30 mg vitamin C, 200 IU vitamin D3, 15 IU vitamin E, 125 mg calcium, 100 mg magnesium, 125 mg phosphorus, 5 mg iron, 1 mg copper, 1 mg manganese, 7.5 mg zinc 250 ml), plus oral supplement as above, and standard hospital diet

Q: Nutrition only intervention: Fortisip (Nutricia Australia Pty Ltd) oral protein and energy supplement (1.5 kcal/ml, 16% protein, 35% fat, 49% carbohydrate) to provide 45% of estimated energy intakes. (Individually prescribed and delivered.) Four doses of equal volume given by nurses from drug trolley, continued after hospital discharge as twice per day or more. Once weekly visits on weeks 7 to 12.

R: Boost HP high protein liquid supplement (Mead Johnson, Evansville, Indiana, USA) providing per 8 oz can: 240 kcal, 15 g protein, 33 g carbohydrate, 6 g fat, 1110 IU vitamin A, 89 IU vitamin D, 6. 7 IU vitamin E, 27 mcg vitamin K, 13.3 mg vitamin C, 89 mcg folic acid, 0.33 mg thiamin, 0.4 mg riboflavin, 0.47 mg vitamin B6, 1.33 mcg vitamin B12, 4.7 mg niacin, 56 mg choline, 67 mcg biotin, 2. 3 mg pantothenic acid, 220 mg sodium, 490 mg potassium, 350 mg chloride, 240 mg calcium, 220 mg phosphorus, 90 mg magnesium, 33mg iodine, 0.67 mg manganese, 0.47 mg copper, 3.3 mg zinc, 4 mg

iron, 15.8 mcg selenium, 27 mcg chromium, 16.9 mcg molybdenum

S: Oral protein supplement (1.05 MJ or 250 kcal, 20 g protein, 3.1 g fat, 35.7 g carbohydrate, 1000

IU vitamin A, 30 mcg vitamin K1, 20 mg vitamin C, 550 mg calcium, 91 mg magnesium, 429 mg

phosphorus, 228 mg sodium) plus oral 200,000 IU vitamin D3 once at baseline during study

T: Encouraged to drink flavoured, Carnation Instant Breakfast in 300 ml milk (1.34 MJ or 320 kcal, 18. 5 g protein, 11 g fat, 40 g carbohydrate, vitamins and minerals) plus ward diet

U: Nasogastric feeding via small bowel (or more proximally if low risk of aspiration): 1375 ml of polymeric enteral formula (Promote, Ross Laboratories, 85.8 g protein, 4.31 MJ or 1031 kcal non-nitrogenous energy, 71.5 g carbohydrate, 35.8 g fat, 88 mcg vitamin K, 77 mcg selenium, 110 mcg chromium, 165 mcg molybdenum, 165 mg carnitine, 165 mg taurine), given at 125 ml/h over 11 hours, plus standard care of 3 meals daily

V: Harris-Benedict equation with stress and activity factors used to predict requirements to make up deficit after food intake calculated - given as Promote (Ross Laboratories), 1000 kcal, 62.5 g protein, 130g carbohydrate, 26 g fat per litre, if deficit >480 kcal/day. If deficit 240-480 kcal/day, participant asked to drink supplement instead of tube feeding. Tube feeding begun at 50 ml/hour and increased by 25 ml/hour to maximum of 125 ml/hour. Given with standard care.

W: Fortimel protein rich liquid oral supplement, 20 g protein/200 ml, unclear if 200 or up to 400 ml/day

X: Protein supplement (20.4 g protein from milk) in 250 ml of oral supplement (5.8 g fat, 29.5 g

carbohydrate, 525 mg calcium, 70 mg magnesium, 270 mg phosphorus, 25 IU vitamin D3, 750 IU vitamin A)

Control:

A: Normal ward diet, with free access to snacks and drinks

B: Pro-up (defined formula peptide supplement, 0.293 MJ or 70 kcal, 2.73 g N), presumed orally

C: no oral nutrition supplements

D: Normal hospital diet

E: Routine care

F: No supplement

G: Standard hospital diet

H: Nurse and dietitian led care, including routine provision of oral nutritional supplements to all participants

I: Usual hospital diet.

J: 200 ml oral supplement in 3 flavours (0.65 MJ or 155 kcal as 25.3 g carbohydrate and 6 g fat),

prepared by pharmaceutical company

K: Normal diet and snacks

L: Standard hospital diet

M: Standard hospital diet

N: Placebo and 1 g calcium as calcium carbonate daily

O: Placebo supplement was a non-caloric, water-based drink with sweeteners, colourants and flavourings

in similar packaging, look and taste not identical to active supplement; and regular diet

P: standard hospital diet

Q: Attention control. Usual care and general nutrition and exercise advice. Twice weekly visits on weeks

1 to 6, once weekly on weeks 7 to 12.

R: Ensure liquid supplement (Ross Labs, Columbus, Ohio, USA) providing per 8 oz can: 250 kcal, 8.

8 g protein, 40 g carbohydrate, 6.1 g fat, 1250 IU vitamin A, 100 IU vitamin D, 7.5 IU vitamin E, 20

mcg vitamin K, 30 mg vitamin C, 100 mcg folic acid, 0.38 mg thiamin, 0.43 mg riboflavin, 0.50 mg

vitamin B6, 1.50 mcg vitamin B12, 5.0 mg niacin, 100 mg choline, 75 mcg biotin, 2.5 mg pantothenic

acid, 200 mg sodium, 370 mg potassium, 310 mg chloride, 300 mg calcium, 300 mg phosphorus, 100

mg magnesium, 38 mcg iodine, 1.3 mg manganese, 0.50 mg copper, 3.8 mg zinc, 4.5 mg iron, 18 mcg

selenium, 30 mcg chromium, 38 mcg molybdenum

S: Placebo without protein made isocaloric by addition of maltodextrins, plus oral 200,000 IU vitamin D3 once at baseline during study

T: Ward diet alone

U: Standard care of 3 meals daily

V: Standard care

W: Standard treatment

X: 250 ml of oral supplement alone

1. Mortality (all cause)

Effect measure: RR [99% CI]:

A: 0.70 [ 0.21, 2.37 ]

B: Not estimable

C: Not estimable

D: Not estimable

E: 1.18 [ 0.09, 14.78 ]

F: 0.37 [ 0.33, 5.62 ]

G: 0.71 [ 0.23, 2.24 ]

H: 0.57 [ 0.29, 1.11 ]

I: 0.11 [ 0.00, 4.95 ]

J: 1.63 [ 0.72, 3.71 ]

K: Not estimable

L: 0.41 [ 0.05, 3.13 ]

M: 15.00 [ 0.36, 629.78 ]

N: Not reported

O: Not estimable

P: 6.16 [ 0.15, 255.68 ]

Q: 0.22 [ 0.01, 3.47 ]

R: Not reported

S: 1.33 [ 0.20, 8.77 ]

T: Not estimable

U: 0.11 [ 0.00, 4.17 ]

V: 0.74 [ 0.16, 3.37 ]

W: 0.22 [ 0.01, 3.47 ]

X: 0.66 [ 0.10, 4.21 ]

2. Morbidity/Complications (e.g. wound infections, pressure sores, deep venous thrombosis, respiratory and urinary infections, cardiovasculair events)

Effect measure: RR [99% CI]:

A: Not reported

B: Not estimable

C: 1.07 [ 0.61, 1.87 ]

D: Not reported

E: Not reported

F: 1.32 [ 0.65, 2.69 ]

G: 0.43 [ 0.11, 1.66 ]

H: 0.90 [ 0.71. 1.15 ]

I: 0.21 [ 0.08, 0.59 ]

J: 0.85 [ 0.66, 1.08 ]

K: Not reported

L: 0.59 [ 0.17, 1.99 ]

M: Not reported

N: 2.84 [ 0.41, 19.48 ]

O: Not reported

P: 1.00 [ 0.26, 3.89 ]

Q: Not reported

R: Not reported

S: Not reported

T: Not estimable

U: 1.09 [ 0.64, 1.86 ]

V: 1.11 [ 0.66, 1.87 ]

W: 0.60 [ 0.11, 3.27 ]

X: Not reported

3. Length of hospital and rehabilitation unit stay

Mean difference (days) [99% CI]:

A: Not estimable

B: Not estimable

C: Not estimable

D: -21.00 [ -65.15 to 23.15 ]

E: 1.10 [ -3.53, 5.73 ]

F: 6 [ -15.75, 27.75 ]

G: Not estimable

H: Not estimable

I: Not estimable

J: -0.8 [ -3.62, 2.02 ]

K: Not estimable

L: Not estimable

M: Not estimable

N: Not reported

O: Not reported

P: 1.00 [ -8.51, 10.51 ]

Q: Not estimable

R: -4.8 [-12.29, 2.69 ]

S: Not estimable

T: Not reported

U: 14.50 [ -24.34, 53.34 ]

V: Not estimable

W: Not estimable

X: Not estimable

Interventions could be divided into 5 groups:

1. Multinutrient supplements vs control

a. Oral supplements (C, D, E, G, L, O, P, Q, T, W)

b. Nasogastric tube feeding (A, K, M, U)

c. Nasogastric tube feeding and oral supplements (V)

d. Intravenous feeding and oral supplements (I)

2. High protein supplements vs low- or non-protein supplements (J, R, S, X)

3. Vitamin supplement vs control (F, N)

4. Isonitrogenous ornithine alpha-ketogluterate vs peptide supplement (B)

5. Dietetic assistants vs usual care (H)

For no intervention group statistically significant effects on mortality or morbidity/ complications were found.

Study reference

(first author, publication year)

Appropriate and clearly focused question?¹

Yes/no/unclear

Comprehensive and systematic literature search?²

Yes/no/unclear

Description of included and excluded studies?³

Yes/no/unclear

Description of relevant characteristics of included studies?⁴

Yes/no/unclear

Appropriate adjustment for potential confounders in observational studies?⁵

Yes/no/unclear/notapplicable

Assessment of scientific quality of included studies?⁶

Yes/no/unclear

Enough similarities between studies to make combining them reasonable?⁷

Yes/no/unclear

Potential risk of publication bias taken into account?⁸

Yes/no/unclear

Avenell, 2010

yes

yes

yes

yes

Not applicable

yes

yes

yes

Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

Follow-up

Outcome measures and effect size

Comments

Anbar, 2013

Type of study:

Unblinded RCT

Setting: Ortho-geriatric unit.

Country: Israel

Source of funding: Not reported

Inclusion criteria:

Patients >65 yr submitted to surgery for hip fracture

Exclusion criteria:

Presented >48h after injury, receiving steroids and/or immunosuppression therapie, oncologic diseases, multiple fractures, diagnosed dementia or in need for supplemental nasal oxygen which precludes measurement of REE.

N total: 50

N intervention: 22

N control: 28

Age ± SD:

I: 82.3 ±6.1

C: 83.7 ±6.4

Sex:

I: 27.3% M

C: 39.3% M

Groups comparable at baseline?

yes

Hospital food + oral nutritional supplements with an energy goal determined by repeated resting energy expenditure (REE) measurement using indirect calorimetry (IC).

Supplements were started 24h after surgery and were provided in the form of Ensure plus, containing 355 kcal and 13.5 g protein, or Glucerna, containing 237 kcal and 9.9 g protein.

Patient, family and caregivers were educated regarding the importance of nutritional support and more attention was given to personal food preferences.

Usual hospital food (1800 kcal and 80 g protein) and a fixed dose of ONS if already prescribed prior to hospitalization.

Length of follow-up: Unclear (until discharge?)

Loss-to-follow-up:
All patients completed the study, no drop-outs.

Mortality:

I: 0/22 (0%)

C: 2/28 (7%)

p= 1.0

Complications:

I: 6/22 (27.3%)

C: 18/28 (64.3%)

p= 0.012

Length of stay in hospital:

I: 10.1 ± 3.2

C: 12.5 ±5.5

p= 0.061

Power analyses showed that each group needed at least 33 patients. In view of the slow recruitment the study was discontinued after 50 patients.

Significant lower complication rate in the intervention group was mainly due to a reduction in the number of infectious complications (in particular pneumonia).

Myint, 2013

Type of study:

Single-blinded RCT

Setting: Rehabilitation department

Country: Hong Kong

Source of funding: Funding provided by Kowloon Hospital

Inclusion criteria:

Patients ≥60 yr with low-impact osteoporotic fracture of the procimal femur, surgically repaired within 4 wks before recruitment.

Exclusion criteria:

Requiring tube feeding, unstable medical condition, BMI ≥25, malignancy, conditions with contraindication for high-protein diet, mentally incapacitated and inability to communicate or understand written consent.

N total: 121

N intervention: 61

N control: 60

Age ± SD:

I: 80.9 ± 6.5

C: 81.7 ± 6.4

Sex:

I: 31.1% M

C: 66.7% M

Groups comparable at baseline?

Yes

Oral liquid nutritional supplement (given in two portions, in total 18-24g protein and 500 kcal per day) on top of standard hospital diet (including vitamin D supplement of 800-1000 IU per day and calcium tablets containing 1200 mg of elemental calcium).

Intervention was started within 3 days after hospital admission and given until discharge or 28 days.

Standard hospital diet (including vitamin D supplement of 800-1000 IU per day and calcium tablets containing 1200 mg of elemental calcium).

Length of follow-up:

Deaths until 6 months after discharge. Measurements took place until 4 weeks after discharge.

Loss-to-follow-up intervention:

N (%): 4 patients (7%) defaulted follow-up after discharge

Reasons: 2 refusal, 2 medical complications

Loss-to-follow-up control:

N (%): 4 patients (7%) defaulted follow-up after discharge

Reasons: all refusal

Mortality:

I: 1/61 (1.6%)

C: 1/60 (1.7%)

p= 0.748

Complications:

I: 30/61 (49%)

C: 60/60 (100%)

p= 0.068

Length of stay in hospital:

I: 26.2 ± 8.2

C: 29.9 ± 11.2

p= 0.040

Power was calculated based on serum albumin level as primary outcome.

Overall number of infection episodes showed significant reduction in the intervention group. Total number of complications shows no significant reduction, but a trend.

Study reference

(first author, publication year)

Describe method of randomisation¹

Bias due to inadequate concealment of allocation?²

(unlikely/likely/unclear)

Bias due to inadequate blinding of participants to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of care providers to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of outcome assessors to treatment allocation?³

(unlikely/likely/unclear)

Bias due to selective outcome reporting on basis of the results?⁴

(unlikely/likely/unclear)

Bias due to loss to follow-up?⁵

(unlikely/likely/unclear)

Bias due to violation of

intention to treat analysis?⁶

(unlikely/likely/unclear)

Anbar, 2013

Computer generated

unlikely

unlikely

likely

unlikely

unlikely

unlikely

unlikely

Myint, 2013

Sealed opaque envelope

unlikely

unlikely

unlikely

unlikely

Unlikely

unlikely

unlikely