Neelemaat 2012

Type of study:

RCT

Setting:

From hospital admission until 3 months after discharge

Country:

Netherlands

Source of funding:

ZonMW

Inclusion criteria:

Adults aged ≥ 60 yrs, expected length of stay > 2 days at departments of general internal medicine, rheumatology, gastroenterology, dermatology, nephrology, orthopedics, traumatology, and vascular surgery. body mass index (BMI) of 20.0 kg/m2 or less, 5% or more self-reported unintentional weight loss in the previous month, or 10% or more self-reported unintentional weight loss in the previous 6 months.

Exclusion criteria:

Dementia if diagnosis was documented in the hospital record or in a referral letter from the individual’s primary care or nursing home physician.

N total at baseline:

Intervention: 105

Control: 105

Important prognostic factors²:

age ± SD (yrs):

I: 74.6 ± 9.7

C: 74.4 ± 9.3

Sex:

I: 46.7% M

C: 42.9% M

Body weight (kg)

I: 61.0 ± 13.1

C: 58.9 ± 12.3

BMI (kg/m², %):

I:

<20.0: 55.2

20.0-24.9: 30.5

≥ 25.0: 14.3

C:

<20.0: 53.3

20.0-24.9: 37.1

≥ 25.0: 9.6

Groups comparable at baseline?

Yes, no significant differences between groups.

Standardized nutritional support starting in the hospital

and continuing for 3 months after discharge:

·        Energy- and protein-enriched diet (during the in-hospital period).

·        Two additional servings per day of an ONS (Nutridrink®) were offered.

·        400 IU vitamin D3 and 500 mg calcium per day during the entire study period.

·        Telephone counselling by a dietician was conducted every other week after hospital discharge (six sessions in total) to encourage adherence to the prescribed supplements.

If participants took all of the prescribed supplements after discharge from hospital, this would provide an additional 600 kcal, 24 g of protein, and 600 IU of vitamin D per day.

Usual care (given nutritional support only on prescription from their treating physician). In general, they did not receive post discharge nutritional support.

Length of follow-up:

3 months after discharge.

Loss-to-follow-up:

Intervention:

30 (29%)

Reasons (describe)

Withdrawal (n=16) and died during study (N=14).

Control:

30 (29%)

Reasons (describe)

Withdrawal (n=19) and died during study (n=11)

Incomplete outcome data:

Intervention:

·        Functional limitations (n=5)

·        Physical activities (n=18)

·        Physical performance (n=16)

·        Weight (n=2)

·        Fat free mass (n=27)

·        Hand grip strength (n=10)

·        Falling (n=2)

Reasons to exclude from analysis: Too painful, too ill, logistical problems and errors in measurement

Control:

·        Functional limitations (n=1)

·        Physical activities (n=22)

·        Physical performance (n=27)

·        Weight (n=2)

·        Fat free mass (n=44)

·        Hand grip strength (n=22)

·        Falling (n=1)

Reasons to exclude from analysis:

Too painful, too ill, logistical problems and errors in measurement

Outcome measures and effect size (include 95%CI and p-value if available):

After 3 months: body weight, BMI, hand grip strength, fall incidents, physical activity.

Body weight:

I vs. C:

64.7 ± 14.4 vs. 61.0 ± 12.2 kg (mean difference: 3.7 kg, 95%CI: 0.6-8.1)

BMI:

I vs. C:

22.1 ± 4.5 vs. 21.0 ± 3.7 kg/m² (mean difference 1.1 kg/m², 95%CI: 0.3-2.4)

Hand grip strength:

I vs. C:

Mean increase: 0.2 ± 5.6 vs. 1.0 ± 6.7 (95%CI: 3.0-1.5)

Fall incidents:

I vs. C:

10% vs. 23% had one or more fall incidents. HR=0.41, 95% CI 0.19-0.86, P=0.02

Physical activity:

I vs. C:

Mean improvement score: 0.5 ± 1.5 vs. 0.6 ± 1.5 (95% CI: 0.7-0.5)

Neelemaat 2011

Type of study:

RCT

Setting:

From hospital admission until 3 months after discharge

Country:

Netherlands

Source of funding:

ZonMW

Inclusion criteria:

Adults aged ≥ 60 yrs, expected length of stay > 2 days at departments of general internal medicine, rheumatology, gastroenterology, dermatology, nephrology, orthopedics, traumatology, and vascular surgery. body mass index (BMI) of 20.0 kg/m2 or less, 5% or more self-reported unintentional weight loss in the previous month, or 10% or more self-reported unintentional weight loss in the previous 6 months.

Exclusion criteria:

Dementia if diagnosis was documented in the hospital record or in a referral letter from the individual’s primary care or nursing home physician.

N total at baseline:

Intervention: 105

Control: 105

Important prognostic factors²:

age ± SD (yrs):

I: 74.6 ± 9.7

C: 74.4 ± 9.3

Sex:

I: 46.7% M

C: 42.9% M

Body weight (kg)

I: 61.0 ± 13.1

C: 58.9 ± 12.3

BMI (kg/m², %):

I:

<20.0: 55.2

20.0-24.9: 30.5

≥ 25.0: 14.3

C:

<20.0: 53.3

20.0-24.9: 37.1

≥ 25.0: 9.6

Groups comparable at baseline?

Yes, no significant differences between groups.

Standardized nutritional support starting in the hospital

and continuing for 3 months after discharge:

·        Energy- and protein-enriched diet (during the in-hospital period).

·        Two additional servings per day of an ONS (Nutridrink®) were offered.

·        400 IU vitamin D3 and 500 mg calcium per day during the entire study period.

·        Telephone counselling by a dietician was conducted every other week after hospital discharge (six sessions in total) to encourage adherence to the prescribed supplements.

If participants took all of the prescribed supplements after discharge from hospital, this would provide an additional 600 kcal, 24 g of protein, and 600 IU of vitamin D per day.

Usual care (given nutritional support only on prescription from their treating physician). In general, they did not receive post discharge nutritional support.

Length of follow-up:

3 months after discharge.

Loss-to-follow-up:

Intervention:

N=30 (29%)

Reasons (describe)

Withdrawal (n=16) and died during study (N=14).

Control:

N=30 (29%)

Reasons (describe)

Withdrawal (n=19) and died during study (n=11)

Incomplete outcome data:

Intervention:

·        Functional limitations: n=5; 7%

·        Physical activities: n=18; 24%

·        Physical performance: n=16; 21%

·        Weight: n=2; 3%

·        Fat free mass: n=27; 36%

·        Hand grip strength; n=10; 13%

Reasons: Too painful, too ill, logistical problems and errors in measurement

Control:

·        Functional limitations: n=1; 1%

·        Physical activities: n=22; 29%

·        Physical performance n=27; 36%

·        Weight; n=2; 3%

·        Fat free mass; n=44; 59%

·        Hand grip strength; n=22; 29%

Reasons: Too painful, too ill, logistical problems and errors in measurement

Functional limitations score, physical performance score, physical activity score, body weight, fat free mass, hand grip strength.

Functional limitations score (measured by LASA Functional Limitations Questionnaire):

Changes at 3 month follow up in comparison with baseline

I vs. C:

-0.3 (± 1.2) vs. 0.2 (± 1.5); -0.5 95%CI -1.0 - 0.1

Physical performance score,

Changes at 3 month follow up in comparison with baseline

I vs. C:

3.0 (± 4.2) vs. 2.1 (± 5.4); 0.8 95% CI -1.0 – 2.6)

Physical activity score (LASA Physical Activity

Questionnaire):

Changes at 3 month follow up in comparison with baseline

I vs. C:

0.5 (± 1.5) vs. 0.6 (± 1.5); -0.1 95%CI -0.7-0.5

Body weight (kg, corrected for baseline body weight tertiles):

Changes at 3 month follow up in comparison with baseline

I vs. C:

Total <53.6 kg: 2.2 ± 3.4 vs. 3.0 ± 4.2;-0.8 (-3.2-1.5)

Total 53.6-63.9 kg: 2.7 ± 3.8 vs. 0.9 ± 5.6; 1.8 (-0.9-4.4)

Total > 63.9 kg: 2.5 ± 4.2 vs. -0.9 ± 6.38; 3.4 (0.2-6.6

Fat free mass (kg):

Changes at 3 month follow up in comparison with baseline

I vs. C:

3.3 ± 4.3 vs. 2.8 ± 4.1; 0.5 (-1.5-2.4)

Hand grip strength (kg):

Changes at 3 month follow up in comparison with baseline

I vs. C:

0.2 ± 5.6 vs. 1.0 ± 6.7; -0.8 (-3.0-1.5)

McMurdo, 2009

Type of study:

RCT

Setting:

Community based study in 2 centres

Country:

Great Brittan.

Source of funding:

Health Services Research Committee.

Inclusion criteria:

Community dwelling, aged 70 and older, and admitted to the hospital with an acute illness

Nutritional criteria were body mass index (BMI) less than 24.0 kg/m2 and mid-arm muscle circumference below the 10th centile or weight loss of 5% or more during the hospital stay.

Exclusion criteria:

Barthel score greater than 18, chronic liver disease or renal failure (serum creatinine43.39 mg/dL), residence in a care home, cognitive impairment precluding informed consent, dysphagia, metastatic carcinoma or other terminal illness, acute inflammatory arthritis, stroke affecting both hands, and major surgery within the preceding month were reasons for exclusion.

N total at baseline:

Intervention: 126

Control: 127

Important prognostic factors²:

age ± SD:

I: 81.4 ± 6.2

C: 82.2 ± 6.2

Sex:

I: 32.5% M

C: 44.9% M

BMI (kg/m²):

I:21.2 ± 2.3

C: 21.2 ± 2.7

Weight (kg):

I: 54.9 ± 10.0

C: 56.1 ± 10.1

Groups comparable at baseline?

No, % females higher in intervention group.

Describe intervention (treatment/procedure/test):

Participants were allocated to oral nutritional supplementation (400 mL/d of Fresubin, 600 kcal, 2,520 kJ, 40 g protein, a nutritionally complete liquid protein and energy supplement) for 16 weeks.

Both preparations were packaged in identical 200-mL plain white rectangular cartons and labelled using one of two randomization codes.

Describe control (treatment/procedure/test):

Matching control supplement (based on skim milk containing minimal energy: 200 kcal, 840 kJ, 12.4 g protein content) in identical packaging.

Both preparations were packaged in identical 200-mL plain white rectangular cartons and labelled using one of two randomization codes.

Length of follow-up:

16 weeks.

Loss-to-follow-up:

Intervention:

33 (27%)

Reasons (describe)

·        Withdrew consent

·        Withdrawn by researcher,

·        unwell,

·        died,

·        unable to make visit contact.

Control:

29 (23%)

Reasons (describe)

·        Withdrew consent

·        Withdrawn by researcher,

·        unwell,

·        died,

·        unable to make visit contact

·        Unstable diabetes

Incomplete outcome data:

Intervention:

Not stated

Reasons (describe)

Not stated

Control:

Not stated

Reasons (describe)

Not stated

Outcome measures and effect size (include 95%CI and p-value if available):

Basic activities daily living (Barthel index), body weight, hand grip strength, health-related quality of life, falls, death

Basic activities daily living (Barthel index):

Between group difference adjusted for sex, outcome baseline and supplement adherence

0.28 (95% CI -0.28-0.84, P=0.32)

Body weight:

Between group difference adjusted for sex, outcome baseline and supplement adherence

1.17 (95%CI 0.07-2.27, P=0.04)

Hand grip strength (kg):

Between group difference adjusted for sex, outcome baseline and supplement adherence

1.52 (95%CI 0.50-2.55, P=0.004)

Health-related quality of life (Euroquol, change score):

Between group difference adjusted for sex, outcome baseline and supplement adherence

-0.22(95% CI -56.82-56.38, P=0.99)

Falls, one or more:

I vs. C:

26 vs. 33, p=ns.

Death:

I vs. C:

8 vs. 10

Chapman 2009

Type of study:

RCT

Setting:

Living independently in community

Country:

Australia

Source of funding:

Organon

Inclusion criteria:

aged ≥ 65 y and living independently in the community. undernourished people [Mini Nutritional Assessment score

<24 and low body weight (body mass index, in kg/m2: < 22) or

recent weight loss (>7.5% over 3 mo)]

Exclusion criteria:

inability to comply with the protocol; increased risk of cognitive impairment,

elevated haematocrit (.50%); history of prostate cancer, prostate-specific antigen (PSA) concentrations greater than the age-related normal range, or an irregular prostate on examination; breast cancer; pre-existing androgenic signs or symptoms of concern (deep voice, hirsutism, acne, or androgenic hair loss) in women; risk of depression , cardiac failure corresponding to New York Heart Association class III and above; abnormal liver function tests (alanine aminotransferase, c-glutamyltransferase, bilirubin, or alkaline phosphatase .2 times the upper limit of normal; serum creatinine .0.2 mmol/L); any disease that, in the opinion of the investigator, was likely to lead to death within 1 y; and testosterone or other androgen therapy within 4 mo of starting the study. Women had to be off or on a stable dose of estrogen or other hormone replacement therapy for at least 3 mo before starting the study.

N total at baseline:

Intervention: 13

Control: 13

Important prognostic factors²:

age ± SD:

I:

Male:78 ± 4

Female: 79 ± 2

C:

Male:78 ± 3

Female:74 ± 2

Sex:

I: 46% M

C: 46% M

BMI (kg/m²):

I:

Male: 19.1 ± 0.5

Female: 18.3 ± 0.6

C:

Male: 19.8 ± 0.4

Female: 18.3 ± 0.4

Weight (kg):

I:

Male: 58.4 ± 2.2

Female: 42.2 ± 2.3

C:

Male: 56.3 ± 0.9

Female: 47.2 ± 1.3

Groups comparable at baseline?

Yes

Describe intervention (treatment/procedure/test):

Supplement (SUP): standard care 1 placebo testosterone 1 nutritional supplement [237 ml/d Nova Source 2 (Novartis Pharmaceuticals, North Ryde, Australia; 475 kcal, 18% protein, 43% carbohydrate, 39% fat, and orange or vanilla flavor)]

Describe control (treatment/procedure/test):

No treatment (NT): standard care 1 placebo testosterone capsule

Length of follow-up:

12 months

Loss-to-follow-up:

Intervention: 0

Control: 0

Incomplete outcome data:

Intervention: 3

Reasons (describe)

Died (n=1)

Discontinued or reduced intervention (n=2)

Control: 0

Reasons (describe)

Not applicable

Outcome measures and effect size (include 95%CI and p-value if available):

Grip strength, quality of life (SF-36 physical and mental score), mortality, all after 12 months intervention.

Grip strength (after 12 months, kg)

I: +2.5 ± 1.25

C: -0.09 ± 1.4

P=0.029

quality of life (SF-36 physical and mental score)

Mental:

I:+1.55 ±1.2

C:+0.4 ± 2.3

P=NS

Physical:

I: -0.9 ± 2.6

C: +2.8 ± 2.8

P= NS

Mortality:

I: 1

C: 0

P= NS

Persson 2007

Type of study:

RCT

Setting:

Patients admitted to two wards at the Department of Geriatric Medicine at RosenlundHospital. One ward mainly treated elderly adults after trauma with or without fracture; the other ward mainly took care of acutely ill elderly patients with various somatic disorders.

Country:

Sweden

Source of funding:

Inclusion criteria:

Nutritional status assessed by a short form of the mini nutritional assessment (MNA-SF) within 3 days of admission. Only patients with risk of PEM (MNA ≤10) were asked to participate in the study.

Exclusion criteria:

Patients with malignant disorders, terminal illness or with severe cognitive dysfunction were excluded.

N total at baseline:

Intervention: 51

Control: 57

Important prognostic factors²:

age ± SD:

I: 85 ± 5.9

C: 85 ± 6.1

Sex:

I: 34% M

C: 18% M

BMI (kg/m²):

I: 19.8 ± 1.9

C: 20.6 ± 3

Weight (kg):

I: 54.2 ± 9.1

C: 54.3 ± 8.6

Groups comparable at baseline?

Yes, no significant differences at baseline.

Describe intervention (treatment/procedure/test):

Two individualized counselling sessions by a dietician—once before discharge and then at home within 1 week of discharge. The dietician also had telephone contact at three time points: 1–2 weeks after discharge, once in the middle of the study period and one week before follow-up. The patients were advised to increase their intake of fat by using full-fat milk instead of low-fat milk, cream and creme fraiche in their cooking and to eat more snacks between meals. They were also prescribed a liquid supplement (Sempers, 200 ml/package). Patients could choose between a complete or an incomplete formula corresponding to 85 or 120 kcal, respectively, and 4 or 5 g protein/100 ml. The patients were encouraged to take 1–2 packages/day and they were also prescribed a daily multivitamin supplement: Friggss. Compliance with the prescription, i.e. how many of the prescribed packages that had been consumed, was recorded at all five contacts with the dietician.

Describe control (treatment/procedure/test):

The control group was given brief written dietary advice.

Length of follow-up:

4 months after start of study

Loss-to-follow-up:

Intervention:

N=22 (43%)

Reasons:

Withdrew consent: n=12

Declined follow up: n=4

Died: n=6

Control:

N= 32 (56%)

Reasons:

Withdrew consent: n=5

Prescribed treatment by staff physician: n=8

Declined follow up: n=7

Died: n=12

Outcome measures and effect size (include 95%CI and p-value if available):

Grip strength, ADL index, mental state, quality of life, all after 4 months follow up (intention to treat)

Grip strength (Harpenden Handgrip Dynamometer) kg.

I vs. C:

19.5 ± 7.8 vs. 17.5 ± 7 kg, p=0.2

ADL (Katz index):

I vs. C:

B [A-B] vs. A-B [A-B/C], P<0.05

A: independent, B-G: dependent in one of 6 activities (bathing, dressing, toilet, transfer, continence and feeding)

Mental state (MMSE, 0-30 points):

I vs. C:

25 [20-27] vs. 26 [23-28], P=0.5

Quality of life (SF-36), treated as protocol

I vs. C:

Physical: 219 ± 101 vs. 205 ± 135, p=0.19

Mental: 217 ± 110 vs. 219 ± 121, p=0.91

Rabadi 2008

Type of study:

Randomized, prospective, double-blind, single center study

Setting:

undernourished patients admitted to a stroke service

Country:

USA

Source of funding:

Inclusion criteria:

1. First acute stroke event within 4 weeks of admission to an inpatient rehabilitation facility

2. Hemorrhagic or ischemic stroke documented clinically and by neuroimaging

3. Significant weight loss as indicated by unintentional weight loss of at least 2.5% within 2 weeks following stroke onset

4. Medically stable from a cardiorespiratory standpoint that they could participate in their daily therapies

5. Ability to ingest food including supplements either orally or via the PEG tube

6. Informed consent, if possible from the patient; where it was not possible, proxy consent was obtained from the next of kin according to institutional IRB standards

Exclusion criteria:

1. Patients with prior documented history of alcohol abuse, renal and liver diseases, and malabsorption

2. Patients medically unstable or demented 3. Patients terminally ill (e.g., patients with stroke as a complication of a terminal cancer)

4. Patients participating in any other structured therapeutic trial in the acute care hospital or at Burke

N total at baseline:

Intervention: 58

Control: 58

Important prognostic factors²:

age ± SD:

I: 73.58 ± 13.02

C:75.00 ± 10.58

C

Sex:

I: 60% M

C: 57% M

Weight:

I: 66.6 ± 13.4

C: 65.9 ± 14.5

Groups comparable at baseline?

Yes

Describe intervention (treatment/procedure/test):

The dose of each was 120 mL every 8 hours by mouth, accompanied by multivitamins with minerals.

The “intensive”

nutritional supplement was Novasource® 2.0 Appendix 2 (240 calories, 11 g of proteins). Novasource® 2.0 is a calorically dense, high protein, nutritionally complete formula often used to treat patients with relatively high nutritional requirements, such as in healing wounds. The intensive supplement contained almost twice as many calories per unit volume, because it contained about twice as much protein and four times as much fat.

The only micronutrient to differ significantly between the two preparations was vitamin C, which was 90 mg/dose in the intensive and 36 mg/dose in the routine supplement.

Describe control (treatment/procedure/test):

The dose of each was 120 mL every 8 hours by mouth, accompanied by multivitamins with minerals. The “standard” nutritional supplement was Resource Standard, Appendix 1 (127 calories, 5 g of protein). This nutritionally balanced formula is routinely prescribed for poorly nourished patients as part of clinical care on our stroke rehabilitation service.

Length of follow-up:

Until discharge patient (length of stay for intervention group 25.98 ± 10.12 days and for control group 25.44 ± 7.32 days)

Loss-to-follow-up:

Intervention:

N=3

Reasons:

Transferred to acute facility

Control:

N=3

Reasons:

Transferred to acute facility

Incomplete outcome data:

Intervention:

N= 4

Reasons:

Not described.

Control:

N=4

Reasons:

Not described

Outcome measures and effect size (include 95%CI and p-value if available):

Functional independence measure (FIM), walk test.

Functional independence measure (FIM), difference between admission and discharge (95% CI).

I vs. C:

Total: 31.49 ± 14.26 (3.54; 59.44) vs. 22.94 ± 11.79 (-0.17; 46.05). P=0.001

Motor: 24.25 ± 11.83 (1.06; 47.44) vs. 16.71 ± 9.64 (-2.18; 35.60), P=0.001

Cognitive: 4.61 ± 3.27 (-1.80; 11.02) vs. 4.37 ± 3.53 (-2.55; 11.29), P=0.80

Walk test, difference between admission and discharge (95% CI).

I vs. C:

2-minute walk test:

101.60 ± 79.41 (-54.04; 257.24) vs. 43.98 ± 62.46 (-78.44; 166.40), P<0.001

6-minute walk test:

299.28 ± 201.54 (-95.74; 694.30) vs. 170.59 ± 198.61 (-218.6; 559.87), P<0.001

Starke 2011

Type of study:

RCT

Setting:

In hospital patients

Country:

Switzerland

Source of funding:

Inclusion criteria:

all adult patients consecutively admitted to the general medical ward at “Kantonsspital Liestal” hospital, a nutritional risk (NRS score ≥3).

Exclusion criteria:

no informed consent, terminal condition, expected stay <5 days (judged by physician), previous participation in this study, patient on starvation, on parenteral nutrition, and/or being on dialysis

N total at baseline:

Intervention: 67

Control: 67

Important prognostic factors²:

age ± SD:

I: 70 ± 16

C: 75 ± 11

Sex:

Not stated

BMI (kg/m²):

I:24.± 65.3

C: 24.1 ± 4.9

Weight (kg):

I: 68.1 ± 16.9

C: 66.1 ± 16.2

Groups comparable at baseline?

Yes

Describe intervention (treatment/procedure/test):

individual nutritional care, including a detailed nutritional assessment, individual food supply, fortification of meals with maltodextrin, rapeseed oil, cream and/or protein powder, in-between snacks and oral nutritional supplements. All interventions aimed at meeting the daily energetic requirement according to the individual total energy expenditure (TEE; calculated from resting energy expenditure [REE11] corrected by an individual factor for physical activity level [PAL] and disease [stress factor, SF12]). Protein intake was set at 1.0 g/kg body weight.

Describe control (treatment/procedure/test):

received standard nutritional care, including the prescription of oral nutritional supplements and nutritional therapy prescribed by the physician independently of this study and according to the routine ward management.

Length of follow-up:

6 months after discharge hospital

Loss-to-follow-up:

Intervention:

N=8

Reasons (describe)

Incorrect diagnosis: n=1

Discharge/died before minimum intervention period: n=6

I.C. withdrawal: n=1

Control:

N=8

Reasons (describe)

Incorrect diagnosis: n=1

Discharge/died before minimum intervention period.

Outcome measures and effect size (include 95%CI and p-value if available):

Quality of life, complications, mortality

Quality of life (SF 36) at discharge:

I vs. C:

Physical: 37 ± 11 vs. 32 ± 9, P=0.033

Mental: 50 ± 11 vs. 51 ± 11, p=0.640

Complications:

I vs. C

4 of 66 patients vs. 13 of 66, P=0.035

In I:

Infections, urinary tract infection, decompensated congestive heart failure

In C:

Urinary tract infection, septic arthritis, decubitus, diarrhoea, myocardial infarction, decompensated congestive heart failure, thrombosis, cerebrovascular ischemia.

Mortality

I vs. C:

During study period:

2 vs. 5 (P=0.440)

Follow up:

6/61 vs. 9/64, P=0.585

Neelemaat 2012

Computerized random number generator, blocks of n=10

Unlikely

Likely, patients not blinded. Could affect physical activity or reporting of fall incidents.

Unlikely

Likely, not blinded.

Unlikely

Likely, reasons of withdrawal not described. Participants without complete follow up were older.

Unlikely

Neelemaat 2011

Computerized random number generator, blocks of n=10

Unlikely

Likely, patients not blinded. Could affect physical activity or other reporting.

Unlikely

Likely, not blinded.

Unlikely

Likely, reasons of withdrawal not described. Participants without complete follow up were older.

Likely, modified intention-to-treat. Analyses with imputed data (last-observation-carried-forward principle).

McMurdo 2009

Randomization code on supplement package

Likely, method of randomization code not described.

Unlikely

Unclear, not described

Unclear, not described

Unlikely

Likely, larger % of loss to follow up. Difference in withdrawal of patients between intervention + control.

Likely, intention to treat violated; number of patients randomized is not number of patients analysed.

Chapman 2009

stratification system to ensure a close to equal ratio of ‘‘at-risk of malnutrition’’ (MNA score: 17–23.5) to ‘‘malnourished’’ (MNA score: ,17) subjects and of men to women in the 4 treatment groups.

Unlikely

Likely, patients not blinded.

Unclear, not described

Unclear, not described

Unlikely

Unlikely

Unlikely

Persson 2007

drawing files from a sealed box

Unlikely

Likely, patients not blinded.

Unclear, not described

Unclear, not described

Unlikely

Likely, large % of loss to follow up. Difference in withdrawal of patients between intervention + control.

Unlikely

Rabadi 2008

Sealed opaque envelope block randomization of 10 patients (5 patients in each group) at a time

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely