Early nutritional therapy for malnourished or nutritionally at‐risk adult medical inpatients

Abstract

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:

To assess the effects of early nutritional therapy for malnourished or nutritionally at‐risk adult medical inpatients.

Background

Acute illness is associated with loss of appetite, leading to poor nutritional status and risk of malnutrition, particularly in the elderly and frail medical patient population (Kubrak 2007). This relationship between acute disease, poor appetite and malnutrition may be bi‐directional, with acute illness affecting nutritional status, but reciprocally, dietary factors influencing the course of illness. For example, cytokines such as interleukin (IL)‐6 and tumour necrosis factor alpha (TNFα) are known to interfere with brain satiety centres, inducing loss of appetite, delayed gastric emptying and skeletal muscle catabolism (Kuhlmann 2008; Oner‐Iyidogan 2011; Tisdale 2010). Whether loss of appetite associated with acute illness is indeed a protective physiological response or a therapeutic target needing early corrective nutritional therapy remains controversial.

Despite the lack of high‐quality randomised controlled trials (RCTs), the current clinical approach in general medical inpatients is to provide nutritional therapy to reach nutritional requirements including energy and protein targets, as well as micro‐nutritional requirements (Mueller 2011; Sobotka 2009; Volkert 2006). However, some recent data from critical care suggested harmful effects of aggressive early (over) feeding protocols and glutamine supplementation (Casaer 2011; Heyland 2013; Schetz 2013). Those controversial results may have various explanations: methodological issues such as differences in the patient populations studied or trial design but also factors associated with the nutritional interventions provided such as timing or composition and amounts of nutritional elements provided. In particular, there is an ongoing debate on whether excessive use of nutrition (including glutamine) may have caused the harmful effects. During the acute phase of illness, the body mobilises substrates from muscle and fat tissue to match the increased resting energy expenditure (Vincent 2013). Exogenous calories, then, no longer inhibit gluconeogenesis. Excessive nutrition during the acute phase of illness can thus induce occult overfeeding. These conflicting observations from the critical care setting re‐emphasize that nutritional therapy is a medical intervention with associated risks and costs and questions the current nutritional approach in non‐critically ill medical inpatients.

On the other hand, critical care data cannot unconditionally be transferred to medical inpatients with a lower degree of illness severity. Interestingly, recent research reported benefits of tailored support in carefully selected critically ill patients (Heidegger 2013). Similarly, in the non‐critical care setting, positive effects on health‐related quality of life were found in trials comparing individually tailored early nutritional support with standard care in medical patients (Rufenacht 2010; Starke 2011).These results show that to be beneficial, nutritional strategies may need to be tailored to individual patient requirements according to the pre‐existing degree of malnutrition and severity of disease (Vincent 2013). The lack of high level evidence on the effectiveness and cost benefits of nutritional support and the absence of data showing which patient population does or does not benefit from the intervention may explain why recommendations including ideal nutritional target, route or timing for nutritional therapy in medical inpatients are still missing (Mueller 2011; Sobotka 2009; Volkert 2006).

Description of the condition

Malnutrition is a common condition in hospitalised patients with acute and chronic illnesses. The prevalence of malnutrition at hospital admission ranges from 15% to 50% depending on patient age, geographic region and underlying illness (Edington 2004; Gheorghe 2013; Imoberdorf 2010). Due to acute illness, even well‐nourished patients at admission have a considerable risk of developing protein‐energy malnutrition during the course of their hospital stay. Malnutrition is associated with detrimental metabolic consequences, such as catabolism and muscle wasting, leading to an increased risk of mortality and morbidity as well as prolonged length of stay (LOS) in hospital (Norman 2008; Villet 2005).

Because of its high prevalence in hospitals, considerable efforts are made to detect it in patients at admission. For this purpose, different screening and assessment tools have been developed to estimate the risk of malnutrition (Detsky 2008; Kondrup 2002; Kondrup 2003; Stratton 2004; Stratton 2006). Among the available tools, the nutritional risk score 2002 (NRS) is the most frequently used screening tool in hospitals (Kondrup 2002; Kondrup 2003). Yet, the therapeutic implications of systematic screening remain ambiguous (Koretz 2007; Stratton 2013) as high‐quality clinical trial data supporting the concept of early nutritional support of patients at risk for malnutrition are largely lacking. Still, despite the lack of evidence demonstrating clinical benefits of providing early nutritional therapy in medical inpatients, the strong epidemiological associations of malnutrition and adverse clinical outcomes have led to the current clinical approach of providing early nutritional therapy to patients at risk for malnutrition.

Description of the intervention

→ Focus on the intervention you are actually investigating.

...

Nutritional therapy is a highly complex therapeutic intervention, and includes individualised and standardised nutritional therapy, which may include oral feeding (enriched food, oral nutritional supplements (ONS)), enteral nutrition (EN), and parenteral nutrition (PN) with or without dietary counselling. The intervention is not only variable in type and route of feeding, but also the optimal nutritional targets, and timing may vary. In the clinical practice, caloric, protein as well as micronutrient targets should be ideally individually defined for patients taking in consideration various factors such as age, gender, existing acute and chronic illnesses, nutritional status and food preferences.

Adverse effects of the intervention

Recent data from critically ill patients suggested adverse effects from aggressive early (over) feeding, with excess mortality, questioning therefore the safety of the current approach of nutritional therapy in medical inpatients (Casaer 2011). Unfortunately, there is a lack of systematic reporting of adverse events caused by nutritional therapies, presumably because nutritional interventions are not considered similar to medical treatment, and thus, industries supplying nutritional products do not need to report on safety as rigorously as for pharmacological interventions.

Within this review we will analyse potential adverse effects of nutritional interventions and possible side effects from oral nutrition (e.g. non‐acceptance, nausea, bloating, vomiting, lack of appetite, diarrhoea), enteral nutrition (e.g. tube‐related complications, aspiration, diarrhoea, patients' discomfort), and parenteral nutrition (e.g. catheter‐related complications, hyperglycaemia, electrolyte imbalance).

How the intervention might work

Malnutrition puts patients at increased risk for catabolism, muscle wasting, decline in functional status and other complications. Nutritional support may help to prevent malnutrition and thus those complications. However, if an individualised strategy with dietary counselling and enriched food may improve patient's intake, it can also be time consuming, and depends on the availability of a nutritional team and possibilities of the hospital kitchen (Johansen 2004). Less demanding strategies exist such as providing fixed amounts of calories and proteins using ONS (oral nutritional supplements) in all patients. In cases where oral feeding is not sufficient to improve nutritional status or when it is not possible, enteral and/or parenteral nutrition are used to meet nutritional requirements.

Why it is important to do this review

→ Emphasise lack of clarity as to importance of review question. → If available, compare your project to already existing systematic reviews, meta‐analyses or health‐technology assessment reports and provide substantial justification for your Cochrane review. → If you did not find an already existing systematic review on your topic you should state this finding.

...

Although clinical nutrition is one of the most common interventions in medicine, positive effects of providing early nutritional therapy to unselected medical inpatients remain largely unproven (Koretz 2007). Recent data from critically ill patients found contradictory effects of aggressive early feeding, also challenging the safety of the current nutritional therapy approach in medical inpatients (Casaer 2011). Furthermore, nutritional therapies are expensive, time‐consuming and sometimes not beneficial for patients' subjective well being (e.g. tube feeding). Therefore, our current approach of early nutritional therapy in acutely‐ill medical patients needs to be re‐evaluated. The selection, timing, and doses of nutrition should be evaluated as carefully as with any other drug, with the aim of maximising efficacy and minimising iatrogenic toxicity and costs.

Several smaller trials have investigated the effects of nutritional strategies on selected patient outcomes focusing only on changes in body weight and nutrition‐specific quality of life (Baldwin 2012). In addition, previous trials in this topic were highly heterogeneous in design, patient populations and type of interventions, lacked power to appropriately investigate safety, and, in aggregate, produced inconclusive results (Milne 2009). Therefore, unsurprisingly, previous meta‐analyses confirmed the lack of high quality evidence to endorse or reject the implementation of nutritional support (Baldwin 2011; Baldwin 2012; Koretz 2007; Milne 2009; Potter 1998). These meta‐analyses, however, did not specifically focus on the effect of early nutritional therapy in acutely‐ill medical inpatients. Similarly, an ongoing meta‐analysis is currently investigating the effect of oral supportive interventions on dietary intakes in malnourished or nutritionally at‐risk adults (Gibbs 2012). This review excludes enteral and parenteral interventions, and does not focus specifically on patients hospitalised in medical wards.

Objectives

To assess the effects of early nutritional therapy for malnourished or nutritionally at‐risk adult medical inpatients.

Methods

Criteria for considering studies for this review

Types of studies

We included randomised controlled trials (RCTs) and quasi‐RCTs (for example alternative allocation by date of birth) (Blair 2004; Treasure 1998). The duration of intervention may exceed the hospitalisation period but outcome data had to be assessed and reported before discharge.

Types of participants

→ Do not use the term 'subjects' throughout the review. → Use participants, individuals, persons etc. instead of patients whenever possible and feasible. → Describe diagnostic criteria for all conditions you are evaluating.

...

We included adult patients, malnourished or at risk for malnutrition, aged 18 years or older, hospitalised for an acute exacerbation of a medical illness in non‐critical care wards.

Diagnostic criteria (malnourished or nutritionally at‐risk adults)

Malnutrition should be identified ideally using a nutritional screening and assessment tool (e.g. Subjective Global Assessment (SGA), Malnutrition Universal Screening Tool (MUST), Nutritional Risk Screening (NRS‐2002)) or by measuring body mass index (BMI), particularly in the context of diseases associated with increased risks of developing malnutrition during hospitalisation. Medical inpatients defines patients hospitalised in medical wards of acute care institutions. Medical wards can be found among geriatric or other medical specialties units (e.g. gastroenterology, endocrinology, cardiology, pneumology, general internal medicine, infectious diseases, nephrology, oncology). This definition does not include patients hospitalised in intensive care units or surgical wards including surgical specialities (e.g. general surgery, gynaecology, traumatology, orthopaedic surgery).

Types of interventions

Studies were eligible for inclusion if the intervention consisted of any type of nutritional therapy such as dietary counselling, oral feeding (e.g. fortification of meals, nutritional supplements) enteral nutrition or parenteral nutrition. In our primary analysis we included any type of intervention as well as any combination of different nutritional strategies.

Additionally we defined subgroups to analyse the effects of particular types of interventions and the comparison with particular types of controls.

Early nutritional therapy was defined as starting nutritional support within 48 hours following hospital admission.

Nutritional support was defined as follows.

• Dietary advice: changes to the organisation of nutritional care, e.g. use of dietitians or healthcare assistants, targeted staff training in nutritional care, implementation of nutritional care pathways/protocols, feeding assistance.

• Food fortification: snacks between meals, fortification of meals with protein and/or energy or similar.

• Oral feeding (besides meals): any kind of oral nutritional supplements (ONS).

• Enteral feeding: any kind of total or partial enteral (tube) feeding.

• Parenteral feeding: any kind of total or partial parenteral feeding via central or peripheral access.

We planned to investigate the following comparisions of interventions versus control/comparator.

Intervention

(a) Oral feeding (food fortification or ONS) alone.

(b) Oral feeding (food fortification or ONS) with dietary advice.

(c) Enteral or parenteral nutrition alone.

(d) Enteral or parenteral nutrition with dietary advice.

(e) Mixed feeding strategies.

Comparator

• Usual care (usual nutritional care according to hospitals' daily routine) compared with (a)

• No support (normal hospital food) compared with (b)

• Dietary advice alone compared with (c).

• ONS alone compared with (d).

• Placebo compared with (e).

Concomitant interventions had to be the same in both the intervention and comparator groups to establish fair comparisons.

Minimum duration of intervention

→ Define clinically meaningful minimal duration of intervention (and distinguish this from (minimal) duration of follow‐up).

...

Minimum duration of follow‐up

Minimal duration of follow‐up will be ....

We defined extended follow‐up periods (open‐label extension studies) as follow‐up of participants once the original trial, as specified in the trial protocol, has been terminated. However, such studies are frequently of an observational in nature and we primarily evaluated them for adverse events (Buch 2011; Megan 2012).

Summary of specific exclusion criteria

• We excluded trials including mainly patients hospitalised in critical care units or surgical wards, or residing in nursing homes or long‐term facilities as well as outpatients.

• We also excluded patients with acute pancreatitis as nutritional support in this particular case has important differences compared to other acute medical illnesses. First, delaying the start of oral or enteral nutritional support until day three to five is recommended in mild and moderate forms of acute pancreatitis. Some guidelines recommend early nutritional support in severe pancreatitis, with the precaution to adapt the route of delivery according to the tolerance of individual patients rather than following a strict and uniform nutrition protocol (Meier 2002). Additionally, the strength of evidence in most validated guidelines for nutritional support in severe acute pancreatitis is weak with most trials conducted in intensive care units or surgical wards. Finally, acute pancreatitis differs from most other diseases as it imposes fasting periods often inevitable and part of the treatment for pancreatitis patients.

Types of outcome measures

We d id not exclude a trial b ecause one or several of our primary or secondary outcome measures were not reported in the publication (s) . In case none of our primary or secondary outcomes were reported in the p ublication(s) we did not include this trial but provide d some basic information in an additional table.

Primary outcomes

• All‐cause mortality.

• Change in functional outcomes.

• Adverse events.

Secondary outcomes

• Change in anthropometric measures and body composition.

• Change in health‐related quality of life.

• Elective and non‐elective hospital readmissions.

• Achievement of targeted energy and protein intake.

• Socioeconomic effects.

Method and timing of outcome measurement

• All‐cause mortality: defined as death from any cause and measured at hospital discharge or at follow‐up (four to six weeks).

• Change in functional outcomes: defined as muscular, mobility or cognitive function evaluated by a validated instrument such as Barthel index, handgrip strength, walking distance or similar, and measured from study inclusion until hospital discharge or at follow‐up (four to six weeks).

• Adverse events: for example infection, disease‐specific complications, re‐hospitalisation, intensive care unit admission from medical ward, and measured from study inclusion until hospital discharge or at follow‐up (four to six weeks).

• Change in anthropometric measures: defined as body weight, BMI, lean body mass, and measured from study inclusion until hospital discharge or at follow‐up (four to six weeks).

• Change in health‐related quality of life: evaluated with a validated instrument (e.g. short form 36 questionnaire (SF‐36), Functional Assessment Anorexia‐Cancer Therapy (FAACT), visual analogue scale (VAS)), and measured from study inclusion until hospital discharge or at follow‐up (four to six weeks).

• Elective and non‐elective hospital readmissions: defined as any hospital or emergency department visits and until follow‐up (four to six weeks).

• Achievement of targeted energy and protein intake: defined by the study protocol and measured during the nutritional intervention period.

• Socioeconomic effects: such as length of hospital stay, defined as time from hospital admission to discharge.

'Summary of findings' table

We presented a 'Summary of findings' table reporting the following outcomes listed according to priority.

1. All‐cause mortality.

2. Change in functional outcomes (Barthel score).

3. Change in health‐related quality of life (SF‐36 questionnaire).

4. Adverse events.

5. Hospital readmissions.

6. Change in body weight.

7. Socioeconomic effects.

Search methods for identification of studies

Electronic searches

We searched the following sources from the inception of each database to the specified date.

• Cochrane Central Register of Controlled Trials (CENTRAL) via Cochrane Register of Studies Online (CRSO) (searched year, Issue .).

• MEDLINE Ovid (Epub Ahead of Print, In‐Process & Other Non‐Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R)) (from 1946 to month week year).

• Embase (1974 until December 11th 201X).

• ClinicalTrials.gov (www.clinicaltrials.gov) (searched day month year).

• WHO International Clinical Trials Registry Platform (ICTRP; apps.who.int/trialsearch/) (day month year).

• LILACS (Latin American and Caribbean Health Science Information database) (from 1982 to day months year).

We continuously applied an email alert service for MEDLINE via OvidSP to identify newly published trials using the search strategy detailed in Appendix 1. After we submitted the final update review draft for editorial approval, the Cochrane Metabolic and Endocrine Disorders (CMED) Group performed a complete search update on all databases available at the editorial office and send the results to the review authors. If we detected additional relevant key words during any of the electronic or other searches, we modified the electronic search strategies to incorporate these terms and documented the changes. We placed no restrictions on the language of publication when searching the electronic databases or reviewing reference lists of identified trials.

Searching other resources

We tried to identify other potentially eligible trials or ancillary publications by searching the reference lists of retrieved included trials, (systematic) reviews, meta‐analyses and health technology assessment reports, and by contacting experts in the field and nutrition manufacturers. In addition we contacted authors of included trials to identify any additional information on the retrieved trials and to determine if further trials exist, which we may have missed.

We did not use abstracts or conference proceedings for data extraction because this information source does not fulfil the CONSORT requirements which is "an evidence‐based, minimum set of recommendations for reporting randomized trials" (CONSORT; Scherer 2007) unless full data were available from trial authors. Information on abstracts or conference proceedings were planned to be shown in the table 'Characteristics of studies awaiting classification'.

Data collection and analysis

Selection of studies

Two review authors (NN, NN) independently screened the abstract, title or both, of every record retrieved by the literature searches, to determine which trials we should assess further. We obtained the full‐text of all potentially relevant records. We resolved any disagreements through consensus or by recourse to a third review author (NN). If we could not resolve a disagreement, we categorised the trial as a 'study awaiting classification' and contacted the trial authors for clarification. We presented an adapted PRISMA flow diagram to shown the process of trial selection (Liberati 2009). We listed all articles excluded after full‐text assessment in the Characteristics of excluded studies table and provided the reasons for exclusion.

Data extraction and management

For trials that fulfil our inclusion criteria, two review authors (MB, PB) independently extracted key participant and intervention characteristics. We reported data on efficacy outcomes and adverse events using standardised data extraction sheets from CMED. We resolved any disagreements by discussion or, if required, we consulted a third review author (PS) (for details see Characteristics of included studies; Table 5; Appendix 2; Appendix 3; Appendix 4; Appendix 5; Appendix 7; Appendix 8; Appendix 8; Appendix 9; Appendix 10; Appendix 11; Appendix 12).

Table 1.

Overview of study populations

Description of power and sample size calculation: quote (abbreviated) details from the publication In all tables trials are ordered by year, so that new trials can be added on the top of the table! Intervention(s) / comparator(s): Short description of interventions (e.g. metformin, placebo, usual care etc.). [%] of randomised participants finishing study: one decimal only. Total: calculate from all intervention and comparator groups; sometimes this is the only number available in the publication. Cross‐over trials: specify as follows (e.g. 20 participants with full cross‐over: I = 20 / C = 20 / total = 20). For comments use footnotes.
Trial design	Intervention(s) and comparator(s)	Description of power and sample size calculation	Screened/eligible (N)	Randomised (N)	Analysed (N)	Finishing trial (N)	Randomised finishing trial (%)	Follow‐up (extended follow‐up)a
(28) Study author 2017 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no
	total:
(27) Study author 2016 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no
	total:
(26) Broqvist 1994 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no	I: standard diet plus oral nutritional supplements	‐	/22	9	6	6	67	8 weeks (...)
	C: standard diet plus placebo			13	11	11	85
	total:			22	17	17	76
(25) Bunout 1980 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no	I: standard nutritional therapy plus oral nutritional supplements	‐	/40	17	12	12	71	Until discharge or death, LOS: 20 +/‐ 3 days
	C: standard nutritional therapy			19	17	17	90	Until discharge or death, LOS: 28 +/‐ 4 days
	total:
(24) Cabre 1990 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no	I: enteral nutrition	‐	150 / 35	16	14	14	88	23.3 +/‐ 3 days
	C: standard (low sodium) diet			19	10	10	53	25.3 +/‐ 3.2 days
	total:			35	24	24	70
(23) Calvey 1985 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no	I1: controlled oral diet diet plus conventional protein supplements (oral, enteral, parenteral nutrition, when necessary)	‐	70 / 64	21	14	14	69	17 days, range 2‐23 days
	I2: controlled oral diet diet plus branched chain amino acids supplements (oral, enteral, parenteral nutrition, when necessary)			21	15	15	68	18 days, range 3‐22 days
	C: controlled oral diet			22	15	15	68	14 days, range 4‐25 days
	total:			64	44	44	69
(22) Feldblum 2011 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no	I1: 1 visit by a dietitian in the hospital (followed by a nutritional intervention program) and 3 home visits after discharge	" Sample size calculation used mortality as the key outcome ... Previous studies assessing the effect of supplements on mortality showed a 21% lower risk in mortality after an intervention in undernourished patients than in a control group. The largest sample size calculation, based on alpha = 0.05 (2‐sided) and beta = 0.20 yielded a sample of 62 people in each group, and with an estimated 30% drop‐out rate, the calculated sample size was 78 in each group. In the current study, 78 patients were in the intervention group and 181 in the combined control group "	637 / 259	78	66	66	85	6 months
	I2: 1 visit by a dietitian in the hospital (followed by a nutritional intervention program) and instructions of dietary needs after hospitalisation			73	102	102	56
	C: standard care			108
	total:			259	168	168	70
(21) Gariballa 2006 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no	I: normal hospital diet plus oral liquid supplements		‐ / 445	223	223	223	100	6 months
	C: normal hospital diet plus oral liquid placebo			222	222	222	100
	total:			445	445	445	100
(20) Gazzotti 2003 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no	I: standard hospital diet and oral nutritional supplements		‐ / 99	39	39	32	82	60 days
	C: standard hospital diet			41	41	39	95
	total:			80	80	71	89
(19) Hickson 2004 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no	I: oral nutritional therapy plus support for feeding		1776 / 867	292	300	259	86	From admission until death or discharge; median LOS: 21 days; range 13–36 days
	C: oral nutritional therapy without support for feeding			300	292	250	86	From admission until death or discharge; median LOS: 23 days; range 14–39 days
	total:			592	592	509	86
(18) Hogarth 1996 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no	I: usual care plus oral nutritional supplements	‐	‐	55	55	46	84	1 month
	C: usual care plus placebo			51	51	41	80
	total:			106	43	43	82
(17) Holyday 2011 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no	I: modification and fortification of hospital meals, oral nutritional supplements		‐ / 143	71	71	71	100	6 months
	C: usual nutritional care			72	72	72	100
	total:			143	143	143	100
(16) Johansen 2004 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no	I: motivation of patient and staff, nutritional plan adjusted to estimated protein and energy requirements, ordering of food in collaboration with the patient, securing of the supply of food ordered, advises for patients and staff about when to change to tube feeding or parenteral nutrition		7468 / 310	108	108	103	95	From admission until 28 days maximum, mean LOS: 12.5 +/‐ 0.9 days
	C: usual nutritional care			104	104	99	95	From admission until 28 days maximum, LOS: 11.7 +/‐ 0.9 days
	total:			212	212	202	95
(15) Mc Evoy 1982 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no	I: normal hospital diet plus oral supplements	‐	‐ / 51	26	26	26	100	4 weeks
	C: normal hospital diet			25	25	25	100
	total:			51	51	51	100
(14) McWhirter 1996 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no	I1: normal hospital diet and oral nutritional supplements in patients with inadequate oral intake	‐	‐	35	35	35	100	At the end of feeding period, mean 9.7 days, or at discharge
	I2: normal hospital diet and nocturnal tube feeding in patients with inadequate oral intake			26	26	26	100	At the end of feeding period, mean 11.8 days, or at discharge
	C: normal hospital diet			25	25	25	100	At the end of feeding period, mean 8.9 days, or at discharge
	total:			86	86	86	100
(13) Mulder 1989 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no	I: total enteral and parenteral nutrition	‐	‐	11	11	11	100	21 days
	C: total parenteral nutrition			11	11	11	100
	total:			22	22	22	100
(12) Munk 2014 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no	I: oral a la carte menu of small dishes supplemented with energy and protein		‐ / 105	44	44	41	93	7 days
	C: standard hospital food			40	40	40	100
	total:			84	84	81	97
(11) Neelemaat 2011 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no	I: oral diet, oral supplements, telephone counselling after discharge		3239 / 575	105	105	75	71	3 months
	C: usual care during hospitalisation, no post‐discharge support			105	105	75	71
	total:			210	210	150	71
(10) Ollenschläger 1992 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no	I: menus of free choice and dietetic intervention (assessment, counselling, and modification of oral diet)	‐	‐ / 38	16	16	16	100	25.5 weeks
	C: menus of free choice ad libitum			16	16	16	100
	total:			32	16	16	100
(9) Potter 2001 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no	I: oral sip feed supplements in addition to normal hospital food		‐ / 618	186	186	186	100	From admission until discharge, mean LOS is 16 days, range: 3 ‐ 141 days
	C: normal hospital food and dietetic intervention if recommended by treating physician			195	195	195	100	From admission until discharge, mean LOS is 18 days, range: 2 ‐ 76 days
	total:			381
(8) Rufenacht 2010 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no	I: individual nutritional counselling, nutritional plan including food fortification and supplements	‐	512 / 82	36	27	27	75	From admission until 2 months after discharge
	C: normal hospital food, information about the risks of under nutrition and oral nutritional supplements			36	26	26	72
	total			72	53	53	74
(7) Ryan 2004 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no	I: normal hospital food plus oral nutritional supplements		‐ / 28	17	16	16	100	2 days
	C: normal hospital food			16	17	16	100	1 day
	total:			33	16	16	100
(6) Saudny‐Unterberger 1997 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no	I: traditional hospital food and oral nutritional supplements	‐	‐	17	14	14	82	14 days
	C: traditional hospital food			16	10	10	63
	total:			33	24	24	72
(5) Somanchi 2011 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no	I: nutritional assessment using the Potential Nutrition Risk Screen Criteria at Admission assessment form, clinical nutrition department consultation and nutritional intervention for malnourished patients	‐	‐	229	‐	‐	86	From admission until discharge, mean LOS in subgroup malnourished: 6.1 +/‐ 5.4 days; mean LOS in subgroup severely malnourished: 7.9 +/‐ 6.7 days
	C: standard procedure for nutritional assessment and nutritional intervention			215	‐	‐	93	From admission until discharge
	total:			544	‐	‐	89
(4) Starke 2011 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no	I: individual nutritional care, including nutritional assessment, individual food supply, fortification of meals, in‐between snacks and oral nutritional supplements		676 / 271	67	67	59	87	6 months
	C: standard nutritional care			67	67	59	87
	total:			134	118	118	87
(3) Vermeeren 2004 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no	I: normal hospital food plus oral nutritional supplements	‐	‐	29	23	23	79	From admission until discharge
	C: normal hospital food plus placebo			27	24	24	89
	total:			56	81	81	84
(2) Vlaming 2001 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no	I: normal hospital food plus oral nutritional supplements		‐ / 1561	275	275	275	100	From admission until discharge; LOS 15.8 +/‐ 27.7 days
	C: normal hospital food plus oral placebo drink			274	274	274	100
	total:			549	549	549	100
(1) Volkert 1996 Parallel / cluster / cross‐over / factorial RCT Non‐inferiority/superiority trial Trial terminated early: yes/no	I: standard hospital diet plus oral liquid supplements	‐	‐	35	20	20	57	6 months
	C: standard hospital diet			37	26	26	70
	total:			72	46	46	64
Grand total	All interventions			...		...
	All comparators			...		...
	All interventions and comparators			...		...

• Each abbreviation needs to be explained (alphabetical order)
• Use "‐" for missing information

‐ denotes not reported

^aFollow‐up under randomised conditions until end of trial ( (= duration of intervention + follow‐up post intervention or identical to duration of intervention); extended follow‐up refers to follow‐up of participants once the original trial was terminated as specified in the power calculation

C: comparator; I: intervention; ITT: intention‐to‐treat; N/A: not applicable; RCT: randomised controlled trial

We provided information (including trial identifier) about potentially‐relevant ongoing studies in the Characteristics of ongoing studies table and in the Appendix 5 'Matrix of study endpoints (trial documents)'. We tried to find the protocol of each included study, either in trial registers or in publications of study designs, or both, and specify the data in the Appendix 5.

We contacted all authors of included studies to enquire whether they were willing to answer questions regarding their trials and to share their data with us. We presented the results of this survey in Appendix 13. We thereafter sought relevant missing information on the trial from the primary trial author(s), if required.

Dealing with duplicate and companion publications

In the event of duplicate publications, companion documents or multiple reports of a primary trial, we maximised the information yield by collating all available data and we used the most complete dataset aggregated across all known publications. We listed duplicate publications, companion documents, multiple reports of a primary trial and trial documents of included trials (such as trial registry information) as secondary references under the study identifier (ID) of the included trial. Furthermore, we also listed duplicate publications, companion documents, multiple reports of a trial and trial documents of excluded trials (such as trial registry information) as secondary references under the study ID of the excluded trial.

Data from clinical trials registers

If data from included trials are available as study results in clinical trials registers, such as ClinicalTrials.gov or similar sources, we make full use of this information and extract the data. If there was also a full publication of the trial, we collated and critically appraised all available data. If an included trial was marked as a completed study in a clinical trial register but no additional information (study results, publication or both) is available, we added this trial to the Characteristics of studies awaiting classification table.

Assessment of risk of bias in included studies

Two review authors (MB, LB) independently assessed the risk of bias of each included trial. We resolved any disagreements by consensus or by consulting a third review author (PS). In the case of disagreement, we consulted the remainder of the review author team and we make a judgement based on consensus. If adequate information was unavailable from the trials, trial protocols or both, we contacted the trial authors to request missing data on 'Risk of bias' items.

We used the Cochrane 'Risk of bias' assessment tool (Higgins 2011a; Higgins 2011b), and assign assessments of low, high or unclear risk of bias. We evaluated individual bias items as described in the Cochrane Handbook for Systematic Reviews of Interventions according to the criteria and associated categorisations contained therein(Higgins 2011b).

Random sequence generation (selection bias due to inadequate generation of a randomised sequence) ‐ assessment at trial level

For each included trial we described the method used to generate the allocation sequence in sufficient detail to enable assessment of whether it should produce comparable groups.

• Low risk of bias: the trial authors achieved sequence generation using computer‐generated random numbers or a random numbers table. Drawing of lots, tossing a coin, shuffling cards or envelopes, and throwing dice are adequate if an independent person performed this who was not otherwise involved in the trial. We considered the use of the minimisation technique as equivalent to being random.

• Unclear risk of bias: insufficient information about the sequence generation process.

• High risk of bias: the sequence generation method was non‐random or quasi‐random (e.g. sequence generated by odd or even date of birth; sequence generated by some rule based on date (or day) of admission; sequence generated by some rule based on hospital or clinic record number; allocation by judgement of the clinician; allocation by preference of the participant; allocation based on the results of a laboratory test or a series of tests; or allocation by availability of the intervention).

Allocation concealment (selection bias due to inadequate concealment of allocation prior to assignment) ‐ assessment at trial level

We described for each included trial the method used to conceal allocation to interventions prior to assignment and we assessed whether intervention allocation could have been foreseen in advance of or during recruitment, or changed after assignment.

• Low risk of bias: central allocation (including telephone, interactive voice‐recorder, internet‐based and pharmacy‐controlled randomisation); sequentially numbered drug containers of identical appearance; sequentially numbered, opaque, sealed envelopes.

• Unclear risk of bias: insufficient information about the allocation concealment.

• High risk of bias: using an open random allocation schedule (e.g. a list of random numbers); assignment envelopes were used without appropriate safeguards; alternation or rotation; date of birth; case record number; any other explicitly unconcealed procedure.

We also evaluated trial baseline data to incorporate assessment of baseline imbalance into the 'Risk of bias' judgement for selection bias (Corbett 2014). Chance imbalances may also affect judgements on the risk of attrition bias. In the case of unadjusted analyses, we distinguished between trials we rate as at low risk of bias on the basis of both randomisation methods and baseline similarity, and trials we judge as at low risk of bias on the basis of baseline similarity alone (Corbett 2014). We re‐classified judgements of unclear, low or high risk of selection bias as specified in Appendix XX.

Blinding of participants and study personnel (performance bias due to knowledge of the allocated interventions by participants and personnel during the trial) ‐ assessment at outcome level

We evaluated the risk of detection bias separately for each outcome (Hróbjartsson 2013). We noted whether endpoints were self‐reported, investigator‐assessed or adjudicated outcome measures (see below).

• Low risk of bias: blinding of participants and key study personnel is ensured, and it was unlikely that the blinding could have been broken; no blinding or incomplete blinding, but we judge that the outcome is unlikely to have been influenced by lack of blinding.

• Unclear risk of bias: insufficient information about the blinding of participants and study personnel; the trial does not address this outcome.

• High risk of bias: no blinding or incomplete blinding, and the outcome was likely to have been influenced by lack of blinding; blinding of trial participants and key personnel attempted, but likely that the blinding could have been broken, and the outcome was likely to be influenced by lack of blinding.

Blinding of outcome assessment (detection bias due to knowledge of the allocated interventions by outcome assessment) ‐ assessment at outcome level

We evaluated the risk of detection bias separately for each outcome (Hróbjartsson 2013). We noted whether endpoints were self‐reported, investigator‐assessed or adjudicated outcome measures (see below).

• Low risk of bias: blinding of outcome assessment is ensured, and it was unlikely that the blinding could have been broken; no blinding of outcome assessment, but we judge that the outcome measurement was unlikely to have been influenced by lack of blinding.

• Unclear risk of bias: insufficient information about the blinding of outcome assessors; the trial did not address this outcome.

• High risk of bias: no blinding of outcome assessment, and the outcome measurement was likely to have been influenced by lack of blinding; blinding of outcome assessment, but likely that the blinding could have been broken, and the outcome measurement was likely to be influenced by lack of blinding.

Incomplete outcome data (attrition bias due to amount, nature or handling of incomplete outcome data) ‐ assessment at outcome level

For each included trial and or each outcome, we described the completeness of data, including attrition and exclusions from the analyses. We stated whether the trial reported attrition and exclusions, and the number of participants included in the analysis at each stage (compared with the number of randomised participants per intervention/comparator groups). We also noted if the trial reported the reasons for attrition or exclusion and whether missing data were balanced across groups or were related to outcomes. We considered the implications of missing outcome data per outcome such as high dropout rates (e.g. above 15%) or disparate attrition rates (e.g. difference of 10% or more between trial arms).

• Low risk of bias: no missing outcome data; reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to introduce bias); missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk is not enough to have a clinically relevant impact on the intervention effect estimate; for continuous outcome data, plausible effect size (mean difference or standardised mean difference) among missing outcomes is not enough to have a clinically relevant impact on observed effect size; appropriate methods, such as multiple imputation, were used to handle missing data.

• Unclear risk of bias: insufficient information to assess whether missing data in combination with the method used to handle missing data were likely to induce bias; the trial did not address this outcome.

• High risk of bias: reason for missing outcome data is likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce clinically relevant bias in the intervention effect estimate; for continuous outcome data, plausible effect size (mean difference or standardised mean difference) among missing outcomes enough to induce clinically‐relevant bias in observed effect size; 'as‐treated' or similar analysis done with substantial departure of the intervention received from that assigned at randomisation; potentially inappropriate application of simple imputation.

Selective reporting (reporting bias due to selective outcome reporting) ‐ assessment at trial level

We assessed outcome reporting bias by integrating the results of the Appendix 5 'Matrix of trial endpoints (publications and trial documents)' (Boutron 2014; Jones 2015; Mathieu 2009), with those of the Appendix 7 'High risk of outcome reporting bias according to ORBIT classification' (Kirkham 2010). This analysis formed the basis for the judgement of selective reporting.

• Low risk of bias: the trial protocol was available and all the trial's pre‐specified (primary and secondary) outcomes that are of interest in the review were reported in the pre‐specified way; the study protocol was unavailable, but it was clear that the published reports included all expected outcomes (ORBIT classification).

• Unclear risk of bias: insufficient information about selective reporting.

• High risk of bias: not all the trial's prespecified primary outcomes were reported; one or more primary outcomes were reported using measurements, analysis methods or subsets of the data (e.g. subscales) that were not pre‐specified; one or more reported primary outcomes were not pre‐specified (unless clear justification for their reporting is provided, such as an unexpected adverse effect); one or more outcomes of interest in the Cochrane Review were reported incompletely so that we cannot enter them in a meta‐analysis; the trial report failed to include results for a key outcome that we would expect to have been reported for such a trial (ORBIT classification).

Other bias (bias due to problems not covered elsewhere) ‐ assessment at trial level

• Low risk of bias: the trial appeared to be free of other sources of bias.

• Unclear risk of bias: there was insufficient information to assess whether an important risk of bias existed; insufficient rationale or evidence that an identified problem introduced bias.

• High risk of bias: the trial had a potential source of bias related to the specific trial design used; the trial was claimed to be fraudulent; or the trial had some other serious problem.

We presented a 'Risk of bias' graph and a 'Risk of bias' summary figure.

We distinguished between self‐reported, investigator‐assessed and adjudicated outcome measures.

We accepted the following outcomes as self‐reported.

• Health‐related quality of life.

• Adverse events, as reported by participants.

• Change in anthropometric measures, as reported by participants.

• Achievement of targeted energy and protein intake.

We accepted the following outcomes to be investigator‐assessed.

• All‐cause mortality.

• Functional outcomes.

• Adverse events, as measured/reported by trial personnel.

• Elective and non‐elective hospital readmissions.

• Change in anthropometric measures, as measured by study personnel.

• Socioeconomic effects.

Summary assessment of risk of bias

Risk of bias for a trial across outcomes: some 'Risk of bias' domains, such as selection bias (sequence generation and allocation sequence concealment), affect the risk of bias across all outcome measures in a trial. In case of high risk of selection bias, we marked all endpoints investigated in the associated trial as high risk. Otherwise, we not performed a summary assessment of the risk of bias across all outcomes for a trial.

Risk of bias for an outcome within a trial and across domains: we assessed the risk of bias for an outcome measure by including all entries relevant to that outcome (i.e. both trial‐level entries and outcome‐specific entries). We considered low risk of bias to denote a low risk of bias for all key domains, unclear risk to denote an unclear risk of bias for one or more key domains and high risk to denote a high risk of bias for one or more key domains.

Risk of bias for an outcome across trials and across domains: these are the main summary assessments that we incorporated into our judgements about the quality of evidence in the 'Summary of findings' tables. We defined outcomes as at low risk of bias when most information comes from trials at low risk of bias, unclear risk when most information comes from trials at low or unclear risk of bias, and high risk when a sufficient proportion of information comes from trials at high risk of bias.

Measures of treatment effect

We expressed dichotomous data as odds ratios (ORs) or risk ratios (RRs) with 95% confidence intervals (CIs). We expressed continuous data as mean differences (MDs) with 95% CIs.

Unit of analysis issues

We took into account the level at which randomisation occurred, such as cross‐over trials, cluster‐randomised trials and multiple observations for the same outcome. If more than one comparison from the same trial is eligible for inclusion in the same meta‐analysis, we either combined groups to create a single pair‐wise comparison or appropriately reduce the sample size so that the same participants do not contribute multiply (splitting the 'shared' group into two or more groups). While the latter approach offers some solution to adjusting the precision of the comparison, it does not account for correlation arising from the same set of participants being in multiple comparisons (Higgins 2011c).

We attempted to reanalyse cluster‐RCTs that have not appropriately adjusted for potential clustering of participants within clusters in their analyses. The variance of the intervention effects will be inflated by a design effect. Calculation of a design effect involves estimation of an intra‐cluster correlation (ICC). We obtained estimates of ICCs through contact with the trial authors, or impute them using estimates from other included trials that report ICCs, or using external estimates from empirical research (e.g. Bell 2013). We planned to examine the impact of clustering using sensitivity analyses.

Dealing with missing data

If possible, we obtained missing data from the authors of the included trials. We carefully evaluated important numerical data such as screened, randomly assigned participants as well as intention‐to‐treat, and as‐treated and per‐protocol populations. We investigated attrition rates (e.g. dropouts, losses to follow‐up, withdrawals), and we critically appraised issues concerning missing data and use of imputation methods (e.g. last observation carried forward).

In trials where the standard deviation (SD) of the outcome was not available at follow‐up or cannot be recreated, we standardised by the average of the pooled baseline SD from those trials that reported this information.

Where included trials do not reported means and SDs for outcomes and we do not receive the necessary information from trial authors, we imputed these values by estimating the mean and variance from the median, range, and the size of the sample (Hozo 2005).

We investigated the impact of imputation on meta‐analyses by performing sensitivity analyses and we reported per outcome which trials were included with imputed SDs.

Assessment of heterogeneity

In the event of substantial clinical or methodological heterogeneity, we will not report trial results as the pooled effect estimate in a meta‐analysis.

We will identify heterogeneity (inconsistency) by visually inspecting the forest plots and by using a standard Chi² test with a significance level of α = 0.1. In view of the low power of this test, we will also consider the I² statistic, which quantifies inconsistency across trials to assess the impact of heterogeneity on the meta‐analysis (Higgins 2002; Higgins 2003).

When we find heterogeneity, we will attempt to determine the possible reasons for it by examining individual trial and subgroup characteristics.

Assessment of reporting biases

If we included 10 or more trials that investigate a particular outcome, we used funnel plots to assess small‐trial effects. Several explanations may account for funnel plot asymmetry, including true heterogeneity of effect with respect to trial size, poor methodological design (and hence bias of small trials) and publication bias. Therefore we interpreted the results carefully (Sterne 2011).

Data synthesis

We planned to undertake (or display) a meta‐analysis only if we judged participants, interventions, comparisons and outcomes to be sufficiently similar to ensure an answer that is clinically meaningful. Unless good evidence showed homogeneous effects across trials, we primarily summarised low risk of bias data using a random‐effects model (Wood 2008). We interpreted random‐effects meta‐analyses with due consideration to the whole distribution of effects and presented a prediction interval (Borenstein 2017a; Borenstein 2017b). A prediction interval needs at least four trials to be calculated and specifies a predicted range for the true treatment effect in an individual trial (Riley 2011). For rare events such as event rates below 1% we used Peto's OR method, provided that there was no substantial imbalance between intervention and comparator group sizes and intervention effects were not exceptionally large. In addition, we also performed statistical analyses according to the statistical guidelines presented in the Cochrane Handbook for Systematic Reviews of Interventions (Deeks 2011).

Quality of evidence

We presented the overall quality of the evidence for each outcome specified under Types of outcome measures: Summary of findings' according to the GRADE approach, which takes into account issues related not only to internal validity (risk of bias, inconsistency, imprecision, publication bias) and external validity, such as directness of results. Two review authors (NN, NN) independently rated the quality of evidence for each outcome. We have presented a summary of the evidence in Summary of findings table 1. This provides key information about the best estimate of the magnitude of the effect, in relative terms and as absolute differences, for each relevant comparison of alternative management strategies, numbers of participants and trials addressing each important outcome and a rating of overall confidence in effect estimates for each outcome. We created the 'Summary of findings' table based on the methods described in the Cochrane Handbook for Systematic Reviews of Interventions (Schünemann 2011) using Review Manager 5 (RevMan 2014). We included the Appendix 15 'Checklist to aid consistency and reproducibility of GRADE assessments' (Meader 2014), to help with standardisation of the 'Summary of findings' tables. Alternatively, we used the GRADEpro Guideline Development Tool (GDT) software (GRADEproGDT 2015) and present evidence profile tables as the Appendix XX. We have presented the results for the outcomes as described in the Types of outcome measures section. If meta‐analysis was not possible, we presented the results in a narrative format in the 'Summary of findings' table. We justified all decisions to downgrade the quality of trials using footnotes, and we made comments to aid the reader's understanding of the Cochrane Review where necessary.

Subgroup analysis and investigation of heterogeneity

We expected the following characteristics to introduce clinical heterogeneity, and we planned to carry out the following subgroup analyses including investigation of interactions (Altman 2003).

• Type of intervention (route of nutrition, amount of caloric intake).

• Patient population (diagnosis, age).

• Handling of control group.

• Year of study conduct.

• Methodological quality of study.

Sensitivity analysis

We planned to perform sensitivity analyses to explore the influence of the following factors (when applicable) on effect sizes by restricting analysis to the following.

• Published trials.

• The effect of risk of bias, as specified in the Assessment of risk of bias in included studies section.

• Very long or large trials to establish the extent to which they dominate the results.

• Using the following filters: diagnostic criteria, imputation, language of publication, source of funding (industry versus other), or country.

We also tested the robustness of results by repeating the analyses using different measures of effect size (RR, OR, etc) and different statistical models (fixed‐effect and random‐effects models).

Appendices

Appendix 1. Search strategies

Cochrane Library

# 1MeSH descriptor Inpatients explode all trees # 2inpatient* in All Text # 3((hospitali* in All Text near/6 patient* in All Text) or (undernourish* in All Text near/6 patient* in All Text) or (malnourish* in All Text near/6 patient* in All Text) or (feeding in All Text near/6 patient* in All Text)) # 4(#1 or #2 or #3) # 5MeSH descriptor Malnutrition explode all trees with qualifiers: TH # 6MeSH descriptor Nutrition therapy explode all trees # 7MeSH descriptor Counseling explode all trees with qualifiers: ED,MT,ST # 8MeSH descriptor Nutritional support explode all trees # 9MeSH descriptor patient education as topic explode all trees # 10MeSH descriptor dietary supplements explode all trees # 11MeSH descriptor energy intake explode all trees # 12MeSH descriptor enteral nutrition explode all trees # 13MeSH descriptor parenteral nutrition explode all trees # 14MeSH descriptor nutrition assessment explode all trees # 15((nutrition in All Text near/6 therap* in All Text) or (nutrition in All Text near/6 treatment* in All Text)) # 16((nutrition* in All Text near/6 counselling in All Text) or (diet* in All Text near/6 counselling in All Text)) # 17((enteral in All Text near/6 nutrition* in All Text) or (parenteral in All Text near/6 nutrition* in All Text) or (assessment in Author near/6 nutrition* in Author)) # 18(feeding in All Text near/6 support in All Text) # 19(#5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13 or #14 or #15 or #16 or #17 or #18) # 20(#4 and #19)

MEDLINE

1 exp Inpatients/ 2 inpatient*.tw,ot. 3 ((hospitali?* or undernourish* or malnourish* or feeding) adj6 patient*).tw,ot. 4 or/1‐3 5 exp Malnutrition/th [Therapy] 6 exp Nutrition Therapy/ 7 exp Counseling/ed, mt, st [Education, Methods, Standards] 8 *Nutritional Support/ 9 exp Patient education as topic/ 10 *dietary supplements/ 11 *energy intake/ 12 *enteral nutrition/ 13 *parenteral nutrition/ 14 *nutrition assessment/ 15 (nutrition* adj6 (therap* or treatment*)).tw,ot. 16 ((nutrition* or diet*) adj6 counsel?ing).tw,ot. 17 ((enteral or parenteral or assessment) adj3 nutrition*).tw,ot. 18 (feeding adj6 support).tw,ot. 19 or/5‐18 20 randomised controlled trial.pt. 21 controlled clinical trial.pt. 22 randomi?ed.ab. 23 placebo.ab. 24 clinical trials as topic.sh. 25 randomly.ab. 26 trial.ti. 27 or/20‐26 28 Meta‐analysis.pt. 29 exp Technology Assessment, Biomedical/ 30 exp Meta‐analysis/ 31 exp Meta‐analysis as topic/ 32 hta.tw,ot. 33 (health technology adj6 assessment$).tw,ot. 34 (meta analy$ or metaanaly$ or meta?analy$).tw,ot. 35 (search* adj10 (medical databas*or medline or pubmed or embase or cochrane or cinahl or psycinfo or psyclit or healthstar or biosis or current content*)).tw,ot. 36 (systematic adj3 review*).tw,ot. 37 or/28‐36 38 27 or 37 39 (comment or editorial or historical‐article).pt. 40 38 not 39 41 4 and 19 and 40 42 limit 41 to humans

Embase

1 exp hospital patient/ 2 inpatient*.tw,ot. 3 ((hospitali?* or undernourish* or malnourish* or feeding) adj6 patient*).tw,ot. 4 or/1‐3 5 exp malnutrition/th [Therapy] 6 exp nutritional counselling/ 7 exp nutritional support/ 8 exp patient education/ 9 *diet supplementation/ 10 *caloric intake/ 11 *enteric feeding/ 12 *parenteral nutrition/ 13 *nutritional assessment/ 14 (nutrition* adj6 (therap* or intervention* or treatment*)).tw,ot. 15 ((nutrition* or diet*) adj6 counsel?ing).tw,ot. 16 ((enteral or parenteral or assessment) adj3 nutrition*).tw,ot. 17 (feeding adj6 support).tw,ot. 18 exp diet therapy/ 19 or/5‐18 20 exp Randomized Controlled Trial/ 21 exp Controlled Clinical Trial/ 22 exp Drug comparison/ 23 exp Randomization/ 24 exp Crossover procedure/ 25 exp Double blind procedure/ 26 exp Single blind procedure/ 27 exp Placebo/ 28 exp Prospective Study/ 29 (random$ adj6 (allocat$ or assign$ or basis or order$)).ab,ti. 30 ((singl$ or doubl$ or trebl$ or tripl$) adj6 (blind$ or mask$)).ab,ti. 31 (cross over or crossover).ab,ti. 32 exp meta analysis/ 33 (metaanaly$ or meta analy$ or meta?analy$).ab,ti,ot. 34 (search$ adj10 (medical database$ or medline or pubmed or embase or cochrane or cinahl or psycinfo or psyclit or healthstar or biosis or current content$ or systematic$)).ab,ti,ot. 35 exp Literature/ 36 exp Biomedical Technology Assessment/ 37 hta.tw,ot. 38 (health technology adj6 assessment$).tw,ot. 39 or/20‐31 40 or/32‐38 41 39 or 40 42 (comment or editorial or historical‐article).pt. 43 41 not 42 44 4 and 19 and 43 45 limit 44 to human

'My NCBI' alert service (PubMed)

("inpatients"[MeSH Terms] OR "inpatients"[All Fields] OR "inpatient"[All Fields]) AND (("nutritional status"[MeSH Terms] OR ("nutritional"[All Fields] AND "status"[All Fields]) OR "nutritional status"[All Fields] OR "nutrition"[All Fields] OR "nutritional sciences"[MeSH Terms] OR ("nutritional"[All Fields] AND "sciences"[All Fields]) OR "nutritional sciences"[All Fields]) OR ("dietary supplements"[MeSH Terms] OR ("dietary"[All Fields] AND "supplements"[All Fields]) OR "dietary supplements"[All Fields] OR "supplement"[All Fields])) AND Randomized Controlled Trial[ptyp]

What's new

Last assessed as up‐to‐date: 10 June 2014.

Date	Event	Description
14 September 2017	Amended	This protocol has been withdrawn from the Cochrane Library because there is an overlap with the published Cochrane Review on "Nutrition support in hospitalised adults at nutritional risk".

Contributions of authors

All review authors contributed to, read and approved the final protocol draft.

Martina R Bally (MB): protocol draft, search strategy development, acquiring trial reports, trial selection, data extraction, data analysis, data interpretation, review of drafts and future review updates.

Lisa Bonoure (LB): data extraction, data analysis, data interpretation, review of drafts and future review updates.

Prisca Z Blaser Yildirim (PB): protocol draft, search strategy development, acquiring trial reports, trial selection, data extraction, data analysis, data interpretation, review of drafts and future review updates.

Filomena Gomes (FG): data extraction, data analysis, data interpretation, review of drafts and future review updates.

Viktoria L Gloy (VG): data extraction, data analysis, data interpretation, review of drafts and future review updates.

Matthias Briel (MBr): protocol draft, data extraction, data analysis, data interpretation, review of drafts and future review updates.

Philipp Schuetz (PS): protocol draft, search strategy development, acquiring trial reports, trial selection, data extraction, data analysis, data interpretation, review of drafts and future review updates.

Sources of support

Internal sources

• →Note, Other.

  Authors should acknowledge grants that supported the review, and other forms of support, such as support from their university or institution in the form of a salary. Sources of support are divided into 'internal' (provided by the institutions at which the review was produced) and 'external' (provided by other institutions or funding agencies). Each source, its country of origin and what it supported should be provided.

External sources

• Swiss National Science Foundation, Switzerland.

  PS is supported by the Swiss National Science Foundation (SNSF Professorship, PP00P3_150531 / 1).

Declarations of interest

*** TEXT WILL BE DELETED BEFORE PUBLICATION OF THE PROTOCOL ***

Review authors: please note possible conflicts of interests (http://community.cochrane.org/editorial‐and‐publishing‐policy‐resource/conflicts‐interest‐and‐cochrane‐reviews).

For example, 2.2.4. Cochrane Review author also an author on a study listed in the review:

"Cochrane authors who include primary studies (which they had conducted) in their Cochrane Review should declare this in the review in the ‘Declarations of interest’ section. Authors of primary studies should not extract data from their own study or studies. Instead, an editor should extract these data, and check the interpretation against the study report and any available study registration details or protocol. Also, the relevant authorship of the primary studies should be disclosed in Cochrane's disclosure of potential conflicts of interest form and therefore the Cochrane Review."

Please make sure that all statements here are identical to the ones provided in the 'conflict of interest form' before publication of the Cochrane review!

MB: none known.

LB: none known

PB: none known.

FG: none known.

VG: none known.

MBr: none known.

PS: none known.

Notes

This protocol has been withdrawn from the Cochrane Library because there is an overlap with the published Cochrane Review on "Nutrition support in hospitalised adults at nutritional risk".

Withdrawn from publication for reasons stated in the review