Introduction and guideline development
Introduction and guideline development
Background
Head and neck cancer is the fifth most common cancer worldwide. It is well known that causative or risk factors include: extensive use of tobacco and high consumption of alcohol, where these factors account for up to 80% of all cases [1]. Studies have shown that smokers eat less fruit and vegetables than non smokers [2], and consume more energy through fat and less micronutrients [3]. Some of these dietary factors have also been associated with an increased risk of head and neck cancer in epidemiological studies, and include risk factors such as low carotenoid intake, and protective components of fruits and vegetables [1]. Therefore, this population is often nutritionally compromised to some degree from the onset, with malnutrition rates reported between 30-50% [4]. The causes of malnutrition are multifactorial and, as well as the abovementioned lifestyle factors of tobacco and alcohol use and baseline dietary intake, they also include tumour location and burden, and side effects of multi-modal treatment regimens [5]. Furthermore, malnutrition results in impaired wound healing, reduced immunocompetence, a decreased tolerance to treatment, resulting in undesired treatment breaks and unplanned hospital admissions [5]. Consequently nutrition support plays a crucial role in the provision of best practice care to this population.
Nutrition has been recognised as the second most important factor in predicting long term prognosis in head and neck cancer [6], and while recently developed guidelines exist for some aspects of primary radiotherapy treatment [7], there are currently no comprehensive evidence based guidelines for the nutritional management of this complex patient population. Hence, there are inconsistencies in practice and currently no uniform model of care.
In the absence of current Australian guidelines, other international standards such as the National Institute for Health and Clinical Excellence (NICE) Guidance on Cancer Services: Improving Outcomes in Head and Neck Cancers provides a best practice framework including aspects of multidisciplinary care such as service requirements for nutrition intervention [8]. Whilst this document does not fulfill the role of clinical practice guidelines regarding specific nutrition management of patients with head and neck cancer, it does however, outline the resource framework required for optimum multidisciplinary team care. The guidance highlights how timely and appropriate dietetic intervention is important at all points in the head and neck cancer patient care pathway, such as referral, structure of services, initial investigation and diagnosis, pre treatment assessment and management, primary treatment, after care and rehabilitation, follow up and recurrent disease, and palliative interventions and care.
Other factors to consider which impact upon nutritional status and the desire or ability to adhere to nutrition advice given, include numerous psychosocial issues, such as anxiety, depression, body image concerns, and availability of social supports from family, friends or carers. The rate of psychosocial morbidity among patients with head and neck cancers is reported at 33% [9] and 35% [10]. Additionally, patients may also be affected by interrelated physical problems impacting on their psychological wellbeing including chemotherapy induced nausea and vomiting, pain, poor appetite, swallowing and communication difficulties, lymphoedema, fatigue, disfigurement, and oral and respiratory symptoms. Anorexia can be as a result of tumour-induced metabolic changes or due to treatment side effects, but can also be related to depression. The Clinical Practice Guidelines for the Psychosocial Care of Adults with Cancer, reports that patients with head and neck cancer can suffer with severe and chronic pain, with incidence rates of 6% at 2 years post treatment [11], which can adversely impact on both appetite and the patient’s physical ability to eat. It has also been shown that patients who are alcohol dependent or who have low motivation or poor social supports or who are undergoing rehabilitation for oral cavity tumour resections, are less likely to achieve effective swallowing, and are therefore more prone to malnutrition [12]. Nicotine is negatively associated with hunger and food consumption, and positively associated with satiety and fullness [13]. Therefore, ceasing smoking during treatment should have beneficial effects on nutritional intake. Smoking increases treatment related toxicities, with patients who smoke >20 per day having an increased likelihood of requiring enteral tube feeding [14]. Cessation of smoking prior to treatment may improve patient and disease outcomes, with active smokers during treatment having significantly worse 5-year survival, locoregional control and disease free survival [15]. As a result, multidisciplinary management of this patient group is essential, with psychological interventions shown to play an important role in improving aspects of quality of life such as; mood, self-esteem, coping, sense of personal self control and physical/functional adjustment [11].
Purpose and scope
Development of national evidence based guidelines will assist in standardisation of the nutritional management of patient care for head and neck cancer. They will provide clinicians, involved in the care of this complex population, with a clinical tool to guide decision-making and are intended to enhance multidisciplinary team (MDT) care and improve patient outcomes. They will be beneficial for new health professionals working in the clinical area, and will assist in writing business cases for further dietetics resources in this field. The guidelines will also highlight the gaps in the evidence that exist and thus identify areas for future research, which will develop national and international networks of health professionals to pursue collaborative studies.
The purpose of these guidelines is to provide the multidisciplinary team of health professionals with a summary of evidence-based clinical questions related to the nutrition management of adult patients with head and neck cancer. The guidelines focus on primary mucosal head and neck cancers, and not other head and neck cancer types such as lymphomas, salivary gland tumours and advanced skin cancers. The guidelines are also primarily focused on the curative management of head and neck cancer, with some information on palliative care aspects. The treatment modalities that are covered include; surgery, post operative radiotherapy, and definitive (chemo) radiotherapy. Due to the limited number of high quality nutrition intervention studies that have been undertaken in this area, it was decided to group the evidence from post operative radiotherapy and definitive radiotherapy together.
The scope will include: nutrition guidelines throughout the continuum of care for adult patients (>18 years old) with head and neck cancer. The clinical questions and recommendations will aim to address some of the key dietetic issues in the management of this patient group such as; screening and referral, management during surgery including the use of immunonutrition, management during radiotherapy including the optimal method and timing of tube feeding, as well as recommendations for follow up and rehabilitation. They will also consider the impact of evolving treatment modalities such as Intensity Modulated Radiotherapy (IMRT) and other systemic agents such as Epidermal Growth Factor Receptor (EGFR)-inhibitors.
The guidelines will not include: cancer prevention, paediatric management, cancer cachexia, chyle leaks and the clinical management of other factors requiring intervention by a multidisciplinary team. While it is acknowledged that other factors impact on nutrition such as; dentition, dysphagia, mouth care, mucositis, pain, exercise, pharmaceuticals (including complementary and alternative therapies), alcoholism, depression, and smoking cessation, these were deemed beyond the scope of these guidelines. Management of these issues should be undertaken by referral to the appropriate member of the multidisciplinary team and/or referral to other existing resources. In addition, patients with co-morbidities may require additional dietetic intervention (e.g. diabetes, inflammatory bowel disease, renal disease etc) hence clinical judgment and expertise should be applied in the management of individuals. Patients with co-morbidities must be managed in the context of their relevant disease states, and nutritional management should be individualised and subject to the health professional’s judgment in each individual case. Other strategic dietetics issues such as home enteral nutrition processes will not be addressed in these guidelines.
Consultation process
A Steering Committee of dietitians with clinical and research expertise in evidence based guideline development and the nutritional management of patients with head and neck cancer was convened in July 2009 following successful allocation of funding from Cancer Institute NSW Oncology Group (Head and Neck) for a Project Dietitian. The Project Dietitian fulfilled the central role of coordinating the development of the guidelines in liaison with the Project Directors responsible for overseeing the project. Based on the model of previous guidelines developed for the nutritional management of disease, the dietitian committee produced the first draft of the evidence based guidelines in January 2011. The first draft was reviewed by the Multidisciplinary Steering Committee including representatives from the following disciplines; dietetics, head and neck surgery, radiation oncology, medical oncology, palliative care, oral medicine, nursing, psychiatry, social work, pharmacy, speech pathology, and radiotherapy. Consumer/patient representation was also included on the committee through Cancer Voices Australia. Representation was also sought from the Clinical Oncological Society of Australia, Cancer Council Australia and Cancer Australia. Feedback from this committee was incorporated into the guidelines.
In April 2011, the second draft was uploaded onto the Cancer Council Australia website using wiki technology for wider stakeholder review. The guidelines were open for comment for 1 month, and several key stakeholder organisations were notified, including: Clinical Oncological Society of Australia, Cancer Institute NSW Oncology Group (Head and Neck), Australia and New Zealand Head and Neck Cancer Society, Cancer Council, Cancer Australia, Dietitian Association of Australia Oncology Interest Group, and the British Dietetic Association Oncology Interest Group. Participant feedback from these processes was incorporated into the final document, which was submitted to Clinical Oncological Society of Australia, Cancer Institute NSW Oncology Group (Head and Neck), Dietitian Association of Australia, Dietitians New Zealand, Australia and New Zealand Head and Neck Cancer Society and the British Dietetic Association for endorsement. For endorsement by the Dietitian Association of Australia and Dietitians New Zealand a panel of oncology dietitian experts was formed to review the guidelines and assess using the AGREE tool. Similarly for endorsement by the British Dietetic Association, a sub group of dietitians from the oncology interest group, reviewed the guidelines and provided feedback. The authors responded to these comments and incorporated into the final draft of the guidelines when appropriate.
The development of these guidelines have been presented to multidisciplinary audiences including oncologists, surgeons, nurses, pharmacists, radiation therapists and speech pathologists attending the Australia and New Zealand Head and Neck Cancer Society and Clinical Oncological Society of Australia Annual Scientific Meetings in 2009 and 2010.
Methods
Framework
The framework (Appendix 5.1) was based on integrating the evidence into a recognised Nutrition Care Model [16][17]. This is outlined below and is based on; an initial trigger event which identifies where and how the patient is identified for nutrition care; the nutrition care process which specifies the cycle of essential components of effective care; and the nutrition-related outcomes which lists the most likely areas to observe results produced by or influenced by nutrition care:
- Appropriate Access to Nutrition Care
(Nutrition Screening; Nutrition Assessment; Collection of Evidence)
- Quality Nutrition Care – Nutrition Diagnosis, Nutrition Intervention
(Establishing Goals; Prescription and Implementation)
- Nutrition Monitoring and Evaluation - Outcomes
(Measuring and Evaluating Outcomes)
Although the nutrition care process is common to the nutritional management of many clinical conditions, in these guidelines, the questions developed and the outcomes measured are specific to the nutritional management of patients with head and neck cancer. The outcomes have been assessed following an additional suggested framework, which recognises a cascade of events following quality nutrition care to result in a number of outcomes [18]. The initial intermediate outcomes following the intervention relate to improvements in nutritional intake, resulting in changes to physical measures such as weight and lean body mass. In turn, these changes can affect other clinical, cost and patient centred outcomes, such as prevention of adverse effects which will reduce the associated costs (treatment of adverse effects and complications, hospital admissions, length of stay), and ultimately improve patient quality of life, minimising death, disease, disability, discomfort and dissatisfaction.
Literature search
The Cochrane Database of Systematic Reviews, CENTRAL, MEDLINE, EMBASE, CINAHL and AMED databases were searched in December 2009 and repeated in January 2011. Search terms included MESH terms and keywords for each database to encompass; head and neck cancer; AND any form of treatment – surgical, oncological, or palliative; AND any form of nutrition intervention. Full details of the search terms used are available in the appendix (Appendix 5.2). The search included literature published in the last 30 years from 1980 from adult human studies. Non-English papers were excluded, as were papers on oesophageal cancers and thyroid cancers, and patients <18 years old. The search terms and the respective results for each of the databases are available for review. The search achieved a total of 2226 hits. The abstracts and titles were independently reviewed by the project dietitian and project director to include nutrition intervention and/or nutrition outcome studies and 264 suitable articles were identified for full review, with a further 24 articles identified through hand searching of reference lists. Some articles were excluded following full review due to; non-nutrition related outcomes or interventions, case reports, expert opinion reviews, editorials/letters and abstracts.
Literature critique
The strength of the evidence was assessed using the level of evidence rating system recommended by the National Health and Medical Research Council (NHMRC) publication, NHMRC Levels of Evidence and Grades for Recommendations for Developers of Guidelines[19] For intervention studies, Level I is recommended as the gold standard. Clinical nutrition studies are difficult to complete in a blinded fashion and often the group most likely to benefit from the intervention is excluded for ethical reasons. For these reasons, recommendations based on lower levels of evidence but with strong design quality, strength of effect and relevance are included. Prognosis studies were also quite significant in this literature review, when looking at prognostic features of malnutrition or factors predicting tube feeding or weight loss. It is important that the difference in study designs is noted.
Table: NHMRC Levels of Evidence for Intervention and Prognosis Studies
Level of evidence | Intervention Study | Prognosis |
---|---|---|
Level I | Evidence obtained from a systematic review of all relevant randomised controlled trials | A systematic review of level II studies |
Level II | Evidence obtained from at least one properly designed randomised controlled trial | A prospective cohort study |
Level III-1 | Evidence obtained from well-designed pseudo-randomised controlled trials (alternate allocation or some other method) | All or none
(All or none of the people with the risk factor(s) experience the outcome; and the data arises from an unselected or representative case series which provides an unbiased representation of the prognostic effect) |
Level III-2 | Evidence obtained from comparative studies with concurrent control and allocation not randomised (cohort studies), case-control studies, or interrupted time series with a control group | Analysis of prognostic factors amongst persons in a single arm of a randomised controlled trial |
Level III-3 | Evidence obtained from comparative studies with historical control, two or more single arm studies, or interrupted time series without a parallel group | A retrospective cohort study |
Level IV | Evidence obtained from case studies, either post-test or pre- and post-test. | Case series, or cohort study of persons at different stages of disease |
The quality of each study was assessed using the American Dietetic Association: Evidence Analysis Manual. Steps in the ADA Evidence Analysis Process [20]. A quality criteria checklist was utilised including four relevance questions and ten validity questions to assess the strength of the study design. This assessment provided an overall quality rating of positive, neutral or negative. A summary table was developed to collate the evidence for each clinical question to be addressed (Appendix 5.3).
Quality | Definition of Quality for Primary Research |
---|---|
Positive | If most of the answers to the above validity questions are yes (including criteria 2,3,6, 7 and at least one additional yes), the report should be designated with a plus symbol (+) |
Neutral | If the answers to validity criteria questions 2,3,6, and 7 do not indicate that the study is exceptionally strong, the report should be designated with a neutral symbol (Ø) |
Negative | If most (six or more) of the answers to the above validity questions are no, the review should be designated with a minus symbol (-) |
Quality | Definition of Quality for Review Articles |
---|---|
Positive | If most of the answers to the above validity questions are yes (must include criteria 1,2,3,4), the review should be designated with a plus symbol (+) |
Neutral | If the answers to any of the first four validity questions (1-4) is no, but other criteria indicate strengths, the review should be designated with a neutral symbol (Ø) |
Negative | If most (six or more) of the answers to the above validity questions are no, the review should be designated with a minus symbol (-) |
Each article was appraised independently by two members of the steering committee. To ensure consistency of appraisal methodology, the project dietitian reviewed all articles. If consensus was not reached on first review, each dietitian carried out a second review, and if required consensus was achieved through a third review by another member of the committee using the majority vote. In complex cases, teleconferences and face to face discussions were held.
The body of evidence for each clinical question was then assessed using the NHMRC Levels of Evidence and Grades for Recommendations for Developers of Guidelines [19]. The five components that are considered in judging the body of evidence are the volume of evidence, consistency of the results, potential clinical impact of the proposed recommendation, the generalisability and applicability of the body of evidence to the Australian healthcare context. This is illustrated in the matrix below.
Component | A | B | C | D |
---|---|---|---|---|
Excellent | Good | Satisfactory | Poor | |
Evidence base | One or more level I studies with a low risk of bias or several level II studies with a low risk of bias | One or two level II studies with a low risk of bias or a SR/several level III studies with a low risk of bias | One or two level III studies with a low risk of bias, or level I or II studies with a moderate risk of bias | Level IV studies, or level I to III studies/SRs with a high risk of bias |
Consistency | All studies consistent | Most studies consistent and inconsistency may be explained | Some inconsistency reflecting genuine uncertainty around clinical question | Evidence is inconsistent |
Clinical impact | Very large | Substantial | Moderate | Slight or restricted |
Generalisability | Population/s studied in body of evidence are the same as the target population for the guidelines | Population/s studied in the body of evidence are similar to the target population for the guideline | Population/s studied in the body of evidence differ to the target population for guideline but it is clinically sensible to apply this evidence to target population | Population/s studied in body of evidence differ to target population and hard to judge whether it is sensible to generalise to target population |
Applicability | Directly applicable to Australian healthcare context | Applicable to Australian healthcare context with few caveats | Probably applicable to Australian healthcare context with some caveats | Not applicable to Australian healthcare context |
Each component is given a grade A to D, and then an overall grade for the recommendation is formulated which provides an indication to the strength of each guideline recommendation. A recommendation cannot be graded as A or B unless the volume and consistency of the evidence components are both graded A or B. The project directors and project dietitian independently graded each recommendation, and discussed to reach consensus where necessary. These gradings were then reviewed by the dietitian and multidisciplinary committees for final review.
Table: NHMRC Grades of Recommendation - Explanation
Grade | Recommendation |
---|---|
A | Body of evidence can be trusted to guide practice |
B | Body of evidence can be trusted to guide practice in most situations |
C | Body of evidence provides some support for recommendation(s) but care should be taken in its application |
D | Body of evidence is weak and recommendation(s) must be applied with caution |
Addressing potential barriers and evaluation of guidelines
As some of the recommendations overlap with existing evidence based guidelines The Evidence Based Practice Guidelines for Nutritional Management of Malnutrition in Adult Patients Across the Continuum of Care [21], and The Evidence Based Practice Guidelines for Nutritional Management of Patients Receiving Radiation Therapy [7], some services may have already addressed some of the barriers to implementation. For example: the guidelines recommend intensive dietary counselling, which may include the use of oral nutritional supplements and or tube feeding, at various stages of the patients’ treatment including pretreatment, during treatment, for up to 6 months post treatment, and in some cases, follow up may be required beyond this. These recommendations have potential resource implications that may include change to staff roles, extra staff and increased use of supplements or tube feeding. Therefore, when using these guidelines the potential organisational and cost barriers need to be considered. Some suggested strategies to facilitate overcoming these barriers include: using the guidelines as a framework to develop business cases to advocate for further resources or to justify increased costs of supplements or enteral feeds; liaison with the multidisciplinary team to facilitate any organisational change; consideration to facilities’ staffing and resources for tube placement; education amongst dietitians and the multidisciplinary team to enable understanding of the guidelines content and how to apply to their particular role or context.
To further facilitate implementation of the guidelines, the committee have applied for funding to hold an implementation workshop at the COSA Annual Scientific Meeting 2011 and also plan to submit an abstract for a workshop at the International Congress of Dietetics, 2012.
A baseline survey of current dietetic practice was undertaken in October 2010 via the Dietitians Association of Australia Oncology Interest Group, to which there were 61 respondents. To evaluate the impact of the guidelines, a further evaluation is planned approximately 12 months post guideline implementation.
Review process
As the guidelines are published on a wiki website, it is planned that they will be continually reviewed as new literature is published to maintain their currency. The review process will need to include ongoing systematic literature reviews, but will also enable other key stakeholders to suggest new articles for inclusion as they are published. It will also be important to acknowledge the evolving nature of treatment techniques and the impact this may have on the recommendations. The review process will be the responsibility of the project directors and the committees. The frequency of review will be dependent on successful acquisition of ongoing funding for guideline maintenance. Ideally the first planned review is within 6 months.
Editorial independence
The guidelines were developed with the assistance of external funding from the Cancer Institute NSW Oncology Group (Head and Neck). This did not influence the content of the guidelines. Where guideline development team members were authors of a published article, other team members of the guideline Steering Committee evaluated the article for levels of evidence. There are no conflicts of interest to declare.
Membership and roles of steering committees
The roles of the steering committee for each stage of the project are outlined below.
Initiating: Project director (MF) initiated the project, developed the proposal and obtained funding for the project.
Planning: The project directors (MF, JB) and project facilitator (MMcJ) planned the project including scope, methodology and reporting.
Executing: The project dietitian (TB) coordinated the project and established the committee memberships. Both committees were involved in determining the scope of the project and the clinical questions to be addressed. The project dietitian completed the literature search and in conjunction with the project directors and dietitian steering committee undertook the literature review. The project dietitian chaired the relevant committee meetings and was responsible for ensuring consensus was reached. The project dietitian summarised the evidence and formulated the first draft of the recommendation statements and the guidelines document. The project directors provided direction and support to the project dietitian and guidance regarding the literature review, grading of the recommendations, guidelines document and critical review of the final draft. The project directors, project dietitian and dietitian steering committee graded the recommendation statements. Both committees provided feedback on the final draft of the guidelines and the multidisciplinary committee members provided expert knowledge and guidance in their specialist areas.
Monitoring: The project directors and project facilitator ensured the project milestones were achieved. The project dietitian monitored project status on a daily basis and submitted project status reports at key milestones of the project phases.
Maintenance and updates: The project directors continue to oversee the maintenance of the guidelines on the wiki platform. The newly appointed project dietitian (ES) continues to perform literature searches at frequent intervals and co-ordinates the literature review and appraisal with members of the dietitian steering committee. Each committee member has been assigned clinical questions to manage. The project dietitian adds the new literature summaries and references to the guidelines. If new significant evidence was found which would warrant a change in recommendations – a meeting of the steering committee members is to be called to discuss and reach consensus.
References
- ↑ 1.0 1.1 Stenson KM. Epidemiology and risk factors for head and neck cancer. In: Rose, B, editor, UpToDate. Waltham, MA: UpToDate; 2010 Sep Available from: http://www.uptodate.com/contents/epidemiology-and-risk-factors-for-head-and-neck-cancer?source=search_result&selectedTitle=9%7E150.
- ↑ Birkett NJ. Intake of fruits and vegetables in smokers. Public Health Nutr 1999 Jun;2(2):217-22 Available from: http://www.ncbi.nlm.nih.gov/pubmed/10447250.
- ↑ .
- ↑ .
- ↑ 5.0 5.1 Matthews TW, Lampe HB, Dragosz K. Nutritional status in head and neck cancer patients. J Otolaryngol 1995 Apr;24(2):87-91 Available from: http://www.ncbi.nlm.nih.gov/pubmed/7602677.
- ↑ Brookes GB. Nutritional status--a prognostic indicator in head and neck cancer. Otolaryngol Head Neck Surg 1985 Feb;93(1):69-74 Available from: http://www.ncbi.nlm.nih.gov/pubmed/3920627.
- ↑ 7.0 7.1 Isenring E. Evidence based practice guidelines for the nutritional management of patients receiving radiation therapy. Nutrition & Dietetics 2008;65:1-20. Available from: http://www.clinicalguidelines.gov.au/search.php?pageType=2&fldglrID=1256&.
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tag; name "Citation:Isenring E 2008" defined multiple times with different content - ↑ National Institute for Health and Clinical Excellence.. Guidance on Cancer Services: Improving Outcomes in Head and Neck Cancers - The Manual. London: National Institute for Health and Clinical Excellence 2004 Available from: http://www.nice.org.uk/nicemedia/live/10897/28851/28851.pdf.
- ↑ Brintzenhofe-Szoc KM, Levin TT, Li Y, Kissane DW, Zabora JR. Mixed anxiety/depression symptoms in a large cancer cohort: prevalence by cancer type. Psychosomatics 2009;50(4):383-91 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19687179.
- ↑ Zabora J, BrintzenhofeSzoc K, Curbow B, Hooker C, Piantadosi S. The prevalence of psychological distress by cancer site. Psychooncology 2001;10(1):19-28 Available from: http://www.ncbi.nlm.nih.gov/pubmed/11180574.
- ↑ 11.0 11.1 National Breast Cancer Centre, National Cancer Control Initiative. Clinical practice guidelines for the psychosocial care of adults with cancer. Camperdown, NSW: National Breast Cancer Centre 2003 Jan 1 Available from: http://www.nhmrc.gov.au/_files_nhmrc/file/publications/synopses/cp90.pdf.
- ↑ Shapiro PA, Kornfeld DS. Psychiatric aspects of head and neck cancer surgery. Psychiatr Clin North Am 1987 Mar;10(1):87-100 Available from: http://www.ncbi.nlm.nih.gov/pubmed/3554183.
- ↑ Jessen A, Buemann B, Toubro S, Skovgaard IM, Astrup A. The appetite-suppressant effect of nicotine is enhanced by caffeine. Diabetes Obes Metab 2005 Jul;7(4):327-33 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15955118.
- ↑ Mangar S, Slevin N, Mais K, Sykes A. Evaluating predictive factors for determining enteral nutrition in patients receiving radical radiotherapy for head and neck cancer: a retrospective review. Radiother Oncol 2006 Feb;78(2):152-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/16466819.
- ↑ .
- ↑ Lacey K, Pritchett E. Nutrition Care Process and Model: ADA adopts road map to quality care and outcomes management. J Am Diet Assoc 2003 Aug;103(8):1061-72 Available from: http://www.ncbi.nlm.nih.gov/pubmed/12891159.
- ↑ Hakel-Smith N, Lewis NM. A standardized nutrition care process and language are essential components of a conceptual model to guide and document nutrition care and patient outcomes. J Am Diet Assoc 2004 Dec 1;104(12):1878-84 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15565085.
- ↑ Splett PL. Cost Outcomes of Nutrition Intervention. Part 2. New York: Mead Johnson and Company 1996.
- ↑ 19.0 19.1 National Health and Medical Research Council. NHMRC levels of evidence and grades for recommendations for guideline developers. Canberra: National Health and Medical Research Council; 2009 Available from: https://www.nhmrc.gov.au/_files_nhmrc/file/guidelines/developers/nhmrc_levels_grades_evidence_120423.pdf.
- ↑ American Dietetic Association. American Dietetic Association: Evidence Analysis Manual. Steps in the ADA Evidence Anaysis Process. 2008;Chicago: Scientific Affairs and Research Available from: http://www.adaevidencelibrary.com/files/Docs/201001_ADA%20EA%20Manual.pdf.
- ↑ .