Home Enteral Nutrition in Adults: Effectiveness of Nutritional Therapy and Educational Programme

Purpose Home Enteral Nutrition (HEN) is used to prevent or correct malnutrition in outpatients. Due to the complexity of this process, the indication, follow-up, and results of an educational programme of HEN patients was evaluated. Methods A prospective, observational, real-life, multicentre study of patients receiving HEN by nasogastric tube or ostomy in 21 hospitals was conducted. The following variables were collected: age, gender, HEN indication, type of formula, nutritional requirements, laboratory variables, complications, and quality standards of the educational programme. All data were analysed using SPSS.24. Results 414 patients were included. Most conditions diagnosed were neurodegenerative diseases (64.8%). 100 patients (25.3%) were diabetic. The mean weight was 59.3±10.4kg and BMI 22.6±3.2. Moderate protein-calorie malnutrition was predominant at baseline (46.4%). Improvement in nutritional status at six months was recorded in more than 75% of patients (p<0.05). Tolerance problems, diarrhoea and abdominal distension fell between the 3- and 6-month visits (p <0.05). Patients who received intermittent Enteral Nutrition (EN) had fewer tolerance-related effects (OR: 0.042; 95% CI: 0.006-0.279) and less diarrhoea (OR: 0.042; 95% CI: 0.006-0.279), while those who received EN via nasogastric tube had fewer tolerance-related effects (OR: 0.042; 95% CI: 0.006-0.279). At the baseline and 6-month visits, compliance with the educational measures proposed by the prescriber was ≥ 99%. The to prescribe individualised HEN each together with educational measures and lymphocytes (mg/dl).


Introduction
Home Enteral Nutrition (HEN) or the administration of enteral formula via the digestive tract, usually by tube, is used to prevent or correct malnutrition in patients cared for at home [1]. HEN is a type of nutritional support that is being increasingly prescribed. In the US, the population receiving HEN in 1992 was 415 patients per million inhabitants [2], which had increased to 1,385 patients per million population by 2013 [3]. This therapy brings a number of bene ts to patients, their families and the healthcare network that provides it [4]. It entails a reduction in costs, with an estimated saving of 75% with the uptake of home treatment [5].
One of the objectives of healthcare professionals is to ensure that patients are monitored at home and that the established treatment is correctly maintained, as well as to control and minimise possible side effects, to ensure the therapeutic goals are met [6]. For patients receiving HEN, it is important to remember the importance of ensuring adequate nutrient intake, as malnutrition is associated with increased morbidity and risk of complications in a wide range of patients. This includes patients with chronic obstructive disease, post-stroke patients or bedridden patients at increased risk of pressure ulcers [7,8], and surgical patients (pre-and post-operative) [9], but especially multimorbid and chronic patients where the incidence of the population with swallowing di culty primarily due to neurodegenerative problems is very high [10]. The selection of the most appropriate formula for each patient has been shown to achieve both energy and nutrient therapeutic goals [11] and improve nutritional status.
Adequate patient and/or family training by a quali ed professional is necessary for HEN to be feasible [6, 12,13]. This process has been hampered in the last year by the COVID-19 pandemic and may in uence adherence/compliance to treatment where telemedicine has become an essential tool to support these patients [14].
In terms of patient monitoring and follow-up, the coordination of a multidisciplinary team is essential to prevent complications such as malnutrition and dehydration in these patients [8], as well as complications caused by the EN itself, such as vomiting, diarrhoea, constipation, abdominal distension, and complications arising from the access route (nasogastric tube [NGT], percutaneous endoscopic gastrostomy [PEG] and percutaneous radiological gastrostomy [PRG]), such as obstruction [15].
Due to the complexity of this process and the high impact that the initiation of these treatments and the associated complications can have on the Spanish National Health System (NHS), it was considered necessary to analyse data on the indication, treatment and follow-up of a group of patients included in the HEN.1 study, as well as the results of an educational programme, with the main objective of improving quality of care of the HEN process and optimising the use of this resource within the Spanish NHS.

STUDY DESIGN
A prospective, observational, multicentre real-life study was conducted.

STUDY POPULATION
All patients 18 years of age and over prescribed HEN treatment with nasogastric tube or ostomy by the corresponding Clinical Nutrition Unit of 21 hospitals, who maintained their treatment at home or in a residence from 1 July 2016 to 1 July 2020, with stabilised underlying disease, who had accepted and signed the informed consent (patient or caregivers) and who ful lled a series of the following clinical indications were included: Mechanical impairment of swallowing or transit with severe aphagia or dysphagia requiring a feeding tube and/or ostomy.
Neuromotor disorders that prevent swallowing or transit requiring a feeding tube and/or ostomy.
Patients with special energy and/or nutrient requirements requiring a feeding tube and/or ostomy.
The exclusion criteria were as follows: pregnant women, expected survival under 180 days, unstable patients, lack of support from family or carers and a failure to sign the informed consent for any reason.

CLINICAL, BIOCHEMICAL AND NUTRITIONAL VARIABLES
The variables were collected at face-to-face, telephone and/or home visits (baseline, 3 and 6 months). At the initial visit, the following variables were collected: age, gender, comorbidity, diagnosis that led to the indication for HEN (neurological disease, neoplastic disease, stroke) and presence of malnutrition, and a nutritional assessment was performed.
Parameters concerning the initiation and adequacy of HEN support according to the needs and clinical course of the patients were collected: calculation of calorie-protein requirements, type of EN formula (hyperproteic/hypercaloric [HP/HC], normoproteic/normocaloric [NP/NC] and diabetic), volume of nutritional formula, administration regimen, access route, average duration of use of enteral support and HEN-related complications. The type of calorie, protein and protein-calorie malnutrition was determined according to the criteria of the "SENPE-SEDOM Document on the coding of hospital malnutrition" [16]. Improved nutritional status was also assessed in terms of a reduction in severity of energy or protein malnutrition between the initial visit and 6 months (severe to moderate, moderate to mild or mild to well nourished). Patients who experienced one or more problems (nausea, vomiting, diarrhoea, constipation, abdominal distension and regurgitation) were considered to have tolerance issues.

EDUCATIONAL PROGRAMME COMPLIANCE VARIABLES
An educational programme was prepared with an initial session on the main complications of the feeding tube, delivery of written information and subsequent regular telephone sessions. It was recorded whether the clinical report and educational material had been delivered, if it had been adequately explained to the patient how to manage and maintain the diet, and the access route details, as well as any interim or nal suspensions.

STATISTICAL ANALYSIS
The data obtained were entered into an Access databaseÒ. Statistics of central tendency were used to describe the variables (mean, standard deviation) because tests of normality of the data indicated that the data are normally distributed (Kolmogorov-Smirnov and Shapiro-Wilk tests). Qualitative variables were described by frequency and proportion. To assess any signi cant differences during the treatment period (baseline visit and 6-month visit), a paired mean difference (t-test for related data) or a Chi-square test (or Fisher's exact test when the conditions for applying the chi-square were not met) and McNemar's test were used as appropriate. If three periods were evaluated (baseline, 3 months and 6 months), an ANOVA was performed for repeated measures. Finally, a logistic regression model was used to identify the risk factors related to tolerance and adverse effects of supplementation. The signi cance level used was 5% (p-value <0.05). All data were analysed using version 24 of the SPSS statistical software.

STUDY POPULATION AND PRESCRIBED ENTERAL NUTRITION FORMULAS
In total, 414 patients were included, 254/414 (61.4%) of whom were women. The most prescribed EN formula was hyperproteic/hypercaloric without bre (145/414; 35.0%). The main conditions diagnosed were neurodegenerative disease (Alzheimer's, Parkinson's, dementia) in 64.8% of cases (n=256), and stroke in 22.8% of cases (n=90). One hundred patients (25.3%) of the total sample were diagnosed with diabetes mellitus. The patients had a mean weight of 59.3 ± 10.4 kg and a BMI of 22.6 ± 3.2 Kg/m 2 ( Table 1). The prevalence of cardiovascular and neurodegenerative disease was higher in the female population compared to cancer patients (p<0.001). The prescription of an HP/HC formula with bre was higher in cancer patients compared to patients with cardiovascular and neurodegenerative disease (p<0.001). However, the prescription of an NP/NC formula with bre was higher in patients with cardiovascular and neurodegenerative disease compared to cancer patients (p<0.001) ( Table 2).

NUTRITIONAL STATUS
At baseline, moderate protein-calorie malnutrition was predominant among the patients recruited for the study (n=192, 46.4%). The change at 6 months showed a signi cant improvement in nutritional status (Table 3). According to the changes that occurred between one period and another, nutritional status improved in more than 75% of patients (Table 4).

ADVERSE EFFECTS
Adverse effects were recorded in no more than 6% of cases, except for tolerance problems, where the percentage was 16.3%. There was a reduction in all adverse effects between the 3-month and 6-month visits, with signi cant reductions observed for tolerance problems, diarrhoea and abdominal distension (Table 6).

ADMINISTRATION ROUTE AND ADVERSE EFFECTS
At 3 months there was a slight increase in NGT administration (58.3% to 63.2%) to the detriment of ostomies (41.7% to 36.8%). When analysing the association between the occurrence of adverse reactions and the access route, a higher occurrence of diarrhoea was observed in patients with NGT vs ostomy at 3 months (7.9% vs 2.3%; p=0.015).
The most commonly used administration regimen was intermittent in 300 patients (96.8%). Patients with intermittent administration had greater tolerance and diarrhoea problems than patients with continuous administration at 6 months (23.1% vs 4.3%; p=0.021 and 15.4% vs 0.8%; p=0.009, respectively). The most commonly used feedings/day regimens were 4 or 5 per day (41.1% n=156 and 53.7% n=204, respectively). When the association between the occurrence of abdominal distension and feedings/day at 3 months was analysed, it was found that the higher the number of feedings per day, the lower the occurrence of constipation (p=0.039). In the case of abdominal distension, the 5 feedings/day regimen was associated with greater nausea (p=0.001).

NUTRITIONAL REQUIREMENTS
The established energy and protein requirements remained constant throughout the follow-up of the patients in the study. The mean energy requirements were 1548 ± 297, 1465 ± 295 and 1550 ± 291 kcal/day at baseline, 3 months and 6 months, respectively. Protein requirements were also very constant over the three visits; 70.7 ± 15, 70.5 ± 15.7 and 70.8 ± 15 g/day, respectively. In relation to the requirements by condition described, both protein and energy requirements were found to be higher in patients diagnosed with neoplastic disease than for the other conditions (p-value <0.05) (Table S1). When analysing the relationship between the onset of adverse reactions at 3 months with the need to adjust nutritional requirements, it was observed that these differences were signi cant for abdominal distension (p<0.001) and nausea (p=0.017). This statistical signi cance was maintained for abdominal distension at 6 months (p<0.001).

EDUCATIONAL PROGRAMME COMPLIANCE
At the baseline visit, compliance with the measures proposed by the prescriber was: delivery of clinical report (392; 100%), delivery of educational material (392; 100%), correct adherence to the diet (383; 100%), indications for access route (391; 100%) and proper handling of the diet (407; 99.3%), and at 6 months, correct adherence to the diet (387; 99.7%), indications for access route (382; 99.2%) and proper handling of the diet (381; 99.0%). There were very few interim and nal suspensions (1; 0.3% and 2; 0.5%, respectively) in the 6-month review. However, 20% of patients required an adjustment to their nutritional regimen for various reasons. From the baseline to the 3-month visit, of all patients who had tolerance problems, almost 40% (39.4%, n=66) were offered an adjustment to requirements and/or feeding regimens (p-value <0.001), and between the 3-month and 6-month visit, 40% (n=20) of patients who had tolerance problems were also offered an adjustment to requirements and/or feeding regimens (p-value <0.001).

Discussion
HEN may improve the nutritional status and quality of life of patients and their families. Healthcare professionals must therefore ensure that the prescribed formulas are appropriate for each individual patient and that nutritional requirements are adjusted on a case-by-case basis. Patient and family training for the proper use of preparations and monitoring at home is key to ensuring correct adherence to the established treatment, controlling and minimising possible side effects and thereby ensuring the therapeutic goals are met. This study assessed the 6-month evolution of the prescribed nutritional requirements, nutritional status, adverse effects and compliance with the proposed regimens for the correct use of EN in 414 patients included in the HEN.1 study.
HEN led to an improvement in nutritional status in more than 75% of patients across all conditions, with adverse effect rates of less than 5%, except for tolerance problems, which were 16.3%.
In our study, the most common reason for indicating EN was neurodegenerative diseases (64.5%), consistent with the Spanish HEN registry (NADYA) (59%) [17]. However, the average age of our population was somewhat higher at 78 vs 71 years [17], perhaps because neurodegenerative disease, the most frequent reason for prescribing HEN in both this study and in the registry, is more common in elderly people. Cancer patients had a higher use of HP/HC formulas with bre (26.6%) than the rest of the conditions (p < 0.001) ( Table 2). This was due to their higher energy and protein requirements (Table S1), in line with the recommendations of the European guidelines on nutrition in cancer patients [18], which specify energy requirements of 25-30 kcal/kg/day and a high protein intake, as this promotes muscle protein anabolism in cancer patients [19].
At 6 months there was a statistically signi cant improvement in nutritional status (Table 3) and more than 75% across all conditions (Table 4). This improvement in nutritional status was also re ected in the evolution of the laboratory parameters, with a statistically signi cant improvement between baseline and 6 months ( Table 5). These ndings are consistent with a study of 102 patients (56.9% with HEN and 43.1% with hospital EN) treated with a hyperproteic/hypercaloric formula for 8 weeks, which also found improved weight, BMI, albumin and prealbumin parameters [20].
In a systematic review of elderly people with dementia and tube feeding, no improvement in nutritional status was seen [21]. However, PEG placement in patients with dysphagia resulted in a signi cant increase in caloric intake by 30.5%, protein intake by 26.0% and a conversion of the protein balance from negative to neutral in a study of 117 patients in a geriatric centre [22]. For cancer patients, a recent metaanalysis that included 1059 patients with upper gastrointestinal tract cancer showed that HEN also reduced the incidence of malnutrition and latent malnutrition (RR: 0.54; p < 0.01) [23].
The adverse effects experienced by the patients in our study did not exceed 6% of cases, except for tolerance problems, which was 16.3% at 3 months. In all cases, a favourable clinical course was observed from one visit to the next, with a statistically signi cant reduction in gastrointestinal symptoms at the 3and 6-month visits in terms of tolerance problems, diarrhoea and abdominal distension (Table 6). These ndings are consistent with the Ballesteros et al. study in which gastrointestinal adverse reactions were also reduced (nausea, regurgitation, constipation, diarrhoea, atulence and distension), p < 0.05 [24]. A factor that may have affected the good tolerability of HEN may be that 96.8% of our patients had intermittent EN instead of continuous administration. In the CAFANE study in which HEN was administered to 304 patients, intermittent EN use was a protective factor against vomiting (OR: 0.4; p = 0.037), regurgitation (OR: 0.3; p = 0.002), constipation (OR: 0.3; p = 0.000), diarrhoea (OR: 0.4; p = 0.007) and abdominal distension (OR: 0.4; p = 0.006) compared with bolus administration [15]. Our results were similar, as intermittent EN administration was also a protective factor against tolerance problems (OR: 0.042; p = 0.001) and diarrhoea (OR: 0.042; p = 0.001), con rming that whenever possible, EN should be administered with this regimen.
At 6 months, only one interim suspension (1/390; 0.3%) and two nal suspensions (2/390; 0.5%) occurred from all included patients who had received EN via NGT or ostomy. This fact, together with the low incidence of reported adverse reactions, suggests that overall tolerance must have been good, as was the case in a cohort of 51 patients with HEN treated with a hyperproteic/hypercaloric formula [25].
Prescriber compliance was recorded for some proposed measures such as quality indices of the service provided and patient/caregiver educational measures. Compliance > 99% was obtained for all measures, both at the baseline and 6-month visits. Up to 68% of NGT patients did not comply with the prescribed HEN programmes in a study of head and neck cancer patients in which 36/88 had PEG [26]. Moreover, an average of 5.4 unscheduled medical care contacts were necessary to resolve the complications experienced by 8 patients with HEN over a mean follow-up time of 10.5 months [6]. The technical training of patients/caregivers for correct EN administration and to resolve any equipment-and tube-related problems is essential for optimising treatment [1,27].
The most important limitation of our study is that it is a prospective, observational design with no control group. GLIM criteria were not considered since our study was prior to the publication of the consensus. On the other hand, we consider the fact that it was a multicentre study involving a large number of patients and in real-life conditions to be a strength. It is the only study published to date with such a high number of patients with HEN and with a 6-month follow-up.

Conclusions
The nutritional assessment to prescribe individualised HEN to each patient, together with educational measures and training in the proper use of this treatment for both patients and trainers, improves nutritional status and reduces the onset of adverse reactions.

FUNDING STATEMENT
This study received support from Fresenius Kabi España for the statistical analysis of the data and translation to English.

CONFLICT OF INTEREST
There was no con ict of interest of the authors about the development of the study.

AUTHOR CONTRIBUTION
AMP and MLFS equally contributed to the conception and design of the research; MSLM and VAR contributed to the design of the research; CYD, VLL, JBM, JALM, PS y MDRR contributed to the acquisition of the data; AMP, MLFS and MSLM equally contributed to the acquisition, analysis, and interpretation of the data. All authors drafted the manuscript, critically revised the manuscript, agree to be fully accountable for ensuring the integrity and accuracy of the work, and read and approved the nal manuscript.

INSTITUTIONAL REVIEW BOARD STATEMENT
The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee) of Hospital San Cecilio (Granada

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