The health economic impact of cow's milk allergy in childhood: A retrospective cohort study.

BACKGROUND: Cow's milk allergy (CMA) is one of the most common food allergies among children. Whilst avoidance of cow's milk protein is the cornerstone of management, further treatment of symptoms including those affecting the gastrointestinal, skin and respiratory systems plus other allergic comorbidities, maybe required. This study aimed to quantify the wider economic impact of CMA and its management in the United Kingdom (UK). METHODS: We conducted a retrospective matched cohort study on children with CMA (diagnosis read code and/or hypoallergenic formula prescription for ≥3 months) examining healthcare data (medication prescriptions and healthcare professional contacts) from case records within The Health Improvement Network (A Cegedim Proprietary Database) in the UK. A comparative cost analysis was calculated based on healthcare tariff and unit costs in the UK. RESULTS: 6998 children (54% male; mean observation period 4.2 years) were included (n = 3499 with CMA, mean age at diagnosis 4.04 months; n = 3499 matched controls without CMA). Compared to those without CMA, medications were prescribed to significantly more children with CMA (p < 0.001) at a higher rate (p < 0.001). Children with CMA also required significantly more healthcare contacts (p < 0.001) at higher rate (p < 0.001) compared to those without CMA. CMA was associated with additional potential healthcare costs of £1381.53 per person per year. CONCLUSION: The findings of this large cohort study suggest that CMA and its associated co-morbidities presents a significant additional healthcare burden with economic impact due to higher prescribing of additional medications. Further research into management approaches that may impact these clinical and economic outcomes of CMA is warranted.

Synbiotic containing extensively hydrolyzed formula improves gastrointestinal and atopic symptom severity, growth, caregiver quality of life, and hospital-related healthcare use in infants with cow's milk allergy.

BACKGROUND: Healthy gut microbiota is important for prognosis in cow's milk allergy (CMA). The application of synbiotics (specific pre- and probiotics) in extensively hydrolyzed formulae (eHFs) is a relatively new concept. AIMS: To evaluate a synbiotic-containing, whey-based eHF (SeHF) with galacto-oligosaccharides, fructo-oligosaccharides, and bifidobacterium breve M-16V in infants with CMA. MATERIALS AND METHODS: A 31-day one-arm pilot study in 29 infants with CMA (mean age 30.8 weeks [SD 11]) was undertaken, with outcomes including gastrointestinal tolerance, atopic dermatitis symptoms, dietary intake, growth, SeHF acceptability, caregiver quality of life, and hospital-related healthcare use. RESULTS: Significant improvements (p < .05) in the severity of abdominal pain (in 57%), burping (in 46%), flatulence (in 79%), constipation (in 14%), rhinitis (41%), and itchy eyes (73%), as well as atopic dermatitis in those with severe baseline symptoms (PO-SCORAD© reduction: 34.7-18.2 (p = .003), n = 6) were observed over time. Growth and caregiver quality of life scores significantly increased (+26.7%, p < .05) over time. Hospital visits and medications significantly reduced (-1.61 and -2.23, respectively, p < .005) in the 6 months after SeHF initiation. DISCUSSION: In this small, single-arm, pilot study, the use of SeHF enhanced the management of infants with non-IgE mediated CMA who were already established on eHF. CONCLUSION: Whilst this study adds to the evidence base for the use of SeHF in CMA, further robust research to explore the longer-term benefits of synbiotics, specifically the blend used in this study, for the clinical management of infants with CMA is warranted.

The clinical burden of cow's milk allergy in early childhood: A retrospective cohort study.

INTRODUCTION: Cow's milk allergy (CMA) is common in infants and children. Clinical presentations may vary, with a range of symptoms affecting the gastrointestinal (GI), skin and respiratory systems. Whilst the primary focus of research to date has been on the management of these symptoms, studies investigating the broader clinical burden of CMA are limited. METHODS: We performed a retrospective matched cohort study examining clinical data, including allergic symptoms and infections, extracted from case records within The Health Improvement Network database. A total of 6998 children (54% male) were included in the study, including 3499 with CMA (mean age at diagnosis 4.04 months) and 3499 matched controls without CMA, observed for a mean period of 4.2 years. RESULTS: GI, skin and respiratory symptoms affected significantly more children with CMA (p < .001), which recurred more often (p < .001), compared with children without CMA. More children with CMA had symptoms affecting multiple systems (p < .001). CMA was associated with a greater probability of these symptoms requiring hypoallergenic formula (HAF) prescription persisting over time (log-rank test p < .0001, unadjusted hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.76-0.85, p < .001), with a longer median duration of symptoms and HAF prescription compared with the duration of symptoms in those without CMA (3.48 vs. 2.96 years). GI, skin, respiratory and ear infections affected significantly more children with CMA than those without, increasing by 74% (p < .001), 20% (p < .001), 9% (p < .001), and 30% (p < .001) respectively. These infections also recurred more often among children with CMA, increasing by 62% for GI infections, 37% for skin and respiratory infections, and 44% for ear infections (p < .001). CONCLUSIONS: This real-world study provides evidence to suggest that CMA presents a significant clinical burden to children, which has implications for the healthcare system. Further research is warranted to understand the health economic impact of this, and the phenotypes, factors and management approaches which may affect clinical outcomes.

The Use of an Amino Acid Formula Containing Synbiotics in Infants with Cow's Milk Protein Allergy-Effect on Clinical Outcomes.

Cow's milk protein allergy (CMPA) is common and costly. Clinical trials of infants with CMPA have shown that the use of an amino acid formula containing pre- and probiotics (synbiotics) (AAF-Syn) may lead to significant reductions in infections, medication prescriptions and hospital admissions, compared to AAF without synbiotics. These effects have not yet been confirmed in real-world practice. This retrospective matched cohort study examined clinical and healthcare data from The Health Improvement Network database, from 148 infants with CMPA (54% male, mean age at diagnosis 4.69 months), prescribed either AAF-Syn (probiotic Bifidobacterium breve M16-V and prebiotics, including chicory-derived oligo-fructose and long-chain inulin) or AAF. AAF-Syn was associated with fewer symptoms (-37%, p < 0.001), infections (-35%, p < 0.001), medication prescriptions (-19%, p < 0.001) and healthcare contacts (-18%, p = 0.15) vs. AAF. Infants prescribed AAF-Syn had a significantly higher probability of achieving asymptomatic management without hypoallergenic formula (HAF) (adjusted HR 3.70, 95% CI 1.97-6.95, p < 0.001), with a shorter clinical course of symptoms (median time to asymptomatic management without HAF 1.35 years vs. 1.95 years). AAF-Syn was associated with potential cost-savings of £452.18 per infant over the clinical course of symptoms. These findings may be attributable to the effect of the specific synbiotic on the gut microbiome. Further research is warranted to explore this. This real-world study provides evidence consistent with clinical trials that AAF-Syn may produce clinical and healthcare benefits with potential economic impact.

Amino Acid Formula Containing Synbiotics in Infants with Cow's Milk Protein Allergy: A Systematic Review and Meta-Analysis.

Cow's milk protein allergy (CMPA) is associated with dysbiosis of the infant gut microbiome, with allergic and immune development implications. Studies show benefits of combining synbiotics with hypoallergenic formulae, although evidence has never been systematically examined. This review identified seven publications of four randomised controlled trials comparing an amino acid formula (AAF) with an AAF containing synbiotics (AAF-Syn) in infants with CMPA (mean age 8.6 months; 68% male, mean intervention 27.3 weeks, n = 410). AAF and AAF-Syn were equally effective in managing allergic symptoms and promoting normal growth. Compared to AAF, significantly fewer infants fed AAF-Syn had infections (OR 0.35 (95% CI 0.19-0.67), p = 0.001). Overall medication use, including antibacterials and antifectives, was lower among infants fed AAF-Syn. Significantly fewer infants had hospital admissions with AAF-Syn compared to AAF (8.8% vs. 20.2%, p = 0.036; 56% reduction), leading to potential cost savings per infant of £164.05-£338.77. AAF-Syn was associated with increased bifidobacteria (difference in means 31.75, 95% CI 26.04-37.45, p < 0.0001); reduced Eubacterium rectale and Clostridium coccoides (difference in means -19.06, 95% CI -23.15 to -14.97, p < 0.0001); and reduced microbial diversity (p < 0.05), similar to that described in healthy breastfed infants, and may be associated with the improved clinical outcomes described. This review provides evidence that suggests combining synbiotics with AAF produces clinical benefits with potential economic implications.

A Review of Nutrition Support Guidelines for Individuals with or Recovering from COVID-19 in the Community.

COVID-19 negatively impacts nutritional status and as such identification of nutritional risk and consideration of the need for nutrition support should be fundamental in this patient group. In recent months, clinical nutrition professional organisations across the world have published nutrition support recommendations for health care professionals. This review summarises key themes of those publications linked to nutrition support of adults with or recovering from COVID-19 outside of hospital. Using our search criteria, 15 publications were identified from electronic databases and websites of clinical nutrition professional organisations, worldwide up to 19th June 2020. The key themes across these publications included the importance in the community setting of: (i) screening for malnutrition, which can be achieved by remote consultation; (ii) care plans with appropriate nutrition support, which may include food based strategies, oral nutritional supplements and referral to a dietitian; (iii) continuity of nutritional care between settings including rapid communication at discharge of malnutrition risk and requirements for ongoing nutrition support. These themes, and indeed the importance of nutritional care, are fundamental and should be integrated into pathways for the rehabilitation of patients recovering from COVID-19.

Ready-Made Oral Nutritional Supplements Improve Nutritional Outcomes and Reduce Health Care Use-A Randomised Trial in Older Malnourished People in Primary Care.

Large trials assessing oral nutritional supplements (ONS) and dietary advice (DA) in primary care are lacking. This study examined effects of ONS + DA versus DA on intake, weight, QoL, healthcare use and satisfaction in malnourished free-living older people. Three hundred and eight people (71.5 ± 10.7y) were randomised to receive ONS + DA (n154) or DA (n154) for 12 weeks. At baseline, 4, 8, 12 weeks, intake, weight, QoL, healthcare use and satisfaction were measured. ONS + DA group (mean daily intake ONS 480 kcal; 21 g protein; 80% compliance) had significantly greater total energy and protein intakes (+401 kcal/d, p < 0.001; +15 g/d, p < 0.001) and weight gain (+0.8 kg; p < 0.001) compared to DA. QoL improved in both groups over time with a significant improvement in index with ONS + DA (p = 0.009). Significantly more participants found ONS + DA made a difference for them (p = 0.011), but no differences were found between groups using Euroqol. Compared to DA, healthcare use reduced with ONS + DA, (HCP visits by 34%, emergency admissions 50%, LOS 62%). Acceptability of both interventions was high (ONS 96%, DA 95%), with significantly more participants satisfied with ONS (89%) than DA (73%) (p = 0.009). This trial in primary care indicates that ONS are acceptable, make a difference to patients, significantly improve intake and weight, and reduce health care use with potential savings.

Nutritional self-screening in <1 min: Evaluation of a measuring station using sonic measurement of height.

OBJECTIVE: Since nutritional screening is not routinely and accurately performed by busy care workers, the aim of this study was to evaluate a self-screening electronic measuring station that includes sonic height measurements. METHODS: In all, 114 patients, 18 to 85 y of age and attending gastrointestinal outpatient clinics, followed automatically triggered audio-recorded instructions for weight and height measurements. The patients also provided information about unintentional weight loss to establish malnutrition risk using the Malnutrition Universal Screening Tool (MUST). In 56 healthy individuals, the effect of head/foot positions on height was examined using video-recordings. Laboratory studies examined the effects of hair/wigs, the position of a skull and horizontal plates and ambient conditions. Measurements were also made on a mechanical machine for comparison. RESULTS: Of the patients, 21.9% were malnourished, with 99% agreement between sonic and mechanical machine categorization. Patients self-screened in only 35.6 ± 14.8 s (median 32 s) and 77% rated the screening as very easy (22%, easy), despite encountering some remediable snags. Within-subject precision for height was 0.186 cm in healthy individuals and 0.368 cm in patients. Humidity and barometric pressure had negligible/undetectable effects on height measurements, but temperature corrections were confounded by calibration errors. In the most lateral standing positions, height was underestimated curvilinearly. In healthy individuals, height measurements were 0.353 ± 0.542 cm lower on the sonic than mechanical device, which was inadequately explained by standing position or body tilt, although hair was found to be "invisible" only to the sonic machine. CONCLUSION: A method has been developed to rapidly and reliably self-screen for malnutrition using MUST, avoiding calculation and categorization errors, while providing results that can be immediately printed or transmitted electronically into patient notes.

'Self-screening' for malnutrition with an electronic version of the Malnutrition Universal Screening Tool ('MUST') in hospital outpatients: concurrent validity, preference and ease of use.

Self-screening using an electronic version of the Malnutrition Universal Screening Tool ('MUST') has been developed but its implementation requires investigation. A total of 100 outpatients (mean age 50 (sd 16) years; 57 % male) self-screened with an electronic version of 'MUST' and were then screened by a healthcare professional (HCP) to assess concurrent validity. Ease of use, time to self-screen and prevalence of malnutrition were also assessed. A further twenty outpatients (mean age 54 (sd 15) years; 55 % male) examined preference between self- screening with paper and electronic versions of 'MUST'. For the three-category classification of 'MUST' (low, medium and high risk), agreement between electronic self-screening and HCP screening was 94 % (κ=0·74, se 0·092; P<0·001). For the two-category classification (low risk; medium+high risk) agreement was 96 % (κ=0·82, se 0·085; P<0·001), comparable with the previously reported paper-based self-screening. In all, 15 % of patients categorised themselves 'at risk' of malnutrition (5 % medium, 10 % high). Electronic self-screening took 3 min (sd 1·2 min), 40 % faster than previously reported for the paper-based version. Patients found the tool easy or very easy to understand (99 %) and complete (98 %). Patients that assessed both tools found the electronic tool easier to complete (65 %) and preferred it (55 %) to the paper version. Electronic self-screening using 'MUST' in a heterogeneous group of hospital outpatients is acceptable, user-friendly and has 'substantial to almost-perfect' agreement with HCP screening. The electronic format appears to be as agreeable and often the preferred format when compared with the validated paper-based 'MUST' self-screening tool.

Cost-effectiveness of oral nutritional supplements in older malnourished care home residents.

BACKGROUND & AIMS: Malnutrition is common in care home residents, but information on the cost-effectiveness of nutritional interventions is lacking. This study, involving a randomised trial in care home residents, aimed to examine whether oral nutritional supplements (ONS) are cost-effective relative to dietary advice. METHODS: An incremental cost-effectiveness analysis was undertaken prospectively in 104 older care home residents (88 ± 8 years) without overt dementia, who were randomised to receive either ONS or dietary advice for 12 weeks. Costs were estimated from resource use and quality adjusted life years (QALYs) from health-related quality of life, assessed using EuroQoL (EQ-5D-3L, time-trade-off) and mortality. The incremental cost-effectiveness ratio (ICER) was calculated using 'intention to treat' and 'complete case' analyses. RESULTS: The ONS group gained significantly more QALYs than the dietary advice group at significantly greater costs. The ICER (extra cost per QALY gained), adjusted for nutritional status, type of care, baseline costs and quality of life, was found to be £10,961 using the 'intention to treat' analysis (£190.60 (cost)/0.0174 (QALYs); n = 104) and £11,875 using 'complete case' analysis (£217.30/0.0183; n = 76) (2016 prices). Sensitivity analysis based on 'intention to treat' data indicated an 83% probability that the ICER was ≤£20,000 and 92% that it was ≤£30,000. With the 'complete case data' the probabilities were 80% and 90% respectively. CONCLUSION: This pragmatic randomised trial involving one of the oldest populations subjected to a cost-utility analysis, suggests that use of oral nutritional supplements in care homes are cost-effective relative to dietary advice.

Oral nutritional supplements in a randomised trial are more effective than dietary advice at improving quality of life in malnourished care home residents.

BACKGROUND & AIMS: Few trials have explored the effect of nutrition support on quality of life (QoL). This study examined the effects of oral nutritional supplements (ONS) vs dietary advice on QoL in malnourished care home residents. METHODS: 104 malnourished, care home residents (medium + high risk), identified using the Malnutrition Universal Screening Tool ('MUST'), (mean age 88.5 ± 7.9y) were randomised to receive either oral nutritional supplements (ONS) (n = 53) or dietary advice (n = 51) for 12 weeks. Dietary intake was measured using 24 h dietary recall, and QoL assessed using EuroQol (EQ-5D), including time trade off (TTO) (range -0.59 to 1) and visual analogue scale (VAS) (score 0 to 100) for self-perceived health. RESULTS: QoL (adjusted for baseline QOL, malnutrition risk, type of care received (nursing or residential)) was significantly higher in the ONS than the dietary advice group (intention to treat analysis at week 12; n = 104 ). EQ-5D TTO scores (mean ± SE) were 0.50 ± 0.04 vs 0.36 ± 0.05 (P = 0.005), VAS rescaled scores were 0.54 + 0.03 vs 0.046 + 0.03 (P = 0.006) and VAS scores were 61.3 ± 4.5 vs 54.6 ± 6.3 (P = 0.533) for ONS vs dietary advice respectively. Total energy, protein and the majority of micronutrient intakes were significantly greater in the ONS group, with energy intake being 423 kcal greater in the ONS than the dietary advice group at week 12. CONCLUSIONS: This study in malnourished care home residents indicates that ONS can improve QoL and nutritional intake more effectively than dietary advice alone. CLINICAL TRIAL REGISTRY: This trial was registered with clinicaltrials.gov on 10th August 2007. Clinical trials identifier is NCT00515125http://www.clinicaltrials.gov/ct2/show/NCT00515125?term=nutrition+support&rank=60.

Limited impact of 2 g/day omega-3 fatty acid ethyl esters (Omacor®) on plasma lipids and inflammatory markers in patients awaiting carotid endarterectomy.

The objective of this study was to determine the effects of prescription omega-3 (n-3) fatty acid ethyl esters (Omacor®) on blood pressure, plasma lipids, and inflammatory marker concentrations in patients awaiting carotid endarterectomy. Patients awaiting carotid endarterectomy (n = 121) were randomised to Omacor® or olive oil as placebo (2 g/day) until surgery (median 21 days). Blood pressure, plasma lipids, and plasma inflammatory markers were determined. There were significant decreases in systolic and diastolic blood pressure and in plasma triglyceride, total cholesterol, low density lipoprotein-cholesterol, soluble vascular cellular adhesion molecule 1, and matrix metalloproteinase 2 concentrations, in both groups. The extent of triglyceride lowering was greater with Omacor® (25%) compared with placebo (9%). Soluble E-selectin concentration was significantly decreased in the Omacor® group but increased in the placebo group. At the end of the supplementation period there were no differences in blood pressure or in plasma lipid and inflammatory marker concentrations between the two groups. It is concluded that Omacor® given at 2 g/day for an average of 21 days to patients with advanced carotid atherosclerosis lowers triglycerides and soluble E-selectin concentrations, but has limited broad impact on the plasma lipid profile or on inflammatory markers. This may be because the duration of intervention was too short or the dose of n-3 fatty acids was too low.

Malnutrition self-screening by using MUST in hospital outpatients: validity, reliability, and ease of use.

BACKGROUND: Although nutritional screening with a tool such as the Malnutrition Universal Screening Tool (MUST) is recommended for outpatients, staff are under pressure to undertake a variety of other tasks. Little attention has been paid to the validity of patient self-screening with MUST. OBJECTIVE: This study in 205 outpatients with a mean (±SD) age of 55 ± 17 y (56% male) assessed the practicalities of self-screening, its agreement with screening undertaken by a trained health care professional (HCP), and its test-retest reliability. DESIGN: After the participants provided consent, screening was undertaken by the patients themselves and then by a trained HCP who was unaware of the self-screening results. All patients completed an ease-of-use questionnaire. Test-retest reliability of self-screening was established in a subset of 60 patients. RESULTS: A total of 19.6% of patients categorized themselves as "at risk" of malnutrition (9.8% medium, 9.8% high). For the 3-category classification of MUST (low, medium, high), agreement between self-screening and HCP screening was 90% (κ = 0.70; SE = 0.058, P < 0.001). For the 2-category classification (low risk, medium + high risk), agreement was 93% (κ = 0.78, SE = 0.057, P < 0.001). Disagreements were not systematically under- or overcategorized. Test-retest reliability was almost perfect (κ = 0.94, P < 0.001). Most patients (71%) completed self-screening in <5 min. Patients found the tool easy or very easy to understand (96%) and complete (98%), with 94% reporting that they were happy to screen themselves. CONCLUSION: Self-screening involving MUST in outpatients is acceptable to patients, user-friendly, reliable, and associated with good agreement with HCP screening. This trial was registered at clinicaltrials.gov as NCT00714324.

Eicosapentaenoic acid (EPA) from highly concentrated n-3 fatty acid ethyl esters is incorporated into advanced atherosclerotic plaques and higher plaque EPA is associated with decreased plaque inflammation and increased stability.

OBJECTIVE: To examine n-3 polyunsaturated fatty acid (PUFA) incorporation into atherosclerotic plaques and the association with plaque inflammation and stability. METHODS AND RESULTS: Patients awaiting carotid endarterectomy (n=121) were randomised to consume control capsules or n-3 PUFA ethyl ester capsules until surgery (median 21 days). The fatty acid compositions of plasma and carotid plaque phospholipids, plaque features, and expression of inflammatory genes were determined. The proportion of eicosapentaenoic acid (EPA) was higher (P<0.0001) in carotid plaque phospholipids in patients in the n-3 PUFA group. Plaques from patients in the n-3 PUFA group had fewer foam cells (P=0.0390). There were no other differences between plaques in the two groups with regard to histological characteristics or morphology. Plaque stability was not different between the two groups. However, the EPA content of plaque phospholipids was inversely associated with plaque instability (P=0.0209), plaque inflammation (P=0.0108), the number of T cells in the plaque (P=0.0097) and a summary score considering a range of plaque features (P=0.0425). Plaques from patients who received n-3 PUFAs had significantly lower levels of mRNA for matrix metalloproteinases (MMP)-7 (P=0.0055), -9 (P=0.0048) and -12 (P=0.0044) and for interleukin-6 (P=0.0395) and intercellular adhesion molecule 1 (P=0.0142). CONCLUSIONS: Atherosclerotic plaques readily incorporate EPA. A higher plaque EPA content is associated with a reduced number of foam cells and T cells, less inflammation and increased stability.

Is there a case for n-3 fatty acid supplementation in cystic fibrosis?

PURPOSE OF REVIEW: This review evaluates our current knowledge on the association of fatty acid abnormalities in cystic fibrosis with the disease process, and makes a case for a well-designed clinical trial to evaluate the clinical efficacy of long chain n-3 fatty acids. RECENT FINDINGS: It has long been known that cystic fibrosis patients exhibit fatty acid abnormalities, but these have not been well investigated in tissues affected by the disease. Recent studies have demonstrated that such tissues do indeed show abnormalities in the proportions of linoleic, arachidonic and docosahexaenoic acids, and have demonstrated alterations in fatty acid and phospholipid metabolism in cystic fibrosis. Work in other areas has identified novel anti-inflammatory actions of long chain n-3 fatty acids that might be relevant to cystic fibrosis. A recent systematic review of fish oil supplementation in cystic fibrosis did not allow firm conclusions to be drawn, but suggested that there may be some benefits. SUMMARY: The restoration of abnormal fatty acid profiles may be beneficial in cystic fibrosis, but this approach has not been evaluated in studies with a suitable design to permit firm conclusions to be drawn. There is a need for a long-term randomized controlled study to evaluate the therapeutic benefit of fish oil supplementation in cystic fibrosis.