Margot Gosney

Background: Malnutrition worsens the health of frail older adults. Current treatments for malnutrition may include prescribed oral nutritional supplements, which are multinutrient products containing macronutrients and micronutrients. Objective: To assess the effectiveness and cost-effectiveness of oral nutritional supplements (with or without other dietary interventions) in frail older people who are malnourished or at risk of malnutrition. Data sources: MEDLINE, EMBASE, Cochrane Library, Scopus, CINAHL (Cumulative Index to Nursing and Allied Health Literature) and grey literature were searched from inception to 13 September 2021. Review methods: A systematic review and meta-analysis was conducted to evaluate the effectiveness and cost-effectiveness of oral nutritional supplements in frail older people (aged ≥ 65 years) who are malnourished or at risk of malnutrition (defined as undernutrition as per National Institute for Health and Care Excellence guidelines). Meta-analysis and network meta-analysis were undertaken, where feasible, along with a narrative synthesis. A cost-effectiveness review was reported narratively. A de novo model was developed using effectiveness evidence identified in the systematic review to estimate the cost-effectiveness of oral nutritional supplements. Results: Eleven studies (n = 822 participants) were included in the effectiveness review, six of which were fully or partly funded by industry. Meta-analyses suggested positive effects of oral nutritional supplements compared with standard care for energy intake (kcal) (standardised mean difference 1.02, 95% confidence interval 0.15 to 1.88; very low quality evidence) and poor mobility (mean difference 0.03, p < 0.00001, 95% confidence interval 0.02 to 0.04; very low quality evidence) but no evidence of an effect for body weight (mean difference 1.31, 95% confidence interval –0.05 to 2.66; very low quality evidence) and body mass index (mean difference 0.54, 95% confidence interval –0.03 to 1.11; very low quality evidence). Pooled results for other outcomes were statistically non-significant. There was mixed narrative evidence regarding the effect of oral nutritional supplements on quality of life. Network meta-analysis could be conducted only for body weight and grip strength; there was evidence of an effect for oral nutritional supplements compared with standard care for body weight only. Study quality was mixed; the randomisation method was typically poorly reported. One economic evaluation, in a care home setting, was included. This was a well-conducted study showing that oral nutritional supplements could be cost-effective. Cost-effectiveness analysis suggested that oral nutritional supplements may only be cost-effective for people with lower body mass index (< 21 kg/m²) using cheaper oral nutritional supplements products that require minimal staff time to administer. Limitations: The review scope was narrow in focus as few primary studies used frailty measures (or our proxy criteria). This resulted in only 11 included studies. The small evidence base and varied quality of evidence meant that it was not possible to determine accurate estimates of the effectiveness or cost-effectiveness of oral nutritional supplements. Furthermore, only English-language publications were considered. Conclusions: Overall, the review found little evidence of oral nutritional supplements having significant effects on reducing malnutrition or its adverse outcomes in frail older adults. Future work: Future research should focus on independent, high-quality, adequately powered studies to investigate oral nutritional supplements alongside other nutritional interventions, with longer-term follow-up and detailed analysis of determinants, intervention components and cost-effectiveness. Study registration: This study is registered as PROSPERO CRD42020170906. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 51. See the NIHR Journals Library website for further project information.

Background: In breast cancer management, age-related practice variation is widespread, with older women having lower rates of surgery and chemotherapy than younger women, based on the premise of reduced treatment tolerance and benefit. This may contribute to inferior outcomes. There are currently no age- and fitness-stratified guidelines on which to base treatment recommendations. Aim: We aimed to optimise treatment choice and outcomes for older women (aged ≥ 70 years) with operable breast cancer. Objectives: Our objectives were to (1) determine the age, comorbidity, frailty, disease stage and biology thresholds for endocrine therapy alone versus surgery plus adjuvant endocrine therapy, or adjuvant chemotherapy versus no chemotherapy, for older women with breast cancer; (2) optimise survival outcomes for older women by improving the quality of treatment decision-making; (3) develop and evaluate a decision support intervention to enhance shared decision-making; and (4) determine the degree and causes of treatment variation between UK breast units. Design: A prospective cohort study was used to determine age and fitness thresholds for treatment allocation. Mixed-methods research was used to determine the information needs of older women to develop a decision support intervention. A cluster-randomised trial was used to evaluate the impact of this decision support intervention on treatment choices and outcomes. Health economic analysis was used to evaluate the cost–benefit ratio of different treatment strategies according to age and fitness criteria. A mixed-methods study was used to determine the degree and causes of variation in treatment allocation. Main outcome measures: The main outcome measures were enhanced age- and fitness-specific decision support leading to improved quality-of-life outcomes in older women (aged ≥ 70 years) with early breast cancer. Results: (1) Cohort study: the study recruited 3416 UK women aged ≥ 70 years (median age 77 years). Follow-up was 52 months. (a) The surgery plus adjuvant endocrine therapy versus endocrine therapy alone comparison: 2854 out of 3416 (88%) women had oestrogen-receptor-positive breast cancer, 2354 of whom received surgery plus adjuvant endocrine therapy and 500 received endocrine therapy alone. Patients treated with endocrine therapy alone were older and frailer than patients treated with surgery plus adjuvant endocrine therapy. Unmatched overall survival and breast-cancer-specific survival were higher in the surgery plus adjuvant endocrine therapy group (overall survival: hazard ratio 0.27, 95% confidence interval 0.23 to 0.33; p < 0.001; breast-cancer-specific survival: hazard ratio 0.41, 95% confidence interval 0.29 to 0.58; p < 0.001) than in the endocrine therapy alone group. In matched analysis, surgery plus adjuvant endocrine therapy was still associated with better overall survival (hazard ratio 0.72, 95% confidence interval 0.53 to 0.98; p = 0.04) than endocrine therapy alone, but not with better breast-cancer-specific survival (hazard ratio 0.74, 95% confidence interval 0.40 to 1.37; p = 0.34) or progression-free-survival (hazard ratio 1.11, 95% confidence interval 0.55 to 2.26; p = 0.78). (b) The adjuvant chemotherapy versus no chemotherapy comparison: 2811 out of 3416 (82%) women received surgery plus adjuvant endocrine therapy, of whom 1520 (54%) had high-recurrence-risk breast cancer [grade 3, node positive, oestrogen receptor negative or human epidermal growth factor receptor-2 positive, or a high Oncotype DX^® (Genomic Health, Inc., Redwood City, CA, USA) score of > 25]. In this high-risk population, there were no differences according to adjuvant chemotherapy use in overall survival or breast-cancer-specific survival after propensity matching. Adjuvant chemotherapy was associated with a lower risk of metastatic recurrence than no chemotherapy in the unmatched (adjusted hazard ratio 0.36, 95% confidence interval 0.19 to 0.68; p = 0.002) and propensity-matched patients (adjusted hazard ratio 0.43, 95% confidence interval 0.20 to 0.92; p = 0.03). Adjuvant chemotherapy improved the overall survival and breast-cancer-specific survival of patients with oestrogen-receptor-negative disease. (2) Mixed-methods research to develop a decision support intervention: an iterative process was used to develop two decision support interventions (each comprising a brief decision aid, a booklet and an online tool) specifically for older women facing treatment choices (endocrine therapy alone or surgery plus adjuvant endocrine therapy, and adjuvant chemotherapy or no chemotherapy) using several evidence sources (expert opinion, literature and patient interviews). The online tool was based on models developed using registry data from 23,842 patients and validated on an external data set of 14,526 patients. Mortality rates at 2 and 5 years differed by < 1% between predicted and observed values. (3) Cluster-randomised clinical trial of decision support tools: 46 UK breast units were randomised (intervention, n = 21; usual care, n = 25), recruiting 1339 women (intervention, n = 670; usual care, n = 669). There was no significant difference in global quality of life at 6 months post baseline (difference –0.20, 95% confidence interval –2.7 to 2.3; p = 0.90). In women offered a choice of endocrine therapy alone or surgery plus adjuvant endocrine therapy, knowledge about treatments was greater in the intervention arm than the usual care arm (94% vs. 74%; p = 0.003). Treatment choice was altered, with higher rates of endocrine therapy alone than of surgery in the intervention arm. Similarly, chemotherapy rates were lower in the intervention arm (endocrine therapy alone rate: intervention sites 21% vs. usual-care sites 15%, difference 5.5%, 95% confidence interval 1.1% to 10.0%; p = 0.02; adjuvant chemotherapy rate: intervention sites 10% vs. usual-care site 15%, difference 4.5%, 95% confidence interval 0.0% to 8.0%; p = 0.013). Survival was similar in both arms. (4) Health economic analysis: a probabilistic economic model was developed using registry and cohort study data. For most health and fitness strata, surgery plus adjuvant endocrine therapy had lower costs and returned more quality-adjusted life-years than endocrine therapy alone. However, for some women aged > 90 years, surgery plus adjuvant endocrine therapy was no longer cost-effective and generated fewer quality-adjusted life-years than endocrine therapy alone. The incremental benefit of surgery plus adjuvant endocrine therapy reduced with age and comorbidities. (5) Variation in practice: analysis of rates of surgery plus adjuvant endocrine therapy or endocrine therapy alone between the 56 breast units in the cohort study demonstrated significant variation in rates of endocrine therapy alone that persisted after adjustment for age, fitness and stage. Clinician preference was an important determinant of treatment choice. Conclusions: This study demonstrates that, for older women with oestrogen-receptor-positive breast cancer, there is a cohort of women with a life expectancy of < 4 years for whom surgery plus adjuvant endocrine therapy may offer little benefit and simply have a negative impact on quality of life. The Age Gap decision tool may help make this shared decision. Similarly, although adjuvant chemotherapy offers little benefit and has a negative impact on quality of life for the majority of older women with oestrogen-receptor-positive breast cancer, for women with oestrogen-receptor-negative breast cancer, adjuvant chemotherapy is beneficial. The negative impacts of adjuvant chemotherapy on quality of life, although significant, are transient. This implies that, for the majority of fitter women aged ≥ 70 years, standard care should be offered. Limitations: As with any observational study, despite detailed propensity score matching, residual bias cannot be excluded. Follow-up was at median 52 months for the cohort analysis. Longer-term follow-up will be required to validate these findings owing to the slow time course of oestrogen-receptor-positive breast cancer. Future work: The online algorithm is now available (URL: https://agegap.shef.ac.uk/; accessed May 2022). There are plans to validate the tool and incorprate quality-of-life and 10-year survival outcomes. Trial registration: This trial is registered as ISRCTN46099296. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 10, No. 6. See the NIHR Journals Library website for further project information.

Although there are numerous high protein products on the market, they are typically not designed with, or for, older consumers. This is surprising considering that dietary guidelines recognise the need for higher protein intake in later life. Protein fortified products are, however, associated with negative sensory attributes and poor consumer acceptance. This paper investigates the extent of mouthdrying sensations within a high protein solid food matrix, along with the effect of age and saliva flow. Solid models using cakes and biscuits, with or without protein fortification, were investigated. The sensory profile and physical properties were analysed and two volunteer studies (n = 84; n = 70) were carried out using two age groups (18–30; 65+). Volunteers rated individual perception and liking of products, and salivary flow rates (mL/min) were measured. Unstimulated salivary flow rates were significantly lower (p < 0.05) in older adults, although this was not found to influence product perception. Protein fortification of cakes and biscuits significantly increased (p < 0.05) perceived mouthdrying, hardness and “off” flavours, and significantly reduced (p < 0.05) melting rate, moistness and liking compared with the control versions. There is a clear need to address negative sensory attributes associated with protein fortification of cakes and biscuits to ensure product suitability for older adults.

Protein fortified products are regularly recommended to older adults to improve nutritional status and limit sarcopenia. However protein fortification can elicit negative sensory attributes such as mouthdrying. Sensitivity to mouthdrying can increase with age, yet the influence of saliva flow and mucoadhesion remain uncertain. Here, two studies tested different whey protein beverages (WPB); 22 healthy younger volunteers completed a pilot and 84 healthy volunteers from two age groups (18–30; 65+) completed the main study. In both studies salivary flow rates (mL/min) were measured and saliva samples were collected at time intervals post beverage consumption to measure mucoadhesion to the oral cavity, where protein concentration was analysed by Bradford Assay. Volunteers rated perception and acceptability of WPBs in the main study. WPB consumption resulted in significantly increased protein concentration (p < 0.0001) in saliva samples compared with a control whey permeate beverage. Older adults had significantly lower unstimulated saliva flow (p = 0.003) and significantly increased protein concentration (p = 0.02) in saliva samples, compared with younger adults. Heating of WPB significantly (p < 0.05) increased mouthdrying and thickness perception and reduced sweetness compared with unheated WPB. Mucoadhesion is concluded to be a true phenomenon in WPBs and increases with age.