Bridging The Age Gap: observational cohort study of effects of chemotherapy and trastuzumab on recurrence, survival and quality of life in older women with early breast cancer.

BACKGROUND: Chemotherapy improves outcomes for high risk early breast cancer (EBC) patients but is infrequently offered to older individuals. This study determined if there are fit older patients with high-risk disease who may benefit from chemotherapy. METHODS: A multicentre, prospective, observational study was performed to determine chemotherapy (±trastuzumab) usage and survival and quality-of-life outcomes in EBC patients aged ≥70 years. Propensity score-matching adjusted for variation in baseline age, fitness and tumour stage. RESULTS: Three thousands four hundred sixteen women were recruited from 56 UK centres between 2013 and 2018. Two thousands eight hundred eleven (82%) had surgery. 1520/2811 (54%) had high-risk EBC and 2059/2811 (73%) were fit. Chemotherapy was given to 306/1100 (27.8%) fit patients with high-risk EBC. Unmatched comparison of chemotherapy versus no chemotherapy demonstrated reduced metastatic recurrence risk in high-risk patients(hazard ratio [HR] 0.36 [95% CI 0.19-0.68]) and in 541 age, stage and fitness-matched patients(adjusted HR 0.43 [95% CI 0.20-0.92]) but no benefit to overall survival (OS) or breast cancer-specific survival (BCSS) in either group. Chemotherapy improved survival in women with oestrogen receptor (ER)-negative cancer (OS: HR 0.20 [95% CI 0.08-0.49];BCSS: HR 0.12 [95% CI 0.03-0.44]).Transient negative quality-of-life impacts were observed. CONCLUSIONS: Chemotherapy was associated with reduced risk of metastatic recurrence, but survival benefits were only seen in patients with ER-negative cancer. Quality-of-life impacts were significant but transient. TRIAL REGISTRATION: ISRCTN 46099296.

Effect of a synbiotic on the response to seasonal influenza vaccination is strongly influenced by degree of immunosenescence.

BACKGROUND: Ageing increases risk of respiratory infections and impairs the response to influenza vaccination. Pre- and probiotics offer an opportunity to modulate anti-viral defenses and the response to vaccination via alteration of the gut microbiota. This study investigated the effect of a novel probiotic, Bifidobacterium longum bv. infantis CCUG 52,486, combined with a prebiotic, gluco-oligosaccharide (B. longum + Gl-OS), on the response to seasonal influenza vaccination in young and older subjects in a double-blind, randomized controlled trial, taking into account the influence of immunosenescence markers at baseline. RESULTS: Vaccination resulted in a significant increase in total antibody titres, vaccine-specific IgA, IgM and IgG and seroprotection to all three subunits of the vaccine in both young and older subjects, and in general, the increases in young subjects were greater. There was little effect of the synbiotic, although it tended to reduce seroconversion to the Brisbane subunit of the vaccine and the vaccine-specific IgG response in older subjects. Immunological characterization revealed that older subjects randomized to the synbiotic had a significantly higher number of senescent (CD28(-)CD57(+)) helper T cells at baseline compared with those randomized to the placebo, and they also had significantly higher plasma levels of anti-CMV IgG and a greater tendency for CMV seropositivity. Moreover, higher numbers of CD28(-)CD57(+) helper T cells were associated with failure to seroconvert to Brisbane, strongly suggesting that the subjects randomized to the synbiotic were already at a significant disadvantage in terms of likely ability to respond to the vaccine compared with those randomized to the placebo. CONCLUSIONS: Ageing was associated with marked impairment of the antibody response to influenza vaccination in older subjects and the synbiotic failed to reverse this impairment. However, the older subjects randomized to the synbiotic were at a significant disadvantage due to a greater degree of immunosenscence at baseline compared with those randomized to the placebo. Thus, baseline differences in immunosenescence between the randomized groups are likely to have influenced the outcome of the intervention, highlighting the need for detailed immunological characterization of subjects prior to interventions. TRIAL REGISTRATION: Clinicaltrials.gov NCT01066377.

Novel flavours paired with glutamate condition increased intake in older adults in the absence of changes in liking.

Previous research on the repeat exposure to a novel flavour combined with monosodium glutamate (MSG) has shown an increase in liking and consumption for the particular flavour. The aim of the current work was to investigate whether this could also be observed in the case of older people, since they are most affected by undernutrition in the developed world and ways to increase consumption of food are of significant importance for this particular age group. For this study, 40 older adults (age 65-88) repeatedly consumed potato soup with two novel flavours (lemongrass and cumin) which were either with or without a high level of MSG (5% w/w). A randomized single blind within-subject design was implemented, where each participant was exposed to both soup flavours three times over 6 days, with one of the soup flavours containing MSG. After three repeat exposures, consumption increased significantly for the soups where the flavours had contained MSG during the repeated exposure (mean weight consumed increased from 123 to 164 g, p = 0.017), implying that glutamate conditioned for increased wanting and consumption, despite the fact that the liking for the soup had not increased.

The effect of macro- and micro-nutrient fortification of biscuits on their sensory properties and on hedonic liking of older people.

BACKGROUND: Under-nutrition in older adults is widespread. Oral nutritional supplement beverages (ONS) are prescribed, yet consumption by older people is often insufficient. A variety of supplement formats may improve nutrient intake. This study developed protein and micro-nutrient fortified biscuits and evaluated their sensory attributes and liking by older people. Two micro-nutrient strategies were taken, to match typical ONS and to customise to the needs of older people. RESULTS: Oat biscuits and gluten-free biscuits developed contained over 12% protein and over 460 kcal 100 g(-1). Two small (40 g) biscuits developed to match ONS provided approximately 40% of an ONS portion of micro-nutrients and 60% of macro-nutrients; however, the portion size was considered realistic whereas the average ONS portion (200 mL) is excessive. Biscuits developed to the needs of older adults provided, on average, 18% of the reference nutrient intake of targeted micro-nutrients. Sensory characteristics were similar between biscuits with and without micro-nutrient fortification, leading to no differences in liking. Fortified oat biscuits were less liked than commercial oat biscuits, partly attributed to flavour imparted by whey protein fortification. CONCLUSION: Macro- and micro-nutrient fortification of biscuits could provide an alternative fortified snack to help alleviate malnutrition in older adults.

Maximising umami taste in meat using natural ingredients: effects on chemistry, sensory perception and hedonic liking in young and old consumers.

BACKGROUND: Umami taste in foods is elicited predominantly by the presence of glutamic acid and 5'-ribonucleotides, which act synergistically. This study aimed to use natural ingredients to maximise umami taste of a meat formulation and determine effects on liking of older consumers. Cooked meat products with added natural ingredients (yeast extract, mycoscent, shiitake extract, tomato puree, soy sauce and soybean paste) or monosodium glutamate (MSG) were prepared and compared with a control sample analytically (umami compounds), sensorially (sensory profile) and hedonically (liking by younger and older volunteers). Taste detection thresholds of sodium chloride and MSG of volunteers were collected. RESULTS: Four of the seven cooked meat products developed had a significantly higher content of umami-contributing compounds compared with the control. All products, except those containing MSG or tomato puree, were scored (by trained sensory panel) perceptually significantly higher in umami and/or salty taste compared with the control. Consumer tests showed a correlation of liking by the older cohort with perceived saltiness (ρ = 0.76). CONCLUSION: The addition of natural umami-containing ingredients during the cooking of meat can provide enhanced umami and salty taste characteristics. This can lead to increased liking by some consumers, particularly those with raised taste detection thresholds.

Sexuality in older age: essential considerations for healthcare professionals.

This review describes the fact that many elderly people enjoy an active sex life and examines the evidence against the general perception of an 'asexual' old age. It offers an overview of the evidence for healthcare professionals who had not previously considered the sexuality of their older patients. It also describes some of the sexual problems faced by older people, especially the difficulties experienced in disclosing such problems to healthcare professionals. It examines why healthcare professionals routinely avoid discussing sexual problems with older patients, and how this can be improved. It also offers some recommendations for future research in the area, as well as a word of caution regarding the temptation of over-sexualising the ageing process.

Hospital catering systems and their impact on the sensorial profile of foods provided to older patients in the UK.

Impaired sensorial perception is very common in older people and low sensorial quality of foods is associated with decreased appetite and dietary intake. Hospital undernutrition in older patients could be linked to sensorial quality of hospital food if the quality were low or inappropriate for older people. The aim of this study was to examine changes in the sensorial quality of different foods that occur as a result of the food journey (i.e. freezing, regeneration, etc.) in the most common hospital catering systems in the UK. A trained sensory panel assessed sensorial descriptors of certain foods with and without the hospital food journey as it occurs in the in-house and cook/freeze systems. The results showed effects of the food journey on a small number of sensorial descriptors related to flavour, appearance and mouthfeel. The majority of these effects were due to temperature changes, which caused accumulation of condensation. A daily variation in sensorial descriptors was also detected and in some cases it was greater than the effect of the food journey. This study has shown that changes occur in the sensory quality of meals due to hospital food journeys, however these changes were small and are not expected to substantially contribute to acceptability or have a major role in hospital malnutrition.

Observational cohort study in older women with early breast cancer: Use of radiation therapy and impact on health-related quality of life and mortality.

BACKGROUND: Radiotherapy reduces in-breast recurrence risk in early breast cancer (EBC) in older women. This benefit may be small and should be balanced against treatment effect and holistic patient assessment. This study described treatment patterns according to fitness and impact on health-related quality-of-life (HRQoL). METHODS: A multicentre, observational study of EBC patients aged ≥ 70 years, undergoing breast-conserving surgery (BCS) or mastectomy, was undertaken. Associations between radiotherapy use, surgery, clinico-pathological parameters, fitness based on geriatric parameters and treatment centre were determined. HRQoL was measured using the European Organisation for the Research and Treatment of Cancer (EORTC) questionnaires. RESULTS: In 2013-2018 2811 women in 56 UK study centres underwent surgery with a median follow-up of 52 months. On multivariable analysis, age and tumour risk predicted radiotherapy use. Among healthier patients (based on geriatric assessments) with high-risk tumours, 534/613 (87.1%) having BCS and 185/341 (54.2%) having mastectomy received radiotherapy. In less fit individuals with low-risk tumours undergoing BCS, 149/207 (72.0%) received radiotherapy. Radiotherapy effects on HRQoL domains, including breast symptoms and fatigue were seen, resolving by 18 months. CONCLUSION: Radiotherapy use in EBC patients ≥ 70 years is affected by age and recurrence risk, whereas geriatric parameters have limited impact regardless of type of surgery. There was geographical variation in treatment, with some fit older women with high-risk tumours not receiving radiotherapy, and some older, low-risk, EBC patients receiving radiotherapy after BCS despite evidence of limited benefit. The impact on HRQoL is transient.

Bridging the Age Gap in breast cancer: Impact of chemotherapy on quality of life in older women with early breast cancer.

INTRODUCTION: Older patients with early breast cancer (EBC) derive modest survival benefit from chemotherapy but have increased toxicity risk. Data on the impact of chemotherapy for EBC on quality of life in older patients are limited, but this is a key determinant of treatment acceptance. We aimed to investigate its effect on quality of life in older patients enrolled in the Bridging the Age Gap study. MATERIALS AND METHODS: A prospective, multicentre, observational study of EBC patients ≥70 years old was conducted in 2013-2018 at 56 UK hospitals. Demographics, patient, tumour characteristics, treatments and adverse events were recorded. Quality of life was assessed using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaires (EORTC-QLQ) C30, BR23 and ELD 15 plus the Euroqol-5D (eq-5d) over 24 months and analysed at each time point using baseline adjusted linear regression analysis and propensity score-matching. RESULTS: Three thousand and four hundred sixteen patients were enrolled in the study; 1520 patients undergoing surgery and who had high-risk EBC were included in this analysis. 376/1520 (24.7%) received chemotherapy. At 6 months, chemotherapy had a significant negative impact in several EORTC-QLQ-C30 domains, including global health score, physical, role, social functioning, cognition, fatigue, nausea/vomiting, dyspnoea, appetite loss, diarrhoea and constipation. Similar trends were documented on other scales (EORTC-QLQ-BR23, EORTC-QLQ-ELD15 and EQ-5D-5L). Its impact was no longer significant at 18-24 months in unmatched and matched cohorts. CONCLUSIONS: The negative impact of chemotherapy on quality-of-life is clinically and statistically significant at 6 months but resolves by 18 months, which is crucial to inform decision-making for older patients contemplating chemotherapy. TRIAL REGISTRATION NUMBER ISRCTN: 46099296.

Effect of patient age on management decisions in breast cancer: consensus from a national consultation.

This qualitative study investigated the attitudes, perceptions, and practices of breast cancer specialists with reference to the effect of patient age on management decisions in breast cancer, and attempted to identify national consensus on this issue. One hundred thirty-three relevant specialists, including 75 surgeons and 43 oncologists, participated in a virtual consultation using e-mailed questionnaires and open-ended discussion documents, culminating in the development of proposed consensus statements sent to participants for validation. A strong consensus was seen in favor of incorporating minimum standards of diagnostic services, treatment, and care for older patients with breast cancer into relevant national guidance, endorsed by professional bodies. Similarly, an overwhelming majority of participants agreed that simple, evidence-based protocols or guidelines on standardizing assessment of biological and chronological age should be produced by the National Institute for Health and Clinical Excellence and the Scottish Medicines Consortium, developed in collaboration with specialist oncogeriatricians, and endorsed by professional bodies. A further recommendation that all breast cancer patient treatment and diagnostic procedures be undertaken in light of up-to-date, relevant scientific data met with majority support. This study was successful in gauging national specialist opinion regarding the effect of patient age on management decisions in breast cancer in the U.K.

An Investigation of the Influence of Age and Saliva Flow on the Oral Retention of Whey Protein and Its Potential Effect on the Perception and Acceptance of Whey Protein Beverages.

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.

Consistent Effects of Whey Protein Fortification on Consumer Perception and Liking of Solid Food Matrices (Cakes and Biscuits) Regardless of Age and Saliva Flow.

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.

Age-Related Changes in the Natural Killer Cell Response to Seasonal Influenza Vaccination Are Not Influenced by a Synbiotic: a Randomised Controlled Trial.

Natural killer (NK) cells are an important component of the immune response to influenza infection, but are subject to alteration during aging, which may play a role in impaired response to infection and vaccination in older people. Enhancement of NK cell activity could, therefore, present a means to improve the immune response to vaccination in older subjects, and pre- and probiotics offer an opportunity to modulate antiviral defenses via alteration of the gut microbiota. This study investigated the effect of a novel probiotic, Bifidobacterium longum bv. infantis CCUG 52486, combined with a prebiotic, gluco-oligosaccharide (B. longum + Gl-OS), on the NK cell response to seasonal influenza vaccination in young and older subjects in a double-blind, randomized controlled trial. There were significant effects of aging on NK cell phenotype, the most notable of which were an increase in CD56dim cells, mainly reflected in the CD16+ subset, a decrease in CD56bright cells, mainly reflected in the CD16- subset, and greater expression of the immunosenescence marker, CD57, on NK cell subsets. However, these changes only partially translated to differences in NK cell activity, observed as trends toward reduced NK cell activity in older subjects when analyzed on a per cell basis. Influenza vaccination increased the proportion of CD56bright cells and decreased the proportion of CD56dim cells, in young, but not older subjects. Although NK cell activity in response to vaccination was not significantly different between the young and older subjects, low post-vaccination NK cell activity was associated with poor seroconversion in only the older subjects. There was no influence of the synbiotic on NK cell phenotype or activity, either before or after influenza vaccination. In conclusion, aging is associated with marked alteration of the phenotype of the NK cell population and there was evidence of an impaired NK cell response to influenza vaccination in older subjects. The effects of aging on NK cell phenotype and activity could not be offset by B. longum + Gl-OS. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01066377.

Enterobacter sakazakii in the mouths of stroke patients and its association with aspiration pneumonia.

BACKGROUND: Previous studies by our group have identified a high prevalence of Gram-negative bacilli in the mouths of stroke patients. Eradication of such organisms by selective decontamination of the digestive tract (SDD) has not previously been studied. Enterobacter sakazakii is a rarely found organism that has previously been identified as a cause of neonatal meningitis and sepsis but that has rarely been reported as a pathogen in older people. The purpose of this study was to look specifically for E. sakazakii in the mouths of stroke patients and to correlate its isolation with response to SDD gel and the presence of clinical complications such as pneumonia. METHODS: Following an acute stroke, 203 patients were recruited for the study and received placebo or SDD in a 50:50 ratio. Oral swabs were obtained on nine separate occasions and E. sakazakii was cultured from them. Clinical data were prospectively collected and analysed. RESULTS: E. sakazakii was identified in 7 of 203 patients. The organism was almost exclusively removed by SDD gel, but in those patients in whom an abnormal swallow was present, pneumonia was found in two of the four cases. CONCLUSION: E. sakazakii may colonise the mouths of acute stroke patients. Since SDD gel is not routinely administered to such patients, this organism may be implicated in patients who subsequently develop aspiration pneumonia.

The effect of nutrient fortification of sauces on product stability, sensory properties, and subsequent liking by older adults.

There are potential nutritional and sensory benefits of adding sauces to hospital meals. The aim of this study was to develop nutrient fortified sauces with acceptable sensory properties suitable for older people at risk of undernutrition. Tomato, gravy, and white sauce were fortified with macro- and micronutrients using food ingredients rich in energy and protein as well as vitamin and mineral premixes. Sensory profile was assessed by a trained panel. Hedonic liking of fortified compared with standard sauces was evaluated by healthy older volunteers. The fortified sauces had higher nutritional value than the conventional ones, for example the energy content of the fortified tomato, white sauce, and gravy formulations were increased between 2.5- and 4-fold compared to their control formulations. Healthy older consumers preferred the fortified tomato sauce compared with unfortified. There were no significant differences in liking between the fortified and standard option for gravy. There were limitations in the extent of fortification with protein, potassium, and magnesium, as excessive inclusion resulted in bitterness, undesired flavors, or textural issues. This was particularly marked in the white sauce to the extent that their sensory characteristics were not sufficiently optimized for hedonic testing. It is proposed that the development of fortified sauces is a simple approach to improving energy intake for hospitalized older people, both through the nutrient composition of the sauce itself and due to the benefits of increasing sensorial taste and lubrication in the mouth.

Can a short period of micronutrient supplementation in older institutionalized people improve response to influenza vaccine? A randomized, controlled trial.

OBJECTIVES: To test the hypothesis that a micronutrient supplement can improve seroconversion after influenza immunization in older institutionalized people. DESIGN: : Randomized, double-blind, placebo-controlled study. SETTING: Nursing and residential homes in Liverpool, United Kingdom. PARTICIPANTS: One hundred sixty-four residents aged 60 and older from 31 homes were initially randomized; of these, 119 (72.6%) completed the study. INTERVENTION: Participants were randomized to receive a micronutrient supplement providing the reference nutrient intake for all vitamins and trace elements or identical placebo. Tablets were taken over an 8-week period during September and October 2000; influenza vaccine was administered 4 weeks after their commencement. MEASUREMENTS: The hemagglutination-inhibiting antibody response as defined by a fourfold or greater titer rise over 4 weeks and assessed separately for each of the three antigens contained in the 2000/2001 influenza vaccine (A/New Caledonia/20/99 (H1N1), A/Moscow/10/99 (H3N2), B/Beijing/184/93 (B)). RESULTS: Despite a significant increase in serum concentrations of vitamins A, C, D3, E, folate, and selenium in the supplemented group, there was no significant difference between groups (supplemented vs placebo, respectively) in the proportion of participants seroconverting to H1N1 (41% vs 49%, P=.374), H3N2 (49% vs 58%, P=.343), or B (41% vs 40%, P=.944). CONCLUSION: A micronutrient supplement providing the reference nutrient intake administered over 8 weeks had no beneficial effect on antibody response to influenza vaccine in older people living in long-term care.

Opportunistic hearing screening in elderly inpatients.

OBJECTIVE: To determine the prevalence of occult hearing loss in elderly inpatients, to evaluate feasibility of opportunistic hearing screening and to determine subsequent provision of hearing aids. MATERIALS AND METHODS: Subjects (>65 years) were recruited from five elderly care wards. Hearing loss was detected by a ward-based hearing screen comprising patient-reported assessment of hearing disability and a whisper test. Subjects failing the whisper test or reporting hearing difficulties were offered formal audiological assessment. RESULTS: Screening was performed on 51 patients aged between 70 and 95 years. Of the patients, 21 (41%) reported hearing loss and 16 (31%) failed the whisper test. A total of 37 patients (73%) were referred for audiological assessment with 17 (33%) found to have aidable hearing loss and 11 were fitted with hearing aids (22%). DISCUSSION: This study highlights the high prevalence of occult hearing loss in elderly inpatients. Easy two-step screening can accurately identify patients with undiagnosed deafness resulting in significant proportions receiving hearing aids. KEY SENTENCES: Approximately 14% of the elderly population use hearing aids despite a reported prevalence of deafness in up to 55%.The use of hearing aids is associated with an improvement in physical, emotional, mental and social well-being.An easy screening test for hearing loss consists of patient-reported hearing loss and a whisper test.Opportunistic screening of elderly inpatients resulted in referral of 73% of screened patients for formal audiology.Of the screened patients, 22% were provided with hearing aids.

Use of nutritional complete supplements in older adults with dementia: systematic review and meta-analysis of clinical outcomes.

BACKGROUND & AIMS: Malnutrition is prevalent in people diagnosed with dementia however ensuring adequate oral intake within this group is often problematic. It is important to determine whether providing nutritionally complete oral nutritional supplements (ONS) drinks is an effective way of improving clinical outcomes for older people with dementia. This paper systematically reviewed clinical, wellbeing and nutritional outcomes in people with long-term cognitive impairment. METHODS: The CINAHL, Medline and EMBASE databases were searched from their inception until January 2012. Reference lists of the included papers, foreign language papers and review articles obtained were manually searched. RESULTS: Twelve articles were included in the review containing 1076 people in the supplement groups (intervention) and 748 people in the control groups. Meta-analysis shows there was a significant improvement in weight (p = <0.0001), Body Mass Index (BMI) (p = <0.0001) and cognition at 6.5 ± 3.9 month follow-up (p = 0.002) when supplements were given compared to the control group. CONCLUSIONS: Providing ONS drinks has a positive effect on weight gain and cognition at follow-up in older people with dementia. Additional research is required in both comparing nutritional supplements to vitamin/mineral tablets and high protein/calorie shots and clinical outcomes relevant to people with dementia.