Bridging the age gap in breast cancer: impact of omission of breast cancer surgery in older women with oestrogen receptor-positive early breast cancer on quality-of-life outcomes.

BACKGROUND: Primary endocrine therapy may be an alternative treatment for less fit women with oestrogen receptor (ER)-positive breast cancer. This study compared quality-of-life (QoL) outcomes in older women treated with surgery or primary endocrine therapy. METHODS: This was a multicentre, prospective, observational cohort study of surgery or primary endocrine therapy in women aged over 70 years with operable breast cancer. QoL was assessed using European Organisation for Research and Treatment of cancer QoL questionnaires QLQ-C30, -BR23, and -ELD14, and the EuroQol Five Dimensions 5L score at baseline, 6 weeks, and 6, 12, 18, and 24 months. Propensity score matching was used to adjust for baseline variation in health, fitness, and tumour stage. RESULTS: The study recruited 3416 women (median age 77 (range 69-102) years) from 56 breast units. Of these, 2979 (87.2 per cent) had ER-positive breast cancer; 2354 women had surgery and 500 received primary endocrine therapy (125 were excluded from analysis due to inadequate data or non-standard therapy). Median follow-up was 52 months. The primary endocrine therapy group was older and less fit. Baseline QoL differed between the groups; the mean(s.d.) QLQ-C30 global health status score was 66.2(21.1) in patients who received primary endocrine therapy versus 77.1(17.8) among those who had surgery plus endocrine therapy. In the unmatched analysis, changes in QoL between 6 weeks and baseline were noted in several domains, but by 24 months most scores had returned to baseline levels. In the matched analysis, major surgery (mastectomy or axillary clearance) had a more pronounced adverse impact than primary endocrine therapy in several domains. CONCLUSION: Adverse effects on QoL are seen in the first few months after surgery, but by 24 months these have largely resolved. Women considering surgery should be informed of these effects.

Bridging the age gap in breast cancer: cluster randomized trial of two decision support interventions for older women with operable breast cancer on quality of life, survival, decision quality, and treatment choices.

BACKGROUND: Rates of surgery and adjuvant therapy for breast cancer vary widely between breast units. This may contribute to differences in survival. This cluster RCT evaluated the impact of decision support interventions (DESIs) for older women with breast cancer, to ascertain whether DESIs influenced quality of life, survival, decision quality, and treatment choice. METHODS: A multicentre cluster RCT compared the use of two DESIs against usual care in treatment decision-making in older women (aged at least ≥70 years) with breast cancer. Each DESI comprised an online algorithm, booklet, and brief decision aid to inform choices between surgery plus adjuvant endocrine therapy versus primary endocrine therapy, and adjuvant chemotherapy versus no chemotherapy. The primary outcome was quality of life. Secondary outcomes included decision quality measures, survival, and treatment choice. RESULTS: A total of 46 breast units were randomized (21 intervention, 25 usual care), recruiting 1339 women (670 intervention, 669 usual care). There was no significant difference in global quality of life at 6 months after the baseline assessment on intention-to-treat analysis (difference -0.20, 95 per cent confidence interval (C.I.) -2.69 to 2.29; P = 0.900). In women offered a choice of primary endocrine therapy versus surgery plus endocrine therapy, knowledge about treatments was greater in the intervention arm (94 versus 74 per cent; P = 0.003). Treatment choice was altered, with a primary endocrine therapy rate among women with oestrogen receptor-positive disease of 21.0 per cent in the intervention versus 15.4 per cent in usual-care sites (difference 5.5 (95 per cent C.I. 1.1 to 10.0) per cent; P = 0.029). The chemotherapy rate was 10.3 per cent at intervention versus 14.8 per cent at usual-care sites (difference -4.5 (C.I. -8.0 to 0) per cent; P = 0.013). Survival was similar in both arms. CONCLUSION: The use of DESIs in older women increases knowledge of breast cancer treatment options, facilitates shared decision-making, and alters treatment selection. Trial registration numbers: EudraCT 2015-004220-61 (https://eudract.ema.europa.eu/), ISRCTN46099296 (http://www.controlled-trials.com).

Potential sources of mouth drying in beverages fortified with dairy proteins: A comparison of casein- and whey-rich ingredients.

Oral nutritional supplement drinks (ONS) are beverages high in dairy proteins that are prescribed to individuals at risk of malnutrition. Consumption of ONS is poor in elderly care facilities, with patients commenting that the sensory attributes of these drinks reduce their enjoyment and willingness to consume. Mouth drying is an attribute of ONS found to build with repeated consumption, which may further limit liking of these products. This study investigated the sources of drying sensations by sequential profiling, with a trained sensory panel rating a range of model milk systems and ONS over repeated sips and during after-effects. Sequential profiling found that fortification of milk with both caseinate and whey protein concentrate significantly increased the perception of mouth drying over repeated consumption, increasing by between 35 and 85% over consumption of 40mL. Enrichment of ONS with either whey protein concentrate or milk protein concentrate to a total protein content of 8.7% (wt/wt) resulted in whey and casein levels of 4.3:4.4% and 1.7:7.0% respectively. The product higher in whey protein was substantially more mouth drying, implying that whey proteins may be the most important contributor to mouth drying in ONS. However, efforts to mask mouth drying of protein-fortified milk by increasing sweetness or fat level were unsuccessful at the levels tested. Increasing the viscosity of protein-fortified milk led to a small but significant reduction in mouth drying. However, this approach was not successful when tested within complete ONS. Further analysis is required into the mechanism of protein-derived mouth drying to mask negative sensations and improve the enjoyment and consumption of protein-rich ONS.

Adjuvant chemotherapy in older women (ACTION) study - what did we learn from the pilot phase?

BACKGROUND: The ACTION trial was initiated to provide evidence from a randomised trial on the effects of chemotherapy in women aged over 70 years where evidence for risk and benefit are lacking. METHODS: This was a randomised, phase III clinical trial for high risk, oestrogen receptor (ER) negative/ER weakly positive early breast cancer. The trial planned to recruit 1000 women aged 70 years and older, randomised to receive 4 cycles of anthracycline chemotherapy or observation. The primary endpoint was relapse-free interval. The trial included a pilot phase to assess the acceptability and feasibility of recruitment. RESULTS: The trial opened at 43 UK centres. Information on number of patients approached was available from 38 centres. Of the 43 eligible patients that were approached, 39 were not randomised due to patients declining entry. After 10 months only 4 patients had been randomised and after discussion with the research funder, the trial was closed and funding terminated. CONCLUSION: Despite widespread support at several public meetings, input from patient groups including representation on the Trial Management Group, the trial failed to recruit due to the inability to convince patients to accept randomisation. It would therefore seem that randomising the patients to receive chemotherapy vs observation is not a viable design in the current era for this patient population.

Treatment of the elderly colorectal cancer patient: SIOG expert recommendations.

Colorectal cancer (CRC) is one of the commonest malignancies of Western countries, with approximately half the incidence occurring in patients >70 years of age. Elderly CRC patients, however, are understaged, undertreated and underrepresented in clinical trials. The International Society of Geriatric Oncology created a task force with a view to assessing the potential for developing guidelines for the treatment of elderly (geriatric) CRC patients. A review of the evidence presented by the task force members confirmed the paucity of clinical trial data in elderly people and the lack of evidence-based guidelines. However, recommendations have been proposed on the basis of the available data and on the emerging evidence that treatment outcomes for fit, elderly CRC patients can be similar to those of younger patients. It is hoped that these will pave the way for formal treatment guidelines based upon solid scientific evidence in the future.

General care of the older cancer patient.

With increasing age, there are greater numbers of older people who will be diagnosed with cancer. It must be remembered that such individuals have increased frailty and have a number of geriatric syndromes and conditions particularly pertinent to older age, including incontinence, poor cognition and impaired nutrition. It is often difficult to define the effects of cancer and its treatment or complications, and separate these from the effects of normal ageing and geriatric syndromes. The documentation of poor nutrition and its management must combine knowledge from both geriatric medicine and oncology. Nutrition serves to identify key healthcare professionals who are all essential in any patient at risk or suffering from malnutrition. Incontinence must be actively sought, its cause identified and efforts made to either 'cure' it or, in certain circumstances, 'manage' it. Older patients with cancer are cared for predominantly by older relations and informal care mechanisms and special consideration of their physical and practical needs are paramount. In this area, nurses, doctors, therapists and social workers should work to identify formal and informal mechanisms to support particularly the older carer.

Effect of micronutrient supplementation on mood in nursing home residents.

One third of older people in nursing and/or residential homes have significant symptoms of depression. In younger people, deficiencies in selenium, vitamin C and folate are associated with depression. This study examines the association between micronutrient status and mood before and after supplementation. The objective was to determine whether the administration of selenium, vitamin C and folate improved mood in frail elderly nursing home residents. Mood was assessed using the Hospital Anxiety and Depression rating scale (HAD), and Montgomery-Asberg Depression Rating Scale (MADRS). Micronutrient supplementation was provided for 8 weeks in a double-blinded randomised controlled trial. Significant symptoms of depression (29%) and anxiety (24%) were found at baseline. 67% of patients had low serum concentrations of vitamin C, but no-one was below the reference range for selenium. Depression was significantly associated with selenium levels, but not with folate or vitamin C levels. No individual with a HAD depression score of >or=8, had selenium levels >1.2 microM. In those patients with higher HAD depression scores, there was a significant reduction in the score and a significant increase in serum selenium levels after 8 weeks of micronutrient supplementation. Placebo group scores were unchanged. This small study concluded that depression was associated with low levels of selenium in frail older individuals. Following 8 weeks of micronutrient supplementation, there was a significant increase in selenium levels and improved symptoms of depression occurred in a subgroup.

The knowledge of healthcare professionals regarding elderly persons' oral care.

OBJECTIVE: The aim of this study was to compare the knowledge and views of nursing staff on both acute elderly care and rehabilitation wards regarding elderly persons' oral care with that of carers in nursing homes. SUBJECTS: One hundred nurses working on acute, sub-acute and rehabilitation wards for elderly people (Group 1) and 75 carers in nursing homes (Group 2) were surveyed. DESIGN: A semi-structured questionnaire. RESULTS: Similar percentages of each group of nurses were registered with a dentist (86% and 88% respectively), although more hospital-based nurses were anxious about dental treatment compared with the nursing home group (40% and 28% respectively). More carers in nursing homes gave regular advice about oral care than the hospital-based nurses (54% and 43% respectively). Eighteen per cent of each group thought that edentulous individuals did not require regular oral care. Eighty-five per cent of hospital-based nurses and 95% of nursing home carers incorrectly thought that dentures were 'free' on the NHS. Although trends were observed between the two groups, no comparisons were statistically significant (Chi-square; level p < 0.05). CONCLUSIONS: Deficiencies exist in the knowledge of health care workers both in hospital and in the community setting, although the latter were less knowledgeable but more likely to give advice to older people.

Over-expression of p53-protein and cigarette-smoking in bronchial-carcinoma.

A recessive gene on chromosome 17 encodes a protein, known as p53, which normally acts to regulate the cell cycle, its mutation and over-expression being amongst the commonest genetic abnormalities in human malignant neoplasms. As detected by immunolabelling using the anti-p53 protein antibodies PAb1801, DO7 and CM1, over-expression was demonstrable in 13 of 59 tissue biopsy specimens from a series of patients with newly-diagnosed primary bronchial carcinoma from whom accurate data on smoking history had been obtained prior to bronchoscopy. There was a statistically significant relationship between over-expression and total exposure to cigarette smoke (p53-positive, median 46 pack-years; p53-negative, median 32 pack-years; P<0.001) and between over-expression and intensity of exposure (p53-positive, median 20 cigarettes/day; p-53 negative, median 14 cigarettes/day; P<0.001), but no difference between the two groups in terms of total duration of this exposure (p53-positive, median 47 y; p53-negative, median 46 y). These data confirm findings of previous studies suggesting a possible link between cigarette smoke and those derangements of the structure or function of the p53-encoding gene which lead to its over-expression by malignant bronchial tumours. They support, in addition, a specific mutagenic role for the chemical carcinogens it contains. Over-expression of p53 did not appear to influence survival.

Assessing attentiveness in older hospital patients: global assessment versus tests of attention.

OBJECTIVES: Impairment of attentiveness is a cardinal symptom of delirium. We examined the relationship between bedside tests of attention and a global rating of attentiveness in older hospital patients and sought to identify cut-off points on the tests of attention that might be helpful in the diagnosis of delirium. SETTING AND PARTICIPANTS: Subjects were 110 patients admitted to an acute geriatric unit. MEASUREMENTS: Subjects were assessed by two physicians. One physician rated global attentiveness on a 10-cm visual analog scale following general conversation with the patient. The second physician determined whether patients met DSM-3 criteria for delirium or dementia and administered four tests of attentiveness: Digit Span Forwards (DSF), Digit Span Backwards (DSB), Vigilance "A' test (VAT), and a timed Digit Cancellation Test (DCT). MAIN RESULTS: Of the 87 patients who completed the study, 18 were delirious and 17 demented. There was no difference between demented and delirious patients on the VAT, DSF, or MMSE tests; other comparisons between demented and delirious patients and between delirious patients and those with neither delirium nor dementia were significant. All tests of attention except DSF were significantly correlated with the global rating. CONCLUSION: Simple bedside tests of attention can aid identification of delirium.

Orthostatic hypotension and vasodilatory peptides in bronchial carcinoma.

AIM: To determine whether inappropriately secreted vasodilatory peptides have a role in the pathogenesis of orthostatic (postural) hypotension, a recognised paraneoplastic effect of bronchial malignancies usually attributed to immune mediated destruction of autonomic ganglia. METHODS: Serum concentrations of three vasodilatory peptides, atrial natriuretic peptide (ANP), vasoactive intestinal polypeptide (VIP) and calcitonin gene related peptide (CGRP), were measured in 111 patients with bronchial carcinoma and 35 controls prospectively screened for orthostatic hypotension (> 20 mmHg drop in systolic blood pressure on repeated occasions on standing from the supine position) and in whom other causes of this condition were excluded. RESULTS: Twenty two (20%) patients with carcinoma and two (6%) controls had orthostatic hypotension according to the criteria used. Serum concentrations of ANP, VIP and CGRP were elevated above normal in, respectively, 25 (23%), 10 (9%) and eight (7%) patients with carcinoma and in six (18%), zero and three (9%) controls. There was no correlation between orthostatic hypotension and concentrations of any of the vasodilatory peptides. CONCLUSION: Elevated serum concentrations of ANP and CGRP were no more frequent in subjects with bronchial carcinoma than in controls and could not be attributed to the tumour, although there was a possible association for VIP. Orthostatic hypotension was more common in patients with carcinoma, but there was no evidence that the peptides measured played a role in its pathogenesis.

Exposure to cigarette smoke and expression of the protein encoded by the p53 gene in bronchial carcinoma.

Mutation of the onco-suppressor gene encoding the protein known as p53 may cause synthesis of a mutant p53 protein which can bind to and inactivate its wild-type equivalent. This protein is detectable in many malignant neoplasms, including bronchial carcinoma, and has been associated with cigarette smoking. Of 59 tissue biopsy specimens of primary bronchial malignancies immunolabeled for p53 by the avidin-biotin technique using the antibodies PAb 1801, CM1, and D07, 13 (22%) expressed the protein. Of these 13 patients, 10 (77%) smoked more than 20 cigarettes a day and their mean total exposure was 53 pack-years. Corresponding figures for those with p53-negative tumors were 21 (46%) smoking more than 20 cigarettes a day with a mean total exposure of 36 pack-years. There was, however, no difference between the groups in total duration of exposure (46 vs. 47 years). Although p53 was expressed more commonly in adenocarcinoma (30% of 10) and squamous carcinoma (28% of 29) than in small cell tumors (10% of 20), this could be accounted for by the smoking history. This study supports a relationship between mutations of the p53-encoding gene associated with overexpression of its protein product and intensity of exposure to cigarette smoke.

Cost-benefit evaluation of routine influenza immunisation in people 65-74 years of age.

OBJECTIVES: To determine the cost-effectiveness of influenza vaccination in people aged 65-74 years in the absence of co-morbidity. DESIGN: Primary research: randomised controlled trial. SETTING: Primary care. PARTICIPANTS: People without risk factors for influenza or contraindications to vaccination were identified from 20 general practitioner (GP) practices in Liverpool in September 1999 and invited to participate in the study. There were 5875/9727 (60.4%) people aged 65-74 years identified as potentially eligible and, of these, 729 (12%) were randomised. INTERVENTION: Participants were randomised to receive either influenza vaccine or placebo (ratio 3:1), with all individuals receiving pneumococcal vaccine unless administered in the previous 10 years. Of the 729 people randomised, 552 received vaccine and 177 received placebo; 726 individuals were administered pneumococcal vaccine. MAIN OUTCOME MEASURES AND METHODOLOGY OF ECONOMIC EVALUATION: GP attendance with influenza-like illness (ILI) or pneumonia (primary outcome measure); or any respiratory symptoms; hospitalisation with a respiratory illness; death; participant self-reported ILI; quality of life (QoL) measures at 2, 4 and 6 months post-study vaccination; adverse reactions 3 days after vaccination. A cost-effectiveness analysis was undertaken to identify the incremental cost associated with the avoidance of episodes of influenza in the vaccination population and an impact model was used to extrapolate the cost-effectiveness results obtained from the trial to assess their generalisability throughout the NHS. RESULTS: In England and Wales, weekly consultations for influenza and ILI remained at baseline levels (less than 50 per 100,000 population) until week 50/1999 and then increased rapidly, peaking during week 2/2000 with a rate of 231/100,000. This rate fell within the range of 'higher than expected seasonal activity' of 200-400/100,000. Rates then quickly declined, returning to baseline levels by week 5/2000. The predominant circulating strain during this period was influenza A (H3N2). Five (0.9%) people in the vaccine group were diagnosed by their GP with an ILI compared to two (1.1%) in the placebo group [relative risk (RR), 0.8; 95% confidence interval (CI) = 0.16 to 4.1]. No participants were diagnosed with pneumonia by their GP and there were no hospitalisations for respiratory illness in either group. Significantly fewer vaccinated individuals self-reported a single ILI (4.6% vs 8.9%, RR, 0.51; 95% CI for RR, 0.28 to 0.96). There was no significant difference in any of the QoL measurements over time between the two groups. Reported systemic side-effects showed no significant differences between groups. Local side-effects occurred with a significantly increased incidence in the vaccine group (11.3% vs 5.1%, p = 0.02). Each GP consultation avoided by vaccination was estimated from trial data to generate a net NHS cost of 174 pounds. CONCLUSIONS: No difference was seen between groups for the primary outcome measure, although the trial was underpowered to demonstrate a true difference. Vaccination had no significant effect on any of the QoL measures used, although vaccinated individuals were less likely to self-report ILI. The analysis did not suggest that influenza vaccination in healthy people aged 65-74 years would lead to lower NHS costs. Future research should look at ways to maximise vaccine uptake in people at greatest risk from influenza and also the level of vaccine protection afforded to people from different age and socio-economic populations.

c-myc oncoprotein in bronchial carcinoma: expression in all major morphological types.

We have studied the prevalence of a 62 kd protein product of the c-myc oncogene in tissue biopsies from 79 primary bronchial carcinomata using the monoclonal antibody Myc 1-9E10 and the avidin-biotin complex (ABC) technique. This oncoprotein was strongly expressed in 43% of 37 squamous lesions, 29% of 14 adenocarcinomata, 42% of 7 non-small cell lesions not further classifiable and 19% of 21 small cell neoplasms, all of classical morphology. There was no statistical difference between groups in the prevalence of its expression, nor was it related to survival. This oncoprotein is commonly expressed in non-small cell as well as small cell bronchial carcinomata and, in the latter, is not confined to those variant tumours which possess a "large cell" morphology and carry a poor prognosis.

Pseudomonas aeruginosa septicaemia from an oral source.

Oral colonisation with aerobic Gram-negative bacilli (AGNB) is abnormal and usually indicates a medically compromised state in the host. It has been postulated that oral colonisation with AGNB may predispose a patient to serious systemic infection, but proof of this assertion is lacking. This report describes an elderly patient who had oral colonisation of Pseudomonas aeruginosa and developed septicaemia from an identical strain of this bacterium.

Murmurs, infective endocarditis and dentistry.

Patients with cardiac murmurs may have a predisposition to infective endocarditis, and the dental practitioner must be aware of this potential problem. This article reviews cardiac murmurs and how they are investigated by physicians to assess their significance. Practical advice is offered concerning the need to refer patients with a suspected heart murmur. The emergency and elective dental management of patients with heart murmurs is included, together with recommended regimens for antibiotic prophylaxis.

The influence of nutritional supplement drinks on providing adequate calorie and protein intake in older adults with dementia.

OBJECTIVES: Investigate the impact of the provision of ONS on protein and energy intake from food and ability to meet protein and calorie requirements in people with dementia. DESIGN: After consent by proxy was obtained, participants took part in a cross over study comparing oral intake on an intervention day to an adjacent control day. SETTING: The study occurred in Nursing homes and hospitalised settings. PARTICIPANTS: Older adults with dementia over the age of 65 were recruited. 26 participants (aged 83.9+/-8.4years, MMSE 13.08+/-8.13) took part. Intervention (if any): On the intervention day nutritional supplement drinks were provided three times. Each drink provided 283.3+/-41.8 Kcal of energy and 13.8+/-4.7g of protein. Supplements were removed approximately 1 hour before meals were served and weighed waste (g) was obtained. MEASUREMENTS: Intake of food consumed was determined on intervention and control days using the quartile method (none, quarter, half, three quarters, all) for each meal component. RESULTS: More people achieved their energy and protein requirements with the supplement drink intervention with no sufficient impact on habitual food consumption. CONCLUSION: Findings from these 26 participants with dementia indicate that supplement drinks may be beneficial in reducing the prevalence of malnutrition within the group as more people meet their nutritional requirements. As the provision of supplement drinks is also demonstrated to have an additive effect to consumption of habitual foods these can be used alongside other measures to also improve oral intake.

Psychosocial impact of visual impairment in working-age adults.

AIM: To review the evidence for the presence of lower levels of psychosocial well-being in working-age adults with visual impairment and for interventions to improve such levels of psychosocial well-being. METHODS: Systematic review of quantitative studies published in English from 2001 to July 2008 that measured depression/mental health, anxiety, quality of life, social functioning or social support. RESULTS: Included were 29 studies that measured one or more outcomes (N = 52). Working-age adults with visual impairment were significantly more likely to report lower levels of mental health (mean difference = 14.51/100), social functioning (MD = 11.55/100) and quality of life. Studies regarding the prevalence of depressive symptoms produced inconsistent results but had methodological limitations. CONCLUSIONS: Future research is required into the prevalence of loneliness, anxiety and depression in adults with visual impairment, and to evaluate the effectiveness of interventions for improving psychosocial well-being such as counselling, peer support and employment programmes.