Effect of Probiotic Use on Antibiotic Administration Among Care Home Residents: A Randomized Clinical Trial.

Importance: Probiotics are frequently used by residents in care homes (residential homes or nursing homes that provide residents with 24-hour support for personal care or nursing care), although the evidence on whether probiotics prevent infections and reduce antibiotic use in these settings is limited. Objective: To determine whether a daily oral probiotic combination of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp lactis BB-12 compared with placebo reduces antibiotic administration in care home residents. Design, Setting, and Participants: Placebo-controlled randomized clinical trial of 310 care home residents, aged 65 years and older, recruited from 23 care homes in the United Kingdom between December 2016 and May 2018, with last follow-up on October 31, 2018. Interventions: Study participants were randomized to receive a daily capsule containing a probiotic combination of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp lactis BB-12 (total cell count per capsule, 1.3 × 1010 to 1.6 × 1010) (n = 155), or daily matched placebo (n = 155), for up to 1 year. Main Outcomes and Measures: The primary outcome was cumulative antibiotic administration days for all-cause infections measured from randomization for up to 1 year. Results: Among 310 randomized care home residents (mean age, 85.3 years; 66.8% women), 195 (62.9%) remained alive and completed the trial. Participant diary data (daily data including study product use, antibiotic administration, and signs of infection) were available for 98.7% randomized to the probiotic group and 97.4% randomized to placebo. Care home residents randomized to the probiotic group had a mean of 12.9 cumulative systemic antibiotic administration days (95% CI, 0 to 18.05), and residents randomized to placebo had a mean of 12.0 days (95% CI, 0 to 16.95) (absolute difference, 0.9 days [95% CI, -3.25 to 5.05]; adjusted incidence rate ratio, 1.13 [95% CI, 0.79 to 1.63]; P = .50). A total of 120 care home residents experienced 283 adverse events (150 adverse events in the probiotic group and 133 in the placebo group). Hospitalizations accounted for 94 of the events in probiotic group and 78 events in the placebo group, and deaths accounted for 33 of the events in the probiotic group and 32 of the events in the placebo group. Conclusions and Relevance: Among care home residents in the United Kingdom, a daily dose of a probiotic combination of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp lactis BB-12 did not significantly reduce antibiotic administration for all-cause infections. These findings do not support the use of probiotics in this setting. Trial Registration: ISRCTN Identifier:16392920.

The role of biomarkers and imaging in the clinical diagnosis of dementia.

Recognition of dementia relies on a good clinical history, supported by formal cognitive testing, but identifying the subtype of dementia may be wrong in 20% or more of cases. Accuracy may be improved by use of imaging and cerebrospinal fluid (CSF) biomarkers. Structural neuroimaging is recommended for most patients, not just to identify potentially reversible surgical pathology, but also to detect vascular changes and patterns of cerebral atrophy. Functional imaging can help to confirm neurodegeneration and to distinguish dementia subtypes when structural imaging has been inconclusive. Amyloid-positron emission tomography scans reflect neuritic plaque burden and identify the earliest pathological changes in Alzheimer's disease, but their value outside research settings is still uncertain. A combination of low CSF amyloid ß1-42 and high CSF total-tau or phospho-tau also has high predictive power for AD pathology, but diagnostic usefulness decreases with age because of the increased prevalence of AD-type pathology in non-demented people. The need to use biomarkers more routinely will become necessary as disease-modifying treatments become available and accurate subtype diagnosis will be required at an early (ideally pre-dementia) stage. Clinicians should be considering the resources and expertise that will soon be needed for optimal dementia diagnosis.

Perception and Reality of Cognitive Function: Information Processing Speed, Perceived Memory Function, and Perceived Task Difficulty in Older Adults.

This study examines the relationships between two measures of information processing speed associated with executive function (Trail Making Test and a computer-based visual search test), the perceived difficulty of the tasks, and perceived memory function (measured by the Memory Functioning Questionnaire) in older adults (aged 50+ y) with normal general health, cognition (Montreal Cognitive Assessment score of 26+), and mood. The participants were recruited from the community rather than through clinical services, and none had ever sought or received help from a health professional for a memory complaint or mental health problem. For both the trail making and the visual search tests, mean information processing speed was not correlated significantly with perceived memory function. Some individuals did, however, reveal substantially slower information processing speeds (outliers) that may have clinical significance and indicate those who may benefit most from further assessment and follow up. For the trail making, but not the visual search task, higher levels of subjective memory dysfunction were associated with a greater perception of task difficulty. The relationship between actual information processing speed and perceived task difficulty also varied with respect to the task used. These findings highlight the importance of taking into account the type of task and metacognition factors when examining the integrity of information processing speed in older adults, particularly as this measure is now specifically cited as a key cognitive subdomain within the diagnostic framework for neurocognitive disorders.

An evaluation of the effectiveness of a multi-modal intervention in frail and pre-frail older people with type 2 diabetes--the MID-Frail study: study protocol for a randomised controlled trial.

BACKGROUND: Diabetes, a highly prevalent, chronic disease, is associated with increasing frailty and functional decline in older people, with concomitant personal, social, and public health implications. We describe the rationale and methods of the multi-modal intervention in diabetes in frailty (MID-Frail) study. METHODS/DESIGN: The MID-Frail study is an open, randomised, multicentre study, with random allocation by clusters (each trial site) to a usual care group or an intervention group. A total of 1,718 subjects will be randomised with each site enrolling on average 14 or 15 subjects. The primary objective of the study is to evaluate, in comparison with usual clinical practice, the effectiveness of a multi-modal intervention (specific clinical targets, education, diet, and resistance training exercise) in frail and pre-frail subjects aged ≥70 years with type 2 diabetes in terms of the difference in function 2 years post-randomisation. Difference in function will be measured by changes in a summary ordinal score on the short physical performance battery (SPPB) of at least one point. Secondary outcomes include daily activities, economic evaluation, and quality of life. DISCUSSION: The MID-Frail study will provide evidence on the clinical, functional, social, and economic impact of a multi-modal approach in frail and pre-frail older people with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01654341.

The impact of frailty and delirium on mortality in older inpatients.

BACKGROUND: delirium and frailty are common among hospitalised older people but delirium is often missed and frailty considered difficult to measure in clinical practice. OBJECTIVE: to explore the relationship between delirium and frailty in older inpatients and determine their impact on survival. DESIGN AND SETTING: the prospective cohort study of 273 patients aged ≥75 years. MEASURES: patients were screened for delirium at presentation and on alternate days throughout their hospital stay. Frailty status was measured by an index of accumulated deficits (FI), giving a potential score from 0 (no deficits) to 1.0 (all 33 deficits), with 0.25 used as the cut-off between 'fit' and 'frail'. RESULTS: delirium was detected in 102 patients (mean FI: 0.33) and excluded in 171 (mean FI: 0.18) (P < 0.005); 111 patients were frail. Among patients with delirium, the median survival in fit patients was 359 days (95% CI: 118-600) compared with 88 days for those who were frail (95% CI: 5-171; P < 0.05). CONCLUSION: delirium was associated with higher levels of frailty: the identification of frail patients may help to target those at a greatest risk of delirium. Survival following delirium was poor with the combination of frailty and delirium conferring a particularly bleak prognosis.

Visual search in mild cognitive impairment: a longitudinal study.

In the study of Alzheimer's disease, a multidisciplinary research approach has identified significant abnormality in several areas of visual and visual attention-related brain function in addition to those typically measured as part of clinical diagnosis. This raises the possibility that a similar approach applied to amnestic mild cognitive impairment (aMCI) will increase our understanding of its theoretical and clinical constructs, particularly if functions whose integrity is heterogeneous with respect to etiological outcome can be found. In this study we examined visual search performance (the brain's ability to search effectively throughout the environment for a particular object) in aMCI compared to healthy aging. Cross-sectionally, visual search performance in aMCI was significantly poorer than in healthy aging, with greater intra-group performance heterogeneity in the aMCI compared to the healthy older adult group. This outcome illustrates that although individuals within an aMCI group ostensibly have the same condition they can differ substantially with respect to the integrity of aspects of brain function. Such findings may have implications for the clinical management of the individual patient. The results from the longitudinal aspect of this study also illustrate how heterogeneity in the performance of brain operations other than memory in aMCI may help to inform the likelihood of their developing dementia, as those patients who were diagnosed with dementia within 2.5 years of baseline measurement showed significantly poorer visual search performance compared to those who did not.

Sleep disturbance and daytime sleepiness predict vascular dementia.

BACKGROUND: Disturbed sleep is common throughout the community and is associated with an increase in daytime sleepiness, both of which, in turn are associated with an increased risk of ischaemic vascular disease. The hypothesis that sleep disturbances are predictive of dementia, and in particular vascular dementia was tested in a large community-based cohort of older men. METHODS: A questionnaire on sleep disturbances was administered to 1986 men aged 55-69 years in the Caerphilly Cohort Study and 10 years later the men were examined clinically for evidence of dementia or cognitive impairment with no dementia (CIND). FINDINGS: Approximately 20% of the men reported disturbed sleep and 30% reported 'severe' daytime sleepiness. Ten years later 1,225 men (75% of the surviving men in the cohort) were tested and 268 (22%) were found to be cognitively impaired with 93 (7.6%) showing clear evidence of dementia and the remaining 175 (14.3%) showing evidence of CIND. After adjustment for possible confounding, including cognitive function and the taking of sleeping tablets at baseline, sleep disturbances appeared to be predictive of dementia and CIND of vascular origin, while there was no suggestion of prediction of non-vascular cognitive impairment by sleep. Prediction of vascular dementia appeared to be particularly strong for daytime sleepiness, with an adjusted OR of 4.44 (95% CI 2.05 to 9.61). Further adjustments for psychological distress at baseline reduced the size of the relationships, but the ORs remain large, consistent with a direct positive effect of sleep disturbance on vascular dementia. INTERPRETATION: Sleep disturbances, and in particular severe daytime sleepiness, appear to be strongly predictive of vascular dementia, but have no predictive power for non vascular dementia.

Hospital use, institutionalisation and mortality associated with delirium.

BACKGROUND: Delirium is a disorder affecting consciousness, which gives rise to core clinical features and associated symptoms. Older patients are particularly prone, owing to higher rates of pre-existing cognitive impairment, frailty, co-morbidity and polypharmacy. OBJECTIVES: The aim of this study was to investigate the hypotheses that delirium affects the most vulnerable older adults and is associated with long-term adverse health outcome. METHODS: This prospective cohort study evaluated 278 medical patients aged > or = 75 years admitted acutely to a district general hospital in South Wales. Patients were screened for delirium at presentation and on alternate days throughout their hospital stay. Assessments also included illness severity, preadmission cognition, co-morbidity and functional status. Patients were followed for 5 years to determine rates of institutionalisation and mortality. Number of days in hospital in the 4 years prior to and 5 years after index admission were recorded. RESULTS: Delirium was detected in 103 patients and excluded in 175. Median time to death was 162 days (interquartile range 21-556) for those with delirium compared with 1,444 days (25% mortality 435 days, 75% mortality>5 years) for those without (P < 0.001). After adjusting for multiple confounders, delirium was associated with an increased risk of death (hazard ratio range 2.0-3.5; P < or = 0.002). Institutionalisation was higher in the first year following delirium (P = 0.03). While those with delirium tended to be older with more preadmission cognitive impairment, greater functional dependency and more co-morbidity, they did not spend more days in hospital in the 4 years prior to index admission. CONCLUSIONS: Delirium is associated with high rates of institutionalisation and an increased risk of death up to 5 years after index event. Prior to delirium, individuals seem to compensate for their vulnerability. The impact of delirium itself, directly or indirectly, may convert vulnerability into adverse outcome.

Impact of diabetes on physical function in older people.

OBJECTIVE: To explore the nature of functional impairment in older people with diabetes. RESEARCH DESIGN AND METHODS: A population-based case-control study with detailed assessment of diabetes and functional status was undertaken. RESULTS: Altogether, 403 case subjects and 403 matched control subjects were studied (median age 75 years, 51% female). Subjects with diabetes had more comorbidities than control subjects (mean 2.5 vs. 1.9, P < 0.0001) and were more likely to have severe functional impairment (4 vs. 1%, Barthel score <5, P < 0.001). Health status pertaining to physical function was reduced in case subjects (SF36 60 vs. 40, P < 0.0001). In a multivariate model controlling for age, hypertension, cerebrovascular disease, chronic obstructive pulmonary disease, cancer, osteoarthritis, and dementia, diabetes remained significantly associated with mobility limitation (odds ratio 2.1, P < 0.001). CONCLUSIONS: Older people with diabetes have considerable functional impairment associated with reduced health status. This population may benefit from comprehensive geriatric assessment and tailored diabetes management.

ApoE gene and familial risk of Alzheimer's disease as predictors of odour identification in older adults.

The study examined odour identification ability in healthy older adults at increased risk for developing Alzheimer's disease (AD). We recruited a sample (n = 24) of siblings related to probable AD cases and an age-matched control sample (n = 47). All participants were genotyped for the presence of the ApoE epsilon4 allele. Performance on a simple olfactory task of odour identification was compared according to positive family history of AD and ApoE epsilon4 status. The sibling group showed an odour identification deficit compared to the control group. Whilst there was no independent influence of ApoE epsilon4 status on odour identification, there was a significant interaction between positive family history and ApoE epsilon4 status. Sibling epsilon4 carriers showed the greatest odour identification deficit and their performance was significantly poorer than both the sibling non-epsilon4 carrier and control epsilon4 carrier groups. Odour identification deficits like those reported here are considered to be early cognitive markers of incipient AD. In this respect, these findings support the need to both monitor individuals at increased risk of the disease and introduce olfactory-mediated cognitive tasks into the diagnostic setting.

Post-discharge home-based support for older cardiac patients: a randomised controlled trial.

BACKGROUND: Hospital and exercise-based cardiac rehabilitation programmes do not suit many older patients and home-based rehabilitation may be more effective. OBJECTIVE: To evaluate a home-based intervention for patients aged 65 years or over discharged home from hospital after emergency admission for suspected myocardial infarction. DESIGN: A single-blind randomised controlled trial comparing home-based intervention by a nurse with usual care. SUBJECTS: Patients aged 65 years or over discharged home after hospitalisation with suspected myocardial infarction (n= 324). INTERVENTION: Home-based intervention (n = 163) consisted of home visits at 1-2 and 6-8 weeks after hospital discharge by a nurse who encouraged compliance with and knowledge of their treatment regimen, offered support and guidance about resuming daily activities, and involved other community services as appropriate. MEASUREMENTS: Up to 100 days after admission, data were collected on deaths, hospital readmissions and use of outpatient services. Survivors were sent a postal questionnaire to assess activities of daily living and quality of life. RESULTS: At 100 day follow-up there was no difference in deaths, activities of daily living or overall quality of life, but those in the intervention group scored significantly better on the confidence and self-esteem subsections. The intervention group had fewer hospital readmissions (35 versus 51, relative risk 0.68, 95% CI 0.47-0.98, P < 0.05) and fewer days of hospitalisation after initial discharge (mean difference -1.7, 95% CI -2.09 to -1.31, P < 0.05). A total of 42/43 individuals in the intervention group had resumed driving at follow-up, compared with 32/43 in the usual care group (observed difference between proportions 23%, 95% CI 9-37%, P < 0.05). CONCLUSION: Amongst older patients discharged home after hospitalisation for suspected myocardial infarction, home-based nurse intervention may improve confidence and self-esteem, and reduce early hospital readmissions.