Marion E. T. McMurdo

Characterization of Bacterial Communities in Feces from Healthy Elderly Volunteers and Hospitalized Elderly Patients by Using Real-Time PCR and Effects of Antibiotic Treatment on the Fecal Microbiota

ABSTRACT Fecal bacteria were studied in healthy elderly volunteers (age, 63 to 90 years; n = 35) living in the local community, elderly hospitalized patients (age, 66 to 103; n = 38), and elderly hospitalized patients receiving antibiotic treatment (age, 65 to 100; n = 21). Group- and species-specific primer sets targeting 16S rRNA genes were used to quantitate intestinal bacteria by using DNA extracted from feces and real-time PCR. The principal difference between healthy elderly volunteers and both patient cohorts was a marked reduction in the Bacteroides-Prevotella group following hospitalization. Reductions in bifidobacteria, Desulfovibrio spp., Clostridium clostridiiforme, and Faecalibacterium prausnitzii were also found in the hospitalized patients. However, total 16S rRNA gene copy numbers (per gram of wet weight of feces) were generally lower in the stool samples of the two groups of hospitalized patients compared to the number in the stool samples of elderly volunteers living in the community, so the relative abundance (percentage of the group- and species-specific rRNA gene copies in relation to total bacterial rRNA gene copies) of bifidobacteria, Desulfovibrio spp., C. clostridiiforme, and F. prausnitzii did not change. Antibiotic treatment resulted in further reductions in the numbers of bacteria and their prevalence and, in some patients, complete elimination of certain bacterial communities. Conversely, the numbers of enterobacteria increased in the hospitalized patients who did not receive antibiotics, and due to profound changes in fecal microbiotas during antibiotic treatment, the opportunistic species Enterococcus faecalis proliferated.

Exercise for depression

Depression is a common and important cause of morbidity and mortality worldwide. It is commonly treated with anti depressants and/or psychological therapy, but some people prefer alternative approaches such as exercise. There are a number of theoretical reasons why exercise may improve depression.

Comparison of Compositions and Metabolic Activities of Fecal Microbiotas in Young Adults and in Antibiotic-Treated and Non-Antibiotic-Treated Elderly Subjects

ABSTRACT The colonic microbiota mediates many cellular and molecular events in the host that are important to health. These processes can be affected in the elderly, because in some individuals, the composition and metabolic activities of the microbiota change with age. Detailed characterizations of the major groups of fecal bacteria in healthy young adults, in healthy elderly people, and in hospitalized elderly patients receiving antibiotics were made in this study, together with measurements of their metabolic activities, by analysis of fecal organic acid and ammonia concentrations. The results showed that total anaerobe numbers remained relatively constant in old people; however, individual bacterial genera changed markedly with age. Reductions in numbers of bacteroides and bifidobacteria in both elderly groups were accompanied by reduced species diversity. Bifidobacterial populations in particular showed marked variations in the dominant species, with Bifidobacterium angulatum and Bifidobacterium adolescentis being frequently isolated from the elderly and Bifidobacterium longum, Bifidobacterium catenulatum, Bifidobacterium boum, and Bifidobacterium infantis being detected only from the healthy young volunteers. Reductions in amylolytic activities of bacterial isolates in healthy elderly subjects and reduced short-chain fatty acid concentrations supported these findings, since bifidobacteria and bacteroides are important saccharolytic groups in the colon. Conversely, higher numbers of proteolytic bacteria were observed with feces samples from the antibiotic-treated elderly group, which were also associated with increased proteolytic species diversity (fusobacteria, clostridia, and propionibacteria). Other differences in the intestinal ecosystem in elderly subjects were observed, with alterations in the dominant clostridial species in combination with greater numbers of facultative anaerobes.

Adapting clinical guidelines to take account of multimorbidity

Care of patients with multimorbidity could be improved if new technology is used to bring together guidelines on individual conditions and tailor advice to each patient’s circumstances, say Bruce Guthrie and colleagues

Guidelines for people not for diseases: the challenges of applying UK clinical guidelines to people with multimorbidity

BACKGROUND currently one of the major challenges facing clinical guidelines is multimorbidity. Current guidelines are not designed to consider the cumulative impact of treatment recommendations on people with several conditions, nor to allow comparison of relative benefits or risks. This is despite the fact that multimorbidity is a common phenomenon. OBJECTIVE to examine the extent to which National Institute of Health and Clinical Excellence (NICE) guidelines address patient comorbidity, patient centred care and patient compliance to treatment recommendations. METHODS five NICE clinical guidelines were selected for review (type-2 diabetes mellitus, secondary prevention for people with myocardial infarction, osteoarthritis, chronic obstructive pulmonary disease and depression) as these conditions are common causes of comorbidity and the guidelines had all been produced since 2007. Two authors extracted information from each full guideline and noted the extent to which the guidelines accounted for patient comorbidity, patient centred care and patient compliance. The cumulative recommended treatment, follow-up and self-care regime for two hypothetical patients were then created to illustrate the potential cumulative impact of applying single disease recommendations to people with multimorbidity. RESULTS comorbidity and patient adherence were inconsistently accounted for in the guidelines, ranging from extensive discussion to none at all. Patient centred care was discussed in generic terms across the guidelines with limited disease-specific recommendations for clinicians. Explicitly following guideline recommendations for our two hypothetical patients would lead to a considerable treatment burden, even when recommendations were followed for mild to moderate conditions. In addition, the follow-up and self-care regime was complex potentially presenting problems for patient compliance. CONCLUSION clinical guidelines have played an important role in improving healthcare for people with long-term conditions. However, in people with multimorbidity current guideline recommendations rapidly cumulate to drive polypharmacy, without providing guidance on how best to prioritise recommendations for individuals in whom treatment burden will sometimes be overwhelming.

Heart failure in frail elderly patients: diagnostic difficulties, co-morbidities, polypharmacy and treatment dilemmas

Heart failure (HF) is difficult to diagnose and treat in older patients. Symptoms may be non‐specific and the presence of co‐morbidities and polypharmacy complicate treatment strategies. There are, however, few data to quantify the extent of these problems in the very elderly.

Microbiological effects of consuming a synbiotic containing Bifidobacterium bifidum, Bifidobacterium lactis, and oligofructose in elderly persons, determined by real-time polymerase chain reaction and counting of viable bacteria.

BACKGROUND Because of changes in gut physiology, immune system reactivity, and diet, elderly people are more susceptible to gastrointestinal infections than are younger adults. The gut microflora, which provides a natural defense against invading microorganisms, changes in elderly people with the development of potentially damaging bacterial populations, which may lead to alterations in bacterial metabolism and higher levels of infection. METHODS A randomized, double-blind, controlled feeding trial was done with 18 healthy elderly volunteers (age, >62 years) using a synbiotic comprising Bifidobacterium bifidum BB-02 and Bifidobacterium lactis BL-01 (probiotics) together with an inulin-based prebiotic (Synergy 1; Orafti). Real-time PCR was employed to quantitate total bifidobacteria, B. bifidum, and B. lactis in fecal DNA before, during, and after synbiotic consumption. Counting all viable anaerobes, bifidobacteria, and lactobacilli and identification of bacterial isolates to species level was also done. RESULTS Throughout feeding, both bifidobacteria species were detected in fecal samples obtained from all subjects receiving the synbiotic, with significant increases in the number of copies of the 16S rRNA genes of B. bifidum, B. lactis, and total bifidobacteria, compared with the control week and the placebo group. At least 1 of these species remained detectable in fecal samples 3 weeks after feeding in individuals that had no fecal B. bifidum and/or B. lactis in the control week, indicating that the probiotics persisted in the volunteers. Counting of viable organisms showed significantly higher total numbers of fecal bifidobacteria, total numbers of lactobacilli, and numbers of B. bifidum during synbiotic feeding. CONCLUSION Synbiotic consumption increased the size and diversity of protective fecal bifidobacterial populations, which are often very much reduced in older people.

Effect of perindopril on physical function in elderly people with functional impairment: a randomized controlled trial

Background: Physical function and exercise capacity decline with age and are a major source of disability in older people. Recent evidence suggests a potential role for the renin–angiotensin system in modulating muscle function. We sought to examine the effect of the angiotensin-converting-enzyme (ACE) inhibitor perindopril on physical function in elderly people with functional impairment who had no heart failure or left ventricular systolic dysfunction. Methods: In this double-blind randomized controlled trial, participants aged 65 years and older who had problems with mobility or functional impairment were randomly assigned to receive either perindopril or placebo for 20 weeks. The primary outcome was the change in the 6-minute walking distance over the 20 weeks. Secondary outcomes were changes in muscle function, daily activity levels, self-reported function and health-related quality of life. Results: A total of 130 participants were enrolled in the study (mean age 78.7, standard deviation 7.7 years); 95 completed the trial. At 20 weeks, the mean 6-minute walking distance was significantly improved in the perindopril group relative to the placebo group (mean between-group difference 31.4 m, 95% confidence interval [CI] 10.8 to 51.9 m; p = 0.003). There was a significant impact on health-related quality of life: although the mean score for part 1 of the EQ-5D questionnaire deteriorated over time in the placebo group, quality of life was maintained in the perindopril group, for a between-group difference of 0.09 (p = 0.046). There were no significant differences between the 2 groups in the other outcomes. Interpretation: Use of the ACE inhibitor perindopril improved exercise capacity in functionally impaired elderly people who had no heart failure and maintained health-related quality of life. The degree of improvement was equivalent to that reported after 6 months of exercise training. (International Standard Randomised Controlled Trial Register no. ISRCTN67679521).

A Randomized Controlled Trial of Fall Prevention Strategies in Old Peoples’ Homes

Background: Falls are a major cause of morbidity in old age. A small number of fall prevention trials in cognitively intact community-dwelling older people have been effective. This study set out to examine the preventability of falls in older people living in institutional care. Objective: To evaluate the effectiveness of falls risk factor assessment/modification and seated balance exercise training in reducing falls among elderly people living in residential care. Methods: 133 residents with a mean age of 84± (SD) 6.8 years were allocated at random by home to receive either a 6-month falls risk factor assessment/modification and seated balance exercise training programme (n = 77) or 6 months of reminiscence therapy (n = 56). The risk factors targeted were postural hypotension, polypharmacy, visual acuity, and ambient lighting levels. Falls risk factor assessments and recommendation for modifications were performed at baseline in the intervention group and assessments repeated at 6 months. Functional reach, reaction time, timed up-and- go, grip strength, spinal flexibility, and Philadelphia Geriatric Centre Morale Scale and Mini-Mental State Examination scores were determined at baseline and at 6 months by a ‘blind’ observer. Falls and fractures were then monitored in both groups during a 7- to 12-month falls-monitoring follow-up period. Results: Only 90 of 133 (67.7%) residents completed the 6-month intervention period, and 84 (63.2%) completed the 7- to 12-month falls-monitoring follow-up period. Both prevalence of postural hypotension (p = 0.0005) and poor visual acuity (p = 0.04) were reduced in the intervention group. There was no difference between the groups in the number of falls sustained, the risk of falling [odds ratio 0.45 (95% CI 0.19–1.14)], or in the risk of recurrent falling [odds ratio 1.07 (95% CI 0.40–2.97)]. No significant differences were found between the groups with regard to change in other outcome measures. Conclusions: The high drop-out rate reduced the power of this study to detect any effect of the interventions used. It is possible that either the exercises were not sufficiently vigorous or that to improve balance exercises must be performed standing. Further research is required to identify effective fall prevention strategies for elderly people in residential settings.

Including older people in clinical research.

Benefits shown in trials in younger people may not apply to older people T here are more old people alive today than at any time in history. Older people are, quite rightly, “the core business of the NHS.”1 The need to be able to draw on the results of good quality research to inform best practice in the specific management of older people is compelling. So we might expect that researchers would have eagerly embraced the participation of older people in clinical trials. Yet this is not the case. What do clinicians and researchers have to do to redress the serious bias against older people in clinical research? The evidence that older people are being excluded from clinical research is widespread. Although the world is facing a global increase in the prevalence of diabetes mellitus, and by 2030 it is estimated that over 48 million older people in developed countries will have diabetes, the mean age of participants in the United Kingdom Progression of Diabetes Study was only 53 years. Guidelines on older people with diabetes have acknowledged …