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Probiotics reduce self-reported symptoms of upper respiratory tract infection in overweight and obese adults: should we be considering probiotics during viral pandemics?
Mullish, BH, Marchesi, JR, McDonald, JAK, Pass, DA, Masetti, G, Michael, DR, Plummer, S, Jack, AA, Davies, TS, Hughes, TR, et al
Gut microbes. 2021;(1):1-9
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Abstract
Gut microbiome manipulation to alter the gut-lung axis may potentially protect humans against respiratory infections, and clinical trials of probiotics show promise in this regard in healthy adults and children. However, comparable studies are lacking in overweight/obese people, who have increased risks in particular of viral upper respiratory tract infections (URTI). This Addendum further analyses our recent placebo-controlled trial of probiotics in overweight/obese people (focused initially on weight loss) to investigate the impact of probiotics upon the occurrence of URTI symptoms. As well as undergoing loss of weight and improvement in certain metabolic parameters, study participants taking probiotics experienced a 27% reduction in URTI symptoms versus control, with those ≥45 years or BMI ≥30 kg/m2 experiencing greater reductions. This symptom reduction is apparent within 2 weeks of probiotic use. Gut microbiome diversity remained stable throughout the study in probiotic-treated participants. Our data provide support for further trials to assess the potential role of probiotics in preventing viral URTI (and possibly also COVID-19), particularly in overweight/obese people.
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Long term extension of a randomised controlled trial of probiotics using electronic health records.
Davies, G, Jordan, S, Brooks, CJ, Thayer, D, Storey, M, Morgan, G, Allen, S, Garaiova, I, Plummer, S, Gravenor, M
Scientific reports. 2018;(1):7668
Abstract
Most randomised controlled trials (RCTs) are relatively short term and, due to costs and available resources, have limited opportunity to be re-visited or extended. There is no guarantee that effects of treatments remain unchanged beyond the study. Here, we illustrate the feasibility, benefits and cost-effectiveness of enriching standard trial design with electronic follow up. We completed a 5-year electronic follow up of a RCT investigating the impact of probiotics on asthma and eczema in children born 2005-2007, with traditional fieldwork follow up to two years. Participants and trial outcomes were identified and analysed after five years using secure, routine, anonymised, person-based electronic health service databanks. At two years, we identified 93% of participants and compared fieldwork with electronic health records, highlighting areas of agreement and disagreement. Retention of children from lower socio-economic groups was improved, reducing volunteer bias. At 5 years we identified a reduced 82% of participants. These data allowed the trial's first robust analysis of asthma endpoints. We found no indication that probiotic supplementation to pregnant mothers and infants protected against asthma or eczema at 5 years. Continued longer-term follow up is technically straightforward.
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Evaluation of a "Just-in-Time" Nurse Consultation on Bone Health: A Pilot Randomized Controlled Trial.
Roblin, DW, Zelman, D, Plummer, S, Robinson, BE, Lou, Y, Edmonds, SW, Wolinsky, FD, Saag, KG, Cram, P
The Permanente journal. 2017;:16-112
Abstract
CONTEXT Evidence is inconclusive whether a nurse consultation can improve osteoporosis-related patient outcomes. OBJECTIVE To evaluate whether a nurse consultation immediately after dual-energy x-ray absorptiometry (DXA) produced better osteoporosis-related outcomes than a simple intervention to activate adults in good bone health practices or usual care. DESIGN Pilot randomized controlled trial, conducted within the larger Patient Activation After DXA Result Notification (PAADRN) trial (NCT01507662). After DXA, consenting adults age 50 years or older were randomly assigned to 3 groups: nurse consultation, PAADRN intervention (mailed letter with individualized fracture risk and an educational brochure), or usual care (control). Nurse consultation included reviewing DXA results, counseling on bone health, and ordering needed follow-up tests or physician referrals. MAIN OUTCOME MEASURES Change from baseline to 52 weeks in participant-reported osteoporosis-related pharmacotherapy, lifestyle, activation and self-efficacy, and osteoporosis care satisfaction. RESULTS Nurse consultation participants (n = 104) reported 52-week improvements in strengthening and weight-bearing exercise (p = 0.09), calcium intake (p < 0.01), osteoporosis knowledge (p = 0.04), activation (p < 0.01), dietary self-efficacy (p = 0.06), and osteoporosis care satisfaction (p < 0.01). Compared with PAADRN intervention participants (n = 39), nurse consultation participants had improved dietary self-efficacy (p = 0.07) and osteoporosis care satisfaction (p = 0.05). No significant improvements in osteoporosis-related outcomes were achieved vs PAADRN controls (n = 70). CONCLUSION "Just-in-time" nurse consultation yielded a few improvements over 52 weeks in osteoporosis-related outcomes; however, most changes were not different from those obtained through the lower-cost PAADRN intervention or usual care.
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The Neuroprotective Properties of the Amyloid Precursor Protein Following Traumatic Brain Injury.
Plummer, S, Van den Heuvel, C, Thornton, E, Corrigan, F, Cappai, R
Aging and disease. 2016;(2):163-79
Abstract
Despite the significant health and economic burden that traumatic brain injury (TBI) places on society, the development of successful therapeutic agents have to date not translated into efficacious therapies in human clinical trials. Injury to the brain is ongoing after TBI, through a complex cascade of primary and secondary injury events, providing a valuable window of opportunity to help limit and prevent some of the severe consequences with a timely treatment. Of note, it has been suggested that novel treatments for TBI should be multifactorial in nature, mimicking the body's own endogenous repair response. Whilst research has historically focused on the role of the amyloid precursor protein (APP) in the pathogenesis of Alzheimer's disease, recent advances in trauma research have demonstrated that APP offers considerable neuroprotective properties following TBI, suggesting that APP is an ideal therapeutic candidate. Its acute upregulation following TBI has been shown to serve a beneficial role following trauma and has lead to significant advances in understanding the neuroprotective and neurotrophic functions of APP and its metabolites. Research has focused predominantly on the APP derivative sAPPα, which has consistently demonstrated neuroprotective and neurotrophic functions both in vitro and in vivo following various traumatic insults. Its neuroprotective activity has been narrowed down to a 15 amino acid sequence, and this region is linked to both heparan binding and growth-factor-like properties. It has been proposed that APP binds to heparan sulfate proteoglycans to exert its neuroprotective action. APP presents us with a novel therapeutic compound that could overcome many of the challenges that have stalled development of efficacious TBI treatments previously.
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A multicentre randomised controlled trial evaluating lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea in older people admitted to hospital: the PLACIDE study protocol.
Allen, SJ, Wareham, K, Bradley, C, Harris, W, Dhar, A, Brown, H, Foden, A, Cheung, WY, Gravenor, MB, Plummer, S, et al
BMC infectious diseases. 2012;:108
Abstract
BACKGROUND Antibiotic associated diarrhoea complicates 5-39% of courses of antibiotic treatment. Major risk factors are increased age and admission to hospital. Of particular importance is C. difficile associated diarrhoea which occurs in about 4% of antibiotic courses and may result in severe illness, death and high healthcare costs. The emergence of the more virulent 027 strain of C. difficile has further heightened concerns. Probiotics may prevent antibiotic associated diarrhoea by several mechanisms including colonization resistance through maintaining a healthy gut flora. METHODS This study aims to test the hypothesis that administration of a probiotic comprising two strains of lactobacilli and two strains of bifidobacteria alongside antibiotic treatment prevents antibiotic associated diarrhoea. We have designed a prospective, parallel group trial where people aged 65 years or more admitted to hospital and receiving one or more antibiotics are randomly allocated to receive either one capsule of the probiotic or a matching placebo daily for 21 days. The primary outcomes are the frequency of antibiotic associated and C. difficile diarrhoea during 8-12 weeks follow-up. To directly inform routine clinical practice, we will recruit a sufficient number of patients to demonstrate a 50% reduction in the frequency of C. difficile diarrhoea with a power of 80%. To maximize the generalizability of our findings and in view of the well-established safety record of probiotics, we will recruit a broad range of medical and surgical in-patients from two different health regions within the UK. DISCUSSION Antibiotic associated diarrhoea constitutes a significant health burden. In particular, current measures to prevent and control C. difficile diarrhoea are expensive and disrupt clinical care. This trial may have considerable significance for the prevention of antibiotic associated diarrhoea in hospitals. TRIAL REGISTRATION International Standard Randomised Controlled Trial Number Register ISRCTN70017204.
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Clinical trial: a multistrain probiotic preparation significantly reduces symptoms of irritable bowel syndrome in a double-blind placebo-controlled study.
Williams, EA, Stimpson, J, Wang, D, Plummer, S, Garaiova, I, Barker, ME, Corfe, BM
Alimentary pharmacology & therapeutics. 2009;(1):97-103
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Abstract
BACKGROUND The efficacy of probiotics in alleviating the symptoms of irritable bowel syndrome (IBS) appears to be both strain- and dose-related. AIM: To investigate the effect of LAB4, a multistrain probiotic preparation on symptoms of IBS. This probiotic preparation has not previously been assessed in IBS. METHODS Fifty-two participants with IBS, as defined by the Rome II criteria, participated in this double blind, randomized, placebo-controlled study. Participants were randomized to receive either a probiotic preparation comprising two strains of Lactobacillus acidophilus CUL60 (NCIMB 30157) and CUL21 (NCIMB 30156), Bifidobacterium lactis CUL34 (NCIMB 30172) and Bifidobacterium bifidum CUL20 (NCIMB 30153) at a total of 2.5 × 10(10) cfu/capsule or a placebo for 8 weeks. Participants reported their IBS symptoms using a questionnaire fortnightly during the intervention and at 2 weeks post-intervention. RESULTS A significantly greater improvement in the Symptom Severity Score of IBS and in scores for quality of life, days with pain and satisfaction with bowel habit was observed over the 8-week intervention period in the volunteers receiving the probiotic preparation than in the placebo group. CONCLUSION LAB4 multistrain probiotic supplement may benefit subjects with IBS.
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Clostridium difficile pilot study: effects of probiotic supplementation on the incidence of C. difficile diarrhoea.
Plummer, S, Weaver, MA, Harris, JC, Dee, P, Hunter, J
International microbiology : the official journal of the Spanish Society for Microbiology. 2004;(1):59-62
Abstract
Colonic infection with Clostridium difficile, leading to pseudomembranous colitis, is a common complication of antibiotic therapy, especially in elderly patients. It has been suggested that non-pathogenic probiotic bacteria might prevent the development and recurrence of C. difficile infection. This double-blind, placebo-controlled study examines the role of probiotic administration in the prevention of C. difficile-associated diarrhoea (CDAD) in elderly patients receiving antibiotic therapy. Consecutive patients (150) receiving antibiotic therapy were randomised to receive either a probiotic containing both Lactobacillus and Bifidobacterium or placebo for 20 days. Upon admission to hospital, bowel habit was recorded and a faecal sample taken. Trial probiotic or placebo was taken within 72 h of prescription of antibiotics, and a second stool sample was taken in the event of development of diarrhoea during hospitalisation or after discharge. Of the randomised patients, 138 completed the study, 69 with probiotics in conjunction with antibiotics and 69 with antibiotics alone. On the basis of development of diarrhoea, the incidence of samples positive for C. difficile-associated toxins was 2.9% in the probiotic group compared with 7.25% in the placebo-control group. When samples from all patients were tested (rather than just those developing diarrhoea) 46% of probiotic patients were toxin-positive compared with 78% of the placebo group.
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Antimicrobial properties of Allium sativum (garlic).
Harris, JC, Cottrell, SL, Plummer, S, Lloyd, D
Applied microbiology and biotechnology. 2001;(3):282-6
Abstract
Although garlic has been used for its medicinal properties for thousands of years, investigations into its mode of action are relatively recent. Garlic has a wide spectrum of actions; not only is it antibacterial, antiviral, antifungal and antiprotozoal, but it also has beneficial effects on the cardiovascular and immune systems. Resurgence in the use of natural herbal alternatives has brought the use of medicinal plants to the forefront of pharmacological investigations, and many new drugs are being discovered. This review aims to address the historical use of garlic and its sulfur chemistry, and to provide a basis for further research into its antimicrobial properties.