Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial

BACKGROUND: Antibiotic-associated diarrhoea (AAD) occurs most frequently in older (≥65 years) inpatients exposed to broad-spectrum antibiotics. When caused by Clostridium difficile, AAD can result in life-threatening illness. Although underlying disease mechanisms are not well understood, microbial preparations have been assessed in the prevention of AAD. However, studies have been mostly small single-centre trials with varying quality, providing insufficient data to reliably assess effectiveness. We aimed to do a pragmatic efficacy trial in older inpatients who would be representative of those admitted to National Health Service (NHS) and similar secondary care institutions and to recruit a sufficient number of patients to generate a definitive result. METHODS: We did a multicentre, randomised, double-blind, placebo-controlled, pragmatic, efficacy trial of inpatients aged 65 years and older and exposed to one or more oral or parenteral antibiotics. A computer-generated randomisation scheme was used to allocate participants (in a 1:1 ratio) to receive either a multistrain preparation of lactobacilli and bifidobacteria, with a total of 6 × 10(10) organisms, one per day for 21 days, or an identical placebo. Patients, study staff, and specimen and data analysts were masked to assignment. The primary outcomes were occurrence of AAD within 8 weeks and C difficile diarrhoea (CDD) within 12 weeks of recruitment. Analysis was by modified intention-to-treat. This trial is registered, number ISRCTN70017204. FINDINGS: Of 17,420 patients screened, 1493 were randomly assigned to the microbial preparation group and 1488 to the placebo group. 1470 and 1471, respectively, were included in the analyses of the primary endpoints. AAD (including CDD) occurred in 159 (10·8%) participants in the microbial preparation group and 153 (10·4%) participants in the placebo group (relative risk [RR] 1·04; 95% CI 0·84-1·28; p=0·71). CDD was an uncommon cause of AAD and occurred in 12 (0·8%) participants in the microbial preparation group and 17 (1·2%) participants in the placebo group (RR 0·71; 95% CI 0·34-1·47; p=0·35). 578 (19·7%) participants had one or more serious adverse event; the frequency of serious adverse events was much the same in the two study groups and none was attributed to participation in the trial. INTERPRETATION: We identified no evidence that a multistrain preparation of lactobacilli and bifidobacteria was effective in prevention of AAD or CDD. An improved understanding of the pathophysiology of AAD is needed to guide future studies. FUNDING: Health Technology Assessment programme; National Institute for Health Research, UK

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

<p>Abstract</p> <p>Background</p> <p>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 <it>C. difficile</it> 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 <it>C. difficile</it> has further heightened concerns. Probiotics may prevent antibiotic associated diarrhoea by several mechanisms including colonization resistance through maintaining a healthy gut flora.</p> <p>Methods</p> <p>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 <it>C. difficile</it> 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 <it>C. difficile</it> 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.</p> <p>Discussion</p> <p>Antibiotic associated diarrhoea constitutes a significant health burden. In particular, current measures to prevent and control <it>C. difficile</it> diarrhoea are expensive and disrupt clinical care. This trial may have considerable significance for the prevention of antibiotic associated diarrhoea in hospitals.</p> <p>Trial registration</p> <p>International Standard Randomised Controlled Trial Number Register ISRCTN70017204.</p

Influencing referral practice using feedback of adherence to NICE guidelines: a quality improvement report for dyspepsia

Contains fulltext : 53222.pdf (publisher's version ) (Closed access)PROBLEM: Rising demand and increasing waiting times for upper gastrointestinal endoscopy (gastroscopy). DESIGN: Quality improvement study with pre- and post-intervention data collection. SETTING: Three endoscopy units in two hospital trusts (Singleton, Morriston and Baglan Hospitals endoscopy units), UK. KEY MEASURES FOR IMPROVEMENT: Number of gastroscopy requests from general practitioners (GPs) and hospital doctors; their adherence to dyspepsia referral guidelines and the referral-to-procedure interval for upper gastroscopy. Data collected for six months before and for five months after the intervention. STRATEGY FOR CHANGE: Referrals were assessed against the National Institute for Health and Clinical Excellence (NICE) guidelines for the management of dyspepsia by two part-time GPs and feedback sent to clinicians where requests did not adhere to the referrals criteria EFFECTS OF CHANGE: Adherence to guideline criteria increased significantly among GPs after the intervention (from 55% to 75%). There was no similar effect for hospital doctors, although their adherence rate (70%) was at a higher level than that of GPs before the intervention. The number of gastroscopy referrals for dyspepsia declined after the intervention, particularly from hospital doctors where a drop of 31% was observed, from 26.6 to 18.4 referrals per week. With the inclusion of seasonal effects, an estimated drop of 3.2 referrals per week from general practice was not significant (p = 0.065) while an estimated drop of 10.0 referrals per week for hospital doctors was very significant (p<0.001). LESSONS LEARNT: Referral assessment can be successfully introduced and shows promise as a way of improving the quality of referrals and reducing demand. Hospital clinicians are more resistant than GPs to referral assessment but nevertheless responded to the feedback by reducing their endoscopy gastroscopy requests. Most such referrals are generated in hospitals rather than in primary care: this finding has important implications for demand management

Autologous fascial slings for stress urinary incontinence: a 17-year follow-up of a randomised controlled study

Introduction and hypothesis: safety concerns with the use of mesh in vaginal surgery have been ongoing. Autologous fascial slings (AFS) avoid foreign body complications. We compared the long-term (17-year) outcomes of two AFS repair methods—the standard sling and short sling (sling-on-string), and assessed durability and patient satisfaction of these for the treatment of stress urinary incontinence (SUI).Methods: a total of 107 patients from three urogynaecology units who had participated in a randomised controlled trial assessing standard (n = 52) and short (n = 55) slings were followed up for a median period of 17 years. Primary outcomes were Incontinence Impact Questionnaire (IIQ-7) and Urogenital Distress Inventory (UDI-6) scores to assess the impact on the quality of life and symptom distress. Logistic quantile regression was employed to compare the two methods. Secondary outcomes included long-term complications and patient satisfaction.Results: mean scores showed no statistically significant difference between the standard and short slings at the 17-year follow-up relating to IIQ and UDI scores, leakage or urgency (p &gt; 0.05). Improved bladder function was observed at 17 years compared with baseline (standard sling—IIQ scores mean difference [MD] 1.22 [CI: 0.69, 1.74], UDI scores MD 0.83 [CI: 0.70, 0.97]; short sling—IIQ score MD 1.14 [CI: 0.73, 1.54], UDI scores MD 0.54 [CI: 0.40, 0.67]) with age-related deterioration over time. Re-operation rates were low and patient satisfaction rates were high (67.2%) at follow-up.Conclusions: autologous fascial slings are an effective and durable option for management of SUI and the short sling procedure can be recommended owing to plausible surgical advantages

Randomized, controlled, parallel-group prospective study to investigate the clinical effectiveness of early insulin treatment in patients with latent autoimmune diabetes in adults

Abstract Background Latent autoimmune diabetes in adults [LADA] is a type 1 diabetes that is slowly developing. This means many people are treated as having type 2 diabetes at diagnosis as they are adults who are not immediately insulin dependent. LADA can be distinguished from type 2 diabetes by antibody tests. Patients who are antibody positive have an autoimmune reaction which is similar to that of type 1 diabetes and is not found in type 2 diabetes. We would like to examine the best way of treating LADA in the early phase of the conditions, with tablets (similar to type 2 diabetes) or with insulin (similar to type 1 diabetes). Methods/design This is an open parallel group prospective randomised trial. Participants need to have a GAD antibody test results of 101 WHO units or more and a diagnosis of diabetes not requiring insulin at diagnosis. Participants will need to have been diagnosed within 12 months and not treated with insulin at study entry. They will be randomised to receive either insulin (NovoMix 30) or tablets (diet treated followed by metformin followed by glitazone (with or without metformin) followed by insulin). Primary outcome assessment will be for change in HbA1c and change in fasting C-peptide over 24 months. Secondary outcome measures will include Quality of life, GAD antibody levels, adverse events, inflammatory markers, insulin resistance, and markers of the metabolic syndrome. Discussion This study seeks the best treatment for early LADA in terms of maintaining glycaemic control and maintaining natural insulin production. Trial registration ISRCTN63815121</p