Quality of internet information to aid patient decision making in locally advanced and recurrent rectal cancer.

BACKGROUND: To review whether online decision aids are available for patients contemplating pelvic exenteration (PE) for locally advanced and recurrent rectal cancer (LARC and LRRC). METHODS: A grey literature review was carried out using the Google Search™ engine undertaken using a predefined search strategy (PROSPERO database CRD42019122933). Written health information was assessed using the DISCERN criteria and International Patient Decision Aids Standards (IPDAS) with readability content assessed using the Flesch-Kincaid reading ease test and Flesch-Kincaid grade level score. RESULTS: Google search yielded 27, 782, 200 results for the predefined search criteria. 131 sources were screened resulting in the analysis of 6 sources. No sources were identified as a decision aid according to the IPDAS criteria. All sources provided an acceptable quality of written health information, scoring a global score of 3 for the DISCERN written assessment. The median Flesch-Kincaid reading ease was 50.85 (32.5-80.8) equating to a reading age of 15-18 years and the median Flesch-Kincaid grade level score was 7.65 (range 3-9.7), which equates to a reading age of 13-14. CONCLUSIONS: This study has found that there is a paucity of online information for patients contemplating PE. Sources that are available are aimed at a high health literate patient. Given the considerable morbidity associated with PE surgery there is a need for high quality relevant information in this area. A PDA should be developed to improve decision making and ultimately improve patient experience.

The association of smoking and socioeconomic status on cutaneous melanoma: a population-based, data-linkage, case-control study.

BACKGROUND: Previous studies have identified an inverse association between melanoma and smoking; however, data from population-based studies are scarce. OBJECTIVES: To determine the association between smoking and socioeconomic (SES) on the risk of development of melanoma. Furthermore, we sought to determine the implications of smoking and SES on survival. METHODS: We conducted a population-based case-control study. Cases were identified from the Welsh Cancer Intelligence and Surveillance Unit (WCISU) during 2000-2015 and controls from the general population. Smoking and SES were obtained from data linkage with other national databases. The association of smoking status and SES on the incidence of melanoma were assessed using binary logistic regression. Multivariate survival analysis was performed on a melanoma cohort using a Cox proportional hazard model using survival as the outcome. RESULTS: During 2000-2015, 9636 patients developed melanoma. Smoking data were obtained for 7124 (73·9%) of these patients. There were 26 408 controls identified from the general population. Smoking was inversely associated with melanoma incidence [odds ratio (OR) 0·70, 95% confidence interval (CI) 0·65-0·76]. Smoking was associated with an increased overall mortality [hazard ratio (HR) 1·30, 95% CI 1·09-1·55], but not associated with melanoma-specific mortality. Patients with higher SES had an increased association with melanoma incidence (OR 1·58, 95% CI 1·44-1·73). Higher SES was associated with an increased chance of both overall (HR 0·67, 95% CI 0·56-0·81) and disease-specific survival (HR 0·69, 95% CI 0·53-0·90). CONCLUSIONS: Our study has demonstrated that smoking appeared to be associated with reduced incidence of melanoma. Although smoking increases overall mortality, no association was observed with melanoma-specific mortality. Further work is required to determine if there is a biological mechanism underlying this relationship or an alternative explanation, such as survival bias. What's already known about this topic? Previous studies have been contradictory with both negative and positive associations between smoking and the incidence of melanoma reported. Previous studies have either been limited by publication bias because of selective reporting or underpowered. What does this study add? Our large study identified an inverse association between smoking status and melanoma incidence. Although smoking status was negatively associated with overall disease survival, no significant association was noted in melanoma-specific survival. Socioeconomic status remains closely associated with melanoma. Although higher socioeconomic populations are more likely to develop the disease, patients with lower socioeconomic status continue to have a worse prognosis.

Patient-reported outcome measures for facial skin cancer: a systematic review and evaluation of the quality of their measurement properties.

BACKGROUND: Skin cancer is the commonest malignancy worldwide, often occurring on the face. Both the condition and treatment can lead to scarring and facial disfigurement, affecting a patient's health-related quality of life (HRQoL), which can be measured using patient-reported outcome measures (PROMs). OBJECTIVES: This systematic review identifies PROMs for facial skin cancer and appraises their methodological quality and psychometric properties using up-to-date methods. METHODS: MEDLINE, Embase, PsycINFO, Cochrane and CINAHL were searched systematically in accordance with PRISMA guidelines, identifying all PROMs designed for or validated in facial skin cancer. Methodological quality and evidence of psychometric properties were assessed using the COnsensus-based Standards for the Selection of Health Measurement INstruments (COSMIN) checklist and criteria proposed by Terwee and colleagues. A best-evidence synthesis and assessment of instrument focus on post-resection reconstruction was also performed. RESULTS: We included 24 studies on 11 PROMs. Methodological quality and psychometric evidence was variable, with the Patient Outcome of Surgery - Head/Neck (POS-H/N), Skin Cancer Index (SCI), Skin Cancer Quality of Life Impact Tool (SCQOLIT) and Essers and colleagues demonstrating the greatest level of validation. None scored well in their relevance to post-skin cancer reconstruction of the face. CONCLUSIONS: This systematic review critically appraises PROMs for facial skin cancer using internationally accepted criteria. The identified PROMs demonstrate a variation in the quality of validation performed, with a need to improve this across all PROMs in the field. Only through improving the quality of available PROMs and their focus on the post-treatment aesthetic and functional outcome will we be able to truly appreciate the concerns of our patients and improve the management of facial skin cancer.

Health sequelae of human cryptosporidiosis-a 12-month prospective follow-up study.

To investigate long-term health sequelae of cryptosporidiosis, with especial reference to post-infectious irritable bowel syndrome (PI-IBS). A prospective cohort study was carried out. All patients with laboratory-confirmed, genotyped cryptosporidiosis in Wales, UK, aged between 6 months and 45 years of age, over a 2-year period were contacted. Five hundred and five patients agreed to participate and were asked to complete questionnaires (paper or online) at baseline, 3 and 12 months after diagnosis. The presence/absence of IBS was established using the Rome III criteria for different age groups. Two hundred and five of 505 cases completed questionnaires (40% response rate). At 12 months, over a third of cases reported persistent abdominal pain and diarrhoea, 28% reported joint pain and 26% reported fatigue. At both 3 and 12 months, the proportion reporting fatigue and abdominal pain after Cryptosporidium hominis infection was statistically significantly greater than after C. parvum. Overall, 10% of cases had sufficient symptoms to meet IBS diagnostic criteria. A further 27% met all criteria except 6 months' duration and another 23% had several features of IBS but did not fulfil strict Rome III criteria. There was no significant difference between C. parvum and C. hominis infection with regard to PI-IBS. Post-infectious gastrointestinal dysfunction and fatigue were commonly reported after cryptosporidiosis. Fatigue and abdominal pain were significantly more common after C. hominis compared to C. parvum infection. Around 10% of people had symptoms meriting a formal diagnosis of IBS following cryptosporidiosis. Using age-specific Rome III criteria, children as well as adults were shown to be affected.

Construct validity of the anglicised FACE-Q skin cancer module.

OBJECTIVES: The FACE-Q Skin Cancer module is a patient-reported outcome measure (PROM) for facial skin cancer. It has been anglicised for the UK population and undergone psychometric testing using classical test theory. In this study, further evaluation of construct validity using Rasch measurement theory and hypothesis testing was performed. METHODS: Patients were prospectively recruited to the Patient-Reported Outcome Measures In Skin Cancer Reconstruction (PROMISCR) study and asked to complete the anglicised FACE-Q Skin Cancer module. The scalability and unidimensionality of the data were assessed with a Mokken analysis prior to Rasch analysis. Response thresholds, targeting, fit statistics, local dependency, and internal consistency were examined for all items and subscales. Four a priori hypotheses were tested to evaluate the convergent and divergent validity. We additionally hypothesised that the median 'cancer worry' score would be lower in post-operative than pre-operative patients. RESULTS: 239 patients self-completed the questionnaire between August 2017 and May 2019. Of the ten subscales assessed, five showed relative fit to the Rasch model. Unidimensionality was present for all five subscales, with most demonstrating ordered item thresholds and appropriate fit statistics. Two items in the 'cancer worry' subscale had either disordered or very close response thresholds. Subscales of the FACE-Q Skin Cancer module demonstrated convergent and divergent validity with relevant Skin Cancer Index comparators (p < 0.001). Median 'cancer worry' was lower in post-operative patients (44 vs 39, p < 0.001). CONCLUSION: The anglicised FACE-Q Skin Cancer module shows psychometric validity through hypothesis testing, and both classical and modern test theory.

A study protocol for a double-blind randomised placebo-controlled trial evaluating the efficacy of carrageenan nasal and throat spray for COVID-19 prophylaxis-ICE-COVID.

INTRODUCTION: At present, vaccines form the only mode of prophylaxis against COVID-19. The time needed to achieve mass global vaccination and the emergence of new variants warrants continued research into other COVID-19 prevention strategies. The severity of COVID-19 infection is thought to be associated with the initial viral load, and for infection to occur, viruses including SARS-CoV-2 must first penetrate the respiratory mucus and attach to the host cell surface receptors. Carrageenan, a sulphated polysaccharide extracted from red edible seaweed, has shown efficacy against a wide range of viruses in clinical trials through the prevention of viral entry into respiratory host cells. Carrageenan has also demonstrated in vitro activity against SARS-CoV-2. METHODS AND ANALYSIS: A single-centre, randomised, double-blinded, placebo-controlled phase III trial was designed. Participants randomised in a 1:1 allocation to either the treatment arm, verum Coldamaris plus (1.2 mg iota-carrageenan (Carragelose®), 0.4 mg kappa-carrageenan, 0.5% sodium chloride and purified water), or placebo arm, Coldamaris sine (0.5% sodium chloride) spray applied daily to their nose and throat for 8 weeks, while completing a daily symptom tracker questionnaire for a total of 10 weeks. PRIMARY OUTCOME: Acquisition of COVID-19 infection as confirmed by a positive PCR swab taken at symptom onset or seroconversion during the study. Secondary outcomes include symptom type, severity and duration, subsequent familial/household COVID-19 infection and infection with non-COVID-19 upper respiratory tract infections. A within-trial economic evaluation will be undertaken, with effects expressed as quality-adjusted life years. DISCUSSION: This is a single-centre, phase III, double-blind, randomised placebo-controlled clinical trial to assess whether carrageenan nasal and throat spray reduces the risk of development and severity of COVID-19. If proven effective, the self-administered prophylactic spray would have wider utility for key workers and the general population. TRIAL REGISTRATION: NCT04590365; ClinicalTrials.gov NCT04590365. Registered on 19 October 2020.

Burns in young children: a retrospective matched cohort study of health and developmental outcomes.

BACKGROUND: Unintentional injuries are a major cause of death and disability in childhood. Most burns are unintentional, the majority occurring in pre-school children. Little is known about the outcomes of young children following burns. The purpose of this study was to examine the presenting features of burned children and compare their health and developmental outcomes with controls. METHODS: Children under 3 years admitted to the Welsh Regional Burns Centre between September 1994 and August 1997 were studied up to their sixth birthday (final data collection 2003) to ascertain the nature, course and cause of their burn. One hundred and forty-five burned children were matched with 145 controls. Their physical, psychosocial and educational health status was compared. Retrospective data were gathered from hospital notes, social services, emergency department databases, child health surveillance records and schools. RESULTS: Burns peaked at age 13-18 months were typically sustained by scalding, drink spillage and contact with hot objects. They occurred most frequently at mealtimes and 89.7% were judged to be unintentional. There was a high rate of non-attendance for follow-up - 24%. The families of children admitted with burns were more likely to have moved home than those of controls (P = 0.001). By age 6 significantly more cases were admitted to hospital with an unrelated condition (P = 0.018). There were no differences between the cases and controls in immunization status, development, school attendance and educational progress up to the age of 6 years (P > 0.05). CONCLUSIONS: We found important findings in relation to unintentional injury prevention and also noted markers that may indicate inequalities in health service utilization between cases and controls. There were no major differences between developmental and educational outcomes in the two groups.

Recent trends in the incidence of anxiety and prescription of anxiolytics and hypnotics in children and young people: An e-cohort study.

BACKGROUND: Little is known regarding the recognition of anxiety in children and young people (CYP) in primary care. This study examined trends in the presentation, recognition and recording of anxiety and of anxiolytic and hypnotic prescriptions for CYP in primary care. METHOD: A population-based retrospective electronic cohort of individuals aged 6-18 years between 2003 and 2011 within the Secure Anonymised Information Linkage (SAIL) Databank primary care database was created. Incidence rates were calculated using person years at risk (PYAR) as a denominator accounting for deprivation, age and gender. RESULTS: We identified a cohort of 311,343 registered individuals providing a total of 1,546,489 person years of follow up. The incidence of anxiety symptoms more than tripled over the study period (Incidence Rate Ratio (IRR)=3.55, 95% CI 2.65-4.77) whilst that of diagnosis has remained stable. Anxiolytic/hypnotic prescriptions for the cohort as a whole did not change significantly over time; however there was a significant increase in anxiolytic prescriptions for the 15-18 year age group (IRR 1.62, 95% CI 1.30-2.02). LIMITATIONS: There was a lack of reliable information regarding other interventions available or received at a primary, secondary or tertiary level such as psychological treatments. CONCLUSIONS: There appears to be a preference over time for the recording of general symptoms over diagnosis for anxiety in CYP. The increase in anxiolytic prescriptions for 15-18 year olds is discrepant with current prescribing guidelines. Specific guidance is required for the assessment and management of CYP presenting with anxiety to primary care, particularly older adolescents.

Signal relays in the VEGF system.

A considerable progress has been made during the past years in elucidating the molecular actors of angiogenesis. Vascular endothelial growth factor turned out to represent the major inducer of angiogenesis. Optional splicing of its pre messenger RNA generates various isoforms which differ not only by their storage in the extracellular matrix but also by their signaling pathways. VEGF binds and activates two tyrosine kinase receptors called VEGFR1 and VEGFR2 and neuropilin-1. The elucidation of the transduction pathways of each receptor suggests that VEGFR1 mediates cell migration whereas VEGFR2 mediates cell proliferation. The construction of internal images of VEGF by the anti-idiotypic antibody strategy allowed us to determine that quiescent endothelial cells need to be activated by so far unknown factors to become competent to respond to mitogenic signals and acquire an angiogenic phenotype. The discovery of the mechanisms of action of the VEGF system has allowed the design of promising drugs which already entered the pre-clinical or clinical assays.

The total cost of care and the use of pharmaceuticals in the management of rheumatoid arthritis: the Medi-Cal program.

Medicaid claims data were analyzed to investigate the prevalence and cost of rheumatoid arthritis (RA) in the Medi-Cal program. It was estimated that approximately 24,000 Medi-Cal recipients receive treatment for RA each year. The sample of Medi-Cal RAs studied averaged more than $2500 annually in total direct health care expenditures. The total cost of RA to Medi-Cal is projected to be $19.26 million (+/- $0.90 million) annually. Inclusion of possible gastrointestinal side effects of drug therapy increases the total cost to $20.49 million (+/- $0.91 million). While only 6.5% of the sample of RAs were hospitalized and 4.9% received nursing home care annually, these services are estimated to account for nearly 70% of RA-related expenditures. Less than 7% of Medi-Cal RAs receive disease modifying antirheumatic drugs (DMARDs). More than 75% of Medi-Cal RAs received aspirin or NSAIDs. These relieve pain and inflammation, but have not been demonstrated to halt the process of joint destruction.

Can randomised trials rely on existing electronic data? A feasibility study to explore the value of routine data in health technology assessment.

OBJECTIVES: To estimate the feasibility, utility and resource implications of electronically captured routine data for health technology assessment by randomised controlled trials (RCTs), and to recommend how routinely collected data could be made more effective for this purpose. DATA SOURCES: Four health technology assessments that involved patients under care at five district general hospitals in the UK using four conditions from distinct classical specialties: inflammatory bowel disease, obstructive sleep apnoea, female urinary incontinence, and total knee replacement. Patient-identifiable, electronically stored routine data were sought from the administration and clinical database to provide the routine data. REVIEW METHODS: Four RCTs were replicated using routine data in place of the data already collected for the specific purpose of the assessments. This was done by modelling the research process from conception to final writing up and substituting routine for designed data activities at appropriate points. This allowed a direct comparison to be made of the costs and outcomes of the two approaches to health technology assessment. The trial designs were a two-centre randomised trial of outpatient follow-up; a single-centre randomised trial of two investigation techniques; a three-centre randomised trial of two surgical operations; and a single-centre randomised trial of perioperative anaesthetic intervention. RESULTS: Generally two-thirds of the research questions posed by health technology assessment through RCTs could be answered using routinely collected data. Where these questions required analysis of NHS resource use, data could usually be identified. Clinical effectiveness could also be judged, using proxy measures for quality of life, provided clinical symptoms and signs were collected in sufficient detail. Patient and professional preferences could not be identified from routine data but could be collected routinely by adapting existing instruments. Routine data were found potentially to be cheaper to extract and analyse than designed data, and they also facilitate recruitment as well as have the potential to identify patient outcomes captured in remote systems that may be missed in designed data collection. The study confirmed previous evidence that the validity of routinely collected data is suspect, particularly in systems that are not under clinical and professional control. Potential difficulties were also found in identifying, accessing and extracting data, as well as in the lack of uniformity in data structures, coding systems and definitions. CONCLUSIONS: Routine data have the potential to support health technology assessment by RCTs. The cost of data collection and analysis is likely to fall, although further work is required to improve the validity of routine data, particularly in central returns. Better knowledge of the capability of local systems and access to the data held on them is also essential. Routinely captured clinical data have real potential to measure patient outcomes, particularly if the detail and precision of the data could be improved.

Assessing organisational development in primary medical care using a group based assessment: the Maturity Matrix.

OBJECTIVE: To design and develop an instrument to assess the degree of organisational development achieved in primary medical care organisations. DESIGN: An iterative development, feasibility and validation study of an organisational assessment instrument. SETTING: Primary medical care organisations. PARTICIPANTS: Primary care teams and external facilitators. MAIN OUTCOME MEASURES: Responses to an evaluation questionnaire, qualitative process feedback, hypothesis testing, and quantitative psychometric analysis (face and construct validity) of the results of a Maturity Matrix assessment in 55 primary medical care organisations. RESULTS: Evaluations by 390 participants revealed high face validity with respect to its usefulness as a review and planning tool at the practice level. Feedback from facilitators suggests that it helped practices to prioritise their organisational development. With respect to construct validity, there was some support for the hypothesis that training and non-training status affected the degree and pattern of organisational development. The size of the organisation did not have a significant impact on the degree of organisational development. CONCLUSION: This practice based facilitated group evaluation method was found to be both useful and enjoyable by the participating organisations. Psychometric validation revealed high face validity. Further developments are in place to ensure acceptability for summative work (benchmarking) and formative feedback processes (quality improvement).

Sarcoidosis: a long-term follow up study.

BACKGROUND AND AIM OF WORK: The study investigated the occurrence, time and mode of presentation, clinical features, course of pulmonary disease and prognosis of all patients with sarcoidosis looked after by one physician in a district general hospital during the period 1965-1996. The hospital covered a catchment population of 150,000. METHODS: A detailed review of 212 patient notes was carried out with the aid of a purposely designed structured data collection form. Postal questionnaires were sent to those patients not currently attending to determine survival/state of health. Death certificates were analysed to determine the cause of death. RESULTS: A diagnosis of sarcoidosis was based on clinical grounds in 63 of the 212 cases, with histological proof confirming sarcoidosis in 149 cases. There was a slightly higher incidence in females than males, with four familial instances documented. There was pulmonary involvement in 192 cases classified in the usual way at presentation and the course of these patients was studied. Patients with Stage 1 and 2 disease had resolution rates in excess of 80%, and Stage 3 50%. For the remainder, two patterns emerged: one group with persistent infiltration or fibrosis but little disability or disease progression, and another with advancing disease refractory to steroid therapy with a bad prognosis. CONCLUSIONS: The good prognosis of patients with Stage 1 disease was confirmed. There were fewer patients presenting with Stage 2 and 3 disease and their prognosis was better than in other published studies. Overall, the numbers of patients progressing from one stage to another was small. Although there was a small group of patients with steroid-refractory, progressive, fibrosis with a bad prognosis, the mortality rate from sarcoidosis in this study was small.

Voluntary suppression of cough induced by inhalation of capsaicin in healthy volunteers.

The aim of the present study was to investigate the voluntary suppression of cough in response to capsaicin inhalation in healthy volunteers, and to determine if the dose-response curve to capsaicin was significantly altered when volunteers were asked to suppress their cough response. The quantification of the degree of voluntary suppression of induced cough could provide a new methodology for screening antitussive agents as antitussives may act by influencing voluntary control of cough. Cough was induced by inhalation of capsaicin. Two challenges were given 5 min apart, each comprising five ascending concentrations of capsaicin (1 x 10(-5) M-3.33 x 10(-4) M). During one of these challenges the volunteer was allowed to cough when required, and during the other they were asked to suppress cough. These two conditions were given in random order. The cough response was recorded by means of a microphone with the integrated sound trace displayed on a chart recorder. A dose-response relationship was obtained on administration of ascending concentrations of capsaicin. In the non-suppressed challenge 23/24 subjects coughed on inhalation of capsaicin (3.33 x 10(-4) M) with a mean number of coughs of 2.92 +/- 0.34, whereas in the suppressed challenge only 3/24 subjects coughed with a mean number of coughs of 0.29 +/- 0.18 (P < 0.001). These results demonstrate that cough induced by inhalation of capsaicin can be voluntarily suppressed. The mechanism of voluntary suppression of cough is discussed in relation to capsaicin challenge and the screening of antitussive medications.

The relationship between nasalance and nasal resistance to airflow.

The relationship between nasal airway resistance and nasalance in healthy volunteers and in subjects suffering from symptoms of acute rhinitis was investigated. A non-invasive objective measure of nasalance using the Nasometer (Kay Electronics) was used and an inverse correlation between airway resistance and nasalance was found (r = 0.67, r2 = 0.46, p less than 0.0001). The effect of a topical nasal decongestant on nasal airway resistance and nasalance was investigated, and significant changes were seen both in resistance and nasalance (p less than 0.0001) with a correlation in the changes seen in both parameters (r = 0.82, r2 = 0.66, p less than 0.0001). The measure of nasalance may be useful in assessing various forms of nasal treatment including nasal, adenoidal and palatal surgery. The measurement of nasalance is well tolerated by subjects of all ages and is particularly useful in subjects with high nasal resistance where rhinomanometry tends to be unstable.

Protocol for a prospective multicentre cohort study to develop and validate two new outcome measures for patients with inflammatory bowel disease.

INTRODUCTION: Most of the health-related quality of life (HRQoL) measures for patients with inflammatory bowel disease (IBD) were designed to be used in outpatient settings and are therefore not suitable for use in acute inpatient settings. None of the currently used clinical severity indices for patients with IBD have been properly validated. The aim of this study was to describe the development of a new HRQoL questionnaire and a clinical severity index for patients with ulcerative colitis or Crohn's disease that were short, valid and suitable at any stage of their disease. The new HRQoL and disease severity index will be easily used at the point of care, and invaluable monitoring tools for clinical care, audit and research. METHODS AND ANALYSIS: This is a prospective multisite validation study of two new outcome measures, the Crohn's and Colitis quality of life (CCQ) questionnaire and the Clinical IBD severity score (CISS). We plan to recruit patients with ulcerative colitis or Crohn's disease. The questionnaire items will be selected through extensive literature review and a focus group involving patients, methodologists, statisticians and IBD specialists. The CCQ questionnaire will be completed by patients attending IBD clinics, having endoscopy procedures or when admitted to hospital. CISS will be completed by clinicians while assessing patients with IBD. Psychometric analysis will be carried out to test the validity and reliability of the questionnaires and to determine the potential to produce shorter versions of CISS and CCQ. The construct validity of CCQ will be tested against short form-12 and the European Quality of Life Five Dimensions. The construct validity of CISS will be tested against biochemical markers, clinical and endoscopic indices to assess severity. ETHICS: This study was approved by the South East Wales Research Ethics Committee (Ref 11/WA/0239).

A high-dose preparation of lactobacilli and bifidobacteria in the prevention of antibiotic-associated and Clostridium difficile diarrhoea in older people admitted to hospital: a multicentre, randomised, double-blind, placebo-controlled, parallel arm trial (PLACIDE).

BACKGROUND: Antibiotic-associated diarrhoea (AAD) occurs most commonly in older people admitted to hospital and within 12 weeks of exposure to broad-spectrum antibiotics. Although usually a mild and self-limiting illness, the 15-39% of cases caused by Clostridium difficile infection [C. difficile diarrhoea (CDD)] may result in severe diarrhoea and death. Previous research has shown that probiotics, live microbial organisms that, when administered in adequate numbers, are beneficial to health, may be effective in preventing AAD and CDD. OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of a high-dose, multistrain probiotic in the prevention of AAD and CDD in older people admitted to hospital. DESIGN: A multicentre, randomised, double-blind, placebo-controlled, parallel-arm trial. SETTING: Medical, surgical and elderly care inpatient wards in five NHS hospitals in the UK. PARTICIPANTS: Eligible patients were aged ≥ 65 years, were exposed to one or more oral or parenteral antibiotics and were without pre-existing diarrhoeal disorders, recent CDD or at risk of probiotic adverse effects. Out of 17,420 patients screened, 2981 (17.1%) were recruited. Participants were allocated sequentially according to a computer-generated random allocation sequence; 1493 (50.1%) were allocated to the probiotic and 1488 (49.9%) to the placebo arm. INTERVENTIONS: Vegetarian capsules containing two strains of lactobacilli and two strains of bifidobacteria (a total of 6 × 10(10) organisms per day) were taken daily for 21 days. The placebo was inert maltodextrin powder in identical capsules. MAIN OUTCOME MEASURES: The occurrence of AAD within 8 weeks and CDD within 12 weeks of recruitment was determined by participant follow-up and checking hospital laboratory records by research nurses who were blind to arm allocation. RESULTS: Analysis based on the treatment allocated included 2941 (98.7%) participants. Potential risk factors for AAD at baseline were similar in the two study arms. Frequency of AAD (including CDD) was similar in the probiotic (159/1470, 10.8%) and placebo arms [153/1471, 10.4%; relative risk (RR) 1.04; 95% confidence interval (CI) 0.84 to 1.28; p = 0.71]. CDD was an uncommon cause of AAD and occurred in 12/1470 (0.8%) participants in the probiotic and 17/1471 (1.2%) in the placebo arm (RR 0.71; 95% CI 0.34 to 1.47; p = 0.35). Duration and severity of diarrhoea, common gastrointestinal symptoms, serious adverse events and quality of life measures were also similar in the two arms. Total health-care costs per patient did not differ significantly between the probiotic (£8020; 95% CI £7620 to £8420) and placebo (£8010; 95% CI £7600 to £8420) arms. CONCLUSION: We found no evidence that probiotic administration was effective in preventing AAD. Although there was a trend towards reduced CDD in the probiotic arm, on balance, the administration of this probiotic seems unlikely to benefit older patients exposed to antibiotics. A better understanding of the pathogenesis of AAD and CDD and the strain-specific effects of probiotics is needed before further clinical trials of specific microbial preparations are undertaken. Evaluation of the effectiveness of other probiotics will be difficult where other measures, such as antibiotic stewardship, have reduced CDD rates. TRIAL REGISTRATION: This trial is registered as ISRCTN70017204. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 57. See the NIHR Journals Library website for further project information.