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1.
Eur Heart J Open ; 3(3): oead047, 2023 May.
Article in English | MEDLINE | ID: mdl-37205320

ABSTRACT

Aims: Atrial fibrillation (AF) is an important risk factor for stroke, which is commonly asymptomatic, particularly in older patients, and often undetected until cardiovascular events occur. Development of novel technology has helped to improve detection of AF. However, the longer-term benefit of systematic electrocardiogram (ECG) screening on cardiovascular outcomes is unclear. Methods and results: In the original REHEARSE-AF study, patients were randomized to twice-weekly portable electrocardiogram (iECG) assessment or routine care. After discontinuing the trial portable iECG assessment, electronic health record data sources provided longer-term follow-up analysis. Cox regression was used to provide unadjusted and adjusted hazard ratios (HR) [95% confidence intervals (CI)] for clinical diagnosis, events, and anticoagulant prescriptions during the follow-up period. Over the median 4.2-year follow-up, although a greater number of patients were diagnosed with AF in the original iECG group (43 vs. 31), this was not significant (HR 1.37, 95% CI 0.86-2.19). No differences were seen in the number of strokes/systemic embolisms or deaths between the two groups (HR 0.92, 95% CI 0.54-1.54; HR 1.07, 95% CI 0.66-1.73). Findings were similar when restricted to those with CHADS-VASc ≥ 4. Conclusion: A 1-year period of home-based, twice-weekly screening for AF increased diagnoses of AF for the screening period but did not lead to increased diagnoses of AF or a reduction in cardiovascular-related events or all-cause death over a median of 4.2 years, even in those at highest risk of AF. These results suggest that benefits of regular ECG screening over a 1-year period are not maintained after cessation of the screening protocol.

2.
Vaccines (Basel) ; 11(3)2023 Mar 17.
Article in English | MEDLINE | ID: mdl-36992264

ABSTRACT

In the context of the WHO's measles and rubella elimination targets and European Immunization Agenda 2030, this large cross-sectional study aimed to identify inequalities in measles vaccination coverage in Wales, UK. The vaccination status of individuals aged 2 to 25 years of age, alive and resident in Wales as of 31 August 2021, was ascertained through linkage of the National Community Child Health Database and primary care data. A series of predictor variables were derived from five national datasets and all analysis was carried out in the Secure Anonymised Information Linkage Databank at Swansea University. In these 648,895 individuals, coverage of the first dose of measles-containing vaccine (due at 12-13 months of age) was 97.1%, and coverage of the second dose (due at 3 years and 4 months) in 4 to 25-year-olds was 93.8%. In multivariable analysis, excluding 0.7% with known refusal, the strongest association with being unvaccinated was birth order (families with six or more children) and being born outside of the UK. Living in a deprived area, being eligible for free school meals, a lower level of maternal education, and having a recorded language other than English or Welsh were also associated with lower coverage. Some of these factors may also be associated with refusal. This knowledge can be used to target future interventions and prioritise areas for catch up in a time of limited resource.

3.
Eur Heart J Open ; 2(6): oeac066, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36415305

ABSTRACT

Aims: Guidelines recommend anticoagulation (AC) in atrial fibrillation (AF) to reduce stroke and systemic embolism (SSE) risk; however, implementation has been slow across many populations. This study aimed to quantify the potential impact of changing prevalence of AF, associated risk, and AC prescribing on SSE hospitalizations and death. Methods and results: We evaluated temporal trends of AF, CHA2DS2-VASc, antithrombotic prescriptions, SSE hospitalizations, death, and their associations between 2012 and 2018 in a longitudinal cohort of AF patients in Wales UK. Multi-state Markov models were used to estimate expected SSE rates given the AC coverage, adjusting for CHA2DS2-VASc scores. SSE rates were modelled for various past and future AC scenarios. A total of 107 137 AF patients were evaluated (mean age = 74 years, 45% female). AF prevalence increased from 1.75 to 2.22% (P-value <0.001). SSE hospitalizations decreased by 18% (2.34-1.92%, P-value <0.001). Increased AC coverage from 50 to 70% was associated with a 37% lower SSE rate, after adjustment for individual time-dependent CHA2DS2VASc scores. The observed AC increase accounted for approximately 80 fewer SSE hospitalizations per 100 000/year. If 90% AC coverage had been achieved since 2012, an estimated 279 SSE per 100 000/year may have been prevented. Our model also predicts that improving AC coverage to 90% over the next 9 years could reduce annual SSE rates by 9%. Conclusion: We quantified the relationship between observed AC coverage, estimating the potential impact of variation in the timing of large-scale implementation. These data emphasize the importance of timely implementation and the considerable opportunity to improve clinical outcomes in the Wales-AF population.

4.
Sci Rep ; 12(1): 16406, 2022 09 30.
Article in English | MEDLINE | ID: mdl-36180455

ABSTRACT

There is a need for better understanding of the risk of thrombocytopenic, haemorrhagic, thromboembolic disorders following first, second and booster vaccination doses and testing positive for SARS-CoV-2. Self-controlled cases series analysis of 2.1 million linked patient records in Wales between 7th December 2020 and 31st December 2021. Outcomes were the first diagnosis of thrombocytopenic, haemorrhagic and thromboembolic events in primary or secondary care datasets, exposure was defined as 0-28 days post-vaccination or a positive reverse transcription polymerase chain reaction test for SARS-CoV-2. 36,136 individuals experienced either a thrombocytopenic, haemorrhagic or thromboembolic event during the study period. Relative to baseline, our observations show greater risk of outcomes in the periods post-first dose of BNT162b2 for haemorrhagic (IRR 1.47, 95%CI: 1.04-2.08) and idiopathic thrombocytopenic purpura (IRR 2.80, 95%CI: 1.21-6.49) events; post-second dose of ChAdOx1 for arterial thrombosis (IRR 1.14, 95%CI: 1.01-1.29); post-booster greater risk of venous thromboembolic (VTE) (IRR-Moderna 3.62, 95%CI: 0.99-13.17) (IRR-BNT162b2 1.39, 95%CI: 1.04-1.87) and arterial thrombosis (IRR-Moderna 3.14, 95%CI: 1.14-8.64) (IRR-BNT162b2 1.34, 95%CI: 1.15-1.58). Similarly, post SARS-CoV-2 infection the risk was increased for haemorrhagic (IRR 1.49, 95%CI: 1.15-1.92), VTE (IRR 5.63, 95%CI: 4.91, 6.4), arterial thrombosis (IRR 2.46, 95%CI: 2.22-2.71). We found that there was a measurable risk of thrombocytopenic, haemorrhagic, thromboembolic events after COVID-19 vaccination and infection.


Subject(s)
COVID-19 Vaccines , COVID-19 , Thrombocytopenia , Venous Thromboembolism , BNT162 Vaccine , COVID-19/complications , COVID-19/epidemiology , COVID-19 Vaccines/adverse effects , Hemorrhage , Humans , SARS-CoV-2 , Thrombocytopenia/chemically induced , Thrombocytopenia/epidemiology , Vaccination/adverse effects , Venous Thromboembolism/chemically induced , Wales/epidemiology
5.
Hum Vaccin Immunother ; 18(1): 2031774, 2022 12 31.
Article in English | MEDLINE | ID: mdl-35239462

ABSTRACT

Vaccination programs against COVID-19 vary globally with estimates of vaccine effectiveness (VE) affected by vaccine type, schedule, strain, outcome, and recipient characteristics. This study assessed VE of BNT162b2 and ChAdOx1 vaccines against PCR positive SARS-CoV-2 infection, hospital admission, and death among adults aged 50 years and older in Wales, UK during the period 7 December 2020 to 18 July 2021, when Alpha, followed by Delta, were the predominant variants. We used individual-level linked routinely collected data within the Secure Anonymized Information Linkage (SAIL) Databank. Data were available for 1,262,689 adults aged 50 years and over; coverage of one dose of any COVID-19 vaccine in this population was 92.6%, with coverage of two doses 90.4%. VE against PCR positive infection at 28-days or more post first dose of any COVID-19 vaccine was 16.0% (95%CI 9.6-22.0), and 42.0% (95%CI 36.5-47.1) seven or more days after a second dose. VE against hospital admission was higher at 72.9% (95%CI 63.6-79.8) 28 days or more post vaccination with one dose of any vaccine type, and 84.9% (95%CI 78.2-89.5) at 7 or more days post two doses. VE for one dose against death was estimated to be 80.9% (95%CI 72.1-86.9). VE against PCR positive infection and hospital admission was higher for BNT162b2 compared to ChAdOx1. In conclusion, vaccine uptake has been high among adults in Wales and VE estimates are encouraging, with two doses providing considerable protection against severe outcomes. Continued roll-out of the vaccination programme within Wales, and globally, is crucial in our fight against COVID-19.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , Aged , BNT162 Vaccine , COVID-19/epidemiology , COVID-19/prevention & control , Humans , Middle Aged , SARS-CoV-2 , Wales/epidemiology
6.
PLoS One ; 17(2): e0264529, 2022.
Article in English | MEDLINE | ID: mdl-35213664

ABSTRACT

AIMS: To explore differences in the use of lipid lowering therapy and/or achievement of lipid guideline targets in patients with and without prior depression and influence of sex in very high-risk coronary patients. METHODS & FINDINGS: A retrospective observational cohort study was conducted using individual-level linked electronic health record data in patients who underwent percutaneous coronary intervention (2012-2017) in Wales. The cohort comprised of 13,781 patients (27.4% female), with 26.1% having prior depression. Lipid levels were recorded in 10,050 patients of whom 25% had depression. History of depression was independently associated with not having lipids checked (OR 0.79 95%CI 0.72-0.87 p<0.001). Patients with prior depression were less likely to achieve targets for low density lipoprotein cholesterol (LDL-C <1.8mmol/l), non-high density lipoprotein cholesterol (non-HDL-C <2.6mmol/l) and triglycerides (<2.3mmol/l) than patients without depression (OR 0.86 95%CI 0.78-0.96 p = 0.007, OR 0.80 95%CI 0.69-0.92 p = 0.003 & OR 0.69 95CI% 0.61-0.79 p<0.001 respectively). Females were less likely to achieve targets for LDL-C and non-HDL-C than males (OR 0.55 95%CI 0.50-0.61 p<0.001 & OR 0.63 95%CI 0.55-0.73 p<0.001). There was an additive effect of depression and sex; females with depression were not only least likely to be tested (OR 0.74 95%CI 0.65-0.84 p<0.001) but also (where levels were known) less likely to achieve LDL-C (OR 0.47 95%CI 0.41-0.55 p<0.001) and non-HDL-C targets (OR 0.50 95%CI 0.41-0.60 p<0.001). It was not possible to look at the influence of medication adherence on achievement of lipid targets due to limitations of the use of anonymised routinely-held clinical care data. CONCLUSION: Patients with prior depression were less likely to have their lipids monitored and achieve guideline targets within 1-year. Females with depression are the least likely to be tested and achieve lipid targets, suggesting not only a greater risk of future events, but also an opportunity to improve care.


Subject(s)
Cholesterol, HDL/blood , Cholesterol, LDL/blood , Depression/pathology , Triglycerides/blood , Aged , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/surgery , Female , Humans , Logistic Models , Male , Middle Aged , Odds Ratio , Percutaneous Coronary Intervention , Practice Guidelines as Topic , Retrospective Studies , Risk Factors , Sex Factors , Societies, Medical , Wales
7.
PLoS One ; 17(2): e0264023, 2022.
Article in English | MEDLINE | ID: mdl-35226680

ABSTRACT

INTRODUCTION: School-based COVID-19 mitigation strategies have greatly impacted the primary school day (children aged 3-11) including: wearing face coverings, two metre distancing, no mixing of children, and no breakfast clubs or extra-curricular activities. This study examines these mitigation measures and association with COVID-19 infection, respiratory infection, and school staff wellbeing between October to December 2020 in Wales, UK. METHODS: A school staff survey captured self-reported COVID-19 mitigation measures in the school, participant anxiety and depression, and open-text responses regarding experiences of teaching and implementing measures. These survey responses were linked to national-scale COVID-19 test results data to examine association of measures in the school and the likelihood of a positive (staff or pupil) COVID-19 case in the school (clustered by school, adjusted for school size and free school meals using logistic regression). Linkage was conducted through the SAIL (Secure Anonymised Information Linkage) Databank. RESULTS: Responses were obtained from 353 participants from 59 primary schools within 15 of 22 local authorities. Having more direct non-household contacts was associated with a higher likelihood of COVID-19 positive case in the school (1-5 contacts compared to none, OR 2.89 (1.01, 8.31)) and a trend to more self-reported cold symptoms. Staff face covering was not associated with a lower odds of school COVID-19 cases (mask vs. no covering OR 2.82 (1.11, 7.14)) and was associated with higher self-reported cold symptoms. School staff reported the impacts of wearing face coverings on teaching, including having to stand closer to pupils and raise their voices to be heard. 67.1% were not able to implement two metre social distancing from pupils. We did not find evidence that maintaining a two metre distance was associated with lower rates of COVID-19 in the school. CONCLUSIONS: Implementing, adhering to and evaluating COVID-19 mitigation guidelines is challenging in primary school settings. Our findings suggest that reducing non-household direct contacts lowers infection rates. There was no evidence that face coverings, two metre social distancing or stopping children mixing was associated with lower odds of COVID-19 or cold infection rates in the school. Primary school staff found teaching challenging during COVID-19 restrictions, especially for younger learners and those with additional learning needs.


Subject(s)
COVID-19 , Physical Distancing , SARS-CoV-2 , Schools , Students , Adolescent , Adult , COVID-19/epidemiology , COVID-19/prevention & control , Child , Humans , Male , Middle Aged , Wales/epidemiology
8.
Vaccine ; 39(42): 6256-6261, 2021 10 08.
Article in English | MEDLINE | ID: mdl-34544601

ABSTRACT

The COVID-19 pandemic has highlighted existing health inequalities for ethnic minority groups and those living in more socioeconomically deprived areas in the UK. With higher levels of severe outcomes in these groups, equitable vaccination coverage should be prioritised. The aim of this study was to identify inequalities in coverage of COVID-19 vaccination in Wales, UK and to highlight areas which may benefit from routine enhanced surveillance and targeted interventions. Records within the Wales Immunisation System (WIS) population register were linked to the Welsh Demographic Service Dataset (WDSD) and central list of shielding patients, held within the Secure Anonymised Information Linkage (SAIL) Databank. Ethnic group was derived from the 2011 census and over 20 administrative electronic health record (EHR) data sources. Uptake of first dose of any COVID-19 vaccine was analysed over time, with the odds of being vaccinated as at 25th April 2021 by sex, health board of residence, rural/urban classification, deprivation quintile and ethnic group presented. Using logistic regression models, analyses were adjusted for age group, care home resident status, health and social care worker status and shielding status. This study included 1,256,412 individuals aged 50 years and over. Vaccine coverage increased steadily from 8th December 2020 until mid-April 2021. Overall uptake of first dose of COVID-19 vaccine in this group was 92.1%. After adjustment the odds of being vaccinated were lower for individuals who were male, resident in the most deprived areas, resident in an urban area and an ethnic group other than White. The largest inequality was seen between ethnic groups, with the odds of being vaccinated 0.22 (95 %CI 0.21-0.24) if in any Black ethnic group compared to any White ethnic group. Ongoing monitoring of inequity in uptake of vaccinations is required, with better targeted interventions and engagement with deprived and ethnic communities to improve vaccination uptake.


Subject(s)
COVID-19 Vaccines , COVID-19 , Aged , Cross-Sectional Studies , Ethnicity , Humans , Male , Middle Aged , Minority Groups , Pandemics , Registries , SARS-CoV-2 , United Kingdom , Vaccination , Wales/epidemiology
10.
Circulation ; 136(19): 1784-1794, 2017 Nov 07.
Article in English | MEDLINE | ID: mdl-28851729

ABSTRACT

BACKGROUND: Asymptomatic atrial fibrillation (AF) is increasingly common in the aging population and implicated in many ischemic strokes. Earlier identification of AF with appropriate anticoagulation may decrease stroke morbidity and mortality. METHODS: We conducted a randomized controlled trial of AF screening using an AliveCor Kardia monitor attached to a WiFi-enabled iPod to obtain ECGs (iECGs) in ambulatory patients. Patients ≥65 years of age with a CHADS-VASc score ≥2 free from AF were randomized to the iECG arm or routine care (RC). iECG participants acquired iECGs twice weekly over 12 months (plus additional iECGs if symptomatic) onto a secure study server with overread by an automated AF detection algorithm and by a cardiac physiologist and/or consultant cardiologist. Time to diagnosis of AF was the primary outcome measure. The overall cost of the devices, ECG interpretation, and patient management were captured and used to generate the cost per AF diagnosis in iECG patients. Clinical events and patient attitudes/experience were also evaluated. RESULTS: We studied 1001 patients (500 iECG, 501 RC) who were 72.6±5.4 years of age; 534 were female. Mean CHADS-VASc score was 3.0 (heart failure, 1.4%; hypertension, 54%; diabetes mellitus, 30%; prior stroke/transient ischemic attack, 6.5%; arterial disease, 15.9%; all CHADS-VASc risk factors were evenly distributed between groups). Nineteen patients in the iECG group were diagnosed with AF over the 12-month study period versus 5 in the RC arm (hazard ratio, 3.9; 95% confidence interval=1.4-10.4; P=0.007) at a cost per AF diagnosis of $10 780 (£8255). There was a similar number of stroke/transient ischemic attack/systemic embolic events (6 versus 10, iECG versus RC; hazard ratio=0.61; 95% confidence interval=0.22-1.69; P=0.34). The majority of iECG patients were satisfied with the device, finding it easy to use without restricting activities or causing anxiety. CONCLUSIONS: Screening with twice-weekly single-lead iECG with remote interpretation in ambulatory patients ≥65 years of age at increased risk of stroke is significantly more likely to identify incident AF than RC over a 12-month period. This approach is also highly acceptable to this group of patients, supporting further evaluation in an appropriately powered, event-driven clinical trial. CLINICAL TRIAL REGISTRATION: URL: https://www.isrctn.com. Unique identifier: ISRCTN10709813.


Subject(s)
Atrial Fibrillation/diagnosis , Computers, Handheld , Electrocardiography, Ambulatory/instrumentation , Heart Conduction System/physiopathology , Heart Rate , Remote Sensing Technology/instrumentation , Telemedicine/instrumentation , Telemetry/instrumentation , Action Potentials , Aged , Algorithms , Asymptomatic Diseases , Atrial Fibrillation/economics , Atrial Fibrillation/physiopathology , Computers, Handheld/economics , Cost-Benefit Analysis , Electrocardiography, Ambulatory/economics , Equipment Design , Female , Health Care Costs , Humans , Male , Mobile Applications , Predictive Value of Tests , Prognosis , Prospective Studies , Remote Sensing Technology/economics , Reproducibility of Results , Signal Processing, Computer-Assisted , Telemedicine/economics , Telemetry/economics , Time Factors , Wales
11.
Math Biosci ; 274: 45-57, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26877075

ABSTRACT

We consider the epidemic dynamics in stochastic interacting population centers coupled by random migration. Both the epidemic and the migration processes are modeled by Markov chains. We derive explicit formulae for the probability distribution of the migration process, and explore the dependence of outbreak patterns on initial parameters, population sizes and coupling parameters, using analytical and numerical methods. We show the importance of considering the movement of resident and visitor individuals separately. The mean field approximation for a general migration process is derived and an approximate method that allows the computation of statistical moments for networks with highly populated centers is proposed and tested numerically.


Subject(s)
Communicable Diseases/epidemiology , Epidemics/statistics & numerical data , Communicable Diseases/transmission , Computer Simulation , Human Migration/statistics & numerical data , Humans , Markov Chains , Mathematical Concepts , Models, Biological , Population Density , Probability , Stochastic Processes
12.
BMC Public Health ; 14: 764, 2014 Jul 29.
Article in English | MEDLINE | ID: mdl-25074589

ABSTRACT

BACKGROUND: Fitness and physical activity are important for cardiovascular and mental health but activity and fitness levels are declining especially in adolescents and among girls. This study examines clustering of factors associated with low fitness in adolescents in order to best target public health interventions for young people. METHODS: 1147 children were assessed for fitness, had blood samples, anthropometric measures and all data were linked with routine electronic data to examine educational achievement, deprivation and health service usage. Factors associated with fitness were examined using logistic regression, conditional trees and data mining cluster analysis. Focus groups were conducted with children in a deprived school to examine barriers and facilitators to activity for children in a deprived community. RESULTS: Unfit adolescents are more likely to be deprived, female, have obesity in the family and not achieve in education. There were 3 main clusters for risk of future heart disease/diabetes (high cholesterol/insulin); children at low risk (not obese, fit, achieving in education), children 'visibly at risk' (overweight, unfit, many hospital/GP visits) and 'invisibly at risk' (unfit but not overweight, failing in academic achievement). Qualitative findings show barriers to physical activity include cost, poor access to activity, lack of core physical literacy skills and limited family support. CONCLUSIONS: Low fitness in the non-obese child can reveal a hidden group who have high risk factors for heart disease and diabetes but may not be identified as they are normal weight. In deprived communities low fitness is associated with non-achievement in education but in non-deprived communities low fitness is associated with female gender. Interventions need to target deprived families and schools in deprived areas with community wide campaigns.


Subject(s)
Diabetes Mellitus/etiology , Exercise , Heart Diseases/etiology , Obesity , Physical Fitness , Achievement , Adolescent , Child , Cholesterol/blood , Diabetes Mellitus/blood , Educational Status , Family , Female , Health Promotion , Health Services Accessibility , Heart Diseases/blood , Humans , Insulin/blood , Logistic Models , Male , Obesity/complications , Overweight , Poverty , Reference Values , Risk Factors , Schools
13.
Arch Dis Child ; 99(11): 1014-9, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24947281

ABSTRACT

OBJECTIVE: To evaluate a multistrain, high-dose probiotic in the prevention of eczema. DESIGN: A randomised, double-blind, placebo-controlled, parallel group trial. SETTINGS: Antenatal clinics, research clinic, children at home. PATIENTS: Pregnant women and their infants. INTERVENTIONS: Women from 36 weeks gestation and their infants to age 6 months received daily either the probiotic (Lactobacillus salivarius CUL61, Lactobacillus paracasei CUL08, Bifidobacterium animalis subspecies lactis CUL34 and Bifidobacterium bifidum CUL20; total of 10(10) organisms/day) or matching placebo. MAIN OUTCOME MEASURE: Diagnosed eczema at age 2 years. Infants were followed up by questionnaire. Clinical examination and skin prick tests to common allergens were done at 6 months and 2 years. RESULTS: The cumulative frequency of diagnosed eczema at 2 years was similar in the probiotic (73/214, 34.1%) and placebo arms (72/222, 32.4%; OR 1.07, 95% CI 0.72 to 1.6). Among the secondary outcomes, the cumulative frequency of skin prick sensitivity at 2 years was reduced in the probiotic (18/171; 10.5%) compared with the placebo arm (32/173; 18.5%; OR 0.52, 95% CI 0.28 to 0.98). The statistically significant differences between the arms were mainly in sensitisation to cow's milk and hen's egg proteins at 6 months. Atopic eczema occurred in 9/171 (5.3%) children in the probiotic arm and 21/173 (12.1%) in the placebo arm (OR 0.40, 95% CI 0.18 to 0.91). CONCLUSIONS: The study did not provide evidence that the probiotic either prevented eczema during the study or reduced its severity. However, the probiotic seemed to prevent atopic sensitisation to common food allergens and so reduce the incidence of atopic eczema in early childhood. TRIAL REGISTRATION NUMBER: ISRCTN26287422.


Subject(s)
Eczema/prevention & control , Probiotics/therapeutic use , Adult , Child , Child, Preschool , Double-Blind Method , Eczema/epidemiology , Female , Follow-Up Studies , Humans , Incidence , Infant , Infant, Newborn , Male , Pregnancy , Skin Tests , Surveys and Questionnaires
15.
Lancet ; 382(9900): 1249-57, 2013 Oct 12.
Article in English | MEDLINE | ID: mdl-23932219

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/adverse effects , Bifidobacterium , Clostridioides difficile , Diarrhea/prevention & control , Enterocolitis, Pseudomembranous/prevention & control , Lactobacillus , Probiotics/administration & dosage , Aged , Aged, 80 and over , Double-Blind Method , Female , Humans , Length of Stay , Male , Medication Adherence
16.
BMC Infect Dis ; 12: 108, 2012 May 06.
Article in English | MEDLINE | ID: mdl-22559011

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.


Subject(s)
Anti-Bacterial Agents/adverse effects , Bifidobacterium/physiology , Clinical Protocols , Clostridium Infections/prevention & control , Diarrhea/prevention & control , Lactobacillus/physiology , Probiotics/administration & dosage , Administration, Oral , Aged , Aged, 80 and over , Bifidobacterium/growth & development , Bifidobacterium/metabolism , Capsules/administration & dosage , Clostridium Infections/chemically induced , Diarrhea/chemically induced , Hospitals , Humans , Inpatients , Lactobacillus/growth & development , Lactobacillus/metabolism , Male , Placebos/administration & dosage , Prospective Studies , Treatment Outcome , United Kingdom
17.
Proc Biol Sci ; 279(1728): 465-73, 2012 Feb 07.
Article in English | MEDLINE | ID: mdl-21752825

ABSTRACT

Over-fishing may lead to a decrease in fish abundance and a proliferation of jellyfish. Active movements and prey search might be thought to provide a competitive advantage for fish, but here we use data-loggers to show that the frequently occurring coastal jellyfish (Rhizostoma octopus) does not simply passively drift to encounter prey. Jellyfish (327 days of data from 25 jellyfish with depth collected every 1 min) showed very dynamic vertical movements, with their integrated vertical movement averaging 619.2 m d(-1), more than 60 times the water depth where they were tagged. The majority of movement patterns were best approximated by exponential models describing normal random walks. However, jellyfish also showed switching behaviour from exponential patterns to patterns best fitted by a truncated Lévy distribution with exponents (mean µ=1.96, range 1.2-2.9) close to the theoretical optimum for searching for sparse prey (µopt≈2.0). Complex movements in these 'simple' animals may help jellyfish to compete effectively with fish for plankton prey, which may enhance their ability to increase in dominance in perturbed ocean systems.


Subject(s)
Predatory Behavior , Scyphozoa/physiology , Animals , Ecosystem , Gastrointestinal Contents , Models, Biological , Motor Activity , Movement , Seasons , Telemetry , Wales
18.
Math Biosci ; 234(2): 108-17, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21968464

ABSTRACT

The evolution of an infectious disease outbreak in an isolated population is split into two stages: a stochastic Markov process describing the initial contamination and a linked deterministic dynamical system with random initial conditions for the continued development of the outbreak. The initial contamination stage is well approximated by the randomized SI (susceptible/infected) model. We obtain the probability density function for the early behavior of the epidemic. This provides an appropriate distribution for the initial conditions with which to describe the subsequent deterministic evolution of the system. We apply the method of matching asymptotic expansions to link the two stages. This allows us to estimate the standard deviation of the number of infectives in the developed outbreak, and the statistical characteristics of the outbreak time. The potential trajectories caused by the stochastic nature of the contamination stage show greatest divergence at the initial and fade-out stages and coincide most tightly just after the peak of the epidemic. The time to the peak of the outbreak is not strongly dependent on the initial trajectory.


Subject(s)
Communicable Diseases/epidemiology , Disease Outbreaks , Models, Biological , Models, Statistical , Computer Simulation , Humans , Stochastic Processes
19.
BMC Public Health ; 11: 14, 2011 Jan 06.
Article in English | MEDLINE | ID: mdl-21210998

ABSTRACT

BACKGROUND: Physical activity is associated with better health. Two sources of activity for children are walking to school and taking part in organised sports and activities. This study uses a large national cohort to examine factors associated with participation in these activities. METHODS: The Millennium Cohort study contains 5 year follow-up of 17,561 singleton children recruited between 2000-2002 in the UK. All participants were interviewed in their own homes at 9 months, 3 years and 5 years follow-up and all measures were self reports. Logistic regression and likelihood ratio tests were used. RESULTS: Children are less likely to walk to school as income and parental education increase [Adjusted odds: 0.7 (95%CI: 0.6-0.8) for higher income/education compared to low income/no qualifications]. However, if the parent plays with the child in high income families the child is more likely to walk to school [Adjusted odds: 1.67 (95%CI: 1.3-2.1)]. Children taking part in organised activities are from higher income, higher education families, with a car, in a "good" area with non-working mothers. However, in low socio-economic families where the parent plays with the child the child is more likely to take part in organised activities [Adjusted odds: 2.0 (95% CI: 1.5-2.7)]. CONCLUSIONS: Income is an important determinant of the type of activity available to children. Families that report good health behaviours (non-smoking, low TV viewing) and play with their children show higher levels of physical activity. Thus, parenting practice appears to have a strong impact on their child's physical activity.


Subject(s)
Parents , Sports/statistics & numerical data , Walking/statistics & numerical data , Child, Preschool , Cohort Studies , Female , Follow-Up Studies , Health Behavior , Health Promotion/methods , Humans , Interviews as Topic , Male , Odds Ratio , Regression Analysis , Risk Factors , Schools , Socioeconomic Factors , United Kingdom , Urban Population
20.
Math Med Biol ; 28(2): 165-83, 2011 Jun.
Article in English | MEDLINE | ID: mdl-20819905

ABSTRACT

A 1D lattice of coupled susceptible/infected/removed (SIR) epidemic centres is considered numerically and analytically. We describe a mechanism for the interaction between nodes in an SIR network, i.e. for the migration process of individuals between epidemic centres with a finite-characteristic time. More specifically, we study a model for a weakly coupled population distributed between the interacting centres with a diffusion-type migration process. A 1D lattice of SIR nodes is studied numerically. Travelling wave-like solutions preserving their shape and speed are found over a wide parameter range. For weak coupling, the main part of the travelling wave is well approximated by the limiting SIR solution. Explicit formulae are found for the speed of the travelling waves and compared with the results of numerical simulation.


Subject(s)
Communicable Diseases/epidemiology , Epidemics , Models, Biological , Animals , Numerical Analysis, Computer-Assisted
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