BACKGROUND: Trials have identified antimicrobial stewardship (AMS) strategies that effectively reduce antibiotic use in primary care. However, many are not commonly used in England. The authors co-developed an implementation intervention to improve use of three AMS strategies: enhanced communication strategies, delayed prescriptions, and point-of-care C-reactive protein tests (POC-CRPTs). AIM: To investigate the use of the intervention in high-prescribing practices and its effect on antibiotic prescribing. DESIGN AND SETTING: Nine high-prescribing practices had access to the intervention for 12 months from November 2019. This was primarily delivered remotely via a website with practices required to identify an 'antibiotic champion'. METHOD: Routinely collected prescribing data were compared between the intervention and the control practices. Intervention use was assessed through monitoring. Surveys and interviews were conducted with professionals to capture experiences of using the intervention. RESULTS: There was no evidence that the intervention affected prescribing. Engagement with intervention materials differed substantially between practices and depended on individual champions' preconceptions of strategies and the opportunity to conduct implementation tasks. Champions in five practices initiated changes to encourage use of at least one AMS strategy, mostly POC-CRPTs; one practice chose all three. POC-CRPTs was used more when allocated to one person. CONCLUSION: Clinicians need detailed information on exactly how to adopt AMS strategies. Remote, one-sided provision of AMS strategies is unlikely to change prescribing; initial clinician engagement and understanding needs to be monitored to avoid misunderstanding and suboptimal use..

OBJECTIVES: To explore the characteristics of the General Practice Patient Survey (GPPS) respondents using the different functionalities of the online services in the context of England's National Health Service General Practices. We hypothesised that respondents who are older, with lower socioeconomic status and non-white ethnicity would be less likely to use online services, while long-term conditions might increase their usage. DESIGN: Cross-sectional study using respondent-level data from the GPPS in England of the years 2018, 2019 and 2020. We assessed the association between online services use and respondent characteristics using two-level mixed-effects logistic regression. PARTICIPANTS: Survey respondents of the GPPS 2018-2020. PRIMARY OUTCOME MEASURES: Online appointment booking and online repeat prescription ordering. RESULTS: 1 807 049 survey respondents were included in this study. 15% (n=263 938) used online appointment booking in the previous 12 months, and 19% (n=339 449) had ordered a repeat prescription in the previous 12 months. Respondents with a long-term condition, on regular multiple medications, who have deafness or hearing loss and who are from the lowest deprivation quintile were more likely to have used online services. Male respondents (compared with females) and respondents with black and other ethnicity compared with white ethnicity were less likely to use online services. Respondents over 85 years old were less likely to use online appointment booking and online repeat prescription ordering compared with the younger age groups. CONCLUSIONS: Specific groups of respondents were more likely to use online services such as patients with long-term conditions or those with deafness or hearing loss. While online services could provide efficiency to patients and practices it is essential that alternatives continue to be provided to those that cannot use or choose not to use online services. Understanding the different patients' needs could inform solutions to increase the uptake and use of the services..

BACKGROUND: Technological advances have led to the use of patient portals that give people digital access to their personal health information. The NHS App was launched in January 2019 as a 'front door' to digitally enabled health services. AIM: To evaluate patterns of uptake of the NHS App, subgroup differences in registration, and the impact of COVID-19. DESIGN AND SETTING: An observational study using monthly NHS App user data at general-practice level in England was conducted. METHOD: Descriptive statistics and time-series analysis explored monthly NHS App use from January 2019-May 2021. Interrupted time-series models were used to identify changes in the level and trend of use of different functionalities, before and after the first COVID-19 lockdown. Negative binomial regression assessed differences in app registration by markers of general-practice level sociodemographic variables. RESULT: Between January 2019 and May 2021, there were 8 524 882 NHS App downloads and 4 449 869 registrations, with a 4-fold increase in App downloads when the COVID Pass feature was introduced. Analyses by sociodemographic data found 25% lower registrations in the most deprived practices (P<0.001), and 44% more registrations in the largest sized practices (P<0.001). Registration rates were 36% higher in practices with the highest proportion of registered White patients (P<0.001), 23% higher in practices with the largest proportion of 15-34-year-olds (P<0.001) and 2% lower in practices with highest proportion of people with long-term care needs (P<0.001). CONCLUSION: The uptake of the NHS App substantially increased post-lockdown, most significantly after the NHS COVID Pass feature was introduced. An unequal pattern of app registration was identified, and the use of different functions varied. Further research is needed to understand these patterns of inequalities and their impact on patient experience..

The architectural design of hospitals worldwide is centred around individual departments, which require the movement of patients between wards. However, patients do not always take the simplest route from admission to discharge, but can experience convoluted movement patterns, particularly when bed availability is low. Few studies have explored the impact of these rarer, atypical trajectories. Using a mixed-method explanatory sequential study design, we firstly used three continuous years of electronic health record data prior to the Covid-19 pandemic, from 55,152 patients admitted to a London hospital network to define the ward specialities by patient type using the Herfindahl-Hirschman index. We explored the impact of 'regular transfers' between pairs of wards with shared specialities, 'atypical transfers' between pairs of wards with no shared specialities and 'site transfers' between pairs of wards in different hospital site locations, on length of stay, 30-day readmission and mortality. Secondly, to understand the possible reasons behind atypical transfers we conducted three focus groups and three in-depth interviews with site nurse practitioners and bed managers within the same hospital network. We found that at least one atypical transfer was experienced by 12.9% of patients. Each atypical transfer is associated with a larger increase in length of stay, 2.84 days (95% CI 2.56-3.12), compared to regular transfers, 1.92 days (95% CI 1.82-2.03). No association was found between odds of mortality, or 30-day readmission and atypical transfers after adjusting for confounders. Atypical transfers appear to be driven by complex patient conditions, a lack of hospital capacity, the need to reach specific services and facilities, and more exceptionally, rare events such as major incidents. Our work provides an important first step in identifying unusual patient movement and its impacts on key patient outcomes using a system-wide, data-driven approach. The broader impact of moving patients between hospital wards, and possible downstream effects should be considered in hospital policy and service planning..

OBJECTIVE: To explore the impact of the measures taken to combat COVID-19 on the patterns of acute illness in children presenting to primary and secondary care for North West London. DESIGN/SETTING/PARTICIPANTS: Retrospective analysis of 8 309 358 primary and secondary healthcare episodes of children <16 years registered with a North West London primary care practice between 2015 and 2021. MAIN OUTCOME MEASURES: Numbers of primary care consultations, emergency department (ED) attendances and emergency admissions during the pandemic were compared with those in the preceding 5 years. Trends were examined by age and for International Statistical Classification of Diseases and Related Health Problems 10th Revision-coded diagnoses of: infectious diseases, and injuries and poisonings for admitted children. RESULTS: Comparing 2020 to the 2015-2019 mean, primary care consultations were 22% lower, ED attendances were 38% lower and admissions 35% lower. Following the first national lockdown in April 2020, primary care consultations were 39% lower compared with the April 2015-2019 mean, ED attendances were 72% lower and unscheduled hospital admissions were 63% lower. Admissions >48 hours were on average 13% lower overall during 2020, and 36% lower during April 2020. The reduction in admissions for infections (61% lower than 2015-2019 mean) between April and August 2020 was greater than for injuries (31% lower). CONCLUSION: The COVID-19 pandemic was associated with an overall reduction in childhood illness presentations to health services in North West London, most prominent during periods of national lockdown, and with a greater impact on infections than injuries. These reductions demonstrate the impact on children of measures taken to combat COVID-19 across the health system..

BACKGROUND: COVID-19 is typically characterised by a triad of symptoms: cough, fever and loss of taste and smell, however, this varies globally. This study examines variations in COVID-19 symptom profiles based on underlying chronic disease and geographical location. METHODS: Using a global online symptom survey of 78,299 responders in 190 countries between 09/04/2020 and 22/09/2020, we conducted an exploratory study to examine symptom profiles associated with a positive COVID-19 test result by country and underlying chronic disease (single, co- or multi-morbidities) using statistical and machine learning methods. FINDINGS: From the results of 7980 COVID-19 tested positive responders, we find that symptom patterns differ by country. For example, India reported a lower proportion of headache (22.8% vs 47.8%, p<1e-13) and itchy eyes (7.3% vs. 16.5%, p=2e-8) than other countries. As with geographic location, we find people differed in their reported symptoms if they suffered from specific chronic diseases. For example, COVID-19 positive responders with asthma (25.3% vs. 13.7%, p=7e-6) were more likely to report shortness of breath compared to those with no underlying chronic disease. INTERPRETATION: We have identified variation in COVID-19 symptom profiles depending on geographic location and underlying chronic disease. Failure to reflect this symptom variation in public health messaging may contribute to asymptomatic COVID-19 spread and put patients with chronic diseases at a greater risk of infection. Future work should focus on symptom profile variation in the emerging variants of the SARS-CoV-2 virus. This is crucial to speed up clinical diagnosis, predict prognostic outcomes and target treatment. FUNDING: We acknowledge funding to AAF by a UKRI Turing AI Fellowship and to CEC by a personal NIHR Career Development Fellowship (grant number NIHR-2016-090-015). JKQ has received grants from The Health Foundation, MRC, GSK, Bayer, BI, Asthma UK-British Lung Foundation, IQVIA, Chiesi AZ, and Insmed. This work is supported by BREATHE - The Health Data Research Hub for Respiratory Health [MC_PC_19004]. BREATHE is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Imperial College London is grateful for the support from the Northwest London NIHR Applied Research Collaboration. The views expressed in this publication are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care..

BACKGROUND: A single dose strategy may be adequate to confer population level immunity and protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, especially in low- and middle-income countries where vaccine supply remains limited. We compared the effectiveness of a single dose strategy of the Oxford-AstraZeneca or Pfizer-BioNTech vaccines against SARS-CoV-2 infection across all age groups and over an extended follow-up period. METHODS: Individuals vaccinated in North-West London, UK, with either the first dose of the Oxford-AstraZeneca or Pfizer-BioNTech vaccines between January 12, 2021 and March 09, 2021, were matched to each other by demographic and clinical characteristics. Each vaccinated individual was additionally matched to an unvaccinated control. Study outcomes included SARS-CoV-2 infection of any severity, COVID-19 hospitalisation, COVID-19 death, and all-cause mortality. FINDINGS: Amongst matched individuals, 63,608 were in each of the vaccine groups and 127,216 were unvaccinated. Between 14 and 84 days of follow-up after matching, there were 534 SARS-CoV-2 infections, 65 COVID-19 hospitalisations, and 190 deaths, of which 29 were categorized as due to COVID-19. The incidence rate ratio (IRR) for SARS-CoV-2 infection was 0.85 (95% confidence interval [CI], 0.69 to 1.05) for Oxford-Astra-Zeneca, and 0.69 (0.55 to 0.86) for Pfizer-BioNTech. The IRR for both vaccines was the same at 0.25 (0.09 to 0.55) and 0.14 (0.02 to 0.58) for reducing COVID-19 hospitalization and COVID-19 mortality, respectively. The IRR for all-cause mortality was 0.25 (0.15 to 0.39) and 0.18 (0.10 to 0.30) for the Oxford-Astra-Zeneca and Pfizer-BioNTech vaccines, respectively. Age was an effect modifier of the association between vaccination and SARS-CoV-2 infection of any severity; lower hazard ratios for increasing age. INTERPRETATION: A single dose strategy, for both vaccines, was effective at reducing COVID-19 mortality and hospitalization rates. The magnitude of vaccine effectiveness was comparatively lower for SARS-CoV-2 infection, although this was variable across the age range, with higher effectiveness seen with older adults. Our results have important implications for health system planning -especially in low resource settings where vaccine supply remains constrained..

Neonates and children in low-income and middle-income countries (LMICs) contribute to the highest number of sepsis-associated deaths globally. Interventions to prevent sepsis mortality are hampered by a lack of comprehensive epidemiological data and pathophysiological understanding of biological pathways. In this review, we discuss the challenges faced by LMICs in diagnosing sepsis in these age groups. We highlight a role for multi-omics and health care data to improve diagnostic accuracy of clinical algorithms, arguing that health-care systems urgently need precision medicine to avoid the pitfalls of missed diagnoses, misdiagnoses, and overdiagnoses, and associated antimicrobial resistance. We discuss ethical, regulatory, and systemic barriers related to the collection and use of big data in LMICs. Technologies such as cloud computing, artificial intelligence, and medical tricorders might help, but they require collaboration with local communities. Co-partnering (joint equal development of technology between producer and end-users) could facilitate integration of these technologies as part of future care-delivery systems, offering a chance to transform the global management and prevention of sepsis for neonates and children..

BACKGROUND: Escherichia coli are Gram-negative bacteria associated with an increasing burden of antimicrobial resistance (AMR) in England. OBJECTIVES: To create a comprehensive epidemiological picture of E. coli bacteraemia resistance trends and risk factors in England by linking national microbiology data sources and performing a longitudinal analysis of rates. METHODS: A retrospective observational study was conducted on all national records for antimicrobial susceptibility testing on E. coli bacteraemia in England from 1 January 2013 to 31 December 2018 from the UK Health Security Agency (UKHSA) and the BSAC Resistance Surveillance Programme (BSAC-RSP). Trends in AMR and MDR were estimated using iterative sequential regression. Logistic regression analyses were performed on UKHSA data to estimate the relationship between risk factors and AMR or MDR in E. coli bacteraemia isolates. RESULTS: An increase in resistance rates was observed in community- and hospital-onset bacteraemia for third-generation cephalosporins, co-amoxiclav, gentamicin and ciprofloxacin. Among community-acquired cases, and after adjustment for other factors, patients aged >65 years were more likely to be infected by E. coli isolates resistant to at least one of 11 antibiotics than those aged 18-64 years (OR: 1.21, 95% CI: 1.18-1.25; P < 0.05). In hospital-onset cases, E. coli isolates from those aged 1-17 years were more likely to be resistant than those aged 18-64 years (OR: 1.33, 95% CI: 1.02-1.73; P < 0.05). CONCLUSIONS: Antibiotic resistance rates in E. coli-causing bacteraemia increased between 2013 and 2018 in England for key antimicrobial agents. Findings of this study have implications for guiding future policies on a prescribing of antimicrobial agents, for specific patient populations in particular..

BACKGROUND: School-based physical activity interventions such as The Daily Mile (TDM) are widely promoted in children's physical activity guidance. However, targeting such interventions to areas of greatest need is challenging since determinants vary across geographical areas. Our study aimed to identify local authorities in England with the greatest need to increase children's physical activity and assess whether TDM reaches school populations in areas with the highest need. METHODS: This was a cross-sectional study using routinely collected data from Public Health England. Datasets on health, census and the built environment were linked. We conducted a hierarchical cluster analysis to group local authorities by 'need' and estimated the association between 'need' and registration to TDM. RESULTS: We identified three clusters of high, medium and low need for physical activity interventions in 123 local authorities. Schools in high-need areas were more likely to be registered with TDM (incidence rate ratio 1.25, 95% confidence interval: 1.12-1.39) compared with low-need areas. CONCLUSIONS: Determinants of children's physical activity cluster geographically across local authorities in England. TDM appears to be an equitable intervention reaching schools in local authorities with the highest needs. Health policy should account for clustering of health determinants to match interventions with populations most in need..

OBJECTIVES: Escherichia coli bloodstream infections have shown a sustained increase in England, for reasons that are unknown. Furthermore, the contribution of MDR lineages such as ST131 to overall E. coli disease burden and outcome is undetermined. METHODS: We genome-sequenced E. coli blood isolates from all patients with E. coli bacteraemia in north-west London from July 2015 to August 2016 and assigned MLST genotypes, virulence factors and AMR genes to all isolates. Isolate STs were then linked to phenotypic antimicrobial susceptibility, patient demographics and clinical outcome data to explore relationships between the E. coli STs, patient factors and outcomes. RESULTS: A total of 551 E. coli genomes were analysed. Four STs (ST131, 21.2%; ST73, 14.5%; ST69, 9.3%; and ST95, 8.2%) accounted for over half of cases. E. coli genotype ST131-C2 was associated with phenotypic non-susceptibility to quinolones, third-generation cephalosporins, amoxicillin, amoxicillin/clavulanic acid, gentamicin and trimethoprim. Among 300 patients from whom outcome was known, an association between the ST131-C2 lineage and longer length of stay was detected, although multivariable regression modelling did not demonstrate an association between E. coli ST and mortality. Several unexpected associations were identified between gentamicin non-susceptibility, ethnicity, sex and adverse outcomes, requiring further research. CONCLUSIONS: Although E. coli ST was associated with defined antimicrobial non-susceptibility patterns and prolonged length of stay, E. coli ST was not associated with increased mortality. ST131 has outcompeted other lineages in north-west London. Where ST131 is prevalent, caution is required when devising empiric regimens for suspected Gram-negative sepsis, in particular the pairing of β-lactam agents with gentamicin..

Harnessing Real World Data is vital to improve health care in the 21st Century. Data from Electronic Health Records (EHRs) are a rich source of patient centred data, including information on the patient's clinical condition, laboratory results, diagnoses and treatments. They thus reflect the true state of health systems. However, access and utilisation of EHR data for research presents specific challenges. We assert that using data from EHRs effectively is dependent on synergy between researchers, clinicians and health informaticians, and only this will allow state of the art methods to be used to answer urgent and vital questions for patient care. We propose that there needs to be a paradigm shift in the way this research is conducted - appreciating that the research process is iterative rather than linear. We also make specific recommendations for organisations, based on our experience of developing and using EHR data in trusted research environments..

Abstract ProMED-mail (Program for Monitoring Emerging Disease) is an international disease outbreak monitoring and early warning system. Every year, users contribute thousands of reports that include reference to infectious diseases and toxins. However, due to the uneven distribution of the reports for each disease, traditional statistics-based text mining techniques, represented by term frequency-related algorithm, are not suitable. Thus, we conducted a study in three steps (i) report filtering, (ii) keyword extraction from reports and finally (iii) word co-occurrence network analysis to fill the gap between ProMED and its utilization. The keyword extraction was performed with the TextRank algorithm, keywords co-occurrence networks were then produced using the top keywords from each document and multiple network centrality measures were computed to analyse the co-occurrence networks. We used two major outbreaks in recent years, Ebola, 2014 and Zika 2015, as cases to illustrate and validate the process. We found that the extracted information structures are consistent with World Health Organisation description of the timeline and phases of the epidemics. Our research presents a pipeline that can extract and organize the information to characterize the evolution of epidemic outbreaks. It also highlights the potential for ProMED to be utilized in monitoring, evaluating and improving responses to outbreaks..

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OBJECTIVE: To examine primary school and local authority characteristics associated with registration for The Daily Mile (TDM), an active mile initiative aimed at increasing physical activity in children. DESIGN: A cross-sectional linkage study using routinely collected data. SETTING: All state-funded primary schools in England from 2012 to 2018 (n=15,815). RESULTS: 3,502 of all 15,815 (22.1%) state-funded primary schools in England were registered to do TDM, ranging from 16% in the East Midlands region to 31% in Inner London. Primary schools registered for TDM had larger mean pupil numbers compared with schools that had not registered (300 vs 269, respectively). There was a higher proportion of TDM-registered schools in urban areas compared with non-urban areas. There was local authority variation in the likelihood of school registration (intraclass correlation coefficient: 0.094). After adjusting for school and local authority characteristics, schools located in a major urban conurbation (OR 1.46 (95% CI 1.24 to 1.71) urban vs rural) and schools with a higher proportion of disadvantaged pupils had higher odds of being registered for TDM (OR 1.16 (95% CI 1.02 to 1.33)). Area-based physical activity and schools' educational attainment were not significantly associated with registration to TDM. CONCLUSION: One in five primary schools in England has registered for TDM since 2012. TDM appears to be a wide-reaching school-based physical activity intervention that is reaching more disadvantaged primary school populations in urban areas where obesity prevalence is highest. TDM-registered schools include those with both high and low educational attainment and are in areas with high and low physical activity..

BACKGROUND: Intrahospital transfers have become more common as hospital staff balance patient needs with bed availability. However, this may leave patients more vulnerable to potential pathogen transmission routes via increased exposure to contaminated surfaces and contacts with individuals. OBJECTIVE: This study aimed to quantify the association between the number of intrahospital transfers undergone during a hospital spell and the development of a hospital-acquired infection (HAI). METHODS: A retrospective case-control study was conducted using data extracted from electronic health records and microbiology cultures of non-elective, medical admissions to a large urban hospital network which consists of three hospital sites between 2015 and 2018 (n=24 240). As elderly patients comprise a large proportion of hospital users and are a high-risk population for HAIs, the analysis focused on those aged 65 years or over. Logistic regression was conducted to obtain the OR for developing an HAI as a function of intrahospital transfers until onset of HAI for cases, or hospital discharge for controls, while controlling for age, gender, time at risk, Elixhauser comorbidities, hospital site of admission, specialty of the dominant healthcare professional providing care, intensive care admission, total number of procedures and discharge destination. RESULTS: Of the 24 240 spells, 2877 cases were included in the analysis. 72.2% of spells contained at least one intrahospital transfer. On multivariable analysis, each additional intrahospital transfer increased the odds of acquiring an HAI by 9% (OR=1.09; 95% CI 1.05 to 1.13). CONCLUSION: Intrahospital transfers are associated with increased odds of developing an HAI. Strategies for minimising intrahospital transfers should be considered, and further research is needed to identify unnecessary transfers. Their reduction may diminish spread of contagious pathogens in the hospital environment..

INTRODUCTION: Emergency department (ED) attendances fell across the UK after the 'lockdown' introduced on 23rd March 2020 to limit the spread of coronavirus disease 2019 (COVID-19). We hypothesised that reductions would vary by patient age and disease type. We examined pre- and in-lockdown ED attendances for two COVID-19 unrelated diagnoses: one likely to be affected by lockdown measures (gastroenteritis), and one likely to be unaffected (appendicitis). METHODS: We conducted a retrospective cross-sectional study across two EDs in one London hospital Trust. We compared all adult and paediatric ED attendances, before (January 2020) and during lockdown (March/April 2020). Key patient demographics, method of arrival, and discharge location were compared. We used Systemised Nomenclature of Medicine codes to define attendances for gastroenteritis and appendicitis. RESULTS: ED attendances fell from 1129 per day before lockdown to 584 in lockdown, 51.7% of pre-lockdown rates. In-lockdown attendances were lowest for under-18s (16.0% of pre-lockdown). The proportion of patients admitted to hospital increased from 17.3% to 24.0%, and the proportion admitted to intensive care increased fourfold. Attendances for gastroenteritis fell from 511 to 103, 20.2% of pre-lockdown rates. Attendances for appendicitis also decreased, from 144 to 41, 28.5% of pre-lockdown rates. CONCLUSION: ED attendances fell substantially following lockdown implementation. The biggest reduction was for under-18s. We observed reductions in attendances for gastroenteritis and appendicitis. This may reflect lower rates of infectious disease transmission, although the fall in appendicitis-related attendances suggests that behavioural factors were also important. Larger studies are urgently needed to understand changing patterns of ED use and access to emergency care during the coronavirus 2019 pandemic..

BACKGROUND: Delayed (or "backup") antibiotic prescription, where the patient is given a prescription but advised to delay initiating antibiotics, has been shown to be effective in reducing antibiotic use in primary care. However, this strategy is not widely used in the United Kingdom. This study aimed to identify factors influencing preferences among the UK public for delayed prescription, and understand their relative importance, to help increase appropriate use of this prescribing option. METHODS AND FINDINGS: We conducted an online choice experiment in 2 UK general population samples: adults and parents of children under 18 years. Respondents were presented with 12 scenarios in which they, or their child, might need antibiotics for a respiratory tract infection (RTI) and asked to choose either an immediate or a delayed prescription. Scenarios were described by 7 attributes. Data were collected between November 2018 and February 2019. Respondent preferences were modelled using mixed-effects logistic regression. The survey was completed by 802 adults and 801 parents (75% of those who opened the survey). The samples reflected the UK population in age, sex, ethnicity, and country of residence. The most important determinant of respondent choice was symptom severity, especially for cough-related symptoms. In the adult sample, the probability of choosing delayed prescription was 0.53 (95% confidence interval (CI) 0.50 to 0.56, p < 0.001) for a chesty cough and runny nose compared to 0.30 (0.28 to 0.33, p < 0.001) for a chesty cough with fever, 0.47 (0.44 to 0.50, p < 0.001) for sore throat with swollen glands, and 0.37 (0.34 to 0.39, p < 0.001) for sore throat, swollen glands, and fever. Respondents were less likely to choose delayed prescription with increasing duration of illness (odds ratio (OR) 0.94 (0.92 to 0.96, p < 0.001)). Probabilities of choosing delayed prescription were similar for parents considering treatment for a child (44% of choices versus 42% for adults, p = 0.04). However, parents differed from the adult sample in showing a more marked reduction in choice of the delayed prescription with increasing duration of illness (OR 0.83 (0.80 to 0.87) versus 0.94 (0.92 to 0.96) for adults, p for heterogeneity p < 0.001) and a smaller effect of disruption of usual activities (OR 0.96 (0.95 to 0.97) versus 0.93 (0.92 to 0.94) for adults, p for heterogeneity p < 0.001). Females were more likely to choose a delayed prescription than males for minor symptoms, particularly minor cough (probability 0.62 (0.58 to 0.66, p < 0.001) for females and 0.45 (0.41 to 0.48, p < 0.001) for males). Older people, those with a good understanding of antibiotics, and those who had not used antibiotics recently showed similar patterns of preferences. Study limitations include its hypothetical nature, which may not reflect real-life behaviour; the absence of a "no prescription" option; and the possibility that study respondents may not represent the views of population groups who are typically underrepresented in online surveys. CONCLUSIONS: This study found that delayed prescription appears to be an acceptable approach to reducing antibiotic consumption. Certain groups appear to be more amenable to delayed prescription, suggesting particular opportunities for increased use of this strategy. Prescribing choices for sore throat may need additional explanation to ensure patient acceptance, and parents in particular may benefit from reassurance about the usual duration of these illnesses..

BACKGROUND: Antimicrobial resistance is a major global health concern, driven by overuse of antibiotics. We aimed to assess the effectiveness of a national antimicrobial stewardship intervention, the National Health Service (NHS) England Quality Premium implemented in 2015-16, on broad-spectrum antibiotic prescribing and Escherichia coli bacteraemia resistance to broad-spectrum antibiotics in England. METHODS: In this quasi-experimental, ecological, data linkage study, we used longitudinal data on bacteraemia for patients registered with a general practitioner in the English National Health Service and patients with E coli bacteraemia notified to the national mandatory surveillance programme between Jan 1, 2013, and Dec 31, 2018. We linked these data to data on antimicrobial susceptibility testing of E coli from Public Health England's Second-Generation Surveillance System. We did an ecological analysis using interrupted time-series analyses and generalised estimating equations to estimate the change in broad-spectrum antibiotics prescribing over time and the change in the proportion of E coli bacteraemia cases for which the causative bacteria were resistant to each antibiotic individually or to at least one of five broad-spectrum antibiotics (co-amoxiclav, ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin), after implementation of the NHS England Quality Premium intervention in April, 2015. FINDINGS: Before implementation of the Quality Premium, the rate of antibiotic prescribing for all five broad-spectrum antibiotics was increasing at rate of 0·2% per month (incidence rate ratio [IRR] 1·002 [95% CI 1·000-1·004], p=0·046). After implementation of the Quality Premium, an immediate reduction in total broad-spectrum antibiotic prescribing rate was observed (IRR 0·867 [95% CI 0·837-0·898], p<0·0001). This effect was sustained until the end of the study period; a 57% reduction in rate of antibiotic prescribing was observed compared with the counterfactual situation (ie, had the Quality Premium not been implemented). In the same period, the rate of resistance to at least one broad-spectrum antibiotic increased at rate of 0·1% per month (IRR 1·001 [95% CI 0·999-1·003], p=0·346). On implementation of the Quality Premium, an immediate reduction in resistance rate to at least one broad-spectrum antibiotic was observed (IRR 0·947 [95% CI 0·918-0·977], p=0·0007). Although this effect was also sustained until the end of the study period, with a 12·03% reduction in resistance rate compared with the counterfactual situation, the overall trend remained on an upward trajectory. On examination of the long-term effect following implementation of the Quality Premium, there was an increase in the number of isolates resistant to at least one of the five broad-spectrum antibiotics tested (IRR 1·002 [1·000-1·003]; p=0·047). INTERPRETATION: Although interventions targeting antibiotic use can result in changes in resistance over a short period, they might be insufficient alone to curtail antimicrobial resistance. FUNDING: National Institute for Health Research, Economic and Social Research Council, Rosetrees Trust, and The Stoneygate Trust..

BACKGROUND: Trials show that antimicrobial stewardship (AMS) strategies, including communication skills training, point-of-care C-reactive protein testing (POC-CRPT) and delayed prescriptions, help optimise antibiotic prescribing and use in primary care. However, the use of these strategies in general practice is limited and inconsistent. We aimed to develop an intervention to enhance uptake and implementation of these strategies in primary care. METHODS: We drew on the Person-Based Approach to develop an implementation intervention in two stages. (1) Planning and design: We defined the problem in behavioural terms drawing on existing literature and conducting primary qualitative research (nine focus groups) in high-prescribing general practices. We identified 'guiding principles' with intervention objectives and key features and developed logic models representing intended mechanisms of action. (2) Developing the intervention: We created prototype intervention materials and discussed and refined these with input from 13 health professionals and 14 citizens in two sets of design workshops. We further refined the intervention materials following think-aloud interviews with 22 health professionals. RESULTS: Focus groups highlighted uncertainties about how strategies could be used. Health professionals in the workshops suggested having practice champions, brief summaries of each AMS strategy and evidence supporting the AMS strategies, and they and citizens gave examples of helpful communication strategies/phrases. Think-aloud interviews helped clarify and shorten the text and user journey of the intervention materials. The intervention comprised components to support practice-level implementation: antibiotic champions, practice meetings with slides provided, and an 'implementation support' website section, and components to support individual-level uptake: website sections on each AMS strategy (with evidence, instructions, links to electronic resources) and material resources (patient leaflets, POC-CRPT equipment, clinician handouts). CONCLUSIONS: We used a systematic, user-focussed process of developing a behavioural intervention, illustrating how it can be used in an implementation context. This resulted in a multicomponent intervention to facilitate practice-wide implementation of evidence-based strategies which now requires implementing and evaluating. Focusing on supporting the uptake and implementation of evidence-based strategies to optimise antibiotic use in general practice is critical to further support appropriate antibiotic use and mitigate antimicrobial resistance..

BACKGROUND: Hospitals in England have undergone considerable change to address the surge in demand imposed by the COVID-19 pandemic. The impact of this on emergency department (ED) attendances is unknown, especially for non-COVID-19 related emergencies. METHODS: This analysis is an observational study of ED attendances at the Imperial College Healthcare NHS Trust (ICHNT). We calibrated auto-regressive integrated moving average time-series models of ED attendances using historic (2015-2019) data. Forecasted trends were compared to present year ICHNT data for the period between March 12, 2020 (when England implemented the first COVID-19 public health measure) and May 31, 2020. We compared ICHTN trends with publicly available regional and national data. Lastly, we compared hospital admissions made via the ED and in-hospital mortality at ICHNT during the present year to the historic 5-year average. RESULTS: ED attendances at ICHNT decreased by 35% during the period after the first lockdown was imposed on March 12, 2020 and before May 31, 2020, reflecting broader trends seen for ED attendances across all England regions, which fell by approximately 50% for the same time frame. For ICHNT, the decrease in attendances was mainly amongst those aged < 65 years and those arriving by their own means (e.g. personal or public transport) and not correlated with any of the spatial dependencies analysed such as increasing distance from postcode of residence to the hospital. Emergency admissions of patients without COVID-19 after March 12, 2020 fell by 48%; we did not observe a significant change to the crude mortality risk in patients without COVID-19 (RR 1.13, 95%CI 0.94-1.37, p = 0.19). CONCLUSIONS: Our study findings reflect broader trends seen across England and give an indication how emergency healthcare seeking has drastically changed. At ICHNT, we find that a larger proportion arrived by ambulance and that hospitalisation outcomes of patients without COVID-19 did not differ from previous years. The extent to which these findings relate to ED avoidance behaviours compared to having sought alternative emergency health services outside of hospital remains unknown. National analyses and strategies to streamline emergency services in England going forward are urgently needed..

BACKGROUND: Trials have shown that delayed antibiotic prescriptions (DPs) and point-of-care C-Reactive Protein testing (POC-CRPT) are effective in reducing antibiotic use in general practice, but these were not typically implemented in high-prescribing practices. We aimed to explore views of professionals from high-prescribing practices about uptake and implementation of DPs and POC-CRPT to reduce antibiotic use. METHODS: This was a qualitative focus group study in English general practices. The highest antibiotic prescribing practices in the West Midlands were invited to participate. Clinical and non-clinical professionals attended focus groups co-facilitated by two researchers. Focus groups were audio-recorded, transcribed verbatim and analysed thematically. RESULTS: Nine practices (50 professionals) participated. Four main themes were identified. Compatibility of strategies with clinical roles and experience - participants viewed the strategies as having limited value as 'clinical tools', perceiving them as useful only in 'rare' instances of clinical uncertainty and/or for those less experienced. Strategies as 'social tools' - participants perceived the strategies as helpful for negotiating treatment decisions and educating patients, particularly those expecting antibiotics. Ambiguities - participants perceived ambiguities around when they should be used, and about their impact on antibiotic use. Influence of context - various other situational and practical issues were raised with implementing the strategies. CONCLUSIONS: High-prescribing practices do not view DPs and POC-CRPT as sufficiently useful 'clinical tools' in a way which corresponds to the current policy approach advocating their use to reduce clinical uncertainty and improve antimicrobial stewardship. Instead, policy attention should focus on how these strategies may instead be used as 'social tools' to reduce unnecessary antibiotic use. Attention should also focus on the many ambiguities (concerns and questions) about, and contextual barriers to, using these strategies that need addressing to support wider and more consistent implementation..

Antibiotic prescribing in England varies considerably between Clinical Commissioning Groups (CCGs) and general practices. We aimed to assess social and contextual factors affecting antibiotic prescribing and engagement with antimicrobial stewardship (AMS) initiatives. Semi-structured telephone interviews were conducted with 22 CCG professionals and 19 general practice professionals. Interviews were audio-recorded, transcribed, and analyzed thematically. Social/contextual influences were grouped into the following four categories: (1) Immediate context, i.e., patients' social characteristics (e.g., deprivation and culture), clinical factors, and practice and clinician characteristics (e.g., "struggling" with staff shortage/turnover) were linked to higher prescribing. (2) Wider context, i.e., pressures on the healthcare system, limited resources, and competing priorities were seen to reduce engagement with AMS. (3) Collaborative and whole system approaches, i.e., communication, multidisciplinary networks, leadership, and teamwork facilitated prioritizing AMS, learning, and consistency. (4) Relativity of appropriate prescribing, i.e., "high" or "appropriate" prescribing was perceived as relative, depending on comparators, and disregarding different contexts, but social norms around antibiotic use among professionals and patients seemed to be changing. Further optimization of antibiotic prescribing would benefit from addressing social/contextual factors and addressing wider health inequalities, not only targeting individual clinicians. Tailoring and adapting to local contexts and constraints, ensuring adequate time and resources for AMS, and collaborative, whole system approaches to promote consistency may help promote AMS..

BACKGROUND: The Quality Premium (QP) was introduced for Clinical Commissioning Groups (CCGs) in England to optimize antibiotic prescribing, but it remains unclear how it was implemented. OBJECTIVES: To understand responses to the QP and how it was perceived to influence antibiotic prescribing. METHODS: Semi-structured telephone interviews were conducted with 22 CCG and 19 general practice professionals. Interviews were analysed thematically. RESULTS: The findings were organized into four categories. (i) Communication: this was perceived as unstructured and infrequent, and CCG professionals were unsure whether they received QP funding. (ii) Implementation: this was influenced by available local resources and competing priorities, with multifaceted and tailored strategies seen as most helpful for engaging general practices. Many antimicrobial stewardship (AMS) strategies were implemented independently from the QP, motivated by quality improvement. (iii) Mechanisms: the QP raised the priority of AMS nationally and locally, and provided prescribing targets to aim for and benchmark against, but money was not seen as reinvested into AMS. (iv) Impact and sustainability: the QP was perceived as successful, but targets were considered challenging for a minority of CCGs and practices due to contextual factors (e.g. deprivation, understaffing). CCG professionals were concerned with potential discontinuation of the QP and prescribing rates levelling off. CONCLUSIONS: CCG and practice professionals expressed positive views of the QP and associated prescribing targets and feedback. The QP helped influence change mainly by raising the priority of AMS and defining change targets rather than providing additional funding. To maximize impact, behavioural mechanisms of financial incentives should be considered pre-implementation..

OBJECTIVE: The study sought to determine the impact of a digital sepsis alert on patient outcomes in a UK multisite hospital network. MATERIALS AND METHODS: A natural experiment utilizing the phased introduction (without randomization) of a digital sepsis alert into a multisite hospital network. Sepsis alerts were either visible to clinicians (patients in the intervention group) or running silently and not visible (the control group). Inverse probability of treatment-weighted multivariable logistic regression was used to estimate the effect of the intervention on individual patient outcomes. OUTCOMES: In-hospital 30-day mortality (all inpatients), prolonged hospital stay (≥7 days) and timely antibiotics (≤60 minutes of the alert) for patients who alerted in the emergency department. RESULTS: The introduction of the alert was associated with lower odds of death (odds ratio, 0.76; 95% confidence interval [CI], 0.70-0.84; n = 21 183), lower odds of prolonged hospital stay ≥7 days (OR, 0.93; 95% CI, 0.88-0.99; n = 9988), and in patients who required antibiotics, an increased odds of receiving timely antibiotics (OR, 1.71; 95% CI, 1.57-1.87; n = 4622). DISCUSSION: Current evidence that digital sepsis alerts are effective is mixed. In this large UK study, a digital sepsis alert has been shown to be associated with improved outcomes, including timely antibiotics. It is not known whether the presence of alerting is responsible for improved outcomes or whether the alert acted as a useful driver for quality improvement initiatives. CONCLUSIONS: These findings strongly suggest that the introduction of a network-wide digital sepsis alert is associated with improvements in patient outcomes, demonstrating that digital based interventions can be successfully introduced and readily evaluated..

Professional education and public engagement are fundamental components of any antimicrobial stewardship (AMS) strategy. The National Institute for Health and Care Excellence (NICE), Public Health England (PHE), Health Education England (HEE) and other professional organisations, develop and publish resources to support AMS activity in primary care settings. The aim of this study was to explore the adoption and use of education/training and supporting AMS resources within NHS primary care in England. Questionnaires were sent to the medicines management teams of all 209 Clinical Commissioning Groups (CCGs) in England, in 2017. Primary care practitioners in 168/175 (96%) CCGs received AMS education in the last two years. Respondents in 184/186 (99%) CCGs reported actively promoting the TARGET Toolkit to their primary care practitioners; although 137/176 (78%) did not know what percentage of primary care practitioners used the TARGET toolkit. All respondents were aware of Antibiotic Guardian and 132/167 (79%) reported promoting the campaign. Promotion of AMS resources to general practices is currently excellent, but as evaluation of uptake or effect is poor, this should be encouraged by resource providers and through quality improvement programmes. Trainers should be encouraged to promote and highlight the importance of action planning within their AMS training. AMS resources, such as leaflets and education, should be promoted across the whole health economy, including Out of Hours and care homes. Primary care practitioners should continue to be encouraged to display a signed Antibiotic Guardian poster as well as general AMS posters and videos in practice, as patients find them useful and noticeable..

BACKGROUND: Studies estimating excess length of stay (LOS) attributable to nosocomial infections have failed to address time-varying confounding, likely leading to overestimation of their impact. We present a methodology based on inverse probability-weighted survival curves to address this limitation. METHODS: A case study focusing on intensive care unit-acquired bacteremia using data from 2 general intensive care units (ICUs) from 2 London teaching hospitals were used to illustrate the methodology. The area under the curve of a conventional Kaplan-Meier curve applied to the observed data was compared with that of an inverse probability-weighted Kaplan-Meier curve applied after treating bacteremia as censoring events. Weights were based on the daily probability of acquiring bacteremia. The difference between the observed average LOS and the average LOS that would be observed if all bacteremia cases could be prevented was multiplied by the number of admitted patients to obtain the total excess LOS. RESULTS: The estimated total number of extra ICU days caused by 666 bacteremia cases was estimated at 2453 (95% confidence interval [CI], 1803-3103) days. The excess number of days was overestimated when ignoring time-varying confounding (2845 [95% CI, 2276-3415]) or when completely ignoring confounding (2838 [95% CI, 2101-3575]). CONCLUSIONS: ICU-acquired bacteremia was associated with a substantial excess LOS. Wider adoption of inverse probability-weighted survival curves or alternative techniques that address time-varying confounding could lead to better informed decision making around nosocomial infections and other time-dependent exposures..

OBJECTIVES: To identify and explore strategies that English NHS commissioning organizations implemented to improve antimicrobial stewardship (AMS) within primary care. METHODS: Questionnaire sent to the medicines management teams (MMTs) of all 209 clinical commissioning groups (CCGs) in England, in 2017. RESULTS: A total of 89% (187/209) of all English CCGs responded to the questionnaire; 74% of responding CCGs (123/167) had a prescribing incentive/engagement scheme, with MMTs representing 88% (90/102) considering incentive schemes successful or very successful for prioritizing AMS in primary care, especially when linked to prescribing NHS Quality Premium indicators. AMS audits were considered successful or very successful by 91% (126/138) of responding CCGs, as they identify reasons for inappropriate prescribing and opportunities for future improvement. All responding MMTs (169/169 CCGs) reported feeding back local/national antimicrobial prescribing data to the general practices they commission, 85% (142/168) to their CCG/Commissioning Support Unit (CSU) board and only 33% (56/169) to out-of-hours services. Benchmarking prescribing data was reported as a powerful tool to engage practices, facilitating an element of competition and peer pressure. CONCLUSIONS: National antimicrobial resistance improvement schemes, in particular the NHS England Quality Premium, have influenced CCG improvement priorities. Most CCGs now report successful improvement strategies including the use of both local and national antibiotic prescribing data to motivate improvements; these should be continued and extended to out-of-hours providers. As local audit data have helped to identify reasons for inappropriate prescribing and inform improvement planning, all organizations should adopt this strategy and include it in local quality improvement schemes, ensuring performance reporting to organizational board level..

BACKGROUND: In 2017, approximately 73% of antibiotics in England were prescribed from primary care practices. It has been estimated that 9%-23% of antibiotic prescriptions between 2013 and 2015 were inappropriate. Reducing antibiotic prescribing in primary care was included as one of the national priorities in a financial incentive scheme in 2015-2016. AIM: To investigate whether the effects of the Quality Premium (QP), which provided performance-related financial incentives to clinical commissioning groups (CCGs), could be explained by practice characteristics that contribute to variations in antibiotic prescribing. DESIGN & SETTING: Longitudinal monthly prescribing data were analysed for 6251 primary care practices in England from April 2014 to March 2016. METHOD: Linear generalised estimating equations models were fitted, examining the effect of the 2015-2016 QP on the number of antibiotic items per specific therapeutic group age-sex related prescribing unit (STAR-PU) prescribed, adjusting for seasonality and months since implementation. Consistency of effects after further adjustment for variations in practice characteristics were also examined, including practice workforce, comorbidities prevalence, prescribing rates of non-antibiotic drugs, and deprivation. RESULTS: Antibiotics prescribed in primary care practices in England reduced by -0.172 items per STAR-PU (95% confidence interval [CI] = -0.180 to -0.171) after 2015-2016 QP implementation, with slight increases in the months following April 2015 (+0.014 items per STAR-PU; 95% CI = +0.013 to +0.014). Adjusting the model for practice characteristics, the immediate and month-on-month effects following implementation remained consistent, with slight attenuation in immediate reduction from -0.172 to -0.166 items per STAR-PU. In subgroup analysis, the QP effect was significantly greater among the top 20% prescribing practices (interaction p<0.001). Practices with low workforce and those with higher diabetes prevalence had greater reductions in prescribing following 2015-2016 QP compared with other practices (interaction p<0.001). CONCLUSION: In high-prescribing practices, those with low workforce and high diabetes prevalence had more reduction following the QP compared with other practices, highlighting the need for targeted support of these practices and appropriate resourcing of primary care..

BACKGROUND: The Singapore GSDCS score was developed to enable clinicians predict the risk of nosocomial multidrug-resistant Gram-negative bacilli (RGNB) infection in critically ill patients. We aimed to validate this score in a UK setting. METHOD: A retrospective case-control study was conducted including patients who stayed for more than 24h in intensive care units (ICUs) across two tertiary National Health Service hospitals in London, UK (April 2011-April 2016). Cases with RGNB and controls with sensitive Gram-negative bacilli (SGNB) infection were identified. RESULTS: The derived GSDCS score was calculated from when there was a step change in antimicrobial therapy in response to clinical suspicion of infection as follows: prior Gram-negative organism, Surgery, Dialysis with end-stage renal disease, prior Carbapenem use and intensive care Stay of more than 5 days. A total of 110 patients with RGNB infection (cases) were matched 1:1 to 110 geotemporally chosen patients with SGNB infection (controls). The discriminatory ability of the prediction tool by receiver operating characteristic curve analysis in our validation cohort was 0.75 (95% confidence interval 0.65-0.81), which is comparable with the area under the curve of the derivation cohort (0.77). The GSDCS score differentiated between low- (0-1.3), medium- (1.4-2.3) and high-risk (2.4-4.3) patients for RGNB infection (P<0.001) in a UK setting. CONCLUSION: A simple bedside clinical prediction tool may be used to identify and differentiate patients at low, medium and high risk of RGNB infection prior to initiation of prompt empirical antimicrobial therapy in the intensive care setting..

BACKGROUND: Patient portal use could help improve the care and health outcomes of patients with diabetes owing to functionalities, such as appointment booking, electronic messaging (e-messaging), and repeat prescription ordering, which enable patient-centered care and improve patient self-management of the disease. OBJECTIVE: This review aimed to summarize the evidence regarding patient portal use (portals that are connected to electronic health care records) or patient portal functionality use (eg, appointment booking and e-messaging) and their reported associations with health and health care quality outcomes among adult patients with diabetes. METHODS: We searched the MEDLINE, Embase, and Scopus databases and reported the review methodology using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Three independent reviewers screened titles and abstracts, and two reviewers assessed the full texts of relevant studies and performed data extraction and quality assessments of the included studies. We used the Cochrane Collaboration Risk of Bias Tool and the National Heart, Lung and Blood Institute (NHLBI) Study Quality Assessment Tool to assess the risk of bias of the included studies. Data were summarized through narrative synthesis. RESULTS: Twelve studies were included in this review. Five studies reported overall patient portal use and its association with diabetes health and health care quality outcomes. Six studies reported e-messaging or email use-associated outcomes, and two studies reported prescription refill-associated outcomes. The reported health outcomes included the associations of patient portal use with blood pressure, low-density lipoprotein cholesterol, and BMI. Few studies reported health care utilization outcomes such as office visits, emergency department visits, and hospitalizations. A limited number of studies reported overall quality of care for patients with diabetes who used patient portals. CONCLUSIONS: The included studies mostly reported improved glycemic control outcomes for patients with diabetes who used patient portals. However, limitations of studying the effects of patient portals exist, which do not guarantee whether the outcomes reported are completely the result of patient portal use or if confounding factors exist. Randomized controlled trials and mixed-methods studies could help understand the mechanisms involved in health outcome improvements and patient portal use among patients with diabetes. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) CRD42019141131; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019141131. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/14975..

Background: In order to tackle the public health threat of antimicrobial resistance, improvement in antibiotic prescribing in primary care was included as one of the priorities of the Quality Premium (QP) financial incentive scheme for Clinical Commissioning Groups (CCGs) in England. This paper briefly reports the outcome of a workshop exploring the experiences of antimicrobial stewardship (AMS) leads within CCGs in selecting and adopting strategies to help achieve the QP antibiotic targets. Methods: We conducted a thematic analysis of the notes on discussions and observations from the workshop to identify key themes. Results: Practice visits, needs assessment, peer feedback and audits were identified as strategies integrated in increasing engagement with practices towards the QP antibiotic targets. The conceptual model developed by AMS leads demonstrated possible pathways for the impact of the QP on antibiotic prescribing. Participants raised a concern that the constant targeting of high prescribing practices for AMS interventions might lead to disengagement by these practices. Most of the participants suggested that the effect of the QP might be less about the financial incentive and more about having national targets and guidelines that promote antibiotic prudency. Conclusions: Our results suggest that national targets, rather than financial incentives are key for engaging stakeholders in quality improvement in antibiotic prescribing..

BACKGROUND: Patient portals are digital health tools adopted by health care organizations. The portals are generally connected to the electronic health record of the health care organization and offer patients functionalities such as access to the medical record, ability to order repeat prescriptions, make appointments, or message the health care provider. Patient portals may be beneficial for both patients and the health care system. Patient portals can widely differ from one context to another due to the differences in the portal functionalities and capabilities and it is anticipated that outcomes associated with the functionalities also differ. Current systematic reviews report outcomes associated with patient portal uptake but do not explicitly specify the patient portal functionalities. OBJECTIVE: The aim of this systematic review is to synthesize the evidence on health and health care quality outcomes associated with patient portal use among adult (18 years or older) patients. The review research questions are as follows: What kind of health outcomes do tethered patient portals and patient portal functionalities contribute to in adult patients (18 years or older)? and What kind of health care quality outcomes, including health care utilization outcomes, do tethered patient portals and patient portal functionalities contribute to in adult patients (18 years or older)? METHODS: The systematic review will be conducted by searching the MEDLINE, EMBASE, and Scopus databases for relevant literature. The review inclusion criteria will be studies about adult patients (18 years or older), studies only about tethered patient portals, and studies with or without a comparator. We will report patient portal-associated health and health care quality outcomes based on the patient portal functionalities. All quantitative primary study types will be included. Risk of bias of included studies will be assessed using the Cochrane Collaboration's tool for assessing risk of bias in randomized trials and the National Heart, Lung, and Blood Institute's quality assessment tools. Data will be synthesized using narrative synthesis and will be reported according to the patient portal functionalities, country, disease, and health care system model. RESULTS: Searches will be conducted in September 2019, and the review is anticipated to be completed by the end of June 2020. CONCLUSIONS: This systematic review will provide an overview of health and health care quality outcomes associated with patient portal use among adult patients, providing detailed information about the functionalities of the portals and their associations with the outcomes. The review could potentially help patient portal evaluation studies by providing insights into outcomes associated with the different functionalities of patient portals. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) CRD42019141131; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=141131. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/14975..

INTRODUCTION: The persistent development and spread of resistance to antibiotics remain an important public health concern in the UK and globally. About 74% of antibiotics prescribed in England in 2016 was in primary care. The Quality Premium (QP) initiative that rewards Clinical Commissioning Groups (CCGs) financially based on the quality of specific health services commissioned is one of the National Health Service (NHS) England interventions to reduce antimicrobial resistance through reduced prescribing. Emerging evidence suggests a reduction in antibiotic prescribing in primary care practices in the UK following QP initiative. This study aims to investigate the mechanism of impact of this high-cost health-system level intervention on antibiotic prescribing in primary care practices in England. METHODS AND ANALYSIS: The study will constitute secondary analyses of antibiotic prescribing data for almost all primary care practices in England from the NHS England Antibiotic Quality Premium Monitoring Dashboard and OpenPrescribing covering the period 2013 to 2018. The primary outcome is the number of antibiotic items per Specific Therapeutic group Age-sex Related Prescribing Unit (STAR-PU) prescribed monthly in each practice or CCG. We will first conduct an interrupted time series using ordinary least square regression method to examine whether antibiotic prescribing rate in England has changed over time, and how such changes, if any, are associated with QP implementation. Single and sequential multiple-mediator models using a unified approach for the natural direct and indirect effects will be conducted to investigate the relationship between QP initiative, the potential mediators and antibiotic prescribing rate with adjustment for practice and CCG characteristics. ETHICS AND DISSEMINATION: This study will use secondary data that are anonymised and obtained from studies that have either undergone ethical review or generated data from routine collection systems. Multiple channels will be used in disseminating the findings from this study to academic and non-academic audiences..

BACKGROUND: Bronchiolitis causes significant infant morbidity worldwide from hospital admissions. However, studies quantifying the subsequent respiratory burden in children under 5 years are lacking. OBJECTIVE: To estimate the risk of subsequent respiratory hospital admissions in children under 5 years in England following bronchiolitis admission in infancy. DESIGN: Retrospective population-based birth cohort study. SETTING: Public hospitals in England. PATIENTS: We constructed a birth cohort of 613 377 infants born between 1 April 2007 and 31 March 2008, followed up until aged 5 years by linking Hospital Episode Statistics admissions data. METHODS: We compared the risk of respiratory hospital admission due to asthma, wheezing and lower and upper respiratory tract infections (LRTI and URTI) in infants who had been admitted for bronchiolitis with those who had not, using Cox proportional hazard regression. We adjusted hazard ratios (HR) for known respiratory illness risk factors including living in deprived households, being born preterm or with a comorbid condition. RESULTS: We identified 16 288/613 377 infants (2.7%) with at least one admission for bronchiolitis. Of these, 21.7% had a further respiratory hospital admission by age 5 years compared with 8% without a previous bronchiolitis admission (HR (adjusted) 2.82, 95% CI 2.72 to 2.92). The association was greatest for asthma (HR (adjusted) 4.35, 95% CI 4.00 to 4.73) and wheezing admissions (HR (adjusted) 5.02, 95% CI 4.64 to 5.44), but were also significant for URTI and LRTI admissions. CONCLUSIONS: Hospital admission for bronchiolitis in infancy is associated with a threefold to fivefold risk of subsequent respiratory hospital admissions from asthma, wheezing and respiratory infections. One in five infants with bronchiolitis hospital admissions will have a subsequent respiratory hospital admission by age 5 years..

Outpatient parenteral antibiotic therapy (OPAT) is an established antimicrobial delivery method in the UK. OPAT services differ nationwide, with a paucity of high-quality outcome data to enable benchmarking. A retrospective review of clinical outcomes and adverse events (AEs) of all patients treated during 2008-2017 was performed to identify factors associated with success and failure. Regression models were used to identify factors associated with OPAT success, and AEs were described for the study population using definitions recommended by BSAC. In the 10-year period, 2870 patient episodes resulted in 69 610 days of treatment, with a 91.7% rate of successful therapy completion and 92.0% of infections cured or improved. We encountered 196 AEs, including 1 case of Clostridium difficile-associated diarrhoea. AEs occurred in 10.9% of patient episodes. Adverse drug and line events occurred at a rate of 3.3 and 1.78 per 1000 treatment days, respectively. Rashes, blood dyscrasias and hepatitis were the most common drug AEs. The odds of OPAT success was greater for patients who spent more time (>14 days) on OPAT therapy (OR = 2.32; P < 0.01), utilised a peripheral line (OR = 1.83; P < 0.01), were treated in the clinic compared with self-administration (OR = 2.1; P < 0.02) and did not experience an AE (OR = 0.23; P < 0.01). In our setting, the odds of a successful OPAT episode were associated with longer treatment course, OPAT delivered via a peripheral line, administration in an OPAT clinic setting, and no adverse line or drug events..

BACKGROUND: Inappropriate antibiotic prescription is one of the key contributors to antibiotic resistance, which is managed with a range of interventions including education. OBJECTIVE: We aimed to summarize evidence on the effectiveness of digital education of antibiotic management compared to traditional education for improving health care professionals' knowledge, skills, attitudes, and clinical practice. METHODS: Seven electronic databases and two trial registries were searched for randomized controlled trials (RCTs) and cluster RCTs published between January 1, 1990, and September 20, 2018. There were no language restrictions. We also searched the International Clinical Trials Registry Platform Search Portal and metaRegister of Controlled Trials to identify unpublished trials and checked the reference lists of included studies and relevant systematic reviews for study eligibility. We followed Cochrane methods to select studies, extract data, and appraise and synthesize eligible studies. We used random-effect models for the pooled analysis and assessed statistical heterogeneity by visual inspection of a forest plot and calculation of the I2 statistic. RESULTS: Six cluster RCTs and two RCTs with 655 primary care practices, 1392 primary care physicians, and 485,632 patients were included. The interventions included personal digital assistants; short text messages; online digital education including emails and websites; and online blended education, which used a combination of online digital education and traditional education materials. The control groups received traditional education. Six studies assessed postintervention change in clinical practice. The majority of the studies (4/6) reported greater reduction in antibiotic prescription or dispensing rate with digital education than with traditional education. Two studies showed significant differences in postintervention knowledge scores in favor of mobile education over traditional education (standardized mean difference=1.09, 95% CI 0.90-1.28; I2=0%; large effect size; 491 participants [2 studies]). The findings for health care professionals' attitudes and patient-related outcomes were mixed or inconclusive. Three studies found digital education to be more cost-effective than traditional education. None of the included studies reported on skills, satisfaction, or potential adverse effects. CONCLUSIONS: Findings from studies deploying mobile or online modalities of digital education on antibiotic management were complementary and found to be more cost-effective than traditional education in improving clinical practice and postintervention knowledge, particularly in postregistration settings. There is a lack of evidence on the effectiveness of other digital education modalities such as virtual reality or serious games. Future studies should also include health care professionals working in settings other than primary care and low- and middle-income countries. CLINICAL TRIAL: PROSPERO CRD42018109742; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=109742..

BACKGROUND: All-cause antibiotic prescribing affects bowel flora antimicrobial susceptibility, and may increase risk of urinary autoinoculation with antibiotic-resistant microbes. However, little is known about relative prevalence of, or risk factors for, antimicrobial resistance among potentially pathogenic microbes thought to be contaminating and infecting urine. METHODS: Secondary analysis of 824 children under 5 years of age consulting in primary care for an acute illness and their Escherichia coli isolates cultured at ≥103 cfu/mL from the Diagnosis of Urinary Tract infection in Young children (DUTY) study. Multivariable logistic regression investigating risk factors for resistance to amoxicillin, co-amoxiclav, cefalexin, ciprofloxacin, trimethoprim, nitrofurantoin and cefpodoxime in microbes meeting the laboratory criteria for urinary tract infection: 'pathogens' (>105 cfu/mL, n = 79) and 'contaminants' (103 to 105 cfu/mL, n = 745). RESULTS: Forty-three percent of E. coli were resistant to at least one tested antibiotic, with resistance highest to amoxicillin (49.37% pathogenic versus 37.32% contaminant, P = 0.04), trimethoprim (27.85% versus 16.52%, P = 0.01) and co-amoxiclav (16.46% versus 21.48%, P = 0.30). Multidrug resistance (to ≥3 antibiotic groups) was present in 17.07% of pathogens and 30.13% of contaminants (P = 0.04). No isolates were resistant to nitrofurantoin. Recent (0-3 months) exposure to antibiotics was associated with resistance in both pathogens (aOR: 1.10, 95% CI: 1.01-4.39) and contaminants (1.69, 1.09-2.67). CONCLUSIONS: Prevalence of resistance (including multidrug) was high, but there was no consistent relationship between isolate pathogen/contamination status and resistance. Recent all-cause antibiotic prescribing increased the probability of antimicrobial resistance in both pathogenic and contaminating urinary E. coli in children in primary care..

OBJECTIVES: To assess the impact of the 2015/16 NHS England Quality Premium (which provided a financial incentive for Clinical Commissioning Groups to reduce antibiotic prescribing in primary care) on antibiotic prescribing by General Practitioners (GPs) for respiratory tract infections (RTIs). METHODS: Interrupted time series analysis using monthly patient-level consultation and prescribing data obtained from the Clinical Practice Research Datalink (CPRD) between April 2011 and March 2017. The study population comprised patients consulting a GP who were diagnosed with an RTI. We assessed the rate of antibiotic prescribing in patients (both aggregate and stratified by age) with a recorded diagnosis of uncomplicated RTI, before and after the implementation of the Quality Premium. RESULTS: Prescribing rates decreased over the 6 year study period, with evident seasonality. Notably, there was a 3% drop in the rate of antibiotic prescribing (equating to 14.65 prescriptions per 1000 RTI consultations) (P < 0.05) in April 2015, coinciding with the introduction of the Quality Premium. This reduction was sustained, such that after 2 years there was a 3% decrease in prescribing relative to that expected had the pre-intervention trend continued. There was also a concurrent 2% relative reduction in the rate of broad-spectrum antibiotic prescribing. Antibiotic prescribing for RTIs diagnosed in children showed the greatest decline with a 6% relative change 2 years after the intervention. Of the RTI indications studied, the greatest reductions in antibiotic prescribing were seen for patients with sore throats. CONCLUSIONS: Community prescribing of antibiotics for RTIs significantly decreased following the introduction of the Quality Premium, with the greatest reduction seen in younger patients..

This study quantified the association between antibiotic prescribing for urinary tract infections (UTIs) and the incidence/antimicrobial susceptibility of UTI-related Escherichia coli bacteraemia in adult women in England. A national ecological study was conducted with data aggregated at GP practice level. The study population was adult female patients (>18 years) with reported UTI-related E. coli bacteraemia in England (2012-2014). Reports of bacteraemia from the national mandatory surveillance scheme were linked with E. coli blood culture susceptibility data (where available) and the correlation with primary care exposure to trimethoprim and nitrofurantoin was quantified using longitudinal multilevel models. The study included 19 874 patients from 5916 practices. The overall incidence of UTI-related E. coli bacteraemia in the study group did not change significantly (1.3% increase, 95% CI 0.1-2.7%; P = 0.074). However, after adjusting for practice characteristics, UTI-related E. coli bacteraemia incidence increased by 3.0% (P < 0.001) and 1.5% (P < 0.01) with each increasing quintile in trimethoprim and nitrofurantoin prescribing, respectively. The incidence of trimethoprim-resistant bacteraemia increased by 4.5% (P = 0.032) with each increasing quintile in trimethoprim prescribing and was not associated with nitrofurantoin prescribing. This study demonstrated an association between GP prescribing for UTIs and UTI-related E. coli bacteraemia incidence at the practice level and showed that higher prescribing of trimethoprim is associated with higher incidence of trimethoprim-resistant bacteraemia. Evidence is provided of the importance of prudent antibiotic prescribing in primary care to prevent the development of antibiotic resistance, placing patients at risk of subsequent severe infections..

BACKGROUND: Antibiotic-resistant bacteria (ARB) are selected by the use of antibiotics. The rational design of interventions to reduce levels of antibiotic resistance requires a greater understanding of how and where ARB are acquired. Our aim was to determine whether acquisition of ARB occurs more often in the community or hospital setting. METHODS: We used a mathematical model of the natural history of ARB to estimate how many ARB were acquired in each of these two environments, as well as to determine key parameters for further investigation. To do this, we explored a range of realistic parameter combinations and considered a case study of parameters for an important subset of resistant strains in England. RESULTS: If we consider all people with ARB in the total population (community and hospital), the majority, under most clinically derived parameter combinations, acquired their resistance in the community, despite higher levels of antibiotic use and transmission of ARB in the hospital. However, if we focus on just the hospital population, under most parameter combinations a greater proportion of this population acquired ARB in the hospital. CONCLUSIONS: It is likely that the majority of ARB are being acquired in the community, suggesting that efforts to reduce overall ARB carriage should focus on reducing antibiotic usage and transmission in the community setting. However, our framework highlights the need for better pathogen-specific data on antibiotic exposure, ARB clearance and transmission parameters, as well as the link between carriage of ARB and health impact. This is important to determine whether interventions should target total ARB carriage or hospital-acquired ARB carriage, as the latter often dominated in hospital populations..

BACKGROUND: Improved antibiotic stewardship (AS) and reduced prescribing in primary care, with a parallel increase in personal internet use, could lead citizens to obtain antibiotics from alternative sources online. OBJECTIVES: A cross-sectional analysis was performed to: (i) determine the quality and legality of online pharmacies selling antibiotics to the UK public; (ii) describe processes for obtaining antibiotics online from within the UK; and (iii) identify resulting AS and patient safety issues. METHODS: Searches were conducted for 'buy antibiotics online' using Google and Yahoo. For each search engine, data from the first 10 web sites with unique URL addresses were reviewed. Analysis was conducted on evidence of appropriate pharmacy registration, prescription requirement, whether antibiotic choice was 'prescriber-driven' or 'consumer-driven', and whether specific information was required (allergies, comorbidities, pregnancy) or given (adverse effects) prior to purchase. RESULTS: Twenty unique URL addresses were analysed in detail. Online pharmacies evidencing their location in the UK ( n  = 5; 25%) required a prescription before antibiotic purchase, and were appropriately registered. Online pharmacies unclear about the location they were operating from ( n  = 10; 50%) had variable prescription requirements, and no evidence of appropriate registration. Nine (45%) online pharmacies did not require a prescription prior to purchase. For 16 (80%) online pharmacies, decisions were initially consumer-driven for antibiotic choice, dose and quantity. CONCLUSIONS: Wide variation exists among online pharmacies in relation to antibiotic practices, highlighting considerable patient safety and AS issues. Improved education, legislation, regulation and new best practice stewardship guidelines are urgently needed for online antibiotic suppliers..

OBJECTIVE: The aim of this study was to evaluate the efficacy and effectiveness of homeopathic intervention in the treatment of seasonal or perennial allergic rhinitis (AR). METHOD: Randomized controlled trials evaluating all forms of homeopathic treatment for AR were included in a systematic review (SR) of studies published up to and including December 2015. Two authors independently screened potential studies, extracted data, and assessed risk of bias. Primary outcomes included symptom improvement and total quality-of-life score. Treatment effect size was quantified as mean difference (continuous data), or by risk ratio (RR) and odds ratio (dichotomous data), with 95% confidence intervals (CI). Meta-analysis was performed after assessing heterogeneity and risk of bias. RESULTS: Eleven studies were eligible for SR. All trials were placebo-controlled except one. Six trials used the treatment approach known as isopathy, but they were unsuitable for meta-analysis due to problems of heterogeneity and data extraction. The overall standard of methods and reporting was poor: 8/11 trials were assessed as "high risk of bias"; only one trial, on isopathy for seasonal AR, possessed reliable evidence. Three trials of variable quality (all using Galphimia glauca for seasonal AR) were included in the meta-analysis: nasal symptom relief at 2 and 4 weeks (RR = 1.48 [95% CI 1.24-1.77] and 1.27 [95% CI 1.10-1.46], respectively) favored homeopathy compared with placebo; ocular symptom relief at 2 and 4 weeks also favored homeopathy (RR = 1.55 [95% CI 1.33-1.80] and 1.37 [95% CI 1.21-1.56], respectively). The single trial with reliable evidence had a small positive treatment effect without statistical significance. A homeopathic and a conventional nasal spray produced equivalent improvements in nasal and ocular symptoms. CONCLUSIONS: The low or uncertain overall quality of the evidence warrants caution in drawing firm conclusions about intervention effects. Use of either Galphimia glauca or a homeopathic nasal spray may have small beneficial effects on the nasal and ocular symptoms of AR. The efficacy of isopathic treatment of AR is unclear..

BACKGROUND: Antibiotic resistance (ABR) is an urgent problem globally, with overuse and misuse of antibiotics being one of the main drivers of antibiotic-resistant infections. There is increasing evidence that the burden of community-acquired infections such as urinary tract infections and bloodstream infections (both susceptible and resistant) may differ by ethnicity, although the reasons behind this relationship are not well defined. It has been demonstrated that socioeconomic status and ethnicity are often highly correlated with each other; however, it is not yet known whether accounting for deprivation completely explains any discrepancy seen in infection risk. There have currently been no systematic reviews summarising the evidence for the relationship between ethnicity and antibiotic resistance or prescribing. METHODS: This protocol will outline how we will conduct this systematic literature review and meta-analysis investigating whether there is an association between patient ethnicity and (1) risk of antibiotic-resistant infections or (2) levels of antibiotic prescribing in high-income countries. We will search PubMed/MEDLINE, EMBASE, Global Health, Scopus and CINAHL using MESH terms where applicable. Two reviewers will conduct title/abstract screening, data extraction and quality assessment independently. The Critical Appraisal Skills Programme (CASP) checklist will be used for cohort and case-control studies, and the Cochrane collaboration's risk of bias tool will be used for randomised control trials, if they are included. Meta-analyses will be performed by calculating the minority ethnic group to majority ethnic group odds ratios or risk ratios for each study and presenting an overall pooled odds ratio for the two outcomes. The Grading of Recommendations, Assessments, Development and Evaluation (GRADE) approach will be used to assess the overall quality of the body of evidence. DISCUSSION: In this systematic review and meta-analysis, we will aim to collate the available evidence of whether there is a difference in rates of AMR and/or antibiotic prescribing in minority vs. majority ethnic groups in high-income countries. Additionally, this review will highlight areas where more research needs to be conducted and may provide insight into what may cause differences in this relationship, should they be seen. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ( CRD42016051533 )..

BACKGROUND: Negative symptoms of schizophrenia represent deficiencies in emotional responsiveness, motivation, socialisation, speech and movement. When persistent, they are held to account for much of the poor functional outcomes associated with schizophrenia. There are currently no approved pharmacological treatments. While the available evidence suggests that a combination of antipsychotic and antidepressant medication may be effective in treating negative symptoms, it is too limited to allow any firm conclusions. OBJECTIVE: To establish the clinical effectiveness and cost-effectiveness of augmentation of antipsychotic medication with the antidepressant citalopram for the management of negative symptoms in schizophrenia. DESIGN: A multicentre, double-blind, individually randomised, placebo-controlled trial with 12-month follow-up. SETTING: Adult psychiatric services, treating people with schizophrenia. PARTICIPANTS: Inpatients or outpatients with schizophrenia, on continuing, stable antipsychotic medication, with persistent negative symptoms at a criterion level of severity. INTERVENTIONS: Eligible participants were randomised 1 : 1 to treatment with either placebo (one capsule) or 20 mg of citalopram per day for 48 weeks, with the clinical option at 4 weeks to increase the daily dosage to 40 mg of citalopram or two placebo capsules for the remainder of the study. MAIN OUTCOME MEASURES: The primary outcomes were quality of life measured at 12 and 48 weeks assessed using the Heinrich's Quality of Life Scale, and negative symptoms at 12 weeks measured on the negative symptom subscale of the Positive and Negative Syndrome Scale. RESULTS: No therapeutic benefit in terms of improvement in quality of life or negative symptoms was detected for citalopram over 12 weeks or at 48 weeks, but secondary analysis suggested modest improvement in the negative symptom domain, avolition/amotivation, at 12 weeks (mean difference -1.3, 95% confidence interval -2.5 to -0.09). There were no statistically significant differences between the two treatment arms over 48-week follow-up in either the health economics outcomes or costs, and no differences in the frequency or severity of adverse effects, including corrected QT interval prolongation. LIMITATIONS: The trial under-recruited, partly because cardiac safety concerns about citalopram were raised, with the 62 participants recruited falling well short of the target recruitment of 358. Although this was the largest sample randomised to citalopram in a randomised controlled trial of antidepressant augmentation for negative symptoms of schizophrenia and had the longest follow-up, the power of statistical analysis to detect significant differences between the active and placebo groups was limited. CONCLUSION: Although adjunctive citalopram did not improve negative symptoms overall, there was evidence of some positive effect on avolition/amotivation, recognised as a critical barrier to psychosocial rehabilitation and achieving better social and community functional outcomes. Comprehensive assessment of side-effect burden did not identify any serious safety or tolerability issues. The addition of citalopram as a long-term prescribing strategy for the treatment of negative symptoms may merit further investigation in larger studies. FUTURE WORK: Further studies of the viability of adjunctive antidepressant treatment for negative symptoms in schizophrenia should include appropriate safety monitoring and use rating scales that allow for evaluation of avolition/amotivation as a discrete negative symptom domain. Overcoming the barriers to recruiting an adequate sample size will remain a challenge. TRIAL REGISTRATION: European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2009-009235-30 and Current Controlled Trials ISRCTN42305247. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 29. See the NIHR Journals Library website for further project information..

BACKGROUND: Current advances in modern technology have enabled the development and utilization of electronic medical software apps for both mobile and desktop computing devices. A range of apps on a large variety of clinical conditions for patients and the public are available, but very few target antimicrobials or infections. OBJECTIVE: We sought to explore the use of different antimicrobial information resources with a focus on electronic platforms, including apps for portable devices, by outpatients at two large, geographically distinct National Health Service (NHS) teaching hospital trusts in England. We wanted to determine whether there is demand for an evidence-based app for patients, to garner their perceptions around infections/antimicrobial prescribing, and to describe patients' experiences of their interactions with health care professionals in relation to this topic. METHODS: A cross-sectional survey design was used to investigate aspects of antimicrobial prescribing and electronic devices experienced by patients at four hospitals in London and a teaching hospital in the East of England. RESULTS: A total of 99 surveys were completed and analyzed. A total of 82% (80/98) of respondents had recently been prescribed antimicrobials; 87% (85/98) of respondents were prescribed an antimicrobial by a hospital doctor or through their general practitioner (GP) in primary care. Respondents wanted information on the etiology (42/65, 65%) and prevention and/or management (32/65, 49%) of their infections, with the infections reported being upper and lower respiratory tract, urinary tract, oral, and skin and soft tissue infections. All patients (92/92, 100%) desired specific information on the antimicrobial prescribed. Approximately half (52/95, 55%) stated it was "fine" for doctors to use a mobile phone/tablet computer during the consultation while 13% (12/95) did not support the idea of doctors accessing health care information in this way. Although only 30% (27/89) of respondents reported on the use of health care apps, 95% (81/85) offered information regarding aspects of antimicrobials or infections that could be provided through a tailored app for patients. Analysis of the comments revealed the following main global themes: knowledge, technology, and patient experience. CONCLUSIONS: The majority of respondents in our study wanted to have specific etiological and/or infection management advice. All required antimicrobial-related information. Also, most supported the use of electronic resources of information, including apps, by their doctors. While a minority of people currently use health apps, many feel that apps could be used to provide additional support/information related to infections and appropriate use of antimicrobials. In addition, we found that there is a need for health care professionals to engage with patients and help address common misconceptions around the generation of antimicrobial resistance..

There is currently a lot of interest in pilot studies conducted in preparation for randomised controlled trials. This paper focuses on sample size requirements for external pilot studies for cluster randomised trials. We consider how large an external pilot study needs to be to assess key parameters for input to the main trial sample size calculation when the primary outcome is continuous, and to estimate rates, for example recruitment rates, with reasonable precision. We used simulation to provide the distribution of the expected number of clusters for the main trial under different assumptions about the natural cluster size, intra-cluster correlation, eventual cluster size in the main trial, and various decisions made at the piloting stage. We chose intra-cluster correlation values and pilot study size to reflect those commonly reported in the literature. Our results show that estimates of sample size required for the main trial are likely to be biased downwards and very imprecise unless the pilot study includes large numbers of clusters and individual participants. We conclude that pilot studies will usually be too small to estimate parameters required for estimating a sample size for a main cluster randomised trial (e.g. the intra-cluster correlation coefficient) with sufficient precision and too small to provide reliable estimates of rates for process measures such as recruitment or follow-up rates..

OBJECTIVES: To systematically review studies investigating the prevalence of antibiotic resistance in urinary tract infections caused by Escherichia coli in children and, when appropriate, to meta-analyse the relation between previous antibiotics prescribed in primary care and resistance. DESIGN AND DATA ANALYSIS: Systematic review and meta-analysis. Pooled percentage prevalence of resistance to the most commonly used antibiotics in children in primary care, stratified by the OECD (Organisation for Economic Co-operation and Development) status of the study country. Random effects meta-analysis was used to quantify the association between previous exposure to antibiotics in primary care and resistance. DATA SOURCES: Observational and experimental studies identified through Medline, Embase, Cochrane, and ISI Web of Knowledge databases, searched for articles published up to October 2015. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies were eligible if they investigated and reported resistance in community acquired urinary tract infection in children and young people aged 0-17. Electronic searches with MeSH terms and text words identified 3115 papers. Two independent reviewers assessed study quality and performed data extraction. RESULTS: 58 observational studies investigated 77,783 E coli isolates in urine. In studies from OECD countries, the pooled prevalence of resistance was 53.4% (95% confidence interval 46.0% to 60.8%) for ampicillin, 23.6% (13.9% to 32.3%) for trimethoprim, 8.2% (7.9% to 9.6%) for co-amoxiclav, and 2.1% (0.8 to 4.4%) for ciprofloxacin; nitrofurantoin was the lowest at 1.3% (0.8% to 1.7%). Resistance in studies in countries outside the OECD was significantly higher: 79.8% (73.0% to 87.7%) for ampicillin, 60.3% (40.9% to 79.0%) for co-amoxiclav, 26.8% (11.1% to 43.0%) for ciprofloxacin, and 17.0% (9.8% to 24.2%) for nitrofurantoin. There was evidence that bacterial isolates from the urinary tract from individual children who had received previous prescriptions for antibiotics in primary care were more likely to be resistant to antibiotics, and this increased risk could persist for up to six months (odds ratio 13.23, 95% confidence interval 7.84 to 22.31). CONCLUSIONS: Prevalence of resistance to commonly prescribed antibiotics in primary care in children with urinary tract infections caused by E coli is high, particularly in countries outside the OECD, where one possible explanation is the availability of antibiotics over the counter. This could render some antibiotics ineffective as first line treatments for urinary tract infection. Routine use of antibiotics in primary care contributes to antimicrobial resistance in children, which can persist for up to six months after treatment..

BACKGROUND: The faecal reservoir provides optimal conditions for the transmission of resistance genes within and between bacterial species. As key transmitters of infection within communities, children are likely important contributors to endemic community resistance. We sought to determine the prevalence of antibiotic-resistant faecal Escherichia coli from asymptomatic children aged between 0 and 17 years worldwide, and investigate the impact of routinely prescribed primary care antibiotics to that resistance. METHODS: A systematic search of Medline, Embase, Cochrane and Web of Knowledge databases from 1940 to 2015. Pooled resistance prevalence for common primary care antibiotics, stratified by study country OECD status. Random-effects meta-analysis to explore the association between antibiotic exposure and resistance. RESULTS: Thirty-four studies were included. In OECD countries, the pooled resistance prevalence to tetracycline was 37.7 % (95 % CI: 25.9-49.7 %); ampicillin 37.6 % (24.9-54.3 %); and trimethoprim 28.6 % (2.2-71.0 %). Resistance in non-OECD countries was uniformly higher: tetracycline 80.0 % (59.7-95.3 %); ampicillin 67.2 % (45.8-84.9 %); and trimethoprim 81.3 % (40.4-100 %). We found evidence of an association between primary care prescribed antibiotics and resistance lasting for up to 3 months post-prescribing (pooled OR: 1.65, 1.36-2.0). CONCLUSIONS: Resistance to many primary care prescribed antibiotics is common among faecal E. coli carried by asymptomatic children, with higher resistance rates in non-OECD countries. Despite tetracycline being contra-indicated in children, tetracycline resistance rates were high suggesting children could be important recipients and transmitters of resistant bacteria, or that use of other antibiotics is leading to tetracycline resistance via inter-bacteria resistance transmission..

BACKGROUND: Despite World Health Organization guidelines on health service responses to intimate partner violence (IPV) against women general practitioners (GPs) often overlook the problem. Training on IPV addresses GPs' barriers to asking women patients about abuse and responding appropriately. One of the barriers is stereotype of women as passive victims. Little is known about coping behaviour of women patients with a history of IPV. OBJECTIVES: The objectives are (i) to compare problem- and emotion-focused coping used by patients who have experienced IPV with those who have not; (ii) to examine whether greater coping resources (health, education, employment and income) would be associated with more problem-focused coping. METHODS: The Russian Ways of Coping Questionnaire was administered to every fifth woman who participated in a cross-sectional survey on IPV prevalence in 24 St Petersburg general practices. Linear regression was used (n = 159) to test associations between life-time IPV, coping resources and ways of coping. RESULTS: Mean problem-focused coping scores were 0.2-4.7 units higher in those patients who have experienced IPV compared with those who have not [95% confidence interval (CI): -4.2, 11.9; P = 0.16-0.92], while mean emotion-focused coping scores were 2.5-4.2 units higher (95% CI: -3.0, 11.0; P = 0.12-0.57). After adjustment for coping resources there was no evidence for an association between IPV and problem-focused coping. CONCLUSIONS: Patients who have experienced IPV use as much problem-focused and emotion-focused coping, as those patients who have not experienced IPV. These findings should be incorporated into training on IPV to address GPs' stereotypes towards patients who have experienced IPV..

OBJECTIVES: To investigate the feasibility of recruitment, adherence and likely effectiveness of an e-learning intervention for managers to improve employees' well-being and reduce sickness absence. METHODS: The GEM Study (guided e-learning for managers) was a mixed methods pilot cluster randomised trial. Employees were recruited from four mental health services prior to randomising three services to the intervention and one to no-intervention control. Intervention managers received a facilitated e-learning programme on work-related stress. Main outcomes were Warwick Edinburgh Mental Wellbeing Scale (WEMWBS), 12-item GHQ and sickness absence <21 days from human resources. 35 in-depth interviews were undertaken with key informants, managers and employees, and additional observational data collected. RESULTS: 424 of 649 (65%) employees approached consented, of whom 350 provided WEMWBS at baseline and 284 at follow-up; 41 managers out of 49 were recruited from the three intervention clusters and 21 adhered to the intervention. WEMWBS scores fell from 50.4-49.0 in the control (n=59) and 51.0-49.9 in the intervention (n=225), giving an intervention effect of 0.5 (95% CI -3.2 to 4.2). 120/225 intervention employees had a manager who was adherent to the intervention. HR data on sickness absence (n=393) showed no evidence of effect. There were no effects on GHQ score or work characteristics. Online quiz knowledge scores increased across the study in adherent managers. Qualitative data provided a rich picture of the context within which the intervention took place and managers' and employees' experiences of it. CONCLUSIONS: A small benefit from the intervention on well-being was explained by the mixed methods approach, implicating a low intervention uptake by managers and suggesting that education alone may be insufficient. A full trial of the guided e-learning intervention and economic evaluation is feasible. Future research should include more active encouragement of manager motivation, reflection and behaviour change. TRIAL REGISTRATION NUMBER: ISRCTN58661009..

BACKGROUND: Allergic rhinitis is a global health problem that is often treated with homeopathy. The objective of this review will be to evaluate the effectiveness of homeopathic treatment of allergic rhinitis. METHODS/DESIGN: The authors will conduct a systematic review. We will search Medline, CENTRAL, CINAHL, EMBASE, AMED, CAM-Quest, Google Scholar and reference lists of identified studies up to December 2013.The review will include randomized controlled trials that evaluate homeopathic treatment of allergic rhinitis. Studies with participants of all ages, with acute or chronic comorbidities will be included. Patients with immunodeficiency will not be included. The diagnosis will be based on the published guidelines of diagnosis and classification. Studies of all homeopathy modalities (clinical, complex and classical homeopathy, and isopathy) will be included. We will include trials with both active controls (conventional therapy, standard care) and placebo controls.The primary outcomes are: an improvement of global symptoms recorded in validated daily or weekly diaries and any scores from validated visual analogue scales; the total Quality of Life Score (such as the Juniper RQLQ);individual symptoms scores which include any appropriate measures of nasal obstruction, runny nose, sneezing, itching, and eye symptoms; and number of days requiring medication. Secondary outcomes selected will include serum immunoglobin E (IgE) levels, individual ocular symptoms, adverse events, and the use of rescue medication.Treatment effects will be measured by calculating the mean difference and the standardized mean difference with 95% confidence interval (CI) for continuous data. Risk ratio or, if feasible, odds ratio will be calculated with 95% CI for dichotomous data. After assessing clinical and statistical heterogeneity, meta-analysis will be performed, if appropriate. The individual participant will be the unit of analysis. Descriptive information on missing data will be included about participants missing due to drop out, whether there was intention to treat or per protocol analysis and missing statistics. A number of subgroups, homeopathic potency, age groups, and types of allergic rhinitis (seasonal or perennial) will be analyzed. Sensitivity analysis will be performed to explore the impact of risk of bias on overall treatment effect. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42013006741..

There is growing evidence that primary care prescribed antibiotics lead to antibiotic resistance in bacteria causing minor infections or being carried by asymptomatic adults, but little research to date has investigated links between primary care prescribed antibiotics and resistance among more serious infections requiring hospital care. Knowledge of these effects is likely to have a major influence on public expectations for, and primary care use of, antibiotics. This study aimed to assess the feasibility of recruiting symptomatic adult patients admitted to hospital with urinary infections and to link primary and secondary data information to investigate the relationship between primary care prescribed antibiotics and antimicrobial resistance in these patients. A microbiology database search of in patients who had submitted a urine sample identified 740 patients who were potentially eligible to take part in the study. Of these, 262 patients did not meet the eligibility criteria, mainly due to use of a urinary catheter (40%). Two-hundred and forty three patients could not be recruited as the nurse was unable to visit the patients prior to discharge, as they were too unwell. Eighty patients provided complete information. Results indicate that there is evidence that prior antibiotic use is associated with resistant infections in hospital patients. A fully powered study, conducted using routinely collected data is proposed to fully clarify the precision of the association..

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BACKGROUND: Recruitment to primary care trials, particularly those involving young children, is known to be difficult. There are limited data available to inform researchers about the effectiveness of different trial recruitment strategies and their associated costs. PURPOSE: To describe, evaluate, and investigate the costs of three strategies for recruiting febrile children to a community-based randomised trial of antipyretics. METHODS: The three recruitment strategies used in the trial were termed as follows: (1) 'local', where paediatric research nurses stationed in primary care sites invited parents of children to participate; (2) 'remote', where clinicians at primary care sites faxed details of potentially eligible children to the trial office; and (3) 'community', where parents, responding to trial publicity, directly contacted the trial office when their child was unwell. RESULTS: Recruitment rates increased in response to the sequential introduction of three recruitment strategies, which were supplemented by additional recruiting staff, flexible staff work patterns, and improved clinician reimbursement schemes. The three strategies yielded different randomisation rates. They also appeared to be interdependent and highly effective together. Strategy-specific costs varied from £297 to £857 per randomised participant and represented approximately 10% of the total trial budget. LIMITATIONS: Because the recruitment strategies were implemented sequentially, it was difficult to measure their independent effects. The cost analysis was performed retrospectively. CONCLUSIONS: Trial recruiter expertise and deployment of several interdependent, illness-specific strategies were key factors in achieving rapid recruitment of young children to a community-based randomised controlled trial (RCT). The 'remote' recruitment strategy was shown to be more cost-effective compared to 'community' and 'local' strategies in the context of this trial. Future trialists should report recruitment costs to facilitate a transparent evaluation of recruitment strategy cost-effectiveness..

The objectives of this study were to investigate the relationship between primary care antibiotics prescribed within 2 months and 12 months and the carriage of meticillin-resistant Staphylococcus aureus (MRSA) in nasal flora from a large representative sample of community-resident adults. S. aureus isolates were obtained from nasal samples submitted by UK resident adults aged ≥ 16 years registered with 12 general practices in the former Avon and Gloucestershire health authority areas. Individual-level antibiotic exposure data during the 12 months prior to providing the samples were collected from the primary care electronic records. MRSA status was determined by measuring resistance to cefoxitin. In total, 6937 adults were invited to take part, of whom 5917 returned a nasal sample. S. aureus was identified in 946 samples and a total of 761 participants consented to primary care record review and had complete data for the analyses. There was no evidence of an association between any antibiotic in the previous 2 months and MRSA isolation, with an adjusted odds ratio (aOR) of 1.33 [95% confidence interval (CI) 0.12-15; P=0.8]. There was a suggestion of an association between any antibiotic use in the previous 12 months and MRSA, with an aOR of 2.45 (95% CI 0.95-6.3; P=0.06). In conclusion, there is a suggestion that antibiotics prescribed within 12 months is associated with the carriage of MRSA, but not within 2 months, although the 2-month analysis had fewer data subjects and was therefore underpowered to detect this association. A larger study would be able to clarify these associations further..

OBJECTIVE: To investigate the effectiveness of facilitated physical activity as an adjunctive treatment for adults with depression presenting in primary care. DESIGN: Pragmatic, multicentre, two arm parallel randomised controlled trial. SETTING: General practices in Bristol and Exeter. PARTICIPANTS: 361 adults aged 18-69 who had recently consulted their general practitioner with symptoms of depression. All those randomised had a diagnosis of an episode of depression as assessed by the clinical interview schedule-revised and a Beck depression inventory score of 14 or more. INTERVENTIONS: In addition to usual care, intervention participants were offered up to three face to face sessions and 10 telephone calls with a trained physical activity facilitator over eight months. The intervention was based on theory and aimed to provide individually tailored support and encouragement to engage in physical activity. MAIN OUTCOME MEASURES: The primary outcome was self reported symptoms of depression, assessed with the Beck depression inventory at four months post-randomisation. Secondary outcomes included use of antidepressants and physical activity at the four, eight, and 12 month follow-up points, and symptoms of depression at eight and 12 month follow-up. RESULTS: There was no evidence that participants offered the physical activity intervention reported improvement in mood by the four month follow-up point compared with those in the usual care group; adjusted between group difference in mean Beck depression inventory score -0.54 (95% confidence interval -3.06 to 1.99; P=0.68). Similarly, there was no evidence that the intervention group reported a change in mood by the eight and 12 month follow-up points. Nor was there evidence that the intervention reduced antidepressant use compared with usual care (adjusted odds ratio 0.63, 95% confidence interval 0.19 to 2.06; P=0.44) over the duration of the trial. However, participants allocated to the intervention group reported more physical activity during the follow-up period than those allocated to the usual care group (adjusted odds ratio 2.27, 95% confidence interval 1.32 to 3.89; P=0.003). CONCLUSIONS: The addition of a facilitated physical activity intervention to usual care did not improve depression outcome or reduce use of antidepressants compared with usual care alone. TRIAL REGISTRATION: Current Controlled Trials ISRCTN16900744..

BACKGROUND: Primary care providers and researchers wishing to estimate study recruitment rates need estimates of illness frequency in primary care. Previous studies of children's symptoms have found that presentations are most common for the symptoms: cough, fever, earache, rash, diarrhoea and vomiting. Since 2000, primary care provision in the United Kingdom has changed with the introduction of Walk-in-Centres (WICs) and new Out of Hours (OoHs) providers. AIMS: To describe the type and frequency of parent-reported presenting symptoms at a range of primary care sites between 2005 and 2007. METHODS: Parent-reported presenting symptoms, recorded in their own words, were extracted from data collected from all children aged six months to six years during recruitment to a randomised controlled trial. Presenting symptoms were coded and presented as frequency per 100 'consulting sessions' by type of primary care site. FINDINGS: Results were evaluated from 2491 episodes of illness at 35 sites. When grouped by primary care site, respiratory symptoms were the most common at OoHs centres, the WIC and general practitioner (GP) surgeries. Trauma symptoms were common in the Emergency Department, but unexpectedly, diarrhoea and vomiting were more common in the Emergency Department and skin presenting symptoms more common at the WIC than at GP sites. CONCLUSIONS: We report the relative frequency of acute symptoms by type of primary care provider. These data may be useful to those planning recruitment to primary care paediatric studies and policy makers for planning primary care service provision..

OBJECTIVE: To determine the accuracy with which parents can estimate preschool children's weight using home scales in order to calculate antipyretic dose. DESIGN: Cross-sectional, method comparison study. SETTING AND PARTICIPANTS: 156 preschool children aged 6 months to 6 years recruited from primary care and the community to an antipyretic strategies trial and managed at home. COMPARISON AND OUTCOME MEASURES: Research nurse weight estimate using Seca 835-2 digital paediatric scales compared with parental weight estimate using usual home scales. RESULTS: Parents of 62 (40%) preschool children had home scales. Research scale estimated weights were heavier than home scale weight estimates, with a mean difference of 0.41 kg (95% CI -0.24 to 0.74 kg), with 95% limits of agreement of -2.44 to 1.47 kg. CONCLUSION: Weight can be estimated accurately enough to calculate antipyretic medicine doses by the minority of parents having scales that can be used to estimate their child's weight..

OBJECTIVE: To systematically review the literature and, where appropriate, meta-analyse studies investigating subsequent antibiotic resistance in individuals prescribed antibiotics in primary care. DESIGN: Systematic review with meta-analysis. DATA SOURCES: Observational and experimental studies identified through Medline, Embase, and Cochrane searches. Review methods Electronic searches using MeSH terms and text words identified 4373 papers. Two independent reviewers assessed quality of eligible studies and extracted data. Meta-analyses were conducted for studies presenting similar outcomes. RESULTS: The review included 24 studies; 22 involved patients with symptomatic infection and two involved healthy volunteers; 19 were observational studies (of which two were prospective) and five were randomised trials. In five studies of urinary tract bacteria (14 348 participants), the pooled odds ratio (OR) for resistance was 2.5 (95% confidence interval 2.1 to 2.9) within 2 months of antibiotic treatment and 1.33 (1.2 to 1.5) within 12 months. In seven studies of respiratory tract bacteria (2605 participants), pooled ORs were 2.4 (1.4 to 3.9) and 2.4 (1.3 to 4.5) for the same periods, respectively. Studies reporting the quantity of antibiotic prescribed found that longer duration and multiple courses were associated with higher rates of resistance. Studies comparing the potential for different antibiotics to induce resistance showed no consistent effects. Only one prospective study reported changes in resistance over a long period; pooled ORs fell from 12.2 (6.8 to 22.1) at 1 week to 6.1 (2.8 to 13.4) at 1 month, 3.6 (2.2 to 6.0) at 2 months, and 2.2 (1.3 to 3.6) at 6 months. CONCLUSIONS: Individuals prescribed an antibiotic in primary care for a respiratory or urinary infection develop bacterial resistance to that antibiotic. The effect is greatest in the month immediately after treatment but may persist for up to 12 months. This effect not only increases the population carriage of organisms resistant to first line antibiotics, but also creates the conditions for increased use of second line antibiotics in the community..

OBJECTIVES: To establish the relative clinical effectiveness and cost-effectiveness of paracetamol plus ibuprofen compared with paracetamol and ibuprofen separately for time without fever, and the relief of fever-associated discomfort in young children who can be managed at home. DESIGN: The trial design was a single-centre (multisite), individually randomised, blinded, three-arm trial comparing paracetamol and ibuprofen together with paracetamol or ibuprofen separately. SETTING: There were three recruitment settings, as follows: 'local' where research nurses were recruited from NHS primary care sites; 'remote' where NHS sites notified the study of potentially eligible children; and 'community' where parents contacted the study in response to local media advertisements. PARTICIPANTS: Children aged between 6 months and 6 years with fever > or = 37.8 degrees C and < or = 41 degrees C due to an illness that could be managed at home. INTERVENTIONS: The intervention was the provision of, and advice to give, the medicines for up to 48 hours: paracetamol every 4-6 hours (maximum of four doses in 24 hours) and ibuprofen every 6-8 hours (maximum of three doses in 24 hours). Every parent received two bottles, with at least one containing an active medicine. Parents, research nurses and investigators were blinded to treatment allocation by the use of identically matched placebo medicines. The dose of medicine was determined by the child's weight: paracetamol 15 mg/kg and ibuprofen 10 mg/kg per dose. RESULTS: For additional time without fever in the first 4 hours, use of both medicines was superior to use of paracetamol alone [adjusted difference 55 minutes, 95% confidence interval (CI) 33 to 77 minutes; p < 0.001] and may have been as good as ibuprofen (adjusted difference 16 minutes, 95% CI -6 to 39 minutes; p = 0.2). Both medicines together cleared the fever 23 minutes (95% CI 2-45 minutes; p = 0.015) faster than paracetamol alone, but no faster than ibuprofen alone (adjusted difference -3 minutes, 95% CI 24-18 minutes; p = 0.8). For additional time without fever in the first 24 hours, both medicines were superior to paracetamol (adjusted difference 4.4 hours, 95% CI 2.4-6.3 hours; p < 0.001) or ibuprofen (adjusted difference 2.5 hours, 95% CI 0.6-4.5 hours; p = 0.008) alone. No reduction in discomfort or other fever-associated symptoms was found, although power was low for these outcomes. An exploratory analysis showed that children with higher discomfort levels had higher mean temperatures. No difference in adverse effects was observed between treatment groups. The recommended maximum number of doses of paracetamol and ibuprofen in 24 hours was exceeded in 8% and 11% of children respectively. Over the 5-day study period, paracetamol and ibuprofen together was the cheapest option for the NHS due to the lower use of health-care services:14 pounds [standard deviation (SD) 23 pounds] versus 20 pounds (SD 38 pounds) for paracetamol and 18 pounds (SD 40 pounds) for ibuprofen. Both medicines were also cheapest for parents because the lower use of health care services resulted in personal saving on travel costs and less time off work: 24 pounds (SD 46 pounds) versus 26 pounds (SD 63 pounds) for paracetamol and 30 pounds (SD 91 pounds) for ibuprofen. This more than compensated for the extra cost of medication. However, statistical evidence for these differences was weak due to lack of power. Overall, a quarter of children were 'back to normal' by 48 hours and one-third by day 5. Five (3%) children were admitted to hospital, two with pneumonia, two with bronchiolitis and one with a severe, but unidentified 'viral illness'. CONCLUSIONS: Young children who are unwell with fever should be treated with ibuprofen first, but the relative risks (inadvertently exceeding the maximum recommended dose) and benefits (extra 2.5 hours without fever) of using paracetamol plus ibuprofen over 24 hours should be considered. However, if two medicines are used, it is recommended that all dose times are carefully recorded to avoid accidentally exceeding the maximum recommended dose. Manufacturers should consider supplying blank charts for this purpose. Use of both medicines should not be discouraged on the basis of cost to either parents or the NHS. Parents and clinicians should be aware that fever is a relatively short-lived symptom, but may have more serious prognostic implications than the other common symptom presentations of childhood..

OBJECTIVE: To investigate whether paracetamol (acetaminophen) plus ibuprofen are superior to either drug alone for increasing time without fever and the relief of fever associated discomfort in febrile children managed at home. DESIGN: Individually randomised, blinded, three arm trial. SETTING: Primary care and households in England. PARTICIPANTS: Children aged between 6 months and 6 years with axillary temperatures of at least 37.8 degrees C and up to 41.0 degrees C. INTERVENTION: Advice on physical measures to reduce temperature and the provision of, and advice to give, paracetamol plus ibuprofen, paracetamol alone, or ibuprofen alone. MAIN OUTCOME MEASURES: Primary outcomes were the time without fever (<37.2 degrees C) in the first four hours after the first dose was given and the proportion of children reported as being normal on the discomfort scale at 48 hours. Secondary outcomes were time to first occurrence of normal temperature (fever clearance), time without fever over 24 hours, fever associated symptoms, and adverse effects. RESULTS: On an intention to treat basis, paracetamol plus ibuprofen were superior to paracetamol for less time with fever in the first four hours (adjusted difference 55 minutes, 95% confidence interval 33 to 77; P<0.001) and may have been as good as ibuprofen (16 minutes, -7 to 39; P=0.2). For less time with fever over 24 hours, paracetamol plus ibuprofen were superior to paracetamol (4.4 hours, 2.4 to 6.3; P<0.001) and to ibuprofen (2.5 hours, 0.6 to 4.4; P=0.008). Combined therapy cleared fever 23 minutes (2 to 45; P=0.025) faster than paracetamol alone but no faster than ibuprofen alone (-3 minutes, 18 to -24; P=0.8). No benefit was found for discomfort or other symptoms, although power was low for these outcomes. Adverse effects did not differ between groups. CONCLUSION: Parents, nurses, pharmacists, and doctors wanting to use medicines to supplement physical measures to maximise the time that children spend without fever should use ibuprofen first and consider the relative benefits and risks of using paracetamol plus ibuprofen over 24 hours. TRIAL REGISTRATION: Current Controlled Trials ISRCTN26362730..

Similarity in structure and sequence homology has led to the identification of new members of the interleukin-1 (IL-1) ligand and receptor superfamilies. IL-1F6, IL-1F8 and IL-1F9 have been shown to signal through IL-1R-related protein 2 and IL-1 receptor accessory protein leading to activation of NFkappaB, while IL-1F7 and IL-1F10 interact with the IL-18 receptor and the soluble IL-1 receptor type I respectively. In contrast, identification of a biological role for IL-1F5 has remained elusive, with conflicting data relating to its possible ability to antagonize IL-1F9-stimulated activation of NFkappaB in Jurkat cells transfected with IL-1R-related protein 2. In this study, we set out to investigate a possible role for IL-1F5 in the brain and report that it antagonizes the inflammatory effects of IL-1beta and lipopolysaccharide (LPS) in vivo and in vitro including the inhibitory effect on long-term potentiation (LTP) in rat hippocampus. We demonstrate that IL-1F5 induces IL-4 mRNA and protein expression in glia in vitro and enhances hippocampal expression of IL-4 following intracerebroventricular (i.c.v.) injection. The inhibitory effect of IL-1F5 on LPS-induced IL-1beta is attenuated in cells from IL-4-defective (IL-4-/- mice). Our findings suggest that IL-1F5 mediates anti-inflammatory effects through its ability to induce IL-4 production and that this is a consequence of its interaction with the orphan receptor, single Ig IL-1R-related molecule (SIGIRR)/TIR8, as the effects were not observed in SIGIRR-/- mice. In contrast to its effects in brain tissue, IL-1F5 did not attenuate LPS-induced changes, or up-regulated IL-4 in macrophages or dendritic cells, suggesting that the effect is confined to the brain..

OBJECTIVE: To estimate the cost to the NHS and to parents and carers of treating febrile preschool children with paracetamol, ibuprofen, or both, and to compare these costs with the benefits of each treatment regimen. DESIGN: Cost consequences analysis and cost effectiveness analysis conducted as part of a three arm, randomised controlled trial. PARTICIPANTS: Children between the ages of 6 months and 6 years recruited from primary care and the community with axillary temperatures >or=37.8 degrees C and

It has been shown that Abeta inhibits long-term potentiation (LTP) in the rat hippocampus and this is accompanied by an increase in hippocampal concentration of IL-1beta. Abeta also increases microglial activation, which is the likely cell source of IL-1beta. Because IL-4 attenuates the effects of IL-1beta in hippocampus, and microglial activation is inhibited by minocycline, we assessed the ability of both IL-4 and minocycline to modulate the effects of Abeta on LTP and IL-1beta concentration. Following treatment with Abeta, IL-4 or minocycline, rats were assessed for their ability to sustain LTP in perforant path-granule cell synapses. We report that the Abeta-induced inhibition of LTP was associated with increases in expression of MHCII, JNK phosphorylation and IL-1beta concentration, and that these changes were attenuated by treatment of rats with IL-4 and minocycline. We also report that Abeta-induced increases in expression of MHCII and IL-1beta were similarly attenuated by IL-4 and minocycline in glial cultures prepared from neonatal rats. These data suggest that glial cell activation and the consequent increase in IL-1beta concentration mediate the inhibitory effect of Abeta on LTP and indicate that IL-4, by down-regulating glial cell activation, antagonizes the effects of Abeta..