Long-term consequences of urinary tract infection in childhood: an electronic population-based cohort study in Welsh primary and secondary care.

BACKGROUND: Childhood urinary tract infection (UTI) can cause renal scarring, and possibly hypertension, chronic kidney disease (CKD), and end-stage renal failure (ESRF). Previous studies have focused on selected populations, with severe illness or underlying risk factors. The risk for most children with UTI is unclear. AIM: To examine the association between childhood UTI and outcomes in an unselected population of children. DESIGN AND SETTING: A retrospective population-based cohort study using linked GP, hospital, and microbiology records in Wales, UK. METHOD: Participants were all children born in 2005-2009, with follow-up until 31 December 2017. The exposure was microbiologically confirmed UTI before the age of 5 years. The key outcome measures were renal scarring, hypertension, CKD, and ESRF. RESULTS: In total, 159 201 children were included; 77 524 (48.7%) were female and 7% (n = 11 099) had UTI before the age of 5 years. A total of 0.16% (n = 245) were diagnosed with renal scarring by the age of 7 years. Odds of renal scarring were higher in children by age 7 years with UTI (1.24%; adjusted odds ratio 4.60 [95% confidence interval [CI] = 3.33 to 6.35]). Mean follow-up was 9.53 years. Adjusted hazard ratios were: 1.44 (95% CI = 0.84 to 2.46) for hypertension; 1.67 (95% CI = 0.85 to 3.31) for CKD; and 1.16 (95% CI = 0.56 to 2.37) for ESRF. CONCLUSION: The prevalence of renal scarring in an unselected population of children with UTI is low. Without underlying risk factors, UTI is not associated with CKD, hypertension, or ESRF by the age of 10 years. Further research with systematic scanning of children's kidneys, including those with less severe UTI and without UTI, is needed to increase the certainty of these results, as most children are not scanned. Longer follow-up is needed to establish if UTI, without additional risk factors, is associated with hypertension, CKD, or ESRF later in life.

Predicting type 1 diabetes in children using electronic health records in primary care in the UK: development and validation of a machine-learning algorithm.

BACKGROUND: Children presenting to primary care with suspected type 1 diabetes should be referred immediately to secondary care to avoid life-threatening diabetic ketoacidosis. However, early recognition of children with type 1 diabetes is challenging. Children might not present with classic symptoms, or symptoms might be attributed to more common conditions. A quarter of children present with diabetic ketoacidosis, a proportion unchanged over 25 years. Our aim was to investigate whether a machine-learning algorithm could lead to earlier detection of type 1 diabetes in primary care. METHODS: We developed the predictive algorithm using Welsh primary care electronic health records (EHRs) linked to the Brecon Dataset, a register of children newly diagnosed with type 1 diabetes. Children were included from their first primary care record within the study period of Jan 1, 2000, to Dec 31, 2016, until either type 1 diabetes diagnosis, they turned 15 years of age, or study end. We developed an ensemble learner (SuperLearner) using 26 potential predictors. Validation of the algorithm was done in English EHRs from the Clinical Practice Research Datalink (primary care) and Hospital Episode Statistics, focusing on the ability of the algorithm to identify children who went on to develop type 1 diabetes and the time by which diagnosis could be anticipated. FINDINGS: The development dataset comprised 34 754 400 primary care contacts, relating to 952 402 children, and the validation dataset comprised 43 089 103 primary care contacts, relating to 1 493 328 children. Of these, 1829 (0·19%) children younger than 15 years in the development dataset, and 1516 (0·10%) in the validation dataset had a reliable date of type 1 diabetes diagnosis. If set to give an alert in 10% of contacts, an estimated 71·6% (95% CI 68·8-74·4) of the children with type 1 diabetes would receive an alert by the algorithm in the 90 days before diagnosis, with diagnosis anticipated, on average, by an estimated 9·34 days (95% CI 7·77-10·9). INTERPRETATION: If implemented into primary care settings, this predictive algorithm could substantially reduce the proportion of patients with new-onset type 1 diabetes presenting in diabetic ketoacidosis. Acceptability of alert thresholds should be explored in primary care. FUNDING: Diabetes UK.

Adverse respiratory outcomes among patients with resolved asthma: matched retrospective cohort study.

BACKGROUND: Patients with asthma may have symptom remission leading to a primary care code of resolved asthma. Little is known about subsequent rates of exacerbations and respiratory tract infections (RTIs). AIM: To assess the risk of adverse respiratory outcomes for people with resolved asthma compared with those with active asthma and without asthma. DESIGN AND SETTING: This was a retrospective cohort study of patients aged >5 years, registered with a general practice in England contributing data to the Clinical Practice Research Datalink between January 2010 and December 2019. METHOD: Patients with resolved asthma were matched to non-asthma controls and active asthma controls for age, sex, and practice. Negative binomial regression was used to estimate incidence rate ratios (IRRs) with 95% confidence intervals (CIs) for asthma exacerbations, RTIs, flu/pneumonia, and antibiotic prescriptions. RESULTS: Cohorts included 16 023 patients (8720 (54.4%) females, mean age 37 years). Compared with the active asthma cohort, the resolved cohort had fewer hospital admissions (adjusted IRR 0.29, 95% CI = 0.27 to 0.32) and general practice consultations (adjusted IRR 0.05, 95% CI = 0.04 to 0.07) for asthma exacerbations. The resolved and non-asthma cohorts had similar rates of hospital admissions for RTIs or flu/pneumonia. However, the resolved cohort had significantly greater incidence of general practice consultations for lower RTIs (adjusted IRR 2.34, 95% CI = 2.08 to 2.64) and antibiotic prescriptions (adjusted IRR 1.37, 95% CI = 1.30 to 1.44). CONCLUSION: Patients with resolved asthma had greater risk of general practice RTI and antibiotic prescription than the general population and may benefit from defined strategies for reassessing symptoms and reinitiating asthma therapy.

Impact of the COVID-19 pandemic on domiciliary care workers in Wales, UK: a data linkage cohort study using the SAIL Databank.

OBJECTIVES: To quantify population health risks for domiciliary care workers (DCWs) in Wales, UK, working during the COVID-19 pandemic. DESIGN: A population-level retrospective study linking occupational registration data to anonymised electronic health records maintained by the Secure Anonymised Information Linkage Databank in a privacy-protecting trusted research environment. SETTING: Registered DCW population in Wales. PARTICIPANTS: Records for all linked DCWs from 1 March 2020 to 30 November 2021. PRIMARY AND SECONDARY OUTCOME MEASURES: Our primary outcome was confirmed COVID-19 infection; secondary outcomes included contacts for suspected COVID-19, mental health including self-harm, fit notes, respiratory infections not necessarily recorded as COVID-19, deaths involving COVID-19 and all-cause mortality. RESULTS: Confirmed and suspected COVID-19 infection rates increased over the study period to 24% by 30 November 2021. Confirmed COVID-19 varied by sex (males: 19% vs females: 24%) and age (>55 years: 19% vs <35 years: 26%) and were higher for care workers employed by local authority social services departments compared with the private sector (27% and 23%, respectively). 34% of DCWs required support for a mental health condition, with mental health-related prescribing increasing in frequency when compared with the prepandemic period. Events for self-harm increased from 0.2% to 0.4% over the study period as did the issuing of fit notes. There was no evidence to suggest a miscoding of COVID-19 infection with non-COVID-19 respiratory conditions. COVID-19-related and all-cause mortality were no greater than for the general population aged 15-64 years in Wales (0.1% and 0.034%, respectively). A comparable DCW workforce in Scotland and England would result in a comparable rate of COVID-19 infection, while the younger workforce in Northern Ireland may result in a greater infection rate. CONCLUSIONS: While initial concerns about excess mortality are alleviated, the substantial pre-existing and increased mental health burden for DCWs will require investment to provide long-term support to the sector's workforce.

Visualisation and optimisation of alcohol-related hospital admissions ICD-10 codes in Welsh e-cohort data.

INTRODUCTION: The excessive consumption of alcohol is detrimental to long term health and increases the likelihood of hospital admission. However, definitions of alcohol-related hospital admission vary, giving rise to uncertainty in the effect of alcohol on alcohol-related health care utilization. OBJECTIVES: To compare diagnostic codes on hospital admission and discharge and to determine the ideal combination of codes necessary for an accurate determination of alcohol-related hospital admission. METHODS: Routine population-linked e-cohort data were extracted from the Secure Anonymised Information Linkage (SAIL) Databank containing all alcohol-related hospital admissions (n,= 92,553) from 2006 to 2011 in Wales, United Kingdom. The distributions of the diagnostic codes recorded at admission and discharge were compared. By calculating a misclassification rate (sensitivity-like measure) the appropriate number of coding fields to examine for alcohol-codes was established. RESULTS: There was agreement between admission and discharge codes. When more than ten coding fields were used the misclassification rate was less than 1%. CONCLUSION: With the data at present and alcohol-related codes used, codes recorded at admission and discharge can be used equivalently to identify alcohol-related admissions. The appropriate number of coding fields to examine was established: fewer than ten is likely to lead to under-reporting of alcohol-related admissions. The methods developed here can be applied to other medical conditions that can be described using a certain set of diagnostic codes, each of which can be a known sole cause of the condition and recorded in multiple positions in e-cohort data.

Healthcare use by children and young adults with cerebral palsy.

AIM: To link routinely collected health data to a cerebral palsy (CP) register in order to enable analysis of healthcare use by severity of CP. METHOD: The Northern Ireland Cerebral Palsy Register was linked to hospital data. Data for those on the CP register born between 1st January 1981 and 31st December 2009 and alive in 2004 were extracted, forming a CP cohort (n=1684; 57% males, 43% females; aged 0-24y). Frequencies of healthcare events, and the reasons for them, were reported according to CP severity and compared with those without CP who had had at least one hospital attendance in Northern Ireland within the study period. RESULTS: Cases of CP represented 0.3% of the Northern Ireland population aged 0 to 24 years but accounted for 1.6% of hospital admissions and 1.6% of outpatient appointments. They had higher rates of elective admissions and multi-day hospital stays than the general population. Respiratory conditions were the most common reason for emergency admissions. Those with most severe CP were 10 times more likely to be admitted, and four times more likely to attend outpatients, than those with mild CP. INTERPRETATION: Linkage between a register and routinely collected healthcare data provided a confirmed cohort of cases of CP that was sufficiently detailed to analyse healthcare use by disease severity.

Agreement between ophthalmologists and optometrists in the certification of vision impairment.

BACKGROUND/OBJECTIVES: The certification process to register patients as sight impaired or severely sight impaired is undertaken by consultant ophthalmologists, in the UK. We sought to assess the agreement between optometrists and a consensus panel, in identifying patient eligibility for certification, relative to the agreement between ophthalmologists and the consensus panel. METHODS: The consensus panel (4 consultant ophthalmologists and 3 optometrists with a formal accreditation in low vision), 30 consultant ophthalmologists and 99 low vision optometrists reviewed 40 randomly selected abridged cases. The eligibility outcomes from the ophthalmologists and the optometrists were compared with the consensus panel outcomes. RESULTS: For ophthalmologists and optometrists, the median (IQR) number of cases in which there was agreement with the consensus panel was 33.0 (31.0, 33.0) and 36.0 (34.0, 36.5), respectively. In severely sight impaired cases, the probabilities of agreeing on eligibility for certification were 76.0% (95% CIs 71.4%, 80.1%) for ophthalmologists and 61.8% (59.0%, 64.6%) for optometrists. In sight impaired cases, the corresponding values were 51.6% (46.7%, 56.4%) for ophthalmologists and 72.2% (69.8%, 74.5%) for optometrists. In cases of bilateral atrophic age-related macular degeneration (AMD), both groups were more likely to agree with the consensus panel and the differences between optometrists and ophthalmologists were less marked. CONCLUSIONS: Optometrists demonstrated a comparable agreement relative to ophthalmologists, with the consensus panel on the eligibility of randomly selected, abridged cases for certification. The findings support the clinical decision-making ability of low vision optometrists in the certification of patients with vision impairment and provide evidence in support of policy change to allow low vision optometrists to certify individuals with atrophic AMD.

Antibiotic use and deprivation: an analysis of Welsh primary care antibiotic prescribing data by socioeconomic status.

OBJECTIVES: To examine the association between socioeconomic status (SES) and antibiotic prescribing, controlling for the presence of common chronic conditions and other potential confounders and variation amongst GP practices and clusters. METHODS: This was an electronic cohort study using linked GP and Welsh Index of Multiple Deprivation (WIMD) data. The setting was GP practices contributing to the Secure Anonymised Information Linkage (SAIL) Databank 2013-17. The study involved 2.9 million patients nested within 339 GP practices, nested within 67 GP clusters. RESULTS: Approximately 9 million oral antibiotics were prescribed between 2013 and 2017. Antibiotic prescribing rates were associated with WIMD quintile, with more deprived populations receiving more antibiotics. This association persisted after controlling for patient demographics, smoking, chronic conditions and clustering by GP practice and cluster, with those in the most deprived quintile receiving 18% more antibiotic prescriptions than those in the least deprived quintile (incidence rate ratio = 1.18; 95% CI = 1.181-1.187). We found substantial unexplained variation in antibiotic prescribing rates between GP practices [intra-cluster correlation (ICC) = 47.31%] and GP clusters (ICC = 12.88%) in the null model, which reduced to ICCs of 3.50% and 0.85% for GP practices and GP clusters, respectively, in the final adjusted model. CONCLUSIONS: Antibiotic prescribing in primary care is increased in areas of greater SES deprivation and this is not explained by differences in the presence of common chronic conditions or smoking status. Substantial unexplained variation in prescribing supports the need for ongoing antimicrobial stewardship initiatives.

Establishing the impact of COVID-19 on the health outcomes of domiciliary care workers in Wales using routine data: a protocol for the OSCAR study.

INTRODUCTION: Domiciliary care workers (DCWs) continued providing social care to adults in their own homes throughout the COVID-19 pandemic. Evidence of the impact of COVID-19 on health outcomes of DCWs is currently mixed, probably reflecting methodological limitations of existing studies. The risk of COVID-19 to workers providing care in people's homes remains unknown. OBJECTIVES: To quantify the impact of COVID-19 upon health outcomes of DCWs in Wales, to explore causes of variation, and to extrapolate to the rest of the UK DCW population. METHODS: Mixed methods design comprising cohort study of DCWs and exploratory qualitative interviews. Data for all registered DCWs in Wales is available via the SAIL Databank using a secured, privacy-protecting encrypted anonymisation process. Occupational registration data for DCWs working during the pandemic will be combined with EHR outcome data within the SAIL Databank including clinical codes that identify suspected and confirmed COVID-19 cases. We will report rates of suspected and confirmed COVID-19 infections and key health outcomes including mortality and explore variation (by factors such as age, sex, ethnicity, deprivation quintile, rurality, employer, comorbidities) using regression modelling, adjusting for clustering of outcome within Health Board, region and employer. A maximum variation sample of Welsh DCWs will be approached for qualitative interview using a strategy to include participants that vary across factors such as sex, age, ethnicity and employer. The interviews will inform the quantitative analysis modelling. We will generalise the quantitative findings to other UK nations. DISCUSSION: Using anonymised linked occupational and EHR data and qualitative interviews, the OSCAR study will quantify the risk of COVID-19 on DCWs' health and explore sources of variation. This will provide a secure base for informing public health policy and occupational guidance.

Incidence of medically attended paediatric burns across the UK.

OBJECTIVE: Childhood burns represent a burden on health services, yet the full extent of the problem is difficult to quantify. We estimated the annual UK incidence from primary care (PC), emergency attendances (EA), hospital admissions (HA) and deaths. METHODS: The population was children (0-15 years), across England, Wales, Scotland and Northern Ireland (NI), with medically attended burns 2013-2015. Routinely collected data sources included PC attendances from Clinical Practice Research Datalink 2013-2015), EAs from Paediatric Emergency Research in the United Kingdom and Ireland (PERUKI, 2014) and National Health Services Wales Informatics Services, HAs from Hospital Episode Statistics, National Services Scotland and Social Services and Public Safety (2014), and mortality from the Office for National Statistics, National Records of Scotland and NI Statistics and Research Agency 2013-2015. The population denominators were based on Office for National Statistics mid-year population estimates. RESULTS: The annual PC burns attendance was 16.1/10 000 persons at risk (95% CI 15.6 to 16.6); EAs were 35.1/10 000 persons at risk (95% CI 34.7 to 35.5) in England and 28.9 (95% CI 27.5 to 30.3) in Wales. HAs ranged from 6.0/10 000 person at risk (95% CI 5.9 to 6.2) in England to 3.1 in Wales and Scotland (95% CI 2.7 to 3.8 and 2.7 to 3.5, respectively) and 2.8 (95% CI 2.4 to 3.4) in NI. In England, Wales and Scotland, 75% of HAs were aged <5 years. Mortality was low with 0.1/1 000 000 persons at risk (95% CI 0.06 to 0.2). CONCLUSIONS: With an estimated 19 574 PC attendances, 37 703 EAs (England and Wales only), 6639 HAs and 1-6 childhood deaths annually, there is an urgent need to improve UK childhood burns prevention.

Epidemiology of eating disorders in primary care in children and young people: a Clinical Practice Research Datalink study in England.

OBJECTIVES: Examination of current temporal trends and clinical management patterns of eating disorders (ED) in primary care is lacking. We aimed to calculate annual incidence rates of EDs in primary care by age, sex and deprivation. We also explored the care received through referrals, psychotropic prescriptions and associated secondary care service use. PARTICIPANTS AND SETTINGS: A retrospective electronic cohort study was conducted using the Clinical Practice Research Datalink in those aged 11-24 years between 2004 and 2014 in England (n=1 135 038). RESULTS: A total of 4775 individuals with a first ever recorded ED diagnosis were identified. The crude incidence rate was 100.1 per 100 000 person years at risk (95% CI 97.2 to 102.9). Incidence rates were highest in females (189.3 per 100 000 person years, 95% CI 183.7 to 195.0, n=4336), 16-20 years of age (141.0 per 100 000 person years, 95% CI 135.4 to 146.9, n=2348) and individuals from the least deprived areas (115.8 per 100 000 person years (95% CI 109.3 to 122.5, n=1203). Incidence rates decreased across the study period (incidence rate ratio (IRR) 0.6, 95% CI 0.5 to 0.8), particularly for individuals with bulimia nervosa (IRR 0.5, 95% CI 0.3 to 0.7) and from the most deprived areas (IRR 0.5, 95% CI 0.4 to 0.7). A total of 17.4% (95% CI 16.3 to 18.5, n=831) of first ever recorded ED cases were referred from primary to secondary care. 27.1% (95% CI 25.9 to 28.4, n=1294) of individuals had an inpatient admission 6 months before or 12 months after an incident ED diagnosis and 53.4% (95% CI 52.0 to 54.9, n=2550) had an outpatient attendance. Antidepressants were the most commonly prescribed psychotropic medication. CONCLUSIONS: New ED presentations in primary care are reducing. Understanding the cause of this decrease (coding behaviours, changes in help-seeking or a genuine reduction in new cases) is important to plan services, allocate resources and deliver effective care.

Identifying cerebral palsy from routinely-collected data in England and Wales.

Purpose: An observational study using routinely-collected health care data to describe the extent to which children and young people (CYP) with cerebral palsy (CP) can be identified and the prevalence of CP can be estimated. Patients and methods: Routinely-collected anonymized data, for CYP (aged 0-25 years old between 1 January 2004 and 31 December 2014) were analyzed in two linked datasets, from England and Wales respectively. Datasets included National Health Service; General Practitioner (GP), inpatients, outpatients, and national mortality records. CP was identified using ICD-10 codes G80.0-G83.3 and equivalent Read v2 codes. Ascertainment rates of CP were identified for each data source and compared between countries. Frequency and consistency of coding were investigated, and prevalence of CP estimated. Results: A total of 7,113 and 5,218 CYP with CP were identified in the English and Welsh datasets respectively. Whilst the majority of CYP with CP would be expected to attend their GP, 65.3% (4,646/7,113) of English and 65.1% (3,396/5,218) of Welsh cases were ascertained from GP datasets. Further cases were identified solely in inpatient datasets (2,410 in England, 1,813 in Wales). Few cases were coded for CP within outpatient datasets. Four character codes that specified CP type were rarely used; one in five health care records were coded both with G80 codes (explicitly CP) and with G81-83 codes (other paralytic syndromes) or equivalent Read codes. Estimated period prevalence of CYP with CP was 2.5-3.4 per 1,000 in England and 2.4-3.2 per 1,000 in Wales. Conclusion: In England and Wales, coding of CP in routine data is infrequent, inconsistent, non-specific, and difficult to isolate from conditions with similar physical signs. Yet the prevalence estimates of CP were similar to those reported elsewhere. To optimize case recognition we recommend improved coding quality and the use of both primary and secondary care datasets as a minimum.

Long-term outcomes of urinary tract infection (UTI) in Childhood (LUCI): protocol for an electronic record-linked cohort study.

INTRODUCTION: Current guidelines advise the prompt diagnosis and treatment of urinary tract infection (UTI) in children to improve both short and longer term outcomes. However, the risk of long-term complications following childhood UTI is unclear.UTI is relatively common but difficult to diagnose in children as symptoms are non-specific. Diagnosis requires a urine sample, but sampling is difficult and infrequent, and it is not clear if sampling should be given greater priority in primary care. The LUCI study will assess the short, medium and longer term outcomes of childhood UTI associated with routine and systematic sampling practices. METHODS AND ANALYSIS: Two data sets will be established. The first will consist of routinely collected data (hospital, general practice (GP), microbiology) from children born and resident in Wales, linked via the Secure Anonymised Information Linkage (SAIL) Databank (an 'e-cohort'). Urine sampling in this data set reflects normal practice 'routine sampling'. Outcomes (including renal scarring, hypertension, end-stage renal failure, hospital admissions, GP consultations, antibiotic prescriptions) for children with at least one UTI confirmed with microbiological culture (mcUTI) or no mcUTI before the age of 5 will be compared.The second will combine data from two prospective observational studies ('DUTY' and 'EURICA') employing systematic urine sampling for children presenting to primary care with acute, undifferentiated illness, linked to routine data via SAIL (Wales) and NHS Digital (England). Outcomes (as above, plus features of mcUTI) for children with an mcUTI in this data set, identified through systematic urine sampling, will be compared with those with an mcUTI identified through routine urine sampling (data set 1). ETHICS AND DISSEMINATION: The study protocol has been approved by NHS Wales Research Ethics Committee and the Health Research Authority's Confidentiality Advisory Group. Methods of innovative study design and findings will be disseminated through peer-review journals and conferences. Results will be of interest to clinical and policy stakeholders in the UK.

Antibiotic prophylaxis and clinical outcomes among older adults with recurrent urinary tract infection: cohort study.

BACKGROUND: clinical guidelines recommend antibiotic prophylaxis for preventing recurrent urinary tract infections (UTIs), but there is little evidence for their effectiveness in older adults. METHODS: this was a retrospective cohort study of health records from 19,696 adults aged ≥65 with recurrent UTIs. We used prescription records to ascertain ≥3 months' prophylaxis with trimethoprim, cefalexin or nitrofurantoin. We used random effects Cox recurrent event models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for risks of clinical recurrence (primary outcome), acute antibiotic prescribing and hospitalisation. RESULTS: of 4,043 men and 15,653 women aged ≥65 with recurrent UTIs, 508 men (12.6%) and 2,229 women (14.2%) were prescribed antibiotic prophylaxis. In men, prophylaxis was associated with a reduced risk of clinical recurrence (HR, 0.49; 95% CI, 0.45-0.54), acute antibiotic prescribing (HR, 0.54; 95% CI, 0.51-0.57) and UTI-related hospitalisation (HR, 0.78; 95% CI, 0.64-0.94). In women, prophylaxis was also associated with a reduced risk of clinical recurrence (HR, 0.57; 95% CI, 0.55-0.59) and acute antibiotic prescribing (HR, 0.61; 95% CI, 0.59-0.62), but estimates of the risk of UTI-related hospitalisation were inconsistent between our main analysis (HR, 1.16; 95% CI, 1.05-1.28) and sensitivity analysis (HR, 0.82; 95% CI, 0.72-0.94). CONCLUSIONS: antibiotic prophylaxis was associated with lower rates of UTI recurrence and acute antibiotic prescribing in older adults. To fully understand the benefits and harms of prophylaxis, further research should determine the frequency of antibiotic-related adverse events and the impact on antimicrobial resistance and quality of life.

Incidence and antibiotic prescribing for clinically diagnosed urinary tract infection in older adults in UK primary care, 2004-2014.

Urinary tract infections (UTI) are an important cause of morbidity and antibiotic use in older adults but there are little data describing disease burden in primary care. The aim of this study was to estimate the incidence of clinically diagnosed UTI and examine associated empirical antibiotic prescribing. We conducted a retrospective observational study using linked health records from almost one million patients aged ≥65 years old, registered with 393 primary care practices in England. We estimated incidence of clinically diagnosed UTI between March 2004 and April 2014, and used multilevel logistic regression to examine trends in empiric antibiotic prescribing. Of 931,945 older adults, 196,358 (21%) had at least one clinically diagnosed UTI over the study period. In men, the incidence of clinically diagnosed UTI per 100 person-years at risk increased from 2.81 to 3.05 in those aged 65-74, 5.90 to 6.13 in those aged 75-84, and 8.08 to 10.54 in those aged 85+. In women, incidence increased from 9.03 to 10.96 in those aged 65-74, 11.35 to 14.34 in those aged 75-84, and 14.65 to 19.80 in those aged 85+. Prescribing of broad-spectrum antibiotics decreased over the study period. There were increases in the proportion of older men (from 45% to 74%) and women (from 55% to 82%) with UTI, prescribed a UTI specific antibiotic. There were also increases in the proportion of older men (42% to 69%) and women (15% to 26%) prescribed antibiotics for durations recommended by clinical guidelines. This is the first population-based study describing the burden of UTI in UK primary care. Our findings suggest a need to better understand reasons for increasing rates of clinically diagnosed UTI and consider how best to address this important clinical problem.

Identification of novel HLA class II target epitopes for generation of donor-specific T regulatory cells.

Therapies capable of generating host T regulatory cells (T(R)) responsive to donor-specific HLA-class II minor histocompatibility antigens have the potential to promote tolerance of a transplanted organ. Our group has developed a novel approach for the identification of potentially therapeutic T(R) target antigens. We perform parallel non-synonymous SNP genotyping of HLA-identical subject pairs to identify peptide variations expressed by only one of the two subjects. Variant peptide pairs are then evaluated for binding a shared HLA-class II allele. Minor peptides predicted to bind HLA-class II with greater affinity than the common variant peptide are tested for HLA class II binding and in vitro induction of suppressive CD4+ T cells. Using this approach we have identified multiple pairs of variant peptides capable of differential binding and induction of suppressive CD4+ T cells. These data demonstrate the feasibility of identifying potentially therapeutic HLA class II minor antigens for generation of donor-specific T(R).

Effects of prior exposure to office noise and music on aspects of working memory.

Previous research has suggested that prior exposure to noise reduces the effect of subsequent exposure due to habituation. Similarly, a number of studies have shown that exposure to Mozart's music leads to better subsequent spatial reasoning performance. Two studies were conducted to extend these findings. The first one examined whether habituation occurs to office noise (including speech) and, if so, how long it takes to develop. Thirty-six young adults participated in the first study which compared effects of office noise with quiet on the performance of a maths task. The study also examined the effects of prior exposure to the office noise on the subsequent effect of the noise. The results showed that performance was initially impaired by the office noise but that the effects of the noise were removed by 10 minutes of exposure between tasks. The second experiment attempted to replicate the "Mozart effect" which represents an improvement in spatial reasoning following listening to Mozart. The study also examined whether the Mozart effect could be explained by changes in mood. Twenty-four young adults participated in the study. The results replicated the Mozart effect and showed that it was not due to changes in mood. Overall, these results show that prior exposure to noise or music can influence aspects of working memory. Such effects need to be incorporated into models of effects of noise on cognition and attempts have to be made to eliminate alternative explanations rather than just describing changes that occur in specific contexts.