Knowledge support for optimising antibiotic prescribing for common infections in general practices: evaluation of the effectiveness of periodic feedback, decision support during consultations and peer comparisons in a cluster randomised trial (BRIT2) - study protocol.

Introduction: This project applies a Learning Healthcare System (LHS) approach to antibiotic prescribing for common infections in primary care. The approach involves iterations of data analysis, feedback to clinicians and implementation of quality improvement activities by the clinicians. The main research question is, can a knowledge support system (KSS) intervention within an LHS implementation improve antibiotic prescribing without increasing the risk of complications?

Methods And Analysis: A pragmatic cluster randomised controlled trial will be conducted, with randomisation of at least 112 general practices in North-West England.

Clinician acceptability of an antibiotic prescribing knowledge support system for primary care: a mixed-method evaluation of features and context.

Background: Overprescribing of antibiotics is a major concern as it contributes to antimicrobial resistance. Research has found highly variable antibiotic prescribing in (UK) primary care, and to support more effective stewardship, the BRIT Project (Building Rapid Interventions to optimise prescribing) is implementing an eHealth Knowledge Support System. This will provide unique individualised analytics information to clinicians and patients at the point of care.

The long-term impact of loneliness and social isolation on depression and anxiety in memory clinic attendees and their care partners: A longitudinal actor-partner interdependence model.

Introduction: This study examined the long-term influence of loneliness and social isolation on mental health outcomes in memory assessment service (MAS) attendees and their care partners, with a focus on interdependence and bidirectionality.

Methods: Longitudinal data from 95 clinic attendees with cognitive impairment, and their care partners (dyads), from four MAS in the North of England were analyzed. We applied the actor-partner interdependence model, seeking associations within the dyad.

Co-design of a Smartphone App for People Living With Dementia by Applying Agile, Iterative Co-design Principles: Development and Usability Study.

Background: The benefits of involving those with lived experience in the design and development of health technology are well recognized, and the reporting of co-design best practices has increased over the past decade. However, it is important to recognize that the methods and protocols behind patient and public involvement and co-design vary depending on the patient population accessed. This is especially important when considering individuals living with cognitive impairments, such as dementia, who are likely to have needs and experiences unique to their cognitive capabilities.

Developing an Intervention to Implement Electronic Patient-Reported Outcomes in Renal Services in the UK.

Routinely collecting and using electronic patient-reported outcome (ePRO) data in clinical practice can improve patients' experience and outcomes, but implementing this at scale has proved challenging. As part of the Optimising routine collection of electronic patient-reported outcomes (OPT-ePRO) study, we therefore developed an intervention that aimed to facilitate the implementation of ePROs. We are conducting OPT-ePRO in the context of secondary care for people with chronic kidney disease in the UK, with three renal units participating as our study sites.

Assessing and managing concurrent hearing, vision and cognitive impairments in older people: an international perspective from healthcare professionals.

Background: there is a significant gap in the understanding, assessment and management of people with dementia and concurrent hearing and vision impairments.

Objective: from the perspective of professionals in dementia, hearing and vision care, we aimed to: (1) explore the perceptions of gaps in assessment and service provision in ageing-related hearing, vision and cognitive impairment; (2) consider potential solutions regarding this overlap and (3) ascertain the attitudes, awareness and practice, with a view to implementing change.

Methods: our two-part investigation with hearing, vision, and dementia care professionals involved: (1) an in-depth, interdisciplinary, international Expert Reference Group (ERG; n = 17) and (2) a wide-scale knowledge, attitudes and practice survey (n = 653).

Variations in inflammation-related genes may be associated with childhood febrile seizure susceptibility.

Purpose: To investigate whether genetic variants in inflammation-related genes are associated with increased risk of childhood-onset febrile seizures.

Method: Tagging single nucleotide polymorphisms (SNPs) from 19 inflammation-related candidate genes were identified and genotyped on the Sequenom platform in a sample of Caucasian childhood-onset febrile seizures cases (n=98) compared to ethnicity, age and gender matched febrile controls presenting without seizures (n=123). Tests for allelic association were carried out using PLINK.

Sources of variability between biobanks in the estimation of DNA concentration.

In biobank networks, accrual, aggregation, and retrieval of samples and data are impeded if minimal standards are not agreed in advance by the network members. The critical requirement is that outputs be standardized between biobanks. To start to address this problem of minimal standards, we undertook a pilot study and now report a follow-up study with 79 centers to identify sources of variability in a common measurement-the estimation of DNA concentration.

Does inflammation predispose to recurrent vascular events after recent transient ischaemic attack and minor stroke? The North West of England transient ischaemic attack and minor stroke (NORTHSTAR) study.

Background And Hypothesis: Inflammation is implicated in the pathogenesis and outcome of ischaemic injury. Poststroke inflammation is associated with outcome but it remains unclear whether such inflammation precedes or results from ischaemic injury. We hypothesised that inflammatory markers are associated with an increased risk of recurrent vascular events soon after transient ischaemic attack and minor stroke.

Development of a multiplex primer extension assay for rapid detection of Salmonella isolates of diverse serotypes.

Food-borne salmonellosis is a major manifestation of gastrointestinal disease in humans across the globe. Accurate and rapid identification methods could positively impact the identification of isolates, enhance outbreak investigation, and aid infection control. The SNaPshot multiplex system is a primer extension-based method that enables multiplexing of single nucleotide polymorphisms (SNPs).

The direct assessment of genetic heterozygosity through scent in the mouse.

The role of individual genetic heterozygosity in mate choice is the subject of much current debate. Several recent studies have reported female preference for more heterozygous males, but the mechanisms underlying heterozygote preference remain largely unknown. Females could favor males that are more successful in intrasexual competition, but they could also assess male heterozygosity directly at specific polymorphic genetic markers.

The genetic basis of inbreeding avoidance in house mice.

Animals might be able to use highly polymorphic genetic markers to recognize very close relatives and avoid inbreeding. The major histocompatibility complex (MHC) is thought to provide such a marker because it influences individual scent in a broad range of vertebrates. However, direct evidence is very limited.

The genetic basis of individual-recognition signals in the mouse.

The major histocompatibility complex (MHC) is widely assumed to be a primary determinant of individual-recognition scents in many vertebrates [1-6], but there has been no functional test of this in animals with normal levels of genetic variation. Mice have evolved another polygenic and highly polymorphic set of proteins for scent communication, the major urinary proteins (MUPs) [7-12], which may provide a more reliable identity signature ([13, 14] and A.L.

Genetic susceptibility to total hip arthroplasty failure--positive association with mannose-binding lectin.

Mannose-binding lectin (MBL) may be involved in the biologic cascade of events initiated by wear debris and bacterial infection around loosened total hip arthroplasties (THAs). Individual responses to such stimuli may be dictated by genetic variation caused by single nucleotide polymorphisms (SNPs). We performed a case-control study on 4 MBL SNPs using case patients (n = 91) with aseptic loosening or deep infection (n = 71).

Endotoxin exposure, CD14, and allergic disease: an interaction between genes and the environment.

Rationale: High endotoxin exposure may reduce the risk of allergic sensitization.

Objective: To determine the relationship between a promoter polymorphism in the CD14 gene (CD14/-159 C to T) and endotoxin exposure in relation to the development of allergic sensitization, eczema, and wheeze within the setting of a birth cohort.

Methods: We genotyped 442 children (CD14/-159 C to T; rs2569190).

Polymorphisms in a disintegrin and metalloprotease 33 (ADAM33) predict impaired early-life lung function.

Rationale: Asthma commonly originates in early life in association with impaired lung function, which tracks to adulthood.

Objectives: Within the context of a prospective birth cohort study, we investigated the association between single nucleotide polymorphisms (SNPs) in a disintegrin and metalloprotease 33 (ADAM33) gene and early-life lung function.

Methods: Children were genotyped for 17 SNPs in ADAM33.

Macrophage migration inhibitory factor gene polymorphism is associated with psoriasis.

Macrophage migration inhibitory factor (MIF), an important pro-inflammatory cytokine, is over-expressed in plaques of psoriasis and increased levels are found in the sera of patients with psoriasis. Promoter polymorphisms of the MIF gene are associated with increased production of MIF and have been found to confer increased risk of susceptibility to chronic inflammatory diseases. We investigated whether there is an association between promoter polymorphisms of the MIF gene and chronic plaque psoriasis.

A functional promoter haplotype of macrophage migration inhibitory factor is linked and associated with juvenile idiopathic arthritis.

Objective: To establish linkage and replicate the association of macrophage migration inhibitory factor (MIF) with juvenile idiopathic arthritis (JIA).

Methods: Three hundred twenty-one Caucasian simplex families from the UK were genotyped for polymorphisms of MIF using SNaPshot ddNTP primer extension, or by a fluorescently labeled primer method, and capillary gel electrophoresis. The functional significance of the promoter polymorphisms was studied using luciferase-based reporter gene assays in human T lymphoblast and epithelial cell lines.

Haplotype analysis in simplex families and novel analytic approaches in a case-control cohort reveal no evidence of association of the CTLA-4 gene with rheumatoid arthritis.

Objective: Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a negative regulator of T cells and is, therefore, a strong candidate susceptibility gene for T cell-mediated autoimmune diseases. The association of CTLA-4 single-nucleotide polymorphisms (SNPs) with rheumatoid arthritis (RA) has been investigated previously, with inconsistent results. Recently, SNPs mapping to the gene (and not previously investigated in RA) have been associated with both type 1 diabetes mellitus and Graves' disease.