Risk of ovarian cancer in women with symptoms in primary care: population based case-control study.

addresses: NIHR School for Primary Care Research, Department of Community Based Medicine, University of Bristol, Bristol BS8 2AA, UK. [email protected]: PMCID: PMC2731836types: Journal Article; Multicenter Study; Research Support, Non-U.S. Gov'tCopyright © 2009 by the BMJ Publishing Group Ltd. This articles was first published in: BMJ, 2009, Vol. 339, pp. b2998 -To identify and quantify symptoms of ovarian cancer in women in primary care

Ethnic inequities in routine childhood vaccinations in England 2006–2021: an observational cohort study using electronic health records

Background: Population groups that are underserved by England's childhood vaccination programme must be identified to address the country's declining vaccination coverage. We examined routine childhood vaccination coverage in England by maternal ethnicity between 2006 and 2021. Methods: We created first, second and fifth birthday cohorts using mother-child linked electronic health records from the Clinical Practice Research Datalink (CPRD) Aurum. After validation against the UK Health Security Agency (UKHSA) and National Health Service England (NHSE) annual statistical reports, we described vaccination coverage for each vaccine by ethnicity and year. We used modified Poisson regression to analyse the effect of ethnicity on receiving the primary and full course of each vaccine. Findings: Up to 1,170,804 children born after 1 April 2006 were included in the first birthday cohort, reducing to 645,492 by the fifth birthday. Children were followed up until 31 March 2021 at the latest. Children born to mothers in 9 minority ethnic groups and those of unknown ethnicity had lower vaccination coverage (61.3–97.5%) than the White British group (79.9–97.8%) for all vaccines. Indian, Pakistani, Bangladeshi, Chinese, Any other Asian background, and White and Asian ethnic groups had similar vaccination coverage to the White British group (above 90% for most vaccines in most years). Inequities particularly affected the Caribbean group (e.g. 61% coverage for the 6/5/4-in-1 full course in 2020–21 by children's fifth birthday; RR 0.66, 95% CI 0.6–0.74 compared with the White British group) and Any other Black, African and Caribbean background (e.g. coverage 68% for the MMR primary course in 2020–21; RR 0.71, 95% CI 0.64–0.78). These inequities widened over the study period. For example, the absolute difference in coverage between the Caribbean and White British groups for the full course of MMR increased from 12% in 2011–12 to 22% in 2019–20. These inequities remained even after accounting for sociodemographic, maternal and birth related factors, and also widened from primary course to full course. Interpretation: Our findings suggest that urgent policy action is needed to address the ethnic inequities throughout England's routine childhood vaccination programme, which have been worsening over time

A Simulation Framework to Investigate in vitro Viral Infection Dynamics

AbstractVirus infection is a complex biological phenomenon for which in vitro experiments provide a uniquely concise view where data is often obtained from a single population of cells, under controlled environmental conditions. Nonetheless, data interpretation and real understanding of viral dynamics is still hampered by the sheer complexity of the various intertwined spatio-temporal processes. In this paper we present a tool to address these issues: a cellular automata model describing critical aspects of in vitro viral infections taking into account spatial characteristics of virus spreading within a culture well. The aim of the model is to understand the key mechanisms of SARS-CoV infection dynamics during the first 24hours post infection. We interrogate the model using a Latin Hypercube sensitivity analysis to identify which mechanisms are critical to the observed infection of host cells and the release of measured virus particles

Characterization of a murine mixed neuron-glia model and cellular responses to regulatory T cell-derived factors

Abstract One of the unmet clinical needs in demyelinating diseases such as Multiple Sclerosis (MS) is to provide therapies that actively enhance the process of myelin regeneration (remyelination) in the central nervous system (CNS). Oligodendrocytes, the myelinating cells of the CNS, play a central role in remyelination and originate from oligodendrocyte progenitor cells (OPCs). We recently showed that depletion of regulatory T cells (Treg) impairs remyelination in vivo, and that Treg-secreted factors directly enhance oligodendrocyte differentiation. Here we aim to further characterize the dynamics of Treg-enhanced oligodendrocyte differentiation as well as elucidate the cellular components of a murine mixed neuron-glia model. Murine mixed neuron-glia cultures were generated from P2–7 C57BL/6 mice and characterized for percentage of neuronal and glial cell populations prior to treatment at 7 days in vitro (div) as well as after treatment with Treg-conditioned media at multiple timepoints up to 12 div. Mixed neuron-glia cultures consisted of approximately 30% oligodendroglial lineage cells, 20% neurons and 10% microglia. Furthermore, a full layer of astrocytes, that could not be quantified, was present. Treatment with Treg-conditioned media enhanced the proportion of MBP+ oligodendrocytes and decreased the proportion of PDGFRα+ OPCs, but did not affect OPC proliferation or survival. Treg-enhanced oligodendrocyte differentiation was not caused by Treg polarizing factors, was dependent on the number of activation cycles Treg underwent and was robustly achieved by using 5% conditioned media. These studies provide in-depth characterization of a murine mixed neuron-glia model as well as further insights into the dynamics of Treg-enhanced oligodendrocyte differentiation

CASNET2: Evaluation of an Electronic Safety Netting cancer toolkit for the primary care electronic health record: protocol for a pragmatic stepped-wedge RCT

Introduction: Safety-netting in primary care is the best practice in cancer diagnosis, ensuring that patients are followed up until symptoms are explained or have resolved. Currently, clinicians use haphazard manual solutions. The ubiquitous use of electronic health records provides an opportunity to standardise safety-netting practices. A new electronic safety-netting toolkit has been introduced to provide systematic ways to track and follow up patients. We will evaluate the effectiveness of this toolkit, which is embedded in a major primary care clinical system in England:Egerton Medical Information System(EMIS)-Web. Methods and analysis: We will conduct a stepped-wedge cluster RCT in 60 general practices within the RCGP Research and Surveillance Centre (RSC) network. Groups of 10 practices will be randomised into the active phase at 2-monthly intervals over 12 months. All practices will be activated for at least 2 months. The primary outcome is the primary care interval measured as days between the first recorded symptom of cancer (within the year prior to diagnosis) and the subsequent referral to secondary care. Other outcomes include referrals rates and rates of direct access cancer investigation. Analysis of the clustered stepped-wedge design will model associations using a fixed effect for intervention condition of the cluster at each time step, a fixed effect for time and other covariates, and then include a random effect for practice and for patient to account for correlation between observations from the same centre and from the same participant. Ethics and dissemination: Ethical approval has been obtained from the North West—Greater Manchester West National Health Service Research Ethics Committee (REC Reference 19/NW/0692). Results will be disseminated in peer-reviewed journals and conferences, and sent to participating practices. They will be published on the University of Oxford Nuffield Department of Primary Care and RCGP RSC websites

What is the psychological impact of mammographic screening on younger women with a family history of breast cancer? Findings from a prospective cohort study (PIMMS)

PURPOSE: Studies are underway to establish the clinical effectiveness of annual mammographic screening in women younger than 50 years with a family history of breast cancer. This study investigated both the positive and negative psychological effects of screening on these women. PATIENTS AND METHODS: Women who received an immediate all-clear result after mammography (n = 1,174) and women who were recalled for additional tests before receiving an all-clear result (false positive; n = 112) completed questionnaires: 1 month before mammography, and 1 and 6 months after receiving final results. The questionnaires included measures of cancer worry, psychological consequences, and perceived benefits of breast screening. RESULTS: Women who received an immediate all-clear result experienced a decrease in cancer worry and negative psychological consequences immediately after the result, whereas women who were recalled for additional tests did not. By 6 months this cancer-specific distress had reduced significantly in both groups. Changes in levels of distress were significantly different between the two groups, but in absolute terms the differences were not large. Recalled women reported significantly greater positive psychological consequences of screening immediately after the result, and were also more positive about the benefits of screening compared with women who received an immediate all-clear result. CONCLUSION: For women receiving an immediate all-clear result, participating in annual mammographic screening is psychologically beneficial. Furthermore, women who are recalled for additional tests do not appear to be harmed by screening: these women's positive views about mammography suggest that they view any distress caused by recall as an acceptable part of screening

Risk factors for influenza-related complications in children during the 2009/10 pandemic: a UK primary care cohort study using linked routinely collected data.

Primary care clinicians have a central role in managing influenza/influenza-like illness (ILI) during influenza pandemics. This study identifies risk factors for influenza-related complications in children presenting with influenza/ILI in primary care. We conducted a cohort study using routinely collected linked data from the Clinical Practice Research Datalink on children aged 17 years and younger who presented with influenza/ILI during the 2009/10 pandemic. We calculated odds ratios (ORs) for potential risk factors in relation to influenza-related complications, complications requiring intervention, pneumonia, all-cause hospitalisation and hospitalisation due to influenza-related complications within 30 days of presentation. Analyses were adjusted for potential confounders including age, vaccination and socio-economic deprivation. Asthma was a risk factor for influenza-related complications (adjusted OR 1.48, 95% confidence interval (CI) 1.21-1.80, P < 0.001), complications requiring intervention (adjusted OR 1.44, 95% CI 1.11-1.88; P = 0.007), pneumonia (adjusted OR 1.64, 95% CI 1.07-2.51, P = 0.024) and hospitalisation due to influenza-related complications (adjusted OR 2.46, 95% CI 1.09-5.56, P = 0.031). Neurological conditions were risk factors for all-cause hospitalisation (adjusted OR 4.25, 95% CI 1.50-12.07, P = 0.007) but not influenza-related complications (adjusted OR 1.46, 95% CI 0.83-2.56, P = 0.189). Community-based early interventions to prevent influenza-related clinical deterioration should therefore be primarily targeted at children with asthma and neurological conditions