484 research outputs found

    Diagnosing Influenza for Research

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    The role of influenza and acute respiratory infections as triggers for acute myocardial infarction

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    Background: Influenza is an important global cause of morbidity and mortality. Though some cardiac complications of influenza, such as myocarditis, are well-recognised, its role as a trigger for acute cardiovascular events is less clear. Improved understanding of this relationship will add to evidence to support appropriate prevention and treatment strategies. Methods: I investigated evidence that influenza and acute respiratory infections could trigger acute myocardial infarction (AMI) through a systematic literature review and meta-analysis (chapter 2) and original research studies (chapters 3-7). These were an ecological weekly time series study using Poisson regression models adjusted for temporal and environmental confounders in England & Wales and Hong Kong (chapter 3); two self-controlled case series analyses using the General Practice Research Database linked to influenza surveillance data (chapter 4) and to cardiac disease registry and hospitalisation data (chapter 5); a case control study in AMI patients and surgical controls during the 2009 influenza pandemic in London (chapter 6); an exploratory mechanistic study (chapter 7). Key findings: • Acute respiratory infections, and seasonal influenza, triggered AMI • A triggering effect may be greater for influenza than for other respiratory infections (p=0.011) • AMI risk was highest in the first three days after acute infection – adjusted incidence ratio 4.19 (95% CI 3.18-5.53) – and persisted for around 28 days • The proportion of AMI deaths due to seasonal influenza ranged from 3-5%, rising to 13% in periods of highest influenza circulation • The relative risk of AMI after acute respiratory infection was highest in people aged ≥80 years • Influenza vaccination protected against some adverse cardiac outcomes in people with existing cardiovascular disease Conclusions: Reducing the burden of influenza would benefit cardiovascular health. Questions remain about key groups to target, as well as the optimal type and delivery of interventions to reduce influenza-associated AMI risk

    Herpes Zoster: Epidemiological Links With Stroke and Myocardial Infarction.

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    Routine data from electronic health records (EHRs) provide insights into links between herpes zoster (HZ) and cardiovascular complications such as stroke or myocardial infarction (MI) in different populations worldwide. Evidence from large EHR studies using both self-controlled case series and traditional cohort designs suggests that there is a transient increase in the risk of stroke after HZ, which gradually resolves over 6-12 months. In these studies, herpes zoster ophthalmicus was associated with a higher risk of stroke than HZ at other sites. A larger effect size was seen in people aged under 40 years. Existing studies also suggest that HZ may have a triggering effect on MI, although fewer studies examined this outcome. Further evidence is needed on the effectiveness and cost-effectiveness of vaccine and antiviral drugs to reduce cardiovascular complications after HZ from studies that are designed to minimize selection biases and confounding by indication

    Implications of using whole genome sequencing to test unselected populations for high risk breast cancer genes: a modelling study.

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    BACKGROUND: The decision to test for high risk breast cancer gene mutations is traditionally based on risk scores derived from age, family and personal cancer history. Next generation sequencing technologies such as whole genome sequencing (WGS) make wider population testing more feasible. In the UK's 100,000 Genomes Project, mutations in 16 genes including BRCA1 and BRCA2 are to be actively sought regardless of clinical presentation. The implications of deploying this approach at scale for patients and clinical services are unclear. In this study we aimed to model the effect of using WGS to test an unselected UK population for high risk BRCA1 and BRCA2 gene variants to inform the debate around approaches to secondary genomic findings. METHODS: We modelled the test performance of WGS for identifying pathogenic BRCA1 and BRCA2 mutations in an unselected hypothetical population of 100,000 UK women, using published literature to derive model input parameters. We calculated analytic and clinical validity, described potential health outcomes and highlighted current areas of uncertainty. We also performed a sensitivity analysis in which we re-ran the model 100,000 times to investigate the effect of varying input parameters. RESULTS: In our models WGS was predicted to identify correctly 93 pathogenic BRCA1 mutations and 151 BRCA2 mutations in 120 and 200 women respectively, resulting in an analytic sensitivity of 75.5-77.5 %. Of 244 women with identified pathogenic mutations, we estimated that 132 (range 121-198) would develop breast cancer, so could potentially be helped by intervention. We also predicted that breast cancer would occur in 41 women (range 36-62) incorrectly identified with no pathogenic mutations and in 12,460 women without BRCA1 or BRCA2 mutations. There was considerable uncertainty about the penetrance of mutations in people without a family history of disease and the appropriate threshold of absolute disease risk for clinical action, which impacts on judgements about the clinical utility of intervention. CONCLUSIONS: This simple model demonstrates the need for robust processes to support the testing for secondary genomic findings in unselected populations that acknowledge levels of uncertainty about the clinical validity and clinical utility of testing positive for a cancer risk gene

    Laboratory-confirmed respiratory infections as triggers for acute myocardial infarction and stroke: a self-controlled case series analysis of national linked datasets from Scotland

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    While acute respiratory tract infections can trigger cardiovascular events, the differential effect of specific organisms is unknown. This is important to guide vaccine policy.Using national infection surveillance data linked to the Scottish Morbidity Record, we identified adults with a first myocardial infarction or stroke from January 1, 2004 to December 31, 2014 and a record of laboratory-confirmed respiratory infection during this period. Using self-controlled case series analysis, we generated age- and season-adjusted incidence ratios (IRs) for myocardial infarction (n=1227) or stroke (n=762) after infections compared with baseline time.We found substantially increased myocardial infarction rates in the week after Streptococcus pneumoniae and influenza virus infection: adjusted IRs for days 1-3 were 5.98 (95% CI 2.47-14.4) and 9.80 (95% CI 2.37-40.5), respectively. Rates of stroke after infection were similarly high and remained elevated to 28 days: day 1-3 adjusted IRs 12.3 (95% CI 5.48-27.7) and 7.82 (95% CI 1.07-56.9) for S. pneumoniae and influenza virus, respectively. Although other respiratory viruses were associated with raised point estimates for both outcomes, only the day 4-7 estimate for stroke reached statistical significance.We showed a marked cardiovascular triggering effect of S. pneumoniae and influenza virus, which highlights the need for adequate pneumococcal and influenza vaccine uptake. Further research is needed into vascular effects of noninfluenza respiratory viruses

    Investigating the effects of population density of residence and rural/urban classification on rate of influenza-like illness symptoms in England and Wales.

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    BACKGROUND: Better understanding of risk factors for influenza could help improve seasonal and pandemic planning. There is a dearth of literature on area-level risk factors such as population density and rural/urban living. METHODS: We used data from Flusurvey, an online community-based cohort that records influenza events. The study outcome was symptoms of influenza-like illness (ILI). Multivariable Poisson regression analysis was used to explore associations of both population density and rural/urban status with rate of ILI symptoms and whether these effects differed by vaccination status. RESULTS: Of the 6177 study participants, the median age was 45 (IQR 32-57), 65.73% were female, and 66% reported at least one episode of ILI symptoms between 2011 and 2016. We found no evidence to suggest that the rate of ILI symptoms was higher in the medium [RR 1.02 (95% CI 0.95-1.09)] or high [RR 1.02 (95% CI 0.96-1.09)] population density group versus the low population density group. This was the same for the effect of urban living [RR 0.96 (95% CI 0.90-1.03)] versus rural living on symptom rate. There was weak evidence to suggest that the ILI symptom rate was lower in urban areas compared with rural areas among unvaccinated individuals only [RR 0.90 (95% CI 0.83-0.99)], whereas no difference was seen among vaccinated individuals [1.04 (95% CI 0.94-1.16)]. CONCLUSIONS: Although neither population density nor rural/urban status was associated with ILI symptom rate in this community cohort, future research that incorporates activity and contact patterns will help to elucidate this relationship further
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