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

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

Viral load and antibody boosting following herpes zoster diagnosis

BACKGROUND: Acute varicella zoster virus (VZV) replication in shingles is accompanied by VZV antibody boosting. It is unclear whether persisting virus shedding affects antibody levels. OBJECTIVES: To investigate the relationship between VZV viral load and antibody titres in shingles patients during six months following diagnosis and assess whether VZV antibody titre could discriminate patients with recent shingles from healthy population controls. STUDY DESIGN: A prospective study of 63 patients with active zoster. Blood samples were collected at baseline, one, three and six months to measure VZV DNA and IgG antibody titre. We compared VZV antibody titres of zoster patients and 441 controls. RESULTS: In acute zoster, viral load was highest at baseline and declined gradually over the following six months. Mean antibody titres rose fourfold, peaking at one month and remaining above baseline levels throughout the study. Antibody levels at one, three and six months after zoster were moderately correlated with baseline but not subsequent viral load. Regarding use of antibody titres to identify recent shingles, to achieve 80% sensitivity, specificity would be 23.4%, 67.7%, 64.8% and 52.6%, at baseline, visit 2, 3 and 4 respectively, whilst to achieve 80% specificity, sensitivity would be 28.3%, 66.1%, 52.6%, 38.6%, at baseline, visit 2, 3 and 4 respectively. CONCLUSIONS: Clinical VZV reactivation boosted VZV antibody levels and the level of boosting was dependent upon baseline viral replication. While antibody titres could discriminate patients with shingles 1-6 months earlier from blood donor controls, there was a large trade-off between sensitivity and specificity

Investigating obesity as a risk factor for influenza-like illness during the 2009 H1N1 influenza pandemic using the Health Survey for England.

BACKGROUND: Following the 2009 H1N1 influenza pandemic, obesity was shown to be associated with severe influenza outcomes. It remains unclear whether obesity was a risk factor for milder influenza-like illness (ILI). OBJECTIVES: To determine whether obesity was associated with an increased risk of self-reported ILI during the 2009 H1N1 influenza pandemic using Health Survey for England (HSE) 2010 cross-sectional data. METHODS: This study used HSE data collected from English households between January and December 2010. Weight and height measurements were taken by trained fieldworkers to determine obesity. ILI was defined as a positive response to the question "Have you had a flu-like illness where you felt feverish and had a cough or sore throat?" with illness occurring between May and December 2009. Multivariable logistic regression was used to evaluate the association between obesity and ILI. RESULTS: The study comprised 8407 participants (6984 adults, 1436 children), among whom 24.7% (95% CI: 23.6-25.9) were classified as obese. Of obese participants, 12.8% (95% CI: 11.1-14.8) reported ILI compared to 11.8% (95% CI: 10.8-12.8) of non-obese participants. The adjusted OR for ILI associated with obesity was 1.16 (95% CI: 0.98-1.38, P=.093). For adults and children, the adjusted ORs were 1.16 (95% CI: 0.97-1.38, P=.101) and 1.26 (95% CI: 0.72-2.21, P=.422), respectively. CONCLUSION: Household survey data showed no evidence that obesity was associated with an increase in self-reported ILI during the 2009 H1N1 influenza pandemic in England. Further studies using active prospective ILI surveillance combined with laboratory reporting would reduce bias and improve accuracy of outcome measurements

Validity of Acute Cardiovascular Outcome Diagnoses Recorded in European Electronic Health Records: A Systematic Review.

Background: Electronic health records are widely used in cardiovascular disease research. We appraised the validity of stroke, acute coronary syndrome and heart failure diagnoses in studies conducted using European electronic health records. Methods: Using a prespecified strategy, we systematically searched seven databases from dates of inception to April 2019. Two reviewers independently completed study selection, followed by partial parallel data extraction and risk of bias assessment. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value estimates were narratively synthesized and heterogeneity between sensitivity and PPV estimates were assessed using I2. Results: We identified 81 studies, of which 20 validated heart failure diagnoses, 31 validated acute coronary syndrome diagnoses with 29 specifically recording estimates for myocardial infarction, and 41 validated stroke diagnoses. Few studies reported specificity or negative predictive value estimates. Sensitivity was ≤66% in all but one heart failure study, ≥80% for 91% of myocardial infarction studies, and ≥70% for 73% of stroke studies. PPV was ≥80% in 74% of heart failure, 88% of myocardial infarction, and 70% of stroke studies. PPV by stroke subtype was variable, at ≥80% for 80% of ischaemic stroke but only 44% of haemorrhagic stroke. There was considerable heterogeneity (I2 >75%) between sensitivity and PPV estimates for all diagnoses. Conclusion: Overall, European electronic health record stroke, acute coronary syndrome and heart failure diagnoses are accurate for use in research, although validity estimates for heart failure and individual stroke subtypes were lower. Where possible, researchers should validate data before use or carefully interpret the results of previous validation studies for their own study purposes

Association Between Common Infections and Incident Post-Stroke Dementia:A Cohort Study Using the Clinical Practice Research Datalink

PURPOSE: To investigate the association between common infections and post-stroke dementia in a UK population-based cohort. MATERIALS AND METHODS: A total of 60,392 stroke survivors (51.2% male, median age 74.3 years, IQR 63.9-82.4 years) were identified using primary care records from the Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics (HES) with no history of dementia. Primary exposure was any GP-recorded infection (lower respiratory tract infection (LRTI), urinary tract infection (UTI) requiring antibiotics, skin and soft tissue infection requiring antibiotics) occurring after stroke. The primary outcome was incident all-cause dementia recorded in primary care records. In sensitivity analyses, we restricted to individuals with linked hospital records and expanded definitions to include ICD-10 coded hospital admissions. We used multivariable Cox regression to investigate the association between common infections and dementia occurring from 3 months to 5 years after stroke. RESULTS: Of 60,392 stroke survivors, 20,969 (34.7%) experienced at least one infection and overall 4512 (7.5%) developed dementia during follow-up. Early dementia (3 months to 1-year post-stroke) risk was increased in those with at least one GP-recorded infection (HR 1.44, 95% CI 1.21-1.71), with stronger associations when hospitalised infections were included (HR 1.84, 95% CI 1.58-2.14). Late dementia (1-5 years) was only associated with hospitalised, but not with GP-recorded, infections. CONCLUSION: There was evidence of an association between common infections and post-stroke dementia, strongest in the 3-12 months following stroke. Better understanding of this relationship could help inform knowledge of pathways to dementia post-stroke and targeting of preventive interventions

Validity of acute cardiovascular outcome diagnoses in European electronic health records: a systematic review protocol

INTRODUCTION: Cardiovascular diseases (CVDs) are among the leading causes of death globally. Electronic health records (EHRs) provide a rich data source for research on CVD risk factors, treatments and outcomes. Researchers must be confident in the validity of diagnoses in EHRs, particularly when diagnosis definitions and use of EHRs change over time. Our systematic review provides an up-to-date appraisal of the validity of stroke, acute coronary syndrome (ACS) and heart failure (HF) diagnoses in European primary and secondary care EHRs. METHODS AND ANALYSIS: We will systematically review the published and grey literature to identify studies validating diagnoses of stroke, ACS and HF in European EHRs. MEDLINE, EMBASE, SCOPUS, Web of Science, Cochrane Library, OpenGrey and EThOS will be searched from the dates of inception to April 2019. A prespecified search strategy of subject headings and free-text terms in the title and abstract will be used. Two reviewers will independently screen titles and abstracts to identify eligible studies, followed by full-text review. We require studies to compare clinical codes with a suitable reference standard. Additionally, at least one validation measure (sensitivity, specificity, positive predictive value or negative predictive value) or raw data, for the calculation of a validation measure, is necessary. We will then extract data from the eligible studies using standardised tables and assess risk of bias in individual studies using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Data will be synthesised into a narrative format and heterogeneity assessed. Meta-analysis will be considered when a sufficient number of homogeneous studies are available. The overall quality of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation tool. ETHICS AND DISSEMINATION: This is a systematic review, so it does not require ethical approval. Our results will be submitted for peer-review publication. PROSPERO REGISTRATION NUMBER: CRD42019123898

Influenza-like illness in acute myocardial infarction patients during the winter wave of the influenza A H1N1 pandemic in London: a case-control study.

OBJECTIVE: To investigate recent respiratory and influenza-like illnesses (ILIs) in acute myocardial infarction patients compared with patients hospitalised for acute non-vascular surgical conditions during the second wave of the 2009 influenza A H1N1 pandemic. DESIGN: Case-control study. SETTING: Coronary care unit, acute cardiology and acute surgical admission wards in a major teaching hospital in London, UK. PARTICIPANTS: 134 participants (70 cases and 64 controls) aged ≥40 years hospitalised for acute myocardial infarction and acute surgical conditions between 21 September 2009 and 28 February 2010, frequency-matched for gender, 5-year age-band and admission week. PRIMARY EXPOSURE: ILI (defined as feeling feverish with either a cough or sore throat) within the last month. SECONDARY EXPOSURES: Acute respiratory illness within the last month not meeting ILI criteria; nasopharyngeal and throat swab positive for influenza virus. RESULTS: 29 of 134 (21.6%) participants reported respiratory illness within the last month, of whom 13 (9.7%) had illnesses meeting ILI criteria. The most frequently reported category for timing of respiratory symptom onset was 8-14 days before admission (31% of illnesses). Cases were more likely than controls to report ILI-adjusted OR 3.17 (95% CI 0.61 to 16.47)-as well as other key respiratory symptoms, and were less likely to have received influenza vaccination-adjusted OR 0.46 (95% CI 0.19 to 1.12)-although the differences were not statistically significant. No swabs were positive for influenza virus. CONCLUSIONS: Point estimates suggested that recent ILI was more common in patients hospitalised with acute myocardial infarction than with acute surgical conditions during the second wave of the influenza A H1N1 pandemic, and influenza vaccination was associated with cardioprotection, although the findings were not statistically significant. The study was underpowered, partly because the age groups typically affected by acute myocardial infarction had low rates of infection with the pandemic influenza strain compared with seasonal influenza

Herpes simplex virus and rates of cognitive decline or whole brain atrophy in the Dominantly Inherited Alzheimer Network

OBJECTIVE: To investigate whether herpes simplex virus type 1 (HSV-1) infection was associated with rates of cognitive decline or whole brain atrophy among individuals from the Dominantly Inherited Alzheimer Network (DIAN). METHODS: Among two subsets of the DIAN cohort (age range 19.6-66.6 years; median follow-up 3.0 years) we examined (i) rate of cognitive decline (N = 164) using change in mini-mental state examination (MMSE) score, (ii) rate of whole brain atrophy (N = 149), derived from serial MR imaging, calculated using the boundary shift integral (BSI) method. HSV-1 antibodies were assayed in baseline sera collected from 2009-2015. Linear mixed-effects models were used to compare outcomes by HSV-1 seropositivity and high HSV-1 IgG titres/IgM status. RESULTS: There was no association between baseline HSV-1 seropositivity and rates of cognitive decline or whole brain atrophy. Having high HSV-1 IgG titres/IgM was associated with a slightly greater decline in MMSE points per year (difference in slope - 0.365, 95% CI: -0.958 to -0.072), but not with rate of whole brain atrophy. Symptomatic mutation carriers declined fastest on both MMSE and BSI measures, however, this was not influenced by HSV-1. Among asymptomatic mutation carriers, rates of decline on MMSE and BSI were slightly greater among those who were HSV-1 seronegative. Among mutation-negative individuals, no differences were seen by HSV-1. Stratifying by APOE4 status yielded inconsistent results. INTERPRETATION: We found no evidence for a major role of HSV-1, measured by serum antibodies, in cognitive decline or whole brain atrophy among individuals at high risk of early-onset AD