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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.

Aim: To investigate whether there is a bidirectional longitudinal association of depression with HbA1c. \ud \ud \ud Methods: We conducted a systematic literature search in PubMed, PsycINFO, CINAHL and EMBASE for observational, longitudinal studies published from January 2000 to September 2020, assessing the association between depression and HbA in adults. We assessed study quality with the Newcastle-Ottawa-Scale. Pooled effect estimates were reported as partial correlation coefficients (rp) or odds ratios (OR). \ud \ud \ud Results: We retrieved 1,642 studies; 26 studies were included in the systematic review and eleven in the meta-analysis. Most studies (16/26) focused on type 2 diabetes. Study quality was rated as good (n = 19), fair (n = 2) and poor (n = 5). Of the meta-analysed studies, six investigated the longitudinal association between self-reported depressive symptoms and HbA1c and five the reverse longitudinal association, with a combined sample size of n = 48,793 and a mean follow-up of 2 years. Higher levels of baseline depressive symptoms were associated with subsequent higher levels of HbA1c (partial r = 0.07; [95% CI 0.03, 0.12]; I238%). Higher baseline HbA1c values were also associated with 18% increased risk of (probable) depression (OR = 1.18; [95% CI 1.12,1.25]; I20.0%).\ud \ud \ud Conclusions: Our findings support a bidirectional longitudinal association between depressive symptoms and HbA1c. However, the observed effect sizes were small and future research in large-scale longitudinal studies is needed to confirm this association. Future studies should investigate the role of type of diabetes and depression, diabetes distress and diabetes self-management behaviours. Our results may have clinical implications, as depressive symptoms and HbA1c levels could be targeted concurrently in the prevention and treatment of diabetes and depression.\ud \ud \ud Registration: PROSPERO ID CRD42019147551.

BACKGROUND: Bacterial infections may be associated with dementia, but the temporality of any relationship remains unclear. OBJECTIVES: To summarize existing literature on the association between common bacterial infections and the risk of dementia and cognitive decline in longitudinal studies. METHODS: We performed a comprehensive search of 10 databases of published and grey literature from inception to 18 March 2019 using search terms for common bacterial infections, dementia, cognitive decline, and longitudinal study designs. Two reviewers independently performed the study selection, data extraction, risk of bias and overall quality assessment. Data were summarized through a narrative synthesis as high heterogeneity precluded a meta-analysis. RESULTS: We identified 3,488 studies. 9 met the eligibility criteria; 6 were conducted in the United States and 3 in Taiwan. 7 studies reported on dementia and 2 investigated cognitive decline. Multiple infections were assessed in two studies. All studies found sepsis (n = 6), pneumonia (n = 3), urinary tract infection (n = 1), and cellulitis (n = 1) increased dementia risk (HR 1.10; 95% CI 1.02-1.19) to (OR 2.60; 95% CI 1.84-3.66). The range of effect estimates was similar when limited to three studies with no domains at high risk of bias. However, the overall quality of evidence was rated very low. Studies on cognitive decline found no association with infection but had low power. CONCLUSION: Our review suggests common bacterial infections may be associated with an increased risk of subsequent dementia, after adjustment for multiple confounders, but further high-quality, large-scale longitudinal studies, across different healthcare settings, are recommended to further explore this association.

Aims/hypothesis Depression is twice as common in individuals with type 2 diabetes as in the general population. However, it remains unclear whether hyperglycaemia and insulin resistance are directly involved in the aetiology of depression. Therefore, we investigated the association of markers of hyperglycaemia and insulin resistance, measured as continuous variables, with incident depressive symptoms over 4 years of follow-up. Methods We used data from the longitudinal population-based Maastricht Study (n = 2848; mean age 59.9 ± 8.1 years, 48.8% women, 265 incident depression cases, 10,932 person-years of follow-up). We assessed hyperglycaemia by fasting and 2 h post-load OGTT glucose levels, HbA1c and skin autofluorescence (reflecting AGEs) at baseline. We used the Matsuda insulin sensitivity index and HOMA-IR to calculate insulin resistance at baseline. Depressive symptoms (nine-item Patient Health Questionnaire score ≥10) were assessed at baseline and annually over 4 years. We used Cox regression analyses, and adjusted for demographic, cardiovascular and lifestyle risk factors. Results Fasting plasma glucose, 2 h post-load glucose and HbA1c levels were associated with an increased risk for incident depressive symptoms after full adjustment (HR 1.20 [95% CI 1.08, 1.33]; HR 1.25 [1.08, 1.44]; and HR 1.22 [1.09, 1.37] per SD, respectively), while skin autofluorescence, insulin sensitivity index and HOMA-IR were not (HR 0.99 [0.86, 1.13]; HR 1.02 [0.85, 1.25]; and HR 0.93 [0.81, 1.08], per SD, respectively). Conclusions/interpretation The observed temporal association between hyperglycaemia and incident depressive symptoms in this study supports the presence of a mechanistic link between hyperglycaemia and the development of depressive symptoms.

To investigate whether there is a bidirectional longitudinal association of depression with HbAWe conducted a systematic literature search in PubMed, PsycINFO, CINAHL and EMBASE for observational, longitudinal studies published from January 2000 to September 2020, assessing the association between depression and HbAWe retrieved 1642 studies; 26 studies were included in the systematic review and eleven in the meta-analysis. Most studies (16/26) focused on type 2 diabetes. Study quality was rated as good (n = 19), fair (n = 2) and poor (n = 5). Of the meta-analysed studies, six investigated the longitudinal association between self-reported depressive symptoms and HbAOur findings support a bidirectional longitudinal association between depressive symptoms and HbAPROSPERO ID CRD42019147551.

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.

IntroductionCardiovascular 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 analysisWe 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 disseminationThis is a systematic review, so it does not require ethical approval. Our results will be submitted for peer-review publication.PROSPERO registration numberCRD42019123898

Introduction The global burden of dementia is rising, emphasising the urgent need to develop effective approaches to risk reduction. Recent evidence suggests that common bacterial infections may increase the risk of dementia, however the magnitude and timing of the association as well as the patient groups affected remains unclear. We will review existing evidence of the association between common bacterial infections and incident cognitive decline or dementia. Methods and analysis We will conduct a comprehensive search of published and grey literature from inception to 18 March 2019. The following electronic databases will be searched; MEDLINE, EMBASE, Global health, PsycINFO, Web of Science, Scopus, Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature, Open Grey and the British Library of Electronic Theses databases. There will be no restrictions on the date, language or geographical location of the studies. We will include longitudinal studies with a common clinically symptomatic bacterial infection as an exposure and incident cognitive decline or dementia as an outcome. Study selection, data extraction and risk of bias will be performed independently by two researchers. We will assess the risk of bias using the Cochrane collaboration approach. The overall quality of the studies will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations criteria. We will explore the heterogeneity of relevant studies and, if feasible, a meta-analysis will be performed, otherwise we will present a narrative synthesis. We will group the results by exposure and outcome definitions and differences will be described by subgroups and outcomes. Ethics and dissemination Ethical approval will not be required as this is a systematic review of existing research in the public domain. Results will be disseminated in a peer-reviewed journal and presented at national and international meetings and conferences. PROSPERO registration number CRD42018119294.