Validity of asthma diagnoses in the Danish National Registry of Patients, including an assessment of impact of misclassification on risk estimates in an actual dataset

Annette Østergaard Jensen1, Gunnar Lauge Nielsen2, Vera Ehrenstein11Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Medicine, Himmerland Hospital, Farsø, DenmarkObjective: Asthma diagnoses recorded in the Danish National Registry of Patients (DNRP) are a misclassified measure of the actual asthma status. We quantified this misclassification and examined its impact on the results of an epidemiologic study on asthma.Study design and setting: We validated the DNRP asthma diagnoses against records of asthma diagnosed at medical examinations conducted during mandatory conscription evaluation. We had data on 22,177 male conscripts who were born from January 1st, 1977 to December 31st, 1983, in a conscription district in northern Denmark. We obtained asthma diagnoses recorded among the conscripts in the DNRP from January 1st, 1977 through December 31st, 2003. We estimated sensitivity, specificity, and positive predictive value (PPV) of the DNRP asthma diagnoses. We then conducted sensitivity analysis to quantify the impact of nondifferential misclassification on the rate ratios measuring the association between asthma and risks of different skin cancers.Results: The sensitivity of the DNRP for detecting an asthma diagnosis was 0.44 (95% confidence interval [CI]: 0.42–0.47), the specificity was 0.98 (95% CI: 0.98–0.99) and the PPV was 0.65 (95% CI: 0.62–0.68). Both direct and inverse associations between asthma and the different types of skin cancers became more pronounced after correcting for the misclassification.Conclusion: The DNRP registered asthma diagnosis may be used to measure asthma status in epidemiologic studies seeking to estimate relative effects of asthma. Even at low values of DNRP sensitivity of asthma diagnoses were not sufficient to nullify observed relative associations in an actual dataset. The specificity of DNRP asthma diagnosis is high.Keywords: asthma, validity, registry data, epidemiolog

Temporal changes in cardiovascular disease and infections in dialysis across a 22-year period:a nationwide study

Abstract Background Cardiovascular diseases (CVD) and infections are recognized as serious complications in patients with end stage kidney disease. However, little is known about the change over time in incidence of these complications. This study aimed to investigate temporal changes in CVD and infective diseases across more than two decades in chronic dialysis patients. Methods All patients that initiated peritoneal dialysis (PD) or hemodialysis (HD) between 1996 and 2017 were identified and followed until outcome (CVD, pneumonia, infective endocarditis (IE) or sepsis), recovery of kidney function, end of dialysis treatment, death or end of study (December 31st, 2017). The calendar time was divided into 5 periods with period 1 (1996–2000) being the reference period. Adjusted rate ratios were assessed using Poisson regression. Results In 4285 patients with PD (63.7% males) the median age increased across the calendar periods from 65 [57–73] in 1996–2000 to 69 [55–76] in 2014–2017, (p <  0.0001). In 9952 patients with HD (69.2% males), the overall median age was 71 [61–78] without any changes over time. Among PD, an overall non-significant decreasing trend in rate ratios (RR) of CVD was found, (p = 0,071). RR of pneumonia increased significantly throughout the calendar with an almost two-fold increase of the RR in 2014–2017 (RR 1.71; 95% CI 1.46–2.0), (p <  0.001), as compared to the reference period. The RR of IE decreased significantly until 2009 (RR 0.43; 95% CI 0.21–0.87), followed by a return to the reference level in 2010–2013 (RR 0.87; 95% CI 0.47–1.60 and 2014–2017 (RR 1.1; 95% CI 0.59–2.04). A highly significant (p <  0.001) increase in sepsis was revealed across the calendar periods with an almost 5-fold increase in 2014–2017 (RR 4.69 95% CI 3.69–5.96). In HD, the RR of CVD decreased significantly (p <  0.001) from 2006 to 2017 (RR 0.85; 95% CI 0.79–0.92). Compared to the reference period, the RR for pneumonia was high during all calendar periods (p <  0.05). The RR of IE was initially unchanged (p = 0.4) but increased in 2010–2013 (RR 2.02; 95% CI 1.43–2.85) and 2014–2017 (RR 3.39; 95% CI 2.42–4.75). No significant changes in sepsis were seen. Conclusion Across the two last decades the RR of CVD has shown a decreasing trend in HD and PD patients, while RR of pneumonia increased significantly, both in PD and in HD. Temporal trends of IE in HD, and particularly of sepsis in PD were upwards across the last decades

Proposal for the use of echocardiography in bloodstream infections due to different streptococcal species

BACKGROUND: Infective endocarditis (IE) is diagnosed in 7–8% of streptococcal bloodstream infections (BSIs), yet it is unclear when to perform transthoracic (TTE) and transoesophageal echocardiography (TOE) according to different streptococcal species. The aim of this sub-study was to propose a flowchart for the use of echocardiography in streptococcal BSIs. METHODS: In a population-based setup, we investigated all patients admitted with streptococcal BSIs and crosslinked data with nationwide registries to identify comorbidities and concomitant hospitalization with IE. Streptococcal species were divided in four groups based on the crude risk of being diagnosed with IE (low-risk  30%). Based on number of positive blood culture (BC) bottles and IE risk factors (prosthetic valve, previous IE, native valve disease, and cardiac device), we further stratified cases according to probability of concomitant IE diagnosis to create a flowchart suggesting TTE plus TOE (IE > 10%), TTE (IE 3–10%), or “wait & see” (IE < 3%). RESULTS: We included 6393 cases with streptococcal BSIs (mean age 68.1 years [SD 16.2], 52.8% men). BSIs with low-risk streptococci (S. pneumoniae, S. pyogenes, S. intermedius) are not initially recommended echocardiography, unless they have ≥3 positive BC bottles and an IE risk factor. Moderate-risk streptococci (S. agalactiae, S. anginosus, S. constellatus, S. dysgalactiae, S. salivarius, S. thermophilus) are guided to “wait & see” strategy if they neither have a risk factor nor ≥3 positive BC bottles, while a TTE is recommended if they have either ≥3 positive BC bottles or a risk factor. Further, a TTE and TOE are recommended if they present with both. High-risk streptococci (S. mitis/oralis, S. parasanguinis, G. adiacens) are directed to a TTE if they neither have a risk factor nor ≥3 positive BC bottles, but to TTE and TOE if they have either ≥3 positive BC bottles or a risk factor. Very high-risk streptococci (S. gordonii, S. gallolyticus, S. mutans, S. sanguinis) are guided directly to TTE and TOE due to a high baseline IE prevalence. CONCLUSION: In addition to the clinical picture, this flowchart based on streptococcal species, number of positive blood culture bottles, and risk factors, can help guide the use of echocardiography in streptococcal bloodstream infections. Since echocardiography results are not available the findings should be confirmed prospectively with the use of systematic echocardiography. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-021-06391-2

Temporal Changes, Patient Characteristics, and Mortality, According to Microbiological Cause of Infective Endocarditis:A Nationwide Study

BACKGROUND: Monitoring of microbiological cause of infective endocarditis (IE) remains key in the understanding of IE; however, data from large, unselected cohorts are sparse. We aimed to examine temporal changes, patient characteristics, and in‐hospital and long‐term mortality, according to microbiological cause in patients with IE from 2010 to 2017. METHODS AND RESULTS: Linking Danish nationwide registries, we identified all patients with first‐time IE. In‐hospital and long‐term mortality rates were assessed according to microbiological cause and compared using multivariable adjusted logistic regression analysis and Cox proportional hazard analysis, respectively. A total of 4123 patients were included. Staphylococcus aureus was the most frequent cause (28.1%), followed by Streptococcus species (26.0%), Enterococcus species (15.5%), coagulase‐negative staphylococci (6.2%), and “other microbiological causes” (5.3%). Blood culture–negative IE was registered in 18.9%. The proportion of blood culture–negative IE declined during the study period, whereas no significant changes were seen for any microbiological cause. Patients with Enterococcus species were older and more often had a prosthetic heart valve compared with other causes. For Streptococcus species IE, in‐hospital and long‐term mortality (median follow‐up, 2.3 years) were 11.1% and 58.5%, respectively. Compared with Streptococcus species IE, the following causes were associated with a higher in‐hospital mortality: S aureus IE (odds ratio [OR], 3.48 [95% CI, 2.74–4.42]), Enterococcus species IE (OR, 1.48 [95% CI, 1.11–1.97]), coagulase‐negative staphylococci IE (OR, 1.79 [95% CI, 1.21–2.65]), “other microbiological cause” (OR, 1.47 [95% CI, 0.95–2.27]), and blood culture–negative IE (OR, 1.99 [95% CI, 1.52–2.61]); and the following causes were associated with higher mortality following discharge (median follow‐up, 2.9 years): S aureus IE (hazard ratio [HR], 1.39 [95% CI, 1.19–1.62]), Enterococcus species IE (HR, 1.31 [95% CI, 1.11–1.54]), coagulase‐negative staphylococci IE (HR, 1.07 [95% CI, 0.85–1.36]), “other microbiological cause” (HR, 1.45 [95% CI, 1.13–1.85]), and blood culture–negative IE (HR, 1.05 [95% CI, 0.89–1.25]). CONCLUSIONS: This nationwide study showed that S aureus was the most frequent microbiological cause of IE, followed by Streptococcus species and Enterococcus species. Patients with S aureus IE had the highest in‐hospital mortality

Ischemic Stroke Severity and Mortality in Patients With and Without Atrial Fibrillation

Background Our objective was to investigate stroke severity and subsequent rate of mortality among patients with and without atrial fibrillation (AF). Contemporary data on stroke severity and prognosis in patients with AF are lacking. Methods and Results First‐time ischemic stroke patients from the Danish Stroke Registry (January 2005–December 2016) were included in an observational study. Patients with AF were matched 1:1 by sex, age, calendar year, and CHA2DS2‐VASc score with patients without AF. Stroke severity was determined by the Scandinavian Stroke Scale (0–58 points). The rate of death was estimated by Kaplan‐Meier plots and multivariable Cox regression. Among 86 458 identified patients with stroke, 17 205 had AF. After matching, 14 662 patients with AF and 14 662 patients without AF were included (51.8% women; median age, 79.6 years [25th–75th percentile, 71.8–86.0]). More patients with AF had very severe stroke (0–14 points) than patients without AF (13.7% versus 7.9%, P<0.01). The absolute rates of 30‐day and 1‐year mortality were significantly higher for patients with AF (12.1% and 28.4%, respectively) versus patients without AF (8.7% and 21.8%, respectively). This held true in adjusted models for 30‐day mortality (hazard ratio [HR], 1.40 [95% CI, 1.30–1.51]). However, this association became nonsignificant when additionally adjusting for stroke severity (HR, 1.10 [95% CI, 1.00–1.23]). AF was associated with a higher rate of 1‐year mortality (HR, 1.39 [95% CI, 1.32–1.46]), although it was mediated by stroke severity (HR, 1.15 [95% CI, 1.09–1.23], model including stroke severity). Conclusions In a contemporary nationwide cohort of patients with ischemic stroke, patients with AF had more severe strokes and higher mortality than patients without AF. The difference in mortality was mainly driven by stroke severity