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Coagulopathy is a key feature of COVID-19 and D-dimer has been reported as a predictor of severity. However, because D-dimer test results vary considerably among assays, resolving harmonization issues is fundamental to translate findings into clinical practice. In this retrospective multicenter study (BIOCOVID study), we aimed to analyze the value of harmonized D-dimer levels upon admission for the prediction of in-hospital mortality in COVID-19 patients. All-cause in-hospital mortality was defined as endpoint. For harmonization of D-dimer levels, we designed a model based on the transformation of method-specific regression lines to a reference regression line. The ability of D-dimer for prediction of death was explored by receiver operating characteristic curves analysis and the association with the endpoint by Cox regression analysis. Study population included 2663 patients. In-hospital mortality rate was 14.3%. Harmonized D-dimer upon admission yielded an area under the curve of 0.66, with an optimal cut-off value of 0.945 mg/L FEU. Patients with harmonized D-dimer >= 0.945 mg/L FEU had a higher mortality rate (22.4% vs. 9.2%; p < 0.001). D-dimer was an independent predictor of in-hospital mortality, with an adjusted hazard ratio of 1.709. This is the first study in which a harmonization approach was performed to assure comparability of D-dimer levels measured by different assays. Elevated D-dimer levels upon admission were associated with a greater risk of in-hospital mortality among COVID-19 patients, but had limited performance as prognostic test.

BACKGROUND: Myocardial injury is a common finding in COVID-19 strongly associated with severity. We analysed the prevalence and prognostic utility of myocardial injury, characterized by elevated cardiac troponin, in a large population of COVID-19 patients, and further evaluated separately the role of troponin T and I. METHODS: This is a multicentre, retrospective observational study enrolling patients with laboratory-confirmed COVID-19 who were hospitalized in 32 Spanish hospitals. Elevated troponin levels were defined as values above the sex-specific 99th percentile upper reference limit, as recommended by international guidelines. Thirty-day mortality was defined as endpoint. RESULTS: A total of 1280 COVID-19 patients were included in this study, of whom 187 (14.6%) died during the hospitalization. Using a nonspecific sex cut-off, elevated troponin levels were found in 344 patients (26.9%), increasing to 384 (30.0%) when a sex-specific cut-off was used. This prevalence was significantly higher (42.9% vs 21.9%; P

Identification of predictors for severe disease progression is key for risk stratification in COVID-19 patients. We aimed to describe the main characteristics and identify the early predictors for severe outcomes among hospitalized patients with COVID-19 in Spain. This was an observational, retrospective cohort study (BIOCOVID-Spain study) including COVID-19 patients admitted to 32 Spanish hospitals. Demographics, comorbidities and laboratory tests were collected. Outcome was in-hospital mortality. For analysis, laboratory tests values were previously adjusted to assure the comparability of results among participants. Cox regression was performed to identify predictors. Study population included 2873 hospitalized COVID-19 patients. Nine variables were independent predictors for in-hospital mortality, including creatinine (Hazard ratio [HR]:1.327; 95% Confidence Interval [CI]: 1.040-1.695, p = .023), troponin (HR: 2.150; 95% CI: 1.155-4.001; p = .016), platelet count (HR: 0.994; 95% CI: 0.989-0.998; p = .004) and C-reactive protein (HR: 1.037; 95% CI: 1.006-1.068; p = .019). This is the first multicenter study in which an effort was carried out to adjust the results of laboratory tests measured with different methodologies to guarantee their comparability. We reported a comprehensive information about characteristics in a large cohort of hospitalized COVID-19 patients, focusing on the analytical features. Our findings may help to identify patients early at a higher risk for an adverse outcome.

Statin therapy response is highly variable. Variants of lipid metabolism genes and statin pharmacokinetic modulators could play a role, however, the impact of most of these variants remains unconfirmed. A prospective and multicenter study included 252 patients was carried out in order to assess, according to achievement of LDL-C or non-HDL-C therapeutic targets and quantitative changes in lipid profiles, the impact of CETP, ABCA1, CYP2D6, and CYP2C9 gene candidate variants on the simvastatin, atorvastatin, and rosuvastatin response. Patients carrier ABCA1 rs2230806 and CYP2D6*3 variants are less likely to achieve therapeutic lipid targets (p = 0.020, OR = 0.59 [0.37, 0.93]; p = 0.040, OR = 0.23 [0.05, 0.93], respectively). Among CETP variants, rs708272 was linked to a 10.56% smaller reduction in LDL-C with rosuvastatin (95% CI = [1.27, 19.86] %; p = 0.028). In contrast, carriers of rs5882 had a 13.33% greater reduction in LDL-C (95% CI = [25.38, 1.28]; p = 0.032). If these findings are confirmed, ABCA1, CYP2D6, and CETP genotyping could be used to help predict which statin and dosage is appropriate in order to improve personalized medicine.

INTRODUCTION Most of the cost-effectiveness analyses are based on estimations to make decisions on the future implementation of a test. However, the model should be verified with real data to prove that previous estimations have been successfully fulfilled. OBJECTIVE To study the economic impact of the systematic HLA-B*57:01 genotyping in preventing hypersensitivity reactions (HSRs) in the patient population of a tertiary-care hospital treated with abacavir (ABC) using retrospective data of 5 years of experience. METHODS A retrospective study was carried out with two cohorts including 780 and 473 patients before and after the implementation of the systematic HLA-B*57:01 genotyping before ABC treatment. Cost-effectiveness analysis was carried out by the parameter 'cost per HSR avoided'. The clinical utility of the test was verified by evaluating the differences in HSR incidence between both cohorts. Finally, a sensitivity analysis including all variables was carried out. RESULTS In the population studied, systematic genotyping represents an additional cost of O306 per HSR avoided. In the sensitivity analysis, pharmacological therapy cost is the major influencing factor found in the estimation of the 'cost per HSR avoided'. In terms of clinical utility, the incidence ratio was 0.040 (95% confidence interval 0.0009-0.2399) and statistically significant differences were found between both groups (P=1.40×10). CONCLUSION Retrospective data from 5 years of experience have confirmed the cost-effectiveness of the systematic genotyping in candidate patients for ABC therapy, and have shown that cost-effectiveness is a dynamic parameter closely linked to allele prevalence and pharmacological therapy costs.

Background The APOE Christchurch (APOECh) is a rare variant (c.543C>A) in codon 154. It was first described in an E2 patient with type III dyslipidemia, and thus initially called E2Ch. Its prevalence and the lipid profile of carriers remain unclear. Methods E2, E3, and E4 screening for the APOE gene was performed by PCR-RFLP. The rare APOECh variant was firstly found after detecting an unexpected 109 base-pair band in the high-resolution agarose gel electrophoresis leading to a genotype misinterpretation: the presence of APOECh alters the restriction-bands pattern. To confirm the Ch variant, a second PCR-RFLP method was specifically designed to detect this variant and Sanger sequencing was also performed for all positive samples. Results We identified 12 unrelated subjects for the APOECh among a cohort of 2,560 patients: nine E3/E3Ch, two E3Ch/E4, and one E2/E3Ch or E2Ch/E3. The frequency of the variant is 0.4% in our study population, which represents the highest percentage published so far. If there is a 109 bp band, it is easy to recognize the presence of the variant. However, in APOE routine genotyping, an E4Ch allele is indistinguishable from a standard E3. Therefore, E4Ch alleles might be underrepresented in the results. Conclusion We recommend APOE exon 4 sequencing to unequivocally detect the common three variants E2, E3, and E4 and the rare variants as well, to find out the real role they play in atherosclerosis and to estimate its real frequency which is nowadays unclear, in part by the small number of cases identified.