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1.
Anal Bioanal Chem ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900530

RESUMO

An analytical method using 2D high-performance liquid chromatography followed by tandem mass spectrometry for the quantification of the beta-lactam antibiotics amoxicillin, flucloxacillin, piperacillin, benzylpenicillin, the beta-lactamase inhibitors clavulanic acid, and tazobactam, as well as the macrolide antibiotic clindamycin, is presented. All analytes were measured in human plasma, while amoxicillin, clavulanic acid, flucloxacillin, and clindamycin were also analyzed in human tissue samples. Because of its high-protein binding, additionally, the free fraction of flucloxacillin was measured after ultrafiltration. As internal standards, deuterated forms of the beta-lactams were used. Sample preparation for all matrices was protein precipitation followed by online extraction on a TurboFlow MAX column, while sample separation was performed on an Accucore XL C18 column. Calibration curves were linear over 0.2-25 mg/kg for the tissue samples and 0.05-20 mg/l for the free fraction of flucloxacillin. In plasma, the calibration curves for amoxicillin and piperacillin were linear over 3.125-125 mg/l, for clavulanic acid and tazobactam over 1-40 mg/l, for benzylpenicillin 0.25-40 mg/l, and for flucloxacillin and clindamycin over 1.5-60 mg/l and 0.05-8 mg/l respectively. In plasma and plasma ultrafiltrate, inaccuracy and imprecision for any analyte were always less than 15%. In tissue, the accuracy and precision varied up to 16%, respectively, 20%, when various tissues were analyzed using a calibration in water. Graphical abstract.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31866308

RESUMO

BACKGROUND: Circadian and sleep-homeostatic mechanisms regulate timing and quality of wakefulness. To enhance wakefulness, daily consumption of caffeine in the morning and afternoon is highly common. However, the effects of such a regular intake pattern on circadian sleep-wake regulation are unknown. Thus, we investigated if daily daytime caffeine intake and caffeine withdrawal affect circadian rhythms and wake-promotion in habitual consumers. METHODS: Twenty male young volunteers participated in a randomised, double-blind, within-subject study with three conditions: i) caffeine (150 mg 3 x daily for 10 days), ii) placebo (3 x daily for 10 days) and iii) withdrawal (150 mg caffeine 3 x daily for eight days, followed by a switch to placebo for two days). Starting on day nine of treatment, salivary melatonin and cortisol, evening nap sleep as well as sleepiness and vigilance performance throughout day and night were quantified during 43 h in an in-laboratory, light and posture-controlled protocol. RESULTS: Neither the time course of melatonin (i.e. onset, amplitude or area under the curve) nor the time course of cortisol was significantly affected by caffeine or withdrawal. During withdrawal, however, volunteers reported increased sleepiness, showed more attentional lapses as well as polysomnography-derived markers of elevated sleep propensity in the late evening compared to both the placebo and caffeine condition. CONCLUSIONS: The typical pattern of caffeine intake with consumption in both the morning and afternoon hours may not necessarily result in a circadian phase shift in the evening nor lead to clear-cut benefits in alertness. The time-of-day independent effects of caffeine withdrawal on evening nap sleep, sleepiness and performance suggest an adaptation to the substance, presumably in the homeostatic aspect of sleep-wake regulation.

3.
Front Med (Lausanne) ; 6: 221, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681778

RESUMO

Background: Artemisia annua is a Chinese medicinal herb. Artemisinin-derivatives are recommended as part of a combination treatment for uncomplicated malaria. Herbal and dietary supplements (HDS) are increasingly used worldwide and HDS-induced liver injury is becoming a growing concern. Case Report: We present the first case of severe acute cholestatic hepatitis due to the intake of Artemisia annua tea as chemoprophylaxis for malaria in a patient returning from Ethiopia. The patients presented with jaundice, elevated transaminases, and parameters of cholestasis (total bilirubin 186.6 µmol/L, conjugated bilirubin 168.5 µmol/L). A liver biopsy showed a portal hepatitis with lymphocytic infiltration of the bile ducts and diffuse intra-canalicular and intra-cytoplasmic bilirubinostasis. The toxicologic analysis of the Artemisia tea revealed the ingredients arteannuin b, deoxyartemisin, campher, and scopoletin. There were no other identifiable etiologies of liver disease. The Roussel Uclaf Causality Assessment Method (RUCAM) score assessed a "probably" causal relationship. Sequencing of genes encoding for hepatic transporters for bile acid homeostasis (BSEP, MDR3, and FIC1) found no genetic variants typically associated with hereditary cholestasis syndromes. Normalization of bilirubin occurred 3 months after the onset of disease. Conclusion: The use of artemisinin-derivatives for malaria prevention is ineffective and potentially harmful and should thus be discouraged. Moreover, the case demonstrates our as yet inadequate understanding of the pathophysiology and susceptibility to HDS induced liver injury.

5.
Int J Cardiol ; 286: 104-110, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30853296

RESUMO

BACKGROUND: Relative hypochromia of erythrocytes defined as a reduced mean corpuscular hemoglobin concentration (MCHC) is a surrogate of iron deficiency. We aimed to evaluate the prevalence and prognostic impact of relative hypochromia in acute heart failure (AHF). METHODS: We prospectively characterized 1574 patients presenting with an adjudicated diagnosis of AHF to the emergency department. Relative hypochromia was defined as a MCHC ≤330 g/l and determined at presentation. The presence of AHF was adjudicated by two independent cardiologists. All-cause mortality and AHF-rehospitalization were the primary prognostic end-points. RESULTS: Overall, 455 (29%) AHF patients had relative hypochromia. Patients with relative hypochromia had higher hemodynamic cardiac stress as quantified by NT-proBNP concentrations (p < 0.001), more extensive cardiomyocyte injury as quantified by high-sensitive cardiac troponin T (hs-cTnT) concentrations (p < 0.001), and lower estimated glomerular filtration rate (eGFR; p < 0.001) as compared to AHF patients without hypochromia. Cumulative incidences for all-cause mortality and AHF-rehospitalization at 720-days were 50% and 55% in patients with relative hypochromia as compared to 33% and 39% in patients without hypochromia, respectively (both p < 0.0001). The association between relative hypochromia and increased mortality (HR 1.7, 95% CI 1.4-2-0) persisted after adjusting for anemia (HR 1.5, 95% CI 1.3-1.8), and after adjusting for hemodynamic cardiac stress (HR 1.46, 95% CI 1.21-1.76) and eGFR (HR 1.5, 95% CI 1.3-1.8, p < 0.001). CONCLUSIONS: Relative hypochromia is common and a strong and independent predictor of increased mortality in AHF. Given the direct link to diagnostic (endoscopy) and therapeutic interventions to treat functional iron deficiency, relative hypochromia deserves increased attention as an inexpensive and universally available biomarker.

6.
Int J Cardiol ; 275: 20-25, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30340850

RESUMO

BACKGROUND: Inflammation plays a major role in the pathogenesis of coronary artery disease (CAD). METHODS: We hypothesized, that quantifying inflammation by measuring circulating interleukin-6 concentrations help in the diagnosis and/or prediction of functionally relevant CAD. Among consecutive patients with symptoms suggestive of CAD, functionally relevant CAD was adjudicated in two domains: first, diagnosis according to myocardial perfusion single photon emission tomography (MPI-SPECT) and coronary angiography; second, cardiovascular death and all-cause death during 2-years follow-up. Adjudication was done blinded to the interleukin-6 concentrations. RESULTS: Among 1553 patients, symptoms were adjudicated to be causally related to CAD in 43% (665/1553). Interleukin-6 concentrations were higher in patients with functionally relevant CAD as compared to those without (1.56 pg/mL versus 1.30 pg/mL, p < 0.001), but overall had only low-to-modest diagnostic accuracy (area under the curve [AUC]: 0.57, 95%CI 0.55-0.61) and were no independent predictor of functionally relevant CAD after multivariable adjustment (p = 0.068). Interleukin-6 concentrations had moderate-to-high accuracy in the prediction of cardiovascular death (AUC 0.75, 95%CI 0.69-0.82) and all-cause death (AUC 0.72, 95%CI 0.66-0.78) at 2-years, and remained a significant predictor after multivariable adjustment (p < 0.001). Compared to patients with interleukin-6 concentrations below the median (1.41 pg/mL), patients with concentrations above the median had a significantly higher cumulative incidence of cardiovascular death (1% vs. 4%, log-rank p < 0.001) and all-cause death (2% vs. 8%, log-rank p < 0.001) at 2 years. CONCLUSION: Interleukin-6 concentrations are strong and independent predictors of cardiovascular death and all-cause death.


Assuntos
Doença da Artéria Coronariana/diagnóstico , Diagnóstico Precoce , Interleucina-6/sangue , Idoso , Biomarcadores/sangue , Causas de Morte/tendências , Angiografia Coronária , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/mortalidade , Teste de Esforço , Feminino , Seguimentos , Humanos , Imunoensaio , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Taxa de Sobrevida/tendências , Suíça/epidemiologia , Tomografia Computadorizada de Emissão de Fóton Único/métodos
7.
Clin Chem ; 65(2): 302-312, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30518662

RESUMO

BACKGROUND: The early diagnosis of urgent abdominal pain (UAP) is challenging. Most causes of UAP are associated with extensive inflammation. Therefore, we hypothesized that quantifying inflammation using interleukin-6 and/or procalcitonin would provide incremental value in the emergency diagnosis of UAP. METHODS: This was an investigator-initiated prospective, multicenter diagnostic study enrolling patients presenting to the emergency department (ED) with acute abdominal pain. Clinical judgment of the treating physician regarding the presence of UAP was quantified using a visual analog scale after initial clinical and physician-directed laboratory assessment, and again after imaging. Two independent specialists adjudicated the final diagnosis and the classification as UAP (life-threatening, needing urgent surgery and/or hospitalization for acute medical reasons) using all information including histology and follow-up. Interleukin-6 and procalcitonin were measured blinded in a central laboratory. RESULTS: UAP was adjudicated in 376 of 1038 (36%) patients. Diagnostic accuracy for UAP was higher for interleukin-6 [area under the ROC curve (AUC), 0.80; 95% CI, 0.77-0.82] vs procalcitonin (AUC, 0.65; 95% CI, 0.62-0.68) and clinical judgment (AUC, 0.69; 95% CI, 0.65-0.72; both P < 0.001). Combined assessment of interleukin-6 and clinical judgment increased the AUC at presentation to 0.83 (95% CI, 0.80-0.85) and after imaging to 0.87 (95% CI, 0.84-0.89) and improved the correct identification of patients with and without UAP (net improvement in mean predicted probability: presentation, +19%; after imaging, +15%; P < 0.001). Decision curve analysis documented incremental value across the full range of pretest probabilities. A clinical judgment/interleukin-6 algorithm ruled out UAP with a sensitivity of 97% and ruled in UAP with a specificity of 93%. CONCLUSIONS: Interleukin-6 significantly improves the early diagnosis of UAP in the ED.


Assuntos
Dor Abdominal/diagnóstico , Biomarcadores/sangue , Abdome/diagnóstico por imagem , Adulto , Idoso , Algoritmos , Área Sob a Curva , Serviço Hospitalar de Emergência , Feminino , Humanos , Interleucina-6/sangue , Julgamento , Masculino , Pessoa de Meia-Idade , Pró-Calcitonina/sangue , Estudos Prospectivos , Curva ROC , Tomografia Computadorizada por Raios X
8.
Heart ; 105(11): 826-833, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30541757

RESUMO

OBJECTIVE: Recently, daytime variation in perioperative myocardial injury (PMI) has been observed in patients undergoing cardiac surgery. We aim at investigating whether daytime variation also occurs in patients undergoing non-cardiac surgery. METHODS: In a prospective diagnostic study, we evaluated the presence of daytime variation in PMI in patients at increased cardiovascular risk undergoing non-cardiac surgery, as well as its possible impact on the incidence of acute myocardial infarction (AMI), and death during 1-year follow-up in a propensity score-matched cohort. PMI was defined as an absolute increase in high-sensitivity cardiac troponin T (hs-cTnT) concentration of ≥14 ng/L from preoperative to postoperative measurements. RESULTS: Of 1641 patients, propensity score matching defined 630 with similar baseline characteristics, half undergoing non-cardiac surgery in the morning (starting from 8:00 to 11:00) and half in the afternoon (starting from 14:00 to 17:00). There was no difference in PMI incidence between both groups (morning: 50, 15.8% (95% CI 12.3 to 20.3); afternoon: 52, 16.4% (95% CI 12.7 to 20.9), p=0.94), nor if analysing hs-cTnT release as a quantitative variable (median morning group: 3 ng/L (95% CI 1 to 7 ng/L); median afternoon group: 2 ng/L (95% CI 0 to 7 ng/L; p=0.16). During 1-year follow-up, the incidence of AMI was 1.2% (95% CI 0.4% to 3.2%) among morning surgeries versus 4.1% (95% CI 2.3% to 6.9%) among the afternoon surgeries (corrected HR for afternoon surgery 3.44, bootstrapped 95% CI 1.33 to 10.49, p log-rank=0.03), whereas no difference in mortality emerged (p=0.70). CONCLUSIONS: Although there is no daytime variation in PMI in patients undergoing non-cardiac surgery, the incidence of AMI during follow-up is increased in afternoon surgeries and requires further study. CLINICAL TRIAL REGISTRATION: NCT02573532;Results.

11.
Int J Cardiol ; 269: 114-121, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30224031

RESUMO

BACKGROUND: Various scores have been derived for the assessment of syncope patients in the emergency department (ED) but stay inconsistently validated. We aim to compare their performance to the one of a common, easy-to-use CHADS2 score. METHODS: We prospectively enrolled patients ≥ 40 years old presenting with syncope to the ED in a multicenter study. Early clinical judgment (ECJ) of the treating ED-physician regarding the probability of cardiac syncope was quantified. Two independent physicians adjudicated the final diagnosis after 1-year follow-up. Major cardiovascular events (MACE) and death were recorded during 2 years of follow-up. Nine scores were compared by their area under the receiver-operator characteristics curve (AUC) for death, MACE or the diagnosis of cardiac syncope. RESULTS: 1490 patients were available for score validation. The CHADS2-score presented a higher or equally high accuracy for death in the long- and short-term follow-up than other syncope-specific risk scores. This score also performed well for the prediction of MACE in the long- and short-term evaluation and stratified patients with accuracy comparative to OESIL, one of the best performing syncope-specific risk score. All scores performed poorly for diagnosing cardiac syncope when compared to the ECJ. CONCLUSIONS: The CHADS2-score performed comparably to more complicated syncope-specific risk scores in the prediction of death and MACE in ED syncope patients. While better tools incorporating biochemical and electrocardiographic markers are needed, this study suggests that the CHADS2-score is currently a good option to stratify risk in syncope patients in the ED. TRIAL REGISTRATION: NCT01548352.


Assuntos
Eletrocardiografia/normas , Serviço Hospitalar de Emergência/normas , Síncope/diagnóstico , Síncope/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Eletrocardiografia/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
12.
Eur Heart J ; 39(42): 3780-3794, 2018 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-30169752

RESUMO

Aims: We aimed to evaluate the impact of age on the performance of the European Society of Cardiology (ESC) 0/1h-algorithms and to derive and externally validate alternative cut-offs specific to older patients. Methods and results: We prospectively enrolled patients presenting to the emergency department (ED) with symptoms suggestive of acute myocardial infarction in three large diagnostic studies. Final diagnoses were adjudicated by two independent cardiologists. High-sensitivity cardiac troponin (hs-cTn) T and I concentrations were measured at presentation and after 1 h. Patients were stratified according to age [<55 years (young), ≥55 to <70 years (middle-age), ≥70 years (old)]. Rule-out safety of the ESC hs-cTnT 0/1h-algorithm was very high in all age-strata: sensitivity 100% [95% confidence interval (95% CI) 94.9-100] in young, 99.3% (95% CI 96.0-99.9) in middle-age, and 99.3% (95% CI 97.5-99.8) in old patients. Accuracy of rule-in decreased with age: specificity 97.0% (95% CI 95.8-97.9) in young, 96.1% (95% CI 94.5-97.2) in middle-age, and 92.7% (95% CI 90.7-94.3) in older patients. Triage efficacy decreased with increasing age (young 93%, middle-age 80%, old 55%, P < 0.001). Similar results were found for the ESC hs-cTnT 0/1h-algorithm. Alternative, slightly higher cut-off concentrations optimized for older patients maintained very high safety of rule-out, increased specificity of rule-in (P < 0.01), reduced overall efficacy for hs-cTnT (P < 0.01), while maintaining efficacy for hs-cTnI. Findings were confirmed in two validation cohorts (n = 2767). Conclusion: While safety of the ESC 0/1h-algorithms remained very high, increasing age significantly reduced overall efficacy and the accuracy of rule-in. Alternative slightly higher cut-off concentrations may be considered for older patients, particularly if using hs-cTnI. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT00470587, number NCT00470587 and NCT02355457 (BACC).


Assuntos
Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Adulto , Fatores Etários , Idoso , Algoritmos , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Sensibilidade e Especificidade , Troponina/sangue
13.
Clin Chem ; 64(11): 1596-1606, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30097496

RESUMO

BACKGROUND: We aimed to directly compare high-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity cardiac troponin T (hs-cTnT) in the detection of functionally relevant coronary artery disease (fCAD). METHODS: Consecutive patients referred with clinical suspicion of fCAD and no structural heart disease other than coronary artery disease were included. The presence of fCAD was based on rest/stress myocardial perfusion single-photon emission computed tomography/computed tomography and coronary angiography. hs-cTnI and hs-cTnT concentrations were measured in a blinded fashion. Diagnostic accuracy was quantified using the area under the ROC curve (AUC) and evaluated both for uniform use in all patients and for sex-specific use in women and men separately. The prognostic end point was major adverse cardiac events (MACEs; cardiovascular death or myocardial infarction) within 2 years. For the prognostic performance, we used a multivariable model comparison with the Akaike information criterion (AIC). RESULTS: fCAD was detected in 613 of 2062 patients (29.7%) overall, 112 of 664 of women (16.9%), and 501 of 1398 of men (35.8%). hs-cTnI and hs-cTnT had comparable diagnostic accuracy when assessed for uniform use in all patients (AUC, 0.68 vs 0.66; P = 0.107) and separately in women (AUC, 0.68 vs 0.63; P = 0.068) and men (AUC, 0.65 vs 0.64; P = 0.475). However, women required lower rule-out cutoffs to achieve high sensitivity, and men needed higher rule-in cutoffs to achieve high specificity. hs-cTnI and hs-cTnT were strongly and independently associated with MACE within 2 years (P < 0.001), with comparable prognostic accuracies by the AIC. CONCLUSIONS: hs-cTnI and hs-cTnT provide moderate and comparable diagnostic accuracy. Sex-specific cutoffs may be preferred. The prognostic utility of both troponins is comparable.


Assuntos
Doença da Artéria Coronariana/sangue , Troponina I/sangue , Troponina T/sangue , Área Sob a Curva , Biomarcadores/sangue , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Diagnóstico Precoce , Feminino , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Sensibilidade e Especificidade , Fatores Sexuais , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único
14.
Am Heart J ; 203: 67-73, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30041065

RESUMO

BACKGROUND: We aimed to directly compare preoperative high-sensitivity cardiac troponin (hs-cTn) I and T concentration for the prediction of major cardiac complications after non-cardiac surgery. METHODS: We measured hs-cTnI and hs-cTnT preoperatively in a blinded fashion in 1022 patients undergoing non-cardiac surgery. The primary endpoint was a composite of major cardiac complications including cardiac death, cardiac arrest, myocardial infarction, clinically relevant arrhythmias, and acute heart failure within 30 days. We hypothesized that the type of surgery may impact on the predictive accuracy of hs-cTnI/T and stratified all analyses according to the type of surgery. RESULTS: Major cardiac complications occurred in 108 (11%) patients, 58/243 (24%) patients undergoing vascular surgery and 50/779 (6%, P < .001) patients undergoing non-vascular surgery. Using regulatory-approved 99th percentile cut-off concentrations, preoperative hs-cTnI elevations were less than one-fifth as common as preoperative hs-cTnT elevations (P < .001). Among patients undergoing vascular surgery, preoperative hs-cTnI concentrations, but not hs-cTnT, was an independent predictor of cardiac complications (adjusted odds ratio (aOR) 1.5, 95% confidence interval (95% CI) 1.0-2.1). The area under the receiver-operating characteristics curve (AUC) was 0.67 (95% CI, 0.59-0.75) for hs-cTnI versus 0.59 (95% CI 0.51-0.67, P = .012) for hs-cTnT. In contrast, among patients undergoing non-vascular surgery both preoperative hs-cTnI and hs-cTnT were independent predictors of the primary endpoint (aOR 1.6, 95% CI 1.3-2.0, and aOR 3.0, 95% CI 2.0-4.6, respectively) and showed higher predictive accuracy (AUC 0.77, 95% CI, 0.71-0.83, and 0.79, 95% CI 0.73-0.85, P = ns). CONCLUSIONS: Preoperative hs-cTnI and hs-cTnT concentrations predict major cardiac complications after non-vascular surgery, while, in patients undergoing vascular surgery, hs-cTnI may have better accuracy.


Assuntos
Infarto do Miocárdio/sangue , Complicações Pós-Operatórias/sangue , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Troponina I/sangue , Troponina T/sangue , Idoso , Biomarcadores/sangue , Brasil/epidemiologia , Angiografia Coronária , Ecocardiografia , Eletrocardiografia , Feminino , Seguimentos , Humanos , Imunoensaio , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Imagem de Perfusão do Miocárdio , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Suíça/epidemiologia , Fatores de Tempo
15.
Clin Chem ; 64(9): 1347-1360, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29941469

RESUMO

BACKGROUND: Clinical performance of the novel high-sensitivity cardiac troponin I (Siemens-hs-cTnI-Centaur) assay is unknown. We aimed to clinically validate the Siemens-hs-cTnI-Centaur assay and develop 0/1-h and 0/2-h algorithms. METHODS: We enrolled patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction (AMI). Final diagnoses were centrally adjudicated by 2 independent cardiologists including all clinical information twice: first, using serial hs-cTnT (Roche-Elecsys, primary analysis); second, using hs-cTnI (Abbott-Architect, secondary analysis) measurements in addition to the clinically applied (hs)-cTn. Siemens-hs-cTnI-Centaur was measured at presentation, 1 h, and 2 h. The primary objective was a direct comparison of diagnostic accuracy, quantified by the area under the ROC curve (AUC), of Siemens-hs-cTnI-Centaur vs the 2 established hs-cTn assays (Roche-hs-cTnT-Elecsys, Abbott-hs-cTnI-Architect). Secondary objectives included the development of Siemens-hs-cTnI-Centaur-specific 0/1-h and 0/2-h algorithms. RESULTS: AMI was the final diagnosis in 318 of 1755 (18%) patients (using Roche-hs-cTnT-Elecsys for adjudication). The AUC at presentation for Siemens-hs-cTnI-Centaur was 0.94 (95% CI, 0.92-0.96) and comparable with 0.95 (95% CI, 0.93-0.97) for Roche-hs-cTnT-Elecsys and 0.93 (95% CI, 0.90-0.96) for Abbott-hs-cTnI-Architect. Applying the derived Siemens-hs-cTnI-Centaur 0/1-h algorithm to the validation cohort, 46% of patients were ruled out (sensitivity, 99.1%; 95% CI, 95.3-100), and 18% of patients were ruled in (specificity, 94.1%; 95% CI, 91.8-95.9). The Siemens-hs-cTnI-Centaur 0/2-h algorithm ruled out 55% of patients (sensitivity, 100%; 95% CI, 94.1-100), and ruled in 18% of patients (specificity, 96.0%; 95% CI, 93.1-97.9). Findings were confirmed in the secondary analyses using serial measurements of Abbott-hs-cTnI-Architect for adjudication. CONCLUSIONS: Diagnostic accuracy and clinical utility of the novel Siemens-hs-cTnI-Centaur assay are high and comparable with the established hs-cTn assays. ClinicalTrials.gov Identifier: NCT00470587.


Assuntos
Infarto do Miocárdio/diagnóstico , Troponina I/sangue , Algoritmos , Dor no Peito , Diagnóstico Precoce , Eletrocardiografia , Feminino , Humanos , Masculino , Infarto do Miocárdio/fisiopatologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
17.
Circulation ; 138(10): 989-999, 2018 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-29691270

RESUMO

BACKGROUND: Combining 2 signals of cardiomyocyte injury, cardiac troponin I (cTnI) and T (cTnT), might overcome some individual pathophysiological and analytical limitations and thereby increase diagnostic accuracy for acute myocardial infarction with a single blood draw. We aimed to evaluate the diagnostic performance of combinations of high-sensitivity (hs) cTnI and hs-cTnT for the early diagnosis of acute myocardial infarction. METHODS: The diagnostic performance of combining hs-cTnI (Architect, Abbott) and hs-cTnT (Elecsys, Roche) concentrations (sum, product, ratio, and a combination algorithm) obtained at the time of presentation was evaluated in a large multicenter diagnostic study of patients with suspected acute myocardial infarction. The optimal rule-out and rule-in thresholds were externally validated in a second large multicenter diagnostic study. The proportion of patients eligible for early rule-out was compared with the European Society of Cardiology 0/1 and 0/3 hour algorithms. RESULTS: Combining hs-cTnI and hs-cTnT concentrations did not consistently increase overall diagnostic accuracy as compared with the individual isoforms. However, the combination improved the proportion of patients meeting criteria for very early rule-out. With the European Society of Cardiology 2015 guideline recommended algorithms and cut-offs, the proportion meeting rule-out criteria after the baseline blood sampling was limited (6% to 24%) and assay dependent. Application of optimized cut-off values using the sum (9 ng/L) and product (18 ng2/L2) of hs-cTnI and hs-cTnT concentrations led to an increase in the proportion ruled-out after a single blood draw to 34% to 41% in the original (sum: negative predictive value [NPV] 100% [95% confidence interval (CI), 99.5% to 100%]; product: NPV 100% [95% CI, 99.5% to 100%]) and in the validation cohort (sum: NPV 99.6% [95% CI, 99.0-99.9%]; product: NPV 99.4% [95% CI, 98.8-99.8%]). The use of a combination algorithm (hs-cTnI <4 ng/L and hs-cTnT <9 ng/L) showed comparable results for rule-out (40% to 43% ruled out; NPV original cohort 99.9% [95% CI, 99.2-100%]; NPV validation cohort 99.5% [95% CI, 98.9-99.8%]) and rule-in (positive predictive value [PPV] original cohort 74.4% [95% Cl, 69.6-78.8%]; PPV validation cohort 84.0% [95% Cl, 79.7-87.6%]). CONCLUSIONS: New strategies combining hs-cTnI and hs-cTnT concentrations may significantly increase the number of patients eligible for very early and safe rule-out, but do not seem helpful for the rule-in of acute myocardial infarction. CLINICAL TRIAL REGISTRATION: URL (APACE): https://www.clinicaltrial.gov . Unique identifier: NCT00470587. URL (ADAPT): www.anzctr.org.au . Unique identifier: ACTRN12611001069943.


Assuntos
Infarto do Miocárdio/diagnóstico , Troponina I/sangue , Troponina T/sangue , Austrália , Biomarcadores/sangue , Diagnóstico Precoce , Europa (Continente) , Humanos , Infarto do Miocárdio/sangue , Nova Zelândia , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Tempo , Regulação para Cima
18.
BMC Pulm Med ; 18(1): 51, 2018 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-29562888

RESUMO

BACKGROUND: Interferon lambdas (IFNLs) have important anti-viral/bacterial and immunomodulatory functions in the respiratory tract. How do IFNLs impact COPD and its exacerbations? METHODS: Five hundred twenty eight patients were recruited in a prospective observational multicentre cohort (PROMISE) study. The genetic polymorphisms (rs8099917 and rs12979860) within the IFNL3/4 gene region and circulating levels of IFNL3 in COPD patients were determined and associated with disease activity and outcome during a median follow-up of 24 months. RESULTS: The GG genotype significantly influenced severe exacerbation rate (42 vs. 23%; p = 0.032) and time to severe exacerbation (HR = 2.260; p = 0.012). Compared to the TT or TG genotypes, the GG genotype was associated with severe dyspnoea (modified medical research council score ≥ median 3; 22 vs 42%, p = 0.030). The CC genotype of the rs12979860 SNP was associated with a poorer prognosis (body mass index, airflow obstruction, dyspnea and exercise capacity index ≥ median 4; 46 vs. 36% TC vs. 20.5% TT; p = 0.031). Patients with stable COPD and at exacerbation had significantly lower circulating IFNL3 compared to healthy controls (p < 0.001 and p < 0.001, respectively). Circulating IFNL3 correlated to post-bronchodilator FEV1%predicted and the tissue maturation biomarker Pro-collagen 3. CONCLUSION: IFNL3/4 polymorphisms and circulating IFNL3 may be associated with disease activity and outcomes in COPD. TRIAL REGISTRATION: Clinical Trial registration http://www.isrctn.com/ identifier ISRCTN99586989 on 16 April 2008.


Assuntos
Interleucinas/genética , Doença Pulmonar Obstrutiva Crônica/genética , Adrenomedulina/sangue , Idoso , Fator Natriurético Atrial/sangue , Estudos de Casos e Controles , Estudos de Coortes , Progressão da Doença , Dispneia , Feminino , Volume Expiratório Forçado , Glicopeptídeos/sangue , Humanos , Interferons , Interleucinas/sangue , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Pró-Calcitonina/sangue , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Precursores de Proteínas/sangue , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Índice de Gravidade de Doença
19.
Int J Public Health ; 63(2): 233-239, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28924741

RESUMO

OBJECTIVES: Our study aimed at determining the prevalence of selected infectious diseases among recently arrived Eritrean refugees in Switzerland. METHODS: In this cross-sectional study, asymptomatic Eritrean migrants aged ≥16 years who arrived <24 months ago were recruited at refugee centres in Switzerland. Infectious disease screening included serology for HIV, hepatitis B and C, syphilis and schistosomiasis, polymerase chain reaction (PCR) for malaria, stool microscopy for helminths and intestinal protozoa and circulating cathodic antigen (CCA) testing in urine for schistosomiasis. RESULTS: Among 107 participating Eritrean refugees, point-of-care CCA urine test for Schistosoma mansoni was positive in 43 patients (40.2%; 95% CI 31.9-49.5). Stool microscopy detected eggs of S. mansoni in 23 (21.5%; 95% CI 13.7-29.3), Hymenolepis nana in 11 (10.3%; 95% CI 4.5-16.0), and cysts of Giardia intestinalis in 7 participants (6.5%: 95% CI 1.9-11.2). Two tested positive for hepatitis B (1.9%; 95% CI 0.0-4.4) and one for syphilis (0.9%; 95% CI 0.0-2.8), none tested positive for HIV or hepatitis C. Malaria PCR was positive in six participants (5.6%; 95% CI: 1.2-9.9). CONCLUSIONS: Given the high prevalence of S. mansoni infection and potentially severe long-term sequelae of untreated schistosomiasis, routine screening for schistosomiasis in refugees from Schistosoma-endemic regions should be recommended.


Assuntos
Doenças Transmissíveis/epidemiologia , Refugiados/estatística & dados numéricos , Esquistossomose mansoni/epidemiologia , Migrantes/estatística & dados numéricos , Adulto , Animais , Estudos Transversais , Eritreia/etnologia , Feminino , Humanos , Masculino , Programas de Rastreamento , Prevalência , Schistosoma mansoni/isolamento & purificação , Suíça/epidemiologia , Adulto Jovem
20.
Circulation ; 137(5): 436-451, 2018 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-29101287

RESUMO

BACKGROUND: The European Society of Cardiology recommends a 0/1-hour algorithm for rapid rule-out and rule-in of non-ST-segment elevation myocardial infarction using high-sensitivity cardiac troponin (hs-cTn) concentrations irrespective of renal function. Because patients with renal dysfunction (RD) frequently present with increased hs-cTn concentrations even in the absence of non-ST-segment elevation myocardial infarction, concern has been raised regarding the performance of the 0/1-hour algorithm in RD. METHODS: In a prospective multicenter diagnostic study enrolling unselected patients presenting with suspected non-ST-segment elevation myocardial infarction to the emergency department, we assessed the diagnostic performance of the European Society of Cardiology 0/1-hour algorithm using hs-cTnT and hs-cTnI in patients with RD, defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2, and compared it to patients with normal renal function. The final diagnosis was centrally adjudicated by 2 independent cardiologists using all available information, including cardiac imaging. Safety was quantified as sensitivity in the rule-out zone, accuracy as the specificity in the rule-in zone, and efficacy as the proportion of the overall cohort assigned to either rule-out or rule-in based on the 0- and 1-hour sample. RESULTS: Among 3254 patients, RD was present in 487 patients (15%). The prevalence of non-ST-segment elevation myocardial infarction was substantially higher in patients with RD compared with patients with normal renal function (31% versus 13%, P<0.001). Using hs-cTnT, patients with RD had comparable sensitivity of rule-out (100.0% [95% confidence interval {CI}, 97.6-100.0] versus 99.2% [95% CI, 97.6-99.8]; P=0.559), lower specificity of rule-in (88.7% [95% CI, 84.8-91.9] versus 96.5% [95% CI, 95.7-97.2]; P<0.001), and lower overall efficacy (51% versus 81%, P<0.001), mainly driven by a much lower percentage of patients eligible for rule-out (18% versus 68%, P<0.001) compared with patients with normal renal function. Using hs-cTnI, patients with RD had comparable sensitivity of rule-out (98.6% [95% CI, 95.0-99.8] versus 98.5% [95% CI, 96.5-99.5]; P=1.0), lower specificity of rule-in (84.4% [95% CI, 79.9-88.3] versus 91.7% [95% CI, 90.5-92.9]; P<0.001), and lower overall efficacy (54% versus 76%, P<0.001; proportion ruled out, 18% versus 58%, P<0.001) compared with patients with normal renal function. CONCLUSIONS: In patients with RD, the safety of the European Society of Cardiology 0/1-hour algorithm is high, but specificity of rule-in and overall efficacy are decreased. Modifications of the rule-in and rule-out thresholds did not improve the safety or overall efficacy of the 0/1-hour algorithm. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00470587.


Assuntos
Algoritmos , Técnicas de Apoio para a Decisão , Taxa de Filtração Glomerular , Nefropatias/fisiopatologia , Rim/fisiopatologia , Infarto do Miocárdio sem Supradesnível do Segmento ST/sangue , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico , Triagem , Troponina/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Creatinina/sangue , Europa (Continente)/epidemiologia , Feminino , Humanos , Nefropatias/sangue , Nefropatias/diagnóstico , Nefropatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio sem Supradesnível do Segmento ST/epidemiologia , Valor Preditivo dos Testes , Prevalência , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Fatores de Tempo , Regulação para Cima
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