External validation of three diabetes prediction scores in a Spanish cohort: does adding high risk for depression improve the validation of the FINDRISC score (FINDRISC-MOOD)?

OBJECTIVES: To evaluate the external validity of the FINDRISC, DESIR and ADA risk scores for the prediction of diabetes in a Spanish population aged >45 years and to test the possible improvement of FINDRISC by adding a new variable of high risk of depression when Patient Health Questionnaire-9 (PHQ-9) questionnaire score ≥10 (FINDRISC-MOOD). DESIGN: Prospective population-based cohort study. SETTING: 10 primary healthcare centres in the north of the city of Madrid (Spain). PARTICIPANTS: A total of 1242 participants without a history of diabetes and with 2-hour oral glucose tolerance test (OGTT) plasma glucose <200 mg/dL (<11.1 mmol/L) were followed up for 7.3 years (median) using their electronic health records (EHRs) and telephone contact. PRIMARY AND SECONDARY OUTCOME MEASURES: Diabetes risk scores (FINDRISC, DESIR, ADA), PHQ-9 questionnaire and 2-hour-OGTT were measured at baseline. Incident diabetes was defined as treatment for diabetes, fasting plasma glucose ≥126 mg/dL (≥7.0 mmol/L), new EHR diagnosis or self-reported diagnosis. External validation was performed according to optimal cut-off, sensitivity, specificity and Youden Index. Comparison between diabetes risk scores, including FINDRISC-MOOD (original FINDRISC score plus five points if PHQ-9 ≥10), was measured by area under the receiver operating characteristic curve (AUROC). RESULTS: During follow-up, 104 (8.4%; 95% CI, 6.8 to 9.9) participants developed diabetes and 185 had a PHQ-9 score ≥10. The AUROC values were 0.70 (95% CI, 0.67 to 0.72) for FINDRISC-MOOD and 0.68 (95% CI, 0.65 to 0.71) for the original FINDRISC. The AUROCs for DESIR and ADA were 0.66 (95% CI, 0.63 to 0.68) and 0.66 (95% CI, 0.63 to 0.69), respectively. There were no significant differences in AUROC between FINDRISC-MOOD and the other scores. CONCLUSIONS: The results of FINDRISC-MOOD were like those of the other risk scores and do not allow it to be recommended for clinical use.

Usefulness of mid-regional proadrenomedullin levels in the resuscitation phase of severely burned patients and its utility in early sepsis detection.

INTRODUCTION: Mid-regional proadrenomedullin (MR-proADM) reflects the adrenomedullin level, which has vasodilatory activity, decreases endothelial permeability, and downregulates proinflammatory cytokines. Sepsis diagnosis in these patients is difficult, and MR-proADM is a widely studied sepsis biomarker. This study evaluates MR-proADM levels during the resuscitation phase, considering the potential influence of haemodynamic changes and its usefulness for the early sepsis detection in burn patients. METHODS: A prospective observational study performed in the Critical Burn Unit. Demographic data, burn characteristics, comorbidities, prognostic/severity scales, and haemodynamic parameters were collected. The resuscitation protocol guided by diuresis, transpulmonary thermodilution, and lactate levels was followed. Blood samples were collected at various time points for biomarker measurement. Biomarker levels, including MR-proADM, C-reactive protein, and procalcitonin were measured during the resuscitation phase and septic episodes. RESULTS: Twenty-seven patients were included, with a mean age of 51 years, a mean total body surface area burn of 41.8%, a mean Abbreviated Burn Severity Index of 9.7, and a mean Baux score of 92. MR-proADM levels were elevated on admission (0.9 ± 0.5 nmol/l) and continued to increase slightly during the resuscitation phase (2.4 ± 2.2 nmol/l). Haemodynamic changes during resuscitation did not significantly affect MR-proADM levels. Twelve of the 27 patients developed sepsis, whose MR-proADM levels were significantly elevated on the day of clinical diagnosis (3.91 ± 2.99 nmol/l) and even the day before (2.57 ± 3.37). Higher MR-proADM levels were associated with greater severity as measured by the Sequential Organ Failure Assessment score. The mean MR-proadrenomedullin values during resuscitation in the patients who died was 3.51 ± 2.30 nmol/l, whereas in the survivors it was 1.28 ± 1.10 nmol/l (p = 0.0001). CONCLUSION: MR-proadrenomedullin values are elevated after thermal injury but are not affected by haemodynamic changes. During septic episodes in burn patients, MR-proADM rises early (the day before sepsis diagnosis). Higher levels of MR-proADM are associated with greater organ dysfunction and mortality.

Design of an algorithm for the detection of intravenous fluid contamination in clinical laboratory samples.

OBJECTIVES: Contamination of blood samples from patients receiving intravenous fluids is a common error with potential risk to the patient. Algorithms based on the presence of aberrant results have been described but have the limitation that not all infusion fluids have the same composition. Our objective is to develop an algorithm based on the detection of the dilution observed on the analytes not usually included in infusion fluids. METHODS: A group of 89 cases was selected from samples flagged as contaminated. Contamination was confirmed by reviewing the clinical history and comparing the results with previous and subsequent samples. A control group with similar characteristics was selected. Eleven common biochemical parameters not usually included in infusion fluids and with low intraindividual variability were selected. The dilution in relation to the immediate previous results was calculated for each analyte and a global indicator, defined as the percentage of analytes with significant dilution, was calculated. ROC curves were used to define the cut-off points. RESULTS: A cut-off point of 20 % of dilutional effect requiring also a 60 % dilutional ratio achieved a high specificity (95 % CI 91-98 %) with an adequate sensitivity (64 % CI 54-74 %). The Area Under Curve obtained was 0.867 (95 % CI 0.819-0.915). CONCLUSIONS: Our algorithm based on the global dilutional effect presents a similar sensitivity but greater specificity than the systems based on alarming results. The implementation of this algorithm in the laboratory information systems may facilitate the automated detection of contaminated samples.

Laboratory interpretative comments and guidance: clinical and operative outcomes on moderate to severe hyponatraemia patient management.

AIMS: Hyponatraemia is the most common body fluid disorders but often goes unnoticed. Our laboratory incorporated a standardised procedure to help clinicians detect moderate/severe hyponatraemia. The study aims were to evaluate the outcomes on patient care and clinicians' satisfaction. METHODS: The study, observational and retrospective, included 1839 cases, adult and paediatric patients, with sodium concentration <130 mmol/L. The procedure consisted of interpretative comments in the emergency and core laboratories report and the point-of-care testing blood gas network report. We evaluated hyponatraemia length in two equal periods: before and after the implementation. We conducted a survey addressed to the staff of the clinical settings involved to know their satisfaction. RESULTS: The median hyponatraemia length decreased significantly from 4.95 hours (2.08-16.57) in the first period to 2.17 hours (1.06-5.39) in the second period. The lack of hyponatraemia patients follow-up was significantly less after the procedure implementation. The survey was answered by 92 (60 senior specialists and 32 residents) out of 110 clinicians surveyed. Ninety of them (98%) answered positively. CONCLUSIONS: We have demonstrated the reduction in the time for diagnosing and management by physicians, the higher uniformity in the time required to solve hyponatraemia episodes following our laboratory procedure and the clinicians' satisfaction.

ANN-Based Discernment of Septic and Inflammatory Synovial Fluid: A Novel Method Using Viscosity Data from a QCR Sensor.

The synovial fluid (SF) analysis involves a series of chemical and physical studies that allow opportune diagnosing of septic, inflammatory, non-inflammatory, and other pathologies in joints. Among the variety of analyses to be performed on the synovial fluid, the study of viscosity can help distinguish between these conditions, since this property is affected in pathological cases. The problem with viscosity measurement is that it usually requires a large sample volume, or the necessary instrumentation is bulky and expensive. This study compares the viscosity of normal synovial fluid samples with samples with infectious and inflammatory pathologies and classifies them using an ANN (Artificial Neural Network). For this purpose, a low-cost, portable QCR-based sensor (10 MHz) was used to measure the viscous responses of the samples by obtaining three parameters: Δf, ΔΓ (parameters associated with the viscoelastic properties of the fluid), and viscosity calculation. These values were used to train the algorithm. Different versions of the ANN were compared, along with other models, such as SVM and random forest. Thirty-three samples of SF were analyzed. Our study suggests that the viscosity characterized by our sensor can help distinguish infectious synovial fluid, and that implementation of ANN improves the accuracy of synovial fluid classification.

Peripheral Atherosclerosis in Patients With Erectile Dysfunction: A Population-Based Study.

INTRODUCTION: The presence of erectile dysfunction (ED) could be a warning of vascular disease in different arterial territories. AIM: The aim of this study was to investigate the association between ED and the presence of atherosclerosis in 2 different vascular beds: carotid and lower limbs. METHODS: A total of 614 volunteers between 45 and 74 years of age (mean age 61.0 years) were randomly selected from the general population. ED was assessed using the International Index of Erectile Function (IIEF-5). Ankle-brachial index (ABI) measurement and carotid atherosclerosis were evaluated by echo-Doppler. MAIN OUTCOME MEASURES: Mean carotid intima-media thickness (IMT), prevalence of carotid plaques, mean ABI, and prevalence of ABI < 0.9 were the main outcome measures. RESULTS: ED was present in 373 subjects (59.7%). Mean carotid IMT was significantly higher in men with ED (0.762 ± 0.151 mm vs 0.718 ± 0.114 mm, P < .001). Also the global prevalence of carotid plaques was more frequent in men with ED (63.8% vs 44.8%, P < .001), even after adjusting by age, cardiovascular risk factors, and ongoing treatment (P = .039). Both the IMT and the prevalence of carotid plaques increased significantly with ED severity (P trend .004 and <.001, respectively). There were no significant differences between groups neither in mean ABI nor in the prevalence of subjects with ABI < 0.9. However, there was a trend to a lower ABI and a higher prevalence of ABI < 0.9 with increasing ED severity. CONCLUSION: In the general population, the presence of ED identifies subjects with higher atherosclerosis burden in carotid arteries but not in the lower extremities.

Previous Exposure to the Fish Parasite Anisakis as a Potential Risk Factor for Gastric or Colon Adenocarcinoma.

Anisakiasis is a global disease caused by consumption of raw or lightly cooked fish contaminated with L3 Anisakis spp. larvae. High rates of parasitization of fish worldwide make Anisakis a serious health hazard. In fact, anisakiasis is a growing disease in countries such as Spain, Italy, and Japan, where consumption of raw/marinated fish is high. Some parasitic infections have been recognized as a causative factor for human cancer. Suggested mechanisms include chronic inflammation elicited by the parasite, and a possible tumorigenic effect from certain parasitic secretions. Anisakis can produce persistent local inflammation and granuloma, and larvae have been incidentally found in gastrointestinal (GI) tumors. Our aim was to discover possible differences in the prevalence of unnoticed or asymptomatic previous Anisakis infection in GI cancer patients compared with healthy individuals. Serum levels of specific antibodies against Anisakis antigens were used as a reliable marker of previous contact with their larvae. Ninety-four participants without a previous history of Anisakis infection were prospectively allocated into 1 of 2 groups: 47 patients with GI cancer and 47 controls. Specific IgE, IgA1, and IgG1 against the Anisakis recombinant antigens Ani s 1, Ani s 5, Ani s 9, and Ani s 10 were determined by an ELISA assay. The ratio of positivity to sIgA1, rAni s 1, or rAni s 5 was significantly higher in the cancer patients than in the controls (38.30% vs 6.38%, P < 0.001) and (42.55% vs 10.64%, P < 0.001, respectively). When disaggregated by type of tumor, the patients with gastric cancer showed a higher proportion of positive results for sIgA1 to rAni s 1 (P < 0.001), whereas a higher proportion of colon cancer patients were shown to be positive for sIgA1 to both rAni s 1 (P < 0.05) and rAni s 5 (P < 0.01). Earlier Anisakis infection might be a risk factor for the development of stomach or colon cancer.

Validating prediction scales of type 2 diabetes mellitus in Spain: the SPREDIA-2 population-based prospective cohort study protocol.

INTRODUCTION: The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide. When diagnosed, many patients already have organ damage or advance subclinical atherosclerosis. An early diagnosis could allow the implementation of lifestyle changes and treatment options aimed at delaying the progression of the disease and to avoid cardiovascular complications. Different scores for identifying undiagnosed diabetes have been reported, however, their performance in populations of southern Europe has not been sufficiently evaluated. The main objectives of our study are: to evaluate the screening performance and cut-off points of the main scores that identify the risk of undiagnosed T2DM and prediabetes in a Spanish population, and to develop and validate our own predictive models of undiagnosed T2DM (screening model), and future T2DM (prediction risk model) after 5-year follow-up. As a secondary objective, we will evaluate the atherosclerotic burden of the population with undiagnosed T2DM. METHODS AND ANALYSIS: Population-based prospective cohort study with baseline screening, to evaluate the performance of the FINDRISC, DANISH, DESIR, ARIC and QDScore, against the gold standard tests: Fasting plasma glucose, oral glucose tolerance and/or HbA1c. The sample size will include 1352 participants between the ages of 45 and 74 years. ANALYSIS: sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio positive, likelihood ratio negative and receiver operating characteristic curves and area under curve. Binary logistic regression for the first 700 individuals (derivation) and last 652 (validation) will be performed. All analyses will be calculated with their 95% CI; statistical significance will be p<0.05. ETHICS AND DISSEMINATION: The study protocol has been approved by the Research Ethics Committee of the Carlos III Hospital (Madrid). The score performance and predictive model will be presented in medical conferences, workshops, seminars and round table discussions. Furthermore, the predictive model will be published in a peer-reviewed medical journal to further increase the exposure of the scores.

Acute respiratory distress syndrome after convalescent plasma use: treatment of a patient with Ebola virus disease contracted in Madrid, Spain.

BACKGROUND: In the current epidemic of Ebola virus disease, health-care workers have been transferred to Europe and the USA for optimised supportive care and experimental treatments. We describe the clinical course of the first case of Ebola virus disease contracted outside of Africa, in Madrid, Spain. METHODS: Herein we report clinical, laboratory, and virological findings of the treatment of a female nurse assistant aged 44 years who was infected with Ebola virus around Sept 25-26, 2014, while caring for a Spanish missionary with confirmed Ebola virus disease who had been medically evacuated from Sierra Leone to La Paz-Carlos III University Hospital, Madrid. We also describe the use of experimental treatments for Ebola virus disease in this patient. FINDINGS: The patient was symptomatic for 1 week before first hospital admission on Oct 6, 2014. We used supportive treatment with intravenous fluids, broad-spectrum antibiotics, and experimental treatments with convalescent plasma from two survivors of Ebola virus disease and high-dose favipiravir. On day 10 of illness, she had acute respiratory distress syndrome, possibly caused by transfusion-related acute lung injury, which was managed without mechanical ventilation. Discharge was delayed because of the detection of viral RNA in several bodily fluids despite clearance of viraemia. The patient was discharged on day 34 of illness. At the time of discharge, the patient had possible subacute post-viral thyroiditis. None of the people who had contact with the patient before and after admission became infected with Ebola virus. INTERPRETATION: This report emphasises the uncertainties about the efficacy of experimental treatments for Ebola virus disease. Clinicians should be aware of the possibility of transfusion-related acute lung injury when using convalescent plasma for the treatment of Ebola virus disease. FUNDING: La Paz-Carlos III University Hospital.

The Laboratory Medicine and the care of patients infected by the Ebola virus. Experience in a reference hospital of Madrid, Spain.

The ongoing Ebola virus outbreak in several countries in West Africa was considered by the World Health Organisation (WHO) as a public health emergency of international concern. Healthcare providers must be prepared by organising specific procedures in our hospitals based on recommendations from national and international healthcare organisations. Two aims should be considered: appropriate medical care for patients with suspected or confirmed disease must be ensured, as must measures to prevent transmission to healthcare workers. The clinical laboratory plays an important role and must define and establish its own procedures in accordance with clinicians and integrated into those of the institution, starting with the definition of the organisation model in the laboratory to achieve those goals. In this review we present our experience based on the care of three patients with confirmed cases. We hope it will help other colleagues to plan for Ebola.

Actuación del laboratorio en la atención a pacientes con infección por el virus Ébola. Experiencia en el Hospital Universitario La Paz / Clinical laboratory role in the management of patients with Ebola virus infection. Experience at La Paz University Hospital

El actual brote de enfermedad por el virus del Ébola en África Occidental fue considerado por la Organización Mundial de la Salud como una alerta sanitaria que constituye una urgencia de salud pública de importancia internacional. Los profesionales sanitarios debemos estar preparados estableciendo en nuestros hospitales procedimientos y protocolos de actuación basados en recomendaciones de instituciones sanitarias nacionales e internacionales con dos objetivos, garantizar la atención y manejo de pacientes con sospecha o confirmación de la enfermedad y la seguridad y salud de los trabajadores. El laboratorio clínico desempeña un papel fundamental y como tal ha de definir y establecer procedimientos específicos consensuados con los clínicos e integrados en los del propio centro, definiendo en primer lugar el modelo de organización que permita conseguir ambos objetivos. En esta revisión exponemos además nuestra experiencia basada en la atención a un paciente con la enfermedad confirmada que esperamos pueda servir de ayuda a otros centros (AU)

The ongoing Ebola virus outbreak in several countries in West Africa was considered by the World Health Organization as a public health emergency of international concern. Healthcare providers must be prepared in our hospitals by organizing specific procedures based on recommendations from national and international healthcare organizations. Two aims should be considered, appropriate medical care for patients with suspected or confirmed disease must be assured, as well as measures to prevent transmission to health-care workers. The clinical laboratory plays an important role and must define and establish its own procedures in agreement with clinicians and integrated into those of the institution, starting with the definition of the organization model in the laboratory to achieve those goals. Our experience based on the care of a patient with a confirmed case is presented, and it is hoped that it will help other colleagues to plan for Ebola (AU)