[Comparative severity of COVID-19 cases caused by Alpha, Delta or Omicron SARS-CoV-2 variants and its association with vaccination]. / Gravedad comparativa de los casos de COVID-19 causados por las variantes Alfa, Delta u Ómicron de SARS-CoV-2 y su asociación con la vacunación.

BACKGROUND: This study compares the severity of SARS-CoV-2 infections caused by Alpha, Delta or Omicron variants in periods of co-circulation in Spain, and estimates the variant-specific association of vaccination with severe disease. METHODS: SARS-CoV-2 infections notified to the national epidemiological surveillance network with information on genetic variant and vaccination status were considered cases if they required hospitalisation or controls otherwise. Alpha and Delta were compared during June-July 2021; and Delta and Omicron during December 2021-January 2022. Adjusted Odds Ratios (aOR) were estimated using logistic regression, comparing variant and vaccination status between cases and controls. RESULTS: We included 5,345 Alpha and 11,974 Delta infections in June-July and, 5,272 Delta and 10,578 Omicron in December-January. Unvaccinated cases of Alpha (aOR: 0.57; 95% CI: 0.46-0.69) or Omicron (0.28; 0.21-0.36) had lower probability of hospitalisation vs. Delta. Complete vaccination reduced hospitalisation, similarly for Alpha (0.16; 0.13-0.21) and Delta (June-July: 0.16; 0.14-0.19; December-January: 0.36; 0.30-0.44) but lower from Omicron (0.63; 0.53-0.75) and individuals aged 65+ years. CONCLUSION: Results indicate higher intrinsic severity of the Delta variant, compared with Alpha or Omicron, with smaller differences among vaccinated individuals. Nevertheless, vaccination was associated to reduced hospitalisation in all groups.

Intermittent endoscopic ultrasound guided fine-needle aspiration for the diagnosis of solid pancreatic lesions. A pilot study.

BACKGROUND AND PURPOSE: endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) is the method of choice for sampling pancreatic solid lesions. However, there is significant heterogeneity in terms of the technique used. Intermittent aspiration has not been evaluated in pancreatic solid lesions and could improve the diagnostic performance. METHODS: a single-blind, non-inferiority pilot study was performed. Patients with solid pancreatic lesions and an indication for EUS-FNA were prospectively included. Patients were randomly assigned to intermittent (IS) or continuous (CS) suction techniques. Diagnostic performance, cellularity, blood contamination and the number of passes required to reach a diagnosis were evaluated. MAIN RESULTS: thirty-three patients were assigned to CS (16 patients) or IS (17 patients). Diagnostic performance was 87.5 % for CS and 94.1 % for IS (OR 2.29, 95 % CI: 0.19-27.99, p = 0.51). In the IS group, samples had a higher cellularity (OR 1.83, 95 % CI: 0.48-6.91, p = 0.37) and lower blood contamination (OR 0.38, 95 % CI: 0.09-1.54, p = 0.18). The number of passes required to reach a diagnosis was 2.12 for CS and 1.94 for IS (p = 0.64). Liquid cytology was obtained in 73.3 % of IS and 61.5 % of CS (OR 1.72, 95 % CI: 0.35-8.50). CONCLUSIONS: the IS technique was not inferior to CS in terms of diagnostic accuracy in the evaluation of pancreatic solid lesions, with a tendency to obtain higher cellularity, lower blood contamination and the frequent presence of cell block.

Predictors of perfusion computed tomography alterations in stroke mimics attended as stroke code.

BACKGROUND AND PURPOSE: Stroke mimics (SMs) account for a significant number of patients attended as stroke code (SC) with an increasing number over the years. Recent studies show perfusion computed tomography (PCT) alterations in some SMs, especially in seizures. The objective of our study was to evaluate the clinical characteristics and PCT alterations in SMs attended as SC in order to identify potential predictors of PCT alterations in SMs. METHODS: A retrospective study was performed including all SC activations undergoing a multimodal CT study including non-enhanced computed tomography (CT), CT angiography and PCT, as part of our SC protocol, over 39 months. Patients with a final diagnosis of SM after complete diagnosis work-up were therefore selected. Clinical variables, diagnosis, PCT alteration patterns and type of map affected (Tmax or time to peak, cerebral blood flow and cerebral blood volume) were registered. RESULTS: Stroke mimics represent up to 16% (284/1761) of SCs with a complete multimodal study according to our series. Amongst SMs, 26% (74/284) showed PCT alterations. PCT abnormalities are more prevalent in seizures and status epilepticus and the main pattern is alteration of the time to peak map, of unilateral hemispheric distribution or of non-vascular territory. In our series, the independent predictors of alteration in PCT in SMs are aphasia, female sex and older age. CONCLUSIONS: Perfusion computed tomography alterations can be found amongst almost a third of SMs attended as SC, especially older women presenting with aphasia with a final diagnosis of epileptic seizures and status epilepticus.

Pharmacokinetic variability of eslicarbazepine in real clinical practice.

INTRODUCTION: Eslicarbazepine acetate (ESL) is a sodium channel blocker indicated for partial-onset seizures with or without secondary generalization, at a single daily dose. There are very few publications on the levels of ESL metabolites in real clinical practice. OBJECTIVE: To describe the serum levels of licarbazepine (main metabolite of ESL) in patients with refractory epilepsy in real clinical practice. To evaluate the influence of age, sex, and polytherapy on levels and adverse effects. METHODS: This study involved a retrospective analysis of patients diagnosed with epilepsy treated with ESL for whom plasma levels of licarbazepine were available, measured by spectrophotometry. RESULTS: Sixty-four patients were included. One patient had licarbazepine levels of 0 (admitted not taking the drug) was not analyzed. Mean licarbazepine levels of 7.66 µg/mL (400 mg/day dose), 16.56 µg/mL (800-mg dose), and 20.80 µg/mL (1200 mg) were significantly different. There was a significant correlation between daily dose and serum levels (p < 0.05) and between the concentration/dose ratio and lower to higher doses (p < 0.05). Pharmacokinetic variability (coefficient of variation for the concentration/dose ratio) was 33.2%. We found a decrease in the concentration/dose ratio in the 1200 mg/day dose, compared to lower doses. We did not find differences by sex or intake of other antiepileptic inducers or metabolic inhibitors. Fifteen patients (23.8%) had mild nonsymptomatic hyponatremia. CONCLUSION: These results suggest that it is not necessary to routinely determine licarbazepine levels. In specific cases, licarbazepine levels can be useful to assess adherence to treatment and for personalized dose adjustment.

A Multimodal Approach for Myofascial Pain Syndrome: A Prospective Study.

OBJECTIVE: The purpose of this study was to analyze pain intensity in patients with myofascial pain syndrome (MPS) following a multimodal rehabilitation protocol. METHODS: A prospective study was carried out following the Template for Intervention Description and Replication criteria. Patients were recruited from the rehabilitation unit of a university hospital in Spain between 2009 and 2013. Patients were included if they had a medical diagnosis of MPS in any of the following regions: cervicobrachial (n = 102), lumbosacral (n = 30), elbow (n = 14), ankle and foot (n = 10), and temporomandibular jaw (n = 1). The multimodal rehabilitation protocol included myofascial trigger point dry needling, spray and stretching, Kinesio taping, eccentric exercise, and patient education. The protocol was applied for 4 weeks (5 sessions) for the active and/or latent myofascial trigger points in each body region. Pain intensity was measured by using the visual analog scale (VAS) immediately before beginning of the study and 1 week after completion of the protocol. RESULTS: The study sample comprised 150 patients (mean ± standard deviation age, 51.5 ± 1.19 years). Statistically significant differences were obtained for reduction in pain intensity (4 ± 2.03; P = .002). Clinically relevant reductions (VAS ≥30 mm; P < .001) were obtained in 78.7% of the interventions. Four treatment sessions reduced the VAS score by 10 mm in 83.55% of the sample. There were no statistically significant differences (P = .064) for reduction in pain intensity in the different body regions. CONCLUSIONS: A multimodal rehabilitation protocol showed clinically relevant differences in the reduction in pain intensity in different body regions in patients with MPS.

High levels of preoperative and postoperative N terminal B-type natriuretic propeptide influence mortality and cardiovascular complications after noncardiac surgery: A prospective cohort study.

BACKGROUND: Major noncardiac surgery is associated with a 5% incidence of serious cardiovascular complications and with a 1 to 2% probability of death from cardiac causes. Over the last few decades, researchers have assessed the perioperative predictive power of several risk indices. Research is currently focused on the evaluation of biomarkers. OBJECTIVES: The objective was to determine the incidence of high serum levels of N terminal B-type natriuretic propeptide (NT-proBNP) before and after surgery in adults undergoing elective major noncardiac procedures and to evaluate its relationship with mortality and cardiovascular complications occurring up to 30 days after surgery. DESIGN: Prospective cohort study. SETTING: Enrolment was undertaken at a university hospital from October 2011 to July 2013. PATIENTS: A total of 304 adults with cardiovascular risk factors who underwent noncardiac elective surgery. MAIN OUTCOME MEASURES: The relationship between preoperative and postoperative NT-proBNP serum levels and the emergence of cardiovascular complications, including all-cause mortality, during the first 30 days after surgery. RESULTS: The incidence of cardiovascular complications was 7.8% (n = 25), and the mortality rate was 4.3% (n = 13). Higher-than-normal NT-proBNP serum levels were found before surgery in 48.4% (n = 147) and after surgery in 50.7% (n = 154) of patients. The variables found to be independent predictors of cardiovascular complications, including all-cause 30-day mortality, were levels of NT-proBNP more than 300 pg ml before surgery and levels more than 1000 pg ml both before and after surgery. CONCLUSION: High levels of preoperative and postoperative NT-proBNP are predictors of cardiovascular complications, including all-cause mortality, during the first 30 days after noncardiac surgery in adults with cardiovascular risk factors.

[ESTIMATE OF THE INTRINSIC ERROR OF THE MEASURING INSTRUMENT OF THE LABORATORY FOR ANALYTICAL DETERMINATIONS OF THE CRITICAL PATIENT]. / Estimación del error intrínseco del instrumento de medida del laboratorio. PARA LAS DETERMINACIONES ANALÍTICAS DEL PACIENTE CRÍTICO.

Decrease blood loss associated with the analytical laboratory is a determinant of safety and quality in the preanalytical phase, in order to achieve an optimal level of care, where nurses have leading role to be responsible for the care of the critically ill patient.

Prevalence and risk factors for biopsy-proven non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in a prospective cohort of adult patients with gallstones.

BACKGROUND & AIMS: Relationship between gallstones and non-alcoholic fatty liver disease (NAFLD), and largely non-alcoholic steatohepatitis (NASH), is uncertain. AIM: To determine the prevalence, non-invasive fibrosis markers profile and risk factors for biopsy-proven NAFLD and NASH among patients with gallstones. METHODS: Anthropometric and laboratory evaluation, an abdominal ultrasound and a liver biopsy were performed to 215 consecutive patients with gallstones referred for cholecystectomy. RESULTS: Prevalence of NASH was 10.2% whereas that of simple steatosis (SS) was 41.4%. In the cohort of NAFLD patients, negative predictive values for advanced fibrosis of FIB-4 and NAFLD fibrosis score were 96 and 95% respectively. Gallstone patients with NASH had a higher mean homeostatic model assessment (HOMA) score than those with SS (P = 0.015). Noteworthy, NASH was 2.5-fold more frequent in patients with gallstones who had metabolic syndrome than in those who did not (P < 0.001). Fatty liver on ultrasound was observed in 90.9% of gallstone patients with NASH compared with 61.8% of those with SS (P = 0.044). Using multivariate logistic regression, increased HOMA score (OR, 3.47; 95% CI, 1.41-8.52; P = 0.007) and fatty liver on ultrasound (OR, 23.27; 95% CI, 4.15-130.55; P < 0.001) were the only factors independently associated with NASH. CONCLUSIONS: Prevalence of NASH among patients with gallstones is lower than estimated previously, but NASH is frequent particularly in those patients with concurrent metabolic syndrome. The combination of an increased HOMA score with fatty liver on ultrasound has a good accuracy for predicting NASH in patients with gallstones.

The incidence of cardiovascular events after hospitalization due to CAP and their association with different inflammatory markers.

BACKGROUND: Late prognosis of Community-Acquired Pneumonia (CAP) patients is related to cardiovascular events. Persistence of inflammation-related markers, defined by high circulatory levels of interleukin 6 and 10 (IL-6/IL-10), is associated with a higher post-event mortality rate for CAP patients. However, association between these markers and other components of the immune response, and the risk of cardiovascular events, has not been adequately explored. The main objectives of this study are: 1) to quantify the incidence of cardiovascular disease, in the year post-dating their hospital admittance due to CAP and, 2) to describe the distribution patterns of a wide spectrum of inflammatory markers upon admittance to and release from hospital, and to determine their relationship with the incidence of cardiovascular disease. METHODS/DESIGN: A cohort prospective study. All patients diagnosed and hospitalized with CAP will be candidates for inclusion. The study will take place in the Universitary Hospital La Princesa, Spain, during two years. Two samples of blood will be taken from each patient: the first upon admittance and the second one prior to release, in order to analyse various immune agents. The main determinants are: pro-adrenomedullin, copeptin, IL-1, IL-6, TNF-α, IL-17, IFN-γ, IL-10 and TGF-ß, E-Selectin, ICAM-1, VCAM-1 and subpopulations of peripheral T lymphocytes (T regulator, Th1 and Th17), together with other clinical and analytical variables. Follow up will start at admittance and finish a year after discharge, registering incidence of death and cardiovascular events. The main objective is to establish the predictive power of different inflammatory markers in the prognosis of CAP, in the short and long term, and their relationship with cardiovascular disease. DISCUSSION: The level of some inflammatory markers (IL-6/IL-10) has been proposed as a means to differentiate the degree of severity of CAP, but their association with cardiovascular risk is not well established. In this study we aim to define new inflammatory markers associated with cardiovascular disease that could be helpful for the prognosis of CAP patients, by describing the distribution of a wide spectrum of inflammatory mediators and analyzing their association with the incidence of cardiovascular disease and mortality one year after release from hospital.

Seasonality, smoking and history of poor treatment compliance are strong predictors of dropout in a naturalistic 6 year follow-up of bipolar patients.

Bipolar disorder is a highly recurrent disease which requires long-term treatment. Dropout is a major problem, poorly understood. The objectives of this study were to know the risk of dropout of a cohort of bipolar patients under ambulatory treatment and to identify the clinical profile of patients more likely to abandon the follow-up. A sample of 285 BD I and II patients was followed up for a mean of 2.87 years. A significant proportion of patients failed regular follow-up. The dropout rates were 6.3 % at three months, 12.7 % at 6 months, and 17.6, 27.2, 37.3, 44.0, 47.2 and 49.0 % at 1, 2, 3, 4, 5 and 6 years respectively. Very few variables at baseline predicted dropout. Patients under 35 years of age were more likely to dropout than older cases. Seasonality, smoking and specially history of poor treatment compliance were strong predictors of dropout. Given the magnitude of dropout, additional early clinical interventions should be considered for high-risk patients.

Comparative severity of COVID-19 cases caused by Alpha, Delta or Omicron SARS-CoV-2 variants and its association with vaccination.

BACKGROUND: This study compares the severity of SARS-CoV-2 infections caused by Alpha, Delta or Omicron variants in periods of co-circulation in Spain, and estimates the variant-specific association of vaccination with severe disease. METHODS: SARS-CoV-2 infections notified to the national epidemiological surveillance network with information on genetic variant and vaccination status were considered cases if they required hospitalisation or controls otherwise. Alpha and Delta were compared during June-July 2021; and Delta and Omicron during December 2021-January 2022. Adjusted odds ratios (aOR) were estimated using logistic regression, comparing variant and vaccination status between cases and controls. RESULTS: We included 5,345 Alpha and 11,974 Delta infections in June-July and 5,272 Delta and 10,578 Omicron in December-January. Unvaccinated cases of Alpha (aOR: 0.57; 95% CI: 0.46-0.69) or Omicron (0.28; 0.21-0.36) had lower probability of hospitalisation vs. Delta. Complete vaccination reduced hospitalisation, similarly for Alpha (0.16; 0.13-0.21) and Delta (June-July: 0.16; 0.14-0.19; December-January: 0.36; 0.30-0.44) but lower from Omicron (0.63; 0.53-0.75) and individuals aged 65+ years. CONCLUSION: Results indicate higher intrinsic severity of the Delta variant, compared with Alpha or Omicron, with smaller differences among vaccinated individuals. Nevertheless, vaccination was associated to reduced hospitalisation in all groups.

Severity of respiratory syncytial virus compared with SARS-CoV-2 and influenza among hospitalised adults ≥65 years.

INTRODUCTION: Our aim was to estimate the risk of pneumonia, admission to intensive care unit (ICU) or death in individuals ≥65 years old admitted to hospital with RSV, compared to influenza or COVID-19. METHODS: We included hospitalised patients from Severe Acute Respiratory Infection Surveillance in Spain between 2021-2024, aged ≥65 years, laboratory confirmed for RSV, influenza or SARS-CoV-2. Using a binomial regression with logarithmic link, we estimated the relative risk (RR) of pneumonia, ICU admission and in-hospital mortality, in patients with RSV compared to influenza or SARS-CoV-2, adjusting for age, sex, season and comorbidities. We stratified the estimates by vaccination status for influenza or SARS-CoV2. RESULTS: Among patients unvaccinated for influenza or SARS-CoV-2, those with RSV had similar or lower risk of pneumonia [vs. influenza: RR= 0.91 (95% Confidence Interval: 0.72-1.16); vs. SARS-CoV-2: 0.81 (0.67-0.98)], ICU admission [vs. influenza: 0.93 (0.41-2.08); vs. SARS-CoV-2: 1.10 (0.61-1.99)] and mortality [vs. influenza: 0.64 (0.32-1.28); vs. SARS-CoV-2: 0.56 (0.30-1.04)]. Among the vaccinated, results were largely similar except for a higher risk of ICU admission with RSV [vs. influenza: 2.13(1.16-3.89); vs. SARS-CoV-2: 1.83 (1.02-3.28)] CONCLUSIONS: RSV presented similar or lower intrinsic severity than influenza or SARS-CoV2. Among vaccinated patients, RSV was associated to higher ICU-admission, suggesting the potential for preventive RSV vaccination.

[Effectiveness of vaccines against SARS-CoV-2 used in Spain: infection, hospitalization and mortality in people aged fifty/fifty-nine.] / Efectividad de las vacunas frente a SARS-CoV-2 utilizadas en España: infección, hospitalización y mortalidad en personas de cincuenta a cincuenta y nueve años.

In this paper we compared brand-specific COVID-19 vaccine effectiveness (VE) during August 2021 in persons born 1962-1971 and vaccinated during June. For SARS-CoV-2 symptomatic infection, protection was lower for Janssen (56%; CI95%: 53-59) or AstraZeneca [Vaxzevria] (68%; CI95%: 65-70), compared to Pfizer-BioNTech [Comirnaty] (78%; CI95%: 77-78), AstraZeneca/Pfizer (86%; CI95%: 80-90) or Moderna [Spikevax] (89%; CI95%: 88-90). VE against hospitalization was ranged 86% for Janssen to 97%-98% for other vaccines.

En este trabajo se comparó la efectividad de la vacuna contra la COVID-19 (EV) durante agosto de 2021, en personas nacidas entre 1962 y 1971 y vacunadas durante junio, según la marca utilizada. La protección frente a infección por SARS-CoV-2 sintomática fue menor para la vacuna de Janssen (56%; IC95%: 53-59) y AstraZeneca [Vaxzevria] (68%; IC95%: 65-70), en comparación con Pfizer [Comirnaty] (78%; IC95%: 77-78), AZ/Pfizer (86%; IC95%: 80-90) y Moderna [Spikevax] (89%; IC95%: 88-90). La EV contra la hospitalización osciló entre el 86% de Janssen y el 97%-98% de las demás vacunas.

Correction: Bed-side measures for diagnosis of low muscle mass, sarcopenia, obesity, and sarcopenic obesity in patients with chronic kidney disease under non-dialysis-dependent, dialysis dependent and kidney transplant therapy.

[This corrects the article DOI: 10.1371/journal.pone.0242671.].

Performance of Bioelectrical Impedance and Anthropometric Predictive Equations for Estimation of Muscle Mass in Chronic Kidney Disease Patients.

Background: Patients with chronic kidney disease (CKD) are vulnerable to loss of muscle mass due to several metabolic alterations derived from the uremic syndrome. Reference methods for body composition evaluation are usually unfeasible in clinical settings. Aims: To evaluate the accuracy of predictive equations based on bioelectrical impedance analyses (BIA) and anthropometry parameters for estimating fat free mass (FFM) and appendicular FFM (AFFM), compared to dual energy X-ray absorptiometry (DXA), in CKD patients. Methods: We performed a longitudinal study with patients in non-dialysis-dependent, hemodialysis, peritoneal dialysis and kidney transplant treatment. FFM and AFFM were evaluated by DXA, BIA (Sergi, Kyle, Janssen and MacDonald equations) and anthropometry (Hume, Lee, Tian, and Noori equations). Low muscle mass was diagnosed by DXA analysis. Intra-class correlation coefficient (ICC), Bland-Altman graphic and multiple regression analysis were used to evaluate equation accuracy, linear regression analysis to evaluate bias, and ROC curve analysis and kappa for reproducibility. Results: In total sample and in each CKD group, the predictive equation with the best accuracy was AFFMSergi (men, n = 137: ICC = 0.91, 95% CI = 0.79-0.96, bias = 1.11 kg; women, n = 129: ICC = 0.94, 95% CI = 0.92-0.96, bias = -0.28 kg). AFFMSergi also presented the best performance for low muscle mass diagnosis (men, kappa = 0.68, AUC = 0.83; women, kappa = 0.65, AUC = 0.85). Bias between AFFMSergi and AFFMDXA was mainly affected by total body water and fat mass. None of the predictive equations was able to accurately predict changes in AFFM and FFM, with all ICC lower than 0.5. Conclusion: The predictive equation with the best performance to asses muscle mass in CKD patients was AFFMSergi, including evaluation of low muscle mass diagnosis. However, assessment of changes in body composition was biased, mainly due to variations in fluid status together with adiposity, limiting its applicability for longitudinal evaluations.

Are doctors accurate when diagnosing themselves with migraine? A study on migraine prevalence among doctors in a tertiary care hospital.

Migraine is considered an underdiagnosed disease in general population. Different studies show a higher prevalence in neurologists. However, there are few studies about its prevalence in doctors of other specialties, where it could also be superior than in general population. Our aim was to define migraine lifetime prevalence among doctors according to three parameters (previous diagnosis, self-diagnosis and positivity of a screening test). Single-center, descriptive, cross-sectional study based on online surveys with collection of sociodemographic and clinical variables, addressed to doctors of a tertiary hospital. Participants who reported 5 or more headaches throughout their lives were considered "headache sufferers" and were divided in different groups according to their position (specialists or trainees) and their specialty (medical, medical-surgical and surgical or specialties with no direct contact with the patient). The Spanish validated version of the Migraine Screen Questionnaire (MS-Q) was used as screening test. There were 217 participants (response rate of 29%), 72% were women and 56% trainees, mean age 34 years (SD10). 77% were "headache sufferers" Among all participants, migraine lifetime prevalence according to diagnosis by another physician was 15.2%, self-diagnosis 38.2% and positivity of the MS-Q 20.3%; those categories were not mutually exclusive Greater but not statistically significant coexistence of self-diagnosis and positive MS-Q was seen in specialists compared to trainees and in medical specialties. Migraine prevalence among doctors in a tertiary care hospital was higher than in general population, according to all three parameters analyzed. Self-diagnosis was the highest which could reflect an overdiagnosis; further studies are needed to determine this possibility.

Comparison between dual-energy x-ray absorptiometry and bioelectrical impedance for body composition measurements in adults with chronic kidney disease: A cross-sectional, longitudinal, multi-treatment analysis.

OBJECTIVE: The aim of this study was to evaluate the agreement between bioelectrical impedance spectroscopy (BIS) and dual-energy x-ray absorptiometry (DXA) for assessment of body composition in patients with chronic kidney disease (CKD). METHODS: We performed cross-sectional and prospective analyses by DXA and BIS in whole body (BISWB) and segmental (BISSEG) protocols in CKD non-dialysis-dependent (n = 81), hemodialysis (n = 83), peritoneal dialysis (n = 24), and renal transplantation (n = 80) patients. Intraclass correlation coefficient (ICC) and Bland-Altman plots were evaluated. Linear regression analysis was performed for bias assessment and development of equations. Receiver operating characteristics curve was constructed for diagnosis of inadequate error tolerance (DXA - BIS >±2kg). RESULTS: The agreement with DXA was greater for BISWB than BISSEG; for fat mass (FM; ICC men = 0.894; women = 0.931) than fat-free mass (FFM; ICC men = 0.566; women = 0.525), with greater bias for FFM as muscle increases and for FM in body fat extremes. The agreement was lower for body change analysis (ICC FFM men = 0.196; women = 0.495; ICC FM men = 0.465; women = 0.582). The ratio of extra- to intracellular water (ECW/ICW), body mass index, fat mass index, waist circumference, resistance, and reactance interfered in bias between methods. An ECW/ICW cutoff point of ≥0.7250 for inadequate error tolerance was determined. New prediction equations for FFM (r2 = 0.913) and FM (r2 = 0.887) presented adequate error tolerance in 55% and 63% compared with 30% and 39% of the original equation, respectively. CONCLUSION: For body composition evaluation in patients with CKD, BIS applied using the whole body protocol, in normal hydration patients with CKD is as reliable as DXA; BIS must be used with caution in overhydration patients with ECW/ICW ≥ 0.7250. The newly developed equations are indicated for greater precision.

The Impact of COVID-19 on Mortality in Spain: Monitoring Excess Mortality (MoMo) and the Surveillance of Confirmed COVID-19 Deaths.

Measuring mortality has been a challenge during the COVID-19 pandemic. Here, we compared the results from the Spanish daily mortality surveillance system (MoMo) of excess mortality estimates, using a time series analysis, with those obtained for the confirmed COVID-19 deaths reported to the National Epidemiological Surveillance Network (RENAVE). The excess mortality estimated at the beginning of March 2020 was much greater than what has been observed in previous years, and clustered in a very short time. The cumulated excess mortality increased with age. In the first epidemic wave, the excess mortality estimated by MoMo was 1.5 times higher than the confirmed COVID-19 deaths reported to RENAVE, but both estimates were similar in the following pandemic waves. Estimated excess mortality and confirmed COVID-19 mortality rates were geographically distributed in a very heterogeneous way. The greatest increase in mortality that has taken place in Spain in recent years was detected early by MoMo, coinciding with the spread of the COVID-19 pandemic. MoMo is able to identify risk situations for public health in a timely manner, relying on mortality in general as an indirect indicator of various important public health problems.

Evaluation of Natalizumab Pharmacokinetics and Pharmacodynamics: Toward Individualized Doses.

Background: Plasma concentration of natalizumab falls above the therapeutic threshold in many patients who, therefore, receive more natalizumab than necessary and have higher risk of progressive multifocal leukoencephalopathy. Objective: To assess in a single study the individual and treatment characteristics that influence the pharmacokinetics and pharmacodynamics of natalizumab in multiple sclerosis (MS) patients in the real-world practice. Methods: Prospective observational study to analyse the impact of body weight, height, body surface area, body mass index, gender, age, treatment duration, and dosage scheme on natalizumab concentrations and the occupancy of α4-integrin receptor (RO) by natalizumab. Results: Natalizumab concentrations ranged from 0.72 to 67 µg/ml, and RO from 26 to 100%. Body mass index inversely associated with natalizumab concentration (beta = -1.78; p ≤ 0.001), as it did body weight (beta = -0.34; p = 0.001), but not height, body surface area, age or gender Extended vs. standard dose scheme, but not treatment duration, was inversely associated with natalizumab concentration (beta = -7.92; p = 0.016). Similar to natalizumab concentration, body mass index (beta = -1.39; p = 0.001) and weight (beta = -0.31; p = 0.001) inversely impacted RO. Finally, there was a strong direct linear correlation between serum concentrations and RO until 9 µg/ml (rho = 0.71; p = 0.003). Nevertheless, most patients had higher concentrations of natalizumab resulting in the saturation of the integrin. Conclusions: Body mass index and dosing interval are the main variables found to influence the pharmacology of natalizumab. Plasma concentration of natalizumab and/or RO are wide variable among patients and should be routinely measured to personalize treatment and, therefore, avoid either over and underdosing.

Molecular analysis of pancreatic cystic neoplasm in routine clinical practice.

BACKGROUND: Cystic pancreatic lesions consist of a wide variety of lesions that are becoming increasingly diagnosed with the growing use of imaging techniques. Of these, mucinous cysts are especially relevant due to their risk of malignancy. However, morphological findings are often suboptimal for their differentiation. Endoscopic ultrasound fine-needle aspiration (EUS-FNA) with molecular analysis has been suggested to improve the diagnosis of pancreatic cysts. AIM: To determine the impact of molecular analysis on the detection of mucinous cysts and malignancy. METHODS: An 18-month prospective observational study of consecutive patients with pancreatic cystic lesions and an indication for EUS-FNA following European clinical practice guidelines was conducted. These cysts included those > 15 mm with unclear diagnosis, and a change in follow-up or with concerning features in which results might change clinical management. EUS-FNA with cytological, biochemical and glucose and molecular analyses with next-generation sequencing were performed in 36 pancreatic cysts. The cysts were classified as mucinous and non-mucinous by the combination of morphological, cytological and biochemical analyses when surgery was not performed. Malignancy was defined as cytology positive for malignancy, high-grade dysplasia or invasive carcinoma on surgical specimen, clinical or morphological progression, metastasis or death related to neoplastic complications during the 6-mo follow-up period. Next-generation sequencing results were compared for cyst type and malignancy. RESULTS: Of the 36 lesions included, 28 (82.4%) were classified as mucinous and 6 (17.6%) as non-mucinous. Furthermore, 5 (13.9%) lesions were classified as malignant. The amount of deoxyribonucleic acid obtained was sufficient for molecular analysis in 25 (69.4%) pancreatic cysts. The amount of intracystic deoxyribonucleic acid was not statistically related to the cyst fluid volume obtained from the lesions. Analysis of KRAS and/or GNAS showed 83.33% [95% confidence interval (CI): 63.34-100] sensitivity, 60% (95%CI: 7.06-100) specificity, 88.24% (95%CI: 69.98-100) positive predictive value and 50% (95%CI: 1.66-98.34) negative predictive value (P = 0.086) for the diagnosis of mucinous cystic lesions. Mutations in KRAS and GNAS were found in 2/5 (40%) of the lesions classified as non-mucinous, thus recategorizing those lesions as mucinous neoplasms, which would have led to a modification of the follow-up plan in 8% of the cysts in which molecular analysis was successfully performed. All 4 (100%) malignant cysts in which molecular analysis could be performed had mutations in KRAS and/or GNAS, although they were not related to malignancy (P > 0.05). None of the other mutations analyzed could detect mucinous or malignant cysts with statistical significance (P > 0.05). CONCLUSION: Molecular analysis can improve the classification of pancreatic cysts as mucinous or non-mucinous. Mutations were not able to detect malignant lesions.