Impact of an enhanced screening program on the detection of non-AIDS neoplasias in patients with human immunodeficiency virus infection.

BACKGROUND: The incidence of non-AIDS defining cancer (NADC) is higher in people living with HIV (PLWH) than in the general population, and it is already one of the leading causes of death in the HIV-infected population. It is estimated that the situation will be aggravated by the progressive aging of PLWH. Early diagnosis through intensive cancer screening may improve the ability for therapeutic interventions and could be critical in reducing mortality, but it might also increase expenditure and harms associated with adverse events. The aim of this study is to evaluate an enhanced screening program for early diagnosis of cancer in PLWH compared to standard practice. The specific objectives are (1) to compare the frequency of cancer diagnosed at an early stage, (2) to analyze safety of the enhanced program: adverse events and unnecessary interventions, (3) to analyze the cost-utility of the program, and (4) to estimate the overall and site-specific incidence of NADC in PLWH. METHODS: We will conduct a multicenter, non-blinded, randomized, controlled trial, comparing two parallel arms: conventional vs enhanced screening. Data will be recorded in an electronic data collection notebook. Conventional intervention group will follow the standard of care screening in the participating centers, according to the European AIDS Clinical Society recommendations, and the enhanced intervention group will follow an expanded screening aimed to early detection of lung, liver, anal, cervical, breast, prostate, colorectal, and skin cancer. The trial will be conducted within the framework of the Spanish AIDS Research Network Cohort (CoRIS). DISCUSSION: The trial will evaluate the efficacy, safety, and efficiency of an enhanced screening program for the early diagnosis of cancer in HIV patients compared to standard of care practice. The information provided will be relevant since there are currently no studies on expanded cancer screening strategies in patients with HIV, and available data estimating cost effectiveness or cost-utility of such as programs are scarce. An enhanced program for NADC screening in patients with HIV could lead to early diagnosis and improve the prognosis of these patients, with an acceptable rate of unnecessary interventions, but it is critical to demonstrate that the benefits clearly outweigh the harms, before the strategy could be implemented. TRIAL REGISTRATION: ClinicalTrials.gov NCT04735445. Registered on 25 June 2019.

Combination of white matter hyperintensities and Aß burden is related to cognitive composites domain scores in subjective cognitive decline: the FACEHBI cohort.

BACKGROUND: To explore whether the combination of white matter hyperintensities (WMHs) and amyloid-beta (Aß) deposition is associated with worse cognitive performance on cognitive composites (CCs) domain scores in individuals with subjective cognitive decline (SCD). METHODS: Two hundred participants from the FACEHBI cohort underwent structural magnetic resonance imaging (MRI), 18F-florbetaben positron emission tomography (FBB-PET), and neuropsychological assessment. WMHs were addressed through the Fazekas scale, the Age-Related White Matter Changes (ARWMC) scale, and the FreeSurfer pipeline. Eight CCs domain scores were created using the principal component analysis (PCA). Age, sex, education, and apolipoprotein E (APOE) were used as adjusting variables. RESULTS: Adjusted multiple linear regression models showed that FreeSurfer (B - .245; 95% CI - .1.676, - .393, p = .016) and ß burden (SUVR) (B - .180; 95% CI - 2.140, - .292; p = .070) were associated with face-name associative memory CCs domain score, although the latest one was not statistically significant after correction for multiple testing (p = .070). There was non-significant interaction of these two factors on this same CCs domain score (p = .54). However, its cumulative effects on face-name associative performance indicated that those individuals with either higher WMH load or higher Aß burden showed the worst performance on the face-name associative memory CCs domain score. CONCLUSIONS: Our results suggest that increased WMH load and increased Aß are independently associated with poorer episodic memory performance in SCD individuals, indicating a cumulative effect of the combination of these two pathological conditions in promoting lower cognitive performance, an aspect that could help in terms of treatment and prevention.

Experience with the use of siltuximab in patients with SARS-CoV-2 infection.

OBJECTIVE: The study aims to describe characteristics and clinical outcome of patients with SARS-CoV-2 infection that received siltuximab according to a protocol that aimed to early block the activity of IL-6 to avoid the progression of the inflammatory flare. METHODS: Retrospective review of the first 31 patients with SARS-CoV-2 treated with siltuximab, in Hospital Clinic of Barcelona or Hospital Universitario Salamanca, from March to April 2020 with positive polymerase-chain reaction (PCR) from a nasopharyngeal swab. RESULTS: The cohort included 31 cases that received siltuximab with a median (IQR) age of 62 (56-71) and 71% were males. The most frequent comorbidity was hypertension (48%). The median dose of siltuximab was 800 mg ranging between 785 and 900 mg. 7 patients received siltuximab as a salvage therapy after one dose of tocilizumab. At the end of the study, a total of 26 (83.9) patients had been discharged alive and the mortality rate was 16.1% but only 1 out of 24 that received siltuximab as a first line option (4%). CONCLUSIONS: Siltuximab is a well-tolerated alternative to tocilizumab when administered as a first line option in patients with COVID-19 pneumonia within the first 10 days from symptoms onset and high C-reactive protein.

Tocilizumab reduces the risk of ICU admission and mortality in patients with SARS-CoV-2 infection.

OBJECTIVE: In some patients the immune response triggered by SARS-CoV-2 is unbalanced, presenting an acute respiratory distress syndrome which in many cases requires intensive care unit (ICU) admission. The limitation of ICU beds has been one of the major burdens in the management around the world; therefore, clinical strategies to avoid ICU admission are needed. We aimed to describe the influence of tocilizumab on the need of transfer to ICU or death in non-critically ill patients. METHODS: A retrospective study of 171 patients with SARS-CoV-2 infection that did not qualify as requiring transfer to ICU during the first 24h after admission to a conventional ward, were included. The criteria to receive tocilizumab was radiological impairment, oxygen demand or an increasing of inflammatory parameters, however, the ultimate decision was left to the attending physician judgement. The primary outcome was the need of ICU admission or death whichever came first. RESULTS: A total of 77 patients received tocilizumab and 94 did not. The tocilizumab group had less ICU admissions (10.3% vs. 27.6%, P=0.005) and need of invasive ventilation (0 vs 13.8%, P=0.001). In the multivariable analysis, tocilizumab remained as a protective variable (OR: 0.03, CI 95%: 0.007-0.1, P=0.0001) of ICU admission or death. CONCLUSIONS: Tocilizumab in early stages of the inflammatory flare could reduce an important number of ICU admissions and mechanical ventilation. The mortality rate of 10.3% among patients receiving tocilizumab appears to be lower than other reports. This is a non-randomized study and the results should be interpreted with caution.

Correlations between plasma and PET beta-amyloid levels in individuals with subjective cognitive decline: the Fundació ACE Healthy Brain Initiative (FACEHBI).

BACKGROUND: Peripheral biomarkers that identify individuals at risk of developing Alzheimer's disease (AD) or predicting high amyloid beta (Aß) brain burden would be highly valuable. To facilitate clinical trials of disease-modifying therapies, plasma concentrations of Aß species are good candidates for peripheral AD biomarkers, but studies to date have generated conflicting results. METHODS: The Fundació ACE Healthy Brain Initiative (FACEHBI) study uses a convenience sample of 200 individuals diagnosed with subjective cognitive decline (SCD) at the Fundació ACE (Barcelona, Spain) who underwent amyloid florbetaben(18F) (FBB) positron emission tomography (PET) brain imaging. Baseline plasma samples from FACEHBI subjects (aged 65.9 ± 7.2 years) were analyzed using the ABtest (Araclon Biotech). This test directly determines the free plasma (FP) and total plasma (TP) levels of Aß40 and Aß42 peptides. The association between Aß40 and Aß42 plasma levels and FBB-PET global standardized uptake value ratio (SUVR) was determined using correlations and linear regression-based methods. The effect of the APOE genotype on plasma Aß levels and FBB-PET was also assessed. Finally, various models including different combinations of demographics, genetics, and Aß plasma levels were constructed using logistic regression and area under the receiver operating characteristic curve (AUROC) analyses to evaluate their ability for discriminating which subjects presented brain amyloidosis. RESULTS: FBB-PET global SUVR correlated weakly but significantly with Aß42/40 plasma ratios. For TP42/40, this observation persisted after controlling for age and APOE ε4 allele carrier status (R2 = 0.193, p = 1.01E-09). The ROC curve demonstrated that plasma Aß measurements are not superior to APOE and age in combination in predicting brain amyloidosis. It is noteworthy that using a simple preselection tool (the TP42/40 ratio with an empirical cut-off value of 0.08) optimizes the sensitivity and reduces the number of individuals subjected to Aß FBB-PET scanners to 52.8%. No significant dependency was observed between APOE genotype and plasma Aß measurements (p value for interaction = 0.105). CONCLUSION: Brain and plasma Aß levels are partially correlated in individuals diagnosed with SCD. Aß plasma measurements, particularly the TP42/40 ratio, could generate a new recruitment strategy independent of the APOE genotype that would improve identification of SCD subjects with brain amyloidosis and reduce the rate of screening failures in preclinical AD studies. Independent replication of these findings is warranted.

Subclinical cardiovascular disease in patients starting contemporary protease inhibitors.

OBJECTIVES: The aim of the study was to assess changes in and factors associated with anatomical [carotid artery intima-media thickness (CIMT)] and functional (arterial stiffness) markers of subclinical cardiovascular disease progression in antiretroviral-naïve patients starting triple combination antiretroviral therapy containing contemporary protease inhibitors. METHODS: This was a planned substudy of the ATADAR (Metabolic Effects of Atazanavir/Ritonavir Versus Darunavir/Ritonavir in Combination With Tenofovir/Emtricitabine in naïve HIV-1 Infected Patients) clinical trial (ClinicalTrials.gov identifier NCT01274780). ATADAR is a multicentre, randomized, open-label clinical trial comparing the effects of ritonavir-boosted atazanavir and darunavir, both with tenofovir/emtricitabine, in antiretroviral-naïve HIV-infected patients. Common CIMT and aortic augmentation index (AIx@75) were measured at baseline and after 12 months of follow-up. Antiretroviral treatment, traditional cardiovascular risk factors and HIV-related factors were assessed as potential predictors of CIMT and Aix@75 changes using linear regression analysis. RESULTS: Thirty-three patients were included in this pilot study. While CIMT significantly increased in the pooled population [median (interquartile range (IQR)) 68 (-13, 128) µm; P = 0.0511], AIx@75 did not [median (IQR) 1 (-6, 5)%; P = 0.8964]. Patients on darunavir showed a trend to faster CIMT progression than those on atazanavir [median change (IQR) 117 (-2, 143) vs. -6 (-58, 89) µm, respectively; P = 0.0917]. However, after adjustment in the multivariate analysis, a higher baseline Framingham score was the only factor associated with CIMT progression (coefficient 16.02; 95% confidence interval -1.04, 33.08; P = 0.064). AIx@75 change was not associated with any baseline factor. CONCLUSIONS: CIMT was a more sensitive marker of subclinical vascular disease progression than arterial stiffness in antiretroviral-naïve patients starting antiretroviral therapy with contemporary protease inhibitors. Classical risk factors but not antiretroviral therapy were associated with faster CIMT progression.

Tenofovir disoproxil fumarate/emtricitabine plus ritonavir-boosted lopinavir or cobicistat-boosted elvitegravir as a single-tablet regimen for HIV post-exposure prophylaxis.

Objectives: To assess HIV-1 post-exposure prophylaxis (PEP) non-completion at day 28, comparing ritonavir-boosted lopinavir versus cobicistat-boosted elvitegravir as a single-tablet regimen (STR), using tenofovir disoproxil fumarate/emtricitabine with both of these therapies. Methods: A prospective, open, randomized clinical trial was performed. Individuals attending the emergency room due to potential sexual exposure to HIV and who met criteria for PEP were randomized 1:3 into two groups receiving either 400/100 mg of lopinavir/ritonavir (n = 38) or 150/150 mg of elvitegravir/cobicistat (n = 119), with both groups also receiving 245/200 mg of tenofovir disoproxil fumarate/emtricitabine. Five follow-up visits were scheduled at days 1, 10, 28, 90 and 180. The primary endpoint was PEP non-completion at day 28. Secondary endpoints were adherence, adverse effects and rate of seroconversions. Clinical trials.gov number: NCT08431173. Results: Median age was 32 years and 95% were males. PEP non-completion at day 28 was 36% (n = 57), with a trend to be higher in the lopinavir/ritonavir arm [lopinavir/ritonavir 47% (n = 18) versus elvitegravir/cobicistat 33% (n = 39), P = 0.10]. We performed a modified ITT analysis including only those patients who attended on day 1. PEP non-completion in this subgroup was higher in the lopinavir/ritonavir arm than in the elvitegravir/cobicistat arm (33% versus 15%, respectively, P = 0.04). Poor adherence was significantly higher in the lopinavir/ritonavir arm versus the elvitegravir/cobicistat arm (47% versus 9%, respectively, P < 0.0001). Adverse events were reported by 73 patients (59%), and were significantly more common in the lopinavir/ritonavir arm (90% versus 49%, P = 0.0001). A seroconversion was observed in the elvitegravir/cobicistat arm in a patient with multiple exposures before and after PEP. Conclusions: A higher PEP non-completion, poor adherence and adverse events were observed in patients allocated to the lopinavir/ritonavir arm, suggesting that STR elvitegravir/cobicistat is a well-tolerated antiretroviral for PEP.

FACEHBI: A Prospective Study of Risk Factors, Biomarkers and Cognition in a Cohort of Individuals with Subjective Cognitive Decline. Study Rationale and Research Protocols.

BACKGROUND: Long-term longitudinal studies with multimodal biomarkers are needed to delve into the knowledge of preclinical AD. Subjective cognitive decline has been proposed as a risk factor for the development of cognitive impairment. Thus, including individuals with SCD in observational studies may be a cost-effective strategy to increase the prevalence of preclinical AD in the sample. OBJECTIVES: To describe the rationale, research protocols and baseline characteristics of participants in the Fundació ACE Healthy Brain Initiative (FACEHBI). DESIGN: FACEHBI is a clinical trial (EudraCT: 2014-000798-38) embedded within a long-term observational study of individuals with SCD. SETTING: Participants have been recruited at the memory clinic of Fundació ACE (Barcelona) from two different sources: patients referred by a general practitioner and individuals from an Open House Initiative. PARTICIPANTS: 200 individuals diagnosed with SCD with a strictly normal performance in a comprehensive neuropsychological battery. MEASUREMENTS: Individuals will undergo an extensive neuropsychological protocol, risk factor assessment and a set of multimodal biomarkers including florbetaben PET, structural and functional MRI, diffusion tensor imaging, determination of amyloid species in plasma and neurophthalmologic assessment with optical coherence tomography. RESULTS: Two hundred individuals have been recruited in 15 months. Mean age was 65.9 years; mean MMSE was 29.2 with a mean of 14.8 years of education. CONCLUSIONS: FACEHBI is a long-term study of cognition, biomarkers and lifestyle that has been designed upon an innovative symptom-based approach using SCD as target population. It will shed light on the pathophysiology of preclinical AD and the role of SCD as a risk marker for the development of cognitive impairment.

Visual hallucinations in patients with acute stroke: a prospective exploratory study.

BACKGROUND AND PURPOSE: The incidence, underlying physiopathology, features and association with lesion topography of visual hallucinations in acute stroke have scarcely been investigated. METHODS: Patients with a diagnosis of acute stroke (ischaemic or haemorrhagic) in any vascular territory, admitted within 24 h after the onset of symptoms, were consecutively included in the study. Patients with a previous history of psychosis or cognitive impairment were excluded. They and/or their caregivers answered a structured hallucination and sleep questionnaire at admission, within the first 15 days and at the clinical follow-up 3-6 months after discharge. Lesion location (IMAIOS online atlas) and leukoaraiosis (Wahlund scale) were determined by magnetic resonance imaging or computed tomography scan. Subsets of patients also underwent a neuropsychological evaluation (N = 50) and an electroencephalogram (N = 33) before discharge. RESULTS: In all, 77 patients with a mean age of 71 ± 12 years were included of whom 57.1% were men. The incidence of visual hallucinations was 16.7%. These hallucinations were mostly complex, in black and white and self-limited. The appearance of hallucinations was not influenced by age, sex, neuropsychological performance during admission or modified Rankin scale score at discharge. Visual hallucinations were associated with occipital cortex lesions (P = 0.04), and with sleep disturbances during and before admission (P = 0.041 and P = 0.03 respectively). CONCLUSIONS: Visual hallucinations are relatively frequent in patients with acute stroke and they are self-limited. Patients with occipital lesions and sleep disturbances are more likely to suffer them.

Infecciones de transmisión sexual: experiencia de una consulta multidisciplinar en un hospital terciario (2010-2013) / Sexually Transmitted Infections: Experience in a Multidisciplinary Clinic in a Tertiary Hospital (2010-2013)

INTRODUCCIÓN: Las infecciones de transmisión sexual son un motivo de consulta creciente en nuestro medio. El objetivo de este trabajo es describir y analizar las características epidemiológicas, conductuales, clínicas y microbiológicas de los pacientes registrados en una unidad de infecciones de transmisión sexual de un hospital terciario. MÉTODOS: Estudio descriptivo, retrospectivo y unicéntrico realizado en una unidad multidisciplinar especializada en infecciones de transmisión sexual de un hospital terciario entre 2010 y 2013. Se recogieron datos epidemiológicos, clínicos y conductuales mediante entrevista oral abierta y cuestionario estandarizado, y se llevó a cabo la obtención de muestras para estudio microbiológico. RESULTADOS: Se estudiaron 546 pacientes, de los cuales fueron 96% varones, 41% infectados por el VIH, 56% hombres que tienen sexo con hombres. Los motivos de consulta más prevalentes fueron: uretritis, úlceras genitales y/o anales/perianales, proctitis, úlceras orales, contacto sexual de persona con ITS conocida y contacto sexual de riesgo. Los diagnósticos microbiológicos más frecuentes fueron: Neisseria gonorrhoeae en uretritis, Treponema pallidum en úlceras genitales y/o anales/perianales y Chlamydia trachomatis serovares de linfogranuloma venéreo en proctitis. Las principales ITS estudiadas fueron más prevalentes en varones homosexuales e infectados por el VIH. CONCLUSIÓN: Se confirma el incremento en la incidencia de las infecciones de transmisión sexual en los últimos años y las características epidemiológicas de la epidemia VIH/ITS de nuestro entorno

INTRODUCTION: The number of consultations for sexually transmitted infections (STIs) is increasing in Spain. The aim of this study was to describe and analyze the epidemiological, behavioral, clinical, and microbiological characteristics of patients registered at the STI unit of a tertiary hospital. METHODS: This was a retrospective, single-center descriptive study carried out between 2010 and 2013 in a multidisciplinary unit specialized in STIs, situated in a tertiary hospital. Epidemiological, clinical, and behavioral data were gathered using a face-to-face interview and a standardized questionnaire. Samples were collected for microbiology analysis. RESULTS: The study included 546 patients: 96% were men, 41% had human immunodeficiency virus (HIV) infection, and 56% were men who have sex with men. The reasons for consultation were the following: urethritis; genital, anal, or perianal ulcers; proctitis; oral ulcers; sexual contact with a person with a known STI; and high-risk sexual contact. The most common microbiological diagnoses were Neisseria gonorrhoeae in urethritis, Treponema pallidum in genital and anal or perianal ulcers, and Chlamydia trachomatis lymphogranuloma venereum serovars in proctitis. The highest prevalences of the main STIs studied occurred in homosexual men with HIV infection. CONCLUSION: This study confirms the increase in the incidence of STIs in recent years and the epidemiological characteristics of the HIV/STI epidemic in Spain

Sexually Transmitted Infections: Experience in a Multidisciplinary Clinic in a Tertiary Hospital (2010-2013).

INTRODUCTION: The number of consultations for sexually transmitted infections (STIs) is increasing in Spain. The aim of this study was to describe and analyze the epidemiological, behavioral, clinical, and microbiological characteristics of patients registered at the STI unit of a tertiary hospital. METHODS: This was a retrospective, single-center descriptive study carried out between 2010 and 2013 in a multidisciplinary unit specialized in STIs, situated in a tertiary hospital. Epidemiological, clinical, and behavioral data were gathered using a face-to-face interview and a standardized questionnaire. Samples were collected for microbiology analysis. RESULTS: The study included 546 patients: 96% were men, 41% had human immunodeficiency virus (HIV) infection, and 56% were men who have sex with men. The reasons for consultation were the following: urethritis; genital, anal, or perianal ulcers; proctitis; oral ulcers; sexual contact with a person with a known STI; and high-risk sexual contact. The most common microbiological diagnoses were Neisseria gonorrhoeae in urethritis, Treponema pallidum in genital and anal or perianal ulcers, and Chlamydia trachomatis lymphogranuloma venereum serovars in proctitis. The highest prevalences of the main STIs studied occurred in homosexual men with HIV infection. CONCLUSION: This study confirms the increase in the incidence of STIs in recent years and the epidemiological characteristics of the HIV/STI epidemic in Spain.

[EVALUATION OF SEDATION USING THE RICHMOND AGITATION SEDATION SCALE IN PATIENTS WITH PROLONGED MECHANICAL VENTILATION]. / Evaluación de la sedación mediante la escala Richmond Agitation Sedation Scale. EN PACIENTES CON VENTILACIÓN MECÁNICA DE LARGA DURACIÓN.

INTRODUCTION: Sedation is monitored to avoid both under- and oversedation. OBJECTIVES: Determine the most prevalent sedation levels in the ICU according to RASS categories and whether treatment is individualized on the basis of these scores. METHODS: Prospective cohort study of patients connected to mechanical ventilation ≥ 96 hours in the intensive care unit between January 1 and August 31. Daily assessments were recorded in the intensive care unit, together with sedoanalgesic treatment, ventilation modes, or vital signs. RESULTS: We analyzed 1021 RASS scores collected over a total of 220 MV days, categorized in the following ranges: 404 (39.6%) deep sedation, 474 (46.4%) conscious sedation, and 54 (5.3%) agitation; 89 (8.7%) were missing scores. Patients receiving continuous sedoanalgesia were more likely to be in the deep sedation than conscious sedation range (87.1% vs. 32.3%, p < 0.001). Analysis of patients under continuous sedation and in ventilation mode found more changes in the conscious sedation range than in deep sedation (42.5% vs. 22.3% and 12.6% vs. 2.9%, respectively; p < 0.001 in both cases). In conscious sedation range there was increased use of opiates in bolus (6.4%). CONCLUSIONS: Deep sedation was clearly prevalent in patients with mechanical ventilation under continuous sedation, with few changes in ventilation mode, because it is prevalent control ventilation mode and no changes in sedonalagesic perfusion in that range.

Evaluación de la sedación mediante la escala Richmond Agitation Sedation Scale en pacientes con ventilación mecánica de larga duración / Evaluation of sedation using the Richmond Agitation Sedation Scale in patients with prolonged mechanical ventilation

Introducción. Monitorizar la sedación es necesario para evitar la infra o sobresedación. Objetivos. Evaluar los niveles de sedación más prevalentes en la UCI de acuerdo a las categorías de la escala RASS y valorar si el tratamiento es individualizado. Métodos. Estudio prospectivo de cohortes en pacientes conectados a ventilación mecánica ≥ 96 horas por un periodo de 7 meses. Registro de los valores RASS, junto con el tratamiento sedoanalgésico, modos de ventilación mecánica y signos vitales. Resultados. Se analizaron 1021 valores RASS de 220 días de ventilación mecánica, categorizados en los siguientes rangos: 404 (39.6 %) sedación profunda, 474 (46.4 %) sedación consciente y 54 (5.3 %) agitación. Hubo 89 (8.7 %) valores faltantes. Los pacientes que recibieron sedoanalgesia continua estuvieron más tiempo en sedación profunda que consciente (87.1 % frente a 32.3 %, p < 0.001) y se realizaron más cambios de tratamiento en la sedación consciente que en la profunda, tanto en cuanto a sedoanalgesia en perfusión (42.5 % frente a 22.3 %, p < 0.001) como según modo ventilatorio (12.6 % frente a 2.9 %, p < 0.001). Para valores RASS en el rango de la sedación consciente había un incremento del uso de opiáceos en bolo (6.4 %). Conclusiones. La sedación profunda es predominante en pacientes con sedoanalgesia, con pocos cambios en el modo ventilatorio, ya que prevalece la modalidad controlada y no hay cambios en la perfusión de sedoanalgesia (AU)

Introduction. Sedation is monitored to avoid both under- and oversedation. Objectives. Determine the most prevalent sedation levels in the ICU according to RASS categories and whether treatment is individualized on the basis of these scores. Methods. Prospective cohort study of patients connected to mechanical ventilation ≥ 96 hours in the intensive care unit between January 1 and August 31. Daily assessments were recorded in the intensive care unit, together with sedoanalgesic treatment, ventilation modes, or vital signs. Results. We analyzed 1021 RASS scores collected over a total of 220 MV days, categorized in the following ranges: 404 (39.6 %) deep sedation, 474 (46.4 %) conscious sedation, and 54 (5.3 %) agitation; 89 (8.7 %) were missing scores. Patients receiving continuous sedoanalgesia were more likely to be in the deep sedation than conscious sedation range (87.1 % vs. 32.3 %, p < 0.001). Analysis of patients under continuous sedation and in ventilation mode found more changes in the conscious sedation range than in deep sedation (42.5 % vs. 22.3 % and 12.6 % vs. 2.9 %, respectively; p < 0.001 in both cases). In conscious sedation range there was increased use of opiates in bolus (6.4 %). Conclusions. Deep sedation was clearly prevalent in patients with mechanical ventilation under continuous sedation, with few changes in ventilation mode, because it is prevalent control ventilation mode and no changes in sedonalagesic perfusion in that range (AU)

Early lipid changes with atazanavir/ritonavir or darunavir/ritonavir.

OBJECTIVES: Ritonavir-boosted atazanavir and darunavir are protease inhibitors that are recommended for initial treatment of HIV infection because each has shown better lipid effects and overall tolerability than ritonavir-boosted lopinavir. The extent to which lipid effects and overall tolerability differ between treatments with atazanavir and darunavir and whether atazanavir-induced hyperbilirubinaemia may result in more favourable metabolic effects are issues that remain to be resolved. METHODS: A 96-week randomized clinical trial was carried out. The primary endpoint was change in total cholesterol at 24 weeks. Secondary endpoints were changes in lipids other than total cholesterol, insulin sensitivity, total bilirubin, estimated glomerular filtration rate, and CD4 and CD8 cell counts, and the proportion of patients with plasma HIV RNA < 50 HIV-1 RNA copies/mL and study drug discontinuation because of adverse effects at 24 weeks. Analyses were intent-to-treat. RESULTS: One hundred and seventy-eight patients received once-daily treatment with either atazanavir/ritonavir (n = 90) or darunavir/ritonavir (n = 88) plus tenofovir/emtricitabine. At 24 weeks, mean total cholesterol had increased by 7.26 and 11.47 mg/dL in the atazanavir/ritonavir and darunavir/ritonavir arms, respectively [estimated difference -4.21 mg/dL; 95% confidence interval (CI) -12.11 to +3.69 mg/dL; P = 0.75]. However, the ratio of total to high-density lipoprotein (HDL) cholesterol tended to show a greater decrease with atazanavir/ritonavir compared with darunavir/ritonavir (estimated difference -1.02; 95% CI -2.35 to +0.13; P = 0.07). Total bilirubin significantly increased with atazanavir/ritonavir (estimated difference +1.87 mg/dL; 95% CI +1.58 to +2.16 mg/dL; P < 0.01), but bilirubin changes were not associated with lipid changes. Secondary endpoints other than total bilirubin were not significantly different between arms. CONCLUSIONS: Atazanavir/ritonavir and darunavir/ritonavir plus tenofovir/emtricitabine did not show significant differences in total cholesterol change or overall tolerability at 24 weeks. However, there was a trend towards a lower total to HDL cholesterol ratio with atazanavir/ritonavir and this effect was unrelated to bilirubin.

Edulcorantes no nutritivos, riesgos, apetito y ganancia de peso / Non-nutritive sweeteners risks, appetite and weight gain

Artificial sweeteners are substances that provide energy and are added to foods to provide sweetness, increasing the pleasure of eating. The aim of the following review is to report on the current literature regarding artificial sweeteners, risks related to consumption, and possible effects on appetite and weight gain. Since the introduction of the artificial sweeteners, the media have reported the potential risks of cancer, which has undermined the sense of public safety. The role of sweeteners on cancer risk has been widely debated in recent decades. Recent studies indicate no adverse effects on the consumption of saccharin, aspartame, acesulfame k and other sweeteners. This includes data on cancers of the stomach, pancreas and endometrium. Today many artificial sweeteners are combined in current products, the carcinogenic risk of a single substance is difficult to assess. Consumption of sweet flavors in the absence of calories produced significantly different effects compared to the consumption of sweet flavors associated with calories, and over time these effects may contribute to a positive energy balance and increased body weight gain.

Los edulcorantes artificiales son sustancias que no aportan energía y que se agregan a los alimentos para proporcionarles un sabor dulce, incrementando el placer por comer. El objetivo fue revisar la literatura sobre el estado del arte de los edulcorantes artificiales, riesgos de su consumo, posibles efectos en el apetito y ganancia de peso. Desde su introducción, los medios de comunicación han informado sobre los riesgos potenciales de cáncer, lo que ha contribuido a socavar el sentido de la opinión pública de la seguridad. El papel de los edulcorantes en el riesgo de cáncer ha sido ampliamente debatido durante las últimas décadas. Recientes estudios no muestran efectos adversos sobre el consumo de sacarina, aspartame, acesulfamo k y otros edulcorantes, incluyendo datos sobre los cánceres de estómago, páncreas y endometrio. Actualmente muchos edulcorantes artificiales se combinan en los productos actuales, el riesgo cancerígeno de una sustancia única es difícil de evaluar. El consumo de los sabores dulces en la ausencia de calorías produce efectos significativamente diferentes en comparación con el consumo de los sabores dulces asociados con las calorías, y con el tiempo estos efectos pueden contribuir a un balance energético positivo y al aumento de aumento de peso corporal.

Variable induction of vitellogenin genes in the varroa mite, Varroa destructor (Anderson & Trueman), by the honeybee, Apis mellifera L, host and its environment.

Transcript levels of vitellogenins (Vgs) in the varroa mite, Varroa destructor (Anderson & Trueman), were variably induced by interactions between the developing honeybee, Apis mellifera L, as a food source and the capped honeybee cell environment. Transcripts for two Vgs of varroa mites were sequenced and putative Vg protein products characterized. Sequence analysis of VdVg1 and VdVg2 proteins showed that each had greater similarity with Vg1 and Vg2 proteins from ticks, respectively, than between themselves and were grouped separately by phylogenetic analyses. This suggests there was a duplication of the ancestral acarine Vg gene prior to the divergence of the mites and ticks. Low levels of transcript were detected in immature mites, males and phoretic females. Following cell invasion by phoretic females, VdVg1 and VdVg2 transcript levels were up-regulated after cell capping to a maximum at the time of partial cocoon formation by the honeybee. During oviposition the two transcripts were differentially expressed with higher levels of VdVg2 being observed. A bioassay based on assessing the transcript levels was established. Increases in VdVg1 and VdVg2 transcripts were induced experimentally in phoretic females when they were placed inside a cell containing an early metamorphosing last instar bee but not when exposed to the metamorphosing bee alone. The variable response of Vg expression to the food source as well as environmental cues within the capped cell demonstrates that perturbation of host-parasite interactions may provide avenues to disrupt the reproductive cycle of the varroa mites and prevent varroasis.

Aphysiologic performance on dynamic posturography in work-related patients.

It has been suggested that malingering should be suspected in patients suffering from dizziness or imbalance and who had a potential gain associated with insurance and worker's compensation claims. This study aimed to assess and compare the prevalence of aphysiologic performance on computerized dynamic posturography (CDP) in patients with the potential for secondary gain using a retrospective review of two groups of patients: work-related patients referred for dizziness and/or imbalance (Group 1) were compared against a group of patients with complaints of dizziness or imbalance, who had no history of work-related injury, or litigation procedures (Group 2). CDP and videonystagmography (VNG) were carried out in all patients. The Sensory Organization Test summaries were scored as normal, aphysiologic, or vestibular using the scoring method published by Cevette et al. in Otolaryngol Head Neck Surg 112:676-688 (1995). 24 out of 88 (27%) patients had aphysiologic CDP in Group 1 and 9 out of 51 (18%) in Group 2 but these differences were not significant (p > 0.05). Definite signs of vestibular dysfunction were found in 12 out of 24 (50%) of patients with aphysiologic performance in Group 1 although the presence of VNG abnormalities was significantly higher (p = 0.005) in Group 2. The hypothesis that the occupational group could show a significantly higher rate of aphysiologic results than a control group is not confirmed. Furthermore, VNG abnormalities were found in 50% of the work-related cases with non organic sway patterns. These results suggest that patient's complaints should be considered genuine in work-related cases and due caution exercised when evaluating aphysiologic CDP patterns.

Resultados de pruebas de control postural y función vestibular en 51 pacientes con antecedente de latigazo cervical y síntomas de vértigo e inestabilidad / Results of balance control and vestibular function tests in 51 patients with whiplash injury complaining of dizziness and imbalance

Introducción y objetivos. El vértigo y la inestabilidad tienen una importante implicación médico-legal en el paciente con antecedente de latigazo cervical (LC). En estos casos la posturografía dinámica computarizada (PDC) aporta información adicional a las pruebas vestibulares estándar y tiene descritos patrones compatibles con escasa colaboración o falta de sinceridad al esfuerzo, también denominados afisiológicos. El objetivo de este trabajo es valorar las características de las pruebas de equilibrio y función vestibular en pacientes con LC y especialmente, los resultados afisiológicos. Material y métodos. Estudio retrospectivo de pacientes con antecedente de LC con vértigo y/o inestabilidad. Se realizó videonistagmografía (VNG) y PDC. Los resultados de la prueba de organización sensorial (SOT) se valoraron como normales, vestibulares o afisiológicos usando el método de cálculo publicado por Cevette et al. en 1995. Resultados. Cincuenta y uno pacientes (24 varones, 27 mujeres); edad media: 42,2 años; tiempo de evolución medio: 3,8 m; PDC afisiológica: 13 (25,5%); PDC vestibular: 9 (17,6%); PDC normal: 29 (56,9%); VNG normal: 29 (56,9%); VNG alterada: 22 (43,1%); VNG vestibular: (n=11); VNG central: (n=6), y VNG cervical: (n=5). En el 46,2% de pacientes con PDC afisológica la VNG estaba alterada. Conclusiones. La prevalencia de pruebas afisiológicas en la PDC en el LC es relativamente elevada sin que deba suponerse simulación o exageración ya que en muchos casos existen signos objetivos de disfunción vestibular. Sería recomendable realizar pruebas de función vestibular a los pacientes con LC con síntomas vertiginosos. La rehabilitación vestibular podría ser de utilidad en estos casos (AU)

Introduction. The medical legal implications of dizziness and imbalance among patients with whiplash-associated disorders (WAD) are important. In these cases, Computerized Dynamic Posturography (CDP) provides information to standard vestibular tests and patterns consistent with scarce collaboration or lack of sincerity on efforts have been described. Objectives. This work has aimed to assess the prevalence of altered balance and vestibular function tests in patients with whiplash injury, and especially the aphysiologic results. Material and methods. A retrospective review of patients with whiplash injury referred for assessment of dizziness and/or imbalance was carried out. Standard videonistagmophgraphy (VNG) assessment including CDP was performed in all patients. The Sensory Organization Test (SOT) summaries were scored as normal, aphysiologic, or vestibular using the scoring method published by Cevette et al. in 1995. Results. The study included 51 patients (24 men, 27 women) with mean age: 42.2 years. Mean evolution time was 3.8 m. Aphysiologic CDP 13 (25.5%); vestibular CDP 9 (17.6%); normal CDP 29 (56.9%). Normal VNG 29 (56.9%); altered VNG in 22 (43.1%): vestibular VNG (n=11); central VNG (n=6); cervical VNG (n=5). VNG was altered in 46.2% of patients with aphysiologic CDP. Conclusions. The prevalence of aphysiologic results on CDP among whiplash injury patients is relatively high, however, this should not necessarily be consider to be related to malingering or exaggeration since objective signs of vestibular dysfunction are found in many cases. Thus, we recommend these tests should be done in whiplash injury patients complaining of dizziness and imbalance. Vestibular rehabilitation could be of interest in the recovery of these patients (AU)