Tiempos de evaluación ética de protocolos de investigación: resultados de un estudio observacional / Time of ethics review of research proposals: results of an observational study

La evaluación de protocolos de investigación por Comités de Ética en Investigación (CEI), esencialpara garantizar la protección de los participantes, se gestiona en la Ciudad de Buenos Aires a través laplataforma electrónica PRIISA.BA desde enero del 2020. El objetivo del presente estudio fue describirlos tiempos de evaluación ética, su evolución temporal, y los predictores de su duración. Se realizóun estudio observacional que incluyó todos los protocolos evaluados entre enero de 2020 y septiem-bre de 2021. Se calcularon los tiempos al dictamen final y a la primera observación. Se evaluaron lastendencias temporales de los tiempos, y la asociación multivariada entre éstos y características de losprotocolos y de los CEI. Se incluyeron 2781 protocolos evaluados en 62 CEI. La mediana de tiempo aldictamen final fue de 29.11 (RIQ 11.29 a 63.35) días, y del tiempo a la primera observación de 8.92(RIQ 2.05 a 18.18) días. Los tiempos se redujeron significativamente a lo largo del período de estudio.Detectamos como variables independientemente asociadas a menor tiempo a la temática COVID, tenerfinanciamiento y el número de centros a realizarse el estudio y haber sido evaluado en un CEI con másde 10 miembros. La realización de observaciones al protocolo se asoció a mayor tiempo. Los resultadosdel presente trabajo sugieren que los tiempos de evaluación ética se redujeron durante el período deestudio. Además, se identificaron variables asociadas con los tiempos, que podrían ser objeto de inter-venciones para mejorar el proceso.(AU)

The review of research protocols by Research Ethics Committees (RECs), essential to ensure theprotection of participants, has been managed in the City of Buenos Aires through the PRIISA.BA elec-tronic platform since January 2020. The aim of the present study was to describe ethical review times,their temporal evolution, and predictors of their duration. We conducted an observational study thatincluded all the protocols reviewed between January 2020 and September 2021. Times to approvaland to first observation were calculated. Temporal trends in times, and the multivariate associationbetween these and protocol and IRB characteristics were evaluated. 2,781 protocols reviewed in 62RECs were included. The median time to approval was 29.11 (RIQ 11.29 to 63.35) days, and time to firstobservation was 8.92 (RIQ 2.05 to 18.18) days. The times were significantly reduced throughout thestudy period. We detected as variables independently associated with shorter time to approval to bea COVID proposal, having funding and the number of centers to perform the study and having beenreviewed by an RECs with more than 10 members. Making observations to the protocol was associatedwith more time. The results of the present work suggest that ethical review times were reduced duringstudy period. In addition, variables associated with time were identified that could be the object ofinterventions to improve the process.(AU)

Light and focused ion beam microscopy workflow for resin-embedded tissues.

Although the automated image acquisition with the focused ion beam scanning electron microscope (FIB-SEM) provides volume reconstructions, volume analysis of large samples remains challenging. Here, we present a workflow that combines a modified sample protocol of the classical transmission electron microscope with FIB-SEM volume imaging. The proposed workflow enables efficient 3D structural surveys of rabbit ovaries collected at consecutive developmental stages. The precise trimming of the region of interest adds the time dimension to the volume, constructing a virtual 4D electron microscopy. We found filopodia-like processes emitted by oocyte cysts allowing contact between oocytes not previously observed.

Assessment of an electronic system for research ethics committees document management: An observational study.

Since 1 January 2020, the Central Research Ethics Committee of the Health Ministry implemented PRIISA.BA, an in-house developed electronic system for online submission of health research applications to the 63 public and private research ethics committees (RECs) of Buenos Aires City, Argentina. This study though to compare the times to first review and the time to approval among applications submitted prior to PRIISA.BA and thereafter, across public RECs. All public RECs of the city were invited to participate. Overall, 453 applications from 10 RECs (242 pre- and 211 post-PRIISA.BA) were available for the analyses. There was a decrease in the time to first review and an increase in the time to approval after PRIISA.BA implementation. The increase in time to approval was transient and limited to the first three months. The results were consistent with analyses limited to non-COVID applications. Our results show an increase in the times to approval after the implementation of an electronic system for online submission of health research applications that, although transient, was significant. These data could be relevant to other RECs implementing this technology since it emphasizes the need of monitoring potential unnecessary delays in reviews during the critical initial period.

Variability in Ethics Review for Multicenter Protocols in Buenos Aires, Argentina. An Observational Study.

It has been reported that significant variability in the ethics review process affects multisite studies. We analyzed 1,305 applications for multicenter studies (409 unique protocols), from 1st January 2020 to 20th September 2021. We examined the variability in the times to approval and the first observation and the variation in the level of risk assigned. The median [IQR] variabilities were 42.19 [15.23-82.36] days and 8.00 [3.12-16.68] days, for the times to approval and to the first observation, respectively. There was disagreement in the level of risk assigned by the Research Ethics Committee (REC) in 24.0% of cases. Independent predictors of variability included the number of REC members. In our study, we found substantial variability in the ethics review process among health research protocols. Also, we describe methods to readily measure the delays and the variations in the ethics review process.

Neonatal infrared thermography images in the hypothermic ruminant model: Anatomical-morphological-physiological aspects and mechanisms for thermoregulation.

Hypothermia is one factor associated with mortality in newborn ruminants due to the drastic temperature change upon exposure to the extrauterine environment in the first hours after birth. Ruminants are precocial whose mechanisms for generating heat or preventing heat loss involve genetic characteristics, the degree of neurodevelopment at birth and environmental aspects. These elements combine to form a more efficient mechanism than those found in altricial species. Although the degree of neurodevelopment is an important advantage for these species, their greater mobility helps them to search for the udder and consume colostrum after birth. However, anatomical differences such as the distribution of adipose tissue or the presence of type II muscle fibers could lead to the understanding that these species use their energy resources more efficiently for heat production. The introduction of unconventional ruminant species, such as the water buffalo, has led to rethinking other characteristics like the skin thickness or the coat type that could intervene in the thermoregulation capacity of the newborn. Implementing tools to analyze species-specific characteristics that help prevent a critical decline in temperature is deemed a fundamental strategy for avoiding the adverse effects of a compromised thermoregulatory function. Although thermography is a non-invasive method to assess superficial temperature in several non-human animal species, in newborn ruminants there is limited information about its application, making it necessary to discuss the usefulness of this tool. This review aims to analyze the effects of hypothermia in newborn ruminants, their thermoregulation mechanisms that compensate for this condition, and the application of infrared thermography (IRT) to identify cases with hypothermia.

Transient Receptor Potential (TRP) and Thermoregulation in Animals: Structural Biology and Neurophysiological Aspects.

This review presents and analyzes recent scientific findings on the structure, physiology, and neurotransmission mechanisms of transient receptor potential (TRP) and their function in the thermoregulation of mammals. The aim is to better understand the functionality of these receptors and their role in maintaining the temperature of animals, or those susceptible to thermal stress. The majority of peripheral receptors are TRP cation channels formed from transmembrane proteins that function as transductors through changes in the membrane potential. TRP are classified into seven families and two groups. The data gathered for this review include controversial aspects because we do not fully know the mechanisms that operate the opening and closing of the TRP gates. Deductions, however, suggest the intervention of mechanisms related to G protein-coupled receptors, dephosphorylation, and ligands. Several questions emerge from the review as well. For example, the future uses of these data for controlling thermoregulatory disorders and the invitation to researchers to conduct more extensive studies to broaden our understanding of these mechanisms and achieve substantial advances in controlling fever, hyperthermia, and hypothermia.

Retrospective Analysis of EEG in Patients With COVID-19: EEG Recording in Acute and Follow-up Phases.

Background. Interest in electroencephalographic (EEG) coronavirus disease 2019 (COVID-19) findings has been growing, especially in the search for a specific-features EEG of encephalopathy. Methods. We made a retrospective analysis of 29 EEGs recorded in 15 patients with COVID-19 and neurological symptoms. We classified the EEGs as "Acute EEG" and "follow-up EEG." We did a statistical analysis between voltage and respiratory status of the patient, stay or not in the intensive care unit (ICU), days of stay in the ICU, sedative drugs, pharmacological treatment, type of symptoms predominating, and outcome. Results. We found EEG abnormalities in all patients studied. We observed the amplitude of background <20 µV at 93% of "acute EEG," versus only 21.4% of "follow-up EEG." The average voltage went from 12.33 ± 5.09 µV in the acute EEGs to 32.8 ± 20.13 µV in the follow-up EEGs. A total of 60% of acute EEGs showed an intermittent focal rhythmic. We have not found a statistically significant association between voltage of acute EEG and nonneurological clinical status (including respiratory) that may interfere with the EEG findings. Conclusions. Nonspecific diffuse slowing EEG pattern in COVID-19 is the most common finding reported, but we found in addition to that, as a distinctive finding, low voltage EEG, that could explain the low prevalence of epileptic activity published in these patients. A metabolic/hypoxic mechanism seems unlikely on the basis of our EEG findings. This pattern in other etiologies is reminiscent of severe encephalopathy states associated with poor prognosis. However, an unreactive low voltage pattern in COVID-19 patients is not necessarily related to poor prognosis.

Experimental Applications and Factors Involved in Validating Thermal Windows Using Infrared Thermography to Assess the Health and Thermostability of Laboratory Animals.

Evaluating laboratory animals' health and thermostability are fundamental components of all experimental designs. Alterations in either one of these parameters have been shown to trigger physiological changes that can compromise the welfare of the species and the replicability and robustness of the results obtained. Due to the nature and complexity of evaluating and managing the species involved in research protocols, non-invasive tools such as infrared thermography (IRT) have been adopted to quantify these parameters without altering them or inducing stress responses in the animals. IRT technology makes it possible to quantify changes in surface temperatures that are derived from alterations in blood flow that can result from inflammatory, stressful, or pathological processes; changes can be measured in diverse regions, called thermal windows, according to their specific characteristics. The principal body regions that were employed for this purpose in laboratory animals were the orbital zone (regio orbitalis), auricular pavilion (regio auricularis), tail (cauda), and the interscapular area (regio scapularis). However, depending on the species and certain external factors, the sensitivity and specificity of these windows are still subject to controversy due to contradictory results published in the available literature. For these reasons, the objectives of the present review are to discuss the neurophysiological mechanisms involved in vasomotor responses and thermogenesis via BAT in laboratory animals and to evaluate the scientific usefulness of IRT and the thermal windows that are currently used in research involving laboratory animals.

Efficacy and Function of Feathers, Hair, and Glabrous Skin in the Thermoregulation Strategies of Domestic Animals.

The objective of this review is to describe and analyze the effect of feathers, hair, and glabrous (hairless) skin on the thermoregulation of domestic and endotherm animals, especially concerning the uses and scope of infrared thermography (IRT), scientific findings on heat and cold stress, and differences among species of domestic animals. Clinical medicine considers thermoregulation a mechanism that allows animals to adapt to varying thermal environmental conditions, a process in which the presence of feathers, hair, or glabrous skin influences heat loss or heat retention, respectively, under hot and cold environmental conditions. Evaluating body temperature provides vital information on an individual's physiological state and health status since variations in euthermia maintenance in vertebrates reflect a significant cellular metabolism deviation that needs to be assessed and quantified. IRT is a non-invasive tool for evaluating thermal responses under thermal stress conditions in animals, where the presence or absence of feathers, hair, and glabrous skin can affect readings and the differences detected. Therefore, anatomical regions, the characteristics of feathers, hair, glabrous skin such as structure, length, color, and extension, and strategies for dissipating or retaining heat together constitute a broad area of opportunity for future research into the phenomena of dermal thermoregulation in domestic species.

Current Advances in Assessment of Dog's Emotions, Facial Expressions, and Their Use for Clinical Recognition of Pain.

Animals' facial expressions are involuntary responses that serve to communicate the emotions that individuals feel. Due to their close co-existence with humans, broad attention has been given to identifying these expressions in certain species, especially dogs. This review aims to analyze and discuss the advances in identifying the facial expressions of domestic dogs and their clinical utility in recognizing pain as a method to improve daily practice and, in an accessible and effective way, assess the health outcome of dogs. This study focuses on aspects related to the anatomy and physiology of facial expressions in dogs, their emotions, and evaluations of their eyebrows, eyes, lips, and ear positions as changes that reflect pain or nociception. In this regard, research has found that dogs have anatomical configurations that allow them to generate changes in their expressions that similar canids-wolves, for example-cannot produce. Additionally, dogs can perceive emotions similar to those of their human tutors due to close human-animal interaction. This phenomenon-called "emotional contagion"-is triggered precisely by the dog's capacity to identify their owners' gestures and then react by emitting responses with either similar or opposed expressions that correspond to positive or negative stimuli, respectively. In conclusion, facial expressions are essential to maintaining social interaction between dogs and other species, as in their bond with humans. Moreover, this provides valuable information on emotions and the perception of pain, so in dogs, they can serve as valuable elements for recognizing and evaluating pain in clinical settings.

Clinical Applications and Factors Involved in Validating Thermal Windows Used in Infrared Thermography in Cattle and River Buffalo to Assess Health and Productivity.

Infrared thermography (IRT) is a non-ionizing, non-invasive technique that permits evaluating the comfort levels of animals, a topic of concern due to the growing interest in determining the state of health and welfare of production animals. The operating principle of IRT is detecting the heat irradiated in anatomical regions characterized by a high density of near-surface blood vessels that can regulate temperature gain or loss from/to the environment by modifying blood flow. This is essential for understanding the various vascular thermoregulation mechanisms of different species, such as rodents and ruminants' tails. The usefulness of ocular, nasal, and vulvar thermal windows in the orbital (regio orbitalis), nasal (regio nasalis), and urogenital (regio urogenitalis) regions, respectively, has been demonstrated in cattle. However, recent evidence for the river buffalo has detected discrepancies in the data gathered from distinct thermal regions in these large ruminants, suggesting a limited sensitivity and specificity when used with this species due to various factors: the presence of hair, ambient temperature, and anatomical features, such as skin thickness and variations in blood supplies to different regions. In this review, a literature search was conducted in Scopus, Web of Science, ScienceDirect, and PubMed, using keyword combinations that included "infrared thermography", "water buffalo", "river buffalo" "thermoregulation", "microvascular changes", "lacrimal caruncle", "udder", "mastitis", and "nostril". We discuss recent findings on four thermal windows-the orbital and nasal regions, mammary gland in the udder region (regio uberis), and vulvar in the urogenital region (regio urogenitalis)-to elucidate the factors that modulate and intervene in validating thermal windows and interpreting the information they provide, as it relates to the clinical usefulness of IRT for cattle (Bos) and the river buffalo (Bubalus bubalis).

Real life study of the use of omalizumab for pediatric patients with multiple food allergies

Background Multiple food allergies (MFAs) affect 30% of the child population with food allergy. The current treatment is the exclusion diet, which frequently affects the quality of life for these patients. The objective of the study was to describe the effect of omalizumab treatment in children diagnosed with MFAs who experienced frequent anaphylactic reactions and the impact on their quality of life. Material and methods A descriptive observational study. Patients with severe food restrictions and high-risk due to multiple episodes of anaphylaxis were included. The allergy was confirmed by compatible clinical, skin tests, positive specific IgE and oral food challenges (OFCs). Omalizumab treatment was initiated and the impact on the life quality of patients and their families was assessed using the validated Food Allergy Quality of Life Questionnaire-Parent Form. Results Five patients with an average age at diagnosis of 3.58 years (range between 1.5–7.9 years), were diagnosed with MFAs. All patients presented with anaphylaxis. All patients were treated with omalizumab between 2013 and 2019. Omalizumab treatment was initiated at a mean age of 6.05 years (range between 4.5–8.25 years). All patients have undergone OFC to reintroduce food successfully. 2 patients had their dose of omalizumab reduced by half, and 1 patient has had the time interval extended between administrations due to the maintenance of food tolerance. No immediate local or systemic adverse reactions were documented. Two patients have commenced omalizumab administration at home without incident. Conclusions Children with MFAs who are treated with omalizumab do not show reactions in response to most of the foods to which they previously had anaphylaxis. Consequently, these patients were able to significantly expand the variety of their diet, improving the life quality and avoid anaphylaxis following the inadvertent intake of these foods (AU)

Salzburg Criteria, A Useful Tool in Non-Convulsive Status Epilepticus Diagnosis: A Retrospective Study.

Introduction. Non-convulsive status epilepticus (NCSE) has been traditionally a challenging electroencephalographic (EEG) diagnosis. For this reason, Salzburg consensus criteria (SCC) have been proposed to facilitate correct diagnosis. Methods. We retrospectively reanalyzed 41 cases referred to our department (from 2016 to 2018) under the suspicion of NCSE. In this study, we compared the original description (standard criteria) versus the updated description (SCC) of the same EEG. Results. Originally, 15 patients were diagnosed as NCSE (37%) and 26 patients as no NCSE (63%), using the standard criteria. Then, we analyzed EEGs according to the SCC, which led to the following results: 9 patients fulfilled the criteria for definite NCSE (22%), 20 patients were diagnosed as possible NCSE (49%) and 12 patients were diagnosed as no NCSE (29%). Subsequently, when we analyze the outcome of possible NCSE cases, we note that 50% of these patients presented mild-poor outcome (neurological deficits, deceased). Indeed, we observed worse outcomes in patients previously diagnosed as no NCSE and untreated, specifically post-anoxic cases. Conclusions. Salzburg criteria seem to be a useful tool to support NCSE diagnosis, introducing the category of possible NCSE. In our study, we observed that it contributes to improving the prognosis and management of the patients. However, more prospective studies are needed to demonstrate the accuracy of SCC.

Management of Allergic Diseases During COVID-19 Outbreak.

PURPOSE OF REVIEW: The coronavirus disease 2019 (COVID-19) has challenged healthcare system capacities and safety for health care workers, reshaping doctor-patient interaction favoring e-Health or telemedicine. The pandemic situation may make difficult to prioritize patients with allergies diseases (AD), face-to-face evaluation, and moreover concern about the possible COVID-19 diagnosis, since COVID-19 shared many symptoms in common with AD. Being COVID-19 a novel disease, everyone is susceptible; there are some advances on vaccine and specific treatment. We evaluate existing literature on allergic diseases (AD): allergic rhinitis, asthma, food allergy, drug allergy, and skin allergy, and potential underlying mechanisms for any interrelationship between AD and COVID-19. RECENT FINDINGS: There is inconclusive and controversial evidence of the association between AD and the risk of adverse clinical outcomes of COVID-19. AD patients should minimize hospital and face-to-face visits, and those who have used biologics and allergen immunotherapy should continue the treatment. It is essential to wear personal protective equipment for the protection of health care workers. Social distancing, rational use of facemasks, eye protection, and hand disinfection for health care workers and patients deserve further attention and promotion. Teleconsultation during COVID-19 times for AD patients is very encouraging and telemedicine platform can provide a reliable service in patient care.

A comparative two-cohort study of pediatric patients with long term stay in ICUs.

During the last decades, the number of patients with long stay admissions (LSA) in PICU has increased. The purpose of this study was to identify factors associated with PICU LSA, assessing healthcare resources use and changes in the profile of these patients. A retrospective, observational, single-center study was carried out. Characteristics of LSA were compared between two periods (2006-2010 and 2011-2015). During the earlier period there were 2,118 admissions (3.9% of them LSA), whereas during the second period, there were 1,763 (5.4% of them LSA) (p = 0.025). LSA accounted for 33.7% PICU stay days during the first period and 46.7% during the second (p < 0.001). Higher use of non-invasive ventilation (80.2% vs. 37.8%, p = 0.001) and high-flow oxygen therapy (68.8% vs. 37.8%, p = 0.005) was observed in the 2011-2015 cohort, whereas the use of arterial catheter (77.1% vs. 92.6%, p = 0.005), continuous infusion of adrenaline (55.2% vs. 75.9%, p = 0.004), and hemoderivative transfusion (74% vs. 89.2%, p = 0.010) was less frequent. In the 2006-2010 cohort, hospital-acquired infections were more common (95.2% vs. 68.8%, p < 0.001) and mortality was higher (26.8% vs. 13.8%, p = 0.026). The number of long-stay PICU admissions have increased entailing an intensive use of healthcare resources. These patients have a high risk for complications and mortality.

Real life study of the use of omalizumab for pediatric patients with multiple food allergies.

BACKGROUND: Multiple food allergies (MFAs) affect 30% of the child population with food allergy. The current treatment is the exclusion diet, which frequently affects the quality of life for these patients. The objective of the study was to describe the effect of omalizumab treatment in children diagnosed with MFAs who experienced frequent anaphylactic reactions and the impact on their quality of life. MATERIAL AND METHODS: A descriptive observational study. Patients with severe food restrictions and high-risk due to multiple episodes of anaphylaxis were included. The allergy was confirmed by compatible clinical, skin tests, positive specific IgE and oral food challenges (OFCs). Omalizumab treatment was initiated and the impact on the life quality of patients and their families was assessed using the validated Food Allergy Quality of Life Questionnaire-Parent Form. RESULTS: Five patients with an average age at diagnosis of 3.58 years (range between 1.5-7.9 years), were diagnosed with MFAs. All patients presented with anaphylaxis. All patients were treated with omalizumab between 2013 and 2019. Omalizumab treatment was initiated at a mean age of 6.05 years (range between 4.5-8.25 years). All patients have undergone OFC to reintroduce food successfully. 2 patients had their dose of omalizumab reduced by half, and 1 patient has had the time interval extended between administrations due to the maintenance of food tolerance. No immediate local or systemic adverse reactions were documented. Two patients have commenced omalizumab administration at home without incident. CONCLUSIONS: Children with MFAs who are treated with omalizumab do not show reactions in response to most of the foods to which they previously had anaphylaxis. Consequently, these patients were able to significantly expand the variety of their diet, improving the life quality and avoid anaphylaxis following the inadvertent intake of these foods.

Chemosensory dysfunction in COVID-19 out-patients.

BACKGROUND: Since the outbreak in China due to coronavirus disease 2019 (COVID-19) various studies have been published describing olfactory and gustatory dysfunction (OGD). OBJECTIVE: The aim was to investigate the frequency and severity of OGD in SARS-CoV-2 (+) out-patients compared to controls with common cold/flu like symptoms and two negative RT-PCR. METHODS: A multicenter cross-sectional study on SARS-CoV-2-positive out-patients (n = 197) and controls (n = 107) from five Spanish Hospitals. Severity of OGD was categorized by visual analogue scale (VAS). Frequency and severity of the chemosensory impairment were analyzed. RESULTS: The frequencies of smell (70.1%) and taste loss (65%) were significantly higher among COVID-19 subjects than in the controls (20.6% and 19.6%, respectively). Simultaneous OGD was more frequent in the COVID-19 group (61.9% vs 10.3%) and they scored higher in VAS for severity of OGD than controls. In the COVID-19 group, OGD was predominant in young subjects 46.5 ± 14.5 and females (63.5%). Subjects with severe loss of smell were younger (42.7 years old vs 45.5 years old), and recovered later (median = 7, IQR = 5.5 vs median = 4, IQR = 3) than those with mild loss of smell. Subjects with severe loss of taste, recovered later in days (median = 7, IQR = 6 vs median = 2, IQR = 2), compared to those with mild loss. CONCLUSION: OGD is a prevalent symptom in COVID-19 subjects with significant differences compared to controls. It was predominant in young and females subjects. Stratified analysis by the severity of OGD showed that more than 60% of COVID-19 subjects presented a severe OGD who took a longer time to recover compared to those with mild symptoms.

Translation and validation of the short version of the Questionnaire of Olfactory Disorders-Negative Statements to Spanish.

INTRODUCTION: There are more than 400 million of native Spanish speakers around the world, being the second most spoken language in regard to the number of native speakers. For this reason, a valid questionnaire to access the olfaction of our patients is necessary. MATERIAL AND METHODS: Validation and cross-cultural adaptation of the svQOD-NS questionnaire to the Spanish language. Internal consistency of svQOD-NS measured with Cronbach α. RESULTS: 40 patients met the inclusion criteria. 41 ± 153 (range 21-82), and 32 (80%) were female. 20 patients (57,1%) were male and 15 (42,9%) were female. There was a normal distribution among patients included according to the Shapiro-Wilk test (p = 0.175). Internal consistency of svQOD-NS measured with Cronbach α was 0.861. The intraclass correlation coefficient was 0.849 (confidence interval [CI] 95%: 0.766-0.911). CONCLUSION: The Spanish Language is the second most spoken language with regard to the number of native speakers and the svQOD-NS translation represents a valid option for the Spanish-speaking medical community, from which a large number of patients can benefit.

Pérdida del sentido del olfato durante la pandemia COVID-19 / Olfactory dysfunction during COVID-19 pandemic

No disponible