Impact of age on the transmission of SARS-CoV-2 in healthcare workers : Influence of nonoccupational risk factors.

BACKGROUND: The incidence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV­2) infection was highest among older adults early in the COVID-19 pandemic; however, this pattern was later reversed with young adults showing the highest incidence. The aim of this study was to identify risk factors in healthcare workers (HCWs) associated with this evolution. METHODS: We conducted a survey nested within a prospective cohort study of 680 HCWs from a tertiary referral public hospital who received 2 doses of SARS-CoV­2 vaccine in January and February 2021 (VACCICO-VAO cohort). In October 2022 all participants were invited to participate in a survey. Risk factors were tested for association with COVID-19 ever, the number of COVID-19 episodes, and the time to the first episode. RESULTS: Among 350 respondents (51% response rate, 90% female, mean age 48.1 years), 323 COVID-19 episodes were diagnosed during the study period. Multivariable analysis revealed that age < 35 years vs. > 50 years (odds ratio, OR 2.12, 95% confidence interval, CI 1.27-3.51; P = 0.004) and not maintaining social distance at social events (OR: 1.82, 95% CI: 1.16-3.19; P = 0.011) were associated with a higher risk of COVID-19. Age < 35 years (hazard ratio, HR 1.70, 95% CI 1.14-2.54; P = 0.010), and not maintaining social distance (HR 1.34, 95% CI 1.05-1.72; P = 0.020) were also associated with the time to the first episode. CONCLUSIONS: The youngest HCWs had the highest incidence rate of COVID-19, which was not explained by occupational risk factors or health conditions. The increase in nonoccupational exposure since the end of the lockdowns in summer 2020 could by a key factor.

Complete Genome Sequences of Four Mycobacteriophages Involved in Directed Evolution against Undisputed Mycobacterium abscessus Clinical Strains.

Phage therapy is still in its infancy, but it is increasingly promising as a future alternative for treating antibiotic-resistant bacteria. To investigate the effect of phages on Mycobacterium abscessus complex (MABC), we isolated 113 environmental phages, grown them to high titres, and assayed them on MABC clinical strains through the spot test. Of all the phages, only 16 showed killing activity. Their activity was so temperate to MABC that they could not generate any plaque-forming units (PFUs). The Appelmans method of directed evolution was carried out to evolve these 16 phages into more lytic ones. After only 11 of 30 rounds of evolution, every single clinical strain in our collection, including those that were unsusceptible up to this point, could be lysed by at least one phage. The evolved phages were able to form PFUs on the clinical strains tested. Still, they are temperate at best and require further training. The genomes of one random parental phage and three random evolved phages from Round 13 were sequenced, revealing a diversity of clusters and genes of a variety of evolutionary origins, mostly of unknown function. These complete annotated genomes will be key for future molecular characterisations.

Analysis of Phenotypic and Genotypic Susceptibility to Clarithromycin and Amikacin of Mycobacterium abscessus Complex Strains Isolated from Cystic Fibrosis Patients.

Mycobacterium abscessus complex infections are ever on the rise. To curb their increasing evolution, we performed an in-depth study of 43 clinical isolates of cystic fibrosis patients obtained from 2009 to 2020. We identified their subspecies, uncovered their genotypic resistance profiles, characterised their antibiotic-resistant genes, and assessed their phenotypic antibiotic susceptibilities. The phenotypic and genotypic methods showed total agreement in terms of resistance to clarithromycin and amikacin. Of the 43 clinical strains, 28 belonged to M. abscessus subsp. abscessus (65.1%), 13 to M. abscessus subsp. massiliense (30.2%), and 2 to M. abscessus subsp. bolletii (4.6%). The resistant rates for clarithromycin and amikacin, the two main drugs against M. abscessus complex pulmonary infections, were 64.2% and 14.2%, respectively. We found three strains of M. abscessus subsp. abscessus that showed heteroresistance in the rrl and rrs genes, and these strains also presented double-resistance since they were macrolide- and aminoglycoside-resistant. M. abscessus subsp. abscessus showed a high minimum inhibitory concentration (MIC) and a resistant percentage larger than or equal to 88% to cefoxitin, ciprofloxacin, moxifloxacin, doxycycline, imipenem, and trimethoprim-sulfamethoxazole. These results show a panorama of the high resistance of Mycobacterium abscessus complex to current drugs for cystic fibrosis patients. Thus, other treatment methods are urgently needed.

Detection of SARS-CoV-2 Based on Nucleic Acid Amplification Tests (NAATs) and Its Integration into Nanomedicine and Microfluidic Devices as Point-of-Care Testing (POCT).

The coronavirus SARS-CoV-2 has highlighted the criticality of an accurate and rapid diagnosis in order to contain the spread of the virus. Knowledge of the viral structure and its genome is essential for diagnosis development. The virus is still quickly evolving and the global scenario could easily change. Thus, a greater range of diagnostic options is essential to face this threat to public health. In response to the global demand, there has been a rapid advancement in the understanding of current diagnostic methods. In fact, innovative approaches have emerged, leveraging the benefits of nanomedicine and microfluidic technologies. Although this development has been incredibly fast, several key areas require further investigation and optimization, such as sample collection and preparation, assay optimization and sensitivity, cost effectiveness, scalability device miniaturization, and portability and integration with smartphones. Addressing these gaps in the knowledge and these technological challenges will contribute to the development of reliable, sensitive, and user-friendly NAAT-based POCTs for the diagnosis of SARS-CoV-2 and other infectious diseases, facilitating rapid and effective patient management. This review aims to provide an overview of current SARS-CoV-2 detection methods based on nucleic acid detection tests (NAATs). Additionally, it explores promising approaches that combine nanomedicine and microfluidic devices with high sensitivity and relatively fast 'time to answer' for integration into point-of-care testing (POCT).

Programa de prevención y control para disminuir la morbilidad y la mortalidad por COVID-19 en el municipio de la Santísima Trinidad / Prevention and control program to reduce morbidity and mortality from COVID-19 in the municipality of la Santissima Trinidad / Programa de prevenção e controle para reduzir a morbidade e a mortalidade de COVID-19 no município da Santísima Trinidad

La enfermedad COVID-19 ha afectado la salud, la economía y los estilos de vida de la población mundial, la ciudad de la Santísima Trinidad del departamento del Beni - Bolivia sufrió una de las peores tragedias sanitarias de su historia por la pandemia, con el más alto índice de riesgo y elevadas tasas de incidencia de Morbimortalidad. El objetivo de la investigación fue elaborar un programa de prevención y control de COVID-19 para contribuir a disminuir la tasa de incidencia de morbilidad y de mortalidad. Se aplicaron métodos teóricos como fueron el dialéctico, el holístico - holográfico, el sistémico estructural - funcional, la modelación y el histórico; además se trabajó con los métodos empíricos como la observación científica y la medición, aunado a las técnicas para la revisión documental, así como la entrevista y la encuesta. Se observó que las tasas de incidencia de Morbimortalidad fueron las más altas del departamento del Beni y del Estado Plurinacional de Bolivia no se realizó una planificación adecuada para la prevención y control del COVID-19, lo que saturo los establecimientos de salud y colapsó el sistema de salud. Las conclusiones se sistematizó los fundamentos teóricos sobre la morbilidad, mortalidad y programas de prevención y control del COVID-19, se elaboró un modelo teórico, en el cual se precisó la estructura interna, los componentes y sus relaciones y se elaboró un programa de prevención y control contra el COVID-19.

The COVID-19 disease has affected the health, the economy and the lifestyles of de world population, the city of Santísima Trinidad in the department of Beni - Bolivia Suffered one of the worst heajth tragedies in its history due to the pandemic with the highest risk index and high incidence rates of morbidity and mortality. The objective of the research was to develop a program for the prevention and control program of COVID-19 to help reduce the incidence rate of morbidity and mortality. The theoretical methods applied were the dialectic, the holistic - holographic, the systemic structural - functional, modeling and historical; the empirical methods applied were scientific observation and measurement and the techniques applied were the documentary review, the interview and the survey. Results: the incidence rates of morbidity and mortality were the highest in the departament and in the country, adecuate planning was not carried out for the prevention and control of COVID-19, which saturated the health facilities and collapsed the health system. The conclusions of the research work were: the theoretical foundations on morbidity, mortality and prevention and control programs of COVID-19 were systematized, a theorical model was developed, in which the internal structure, the components and their relationships were specified and a prevention and control program against COVID-19 was developed.

A doença COVID-19 afetou a saúde, a economia e os estilos de vida da população mundial. A cidade de Santísima Trinidad no departamento de Beni - Bolívia sofreu uma das piores tragédias sanitárias de sua história devido à pandemia, com o maior índice de risco e altas taxas de incidência de morbidade e mortalidade. O objetivo da pesquisa era desenvolver um programa de prevenção e controle COVID-19 para ajudar a reduzir a taxa de incidência de morbidade e mortalidade. Métodos teóricos como dialético, holístico-holográfico, estrutural-funcional sistêmico, modelagem e métodos históricos foram aplicados, bem como métodos empíricos como observação e medição científica, juntamente com técnicas de revisão documental, entrevista e pesquisa. Observou-se que as taxas de incidência de morbidade e mortalidade foram as mais altas no departamento de Beni e no Estado Plurinacional da Bolívia, e que não houve um planejamento adequado para a prevenção e controle da COVID-19, o que saturou as instalações de saúde e entrou em colapso no sistema de saúde. As conclusões do trabalho de pesquisa foram: os fundamentos teóricos sobre os programas de morbidade, mortalidade e prevenção e controle da COVID-19 foram sistematizados, um modelo teórico foi elaborado, no qual a estrutura interna, os componentes e suas relações foram especificados, e um programa de prevenção e controle contra a COVID-19 foi elaborado.

Clinical and epidemiological characteristics of COVID-19 in children: experience in two hospitals.

BACKGROUND: The COVID-19 pandemic is the most significant current public health crisis. METHODS: We conducted a retrospective case series, including patients under 18 years of age admitted to respiratory triage and hospitalized with COVID-19 infection in two hospital centers. Epidemiological, clinical, laboratory and radiological findings were documented. The diagnosis of COVID-19 was confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR). For the analysis, patients were classified into three groups: no comorbidities, immunocompromised, and with chronic disease. RESULTS: Fifty-four patients with COVID-19 were identified: 40 (74.1%) were admitted through respiratory triage. Of these, 28 (70%) were hospitalized, and 14 (25.9%) were already in the hospital. In addition, 26 (48.1%) presented comorbidities. A mild clinical course was observed in 14 cases (53.7%). The mean age was 6 years, with an interquartile range from 11 months to 13 years. The male sex was more frequent, representing 59.3%. Fever was the most common symptom in 74% of the patients. Lymphopenia was observed in 28.6%, and 69.3% had elevated C-reactive protein. Ground glass injuries were documented in 30.9% of COVID-19 cases; 11.1% of the patients required mechanical ventilation and vasopressor treatment. CONCLUSIONS: Fever was the main symptom, and mild infection was the principal presentation. In hospitalized patients with some comorbidity and COVID-19, the disease was more severe, with a high percentage of mortality.

INTRODUCCIÓN: La pandemia de COVID-19 es la mayor crisis de salud pública actual. MÉTODOS: Análisis de una serie de casos retrospectiva de pacientes menores de 18 años que ingresaron al triaje respiratorio y de pacientes hospitalizados con COVID-19 en dos centros hospitalarios. Se registraron variables epidemiológicas, clínicas, de laboratorio y radiológicas. El diagnóstico de COVID-19 fue confirmado por reacción en cadena de la polimerasa con transcriptasa inversa en tiempo real (RT-PCR). Para el análisis, los pacientes se clasificaron en tres grupos: sin comorbilidad, inmunocomprometidos y con enfermedad crónica. RESULTADOS: Se identificaron 54 pacientes con COVID-19, de los cuales 40 (74.1%) ingresaron por el triaje respiratorio y, de estos, 28 (70%) fueron hospitalizados y 14 (25.9%) ya estaban hospitalizados; 26 pacientes (48.1%) presentaban comorbilidad. El curso clínico leve se observó con mayor frecuencia, en 14 casos (53.7%). La mediana de edad fue de 6 años (rango intercuartílico: 11 meses a 13 años). El sexo masculino fue más frecuente, con el 59.3%. La fiebre fue el síntoma más común, en el 74% de los pacientes. Se observó linfocitopenia en el 28.6%, y el 69.3% presentaron elevación de la proteína C reactiva. Las lesiones en vidrio esmerilado se documentaron en el 30.9% de los casos y el 11.1% de los pacientes requirieron ventilación mecánica y tratamiento vasopresor. CONCLUSIONES: La fiebre fue el síntoma principal y la presentación leve de la enfermedad fue la más frecuente. En los pacientes hospitalizados con alguna comorbilidad e infectados por COVID-19, la gravedad de la enfermedad fue mayor, con un alto porcentaje de mortalidad.

Cause-specific death in hospitalized individuals infected with SARS-CoV-2: more than just acute respiratory failure or thromboembolic events.

Infection with SARS-CoV-2 is becoming the leading cause of death in most countries during the 2020 pandemic. The objective of this study is to assess the association between COVID-19 and cause-specific death. The design is retrospective cohort study. We included data from inpatients diagnosed with COVID-19 between March 18 and April 21, 2020, who died during their hospital stay. Demographic, clinical and management data were collected. Causes of death were ascertained by review of medical records. The sample included 128 individuals. The median age was 84 (IQR 75-89), 57% were men. In 109 patients, the death was caused by SARS-CoV-2 infection, whereas in 19 (14.8%, 95 CI 10-22%), the infection acted only as a precipitating factor to decompensate other pathologies. This second group of patients was older (88y vs 82, p < 0.001). In age-adjusted analysis, they had a greater likelihood of heart failure (OR 3.61 95% CI 1.15-11.32), dependency in activities of daily living (OR 12.07 95% CI 1.40-103.86), frailty (OR 8.73 95% CI 1.37-55.46). The presence of X-ray infiltrates was uncommon (OR 0.07, 95% CI 0.02-0.25). A higher percentage of patient deaths from causes unrelated to COVID-19 complications occurred during the two first weeks of the pandemic. Fifteen percent of patients with COVID-19 infection died from decompensation of other pathologies and the cause of death was unrelated to COVID-19 severe complications. Most of these patients had more comorbidities and were frail and elderly. These findings can partially explain the excess mortality in older people.

Sleep characteristics in health workers exposed to the COVID-19 pandemic.

INTRODUCTION: The development of sleep disorders, and specifically insomnia, has been linked to the exposure to different stressors. In this line, Coronavirus disease 2019 (COVID-19) outbreak caused by the new coronavirus SARS-CoV-2, has caused a huge impact on our environment, and has exposed healthcare workers to an unprecedented threat. In this study, we try to assess sleep quality and the development of sleep disorders in health personnel directly dedicated to the care of COVID-19 patients at the height of the pandemic, compared to the general population. MATERIALS AND METHODS: A cross-sectional, anonymized, self-reported questionnaire survey was carried out at the "12 de Octubre" Hospital, in Madrid, Spain, during the outbreak of COVID-19, from March 1st to April 30th 2020. We compared two groups, healthcare workers who have treated directly COVID-19 patients versus non-healthcare workers. The questionnaire included demographic data, sleep related aspects, Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI) and 17-items Hamilton Rating Scale (HRS). RESULTS: In total 170 participants completed the questionnaire successfully, 100 healthcare workers and 70 non-healthcare workers. Self-reported insomnia, nightmares, sleepwalking, sleep terrors and PSQI>6 were more frequent in the healthcare group (p < 0,05). Shift work was associated to greater risk when performing multiple logistic regression analysis. CONCLUSIONS: We observed that, during the outbreak of COVID-19, healthcare workers on the front line developed more sleep disturbances than non-healthcare professionals, and they had worse quality of sleep. Special attention should be paid to shift workers. Concrete protection and prevention measures for particularly exposed population should be considered in pandemic situations.

Risk factors for poor health and performance in European broiler production systems.

BACKGROUND: Conventional broilers are currently one of the most efficient protein converters. Although decades of progress in genetic selection and feed formulation have lead to high standards of efficient broiler production, still a lot of variability is found between farms and between successive flocks. The aim of this study was to investigate risk- and/or protective factors for poor health and performance in conventional broiler-farms in Europe by developing eight multivariable linear mixed models. Three different models were used to investigate mortality (overall, first week, after first week), three models for performance variables (growth, feed conversion, European production index) and two models were related to slaughterhouse data (i.e. dead on arrival and condemnation rate). RESULTS: Several factors related to management and housing were significantly associated with health and performance of broilers. The following factors were associated with increased mortality: floor quality, neonatal septicemia, ventilation type and other professional activities of the farmer. The factors associated with performance were chick sex, coccidiosis infections, necrotic enteritis, dysbacteriosis, light intensity adaptations, ventilation type, comparing daily flock results with previous flock results by farmer, daily check of feed and water system and type of feed. For dead on arrival three risk factors were identified i.e. daily growth, type of light adaptation and type of drinkers system. For condemnation rate seven risk factors were found, i.e. type of drinking system, daily growth, feed withdrawal time, type of ventilation, house size, septicemia after seven days and type of feed. CONCLUSIONS: These results imply that a multifactorial approach is required with adaptations involving both improvements in management, housing, health programs and an increasing level of professionalism of the farmer in order to improve broiler performance and health.

The Molecular Basis and Biologic Significance of the ß-Dystroglycan-Emerin Interaction.

ß-dystroglycan (ß-DG) assembles with lamins A/C and B1 and emerin at the nuclear envelope (NE) to maintain proper nuclear architecture and function. To provide insight into the nuclear function of ß-DG, we characterized the interaction between ß-DG and emerin at the molecular level. Emerin is a major NE protein that regulates multiple nuclear processes and whose deficiency results in Emery-Dreifuss muscular dystrophy (EDMD). Using truncated variants of ß-DG and emerin, via a series of in vitro and in vivo binding experiments and a tailored computational analysis, we determined that the ß-DG-emerin interaction is mediated at least in part by their respective transmembrane domains (TM). Using surface plasmon resonance assays we showed that emerin binds to ß-DG with high affinity (KD in the nanomolar range). Remarkably, the analysis of cells in which DG was knocked out demonstrated that loss of ß-DG resulted in a decreased emerin stability and impairment of emerin-mediated processes. ß-DG and emerin are reciprocally required for their optimal targeting within the NE, as shown by immunofluorescence, western blotting and immunoprecipitation assays using emerin variants with mutations in the TM domain and B-lymphocytes of a patient with EDMD. In summary, we demonstrated that ß-DG plays a role as an emerin interacting partner modulating its stability and function.

Evolución temporal de los partos múltiples en Castilla y León durante 13 años / Multiple birth trends in the region of Castilla y León (Spain) in a 13 year period

Introducción: La prevalencia del embarazo múltiple está experimentando un ascenso en los últimos años, lo que conlleva un aumento de la morbimortalidad fetal y de la morbilidad materna. El objetivo de este estudio es analizar la evolución de los partos múltiples en Castilla y León durante 13 años y sus implicaciones maternas y fetales. Material y métodos: Estudio de asociación cruzada, sobre el conjunto mínimo básico de datos (CMBD), de altas hospitalarias de la red Sanidad de Castilla y León (SACYL) entre 2001 y 2013. Se realizó un análisis de tendencias mediante regresión lineal de joinpoint, un análisis ritmométrico y un análisis multivariante mediante regresión logística binaria. Resultados: A lo largo de los 13 años de estudio se observa una tendencia creciente en la proporción de partos múltiples, en contraste con los únicos, con un porcentaje anual de cambio del 3,4% (IC del 95%: 2,5-4,4%). Se encontró asociación estadística entre la edad materna, la tolerancia anormal a la glucosa, el parto operatorio, la macrosomía fetal, el parto prematuro, la muerte fetal, las malposiciones fetales, la fecundación in vitro y los estados hipertensivos maternos y el parto gemelar, destacando que la fecundación in vitro se asocia con un exceso de riesgo de 9,3 veces de parto múltiple (IC del 95%: 7,4-11,5), así como la edad de la madre se asocia con un exceso de riesgo del 5% por cada año de edad (OR: 1,05; IC 95%: 1,04-1,05). No se evidenció estacionalidad en los partos múltiples en contraposición con los únicos. Conclusiones: Los partos múltiples experimentaron un continuo ascenso, sin seguir un ritmo estacional, asociados a la extensión del uso de las técnicas de reproducción asistida y al retraso en la edad de la maternidad, lo que conlleva mayor morbimortalidad fetal y materna

Introduction: Multiple pregnancy has increased in prevalence in the last few years, which could lead to more foetal and maternal morbidity issues. The aim of this study is to describe the trend of multiple pregnancy deliveries in Castilla y León during the last 13years and the subsequent impact on foetal and maternal health. Material and methods: Data was collected from the hospital discharge reports registered in the Regional Health-care database (SACYL: Health care in Castilla y León) between 2001 and 2013. A cross sectional descriptive study was conducted, including trend analysis with log-linear joint point model, a rhythm metric study, as well as a risk assessment with multivariate analysis. Results: A pronounced upward trend was observed in the proportion of multiple deliveries in this time period, compared to single ones, with an annual percentage change of 3.4% (95% CI: 2.5-4.4). Multiple pregnancy was significantly correlated with advanced maternal age, abnormal glucose tolerance, dystocia and caesarean section delivery, premature birth, foetal malposition, foetal macrosomia, stillbirth, in vitro fertilisation, and hypertensive episodes of pregnancy. In vitro fertilization showed a 9.3 fold increased risk in multiple pregnancy (95% CI: 7.4-11.5), with maternal age increasing the risk up to 5% per year of age (OR: 1.05: 95%CI: 1.04-1.05). No seasonal rhythm was observed in multiple deliveries compared with single ones. Conclusion: Multiple pregnancy has experienced a continuous increase, with no seasonal trend, and is associated with the increase in assisted reproductive technology and advanced maternal age. This involves more problems regarding foetal and maternal morbidity and mortality

Whole-Genome Sequence of Acinetobacter baumannii HUMV-3743, Isolated from a Human Wound Exudate.

Acinetobacter baumannii strain HUMV-3743 was obtained from wound exudate from an adult patient. Here, we report its complete genome sequence using Illumina-based sequence analysis, which revealed a genome of 4 Mb, which includes 2 predicted plasmids of 78.9 and 107 kb. A total of 3,881 protein-coding genes are predicted from this assembly.

[Multiple birth trends in the region of Castilla y León (Spain) in a 13 year period]. / Evolución temporal de los partos múltiples en Castilla y León durante 13 años.

INTRODUCTION: Multiple pregnancy has increased in prevalence in the last few years, which could lead to more foetal and maternal morbidity issues. The aim of this study is to describe the trend of multiple pregnancy deliveries in Castilla y León during the last 13years and the subsequent impact on foetal and maternal health. MATERIAL AND METHODS: Data was collected from the hospital discharge reports registered in the Regional Health-care database (SACYL: Health care in Castilla y León) between 2001 and 2013. A cross sectional descriptive study was conducted, including trend analysis with log-linear joint point model, a rhythm metric study, as well as a risk assessment with multivariate analysis. RESULTS: A pronounced upward trend was observed in the proportion of multiple deliveries in this time period, compared to single ones, with an annual percentage change of 3.4% (95% CI: 2.5-4.4). Multiple pregnancy was significantly correlated with advanced maternal age, abnormal glucose tolerance, dystocia and caesarean section delivery, premature birth, foetal malposition, foetal macrosomia, stillbirth, in vitro fertilisation, and hypertensive episodes of pregnancy. In vitro fertilization showed a 9.3 fold increased risk in multiple pregnancy (95% CI: 7.4-11.5), with maternal age increasing the risk up to 5% per year of age (OR: 1.05: 95%CI: 1.04-1.05). No seasonal rhythm was observed in multiple deliveries compared with single ones. CONCLUSION: Multiple pregnancy has experienced a continuous increase, with no seasonal trend, and is associated with the increase in assisted reproductive technology and advanced maternal age. This involves more problems regarding foetal and maternal morbidity and mortality.

Alcohol and Road Traffic Injuries in Latin America and the Caribbean: A Case-Crossover Study.

BACKGROUND: This study reports dose-response estimates for the odds ratio (OR) and population attributable risk of acute alcohol use and road traffic injury (RTI). METHODS: Data were analyzed on 1,119 RTI patients arriving at 16 emergency departments (EDs) in Argentina, Brazil, Costa Rica, Dominican Republic, Guatemala, Guyana, Mexico, Nicaragua, Panama, and Trinidad and Tobago. Case-crossover analysis, pair-matching the number of standard drinks consumed within the 6 hours prior to the RTI with 2 control periods (prior d/wk), was performed using fractional polynomial analysis for dose-response. RESULTS: About 1 in 6 RTI patients in EDs were positive for self-reported alcohol 6 hours prior to the injury (country range 8.6 to 24.1%). The likelihood of an RTI with any drinking prior (compared to not drinking) was 5 times higher (country range OR 2.50 to 15.00) and the more a person drinks the higher the risk. Every drink (12.8 g alcohol) increased the risk of an RTI by 13%, even 1 to 2 drinks were associated with a sizable increase in risk of an RTI and a dose-response was found. Differences in ORs for drivers (OR = 3.51; 95% CI = 2.25 to 5.45), passengers (OR = 8.12; 95% CI = 4.22 to 15.61), and pedestrians (OR = 6.30; 95% CI = 3.14 to 12.64) and attributable fractions were noted. Acute use of alcohol was attributable to 14% of all RTIs, varying from 7% for females to 19% for being injured as a passenger. CONCLUSIONS: The finding that the presence of alcohol increases risk among drivers and nondrivers alike may further help to urge interventions targeting passengers and pedestrians. Routine screening and brief interventions in all health services could also have a beneficial impact in decreasing rates of RTIs. Higher priority should be given to alcohol as a risk factor for RTIs, particularly in Latin America and the Caribbean.

Conventional Polysomnography Is Not Necessary for the Management of Most Patients with Suspected Obstructive Sleep Apnea. Noninferiority, Randomized Controlled Trial.

RATIONALE: Home respiratory polygraphy may be a simpler alternative to in-laboratory polysomnography for the management of more symptomatic patients with obstructive sleep apnea, but its effectiveness has not been evaluated across a broad clinical spectrum. OBJECTIVES: To compare the long-term effectiveness (6 mo) of home respiratory polygraphy and polysomnography management protocols in patients with intermediate-to-high sleep apnea suspicion (most patients requiring a sleep study). METHODS: A multicentric, noninferiority, randomized controlled trial with two open parallel arms and a cost-effectiveness analysis was performed in 12 tertiary hospitals in Spain. Sequentially screened patients with sleep apnea suspicion were randomized to respiratory polygraphy or polysomnography protocols. Moreover, both arms received standardized therapeutic decision-making, continuous positive airway pressure (CPAP) treatment or a healthy habit assessment, auto-CPAP titration (for CPAP indication), health-related quality-of-life questionnaires, 24-hour blood pressure monitoring, and polysomnography at the end of follow-up. The main outcome was the Epworth Sleepiness Scale measurement. The noninferiority criterion was -2 points on the Epworth scale. MEASUREMENTS AND MAIN RESULTS: In total, 430 patients were randomized. The respiratory polygraphy protocol was noninferior to the polysomnography protocol based on the Epworth scale. Quality of life, blood pressure, and polysomnography were similar between protocols. Respiratory polygraphy was the most cost-effective protocol, with a lower per-patient cost of 416.7€. CONCLUSIONS: Home respiratory polygraphy management is similarly effective to polysomnography, with a substantially lower cost. Therefore, polysomnography is not necessary for most patients with suspected sleep apnea. This finding could change established clinical practice, with a clear economic benefit. Clinical trial registered with www.clinicaltrials.gov (NCT 01752556).

Non-invasive ventilation in obesity hypoventilation syndrome without severe obstructive sleep apnoea.

BACKGROUND: Non-invasive ventilation (NIV) is an effective form of treatment in patients with obesity hypoventilation syndrome (OHS) who have concomitant severe obstructive sleep apnoea (OSA). However, there is a paucity of evidence on the efficacy of NIV in patients with OHS without severe OSA. We performed a multicentre randomised clinical trial to determine the comparative efficacy of NIV versus lifestyle modification (control group) using daytime arterial carbon dioxide tension (PaCO2) as the main outcome measure. METHODS: Between May 2009 and December 2014 we sequentially screened patients with OHS without severe OSA. Participants were randomised to NIV versus lifestyle modification and were followed for 2 months. Arterial blood gas parameters, clinical symptoms, health-related quality of life assessments, polysomnography, spirometry, 6-min walk distance test, blood pressure measurements and healthcare resource utilisation were evaluated. Statistical analysis was performed using intention-to-treat analysis. RESULTS: A total of 365 patients were screened of whom 58 were excluded. Severe OSA was present in 221 and the remaining 86 patients without severe OSA were randomised. NIV led to a significantly larger improvement in PaCO2 of -6 (95% CI -7.7 to -4.2) mm Hg versus -2.8 (95% CI -4.3 to -1.3) mm Hg, (p<0.001) and serum bicarbonate of -3.4 (95% CI -4.5 to -2.3) versus -1 (95% CI -1.7 to -0.2 95% CI)  mmol/L (p<0.001). PaCO2 change adjusted for NIV compliance did not further improve the inter-group statistical significance. Sleepiness, some health-related quality of life assessments and polysomnographic parameters improved significantly more with NIV than with lifestyle modification. Additionally, there was a tendency towards lower healthcare resource utilisation in the NIV group. CONCLUSIONS: NIV is more effective than lifestyle modification in improving daytime PaCO2, sleepiness and polysomnographic parameters. Long-term prospective studies are necessary to determine whether NIV reduces healthcare resource utilisation, cardiovascular events and mortality. TRIAL REGISTRATION NUMBER: NCT01405976; results.

Incremento en la capacidad de procesamiento para la producción de N-Glicolil GM3 / Increase in processing capacity for N-Glicolil GM3 production

El N-Glicolil GM3 es un monosialilgangliósido utilizado como antígeno y adyuvante en preparaciones vacunales para uso terapéutico contra cáncer de mama, pulmón y melanoma. La obtención de este gangliósido a partir de eritrocitos equinos consta de dos etapas: extracción y purificación, en las que se trabaja para incrementar los volúmenes de procesamiento. La evaluación del incremento en la capacidad de procesamiento, su influencia en el rendimiento y la evaluación del comportamiento del proceso de purificación utilizando Cromatografía Líquida de Alta Resolución Preparativa constituyeron objetivos del presente trabajo. Se compararon los resultados obtenidos entre el procedimiento aprobado y la propuesta de cambio. Se controló el proceso evaluando las características organolépticas y el peso del extracto liofilizado, así como la detección y contenido de N-Glicolil GM3 por Cromatografía de Placa Delgada cualitativa y análisis colorimétrico de ácido siálico; se utilizó el Software STATGRAPHICS para evaluar la variabilidad del proceso. El incremento del volumen de procesamiento respecto al procedimiento establecido mantuvo el rendimiento en la etapa de extracción y aumentó ligeramente el de la purificación, reduciéndose el tiempo de procesamiento con la utilización de la Cromatografía Líquida de Alta Resolución Preparativa. El aumento de la capacidad de procesamiento mantuvo el rendimiento global del proceso en 0,006 g de N-Glicolil GM3/g de Eritrocitos y el producto obtenido mediante el procedimiento propuesto cumplió las especificaciones de calidad establecidas para el mismo; permitiendo un aumento en la productividad de 30 por ciento, menor consumo de energía y desgaste de los recursos humanos, siendo factible implementar el cambio(AU)

The N-Glicolil GM3 is a monosialilganglioside used as antigen and adjuvant in vaccines preparations for therapeutic use against breast, lung and melanoma cancer. The obtaining process of this ganglioside from equine erythrocytes comprises two stages: extraction and purification, in which we work to increment processing volumes. The assessment of increment in the processing capacity, its influence on the performance and the evaluation of purification process behavior by Preparative High-Performance Liquid Chromatography (Prep HPLC) constituted the objectives of this paper. The results obtained from the approved procedure and the proposal of change were compared. The process was controlled by evaluating the organoleptic characteristics and weight of lyophilized extract, as well as the detection and content of N-Glicolyl GM3 by Qualitative Thin Layer Chromatography and colorimetric analysis of sialic acid; STATGRAPHICS software was used to assess the process variability. The increment in processing volume regarding the established procedure remained the extraction stage performance and incremented slightly the purification performance, by reducing the processing time with the use of Prep HPLC. The increment of processing capacity maintained the overall performance of the process in 0,006 g of N-Glicolyl GM3/g of erythrocytes and the product obtained by means of the proposed method fulfilled the quality specifications established for the same; allowing an increment in productivity by 30 percent, less energy consumption and less exhaustion of human resources, being feasible to implement the change(AU)

Eficacia del parche hemático transvaginal endocervical autólogo en ruptura prematura de membranas pretérmino / Effectiveness of transvaginal blood patch endocervical Autologous in Preterm premature rupture of membranes

OBJETIVO: comparar la efectividad terapéutica del parche hemático transvaginal endocervical autólogo en casos de ruptura prematura de membranas pretérmino frente al llamado tratamiento expectante. MÉTODOS: Ensayo controlado, aleatorio y prospectivo teniendo como variables determinantes el tiempo de latencia de la ruptura y la sobrevida de los recién nacidos. En un período de 12 semanas, solo 35 pacientes con edades comprendidas entre 16 y 37 y promedio de 26,5 años, cumplieron los criterios de inclusión. La edad de gestación tuvo una media de 23,5 ± 3,92 semanas. Con distribución aleatoria, se formaron dos grupos independientes y estadísticamente comparables donde el primero con 9 casos (25,7.%) fue tratado con el parche hemático y el segundo considerado grupo control, con 26 casos (74,2.%) recibió el tratamiento expectante. RESULTADOS: Con un nivel de significancia de 0,05 hubo una diferencia significativa tanto en el período de latencia (P=0,002) como en la sobrevida de los recién nacidos (P=0,006) demostrando la efectividad terapéutica del parche frente al tratamiento expectante. No hubo diferencia referente a la edad materna y la edad gestacional. Con el tratamiento con el parche hemático la reducción del riesgo absoluto fue de 54,70 %, el riesgo relativo de muerte de 0,289, la reducción del riesgo relativo de muerte del 71,11 % , el número necesario de pacientes a tratar fue de 1,83 pacientes y "Odds Ratio"= 0,09 (0,086). El parche hemático no evidenció efectos adversos, complicaciones y fue de bajo costo. CONCLUSIONES: Los resultados obtenidos demuestran de manera significativa la efectividad terapéutica del parche hemático frente al tratamiento expectante, mejorando tanto el período de latencia del embarazo como la sobrevida de los recién nacidos con ruptura de membranas ovulares pretermino.

OBJECTIVE: to compare the therapeutic effectiveness of the autologous endocervical transvaginal blood patch, in cases of preterm premature rupture of membranes, versus the so called expectant treatment. METHODS: Controlled, randomized and prospective trial having latency time of the break and survival of newborns as determining variables. In a 12-week period, only 35 patients aged between 16 and 37 and averaging 26,5 years, met the inclusion criteria. Gestational age had an average of 23.5 ± 3.92 weeks. With a random distribution, two independent and statistically comparable groups where formed; where the first one, with nine cases (25.7 %), was treated with the blood patch; and the second one, with 26 (74.2%), and considered the control group, received expectant treatment. RESULTS: With a significance level of 0.05, there was a significant difference in both the latency period (P = 0.002) and the survival of newborns (P = 0.006), demonstrating the therapeutic effectiveness of the patch as compared with the expectant treatment. There was no difference regarding maternal age and gestational age. With the blood patch treatment, Absolute Risk Reduction (ARR) was 54.70 %; the relative risk of death (RR), of 0.289; the reduction of the relative risk of death (RRR), of 71.11 %; the number needed to treat (NNT) was 1.83 patients; and the "Odds ratio" (OR) = 0.09 (0.086). The blood patch did not report adverse effects, complications and was inexpensive. CONCLUSIONS: The results show a significant therapeutic effectiveness of the blood patch versus the expectant treatment, improving both the latency period of pregnancy and the survival of infants in cases of preterm rupture of ovular membranes.