Bispectral index monitoring for sedation in scheduled adult colonoscopy: A randomized controlled trial.

BACKGROUND: Patients should be closely monitored during procedures under sedation outside the operating room, but it is unclear which type of monitoring is best. We investigated the efficacy and safety of BIS monitoring vs conventional monitoring for sedation during colonoscopy. METHODS: We performed a double-blind clinical trial in 180 patients undergoing elective colonoscopy. Patients were randomized to 1) the BIS group or 2) a control group, in which sedation was monitored with a BIS monitor or the Ramsay Sedation Score, respectively. The primary outcome was the rate of sedation-induced adverse events in both groups. Secondary outcomes were the characteristics of patients who developed adverse events, and duration of colonoscopy when these events occurred, propofol and remifentanil dosage, and patient satisfaction. RESULTS: Univariate analysis showed fewer cardiopulmonary complications in the BIS group (41.11% vs 57.78% in controls; p = 0.02). Multivariate analysis found a significantly higher risk of adverse events in older patients (95% CI, 1.013-1.091; p = 0.0087) and in men (95% CI, 1.129-7.668; p = 0.0272). These events were observed at the hepatic flexure. No significant differences between propofol or remifentanil dosage, use of rescue medication, and patient satisfaction were observed between groups. CONCLUSIONS: Our data suggest that BIS monitoring during sedation in scheduled colonoscopies reduces adverse respiratory events. Although its routine use in sedation does not appear to be warranted, clinicians should take steps to identify patients with a higher risk of complications who might benefit from this type of monitoring.

Clinical experience in the treatment of COVID-19 with monoclonal antibodies in solid organ transplant recipients.

Solid organ transplant (SOT) recipients are at high risk for complications from coronavirus disease 2019 (COVID-19). SOT recipients mount lower immunological responses to vaccines than general population and are at high risk for breakthrough COVID-19 infections. Passive immunotherapy in the form of anti-Spike monoclonal antibodies (MoAbs) may be an alternative for the prophylaxis and treatment of COVID-19 in these patients. SARS-CoV-2 has evolved by accumulating resistance mutations that have escaped the neutralizing action of most MoAbs. However, MoAbs directed at more conserved epitopes and that maintain effector functions could maintain efficacy in the treatment of these patients. According to published data, SOT recipients with low anti-spike antibody responses to vaccination could benefit from the use of MoAbs in pre-exposure prophylaxis, in the treatment of COVID-19 mild to moderate and severe COVID-19 with less than 15 days of symptom duration and low oxygen requirements. Combination therapy could be more effective than monotherapy for the treatment of mild-to-moderate SARS-CoV-2 infection.

[Cost-effectiveness analysis high flow oxygen therapy in the treatment of SARS-CoV-2 pneumonia]. / Coste-efectividad de la oxigenoterapia de alto flujo en el tratamiento de la neumonía por SARS-CoV-2.

INTRODUCTION: high-oxygen nasal cannulas in patients with respiratory failure secondary to SARS-CoV-2 pneumonia have not been studied from a cost-effectiveness point of view. METHODS: Retrospective analysis of patients who had entered the COVID-area of an intensive medicine service in a third reference hospital, between March-December 2020. An effectiveness cost analysis was carried out comparing 2therapeutic decisions: the experimental strategy was defined as a mixed strategy consisting of the initial application of high flow nasal oxygen (HFNO) and application of VMI only to HFNO failures. The optimal rational decision was defined as maximizing expected profit, and economic efficiency was assessed by calculating the Incremental Cost-Effectiveness Ratio (ICER) for years of life gained. RESULTS: Of the 185 patients tested, 101 (55%) received invasive mechanical ventilation immediately and 84 (45%) were treated with HFNO at the outset. In the cost-effectiveness analysis, comparing both therapeutic strategies, the probability that the experimental strategy would be more effective was 0.974, reaching statistical significance: Difference in average proportions -0.113; 95% CI:-0.018 to -0.208. This corresponds to an NNT of 9 patients. The optimal decision was HFNO's strategy followed by VMI in HFNO failures. This option had an RCEI of 5582 euros per year of life gained. CONCLUSIONS: It is important to establish in the future reliable markers in the use of HFNO so that this therapy improves its cost-effective benefits.

Patología dermatológica facial asociada al uso de la mascarilla durante la pandemia causada por el virus Sars-CoV-2 / Facial dermatological pathology associated with use of the mask during the pandemic caused by the Sars-CoV-2 virus

The use of facemask has become a key element to prevent the infection of Covid-19. Its prolonged use, both, by health personnel and the general population, has caused the appearance of multiple adverse effects at the facial level; highlighting the report of symptoms such as discomfort with the mask, facial itching, redness, erythema, among others. The appearance of dermatological diseases such as acne, allergic and irritative contact dermatitis, and exacerbation of pre-existing pathologies such as acne, rosacea and seborrheic dermatitis are also frequent. Knowledge of these complications is important for their prevention and proper management. (AU)

Recomendaciones para el empleo de técnicas neurofisiológicas en el diagnóstico de muerte encefálica de la Sociedad de Neurofisiología Clínica de las Comunidades de Valencia y Murcia / Recommendations for the use of neurophysiological techniques in the diagnosis of brain death from the Clinical Neurophysiology Society of the Communities of Valencia and Murcia

En España, el trasplante de órganos constituye uno de los mayores retos y trabajo en equipo de los centros hospitalarios. Se estima que en 2020 España aportó a la Unión Europea el 19% de la totalidad de los donantes. El diagnóstico de apoyo confirmatorio recomienda por ley algunas técnicas complementarias en determinados casos, entre ellas las técnicas neurofisiológicas, en especial el uso del electroencefalograma y los potenciales evocados. Estos casos plantean al neurofisiólogo clínico la toma acertada de decisiones tanto clínicas como técnicas para su correcta realización e interpretación. Hasta ahora no existe a nivel nacional un consenso de realización de estas técnicas. Es una revisión bibliográfica actualizada sobre las técnicas neurofisiológicas (electroencefalograma y potenciales evocados), con análisis mediante método Delphi y juicio de expertos del grupo de trabajo de la Sociedad de Neurofisiología Clínica de las Comunidades de Valencia y Murcia. Las técnicas neurofisiológicas permiten ser un apoyo en el diagnóstico de muerte encefálica, tanto de forma confirmatoria como para acortar tiempos de observación. Para su realización se precisan unos mínimos estándares técnicos que permitan realizar de forma óptima los estudios. Especialmente hay que tener en cuenta la medicación, la situación hemodinámica, la ausencia de hipotermia y el grupo de edad. Presentamos la primera guía en castellano elaborada por la Sociedad de Neurofisiología de las Comunidades de Valencia y Murcia para la realización en nuestros hospitales de las técnicas neurofisiológicas en el diagnóstico de muerte encefálica.(AU)

In Spain organ transplantation constitutes one of the greatest challenges and teamwork of hospital centres. It is estimated that in the year 2020 Spain contributed 19% of all donors to the European Union. The confirmatory support diagnosis recommends by law some complementary techniques in certain cases, including neurophysiological techniques, especially the use of electroencephalogram and evoked potentials. These cases require the clinical neurophysiologist to make the right clinical and technical decisions for the correct performance and interpretation of the same. To date, there is no national consensus on the performance of these techniques. Updated bibliographic review on neurophysiological techniques (electroencephalogram and evoked potentials). Analysis by Delphi method and expert judgment of the working group of the Clinical Neurophysiology Society of the Communities of Valencia and Murcia. Neurophysiological techniques can be a support in the diagnosis of encephalic death, both confirmatory and to shorten observation times. In order to perform them, minimum technical standards are required to allow optimal performance of the studies, especially taking into account medication, hemodynamic situation, absence of hypothermia, and age group. We present the first guide in Spanish elaborated by the Society of Neurophysiology of the Communities of Valencia and Murcia for the performance in our hospitals of neurophysiological techniques in the diagnosis of brain death.(AU)

A comprehensive database of amphibian heat tolerance.

Rising temperatures represent a significant threat to the survival of ectothermic animals. As such, upper thermal limits represent an important trait to assess the vulnerability of ectotherms to changing temperatures. For instance, one may use upper thermal limits to estimate current and future thermal safety margins (i.e., the proximity of upper thermal limits to experienced temperatures), use this trait together with other physiological traits in species distribution models, or investigate the plasticity and evolvability of these limits for buffering the impacts of changing temperatures. While datasets on thermal tolerance limits have been previously compiled, they sometimes report single estimates for a given species, do not present measures of data dispersion, and are biased towards certain parts of the globe. To overcome these limitations, we systematically searched the literature in seven languages to produce the most comprehensive dataset to date on amphibian upper thermal limits, spanning 3,095 estimates across 616 species. This resource will represent a useful tool to evaluate the vulnerability of amphibians, and ectotherms more generally, to changing temperatures.

[Recommendations for the use of neurophysiological techniques in the diagnosis of brain death from the Clinical Neurophysiology Society of the Communities of Valencia and Murcia]. / Recomendaciones para el empleo de técnicas neurofisiológicas en el diagnóstico de muerte encefálica de la Sociedad de Neurofisiología Clínica de las Comunidades de Valencia y Murcia.

In Spain organ transplantation constitutes one of the greatest challenges and teamwork of hospital centres. It is estimated that in the year 2020 Spain contributed 19% of all donors to the European Union. The confirmatory support diagnosis recommends by law some complementary techniques in certain cases, including neurophysiological techniques, especially the use of electroencephalogram and evoked potentials. These cases require the clinical neurophysiologist to make the right clinical and technical decisions for the correct performance and interpretation of the same. To date, there is no national consensus on the performance of these techniques. Updated bibliographic review on neurophysiological techniques (electroencephalogram and evoked potentials). Analysis by Delphi method and expert judgment of the working group of the Clinical Neurophysiology Society of the Communities of Valencia and Murcia. Neurophysiological techniques can be a support in the diagnosis of encephalic death, both confirmatory and to shorten observation times. In order to perform them, minimum technical standards are required to allow optimal performance of the studies, especially taking into account medication, hemodynamic situation, absence of hypothermia, and age group. We present the first guide in Spanish elaborated by the Society of Neurophysiology of the Communities of Valencia and Murcia for the performance in our hospitals of neurophysiological techniques in the diagnosis of brain death.

TITLE: Recomendaciones para el empleo de técnicas neurofisiológicas en el diagnóstico de muerte encefálica de la Sociedad de Neurofisiología Clínica de las Comunidades de Valencia y Murcia.En España, el trasplante de órganos constituye uno de los mayores retos y trabajo en equipo de los centros hospitalarios. Se estima que en 2020 España aportó a la Unión Europea el 19% de la totalidad de los donantes. El diagnóstico de apoyo confirmatorio recomienda por ley algunas técnicas complementarias en determinados casos, entre ellas las técnicas neurofisiológicas, en especial el uso del electroencefalograma y los potenciales evocados. Estos casos plantean al neurofisiólogo clínico la toma acertada de decisiones tanto clínicas como técnicas para su correcta realización e interpretación. Hasta ahora no existe a nivel nacional un consenso de realización de estas técnicas. Es una revisión bibliográfica actualizada sobre las técnicas neurofisiológicas (electroencefalograma y potenciales evocados), con análisis mediante método Delphi y juicio de expertos del grupo de trabajo de la Sociedad de Neurofisiología Clínica de las Comunidades de Valencia y Murcia. Las técnicas neurofisiológicas permiten ser un apoyo en el diagnóstico de muerte encefálica, tanto de forma confirmatoria como para acortar tiempos de observación. Para su realización se precisan unos mínimos estándares técnicos que permitan realizar de forma óptima los estudios. Especialmente hay que tener en cuenta la medicación, la situación hemodinámica, la ausencia de hipotermia y el grupo de edad. Presentamos la primera guía en castellano elaborada por la Sociedad de Neurofisiología de las Comunidades de Valencia y Murcia para la realización en nuestros hospitales de las técnicas neurofisiológicas en el diagnóstico de muerte encefálica.

Fluorescence labeling of mitochondria in living cells by the cationic photosensitizer ZnTM2,3PyPz, and the possible roles of redox processes and pseudobase formation in facilitating dye uptake.

The study of labeling selectivity and mechanisms of fluorescent organelle probes in living cells is of continuing interest in biomedical sciences. The tetracationic phthalocyanine-like ZnTM2,3PyPz photosensitizing dye induces a selective violet fluorescence in mitochondria of living HeLa cells under UV excitation that is due to co-localization of the red signal of the dye with NAD(P)H blue autofluorescence. Both red and blue signals co-localize with the green emission of the mitochondria probe, rhodamine 123. Microscopic observation of mitochondria was improved using image processing and analysis methods. High dye concentration and prolonged incubation time were required to achieve optimal mitochondrial labeling. ZnTM2,3PyPz is a highly cationic, hydrophilic dye, which makes ready entry into living cells unlikely. Redox color changes in solutions of the dye indicate that colorless products are formed by reduction. Spectroscopic studies of dye solutions showed that cycles of alkaline titration from pH 7 to 8.5 followed by acidification to pH 7 first lower, then restore the 640 nm absorption peak by approximately 90%, which can be explained by formation of pseudobases. Both reduction and pseudobase formation result in formation of less highly charged and more lipophilic (cell permeant) derivatives in equilibrium with the parent dye. Some of these are predicted to be lipophilic and therefore membrane-permeant; consequently, low concentrations of such species could be responsible for slow uptake and accumulation in mitochondria of living cells. We discuss the wider implications of such phenomena for uptake of hydrophilic fluorescent probes into living cells.

Factores de riesgo de deterioro clínico en pacientes ingresados por COVID-19: estudio caso-control / Risk factors for clinical deterioration in patients admitted for COVID-19: A case-control study

Introducción: Existe controversia sobre los mejores factores predictores de deterioro clínico en la COVID-19. Objetivo: Identificar factores predictores de riesgo de deterioro en pacientes hospitalizados por COVID-19. Métodos Diseño: caso-control anidado dentro de una cohorte. Ámbito: 13 centros de agudos de Osakidetza-Servicio Vasco de Salud. Participantes: se consideró casos a pacientes hospitalizados por COVID-19 con deterioro clínico, definido como la aparición de síndrome de distrés respiratorio del adulto grave, ingreso en UCI o fallecimiento. Se emparejaron 2controles por caso en función de la edad. Se recogieron variables sociodemográficas, comorbilidades, tratamientos basales, síntomas y fecha de inicio, consultas previas, así como variables clínicas, analíticas y radiológicas. Se creó un modelo explicativo del deterioro clínico mediante regresión logística condicional. Resultados: Se incluyeron 99 casos y 198 controles. Mediante análisis de regresión logística las variables independientes asociadas con deterioro clínico fueron: saturación de O2 en Urgencias ≤ 90% (OR=16,6, IC del 95%, 4-68), radiografía de tórax patológica (OR=5,6, IC del 95%, 1,7-18,4), PCR> 100mg/dL (OR=3,62, IC del 95% 1,62-8) y trombocitopenia <150.000 plaquetas (OR=4, IC del 95%, 1,84-8,6) y, entre los antecedentes, haber padecido infarto agudo de miocardio (OR=15,7, IC del 95%, 3,29-75,09), EPOC (OR=3,05, IC del 95%, 1,43-6,5) o hipertensión arterial (OR=2,21, IC del 95%1,11-4,4). El área bajo la curva alcanzado por el modelo fue 0,86. En el análisis univariado, se asociaron con mejor evolución clínica el sexo femenino, la presencia de tos seca y dolor de garganta, pero no resultaron significativas en el análisis multivariado. Conclusiós:Las variables identificadas podrían ser de utilidad en la práctica clínica para la detección de pacientes con alto riesgo de mala evolución (AU)

Introduction: There is controversy regarding the best predictors of clinical deterioration in COVID-19. Objective: This work aims to identify predictors of risk factors for deterioration in patients hospitalized due to COVID-19. Methods Design: Nested case-control study within a cohort. Setting: 13 acute care centers of the Osakidetza-Basque Health Service. Participants: Patients hospitalized for COVID-19 with clinical deterioration—defined as onset of severe ARDS, ICU admission, or death—were considered cases. Two controls were matched to each case based on age. Sociodemographic data; comorbidities; baseline treatment; symptoms; date of onset; previous consultations; and clinical, analytical, and radiological variables were collected. An explanatory model of clinical deterioration was created by means of conditional logistic regression. Results: A total of 99 cases and 198 controls were included. According to the logistic regression analysis, the independent variables associated with clinical deterioration were: emergency department O2 saturation ≤90% (OR 16.6; 95%CI 4-68), pathological chest X-ray (OR 5.6; 95%CI 1.7-18.4), CRP>100mg/dL (OR 3.62; 95%CI 1.62-8), thrombocytopenia with <150,000 platelets (OR 4; 95%CI 1.84-8.6); and a medical history of acute myocardial infarction (OR 15.7; 95%CI, 3.29-75.09), COPD (OR 3.05; 95%CI 1.43-6.5), or HT (OR 2.21; 95%CI 1.11-4.4). The model's AUC was 0.86. On the univariate analysis, female sex and presence of dry cough and sore throat were associated with better clinical progress, but were not found to be significant on the multivariate analysis. Conclusion: The variables identified could be useful in clinical practice for the detection of patients at high risk of poor outcomes (AU)

[Risk factors for clinical deterioration in patients admitted for COVID-19: A case-control study]. / Factores de riesgo de deterioro clínico en pacientes ingresados por COVID-19: estudio caso-control.

INTRODUCTION: There is controversy regarding the best predictors of clinical deterioration in COVID-19. OBJECTIVE: This work aims to identify predictors of risk factors for deterioration in patients hospitalized due to COVID-19. METHODS DESIGN: Nested case-control study within a cohort. Setting: 13 acute care centers of the Osakidetza-Basque Health Service. Participants: Patients hospitalized for COVID-19 with clinical deterioration-defined as onset of severe ARDS, ICU admission, or death-were considered cases. Two controls were matched to each case based on age. Sociodemographic data; comorbidities; baseline treatment; symptoms; date of onset; previous consultations; and clinical, analytical, and radiological variables were collected. An explanatory model of clinical deterioration was created by means of conditional logistic regression. RESULTS: A total of 99 cases and 198 controls were included. According to the logistic regression analysis, the independent variables associated with clinical deterioration were: emergency department O2 saturation ≤90% (OR 16.6; 95%CI 4-68), pathological chest X-ray (OR 5.6; 95%CI 1.7-18.4), CRP >100 mg/dL (OR 3.62; 95%CI 1.62-8), thrombocytopenia with < 150,000 platelets (OR 4; 95%CI 1.84-8.6); and a medical history of acute myocardial infarction (OR 15.7; 95%CI, 3.29-75.09), COPD (OR 3.05; 95%CI 1.43-6.5), or HT (OR 2.21; 95%CI 1.11-4.4). The model's AUC was 0.86. On the univariate analysis, female sex and presence of dry cough and sore throat were associated with better clinical progress, but were not found to be significant on the multivariate analysis. CONCLUSION: The variables identified could be useful in clinical practice for the detection of patients at high risk of poor outcomes.

Risk factors for clinical deterioration in patients admitted for COVID-19: A case-control study.

INTRODUCTION: There is controversy regarding the best predictors of clinical deterioration in COVID-19. OBJECTIVE: This work aims to identify predictors of risk factors for deterioration in patients hospitalized due to COVID-19. METHODS DESIGN: Nested case-control study within a cohort. SETTING: 13 acute care centers of the Osakidetza-Basque Health Service. PARTICIPANTS: patients hospitalized for COVID-19 with clinical deterioration-defined as onset of severe ARDS, ICU admission, or death-were considered cases. Two controls were matched to each case based on age. Sociodemographic data; comorbidities; baseline treatment; symptoms; date of onset; previous consultations; and clinical, analytical, and radiological variables were collected. An explanatory model of clinical deterioration was created by means of conditional logistic regression. RESULTS: A total of 99 cases and 198 controls were included. According to the logistic regression analysis, the independent variables associated with clinical deterioration were: emergency department O2 saturation ≤90% (OR 16.6; 95%CI 4-68), pathological chest X-ray (OR 5.6; 95%CI 1.7-18.4), CRP > 100 mg/dL (OR 3.62; 95%CI 1.62-8), thrombocytopenia with <150,000 platelets (OR 4; 95%CI 1.84-8.6); and a medical history of acute myocardial infarction (OR 15.7; 95%CI, 3.29-75.09), COPD (OR 3.05; 95%CI 1.43-6.5), or HT (OR 2.21; 95%CI 1.11-4.4). The model's AUC was 0.86. On the univariate analysis, female sex and presence of dry cough and sore throat were associated with better clinical progress, but were not found to be significant on the multivariate analysis. CONCLUSION: The variables identified could be useful in clinical practice for the detection of patients at high risk of poor outcomes.

OLA strategy for ARDS: Its effect on mortality depends on achieved recruitment (PaO2/FiO2) and mechanical power. Systematic review and meta-analysis with meta-regression / Estrategia OLA para el SDRA: su efecto en la mortalidad depende del reclutamiento alcanzado (PaO2/FiO2) y la potencia mecánica. Revisión sistemática y metaanálisis con metarregresión

Objective: The “Open Lung Approach” (OLA), that includes high levels of positive end-expiratory pressure coupled with limited tidal volumes, is considered optimal for adult patients with ARDS. However, many previous meta-analyses have shown only marginal benefits of OLA on mortality but with statistical heterogeneity. It is crucial to identify the most likely moderators of this effect. To determine the effect of OLA strategy on mortality of ventilated ARDS patients. We hypothesized that the degree of recruitment achieved in the control group (PaO2/FiO2 ratio on day 3 of ventilation), and the difference in Mechanical Power (MP) or Driving Pressure (DP) between experimental and control groups will be the most likely sources of heterogeneity. Design: A Systematic Review and Meta-analysis was performed according to PRISMA statement and registered in PROSPERO database. We searched only for randomized controlled trials (RCTs). GRADE guidelines were used for rating the quality of evidence. Publication bias was assessed. For the Meta-analysis, we used a Random Effects Model. Sources of heterogeneity were explored with Meta-Regression, using a priori proposed set of possible moderators. For model comparison, Akaike's Information Criterion with the finite sample correction (AICc) was used. Patients: Fourteen RCTs were included in the study. Results: Evidence of publication bias was detected, and quality of evidence was downgraded. Pooled analysis did not show a significant difference in the 28-day mortality between OLA strategy and control groups. Overall risk of bias was low. The analysis detected statistical heterogeneity. The two “best” explicative meta-regression models were those that used control PaO2/FiO2 on day 3 and difference in MP between experimental and control groups. The DP and MP models were highly correlated. Conclusions: There is no clear benefit of OLA strategy on mortality of ARDS patients, with significant heterogeneity among RCTs. ... (AU)

Objetivo: La Estrategia Open Lung (EOL), que incluye niveles elevados de presión positiva teleespiratoria junto con volumen corriente bajo, es considerada como el «patrón oro» para los pacientes adultos con SDRA. Sin embargo, varios metaanálisis previos han mostrado únicamente beneficios marginales de la EOL en la disminución de la mortalidad, aunque con gran heterogeneidad estadística. Es crucial identificar los moderadores más probables, así como determinar el efecto de la estrategia EOL en la mortalidad de los pacientes ventilados con SDRA. La hipótesis fue que el grado de reclutamiento alcanzado en el grupo control (cociente PaO2/FiO2 en el día3 de ventilación) y la diferencia en potencia mecánica (MP) o driving pressure (DP) entre el grupo experimental y el grupo control son la fuente más probable de heterogeneidad. Diseño Se realizó una revisión sistemática y metaanálisis de acuerdo con la declaración PRISMA, y se registró en la base de datos PROSPERO (N.° CRD42020179778). Se seleccionaron únicamente ensayos clínicos aleatorizados (ECA). Se estratificó la calidad de la evidencia de acuerdo con la metodología GRADE. Se evaluó el sesgo de publicación. Para el metaanálisis se utilizó el modelo de efectos aleatorios. Se exploraron las fuentes de heterogeneidad mediante metarregresión utilizando a priori un conjunto establecido de posibles moderadores. Para el modelo de comparación se utilizó el criterio de información de Akaike con la corrección para muestras pequeñas (AICc). Pacientes Se incluyeron 14 ECA en el estudio. Resultados Se detectó un sesgo de publicación, y la calidad fue degradada. El análisis combinado no mostró una diferencia estadísticamente significativa en la mortalidad en el día28 entre la estrategia EOL y los grupos control. El riesgo total de sesgo fue bajo. El análisis detectó heterogeneidad estadística. ... (AU)

OLA strategy for ARDS: Its effect on mortality depends on achieved recruitment (PaO2/FiO2) and mechanical power. Systematic review and meta-analysis with meta-regression.

OBJECTIVE: The "Open Lung Approach" (OLA), that includes high levels of positive end-expiratory pressure coupled with limited tidal volumes, is considered optimal for adult patients with ARDS. However, many previous meta-analyses have shown only marginal benefits of OLA on mortality but with statistical heterogeneity. It is crucial to identify the most likely moderators of this effect. To determine the effect of OLA strategy on mortality of ventilated ARDS patients. We hypothesized that the degree of recruitment achieved in the control group (PaO2/FiO2 ratio on day 3 of ventilation), and the difference in Mechanical Power (MP) or Driving Pressure (DP) between experimental and control groups will be the most likely sources of heterogeneity. DESIGN: A Systematic Review and Meta-analysis was performed according to PRISMA statement and registered in PROSPERO database. We searched only for randomized controlled trials (RCTs). GRADE guidelines were used for rating the quality of evidence. Publication bias was assessed. For the Meta-analysis, we used a Random Effects Model. Sources of heterogeneity were explored with Meta-Regression, using a priori proposed set of possible moderators. For model comparison, Akaike's Information Criterion with the finite sample correction (AICc) was used. SETTING: Not applicable. PATIENTS: Fourteen RCTs were included in the study. INTERVENTIONS: Not applicable. MAIN VARIABLES OF INTEREST: Not applicable. RESULTS: Evidence of publication bias was detected, and quality of evidence was downgraded. Pooled analysis did not show a significant difference in the 28-day mortality between OLA strategy and control groups. Overall risk of bias was low. The analysis detected statistical heterogeneity. The two "best" explicative meta-regression models were those that used control PaO2/FiO2 on day 3 and difference in MP between experimental and control groups. The DP and MP models were highly correlated. CONCLUSIONS: There is no clear benefit of OLA strategy on mortality of ARDS patients, with significant heterogeneity among RCTs. Mortality effect of OLA is mediated by lung recruitment and mechanical power.

Tapping into non-English-language science for the conservation of global biodiversity.

The widely held assumption that any important scientific information would be available in English underlies the underuse of non-English-language science across disciplines. However, non-English-language science is expected to bring unique and valuable scientific information, especially in disciplines where the evidence is patchy, and for emergent issues where synthesising available evidence is an urgent challenge. Yet such contribution of non-English-language science to scientific communities and the application of science is rarely quantified. Here, we show that non-English-language studies provide crucial evidence for informing global biodiversity conservation. By screening 419,679 peer-reviewed papers in 16 languages, we identified 1,234 non-English-language studies providing evidence on the effectiveness of biodiversity conservation interventions, compared to 4,412 English-language studies identified with the same criteria. Relevant non-English-language studies are being published at an increasing rate in 6 out of the 12 languages where there were a sufficient number of relevant studies. Incorporating non-English-language studies can expand the geographical coverage (i.e., the number of 2° × 2° grid cells with relevant studies) of English-language evidence by 12% to 25%, especially in biodiverse regions, and taxonomic coverage (i.e., the number of species covered by the relevant studies) by 5% to 32%, although they do tend to be based on less robust study designs. Our results show that synthesising non-English-language studies is key to overcoming the widespread lack of local, context-dependent evidence and facilitating evidence-based conservation globally. We urge wider disciplines to rigorously reassess the untapped potential of non-English-language science in informing decisions to address other global challenges. Please see the Supporting information files for Alternative Language Abstracts.