Independent clinic-based evaluation of point-of-care testing for the screening of Chlamydia trachomatis, Neisseria gonorrhoea and Trichomonas vaginalis in women-at-risk in Australia, Guatemala, Morocco, and South Africa.

BACKGROUND: In 2018, the World Health Organization commenced a multi-country validation study of the Cepheid GeneXpert for a range of molecular-based point-of-care (POC) tests in primary care settings. One study arm focused on the evaluation of POC tests for screening 'women at risk' for chlamydia (CT), gonorrhoea (NG) and trichomonas (TV) in four countries - Australia, Guatemala, Morocco and South Africa. METHODS: Study participants completed a pre-test questionnaire which included demographics, clinical information and general questions on POC testing (POCT). Two vaginal swab samples (either self-collected or clinician collected) from each patient were tested on the GeneXpert at the POC and at a reference laboratory using quality-assured nucleic acid amplification tests (NAATs). RESULTS: One thousand three hundred and eighty-three women were enrolled: 58.6% from South Africa, 29.2% from Morocco, 6.2% from Guatemala, and 6.0% from Australia. 1296 samples for CT/NG and 1380 samples for TV were tested by the GeneXpert and the reference NAAT. The rate of unsuccessful tests on the GeneXpert was 1.9% for CT, 1.5% for NG and 0.96% for TV. The prevalence of CT, NG and TV was 31%, 13% and 23%, respectively. 1.5% of samples were positive for all three infections; 7.8% were positive for CT and NG; 2.4% were positive for NG and TV; and 7.3% were positive for CT and TV. Compared to reference NAATs, pooled estimates of sensitivity for the GeneXpert tests were 83.7% (95% confidence intervals 69.2-92.1) for CT, 90.5% (85.1-94.1) for NG and 64.7% (58.1-70.7) for TV (although estimates varied considerably between countries). Estimates for specificity were ≥96% for all three tests both within- and between-countries. Pooled positive and negative likelihood ratios were: 32.7 ([CI] 21.2-50.5) and 0.17 (0.08-0.33) for CT; 95.3 (36.9-245.7) and 0.10 (0.06-0.15) for NG; and 56.5 (31.6-101.1) and 0.35 (0.27-0.47) for TV. CONCLUSION: This multi-country evaluation is the first of its kind world-wide. Positive likelihood ratios, as well as specificity estimates, indicate the GeneXpert POC test results for CT, NG and TV were clinically acceptable for ruling in the presence of disease. However, negative likelihood ratios and variable sensitivity estimates from this study were poorer than expected for ruling out these infections, particularly for TV. TRIAL REGISTRATION: Ethics approval to conduct the ProSPeRo study was granted by the WHO Ethics Review Committee, as well as local ethics committees from all participating countries.

Mental Health of Guatemalan Health Care Workers During the COVID-19 Pandemic: Baseline Findings From the HEROES Cohort Study.

Objectives. To assess the baseline prevalence of mental health conditions and associated exposures in a cohort of health care workers (HCWs) in Guatemala. Methods. We analyzed baseline information from the 2020 Web-based COVID-19 Health Care Workers Study (HEROES)-Guatemala. Outcomes included mental distress and depressive symptoms. Exposures included COVID-19 experiences, sociodemographic characteristics, and job characteristics. We used crude and adjusted Poisson regression models in our analyses. Results. Of the 1801 HCWs who accepted to participate, 1522 (84.5%) completed the questionnaire; 1014 (66.8%) were women. Among the participants, 59.1% (95% confidence interval [CI] = 56.6, 61.5) screened positive for mental distress and 23% (95% CI = 20.9, 25.2) for moderate to severe depressive symptoms. COVID-19 experiences, sociodemographic characteristics, and job characteristics were associated with the study outcomes. Participants who were worried about COVID-19 infection were at higher risk of mental distress (relative risk [RR] = 1.47; 95% CI = 1.30, 1.66) and depressive symptoms (RR = 1.51; 95% CI = 1.17, 1.96). Similarly, the youngest participants were at elevated risk of mental distress (RR = 1.80; 95% CI = 1.24, 2.63) and depressive symptoms (OR = 4.58; 95% CI = 1.51, 13.87). Conclusions. Mental health conditions are highly prevalent among Guatemalan HCWs. (Am J Public Health. 2022;112(S6):S602-S614. https://doi.org/10.2105/AJPH.2021.306648).

[Mental health of Guatemalan health care workers during the COVID-19 pandemic: baseline findings from the HEROES cohort studySaúde mental dos trabalhadores da saúde guatemaltecos durante a pandemia de COVID-19: constatações basais do estudo da coorte HEROES]. / La salud mental de los trabajadores de salud en Guatemala durante la pandemia de COVID-19: resultados de base del estudio de cohortes HÉROES.

Objectives: To assess the baseline prevalence of mental health conditions and associated exposures in a cohort of health care workers (HCWs) in Guatemala. Methods: We analyzed baseline information from the 2020 Web-based COVID-19 Health Care Workers Study (HEROES)-Guatemala. Outcomes included mental distress and depressive symptoms. Exposures included COVID-19 experiences, sociodemographic characteristics, and job characteristics. We used crude and adjusted Poisson regression models in our analyses. Results: Of the 1801 HCWs who accepted to participate, 1522 (84.5%) completed the questionnaire; 1014 (66.8%) were women. Among the participants, 59.1% (95% confidence interval [CI] = 56.6, 61.5) screened positive for mental distress and 23% (95% CI = 20.9, 25.2) for moderate to severe depressive symptoms. COVID-19 experiences, sociodemographic characteristics, and job characteristics were associated with the study outcomes. Participants who were worried about COVID-19 infection were at higher risk of mental distress (relative risk [RR] = 1.47; 95% CI = 1.30, 1.66) and depressive symptoms (RR = 1.51; 95% CI = 1.17, 1.96). Similarly, the youngest participants were at elevated risk of mental distress (RR = 1.80; 95% CI = 1.24, 2.63) and depressive symptoms (OR = 4.58; 95% CI = 1.51, 13.87). Conclusions: Mental health conditions are highly prevalent among Guatemalan.

Objetivos: Avaliar a prevalência basal de condições de saúde mental e exposições associadas em uma coorte de trabalhadores da saúde (TS) na Guatemala. Métodos: Analisamos as informações da linha de base do estudo on-line sobre trabalhadores da saúde e a COVID-19 (HEROES), realizado em 2020 na Guatemala. Os desfechos incluíram angústia debilitante e sintomas de depressão. As exposições incluíram experiências com a COVID-19, características sociodemográficas e características do trabalho. Usamos em nossas análises modelos de regressão bruta e ajustada de Poisson. Resultados: Dos 1801 TS que concordaram em participar, 1522 (84,5%) preencheram o questionário, sendo que 1014 (66,8%) eram mulheres. Dentre esses participantes, 59,1% (intervalo de confiança [IC] de 95%=56,6; 61,5) apresentaram resultado positivo na triagem de angústia debilitante e 23% (IC 95%=20,9, 25,2) apresentaram resultado positivo para sintomas de depressão moderados a graves. Experiências com COVID-19, e características sociodemográficas e de trabalho apresentaram associação com os resultados do estudo. Os participantes que estavam preocupados com infecção por COVID-19 apresentaram maior risco de angústia debilitante (risco relativo [RR]=1,47; IC95%=1,30; 1,66) e sintomas de depressão (RR=1,51; IC 95% =1,17; 1,96). Da mesma maneira, os participantes mais jovens apresentaram alto risco de apresentarem angústia debilitante (RR=1,80; IC 95%=1,24; 2,63) e sintomas de depressão (OR=4,58; IC 95%=1,51; 13,87). Conclusões: Condições de saúde mental são altamente prevalentes entre os guatemaltecos.

The relationship between pay day and violent death in Guatemala: a time series analysis.

OBJECTIVE: To assess if violent deaths were associated with pay days in Guatemala. DESIGN: Interrupted time series analysis. SETTING: Guatemalan national autopsy databases. PARTICIPANTS: Daily violence-related autopsy data for 22 418 decedents from 2009 to 2012. Data were provided by the Guatemalan National Institute of Forensic Sciences. Multiple pay-day lags and other important days such as holidays were tested. OUTCOME MEASURES: Absolute and relative estimates of excess violent deaths on pay days and holidays. RESULTS: The occurrence of violent deaths was not associated with pay days. However, a significant association was observed for national holidays, and this association was more pronounced when national holidays and pay days occurred simultaneously. This effect was observed mainly in males, who constituted the vast majority of violent deaths in Guatemala. An estimated 112 (coefficient=3.12; 95% CI 2.15 to 4.08; p<0.01) more male violent deaths occurred on holidays than were expected. An estimated 121 (coefficient=4.64; 95% CI 3.41 to 5.88; p<0.01) more male violent deaths than expected occurred on holidays that coincided with the first 2 days following a pay day. CONCLUSIONS: Men in Guatemala experience violent deaths at an elevated rate when pay days coincide with national holidays. Efforts to be better prepared for violence during national holidays and to prevent violent deaths by rescheduling pay days when these days co-occur with national holidays should be considered.

Inequality on the frontline: A multi-country study on gender differences in mental health among healthcare workers during the COVID-19 pandemic.

Healthcare workers (HCWs) were at increased risk for mental health problems during the COVID-19 pandemic, with prior data suggesting women may be particularly vulnerable. Our global mental health study aimed to examine factors associated with gender differences in psychological distress and depressive symptoms among HCWs during COVID-19. Across 22 countries in South America, Europe, Asia and Africa, 32,410 HCWs participated in the COVID-19 HEalth caRe wOrkErS (HEROES) study between March 2020 and February 2021. They completed the General Health Questionnaire-12, the Patient Health Questionnaire-9 and questions about pandemic-relevant exposures. Consistently across countries, women reported elevated mental health problems compared to men. Women also reported increased COVID-19-relevant stressors, including insufficient personal protective equipment and less support from colleagues, while men reported increased contact with COVID-19 patients. At the country level, HCWs in countries with higher gender inequality reported less mental health problems. Higher COVID-19 mortality rates were associated with increased psychological distress merely among women. Our findings suggest that among HCWs, women may have been disproportionately exposed to COVID-19-relevant stressors at the individual and country level. This highlights the importance of considering gender in emergency response efforts to safeguard women's well-being and ensure healthcare system preparedness during future public health crises.

Latin American Internet Survey for Men who have Sex with Men (LAMIS-2018): Design, methods and implementation.

Despite men-who-have-sex-with-men (MSM) from Latin America (LA) are still a vulnerable population for known health-related conditions and social problems, availability of comparable data across LA countries for assessment and monitoring purposes is limited. The objective of this article is to present the study design and the questionnaire of LAMIS-2018 (Latin America MSM Internet Survey), its recruitment strategy, rates and sources by country, and the lessons learned from its implementation. LAMIS-2018 was a cross-sectional, internet-based survey targeting MSM living in 18 LA countries (Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Ecuador, El Salvador, Guatemala, Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru, Suriname, Uruguay, and Venezuela) that gathered data about sexual behaviors, HIV/STI and viral hepatitis knowledge, prophylactic use of antiretrovirals, psychosocial health, and access to sexual health services. The survey went online for four months and was available in three languages (Spanish, Portuguese, and Dutch). Promotion was carried out using dating apps, websites, social networks, and by community-based and academic organizations of each participating country directly in gay venues and in their own premises. Overall, 64,655 MSM participated in LAMIS-2018. Dating apps and websites were the most important recruitment source in most countries, except for Honduras, Nicaragua, and Suriname, where community-based organizations recruited most of the participants. Beyond the LAMIS-2018 implementation description, we highlight the feasibility of such a study in this context, based on the collaboration between community-based and academic organizations to obtain a large sample of MSM in the region. LAMIS-2018 data will contribute to identify determinants of risk behaviors and prevention needs of vulnerable MSM populations in each country of the region.

Language interpreter utilization in the emergency department setting: a clinical review.

The emergency department (ED) serves as the entry point into the U.S. health care system for many patients with limited English proficiency (LEP). This paper reviews the literature on language interpreter utilization in the ED setting. We focused on three clinical issues related to professional language interpretation: (1) patient satisfaction, (2) health care delivery, and (3) current interpreter utilization practices. Compared with-English speaking patients, LEP patients report less satisfaction with medical encounters, have different rates of diagnostic testing, and receive less explanation and follow-up. Although professional interpretation has been associated with improvements in patient satisfaction, communication, and health care access, these services are largely under-utilized in ED settings. Reliance on untrained ad hoc interpreters, perceived time and labor associated with obtaining and working with an interpreter, and costs of implementing professional interpreter services serve as barriers to implementation and utilization.

Death inducer-obliterator 1 triggers apoptosis after nuclear translocation and caspase upregulation.

Death inducer-obliterator 1 (DIO-1) is a gene that is upregulated early in apoptosis. Here we report that in healthy cells, the DIO-1 gene product was located in the cytoplasm, where it formed oligomers. After interleukin-3 starvation or c-Myc-induced apoptosis in serum-free conditions, DIO-1 translocated to the nucleus, where it upregulated caspase levels and activity. A nuclear localization signal deletion mutant (DIO-1deltaNLS) was unable to translocate to the nuclear compartment in the absence of interleukin-3 and failed to upregulate procaspase levels or trigger cell death. In addition, cells stably expressing DIO-1deltaNLS were protected from apoptosis induced by interleukin-3 withdrawal. These results indicate that DIO-1 has a relevant role in regulating the early stages of cell death.

La salud mental de los trabajadores de salud en Guatemala durante la pandemia de COVID-19: resultados de base del estudio de cohortes HÉROES / Mental health of Guatemalan health care workers during the COVID-19 pandemic: baseline findings from the HEROES cohort study / Saúde mental dos trabalhadores da saúde guatemaltecos durante a pandemia de COVID-19: constatações basais do estudo da coorte HEROES

RESUMEN Objetivos. Evaluar la prevalencia de base de los trastornos de salud mental y exposiciones conexas en una cohorte de trabajadores de salud de Guatemala. Métodos Se analizó la información de base del estudio HÉROES (por COVID-19 HEalth caRe wOrkeRs Study, sobre los trabajadores de salud durante la pandemia) en Guatemala, realizado en línea en el 2020. Las variables de resultado fueron malestar psicológico y síntomas depresivos. Las exposiciones incluyeron experiencias con la COVID-19, características sociodemográficas y características del trabajo. En los análisis se utilizaron modelos de regresión de Poisson brutos y ajustados. Resultados. De los 1801 trabajadores de salud que aceptaron participar, 1522 (84,5%) completaron el cuestionario; 1014 (66,8%) eran mujeres. De los participantes, 59,1% (intervalo de confianza de 95% [IC 95%] = 56,6-61,5) tuvo un tamizaje positivo para malestar psicológico y 23% (IC 95% = 20,9-25,2) para síntomas depresivos de moderados a graves. Las experiencias con la pandemia de COVID-19, las características sociodemográficas y las características del trabajo se correlacionaron con las variables de resultado del estudio. Los participantes que estaban preocupados por el contagio de la COVID-19 tuvieron un mayor riesgo de malestar psicológico (riesgo relativo [RR] = 1,47; IC 95% = 1,30-1,66) y síntomas depresivos (RR = 1,51; IC 95% = 1,17-1,96). Asimismo, los participantes más jóvenes presentaban un riesgo alto de malestar psicológico (RR = 1,80; IC 95% = 1,24-2,63) y síntomas depresivos (razón de posibilidades [OR] = 4,58; IC 95% = 1,51-13,87). Conclusiones. Las afecciones de salud mental tienen una prevalencia sumamente alta en los trabajadores de salud de Guatemala.

ABSTRACT Objectives. To assess the baseline prevalence of mental health conditions and associated exposures in a cohort of health care workers (HCWs) in Guatemala. Methods. We analyzed baseline information from the 2020 Web-based COVID-19 Health Care Workers Study (HEROES)-Guatemala. Outcomes included mental distress and depressive symptoms. Exposures included COVID-19 experiences, sociodemographic characteristics, and job characteristics. We used crude and adjusted Poisson regression models in our analyses. Results. Of the 1801 HCWs who accepted to participate, 1522 (84.5%) completed the questionnaire; 1014 (66.8%) were women. Among the participants, 59.1% (95% confidence interval [CI] = 56.6, 61.5) screened positive for mental distress and 23% (95% CI = 20.9, 25.2) for moderate to severe depressive symptoms. COVID-19 experiences, sociodemographic characteristics, and job characteristics were associated with the study outcomes. Participants who were worried about COVID-19 infection were at higher risk of mental distress (relative risk [RR] = 1.47; 95% CI = 1.30, 1.66) and depressive symptoms (RR = 1.51; 95% CI = 1.17, 1.96). Similarly, the youngest participants were at elevated risk of mental distress (RR = 1.80; 95% CI = 1.24, 2.63) and depressive symptoms (OR = 4.58; 95% CI = 1.51, 13.87). Conclusions. Mental health conditions are highly prevalent among Guatemalan.

RESUMO Objetivos. Avaliar a prevalência basal de condições de saúde mental e exposições associadas em uma coorte de trabalhadores da saúde (TS) na Guatemala. Métodos. Analisamos as informações da linha de base do estudo on-line sobre trabalhadores da saúde e a COVID-19 (HEROES), realizado em 2020 na Guatemala. Os desfechos incluíram angústia debilitante e sintomas de depressão. As exposições incluíram experiências com a COVID-19, características sociodemográficas e características do trabalho. Usamos em nossas análises modelos de regressão bruta e ajustada de Poisson. Resultados. Dos 1801 TS que concordaram em participar, 1522 (84,5%) preencheram o questionário, sendo que 1014 (66,8%) eram mulheres. Dentre esses participantes, 59,1% (intervalo de confiança [IC] de 95%=56,6; 61,5) apresentaram resultado positivo na triagem de angústia debilitante e 23% (IC 95%=20,9, 25,2) apresentaram resultado positivo para sintomas de depressão moderados a graves. Experiências com COVID-19, e características sociodemográficas e de trabalho apresentaram associação com os resultados do estudo. Os participantes que estavam preocupados com infecção por COVID-19 apresentaram maior risco de angústia debilitante (risco relativo [RR]=1,47; IC95%=1,30; 1,66) e sintomas de depressão (RR=1,51; IC 95% =1,17; 1,96). Da mesma maneira, os participantes mais jovens apresentaram alto risco de apresentarem angústia debilitante (RR=1,80; IC 95%=1,24; 2,63) e sintomas de depressão (OR=4,58; IC 95%=1,51; 13,87). Conclusões. Condições de saúde mental são altamente prevalentes entre os guatemaltecos.

La salud mental de los trabajadores de salud en Guatemala durante la pandemia de COVID-19: resultados de base del estudio de cohortes HÉROES

[RESUMEN]. Objetivos. Evaluar la prevalencia de base de los trastornos de salud mental y exposiciones conexas en una cohorte de trabajadores de salud de Guatemala. Métodos Se analizó la información de base del estudio HÉROES (por COVID-19 HEalth caRe wOrkeRs Study, sobre los trabajadores de salud durante la pandemia) en Guatemala, realizado en línea en el 2020. Las variables de resultado fueron malestar psicológico y síntomas depresivos. Las exposiciones incluyeron expe- riencias con la COVID-19, características sociodemográficas y características del trabajo. En los análisis se utilizaron modelos de regresión de Poisson brutos y ajustados. Resultados. De los 1801 trabajadores de salud que aceptaron participar, 1522 (84,5%) completaron el cues- tionario; 1014 (66,8%) eran mujeres. De los participantes, 59,1% (intervalo de confianza de 95% [IC 95%] = 56,6-61,5) tuvo un tamizaje positivo para malestar psicológico y 23% (IC 95% = 20,9-25,2) para síntomas depresivos de moderados a graves. Las experiencias con la pandemia de COVID-19, las características sociodemográficas y las características del trabajo se correlacionaron con las variables de resultado del estudio. Los participantes que estaban preocupados por el contagio de la COVID-19 tuvieron un mayor riesgo de malestar psicológico (riesgo relativo [RR] = 1,47; IC 95% = 1,30-1,66) y síntomas depresivos (RR = 1,51; IC 95% = 1,17-1,96). Asimismo, los participantes más jóvenes presentaban un riesgo alto de malestar psicoló- gico (RR = 1,80; IC 95% = 1,24-2,63) y síntomas depresivos (razón de posibilidades [OR] = 4,58; IC 95% = 1,51-13,87). Conclusiones. Las afecciones de salud mental tienen una prevalencia sumamente alta en los trabajadores de salud de Guatemala.

[ABSTRACT]. Objectives. To assess the baseline prevalence of mental health conditions and associated exposures in a cohort of health care workers (HCWs) in Guatemala. Methods. We analyzed baseline information from the 2020 Web-based COVID-19 Health Care Workers Study (HEROES)–Guatemala. Outcomes included mental distress and depressive symptoms. Exposures included COVID-19 experiences, sociodemographic characteristics, and job characteristics. We used crude and adjus- ted Poisson regression models in our analyses. Results. Of the 1801 HCWs who accepted to participate, 1522 (84.5%) completed the questionnaire; 1014 (66.8%) were women. Among the participants, 59.1% (95% confidence interval [CI] = 56.6, 61.5) screened positive for mental distress and 23% (95% CI = 20.9, 25.2) for moderate to severe depressive symptoms. COVID-19 experiences, sociodemographic characteristics, and job characteristics were associated with the study outcomes. Participants who were worried about COVID-19 infection were at higher risk of mental distress (relative risk [RR] = 1.47; 95% CI = 1.30, 1.66) and depressive symptoms (RR = 1.51; 95% CI = 1.17, 1.96). Similarly, the youngest participants were at elevated risk of mental distress (RR = 1.80; 95% CI = 1.24, 2.63) and depressive symptoms (OR = 4.58; 95% CI = 1.51, 13.87). Conclusions. Mental health conditions are highly prevalent among Guatemalan.

[RESUMO]. Objetivos. Avaliar a prevalência basal de condições de saúde mental e exposições associadas em uma coorte de trabalhadores da saúde (TS) na Guatemala. Métodos. Analisamos as informações da linha de base do estudo on-line sobre trabalhadores da saúde e a COVID-19 (HEROES), realizado em 2020 na Guatemala. Os desfechos incluíram angústia debilitante e sintomas de depressão. As exposições incluíram experiências com a COVID-19, características sociodemo- gráficas e características do trabalho. Usamos em nossas análises modelos de regressão bruta e ajustada de Poisson. Resultados. Dos 1801 TS que concordaram em participar, 1522 (84,5%) preencheram o questionário, sendo que 1014 (66,8%) eram mulheres. Dentre esses participantes, 59,1% (intervalo de confiança [IC] de 95%=56,6; 61,5) apresentaram resultado positivo na triagem de angústia debilitante e 23% (IC 95%=20,9, 25,2) apresentaram resultado positivo para sintomas de depressão moderados a graves. Experiências com COVID-19, e características sociodemográficas e de trabalho apresentaram associação com os resul- tados do estudo. Os participantes que estavam preocupados com infecção por COVID-19 apresentaram maior risco de angústia debilitante (risco relativo [RR]=1,47; IC95%=1,30; 1,66) e sintomas de depressão (RR=1,51; IC 95% =1,17; 1,96). Da mesma maneira, os participantes mais jovens apresentaram alto risco de apresentarem angústia debilitante (RR=1,80; IC 95%=1,24; 2,63) e sintomas de depressão (OR=4,58; IC 95%=1,51; 13,87). Conclusões. Condições de saúde mental são altamente prevalentes entre os guatemaltecos.

Evidencia disponible sobre el abordaje terapéutico de pacientes con COVID-19: una revisión narrativa / Available evidence regarding therapeutic approach of patients with COVID-19: a narrative review

La ausencia de tratamiento específico para COVID-19 demanda una revisión dinámica de la evidencia científica disponible que permita un manejo dirigido a lograr la mejoría clínica, reducción de complicaciones y una menor mortalidad. Los factores independientes de riesgo asociados a mayor mortalidad, falla ventilatoria y necesidad de ventilación mecánica incluyen edad avanzada, enfermedades crónico-degenerativas, obesidad, elevación de ferritina, LDH, ALT y AST, marcadores de incremento en la generación de trombina, datos de daño cardiaco (elevación de troponinas y NT-pro-BNP) y niveles de IL-6 elevados. En ausencia de antivirales de acción directa, el abordaje terapéutico temprano con terapia anti-IL-6, la supresión de la cascada inflamatoria y transducción de señales mediante uso de glucocorticoides, la profilaxis trombótica y anticoagulación, así como la inhibición de la trombogénesis y noxa cardiaca con el uso de colchicina, pueden ser considerados hasta el momento como medidas plausibles en el manejo de los pacientes con COVID-19 en estado moderado y grave. Remdesivir puede considerarse para el tratamiento de pacientes con lesión pulmonar severa sin falla ventilatoria, tras evidencia sólida que ha demostrado mejoría clínica y reducción de mortalidad. En el subgrupo de pacientes graves y bajo ventilación mecánica, el uso de plasma de paciente convaleciente ha producido mejoría clínica, aunque la evidencia es limitada. La pronación en el paciente despierto y bajo ventilación mecánica puede considerarse como medida para mejorar la oxigenación con poca influencia sobre la mortalidad. Esta revisión plantea las medidas terapéuticas disponibles al momento y la estratificación de riesgo para el manejo de pacientes con infección por SARS-CoV-2.

The absence of a specific treatment for COVID-19 demands a dynamic review of the available scientific evidence that allows a management aimed at achieving clinical improvement, reduction of complications, and lower mortality. Independent risk factors associated with increased respiratory failure, mechanical ventilation requirement, and mortality include older age, chronic illness, obesity, ferritin, LDH, ALT, and AST elevation, thrombin release markers, cardiac damage markers (troponins and NT-proBNP elevation) and elevated levels of IL-6. In the absence of specific antiviral agents, the early treatment of mild to severe COVID-19 using IL-6 inhibitors, suppression of inflammatory cascade and signal transduction by using glucocorticoids, use of antithrombotic prophylaxis and anticoagulation, as well as thrombogenesis and cardiac damage inhibition by using colchicine, could be considered as a plausible route. Another drug to be considered in patients with severe lung injury without respiratory failure is remdesivir, which has shown substantial evidence reducing mortality and clinical improvement. In severe COVID-19 and in those that require ventilatory assistance, convalescent plasma use has resulted in clinical improvement despite limited evidence. Prone positioning in awake and intubated patients might be considered to improve oxygenation with scarce effect on mortality. The present review aims to expose the current therapeutic options and risk stratification course for the management of SARS-CoV-2 positive patients.

Maternal smoking during early pregnancy, GSTP1 and EPHX1 variants, and risk of isolated orofacial clefts.

OBJECTIVE: To examine the interactions between four fetal xenobiotic metabolizing gene polymorphisms, maternal cigarette smoking, and risk for oral cleft defects. DESIGN AND PARTICIPANTS: California population-based case-control study of 431 infants born with isolated orofacial clefts and 299 nonmalformed controls. MAIN OUTCOME MEASURES: Infants were genotyped for functional polymorphisms of the detoxification enzymes microsomal epoxide hydrolase-1 (EPHX1 T-->C [Tyr113His], and A-->G [His139Arg]), and glutathione-S transferase Pi-1 (GSTP1 A-->G [Ile105Val] and C-->T [Ala114Val]), and risks for cleft outcomes were measured for gene only and gene-maternal smoking effects. RESULTS: Although smoking was associated with an increased risk for isolated cleft lip+/-palate, we found no independent associations of genotypes of EPHX1-codon 113 or GSTP1-codon 105 polymorphisms for either isolated cleft lip+/-palate or isolated cleft palate. The heterozygote genotype for the EPHX1-codon 139 polymorphism was associated with an increased risk of isolated cleft palate (odds ratio=1.6 [95% confidence interval, 1.0 to 2.6]). Infant EPHX1 and GTSP1 polymorphic variants did not appreciably alter the risks for clefts associated with maternal smoking, nor were any EPHX1 combined genotype-specific risks found. Infant genotypes of the GSTP1-codon 105 polymorphism, combined with glutathione-S-transferase-mu-1 null genotypes, did not appreciably alter the risk of orofacial clefts. CONCLUSIONS: Our results suggest that genetic variation of the detoxification enzymes EPHX1 and GSTP1 did not increase the risks of orofacial clefting, nor do they influence the risks associated with maternal smoking.

Lacrimoauriculodentodigital syndrome with cleft lip/palate and renal manifestations.

OBJECTIVE: To describe the largest family reported with the lacrimoauriculodentodigital (LADD) syndrome. DESIGN: A family study of eight individuals with LADD syndrome. SETTING: Pediatric Clinical Research Center at Oakland Children's Hospital. PATIENTS: Eight individuals in a four-generation family. MAIN OUTCOME MEASURE: A diagnosis of LADD syndrome was determined by the presence of one or more of the characteristic lacrimal duct, auricular, dental, or digital malformations. Tear function and orofacial clefting were also considered in the final diagnosis of LADD syndrome. RESULTS: Affected family members had the characteristic features of LADD syndrome, including cup-shaped ears; lacrimal duct obstruction; and dental, forearm, and digit malformations. In addition to the cardinal features of LADD syndrome, the proband was born with cleft lip and palate. The mother and sister of the proband have hydronephrosis, a rare feature of the disorder. Family members also have features not previously described in LADD syndrome, including vesicoureteral reflux, recurrent urinary tract infections, camptodactyly, distal thumb symphalangism, and a bicornuate uterus. CONCLUSIONS: The findings suggest that the presence of vesicoureteral reflux and recurrent urinary tract infections should be evaluated in LADD syndrome patients and that the distinction of LADD syndrome from ectrodactyly-ectodermal dysplasia and clefting syndrome by the absence of clefting may need to be reconsidered.

Autosomal recessive frontotemporal pachygyria.

Pachygyria is a cortical malformation that results from the abnormal migration of neurons. Regions of the brain with pachygyria have an abnormally thick cortex that lacks normal folding and has deficient layering. We describe three siblings, born to nonconsanguineous Mexican parents, who have bilateral frontotemporal pachygyria without polymicrogyria. The pachygyria is accompanied by moderate mental retardation, esotropia, and either hypertelorism or telecanthus. They are otherwise morphologically normal and do not have microcephaly. Two experienced a single seizure in infancy. The characteristic phenotype present in this family suggests a new genetic syndrome that is likely inherited as an autosomal recessive trait.