Interest in drug-induced liver injury(DILI) has dramatically increased over the past decade, and it has become a hot topic for clinicians, academics, pharmaceutical companies and regulatory bodies. By investigating th...Interest in drug-induced liver injury(DILI) has dramatically increased over the past decade, and it has become a hot topic for clinicians, academics, pharmaceutical companies and regulatory bodies. By investigating the current state of the art, the latest scientific findings, controversies, and guidelines, this review will attempt to answer the question: Do we know everything? Since the first descriptions of hepatotoxicity over 70 years ago, more than 1000 drugs have been identified to date, however, much of our knowledge of diagnostic and pathophysiologic principles remains unchanged. Clinically ranging from asymptomatic transaminitis and acute or chronic hepatitis, to acute liver failure, DILI remains a leading causes of emergent liver transplant. The consumption of unregulated herbal and dietary supplements has introduced new challenges in epidemiological assessment and clinician management. As such, numerous registries have been created, including the United States Drug-Induced Liver Injury Network, to further our understanding of all aspects of DILI. The launch of Liver Tox and other online hepatotoxicity resources has increased our awareness of DILI. In 2013, the first guidelines for the diagnosis and management of DILI, were offered by the Practice Parameters Committee of the American College of Gastroenterology, and along with the identification of risk factors and predictors of injury, novel mechanisms of injury, refined causality assessment tools, and targeted treatment options have come to define the current state of the art, however, gaps in our knowledge still undoubtedly remain.展开更多
BACKGROUND The coronavirus disease 2019(COVID-19)course may be affected by environmental factors.Ecological studies previously suggested a link between climatological factors and COVID-19 fatality rates.However,indivi...BACKGROUND The coronavirus disease 2019(COVID-19)course may be affected by environmental factors.Ecological studies previously suggested a link between climatological factors and COVID-19 fatality rates.However,individual-level impact of these factors has not been thoroughly evaluated yet.AIM To study the association of climatological factors related to patient location with unfavorable outcomes in patients.METHODS In this observational analysis of the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study:COVID-19 Registry cohort,the latitudes and altitudes of hospitals were examined as a covariate for mortality within 28 d of admission and the length of hospital stay.Adjusting for baseline parameters and admission date,multivariable regression modeling was utilized.Generalized estimating equations were used to fit the models.RESULTS Twenty-two thousand one hundred eight patients from over 20 countries were evaluated.The median age was 62(interquartile range:49-74)years,and 54%of the included patients were males.The median age increased with increasing latitude as well as the frequency of comorbidities.Contrarily,the percentage of comorbidities was lower in elevated altitudes.Mortality within 28 d of hospital admission was found to be 25%.The median hospital-free days among all included patients was 20 d.Despite the significant linear relationship between mortality and hospital-free days(adjusted odds ratio(aOR)=1.39(1.04,1.86),P=0.025 for mortality within 28 d of admission;aOR=-1.47(-2.60,-0.33),P=0.011 for hospital-free days),suggesting that adverse patient outcomes were more common in locations further away from the Equator;the results were no longer significant when adjusted for baseline differences(aOR=1.32(1.00,1.74),P=0.051 for 28-day mortality;aOR=-1.07(-2.13,-0.01),P=0.050 for hospital-free days).When we looked at the altitude’s effect,we discovered that it demonstrated a non-linear association with mortality within 28 d of hospital admission(aOR=0.96(0.62,1.47),1.04(0.92,1.19),0.49(0.22,0.90),and 0.51(0.27,0.98),for the altitude points of 75 MASL,125 MASL,400 MASL,and 600 MASL,in comparison to the reference altitude of 148 m.a.s.l,respectively.P=0.001).We detected an association between latitude and 28-day mortality as well as hospital-free days in this worldwide study.When the baseline features were taken into account,however,this did not stay significant.CONCLUSION Our findings suggest that differences observed in previous epidemiological studies may be due to ecological fallacy rather than implying a causal relationship at the patient level.展开更多
文摘Interest in drug-induced liver injury(DILI) has dramatically increased over the past decade, and it has become a hot topic for clinicians, academics, pharmaceutical companies and regulatory bodies. By investigating the current state of the art, the latest scientific findings, controversies, and guidelines, this review will attempt to answer the question: Do we know everything? Since the first descriptions of hepatotoxicity over 70 years ago, more than 1000 drugs have been identified to date, however, much of our knowledge of diagnostic and pathophysiologic principles remains unchanged. Clinically ranging from asymptomatic transaminitis and acute or chronic hepatitis, to acute liver failure, DILI remains a leading causes of emergent liver transplant. The consumption of unregulated herbal and dietary supplements has introduced new challenges in epidemiological assessment and clinician management. As such, numerous registries have been created, including the United States Drug-Induced Liver Injury Network, to further our understanding of all aspects of DILI. The launch of Liver Tox and other online hepatotoxicity resources has increased our awareness of DILI. In 2013, the first guidelines for the diagnosis and management of DILI, were offered by the Practice Parameters Committee of the American College of Gastroenterology, and along with the identification of risk factors and predictors of injury, novel mechanisms of injury, refined causality assessment tools, and targeted treatment options have come to define the current state of the art, however, gaps in our knowledge still undoubtedly remain.
文摘BACKGROUND The coronavirus disease 2019(COVID-19)course may be affected by environmental factors.Ecological studies previously suggested a link between climatological factors and COVID-19 fatality rates.However,individual-level impact of these factors has not been thoroughly evaluated yet.AIM To study the association of climatological factors related to patient location with unfavorable outcomes in patients.METHODS In this observational analysis of the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study:COVID-19 Registry cohort,the latitudes and altitudes of hospitals were examined as a covariate for mortality within 28 d of admission and the length of hospital stay.Adjusting for baseline parameters and admission date,multivariable regression modeling was utilized.Generalized estimating equations were used to fit the models.RESULTS Twenty-two thousand one hundred eight patients from over 20 countries were evaluated.The median age was 62(interquartile range:49-74)years,and 54%of the included patients were males.The median age increased with increasing latitude as well as the frequency of comorbidities.Contrarily,the percentage of comorbidities was lower in elevated altitudes.Mortality within 28 d of hospital admission was found to be 25%.The median hospital-free days among all included patients was 20 d.Despite the significant linear relationship between mortality and hospital-free days(adjusted odds ratio(aOR)=1.39(1.04,1.86),P=0.025 for mortality within 28 d of admission;aOR=-1.47(-2.60,-0.33),P=0.011 for hospital-free days),suggesting that adverse patient outcomes were more common in locations further away from the Equator;the results were no longer significant when adjusted for baseline differences(aOR=1.32(1.00,1.74),P=0.051 for 28-day mortality;aOR=-1.07(-2.13,-0.01),P=0.050 for hospital-free days).When we looked at the altitude’s effect,we discovered that it demonstrated a non-linear association with mortality within 28 d of hospital admission(aOR=0.96(0.62,1.47),1.04(0.92,1.19),0.49(0.22,0.90),and 0.51(0.27,0.98),for the altitude points of 75 MASL,125 MASL,400 MASL,and 600 MASL,in comparison to the reference altitude of 148 m.a.s.l,respectively.P=0.001).We detected an association between latitude and 28-day mortality as well as hospital-free days in this worldwide study.When the baseline features were taken into account,however,this did not stay significant.CONCLUSION Our findings suggest that differences observed in previous epidemiological studies may be due to ecological fallacy rather than implying a causal relationship at the patient level.
