Suchergebnisse

The media have featured the antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) to treat coronavirus (COVID-19). Political leaders have touted their use and recommended availability to the public. These anti-inflammatory agents have substantial human toxicity with a narrow therapeutic window. CQ and HCQ poisoning cause myocardial depression and profound hypotension due to vasodilation. Bradycardia and ventricular escape rhythms arise from impaired myocardial automaticity and conductivity due to sodium and potassium channel blockade. With cardiotoxicity, ECGs may show widened QRS, atrioventricular heart block and QT interval prolongation. CQ may also cause seizures, often refractory to standard treatment. Of concern is pediatric poisoning, where 1-2 pills of CQ or HCQ can cause serious and potentially fatal toxicity in a toddler. The treatment of CQ/HCQ poisoning includes high-dose intravenous diazepam postulated to have positive ionotropic and antidysrhythmic properties that may antagonize the cardiotoxic effects of CQ. Infusions of epinephrine titrated to treat unstable hypotension, as well as potassium for severe hypokalemia may be required. Current scientific evidence does not support treatment or prophylactic use of these agents for COVID-19 disease. Regulatory and public health authorities recognize that CQ/HCQ may offer little clinical benefit and only add risk requiring further investigation before wider public distribution.

The media have featured the antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) to treat coronavirus (COVID-19). Political leaders have touted their use and recommended availability to the public. These anti-inflammatory agents have substantial human toxicity with a narrow therapeutic window. CQ and HCQ poisoning cause myocardial depression and profound hypotension due to vasodilation. Bradycardia and ventricular escape rhythms arise from impaired myocardial automaticity and conductivity due to sodium and potassium channel blockade. With cardiotoxicity, ECGs may show widened QRS, atrioventricular heart block and QT interval prolongation. CQ may also cause seizures, often refractory to standard treatment. Of concern is pediatric poisoning, where 1-2 pills of CQ or HCQ can cause serious and potentially fatal toxicity in a toddler. The treatment of CQ/HCQ poisoning includes high-dose intravenous diazepam postulated to have positive ionotropic and antidysrhythmic properties that may antagonize the cardiotoxic effects of CQ. Infusions of epinephrine titrated to treat unstable hypotension, as well as potassium for severe hypokalemia may be required. Current scientific evidence does not support treatment or prophylactic use of these agents for COVID-19 disease. Regulatory and public health authorities recognize that CQ/HCQ may offer little clinical benefit and only add risk requiring further investigation before wider public distribution. ; National Institutes of Health (Grant K23DA044874)

The dramatic increase of bioreactive nitrogen entering the Earth's ecosystems continues to attract growing attention. Increasingly large quantities of inorganic nitrogen are flushed from land to water, accelerating freshwater, and marine eutrophication. Multiple, interacting, and potentially countervailing drivers control the future hydrologic export of inorganic nitrogen. In this paper, we attempt to resolve these land-water interactions across boreal/hemiboreal Sweden in the face of a changing climate with help of a versatile modeling framework to maximize the information value of existing measurement time series. We combined 6,962 spatially distributed water chemistry observations spread over 31years with daily streamflow and air temperature records. An ensemble of climate model projections, hydrological simulations, and several parameter parsimonious regression models was employed to project future riverine inorganic nitrogen dynamics across Sweden. The median predicted increase in total inorganic nitrogen export from Sweden (2061-2090) due to climate change was 14% (interquartile range 0-29%), based on the ensemble of 7,500 different predictions for each study site. The overall export as well as the seasonal pattern of inorganic nitrogen loads in a future climate are mostly influenced by longer growing seasons and more winter flow, which offset the expected decline in spring flood. The predicted increase in inorganic nitrogen loading due to climate change means that the political efforts for reducing anthropogenic nitrogen inputs need to be increased if ambitions for reducing the eutrophication of the Baltic Sea are to be achieved.