Right ventricular failure (RVF) increases morbidity and mortality. The RECOVER RIGHT study evaluated the safety and efficacy of a novel percutaneous right ventricular assist device, the Impella RP ...(Abiomed, Danvers, MA), in a prospective, multicenter trial.
Thirty patients with RVF refractory to medical treatment received the Impella RP device at 15 United States institutions. The study population included 2 cohorts: 18 patients with RVF after left ventricular assist device (LVAD) implantation (Cohort A) and 12 patients with RVF after cardiotomy or myocardial infarction (Cohort B). The primary end point was survival to 30 days or hospital discharge (whichever was longer). Major secondary end points included indices of safety and efficacy.
The patients (77% male) were a mean age of 59 ± 15 years, 53% had diabetes, 88.5% had a history of congestive heart failure, and 37.5% had renal dysfunction. Patients were on an average of 3.2 inotropes/pressors. Device delivery was achieved in all but 1 patient. Hemodynamics improved immediately after initiation of Impella RP support, with an increase in cardiac index from 1.8 ± 0.2 to 3.3 ± 0.23 liters/min/m(2) (p < 0.001) and a decrease in central venous pressure from 19.2 ± 4 to 12.6 ± 1 mm Hg (p < 0.001). Patients were supported for an average of 3.0 ± 1.5 days (range, 0.5-7.8 days). The overall survival at 30 days was 73.3%. All patients discharged were alive at 180 days.
In patients with life-threatening RVF, the novel percutaneous Impella RP device was safe, easy to deploy, and reliably resulted in immediate hemodynamic benefit. These data support its probable benefit in this gravely ill patient population.
Myth Busters: Dietary Supplements and COVID-19 Adams, Kathleen K.; Baker, William L.; Sobieraj, Diana M.
The Annals of pharmacotherapy,
08/2020, Letnik:
54, Številka:
8
Journal Article
Recenzirano
Odprti dostop
News and social media platforms have implicated dietary supplements in the treatment and prevention of coronavirus disease 2019 (COVID-19). During this pandemic when information quickly evolves in ...the presence of contradicting messages and misinformation, the role of the pharmacist is essential. Here, we review theoretical mechanisms and evidence related to efficacy and safety of select supplements in the setting of COVID-19, including vitamin C, vitamin D, zinc, elderberry, and silver. Evidence evaluating these supplements in COVID-19 patients is lacking, and providers and patients should not rely on dietary supplements to prevent or treat COVID-19. Rather, reference to evidence-based guidelines should guide treatment decisions.
Fire‐prone dry forests often face increasing fires from climate change with low resistance and resilience due to logging of large, old fire‐resistant trees. Their restoration across large landscapes ...is constrained by limited mature trees, physical settings, and protection. Active restoration has been costly and shown limited effectiveness, but lower cost passive restoration is less studied. I used GIS and machine learning to see whether passive restoration of old trees could overcome constraints in time, by 2060, across 667,000 ha of montane forests in the San Juan Mountains, Colorado, where temperatures are increasing faster than the global average. Random Forest models of physical locations of reconstructed historical old growth (OG) and relatively frequent fire (RFF) show historical OG with RFF was favored between 6.1 and 7.9℃ annual mean temperatures. Random Forest models projected that similar temperature‐suitable locations were moved into the current middle montane ca 2015, and would be extended to just below the upper limit of the montane if the Paris 1.5℃ goal is reached, but beyond if not. US Forest Service common stand exam data, which covered ~15% of the study area and included 26,149 tree ages, show the highest potential for restoring resistance and resilience from old trees is a ≥120‐year age class. This class could become a ≥160‐year age class, which meets old‐growth age criteria, over 81% of the area by ca 2060, nearly fully restoring historical old‐growth levels. Half this age class is already protected, and much of the remainder could be retained using evidence‐based diameter caps. Datasets thus are sufficient to show that passive restoration of old‐tree resistance and resilience to fire is feasible by ca 2060 across a large montane landscape, although contingent on global success in achieving the Paris 1.5℃ goal. Passive restoration may be viable elsewhere.
Fire‐prone dry forests face increasing fires from climate change with low resistance and resilience after logging of large, fire‐resistant trees. Their restoration is difficult due to limited mature trees, incomplete protection, physical constraints, and a short time period; however, machine learning and historical and modern forest and climate data show it is actually feasible to nearly fully restore historical resistance and resilience from old trees by 2060 using passive restoration. This encouraging possibility, illustrated across 667,000 ha of montane forests in the San Juan Mountains, Colorado, is only feasible if the Paris Agreement's 1.5℃ goal is achieved.
Dry forests at low elevations in temperate-zone mountains are commonly hypothesized to be at risk of exceptional rates of severe fire from climatic change and land-use effects. Their setting is ...fire-prone, they have been altered by land-uses, and fire severity may be increasing. However, where fires were excluded, increased fire could also be hypothesized as restorative of historical fire. These competing hypotheses are not well tested, as reference data prior to widespread land-use expansion were insufficient. Moreover, fire-climate projections were lacking for these forests. Here, I used new reference data and records of high-severity fire from 1984-2012 across all dry forests (25.5 million ha) of the western USA to test these hypotheses. I also approximated projected effects of climatic change on high-severity fire in dry forests by applying existing projections. This analysis showed the rate of recent high-severity fire in dry forests is within the range of historical rates, or is too low, overall across dry forests and individually in 42 of 43 analysis regions. Significant upward trends were lacking overall from 1984-2012 for area burned and fraction burned at high severity. Upward trends in area burned at high severity were found in only 4 of 43 analysis regions. Projections for A.D. 2046-2065 showed high-severity fire would generally be still operating at, or have been restored to historical rates, although high projections suggest high-severity fire rotations that are too short could ensue in 6 of 43 regions. Programs to generally reduce fire severity in dry forests are not supported and have significant adverse ecological impacts, including reducing habitat for native species dependent on early-successional burned patches and decreasing landscape heterogeneity that confers resilience to climatic change. Some adverse ecological effects of high-severity fires are concerns. Managers and communities can improve our ability to live with high-severity fire in dry forests.
Context
WUI wildfire disasters are increasing, as fires are pushed by strong winds and drier fuels across landscapes and into communities. Possible disasters make maintaining and restoring ...landscape-scale fire in fire-adapted ecosystems difficult. Rapid action is needed to reduce building loss in WUI wildfire disasters.
Objectives
In a Colorado study, I used distance-based empirical modeling to refine potential risk of building loss in WUI wildfire disasters to focus risk-reduction efforts.
Methods
New empirical modeling showed 95% of USA building loss in WUI wildfire disasters was within 100 m of wildland vegetation. I used modeling to estimate and map potential relative risk of a WUI wildfire disaster for each of 2,185,953 buildings in Colorado.
Results
High-risk buildings were 241,375 or 11% of total buildings. However, the 20–40 m essential defensible space around these buildings covered only 46,767–114,084 ha. Area within 100 m of wildland vegetation, containing these buildings, covered 475,840 ha or 1.8% of Colorado’s 27 million ha. About 95% of at-risk land within 100 m of wildland vegetation is not federally owned, and WUI wildfire disasters are mostly from fires started on private land.
Conclusions
Treating ≤ 114,084 ha of defensible space could leave the 27 million ha of Colorado with lower WUI wildfire disaster-risk to buildings. High risk of building loss is rarely a federal land-management problem. If the goal is rapid reduction of building loss in WUI wildfire disasters, focus resources on defensible space 20–40 m from WUI buildings within 100 m of wildland vegetation.
Sodium-glucose co-transporter 2 (SGLT2) inhibitors represent a new class of antihyperglycemic agents that block renal sodium and glucose reabsorption and may reduce blood pressure (BP). We assessed ...the BP lowering ability of these agents using meta-analytic techniques. PubMed, SCOPUS, and Cochrane Central were searched through October 2013. We included fully published randomized controlled trials (RCTs) that evaluated SGLT2 inhibitors in patients with type-2 diabetes mellitus and reported change in systolic and/or diastolic BP. Subgroup analyses were performed for placebo-controlled trials and those with active controls. We also conducted meta-regression to assess for a dose-response effect, and whether baseline BP, changes in body weight, heart rate, and hematocrit were associated with the BP effects. Twenty-seven RCTs (n = 12,960 participants) were included. SGLT2 inhibitors significantly reduced both systolic BP (weighted mean difference, -4.0 mm Hg; 95% confidence interval, -4.4 to -3.5) and diastolic BP (weighted mean difference, -1.6 mm Hg; 95% confidence interval, -1.9 to -1.3) from baseline. Only canagliflozin had a significant dose-response relationship with SBP (P = .008). Significant reductions in body weight and hematocrit were seen with the SGLTs. SGLTs had no significant effect on the incidence of orthostatic hypotension (P > .05). SGLT2 inhibitors significantly reduce BP in patients with type 2 diabetes.
Organic nitrates are an important aerosol constituent in locations where biogenic hydrocarbon emissions mix with anthropogenic NO x sources. While regional and global chemical transport models may ...include a representation of organic aerosol from monoterpene reactions with nitrate radicals (the primary source of particle-phase organic nitrates in the Southeast United States), secondary organic aerosol (SOA) models can underestimate yields. Furthermore, SOA parametrizations do not explicitly take into account organic nitrate compounds produced in the gas phase. In this work, we developed a coupled gas and aerosol system to describe the formation and subsequent aerosol-phase partitioning of organic nitrates from isoprene and monoterpenes with a focus on the Southeast United States. The concentrations of organic aerosol and gas-phase organic nitrates were improved when particulate organic nitrates were assumed to undergo rapid (τ = 3 h) pseudohydrolysis resulting in nitric acid and nonvolatile secondary organic aerosol. In addition, up to 60% of less oxidized-oxygenated organic aerosol (LO-OOA) could be accounted for via organic nitrate mediated chemistry during the Southern Oxidants and Aerosol Study (SOAS). A 25% reduction in nitrogen oxide (NO + NO2) emissions was predicted to cause a 9% reduction in organic aerosol for June 2013 SOAS conditions at Centreville, Alabama.
Low-severity fires that killed few canopy trees played a significant historical role in dry forests of the western USA and warrant restoration and management, but historical rates of burning remain ...uncertain. Past reconstructions focused on on dating fire years, not measuring historical rates of burning. Past statistics, including mean composite fire interval (mean CFI) and individual-tree fire interval (mean ITFI) have biases and inaccuracies if used as estimators of rates. In this study, I used regression, with a calibration dataset of 96 cases, to test whether these statistics could accurately predict two equivalent historical rates, population mean fire interval (PMFI) and fire rotation (FR). The best model, using Weibull mean ITFI, had low prediction error and R2adj = 0.972. I used this model to predict historical PMFI/FR at 252 sites spanning dry forests. Historical PMFI/FR for a pool of 342 calibration and predicted sites had a mean of 39 years and median of 30 years. Short (< 25 years) mean PMFI/FRs were in Arizona and New Mexico and scattered in other states. Long (> 55 years) mean PMFI/FRs were mainly from northern New Mexico to South Dakota. Mountain sites often had a large range in PMFI/FR. Nearly all 342 estimates are for old forests with a history of primarily low-severity fire, found across only about 34% of historical dry-forest area. Frequent fire (PMFI/FR < 25 years) was found across only about 14% of historical dry-forest area, with 86% having multidecadal rates of low-severity fire. Historical fuels (e.g., understory shrubs and small trees) could fully recover between multidecadal fires, allowing some denser forests and some ecosystem processes and wildlife habitat to be less limited by fire. Lower historical rates mean less restoration treatment is needed before beginning managed fire for resource benefits, where feasible. Mimicking patterns of variability in historical low-severity fire regimes would likely benefit biological diversity and ecosystem functioning.
While chloroquine, a derivative of quinine, has been used as an antimalarial for 70 years, hydroxychloroquine is now used to treat conditions such as rheumatoid arthritis and systemic lupus ...erythematosus. In 2020, hydroxychloroquine (and to a lesser extent chloroquine) also received attention as a possible treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). During investigation for treating coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, concerns for serious adverse events arose.
We review the toxicity associated with hydroxychloroquine and chloroquine use both short-term and long-term and in overdose.
Medline (via OVID) was searched from its inception through June 7 2020 using the following as either MeSH or keyword terms: ("Chloroquine/" or "Hydroxychloroquine/") AND ("Adverse Drug Event/" or "Toxicities, Drug/" or "Toxic.mp." or "Toxicity.mp." or "Overdose.mp."). We limited resultant articles to those published in English and reporting on Human subjects. This search yielded 330 articles, of which 57 were included. Articles were excluded due to lack of relevance, not reporting desired outcomes, or being duplicative in their content. Twenty-five additional articles were identified through screening references of included articles. To identify toxicities in individuals treated with hydroxychloroquine or chloroquine with COVID-19, we searched PubMed on June 10th, 2020: ("Chloroquine" or "Hydroxychloroquine") AND ("Coronavirus" or "COVID-19" or "SARS-CoV-2"). This search resulted in 638 articles. We reviewed articles for reporting of adverse events or toxicities. Most citations were excluded because they did not include original investigations or extrapolated data from subjects that did not have COVID-19; 34 citations were relevant. For the drug-interactions section, relevant classes and agents were identified through a screen of the
https://www.covid19-druginteractions.org/
website. We then conducted targeted searches of PubMed up to June 7th 2020 combining "chloroquine" and "hydroxychloroquine" with terms for specific drug classes and drugs identified from the drug-interaction site as potentially relevant. We found 29 relevant articles.
Gastrointestinal: Gastrointestinal toxicities are the most common to occur following initiation of chloroquine or hydroxychloroquine. Nausea, vomiting, and diarrhea account for most reported intolerances. Glucose abnormalities: Alterations in blood glucose concentrations may occur with hydroxychloroquine but are rare with standard therapeutic use. Cardiotoxicity: Short-term use can produce conduction abnormalities. Evidence from COVID-19 treatment suggests QT/QTc prolongation is of concern, particularly when used in combination with azithromycin, although disagreement exists across studies. Dermatologic: Drug eruptions or rashes, followed by cutaneous hyperpigmentation, pruritis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, may occur within days to weeks of exposure but usually resolve with the discontinuation of therapy. Neuropsychiatric: Reported symptoms include confusion, disorientation, and hallucination within 24-48 h of drug initiation. Other toxicities: Hemolysis and anemia may occur in patients with glucose-6-phosphate dehydrogenase. Chloroquine treatment of COVID-19 was associated with elevation in creatine kinase and creatine kinase-MB activities with more events in the higher-dose group.
Retinopathy: Retinopathy is the major dose-limiting toxicity associated with long-term use; the risk is higher with increasing age, dose, and duration of usage. Cardiotoxicity: Long-term use has been associated with conduction abnormalities, cardiomyopathy, and valvular disorders. Neurotoxicity: Rarely myositis and muscle weakness, extremity weakness, and pseudoparkinsonism have been reported.
Symptoms in overdose manifest rapidly (minutes to hours) and cardiotoxicity such as cardiovascular shock and collapse are most prominent. Neurotoxic effects such as psychosis and seizure may also occur.
Hydroxychloroquine is a generally well-tolerated medication. Short-term (days to weeks) toxicity includes gastrointestinal effects and rarely glucose abnormalities, dermatologic reactions, and neuropsychiatric events. Cardiotoxicity became of increased concern with its use in COVID-19 patients. Long-term (years) toxicities include retinopathy, neuromyotoxicity, and cardiotoxicity (conduction abnormalities, cardiomyopathy). Deaths from overdoses most often result from cardiovascular collapse.
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