Pharmacological management of COVID-19 patients with ARDS (CARDS): A narrative review

Coronavirus disease 2019 (COVID-19) is highly infectious. It has been highlighted that if not expertly and individually managed with consideration of the vasocentric features, a COVID-19 patient with an acute respiratory distress syndrome (CARDS) may eventually develop multiorgan failure. Unfortunately, there is still no definite drug for CARDS that is capable of reducing either short-term or long-term mortality and no specific treatments for COVID-19 exist right now. In this narrative review, based on a selective literature search in EMBASE, MEDLINE, Scopus, The Cochrane Library, Web of Science, and Google Scholar and ClinicalTrials.gov, we have examined the emerging evidence on the possible treatment of CARDS. Although numerous pharmacologic therapies to improve clinical outcomes in CARDS have been studied also in clinical trials, none have shown efficacy and there is great uncertainty about their effectiveness. There is still no recommendation for the therapeutic use of any specific agent to treat CARDS because no drugs are validated to have significant efficacy in clinical treatment of COVID-19 patients in large-scale trials. However, there exist a number of drugs that may be useful at least in some patients. The real challenge now is to link the right patient to the right treatment

Combining triple therapy and pulmonary rehabilitation in patients with advanced COPD: a pilot study.

BACKGROUND: The synergistic interactions between pharmacotherapy and pulmonary rehabilitation has been provided, but it remains to be established whether this may also apply to more severe patients. OBJECTIVES: We have examined whether tiotropium enhances the effects of exercise training in patients with advanced COPD (FEV(1)</=60% predicted, hypoxemia at rest corrected with oxygen supplementation, and limitations of physical activity). METHODS: We enrolled 22 patients that were randomised to tiotropium 18mug or placebo inhalation capsules taken once daily. Both groups (11 patients in each group) underwent an in patient pulmonary rehabilitation program and were under regular treatment with salmeterol/fluticasone twice daily. Each rehabilitation session was held 5 days per week (3h/day) for a total of 4 weeks. RESULTS: Compared to placebo, tiotropium had larger impact on pulmonary function (FEV(1)+0.164L, FVC +0.112L, RV -0.544L after tiotropium, FEV(1)+0.084L, FVC -0.039L, RV -0.036L after placebo). The addition of tiotropium allowed a longer distance walked in 6min (82.3m vs. 67.7m after placebo) and reduced dyspnoea (Borg score) (-0.4 vs. +0.18 after placebo) when compared with baseline (pre pulmonary rehabilitation program). The changes in SGRQ from baseline to the end of treatment were: total score -28.3U, activity -27.8U, impact -14.5U, and symptoms -33.4U in the placebo group; and total score -19.1U, activity -18.9U, impact -16.4U, and symptoms -33.8U in the tiotropium group. CONCLUSIONS: Our study clearly indicates that there is an advantage in combining pulmonary rehabilitation with an aggressive drug therapy in more severe patient

Combining triple therapy and pulmonary rehabilitation in patients with advanced COPD: a pilot study.

BACKGROUND: The synergistic interactions between pharmacotherapy and pulmonary rehabilitation has been provided, but it remains to be established whether this may also apply to more severe patients. OBJECTIVES: We have examined whether tiotropium enhances the effects of exercise training in patients with advanced COPD (FEV(1)</=60% predicted, hypoxemia at rest corrected with oxygen supplementation, and limitations of physical activity). METHODS: We enrolled 22 patients that were randomised to tiotropium 18mug or placebo inhalation capsules taken once daily. Both groups (11 patients in each group) underwent an in patient pulmonary rehabilitation program and were under regular treatment with salmeterol/fluticasone twice daily. Each rehabilitation session was held 5 days per week (3h/day) for a total of 4 weeks. RESULTS: Compared to placebo, tiotropium had larger impact on pulmonary function (FEV(1)+0.164L, FVC +0.112L, RV -0.544L after tiotropium, FEV(1)+0.084L, FVC -0.039L, RV -0.036L after placebo). The addition of tiotropium allowed a longer distance walked in 6min (82.3m vs. 67.7m after placebo) and reduced dyspnoea (Borg score) (-0.4 vs. +0.18 after placebo) when compared with baseline (pre pulmonary rehabilitation program). The changes in SGRQ from baseline to the end of treatment were: total score -28.3U, activity -27.8U, impact -14.5U, and symptoms -33.4U in the placebo group; and total score -19.1U, activity -18.9U, impact -16.4U, and symptoms -33.8U in the tiotropium group. CONCLUSIONS: Our study clearly indicates that there is an advantage in combining pulmonary rehabilitation with an aggressive drug therapy in more severe patient

Self-Evolving Petri Nets

Nowadays, software evolution is a very hot topic. It is particularly complex when it regards critical and nonstopping systems. Usually, these situations are tackled by hard-coding all the foreseeable evolutions in the application design and code. Neglecting the obvious difficulties in pursuing this approach, we also get the application code and design polluted with details that do not regard the current system functionality, and that hamper design analysis, code reuse and application maintenance in general. Petri Nets (PN), as a formalism for modeling and designing distributed/concurrent software systems, are not exempt from this issue. The goal of this work is to propose a PN based reflective framework that lets everyone model a system able to evolve, keeping separated functional aspects from evolutionary ones and applying evolution to the model only if necessary. Such an approach tries to keep system's model as simple as possible, preserving (and exploiting) ability of formally verifying system properties typical of PN, granting at the same time adaptability

Rapid onset of bronchodilation with formoterol/beclomethasone Modulite and formoterol/budesonide Turbuhaler as compared to formoterol alone in patients with COPD

In the present study, we examined whether there is a difference in the onset of bronchodilatation between formoterol/beclomethasone 12/200 μg Modulite and formoterol/budesonide 9/320 μg Turbuhaler in patients with COPD. We enrolled 28 patients with stable COPD. Both formoterol/beclomethasone and formoterol/budesonide elicited a larger mean FEV1–AUC0−15min than formoterol alone, whereas there was no significant difference between their FEV1–AUC0−15min. Also the change in FEV1 15 min after inhalation of formoterol/beclomethasone combination or formoterol/budesonide combination was greater than that induced by formoterol alone. This study confirms the rapid effect of the inhaled corticosteroid component when combined with formoterol and indicates that the onset of bronchodilation of formoterol/beclomethasone Modulite and formoterol/budesonide Turbuhaler are similar and greater than formoterol alone in patients with COPD

Concentration-Dependent Effects of N-3 Long-Chain Fatty Acids on Na,K-ATPase Activity in Human Endothelial Cells

N-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) seem to prevent endothelial dysfunction, a crucial step in atherogenesis, by modulating the levels of vasoactive molecules and by influencing Na,K-ATPase activity of vascular myocytes. The activity of endothelial Na,K-ATPase controls the ionic homeostasis of the neighboring cells, as well as cell function. However, controversy exists with respect to the vascular protective effect of EPA and DHA. We argue that this dispute might be due to the use of different concentrations of EPA and DHA in different studies. Therefore, this study was designed to define an optimal concentration of EPA and DHA to investigate endothelial function. For this purpose, human endothelial cells were exposed for 24 h to different concentrations of DHA or EPA (0\u201320 \u3bcM) to study membrane fluidity, peroxidation potential and Na,K-ATPase activity. EPA and DHA were linearly incorporated and this incorporation was mirrored by the linear increase of unsaturation index, membrane fluidity, and peroxidation potential. Na,K-ATPase activity peaked at 3.75 \u3bcM of EPA and DHA and then gradually decreased. It is noteworthy that DHA effects were always more pronounced than EPA. Concluding, low concentrations of EPA and DHA minimize peroxidation sensitivity and optimize Na,K-ATPase activity

Summary of International Transport Energy Modeling Workshop

The NextSTEPS program at ITS-Davis convened a one-day workshop on international transportation energy modeling (iTEM), focused on comparing the frameworks and scenario projections from four major global transport models: -- Global Change Assessment Model (GCAM) by Pacific Northwest National Laboratory (PNNL) and ITS-Davis, -- MESSAGE-Transport (Model for Energy Supply Strategy Alternatives and their General Environmental Impact) by the International Institute for Applied Systems Analysis (IIASA), -- Mobility Model (MoMo) by the International Energy Agency, and -- Roadmap by the International Council on Clean Transportation (ICCT). Highlights: -- Projections of "baseline" global transportation energy use rise from 98 EJ in 2010 to 160-250 EJ by 2050. -- There are considerable differences in historical data for some modes, both globally and for individual countries (particularly non-OECD countries). Variability in estimates of transportation activity are in most cases much larger than energy differences. -- Global average vehicle ownership rates are projected to range from 270 to 450 per 1,000 people by 2050 with wide ranges across countries: 700-1,075 for the US by the middle of the century (US is around 700 today), 100-650 for China, and 80-380 for India across four models. -- All models rely mainly on GDP to estimate the future demand for freight and hold the base year modal shares (e.g. truck v. rail) roughly constant through 2050. In reality, future evolution will depend on characteristics of products (e.g. type of commodities) being shipped, technologies available for freight and their efficiencies, and policies and infrastructure. -- Current policy commitments toward EVs, PHEVs and H2FCVs (and thus baseline projections) maybe below the numbers suggested by iTEM models as required for meeting climate targets (e.g., 2 degrees C). -- Improvements in data quality and the representation of car ownership and use across the models were identified as priorities. Modeling transport energy use can either be done by estimating how far people travel and what mode of transportation they choose or by estimating how many vehicles there are and how far each one travels. These are complementary approaches, and in theory they should both lead to the same answer. The former approach, used in "service demand" models, seem more intuitive when one wants to model societal shifts in modes of transportation, either in emerging economies as they develop or in developed economies as they decarbonize; but collecting data on service demand is notoriously difficult. In contrast, vehicle stock models use readily-available vehicle sales data, but are harder to use in future-state, what-if scenarios (particularly in estimating modal shift behaviors) and thus require special attention by experts. The four iTEM models are different in terms of scope (GCAM and MESSAGE cover all sectors of the energy system vs. MoMo and Roadmap which cover transportation only) and model structure (GCAM and MESSAGE rely on internal drivers, particularly the costs of technology and travel, to project future changes whereas MoMo and Roadmap rely on experts' judgments and detailed analysis of technology and policies to drive long-term changes). Yet, owing to these differences, the models are highly complementary and in some cases can be used jointly to answer questions that no single model can tackle on its own. The following summary shares some of the comparisons and findings from the workshop

A long-term clinical trial on the efficacy and safety profile of doxofylline in Asthma: The LESDA study.

Doxofylline, an oral methylxanthine with bronchodilator and anti-inflammatory activities, offers a promising alternative to theophylline due to its superior efficacy/safety profile. No long-term studies on the efficacy and safety of doxofylline are currently available in asthma. The aim of the Long-term clinical trial on the Efficacy and Safety profile of Doxofylline in Asthma (LESDA) study was to investigate the safety and efficacy profile of doxofylline administered for one year in asthmatic patients. LESDA was a multicenter, open-label, Phase III, clinical trial in which adult asthmatic patients received the same treatment (oral doxofylline 400 mg t.i.d.) for one year. Efficacy was assessed through periodic pulmonary function tests and by having the subjects keep monthly records of asthma events rates and use of salbutamol as rescue medication. The rate of adverse events (AEs) was recorded during the study. Three-hundred nine patients were screened and allocated in the study. Doxofylline significantly improved the change from baseline in forced expiratory volume in 1 s (FEV1) (+16.90 ± 1.81%, P < 0.001 vs. baseline). Doxofylline also significantly improved the rate of asthma events (events/day: -0.57 ± 0.18, P < 0.05 vs. baseline) and the use of salbutamol as rescue medication (puffs/day: -1.48 ± 0.25, P < 0.01 vs. baseline). The most common AEs were nausea (14.56%), headache (14.24%), insomnia (10.68%), and dyspepsia (10.03%). There were neither serious AEs nor deaths during or shortly after the study. Concluding, doxofylline is effective and well tolerated when administered chronically in asthmatic patients