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AbstractObjectiveTo evaluate the effects of therapeutic heparin compared with prophylactic heparin among moderately ill patients with covid-19 admitted to hospital wards.DesignRandomised controlled, adaptive, open label clinical trial.Setting28 hospitals in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates, and US.Participants465 adults admitted to hospital wards with covid-19 and increased D-dimer levels were recruited between 29 May 2020 and 12 April 2021 and were randomly assigned to therapeutic dose heparin (n=228) or prophylactic dose heparin (n=237).InterventionsTherapeutic dose or prophylactic dose heparin (low molecular weight or unfractionated heparin), to be continued until hospital discharge, day 28, or death.Main outcome measuresThe primary outcome was a composite of death, invasive mechanical ventilation, non-invasive mechanical ventilation, or admission to an intensive care unit, assessed up to 28 days. The secondary outcomes included all cause death, the composite of all cause death or any mechanical ventilation, and venous thromboembolism. Safety outcomes included major bleeding. Outcomes were blindly adjudicated.ResultsThe mean age of participants was 60 years; 264 (56.8%) were men and the mean body mass index was 30.3 kg/m2. At 28 days, the primary composite outcome had occurred in 37/228 patients (16.2%) assigned to therapeutic heparin and 52/237 (21.9%) assigned to prophylactic heparin (odds ratio 0.69, 95% confidence interval 0.43 to 1.10; P=0.12). Deaths occurred in four patients (1.8%) assigned to therapeutic heparin and 18 patients (7.6%) assigned to prophylactic heparin (0.22, 0.07 to 0.65; P=0.006). The composite of all cause death or any mechanical ventilation occurred in 23 patients (10.1%) assigned to therapeutic heparin and 38 (16.0%) assigned to prophylactic heparin (0.59, 0.34 to 1.02; P=0.06). Venous thromboembolism occurred in two patients (0.9%) assigned to therapeutic heparin and six (2.5%) assigned to prophylactic heparin (0.34, 0.07 to 1.71; P=0.19). Major bleeding occurred in two patients (0.9%) assigned to therapeutic heparin and four (1.7%) assigned to prophylactic heparin (0.52, 0.09 to 2.85; P=0.69).ConclusionsIn moderately ill patients with covid-19 and increased D-dimer levels admitted to hospital wards, therapeutic heparin was not significantly associated with a reduction in the primary outcome but the odds of death at 28 days was decreased. The risk of major bleeding appeared low in this trial.Trial registrationClinicalTrials.gov NCT04362085.

The treatment of patients with PNH has been revolutionized by terminal complement C5 inhibitors, which control intravascular hemolysis and thrombosis, reduce morbidity and mortality, and improve life expectancy to that approaching people without PNH. In recent years, approval of proximal inhibitors provides clinicians and patients with additional treatment options such that patients who have residual anemia, ongoing symptoms affecting quality of life, or are intolerant to terminal C5 inhibition now have options to optimize treatment. Here, we provide five questions to guide clinicians involved in the care of patients with PNH in assessing treatment response on terminal inhibitors and identifying patients who might benefit from therapy adjustments. We also provide insights into additional treatment options.

Background: Many patients who experience a venous thromboembolic event have cancer, and thrombosis is much more prevalent in patients with cancer than in those without it. Thrombosis is the second most common cause of death in cancer patients and cancer is associated with a high rate of recurrence of venous thromboembolism (VTE), bleeding, requirement for long-term anticoagulation and poorer quality of life. Methods: A literature review was conducted to identify guidelines and evidence pertaining to anticoagulation prophylaxis and treatment for patients with cancer, with the goal of identifying opportunities for pharmacists to advocate for and become more involved in the care of this population. Results: Many clinical trials and several guidelines providing guidance to clinicians in the treatment and prevention of VTE in patients with cancer were identified. Current clinical evidence and guidelines suggest that cancer patients receiving care in hospital with no contraindications should receive VTE prophylaxis with unfractionated heparin (UFH), a low-molecular-weight heparin (LMWH) or fondaparinux. Patients who require surgery for their cancer should receive prophylaxis with UFH, LMWH or fondaparinux. Cancer patients who have experienced a VTE event should receive prolonged anticoagulant therapy with LMWH (at least 3 months to 6 months). No routine prophylaxis is required for the majority of ambulatory patients with cancer who have not experienced a VTE event. Most publicly funded drug plans in Canada have developed criteria for funding of LMWH therapy for patients with cancer. Conclusions: Evidence suggests that LMWH for 3 to 6 months is the preferred strategy for most cancer patients who have experienced a thromboembolic event and for hospital inpatients, but this is often not implemented in practice. Concerns about adherence with injectable therapy should not prevent use of these agents. Pharmacists should assess cancer patients for their risk of VTE and should advocate for optimal VTE pharmacotherapy as appropriate. If LMWH is the preferred agent, on the basis of the evidence, the pharmacist should educate the patients appropriately and work with the prescriber to ensure best care. Can Pharm J

We present a unifying model for isoprene emission by photosynthesizing leaves based on the hypothesis that isoprene biosynthesis depends on a balance between the supply of photosynthetic reducing power and the demands of carbon fixation. We compared the predictions from our model, as well as from two other widely used models, with measurements of isoprene emission from leaves of Populus nigra and hybrid aspen (Populus tremula × P. tremuloides) in response to changes in leaf internal CO2 concentration (C i) and photosynthetic photon flux density (PPFD) under diverse ambient CO2 concentrations (C a). Our model reproduces the observed changes in isoprene emissions with C i and PPFD, and also reproduces the tendency for the fraction of fixed carbon allocated to isoprene to increase with increasing PPFD. It also provides a simple mechanism for the previously unexplained decrease in the quantum efficiency of isoprene emission with increasing C a. Experimental and modelled results support our hypothesis. Our model can reproduce the key features of the observations and has the potential to improve process-based modelling of isoprene emissions by land vegetation at the ecosystem and global scales.

We present a unifying model for isoprene emission by photosynthesizing leaves based on the hypothesis that isoprene biosynthesis depends on a balance between the supply of photosynthetic reducing power and the demands of carbon fixation. We compared the predictions from our model, as well as from two other widely used models, with measurements of isoprene emission from leaves of Populus nigra and hybrid aspen (Populus tremula × P. tremuloides) in response to changes in leaf internal CO₂ concentration (Cᵢ) and photosynthetic photon flux density (PPFD) under diverse ambient CO₂ concentrations (Cₐ). Our model reproduces the observed changes in isoprene emissions with Cᵢ and PPFD, and also reproduces the tendency for the fraction of fixed carbon allocated to isoprene to increase with increasing PPFD. It also provides a simple mechanism for the previously unexplained decrease in the quantum efficiency of isoprene emission with increasing Cₐ. Experimental and modelled results support our hypothesis. Our model can reproduce the key features of the observations and has the potential to improve process‐based modelling of isoprene emissions by land vegetation at the ecosystem and global scales.

We present a unifying model for isoprene emission by photosynthesizing leaves based on the hypothesis that isoprene biosynthesis depends on a balance between the supply of photosynthetic reducing power and the demands of carbon fixation. We compared the predictions from our model, as well as from two other widely used models, with measurements of isoprene emission from leaves of P opulus nigra and hybrid aspen ( P opulus tremula  ×  P . tremuloides ) in response to changes in leaf internal CO 2 concentration ( C i ) and photosynthetic photon flux density ( PPFD ) under diverse ambient CO 2 concentrations ( C a ). Our model reproduces the observed changes in isoprene emissions with C i and PPFD , and also reproduces the tendency for the fraction of fixed carbon allocated to isoprene to increase with increasing PPFD . It also provides a simple mechanism for the previously unexplained decrease in the quantum efficiency of isoprene emission with increasing C a . Experimental and modelled results support our hypothesis. Our model can reproduce the key features of the observations and has the potential to improve process‐based modelling of isoprene emissions by land vegetation at the ecosystem and global scales.

The increase in aridity, mainly by decreases in precipitation but also by higher temperatures, is likely the main threat to the diversity and survival of Mediterranean forests. Changes in land use, including the abandonment of extensive crop activities, mainly in mountains and remote areas, and the increases in human settlements and demand for more resources with the resulting fragmentation of the landscape, hinder the establishment of appropriate management tools to protect Mediterranean forests and their provision of services and biodiversity. Experiments and observations indicate that if changes in climate, land use and other components of global change, such as pollution and overexploitation of resources, continue, the resilience of many forests will likely be exceeded, altering their structure and function and changing, mostly decreasing, their capacity to continue to provide their current services. A consistent assessment of the impacts of the changes, however, remains elusive due to the difficulty of obtaining simultaneous and complete data for all scales of the impacts in the same forests, areas and regions. We review the impacts of climate change and other components of global change and their interactions on the terrestrial forests of Mediterranean regions, with special attention to their impacts on ecosystem services. Management tools for counteracting the negative effects of global change on Mediterranean ecosystem- services are finally discussed.