IMPORTANCE Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis.OBJECTIVE To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU). DESIGN, SETTING, AND PARTICIPANTSMulticenter randomized trial with a 2 × 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020.INTERVENTIONS Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up. MAIN OUTCOMES AND MEASURESThe primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count <20 ×10 3 /μL). All outcomes were blindly adjudicated. RESULTS Among 600 randomized patients, 562 (93.7%) were included in the primary analysis (median [interquartile range] age, 62 [50-71] years; 237 [42.2%] women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% [95% CI, −6.6% to 9.8%]; odds ratio, 1.06 [95% CI, 0.76-1.48]; P = .70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% [1-sided 97.5% CI, −ϱ to 3.4%]; odds ratio, 1.83 [1-sided 97.5% CI, 0.00-5.93]), not meeting the noninferiority criteria (P for noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% [95% CI, 0.4%-3.8%]; P = .01).CONCLUSIONS AND RELEVANCE Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days...

Background: Thrombotic complications are considered among the main extrapulmonary manifestations of COVID-19. The optimal type and duration of prophylactic antithrombotic therapy in these patients remain unknown. Methods: This manuscript reports the final (90-day) results of the Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) study. Patients with COVID-19 admitted to intensive care were randomized to intermediate-dose versus standard-dose prophylactic anticoagulation for 30 days, irrespective of hospital discharge status. The primary efficacy outcome was a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause death. The main safety outcome was major bleeding. Results: Of 600 randomized patients, 562 entered the modified intention-to-treat analysis (median age [Q1, Q3]; 62 (50, 71) years; 237 (42.2%) women), of whom 336 (59.8%) survived to hospital discharge. The primary outcome occurred in 132 (47.8%) of patients assigned to intermediate-dose and 130 (45.4%) patients assigned to standard-dose prophylactic anticoagulation (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.95-1.55, P=0.11). No significant differences were observed between the two groups for other efficacy outcomes, or in the landmark analysis from days 31-90. Overall, there were 7 (2.5%) major bleeding events in the intermediate-dose group (including 3 fatal events) and 4 (1.4%) major bleeding events in the standard-dose group (none fatal) (HR: 1.82, 95% CI: 0.53-6.24, P=0.33). Conclusion: Intermediate-dose compared with standard-dose prophylactic anticoagulation did not reduce a composite of death, treatment with ECMO, or venous or arterial thrombosis at 90-day follow-up.

Interest in the development of smart and active biodegradable packaging materials is increasing as food manufacturers try to improve the sustainability and environmental impact of their products, while still maintaining their quality and safety. Active packaging materials contain components that enhance their functionality, such as antimicrobials, antioxidants, light blockers, or oxygen barriers. Smart packaging materials contain sensing components that provide an indication of changes in food attributes, such as alterations in their quality, maturity, or safety. For instance, a smart sensor may give a measurable color change in response to a deterioration in food quality. This article reviews recent advances in the development of active and smart biodegradable packaging materials in the food industry. Moreover, studies on the application of these packaging materials to monitor the freshness and safety of food products are reviewed, including dairy, meat, fish, fruit and vegetable products. Finally, the potential challenges associated with the application of these eco-friendly packaging materials in the food industry are discussed, as well as potential future directions.

Background. Several studies have reported that statins have anti-inflammatory effects. Nevertheless, results of clinical trials concerning the effect of statins on the levels of C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP) have been inconsistent. Therefore, we performed a systematic review and meta-analysis of randomized clinical trials (RCTs) evaluating the effect of statins on CRP and hs-CRP levels in patients with cardiovascular diseases (CVDs). Methods. Literature search of the major databases was performed to find eligible RCTs assessing the effect of statins on serum levels of CRP and hs-CRP from the inception until the last week of April 2021. The effect sizes were determined for weighted mean difference (WMD) and 95% confidence intervals (CI). Results. 26 studies were identified (3010 patients and 2968 controls) for hs-CRP and 20 studies (3026 patients and 2968 controls) for CRP. Statins reduced the serum levels of hs-CRP ( WMD = − 0.97   mg / L ; 95% CI: -1.26 to -0.68 mg/L; P < 0.001 ) and CRP ( WMD = − 3.05   mg / L ; 95% CI: -4.86 to -1.25 mg/L; P < 0.001 ) in patients with CVDs. Statins decreased the serum levels of hs-CRP in patients receiving both high-intensity and moderate/low-intensity treatments with these drugs. In addition, the duration of treatment longer than 10 weeks decreased hs-CRP levels. Only high-intensity statin treatment could marginally decrease serum levels of CRP in CVDs patients. Conclusions. This meta-analysis showed the efficacy of statins to reduce the concentrations of CRP and hs-CRP in patients with different types of CVDs.

There is great interest in developing biodegradable biopolymer-based packaging materials whose functional performance is enhanced by incorporating active compounds into them, such as light blockers, plasticizers, crosslinkers, diffusion blockers, antimicrobials, antioxidants, and sensors. However, many of these compounds are volatile, chemically unstable, water-insoluble, matrix incompatible, or have adverse effects on film properties, which makes them difficult to directly incorporate into the packaging materials. These challenges can often be overcome by encapsulating the active compounds within food-grade nanoparticles, which are then introduced into the packaging materials. The presence of these nanoencapsulated active compounds in biopolymer-based coatings or films can greatly improve their functional performance. For example, anthocyanins can be used as light-blockers to retard oxidation reactions, or they can be used as pH/gas/temperature sensors to produce smart indicators to monitor the freshness of packaged foods. Encapsulated botanical extracts (like essential oils) can be used to increase the shelf life of foods due to their antimicrobial and antioxidant activities. The resistance of packaging materials to external factors can be improved by incorporating plasticizers (glycerol, sorbitol), crosslinkers (glutaraldehyde, tannic acid), and fillers (nanoparticles or nanofibers). Nanoenabled delivery systems can also be designed to control the release of active ingredients (such as antimicrobials or antioxidants) into the packaged food over time, which may extend their efficacy. This article reviews the different kinds of nanocarriers available for loading active compounds into these types of packaging materials and then discusses their impact on the optical, mechanical, thermal, barrier, antioxidant, and antimicrobial properties of the packaging materials. Furthermore, it highlights the different kinds of bioactive compounds that can be incorporated into biopolymer-based packaging.