Severe plastic deformation: Nanostructured materials, metal-based and polymer-based nanocomposites: A review.

Significant deformation of the metal structure can be achieved without breaking or cracking the metal. There are several methods for deformation of metal plastics. The most important of these methods are angular channel pressing process, high-pressure torsion, multidirectional forging process, extrusion-cyclic compression process, cumulative climbing connection process, consecutive concreting and smoothing method, high-pressure pipe torsion. The nanocomposite is a multiphase material which the size of one of its phases is less than 100 nm in at least one dimension. Due to some unique properties, metal-based nanocomposites are widely used in engineering applications such as the automotive and aerospace industries. Polymer-based nanocomposites are two-phase systems with polymer-based and reinforcing phases (usually ceramic). These materials have a simpler synthesis process than metal-based nanocomposites and are used in a variety of applications such as the aerospace industry, gas pipelines, and sensors. Severe plastic deformation (SPD) is known to be the best method for producing bulk ultrafine grained and nanostructured materials with excellent properties. Different Severe plastic deformation methods were developed that are suitable for sheet and bulk solid materials. During the past decade, efforts have been made to create effective Severe plastic deformation processes suitable for producing cylindrical tubes. In this paper, we review Severe plastic deformation processes intended to nanostructured tubes, and their effects on material properties and severe plastic deformation is briefly introduced and its common methods for bulk materials, sheets, and pipes, as well as metal background nanocomposites, are concisely introduced and their microstructural and mechanical properties are discussed. The paper will focus on introduction of the tube Severe plastic deformation processes, and then comparison of them based on their advantages and disadvantages from the viewpoints of processing and properties.

Standard dosing of enoxaparin versus unfractionated heparin in critically ill patient with COVID-19: a multicenter propensity-score matched study.

BACKGROUND: Thrombotic events are common in critically ill patients with COVID-19 and have been linked with COVID-19- induced hyperinflammatory state. In addition to anticoagulant effects, heparin and its derivatives have various anti-inflammatory and immunomodulatory properties that may affect patient outcomes. This study compared the effectiveness and safety of prophylactic standard-doses of enoxaparin and unfractionated heparin (UFH) in critically ill patients with COVID-19.  METHODS: A multicenter, retrospective cohort study included critically ill adult patients with COVID-19 admitted to the ICU between March 2020 and July 2021. Patients were categorized into two groups based on the type of pharmacological VTE thromboprophylaxis given in fixed doses (Enoxaparin 40 mg SQ every 24 hours versus UFH 5000 Units SQ every 8 hours) throughout their ICU stay. The primary endpoint was all cases of thrombosis. Other endpoints were considered secondary. Propensity score (PS) matching was used to match patients (1:1 ratio) between the two groups based on the predefined criteria. Multivariable logistic, Cox proportional hazards, and negative binomial regression analysis were used as appropriate.  RESULTS: A total of 306 patients were eligible based on the eligibility criteria; 130 patients were included after PS matching (1:1 ratio). Patients who received UFH compared to enoxaparin had higher all thrombosis events at crude analysis (18.3% vs. 4.6%; p-value = 0.02 as well in logistic regression analysis (OR: 4.10 (1.05, 15.93); p-value = 0.04). Although there were no significant differences in all bleeding cases and major bleeding between the two groups (OR: 0.40 (0.07, 2.29); p-value = 0.31 and OR: 1.10 (0.14, 8.56); p-value = 0.93, respectively); however, blood transfusion requirement was higher in the UFH group but did not reach statistical significance (OR: 2.98 (0.85, 10.39); p-value = 0.09). The 30-day and in-hospital mortality were similar between the two groups at Cox hazards regression analysis. In contrast, hospital LOS was longer in the UFH group; however, it did not reach the statistically significant difference (beta coefficient: 0.22; 95% CI: -0.03, 0.48; p-value = 0.09). CONCLUSION: Prophylactic enoxaparin use in critically ill patients with COVID-19 may significantly reduce all thrombosis cases with similar bleeding risk compared to UFH.

Antibiotics in the pipeline: a literature review (2017-2020).

INTRODUCTION: Antimicrobial resistance (AMR) is an emerging global threat. It increases mortality and morbidity and strains healthcare systems. Health care professionals can counter the rising AMR by promoting antibiotic stewardship and facilitating new drug development. Even with the economic and scientific challenges, it is reassuring that new agents continue to be developed. METHODS: This review addresses new antibiotics in the pipeline. We conducted a review of the literature including Medline, Clinicaltrials.org, and relevant pharmaceutical companies for approved and in pipeline antibiotics in phase 3 or new drug application (NDA). RESULTS: We found a number of new antibiotics and reviewed their current development status, mode of action, spectra of activity, and indications for which they have been approved. The included studies from phase 3 clinical trials were mainly utilized for the treatment of acute bacterial skin and skin structure infections, community-acquired bacterial pneumonia, and pneumonia acquired in the healthcare settings. The number of these agents is limited against high priority organisms. The identified antibiotics were based mainly on previously known molecules or pre-existing antimicrobial agents. CONCLUSION: There are a limited number of antibiotics against high priority organisms such as multi-drug-resistant Pseudomonas aeruginosa, and carbapenem-resistant Enterobacteriaceae. New antimicrobial agents directed against the top priority organisms as classified by the World Health Organization are urgently needed.

A Systematic Review of therapeutic agents for the treatment of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV).

BACKGROUND: The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was first described in 2012 and attracted a great international attention due to multiple healthcare associated outbreaks. The disease carries a high case fatality rate of 34.5%, and there is no internationally or nationally recommended therapy. METHOD: We searched MEDLINE, Science Direct, Embase and Scopus databases for relevant papers published till March 2019 describing in vitro, in vivo or human therapy of MERS. RESULTS: Initial search identified 62 articles: 52 articles were from Medline, 6 from Embase, and 4 from Science Direct. Based on the inclusions and exclusions criteria, 30 articles were included in the final review and comprised: 22 in vitro studies, 8 studies utilizing animal models, 13 studies in humans, and one study included both in vitro and animal model. There are a few promising therapeutic agents on the horizon. The combination of lopinavir/ritonavir and interferon-beta- 1b showed excellent results in common marmosets and currently is in a randomized control trial. Ribavirin and interferon were the most widely used combination and experience comes from a number of observational studies. Although, the data are heterogenous, this combination might be of potential benefit and deserve further investigation. There were no randomized clinical trials to recommend specific therapy for the treatment of MERS-CoV infection. Only one such study is planned for randomization and is pending completion. The study is based on a combination of lopinavir/ritonavir and interferon-beta- 1b. A fully human polyclonal IgG antibody (SAB-301) was safe and well tolerated in healthy individuals and this agent may deserve further testing for efficacy. CONCLUSION: Despite multiple studies in humans there is no consensus on the optimal therapy for MERS-CoV. Randomized clinical trials are needed and potential therapies should be evaluated only in such clinical trials. In order to further enhance the therapeutic aroma for MERS-CoV infection, repurposing old drugs against MERS-CoV is an interesting strategy and deserves further consideration and use in clinical settings.

Benchmarking of antibiotic usage: An adjustment to reflect antibiotic stewardship program outcome in a hospital in Saudi Arabia.

Antimicrobial stewardship program aims to reduce antibiotic use. Periodic measurement and monitoring of antibiotic use and comparison within the institution as well as with other organizations are important indicators. We analyzed antibiotic usage in a general hospital in Saudi Arabia. Antibiotic data were collected retrospectively for 2011 and from 2013 to 2015, and only adult patients (>15year of age) were included in the study. Data were presented as days of therapy (DOT) and defined daily dose (DDD). DDD was adjusted per 100 bed-days and according to the case mix index (CMI). The total DDD was 37,557 in 2013, 36,550 in 2014 and 38,738 in 2015. The DDD per 100 patient-days was 90.7-94.5. There was a discordant findings of antibiotic measurements based on the DDD compared to DOT, and DDD/100 bed-days compared to DOT/100 bed-days. There was a negative correlation between CMI and DDD per 100 bed days (r -0.696), but a positive correlation of CMI with DOT (r +0.93). Adjusted DDD/100 bed-days showed decrease in the usage of antibiotics, reflecting activities of the antibiotic stewardship program. The increase in DOT/100 bed-days may indicate the favorable utilization of combination therapy. Antibiotic usage needs to be adjusted per 100 bed-days and correlated with CMI for better reflection of optimal antibiotic utilization, activities of the antibiotic stewardship program, and to allow benchmarking.

A pilot double-blind trial using verapamil as adjuvant therapy for refractory seizures.

RATIONALE: Given verapamil's property as a glycoprotein inhibitor, this drug could increase the effective concentration of antiepileptic drugs (AEDs) in the epileptic foci, reducing the number of seizures. This pilot study was designed to evaluate the safety and efficacy of verapamil as adjunct therapy in pharmacoresistant patients with focal onset seizures. METHODS: This was a single-centered, randomized, double-blind and placebo-controlled trial evaluating verapamil as an add-on therapy for adult patients with refractory epilepsy. RESULTS: Twenty-two patients were randomized, but five of them withdrew and one patient passed away after consent, having no exposure to either verapamil or placebo; four patients withdrew during or after the double-blind phase due to side effects. From these four patients, only one patient was in the verapamil group. Twelve patients (59%) finished the study. Some patients experienced lower seizure frequencies, but none of them reached 50% reduction. In addition, there was no statistically significant decrease in the seizure frequency of patients receiving verapamil. When comparing the verapamil with the placebo at the double-blind or the open label study phases, the average difference in seizure range also failed to show significance (p=0.41 and p=0.98, respectively). No significant cardiovascular effects were observed, and side effects unique to verapamil were skin rashes and feet edema. Throughout the study, carbamazepine, valproic acid and clobazam levels increased following verapamil intake; minor dosage adjustment was required in one patient on carbamazepine. CONCLUSIONS: This pilot study has shown mild benefits of verapamil use in comparison to placebo as an add-on therapy for a group of non-selected patients with refractory epilepsy. A partial response in a subset of patients was seen. No significant safety problems happened, but adjustments on AEDs may be required during verapamil use.

Epilepsy transition: challenges of caring for adults with childhood-onset seizures.

OBJECTIVES: Children with severe chronic epilepsy are living longer, and they eventually transition to the adult health care system. Additional research is required to better define the population that is being transferred and the qualifications of those who are assuming their care. We aimed to evaluate the complexity of epilepsy patients transitioning between tertiary centers, and to evaluate neurologists' confidence in dealing with childhood-onset epilepsies. METHODS: Patients aged from 18 to 25 years were divided into two groups: Group 1 comprised patients referred from the pediatric tertiary center; and Group 2 comprised patients referred from the community. Clinical data were retrospectively studied and groups were compared using appropriate statistics. We also created a survey to evaluate neurologists' levels of confidence in diagnosing and treating childhood-onset epilepsies. Differences among responders were compared. RESULTS: Group 1 comprised 170 patients, whereas group 2 had 132. Patients in group 1 had earlier seizure onset, longer epilepsy duration (p < 0.001), and more patients with symptomatic etiologies, epileptic encephalopathy, and cognitive delay (p < 0.001). Group 1 patients required more referrals to other specialties (p = 0.001). Treatment with polytherapy (p = 0.003), epilepsy surgery (p < 0.001), ketogenic diet (p < 0.001), and vagus nerve stimulator were more common in group 1 (p < 0.001). In addition, our survey applied to adult (n = 86) and pediatric (n = 29) neurologists indicated that adult neurologists have lower levels of confidence in diagnosing and treating severe forms of childhood-onset epilepsies (p < 0.001), as well as epilepsy associated with cognitive delay (p < 0.001). SIGNIFICANCE: These findings suggest that patients from tertiary centers present more complex health care needs and require more resources than age-matched patients from the community; and that adult neurologists may not feel prepared to diagnose and treat adult patients with some childhood-onset epilepsies.

Hemimegalencephaly: what happens when children get older?

AIMS: Hemimegalencephaly (HME) is a rare congenital malformation of cortical development, usually associated with developmental delay and severe epilepsy. This condition has rarely been reported in adults. The aim of this study was to examine and compare neurological findings in adult patients with HME. METHOD: We retrospectively examined adult patients with HME by evaluating the presence of neurocutaneous disorders, current cognitive development, seizure control, and documentation of therapies for seizure management and outcomes. RESULTS: Five patients were included in the study (three males, two females; mean age 23 y 9 mo [SD 6 y 1 mo], range 18-34 y). Four patients had HME that was associated with neurocutaneous syndromes and the remaining patient had isolated HME. Two patients required surgical treatment for seizures in childhood. One patient had no intellectual disability, while one had mild, and three severe intellectual disability. All patients presented motor deficits ranging from mild hemiparesis in two patients to non-ambulation in one patient. Patients in whom seizure onset occurred after the 7 years of age had better seizure control and psychomotor development in adulthood than patients in whom seizure onset occurred in the first year of life. INTERPRETATION: In our small sample of adults with HME, age at seizure onset, cognitive disability, and seizure control were found to be associated.