Early mobilisation in critically ill COVID-19 patients: a subanalysis of the ESICM-initiated UNITE-COVID observational study

Background Early mobilisation (EM) is an intervention that may improve the outcome of critically ill patients. There is limited data on EM in COVID-19 patients and its use during the first pandemic wave. Methods This is a pre-planned subanalysis of the ESICM UNITE-COVID, an international multicenter observational study involving critically ill COVID-19 patients in the ICU between February 15th and May 15th, 2020. We analysed variables associated with the initiation of EM (within 72 h of ICU admission) and explored the impact of EM on mortality, ICU and hospital length of stay, as well as discharge location. Statistical analyses were done using (generalised) linear mixed-effect models and ANOVAs. Results Mobilisation data from 4190 patients from 280 ICUs in 45 countries were analysed. 1114 (26.6%) of these patients received mobilisation within 72 h after ICU admission; 3076 (73.4%) did not. In our analysis of factors associated with EM, mechanical ventilation at admission (OR 0.29; 95% CI 0.25, 0.35; p = 0.001), higher age (OR 0.99; 95% CI 0.98, 1.00; p ≤ 0.001), pre-existing asthma (OR 0.84; 95% CI 0.73, 0.98; p = 0.028), and pre-existing kidney disease (OR 0.84; 95% CI 0.71, 0.99; p = 0.036) were negatively associated with the initiation of EM. EM was associated with a higher chance of being discharged home (OR 1.31; 95% CI 1.08, 1.58; p = 0.007) but was not associated with length of stay in ICU (adj. difference 0.91 days; 95% CI − 0.47, 1.37, p = 0.34) and hospital (adj. difference 1.4 days; 95% CI − 0.62, 2.35, p = 0.24) or mortality (OR 0.88; 95% CI 0.7, 1.09, p = 0.24) when adjusted for covariates. Conclusions Our findings demonstrate that a quarter of COVID-19 patients received EM. There was no association found between EM in COVID-19 patients' ICU and hospital length of stay or mortality. However, EM in COVID-19 patients was associated with increased odds of being discharged home rather than to a care facility. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021)

Evaluating the knowledge levels of nurses working in pediatric clinics about pain and pain assessment in children

Yüksek Lisans TeziBu araştırma, çocuk servislerinde çalışan hemşirelerin çocuklarda ağrı ve ağrı değerlendirilmesi konularında bir eğitim programı öncesi ve sonrası bilgi düzeylerini değerlendirmek ve arttırmak amacıyla tanımlayıcı olarak yapılmıştır. Araştırma Mayıs 2013- Temmuz 2014 tarihleri arasında Trakya Üniversitesi Eğitim ve Araştırma Hastanesi ve Edirne İl Sağlık Müdürlüğüne bağlı Devlet hastanelerinin çocuk servislerinde çalışan, araştırmaya katılmayı kabul eden, çocuklarda ağrı ve ağrı değerlendirilmesi konusunda eğitim verilen ve anket formlarını eksiksiz dolduran eden 75 hemşire ile gerçekleştirildi. Veriler, ‘Veri Toplama Formu’ ve hemşirelerin çocuklarda ağrı ve ağrı değerlendirilmesi konusundaki bilgi düzeylerini belirleyen 33 sorudan oluşan ‘Ön Test/Son Test Soru Formu’ kullanılarak elde edildi. Verilerin analizinde frekans, ortalama, Student t, Wilcoxon testi, One Way Anova testi, Mann Whitney U testi ve Spearman korelasyon analizi kullanıldı. Hemşirelerin yaş ortalaması 29,54 ± 5,73 (20-46) idi. Hemşirelerin %61,3’ünün lisans mezunu olduğu, %60’ının üniversite hastanesinde ve %33,3’ünün Yenidoğan Yoğun Bakım Ünitesinde çalışmakta olduğu belirlendi. Hemşirelerin eğitim öncesi bilgi düzeyi puan ortalamalarının 28,64 ± 2,84, eğitim sonrası bilgi düzeyi puan ortalamalarının 31,98 ± 1,33 olduğu, eğitim sonrası bilgi düzeyi puan ortalamalarının anlamlı ölçüde arttığı belirlendi (p<0,001). Hemşirelerin yaşı arttıkça eğitim sonrası bilgi düzeyleri arttı (p=0,035). Hemşirelerin çocuk servisinde çalışmayı isteme durumları, hemşirelik ile ilgili etkinliklere katılma durumları ve pediatri hemşireliği ile ilgili etkinliklere katılma durumlarının bilgi düzeylerini etkilediği belirlendi (p<0,05). Bu sonuçlar hemşirelerin çocuklarda ağrı ve ağrı değerlendirilmesi konusunda bilgi eksikliklerinin ve eğitim gereksinimlerinin olduğunu, verilen eğitimin bilgi düzeylerini arttırdığını ve hemşirelerin ağrı değerlendirmesinde bu bilgileri kullandıklarını gösterdi.abstractThis research was about pain and pain assestment in children conducted to assess and increase the level of knowledge of nurses who are working in pediatrics and make a comparison with the level of knowledge after a training program. The research was between May 2013 and July 2014 and included 75 nurses, who agreed to join to the training program about pain and pain assessment and filled out the questionnaire and working in pediatrics service of Trakya University Training and Research Hospital or Public Hospitals in Edirne. Data was obtained using first/final tests, both consisting of 33 questions for nurses that determine the level of knowledge on pain and pain assessment in children.Frequency, mean, Student’s t test, One Way Anova, Wilcoxon, Mann-Whitney U test and Spearman correlation analysis was used in data analysis. The average age of nurses was 29.54+5.73 (20-46). 61.3% of the nurses had a graduate degree, 60% of them were working in the university hospital and 33.3% of them were working in the NICU. It was determined that the average scores of knowledge level of nurses before and after the training were 28.64+2.84 and 31.98+1.33, respectively and increased significantly after the training (p<0.001). The increase in knowledge level was higher in nurses with older age (p=0.035). It was determined that the level of knowledge was affected by nurse’s desire in working pediatrics clinic, and participating in supporting developmental activities about nursing and pediatric nursing (p<0.05). These results indicate that the nurses have a lack of knowledge and educational needs about pain and pain assessment in children and getting this education provides increasing level of knowledge that nurses use this for pain assestment

Evaluation and Comparison of In Vitro Biocompatibility of Poly (Glycolic Acid) and Poly (Lactide-Co-Glycolide Acid) on Mature Spheroids of Tumorigenic and Non-Tumorigenic Cell Lines

WOS: 000290353100001Objective: The aim of this study was to evaluate and compare in vitro biocompatibility and poly(glycolic acid) (PGA) and poly(lactide-co-glycolide acid) (PLGA) on tumorigenic and non-tumorigenic mature spheroids. Material and Methods: This is an in vitro experimental study. Tumorigenic (C6 glioma, SH-SY5Y, MDAH2774, MCF-7) and non-tumorigenic cells [CRL11372, primary osteoblasts (MCPO)] as well as their mature spheroids were cultured alone as a control group as well as in combination with PGA and PLGA. Total cell numbers, bromodeoxyuridine labeling index (BrDU-LI), apoptosis, morphology, and ultrastructure were evaluated. Results: PGA and PLGA significantly decreased the number of SH-SY5Y and C6 glioma cells; MDAH 2774 cells also decreased, but not significantly (p> 0.05). Low BrDU-LI (p< 0.05) with a high level of apoptosis (p< 0.05) at C6 glioma and a high level of BrDU-LI (p< 0.05) with a low level of apoptosis at MDAH2774 (p< 0.01) were noted. These biopolymers mostly decreased the number of CRL-11372 cells (p< 0.05), but indicated an increased apoptosis (p< 0.01) and significant BrDU-LI (p< 0.05). Biopolymers induced chromatin condensation (typical apoptotic ultrastructure) and vacuolization primarily at SH-SY5Y spheroids but rarely at MDAH-2774 spheroids. This apoptotic ultrastucture was most often observed at MCPO spheroids. PLGA and PGA induced similar BrDU-LI decreases among tumorigenic spheroids (p< 0.05), although this decrease was greater at MCF-7 (p< 0.05) in the PGA group. PGA primarily decreased BrDU-LI at CRL 11372 (p< 0.05), although the decrease was almost identical to that at MCPO for the two biopolymers (p< 0.05). A significant attachment affinity was determined at MDAH -2774 and C6 glioma spheroids. Conclusion: This study demonstrated the biocompatibility of PGA and PLGA at mature spheroids of tumorigenic and non-tumorigenic cell lines, which changed according to the cell type

Melatonin ameliorates oxidative damage in hyperglycemia-induced liver injury

Purpose: Melatonin (N-acetyl-5-methoxy-tryptamine) is synthesized mainly by the pineal gland and its antioxidant properties have been demonstrated both in short and long term studies. Our aim was to clarify the effects of hyperglycemia and to administer melatonin on lipid peroxidation, protein oxidation and oxidative DNA damage in rat. Methods: Malondialdehyde (MDA), protein carbonyl (PCO) and total thiol (T-SH) levels were determined in plasma and liver tissue, glutathione (GSH) levels in erythrocyte and liver tissue, and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels in plasma and liver. Thirty-eight male Wistar rats were divided into four groups: 1 - injected with saline (n = 8), 2 - injected with melatonin (n = 10), 3 - injected with STZ (65 mg/kg, i.p.) (diabetic group) (n = 10) and 4 - injected with melatonin (10 mg/kg/day, i.p.) and STZ (65 mg/kg, i.p.) (n = 10) for 8 weeks (diabetic+ melatonin group). Colorimetric methods were used to determine the level of the oxidative stress markers. 8-OhdGwas measured using ELISA. Results: MDA, PCO and 8-OHdG levels in the plasma and the liver homogenates of diabetic rats were higher than controls and were significantly reduced after melatonin treatment. T-SH and GSH levels in samples were markedly reduced in untreated diabetic rats compared with control rats; however, these parameters were increased in diabetic rats following melatonin treatment. Conclusion: Our findings showed that melatonin administration partially ameliorated oxidative damage in liver injury in STZ-induced diabetic rats. The present study suggests that melatonin functions as a potent antioxidant agent in diabetes. Melatonin, a nutritional supplement, may be a good therapeutic option for diabetic patients

Maltodextrin modified liposomes for drug delivery through the blood-brain barrier

Central nervous system acting drugs, when administered intravenously, cannot show their effect in the brain due to the difficulty in crossing the blood-brain barrier (BBB). Levodopa is one of those drugs that are used to treat Parkinson's disease. In this study, a new liposomal levodopa delivery system that is modified with maltodextrin was developed in order to target and enhance transport through the BBB. An antioxidant, glutathione, was co-loaded in liposomes as a supportive agent and its effect on liposome stability and delivery was investigated. Glutathione co-loading had a positive effect on the viabilities of 3T3 and SH-SY5Y cells. Maltodextrin targeted liposomes showed high in vitro levodopa passage in the parallel artificial membrane permeability assay and had superior binding to MDCK cells. Results suggest that maltodextrin modification of liposomes is an effective way of targeting the BBB and the developed liposomal formulation would improve brain delivery of central nervous system agents

Methylprednisolone 100 mg Tablet Formulation With Pea Protein: Experimental Approaches Over Intestinal Permeability and Cytotoxicity

Objective: This study was carried out to transform the hydrolyzed pea protein into a pharmaceutical tablet form by masking methylprednisolone. Significance: This study provides some crucial contributions in showing how functional excipients such as pea protein, which are generally used in food industries, can be used in pharmaceutical product formulations and their effects. Methods: Methylprednisolone was formulated using spray drying technology. Design Expert Software (Version 13) was used for the statistical analysis. The in vitro cytotoxic effects for NIH/3T3 mouse fibroblast cells were investigated by XTT cell viability assay. HPLC was used to analyze the Caco-2 permeability studies and dissolution tests. Results: The optimum formulation was evaluated against the reference product by performing cytotoxicity and cell permeability studies. According to our test results, Papp (apparent permeability) values of Methylprednisolone were measured around 3 10-6 cm/s and Fa (fraction absorbed) values around 30%. These data indicate that Methylprednisolone HCl has ‘moderate permeability’ and our study confirmed that it could have belonged to BCS Class II-IV since both low solubility and moderate permeability. Conclusion: The findings offer valuable information to guide and inform the use of pea protein in pharmaceutical formulations. Significant effects on methylprednisolone tablet formulation designed with the philosophy of quality by design (QbD) of pea protein have been demonstrated by both in vitro and cell studies

Blood Meal Identification of the Mosquito (Diptera: Culicidae) Specimens Belong to Culex pipiens Complex that were Collected from Kayseri Province.

OBJECTIVE: This study aimed to determine the host preferences in blood meal of specimens belonging to Culex pipiens complex.METHODS: A total of 1284 female mosquitos were morphologically examined, and genomic DNA isolations were individually performed on 376 (28.4%) specimens that were determined to be Cx. pipiens complex. PCR was performed with primers to specifically amplify the avian and mammalian mitochondrial cytochrome b (mt-cytb) gene region. Amplicons were cloned, and the obtained plasmids were sequenced to determine host species.RESULTS: Of 376 specimens, 148 (39.4%) were positive for the avian and/or mammalian blood meal. Among the positive specimens, 43, 98, and seven were determined to be positive for only mammalian, avian, and both avian and mammalian blood, respectively. Avian host preference in blood meal of the specimens belonging to Cx. pipiens was found to be significant. Of 15 avian blood positive isolates, nine, three, two, and one were designated as blood meal from avian species in Passeriformes, Accipitriformes, Columbiformes, and Strigiformes orders, respectively. While six, four, three, and two out of 15 mammalian blood-positive specimens were found to be positive for human, cattle, sheep, and dog blood, respectively.CONCLUSION: Molecular data regarding the host preferences of the Cx. pipiens species complex in blood meal were revealed for the first time in Turkey with this study

Imatinib mesylate decreases the cytotoxic effect of roscovitine on human glioblastoma cells in vitro and the role of midkine

The purpose of the present study was to overcome resistance to imatinib (IM) by combining it with roscovitine (ROSC) and to investigate whether or not midkine (MK) had an effect on this combination in the treatment of glioblastoma (GBL). Human T98 GBL cells were used to evaluate the effects of IM (10 μM), ROSC (200 μM) and their combination on the cell proliferation index, apoptotic index, the apoptotic protein and anti-apoptotic protein levels, and ultrastructure. All applications decreased the cell proliferation index and increased the apoptotic index, but ROSC was the most efficient drug and the second most efficient drug was IM. Notably, ROSC increased anti-apoptotic proteins levels (PDGFR-α, AQP-4, hTERT), COX-1 activity and ribosome numbers. The effects of ROSC on hTERT, MK, AQP-4 and MRP-1 levels and COX-1 activity were reported for the first time. ROSC induced the highest increase in caspase-3 levels. Autophagy was not involved in the activity of ROSC in GBL spheroids. The combination of IM with ROSC showed an antagonist effect in the treatment of human GBL cells. The combination group decreased certain anti-apoptotic protein levels (PDGFR-α, EGFR, p-gp, MRP-1 and MK), cAMP levels, COX-1 activity and apoptotic protein levels (caspase-3). However, it induced the highest increase in hTERT levels and COX-2 activity. Ribosome numbers were much lower than those in the ROSC group and no autophagic vacuole was observed. In conclusion, more investigations are required to identify the key regulatory components that are responsible for this antagonism; however, the determination of this combination therapy as a failure therapy may be precautionary for oncologists in the treatment of GBL patients and potentially may contribute to the efficacy of new therapeutic regimens