The hospital frailty risk score effectively predicts adverse outcomes in patients with atrial fibrillation in the intensive care unit.

Background Atrial fibrillation (AF) and frailty are significant global public health problems associated with advancing age. However, the relationship between frailty and older patients with AF in the intensive care unit (ICU) has not been thoroughly investigated. This study aimed to investigate whether the hospital frailty risk score (HFRS) is associated with adverse outcomes in older patients with AF in the ICU. Methods This was the first retrospective analysis of older patients with AF admitted to the ICU between 2008 and 2019 at a tertiary academic medical center in Boston. The HFRS was used to measure frailty severity. The outcomes of interest were in-hospital and 30-day mortality and the incidence of sepsis and ischemic stroke. Results There were 7,792 participants aged approximately 80 years, almost half (44.9%) of whom were female. Among this group, 2,876 individuals were identified as non-frail, while 4,916 were classified as frail. The analysis revealed a significantly greater incidence of in-hospital (18.8% compared to 7.6%) and 30-day mortality (24.5% versus 12.3%) in the frail group. After accounting for potential confounding factors, a multivariate Cox proportional hazards regression analysis revealed that frail participants had a 1.56-fold greater risk of mortality within 30 days (95% CI = 1.38-1.76, p < 0.001). Conclusions Frailty is an independent risk factor for adverse outcomes in older patients with AF admitted to the ICU. Therefore, prioritizing frailty assessment and implementing specific intervention strategies to improve prognostic outcomes are recommended.

Intracellular Pharmacokinetics of Activated Drugs in a Prodrug-Enzyme-Ultrasound System: Evaluations on ZD2767P+CPG2+US.

Intracellular pharmacokinetics (PK) of activated drugs is a window to understanding the pharmacodynamics of prodrug-enzyme-ultrasound therapy. Herein PK of ZD2767D (i.e., activated drug) in the ZD2767P+CPG2+US system on A549, A549/DDP, SKOV3, and SKOV3/DDP cells were evaluated (A549/DDP and SKOV3/DDP were cisplatin-resistant sublines). The noncompartment model under extravascular input mode was deemed appropriate for evaluating drug level vs time curves; Cmax, AUClast, MRTlast, Vz, and Cl can reflect the PK feature, but t1/2, AUCinf, and MRTinf were irrational; higher accumulation and slower elimination characterized the PK mechanism of ZD2767P+CPG2+US; enhanced permeability and retention effect can be assessed with Cmax, AUClast, MRTlast, and tlast; ultrasound equivalently modulated Cmax and AUClast in sensitive and resistant cells. The experimental design and dose proportionality were discussed.

Braden score can independently predict 90-day mortality in critically ill patients with dementia.

BACKGROUND: Dementia is a significant cause of death in the older population and is becoming an important public health issue as the population ages and the prevalence of dementia increases. The Braden score is one of the most commonly used clinical tools to assess the risk of skin pressure injury in patients, and some studies have reported that it may reflect the state of frailty of patients. The present study attempted to explore the association between Braden score and 90-day mortality, pressure injury, and aspiration pneumonia in older patients with dementia in the intensive care unit (ICU). METHODS: The study involved extracting crucial data from the Medical Information Market for Intensive Care IV (MIMIC-IV) database using Structured Query Language, with a license certificate obtained after completing the necessary training and examination available on the MIMIC-IV website. A retrospective analysis was performed on older patients with dementia, aged 65 or older, who were first admitted to the ICU. Ninth and tenth revision International Classification of Diseases codes were used to identify patients with dementia. The primary outcome was 90-day mortality. Cox proportional hazards models were used to determine the association between Braden score and death, and hazard ratios (HR) and 95% confidence intervals (CI) were calculated. Propensity score matching and E-value assessments were employed for sensitivity analysis. RESULTS: A total of 2892 patients with a median age of approximately 85 years (interquartile range 78.74-89.59) were included, of whom 1625 were female (56.2%). Patients had a median Braden score of 14 (interquartile range 12-15) at ICU admission. Braden score at ICU admission was inversely associated with 90-day mortality risk after adjustment for demographics, severity of illness, treatment and medications, delirium, and sepsis (adjusted HR: 0.92, 95% CI: 0.87-0.98, p = 0.006). Patients were divided into two groups with a cut-off value of 15: high-risk group and low-risk group. Compared to the low-risk group (Braden score >15), the risk of 90-day mortality was significantly increased in the high-risk group (Braden score ≤15) (adjusted HR: 1.52, 95% CI: 1.10-2.09, p = 0.011, E-value: 2.01), the risk of pressure injury (adjusted OR: 2.62, 95% CI: 2.02-3.43, E-value: 2.62) and aspiration pneumonia (adjusted OR: 2.55, 95% CI: 1.84-3.61, E-value: 2.57) was also significantly higher. CONCLUSIONS: The Braden score may be a quick and simple screening tool to identify the risk of adverse outcomes in critically ill older adults with dementia.

Phenotypes of patients with systemic sclerosis in the Chinese Han population: a cluster analysis.

OBJECTIVE: Systemic sclerosis (SSc) is a heterogeneous connective tissue disease that is commonly subdivided into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) based on the extent of skin involvement. This subclassification may not reflect the full range of clinical phenotypic variation. This study aimed to investigate clinical features and aggregation of patients with SSc in Chinese based on SSc manifestations and organ involvements, in order to achieve precise treatment of SSc early prevention of complications. METHODS: In total 287 SSc patients were included in this study. A cluster analysis was applied according to 13 clinical and serologic variables to determine subgroups of patients. Survival rates between obtained clusters and risk factors affecting prognosis were also compared. RESULT: In this study, six clusters were observed: cluster 1 (n = 66) represented the skin type, with all patients showing skin thickening. In cluster 2 (n = 56), most patients had vascular and articular involvement. Cluster 3 (n = 14) individuals mostly had cardiac and pulmonary involvement. In cluster 4 (n = 52), the gastrointestinal type, 50 patients presented with stomach symptoms and 28 patients presented with esophageal symptoms. In cluster 5 (n = 50), patients barely had any major organ involvement. Cluster 6 (n = 49) included 46% of all patients presenting with renal crisis. CONCLUSION: The results of our cluster analysis study implied that limiting SSc patient subgroups to those based only on skin involvement might not capture the full heterogeneity of the disease. Organ damage and antibody profiles should be considered when identifying homogeneous patient groups with a specific prognosis. Key Points • Provides a new method of categorizing SSc patients. • Can better explain disease progression and guide subsequent treatment.

Toward Genetic Testing of Rivaroxaban? Insights from a Systematic Review on the Role of Genetic Polymorphism in Rivaroxaban Therapy.

BACKGROUND: Investigations into the rivaroxaban response from the perspective of genetic variation have been relatively recent and wide in scope, whereas there is no consensus on the necessity of genetic testing of rivaroxaban. Thus, this systematic review aims to thoroughly evaluate the relationship between genetic polymorphisms and rivaroxaban outcomes. METHODS: The PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Chinese databases were searched to 23 October 2022. We included cohort studies reporting the pharmacogenetic correlation of rivaroxaban. Outcomes measured included efficacy (all-cause mortality, thromboembolic events and coagulation-related tests), safety (major bleeding, clinically relevant non-major bleeding [CRNMB] and any hemorrhage), and pharmacokinetic outcomes. A narrative synthesis was performed to summarize findings from individual studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the reporting guideline for Synthesis Without Meta-Analysis. RESULTS: A total of 12 studies published between 2019 and 2022 involving 1364 patients were included. Ten, one, and six studies focused on the ABCB1, ABCG2, and CYP gene polymorphisms, respectively. Pharmacokinetic outcomes accounted for the majority of the outcomes reported (n = 11), followed by efficacy (n = 5) [including prothrombin time (PT) or international normalized ratio (n = 3), platelet inhibition rate (PIR) or platelet reactivity units (PRUs; n = 1), thromboembolic events (n = 1)], and safety (n = 5) [including major bleeding (n = 2), CRNMB (n = 2), any hemorrhage (n = 1)]. For ABCB1 gene polymorphism, the relationship between PT and ABCB1 rs1045642 was inconsistent across studies, however there was no pharmacogenetic relationship with other efficacy outcomes. Safety associations were found in ABCB1 rs4148738 and major bleeding, ABCB1 rs4148738 and CRNMB, ABCB1 rs1045642 and CRNMB, and ABCB1 rs2032582 and hemorrhage. Pharmacokinetic results were inconsistent among studies. For ABCG2 gene polymorphism, no correlation was observed between ABCG2 rs2231142 and dose-adjusted trough concentration (Cmin/D). For CYP gene polymorphisms, PIR or PRUs have a relationship with CYP2C19 rs12248560, however bleeding or pharmacokinetic effects did not show similar results. CONCLUSIONS: Currently available data are insufficient to confirm the relationship between clinical or pharmacokinetic outcomes of rivaroxaban and gene polymorphisms. Proactive strategies are advised as a priority in clinical practice rather than detection of SNP genotyping. CLINICAL TRIALS REGISTRATION: PROSPERO registration number CRD42022347907.

Clinical Trials of High-Intensity Focused Ultrasound for Cancer: Concerns Arising from Low Post-Hoc Power.

Prospective controlled trials of high-intensity focused ultrasound for cancers were evaluated. Post-hoc power was <0.80 in 30/47 trials and in 22/39 trials with positive results, indicating low quality in most trials. Unscientific endpoints, small sample sizes, and high dropout rates led to low post-hoc power that caused inter-trial heterogeneity and overestimated the therapeutic effect. The objective response rate was not a substitute for survival time for estimating the sample size and assessing the efficacy. The present data can interpret a paradox: HIFU is considered to have slighter cytotoxicity to non-cancer tissues and no radiation but is frequently combined with chemotherapy and/or radiotherapy in practice.

ICU admission Braden score independently predicts delirium in critically ill patients with ischemic stroke.

BACKGROUND: Delirium is a common and severe complication in intensive care unit (ICU) patients with acute ischemic stroke, exacerbating cognitive and physical impairments. It prolongs hospitalization, increases healthcare costs, and raises mortality risk. Early prediction is crucial because it facilitates prompt interventions that could possibly reverse or alleviate the detrimental consequences of delirium. Braden scores, traditionally used to assess pressure injury risk, could also signal frailty, providing an early warning of delirium and aiding in prompt and effective patient management. OBJECTIVE: To examine the association between the Braden score and delirium. METHODS: A retrospective analysis of adult ischemic stroke patients in the ICU of a tertiary academic medical center in Boston from 2008 to 2019 was performed. Braden scores were obtained on admission for each patient. Delirium, the primary study outcome, was assessed using the Confusion Assessment Method for Intensive Care Unit and a review of nursing notes. The association between Braden score and delirium was determined using Cox proportional hazards modeling, with hazard ratios (HR) and 95% confidence intervals (CI) calculated. RESULTS: The study included 3,680 patients with a median age of 72 years, of whom 1,798 were women (48.9 %). The median Braden score at ICU admission was 15 (interquartile range 13-17). After adjustment for demographics, laboratory tests, severity of illness, and comorbidities, the Braden score was inversely associated with the risk of delirium (adjusted HR: 0.94, 95 % CI: 0.92-0.96, P < 0.001). CONCLUSIONS: The Braden score may serve as a convenient and simple screening tool to identify the risk of delirium in ICU patients with ischemic stroke. IMPLICATION FOR CLINICAL PRACTICE: The use of the Braden score as a predictor of delirium in ischemic stroke patients in the ICU allows early identification of high-risk patients. This facilitates timely intervention, thereby improving patient outcomes and potentially reducing healthcare costs.

Predictors of rapidly progressive interstitial lung disease and prognosis in Chinese patients with anti-melanoma differentiation-associated gene 5-positive dermatomyositis.

Background: Rapidly progressive interstitial lung disease (RP-ILD) is the most serious complication of anti-melanoma differentiation-associated gene 5-positive dermatomyositis (anti-MDA5+ DM). This study was performed to assess the prognostic factors of patients with anti-MDA5+ DM and the clinical characteristics and predictors of anti-MDA5+ DM in combination with RP-ILD. Methods: In total, 73 MDA5+ DM patients were enrolled in this study from March 2017 to December 2021. They were divided into survival and non-survival subgroups and non-RP-ILD and RP-ILD subgroups. Results: The lactate dehydrogenase (LDH) concentration and prognostic nutritional index (PNI) were independent prognostic factors in patients with anti-MDA5+ DM: the elevated LDH was associated with increased mortality (p = 0.01), whereas the elevated PNI was associated with reduced mortality (p < 0.001). The elevated LDH was independent risk prognostic factor for patients with anti-MDA5+ DM (HR 2.42, 95% CI: 1.02-4.83, p = 0.039), and the elevated PNI was independent protective prognostic factor (HR, 0.27; 95% CI, 0.08 - 0.94; p = 0.039). Patients who had anti-MDA5+ DM with RP-ILD had a significantly higher white blood cell count and LDH concentration than those without RP-ILD (p = 0.007 and p = 0.019, respectively). In contrast, PNI was significantly lower in patients with RP-ILD than those without RP-ILD (p < 0.001). The white blood cell count and elevated LDH were independent and significant risk factors for RP-ILD (OR 1.54, 95% CI: 1.12 - 2.13, p = 0.009 and OR 8.68, 95% CI: 1.28 - 58.83, p = 0.027, respectively), whereas the lymphocyte was an independent protective factor (OR, 0.11; 95% CI, 0.01 - 0.81; p = 0.03). Conclusion: The elevated LDH and elevated PNI were independent prognostic factors for patients with anti-MDA5+ DM. The elevated LDH was independent risk factor for RP-ILD. Patients with anti-MDA5+ DM could benefit from the measurement of LDH and PNI, which are inexpensive and simple parameters that could be used for diagnosis as well as prediction of the extent of lung involvement and prognosis.

Status and Quality of Guidelines for Therapeutic Drug Monitoring Based on AGREE II Instrument.

BACKGROUND: With the progress of therapeutic drug monitoring (TDM) technology and the development of evidence-based medicine, many guidelines were developed and implemented in recent decades. OBJECTIVE: The aim was to evaluate the current status of TDM guidelines and provide suggestions for their development and updates based on Appraisal of Guidelines for Research and Evaluation (AGREE) II. METHODS: The TDM guidelines were systematically searched for among databases including PubMed, Embase, China National Knowledge Infrastructure, Wanfang Data, and the Chinese biomedical literature service system and the official websites of TDM-related associations. The search period was from inception to 6 April 2023. Four researchers independently screened the literature and extracted data. Any disagreement was discussed and reconciled by another researcher. The quality of guidelines was assessed using the AGREE II instrument. RESULTS: A total of 92 guidelines were included, including 57 technical guidelines, three management guidelines, and 32 comprehensive guidelines. The number of TDM guidelines has gradually increased since 1979. The United States published the most guidelines (20 guidelines), followed by China (15 guidelines) and the United Kingdom (ten guidelines), and 23 guidelines were developed by international organizations. Most guidelines are aimed at adult patients only, while 28 guidelines include special populations. With respect to formulation methods, there are 23 evidence-based guidelines. As for quality evaluation results based on AGREE II, comprehensive guidelines scored higher (58.16%) than technical guidelines (51.36%) and administrative guidelines (50.00%). CONCLUSION: The number of TDM guidelines, especially technical and comprehensive ones, has significantly increased in recent years. Most guidelines are confronted with the problems of unclear methodology and low quality of evidence according to AGREE II. More evidence-based research on TDM and high-quality guideline development is recommended to promote individualized therapy.

The impact of China's zero markup drug policy on drug costs for managing Parkinson's disease and its complications: an interrupted time series analysis.

Background: In April 2009, the Chinese government launched Zero Markup Drug Policy (ZMDP) to adjust medical institutions' revenue and expenditure structures. Objective: This study evaluated the impact of implementing ZMDP (as an intervention) on the drug costs for managing Parkinson's disease (PD) and its complications from the healthcare providers' perspective. Methods: The drug costs for managing PD and its complications per outpatient visit or inpatient stay were estimated using electronic health data from a tertiary hospital in China from January 2016 to August 2018. An interrupted time series analysis was conducted to evaluate the immediate change following the intervention (step change, ß1) and the change in slope, comparing post-intervention with the pre-intervention period (trend change, ß2). Subgroup analyses were conducted in outpatients within the strata of age, patients with or without health insurance, and whether drugs were listed in the national Essential Medicine List (EML). Results: Overall, 18,158 outpatient visits and 366 inpatient stays were included. Outpatient (ß1 = -201.7, 95%CI: -285.4, -117.9) and inpatient (ß1 = -372.1, 95% CI: -643.6, -100.6) drug costs for managing PD significantly decreased when implementing ZMDP. However, for outpatients without health insurance, the trend change in drug costs for managing PD (ß2 = 16.8, 95% CI: 8.0, 25.6) or PD complications (ß2 = 12.6, 95% CI: 5.5, 19.7) significantly increased. Trend changes in outpatient drug costs for managing PD differed when stratifying drugs listed in EML (ß2 = -1.4, 95% CI: -2.6, -0.2) or not (ß2 = 6.3, 95%CI: 2.0, 10.7). Trend changes of outpatient drug costs for managing PD complications significantly increased in drugs listed in EML (ß2 = 14.7, 95% CI 9.2, 20.3), patients without health insurance (ß2 = 12.6, 95% CI 5.5, 19.7), and age under 65 (ß2 = 24.3, 95% CI 17.3, 31.4). Conclusions: Drug costs for managing PD and its complications significantly decreased when implementing ZMDP. However, the trend in drug costs increased significantly in several subgroups, which may offset the decrease at the implementation.

Risk evaluation of adverse aortic events in patients with non-circular aortic annulus after transcatheter aortic valve implantation: a numerical study.

Transcatheter aortic valve implantation (TAVI) is a micro-invasive surgery used to treat patients with aortic stenosis (AS) efficiently. However, the uneven valve expansion can cause a non-circular annulus, which is one of the main factors leading to complications after TAVI. As a preliminary work, the main purpose of this study was to evaluate the risk of adverse aortic events in patients with a non-circular aortic annulus after TAVI. This study numerically investigated the distribution of four wall shear stress (WSS)-based indicators and three helicity-based indicators in eight patient-specific aortas with different annulus including circular, type I elliptical and type II elliptical shapes. Both elliptical annulus features can significantly enhance the intensity of the helicity (h2) in the ascending aorta (p < 0.001). However, for the type I elliptical annulus, the spiral flow structure was changed into low-velocity and disturbed flow pattern close to the inner side of the aortic arch. For the type II elliptical annulus, the spiral flow remained but became skewed in distribution. The elliptical annulus feature could increase the general level WSS-based indicators, especially in the ascending aorta. However, due to the disturbance of spiral flow or second helical flow in ascending aortas, areas with low TAWSS accompanied by high oscillatory shear index (OSI) and cross flow index (CFI) were observed in all the ascending aortas with non-circular annulus. The elliptical annulus feature can change the hemodynamic environment in the aortic arch, especially in the ascending aorta. Although both elliptical annulus features enhanced the strength of helicity, the uniform distribution of the helical flow was disturbed, especially in the ascending aorta, indicating the potential risk of adverse aortic events may increase. Therefore, for the patients without paravalvular leak but elliptical annulus shape after TAVI treatment, surgeons may be needed to consider further dilatation to make the non-circular annulus become circular.

Efficacy and safety of selegiline for the treatment of Parkinson's disease: A systematic review and meta-analysis.

Background: Drug efficacy generally varies with different durations. There is no systematic review analyzing the effect of selegiline for Parkinson's disease (PD) on different treatment duration. This study aims to analyze how the efficacy and safety of selegiline changes for PD over time. Methods: PubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure and Wanfang Database were systematically retrieved for randomized controlled trials (RCTs) and observational studies of selegiline for PD. The search period was from inception to January 18th, 2022. The efficacy outcomes were measured by the mean change from baseline in the total and sub Unified Parkinson's Disease Rating Scale (UPDRS), Hamilton Depression Rating Scale (HAMD) and Webster Rating Scale (WRS) scores. The safety outcomes were measured by the proportion of participants having any adverse events overall and that in different system organ classes. Results: Among the 3,786 studies obtained, 27 RCTs and 11 observational studies met the inclusion criteria. Twenty-three studies reported an outcome which was also reported in at least one other study, and were included in meta-analyses. Compared with placebo, selegiline was found with a stronger reduction of total UPDRS score with increasing treatment duration [mean difference and 95% CIs in 1 month: -3.56 (-6.67, -0.45); 3 months: -3.32 (-3.75, -2.89); 6 months: -7.46 (-12.60, -2.32); 12 months: -5.07 (-6.74, -3.41); 48 months: -8.78 (-13.75, -3.80); 60 months: -11.06 (-16.19, -5.94)]. A similar trend was also found from the point estimates in UPDRS I, II, III, HAMD and WRS score. The results of observational studies on efficacy were not entirely consistent. As for safety, compared with placebo, selegiline had higher risk of incurring any adverse events [rate: 54.7% vs. 62.1%; odd ratio and 95% CIs: 1.58 (1.02, 2.44)], with the excess adverse events mainly manifested as neuropsychiatric disorders [26.7% vs. 31.6%; 1.36 (1.06, 1.75)] and no significant change over time. The statistically difference in overall adverse event between selegiline and active controls was not found. Conclusion: Selegiline was effective in improving total UPDRS score with increasing treatment duration, and had a higher risk of incurring adverse events, especially the adverse events in the neuropsychiatric system. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: PROSPERO CRD42021233145.

Effect of optimizing the use of endoscope on the efficiency of microdynamic bromhidrosis removal operation.

BACKGROUND: Bromhidrosis, also known as body odor, is a common disease in life, which often occurs in young adults. The histological basis of bromhidrosis is the hyperplasia of apocrine sweat glands. OBJECTIVE: To compare the effects of different methods of endoscopy in microdynamic axillary osmidrosis removal on curative effect, complications, and surgical efficiency. METHODS: A total of 149 patients with axillary osmidrosis were treated in our hospital from January 2020 to December 2021. They were treated with endoscopic assistance in the whole process of operation (Group A) and endoscope-assisted exploration after blind rotary cutter suction (Group B), respectively, and the curative effect, complication rate, and surgical efficiency were evaluated. RESULTS: There was no significant difference in the curative effect and complication rate between the two groups, but the endoscope-assisted exploration group after suction with rotary cutter (Group B) had higher surgical efficiency. CONCLUSION: On the basis of professional use of rotary cutter, it is efficient to choose endoscope to check the excision of sweat gland in the operation area and stop bleeding in time after blind suction.

Potential influence of COVID-19 and dexamethasone on the reproductive system: what we know and can expect.

Dexamethasone is the first and an important therapy that significantly reduces the risk of death in patients with severe COVID-19 disease. Nevertheless, a lot of studies have revealed that it has adverse impacts on multiple systems of the body especially the reproductive system, and dexamethasone exposure during the human foetal period may be associated with various diseases. In this paper, we reviewed the literature regarding the adverse effects of COVID-19 and dexamethasone administration on the reproductive system as well as related disease pathogenesis, in an attempt to clarify the potential harms of dexamethasone treatment in COVID-19 patients. Overall, we strongly support the application of dexamethasone as a pharmaceutical therapy in critical COVID-19 patients before a better therapy is developed, but the adverse side effects that may arise cannot be ignored. Our review will help medical professionals in the prognosis and follow-up of patients treated with dexamethasone. In addition, given that a considerable amount of uncertainty, confusion and even controversy that still remains, further studies and more clinical trials are urgently needed to improve the understanding of the parameters and the effects of dexamethasone on reproductive function of patients with severe acute respiratory syndrome coronavirus 2 infection.

Exploring the Influence of Dysphagia and Tracheostomy on Pneumonia in Patients with Stroke: A Retrospective Cohort Study.

Background: Pneumonia is common in patients with tracheostomy and dysphagia. However, the influence of dysphagia and tracheostomy on pneumonia in patients with stroke remains unclear. The aim of this study was to explore the risk factors related to pneumonia, and the association between dysphagia, tracheostomy and pneumonia in patients with stroke was investigated. Methods: Patients with stroke who experienced tracheostomy and dysphagia were included and divided into two groups based on record of pneumonia at discharge. Clinical manifestations and physical examination were used to diagnose pneumonia, whereas clinical swallowing examination, and videofluoroscopy swallowing studies (VFSS) were used to evaluate swallowing function. Results: There were significant differences between the pneumonia group and the no pneumonia group in total tracheostomy time (6.3 ± 5.9 vs. 4.3 ± 1.7 months, p = 0.003), number of instances of ventilator support (0.41 ± 0.49 vs. 0.18 ± 0.38, p = 0.007), PAS score (5.2 ± 1.92 vs. 4.3 ± 1.79, p = 0.039), impaired or absent cough reflex (76.4 vs. 55.6%, p = 0.035), oropharyngeal phase dysfunction (60.6 vs. 40.8%, p = 0.047), length of hospital stay (36.0 ± 7.2 vs. 30.5 ± 11.7 days, p = 0.025) and direct medical costs (15,702.21 ± 14,244.61 vs. 10,923.99 ± 7250.14 United States dollar [USD], p = 0.042). Multivariate logistic regression showed that the total tracheostomy time (95% confidence interval [CI], 1.966−12.922, p = 0.001), impaired or absent cough reflex (95% CI, 0.084−0.695, p = 0.008), and oropharyngeal phase dysfunction (95% CI, 1.087−8.148, p = 0.034) were risk factors for pneumonia. Spearman's correlation analysis demonstrated that PAS scores were significantly correlated with cough reflex dysfunction (r = 0.277, p = 0.03), oropharyngeal phase dysfunction (r = 0.318, p < 0.01) and total tracheostomy time (r = 0.178, p = 0.045). The oropharyngeal phase dysfunction was significantly correlated with cough reflex (r = 0.549, p < 0.001) and UES opening (r = 0.643, p < 0.01). Conclusions: Tracheostomy and dysphagia increased the risk of pneumonia in patients with stroke. Total tracheostomy time, duration of ventilator support, degree of penetration and aspiration, and oropharyngeal phase dysfunction are risk factors. Given this, we also found that there may be a correlation between tracheostomy and dysphagia.

Experience of Online Learning from COVID-19: Preparing for the Future of Digital Transformation in Education.

COVID-19 has affected traditional instructional activities. Home-based isolation and restrictive movement measures have forced most learning activities to move from an offline to an online environment. Multiple studies have also demonstrated that teaching with virtual tools during the COVID-19 pandemic is always ineffective. This study examines the different characteristics and challenges that virtual tools brought to online education in the pre-pandemic and pandemic era, with the aim of providing experience of how virtual tools supported purely online learning during a health crisis. By searching keywords in public databases and review publications, this study tries to summarize the major topics related to the research theme. These topics are the characteristics of learning supported by technologies in pre-pandemic and pandemic era, the challenges that education systems have faced during the COVID-19 pandemic. This study also compares the functions, advantages and limitations of typical virtual tools, which has rarely been done in previous studies. This study tries to present the features of virtual tools that support online learning and the challenges regarding real-life risk scenarios, and tries to provide educational institutions with a distinct perspective for efficient teaching and learning in future potential health crises.

Ultrasonically Enhanced ZD2767P-Carboxypeptidase G2 Deactivates Cisplatin-Resistant Human Lung Cancer Cells.

The prodrug-enzyme regimen ZD2767P+CPG2 is limited by low efficacy. Here, ultrasound was used to modulate ZD2767P+CPG2 (i.e., ZD2767P+CPG2+US) against cisplatin-resistant human lung cancer cells. A549 and A549/DDP (resistant subline) cells received ZD2767P+CPG2 or ZD2767P+CPG2+US. Either ZD2767P+CPG2 or ZD2767P+CPG2+US led to cell death and apoptosis, and ZD2767P+CPG2+US produced stronger effects; comet assays revealed that these two means directly caused DNA double-strand break. Z-VAD-fmk and/or ferrostatin-1 increased the cell survival percentage, and Z-VAD-fmk decreased the apoptosis percentage. The level of transferrin was increased in treated cells, but those of ferroportin and glutathione peroxidase 4 (GPX4) were reduced, with higher intracellular levels of reactive oxygen species and of iron. Intracellular pharmacokinetics of ZD2767D (activated drug) indicated that the peak level, area under the drug level vs. time curve, and mean residence time in ZD2767P+CPG2+US were higher than those in ZD2767P+CPG2. Both ZD2767P+CPG2 and ZD2767P+CPG2+US were effective on xenograft tumors in nude mice; inhibitory rates were 39.7% and 63.5% in A549 tumors and 50.0% and 70.1% in A549/DDP tumors, respectively. A higher apoptosis level and a lower GPX4 level were noted in tumors receiving treatments. No severe adverse events were observed. These data demonstrated that ZD2767P+CPG2+US deactivated cancer cells via apoptosis and ferroptosis pathways, being a candidate therapy for cisplatin-resistant lung cancer.