Background:
Evaluating the need for palliative care and predicting its mortality play important roles in the emergency department.
Aim:
We developed a screening model for predicting 1-year mortality.
...Design:
A retrospective cohort study was conducted to identify risk factors associated with 1-year mortality. Our risk scores based on these significant risk factors were then developed. Its predictive validity performance was evaluated using area under receiving operating characteristic analysis and leave-one-out cross-validation.
Setting and participants:
Patients aged 15 years or older were enrolled from June 2015 to May 2016 in the emergency department.
Results:
We identified five independent risk factors, each of which was assigned a number of points proportional to its estimated regression coefficient: age (0.05 points per year), qSOFA ⩾ 2 (1), Cancer (4), Eastern Cooperative Oncology Group Performance Status score ⩾ 2 (2), and Do-Not-Resuscitate status (3). The sensitivity, specificity, positive predictive value, and negative predictive value of our screening tool given the cutoff larger than 3 points were 0.99 (0.98–0.99), 0.31 (0.29–0.32), 0.26 (0.24–0.27), and 0.99 (0.98–1.00), respectively. Those with screening scores larger than 9 points corresponding to 64.0% (60.0–67.9%) of 1-year mortality were prioritized for consultation and communication. The area under the receiving operating characteristic curves for the point system was 0.84 (0.83–0.85) for the cross-validation model.
Conclusions:
A-qCPR risk scores provide a good screening tool for assessing patient prognosis. Routine screening for end-of-life using this tool plays an important role in early and efficient physician-patient communications regarding hospice and palliative needs in the emergency department.
Objective
Mutations in the colony‐stimulating factor 1 receptor gene (CSF1R) were identified as a cause of adult‐onset inherited leukoencephalopathy. The present study aims at investigating the ...frequency, clinical characteristics, and functional effects of CSF1R mutations in Taiwanese patients with adult‐onset leukoencephalopathy.
Methods
Mutational analysis of CSF1R was performed in 149 unrelated individuals with leukoencephalopathy by a targeted resequencing panel covering the entire coding regions of CSF1R. In vitro analysis of the CSF1‐induced autophosphorylation activities of mutant CSF1R proteins was conducted to assess the pathogenicity of the CSF1R mutations.
Results
Among the eight CSF1R variants identified in this study, five mutations led to a loss of CSF1‐induced autophosphorylation of CSF1R proteins. Four mutations (p.K586*, p.G589R, p.R777Q, and p.R782C) located within the tyrosine kinase domain of CSF1R, whereas the p.T79M mutation resided in the immunoglobulin‐like domain. The five patients carrying the CSF1R mutations developed cognitive decline at age 41, 43, 50, 79, and 86 years, respectively. Psychiatric symptoms and behavior changes were observed in four of the five patients. The executive function and processing speed were severely impaired at an early stage, and their cognitive function deteriorated rapidly within 3–4 years. Diffusion‐restricted lesions at the subcortical regions and bilateral corticospinal tracts were found in three patients.
Interpretation
CSF1R mutations account for 3.5% (5/149) of the adult‐onset leukoencephalopathy in Taiwan. CSF1R mutations outside the tyrosine kinase domain may also disturb the CSF1R function and lead to the clinical phenotype. Molecular functional validation is important to determine the pathogenicity of novel CSF1R variants.
The spread of the emerging pathogen, named as SARS-CoV-2, has led to an unprecedented COVID-19 pandemic since 1918 influenza pandemic. This review first sheds light on the similarity on global ...transmission, surges of pandemics, and the disparity of prevention between two pandemics. Such a brief comparison also provides an insight into the potential sequelae of COVID-19 based on the inference drawn from the fact that a cascade of successive influenza pandemic occurred after 1918 and also the previous experience on the epidemic of SARS and MERS occurring in 2003 and 2015, respectively. We then propose a systematic framework for elucidating emerging infectious disease (EID) such as COVID-19 with a panorama viewpoint from natural infection and disease process, public health interventions (non-pharmaceutical interventions (NPIs) and vaccine), clinical treatments and therapies (antivirals), until global aspects of health and economic loss, and economic evaluation of interventions with emphasis on mass vaccination. This review not only concisely delves for evidence-based scientific literatures from the origin of outbreak, the spread of SARS-CoV-2 to three surges of pandemic, and NPIs and vaccine uptakes but also provides a new insight into how to apply big data analytics to identify unprecedented discoveries through COVID-19 pandemic scenario embracing from biomedical to economic viewpoints.
As COVID-19 has become a pandemic emerging infectious disease it is important to examine whether there was a spatiotemporal clustering phenomenon in the globe during the rapid spread after the first ...outbreak reported from southern China.
The open data on the number of COVID-19 cases reported at daily basis form the globe were used to assess the evolution of outbreaks with international air link on the same latitude and also including Taiwan. The dynamic Susceptible-Infected-Recovered model was used to evaluate continental transmission from December 2019 to March 2020 before the declaration of COVID-19 pandemic with basic reproductive number and effective reproductive number before and after containment measurements.
For the initial COVID-19 outbreak in China, the estimated reproductive number was reduced from 2.84 during the overwhelming outbreaks in early January to 0.43 after the strict lockdown policy. It is very surprising to find there were three countries (including South Korea, Iran, and Italy) and the Washington state of the USA on the 38° North Latitude involved with large-scale community-acquired outbreaks since the first imported COVID-19 cases from China. The propagation of continental transmission was augmented from hotspot to hotspot with higher reproductive number immediately before the declaration of pandemic. By contrast, there was not any large community-acquired outbreak in Taiwan.
The propagated spatiotemporal transmission from China to other hotspots may explain the emerging pandemic that can only be exempted by timely border control and preparedness of containment measurements according to Taiwan experience.
There is a serious concern over the variation of case fatality of COVID-19 patients that reflects the preparedness of the medical care system in response to the surge of pneumonia patients. We aimed ...to quantify the disease spectrum of COVID-19 on which we are based to develop a key indicator on the probability of progression from pneumonia to acute respiratory disease syndrome (ARDS) for fatal COVID-19. The retrospective cohort on 12 countries that have already experienced the epidemic of COVID-19 with available open data on the conformed cases with detailed information on mild respiratory disease (MRD), pneumonia, ARDS, and deaths were used. The pooled estimates from three countries with detailed information were 73% from MRD to pneumonia and 27% from MRD to recovery and the case-fatality rate of ARDS was 43%. The progression from pneumonia to ARDS varied from 3% to 63%. These key estimates were highly associated with the case fatality rates reported for each country with a statistically significant positive relationship (adjusted R2 = 95%). Such a quantitative model provides key messages for the optimal medical resources allocation to a spectrum of patients requiring quarantine and isolation at home, isolation wards, and intensive care unit in order to reduce deaths from COVID-19.
A "Public Health Emergency of International Concern (PHEIC)" monkeypox outbreak was declared by the World Health Organization on 23 June 2022. More than 16,000 monkeypox cases were reported in more ...than 75 countries across six regions as of July 25. The Bayesian SIR (Susceptible-Infected-Recovered) model with the directed acyclic graphic method was used to estimate the basic/effective reproductive number (R
/R
) and to assess the epidemic spread of monkeypox across the globe. The maximum estimated R
/R
was 1.16 (1.15-1.17), 1.20 (1.20-1.20), 1.34 (1.34-1.35), 1.33 (1.33-1.33) and 2.52 (2.41-2.66) in the United States, Spain, Brazil, the United Kingdom and the Democratic Republic of the Congo, respectively. The values of R
/R
were below 1 after August 2022. The estimated infectious time before isolation ranged from 2.05 to 2.74 days. The PHEIC of the global spreading of human monkeypox has been contained so as to avoid a pandemic in the light of the reasoning-based epidemic model assessment.
The chip side wall crack of semiconductor nanometer packaging process has always been an important technological problem that the global semiconductor packaging industry needs to overcome. This ...research has helped the world's biggest semiconductor package factory to improve the chip side wall crack issue faced by nanometer wafer packaging process, thus enhancing its yield rate. After analyzing the abnormality of nanometer wafer packaging process, this research team found that the chip side wall crack problem was caused by a poor laser waveform during the laser cutting process, resulting in debris along the chip side wall. Subsequently, as the diamond cutter cuts into the chip in the following process, the cutter impacts the debris which then impacts the side wall resulting in a side wall crack. The Teoriya Resheniya Izobreatatelskikh Zadatch (TRIZ) analysis was used to deduce a suitable improvement method. After applying the TRIZ analysis, this research team confirmed that by modifying the laser equipment to create a more uniform laser waveform, the diamond cutter was able to achieve a clean cut of the chip without impacting debris and thus significantly decreased the chip side wall crack occurrences. The shipment yield rate was increased from 92.8% to 99.61% as a result of the team's modifications.
The ubiquitously expressed molecular chaperone GRP78 (78 kDa glucose-regulated protein) generally localizes to the ER (endoplasmic reticulum). GRP78 is specifically induced in cells under the UPR ...(unfolded protein response), which can be elicited by treatments with calcium ionophore A23187 and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase inhibitor TG (thapsigargin). By using confocal microscopy, we have demonstrated that GRP78 was concentrated in the perinuclear region and co-localized with the ER marker proteins, calnexin and PDI (protein disulphide-isomerase), in cells under normal growth conditions. However, treatments with A23187 and TG led to diminish its ER targeting, resulting in redirection into a cytoplasmic vesicular pattern, and overlapping with the mitochondrial marker MitoTracker. Cellular fractionation and protease digestion of isolated mitochondria from ER-stressed cells suggested that a significant portion of GRP78 is localized to the mitochondria and is protease-resistant. Localizations of GRP78 in ER and mitochondria were confirmed by using immunoelectron microscopy. In ER-stressed cells, GRP78 mainly localized within the mitochondria and decorated the mitochondrial membrane compartment. Submitochondrial fractionation studies indicated further that the mitochondria-resided GRP78 is mainly located in the intermembrane space, inner membrane and matrix, but is not associated with the outer membrane. Furthermore, radioactive labelling followed by subcellular fractionation showed that a significant portion of the newly synthesized GRP78 is localized to the mitochondria in cells under UPR. Taken together, our results indicate that, at least under certain circumstances, the ER-resided chaperone GRP78 can be retargeted to mitochondria and thereby may be involved in correlating UPR signalling between these two organelles.
Implementing and lifting social distancing (LSD) is an urgent global issue during the COVID-19 pandemic, particularly when the travel ban is lifted to revive international businesses and economies. ...However, when and whether LSD can be considered is subject to the spread of SARS-CoV-2, the recovery rate, and the case-fatality rate. It is imperative to provide real-time assessment of three factors to guide LSD.
A simple LSD index was developed for health decision makers to do real-time assessment of COVID-19 at the global, country, region, and community level.
Data on the retrospective cohort of 186 countries with three factors were retrieved from a publicly available repository from January to early July. A simple index for guiding LSD was measured by the cumulative number of COVID-19 cases and recoveries, and the case-fatality rate was envisaged. If the LSD index was less than 1, LSD can be considered. The dynamic changes of the COVID-19 pandemic were evaluated to assess whether and when health decision makers allowed for LSD and when to reimplement social distancing after resurgences of the epidemic.
After large-scale outbreaks in a few countries before mid-March (prepandemic phase), the global weekly LSD index peaked at 4.27 in March and lasted until mid-June (pandemic phase), during which most countries were affected and needed to take various social distancing measures. Since, the value of LSD has gradually declined to 0.99 on July 5 (postpandemic phase), at which 64.7% (120/186) of countries and regions had an LSD<1 with the decile between 0 and 1 to refine risk stratification by countries. The LSD index decreased to 1 in about 115 days. In addition, we present the results of dynamic changes of the LSD index for the world and for each country and region with different time windows from January to July 5. The results of the LSD index on the resurgence of the COVID-19 epidemic in certain regions and validation by other emerging infectious diseases are presented.
This simple LSD index provides a quantitative assessment of whether and when to ease or implement social distancing to provide advice for health decision makers and travelers.
There is paucity of the statistical model that is specified for data on imported COVID-19 cases with the unique global information on infectious properties of SARS-CoV-2 variant different from local ...outbreak data used for estimating transmission and infectiousness parameters via the established epidemic models. To this end, a new approach with a four-state stochastic model was proposed to formulate these well-established infectious parameters with three new parameters, including the pre-symptomatic incidence rate, the median of pre-symptomatic transmission time (MPTT) to symptomatic state, and the incidence (proportion) of asymptomatic cases using imported COVID-19 data. We fitted the proposed stochastic model to empirical data on imported COVID-19 cases from D614G to Omicron with the corresponding calendar periods according to the classification GISAID information on the evolution of SARS-CoV-2 variant between March 2020 and Jan 2022 in Taiwan. The pre-symptomatic incidence rate was the highest for Omicron followed by Alpha, Delta, and D614G. The MPTT (in days) increased from 3.45 (first period) ~ 4.02 (second period) of D614G until 3.94–4.65 of VOC Alpha but dropped to 3.93–3.49 of Delta and 2 days (only first period) of Omicron. The proportion of asymptomatic cases increased from 29% of D-614G period to 59.2% of Omicron. Modeling data on imported cases across strains of SARS-CoV-2 not only bridges the link between the underlying natural infectious properties elucidated in the previous epidemic models and different disease phenotypes of COVID-19 but also provides precision quarantine and isolation policy for border control in the face of various emerging SRAS-CoV-2 variants globally.
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