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BackgroundUnderstanding clinical progression of COVID-19 is a key public health priority that informs resource allocation during an emergency. We characterized clinical progression of COVID-19 and determined important predictors for faster clinical progression to key clinical events and longer use of medical resources. Methods and FindingsThe study is a single-center, observational study with prospectively collected data from all 420 patients diagnosed with COVID-19 and hospitalized in Shenzhen between January 11th and March 10th, 2020 regardless of clinical severity. Using competing risk regressions according to the methods of Fine and Gray, we found that males had faster clinical progression than females in the older age group and the difference could not be explained by difference in baseline conditions or smoking history. We estimated the proportion of cases in each severity stage over 80 days following symptom onset using a nonparametric method built upon estimated cumulative incidence of key clinical events. Based on random survival forest models, we stratified cases into risk sets with very different clinical trajectories. Those who progressed to the severe stage (22%,93/420), developed acute respiratory distress syndrome (9%,39/420), and were admitted to the intensive care unit (5%,19/420) progressed on average 9.5 days (95%CI 8.7,10.3), 11.0 days (95%CI 9.7,12.3), and 10.5 days (95%CI 8.2,13.3), respectively, after symptom onset. We estimated that patients who were admitted to ICUs remained there for an average of 34.4 days (95%CI 24.1,43.2). The median length of hospital stay was 21.3 days (95%CI, 20.5,22.2) for cases who did not progress to the severe stage, but increased to 52.1 days (95%CI, 43.3,59.5) for those who required critical care. ConclusionsOur analyses provide insights into clinical progression of cases starting early in the course of infection. Patient characteristics near symptom onset both with and without lab parameters have tremendous potential for predicting clinical progression and informing strategic response.
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BackgroundRapid spread of SARS-CoV-2 in Wuhan prompted heightened surveillance in Shenzhen and elsewhere in China. The resulting data provide a rare opportunity to measure key metrics of disease course, transmission, and the impact of control. MethodsThe Shenzhen CDC identified 391 SARS-CoV-2 cases from January 14 to February 12, 2020 and 1286 close contacts. We compare cases identified through symptomatic surveillance and contact tracing, and estimate the time from symptom onset to confirmation, isolation, and hospitalization. We estimate metrics of disease transmission and analyze factors influencing transmission risk. FindingsCases were older than the general population (mean age 45) and balanced between males (187) and females (204). Ninety-one percent had mild or moderate clinical severity at initial assessment. Three have died, 225 have recovered (median time to recovery is 21 days). Cases were isolated on average 4.6 days after developing symptoms; contact tracing reduced this by 1.9 days. Household contacts and those travelling with a case where at higher risk of infection (ORs 6 and 7) than other close contacts. The household secondary attack rate was 15%, and children were as likely to be infected as adults. The observed reproductive number was 0.4, with a mean serial interval of 6.3 days. InterpretationOur data on cases as well as their infected and uninfected close contacts provide key insights into SARS-CoV-2 epidemiology. This work shows that heightened surveillance and isolation, particularly contact tracing, reduces the time cases are infectious in the community, thereby reducing R. Its overall impact, however, is uncertain and highly dependent on the number of asymptomatic cases. We further show that children are at similar risk of infection as the general population, though less likely to have severe symptoms; hence should be considered in analyses of transmission and control.
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Objective To evaluate the role of calcium channel in the mechanism of the generation and maintenance of bursting firing of substantia nigra pars compacta (SNc) dopaminergic neurons in rats.Methods Using the patch clamp technique,we observed the firing pattern switching features after adding 10 μmol/L N-methyl-D-aspartic acid (NMDA),compared the changes of whole-calcium current and L-type calcium current with or without NMDA,and analyzed the correlation between the generation of burst firing and L-type calcium channel activation.Results After NMDA treatment,the firing pattern of SNc dopaminergic neurons changed to burst firing,which was compromised by a charastistic high plateau potential and series of action potential on it.The current density of L-type calcium current increased significantly after adding NMDA,which,from (2.86 ±0.26) pA/pF (n =28),significantly increased to (3.75 ± 0.18) pA/pF (n =34 ; t =7.52,P =0.002 8).The high plateau potential was almost abolished with the application of verapamil,a specific antagonist of L-type calcium channel.Consiusion NMDA could induce the firing pattern changed to burst firing in SNc dopaminergic neurons,while L-type calcium channel contributes to the process of generation and maintenance of burst firing.
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Objective To evaluate the roles of positron emission tomography (PET) with N-methyl [11C]2-(4' -methylaminophenyi-6-hydroxybenzathiazole) (11C-PIB) in the early diagnosis of Alzheimer's disease (AD).Methods Six AD patients,7 mild cognitive impairment (MCI) patients and 6 normal controls (NC) were diagnosed and assessed with brain PET with 11C-PIB.The emission images obtained at 5,25 and 45 min after 11C-PIB administration were analysed.Results Using visual analysis to summarize the characteristics of the imagings of each group: comparing to NC,the AD patients show high 11C -PIB up take,and low clearance rate of 11C-PIB at 45 min.The imagings of MCI group show heterogeneous,overlapping with AD and NC group.The statistical analysis shows: in AD group,the standard uptake value (SUV) ratio of parietal lobe,frontal lobe,temporal lobe,occipital lobe and hippocampal at 45 min was 1.91±0.21,2.09±0.41,1.92±0.35,1.66±0.41,1.55±0.28 respectively,and were higher than that of NC group (value being 1.48±0.53,1.57±0.64,1.36±0.53,1.27±0.40,1.17±0.33) with statistical significance,t=8.114,5.620,5.705,3.650 and 2.866,P=0.0001,0.0002,0.0002,0.0045 and 0.0170 respectively.In MCI group,the SUV ratio of parietal lobe,frontal lobe,temporal lobe,occipital lobe and hippocampal at 45 min was 1.48 ± 0.53,1.57 ± 0.64,1.36±0.53,1.27 ± 0.40,1.17±0.33 respectively,and were higher than that of NC group,but there was no statistical significance.Conclusion 11C-PIB PET imaging can differentiate AD patients from normal and anticipate the transformation of MCI patients.
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BACKGROUND:At present, some neurological imaging methods, including MRI, fMRI, 2-(1-(6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyi) ethylidene) malononitrile (18F-FDDNP) positron emission tomography (PET), are helpful but not specific for the diagnosis of Alzheimer disease (AD). 18F-FDG is a special marker of beta-amyloid (Aβ), thus AD can be diagnosed by 18F-FDDNP PET at early period.OBJECTIVE: To evaluate the role of 18F-FDDNP PET in the diagnosis of AD, and establish reliable clinical biological indexes for the diagnosis of AD patients.DESIGN: A controlled analysis.SETTINGS : Department of Geriatric Neurology and Department of Nuclear Medicine, the General Hospital of Chinese PLA. PARTICIPANTS: Patients visiting the General Hospital of Chinese PLA from May 2004 to March 2005 were selected. Informed consents were obtained from all the participants. ① AD group (n =7): (74.88±12.03) years old; Accorded with the criteria related to diagnosis of AD in NINCDS/ADRDA (National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer Disease and Related Disease Association) and revision of Diagnostic and statistical Manual (DSM-Ⅳ, 4th ed.); brain CT or magnetic resonance imaging (MRI) examination displayed that inter-uncus distance of temporal lobes was ≥ 30 mm. ② Vascular dementia group (n =6): (73.83±4.75) years old; Accorded with the diagnostic criteria of NINDS-AIREN (National Institute of Neurological Diseases and Stroke, USA) and DSM-Ⅳ for vascular dementia; Inter-uncus distance of temporal lobes ＜ 30 mm. ③ Control group (n =6): (71.17±3.71) years old; Without rarefaction of white matter; Intelligence examination was normal.METHODS: PET was performed in all the subjects. PET scanner type was SEIMENS ECAT EXACT HR. The tracer selected was 18F-FDDNP which had radiochemical purity higher than 95% and error of radioactivity measurement lower than 10%. The images were collected at 5, 25 and 45 minutes after injection of 18F-FDDNP. Horizontal and coronary tomograms of brain were obtained after reconstruction.MAIN OUTCOME MEASURES: Characteristics of 18F-FDDNP brain PET images.RESULTS: ① In the control group, signs of obvious atrophy of brain were not seen. At about 45 minutes, the radioactivity in cortex and subcortical nucleus groups was essentially cleared and the structures of brain could not be differentiated clearly. ② In the vascular dementia group, brain atrophy and enlargement of ventricular system to various degrees could be seen. The clearance of radioactivity at three time points was similar to that in the control images. ③ In the AD group, the brain was obviously atrophied and the ventricular system was enlarged. The clearance of radioactivity at the three time points was significantly different from the images of other two groups. The radioactivity in cortex and hippocampus was cleared slower. At 45 minutes, the gray matter could still be clearly differentiated from the white matter, but the radioactivity in corpus striatum and thalamus was not higher than that in cortex and much radioactivity retention could be seen in cortex and hippocampus.CONCLUSION: 18F-FDDNP PET brain images can differentiate AD and vascular dementia, and it is an effective imaging index for the diagnosis of AD.
