Dose-response relationship between risk factors and incidence of COVID-19 in 325 hospitalized patients:A multicenter retrospective cohort study

BACKGROUND The epidemiological and clinical characteristics of coronavirus disease 2019(COVID-19)patients have been widely reported,but the assessment of doseresponse relationships and risk factors for mortality and severe cases and clinical outcomes remain unclear.AIM To determine the dose-response relationship between risk factors and incidence of COVID-19.METHODS In this retrospective,multicenter cohort study,we included patients with confirmed COVID-19 infection who had been discharged or had died by February 6,2020.We used multivariable logistic regression and Cox proportional hazard models to determine the dose-response relationship between risk factors and incidence of COVID-19.RESULTS It clarified that increasing risk of in-hospital death were associated with older age(HR:1.04,95%CI:1.01-1.09),higher lactate dehydrogenase[HR:1.04,95%confidence interval(CI):1.01-1.10],C-reactive protein(HR:1.10,95%CI:1.01-1.23),and procalcitonin(natural log-transformed HR:1.88,95%CI:1.22-2.88),and D-dimer greater than 1μg/m L at admission(natural log transformed HR:1.63,95%CI:1.03-2.58)by multivariable regression.D-dimer and procalcitonin were logarithmically correlated with COVID-19 mortality risk,while there was a linear dose-response correlation between age,lactate dehydrogenase,D-dimer and procalcitonin,independent of established risk factors.CONCLUSION Higher lactate dehydrogenase,D-dimer,and procalcitonin levels were independently associated with a dose-response increased risk of COVID-19 mortality.

A Study on the Dose-Response Relationship between Asbestos Exposure Level and Asbestosis among Workers in a Chinese Chrysotile Product Factory

The dose-response relationship for asbestos exposure in a chrysotile product factory was studied. The past gravimetric dust concentration values, obtained from different worksites, were converted into fiber concentration values according to conversion factors that were worked out by simultaneous sampling in this study. The conversions were made so that exposure could be expressed in fiber-years (f-yr). Asbestosis was diagnosed on the basis of chest radiographs and occupational histories. Cumulative dust exposure (f-yr) was calculated up to the date of diagnosis for asbestosis patients, and up to September 1982 for the remaining workers. A dose-response relationship expressed as fiber-years exposed vs cumulative prevalence of asbestosis was established by the life table method on the basis of these data. Predicted 3 and 1% prevalence of asbestosis corresponded to 43 and 22 f-yr exposure, respectively. Considering that a worker can work for 35 years, these doses are commensurate with dust concentrations of 1.22 and 0.63 f/ml, respectively. It is recommended that 1 f/ml be taken as the maximum allowable concentration of airborne asbestos dust for the workplace with an anticipated prevalence of about 2% asbestosis after 35 years of exposure. 1990 Academic Press, Inc.

INFLUENCE OF SUCCINYLCHOLINE ON THE DOSE-RESPONSE RELATIONSHIP OF SUBSEQUENTLY ADMINISTERED ROCURONIUN

Objective To investigate the effect of succinylcholine on the dose-response relationship of sub-sequently administered rocuronium in healthy patients. Methods Forty-eight ASA physical status I-II patients,aged 17-65 years, scheduled for elective general surgery, were randomly assigned to either the rocuronium treat-ment group (R) or succinylcholine-rocuronium treatment group (SR). General anesthesia was induced with thio-pental 4 to 6mg/kg and fentanyl 2 to 5/μg/kg intravenously and maintained with 60% nitrous oxide in oxygen. Addi-tional doses of thiopental or fentanyl were administered as required. The dose-response relationship of rocuroniumwas determined by the single dose-response technique. In R group (n =24) , rocuronium was given after induction ofanesthesia. In SR group (n =24) , patients were intubated after 1. 5mg/kg of succinylcholine and rocuronium wasgiven after the complete recovery of neuromuscular blockade from succinylcholine. Patients were further randomlydivided into 4 subgroups receiving 150, 200, 250 or 300μg/kg of rocuronium respectively in both groups. Neuro-muscular function was assessed accelographically with train-of-four (TOF) stimulation at the wrist every 12s (usingthe TOF Guard? accelerometer). The relationship between probit-tranformed percentage depression of first twitchheight (Th) of train-of-four stimulation and logarithm dose of rocuronium was analyzed using linear regression.Results The dose-response curve of rocuronium after succinylcholine was shifted to the left in a parallel fashioncompared with that of rocuronium given alone. ED50 and ED95 of rocuronium were 193 ± 69 and 367 ± 73μg/kg re-spectively in R group, and 158 ±35 and 317 ±80μg/kg respectively in SR group (P <0.05). Conclusion Suc-cinylcholine shifts the dose-response curve of rocuronium to the left and potentiates the effects of the neuromuscularblockade by about 15% of subsequently administered rocuronium. Lower doses of rocuronium are required afterprior succinylcholine.

Dose-response relationship of lung cancer to amount smoked, duration and age starting

AIM： To quantify smoking/lung cancer relationships accurately using parametric modelling.METHODS： Using the International Epidemiological Studies on Smoking and Lung Cancer database of all epidemiological studies of 100＋ lung cancer cases published before 2000, we analyzed 97 blocks of data for amount smoked, 35 for duration of smoking, and 27 for age started. Pseudo-numbers of cases and controls （or at risk） estimated from RRs by dose level formed the data modelled. We fitted various models relating loge RR to dose （d）, including βd, βdY and βloge （1 ＋ Wd）, and investigated goodness-of-fit and heterogeneity between studies.0.833 loge [1 ＋ （8.1c/10）] for cigarettes/d （c）, 0.792 （y/10）0.74 for years smoked （y） and 0.176 [（70 - a）/10]1.44 for age of start （a）. Each model fitted well overall, though some blocks misfitted. RRs rose from 3.86 to 22.31 between c = 10 and 50, from 2.21 to 13.54 be-tween y = 10 and 50, and from 3.66 to 8.94 between a = 30 and 12.5. Heterogeneity （P 〈 0.001） existed by continent for amount, RRs for 50 cigarettes/d being 7.23 （Asia）, 26.36 （North America） and 22.16 （Europe）. Little heterogeneity was seen for duration of smoking or age started.CONCLUSION： The models describe the dose-relation-ships well, though may be biased by factors including misclassification of smoking status and dose.

Comparison of Two Dose-response Relationship of Noise Exposure Evaluation Results with High Frequency Hearing Loss

Background:Complex noise and its relation to hearing loss are difficult to measure and evaluate.In complex noise measurement,individual exposure results may not accurately represent lifetime noise exposure.Thus,the mean LAeq,8 h values of individuals in the same workgroup were also used to represent LAeq,8h in our study.Our study aimed to explore whether the mean exposure levels of workers in the same workgroup represented real noise exposure better than individual exposure levels did.Methods:A cross-sectional study was conducted to establish a model for cumulative noise exposure (CNE) and hearing loss in 205 occupational noise-exposed workers who were recruited from two large automobile manufacturers in China.We used a personal noise dosimeter and a questionnaire to determine the workers' occupational noise exposure levels and exposure times,respectively.A qualified audiologist used standardized audiometric procedures to assess hearing acuity after at least 16 h of noise avoidance.Results:We observed that 88.3％ of workers were exposed to more than 85 dB(A) of occupational noise (mean:89.3 ± 4.2 dB(A)).The personal CNE (CNEp) and workgroup CNE (CNEg) were 100.5 ± 4.7 dB(A) and 100.5 ± 2.9 dB(A),respectively.In the binary logistic regression analysis,we established a regression model with high-frequency hearing loss as the dependent variable and CNE as the independent variable.The Wald value was 5.014 with CNEp as the independent variable and 8.653 with CNEg as the independent variable.Furthermore,we found that the figure for CNEg was more similar to the stationary noise reference than CNEp was.The CNEg model was better than the CNEp model.In this circumstance,we can measure some subjects instead of the whole workgroup and save manpower.Conclusions:In a complex noise environment,the measurements of average noise exposure level of the workgroup can improve the accuracy and save manpower.

Relationship between the use of smart medical services and mental health status

In this editorial,I comment on the article by Zhang et al.To emphasize the importance of the topic,I discuss the relationship between the use of smart medical devices and mental health.Smart medical services have the potential to positively influence mental health by providing monitoring,insights,and inter-ventions.However,they also come with challenges that need to be addressed.Understanding the primary purpose for which individuals use these smart tech-nologies is essential to tailoring them to specific mental health needs and prefe-rences.

Assessment of the hip-spine relationship in total hip arthroplasty for childhood hip disorders sequelae

In this article,we comment on the article by Oommen et al.Oommen et al provided a comprehensive overview of the management of hip centre restoration in total hip arthroplasty(THA)for childhood hip disorder sequelae.Given the developmental disparity in this population,specific preoperative planning is an essential prerequisite for the success of THA procedures.In the review by Oommen et al,assessments of acetabular and femoral anatomic variations were fully described.However,spinal malalignment and stiffness are common in physical and radiological examinations and should be taken into careful consideration when planning surgical procedures.Poor outcomes of THA for patients with comorbid hip and spinopelvic pathologies have been widely reported,especially for hips with childhood disorder sequelae.Therefore,in this editorial,we would like to emphasize the need for a thorough hip-spine evaluation of patients with childhood hip disorder sequelae before THA.

Impact of Climate Change on Crop-cropland Coupling Relationship:A Case Study of the Loess Plateau in China

Climate change brings new challenges to the sustainable development of agriculture in the new era.Accurately grasping the patterns of climate change impacts on agricultural systems is crucial for ensuring agricultural sustainability and food security.Taking the Loess Plateau(LP),China as an example,this study used a coupling coordination degree model and spatial autocorrelation analysis to portray the spatial and temporal features of crop-cropland coupling relationship from 2000 to 2020 and explored the impact law of climate change through geographically and temporally weighted regression(GTWR).The results were as follows:1)the crop-cropland coupling coordination degree of the LP showed a gradual upward trend from 2000 to 2020,forming a spatial pattern with lower values in the central region and higher values in the surrounding areas.2)There was a positive correlation in the spatial distribution of cropcropland coupling coordination degree in the LP from 2000 to 2020,and the high value-low value(H-L)and low value-low value(L-L)agglomerations continued to expand eastward,while the spatial and temporal evolution of the high value-high value(H-H)and low value-high value(L-H)agglomerations was not obvious.3)The impacts of climatic elements on crop-cropland coupling coordination degree in the LP showed strong heterogeneity in time scales.The inhibitory impacts of summer days(SU)and frost days(FD)accounted for a higher proportion,while the annual average temperature(TEM)had both promoting and inhibiting impacts.The impacts proportion and intensity of extreme heavy precipitation day(R25),continuous drought days(CDD),and annual precipitation(PRE)all experienced significant changes.4)In space,the impacts of SU and FD on the crop-cropland coupling coordination degree varied with latitude and altitude.The adaptability of the LP to R25 gradually strengthened,and the extensions of CDD and increase of PRE led to the increasing inhibition beyond the eastern region of LP,and TEM showed a promoting impact in the Fenwei Plain.As an important grainproducing area in China,the LP should actively deal with the impacts of climate change on the crop-cropland coupling relationship,vigorously safeguard food security,and promote sustainable agricultural development.

Dose-response study of spinal hyperbaric ropivacaine for cesarean section

Background： Spinal hyperbaric ropivacaine may produce more predictable and reliable anesthesia than plain ropivacaine for cesarean section. The dose-response relation for spinal hyperbaric ropivacaine is undetermined. This double-blind, randomized, dose-response study determined the ED50 （50% effective dose） and ED95 （95% effective dose） of spinal hyperbaric ropivacaine for cesarean section anesthesia. Methods： Sixty parturients undergoing elective cesarean section delivery with use of combined spinal-epidural anesthesia were enrolled in this study. An epidural catheter was placed at the L1-L2 vertebral interspace then lumbar puncture was performed at the L3-L4 vertebral interspace, and parturients were randomized to receive spinal hyperbaric ropivacaine in doses of 10.5 mg, 12 mg, 13.5 mg, or 15 mg in equal volumes of 3 ml. Sensory levels （pinprick） were assessed every 2.5 min until a T7 level was achieved and motor changes were assessed by modified Bromage Score. A dose was considered effective if an upper sensory level to pin prick of T7 or above was achieved and no intraoperative epidural supplement was required. ED50 and ED95 were determined with use of a logistic regression model. Results： ED50 （95% confidence interval） of spinal hyperbaric ropivacaine was determined to be 10.37 （5.23-11.59） mg and ED95 （95% confidence interval） to be 15.39 （13.81-23.59） mg. The maximum sensory block levels and the duration of motor block and the rate of hypotension, but not onset of anesthesia, were significantly related to the ropivacaine dose. Conclusion： The ED50 and ED95 of spinal hyperbaric ropivacaine for cesarean delivery under the conditions of this study were 10.37 mg and 15.39 mg, respectively. Ropivacaine is suitable for spinal anesthesia in cesarean delivery.

Serum Ferritin and the Risk of Metabolic Syndrome:A Systematic Review and Dose-Response Meta-Analysis of Cross-sectional Studies

Objective This study aims to assess the dose-response relationship between serum ferritin(SF)and metabolic syndrome(MetS)in the two sexes.Methods We searched for articles on PubMed,the Cochrane Library,EMBASE,and the Web of Science databases that were published from 1950 to 2020.The summary odds ratio(OR)and 95%confidence interval(CI)of the association between SF and MetS were estimated using a random-effects model through a meta-analysis.Based on the methods described by Greenland and Longnecker,we explored the dose-response relationship between the two sexes.Results This study included 14 studies and 74,710 samples.The results of the classical meta-analysis showed that SF was positively associated with MetS(OR=1.77,95%CI:1.59–1.98).Regarding the components of MetS(8 studies included),the results showed that SF was positively associated with abdominal obesity(OR=1.42,95%CI:1.24–1.62),elevated fasting plasma glucose(OR=1.84,95%CI:1.50–2.25),elevated blood pressure(OR=1.17,95%CI:1.08–1.26),elevated triglycerides(OR=2.09,95%CI:1.72–2.54),and reduced high-density lipoprotein cholesterol(OR=1.33,95%CI:1.19–1.49).In the linear dose-response meta-analysis,the ORs of males,females,and postmenopausal females were 1.14(95%CI:1.13–1.16),1.32(95%CI:1.26–1.39),and 1.34(95%CI:1.22–1.47),respectively.Conclusions Our study shows that SF is significantly and positively associated with MetS,and the risk in the male population is higher than that in the female population.This finding also supports the recommendation of using SF as an early warning marker of MetS.

Standardization of exercise intensity and consideration of a dose-response is essential.Commentary on "Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer’s models”,by Lourenco et al.,published 2019 in Nature Medicine

Over the past decade,several biochemical pathways have been investigated to understand the underlying mechanisms involved in the beneficial effects of physical exercise on cognition.1,2 Lourenco et al.,3 in an elegant study published in Nature Medicine,examined the relationship between exercise training and hippocampal memory function.Mechanistically,the authors showed that FNDC5/irisin is an important mediator of beneficial effects of physical exercise in a mouse model of Alzheimer's disease.

Atrial fibrillation burden and the risk of stroke:A systematic review and dose-response meta-analysis

BACKGROUND The increased stroke risk associated with atrial fibrillation(AF)burden exceeding 5 min is a matter of debate.In addition,the potential linear or nonlinear relationship between AF burden and stroke risk has been largely unexplored.AIM To determine the association between AF burden>5 min and the increased risk of stroke and explore the potential dose-response relationship between these two factors.METHODS Sixteen studies from six databases with 53141 subjects(mean age 65 years)were included.Fifteen studies were observational studies,and one was a randomized controlled trial study.The potential nonlinear dose-response association was characterized using a restricted cubic splines regression model.AF burden for each 1 h and 2 h was associated with an increased risk of stroke.Trial sequential analysis with a random-effect model was used to evaluate the robustness of the evidence from the included 16 studies.RESULTS AF burden>5 min was associated with an increased risk of clinical AF[adjusted risk ratio(RR)=4.18,95%confidence interval(CI):2.26-7.74].However,no association was found with an increased risk of all-cause mortality(adjusted RR=1.55,95%CI:0.87-2.75).Patients with AF burden>5 min had an increased risk of stroke(adjusted RR=2.49,95%CI:1.79-3.47).Moreover,a dose-response analysis showed that the increased stroke risk was paralleled by an increase in AF burden at a rate of 2.0%per hour(Pnonlinear=0.656,RR=1.02,95%CI:1.01-1.03).Trial sequential analysis provided robust evidence of the association between AF burden>5 min and an increased risk of stroke.CONCLUSION AF burden was a significant risk factor for clinical AF and future stroke.A significant linear association was documented between increased AF burden and risk of future stroke.

Interpreting Dose-Response Relation for Exposure to Multiple Sound Impulses in the Framework of Immunity

Hearing loss is a common military health problem and it is closely related to exposures to impulse noises from blast explosions and weapon firings. In a study based on test data of chinchillas and scaled to humans (Military Medicine, 181: 59-69), an empirical injury model was constructed for exposure to multiple sound impulses of equal intensity. Building upon the empirical injury model, we conduct a mathematical study of the hearing loss injury caused by multiple impulses of non-uniform intensities. We adopt the theoretical framework of viewing individual sound exposures as separate injury causing events, and in that framework, we examine synergy for causing injury (fatigue) or negative synergy (immunity) or independence among a sequence of doses. Starting with the empirical logistic dose-response relation and the empirical dose combination rule, we show that for causing injury, a sequence of sound exposure events are not independent of each other. The phenomenological effect of a preceding event on the subsequent event is always immunity. We extend the empirical dose combination rule, which is applicable only in the case of homogeneous impulses of equal intensity, to accommodate the general case of multiple heterogeneous sound exposures with non-uniform intensities. In addition to studying and extending the empirical dose combination rule, we also explore the dose combination rule for the hypothetical case of independent events, and compare it with the empirical one. We measure the effect of immunity quantitatively using the immunity factor defined as the percentage of decrease in injury probability attributed to the sound exposure in the preceding event. Our main findings on the immunity factor are: 1) the immunity factor is primarily a function of the difference in SELA (A- weighted sound exposure level) between the two sound exposure events;it is virtually independent of the magnitude of the two SELA values as long as the difference is fixed;2) the immunity factor increases monotonically from 0 to 100% as the first dose is varied from being significantly below the second dose, to being moderately above the second dose. The extended dose-response formulation developed in this study provides a theoretical framework for assessing the injury risk in realistic situations.

Finite Mixture Normal Models, with Application to Dose-Response Studies

In this paper, we consider the risk assessment problem under multi-levels and multiple mixture subpopulations. Our result is the generalization of the results of [1-5].1 Finite Mixture Normal ModelsIn dose-response studies, a class of phenomena that frequently occur are that experimental subjects (e.g., mice) may have different responses like ’none, mild, severe’ after a toxicant experiment, or ’getting worse, no change, getting better’ after a medical treatment, etc. These phenomena have attracted the attention of many researchers in recent years. Finite

Generalized Estimating Equations for Repeated Measures Logistic Regression in Mosquito Dose-Response

Dose-response studies in arthropod research usually involve observing and collecting successive information at different times on the same group of insects exposed to different concentrations of stimulus. When the same measure is collected repeatedly over time, the data become correlated and Probit Analysis technique which is the standard method in analyzing bioassay experiments data cannot be used. Lethal time is estimated when the speed of kill is of interest since mortality varies over time. We evaluate a complementary approach, repeated measures logistic regression using Generalized Estimating Equations (GEE), for lethal time determination in mosquito dose response. Mortality data from anopheles larva exposed to 3 botanical extracts (B,C,E) at 4 concentration levels: 500 mg/ml, 250 mg/ml, 50 mg/ml and 12.5 mg/ml were used. The result shows the estimated LT50 values with concentration 500 mg/ml being the most virulent chemical for extract B (LT50 = 10.3 hrs), C (LT50 = 7.2 hrs) and E (LT50 = 10.3 hrs). The least virulent chemical was concentration 12.5 mg/ml for extract B (LT50 = 52.1 hrs), C (LT50 = 70.7 hrs) and E (LT50 = 55.0 hrs). We conclude that repeated measures of logistic regression via GEE can be used as a tool to estimate LT50 more effectively in repeated measures of arthropod data.

A Dose-response Meta-analysis of Egg Intake and Breast Cancer Risk

Aim Eggs are one of the most nutritious foods in nature,but there is no unified conclusion about the association between egg intake and breast cancer risk.Methods The PubMed and Web of Science databases for the literature on egg intake and breast cancer risk were searched for papers published during the last 10 years.These were then filtered according to the inclusion and exclusion criteria.Stata16.0 software was applied to perform a meta-analysis,the generalized least squares method and constrained cubic spline model were used to assess the dose-response trends between egg intake and breast cancer risk.Results A total of 9 articles were included:6 case control studies and 3 cohort studies.The Newcastle-Ottawa scale(NOS)values of the included articles were all≥6 points.The pooled relative risks(RR)of egg intake and breast cancer risk was 0.91(95%CI:0.69-1.19).The dose-response analysis showed a linear trend for egg intake and breast cancer risk(P=0.689).With every 10 g/day increase in egg intake,the incidence of breast cancer increased by 2%(RR=1.02,95%CI:0.99-1.05).However,these results were not statistically significant.Conclusion This meta-analysis found no significant association between egg intake and breast cancer.

Biological transformation,kinetics and dose-response assessments of bound musk ketone hemoglobin adducts in rainbow trout as biomarkers of environmental exposure

Low levels (ng/g) of musk ketone (MK),used as a fragrance additive in the formulation of personal care products,are frequently detected in the water and other environment.Thus,aquatic organisms can be continuously exposed to MK.In this study,kinetics and dose-response assessments of 2-amino-MK (AMK) metabolite,bound to cysteine-hemoglobin (Hb) in rainbow trout,formed by enzymatic nitro-reduction of MK have been demonstrated.Trout were exposed to a single exposure of 0.010,0.030,0.10,and 0.30 mg MK/g fish.Tw...

24-Hour Urinary Sodium Excretion Association with Cardiovascular Events:A Systematic Review and Dose-Response Meta-Analysis

Objective The relationship between sodium intake and cardiovascular(CV)events remains unconfirmed.Therefore,we carried out a systematic review and dose-response meta-analysis for evaluating the potential impact of 24-hour sodium excretion on CV risk.Besides,24-hour sodium excretion was used to replace daily sodium diet intake.Methods We searched ISI Web of Science,Embase,Pub Med,and the Cochrane Library.Our study included cohort studies reporting hazard ratio(HR).The random-effects model was used for summarizing the total relative risks(RRs)between the included studies.In addition,the generalized least-squares regression was employed to fit the study model.Results A total of 9 studies involving 645,006 participants were included in this study.A significant non-linear relationship was observed between sodium excretion and CV events(P^(non-linearity)<0.001).In studies collecting 24-h urine samples,the sodium excretion and CV events risk were associated linearly(RR:1.04;95%CI:1.01,1.07).Conclusion In a linear dose-response manner,every 1 g increase in sodium intake was associated with an increased risk of CV events up to 4%.Further studies are required to validate our conclusions further.

Relationship between Kawasaki disease and abdominal pain

This editorial presents an analysis of an article recently published in the World Journal of Clinical Cases.Kawasaki disease(KD)is a well-known pediatric vasculitis characterized by fever,rash,conjunctivitis,oral mucosal changes,and swelling of the extremities.This editorial aims to delve into the intricate relationship between KD and abdominal pain,drawing insights from recent research findings to provide a comprehensive understanding and potential avenues for future investigation.

Hormesis has emerged as a more common and fundamental dose-response model than the threshold or linear-no-threshold(LNT) models

在回顾传统的有阈和线性无阈的剂量-反应关系的基础上,分析此类该模型被毒理学领域认同的主要原因和其在预测低剂量效应中的缺陷,进而提出了高剂量接触呈现抑制效应,而低剂量却呈现促进或刺激作用这一全面的激效兴奋性剂量-反应关系,弥补了现有模型的不足,并充分论证这种激效性剂量-反应关系在不同种属、接触因素和生物学终点中的普遍性,并探讨了不同物质的激效兴奋作用的可能机制以及激效兴奋模型的三大优点,最后提出了激效模型谋求广泛接受的现实困难和发展趋势。