Value of abnormal circadian rhythm of heart rate predicting the all-cause mortality in stage 5 chronic kidney disease patients / 中华肾脏病杂志

Objective:To investigate the predictive value of abnormal heart rate circadian rhythm for all-cause mortality in stage 5 chronic kidney disease (CKD 5) patients.Methods:The retrospective study was performed in CKD 5 patients enrolled from the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital) and the Affiliated BenQ Hospital of Nanjing Medical University from February, 2011 to December, 2019. A total of 159 healthy volunteers were enrolled as the healthy control group during the same period. The circadian rhythm of heart rate was monitored by 24-hour Holter. Related indices (including 24-hour, daytime and nighttime mean heart rate, night/day heart rate ratio, 24-hour maximum heart rate, 24-hour minimum heart rate and difference between maximum and minimum of 24-hour heart rate) were calculated. Non-dipping heart rate was defined as night/day heart rate ratio greater than 0.9. Cox regression model was used to analyze the risk factors of all-cause mortality in CKD 5 patients. Kaplan-Meier survival curve and Log-rank test were used to compare the differences of cumulative mortality between high ratio group (night/day heart rate ratio>0.91) and low ratio group (night/day heart rate ratio≤0.91). The nonlinear relationship between night/day heart rate ratio and all-cause mortality was analyzed by restricted cubic spline plot. Time-dependent receiver operating characteristic (ROC) curve was used to analyze the predictive value of night/day heart rate ratio for all-cause mortality in CKD 5 patients.Results:A total of 159 healthy volunteers and 221 CKD 5 patients were included in this study. There were 123 males (55.66%) and the age was (52.72±13.13) years old in CKD 5 patients. The total median follow-up time was 50.0 months. Compared with controls, 24-hour, nighttime mean heart rate, 24-hour minimum heart rate in CKD 5 patients were increased (all P<0.05), furthermore, the night/day heart rate ratio was higher [(0.91±0.09) vs (0.81±0.08), P<0.001], showing "non-dipping heart rate". However, the 24-hour maximum heart rate and the difference between maximum and minimum of 24-hour heart rate in CKD 5 patients were lower than controls (both P<0.05). Multivariate Cox regression analysis showed that the increased night/day heart rate ratio (per 0.1 increase, HR=1.557, 95% CI 1.073-2.258, P=0.020) was an independent influencing factor for all-cause mortality in CKD 5 patients. Kaplan-Meier survival curve analysis showed that the cumulative mortality of the high ratio group was significantly increased than that of the low ratio group (Log-rank test χ 2=7.232, P=0.007). From the restricted cubic spline plot, there was a linear effect between night/day heart rate ratio and all-cause mortality ( P=0.141), and when night/day heart rate ratio was above 0.91, the risk of all-cause mortality was significantly increased in CKD 5 patients. According to time-dependent ROC curve, the accuracy of night/day heart rate ratio in predicting all-cause mortality was 70.90% even when the survival time was up to 70.0 months. Conclusions:The circadian rhythm of heart rate in CKD 5 patients displays "non-dipping" state. High night/day heart rate ratio is an independent influencing factor for all-cause mortality in CKD 5 patients.

Effects of parathyroidectomy on heart rate circadian rhythm in patients with stage 5 chronic kidney disease combined with severe secondary hyperparathyroidism / 中华肾脏病杂志

Objective:To observe heart rate circadian rhythm in patients with chronic kidney disease (CKD) stage 5 and to analyze the effects of parathyroidectomy (PTX) on heart rate circadian rhythm in severe secondary hyperparathyroidism (SHPT) patients.Methods:A cross-sectional observation was performed in 213 patients with CKD stage 5 and 96 controls, and the patients were divided into those with severe SHPT (PTX group, n=70) and without severe SHPT (non-PTX group, n=143). Forty-six PTX patients were followed up prospectively. The baseline data were compared among these groups. Holter electrocardiogram was performed for each participant. Non-dipping heart rate was defined as night/day heart rate ratio greater than 0.9. Multiple linear regression analysis was used to analyze the related factors of heart rate circadian rhythm in patients with CKD stage 5. Results:The 24-hour, daytime and nighttime mean heart rate in patients with CKD stage 5 were all higher than those in controls, especially in PTX group (all P<0.05). The night/day heart rate ratios of controls and CKD stage 5 patients were (0.81±0.08) and (0.91±0.08) respectively ( P<0.01). Correlation analysis showed 24-hour and daytime or nighttime mean heart rate in patients with CKD stage 5 were positively correlated with serum levels of phosphorus and ln(alkaline phosphatase), while nighttime mean heart rate and night/day heart rate ratio were positively related with serum intact parathyroid hormone level. After adjusting with postoperative follow-up period (median time: 10.9 months), 24-hour and nighttime mean heart rate, and night/day heart rate ratio in PTX patients all decreased significantly (all P<0.01). Conclusions:Heart rate is increased and circadian rhythm is abnormal in patients with CKD stage 5, which are related with mineral and bone disorder. PTX significantly decreases 24-hour and nighttime mean heart rate in severe SHPT patients, and improves the heart rate circadian rhythm.

Fitting and forecasting the trend of COVID-19 by SEIR+ CAQ dynamic model / 中华流行病学杂志

Objectives@#Fitting and forecasting the trend of COVID-19 epidemics.@*Methods@#Based on SEIR dynamic model, considering the COVID-19 transmission mechanism, infection spectrum and prevention and control procedures, we developed SEIR+ CAQ dynamic model to fit the frequencies of laboratory confirmed cases obtained from the government official websites. The data from January 20, 2020 to February 7, 2020 were used to fit the model, while the left data between February 8-12 were used to evaluate the quality of forecasting.@*Results@#According to the cumulative number of confirmed cases between January 29 to February 7, the fitting bias of SEIR+ CAQ model for overall China (except for cases of Hubei province), Hubei province (except for cases of Wuhan city) and Wuhan city was less than 5%. For the data of subsequent 5 days between February 8 to 12, which were not included in the model fitting, the prediction biases were less than 10%. Regardless of the cases diagnosed by clinical examines, the numbers of daily emerging cases of China (Hubei province not included), Hubei Province (Wuhan city not included) and Wuhan city reached the peak in the early February. Under the current strength of prevention and control, the total number of laboratory- confirmed cases in overall China will reach 80 417 till February 29, 2020, respectively.@*Conclusions@#The proposed SEIR+ CAQ dynamic model fits and forecasts the trend of novel coronavirus pneumonia well and provides evidence for decision making.

Dynamic basic reproduction number based evaluation for current prevention and control of COVID-19 outbreak in China / 中华流行病学杂志

Objective@#To evaluate the current status of the prevention and control of coronavirus disease (COVID-19) outbreak in China, establish a predictive model to evaluate the effects of the current prevention and control strategies, and provide scientific information for decision- making departments.@*Methods@#Based on the epidemic data of COVID-19 openly accessed from national health authorities, we estimated the dynamic basic reproduction number R0(t) to evaluate the effects of the current COVID-19 prevention and control strategies in all the provinces (municipalities and autonomous regions) as well as in Wuhan and the changes in infectivity of COVID-19 over time.@*Results@#For the stability of the results, 24 provinces (municipality) with more than 100 confirmed COVID-19 cases were included in the analysis. At the beginning of the outbreak, the R0(t) showed unstable trend with big variances. As the strengthening of the prevention and control strategies, R0(t) began to show a downward trend in late January, and became stable in February. By the time of data analysis, 18 provinces (municipality) (75%) had the R0(t)s less than 1. The results could be used for the decision making to free population floating conditionally.@* Conclusions@#Dynamic R0(t) is useful in the evaluation of the change in infectivity of COVID-19, the prevention and control strategies for the COVID-19 outbreak have shown preliminary effects, if continues, it is expected to control the COVID-19 outbreak in China in near future.

Principles of dynamics model and its application in forecasting the epidemics and evaluation the efforts of prevention and control interventions / 中华预防医学杂志

During the epidemics of COVID-19 in domestic China and recently continuing rapid spread worldwide, a bunch of studies fitted the epidemics by transmission dynamics model to nowcast and forecast the trend of epidemics of COVID-19. However, due to little known of the new virus in early stage and much uncertainty in the comprehensive strategies of prevention and control for epidemics, majority of models, not surprisingly, predict in less accuracy, although the dynamics model has its great value in better understanding of transmission. This comment discusses the principle assumptions and limitations of the dynamics model in forecasting the epidemic trend, as well as its great potential role in evaluation the efforts of prevention and control strategies.

How to adjust confounders in studies on observational comparative effectiveness: (3) approaches on sensitivity analysis for confounder adjustment / 中华流行病学杂志

Confounders are difficult to avoid in studies on observational comparative effectiveness. It is often unclear whether the confounders have been completely eliminated after controlling the measured or unmeasured potential confounding effects or if sensitivity analysis is needed when using the specific statistical methods, under given circumstances. This manuscript summarizes and evaluates the confounding sensitivity analysis methods. Based on different studies, sensitivity analyses need to use different approaches. The traditional sensitivity analysis can be applied for the measured confounders. Currently, the relatively systematic sensitivity analyses for unmeasured confounders would include confounding function, bounding factor and propensity score calibration. Additionally, more investigations are associated with Monte Carlo and Bayesian sensitivity analysis. Reliability of the research conclusion thus may largely be improved when the sensitivity analysis results are consistent with the main analysis.

Confounder adjustment in observational comparative effectiveness researches: (1) statistical adjustment approaches for measured confounder / 中华流行病学杂志

Observational comparative effectiveness studies have been widely conducted to provide evidence on additional effectiveness and to support randomized controlled findings in research. Although this type of study becomes more important over time, challenges related to the common biases which stemmed from confounders, are difficult to control. This manuscript summarizes some statistical methods used on adjusting measured confounders that often noticed in research, regarding the observational comparative effectiveness. Useful traditional methods would include stratified analysis, paired analysis, covariate model and multivariable model, etc.. Unconventional adjustment approaches such as propensity score and disease risk score methods may also be used in studies, for matching, stratification and adjustment. A good study design should be able to control confounders. The limitations of all the post hoc statistical adjustment methods should also be fully understood before being appropriately applied in practical events.

Application of mendelian randomization methods in causal inference of observational study / 中华预防医学杂志

Mendelian randomization (MR) approach follows the Mendel′s law of inheritance, which is called "Parental alleles randomly assigned to the offspring", and refers to use genetic variants as an instrumental variable to develop causal inference between the exposure factor and the outcome from observational study. In recent years, with the rapid development of genome-wide association study (GWAS) and various omics data,the disclosure of a large number of aggregated data provides an opportunity for the wide application of MR approach in causal inference. We introduce three methods widely used in MR and then apply them to explore causal relationship between blood metabolites and depressive. The advantages and disadvantages of three methods in causal inference are compared in order to provide reference for the application of MR in observational studies.

Statistical P values do not dominate scientific research / 中华预防医学杂志

Statistical P value and its threshold have been controversial worldwide for a while. Recent heated debate was triggered by two practical issues: unexplainable high false positive rate in biomedical research, and global misunderstood of "statistical significance" in scientific community. Thus, part of scientists suggests applying more stringent significance level (from 0.05 to 0.005), or even giving up the use of significance level. We believe that they are throwing the baby out with the bath water. These suggestions will not contribute to any improvement of this unfavorable situation but will lead the scientific decision-making to a more difficult and subjective corner. Scientists should use statistical P value and threshold only if they correctly understand the soul of statistics-uncertainty. Statistical significance is neither sole nor dominant criterion to measure the scientific value, but an honest assistant. Scientific decision-making should initiate from the scientific experimental design, followed by rigorous implementation and transparent analysis, and synthesize a variety of information to reach a tenable conclusion.

Association between the frequency of bowel movements and the risk of colorectal cancer in Chinese adults / 中华流行病学杂志

Objective@#To examine the association between the frequencies of bowel movement (BMF) and the risk of colorectal cancer (CRC).@*Methods@#In this study, 510 134 participants from the China Kadoorie Biobank (CKB) were included, after excluding those who reported as having been diagnosed with cancer at the baseline survey. The baseline survey was conducted from June 2004 to July 2008. The present study included data from baseline and follow-up until December 31, 2016. We used the Cox proportional hazards regression models to estimate the HR and the 95%CI of incident CRC with BMF.@*Results@#During an average follow-up period of 9.9 years, 3 056 participants were documented as having developed colorectal cancer. In the site-specific analysis, 1 548 colon cancer and 1 475 rectal cancer were included. Compared with participants who had bowel movements on the daily base, the multivariable-adjusted HR (95%CI) for those who had more than once of BMF were 1.24 (1.12-1.39) for CRC, 1.12 (0.95-1.31) for colon cancer, and 1.37 (1.18-1.59) for rectal cancer. We further examined the association between BMF and CRC, according to the stages of follow-up, the corresponding HR (95%CI) for CRC, colon and rectal cancer were 1.59 (1.36-1.86), 1.43 (1.14- 1.80), and 1.76 (1.41-2.19) for the first five years, while such associations became statistically insignificant in the subsequent follow-up (P for all interactions were <0.05), as time went on. As for CRC, colon or rectal cancers among participants who had lower bowel movements, the risks were not significantly different from those who had bowel movements everyday.@*Conclusions@#Participants who had BMF more than once a day, appeared an increased risk of CRC in the subsequent five years. Since abnormal increase of bowel movements is easily recognizable, programs should be set up on health self- management and early screening for CRC.

Confounder adjustment in observational comparative effectiveness researches: (2) statistical adjustment approaches for unmeasured confounders / 中华流行病学杂志

Observational study of therapy efficacy comparison has been widely conducted to provide the additional efficacy evidence to support randomized control study. Statistical adjustment for unmeasured confounders is a major challenge in observational study of therapy efficacy comparison. This paper summarizes and evaluates the relative statistical methods. Currently, the most commonly used methods include instrumental variable, difference-in-differences (DiD) model and prior event rate ratio (PERR) adjustment. The instrumental variable method skill fully escapes unmeasured confounders through model structure, but it is not easy to obtain satisfied instrumental variables. Both PERR and DiD require the data prior to exposure which are not always collected in observational studies. Unmeasured confounders could result in new requirements and pose new challenges for statistical methods, which needs further study and improvement.

Investigation of the correlation between serum biochemical parameters and Parkinson's disease risk in the elderly / 中华老年医学杂志

Objective To investigate the correlation between serum biochemical parameters and Parkinson's disease (PD) risk in the elderly.Methods The 277 inpatients with PD as PD group in Jiangsu Province Hospital from January 2009 to December 2013 were selected,at the same time,the 277 age and gender-matched healthy persons were enrolled as control group.The levels of total cholesterol (TG),total bilirubin (TB),uric acid (UA),low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were detected and compared between the two groups.Results The levels of TG,UA,TB,HDL-C and LDL-C were significantly lower in PD group than in control group [(4.35±1.13) mmol/L vs.(4.95±0.98) mmol/L,t=6.63;(278.00± 101.89)μmol/L vs.(380.90 ± 108.28) μmol/L,t =12.44;(13.02 ± 7.56) μmol/L vs.(17.39 ± 7.30)μmol/L,t=7.09;(1.26±0.37) mmol/L vs.(1.34±0.28) mmol/L,t=3.38;(2.59±0.79) mmol/L vs.(3.17±0.91) mmol/L,t=7.42,all P＜0.05].Logistic multiple regression analysis showed that the decreased levels of TB,UA and LDL-C were independently associated with prevalence risk of PD (OR=0.940,0.991 and 0.219,all P＜0.001).The combined score of TB,UA and LDL-C was constructed by using the linear weighted method.ROC curve was drawn to select the higher diagnostic validity index among TB,UA,LDL-C and combined score.The area under the ROC curve for TB,UA,LDL-C and combined score was 0.713,0.765,0.682 and 0.809 (all P＜0.001),and the value of combined score was the highest.Conclusions The decreased levels of TB,UA and LDL-C are independently associated with PD.They possess certain clinical value in evaluating the prevalence risk of PD.

Evaluation of the severity of chronic obstructive pulmonary disease with the percentage of the total cross-sectional area of small pulmonary vessels for the lung area in multi-slice CT / 中华放射学杂志

Objective To investigate the role of the percentage of the total cross-sectional area of small pulmonary vessels for the lung area (%CSA) from multi-slice CT (MSCT) in evaluating the severity of chronic obstructive pulmonary disease (COPD). Methods One hundred and sixty-six COPD patients and 166 normal subjects underwent chest MSCT scans and all data were analyzed retrospectively. COPD patients underwent pulmonary function tests (PFT), including forced expiratory volume in one second (FEV1%) and FEV1/forced vital capacity (FEV1/FVC), and were classified into mild (n=32), moderate (n=65), severe (n=69) groups according to pulmonary function results, respectively. The%CSA less than 5 mm2 and 5—10 mm2 for the lung area (%CSA0.05). FEV1%and FEV1/FVC in COPD patients were (60.38±15.52)%and 57.95±22.27.%CSA<5 in COPD patients correlated positively with both FEV1%and FEV1/FVC (r=0.609 and 0.721, P<0.01, respectively).%CSA5-10 in COPD patients correlated positively with both FEV1%and FEV1/FVC (r=0.271 and 0.288, P<0.01, respectively). Conclusion The measurement of%CSA<5 and%CSA5-10 in MSCT images correlated with PFTs and%CSA<5, which may play an important role in evaluating the severity of COPD.

Research on signal detection methods based on data mining in adverse drug reaction of shuanghuanglian injection / 中国中药杂志

<p><b>OBJECTIVE</b>This paper is aimed to explore the adverse reaction condition of Shuanghuangli an injection with three common used signal detecting methods based on SRS database of Jiangsu province, and to evaluate the performance of three methods.</p><p><b>METHOD</b>Three methods would be used to detect the signals based on the SRS database of Jiangsu province. Consistency of the results of these three methods with that proved in descriptions was evaluated by Kappa test. The trend graph of the confidence intervals of several time points was used to demonstrate the trend of the signal.</p><p><b>RESULT</b>The PRR method was consistent with ROR method in high degree in any situation. The results of BCPNN method was close to PRR and ROR method only when the related report count was larger. PRR and ROR methods had higher false positive rate than BCPNN method.</p><p><b>CONCLUSION</b>PRR or ROR method is proposed for signal detecting when the report count is large. BCPNN method is proposed for trend demonstration of signal with graph.</p>

Sample size calculation in dose-response research / 中国临床药理学与治疗学

AIM:To introduce and evaluate two methods for sample size calculation in doseresponse research.METHODS:The methods used for sample size calculation in dose-response research include Cochran-Armitage trend(CAT) test proposed by Jun-mo Nam and the Unified contrast(CUC) method proposed by Chang. This paper takes the example of binary data,uses the two methods to calculate the required sample size and evaluate the power by simulation under the assumption that the response rate had a linear relationship with dosage under the logit scale.RESULTS:When the probability of response followed a linear trend on the logit scale, the sample sizes estimated from the two methods are approximately equal in various parameter's settings.The simulated power of CAT test was close to the expected one,however,the simulated power of CUC method was obviously affected by the values of contrast coefficient,if a contrast whose coefficients parallel the expected response, the CUC method was more powerful. CONCLUSION:When the probability of response follows a linear trend over dosage on the logit scale,the two methods reach almost the same result,in such circumstance,the Chang's unified contrast method will obtain an increasing power.