Infrastructure and contents of clinical data management plan / 药学学报

Establishment of quality management system (QMS) plays a critical role in the clinical data management (CDM). The objectives of CDM are to ensure the quality and integrity of the trial data. Thus, every stage or element that may impact the quality outcomes of clinical studies should be in the controlled manner, which is referred to the full life cycle of CDM associated with the data collection, handling and statistical analysis of trial data. Based on the QMS, this paper provides consensus on how to develop a compliant clinical data management plan (CDMP). According to the essential requirements of the CDM, the CDMP should encompass each process of data collection, data capture and cleaning, medical coding, data verification and reconciliation, database monitoring and management, external data transmission and integration, data documentation and data quality assurance and so on. Creating and following up data management plan in each designed data management steps, dynamically record systems used, actions taken, parties involved will build and confirm regulated data management processes, standard operational procedures and effective quality metrics in all data management activities. CDMP is one of most important data management documents that is the solid foundation for clinical data quality.

Key issues on the clinical trial data management / 药学学报

This paper is prepared to discuss the common issues in data management, such as building and training of data management team, standard operation procedure, document management, execution and communication, strategies to correct and prevent mistakes, and measures to improve the quality and efficiency of clinical trials and data management.

The impact of relative humidity and atmospheric pressure on mortality in Guangzhou, China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Although many studies have examined the effects of ambient temperatures on mortality, little evidence is on health impacts of atmospheric pressure and relative humidity. This study aimed to assess the impacts of atmospheric pressure and relative humidity on mortality in Guangzhou, China.</p><p><b>METHODS</b>This study included 213,737 registered deaths during 2003-2011 in Guangzhou, China. A quasi-Poisson regression with a distributed lag non-linear model was used to assess the effects of atmospheric pressure/relative humidity.</p><p><b>RESULTS</b>We found significant effect of low atmospheric pressure/relative humidity on mortality. There was a 1.79% (95% confidence interval: 0.38%-3.22%) increase in non-accidental mortality and a 2.27% (0.07%-4.51%) increase in cardiovascular mortality comparing the 5th and 25th percentile of atmospheric pressure. A 3.97% (0.67%-7.39%) increase in cardiovascular mortality was also observed comparing the 5th and 25th percentile of relative humidity. Women were more vulnerable to decrease in atmospheric pressure and relative humidity than men. Age and education attainment were also potential effect modifiers. Furthermore, low atmospheric pressure and relative humidity increased temperature-related mortality.</p><p><b>CONCLUSION</b>Both low atmospheric pressure and relative humidity are important risk factors of mortality. Our findings would be helpful to develop health risk assessment and climate policy interventions that would better protect vulnerable subgroups of the population.</p>

Weighted Youden index and its two-independent-sample comparison based on weighted sensitivity and specificity / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Most indices for evaluating a diagnostic test can be expressed as functions of sensitivity (SEN) and specificity (SPE). Practically, all existing methods suffer from the inability to weight sensitivity and specificity relative to their importance. In this paper, we developed a novel index, the weighted Youden index, that allows Youden index to be a combination of sensitivity and specificity with user-defined weights.</p><p><b>METHODS</b>The weighted Youden index Jw is defined as Jw = 2(w×SEN + (1-w)SPE)-1 (0 ≤ w ≤ 1). It has three properties: (1) the sum of the weights which are attached to sensitivity and specificity should be equal to 1; (2) the range of Jw should be within [-1, 1], which is the range of the Youden index J; (3) Jw should be equal to J when sensitivity and specificity have equal weights. According to the central limit theorem, we obtain the standard error of Jw, and propose a statistical inference method to compare two weighted Youden indices. The monotonicity of the test statistic was discussed.</p><p><b>RESULTS</b>An example of comparing two diagnostic tests for pheochromocytoma was used to demonstrate the weighted Youden index method. Weighted Youden index, the confidence interval for each test and the hypothesis test of comparing two independent diagnostic tests were presented. Assigning the weights is essential to the weighted Youden index approach.</p><p><b>CONCLUSION</b>The weighted Youden index can broaden its applications in diagnostic test development and motivate further research in weighting sensitivity and specificity explicitly.</p>

Impact of heat wave in 2005 on mortality in Guangzhou, China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To assess the impact of the heat wave in 2005 on mortality among the residents in Guangzhou and to identify susceptible subpopulations in Guangzhou, China.</p><p><b>METHODS</b>The data of daily number of deaths and meteorological measures from 2003 to 2006 in Guangzhou were used in this study. Heat wave was defined as ⋝7 consecutive days with daily maximum temperature above 35.0 °C and daily mean temperature above the 97th percentile during the study period. The excess deaths and rate ratio (RR) of mortality in the case period compared with the reference period in the same summer were calculated.</p><p><b>RESULTS</b>During the study period, only one heat wave in 2005 was identified and the total number of excess deaths was 145 with an average of 12 deaths per day. The effect of the heat wave on non-accidental mortality (RR=1.23, 95% CI: 1.11-1.37) was found with statistically significant difference. Also, greater effects were observed for cardiovascular mortality (RR=1.34, 95% CI: 1.13-1.59) and respiratory mortality (RR=1.31, 95% CI: 1.02-1.69). Females, the elderly and people with lower socioeconomic status were at significantly higher risk of heat wave-associated mortality.</p><p><b>CONCLUSION</b>The 2005 heat wave had a substantial impact on mortality among the residents in Guangzhou, particularly among some susceptible subpopulations. The findings from the present study may provide scientific evidences to develop relevant public health policies and prevention measures aimed at reduction of preventable mortality from heat waves.</p>

Current pattern of Chinese dialysis units: a cohort study in a representative sample of units / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Understanding the characteristics of Chinese dialysis patients and the current practice trends is the first step to evaluate the association between practice pattern and outcome in these populations. In the present study, we evaluated the status of medical treatment and characteristic features of chronic dialysis patients in China.</p><p><b>METHODS</b>Through a clustering sampling, we selected 9 centers from the largest dialysis facilities in 6 cities around China. All adult undergoing dialysis in the selected units were screened. A total of 2388 (1775 on hemodialysis (HD) and 613 on peritoneal dialysis (PD)) patients were finally enrolled. All data were collected at enrollment on the bases of review of medical records.</p><p><b>RESULTS</b>In this cohort, 1313 (55.0%) were male. The mean age was 54 years old. The median time for dialysis was 26 months (12 - 51 months). Seventy-five percent of patients were on HD and 25.0% on PD. Among PD patients, about 21% patients did not receive dialysis adequacy. For HD patients, about 14.0% of them did not achieve dialysis adequacy when the target of kt/V was set as 1.2. Only 44.7% of patients achieved blood pressure target of 140/90 mmHg. About 60% of patients did not reach the hemoglobin target of 110 g/L even though 85.0% of them were treated with erythropoietin. In addition, 48.5% of the patients had uncontrolled mineral metabolism revealed by the high calcium-phosphate product. Compared with HD patients, higher level of serum glucose, triglyceride, and total and low density lipoprotein cholesterol were more common in PD patients.</p><p><b>CONCLUSIONS</b>This observational study suggests that many Chinese dialysis patients did not achieve the therapeutic target, particularly in blood pressure control, anemia correction, and mineral balance. PD patients were more likely to suffer metabolic disturbance.</p>

Citation analysis of meta-analysis articles on posttraumatic stress disorder / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In the past two decades enormously scientific researches on posttraumatic stress disorder (PTSD) have been undertaken and many related meta-analyses have been published. Citation analysis was used to get comprehensive perspectives of meta-analysis articles (MA articles) on PTSD for the purpose of facilitating the researchers, physicians and policy-makers to understand the PTSD.</p><p><b>METHODS</b>MA articles on PTSD in any languages from January 1980 to March 2009 were included if they presented meta-analytical methods and received at least one citation recorded in the Web of Science (WoS). Whereas studies, in which any effect sizes of PTSD were not distinguished from other psychological disorders, were excluded. Citations to and by identified MA articles were documented basing on records in WoS. Citation analysis was used to examine distribution patterns of characteristics and citation impact of MA articles on PTSD. Canonical analysis was used to explore the relationship between the characteristics of MA articles and citation impact.</p><p><b>RESULTS</b>Thirty-four MA articles published during 1998 and 2008 were identified and revealed multiple study topics on PTSD: 10 (29.4%) were about epidemiology, 13 (38.2%) about treatment or intervention, 6 (17.6%) about pathophysiology or neurophysiology or neuroendocrine, 3 (8.8%) about childhood and 2 (5.9%) about psychosocial adversity. Two articles cited most frequently with 456 and 145 counts were published in Journal of Consulting and Clinical Psychology by Brewin (2000) and Psychological Bulletin by Ozer (2003), respectively. Mean cited count was 7.48 ± 10.56 and mean age (year 2009 minus article publication year) was (4.24 ± 2.91) years. They had been cited approximately by 67 disciplines and by authors from 42 countries or territories. Characteristics of meta-analysis highly correlated with citation impact and reflected by canonical correlation of 0.899 (P < 0.000 01).</p><p><b>CONCLUSIONS</b>The age of MA articles predicted their citation impact. Citation analysis would serve to capture the global perspectives and topics of MA articles on PTSD.</p>

Multiple comparisons in categorical data analysis / 南方医科大学学报

<p><b>OBJECTIVE</b>To discuss the method for multiple comparisons of categorical data and propose an approach to deal with the percentage data.</p><p><b>METHODS</b>The method of multiple comparisons for percentages was verified based on Bonferroni methodology and Monte Carlo method using SAS 9.13 software.</p><p><b>RESULTS</b>The type I error could be enlarged if the statistical tests were conducted without adjustment of the significant level after dividing the data of several categories or percentages into several four-fold tables. For the percentage data, the correction of adjustment of the significant level was the number of pairwise comparison minus one, as supported by the results of Monte Carlo simulation.</p><p><b>CONCLUSION</b>Multiple comparisons of categorical data should be applied appropriately. Multiple comparisons of percentages data need to be conducted with the number of pairwise comparison minus one.</p>

Diagnosis of liver pathologies based on apparent diffusion coefficient of magnetic resonance diffusion-weighted imaging in a rabbit model of liver fibrosis / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the value of apparent diffusion coefficient (ADC) of magnetic resonance diffusion-weighted imaging (MR-DWI) for diagnosis of the liver pathologies in rabbit model of liver fibrosis.</p><p><b>METHOD</b>MR-DWI with four different b values (200, 500, 300 and 600 s/mm(2)) was performed in 4 normal New Zealand white rabbits and 13 rabbits with experimental liver fibrosis. For each rabbit, 4 ADC values were obtained in the left and right lobes of the liver. According to the ISHAK criteria of liver histopathological scoring and fibrosis staging system, all the liver specimens were histopathologically graded (scores 1-6 for grade I, 7-12 for grade II, and 13-18 for grade III) and assessed for fibrosis staging (stages I to VI). The variation of ADC values were analyzed based on the results of histopathological grading and fibrosis staging.</p><p><b>RESULTS</b>The 4 ADC values were obviously lower in rabbits with liver fibrosis than in the normal control rabbits. Statistical analysis showed significant differences in the ADC values between the normal control and liver fibrosis groups, and between the rabbits with different histopathological grades and fibrosis stages (P=0.000).</p><p><b>CONCLUSIONS</b>Liver fibrosis results in significantly lowered ADC values of the liver depending on the histopathological grades and fibrosis stages. The pathological basis for these changes lies in reduced water content and restricted Brownian motion of water in the liver due to hepatocyte degeneration and swelling, inflammatory cell infiltration, and collagen fiber deposition in the interstitial space.</p>

Construction and application of an ARIMA model for predicting the number of outpatient visits in general hospitals / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the variation patterns of the number of outpatient visits in hospitals to provide references for more effective management of general hospitals.</p><p><b>METHODS</b>The forecasting model of ARIMA(1,0,1)(0,1,1)12 was established using residual error analysis and least squares method according to the sequence stability, long-term trend and seasonal effect after logarithm transformation and differencing.</p><p><b>RESULTS</b>The residual sum of squares was 2.790, AIC=-178.126, SBC=-170.080. The relative predictive error of the model for predicting the outpatient visits in a general hospital in the year 2008 was 6.11%, smaller than that of exponential smoothing (8.78%). This model predicted a number of outpatient visits of 1,501,200 in this hospital in the year 2009.</p><p><b>CONCLUSIONS</b>The ARIMA model provides a means for predicting the number of total outpatient visits, its long-term tendency and seasonal variation. The parameters p,d,q in the ARIMA model may vary between different hospitals, and the ACF and PACF charts of the original sequences are helpful for determining these parameters.</p>

Laparoscopic versus conventional open resection for colorectal cancer: a meta-analysis on recurrence / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare the recurrence between laparoscopic resection and conventional open resection for colorectal cancer with meta-analysis.</p><p><b>METHODS</b>Eligible articles were identified by searches of MEDLINE, EMBASE and the Cochrane database between January 1991 and January 2007 using the terms (laparoscopy, surgery, minimal invasive, colon, intestine, large, colectomy, colonic neoplasms, rectal neoplasms and randomized controlled trial). Prospective randomized clinical trials were eligible if they included patients with colorectal cancer treated by laparoscopic surgery versus open surgery followed-up by recurrence. Data were extracted from these trials by three independent reviewers.</p><p><b>RESULTS</b>Ten trials with recurrence information of 2474 patients were involved. In the combined results, no significant difference in the OR for overall recurrence between the laparoscopic surgery and open surgery group was found (OR 0.95, 95%CI 0.76 to 1.19, P=0.64). Stratified by recurrence type, the combined results of the individual reports showed no significant differences for local recurrence (OR 0.79, 95%CI 0.50 to 1.25,P=0.32), distant metastasis (OR 0.89, 95%CI 0.62 to 1.28, P=0.54) and port-site or wound-site recurrence (OR 1.04,95%CI 0.21 to 5.27,P=0.96) between the two surgical techniques.</p><p><b>CONCLUSION</b>The recurrence rates for patients with colorectal cancer treated by laparoscopic surgery do not differ significantly from those by open surgery. Longer follow up studies will further define outcomes comparing the two techniques in the treatment of colorectal cancer.</p>

Effect of influenza-like diseases on the number of outpatient visits / 南方医科大学学报

<p><b>OBJECTIVE</b>To estimate the effect of influenza-like illness (ILI) on outpatient visits and assess its impact on public health.</p><p><b>METHODS</b>We analyzed the data of weekly number of ILI and outpatient visits in Departments of Internal Medicine, Pediatrics and Emergency at two influenza surveillance hospitals during a period of 137 weeks in Guangzhou. Spectral analysis and time-series analysis were performed to evaluate the variation of outpatient visits over time. The predictive model was fitted with weekly outpatient visits as the dependent variable and weekly number of ILI as the independent variable. The optimal model was established according to the coefficient of determination, Akaike-information criterion and residual analysis. The validity of the model was assessed prospectively using the 31-week data that were not used for the model establishment.</p><p><b>RESULTS</b>The outpatient visits increased significantly over time and showed significant seasonality (P<0.001). A significant correlation was found between the weekly number of ILI and outpatient visits (r=0.568, P<0.001). The residuals of the fitted autoregression model were white-noise series and the coefficient of determination was 75% for the data used to establish the model and 56% for the subsequent 31-week data.</p><p><b>CONCLUSIONS</b>The autoregression model can be used to estimate the effect of weekly number of outpatient visits based on the weekly number of ILI and thus assess the effects of influenza on public health.</p>

Total mesorectal excision versus conventional radical surgery for rectal cancer: a meta analysis / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare treatment outcomes of total mesorectal excision (TME) with those of conventional radical surgery (CRS) for rectal cancer.</p><p><b>METHODS</b>Literature reviews were performed with key words, such as rectal cancer, total mesorectal excision, TME on all studies reported on TME versus CRS for rectal cancer between January 1986 to May 2006. According to the same screening criteria, 17 clinical studies were included in our systematic reviews. Two of our co-authors drew the details of trial design, characteristics of participants, results and so on from the studies included. Data analyses were performed by using RevMan 4.2.</p><p><b>RESULTS</b>Sample volume in this Meta analysis was 5267 rectal cancer cases. Quality and quantity analyses were performed within all included studies, prospective studies (prospective nonrandomized studies and multicenter prospective nonrandomized studies) and retrospective studies. The results showed that postoperative survival rate was significantly increased [OR 1.81 (95%CI 1.55-2.11, P<0.00001), OR 1.79 (95%CI 1.49-2.15, P<0.00001) and OR 1.84 (95%CI 1.39-2.45, P<0.00001)] and local recurrence rate was significantly reduced [OR 0.35 (95%CI 0.29-0.43, P<0.00001), OR 0.41 (95%CI 0.32-0.53, P<0.00001) and OR 0.29 (95%CI 0.22-0.39, P<0.00001)] after TME was used. The results of all study analyses agreed with those from prospective studies analyses, in which postoperative mortality was significantly reduced [OR 0.51 (95%CI 0.32-0.87, P=0.007) and OR 0.56 (95%CI 0.33-0.94, P=0.04)] after TME treatment, meanwhile the results of retrospective study analyses indicated that there was no significant difference between TME group and CRS group in postoperative mortality [OR 0.39 (95%CI 0.14-1.10, P=0.07)]. TME was a risk factor for postoperative anastomotic leak according to the results of all included studies and prospective study analyses, but no difference between TME group and CRS group had been found [OR 1.24 (95%CI 0.84-1.83, P=0.29) OR 1.98 (95%CI 0.85-4.61, P=0.11)].</p><p><b>CONCLUSIONS</b>TME is still the standard operative technique for rectal cancer. As compared with CRS, TME results in lower postoperative local recurrence rate and higher survival rate.</p>