Predicting the incidence of rifampicin resistant tuberculosis in Yunnan, China: a seasonal time series analysis based on routine surveillance data.

BACKGROUND: Rifampicin resistant tuberculosis (RR-TB) poses a growing threat to individuals and communities. This study utilized a seasonal autoregressive integrated moving average (SARIMA) model to quantitatively predict the monthly incidence of RR-TB in Yunnan Province which could guide government health administration departments and the centers for disease control and prevention (CDC) in preventing and controlling the RR-TB epidemic. METHODS: The study utilized routine surveillance reporting data from the infectious Disease Network Surveillance and Reporting System. Monthly incidence rates of RR-TB were collected from January 2019 to December 2022. A time series SARIMA model was used to predict the number of monthly RR-TB cases in Yunnan Province in 2023, and the model was validated using time series plots, seasonal and non-seasonal differencing, autocorrelation and partial autocorrelation analysis, and white noise tests. RESULTS: From 2019 to 2022, the incidence of RR-TB decreases as the incidence of all TB decreases (P < 0.05). There was no significant change in the proportion of RR-TB among all TB cases, which remained within 2.5% (P>0.05). The time series decomposition shows that it presented obvious seasonality, periodicity and randomness after being decomposed. Time series analysis was performed on the original series after 1 non-seasonal difference and 1 seasonal difference, the ADF test showed P < 0.05. According to ACF and PACF, the SARIMA (1, 1, 1) (1, 1, 0)12 model was chosen and statistically significant model parameter estimates (P < 0.05). The predicted seasonal trend of RR-TB incidence in 2019 to 2023 was similar to the actual data. The percentage accuracy in the prediction excesses 80% in 2019 to 2022 and is all within 95% CI. However there was a certain gap between the actual incidence and the predicted value in 2023, and the acutual incidence had increased by 12.4% compared to 2022. The percentage of accuracy in the prediction was only 70% in 2023. CONCLUSIONS: We found the incidence of RR-TB was based on that of all TB in Yunnan. The SARIMA model successfully predicted the seasonal incidence trend of RR-TB in Yunnan Province in 2019 to 2023, but the prediction precision could be influenced by factors such as new infectious disease outbreaks or pandemics, social issues, environmental challenges or other unknown risks. Hence CDCs should pay special attention to the post epidemic effects of new infectious disease outbreaks or pandemics, carry out monitoring and early warning, and better optimize disease prediction models.

Incomplete tuberculosis reporting and registration to the surveillance system in southwestern China of Yunnan Province: an inventory survey.

BACKGROUND: The real-world tuberculosis (TB) surveillance data was generally incomplete due to underreporting and underdiagnosis. The inventory study aimed to assess and quantify the incompletion of surveillance systems in southwestern China. METHODS: The inventory study was conducted at randomly selected health facilities (HF) by multi-stage stratified cluster sampling. The participants were included in the period between August of 2020 in province-level and prefecture-level HF, and in the period between June to December of 2020 in other categories of HF respectively. The clinical committee confirmed medical records were matched to the National Notifiable Disease Reporting System (NNDRS) and the Tuberculosis Information Management System (TBIMS) to define the report and register status. The underreporting and under-register rates were evaluated based on the matched data, and factors associated with underreport and under-register were assessed by the 2-level logistic multilevel model (MLM). RESULTS: We enrolled 7,749 confirmed TB cases in the analysis. The province representative overall underreport rate to NNDRS was 1.6% (95% confidence interval, 95% CI, 1.3 - 1.9), and the overall under-register rate to TBIMS was 9.6% (95% CI, 8.9-10.3). The various underreport and under-register rates were displayed in different stratifications of background TB disease burden, HF level, HF category, and data source of the medical record in HF among prefectures of the province. The intraclass correlation coefficient (ICC) was 0.57 for the underreporting null MLM, indicating the facility-level cluster effect contributes a great share of variation in total variance. The two-level logistic MLM showed the data source of medical records in HF, diagnostic category of TB, and type of TB were associated with underreporting by adjusting other factors (p < 0.05). The ICC for under-register was 0.42, and the HF level, HF category, data source of medical records in HF, diagnostic category of TB and type of TB were associated with under-register by adjusting other factors (p < 0.05). CONCLUSION: The inventory study depicted incomplete TB reporting and registering to NNDRS and TBIMS in southwestern China. It implied that surveillance quality improvement would help advance the TB prevention and control strategy.

Prediction of primary stability via the force feedback of an autonomous dental implant robot.

STATEMENT OF PROBLEM: While the high osteotomy and implant placement accuracy via robotic implant surgery has been verified, whether the force feedback in the osteotomy process can be used to determine appropriate primary implant stability remains unknown. PURPOSE: The purpose of this in vitro study was to explore the relationship between the force feedback and the primary stability of implants placed by using an autonomous dental implant robot. MATERIAL AND METHODS: Five groups (n=7) of wooden and polyurethane foam blocks were used to execute an implant surgery by using an autonomous implant robot. Tapered bone-level titanium dental implant replicas were placed in the blocks. The Young modulus, the maximal vertical and lateral drilling resistances, the position accuracy, and the insertion torque of implants were recorded. Simple linear regression, principal component analysis, and multiple linear regression were used. The osteotomy strategy for the implant site was adjusted according to the maximal vertical resistance of the pilot drill to achieve appropriate insertion torque. The correlation, Gompertz growth curve fitting of the insertion torque, and Young modulus were determined. The effect of the drilling resistances on the insertion torque was analyzed using 2-way ANOVA, simple linear regression, and the principal component analysis. RESULTS: The vertical resistance of the Ø2.2-mm pilot drill, the Ø3.5-mm twist drill, and the Ø4.1-mm profile drill had a strong simple linear correlation with the insertion torque of the implants, and the lateral resistance had a moderate linear correlation with the insertion torque. The contributions of these 6 variables to the implant torque, among which the vertical resistance of the twist drill and the pilot drill ranked first and second, were comparable. Adjustments to the strategy of site preparation according to the vertical resistance of the pilot drill achieved appropriate insertion torque (P<.001). CONCLUSIONS: The force feedback of the autonomous dental implant robot was significantly correlated with the insertion torque of implants, which may fit an interpretable mathematical model, allowing dental implants to be placed with predictable primary stability.

Trends and Projection of the Incidence of Active Pulmonary Tuberculosis in Southwestern China: Age-Period-Cohort Analysis.

BACKGROUND: The control of pulmonary tuberculosis (PTB) is critical for achieving the vision of World Health Organization's End TB goal. OBJECTIVE: This study analyzes the temporal trends in PTB incidence associated with age, period, and birth cohorts from 2006 to 2020 in Yunnan, China; projects the PTB burden till 2030; and explores the drivers of PTB incidence. METHODS: The aggregated PTB incidence rates between 2005 and 2020 were obtained from the National Notifiable Disease Reporting System. We used the age-period-cohort model to evaluate the age, period, and cohort effects on PTB incidence. We applied the Bayesian age-period-cohort model to project future PTB incidence from 2021 to 2030. We applied the decomposition algorithm to attribute the incidence trends to population aging, population growth, and age-specific changes from 2006 to 2030. RESULTS: From 2006 to 2020, the PTB incidence in Yunnan was relatively stable, although the absolute number showed an increase. The net drift was -1.56% (95% CI -2.41% to -0.70%). An M-shaped bimodal local drift and a longitudinal age curve were observed. The overall local drift was below zero for most age groups except for the age groups of 15-19 years (2.37%, 95% CI -0.28% to 5.09%) and 50-54 years (0.41%, 95% CI -1.78% to 2.64%). The highest risk of PTB incidence was observed in the age group of 65-69 years, and another peak was observed in the age group of 20-24 years. Downward trends were observed for both period and cohort effects, but the cohort effect trends were uneven. A higher risk was observed for the birth cohorts of 1961-1970 (rate ratio [RR]1961-1965=1.10, 95% CI 0.88-1.38; RR1966-1970=1.11, 95% CI 0.92-1.37) and 2001-2010 (RR2001-2005=0.92, 95% CI 0.63-1.34; RR2006-2010=0.84, 95% CI 0.45-1.58) than for the adjacent cohorts. The Bayesian age-period-cohort model projected that PTB incidence will continually increase from 2021 to 2030 and that PTB incidence in 2030 will be 2.28 times higher than that in 2006. The age-specific change was the leading cause for the growing PTB disease burden. CONCLUSIONS: Although there are several levels and measures for PTB control, the disease burden is likely to increase in the future. To bridge the gap of TB-free vision, our study suggests that public health policies be put in place soon, including large-scale active case-finding, priority prevention policies for high-risk older adult and young adult populations, and reduction of possible grandparent-grandchildren transmission patterns.

Changing trend analysis on early detection of rifampicin resistant tuberculosis patients in southwestern area of China, 2016-2020.

BACKGROUND: There were no data about prevention and control status of RR-TB in a poor area with high burden of TB in China. In order to develop evidence-based RR-TB response strategies and improve enrollment of RR-TB patients in Yunnan province, China, this study was aimed at analyzing the changing trends in the detection and enrollment of RR-TB patients and examining the factors that may have implication on enrollment in treatment. METHODS: Data, which includes demographics, screening and testing, and treatment enrollment, was collected from the TB Management Information System. Retrospective data analysis and factors analysis were applied. Descriptive statistics, Chi-square test, Rank sum test and logistic regression analysis were used. RESULTS: From 2016 and 2018, the province had been challenged by low levels of screening, detection and enrollment of RR-TB. During the period between 2019 and 2020, a comprehensive model of RR-TB prevention and control was established in Yunnan, characterized by a robust patient-centered approach for RR-TB care and multiple, targeted interventions through the cascade of care from detection to treatment. In 2020, 93.8% of the bacteriologically positive TB patients were screened for RR-TB, which had been significantly increased by 146.9% from 38.0% in 2016. The interval from initial consultation at RR-TB facility to diagnosis (inter-quartile range) was reduced from 29.5 (1-118) days in 2016 to 0 (0-7) days in 2020. Despite the increasing rates of enrollment of RR-TB patients over the years, non-enrollment of those detected was still high (32.3%) in 2020. The main reasons for non-enrollment identified were refusal of treatment due to financial difficulties, loss to follow-up or death before starting treatment. Multivariate analysis showed that the elderly patients aged 65 or above (OR = 2.7, CI: 1.997-3.614), new patients (OR = 0.7, CI: 0.607-0.867), conventional DST used for confirmatory diagnosis of RR-TB (OR = 1.9, CI: 1.620-2.344) and diagnosis of RR-TB being conducted by the RR-TB care facilities at the prefecture and municipal level (OR = 4.4, CI: 3.608-5.250) have implications on RR-TB non-enrollment. CONCLUSIONS: As a comprehensive RR-TB model was implemented in Yunnan with scaled up use of molecular test for rapid detection of RR-TB, initial screening of RR-TB were decentralized to the county- and district-level to strengthen rapid, early detection of RR-TB, achieving a higher coverage of screening in the end. However, there remains a major gap in enrollment of RR-TB. The main barriers include: limited knowledge and awareness of RR-TB and financial burdens among patients, delayed diagnosis, loss to follow-up, difficulties in self care and travel for elderly patients, and limited capacity of clinical management at the lower-level RR-TB care facilities. The situation of the RR-TB epidemic in Yunnan could be improved and contained as soon as possible by continuous strengthening of the comprehensive, patient-centered model with targeted interventions coordinated through multi-sectoral engagement to improve enrollment of RR-TB patients.

Uncovering the Impact of Control Strategies on the Transmission Pattern of SARS-CoV-2 - Ruili City, Yunnan Province, China, February-March 2022.

Introduction: The implementation of public health and social measures (PHSMs) was an effective option for controlling coronavirus disease 2019 (COVID-19). However, evidence is needed to evaluate these PHSMs' effects on the recently emerged variant Omicron. Methods: This study investigated variant Omicron BA.2's outbreak in Ruili City, Yunnan Province, China. The disease transmission dynamics, spatiotemporal interactions, and transmission networks were analyzed to illustrate the effect of PHSM strategies on Omicron spread. Results: A total of 387 cases were related to the outbreak. The time-varying reproduction number was synchronized with PHSM strategies. Spatiotemporal clustering strength presented heterogeneity and hotspots. Restricted strategies suppressed temporal and spatial relative risk compared with routine and upgraded strategies. The transmission network presented a steeper degree distribution and a heavier tail under upgraded strategies. Phase transformation and distinctive transmission patterns were observed from strategy-stratified subnetworks. Conclusions: The tightened response strategy contained reproduction of the virus, suppressed spatiotemporal clustering, and reshaped the networks of COVID-19 Omicron variant transmission. As such, PHSMs against Omicron are likely to benefit future responses as well.

Development and Application of a Multidrug-Resistant Tuberculosis Case Management System - Yunnan Province, China, 2017-2020.

Introduction: Treatment and case management of multidrug-resistant tuberculosis (MDR-TB) is a significant challenge in tuberculosis (TB) control and prevention. This pilot study aims to apply and test a new electronic information system in order to help bolster case management of MDR-TB. Methods: The MDR-TB Case Management System (CMS) was developed and piloted in the Yunnan Tuberculosis Clinical Center (TCC) in 2017. Next, 5 sites in Yunnan were randomly selected and sampled as pilots in 2018. The real-time regular follow-up rate (RFUR) was calculated for pilot sites. Loss to follow-up (LTFU) rates of MDR-TB treatment cohorts between pilot and non-pilot sites were compared by a chi-square test. LTFU for MDR-TB treatment cohorts was then assessed by univariate and multivariate binary logistic regression. Results: The average regular follow-up rate was 90.7% in TCC and 73.7% in five other pilot sites of Yunnan Province respectively. The average LTFU rate for pilot sites (9.0%) was lower than non-pilot sites (20.6%, P<0.01). The risk of LTFU during MDR-TB treatment reduced 61.7% in CMS pilot cases (adjusted odds ratio: 0.38, 95% confidence interval: 0.23-0.60) compared with non-pilot cases. Conclusions: As a significant supplement to the Tuberculosis Information Management System, the CMS strengthened the collection, analysis, and utilization of strategic information for MDR-TB cases. The system improved case management by embedding it as a tool of the Comprehensive Supportive Care service model.

Predicting the risk of active pulmonary tuberculosis in people living with HIV: development and validation of a nomogram.

BACKGROUND: Diagnosis of pulmonary tuberculosis (PTB) among people living with HIV (PLHIV) was challenging. The study aimed to develop and validated a simple, convenient screening model for prioritizing TB among PLHIV. METHODS: The study included eligible adult PLHIV participants who attended health care in Yunnan, China, from January 2016 to July 2019. Participants included before June 2018 were in the primary set; others were in the independent validation set. The research applied the least absolute shrinkage and selection operator regression to identify predictors associated with bacteriological confirmed PTB. The TB nomogram was developed by multivariate logistic regression. The C-index, receiver operating characteristic curve (ROC), the Hosmer-Lemeshow goodness of fit test (H-L), and the calibration curves were applied to evaluate and calibrate the nomogram. The developed nomogram was validated in the validation set. The clinical usefulness was assessed by cutoff analysis and decision curve analysis in the primary set. RESULT: The study enrolled 766 PLHIV, of which 507 were in the primary set and 259 in the validation set, 21.5% and 14.3% individuals were confirmed PTB in two sets, respectively. The final nomogram included 5 predictors: current CD 4 cell count, the number of WHO screen tool, previous TB history, pulmonary cavity, and smoking status (p < 0.05). The C-statistic was 0.72 (95% CI 0.66-0.77) in primary set and 0.68 (95% CI 0.58-0.75) in validation set, ROC performed better than other models. The nomogram calibration was good (H-L χ2 = 8.14, p = 0.15). The area under the decision curve (0.025) outperformed the existing models. The optimal cutoff for screening TB among PLHIV was the score of 100 (sensitivity = 0.93, specificity = 0.35). CONCLUSION: The study developed and validated a discriminative TB nomogram among PLHIV in the moderate prevalence of TB and HIV. The easy-to-use and straightforward nomogram would be beneficial for clinical practice and rapid risk screening in resource-limited settings.

Dose-response relationship between body mass index and tuberculosis in China: a population-based cohort study.

OBJECTIVES: This study aimed to describe and quantify the relationship between body mass index (BMI) and tuberculosis (TB) incidence. DESIGN: A population-based prospective cohort study. SETTING: Ten randomly selected communities in the southwestern mountainous region of China. PARTICIPANTS: Participants who had resided in study sites before screening for at least 6 months were eligible. Those who refused to participate or were temporary residents (who resided less than 6 months during three waves of screening) were excluded. The present research included 26 022 participants aged over 15 years for analyses. INTERVENTIONS: The cohort study conducted three rounds of TB screening from 2013 to 2015. Face-to-face surveys for participants were carried out. TB symptoms positivity suspects underwent chest X-ray and sputum smear test for diagnosis. PRIMARY OUTCOME MEASURES: The study outcome was the diagnosed active TB in the second and third rounds of screening. RESULTS: During the follow-up of 2.25 years, 43 cases developed TB in 44 574.4 person-years. The negative log-linear relationship between BMI and TB incidence was fitted (adjusted R2 =0.76). Overweight or obese was associated with a lower risk of TB compared with normal weight (adjusted HR (aHR) 0.34, 95% CI 0.14 to 0.82). The inverse log-linear associations between continuous BMI and individual TB risk were evaluated. In subgroup analysis, the risk of TB reduced 78% in overweight or obese women (aHR 0.22, 95% CI 0.05 to 0.97), and a 64% reduction in the elderly (aHR 0.36, 95% CI 0.12 to 1.00) compared with those with normal weight, respectively. CONCLUSIONS: The study provided evidence for a negative association between BMI and TB development in Chinese adults. It suggests the inverse dose-response relationship between BMI and TB incidence, and implies an optimal cut-off point of BMI for screening strategy.

Correction to: Role of community-based active case finding in screening tuberculosis in Yunnan province of China.

In the original publication of this article [1] we noticed the Fig. 4 was incorrect. The correct Fig. 4 is as below.

The characteristics of spatial-temporal distribution and cluster of tuberculosis in Yunnan Province, China, 2005-2018.

BACKGROUND: Tuberculosis (TB) makes a big challenge to public health, especially in high TB burden counties of China and Greater Mekong Subregion (GMS). The aim of this study was to identify the spatial-temporal dynamic process and high-risk region of notified pulmonary tuberculosis (PTB), sputum smear-positive tuberculosis (SSP-TB) and sputum smear-negative tuberculosis (SSN-TB) cases in Yunnan, the south-western of China between years of 2005 to 2018. Meanwhile, to evaluate the similarity of prevalence pattern for TB among GMS. METHODS: Data for notified PTB were extracted from the China Information System for Disease Control and Prevention (CISDCP) correspond to population information in 129 counties of Yunnan between 2005 to 2018. Seasonally adjusted time series defined the trend cycle and seasonality of PTB prevalence. Kulldorff's space-time scan statistics was applied to identify temporal, spatial and spatial-temporal PTB prevalence clusters at county-level of Yunnan. Pearson correlation coefficient and hierarchical clustering were applied to define the similarity of TB prevalence among borders with GMS. RESULT: There were a total of 381,855 notified PTB cases in Yunnan, and the average prevalence was 59.1 per 100,000 population between 2005 to 2018. A declined long-term trend with seasonality of a peak in spring and a trough in winter for PTB was observed. Spatial-temporal scan statistics detected the significant clusters of PTB prevalence, the most likely cluster concentrated in the northeastern angle of Yunnan between 2011 to 2015 (RR = 2.6, P < 0.01), though the most recent cluster for PTB and spatial cluster for SSP-TB was in borders with GMS. There were six potential TB prevalence patterns among GMS. CONCLUSION: This study detected aggregated time interval and regions for PTB, SSP-TB, and SSN-TB at county-level of Yunnan province. Similarity prevalence pattern was found in borders and GMS. The localized prevention strategy should focus on cross-boundary transmission and SSN-TB control.

Role of community-based active case finding in screening tuberculosis in Yunnan province of China.

BACKGROUND: The barriers to access diagnosis and receive treatment, in addition to insufficient case identification and reporting, lead to tuberculosis (TB) spreads in communities, especially among hard-to-reach populations. This study evaluated a community-based active case finding (ACF) strategy for the detection of tuberculosis cases among high-risk groups and general population in China between 2013 and 2015. METHODS: This retrospective cohort study conducted an ACF in ten communities of Dongchuan County, located in northeast Yunnan Province between 2013 and 2015; and compared to 136 communities that had passive case finding (PCF). The algorithm for ACF was: 1) screen for TB symptoms among community enrolled residents by home visits, 2) those with positive symptoms along with defined high-risk groups underwent chest X-ray (CXR), followed by sputum microscopy confirmation. TB incidence proportion and the number needed to screen (NNS) to detect one case were calculated to evaluate the ACF strategy compared to PCF, chi-square test was applied to compare the incidence proportion of TB cases' demography and the characteristics for detected cases under different strategies. Thereafter, the incidence rate ratio (IRR) and multiple Fisher's exact test were applied to compare the incidence proportion between general population and high-risk groups. Patient and diagnostic delays for ACF and PCF were compared by Wilcoxon rank sum test. RESULTS: A total of 97 521 enrolled residents were visited with the ACF cumulatively, 12.3% were defined as high-risk groups or had TB symptoms. Sixty-six new TB patients were detected by ACF. There was no significant difference between the cumulative TB incidence proportion for ACF (67.7/100000 population) and the prevalence for PCF (62.6/100000 population) during 2013 to 2015, though the incidence proportion in ACF communities decreased after three rounds active screening, concurrent with the remained stable prevalence in PCF communities. The cumulative NNS were 34, 39 and 29 in HIV/AIDS infected individuals, people with positive TB symptoms and history of previous TB, respectively, compared to 1478 in the general population. The median patient delay under ACF was 1 day (Interquartile range, IQR: 0-27) compared to PCF with 30 days (IQR: 14-61). CONCLUSIONS: This study confirmed that massive ACF was not effective in general population in a moderate TB prevalence setting. The priority should be the definition and targeting of high-risk groups in the community before the screening process is launched. The shorter time interval of ACF between TB symptoms onset and linkage to healthcare service may decrease the risk of TB community transmission. Furthermore, integrated ACF strategy in the National Project of Basic Public Health Service may have long term public health impact.

Prescription practice of anti-tuberculosis drugs in Yunnan, China: A clinical audit.

OBJECTIVES: China has a high burden of drug-resistant tuberculosis (TB). As irrational use and inadequate dosing of anti-TB drugs may contribute to the epidemic of drug-resistant TB, we assessed the drug types and dosages prescribed in the treatment of TB cases in a representative sample of health care facilities in Yunnan. METHODS: We applied multistage cluster sampling using probability proportion to size to select 28 counties in Yunnan. Consecutive pulmonary TB patients were enrolled from either the TB centers of Yunnan Center of Disease Control or designated TB hospitals. Outcomes of interest included the regimen used in the treatment of new and retreatment TB patients; and the proportion of patients treated with adequate dosing of anti-TB drugs. Furthermore, we assess whether there has been reduction in the use of fluoroquinolone and second line injectables in Tuberculosis Clinical Centre (TCC) after the training activity in late 2012. RESULTS: Of 2390 TB patients enrolled, 582 (24.4%) were prescribed second line anti-TB drugs (18.0% in new cases and 60.9% in retreatment cases); 363(15.2%) prescribed a fluoroquinolone. General hospitals (adjusted odds ratio (adjOR) 1.97, 95% confidence interval (CI) 1.47-2.66), retreatment TB cases (adjOR 4.75, 95% CI 3.59-6.27), smear positive cases (adjOR 1.69, 95% CI 1.22-2.33), and extrapulmonary TB (adjOR 2.59, 95% CI 1.66-4.03) were significantly associated with the use of fluoroquinolones. The proportion of patients treated with fluoroquinolones decreased from 41.4% before 2013 to 13.5% after 2013 (adjOR 0.19, 95% CI 0.12-0.28) in TCC. The proportion of patients with correct, under and over dosages of isoniazid was 88.2%, 1.5%, and 10.4%, respectively; of rifampicin was 50.2%, 46.8%, and 2.9%; of pyrazinamide was 67.6%, 31.7% and 0.7%; and of ethambutol was 41.4%, 57.5%, and 1.0%. CONCLUSIONS: The prescribing practice of anti-TB drugs was not standardized, findings with significant programmatic implication.

Screening of patients with diabetes mellitus for tuberculosis in community health settings in China.

OBJECTIVE: To assess the feasibility and results of screening of patients with DM for TB in routine community health services in China. METHOD: Agreement on how to screen patients with DM for TB and monitor and record the results was obtained at a stakeholders meeting. Subsequent training was carried out for staff at 10 community health centres, with activities implemented from June 2013 to April 2014. Patients with DM were screened for TB at each clinical visit using a symptom-based enquiry, and those positive to any symptom were referred to the TB clinic for TB investigation. RESULTS: A total of 2942 patients with DM visited these ten clinics. All patients received at least one screening for TB. Two patients were identified as already known to have TB. In total, 278 (9.5% of those screened) who had positive TB symptoms were referred for TB investigations and 209 arrived at the TB centre or underwent a chest radiograph for TB investigation. One patient (0.5% of those investigated) was newly diagnosed with active TB and was started on anti-TB treatment. The TB case notification rate of those screened was 102/100,000. CONCLUSION: This pilot project shows it is feasible to carry out TB screening among patients with DM in community settings, but further work is needed to better characterise patients with DM at higher risk of TB. This may require a more targeted approach focused on high-risk groups such as those with untreated DM or poorly controlled hyperglycaemia.

AC133 expression associated with poor prognosis in stage II colorectal cancer.

Identification of high-risk prognostic markers for stage II colorectal cancer (CRC) is currently a big challenge. CD133 is one of the most commonly used CRC stem cell markers. However, its specificity is controversial. Recent studies have demonstrated that the AC133 epitope of CD133, not the CD133 protein, is responsible for cancer stem cell identification. The aim of this study was to investigate the clinical significance of AC133 expression in stage II CRC. Two antibodies against CD133, including AC133 and Ab19898, were compared for their expression characteristics. AC133 was chosen for further immunohistochemical assessment on 176 stage II CRC primary tumors with at least 12 examined lymph nodes. The cutoff value for positive rate of AC133 expression was determined by ROC curve analysis. AC133 was analyzed for correlations with clinicopathological and prognostic parameters. The results indicated that AC133 was negative in adjacent noncancerous colorectal mucosa while positive in 116 cases (65.9 %) of primary tumors. AC133 expression was significantly correlated with preoperative serum carcinoembryonic antigen level (p = 0.006) and tumor differentiation grade (p = 0.019). Furthermore, high AC133 expression was identified as a significant predictor for poor disease-free survival and overall survival at both univariate (p = 0.009, 0.013, respectively) and multivariate levels (p = 0.022, 0.026, respectively). Our data suggest that AC133 is an independent adverse prognostic factor and a potential marker for survival classification in stage II CRC patients.

Trends in the survival of patients with nasopharyngeal carcinoma between 1976 and 2005 in Sihui, China: a population-based study.

Both the incidence and mortality of nasopharyngeal carcinoma(NPC) have decreased in Hong Kong and Taiwan but not in mainland China. The goal of this study was to analyze trends in NPC patient survival between 1976 and 2005 in Sihui, an area of mainland China with a population at high risk for NPC. A total of 1,761 patients diagnosed with NPC between 1976 and 2005 according to the records of Sihui Cancer Registry were followed to the end of 2006. We determined their observed and relative survival rates and used Cox proportional hazards regression analysis to predict prognosis. Our results showed that the 5-year and 10-year observed survival rates of NPC patients in Sihui were 50.5% and 36.9%, respectively, and the median survival time was 5.1 years. The 5-year observed survival rate of NPC patients diagnosed after 2000 was 69.8%, significantly higher than that of patients diagnosed between 1976 and 1985 (42.5%; P < 0.001, relative risk = 0.28). Similarly, the 5-year relative survival rate was 84.8% between 2000 and 2005 but 51.8% between 1976 and 1985. Besides date of diagnosis, other prognostic factors included patient sex and age and NPC clinical stage and histologic type. The relative risks of death from NPC were 0.76 [95% confidence interval (CI): 0.65-0.90] for female comparing to male and 1.28 (95% CI: 1.00-1.64) for WHO type I comparing to WHO types II and III. For the eldest age group and the latest clinical stage group, the relative risks were 2.22 (95% CI: 1.73-2.84) and 3.41 (95% CI: 2.34-4.49), respectively. Our results indicate that the survival of NPC patients in Sihui has significantly increased in recent years and this increase is not influenced by patient's sex, age, histologic type, and clinical stage. A reduction in mortality rate is expected in coming years.

Establishment of VCA and EBNA1 IgA-based combination by enzyme-linked immunosorbent assay as preferred screening method for nasopharyngeal carcinoma: a two-stage design with a preliminary performance study and a mass screening in southern China.

A two-stage study was conducted in southern China to determine and validate an optimal combination of Epstein-Barr virus (EBV)-related seromarkers for nasopharyngeal carcinoma (NPC) screening. In the first stage, six seromarkers [VCA-IgA, EA-IgA, Epstein-Barr virus nuclear antigen 1 (EBNA1-IgA), EBNA1-IgG, Zta-IgA and Rta-IgG] were detected by enzyme-linked immunosorbent assay (ELISA) and two traditional NPC screening seromarkers (VCA-IgA and EA-IgA) were detected by immunofluorescence assay (IFA) in serum samples from 191 NPC patients and 337 controls. An optimal combination of seromarkers for NPC diagnosis was selected using logistic regression models. Results showed that the diagnostic performances of VCA-IgA and EA-IgA tested by ELISA were superior to the performances of the same seromarkers by IFA. VCA-IgA combined with EBNA1-IgA by ELISA was identified as the optimal combination, with an area under the receiver operating characteristic (ROC) curve (AUC) up to 0.97, a sensitivity of 95.3% and a specificity of 94.1% for classification of NPCs vs. controls. In the second stage, 5,481 participants aged 30-59 years and without clinical evidence of NPC were recruited into a population-based NPC screening program from May 2008 to February 2009 in Sihui City, China. Their sera were tested simultaneously by both the new and the traditional screening schemes and eight early stage NPC patients were subsequently histopathologically confirmed. The traditional and the new screening schemes had comparable specificity (estimated as 98.5%), but the sensitivity of the new scheme (75.0%) was significantly higher than that of the traditional one (25.0%). The combination of VCA-IgA and EBNA1-IgA by ELISA outperforms the traditional NPC screening scheme and could become the preferred serodiagnostic strategy for NPC screening in high-incidence areas.

Genome-wide analysis reveals the active roles of keratinocytes in oral mucosal adaptive immune response.

To elucidate the roles of oral keratinocytes in the adaptive immune response of oral mucosa, global gene expression analysis was performed by microarray technique and integrating computational methods, including hierarchical clustering, biological process Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, self-organizing maps (SOMs) and biological association network analysis (BAN). Raw data from microarray experiments were uploaded to the Gene Expression Omnibus Database, http://www.ncbi.nlm.nih.gov/geo/ (GEO accession GSE28035). We identified 666 differentially expressed genes in the early stage (48 h) and 993 in the late stage (96 h) of the oral mucosal adaptive immune response. The analysis revealed that oral keratinocytes exerted diverse biological functions in different stages of immune response. Specifically, in 48 h the differentially expressed genes encompassed an array of biological ontology associated with immune response, such as antigen processing and presentation, and positive regulation of T-cell-mediated cytotoxicity. Several pathways which have been reported to be critical in inflammation, including mitogen-activated protein kinase pathway, were activated. Furthermore, after BAN construction, some putative hub genes and networks such as interleukin-1α and its subnetwork were recognized. Taken together, these results give substantial evidence to support the active roles of keratinocytes in the oral mucosal adaptive immune response.