Comparison of yield and relative costs of different screening algorithms for tuberculosis in active case-finding: a cross-section study.

BACKGROUND: Part of tuberculosis (TB) patients were missed if symptomatic screening was based on the main TB likely symptoms. This study conducted to compare the yield and relative costs of different TB screening algorithms in active case-finding in the whole population in China. METHODS: The study population was screened based on the TB likely symptoms through a face-to-face interview in selected 27 communities from 10 counties of 10 provinces in China. If the individuals had any of the enhanced TB likely symptoms, both chest X-ray and sputum tests were carried out for them furtherly. We used the McNemar test to analyze the difference in TB detection among four algorithms in active case-finding. Of four algorithms, two were from WHO recommendations including 1a/1c, one from China National Tuberculosis Program, and one from this study with the enhanced TB likely symptoms. Furthermore, a two-way ANOVA analysis was performed to analyze the cost difference in the performance of active case-finding adjusted by different demographic and health characteristics among different algorithms. RESULTS: Algorithm with the enhanced TB likely symptoms defined in this study could increase the yield of TB detection in active case-finding, compared with algorithms recommended by WHO (p < 0.01, Kappa 95% CI: 0. 93-0.99) and China NTP (p = 0.03, Kappa 95% CI: 0.96-1.00). There was a significant difference in the total costs among different three algorithms WHO 1c/2/3 (F = 59.13, p < 0.01). No significant difference in the average costs for one active TB case screened and diagnosed through the process among Algorithms 1c/2/3 was evident (F = 2.78, p = 0.07). The average costs for one bacteriological positive case through algorithm WHO 1a was about two times as much as the costs for one active TB case through algorithms WHO 1c/2/3. CONCLUSIONS: Active case-finding based on the enhanced symptom screening is meaningful for TB case-finding and it could identify more active TB cases in time. The findings indicated that this enhanced screening approach cost more compared to algorithms recommend by WHO and China NTP, but the increased yield resulted in comparative costs per patient. And it cost much more that only smear/bacteriological-positive TB cases are screened in active case-finding.

Southern East Asian origin and coexpansion of Mycobacterium tuberculosis Beijing family with Han Chinese.

The Beijing family is the most successful genotype of Mycobacterium tuberculosis and responsible for more than a quarter of the global tuberculosis epidemic. As the predominant genotype in East Asia, the Beijing family has been emerging in various areas of the world and is often associated with disease outbreaks and antibiotic resistance. Revealing the origin and historical dissemination of this strain family is important for understanding its current global success. Here we characterized the global diversity of this family based on whole-genome sequences of 358 Beijing strains. We show that the Beijing strains endemic in East Asia are genetically diverse, whereas the globally emerging strains mostly belong to a more homogenous subtype known as "modern" Beijing. Phylogeographic and coalescent analyses indicate that the Beijing family most likely emerged around 30,000 y ago in southern East Asia, and accompanied the early colonization by modern humans in this area. By combining the genomic data and genotyping result of 1,793 strains from across China, we found the "modern" Beijing sublineage experienced massive expansions in northern China during the Neolithic era and subsequently spread to other regions following the migration of Han Chinese. Our results support a parallel evolution of the Beijing family and modern humans in East Asia. The dominance of the "modern" Beijing sublineage in East Asia and its recent global emergence are most likely driven by its hypervirulence, which might reflect adaption to increased human population densities linked to the agricultural transition in northern China.

Later emergence of acquired drug resistance and its effect on treatment outcome in patients treated with Standard Short-Course Chemotherapy for tuberculosis.

BACKGROUNDS: The failure of current Standard Short-Course Chemotherapy (SCC) in new and previously treated cases with tuberculosis (TB) was mainly due to drug resistance development. But little is known on the characteristics of acquired drug resistant TB during SCC and its correlation with SCC failure. The objective of the study is to explore the traits of acquired drug resistant TB emergence and evaluate their impacts on treatment outcomes. METHODS: A prospective observational study was performed on newly admitted smear positive pulmonary TB (PTB) cases without drug resistance pretreatment treated with SCC under China's National TB Control Program (NTP) condition from 2008 to 2010. Enrolled cases were followed up through sputum smear, culture and drug susceptibility testing (DST) at the end of 1, 2, and 5 months after treatment initiation. The effect factors of early or late emergence of acquired drug resistant TB , such as acquired drug resistance patterns, the number of acquired resistant drugs and previous treatment history were investigated by multivariate logistic regression; and the impact of acquired drug resistant TB emergence on treatment failure were further evaluated. RESULTS: Among 1671 enrolled new and previously treated cases with SCC, 62 (3.7%) acquired different patterns of drug resistant TB at early period within 2 months or later around 3-5 months of treatment. Previously treated cases were more likely to develop acquired multi-drug resistant TB (MDR-TB) (OR, 3.8; 95%CI, 1.4-10.4; P = 0.015). Additionally, acquired MDR-TB cases were more likely to emerge at later period around 3-5 months after treatment starting than that of non-MDR-TB mainly appeared within 2 months (OR, 8.3; 95%CI, 1.7-39.9; P = 0.008). Treatment failure was associated with late acquired drug resistant TB emergence (OR, 25.7; 95%CI, 4.3-153.4; P < 0.001) with the reference of early acquired drug resistant TB emergence. CONCLUSIONS: This study demonstrates that later development of acquired drug resistant TB during SCC is liable to suffer treatment failure and acquired MDR-TB pattern may be one of the possible causes.

Transmission of Mycobacterium tuberculosis in China: a population-based molecular epidemiologic study.

BACKGROUND: Understanding the transmission of Mycobacterium tuberculosis is essential for the development of efficient tuberculosis control strategies. China has the second-largest tuberculosis burden in the world. Recent transmission and infection with M. tuberculosis, particularly drug-resistant strains, may account for many new tuberculosis cases. METHODS: We performed a population-based molecular epidemiologic study of pulmonary tuberculosis in China during 1 July 2009 to 30 June 2012. We defined clusters as cases with identical variable number tandem repeat genotype patterns and identified the risk factors associated with clustering, by logistic regression. Relative transmission rates were estimated by the sputum smear status and drug susceptibility status of tuberculosis patients. RESULTS: Among 2274 culture-positive tuberculosis patients with genotyped isolates, there were 705 (31.0%) tuberculosis patients in 287 clusters. Multidrug-resistant (MDR) tuberculosis (adjusted odds ratio [aOR], 1.86; 95% confidence interval [CI], 1.25-2.63) and infection with a Beijing family strain (aOR, 1.56; 95% CI, 1.23-2.96) were associated with clustering. Eighty-four of 280 (30.0%) clusters had a putative source case that was sputum smear negative, and 30.6% of their secondary cases were attributed to transmission by sputum smear-negative patients. The relative transmission rate for sputum smear negative compared with sputum smear-positive patients was 0.89 (95% CI, .68-1.10), and was 1.51 (95% CI, 1.00-2.24) for MDR tuberculosis vs drug-susceptible tuberculosis. CONCLUSIONS: Recent transmission of M. tuberculosis, including MDR strains, contributes substantially to tuberculosis disease in China. Sputum smear-negative cases were responsible for at least 30% of the secondary cases. Interventions to reduce the transmission of M. tuberculosis should be implemented in China.

Preventive use of hepatoprotectors yields limited efficacy on the liver toxicity of anti-tuberculosis agents in a large cohort of Chinese patients.

BACKGROUND AND AIMS: We aimed to explore the effectiveness of preventive usage of hepatoprotectors in patients with tuberculosis (TB) receiving anti-TB treatment. METHODS: With stratified cluster sampling strategy, a prospective cohort with 4488 sputum smears positive pulmonary TB patients was established from 52 counties of four regions in China. During anti-TB treatment, prescriptions of hepatoprotectors were documented in detail, and liver enzymes were routinely monitored. Anti-TB drug-induced liver injury (ATLI) was assessed based on liver enzymes following the criteria of American Thoracic Society. The incidence of ATLI between the preventive usage group and reference group was compared by propensity score adjusted Cox proportional hazard analysis. Preexisting diseases, history of liver disease, hepatitis B surface antigen status, primary/re-treatment of TB, income per year, and liver enzymes before anti-TB treatment were included in the propensity score model. RESULTS: After 6-9 months of follow-up and monitoring, 4304 patients sustained in our cohort. Two thousand seven hundred fifty-two (63.9%) patients preventively took hepatoprotectors with a median course of 183 days. Most frequently used drugs were Hu Gan Pian, silymarin, glucurone, and inosine. Two thousand one hundred forty-four (77.9%) patients took those drugs more than 6 months. Sixty-nine (2.4%) patients of preventive usage group and 37 (2.5%) of reference group experienced ATLI, respectively. Statistical significances were not found by propensity score analysis for the association between using hepatoprotectors (hazard ratio[HR] = 0.99, 95% confidence interval [CI]: 0.65-1.52), using hepatoprotectors in the whole course (HR = 0.94, 95% CI: 0.60-1.48), using Hu Gan Pians, silymarin, glucurone, and inosine with ATLI occurrence. CONCLUSIONS: No preventive effect of hepatoprotectors was observed in patients receiving anti-TB treatment.

Nanofibers with homogeneous heparin distribution and protracted release profile for vascular tissue engineering.

In clinic, controlling acute coagulation after small-diameter vessel grafts transplantation is considered a primary problem. The combination of heparin with high anticoagulant efficiency and polyurethane fiber with good compliance is a good choice for vascular materials. However, blending water-soluble heparin with fat-soluble poly (ester-ether-urethane) urea elastomer (PEEUU) uniformly and preparing nanofibers tubular grafts with uniform morphology is a huge challenge. In this research, we have compounded PEEUU with optimized constant concentration of heparin by homogeneous emulsion blending, then spun into the hybrid PEEUU/heparin nanofibers tubular graft (H-PHNF) for replacing rats' abdominal aorta in situ for comprehensive performance evaluation. The in vitro results demonstrated that H-PHNF was of uniform microstructure, moderate wettability, matched mechanical properties, reliable cytocompatibility, and strongest ability to promote endothelial growth. Replacement of resected abdominal artery with the H-PHNF in rat showed that the graft was capable of homogeneous hybrid heparin and significantly promoted the stabilization of vascular smooth muscle cells (VSMCs) as well as stabilizing the blood microenvironment. This research demonstrates the H-PHNF with substantial patency, indicating their potential for vascular tissue engineering.

Effect of scheduled monitoring of liver function during anti-Tuberculosis treatment in a retrospective cohort in China.

BACKGROUND: Data on effect of regular liver function monitoring during anti-TB treatment is limited in China. This study aimed to evaluate the effects of scheduled liver function monitoring on identification of asymptomatic liver damage and anti-TB treatment outcomes during anti-TB treatment. METHODS: A retrospective analysis was performed based on a national-level cohort study. A total of 273 patients developing liver dysfunction were divided into two groups, 111 patients who were diagnosed through scheduled liver function test within two months after initiation of anti-TB treatment formed scheduled monitoring group, others who were diagnosed due to developing symptoms formed passive detection group (n = 162). The two groups were compared through clinical features, prognosis of liver dysfunction and impact on anti-TB treatment using propensity score weighting analysis. RESULTS: 33.3% of 273 patients did not have any clinical symptoms, including 8 with severe hepatotoxicity. 1.8% in scheduled monitoring group and 11.1% in passive detection group required hospitalization (P = 0.004). Regarding the prognosis of liver dysfunction, most patients recovered, no death happened in scheduled monitoring group while 3 died in passive detection group. In terms of impact on anti-TB treatment, 35.1% in scheduled monitoring group and 56.8% in passive detection group changed their anti-TB treatment (P = 0.001). CONCLUSIONS: Scheduled monitoring is effective in identifying asymptomatic liver damage, reducing hospitalization rate and improving compliance of anti-TB treatment.

Prevalence, Incidence, and Characteristics of Tuberculosis Among Known Diabetes Patients - A Prospective Cohort Study in 10 Sites, 2013-2015.

What is already known about this topic?: The association of diabetes mellitus (DM) with both increased risk of tuberculosis (TB) and unfavorable treatment outcomes has been identified by many studies (1). However, epidemic data for TB cases in DM patients is absent in China. What is added by this report?: This current population-based prospective cohort study, conducted in ten counties located in eastern, central, and western China during 2013-2015, revealed a high prevalence and incidence of TB in known DM patients. Most TB cases were captured by active case-finding and a much higher presence of being asymptomatic among TB/DM patients was obtained. What are the implications for public health practice?: Active case-finding should be carried out in DM patients and populations at high risk for developing TB. A TB symptom screening-based case-finding strategy is not enough; chest radiography check should be done once a year for these patients.

Design and development of a tele-healthcare information system based on web services and HL7 standards.

Information and communication technologies progress rapidly and many novel applications have been developed in many domains of human life. In recent years, the demand for healthcare services has been growing because of the increase in the elderly population. Consequently, a number of healthcare institutions have focused on creating technologies to reduce extraneous work and improve the quality of service. In this study, an information platform for tele- healthcare services was implemented. The architecture of the platform included a web-based application server and client system. The client system was able to retrieve the blood pressure and glucose levels of a patient stored in measurement instruments through Bluetooth wireless transmission. The web application server assisted the staffs and clients in analyzing the health conditions of patients. In addition, the server provided face-to-face communications and instructions through remote video devices. The platform deployed a service-oriented architecture, which consisted of HL7 standard messages and web service components. The platform could transfer health records into HL7 standard clinical document architecture for data exchange with other organizations. The prototyping system was pretested and evaluated in a homecare department of hospital and a community management center for chronic disease monitoring. Based on the results of this study, this system is expected to improve the quality of healthcare services.

[The effect evaluation of a new tuberculosis management model in rural areas of Guangxi].

OBJECTIVE: To explore the effect of new model for tuberculosis (TB) control and management, and provide a scientific basis and justification for making TB control strategies in rural communities. METHODS: Among those townships with low TB service accessibility by the county TB control institute in Guangxi Xingye county (population of 679 thousands), four townships with total population of 152 518 and inconvenient transportation, were selected as the experimental group to conduct a new model research project.Based on the accessibility for community services, setting diagnosis and treatment management centers in township hospitals, employing family treatment supporters to supervise the treatment process. The TB cases of the base-line and the project expiration of the experimental group were 44 and 117. Meanwhile, three townships including Dapingshan, Longan and Gaofeng in the county with the similar condition and total population of 133 303 were selected as the control group. The control group conducted the provisions of national TB control program in the county TB clinic management. The TB cases of the base-line and the project expiration of the control group were 56 and 110. By double-direction comparison method, the effect of the new model was evaluated through TB patients detection, treatment outcomes and TB control management data. SPSS 13.0 statistical software was adopted and Chi-square test was used for analyzing technical data. RESULTS: After two-year project research implementation, in the experimental group the detection rate of new smear-positive TB patients increased from 16.39/100 000 (25/152 518) to 51.14/100 000 (78/152 518) (χ(2) = 27.281, P < 0.01), the cure rate of new smear-positive cases increased from 71.4% (15/21)to 91.1% (51/56) (χ(2) = 4.812, P < 0.05), and the completing treatment rate in newly diagnosed smear-negative cases improved from 23.5% (4/17)to 71.4% (15/21) (χ(2) = 8.622, P < 0.01); the loss rate of newly diagnosed smear-positive cases dropped from 23.8% (5/21) to 0.0% (0/56) (χ(2) = 10.608, P < 0.01), and the loss rate of newly diagnosed smear-negative cases decreased from 64.7% (11/17) to 4.8% (1/21) (χ(2) = 15.624, P < 0.01). Meanwhile, the cure rate of new smear-positive cases in the experimental group, 91.1% (51/56), was higher than the control group, 72.0% (36/50) (χ(2) = 6.531, P < 0.05). The loss rate of newly diagnosed smear-positive cases in the experimental group (0.0% (0/56)) was lower than the control group (16.0% (8/50)) (χ(2) = 7.534, P < 0.01). During the project implementation, in the experimental group the on time rate of taking medicine, 91.5% (107/117) and receiving medicine, 100.0% (117/117), the reexamining sputum ratio, 83.6% (98/117) were higher than that in the control group: 81.8% (90/110), 92.7% (102/110) and 64.5% (71/110). The differences were statistically significant (χ(2) = 4.589, 8.820 and 11.005, P < 0.05). CONCLUSION: The new management model had been proved effective. It can improve TB case detection and cure rates, reduce the loss rate of patients, and improve patient treatment and management conditions as well.

Prevalence and risk factors of active pulmonary tuberculosis among elderly people in China: a population based cross-sectional study.

BACKGROUND: The problem of population aging is a critical public health concern in modern China, and more tuberculosis (TB) control efforts are needed to reach elderly people at high priority. In this study, we aim to determine the prevalence and identify the risk factors of TB among elderly people in China. METHODS: A multistage cluster-sampled cross-sectional survey was conducted in 2013, and 27 clusters were selected from 10 counties of 10 provinces in China. All consenting participants greater than or equal to 65 years of age were screened for pulmonary TB with a chest X-ray (CXR) and a symptom questionnaire. Three sputum specimens for bacteriological examination by microscopy and culture were collected from those whose screening was positive. Prevalence was calculated, a multiple logistic regression model was performed to confirm the risk factors, and population attributable fraction (PAF) of each risk factor was calculated to indicate the public health significance. RESULTS: Of 38 888 eligible people from 27 clusters, 34 269 participants finished both questionnaire and physical examination. There were 193 active pulmonary TB cases, 62 of which were bacteriologically confirmed. The estimated prevalence of active pulmonary TB and bacteriologically confirmed TB in those 65 years of age and older was 563.19 per 100 000 (95% CI: 483.73-642.65) and 180.92 per 100 000 (95% CI: 135.89-225.96), respectively. Male sex, older age, living in rural areas, underweight, diabetes, close contact of pulmonary TB (PTB) and previous TB history are all risk factors for TB. The risk of TB increased with increasing age and decreasing body mass index (BMI) after adjusting for other factors, and there is a positive dose-response relationship. CONCLUSIONS: In China, active case finding (ACF) could be implemented among elderly people aged 65 and above with underweight, diabetes, close contact history and previous TB history as a priority, which will get significant yields and be cost-effective.

Adapting a generic tuberculosis control operational guideline and scaling it up in China: a qualitative case study.

BACKGROUND: The TB operational guideline (the deskguide) is a detailed action guide for county TB doctors aiming to improve the quality of DOTS, while the China national TB policy guide is a guide to TB control that is comprehensive but lacks operational usability for frontline TB doctors. This study reports the process of deskguide adaptation, its scale-up and lessons learnt for policy implications. METHODS: The deskguide was translated, reviewed, and revised in a working group process. Details of the eight adaptation steps are reported here. An operational study was embedded in the adaptation process. Two comparable prefectures were chosen as pilot and control sites in each of two participating provinces. In the pilot sites, the deskguide was used with the national policy guide in routine in-service training and supervisory trips; while in the control sites, only the national policy guide was used. In-depth interviews and focus groups were conducted with 16 county TB doctors, 16 township doctors, 17 village doctors, 63 TB patients and 57 patient family members. Following piloting, the deskguide was incorporated into the national TB guidelines for county TB dispensary use. RESULTS: Qualitative research identified that the deskguide was useful in the daily practice of county TB doctors. Patients in the pilot sites had a better knowledge of TB and better treatment support compared with those in the control sites. CONCLUSION: The adaptation process highlighted a number of general strategies to adapt generic guidelines into country specific ones: 1) local policy-makers and practitioners should have a leading role; 2) a systematic working process should be employed with capable focal persons; and 3) the guideline should be embedded within the current programmes so it is sustainable and replicable for further scale-up.

Drug Resistance in Newly Presenting and Previously Treated Tuberculosis Patients in Guangxi Province, People's Republic of China.

Drug-resistant Mycobacterium tuberculosis strains are a major threat to the control of tuberculosis (TB), but the prevalence of drug-resistant TB is still unknown in the southern ethnic region of China. A cluster-randomized sampling method was used to include the study population. Isolates were tested for resistance to 6 antituberculosis drugs, and genotyped to identify Beijing strains. Overall, 11.3% (139/1229) of new cases and 33.0% (126/382) of retreated cases had drug-resistant tuberculosis. Multiple previous TB treatment episodes and multiple treatment interruptions were risk factors for both drug-resistant and multidrug-resistant TB among retreated cases. A total of 53.2% of the patients were infected with a Beijing strain of M tuberculosis. Infection with a Beijing strain was significantly associated with drug resistance among new cases (odds ratio, 1.44; 95% CI, 1.01-2.07). Novel strategies to rapid diagnosis and effective treatment are urgently needed to prevent the development of drug resistance.

[Feature analysis on patients died from co-infection of Mycobacterium tuberculosis and human immunodeficiency virus in Guangxi, from 2007 to 2012].

OBJECTIVE: To understand the general feature of patients with Mycobacterium tuberculosis (MTB) and human immunodeficiency virus (HIV) co-infectious (TB/HIV) in Guangxi, from 2007 to 2012. METHODS: Information regarding individuals that the contributory causes of death were due to MTB infection among HIV as the underlying cause of death from the Vital Registration System, together with bacterium smear or culture results, onset of TB, time that TB was diagnosed and entered an Internet base TB surveillance system was collected and checked. Data including information on time of death, age, occupation, the underlying cause of death among TB patients, bacterium distribution, average age of death, interval from onset to death, percentage of TB/HIV co-infection patients among all the patients etc, were all analysed. RESULTS: 203 patients died from HIV associated with TB from the Guangxi Vital Registration System were identified between 2007 and 2012. The average percentage of TB/HIV co-infection cases accounted for 8.24% (ranging from 3.94% in 2007 to 13.27% in 2012) among all the deaths of HIV infection while it accounted for 9.90% (ranging from 2.56% to in 2007 to 26.88% in 2012) among patients with MTB infection in the same period. The average percentage of deaths from TB/HIV co-infection in 2010 and 2012 accounted for 10.66% (ranging from 8.83% to 13.27%)and 22.17% (ranging from 20.60% to 26.88%)among patients died of HIV and TB infection respectively. The male-female ratio was 4.21 for 1, with the average age of death as 44.65 (44.65 ± 15.52) years;median time from TB symptoms onset to diagnosis as 37 (mean 94.31, standard deviation 206.07) days, record as (94.31 ± 206.07); median time from diagnosis to death as 46 (165.22 ± 282.19) days, 54.68% TB/HIV patients died within two months of being diagnosed with TB and the median time from TB symptoms onset to death as 131 (257.68 ± 340.79) days. 16.26% of the TB/HIV cases were bacterium confirmed TB cases. CONCLUSION: Compare to those TB patients without HIV, less bacterium evidence was found in TB/HIV patients. High burden caused by HIV disease was seen if they were co-infected with TB. An increasing proportion of deaths was noticed among patients co-infected with HIV and TB in the last three years, suggesting that the coverage of antiretroviral therapy be scaled up together with the strengthening of the capability on early TB case-finding among people live with HIV.

Prevalence and predictors of HIV among Chinese tuberculosis patients by provider-initiated HIV testing and counselling (PITC): a multisite study in South Central of China.

BACKGROUND: Tuberculosis (TB) and HIV are two worldwide public health concerns. Co-infection of these two diseases has been considered to be a major obstacle for the global efforts in reaching the goals for the prevention of HIV and TB. METHOD: A comprehensive cross-sectional study was conducted to recruit TB patients in three provinces (Guangxi, Henan and Sichuan) of China between April 1 and September 30, 2010. RESULTS: A total of 1,032 consenting TB patients attended this survey during the study period. Among the participants, 3.30% were HIV positive; about one quarter had opportunistic infections. Nearly half of the participants were 50 years or older, the majority were male and about one third were from minority ethnic groups. After adjusting for site, gender and areas of residence (using the partial/selective Model 1), former commercial plasma donors (adjusted OR [aOR] = 33.71) and injecting drug users(aOR = 15.86) were found to have significantly higher risk of being HIV-positivity. In addition, having extramarital sexual relationship (aOR = 307.16), being engaged in commercial sex (aOR = 252.37), suffering from opportunistic infections in the past six months (aOR = 2.79), losing 10% or more of the body weight in the past six months (aOR = 5.90) and having abnormal chest X-ray findings (aOR = 20.40) were all significantly associated with HIV seropositivity (each p<0.05). CONCLUSIONS: HIV prevalence among TB patients was high in the study areas of China. To control the dual epidemic, intervention strategies targeting socio-demographic and behavioral factors associated with higher risk of TB-HIV co-infection are urgently called for.

Adverse reactions due to directly observed treatment strategy therapy in Chinese tuberculosis patients: a prospective study.

BACKGROUND: More than 1 million tuberculosis (TB) patients are receiving directly observed treatment strategy (DOTS) therapy in China every year. As to the profile of adverse drug reactions (ADRs) due to DOTS therapy, no consensus has been reached. There is no report regarding ADRs due to DOTS therapy with a large Chinese TB population. This study aimed to determine the incidence and prognosis of ADRs due to DOTS therapy, and to evaluate their impact on anti-TB treatment in China. METHODS: A prospective population-based cohort study was performed during 2007-2008. Sputum smear positive pulmonary TB patients who received DOTS therapy were included and followed up for six to nine months in 52 counties of four regions in China. The suspected ADRs were recorded and reviewed by Chinese State Food and Drug Administration. RESULTS: A total of 4304 TB patients were included in this study. 649 patients (15.08%) showed at least one ADR and 766 cases in total were detected. The incidence (count) of ADR based on affected organ was: liver dysfunction 6.34% (273), gastrointestinal disorders 3.74% (161), arthralgia 2.51% (108), allergic reactions 2.35% (101), neurological system disorders 2.04% (88), renal impairment 0.07% (3) and others 0.05% (2). Most cases of ADRs (95%) had a good clinical outcome, while two with hepatotoxicity and one with renal impairment died. Compared with patients without ADRs, patients with ADRs were more likely to have positive smear test results at the end of the intensive phase (adjusted OR, 2.00; 95%CI, 1.44-2.78) and unsuccessful anti-TB outcomes (adjusted OR, 2.58; 95%CI, 1.43-4.68). CONCLUSIONS: The incidence of ADRs due to DOTS therapy was 15.08%. Those ADRs had a substantial impact on TB control in China. This highlighted the importance of developing strategies to ameliorate ADRs both to improve the quality of patient care and to control TB safely.

Incidence, clinical features and impact on anti-tuberculosis treatment of anti-tuberculosis drug induced liver injury (ATLI) in China.

BACKGROUND: Anti-tuberculosis drug induced liver injury (ATLI) is emerging as a significant threat to tuberculosis control in China, though limited data is available about the burden of ATLI at population level. This study aimed to estimate the incidence of ATLI, to better understand its clinical features, and to evaluate its impact on anti-tuberculosis (TB) treatment in China. METHODOLOGY/PRINCIPAL FINDINGS: In a population-based prospective study, we monitored 4,304 TB patients receiving directly observed treatment strategy (DOTS) treatment, and found that 106 patients developed ATLI with a cumulative incidence of 2.55% (95% Confidence Interval [CI], 2.04%-3.06%). Nausea, vomiting and anorexia were the top three most frequently observed symptoms. There were 35 (33.02%) ATLI patients with no symptoms, including 8 with severe hepatotoxicity. Regarding the prognosis of ATLI, 84 cases (79.25%) recovered, 18 (16.98%) improved, 2 (1.89%) failed to respond to the treatment with continued elevation of serum alanine aminotransferase, and 2 (1.89%) died as result of ATLI. Of all the ATLI cases, 74 (69.81%) cases changed their anti-TB treatment, including 4 (3.77%) cases with medication administration change, 21 (19.81%) cases with drugs replacement, 54 (50.94%) cases with therapy interruption, and 12 (11.32%) cases who discontinued therapy. In terms of treatment outcomes, 53 (51.46%) cases had TB cured in time, 48 (46.60%) cases had therapy prolonged, and 2 (1.94%) cases died. Compared with non-ATLI patients, ATLI patients had a 9.25-fold (95%CI, 5.69-15.05) risk of unsuccessful anti-TB treatment outcomes and a 2.11-fold (95%CI, 1.23-3.60) risk of prolonged intensive treatment phase. CONCLUSIONS/SIGNIFICANCE: ATLI could considerably impact the outcomes of anti-TB treatment. Given the incidence of ATLI and the size of TB population in China, the negative impact is substantial. Therefore, more research and efforts are warranted in order to enhance the diagnosis and the prevention of ATLI.

Performance analysis of distributed and centralized models for electronic medical record exchanges.

Electronic medical record exchanges can save time and reduce cost by eliminating redundant data and typing errors. The major steps of record exchange consist of querying information from database, encoding data into messages, and sending and decoding messages. Three medical-record-exchange models were proposed in the past, including the distributed, centralized, and indexed models. In this paper, the queuing theory is applied to evaluate the performance of the three models. We estimate the service time for each queue of the CPU, database and network, and predict the response time, probable bottlenecks and system capacities of each model.