Solving Patient Allocation Problem during an Epidemic Dengue Fever Outbreak by Mathematical Modelling.

Dengue fever is a mosquito-borne disease that has rapidly spread throughout the last few decades. Most preventive mechanisms to deal with the disease focus on the eradication of the vector mosquito and vaccination campaigns. However, appropriate mechanisms of response are indispensable to face the consequent events when an outbreak takes place. This study applied single and multiple objective linear programming models to optimize the allocation of patients and additional resources during an epidemic dengue fever outbreak, minimizing the summation of the distance travelled by all patients. An empirical study was set in Ciudad del Este, Paraguay. Data provided by a privately run health insurance cooperative was used to verify the applicability of the models in this study. The results can be used by analysts and decision makers to solve patient allocation problems for providing essential medical care during an epidemic dengue fever outbreak.

[Clinical characteristics of and factors related to relapse in chronic hepatitis B patients after nucleoside analogues withdrawal].

OBJECTIVE: To investigate the clinical characteristics of and factors related to relapse in chronic hepatitis B (CHB) patients who had previously achieved cessation criteria and had been withdrawn from nucleoside analogues treatment. METHODS: Sixty CHB patients who experienced relapse after nucleoside analogues withdrawal based on cessation criteria were enrolled in the study retrospectively. Each patient's data on biochemical, serological and viral characteristics corresponding to baseline (treatment initiation), withdrawal and relapse were collected. COX proportional hazard modeling was used to evaluate the factors related to relapse. RESULTS: The hepatitis B e antigen (HBeAg)-positive and -negative patients had similar median antiviral treatment times (38 months (range: 24 - 80) vs. 35 months (30 - 60); Z = -1.313, P more than 0.05). For all patients, the median follow-up time was 12 months (2 - 72), during which 49 (81.7%) patients developed virological breakthrough and 17 (28.3%) developed HBeAg recurrence. The patients who experienced virological breakthrough or HBeAg recurrence had significantly higher baseline levels of HBV DNA than those patients who remained disease-free (t = 2.15 and -2.54 respectively; P less than 0.05). The median relapse time of the HBeAg-positive patients was significantly longer than that of the HBeAg-negative patients (14 months (3 - 72) vs. 6 months (3 - 36); Chi-square test = 7.045, P less than 0.01). HBeAg status at baseline was identified as an independent factor associated with relapse (relative risk = 1.937, 95% confidence interval = 1.14-3.28, P less than 0.05). CONCLUSION: HBeAg-positive and-negative patients showed distinct clinical characteristics of relapse, with the latter being more prone to relapse soon after nucleoside analogues withdrawal. Prolonging the treatment course may be beneficial to HBeAg-negative patients, even if cessation criteria are achieved.

Distinct quasispecies characteristics and positive selection within precore/core gene in hepatitis B virus HBV associated acute-on-chronic liver failure.

BACKGROUND AND AIM: The cause of hepatitis B virus associated acute-on-chronic liver failure (ACLF) remains unclear. Quasispecies can contribute to virus persistence and pathogenesis. We used a bioinformatics-based molecular evolution approach to compare quasispecies characteristics and positive selection sites within HBV precore/core gene between ACLF and chronic hepatitis B (CHB) patients. METHODS: HBV precore/core gene were amplified from 11 ACLF and 10 CHB patients harboring HBV genotype B; following DNA cloning and sequencing quasispecies complexity, diversity, and positive selection sites within the precore/core gene were determined by bioinformatics analysis, and compared between the patient groups. RESULTS: Both quasispecies complexity (P=0.022 at nucleotide level and 0.008 at amino acid level) and diversity (P<0.05) were found to be significantly greater in ACLF than in CHB. The frequency of G1896/A mutation in ACLF (175/298 clones, 58.7%) was also significantly higher than in CHB (100/230 clones, 43.5%) (P=0.0005). Moreover, analysis of positive selection revealed that significantly more patients with such sites were present in ACLF than in CHB (8/11 VS 2/10, P=0.03); the majority of these positive selection sites lay within HLA-restricted epitopes. CONCLUSIONS: The ACLF patients showed distinct quasispecies characteristics with higher complexity and diversity within the HBV precore/core gene. The increased HBV quasispecies complexity and diversity, together with a distinct set of positive selection sites, is likely associated with the development of ACLF.

[The impact of early rapid virological response on the outcomes of hepatitis B associated acute on chronic liver failure during antiviral treatment].

OBJECTIVE: To investigate the impact of early rapid virological response on the outcomes of hepatitis B associated acute on chronic liver failure during antiviral treatment. METHODS: 106 acute on chronic liver failure patients in our hospital from January 2008 to July 2010 were enrolled in present study retrospectively. Besides internal medicine therapy, all patients received lamivudine (100 mg/d) or entecavir (0.5 mg/d) treatment. The profile of liver biochemistry, prothrombin time activity and viral load were detected at baseline and week 4, respectively. The patients were divided into HBV DNA negative group and HBV DNA positive group according to the viral load at week 4. The clinical features and treatment outcomes were compared between groups. Frequency variables were compared by x2 test or Fisher's exact test. Continuous variables were compared using independent samples T-test. The factors that impact on the treatment outcomes were determined using stepwise multivariate logistic regression analysis. RESULTS: At the week 4, the TBil and PTA in HBV DNA positive group [(261.6+/-205.6)mumol/L and 44.7%+/-19.7%, respectively] were significantly different from those in HBV DNA negative group [(160.1+/-173.4) mumol/L and 56.8%+/-23.1%, respectively] ( t = 2.190 and -2.077, respectively, P less than 0.05). The non-effective rate of HBVDNA positive group (50%, 9/18) was significantly higher than that of HBV DNA negative group (14.8%, 13/88) (x2 = 9.235, P less than 0.01). By using stepwise multivariate logistic regression analysis, the disease stage and HBV DNA undetectable at week 4 were the independent factor. The OR values of disease stage and HBV DNA undetectable were 6.559 and 0.209, respectively, and 95% CI was 2.316~18.576 and 0.058~0.747, respectively. CONCLUSION: The rapid suppression of viral load by nucleotide analogue may improve the efficacy of hepatitis B associated acute on chronic liver failure treatment. The early rapid virological response within first 4 weeks may contribute to the prediction of the treatment outcomes.