Optimizing immunization schedules in endemic cholera regions: cost-effectiveness assessment of vaccination strategies for cholera control in Bangladesh.

This study is to examine the cost-effectiveness of deployment strategies of oral cholera vaccines (OCVs) in controlling cholera in Bangladesh. We developed a dynamic compartment model to simulate costs and health outcomes for 12 years for four OCVs deployment scenarios: (1) vaccination of children aged one and above with two doses of OCVs, (2) vaccination of population aged 5 and above with a single dose of OCVs, (3) vaccination of children aged 1-4 with two doses of OCVs; and (4) combined strategy of (2) and (3). We obtained all parameters from the literature and performed a cost-effectiveness analysis from both health systems and societal perspectives, in comparison with the base scenario of no vaccination.The incremental cost-effectiveness ratios (ICERs) for the four strategies from the societal perspective were $2,236, $2,250, $1,109, and $2,112 per DALY averted, respectively, with herd immunity being considered. Without herd immunity, the ICERs increased substantially for all four scenarios except for the scenario that vaccinates children aged 1-4 only. The major determinants of ICERs were the case fatality rate and the incidence of cholera, as well as the efficacy of OCVs. The projection period and frequency of administering OCVs would also affect the cost-effectiveness of OCVs. With the cut-off of 1.5 times gross domestic product per capita, the four OCVs deployment strategies are cost-effective. The combined strategy is more efficient than the strategy of vaccinating the population aged one and above with two doses of OCVs and could be considered in the resource-limited settings.

M6A Demethylase FTO Plays a Tumor Suppressor Role in Thyroid Cancer.

The purpose of this study was to investigate the expression and clinical significance of N6-methyladenosine demethylase FTO in thyroid cancer. Bioinformatic analysis showed that FTO expression was downregulated in thyroid cancer tissues and correlated with lymph node metastasis in thyroid cancer patients. We conducted experimental verification by collecting Asian samples. The results of quantitative reverse transcription-PCR showed that the mRNA expression of FTO in the blood of 30 thyroid cancer patients was lower than that of the control population. At the same time, we found that FTO expression was negative in tissues of 16/56 (28.57%) thyroid cancer cases and 4/40 (10.00%) nontumor thyroid cases through the immunohistochemical method, indicating a lower FTO expression in thyroid cancer tissues than nontumor thyroid tissues (p < 0.05). In addition, the protein expression of FTO was significantly related to the tumor grade and lymph node metastasis in thyroid cancer patients (p < 0.05), but not to other clinicopathological features. Multivariate logistic regression analysis showed that FTO expression was an independent risk factor for tumor grade. Survival analysis showed no significant difference in the disease-free survival time of thyroid cancer patients between high expression and low expression groups of FTO. Furthermore, bioinformatic analysis found that promoter DNA methylation and copy number variation might cause downregulated FTO and then affect TP53 pathways in thyroid cancer. We found that FTO expression was downregulated in thyroid cancer tissues and related to the progression of thyroid cancer, suggesting a tumor suppressor role of FTO in thyroid cancer.

The impact and cost-effectiveness of user fee exemption by contracting out essential health package services in Malawi.

OBJECTIVES: To examine the impact and cost-effectiveness of user fee exemption by contracting out essential health package services to Christian Health Association of Malawi (CHAM) facilities through service-level agreements (SLAs) to inform policy-making in Malawi. METHODS: The analysis was conducted from the government perspective. Financial and service utilisation data were collected for January 2015 through December 2016. The impact of SLAs on utilisation of maternal and child health (MCH) services was examined using propensity score matching and random-effects models. Subsequently, the improved services were converted to quality-adjusted life years (QALYs) gained, using the Lives Saved Tool (LiST), and incremental cost-effectiveness ratios (ICERs) were generated. FINDINGS: Over the 2 years, a total of $1.5 million was disbursed to CHAM facilities through SLAs, equivalent to $1.24 per capita. SLAs were associated with a 13.8%, 13.1%, 19.2% and 9.6% increase in coverage of antenatal visits, postnatal visits, delivery by skilled birth attendants and BCG vaccinations, respectively. This was translated into 434 lives saved (95% CI 355 to 512) or 11 161 QALYs gained (95% CI 9125 to 13 174). The ICER of SLAs was estimated at $134.7/QALYs gained (95% CI $114.1 to $164.7). CONCLUSIONS: The cost per QALY gained for SLAs was estimated at $134.7, representing 0.37 of Malawi's per capita gross domestic product ($363). Thus, MCH services provided with Malawi's SLAs proved cost-effective. Future refinements of SLAs could introduce pay for performance, revising the price list, streamlining the reporting system and strengthening CHAM facilities' financial and monitoring management capacity.

Evaluation of the performance of national health systems in 2004-2011: An analysis of 173 countries.

In an effort to improve health service delivery and achieve better health outcomes, the World Health Organization (WHO) has called for improved efficiency of health care systems to better use the available funding. This study aims to examine the efficiency of national health systems using longitudinal country-level data. Data on health spending per capita, infant mortality rate (IMR), under 5 mortality rate (U5MR), and life expectancy (LE) were collected from or imputed for 173 countries from 2004 through 2011. Data envelopment analyses were used to evaluate the efficiency and regression models were constructed to examine the determinants of efficiency. The average efficiency of the national health system, when examined yearly, was 78.9%, indicating a potential saving of 21.1% of health spending per capita to achieve the same level of health status for children and the entire population, if all countries performed as well as their peers. Additionally, the efficiency of the national health system varied widely among countries. On average, Africa had the lowest efficiency of 67%, while West Pacific countries had the highest efficiency of 86%. National economic status, HIV/AIDS prevalence, health financing mechanisms and governance were found to be statistically associated with the efficiency of national health systems. Taking health financing as an example, a 1% point increase of social security expenses as a percentage of total health expenditure correlated to a 1.9% increase in national health system efficiency. The study underscores the need to enhance efficiency of national health systems to meet population health needs, and highlights the importance of health financing and governance in improving the efficiency of health systems, to ultimately improve health outcomes.

Use of an autologous liver round ligament flap zeros postoperative bile leak after curative resection of hilar cholangiocarcinoma.

BACKGROUND: Postoperative bile leak is a major surgical morbidity after curative resection with hepaticojejunostomy for hilar cholangiocarcinoma, especially in Bismuth-Corlette types III and IV. This retrospective study assessed the effectiveness and safety of an autologous hepatic round ligament flap (AHRLF) for reducing bile leak after hilar hepaticojejunostomy. METHODS: Nine type III and IV hilar cholangiocarcinoma patients were consecutively hospitalized for elective perihilar partial hepatectomy with hilar hepaticojejunostomy using an AHRLF between October 2009 and September 2013. The AHRLF was harvested to reinforce the perihilar hepaticojejunostomy. Main outcome measures included operative time, blood loss, postoperative recovery times, morbidity, bile leak, R0 resection rate, and overall survival. RESULTS: All patients underwent uneventful R0 resection with hilar hepaticojejunostomy. No patient experienced postoperative bile leak. CONCLUSIONS: The AHRLF was associated with lack of bile leak after curative perihilar hepatectomy with hepaticojejunostomy for hilar cholangiocarcinoma, without compromising oncologic safety, and is recommended in selected patients.

Clinical analysis of thyroid carcinoma showing thymus-like differentiation: report of 8 cases.

Thyroid carcinoma showing thymus-like differentiation (CASTLE) is a kind of rare neoplasm of the thyroid gland. Because thyroid CASTLE is rare and difficult to diagnose, its clinicopathologic features have not been well defined, and no universally accepted treatment recommendation is available. We analyzed retrospectively the clinicopathologic data of 8 patients with thyroid CASTLE who underwent surgery and radiotherapy at the Shengjing Hospital of China Medical University between December 2008 and June 2012. All patients accepted radical surgery. All patients accepted postoperative radiotherapy, except one 79-year-old patient. There was no evidence of recurrence or metastasis during the follow-up period. The pattern of immunohistochemical staining was similar to that of thymic carcinoma. Six of 8 CASTLE cases expressed CD5. All 8 CASTLE patients were negatively expressed in thyroglobulin, thyroid transcription factor 1, and calcitonin. Patients with thyroid CASTLE have good outcomes after radical resection and postoperative radiotherapy. Positive CD5 immunoreactivity can contribute to diagnosis of this disease.

Expression of stromal cell-derived factor 1 and CXCR7 in papillary thyroid carcinoma.

Stromal cell-derived factor 1 (SDF-1) is a chemokine that is expressed in some cancer cells and is involved in tumor cell migration and metastasis. CXCR7, a novel receptor for SDF-1, has been identified recently. Researches demonstrated that interaction between SDF-1 and CXCR7 could play an important role in cancer progression. In this study, we aimed to investigate the expressions of SDF-1 and CXCR7 and the relationship between their expressions and clinicopathological characteristics in papillary thyroid carcinoma (PTC). Expressions of SDF-1 and CXCR7 in 33 cases of thyroid benign lesion tissue and 79 cases of PTC tissue and peritumoral non-malignant tissue were detected by immunohistochemical staining. Expressions of SDF-1 and CXCR7 were negative in peritumoral non-malignant tissues. Respectively, positive expression rates of SDF-1 and CXCR7 were 69.6 and 65.8 % in PTC, 12.1 and 30.3 % in thyroid benign tissue. The expression of SDF-1 and CXCR7 were positively correlated with lymph node metastasis. SDF-1 and CXCR7 expressions were related with the lymph nodes metastasis of PTC.

Nanoparticle-mediated local delivery of an antisense TGF-ß1 construct inhibits intimal hyperplasia in autogenous vein grafts in rats.

BACKGROUND: Intimal hyperplasia is one of the most important causes of vascular graft failure. Numerous studies have correlated transforming growth factor-ß1 (TGF-ß1) with extracellular matrix (ECM) deposition, a hallmark of intimal thickening. PRINCIPAL FINDINGS: In the present study, we performed immunohistochemistry, RT-PCR, and Western blot to examine the dynamic expression of TGF-ß1, TGF-ß1 receptor type I (TGF-ß RI), matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) during intimal hyperplasia in grafted veins of a rat model generated by grafting a portion of the right internal jugular vein to the ipisiliary carotid artery. Additionally, we determined whether nanoparticle-mediated delivery of a TGF-ß1 antisense-expressing construct prevented TGF-ß1 expression and intimal hyperplasia in grafted veins. In grafted veins, the expression of TGF-ß1 significantly increased on day 3 after transplantation, peaked on day 7, slightly decreased on day 14, and returned to baseline levels on day 28. The positive expression of TGF-ß RI in grafted veins remarkably increased on day 7, peaked on day 14, and decreased thereafter. MMP-1 expression decreased significantly, while TIMP-1 expression increased, significantly on days 14 and 28. Nanoparticle-mediated delivery of a TGF-ß1 antisense-expressing construct down-regulated TGF-ß1 expression and inhibited intimal hyperplasia in grafted veins. CONCLUSIONS: Our findings provide further evidence that TGF-ß1 plays an integral role in the development of intimal hyperplasia after vascular injury. Nanoparticle-mediated delivery of a TGF-ß1 antisense-expressing construct is a feasible strategy to target TGF-ß1-induced intimal thickening.

Differential expression patterns of capping protein, protein phosphatase 1, and casein kinase 1 may serve as diagnostic markers for malignant melanoma.

Early and accurate diagnosis of malignant melanoma is critical for patient survival. However, currently used diagnostic markers are insufficiently specific, which limits their utility. We aimed to identify molecular markers that are more specific to malignant melanoma, thereby aiding in melanoma diagnosis and treatment. A PCR-based suppression subtractive hybridization was used to identify capping protein Z-line α1, protein phosphatase 1 catalytic subunit ß isoform (PP1CB), and casein kinase 1 α1 (CSNK1A1) as being differentially expressed between melanoma cells and normal melanocytes. Quantitative reverse transcription-PCR and western blot analysis confirmed that these genes were overexpressed in melanoma cells. In addition, immunohistochemical assays revealed that the expression of PP1CB and CSNK1A1 was significantly greater in human melanoma specimens than nevi (P<0.0001). Combined application of PP1CB and CSNK1A showed high sensitivity and specificity for melanoma. Thus, our data suggest that PP1CB and CSNK1A1 are potential biomarkers for distinguishing malignant melanoma from other melanocytic lesions. In addition, because capping protein Z-line α1, PP1CB, and CSNK1A1 are involved in cell motility, which underlies invasion and metastasis of human cancer; they may be novel targets for antimetastatic therapies as well.

[The best concentration ratio of propofol controlled-infusion combined with sevoflurane in anesthesia for patients undergoing laparoscopy].

OBJECTIVE: To investigate the best concentration ratio of propofol controlled-infusion combined with sevoflurane in anesthesia for patients undergoing laparoscopy. METHODS: One hundred patients undergoing cholecystectomy under laparoscopy were randomly divided into 5 equal groups treated with propofol controlled plasma at the concentrations of 1, 2, 3, 4, and 5 microg/ml respectively (Group 1-5). Bispectral index (BIS) was maintained at a range of 50 +/- 5 by adjusting sevoflurane inhalation. The end-tidal concentration of sevoflurane (ETsevo), systolic pressure, diastolic pressure, recovery time, awareness, and post-operative nausea and vomiting (PONV) within 24 h after operation were recorded. The best concentration ratio of propofol controlled-infusion combined with sevoflurane with the definition as the highest ETsevo without PONV decrease along with the increase of propofol concentration. RESULTS: ETsevo was negatively correlated with and propofol concentration. There were nit significant differences in the systolic pressure, diastolic pressure, and recovery time among different groups. No incidence of intra-operative awareness was found. The PONV rates of Group 1 and 2 were both 60%, significantly higher than those of the other 3 groups (all P < 0.05) without significant differences in PONV rate among Group 3 - 5. The best concentration ratio of propofol controlled-infusion combined with sevoflurane was propofol controlled-infusion at the concentration of 1 microg/ml with ETsevo at the concentration as 1 minimal alveolar concentration (MAC). CONCLUSION: Propofol controlled-infusion at the concentration of 1 microg/ml with ETsevo at the concentration as 1 MAC is the best concentration ratio with low PONV rate and a possibility to prevent intra-operative awareness.

[The gene expression of nuclear transcriptional factor-kappa B and I kappa B in autogenous vein graft in rats].

OBJECTIVE: To investigate the gene expression of nuclear transcriptional factor-kappa B (NF-kappa B) p65 and its inhibiting factor I kappa B in autogenous vein graft. METHODS: The right common jugular vein was transplanted to infrarenal abdominal aorta by microsurgical technique among 80 Wistar rats so as to establish an autogenous vein graft model. Ten vein graft samples were harvested 6 hours, 24 hours, 3 days, 7 days, 2 weeks, 4 weeks, 6 weeks, and 8 weeks after surgery. NF kappa B p65 mRNA and I kappa B beta mRNA were measured by reverse transcription-PCR and in situ hybridization. Western blotting and immunohistochemistry were used to detect the protein expression of NF kappa B p65 and I kappa B. RESULTS: The expressions of NF kappa B p65 mRNA and I kappa B beta mRNA 6 hours after the surgery were 16% +/- 4% and 31% +/- 9% respectively (P < 0.01 vs. control vein). The expression of NF kappa B p65 mRNA reached in peak during the period 3 days to 7 days after the surgery (37% +/- 12% and 34% +/- 10% respectively, P< 0.01 vs. other teams), however, the I kappa B beta mRNA expression reached its peak during 1 to 2 weeks after the surgery (53% +/- 17% and 49% +/- 10% respectively, P < 0.01 vs. other teams). The expressions of NF kappa B p65 mRNA and I kappa B beta mRNA recovered to their baseline values 6 weeks after surgery. The expression of p65 protein reached its peak 1 week after the surgery (32% +/- 13%) and then decreased gradually. The expressions of I kappa B alpha and I kappa B beta decreased to 1/3 to 1/2 of the normal vein 6 hours to 24 hours after the surgery and then increased to 5 times that of the control vein 2 weeks after surgery (35% +/- 11% and 44% +/- 13% respectively). CONCLUSION: The NF-kappa B/I kappa B system is activated in autogenous vein graft. The NF kappa B may become a new target for the prevention and therapy of intimal hyperplasia and stenosis after vein graft.