Cost-Effective Method of Gene Synthesis by Sequencing from Microchip-Derived Oligos for Droplet Cloning

Gene synthesis has provided important contributions in various fields including genomics and medicine. Current genes are 7 - 30 cents depending on the assembly and sequencing methods performed. Demand for gene synthesis has been increasing for the past few decades, yet available methods remain expensive. A solution to this problem involves microchip-derived oligonucleotides (oligos), an oligo pool with a substantial number of oligo fragments. Microchips have been proposed as a tool for gene synthesis, but this approach has been criticized for its high error rate during sequencing. This study tests a possible cost-effective method for gene synthesis utilizing fragment assembly and golden gate assembly, which can be employed for quicker manufacturing and efficient execution of genes in the near future. The droplet method was tested in two trials to determine the viability of the method through the accuracy of the oligos sequenced. A preliminary research experiment was performed to determine the efficacy of oligo lengths ranging from two to four overlapping oligos through Gibson assembly. Of the three oligo lengths tested, only two fragment oligos were correctly sequenced. Two fragment oligos were used for the second experiment, which determined the efficacy of the droplet method in reducing gene synthesis cost and speed. The first trial utilized a high-fidelity polymerase and resulted in 3% correctly sequenced oligos, so the second trial utilized a non-high-fidelity polymerase, resulting in 8% correctly sequenced oligos. After calculating, the cost of gene synthesis lowers down to 0.8 cents/base. The final calculated cost of 0.8 cents/base is significantly cheaper than other manufacturing costs of 7 - 30 cents/base. Reducing the cost of gene synthesis provides new insight into the cost-effectiveness of present technologies and protocols and has the potential to benefit the fields of bioengineering and gene therapy.

An ideal point method adopting grey relational entropy to estimate life cycle cost with effectiveness of torpedo

To making the decision of the developing blue prints,ideal point method was selected to estimate the life cycle cost with effectiveness of torpedo.At the same time,the concept of grey relational entropy of the grey system theory was adopted to compute the distance between each blue print and the ideal point(or negative ideal point).The blue print,nearest to the ideal point and farthest to the negative ideal point,is the best one.As an example,four blue prints of torpedo were estimated.The result indicates the practical value of this method.

Modeling Anthrax with Optimal Control and Cost Effectiveness Analysis

Anthrax is an infection caused by bacteria and it affects both human and animal populations. The disease can be categorized under zoonotic diseases and humans can contract infections through contact with infected animals, ingest contaminated dairy and animal products. In this paper, we developed a mathematical model for anthrax transmission dynamics in both human and animal populations with optimal control. The qualitative solution of the model behaviour was analyzed by determining Rhv, equilibrium points and sensitivity analysis. A vaccination class was incorporated into the model with waning immunity. Local and global stability of the model’s equilibria was found to be locally asymptotically stable whenever Rhv Rhv. It was revealed that reducing animal and human interaction rate, would decrease Rhv. We extended the model to optimal control in order to find the best control strategy in reducing anthrax infections. It showed that the effective strategy in combating the anthrax epidemics is vaccination of animals and prevention of humans.

Cost-effectiveness analysis of colon cancer treatments from MOSIAC and No.16968 trials

AIM: To compare XELOX and FOLFOX4 as colon cancer adjuvant chemotherapy based on MOSAIC and No. 16968 trails from Chinese cost-effectiveness perspective. METHODS: A decision-analytic Markov model was developed to compare the FOLFOX4 and XELOX regimens based MOSAIC and No. 16968 trial. Five states were included in our Markov model: well (state 1), minor toxicity (state 2), major toxicity (state 3), quitting adjuvant chemotherapy (state 4), and death due to adjuvant chemotherapy (state 5). Transitions among the 5 states were assumed to be Markovian. Costs were calculated from the perspective of the Chinese health-care payer. The utility data were taken from published studies. Sensitivity analyses were used to explore the impact of uncertainty factors in this cost-effectiveness analysis. RESULTS: Total direct costs of FOLFOX4 and XELOX per patient were $ 19884.96 +/- 4280.30 and $ 18113.25 +/- 3122.20, respectively. The total fees related to adverse events per patient during the entire treatment were $ 204.75 +/- 16.80 for the XELOX group, and $ 873.72 +/- 27.60 for the FOLFOX4 group, and the costs for travel and absenteeism per patient were $ 18495.00 for the XELOX group and $ 21,352.68 for the FOLFOX4 group. The base-case analysis showed that FOLFOX4 was estimated to produce an additional 0.06 in quality adjusted life years (QALYs) at an additional cost of $ 3950.47 when compared to the XELOX regimen over the model time horizon. The cost per QALY gained was $ 8047.30 in the XELOX group, which was $ 900.98 less than in the FOLFOX4 group ($ 8948.28). The one way sensitivity analysis demonstrated that the utility for the well state and minor toxicity state greatly influenced the incremental cost-effectiveness ratio of FOLFOX4. CONCLUSION: In term of cost-comparison, XELOX is expected to dominate FOLFOX4 regimes; Therefore, XELOX provides a more cost-effective adjuvant chemotherapy for colon cancer patients in China. c 2014 Baishideng Publishing Group Inc. All rights reserved.

High-resolution microendoscopy for esophageal cancer screening in China: A cost-effectiveness analysis

AIM:To study the cost-effectiveness of high-resolution microendoscopy(HRME)in an esophageal squamous cell carcinoma(ESCC)screening program in China.METHODS:A decision analytic Markov model of ESCC was developed.Separate model analyses were conducted for cohorts consisting of an averagerisk population or a high-risk population in China.Hypothetical 50-year-old individuals were followed until age 80 or death.We compared three different strategies for both cohorts:(1)no screening;(2)standard endoscopic screening with Lugol’s iodine staining;and(3)endoscopic screening with Lugol’s iodine staining and an HRME.Model parameters were estimated from the literature as well as from GLOBOCAN,the Cancer Incidence and Mortality Worldwide cancer database.Health states in the model included non-neoplasia,mild dysplasia,moderate dysplasia,high-grade dysplasia,intramucosal carcinoma,operable cancer,inoperable cancer,and death.Separate ESCC incidence transition rates were generated for the average-risk and high-risk populations.Costs in Chinese currency were converted to international dollars(I$)and were adjusted to 2012dollars using the Consumer Price Index.RESULTS:The main outcome measurements for this study were quality-adjusted life years(QALYs)and incremental cost-effectiveness ratio(ICER).For the average-risk population,the HRME screening strategy produced 0.043 more QALYs than the no screening strategy at an additional cost of I$646,resulting in an ICER of I$11808 per QALY gained.Standard endoscopic screening was weakly dominated.Among the high-risk population,when the HRME screening strategy was compared with the standard screening strategy,the ICER was I$8173 per QALY.For both the high-risk and average-risk screening populations,the HRME screening strategy appeared to be the most cost-effective strategy,producing ICERs below the willingness-topay threshold,I$23500 per QALY.One-way sensitivity analysis showed that,for the average-risk population,higher specificity of Lugol’s iodine(>40%)and lower specificity of HRME(<70%)could make Lugol’s iodine screening cost-effective.For the high-risk population,the results of the model were not substantially affected by varying the follow-up rate after Lugol’s iodine screening,Lugol’s iodine test characteristics(sensitivity and specificity),or HRME specificity.CONCLUSION:The incorporation of HRME into an ESCC screening program could be cost-effective in China.Larger studies of HRME performance are needed to confirm these findings.

Cost-effectiveness analysis of transcatheter arterial chemoembolization with or without sorafenib for the treatment of unresectable hepatocellular carcinoma

BACKGROUND: Transcatheter arterial chemoembolization(TACE) and TACE in combination with sorafenib(TACEsorafenib) have shown a significant survival benefit for the treatment of unresectable hepatocellular carcinoma(HCC). Adopting either as a first-line therapy carries major cost and resource implications. The objective of this study was to estimate the relative cost-effectiveness of TACE against TACE-sorafenib for unresectable HCC using a decision analytic model.METHODS: A Markov cohort model was developed to compare TACE and TACE-sorafenib. Transition probabilities and utilities were obtained from systematic literature reviews, and costs were obtained from West China Hospital, Sichuan University, China. Survival benefits were reported in quality-adjusted life-years(QALYs). The incremental cost-effectiveness ratio(ICER) was calculated. Sensitive analysis was performed by varying potentially modifiable parameters of the model.RESULTS: The base-case analysis showed that TACE cost $26 951 and yielded survival of 0.71 QALYs, and TACE-sorafenib cost $44 542 and yielded survival of 1.02 QALYs in the entire treatment. The ICER of TACE-sorafenib versus TACE was $56 745 per QALY gained, which was above threshold for cost-effectiveness in China. Sensitivity analysis revealed that the major driver of ICER was the cost post TACE-sorafenib therapy with stable state.CONCLUSION: TACE is a more cost-effective strategy than TACE-sorafenib for the treatment of unresectable HCC.

A cost-effectiveness study on treatment of duodenal ulcer

ＡｃｏｓｔｅｆｅｃｔｉｖｅｎｅｓｓｓｔｕｄｙｏｎｔｒｅａｔｍｅｎｔｏｆｄｕｏｄｅｎａｌｕｌｃｅｒＣＨＥＮＳｈｉＹａｏ，ＷＡＮＧＪｉＹａｏ，ＣＨＥＮＪｉｅ，ＺＨＡＮＧＸｉＤｅａｎｄＺＨＡＮＧＳｈａｎＳｈｅｎＤｅｐａｒｔｍｅｎｔｏｆＧａｓｔｒｏ...

Cost-Effectiveness Analysis of Neoadjuvant Chemotherapy with Zoledronic Acid for HER2-Negative Breast Cancer in Japan: The JONIE1 Study

Objective: Zoledronic acid (ZOL) is a nitrogen-containing bisphosphonate that induces osteoclast apoptosis and inhibits bone resorption. Adding ZOL to neoadjuvant chemotherapy has been shown to have potential anticancer benefits in women with HER2-negative breast cancer. The objective of the present study was to investigate ZOL’s cost-effectiveness from the perspective of health care payers in Japan. Methods: A Markov model was developed to evaluate the costs and effectiveness associated with ZOL + chemotherapy (CTZ) and chemotherapy (CT) alone over a 10-year time horizon. Monthly transition probabilities were estimated according to JONIE1 (Japan Organization of Neoadjuvant Innovative Expert) Study data and an extrapolated Weibull model. Health outcomes were measured in quality-adjusted life years (QALYs). Costs were calculated using year-2018 Japanese yen (JPY) (1.00 US dollars (USD) = 110.4 JPY). Model robustness was addressed through one-way and probabilistic sensitivity analysis. The costs and QALYs were discounted at a rate of 2% per year. Results: In the base case, the use of CTZ was associated with a gain of 3.94 QALYs. The incremental cost per QALY of the CTZ gain was 681,056.1 JPY (6168.99 USD) per QALY. Conclusion: It is convincing that neoadjuvant CTZ for patients with breast cancer would be expected to have statistically significant clinical efficacy. Addition of ZOL to CT might be a cost-effective option compared with CT alone.

Safety,efficiency and cost effectiveness of Bivalirudin:A systematic review

AIM To review the early and more recent studies of Bivalirudin, to assess the safety, effectiveness, and cost benefits of this drug.METHODS Literature search of MEDLINE and Pub Med databases from 1990 to 2017 using keywords as "bivalirubin" and "angiomax", combined with the words "safety", "effectiveness", "efficiency", "side effects", "toxicity", "adverse effect", and "adverse drug reaction".RESULTS A total of 66 publications were reviewed. The changes in clinical practice and differences in clinical protocols make it difficult to do direct comparisons of studies among each other. However, most trials showed decreased bleeding complications with bivalirudin, although ischemic complications and mortality were mostly comparable, with some favor towards bivalirudin.CONCLUSION Bivalirudin and heparin are both acceptable options according to current ACA/AHA guidelines. Authors conclude however, that that due to bivalirudin safer bleeding profile, it should be the preferred medication for anticoagulation.

Cost Effectiveness Analysis of Filgrastim versus Placebo in Post AIIogentic Bone Marrow Transplantation

Filgrastim is used to accelerate hematopoietic recovery after ABMT （allogeneic bone marrow transplantation）. Its impact on the total cost of patient care remains to be explored. We therefore undertook a cost effectiveness analysis in the context of a randomized single blinded clinical trial of Filgrastim versus placebo in post ABMT. A primary endpoint, duration of myelosuppression, and three secondary end points （number of days of fever, length of hospital stay, survival at one hundred days） were used to assess efficacy. Direct costs were evaluated and allowed the calculation of the ICER （incremental cost-effectiveness ratios） for the major endpoint of the trial. Sixteen patients were included in the study. The duration of myelosuppression was significantly decreased in the Filgrastim arm with medians of 15 days vs. 19 days in the placebo arm （p = 0.023）. Cost analysis showed no statistically significant difference between the two arms. According to the calculation of ICER, Filgrastim was more costly and more effective than placebo for the number of days of aplasia avoided and the number of days with fever avoided. Placebo strictly dominated filgrastim for days of hospitalization avoided. Filgrastim has proven effective in reducing the duration of aplasia without increasing costs.

Cost-Effectiveness Analysis of Oral Hypoglycemics for Type-2 Diabetes Mellitus at a Tertiary Care Hospital, Nepal

An observational follow-up study on 63 newly diagnosed Type-Ⅱ diabetic patients was conducted at Tribhuvan University Teaching Hospital, a tertiary care centre, Kathmandu, Nepal. The aims of the study were to determine demographics, prescribing patterns, drug costs and to analyze the effectiveness of different hypoglycemic therapies. The effectiveness of glucose control was analyzed by Wilcoxon signed rank test. The majority of patients (31%) fell into the age strata of 50-60 years. A total of 63 prescriptions were screened including anti-diabetics drugs and other drugs. The average number of drugs per prescription sheet was 2.72 ± 2.23. Eighty-two percent (82%) of the patients were recommended oral hypoglycemic agents. The prescribing frequency of biguanides was more than sulphonylureas. Biguanides were prescribed more frequently than sulfonylureas. The biguanide monotherapy group (p = 0.001) and the combination of biguanide and sulfonylureas (p = 0.028) were the most effective treatment methods, and the p-value of fasting blood glucose was the lowest at follow-up. Nearly 55% of patients receiving the combination achieved glucose control. In summary, this study reflects the best treatment for patients with diabetes. Future studies of larger patient populations need to evaluate existing treatment models to ensure good practice and quality of care.

Innovation Research on Collabora/ve Governance System of theAir Pollution 2 Beijing-Tianjin-Hebei from the Cost-effectiveness Perspective

论文以京津冀大气污染协同治理的成本构成为基础,分析阐述了由于跨区域协同治理的法律法规不完善,有关三地信息共享、利益补偿、监督管理等相关制度、机制不健全,加大了京津冀协同治理的交易成本,使协同治理的效率降低.为此,应加快完善京津冀协同治理的制度与机制创新,重点加强京津冀区域内生态补偿和排污权交易等经济激励机制建设,以实现京津冀协同治理的长效目标.

Cost effectiveness of routine duodenal biopsies in iron deficiency anemia

AIM To investigate the cost effectiveness of routine small bowel biopsies(SBBs) in patients with iron deficiency anemia(IDA) independent of their celiac disease(CD) serology test results.METHODS We used a state transition Markov model. Two strategies were compared: routine SBBs during esophagogastroduodenoscopy(EGD) in all patients with IDA regardless their celiac serology status(strategy A) vs SBBs only in IDA patients with positive serology(strategy B). The main outcomes were quality adjusted life years(QALY),average cost and the incremental cost effectiveness ratio(ICER). One way sensitivity analysis was performed on all variables and two way sensitivity analysis on selected variables were done. In order to validate the results,a Monte Carlo simulation of 100 sample trials with 10,and an acceptability curve were performed.RESULTS Strategy A of routine SBBs yielded 19.888 QALYs with a cost of $218.10 compared to 19.887 QALYs and $234.17 in strategy B. In terms of cost-effectiveness,strategy A was the dominant strategy,as long as the cost of SBBs stayed less than $67. In addition,the ICER of strategy A was preferable,providing the cost of biopsy stays under $77. Monte Carlo simulation demonstrated that strategy A yielded the same QALY but with lower costs than strategy B. CONCLUSION Our model suggests that EGD with routine SBBs is a cost-effective approach with improved QALYs in patients with IDA when the prevalence of CD is 5% or greater. SBBs should be a routine screening tool for CD among patients with IDA,regardless of their celiac antibody status.

Cost-effectiveness in Clostridium difficile treatment decision-making

AIM: To develop a framework for the clinical and health economic assessment for management of Clostridium difficile infection(CDI).METHODS: CDI has vast economic consequences emphasizing the need for innovative and cost effective solutions, which were aim of this study. A guidance model was developed for coverage decisions and guideline development in CDI. The model included pharmacotherapy with oral metronidazole or oral vancomycin, which is the mainstay for pharmacological treatment of CDI and is recommended by most treatment guidelines.RESULTS: A design for a patient-based cost-effectiveness model was developed, which can be used to estimate the cost-effectiveness of current and future treatment strategies in CDI. Patient-based outcomes were extrapolated to the population by including factors like, e.g., person-to-person transmission, isolation precautions and closing and cleaning wards of hospitals. CONCLUSION: The proposed framework for a population-based CDI model may be used for clinical and health economic assessments of CDI guidelines and coverage decisions for emerging treatments for CDI.

Outcomes and Cost Effectiveness of a Respiratory Coordinated Care Program in Patients with Severe or Very Severe COPD

Multidisciplinary community coordinated care programs are widely adopted to optimise care of chronic disease patients, but there is a need for further evaluation in the setting of COPD. This observational study evaluated 147 patients with severe or very severe COPD who were enrolled in a multidisciplinary community respiratory coordinated care program (RCCP) from 2007 to 2012. Comparison was made of hospitalisation rates and length of stay for 12 months prior to joining the program, and the first 12 months after joining the program. This data was used to inform a cost analysis. Enrolment into RCCP halved the annual hospital admission rate from 1.18 to 0.57 admissions per year (relative risk reduction 51.4%, p < 0.001), and annual total length of stay was reduced from 8.06 to 3.59 days per patient per year (p < 0.001). Hospital admissions were reduced from 5.05 days to 2.00 days (p < 0.001). Accounting for the program’s costs, these changes resulted in a $US 906.94 ($AUD 972.80) cost saving per patient per year. A RCCP program can reduce patient hospitalisation and overall costs in the COPD setting.

Cost-Effectiveness of Somatostatin Analogues for the Treatment of Acromegaly in Colombia

Background: Somatostatin analogues have shown to be effective in controlling the levels of growth hormone and are recommended for the treatment of acromegaly. These treatments have high costs of acquisition and their use might be restricted in limited resource settings. Objective: To evaluate the cost-effectiveness of somatostatin analogues for acromegaly in Colombia. Setting/Subjects/Intervention: A decision model was developed using a hypothetical cohort of patients with Acromegaly. Patients were treated according to the clinical practice of the country. Response to treatment and transition probabilities were derived from published literature. Costs and resource utilization were extracted from public and private sources in Colombia. Main Outcome Measure(s): Cost-effectiveness ratio, measured in Colombian pesos in a 2 year time-horizon. Results: The total medical treatment costs for the octreotide group were (Colombian Pesos) COP$ 53,807,616, compared to the total costs for the lanreotide group of COP$ 83,126,567. In the octreotide arm 65.30% of the patients and in the lanreotide arm 59.50% of the patients were successfully controlled. The number of deaths was 295 (13.1%) and 302 (13.4%) for octreotide and lanreotide, respectively. Because the costs are lower and the effectiveness is higher for octreotide in comparison with lanreotide, octreotide is more cost-effective than lanreotide. Probabilistic sensitivity analyses were consistent showing octreotide as the most cost-effective option. Conclusions: Costs and effects of octreotide compare favorably to those of lanreotide in the treatment of acromegaly in Colombia. Sensitivity analysis showed that despite the uncertainty in cost-effectiveness ratio this result is robust.

Effects of Different Combinations of Fertilization and Agrochemical Application on Yield and Cost-effectiveness of Cucumber

This study was conducted to provide reference for rational fertilization and agrochemical application in cucumber plantation,and relieve the problem of environmental pollution and vegetable agrochemical residues. The effects of different combinations of fertilization and agrochemical application on cucumber yield and cost input were investigated. Four treatments were conducted,including T1（ conventional fertilization ＋ conventional agrochemical application,CK）,T2（ conventional fertilization ＋ recommended agrochemical application）,T3（ recommended fertilization ＋ conventional agrochemical application） and T4（ recommended fertilization ＋ recommended agrochemical application）. The results showed that T4 had fewer kinds of fertilizers and agrochemicals than that of T1,and had a yield increasing effect on cucumber,and the yield increase was 7 003. 5 kg/hm^2,with an increasing rate of 19. 25%; and it also had obvious cost-saving and benefit-increasing effects,specifically,the cost was saved by 10 941 yuan/hm^2 and the benefit was increased by 31 951. 5 yuan/hm^2. The results of this experiment were satisfactory,and higher benefit was obtained with lower input. This study will provide reference for cucumber planter to choose fertilizers and agrochemicals,and lays a foundation for alleviating the ecological soil problems.

Cost-effectiveness analysis comparing robotic sacrocolpopexy to a vaginal mesh hysteropexy for treatment of uterovaginal prolapse

Objective: To compare costs and QoL associated with 2 minimally invasive operations to treat uterovaginal prolapse. Study Design: A decision analytic cost-effectiveness model comparing vaginal mesh hysteropexy to robotic-assisted sacrocolpopexy. Costs were derived from a hospital perspective. QoL estimates focused on: recurrent prolapse;erosion;infection;transfusion;cystotomy;chronic pain;lower urinary tract symptoms;and mortality. Actual procedural costs at our institution were calculated. Costs and quality adjusted life years were examined over 1 year. Results: The costs ($21,853) and QALYs (0.9645) for robotic sacrocolpopexy produced a CE Ratio of $22,657 per QALY. The costs ($14,890) and QALYs (0.9309) for vaginal mesh produced a CE Ratio of $15,995 per QALY. The incremental cost per QALYs for robotic surgery was $207,232. Sensitivity analysis on all utilities, cost estimates, and complication estimates didn’t cross any thresholds. Conclusion: Vaginal mesh was more cost-effective than robotic sacrocolpopexy even when the cost of the robot was not factored.

Evaluating and Improving the Effectiveness of Vehicle Inspection and Maintenance Programs: A Cost-Benefit Analysis Framework

Motor vehicle inspection and maintenance (I/M) programs are designed to identify high-emitting vehicles and mitigate their impacts on air quality and climate. I/M programs have been traditionally ranked superior among various vehicle emission control measures by the results of cost-benefit analysis, based on the assumption that these programs will achieve the targeted emission reduction outcomes. However, the actual effects of I/M programs may be greatly uncertain and when this uncertainty is taken into account, these programs may become suboptimal. This study develops a new a cost-benefit analysis framework that links various program design consideration, such as program participation rate, identification rate and effective repair rate, to the public health benefits as well as costs of the programs. This framework helps decision makers to investigate minimum implementation requirements that at least ensure the benefits are greater than the costs of implementing the programs in order to improve the overall effectiveness of the I/M programs. To illustrate the applications of the framework, it was applied to a particulate matter oriented I/M program targeting all diesel-fueled vehicles in the city of Bangkok, Thailand, a large metropolitan area that has been suffering from severe ambient PM pollution mainly attributable to its wide use of diesel-fueled vehicles and motorcycles. It was found that the health benefits achieved from the program are sensitive to several key program design elements, including participation rate and problem vehicle identification rate, fraction of effective repairs and illegal operation rate. Other variables, such as the testing cut-points and vehicle population growth rate, only have modest effects on the overall emission reduction and consequent health benefits. Overall, the performance of multiple variables associated with I/M program design needs to be improved simultaneous in order to achieve the targeted benefits of the program.

Cost effectiveness of robot-assisted urologic oncological surgery in the United States

Urology has been on the forefront of technological advances in minimally invasive surgery, from laparoscopy to robot-assisted surgeries. As with all new technological advances in medicine, the results of new advances are compared to previously established gold standards. When it comes to robot-assisted urology, morbidity, oncological outcomes, and cost between the same surgeries performed in an open fashion vs with robot-assistance should be assessed. Because healthcare spending is increasingly under more scrutiny, there is debate on the cost effectiveness of robot-assisted surgeries given the high acquisition and maintenance cost of robotic systems. This articles aims to critically evaluate the cost effectiveness of robot-assisted surgeries for prostatectomies, cystectomies, and partial nephrectomies in the United States.