Cost-effectiveness and resource allocation (CERA) 18 years of evolution: maturity of adulthood and promise beyond tomorrow.

Since its inception in 2003, Cost Effectiveness and Resource Allocation journal has come a long way over the past 18 years. Possibly much longer than many of its contemporaries in the blossoming science of health economics might have anticipated. Today, entering 2020 it celebrates the Age of Maturity. We believe that in the third decade of XXI century the interdisciplinary science of health economics, will rejuvenate and come back to us younger than ever from its early historical roots almost a century ago. The spreading of economic globalization in several distinctive ways, either led by multinational business corporations or newly emerged Asian leadership, or both, is likely to make challenges for contemporary health systems far more serious. The fourth industrial revolution (cyber physical systems and artificial intelligence technology) and accelerated innovation in the field of E-Health and digital health, will probably change the workflow in medical and health care, and inevitably transform the labour market in the upcoming decades. So, let us be up to the task. Let us provide academic centres, industry-sponsored pharmaceutical and medical device innovation hubs, and governing authorities alike, with a powerful forum for debate on cost-effective resource allocation in the years to come.

Substitution of Formal and Informal Home Care Service Use and Nursing Home Service Use: Health Outcomes, Decision-Making Preferences, and Implications for a Public Health Policy.

OBJECTIVES: The purposes of this study are: (1) to empirically identify decision-making preferences of long-term health-care use, especially informal and formal home care (FHC) service use; (2) to evaluate outcomes vs. costs based on substitutability of informal and FHC service use; and (3) to investigate health outcome disparity based on substitutability. METHODOLOGY AND DATA: The methods of ordinary least squares, a logit model, and a bivariate probit model are used by controlling for socioeconomic, demographic, and physical/mental health factors to investigate outcomes and costs based substitutability of informal and formal health-care use. The data come from the 2013 Japanese Study of Aging and Retirement (JSTAR), which is designed by Keizai-Sangyo Kenkyu-jo, Hitotsubashi University, and the University of Tokyo. The JSTAR is a globally comparable data survey of the elderly. RESULTS: There exists a complement relationship between the informal home care (IHC) and community-based FHC services, and the elasticity's ranges from 0.18 to 0.22. These are reasonable results, which show that unobservable factors are positively related to IHC and community-based FHC, but negatively related to nursing home (NH) services based on our bivariate probit model. Regarding health-care outcome efficiency issue, the IHC is the best one among three types of elderly care: IHC, community-based FHC, and NH services. Health improvement/outcome of elderly with the IHC is heavier concentrated on IHC services than the elderly care services by community-based FHC and NH care services. CONCLUSION: Policy makers need to address a diversity of health outcomes and efficiency of services based on providing services to elderly through resource allocation to the different types of long-term care. A provision of partial or full compensation for elderly care at home is recommendable and a viable option to improve their quality of lives.

Assessment of Intracorporeal Suturing in Single-Port Surgery Using an Experimental Suturing Model.

The aim of this study is to assess the difficulty of intracorporeal suturing in single-port surgery, using experimental suturing model in dry box. Subjects were divided for three groups: seven experienced laparoscopic surgeons, seven surgical residents, and seven interns. An experimental suturing model is developed, and working angle was set from 0° to 90°. The completion rate in 0° was significantly lower than that in the other angles. Completion rate of group A was higher than that of the other groups. Precision of task in group A was significantly higher than that of group B and group C in 0° and 60°. Stress score in 0° were significantly higher than that in the other angles. Our study demonstrated that intracorporeal suturing in single-port surgery seems to be more difficult than conventional laparoscopic surgery. Our data should be taken the institution under consideration for introduction of single-port surgery.

Prognostic and predictive significance of long interspersed nucleotide element-1 methylation in advanced-stage colorectal cancer.

BACKGROUND: Hypomethylation of Long Interspersed Nucleotide Element-1 (LINE-1) is associated with worse prognosis in colorectal cancer (CRC). However, little is known about the relevance of this marker for the prognosis and response to chemotherapy of metastatic and recurrent (advanced-stage) CRC. Our aim was therefore to investigate whether tumor LINE-1 hypomethylation correlates with patient survival and with response to 5-fluorouracil (5-FU)/ oxaliplatin (FOLFOX) chemotherapy in advanced-stage CRC. METHODS: The study included 40 CRC patients who developed metastasis or local recurrence after surgery and subsequently underwent FOLFOX therapy. Progression-free and overall survival were estimated using the Kaplan-Meier method. LINE-1 methylation levels in formalin-fixed and paraffin-embedded primary tumor tissues were measured by MethyLight assay and correlated with patient survival. In vitro analyses were also conducted with human colon cancer cell lines having different LINE-1 methylation levels to examine the effects of 5-FU and oxaliplatin on LINE-1 activity and DNA double-strand-breaks. RESULTS: Patients with LINE-1 hypomethylation showed significantly worse progression-free (median: 6.6 vs 9.4 months; P = 0.02) and overall (median: 16.6 vs 23.2 months; P = 0.01) survival following chemotherapy compared to patients with high methylation. LINE-1 hypomethylation was an independent factor for poor prognosis (P = 0.018) and was associated with a trend for non-response to FOLFOX chemotherapy. In vitro analysis showed that oxaliplatin increased the LINE-1 score in LINE-1-expressing (hypomethylated) cancer cells, thereby enhancing and prolonging the effect of 5-FU against these cells. This finding supports the observed correlation between tumor LINE-1 methylation and response to chemotherapy in CRC patients. CONCLUSIONS: Tumor LINE-1 hypomethylation is an independent marker of poor prognosis in advanced-stage CRC and may also predict non-response to combination FOLFOX chemotherapy. Prospective studies are needed to optimize the measurement of tumor LINE-1 methylation and to confirm its clinical impact, particularly as a predictive marker.

Do Health Reforms Impact Cost Consciousness of Health Care Professionals? Results from a Nation-Wide Survey in the Balkans.

BACKGROUND: Serbia, as the largest market of the Western Balkans, has entered socioeconomic transition with substantial delay compared to most of Eastern Europe. Its health system reform efforts were bold during the past 15 years, but their results were inconsistent in various areas. The two waves of global recession that hit Balkan economies ultimately reflected to the financial situation of healthcare. Serious difficulties in providing accessible medical care to the citizens became a reality. A large part of the unbearable expenses actually belongs to the overt prescription of pharmaceuticals and various laboratory and imaging diagnostic procedures requested by physicians. Therefore, a broad national survey was conducted at all levels of the healthcare system hierarchy to distinguish the ability of cost containment strategies to reshape clinician's mindsets and decision-making in practice. AIMS: Assessment of healthcare professionals' judgment on economic consequences of prescribed medical interventions and evaluation of responsiveness of healthcare professionals to policy measures targeted at increasing cost-consciousness. STUDY DESIGN: Cross-sectional study. METHODS: A nationwide cross-sectional survey was conducted through a hierarchy of medical facilities across diverse geographical regions before and after policy action, from January 2010 to April 2013. In the middle of the observed period, the National Health Insurance Fund (RFZO) adopted severe cost-containment measures. Independently, pharmacoeconomic guidelines targeted at prescribers were disseminated. Administration in large hospitals and community pharmacies was forced to restrict access to high budget-impact medical care. Economic Awareness of Healthcare Professionals Questionnaire-29 (EAHPQ-29), developed in Serbian language, was used in face-to-face interviews. The questionnaire documented clinician's attitudes on: Clinical-Decision-Making-between-Alternative-Interventions (CDMAI), Quality-of-Health-Care (QHC), and Cost-Containment-Policy (CCP). The authors randomly and anonymously recruited 2000 healthcare experts, with a total of 1487 responding; after eliminating incomplete surveys, 649 participants were considered before and 651 after policy intervention. RESULTS: Dentists (1.195±0.560) had a higher mean CDMAI score compared to physicians (1.017±0.453). The surgical group compared to the internist group had a higher total EAHPQ-29 score, CCP score and CDMAI score. Policy intervention had a statistically significant negative impact on the QHC score (F=4.958; df=1; p=0.027). There was no substantial impact of policy interventions on professional behavior and judgment with regard to the CDMAI, CCP, and total EAHPQ-29 scores. CONCLUSION: Although cost savings were forcibly imposed in practice, the effects on clinical decision-making were modest. Clinicians' perceptions of quality of medical care were explained in a less effective manner due to the severely constrained resources allocated to the providers. This pioneering effort in the Balkans exposes the inefficiency of current policies to expand clinicians' cost consciousness.

Reduced port laparoscopic gastrectomy for gastric cancer.

The use of reduced port laparoscopic surgery (RPS) has become increasingly popular. The concept of RPS includes all procedures derived from various efforts minimizing the invasiveness of surgery, with single-incision laparoscopic surgery (SILS) being the ultimate reduced port technique. Reduced-port laparoscopic gastrectomy (RPLG) for gastric cancer has not yet been fully established and still has issues such as feasibility, oncological validity, training, and education. The short-term results of reported studies are acceptable. However, long-term results that verify positive results or radical cure even in cases of cancer have not yet been published. Patients for whom RPLG is indicated should be selected carefully. Prospective multicenter studies should be conducted to establish RPS as a truly evidence-based practice that addresses not only cosmesis but also the appropriate balance between minimal invasiveness and radical cure.

Access disparity and health inequality of the elderly: unmet needs and delayed healthcare.

The purpose of this study is to investigate healthcare access disparity that will cause delayed and unmet healthcare needs for the elderly, and to examine health inequality and healthcare cost burden for the elderly. To produce clear policy applications, this study adapts a modified PRECEDE-PROCEED model for framing theoretical and experimental approaches. Data were collected from a large collection of the Community Tracking Study Household Survey 2003-2004 of the USA. Reliability and construct validity are examined for internal consistency and estimation of disparity and inequality are analyzed by using probit/ols regressions. The results show that predisposing factors (e.g., attitude, beliefs, and perception by socio-demographic differences) are negatively associated with delayed healthcare. A 10% increase in enabling factors (e.g., availability of health insurance coverage, and usual sources of healthcare providers) are significantly associated with a 1% increase in healthcare financing factors. In addition, information through a socio-economic network and support system has a 5% impact on an access disparity. Income, health status, and health inequality are exogenously determined. Designing and implementing easy healthcare accessibility (healthcare system) and healthcare financing methods, and developing a socio-economic support network (including public health information) are essential in reducing delayed healthcare and health inequality.

An evaluation of healthcare information on the Internet: the case of colorectal cancer prevention.

Health information, provided through the Internet, has recently received attention from consumers and healthcare providers as an efficient method of motivating people to get screened for colorectal cancer (CRC). In this study, the primary purpose was to investigate the extent to which consumers were better educated about CRC screening information because of the information available on the Internet. Another purpose was to identify how better-informed consumers, with reliable and trustworthy health information, were enabled to make sound decisions regarding CRC screening. The data used in this study was taken from the 2003 Health Information National Trends Survey. People aged 55 and older were classified based on their compliance with recommended CRC screening. The study applied the PRECEDE-PROCEED model to evaluate the effects of health information taken from the Internet regarding CRC screening. The credibility and reliance of cancer related information on the Internet was significantly associated with patient compliance to be screened for CRC. Experience and knowledge of Internet use had a significant impact on the utilization of CRC screening. This analysis suggests that the design and publishing websites concerning CRC should emphasize credibility and reliance. Websites providing information about CRC must also contain the most current information so that people are able to make educated decisions about CRC screening.

Stabilities of the Divalent Metal Ion Complexes of a Short-Chain Polyphosphate Anion and Its Imino Derivative.

ABSTRACT: The stability constants of ML-type complexes of the two linear triphosphate ligand anion analogues triphosphate ([Formula: see text]) and diimidotriphosphate ([Formula: see text]) were investigated thermodynamically using potentiometric titrations according to Schwarzenbach's procedure. The stability constants of the ML-type complexes of different divalent metal ions with [Formula: see text] are larger than those of the corresponding complexes with [Formula: see text] because of the greater basicity of the imino group. The order of the stability constants for the ML-type complexes follows the Irving-Williams order, indicating that only non-bridging oxygen atoms are coordinated directly to the different metal ions in both ligands, and that the imino groups cannot participate in coordination to the metal ions. In the complexation reactions of the Ca2+, Sr2+, Ba2+-[Formula: see text] and Cu2+, Zn2+, Ni2+-[Formula: see text] systems, each metal ion forms an enthalpically stable complex, and there was no suggestion of a conspicuous entropic effect based on the chelate effect. Monodentate complexes that are strongly coordinated with the ligands were therefore formed, whereas entropically stable bidentate complexes were formed in the complexation reactions of the Cu2+, Zn2+, Ni2+-[Formula: see text] and Ca2+, Ba2+, Sr2+-[Formula: see text] systems. According to the HSAB concept, hard metal cations such as Ca2+, Ba2+ and Sr2+ should bind to the harder oxygen atoms rather than the softer nitrogen atoms of the imidopolyphosphate anions, preventing direct coordination to the imino nitrogen atom.

[A case of advanced gastric cancer diagnosed as stage IV responding to combined modality therapy and surviving for a long duration].

A 47-year-old woman was diagnosed as advanced gastric cancer of cardia(poorly-differentiated adenocarcionoma), with multiple para-aortic lymph node and liver metastasis, in March, 2005. We attempted neo-adjuvant chemotherapy with docetaxel(DOC), cisplatin(CDDP), and S-1(DCS). After 3 courses of DCS, we confirmed that the para-aortic lymph nodes and liver metastasis became small. Then, we were able to perform total gastrectomy, splenectomy, and D2 lymph node dissection. Additionally, we performed an intraoperative radiofrequency ablation to the scar of the liver metastasis. Histopathologically, we identified lymph node metastases in #1 and #16b1 pre. S-1 and DOC were administered as adjuvant chemotherapy. At seven years since the operation, the patient has shown no signs of recurrence. Combined modality therapy for advanced gastric cancer diagnosed with stage IV can be an effective treatment, so we hope that it will be established as a standard therapy.

Intrinsic 31P NMR Chemical Shifts and the Basicities of Phosphate Groups in a Short-Chain Imino Polyphosphate.

ABSTRACT: The stepwise protonation constants of two linear triphosphate ligand anions, triphosphate, [Formula: see text] and di-imidotriphosphate, [Formula: see text], were investigated by potentiometric titration, and the intrinsic chemical shifts of the stepwise protonated species of these anions were determined from the pH-dependence of the 31P NMR chemical shifts. All stepwise protonation constants of [Formula: see text]were found to be larger than those of [Formula: see text], and the 31P NMR signals due to P3O8(NH)2 always appeared at a lower magnetic field compared to the signals due to P3O10. These results indicate higher basicity of the P3O8(NH)2 ligand, because it contains two imino groups in the ligand molecule. The 31P NMR signals for the end phosphate groups appear at a lower magnetic field than those for the middle phosphate groups, indicating that the basicity of the end phosphate group is higher than that of the middle phosphate group. It can be expected that the high basicity of the P3O8(NH)2 ligand brings about the formation of high stability complexes with various metal ions. Furthermore, the only 31P NMR signal due to the middle phosphate group of P3O8(NH)2 ligand molecule clearly showed a low-field shift in the range of pH < 2.5. The reason for this peculiar low-field shift should be the change of the localization of imino protons around the nitrogen atom in P3O8(NH)2.

[A case of recurrent breast cancer with multiple bone metastasis successfully treated with S-1 and zoledronic acid therapy].

For a case of recurrent breast cancer with multiple bone metastasis, an oral pyrimidine fluoride-based anti-cancer drug S -1, and zoledronic acid(a third-generation bisphosphonate formulation), were prescribed in experiments to test their efficacy. S-1 was prescribed orally at doses of 100 mg/day(twice)over a 4-week period with a cessation period of 2 weeks. Zoledronic acid was commenced with a strict administration of 4 mg every 4 weeks, taken intravenously. At the conclusion of the 1st S-1 course, the tumor markers began to improve to a certain extent with an improvement in the symptoms. Following the 16 courses, there was no abnormal accumulation detected by PET. Now, at the end of the 21st course, the treatment is being continued, and there has been no recurrence of inflammation or reoccurring growth detected. No adverse effects of more than Grade 1 occurred during the elapsed process. As a form of combined therapy, we can expect zoledronic acid to be a good anti-cancer drug because of its effectiveness and tolerability in treating recurring breast cancer.

[Clinicopathological characteristics of ten cases of advanced gastric carcinoma after S-1 combined with cisplatin administered as neoadjuvant chemotherapy].

OBJECTIVE: Although neoadjuvant chemotherapy(NAC)has been recognized as an important option for improving the clinical outcome of patients with advanced gastric carcinoma, convincing evidence that it prolongs life and brings about a good prognosis are both lacking. We retrospectively evaluated the efficacy and safety of NAC in ten patients with advanced gastric cancer. METHODS: A total of ten patients with advanced gastric cancer, who received NAC with the combination of S-1 and cisplatin in our hospital from April 2008 to March 2010, were retrospectively investigated. RESULTS: A total of 5 patients responded to neoadjuvant chemotherapy, and 2 patients showed a complete regression of the primary gastric carcinoma. Four of the 5 patients who responded had solid-type poorly-differentiated adenocarcinoma. CONCLUSION: NAC with the combination of S-1 and cisplatin was suggested to be effective for advanced gastric carcinoma, especially for solid-type poorly differentiated adenocarcinomas(por1).

[Two cases of metastatic colorectal cancer in wild-type K-RAS effectively treated by panitumumab].

Case 1 was a 58-year-old woman diagnosed with unresectable liver metastases from advanced rectal cancer. We performed laparoscopic low anterior resection for sigmoid cancer. As the first-line treatment, FOLFOX+bevacizumab(BV)was applied for 16 courses. The second-line treatment, FOLFIRI plus BV, was applied for four courses. However, the disease progressed with worsening liver metastases. The sequencing of K-RAS genes from the biopsy specimens of sigmoid colon cancer revealed an expression of a wild-type K-RAS. As the third-line treatment, panitumumab was applied. After 8 courses of this chemotherapy regimen, a significant reduction in the size of liver metastases was observed. Case 2 was an 81-year-old man diagnosed with unresectable liver metastases from advanced rectal cancer. We obliged the patient by performing laparoscopic rectal resection. As the first-line treatment, XELOX plus BV was applied for 10 courses. As the second-line treatment, IRIS was applied for 6 courses. However, this failed to prevent him from having a progressive disease. As the third-line treatment, panitumumab was applied for 2 courses, and a significant reduction in the size of liver metastases was observed. Our findings suggested that panitumumab has great potential for effective treatment of patients with unresectable stageIV colorectal cancer.

[A case of liver metastases of sigmoid colon cancer treated effectively by oral UFT/LV].

The patient was a 77-year-old woman with multiple liver metastases of sigmoid colon cancer. She underwent low anterior resection for sigmoid colon cancer. After surgery, she selected oral administration of UFT and LV for liver metastases and multiple lymph node metastases. After two courses, the liver metastases had markedly diminished. Thirty-two months later, liver metastases had disappeared on computer tomography. This therapy was continued for five years, and recurrences are no longer shown. Severe adverse effects were not observed. Oral anti-cancer drugs can serve as effective therapy for advanced colorectal cancer of old patients.

[A case of disseminated carcinomatosis of bone marrow treated by S-1 and cisplatin after distal gastrectomy for early gastric cancer].

Patients with bone metastasis originating from gastric cancer experience complications from DIC. They are treated with anticoagulation therapy or platelet transfusion, but their prognosis is poor. Our case was a 50-year-old male who had undergone distal gastrectomy for early gastric cancer[pT1a(M)N0M0, pStage I a]ten years previously. He was admitted to our hospital complaining of backache. As a result of his examination, he was diagnosed with disseminated carcinosis of bone marrow with DIC as a postoperative recurrence of gastric cancer. The patient was treated with combination chemotherapy of S-1 and cisplatin(S-1 80 mg/body, po, day 1-21 and cisplatin 50mg/body, iv, day 8). After one course of treatment, DIC was resolved and his pain was relieved. He survived for about nine months. S-1 and cisplatin are considered to be effective for disseminated carcinosis of bone marrow.

Cervical thymuses exist, but no cervical thymomas develop in thoracic thymoma-prone BUF rats.

To confirm the existence of the cervical thymus and the development of cervical thymoma in thymoma-prone BUF/Mna (BUF) rats, we examined cervical organs and adjacent tissues, and thoracic thymic tissues of the three inbred strains, BUF, ACI/NMna (ACI), and WKY/NCrj (WKY), and 11 congenic strains, in which genetic regions of rat nude (Rnu), thymus enlargement-1 and thymus enlargement-2 (Ten1 and Ten2), thymoma susceptibility of rat-1 (Tsr1), atrophy of fast-twitch muscles-1 (Aftm1) and proteinuria of rat-1 (Pur1) were transferred into BUF, ACI or WKY rats. These organs and tissues were fixed en block in 10% formalin and cut coronally into four to six slices of 3-mm thickness, depending on the age of the rat, and embedded together in one block for each rat. Sections were cut and stained with haematoxylin and eosin and examined microscopically. Cervical thymuses were detected in 12-21% of rats from these inbred and congenic strains. No cervical thymuses were found in BUF-Rnu/Rnu rats, which were athymic. All of 42 BUF, 2 of 55 BUF-Rnu/+ and 28 of 33 ACI-Tsr1/Tsr1 rats survived more than 52 weeks, and developed thoracic thymoma, but no cervical thymomas did. It is therefore clear that cervical thymuses behave differently from thoracic thymuses in spontaneous thymomagenesis in BUF rats.