How adverse selection affects the health insurance market

Adverse selection can be defined as strategic behavior by the more informed partner in a contract against the interest of the less informed partner(s). In the health insurance field, this manifests itself through healthy people choosing managed care and less healthy people choosing more generous plans. Drawing on theoretical literature on the problem of adverse selection in the health insurance market, the author synthesizes concepts developed piecemeal over more than 20 years, using two examples and revisiting the classical contribution of Rothschild and Stiglitz. He highlights key insights, especially from the literature on"equilibrium refinements"and on the theory of"second best."The government can correct spontaneous market dynamics in the health insurance market by directly subsidizing insurance or through regulation; the two forms of intervention provide different results. Providing partial public insurance, even supplemented by the possibility of opting out, can lead to second-best equilibria. The same result holds as long as the government can subsidize contracts with higher-than-average premium-benefit ratios and can tax contracts with lower-than-average premium-benefit ratios. The author analyzes the following policy options relating to the public provision of insurance: a) Full public insurance. b) Partial public insurance with or without the possibility of acquiring supplementary insurance and with or without the possibility of opting out. In recent plans implemented in Germany and the Netherlands, where competition among several health funds and insurance companies was promoted, a public fund was created to discourage risk screening practices by providing the necessary compensation across riks groups. But only"objective"risk adjusters (such as age, gender, and region) were used to decide which contracts to subsidize. Those criteria alone cannot correct the effects of adverse selection. Regulation can exacerbate the problem of adverse selection and lead to chronic market instability, so certain steps must be taken to prevent risk screening and preserve competition for the market. The author considers the following three policy options for regulating the private insurance market: 1) A standard contract with full coverage. 2) Imposition of a minimum insurance requirement. 3) Imposition of premium rate restrictions.Health Economics&Finance,Environmental Economics&Policies,Insurance&Risk Mitigation,Insurance Law,Financial Intermediation

Incentives and the reform of health care systems.

This thesis is a study of the reform of health systems from an international and an economic perspective. Its main unifying theme is to investigate the role played by incentives in the performance of health systems and their reform. In the first part, the thesis reconsiders the economic reasons that form the basis for public intervention in health markets, both in financing as well as in service provision. In fact, one of the key elements introduced with health reforms in the last few years has been greater competition in health insurance and provision, among private as well as public providers. It is thus interesting to start the analysis by revisiting the effects of competition in health markets on the basis of more recent contributions in microeconomic theory, our aim being to ascertain what would be the major deficiencies of unregulated markets, and to investigate into the impact of different public corrective measures. Chapter 2 looks at the effects of competition in the health insurance market and at the impact of different forms of public intervention to correct market failures. Chapter 3 presents a model of oligopolistic competition between two health providers, and it investigates the potential role of quality and/or price regulation as a means to extend coverage/improve quality beyond the point reached in correspondence to the market equilibrium. Then, the thesis focuses on the new resource allocation, contracting mechanisms and payment systems for providers (RAP reforms) implemented over the last few years, within the public sector, or intended to discipline the relationship with health care providers. Chapters 4 gives an introduction to the RAP reforms, their justification and main components. Chapter 5 focuses on payment systems and on efficiency issues, while Chapter 6 on the equity consequences of RAP reforms. Chapter 7 and 8 look at the health reforms implemented over the last decade in the former socialist countries. The evolution of health systems in those countries provides interesting lessons, illuminating the major weaknesses and limitations of the health reform model that has been prevailing and proposed world-wide over the last decade. Chapter 8 presents a qualitative study of the impact of the health reforms in Georgia, focusing specifically on the phenomenon of out-of-pocket payments, formal and informal, which currently are the prevalent source of funding for health in the region. A concluding chapter (Chapter 9) summarises some of the main findings of the thesis

Receptor tyrosine kinase-dependent PI3K activation is an escape mechanism to vertical suppression of the EGFR/RAS/MAPK pathway in KRAS-mutated human colorectal cancer cell lines

Colorectal cancer; Epidermal growth factor receptor (EGFR); MAPK pathwayCàncer colorectal; Receptor epidèrmic de factor del creixement (EGFR); Via MAPKCáncer colorrectal; Receptor epidérmico de factor del crecimiento (EGFR); Vía MAPKBACKGROUND: Previous studies showed that the combination of an anti-Epidermal growth factor (EGFR) and a MEK-inhibitor is able to prevent the onset of resistance to anti-EGFR monoclonal antibodies in KRAS-wild type colorectal cancer (CRC), while the same combination reverts anti-EGFR primary resistance in KRAS mutated CRC cell lines. However, rapid onset of resistance is a limit to combination therapies in KRAS mutated CRC. METHODS: We generated four different KRAS mutated CRC cell lines resistant to a combination of cetuximab (an anti-EGFR antibody) and refametinib (a selective MEK-inhibitor) after continuous exposure to increasing concentration of the drugs. We characterized these resistant cell lines by evaluating the expression and activation status of a panel of receptor tyrosine kinases (RTKs) and intracellular transducers by immunoblot and qRT-PCR. Oncomine comprehensive assay and microarray analysis were carried out to investigate new acquired mutations or transcriptomic adaptation, respectively, in the resistant cell lines. Immunofluorescence assay was used to show the localization of RTKs in resistant and parental clones. RESULTS: We found that PI3K-AKT pathway activation acts as an escape mechanism in cell lines with acquired resistance to combined inhibition of EGFR and MEK. AKT pathway activation is coupled to the activation of multiple RTKs such as HER2, HER3 and IGF1R, though its pharmacological inhibition is not sufficient to revert the resistant phenotype. PI3K pathway activation is mediated by autocrine loops and by heterodimerization of multiple receptors. CONCLUSIONS: PI3K activation plays a central role in the acquired resistance to the combination of anti-EGFR and MEK-inhibitor in KRAS mutated colorectal cancer cell lines. PI3K activation is cooperatively achieved through the activation of multiple RTKs such as HER2, HER3 and IGF1R

Partial and exhaustive hydrolysis of lanthanide N,N-dialkylcarbamato complexes. A viable access to lanthanide mixed oxides

Partial hydrolysis (H2O/Ln molar ratio = ¼) of lanthanum di-iso-propylcarbamato complex, [La(O2CNiPr2)3], 1, afforded the tetranuclear μ-oxo derivative [La4O(O2CNiPr2)10], 2, which was structurally characterized by single crystal X-Ray diffraction studies. The carbonatocarbamato derivative of lanthanum, [La4(CO3)(O2CNBu2)10], 3, was prepared by extraction of lanthanum ions from aqueous solution into heptane by the NHBu2/CO2 system. Partial hydrolysis (H2O/Ln molar ratio = ½ ) of N,N-di-iso-propylcarbamato complexes of neodymium, europium, gadolinium and terbium, [Ln(O2CNiPr2)3], yielded the derivatives [Ln2(CO3)(O2CNiPr2)4] (Ln = Nd, 4, Eu, 5, Gd, 6). Exhaustive hydrolysis of [Ln(O2CNR2)3] (Ln = Nd, Tb, R = Bu; Ln = Eu, Gd, R = iPr, Bu) produced hydrated lanthanide carbonates, Ln2(CO3)3 n H2O. For sake of comparison with a block d metal, the exhaustive hydrolysis of two copper(II) carbamato complexes, [Cu(O2CNEt2)2(NHEt2)]2 and [Cu(O2CNiPr2)2], was carried out with formation in both cases of the hydrated basic carbonate Cu2(OH)2(CO3)nH2O. The exhaustive hydrolysis of mixtures of cerium and lanthanum or cerium and terbium N,N-dibutylcarbamato complexes allowed the preparation of mixed oxides containing the two metals in the desired molar ratio, via the intermediate formation of the corresponding mixed carbonates

Elevated 8-isoprostane levels in basal cell carcinoma and in UVA irradiated skin.

Isoprostanes are prostaglandin isomers produced from the peroxidation of polyunsaturated fatty acids from the cellular membrane. They have been used as a specific index of cellular lipoperoxidation and as an indirect measure of oxidative stress. However, these molecules also present several biological activities. An oxidative environment measured as the presence of other indirect measurements of reactive oxygen species lipoperoxidation has recently been described in basal cell carcinoma, the most frequent type of non-melanoma skin cancer. This study aims to measure the levels of 8-isoprostaglandin F2α, an isoprostane widely studied in other models as a by-product of ROS-induced lipid peroxidation, in basal cell carcinoma and in UVA irradiated healthy skin. We found that 8-iso-PGF2α is present in higher levels in BCC specimens compared to healthy non sun-exposed skin, confirming previous studies on the production of lipoperoxidation in this tumor. Moreover, we demonstrated that topical pre-treatment with a compound containing vitamin E is capable of reducing 8-iso-PGF2α formation in UV irradiated skin suggesting a role for isoprostanes in UV induced inflammation and eventually carcinogenesis and confirming the function of vitamin E as an antioxidant in this model

Synchronous Bilateral Paget's Disease of the Nipple Associated with Bilateral Breast Carcinoma

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A new risk stratification score for the management of ultrasound‐detected B3 breast lesions

To develop a predictive scoring system for ultrasound-detected B3 lesions at ultrasound-guided core needle biopsy (US-CNB). A total of 2724 consecutive US-CNBs performed in our Institution (January 2011 to December 2014) were retrospectively reviewed. Inclusion criteria were as follows: (a) histopathological examination of the entire lesion or (b) availability of radiologic follow-up (FUP) ≥24 months. Patient- and lesion-related variables-patients' age, lesion consistency, lesion size, vascularization, BI-RADS category, and US-CNB result-were analyzed. Positive predictive values (PPVs) for malignancy were calculated correlating US-CNB results with excision histology or FUP. A scoring system for underlying malignancy was developed using risk factors weighting. A total of 102 B3 lesions were included: 27 atypical ductal hyperplasia (26.5%), 5 lobular intraepithelial neoplasia (4.9%), 32 radial scar (31.4%), 37 papillary lesions (36.3%), and 1 fibroepithelial lesion (0.9%). Surgery was performed on 71/102 (69.6%) lesions, and 22/71 were malignant; the remaining 31/102 lesions (30.4%) were unchanged at FUP. The overall PPV for malignancy was 21.6%. Patients' age (odds ratio [OR] = 3.63, P = 0.008), lesion consistency (OR = 5.96, P = 0.001), BI-RADS category (OR = 17.52, P < 0.001), and CNB result (OR = 3.6, P = 0.008) were associated with a higher risk of malignancy underestimation and selected as risk factors in the score definition. Two risk groups were identified: low (0-2 points) and high risk (3-5 points), with significantly different risk of malignancy underestimation (8.0% vs 59.3%, P < 0.001). The proposed score helps to predict the risk of malignancy underestimation and choose the management of B3 lesions at US-CNB

A functional connection between dyskerin and energy metabolism

The human DKC1 gene encodes dyskerin, an evolutionarily conserved nuclear protein whose overexpression represents a common trait of many types of aggressive sporadic cancers. As a crucial component of the nuclear H/ACA snoRNP complexes, dyskerin is involved in a variety of essential processes, including telomere maintenance, splicing efficiency, ribosome biogenesis, snoRNAs stabilization and stress response. Although multiple minor dyskerin splicing isoforms have been identified, their functions remain to be defined. Considering that low-abundance splice variants could contribute to the wide functional repertoire attributed to dyskerin, possibly having more specialized tasks or playing significant roles in changing cell status, we investigated in more detail the biological roles of a truncated dyskerin isoform that lacks the C-terminal nuclear localization signal and shows a prevalent cytoplasmic localization. Here we show that this dyskerin variant can boost energy metabolism and improve respiration, ultimately conferring a ROS adaptive response and a growth advantage to cells. These results reveal an unexpected involvement of DKC1 in energy metabolism, highlighting a previously underscored role in the regulation of metabolic cell homeostasis

Primary systemic treatment and concomitant low dose radiotherapy for breast cancer: final results of a prospective phase II study.

Abstract Background To evaluate the efficacy of preoperative low dose fractionated radiotherapy (LD-FRT) and chemotherapy in breast cancer. Materials and methods Patients with stage IIA–IIIA breast cancer, received LD-FRT (0.40 Gy bid, on day 1 and 2, for 6 cycles) to primary tumor volume and concurrent chemotherapy with non-pegylated liposomal anthracycline and docetaxel. Pathological response was assessed by Mandard Tumor Regression Grade (TRG). We evaluated the pathological major response rate (PMRR) as TRG1 and TRG2. The expected outcome was a PMRR of 60%. The accrual was determined by the single proportion powered analysis ( α = 0.05, power = 0.8). Results Twentyone patients were enrolled. No grade 2–4 acute skin and hematological toxicity was observed. TRG1 was obtained in 3 patients (14.3%), TRG2 in 4 patients (19%). The PMRR was 33.3%; it does not concur with the expected result, but is similar to that of chemotherapy alone. According to molecular subtype, 2/11 luminal A patients and 4/6 luminal B patients obtained a PMRR to preoperative treatment (35.3%); 1/4 basal like patients reported TRG1 (25%). Conclusions LD-FRT concomitant with primary systemic treatment has a good toxicity profile. The response rate is consistent with that of chemotherapy alone, and suggests different interactions between low dose radiotherapy and molecular subtypes. Additional investigations are planned

Preoperative workup in the assessment of adrenal incidentalomas: outcome from 282 consecutive laparoscopic adrenalectomies

Abstract Background: To confirm the efficacy of preoperative workup, the authors analyse the results of a multicentre study in a surgical series of patients diagnosed with an adrenal incidentaloma. Methods: The retrospective review of a prospectively collected database was conducted. The data was obtained by six surgical units operating in the Campania Region, Italy. Five-hundred and six (506) adrenalectomies performed between 1993 and 2011 on 498 patients were analysed. Final histology in patients with a preoperative diagnosis of incidentaloma and studied according to guidelines (230/282 patients group A) was compared with final histology coming from patients presenting the same preoperative diagnosis but studied not according to guidelines (52/282 patients group B). Results: In group A preoperative diagnosis was confirmed at final histology in 76/81 (93.8%) cases of subclinical functioning lesions presenting as an incidentaloma. The preoperative detection of pheochromocytoma and primary adrenocortical cancer (ACC) reached 91.6% and 84.6% respectively. In group B conversion rate to open surgery was higher than in group A (p = 0.02). One pheochromocytoma was missed at preoperative diagnosis whereas one ACC smaller than 4 centimetres (cm) and coming from an incidental lesion was discovered. In both groups a significant association between increasing dimensions of incidentaloma and cancer has been observed (p = 0.001). Conclusions: This surgical series confirm the high efficacy of suggested guidelines. A significant preoperative detection rate of adrenal lesions presenting as incidentaloma is observed. The unnecessary number of adrenalectomies performed in understudied patients, causing higher morbidity, was not associated to a higher detection rate of primary adrenocortical cancer