A Probability Approach to Pharmaceutical Demand and Price Setting: Does the Identity of the Third-Party Payer Mattersfor Prescribing Doctors?

TNF-alpha inhibitors represent one of the most important areas of biopharmaceuticals by sales, with three blockbusters accounting for 8 per cent of total pharmaceutical sale in Norway. Novelty of the paper is to examine, with the use of a unique natural policy experiment in Norway, to what extent the price responsiveness of prescription choices is affected when the identity of the third-party payer changes. The three dominating drugs in this market, Enbrel, Remicade, and Humira, are substitutes, but have had different and varying funding schemes - hospitals and the national insurance plan. A stochastic structural model for the three drugs, covering demand and price setting, is estimated in a joint maximum likelihood approach. We find that doctors are more responsive when the costs are covered by the hospitals compared to when costs are covered by national insurance.pharmaceuticals, discrete choice model, funding-schemes

A probability approach to pharmaceutical demand and price setting: Does the identity of the third-party payer matters for prescribing doctors?

TNF-alpha inhibitors represent one of the most important areas of biopharmaceuticals by sales, with three blockbusters accounting for 8 per cent of total pharmaceutical sale in Norway. Novelty of the paper is to examine, with the use of a unique natural policy experiment in Norway, to what extent the price responsiveness of prescription choices is affected when the identity of the third-party payer changes. The three dominating drugs in this market, Enbrel, Remicade, and Humira, are substitutes, but have had different and varying funding schemes - hospitals and the national insurance plan. A stochastic structural model for the three drugs, covering demand and price setting, is estimated in a joint maximum likelihood approach. We find that doctors are more responsive when the costs are covered by the hospitals compared to when costs are covered by national insurance

Oligophrenin-1 (OPHN1), a gene involved in X-linked intellectual disability, undergoes RNA editing and alternative splicing during human brain development

Oligophrenin-1 (OPHN1) encodes for a Rho-GTPase-activating protein, important for dendritic morphogenesis and synaptic function. Mutations in this gene have been identified in patients with X-linked intellectual disability associated with cerebellar hypoplasia. ADAR enzymes are responsible for A-to-I RNA editing, an essential post-transcriptional RNA modification contributing to transcriptome and proteome diversification. Specifically, ADAR2 activity is essential for brain development and function. Herein, we show that the OPHN1 transcript undergoes post-transcriptional modifications such as A-to-I RNA editing and alternative splicing in human brain and other tissues. We found that OPHN1 editing is detectable already at the 18th week of gestation in human brain with a boost of editing at weeks 20 to 33, concomitantly with OPHN1 expression increase and the appearance of a novel OPHN1 splicing isoform. Our results demonstrate that multiple post-transcriptional events occur on OPHN1, a gene playing an important role in brain function and development

Load following with Small Modular Reactors (SMR): A real options analysis

Load following is the potential for a power plant to adjust its power output as demand and price for electricity fluctuates throughout the day. In nuclear power plants, this is done by inserting control rods into the reactor pressure vessel. This operation is very inefficient as nuclear power generation is composed almost entirely of fixed and sunk costs; therefore, lowering the power output doesn't significantly reduce generating costs and the plant is thermo-mechanical stressed. A more efficient solution is to maintain the primary circuit at full power and to use the excess power for cogeneration. This paper assesses the technical-economic feasibility of this approach when applied to Small Modular Reactors (SMR) with two cogeneration technologies: algae-biofuel and desalinisation. Multiple SMR are of particular interest due to the fractional nature of their power output. The result shows that the power required by an algae-biofuel plant is not sufficient to justify the load following approach, whereas it is in the case of desalination. The successive economic analysis, based on the real options approach, demonstrates the economic viability of the desalination in several scenarios. In conclusion, the coupling of SMR with a desalination plant is a realistic solution to perform efficient load following

Numb Isoforms Deregulation in Medulloblastoma and Role of p66 Isoform in Cancer and Neural Stem Cells

Numb is an intracellular protein with multiple functions. The two prevalent isoforms, Numb p66 and Numb p72, are regulators of differentiation and proliferation in neuronal development. Additionally, Numb functions as cell fate determinant of stem cells and cancer stem cells and its abnormal expression has been described in several types of cancer. Involvement of deregulated Numb expression has been described in the malignant childhood brain tumor medulloblastoma, while Numb isoforms in these tumors and in cancer stem-like cells derived from them, have not been studied to date. Here we show that medulloblastoma stem-like cells and cerebellar neuronal stem cells (NSCs) express Numb p66 where its expression tampers stemness features. Furthermore, medulloblastoma samples evaluated in this study express decreased levels of Numb p66 while overexpressed Numb p72 compared with normal tissues. Our results uncover different roles for the two major Numb isoforms examined in medulloblastoma and a critical role for Numb p66 in regulating stem-like cells and NSCs maintenance

Communicating cancer diagnosis and prognosis: When the target is the elderly patient-a GIOGer study

Background: Effective communication to cancer patients allows better emotional response to diagnosis, coping with health professionals and compliance to treatment. We lack specific studies on patterns of clinical communication in elderly patients, their involvement in decision making and the role of their families. Patients and methods: Structured interviews to collect information on diagnosis and prognosis disclosure, satisfaction with information, compliance to disease experience and willingness toward receiving more information and coping, were administered to patients age 65 years and older and receiving chemotherapy. Results: Six hundred and twenty two patients completed the interviews and were evaluated. Four hundred and twelve (66.2%) were informed, 210 (33.8%) were not informed. Information was associated with age, degree of education, geographical area, ECOG-PS, tumour site and family composition and the patient's perception of being supported in the disease experience. The majority of the patients consider their families as the main source of support in the disease experience (86.5%), wish to have a family member participating in oncology consultation (79.1%) and consider the information received complete and understandable or clear and reassuring (80%). Receiving adequate information facilitates a better patient-health professional relationship for 84.8% of the patients. 63% of the patients dealt positively with cancer and 62.2% showed positive expectations for the future. Informed patients refer better expectation than those not informed. Conclusion: Our study underlines the importance of clinical information for older cancer patients and the need to involve family members in the processes of diagnosis and prognosis disclosure and decision making. Health professionals must consider specific age-related issues including social, cultural and emotional aspects and understand the role that the family members play in the disease experience of elderly patients. Competent caring for elderly cancer patients must provide adequate information and emotional support not only to the patients but also to their family to assure appropriateness of care. © 2008 Elsevier Ltd. All rights reserved

Combined NMDA Inhibitor Use in a Patient With Multisubstance-induced Psychotic Disorder

This document is an Accepted Manuscript reprinted from Journal of Addiction Medicine, Vol. 12 (3): 247-251, May 2018, with permission of Kluwer Law International. Under embargo until 1 May 2019. The Version of Record is available online at DOI: https://doi.org/10.1097/ADM.0000000000000390: Novel psychoactive substance use is a major social concern. Their use may elicit or uncover unpredictably as yet undescribed clinical pictures. We aimed to illustrate a multisubstance use case indistinguishable from paranoid schizophrenia, so to alert clinicians on possibly misdiagnosing substance-induced psychotic disorders. CASE REPORT: We describe a case of a 32-year-old man who started at 18 years with cannabinoids and ketamine, and is currently using N-methyl-D-aspartate (NMDA) antagonists. At age 23, he developed social withdrawal after being assaulted by a stranger, but did not consult psychiatrists until age 26; during this period, he was using internet-purchased methoxetamine and ketamine, and was persecutory, irritable, suspicious, and insomniac and discontinued all received medical prescriptions. He added dextromethorphan to his list of used substances. At age 31, while using phencyclidine, and, for the first time, methoxphenidine, he developed a religious delusion, involving God calling him to reach Him, and the near-death experiences ensured by NMDA antagonists backed his purpose. He received Diagnostic and Statistical Manual of Mental Disorders, 5th Edition diagnosis of multisubstance-induced psychotic disorder and was hospitalized 8 times, 6 of which after visiting the emergency room due to the development of extreme anguish, verbal and physical aggression, and paranoia. He reportedly used methoxphenidine, methoxyphencyclidine, ethylnorketamine, norketamine, and deschlorketamine, to achieve near-death experiences, and eventually to reach God in heavens. CONCLUSIONS: This case points to the need for better control of drugs sold on the internet. It also illustrates that people using NMDA antagonists may present clinical pictures indistinguishable from those of major psychoses and are likely to be misdiagnosed.Peer reviewe

Opposite effects of suicidality and lithium on gray matter volumes in bipolar depression

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Effect of early stress on hippocampal gray matter is influenced by a functional polymorphism in EAAT2 in bipolar disorder

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