Modeling Pharmaceutical Risk-Sharing Agreements

Many new and expensive drugs have been introduced in the past 10 years. However, at the time of introduction, the effectiveness of these drugs outside of clinical trials is often unknown. This creates a risk to third-party payers, as the outcome of these drugs in real-world practice is uncertain at the time of introduction. A pay-for-performance risk-sharing agreement is a type of contract that shares part of this risk with the manufacturer by linking the performance of a drug to the manufacturer’s revenue. This dissertation consists of three essays to examine the performance of two types of pharmaceutical pay-for-performance risk-sharing agreements. In my first essay I examine the performance of a pay-for-performance risk-sharing agreement in which patients are assessed at some evaluation time to determine their response to the drug. The manufacturer rebates to the payer a proportion of the sales from all patients excluding the sales from those responding at the evaluation time. I model disease progression using a continuous time Markov chain with uncertain transition rates. I address the following questions regarding the performance of this agreement: What is the optimum evaluation time and under what conditions will the manufacturer make a profit? What is the distribution of the manufacturer’s profit resulting from different sources of uncertainty? In the second essay I extend the model developed in the first essay to calculate the net monetary benefits of the payer and identify the conditions under which both parties have incentives to introduce the new drug. The third essay focuses on the analysis of a risk-sharing agreement in which patients are prescribed a drug only if their probability of response lies within a range of success probabilities. The payer determines this range such that the use of the drug is cost-effective. I generalize from the existing literature by allowing the rebate to be different from the price of the drug and incorporating two types of administrative costs. I seek to answer two important policy questions: First, under what conditions does the payer benefit from the agreement? Second, under what conditions does the agreement become welfare-improving

Preparation and characterization of self-Nanoemulsifying drug delivery system (SNEDDS) for oral delivery of curcumin

Introduction: Curcumin is a compound possessing different pharmacological effects which is poorly soluble. Also, bioavailability of curcumin is low. In this study we aimed to improve solubility and bioavailability of curcumin by developing a self-nanoemulsifying drug Delivery system (SNEDDS) for oral delivery of curcumin. Methods and Results: Box –behnken was used to design optimum run. Several factors such as concentration of solvent, surfactant, and co-solvent were independent while dependent factors include droplet size, PDI (poly dispersity index), and zeta potential. Although, release test and study EE % (Entrapment efficiency) were done and images were taken using a TEM microscope. Droplet size of optimized formulation SNEDDS was 245.22 nm. PDI and zeta potential were 0 .38 and -1.28 mv, respectively. TEM images showed that the particles were spherical with no sign of aggregation. Also, our results revealed slow release profile. Conclusions: The obtained results indicated that SNEDDS could be considered as a good candidate for oral delivery of curcumin to improve its solubility and bioavailability as an active ingredient

Characterization of continuous kenaf-glass fiber hybrid composites for structural application

Kenaf fibers generally has some advantages such as eco-friendly, biodegradability, renewable nature and lighter than synthetic fibers. However, their mechanical properties are lower than synthetic fibers. Hybridization of bio-fiber with a synthetic fiber could improve the mechanical properties of composites. The aims of the study are to characterize and evaluate the properties of kenaf fiber composites and its hybridizations with glass fiber and also to investigate the performance of biocomposite as the strengthening plate for structural applications. The study was conducted in three stages. Firstly, the raw materials and composites were developed by conducting laboratory tests on physical and mechanical properties. The properties and the effects of different conditions of alkaline treatment on the properties of kenaf fibers were studied due to the various alkaline treatment conditions. Besides, the scanning electron microscopy was employed to observe the specimens appearance, fracture area and fiber diameter. The tensile properties of glass fiber composites, kenaf fiber composites and hybrid kenaf/glass fiber composites were determined with various fiber volume contents. The second stage was the application of composite materials as strengthening plate in reinforced concrete beams and subjected to flexural test under the four points loading system until failure. Fifteen beam specimens were prepared and tested for the study. The third stage was analytical investigations and theoretical development of the properties of composites and performance of strengthened reinforced concrete (RC) beams. According to the results of this study, the average diameter, the density and tensile strength of kenaf fiber were 67.6 μm, 1.2 g/cm3 and 780 MPa, respectively. Meanwhile, the tensile strength of hybrid kenaf/glass bio-composites exhibited almost equivalence to the glass fiber composites and also the highest strain energy density among the composites in the same value of fiber content. It was observed that increasing the glass fiber fraction more than 10% in hybrid composite caused the reduction in the ultimate tensile strain. For the hybrid bio-composites, debonding between the kenaf and glass layers caused the failure of composites. The flexural tests of RC beams showed the equivalent performance of the hybrid kenaf/glass bio-composite and the glass fiber composite strengthening plates. An analytical investigation has validated that the rule of mixture (ROM) could predict reasonably the elastic modulus of composites. The analytical model of this study based on the nonlinear stress–strain curve of concrete predicted well the moment capacity of RC beams as compared to the ACI 440.2R guideline. Therefore, this model was proposed in order to establish the analytical formulations for RC beams strengthened with the composites plates

2,2′-Diamino-5,5′-dimethyl-4,4′-bi-1,3-thia­zolium tetra­chlorido­zincate(II)

In the dianion of the title compound, (C8H12N4S2)[ZnCl4], the ZnII ion is in a slightly distorted tetra­hedral environment. In the cation, the mean planes of the thia­zole rings form a dihedral angle of 67.81 (6) Å. In the crystal structure, anions and cations are linked into a three-dimensional network via inter­molecular N—H⋯Cl hydrogen bonds

Structural and electronic properties of monodomain ultrathin PbTiO3/SrTiO3/PbTiO3/SrRuO3 heterostructures: A first principles approach

First-principles calculations within the local density approximation were carried out to explain the ground state and electronic properties of a vacuum/PbTiO3=SrTiO3=PbTiO3=SrRuO3 multilayer in a monodomain phase. Open-circuit boundary conditions were assumed, considering the electric displacement field, D, as the fundamental electrical variable. The direction and the magnitude of D can be monitored by proper treatment of the PbO surface layer, introducing external fractional charges Q in the surface atomic layers by means of virtual crystal approximation. Different excess or deficit surface charges (from Q ¼ +0:05 to Q ¼ +0:15) were considered, corresponding to small values of the polarization (up to +0:16C=m2) in both directions. The layer-by-layer electric polarization, tetragonality, and the profile of the electrostatic potential were computed, as well as the projected density of states, as a function of electric displacement field. The magnitude of D is preserved across the dielectric layers, which translates into a polarization of the SrTiO3 spacer layer. The tetragonality of the two PbTiO3 layers is different, in good agreement with experimental x-ray diffraction techniques, with the layer closer to the free surface exhibiting a smaller value. This is attributed to the interplay with surface effects that tend to contract the material in order to make the remaining bonds stronger. Our calculations show how the final structure in this complex oxide heterostructure comes from a delicate balance between electrical, mechanical, and chemical boundary conditions.R.M. thanks Professor Emily Hilder and Professor Nikki Stanford for their support. J.J. acknowledges financial support from the Spanish Ministry of Science, Innovation and Universities through Grant No. PGC2018-096955-B-C41

Morphology- and size-controlled synthesis of a metal-organic framework under ultrasound irradiation : an efficient carrier for pH responsive release of anti-cancer drugs and their applicability for adsorption of amoxicillin from aqueous solution

Support of this investigation by Tarbiat Modares University is gratefully acknowledged.In this study, we have reported a biocompatible metal-organic framework (MOF) with ultra-high surface area, which we have shown to have uses as both a cancer treatment delivery system and for environmental applications. Using a sonochemical approach, highly flexible organic H3BTCTB and ditopic 4,4́′-BPDC ligands, along with modulators of acetic acid and pyridine were combined to prepare a Zn(II)-based metal-organic framework, DUT-32, [Zn4O(BPDC)(BTCTB)4/3(DEF)39.7(H2O)11.3]. Powder X-ray diffraction (PXRD), field-emission scanning electron microscopy (FE-SEM), and Fourier transform infrared spectroscopy (FTIR) were used to characterize, the particle size, shape, and structure of the DUT-32. To show the effects of shape and size of DUT-32 micro/nano-structures on doxorubicin (DOX) drug release and amoxicillin (AMX) adsorption, time of sonication, initial reagent concentrations, irradiation frequency, and acetic acid to pyridine molar ratios were optimized. The drug-loaded DUT-32 was soaked in simulated body fluid (SBF) and the drug release ratio was monitored through release time to perform in vitro drug release test. A slow and sustained release was observed for DUT-32 micro/nano-structures, having a considerable drug loading capacity. At the pH values 7.4-4.5, various profiles of pH-responsive release were achieved. Also, the prepared DUT-32 micro/nano-structures are found to be biocompatible with PC3 (prostate cancer) and HeLa (cervical cancer) cell lines, when tested by MTT assay. Moreover, DUT-32 micro/nano-structures were studied to show AMX adsorption from aqueous solution. Finally, kinetic studies indicated that AMX adsorption and drug release of DOX via this MOF are of first-order kinetics.PostprintPeer reviewe

Detection of Epstein Barr Virus by Chromogenic In Situ Hybridization in cases of extra-hepatic biliary atresia

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Synthesis and gas-sensing properties of nano- and meso-porous MoO3-doped SnO2

Nano- and meso-porous SnO2 powders doped with and without 1-10 wt% MoO3 have been synthesized by an ultrasonic spray-pyrolysis method employing a precursor aqueous solution containing tin (IV) chloride pentahydrate (SnCl4·5H2O), ammonium heptamolybdate and polymethylmethacrylate (PMMA) microspheres as a template, and the effects of MoO3-doping and the addition of PMMA microspheres on the structural, morphological and gas-sensing properties of SnO2 were investigated in this study. It is confirmed that control of the amounts of PMMA microspheres in the precursor solution was effective in realizing well-developed nano- and meso-porous structures of SnO2 by X-ray diffraction analysis, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and the measurement of specific surface area and pore size distribution using a N2 adsorption isotherm. Gas-sensing properties of their thick films (about 50 μm thick), which were fabricated by screen-printing to various gases (NO2, C2H5OH and H2) were tested in ambient air. The doped thick films showed a high response and selectivity to 5 ppm NO2 gas in the case of 10 wt% MoO3-doping in both nano- and meso-porous structures of SnO2. We observed that the presence of Mo species in SnO2 lattice can improve the sensor response and selectivity towards NO2 gas. The effect of the MoO3-doping on the sensing characteristics of these films towards NO2 was discussed

Iranian Female Methadone Patients and the Perceived Educational Needs Related to Human Immunodeficiency Virus

Background: Iranian female methadone patients are at risk of human immunodeficiency virus (HIV) due to involvement in high-risk sexual behaviours and/or needle sharing. The present study aimed to explore the perceived educational needs related to HIV among a group of Iranian female methadone patients. Methods:The research design was qualitative and the participants were sampled purposively. Semi-structured interviews were conducted with 34 women and 19 clinicians in Sari, Mashhad, and Tehran, Iran. Then, qualitative content analysis was implemented. Findings: The emergence of three major themes and six minor themes was revealed. Women expressed a need to increase their knowledge including women-specific pathophysiology and disease progression and the modes of the virus transmission and prevention. Women also expressed a need to enhance their knowledge and skills related to the physical management of the virus including self-care and reproductive health. Other themes included perceived psychosocial needs including removing stigma and access to resources in the community. Conclusion: Women reported a wide range of educational needs from basic knowledge to advanced skills. The findings can be used in designing women-specific educational programs related to HIV in Iran. Larger studies are suggested with gender-mixed samples in the Persian contex

The unfinished agenda of communicable diseases among children and adolescents before the COVID-19 pandemic, 1990-2019: a systematic analysis of the Global Burden of Disease Study 2019

BACKGROUND: Communicable disease control has long been a focus of global health policy. There have been substantial reductions in the burden and mortality of communicable diseases among children younger than 5 years, but we know less about this burden in older children and adolescents, and it is unclear whether current programmes and policies remain aligned with targets for intervention. This knowledge is especially important for policy and programmes in the context of the COVID-19 pandemic. We aimed to use the Global Burden of Disease (GBD) Study 2019 to systematically characterise the burden of communicable diseases across childhood and adolescence. METHODS: In this systematic analysis of the GBD study from 1990 to 2019, all communicable diseases and their manifestations as modelled within GBD 2019 were included, categorised as 16 subgroups of common diseases or presentations. Data were reported for absolute count, prevalence, and incidence across measures of cause-specific mortality (deaths and years of life lost), disability (years lived with disability [YLDs]), and disease burden (disability-adjusted life-years [DALYs]) for children and adolescents aged 0-24 years. Data were reported across the Socio-demographic Index (SDI) and across time (1990-2019), and for 204 countries and territories. For HIV, we reported the mortality-to-incidence ratio (MIR) as a measure of health system performance. FINDINGS: In 2019, there were 3·0 million deaths and 30·0 million years of healthy life lost to disability (as measured by YLDs), corresponding to 288·4 million DALYs from communicable diseases among children and adolescents globally (57·3% of total communicable disease burden across all ages). Over time, there has been a shift in communicable disease burden from young children to older children and adolescents (largely driven by the considerable reductions in children younger than 5 years and slower progress elsewhere), although children younger than 5 years still accounted for most of the communicable disease burden in 2019. Disease burden and mortality were predominantly in low-SDI settings, with high and high-middle SDI settings also having an appreciable burden of communicable disease morbidity (4·0 million YLDs in 2019 alone). Three cause groups (enteric infections, lower-respiratory-tract infections, and malaria) accounted for 59·8% of the global communicable disease burden in children and adolescents, with tuberculosis and HIV both emerging as important causes during adolescence. HIV was the only cause for which disease burden increased over time, particularly in children and adolescents older than 5 years, and especially in females. Excess MIRs for HIV were observed for males aged 15-19 years in low-SDI settings. INTERPRETATION: Our analysis supports continued policy focus on enteric infections and lower-respiratory-tract infections, with orientation to children younger than 5 years in settings of low socioeconomic development. However, efforts should also be targeted to other conditions, particularly HIV, given its increased burden in older children and adolescents. Older children and adolescents also experience a large burden of communicable disease, further highlighting the need for efforts to extend beyond the first 5 years of life. Our analysis also identified substantial morbidity caused by communicable diseases affecting child and adolescent health across the world. FUNDING: The Australian National Health and Medical Research Council Centre for Research Excellence for Driving Investment in Global Adolescent Health and the Bill & Melinda Gates Foundation