Since the introduction of the orphan drugs legislation in Europe, it has been suggested that the general method of assessing drugs for reimbursement is not necessarily suitable for orphan drugs. The ...National Institute for Health and Clinical Excellence indicated that several criteria other than cost and efficacy could be considered in reimbursement decisions for orphan drugs. This study sought to explore the multi-criteria decision analysis (MCDA) framework proposed by (Orphanet J Rare Dis 7:74, 2012) to a range of orphan drugs, with a view to comparing the aggregate scores to the average annual cost per patient for each product, and thus establishing the merit of MCDA as a tool for assessing the value of orphan drugs in relation to their pricings.
An MCDA framework was developed using the nine criteria proposed by (Orphanet J Rare Dis 7:74, 2012) for the evaluation of orphan drugs, using the suggested numerical scoring system on a scale of 1 to 3 for each criterion. Correlations between the average annual cost of the drugs and aggregate MCDA scores were tested and plotted graphically. Different weightings for each of the attributes were also tested. A further analysis was conducted to test the impact of including the drug cost as an attribute in the aggregate index scores.
In the drugs studied, the R
, that statistically measures how close the data are to the fitted regression line was 0.79 suggesting a strong correlation between the drug scores and the average annual cost per patient.
Despite several limitations of the proposed model, this quantitative study provided insight into using MCDA and its relationship to the average annual costs of the products.
High-energy gamma-ray emission from supernova remnants (SNRs) has provided a unique perspective for studies of Galactic cosmic-ray acceleration. Tycho's SNR is a particularly good target because it ...is a young, type Ia SNR that has been well-studied over a wide range of energies and located in a relatively clean environment. Since the detection of gamma-ray emission from Tycho's SNR by VERITAS and Fermi-LAT, there have been several theoretical models proposed to explain its broadband emission and high-energy morphology. We report on an update to the gamma-ray measurements of Tycho's SNR with 147 hr of VERITAS and 84 months of Fermi-LAT observations, which represent about a factor of two increase in exposure over previously published data. About half of the VERITAS data benefited from a camera upgrade, which has made it possible to extend the TeV measurements toward lower energies. The TeV spectral index measured by VERITAS is consistent with previous results, but the expanded energy range softens a straight power-law fit. At energies higher than 400 GeV, the power-law index is 2.92 0.42stat 0.20sys. It is also softer than the spectral index in the GeV energy range, 2.14 0.09stat 0.02sys, measured in this study using Fermi-LAT data. The centroid position of the gamma-ray emission is coincident with the center of the remnant, as well as with the centroid measurement of Fermi-LAT above 1 GeV. The results are consistent with an SNR shell origin of the emission, as many models assume. The updated spectrum points to a lower maximum particle energy than has been suggested previously.
Universal coverage of IVF pays off Vélez, M.P; Connolly, M.P; Kadoch, I.-J ...
Human reproduction (Oxford),
06/2014, Letnik:
29, Številka:
6
Journal Article
Recenzirano
Odprti dostop
STUDY QUESTION
What was the clinical and economic impact of universal coverage of IVF in Quebec, Canada, during the first calendar year of implementation of the public IVF programme?
SUMMARY ANSWER
...Universal coverage of IVF increased access to IVF treatment, decreased the multiple pregnancy rate and decreased the cost per live birth, despite increased costs per cycle.
WHAT IS KNOWN ALREADY
Public funding of IVF assures equality of access to IVF and decreases multiple pregnancies resulting from this treatment. Public IVF programmes usually mandate a predominant SET policy, the most effective approach for reducing the incidence of multiple pregnancies.
STUDY DESIGN, SIZE, DURATION
This prospective comparative cohort study involved 7364 IVF cycles performed in Quebec during 2009 and 2011 and included an economic analysis.
PARTICIPANTS/MATERIALS, SETTING, METHODS
IVF cycles performed in the five centres offering IVF treatment in Quebec during 2009, before implementation of the public IVF programme, were compared with cycles performed at the same centres during 2011, the first full calendar year following implementation of the programme. Data were obtained from the Canadian Assisted Reproductive Technologies Register (CARTR). Comparisons were made between the two periods in terms of utilization, pregnancy rates, multiple pregnancy rates and costs.
MAIN RESULTS AND THE ROLE OF CHANCE
The number of IVF cycles performed in Quebec increased by 192% after the new policy was implemented. Elective single-embryo transfer was performed in 1.6% of the cycles during Period I (2009), and increased to 31.6% during Period II (2011) (P < 0.001). Although the clinical pregnancy rate per embryo transfer was lower in 2011 than in 2009 (24.9 versus 39.9%, P < 0.001), the multiple pregnancy rate was greatly reduced (6.4 versus 29.4%, P < 0.001). The public IVF programme increased government costs per IVF treatment cycle from CAD$3730 to CAD$4759. Despite increased costs per cycle, the efficiency defined by the cost per live birth, which factored in downstream health costs up to 1 year post delivery, decreased from CAD$49 517 to CAD$43 362 per baby conceived by either fresh and frozen cycles.
LIMITATIONS, REASONS FOR CAUTION
The costs described in the economic model are likely an underestimate as they do not factor in many of the long-term costs that can occur after 1 year of age. The information collected in the Canadian ART register precludes the calculation of cumulative pregnancy rates.
WIDER IMPLICATIONS OF THE FINDINGS
Our study confirms that the implementation of a public IVF programme favouring eSET not only sharply decreases the incidence of multiple pregnancy, but also reduces the cost per live birth.
STUDY FUNDING/COMPETING INTEREST(S)
M.P.V. holds a fellowship award from the Canadian Institutes of Health Research (CIHR). The economic analysis performed by M.P.C. was supported by an unrestricted grant from Ferring Pharmaceutical.
We present a search for magnetically broadened gamma-ray emission around active galactic nuclei (AGNs), using VERITAS observations of seven hard-spectrum blazars. A cascade process occurs when ...multi-TeV gamma-rays from an AGN interact with extragalactic background light (EBL) photons to produce electron-positron pairs, which then interact with cosmic microwave background photons via inverse-Compton scattering to produce gamma-rays. Due to the deflection of the electron-positron pairs, a non-zero intergalactic magnetic field (IGMF) would potentially produce detectable effects on the angular distribution of the cascade emission. In particular, an angular broadening compared to the unscattered emission could occur. Through non-detection of angularly broadened emission from 1ES 1218+304, the source with the largest predicted cascade fraction, we exclude a range of IGMF strengths around 10−14 G at the 95% confidence level. The extent of the exclusion range varies with the assumptions made about the intrinsic spectrum of 1ES 1218+304 and the EBL model used in the simulation of the cascade process. All of the sources are used to set limits on the flux due to extended emission.
BACKGROUND Despite the growing use of assisted reproductive technologies (ART) worldwide, there is only a limited understanding of the economics of ART to inform policy about effective, safe and ...equitable financing of ART treatment. METHODS A review was undertaken of key studies regarding the costs and consequences of ART treatment, specifically examining the direct and indirect costs of treatment, economic drivers of utilization and clinical practice and broader economic consequences of ART-conceived children. RESULTS The direct costs of ART treatment vary substantially between countries, with the USA standing out as the most expensive. The direct costs generally reflect the costliness of the underlying healthcare system. If unsubsidized, direct costs represent a significant economic burden to patients. The level of affordability of ART treatment is an important driver of utilization, treatment choices, embryo transfer practices and ultimately multiple birth rates. The costs associated with caring for multiple-birth ART infants and their mothers are substantial, reflecting the underlying morbidity associated with such pregnancies. Investment analysis of ART treatment and ART-conceived children indicates that appropriate funding of ART services appears to represent sound fiscal policy. CONCLUSIONS The complex interaction between the cost of ART treatment and how treatments are subsidized in different healthcare settings and for different patient groups has far-reaching consequences for ART utilization, clinical practice and infant outcomes. A greater understanding of the economics of ART is needed to inform policy decisions and to ensure the best possible outcomes from ART treatment.
The Paisley Caves in Oregon record the oldest directly dated human remains (DNA) in the Western Hemisphere. More than 100 high-precision radiocarbon dates show that deposits containing artifacts and ...coprolites ranging in age from 12,450 to 2295 ¹⁴C years ago are well stratified. Western Stemmed projectile points were recovered in deposits dated to 11,070 to 11,340 ¹⁴C years ago, a time contemporaneous with or preceding the Clovis technology. There is no evidence of diagnostic Clovis technology at the site. These two distinct technologies were parallel developments, not the product of a unilinear technological evolution. "Blind testing" analysis of coprolites by an independent laboratory confirms the presence of human DNA in specimens of pre-Clovis age. The colonization of the Americas involved multiple technologically divergent, and possibly genetically divergent, founding groups.
Ice maker machines are extensively used in many commercial and residential areas for the purpose of making ice cubes. As the ice forms a certain amount of dissolved salts will be rejected to the ...remaining residual liquid. However, the degree of separation by freezing, in terms of the salt rejection and water recovery, is dictated by several factors and influences, such as operating conditions and feed quality. In this paper, the potential of an ice maker is investigated for desalting several types of process feed including sodium chloride solutions, Arabian Gulf seawater and reverse osmosis brines. The performance of multi-staging the freeze concentration process was also experimentally assessed. The results show that the process was useful in concentrating reverse osmosis brine and producing a recycle stream for further processing by membrane plant.
► Desalination using readily available commercial equipment. ► Falling film technique for the separation of concentrated RO brines. ► Useful technique for further concentrating waste reverse osmosis brines. ► Produces a recycle stream for further processing by membrane plant.
We report on the detection of a very rapid TeV gamma-ray flare from BL Lacertae on 2011 June 28 with the Very Energetic Radiation Imaging Telescope Array System (VERITAS). The flaring activity was ...observed during a 34.6 minute exposure, when the integral flux above 200 GeV reached (3.4 + or - 0.6) x 10 super(-6) photons m super(-2) s super(-1), roughly 125% of the Crab Nebula flux measured by VERITAS. The light curve indicates that the observations missed the rising phase of the flare but covered a significant portion of the decaying phase. The exponential decay time was determined to be 13 + or - 4 minutes, making it one of the most rapid gamma-ray flares seen from a TeV blazar. The gamma-ray spectrum of BL Lacertae during the flare was soft, with a photon index of 3.6 + or - 0.4, which is in agreement with the measurement made previously by MAGIC in a lower flaring state. Contemporaneous radio observations of the source with the Very Long Baseline Array revealed the emergence of a new, superluminal component from the core around the time of the TeV gamma-ray flare, accompanied by changes in the optical polarization angle. Changes in flux also appear to have occurred at optical, UV, and GeV gamma-ray wavelengths at the time of the flare, although they are difficult to quantify precisely due to sparse coverage. A strong flare was seen at radio wavelengths roughly four months later, which might be related to the gamma-ray flaring activities. We discuss the implications of these multiwavelength results.
Aims/hypothesis
Podocyte loss or injury is one of the earliest features observed in the pathogenesis of diabetic kidney disease (DKD), which is the leading cause of end-stage renal failure worldwide. ...Dysfunction in the IGF axis, including in IGF binding proteins (IGFBPs), is associated with DKD, particularly in the early stages of disease progression. The aim of this study was to investigate the potential roles of IGFBPs in the development of type 2 DKD, focusing on podocytes.
Methods
IGFBP
expression was analysed in the Pima DKD cohort, alongside data from the Nephroseq database, and in ex vivo human glomeruli. Conditionally immortalised human podocytes and glomerular endothelial cells were studied in vitro, where IGFBP-1 expression was analysed using quantitative PCR and ELISAs. Cell responses to IGFBPs were investigated using migration, cell survival and adhesion assays; electrical cell-substrate impedance sensing; western blotting; and high-content automated imaging.
Results
Data from the Pima DKD cohort and from the Nephroseq database demonstrated a significant reduction in glomerular
IGFBP-1
in the early stages of human type 2 DKD. In the glomerulus, IGFBP-1 was predominantly expressed in podocytes and controlled by phosphoinositide 3-kinase (PI3K)–forkhead box O1 (FoxO1) activity. In vitro
,
IGFBP-1 signalled to podocytes via β1-integrins, resulting in increased phosphorylation of focal-adhesion kinase (FAK), increasing podocyte motility, adhesion, electrical resistance across the adhesive cell layer and cell viability.
Conclusions/interpretation
This work identifies a novel role for IGFBP-1 in the regulation of podocyte function and that the glomerular expression of
IGFBP-1
is reduced in the early stages of type 2 DKD, via reduced FoxO1 activity. Thus, we hypothesise that strategies to maintain glomerular IGFBP-1 levels may be beneficial in maintaining podocyte function early in DKD.
Graphical abstract
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