Position Statement of 5 July 2022 on the Decision of the WTO Ministerial Conference on the TRIPS Agreement adopted on 17 June 2022

On 17 June 2022, after nearly one and a half years of intense debate concerning the proposal to waive IP protection in view of the COVID-19 pandemic, the Ministerial Conference of the World Trade Organization adopted a decision on the TRIPS Agreement. It has not waived any intellectual property rights as such but instead mainly clarified the application of the existing TRIPS flexibilities, in particular, regarding compulsory licensing of patents. The Position Statement shows that the Ministerial Decision makes no substantive difference in the existing international legal framework, except for lifting the limitation on the exportation of vaccines manufactured in accordance with the Decision. To the extent that the Decision can make the application of TRIPS flexibilities more expedient, it is to be welcomed. At the same time, it is argued that such facilitating effect should not be limited to, or justified by, the exceptional circumstances of the COVID-19 pandemic. More critically, it should not be restricted to COVID-19 vaccines, of which there is currently no shortage – rather, the same level of TRIPS flexibilities should apply to all medicinal products needed to overcome the COVID-19 pandemic

Improving the measurement of QALYs in dementia: Developing patient- and carer-reported health state classification systems using Rasch analysis

Objectives: Cost-utility analysis is increasingly used to inform resource allocation. This requires a means of valuing health states before and after intervention. Although generic measures are typically used to generate values, these do not perform well with people with dementia. We report the development of a health state classification system amenable to valuation for use in studies of dementia, derived from the DEMQOL system, a measure of health-related quality of life in dementia by patient self-report (DEMQOL) and carer proxy-report (DEMQOL-Proxy). Methods: Factor analysis was used to determine the dimensional structure of DEMQOL and DEMQOL-Proxy. Rasch analysis was subsequently used to investigate item performance across factors in terms of item-level ordering, functioning across subgroups, model fit and severity-range coverage. This enabled the selection of one item from each factor for the classification system. A sample of people with a diagnosis of mild/moderate dementia (n=644) and a sample of carers of those with mild/moderate dementia (n=683) were used. Results: Factor analysis found different 5-factor solutions for DEMQOL and DEMQOL-Proxy. Following item reduction and selection using Rasch analysis, a 5-dimension classification for DEMQOL and a 4-dimension classification for DEMQOL-Proxy were developed. Each item contained 4 health state levels. Conclusion: Combining Rasch and classical psychometric analysis is a valid method of selecting items for dementia health state classifications from both the patient and carer perspectives. The next stage is to obtain preference weights so that the measure can be used in the economic evaluation of treatment, care and support arrangements for dementia

Improving the measurement of QALYs in dementia: developing patient- and carer-reported health state classification systems using Rasch analysis

Objectives: Cost-utility analysis is increasingly used to inform resource allocation. This requires a means of valuing health states before and after intervention. Although generic measures are typically used to generate values, these do not perform well with people with dementia. We report the development of a health state classification system amenable to valuation for use in studies of dementia, derived from the DEMQOL system, a measure of health-related quality of life in dementia by patient self-report (DEMQOL) and carer proxy-report (DEMQOL-Proxy). Methods: Factor analysis was used to determine the dimensional structure of DEMQOL and DEMQOL-Proxy. Rasch analysis was subsequently used to investigate item performance across factors in terms of item-level ordering, functioning across subgroups, model fit and severity-range coverage. This enabled the selection of one item from each factor for the classification system. A sample of people with a diagnosis of mild/moderate dementia (n=644) and a sample of carers of those with mild/moderate dementia (n=683) were used. Results: Factor analysis found different 5-factor solutions for DEMQOL and DEMQOL-Proxy. Following item reduction and selection using Rasch analysis, a 5-dimension classification for DEMQOL and a 4-dimension classification for DEMQOL-Proxy were developed. Each item contained 4 health state levels. Conclusion: Combining Rasch and classical psychometric analysis is a valid method of selecting items for dementia health state classifications from both the patient and carer perspectives. The next stage is to obtain preference weights so that the measure can be used in the economic evaluation of treatment, care and support arrangements for dementia.quality adjusted life years; health related quality of life; Rasch analysis; preference-based measures of health; health states; dementia

Covid-19 and the Role of Intellectual Property - Position Statement of the Max Planck Institute for Innovation and Competition of 7 May 2021

In this Statement, the authors take a position on the waiver of intellectual property (IP) protection currently being considered by the members of the World Trade Organisation. The waiver was initiated by India and South Africa as a measure to enable rapid access to affordable medical products that are necessary to combat Covid-19. The initiative gained momentum after the US decided to support it. The authors do not consider this path to be expedient. The Statement presents factual and legal arguments why a comprehensive waiver of IP protection is unlikely to be a necessary and suitable measure towards the pursued objective. Overall, it argues that IP rights may so far have played an enabling and facilitating rather than hindering role in overcoming Covid-19. The global community might not be better off if IP rights are waived, neither during nor after the pandemic. There are more efficient and direct ways to supply developing countries with vaccines quickly – if the industrialised countries are willing to do their share

Using mixed methods to select optimal mode of administration for a patient-reported outcome instrument for people with pressure ulcers.

BACKGROUND: When developing new measuring instruments or deciding upon one for research, consideration of the 'best' method of administration for the target population should be made. Current evidence is inconsistent in differentiating superiority of any one method in terms of quantity and quality of response. We trialed a novel mixed methods approach in early scale development to determine the best administration method for a new patient-reported outcome instrument for people with pressure ulcers (the PU-QOL). METHODS: Cognitive interviews were undertaken with 35 people with pressure ulcers to determine appropriateness of a self-completed version of the PU-QOL instrument. Quantitative analysis, including Rasch analysis, was carried out on PU-QOL data from 70 patients with pressure ulcers, randomised to self-completed or interview-administered groups, to examine data quality and differential item functioning (DIF). RESULTS: Cognitive interviews identified issues with PU-QOL self-completion. Quantitative analysis supported these findings with a large proportion of self-completed PU-QOLs returned with missing data. DIF analysis indicated administration methods did not impact the way patients from community care settings responded, supporting the equivalence of both administration versions. CONCLUSIONS: Obtaining the best possible health outcomes data requires use of appropriate methods to ensure high quality data with minimal bias. Mixed methods, with the inclusion of Rasch, provided valuable evidence to support selection of the 'best' administration method for people with PUs during early PRO instrument development. We consider our approach to be generic and widely applicable to other elderly or chronically ill populations or suitable for use in limited samples where recruitment to large field tests is often difficult

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Although 5HT2A receptors mediate contractions of normal arteries to serotonin (5HT), in some cardiovascular diseases, other receptor subtypes contribute to the marked increase in serotonin contractions. We hypothesized that enhanced contractions of arteries from diabetics to 5HT are mediated by an increased contribution from multiple 5HT receptor subtypes. We compared responses to selective 5HT receptor agonists and expression of 5HT receptor isoforms (5HT1B, 5HT2A, and 5HT2B) in aorta from nondiabetic (ND) compared to type 2 diabetic mice (DB, BKS.Cg-Dock7m+/+Leprdb/J). 5HT, 5HT2A (TCB2 and BRL54443), and 5HT2B (norfenfluramine and BW723C86) receptor agonists produced concentration-dependent contractions of ND arteries that were markedly increased in DB arteries. Neither ND nor DB arteries contracted to a 5HT1B receptor agonist. MDL11939, a 5HT2A receptor antagonist, and LY272015, a 5HT2B receptor antagonist, reduced contractions of arteries from DB to 5HT more than ND. Expression of 5HT1B, 5HT2A, and 5HT2B receptor subtypes was similar in ND and DB. Inhibition of rho kinase decreased contractions to 5HT and 5HT2A and 5HT2B receptor agonists in ND and DB. We conclude that in contrast to other cardiovascular diseases, enhanced contraction of arteries from diabetics to 5HT is not due to a change in expression of multiple 5HT receptor subtypes

The Effect of Phantom Stimulation and Pseudomonophasic Pulse Shapes on Pitch Perception by Cochlear Implant Listeners

Funder: Oticon Centre of Excellence for Hearing and Speech Sciences (CHeSS)Abstract: It has been suggested that a specialized high-temporal-acuity brainstem pathway can be activated by stimulating more apically in the cochlea than is achieved by cochlear implants (CIs) when programmed with contemporary clinical settings. We performed multiple experiments to test the effect on pitch perception of phantom stimulation and asymmetric current pulses, both supposedly stimulating beyond the most apical electrode of a CI. The two stimulus types were generated using a bipolar electrode pair, composed of the most apical electrode of the array and a neighboring, more basal electrode. Experiment 1 used a pitch-ranking procedure where neural excitation was shifted apically or basally using so-called phantom stimulation. No benefit of apical phantom stimulation was found on the highest rate up to which pitch ranks increased (upper limit), nor on the slopes of the pitch-ranking function above 300 pulses per second (pps). Experiment 2 used the same procedure to study the effects of apical pseudomonophasic pulses, where the locus of excitation was manipulated by changing stimulus polarity. A benefit of apical stimulation was obtained for the slopes above 300 pps. Experiment 3 used an adaptive rate discrimination procedure and found a small but significant benefit of both types of apical stimulation. Overall, the results show some benefit for apical stimulation on temporal pitch processing at high pulse rates but reveal that the effect is smaller and more variable across listeners than suggested by previous research. The results also provide some indication that the benefit of apical stimulation may decline over time since implantation

Andreev reflection at QGP/CFL interface

In this letter we address the question of the phenomena of Andreev reflection between the cold quark-gluon plasma phase and CFL color superconductor. We show that there are two different types of reflections connected to the structure of the CFL phase. We also calculate the probability current at the interface and we show that it vanishes for energy of scattering quarks below the superconducting gap.Comment: 6 pages, 1 figure. Minor changes in the "Conclusions