Financing for pandemic preparedness and response measures: a systematic scoping review.

Objective: To obtain insights into reducing the shortfall in financing for pandemic preparedness and response measures, and reducing the risk of another pandemic with social and economic costs comparable to those of the coronavirus disease. Methods: We conducted a systematic scoping review using the databases ScienceDirect, Scopus, JSTOR, PubMed® and EconLit. We included articles published in any language until 1 August 2023, and excluded grey literature and publications on epidemics. We categorized eligible studies according to the elements of a framework proposed by the World Health Organization Council on the Economy of Health for All: (i) root/structural causes; (ii) social position/foundations; (iii) infrastructure and systems; and (iv) communities, households and individuals. Findings: Of the 188 initially identified articles, we included 60 in our review. Most (53/60) were published after 2020, when academic interest had shifted towards global financing mechanisms. Most (37/60) addressed two or more of the council framework elements. The most frequently addressed element was infrastructure and systems (54/60), discussing topics such as health systems, financial markets and innovation ecosystems. The roots/structural causes were discussed in 25 articles; communities, households and individuals in 22 articles; and social positions/foundations in 11. Conclusion: Our review identified three important gaps: a formal definition of pandemic preparedness and response, impeding the accurate quantification of the financing shortfall; research on the extent to which financing for pandemic preparedness and response has been targeted at the most vulnerable households; and an analysis of specific financial instruments and an evaluation of the feasibility of their implementation.

Administering selected subscales of patient-reported outcome questionnaires to reduce patient burden and increase relevance: a position statement on a modular approach.

Patient-reported outcome (PRO) questionnaires considered in this paper contain multiple subscales, although not all subscales are equally relevant for administration in all target patient populations. A group of measurement experts, developers, license holders, and other scientific-, regulatory-, payer-, and patient-focused stakeholders participated in a panel to discuss the benefits and challenges of a modular approach, defined here as administering a subset of subscales out of a multi-scaled PRO measure. This paper supports the position that it is acceptable, and sometimes preferable, to take a modular approach when administering PRO questionnaires, provided that certain conditions have been met and a rigorous selection process performed. Based on the experiences and perspectives of all stakeholders, using a modular approach can reduce patient burden and increase the relevancy of the items administered, and thereby improve measurement precision and eliminate wasted data without sacrificing the scientific validity and utility of the instrument. The panelists agreed that implementing a modular approach is not expected to have a meaningful impact on item responses, subscale scores, variability, reliability, validity, and effect size estimates; however, collecting additional evidence for the impact of context may be desirable. It is also important to recognize that adequate rationale and evidence (e.g., of fit-for-purpose status and relevance to patients) and a robust consensus process that includes patient perspectives are required to inform selection of subscales, as in any other measurement circumstance, is expected. We believe that the considerations discussed within (content validity, administration context, and psychometric factors) are relevant across multiple therapeutic areas.

Pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, sensitizes cancer cells to VSVΔ51 oncolytic virotherapy.

The clinical efficacy of VSVΔ51 oncolytic virotherapy has been limited by tumor resistance to viral infection, so strategies to transiently repress antiviral defenses are warranted. Pevonedistat is a first-in-class NEDD8-activating enzyme (NAE) inhibitor currently being tested in clinical trials for its antitumor potential. In this study, we demonstrate that pevonedistat sensitizes human and murine cancer cells to increase oncolytic VSVΔ51 infection, increase tumor cell death, and improve therapeutic outcomes in resistant syngeneic murine cancer models. Increased VSVΔ51 infectivity was also observed in clinical human tumor samples. We further identify the mechanism of this effect to operate via blockade of the type 1 interferon (IFN-1) response through neddylation-dependent interferon-stimulated growth factor 3 (ISGF3) repression and neddylation-independent inhibition of NF-κB nuclear translocation. Together, our results identify a role for neddylation in regulating the innate immune response and demonstrate that pevonedistat can improve the therapeutic outcomes of strategies using oncolytic virotherapy.

Remote Sensing Evaluation Drone Herbicide Application Effectiveness for Controlling Echinochloa spp. in Rice Crop in Valencia (Spain).

Rice (Oryza sativa L.) is a staple cereal in the diet of more than half of the world's population. Within the European Union, Spain is a leader in rice production due to its climate and tradition, accounting for 26% of total EU production in 2020. The Valencian rice area covers around 15,000 hectares and is strongly influenced by biotic and abiotic factors. An important biotic factor affecting rice production is weeds, which compete with rice for sunlight, water and nutrients. The dominant weed in Spain is Echinochloa spp., although wild rice is becoming increasingly important. Rice cultivation in Valencia takes place in the area of L'Albufera de Valencia, which is a natural park, i.e., a special protection area. In this natural area, the use of phytosanitary products is limited, so it is necessary to use the minimum amount possible. Therefore, the objective of this work is to evaluate the possibility of using remote sensing effectively to determine the effectiveness of the application of the herbicide cyhalofop-butyl by drone for the control of Echinochloa spp. in rice crops in Valencia. The results will be compared with those obtained by using sterilisation machines (electric backpack sprayers) to apply the herbicide. To evaluate the effectiveness of the application, the reflectance obtained by the satellite sensors in the red and near infrared (NIR) wavelengths, as well as the normalised difference vegetation index (NDVI), were used. The remote sensing results were analysed and complemented by the number of rice plants and weeds per area, plant dry weight, leaf area, BBCH phenological state, SPAD index values, chlorophyll content and relative growth rate. Remote sensing is validated as an effective tool for determining the efficacy of an herbicide in controlling weeds applied by both the drone and the electric backpack sprayer. The weeds slowed down their development after the treatment. Depending on the phenological state of the crop and the active ingredient of the herbicide, these results are applicable to other areas with different climatic and environmental conditions.

Cost-effectiveness and economic investment to eliminate chronic hepatitis C in Mexico.

In July 2020, the Mexican Government initiated the National Program for Elimination of Hepatitis C (HCV) under a procurement agreement, securing universal, free access to HCV screening, diagnosis and treatment for 2020-2022. This analysis quantifies the clinical and economic burden of HCV (MXN) under a continuation (or end) to the agreement. A modelling and Delphi approach was used to evaluate the disease burden (2020-2030) and economic impact (2020-2035) of the Historical Base compared to Elimination, assuming the agreement continues (Elimination-Agreement to 2035) or terminates (Elimination-Agreement to 2022). We estimated cumulative costs and the per-patient treatment expenditure needed to achieve net-zero cost (the difference in cumulative costs between the scenario and the base). Elimination is defined as a 90% reduction in new infections, 90% diagnosis coverage, 80% treatment coverage and 65% reduction in mortality by 2030. A viraemic prevalence of 0.55% (0.50-0.60) was estimated on 1st January 2021, corresponding to 745,000 (95% CI 677,000-812,000) viraemic infections in Mexico. The Elimination-Agreement to 2035 would achieve net-zero cost by 2023 and accrue 31.2 billion in cumulative costs. Cumulative costs under the Elimination-Agreement to 2022 are estimated at 74.2 billion. Under Elimination-Agreement to 2022, the per-patient treatment price must decrease to 11,000 to achieve net-zero cost by 2035. The Mexican Government could extend the agreement through 2035 or reduce the cost of HCV treatment to 11,000 to achieve HCV elimination at net-zero cost.

Evaluating therapeutic benefits of ubrogepant via latent class models: A post hoc exploratory analysis of the ACHIEVE I and ACHIEVE II trials.

OBJECTIVE: To evaluate an alternative method of defining acute treatment success in migraine by combining multiple indicators into a single dichotomous measure of success. BACKGROUND: Migraine is characterized by a symptom complex; combining these features as a single endpoint may improve the measurement of treatment effects and better predict patient satisfaction with treatment. METHODS: We used a confirmatory latent class model (LCM) with two latent classes interpreted as treatment success and treatment failure. Pooled data for placebo and ubrogepant 50 mg from the ACHIEVE I and ACHIEVE II trials and data for ubrogepant 100 mg from ACHIEVE I were used. LCM inputs included pre-dose and 2-h post-dose measures of pain severity (0-3), the presence/absence of associated symptoms (nausea, photophobia, and phonophobia [0 or 1]), and functional disability (0-3). All definitions were validated against satisfaction with study medication (SWSM) at 24 h post-dose; results were compared with 2-hour pain freedom (2hPF). RESULTS: This pooled analysis included 2247 participants. At 2 h post-dose in the ubrogepant 50 and 100 mg dose groups, 53.2% (472/887) and 54.9% (246/448) of participants, respectively, were classified as achieving treatment success using the LCM-based approach, compared to 39.0% (356/912) of participants in the placebo group. The results for treatment success using the 2hPF endpoint were 20.7% (184/887) and 21.5% (96/447) in the ubrogepant 50 and 100 mg dose groups, respectively, compared to 12.7% (116/912) for placebo. Using 24-h SWSM as an external validator, the LCM approach sensitivity and correct classification rates were higher than for 2hPF. CONCLUSION: The LCM approach led to higher rates of treatment success and greater separation between ubrogepant and placebo and was a more sensitive predictor of treatment satisfaction than the regulatory endpoint of 2hPF.

Real-world effectiveness, satisfaction, and optimization of ubrogepant for the acute treatment of migraine in combination with onabotulinumtoxinA: results from the COURAGE Study.

BACKGROUND: Individuals using onabotulinumtoxinA as a preventive migraine treatment often use acute treatments for breakthrough attacks. Data on real-world effectiveness of the small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist ubrogepant in combination with onabotulinumtoxinA are limited. METHODS: COURAGE, a prospective, multiple attack, observational study, evaluated the real-world effectiveness of ubrogepant (50 or 100 mg) for acute treatment of migraine in people receiving onabotulinumtoxinA, an anti-CGRP monoclonal antibody (mAb), or both. This analysis focused only on onabotulinumtoxinA users. The Migraine Buddy app was used to identify eligible participants and track response to treated attacks. For each ubrogepant-treated attack, meaningful pain relief (MPR) and return to normal function (RNF) at 2 and 4 h post-dose over 30 days was assessed. MPR was defined as a level of relief that is meaningful to the participant, usually occurring before the pain is all gone. After 30 days, satisfaction was reported on a 7-point scale and overall acute treatment optimization was evaluated using the migraine Treatment Optimization Questionnaire-4 (mTOQ-4). RESULTS: This analysis included 122 participants who received ubrogepant and onabotulinumtoxinA and reported on 599 ubrogepant-treated attacks. Following the first ubrogepant-treated attack, MPR was achieved in 53.3% of participants 2 h post-dose and in 76.2% of participants 4 h post-dose. RNF was achieved in 25.4% of participants 2 h post-dose and in 45.9% of participants 4 h post-dose. MPR and RNF results were similar across up to 10 ubrogepant-treated attacks. After 30 days, satisfaction with ubrogepant in combination with onabotulinumtoxinA was reported by 69.8% of participants and acute treatment optimization (defined as mTOQ-4 score ≥ 4) was achieved in 77.6%. CONCLUSIONS: In this prospective real-world effectiveness study, ubrogepant treatment in onabotulinumtoxinA users with self-identified migraine was associated with high rates of MPR and RNF at 2 and 4 h as well as satisfaction and acute treatment optimization. Although the lack of a contemporaneous control group limits causal inference, these findings demonstrate the feasibility of using a novel, app-based design to evaluate the real-world effectiveness and satisfaction of treatments.

Burden of overweight and obesity in Mexico from 1990 to 2021.

BACKGROUND: Overweight and obesity (OW/OB) represent a serious challenge in Mexico, with effects on health, society and economy. Demographic, epidemiological, nutritional, social and economic factors have exacerbated this problem. OBJECTIVE: To analyze mortality and years of healthy life lost in Mexico due to OW/OB in the 1990-2021 period. MATERIAL AND METHODS: The Global Burden of Disease and Risk Factors 2021 study was used to analyze data on elevated body mass index (BMI) as a risk factor and its evolution in Mexico. RESULTS: In 2021, 118 thousand deaths attributable to high BMI were recorded, which accounted for 10.6% of total deaths and more than 4.2 million disability-adjusted life years lost. CONCLUSIONS: The obesogenic environment, influenced by social determinants of health, has had a significant impact on mortality, burden of disease, and economic costs. Addressing OW/OB requires multisector interventions to strengthen the Mexican health system.

ANTECEDENTES: El sobrepeso y la obesidad constituyen un grave desafío en México, con efectos en la salud, sociedad y economía. Factores demográficos, epidemiológicos, nutricionales, sociales y económicos han agravado esta problemática. OBJETIVO: Analizar la mortalidad y los años de vida saludable perdidos en México por sobrepeso y obesidad en el período de 1990 a 2021. MATERIAL Y MÉTODOS: Se utilizó el Global Burden of Disease 2021 para analizar los datos sobre índice de masa corporal elevado como factor de riesgo y su evolución en México. RESULTADOS: En 2021 se registraron 118 mil muertes atribuibles a índice de masa corporal elevado, que representaron 10.6 % del total de muertes y más de 4.2 millones de años de vida perdidos ajustados por discapacidad. CONCLUSIONES: El ambiente obesogénico, influido por determinantes sociales, ha tenido un impacto significativo en la mortalidad, la carga de enfermedad y los costos económicos. Abordar el sobrepeso y la obesidad requiere intervenciones multisectoriales para fortalecer el sistema de salud mexicano.

Psychometric validation of the EORTC QLQ-HCC18 in patients with previously treated unresectable hepatocellular carcinoma.

To demonstrate the measurement properties of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Hepatocellular Carcinoma 18-question module (EORTC QLQ-HCC18) within a previously treated, unresectable hepatocellular carcinoma (HCC) clinical trial population that was distinct from the published QLQ-HCC18 validation population. Analyses were conducted using data from BGB-A317-208, an open label, international, clinical trial assessing efficacy and safety of the monoclonal antibody tislelizumab in adult HCC patients. The EORTC Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and QLQ-HCC18 instruments were assessed at baseline and weeks 3 and 9 follow-up visits. Per US Food and Drug Administration guidance, psychometric validation of the QLQ-HCC18 included reliability (internal consistency and test-retest), construct validity (convergent and discriminant validity and known-groups validity), ability to detect change, and meaningful within-patient change (MWPC). Known-groups validity and MWPC analyses were also stratified on several pre-defined subgroups. A total of 248 patients were included. Only the QLQ-HCC18 fatigue, nutrition, and index domains demonstrated acceptable internal consistency; acceptable test-retest reliability was found for fatigue, body image, nutrition, pain, sexual interest, and index domains. The QLQ-HCC18 fatigue domain achieved the pre-specified criterion defining acceptable convergent and discriminant validity for 13 of 16 correlations, whereas the index domain achieved the pre-specified criterion for 14 of 16 correlations. Clear differentiation of the QLQ-HCC18 change scores between improvement and maintenance anchor groups were observed for body image, fatigue, pain, and index domains, whereas differentiation between deterioration and maintenance anchor groups were observed for fever and fatigue domains. MWPC point estimates defining improvement for the QLQ-HCC18 fatigue and index domains were -7.18 and -4.07, respectively; MWPC point estimates defining deterioration were 5.34 and 3.16, respectively. The EORTC QLQ-HCC18 fatigue and index domains consistently demonstrated robust psychometric properties, supporting the use of these domains as suitable patient-reported endpoints within a previously treated, unresectable HCC patient population.

Development of the Multiple Myeloma Symptom and Impact Questionnaire: A New Patient-Reported Outcome Instrument to Assess Symptom and Impacts in Patients With Multiple Myeloma.

OBJECTIVES: This study aimed to develop and assess the content validity of a patient-reported outcomes (PROs) instrument to measure symptoms and impacts experienced by patients with active multiple myeloma (MM). METHODS: The PRO instrument was developed using an iterative, mixed-methods approach. The list of concepts was generated based on a review of existing evidence (qualitative studies and literature) and post hoc psychometric evaluations of 2 PRO instruments in 3 clinical trials. A total of 30 adult patients with MM from the United States participated in hybrid concept elicitation/cognitive debriefing interviews to validate the content validity of the newly developed PRO instrument. Translatability assessment was completed in 8 languages. RESULTS: The item generation process resulted in 17 symptom and 9 impact concepts for evaluation. The concept elicitation interviews and analysis were based on the first 25 participants; evidence of saturation was observed. The cognitive debriefing interviews and analysis were based on the last 23 participants across 4 waves of interviews. On the basis patient feedback, 10 items were removed, and 1 item was added to the PRO instrument. The translatability assessment resulted in 1 minor revision. The multiple myeloma symptom and impact questionnaire (MySIm-Q) includes 11 symptom and 6 impact concepts, organized within 8 hypothesized subdomains, with each concept measured using a 5-point verbal rating scale and a 7-day recall period. CONCLUSIONS: The MySIm-Q instrument was developed using rigorous and mixed methodology and with direct input from patients who received a diagnosis of MM. The MySIm-Q has good content validity and is culturally relevant for use in global clinical trials.

Validation of the Ankylosing Spondylitis Quality of Life assessment tool in patients with non-radiographic axial spondyloarthritis.

PURPOSE: To evaluate the psychometric performance of the Ankylosing Spondylitis Quality of Life (ASQoL) scale in patients with non-radiographic axial spondyloarthritis (nr-axSpA) to assess its appropriateness as an outcome measure in future clinical studies. METHODS: Patients with active axSpA from a Phase III, randomized, double-blind, placebo-controlled trial (RAPID-axSpA, NCT01087762) were included (N = 325). Modified New York (mNY) classification criteria were used to classify patients as having ankylosing spondylitis or nr-axSpA; those with nr-axSpA were further categorized based on objective signs of inflammation. Psychometric properties of the ASQoL were assessed/documented using a mixture of modern psychometric methods and classical test theory methods. These included exploratory factor analysis and item response theory models to assess the domain structure, test the utility of a single domain relative to subdomains, assess bias, and generate statistics to guide an empirical scoring algorithm. The reliability and validity of scores were evaluated via internal consistency, test-retest reliability, concurrent validity, and known-groups validity. Score responsiveness was assessed via anchor-based clinically meaningful change, supplemented with empirical cumulative distribution function visualizations. RESULTS: The ASQoL data were defined by four domains. However, a four-domain solution was found to be inferior to a bifactor solution in which the four domains were included within a total domain. Scoring statistics supported a unit-weighted total score. Within the nr-axSpA population with objective signs of inflammation, the ASQoL mean score had adequate reliability, validity, and ability to detect clinically meaningful change. CONCLUSIONS: Our findings suggest that the ASQoL is an appropriate outcome measure in interventional clinical trials in patients with nr-axSpA.

Application of Phase-Reversal Fresnel Zone Plates for High-Resolution Robotic Ultrasonic Non-Destructive Evaluation.

Nowadays the development of automated inspection systems based on six degrees of freedom robotic manipulators is a highly relevant topic in ultrasonic non-destructive testing. One of the issues associated with such development is the problem of acquiring high-resolution results. In this article, the application Phase-Reversal Fresnel Zone Plates is considered for solving this problem. Such acoustic lenses can solve the task of high-resolution results acquisition by using a single unfocused transducer. Furthermore, Phase-Reversal Fresnel Zone Plates can provide the desired focusing depth with the fixed thickness of the coupling layer. It is important in the case of application of devices which provide localized coupling. In this paper a proper design of Phase-Reversal Fresnel Zone Plate was determined according to the conditions of planned experiments. Its efficiency was verified via the Finite Element Method modeling. In all performed experiments the relative error of flaws size estimation did not exceed 6% whereas the signal-to-noise ratio was not lower than 17.1 dB. Thus, experimental results demonstrate that the application of Phase-Reversal Fresnel Zone Plates allowed to obtain results with high lateral resolution and signal-to-noise ratio. These results demonstrate the reasonability of the development of devices that provide localized coupling and use Phase-Reversal Fresnel Zone Plates.

Transient Analysis of Fresnel Zone Plates for Ultrasound Focusing Applications.

Fresnel Zone Plates are planar lenses that can be used to focus ultrasound beams. This kind of acoustic lenses can play a key role in the resolution of ultrasonic NDT systems. In this type of pulse-echo applications, the pulse duration is an important parameter that specifies the axial resolution, and thus, shorter ultrasound pulses provide higher resolutions. However, acoustic lenses exhibit a transient response that should be considered when setting the pulse duration, as pulses shorter than the transient state duration result in degradation in the response of acoustic lenses in terms of focal intensity, focal displacement, and lateral and axial resolutions. In this work, a thorough analysis of the transient response of Fresnel Zone Plates is discussed, demonstrating that the transient state should be considered in order to achieve optimal focusing performance. Theoretical and numerical results are presented, showing very good agreement.

Bifocal Ultrasound Focusing Using Bi-Fresnel Zone Plate Lenses.

In this work, we present a bifocal Fresnel zone plate (BiFZP) capable of generating focusing profiles with two different foci. The performance of the BiFZP is demonstrated in the ultrasound domain, with a very good agreement between the experimental measurements and the finite element method (FEM) simulations. This lens becomes an appealing alternative to other dual-focusing lenses, in which the foci location can only be set at a limited range of positions, such as M-bonacci zone plates. Moreover, the variation of the operating frequency has also been analyzed, providing an additional dynamic control parameter in this type of lenses.

A psychometric analysis and revalidation of the Yale-Brown Obsessive Compulsive Scale modified for Binge Eating in adults with binge eating disorder.

PURPOSE: The Yale-Brown Obsessive Compulsive Scale modified for Binge Eating (Y-BOCS-BE) assesses the obsessiveness of binge eating thoughts and compulsiveness of binge eating behaviors. The findings of this study extend previously published Y-BOCS-BE psychometric evaluations in adults with binge eating disorder (BED). METHODS: Data from three phase 3 lisdexamfetamine dimesylate studies in adults with BED (two randomized, double-blind, placebo-controlled short-term efficacy studies; one double-blind, placebo-controlled, randomized-withdrawal maintenance-of-efficacy study) were used. Psychometric evaluations included assessment of Y-BOCS-BE dimensionality, internal consistency, convergent validity, test?retest reliability, and determinations of clinically meaningful improvement using distribution- and anchor-based methods. RESULTS: Domain specification analyses determined that the Y-BOCS-BE possessed a bifactor structure composed of a general binge eating severity domain and three subdomains (obsessive/compulsive, restraint, and control). Y-BOCS-BE internal consistency was maximized at week 12 (Cronbach?s ?, 0.95) and test?retest reliability was maximized in the 8-week retest interval from week 4 to week 12 across all no-change anchors (r?=?0.74?0.90). Likewise, convergent validity of the Y-BOCS-BE across all validators was maximized at week 12 (all r???0.66). Meaningful improvement for Y-BOCS-BE total scores was estimated to require score reductions of 12 to 17 points depending on the anchor. CONCLUSIONS: The Y-BOCS-BE is a valuable tool for assessing BED symptoms. Maximization of Y-BOCS-BE reliability and validity at later study time points may be related to both treatment effects and improved insight into BED by participants during the study.

Application of Phase-Reversal Fresnel Zone Plates for Improving The Elevation Resolution in Ultrasonic Testing with Phased Arrays.

Currently, phased arrays have found wide application in ultrasonic nondestructive testing. Volumetric results provided by the.

Design of Acoustical Bessel-Like Beam Formation by a Pupil Masked Soret Zone Plate Lens.

The image performance of acoustic and ultrasound sensors depends on several fundamental parameters such as depth of focus or lateral resolution. There are currently two different types of acoustic diffractive lenses: those that form a diffraction-limited spot with a shallow depth of focus (zone plates) and lenses that form an extended focus (quasi-Bessel beams). In this paper, we investigate a pupil-masked Soret zone plate, which allows the tunability of a normalized angular spectrum. It is shown that the depth of focus and the lateral resolution can be modified, without changing the lens structure, by choosing the size of the pupil mask. This effect is based on the transformation of spherically-converging waves into quasi-conical waves, due to the apodization of the central part of the zone plate. The theoretical analysis is verified with both numerical simulations and experimental measurements. A Soret zone plate immersed in water with D/2F = 2.5 and F = 4.5 λ changes its depth of focus from 2.84 λ to 5.9 λ and the lateral resolution increases from 0.81 λ to 0.64 λ at a frequency of 250 kHz, by modifying the pupil mask dimensions of the Soret zone plate.