Issues, Challenges and Opportunities for Economic Evaluations of Orphan Drugs in Rare Diseases: An Umbrella Review.

BACKGROUND AND OBJECTIVES: There are significant challenges when obtaining clinical and economic evidence for health technology assessments of rare diseases. Many of them have been highlighted in previous systematic reviews but they have not been summarised in a comprehensive manner. For all stakeholders working with rare diseases, it is important to be aware and understand these issues. The objective of this review is to identify the main challenges for the economic evaluation of orphan drugs in rare diseases. METHODS: An umbrella review of systematic reviews of economic studies concerned with orphan and ultra-orphan drugs was conducted. Studies that were not systematic reviews, or on advanced therapeutic medicinal products, personalised medicines or other interventions that were not considered orphan drugs were excluded. The database searches included publications from 2010 to 2023, and were conducted in MEDLINE, EMBASE and the Cochrane library using filters for systematic reviews, and economic evaluations and models. These filters were combined with search terms for rare diseases and orphan drugs. A hand search supplemented the literature searches. The findings were reported by a compliant Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. RESULTS: Two hundred and eighty-two records were identified from the literature searches, of which 64 were duplicates, whereas five reviews were identified from the hand search. A total of 36 reviews were included after screening against inclusion/exclusion criteria, 35 from literature searches and one from hand searching. Of those studies 1, 27 and 8 were low, moderate and high quality, respectively. The reviews highlight the scarcity of evidence for health economic parameters, for example, clinical effectiveness, costs, quality of life and the natural history of disease. Health economic evaluations such as cost-effectiveness and budget-impact analyses were scarce, and generally low-to-moderate quality. The causes were limited health economic parameters, together with publications bias, especially for cost-effectiveness analyses. CONCLUSIONS: The results highlighted issues around a considerable paucity of evidence for economic evaluations and few cost-effectiveness analyses, supporting the notion that a paucity of evidence makes economic evaluations of rare diseases more challenging compared with more prevalent diseases. Furthermore, we provide recommendations for more sustainable approaches in economic evaluations of rare diseases.

Advancing unanchored simulated treatment comparisons: A novel implementation and simulation study.

Population-adjusted indirect comparisons, developed in the 2010s, enable comparisons between two treatments in different studies by balancing patient characteristics in the case where individual patient-level data (IPD) are available for only one study. Health technology assessment (HTA) bodies increasingly rely on these methods to inform funding decisions, typically using unanchored indirect comparisons (i.e., without a common comparator), due to the need to evaluate comparative efficacy and safety for single-arm trials. Unanchored matching-adjusted indirect comparison (MAIC) and unanchored simulated treatment comparison (STC) are currently the only two approaches available for population-adjusted indirect comparisons based on single-arm trials. However, there is a notable underutilisation of unanchored STC in HTA, largely due to a lack of understanding of its implementation. We therefore develop a novel way to implement unanchored STC by incorporating standardisation/marginalisation and the NORmal To Anything (NORTA) algorithm for sampling covariates. This methodology aims to derive a suitable marginal treatment effect without aggregation bias for HTA evaluations. We use a non-parametric bootstrap and propose separately calculating the standard error for the IPD study and the comparator study to ensure the appropriate quantification of the uncertainty associated with the estimated treatment effect. The performance of our proposed unanchored STC approach is evaluated through a comprehensive simulation study focused on binary outcomes. Our findings demonstrate that the proposed approach is asymptotically unbiased. We argue that unanchored STC should be considered when conducting unanchored indirect comparisons with single-arm studies, presenting a robust approach for HTA decision-making.

Enhanced Charge Carrier Dynamics on Sb2 Se3 Photocathodes for Efficient Photoelectrochemical Nitrate Reduction to Ammonia.

Ammonia (NH3 ) is recognized as a transportable carrier for renewable energy fuels. Photoelectrochemical nitrate reduction reaction (PEC NO3 RR) offers a sustainable solution for nitrate-rich wastewater treatment by directly converting solar energy to ammonia. In this study, we demonstrate the highly selective PEC ammonia production from NO3 RR by constructing a CoCu/TiO2 /Sb2 Se3 photocathode. The constructed CoCu/TiO2 /Sb2 Se3 photocathode achieves an ammonia Faraday efficiency (FE) of 88.01 % at -0.2 VRHE and an ammonia yield as high as 15.91 µmol h-1 cm-2 at -0.3 VRHE with an excellent onset potential of 0.43 VRHE . Dynamics experiments and theoretical calculations have demonstrated that the CoCu/TiO2 /Sb2 Se3 photocathode possesses high light absorption capacity, excellent carrier transfer capability, and high charge separation and transfer efficiencies. The photocathode can effectively adsorb the reactant NO3 - and intermediate, and the CoCu co-catalyst increases the maximum Gibbs free energy difference between NO3 RR and HER. Meanwhile, the Co species enhances the spin density of Cu, and increases the density of states near the Fermi level in pdos, which results in a high PEC NO3 RR activity on CoCu/TiO2 /Sb2 Se3 . This work provides a new avenue for the feasibility of efficient PEC ammonia synthesis from nitrate-rich wastewater.

Oligo(phenylenevinylene)-Based Covalent Organic Frameworks with Kagome Lattice for Boosting Photocatalytic Hydrogen Evolution.

Covalent organic frameworks (COFs) have shown great advantages as photocatalysts for hydrogen evolution. However, the effect of linkage geometry and type of linkage on the extent of π-electron conjugation in the plane of the framework and photocatalytic properties of COFs remains a significant challenge. Herein, two Kagome (kgm) topologic oligo(phenylenevinylene)-based COFs are designed and synthesized for boosting photocatalytic hydrogen evolution via a "two in one" strategy. Under visible light irradiation, COF-954 with 5 wt% Pt as cocatalyst exhibits high hydrogen evolution rate (HER) of 137.23 mmol g-1 h-1 , outperforming most reported COF-based photocatalysts. More importantly, even in natural seawater, COF-954 shows an average HER of 191.70 mmol g-1 h-1 under ultraviolet-visible (UV-vis) light irradiation. Additionally, the water-drainage experiments indoors and outdoors demonstrate that 25 and 8 mL hydrogen gas could be produced in 80 min under UV-vis light and natural sunlight, respectively, corresponding to a high HER of 167.41 and 53.57 mmol h-1 g-1 . This work not only demonstrates an effective design strategy toward highly efficient COF-based photocatalysts, but also shows the great potential of using the COF-based photocatalysts for photocatalytic hydrogen evolution.

Porous Organic Polymers as Active Electrode Materials for Energy Storage Applications.

Eco-friendly and efficient energy production and storage technologies are highly demanded to address the environmental and energy crises. Porous organic polymers (POPs) are a class of lightweight porous network materials covalently linked by organic building blocks, possessing high surface areas, tunable pores, and designable components and structures. Due to their unique structural and compositional advantages, POPs have recently emerged as promising electrode materials for energy storage devices, particularly in the realm of supercapacitors and ion batteries. In this work, a comprehensive overview of recent progress and applications of POPs as electrode materials in energy storage devices, including the structural features and synthesis strategies of various POPs, as well as their applications in supercapacitors, lithium batteries, sodium batteries, and potassium batteries are provided. Finally, insights are provided into the future research directions of POPs in electrochemical energy storage technologies. It is anticipated that this work can provide readers with a comprehensive background on the design of POPs-based electrode materials and ignite more research in the development of next-generation energy storage devices.

Cost-effectiveness of therapeutics for COVID-19 patients: a rapid review and economic analysis.

Background: Severe acute respiratory syndrome coronavirus 2 is the virus that causes coronavirus disease 2019. Over six million deaths worldwide have been associated with coronavirus disease 2019. Objective: To assess the cost-effectiveness of treatments used for the treatment of coronavirus disease 2019 in hospital or used in the community in patients with coronavirus disease 2019 at high risk of hospitalisation. Setting: Treatments provided in United Kingdom hospital and community settings. Methods: Clinical effectiveness estimates were taken from the coronavirus disease-network meta-analyses initiative and the metaEvidence initiative. A mathematical model was constructed to explore how the interventions impacted on patient health, measured in quality-adjusted life-years gained. The costs associated with treatment, including those of hospital care, were also estimated and used to form a cost per quality-adjusted life-year gained value which was compared with thresholds published by the National Institute for Health and Care Excellence. Estimates of cost-effectiveness compared against current standard of care were produced in both the hospital and community settings at three different levels of efficacy: mean, low and high. Public list prices were used for interventions with neither confidential patient access schemes nor confidential list prices considered. Results incorporating confidential pricing data were provided to the National Institute for Health and Care Excellence appraisal committee. Results: The treatments were estimated to be clinically effective although not all reached statistical significance. All treatments in the hospital setting, or community, were estimated to plausibly have a cost per quality-adjusted life-year gained value below National Institute for Health and Care Excellence's thresholds when compared with standard of care. However, almost all drugs could plausibly have cost per quality-adjusted life-years above National Institute for Health and Care Excellence's thresholds. However, there is considerable uncertainty in the results as the prevalent severe acute respiratory syndrome coronavirus 2 variant, vaccination status, history of being infected with severe acute respiratory syndrome coronavirus 2 and standard of care have all evolved since the pivotal studies were conducted which could have significant impact on the efficacy of each drug. For drugs used in high-risk patients in the community setting, the proportion of people at high risk who need hospital admission was a large driver of the cost per quality-adjusted life-year. Limitations: No studies were identified that were conducted in current conditions. This may be a large limitation as the severe acute respiratory syndrome coronavirus 2 variant changes. No head-to-head studies of interventions were identified. Conclusions: The results produced could be informative to decision-makers, although conclusions regarding the most clinical - and cost-effectiveness of each intervention should be tentative due to the evolving nature of the decision problem and, in this report, the use of list prices only. Comparisons between interventions should also be treated with caution due to potentially large heterogeneity between studies. Future work: Research assessing the relative clinical effectiveness of interventions within head-to-head studies in current conditions would be beneficial. Contemporary information related to the probability of hospital admission and death for patients at high risk in the community would improve the precision of the estimates generated. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR135564) and will be published in full in Health Technology Assessment; Vol. 27, No. 14. See the NIHR Journals Library website for further project information.

Coronavirus disease 2019 is an infectious disease that can cause death and long-term ill-health. Treatments exist that can be provided in hospital to reduce the number of deaths from coronavirus disease 2019. Treatments also exist which can be provided in the community for people at high risk of needing to be admitted to hospital to reduce the number of admissions and to reduce the number of deaths from coronavirus disease 2019. However, the value for money of these treatments has not been estimated. We took the clinical effectiveness of nine treatments from published literature sources and built a model that estimated the value for money of six treatments compared with care without these treatments. Three treatments were excluded due to confidential prices. The results of the model showed that many treatments in a hospital setting had estimates of cost-effectiveness that would normally be seen to be good value for money using the thresholds published by the National Institute of Health and Care Excellence. The same was true for some treatments in a community setting. However, it is also possible that these treatments are not good value for money. The benefit of the drugs and value for money is highly uncertain as studies trying to estimate the gain have been done with (1) previous variants of the virus causing coronavirus disease 2019 being widespread, (2) where the proportion of people who have had vaccinations or who had previously had coronavirus disease 2019 is low and (3) where standard treatment was that when coronavirus disease 2019 was first identified, and not the drugs used now. Because of these differences, and the unknown price of some interventions, we cannot confidently say which (if any) treatments help patients the most, or which treatment represents the best value for money. Further research, in current conditions, would improve the accuracy of our answers.

Superhydrophilic CoFe Dispersion of Hydrogel Electrocatalysts for Quasi-Solid-State Photoelectrochemical Water Splitting.

Photoelectrochemical (PEC) water splitting is an attractive strategy to convert solar energy to hydrogen. However, the lifetime of PEC devices is restricted by the photocorrosion of semiconductors and the instability of co-catalysts. Herein, we report a feasible in situ inherent cross-linking method for stabilizing semiconductors that uses a CoFe-dispersed polyacrylamide (PAM) hydrogel as a transparent protector. The CoFe-PAM hydrogel protected BiVO4 (BVO) photoanode reached a photocurrent density of 5.7 mA cm-2 at 1.23 VRHE under AM 1.5G illumination with good stability. The PAM hydrogel network improved the loading of Fe sites while enabling the retention of more CoFe co-catalysts and increasing the electron density of the reaction active sites, further improving the PEC performance and stability. More importantly, by tuning the polymerization network, we pioneer the use of quasi-solid-state electrolytes in photoelectrochemistry, where the high concentration of ionic solvent in the PAM hydrogel ensures effective charge transport and good water storage owing to the hydrophilic and porous structure of the hydrogel. This work expands the scope of PEC research by providing a class of three-dimensional hydrogel electrocatalysts and quasi-solid-state electrolytes with huge extension potential, and the versatility of these quasi-solid-state electrolytes can be employed for other semiconductors.

Constructing a 3D Covalent Organic Framework from 2D hcb Nets through Inclined Interpenetration.

Three-dimensional covalent organic frameworks (3D COFs) have been of great interest due to their inherent numerous open sites and pore confinement effect. However, it has remained challenging to build 3D frameworks via interdigitation (also known as inclined interpenetration) by generating an entangled network formed by multiple 2D layers inclined with respect to each other. Herein, we report the first case of constructing a 3D COF, termed COF-904, through interdigitating 2D hcb nets, which was formed via [3+2] imine condensation reactions by the use of 1,3,5-triformylbenzene and 2,3,5,6-tetramethyl-1,4-phenylenediamine. The single-crystal structure of COF-904 is solved, and the locations of all non-hydrogen atoms are determined by 3D electron diffraction with a resolution up to 0.8 Å. These results not only broaden the strategy for achieving 3D COFs via interdigitation but also demonstrate that structurally complex extended frameworks can arise from simple molecules.

Intermediate Formation of Macrocycles for Efficient Crystallization of 2D Covalent Organic Frameworks with Enhanced Photocatalytic Hydrogen Evolution.

Covalent organic frameworks (COFs) have gained significant attention as key photocatalysts for efficient solar light conversion into hydrogen production. Unfortunately, the harsh synthetic conditions and intricate growth process required to obtain highly crystalline COFs greatly hinder their practical application. Herein, we report a simple strategy for the efficient crystallization of 2D COFs based on the intermediate formation of hexagonal macrocycles. Mechanistic investigation suggests that the use of 2,4,6-triformyl resorcinol (TFR) as the asymmetrical aldehyde build block allows the equilibration between irreversible enol-to-keto tautomerization and dynamic imine bonds to produce the hexagonal ß-ketoenamine-linked macrocycles, the formation of which could provide COFs with high crystallinity in half hour. We show that COF-935 with 3 wt % Pt as cocatalyst exhibit a high hydrogen evolution rate of 67.55 mmol g-1 h-1 for water splitting when exposed to visible light. More importantly, COF-935 exhibits an average hydrogen evolution rate of 19.80 mmol g-1 h-1 even at a low loading of only 0.1 wt % Pt, which is a significant breakthrough in this field. This strategy would provide valuable insights into the design of highly crystalline COFs as efficient organic semiconductor photocatalysts.

Rate of Complete Spectacle Independence with a Trifocal Intraocular Lens: A Systematic Literature Review and Meta-Analysis.

INTRODUCTION: A systematic literature review and meta-analysis was conducted to identify and obtain a precise single summary estimate on complete spectacle independence after bilateral implantation of a trifocal intraocular lens (IOL) (AcrySof PanOptix, TFNTXX/TFATXX) for patients undergoing cataract surgery. METHODS: A search was conducted in PubMed from January 2017 to September 2021. Relevant congress presentations were also searched to include data from completed studies not yet published. Search terms included the intervention (TFNTXX, TFATXX, PanOptix) and outcomes of interest (patient-reported spectacle independence rates). A Bayesian random-effects meta-analysis was conducted, providing a pooled estimate (median and its 95% credible interval) of complete spectacle independence rates among cataract surgery patients. Subgroup analyses evaluated spectacle independence after cataract surgery across different working distances (near, intermediate, far). RESULTS: Nineteen unique clinical studies were identified. Based on a meta-analysis of 13 studies (N = 513 patients), the complete spectacle independence rate after cataract surgery with TFNTXX/TFATXX IOL was 91.6% (95% credible interval 86.8-95.9%). Additionally, the spectacle independence rates at each focal point (N = 13 studies, 603 patients) were 89.6% (near), 96.3% (intermediate), and 95.9% (far). CONCLUSIONS: This meta-analysis demonstrated that at least nine out of ten patients receiving TFNTXX/TFATXX trifocal IOL during cataract surgery can expect to achieve complete spectacle independence. This study provides informative data for clinicians and patients to feel confident in the use of trifocal intraocular lenses as presbyopia-correcting IOLs that offer high rates of complete spectacle independence.

Living Health Technology Assessment: Issues, Challenges and Opportunities.

Health technology assessments (HTAs) are typically performed as one-off evaluations and can potentially become out-of-date due to the availability of new data, new comparators, or other factors. Recently, living approaches have been applied to systematic reviews and network meta-analyses to enable evidence syntheses to be updated more easily. In this paper, we provide a definition for 'Living HTA' where such a living approach could be applied to the entire HTA process. Living HTA could involve performing regular or scheduled updates using a traditional manual approach, or indeed in a semi-automated manner leveraging recent technological innovations that automate parts of the HTA process. The practical implementation of living HTA using both approaches (i.e., manual approach and using semi-automation) is described along with the likely issues and challenges with planning and implementing a living HTA process. The time, resources and additional considerations outlined may prohibit living HTA from becoming the norm for every evaluation; however, scenarios where living HTA would be particularly beneficial are discussed.

Isomeric Oligo(Phenylenevinylene)-Based Covalent Organic Frameworks with Different Orientation of Imine Bonds and Distinct Photocatalytic Activities.

Imine-linked covalent organic frameworks (COFs) have been extensively studied in photocatalysis because of their easy synthesis and excellent crystallinity. The effect of imine-bond orientation on the photocatalytic properties of COFs, however, is still rarely studied. Herein, we report two novel COFs with different orientations of imine bonds using oligo(phenylenevinylene) moieties. The COFs showed similar structures but great differences in their photoelectric properties. COF-932 demonstrated a superior hydrogen evolution performance compared to COF-923 when triethanolamine was used as the sacrificial agent. Interestingly, the use of ascorbic acid led to the protonation of the COFs, further altering the direction of electron transfer. The photocatalytic performances were increased to 23.4 and 0.73 mmol g-1 h-1 for protonated COF-923 and COF-932, respectively. This study provides a clear strategy for the design of imine-linked COF-based photocatalysts and advances the development of COFs.

Rapid Detection of Available Nitrogen in Soil by Surface-Enhanced Raman Spectroscopy.

Soil-available nitrogen is the main nitrogen source that plants can directly absorb for assimilation. It is of great significance to detect the concentration of soil-available nitrogen in a simple, rapid and reliable method, which is beneficial to guiding agricultural production activities. This study confirmed that Raman spectroscopy is one such approach, especially after surface enhancement; its spectral response is more sensitive. Here, we collected three types of soils (chernozem, loess and laterite) and purchased two kinds of nitrogen fertilizers (ammonium sulfate and sodium nitrate) to determine ammonium nitrogen (NH4-N) and nitrate nitrogen (NO3-N) in the soil. The spectral data were acquired using a portable Raman spectrometer. Unique Raman characteristic peaks of NH4-N and NO3-N in different soils were found at 978 cm-1 and 1044 cm-1, respectively. Meanwhile, it was found that the enhancement of the Raman spectra by silver nanoparticles (AgNPs) was greater than that of gold nanoparticles (AuNPs). Combined with soil characteristics and nitrogen concentrations, Raman peak data were analyzed by multiple linear regression. The coefficient of determination for the validation (Rp2) of multiple linear regression prediction models for NH4-N and NO3-N were 0.976 and 0.937, respectively, which deeply interpreted the quantitative relationship among related physical quantities. Furthermore, all spectral data in the range of 400-2000 cm-1 were used to establish the partial least squares (PLS), back-propagation neural network (BPNN) and least squares support vector machine (LSSVM) models for quantification. After cross-validation and comparative analysis, the results showed that LSSVM optimized by particle swarm methodology had the highest accuracy and stability from an overall perspective. For all datasets of particle swarm optimization LSSVM (PSO-LSSVM), the Rp2 was above 0.99, the root mean square errors of prediction (RMSEP) were below 0.15, and the relative prediction deviation (RPD) was above 10. The ultra-portable Raman spectrometer, in combination with scatter-enhanced materials and machine learning algorithms, could be a promising solution for high-efficiency and real-time field detection of soil-available nitrogen.

An investigation of the constancy of effect in Cochrane systematic reviews in context with the assumptions for noninferiority trials.

When designing a noninferiority (NI) study one of the most important steps is to set the noninferiority (NI) limit. The NI limit is an acceptable loss of efficacy for a new investigative treatment compared to an active control treatment - often standard care. The limit should be a value so small that the loss efficacy is clinically zero. An approach to the setting of a noninferiority limit such that an effect over placebo can be shown through an indirect comparison to placebo-controlled trials where the active control treatment was compared to placebo. In this context, the setting of the NI limit depends on three assumptions: assay sensitivity, bias minimisation, and the constancy assumption. The last assumption of constancy assumes the effect of the active control over placebo is constant. This paper aims to assess the constancy assumption in placebo-controlled trials. METHODS: 236 Cochrane reviews of placebo-controlled trials published in 2015-2016 were collected and used to assess the relation between the placebo, active treatment, and the standardised treatment different (SMD) with the time (year of publication). RESULTS: The analysis showed that both the size of the study and the treatment effect were associated with year of publication. The three main variables that affect the estimate of any future trial are the estimate from the meta-analysis of previous trials prior to the trial, the year difference in the meta-analysis, and the year of the trial conduction. The regression analysis showed that an increase of one unit in the point estimate of the historical meta-analysis would lead to an increase in the predicted estimate of future trial on the SMD scale by 0.88. This result suggests the final trial results are 12% smaller than that from the meta-analysis of trials until that point. CONCLUSION: The result of this study indicates that assuming constancy of the treatment difference between the active control and placebo can be questioned. It is therefore important to consider the effect of time in estimating the treatment response if indirect comparisons are being used as the basis of a NI limit.

Porous Organic Polymers via Diels-Alder Reaction for the Removal of Cr(VI) from Aqueous Solutions.

The Diels-Alder reaction is striking as a prominent synthetic tool for the rapid construction of complex molecular frameworks, but the synthesis of porous organic polymers (POPs) via the Diels-Alder reaction is rare. Herein, we report the solvothermal synthesis of a new type of POPs (DA-POPs) via the furan/alkynyl Diels-Alder reaction. These polymers show favorable porous properties and high specific surface areas (up to 1041 m2·g-1). Meanwhile, the high porosity in conjuction of ether bridges in the DA-POPs enable a fine adsorption performance for the removal of Cr(VI) from aqueous solutions.

High Sensitivity Strain Sensors Using Four-Core Fibers through a Corner-Core Excitation.

A weakly-coupled multicore fiber can generate supermodes when the multi-cores are closer to enter the evanescent power coupling region. The high sensitivity strain sensors using tapered four-core fibers (FCFs) were demonstrated. The fan-in and fan-out couplers were used to carry out light coupling between singlemode fibers and the individual core of the FCFs. A broadband lightsource from superlumminescent diodes (SLDs) was launched into one of the four cores arranged in a rectangular configuration. When the FCF was substantially tapered, the asymmetric supermodes were produced to generate interferences through this corner-core excitation scheme. During tapering, the supermodes were excited based on a tri-core structure initially and then transited to a rectangular quadruple-core structure gradually to reach the sensitivity of 185.18 pm/µÔ‘ under a tapered diameter of 3 µm. The asymmetric evanescent wave distribution due to the corner-core excitation scheme is helpful to increase the optical path difference (OPD) between supermodes for improving the strain sensitivity.

Rapid Detection of Different Types of Soil Nitrogen Using Near-Infrared Hyperspectral Imaging.

Rapid and accurate determination of soil nitrogen supply capacity by detecting nitrogen content plays an important role in guiding agricultural production activities. In this study, near-infrared hyperspectral imaging (NIR-HSI) combined with two spectral preprocessing algorithms, two characteristic wavelength selection algorithms and two machine learning algorithms were applied to determine the content of soil nitrogen. Two types of soils (laterite and loess, collected in 2020) and three types of nitrogen fertilizers, namely, ammonium bicarbonate (ammonium nitrogen, NH4-N), sodium nitrate (nitrate nitrogen, NO3-N) and urea (urea nitrogen, urea-N), were studied. The NIR characteristic peaks of three types of nitrogen were assigned and regression models were established. By comparing the model average performance indexes after 100 runs, the best model suitable for the detection of nitrogen in different types was obtained. For NH4-N, R2p = 0.92, RMSEP = 0.77% and RPD = 3.63; for NO3-N, R2p = 0.92, RMSEP = 0.74% and RPD = 4.17; for urea-N, R2p = 0.96, RMSEP = 0.57% and RPD = 5.24. It can therefore be concluded that HSI spectroscopy combined with multivariate models is suitable for the high-precision detection of various soil N in soils. This study provided a research basis for the development of precision agriculture in the future.

Smart Synthesis of Hollow Microporous Organic Capsules with a Polyaniline Modified Shell.

In this work, novel hypercrosslinked polymer-based hollow microporous organic capsules with a polyaniline (PANI)-modified shell (PANI@S-HMOCs) are prepared by in-situ polymerization of aniline in the porous structure of the sulfonated hollow microporous organic capsules (S-HMOCs). PANI@S-HMOC1, PANI@S-HMOC2, and PANI@S-HMOC3 are made by adjusting S-HMOCs and aniline weight ratios of 4:1 and 3:1, and 2:1, respectively. The characterizations of PANI@S-HMOCs demonstrate that electrostatic interaction between aniline and sulfonic acid groups plays an important role in encapsulating PANI in the pores of the shell. The content of PANI shows an evident effect on the porosity of PANI@S-HMOCs, and an appropriate polyaniline loading amount may increase the surface area. PANI@S-HMOC1 and PANI@S-HMOC2 have higher BET surface areas (529 and 503 m2 g-1 ) than S-HMOCs (424 m2 g-1 ), but PANI@S-HMOC3 has lower BET surface area (380 m2 g-1 ). Based on the structural and textural features, PANI@S-HMOC2 shows good adsorption performance for Cr(VI) from aqueous media (156 mg g-1 , pH = 2, and 27 mg g-1 , pH = 7).

The Cost-Effectiveness of Belimumab and Voclosporin for Patients with Lupus Nephritis in the United States.

BACKGROUND AND OBJECTIVES: Despite existing therapies, people with lupus nephritis progress to kidney failure and have reduced life expectancy. Belimumab and voclosporin are two new disease-modifying therapies recently approved for the treatment of lupus nephritis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A de novo economic model was developed to estimate the cost-effectiveness of these therapies, including the following health states: "complete response," "partial response," and "active disease" defined by eGFR and proteinuria changes, kidney failure, and death. Short-term data and mean cohort characteristics were sourced from pivotal clinical trials of belimumab (the Belimumab International Study in Lupus Nephritis) and voclosporin (the Aurinia Urinary Protection Reduction Active-Lupus with Voclosporin trial and Aurinia Renal Response in Active Lupus With Voclosporin). Risk of mortality and kidney failure were on the basis of survival modeling using published Kaplan-Meier data. Each drug was compared with the standard of care as represented by the comparator arm in its respective pivotal trial(s) using US health care sector perspective, with a societal perspective also explored. RESULTS: In the health care perspective probabilistic analysis, the incremental cost-effectiveness ratio for belimumab compared with its control arm was estimated to be approximately $95,000 per quality-adjusted life year. The corresponding incremental ratio for voclosporin compared with its control arm was approximately $150,000 per quality-adjusted life year. Compared with their respective standard care arms, the probabilities of belimumab and voclosporin being cost effective at a threshold of $150,000 per quality-adjusted life year were 69% and 49%, respectively. Cost-effectiveness was dependent on assumptions made regarding survival in response states, costs and utilities in active disease, and the utilities in response states. In the analysis from a societal perspective, the incremental ratio for belimumab was estimated to be approximately $66,000 per quality-adjusted life year, and the incremental ratio for voclosporin was estimated to be approximately $133,000 per quality-adjusted life year. CONCLUSIONS: Compared with their respective standard care arms, belimumab but not voclosporin met willingness-to-pay thresholds of $100,000 per quality-adjusted life year. Despite potential clinical superiority in the informing trials, there remains high uncertainty around the cost-effectiveness of voclosporin.

Boosting the Photocatalytic Hydrogen Evolution Activity for D-π-A Conjugated Microporous Polymers by Statistical Copolymerization.

Recently, great progress has been achieved in the design and preparation of conjugated organic polymer photocatalysts for hydrogen generation. However, it is still challenging to develop an organic polymer photocatalyst with high photoconversion efficiency. Rational structure design of organic polymer photocatalysts holds the key point to realize high photocatalytic performance. Herein, a series of donor-π-acceptor (D-π-A) conjugated organic copolymer photocatalysts is developed using statistical copolymerization by tuning the feed molar ratio of pyrene (donor) to dibenzothiophene-S,S-dioxide (acceptor) units. It reveals that the photocatalytic activity of the resulting copolymers is significantly dependent on the molar ratio of donor to acceptor, which efficiently changes the polymer structure and component. When the monomer feed ratio is 25:75, the random copolymer PyBS-3 of 10 mg with Pt cocatalyst shows a high hydrogen evolution rate of 1.05 mmol h-1 under UV/Vis light irradiation using ascorbic acid as the hole-scavenger, and an external quantum efficiency of 29.3% at 420 nm, which represents the state-of-the-art of organic polymer photocatalysts. This work demonstrates that statistical copolymerization is an efficient strategy to optimize the polymer structure for improving the photocatalytic activity of conjugated organic polymer catalysts.