Information criteria for latent factor models: a study on factor pervasiveness and adaptivity.

We study the information criteria extensively under general conditions for high-dimensional latent factor models. Upon carefully analyzing the estimation errors of the principal component analysis method, we establish theoretical results on the estimation accuracy of the latent factor scores, incorporating the impact from possibly weak factor pervasiveness; our analysis does not require the same factor strength of all the leading factors. To estimate the number of the latent factors, we propose a new penalty specification with a two-fold consideration: i) being adaptive to the strength of the factor pervasiveness, and ii) favoring more parsimonious models. Our theory establishes the validity of the proposed approach under general conditions. Additionally, we construct examples to demonstrate that when the factor strength is too weak, scenarios exist such that no information criterion can consistently identify the latent factors. We illustrate the performance of the proposed adaptive information criteria with extensive numerical examples, including simulations and a real data analysis.

Factor-Adjusted Regularized Model Selection.

This paper studies model selection consistency for high dimensional sparse regression when data exhibits both cross-sectional and serial dependency. Most commonly-used model selection methods fail to consistently recover the true model when the covariates are highly correlated. Motivated by econometric and financial studies, we consider the case where covariate dependence can be reduced through the factor model, and propose a consistency strategy named Factor-Adjusted Regularized Model Selection (FarmSelect). By learning the latent factors and idiosyncratic components and using both of them as predictors, FarmSelect transforms the problem from model selection with highly correlated covariates to that with weakly correlated ones via lifting. Model selection consistency, as well as optimal rates of convergence, are obtained under mild conditions. Numerical studies demonstrate the nice finite sample performance in terms of both model selection and out-of-sample prediction. Moreover, our method is flexible in the sense that it pays no price for weakly correlated and uncorrelated cases. Our method is applicable to a wide range of high dimensional sparse regression problems. An R-package FarmSelect is also provided for implementation.

Elevated Hb A2 Levels in a Patient with a Compound Heterozygosity for the (ß⁺) -31 (A > G) and (ß°) Codon 17 (A > T) Mutations Together with a Single α-Globin Gene.

We report the molecular and hematological feature of a Thai woman who had clinical diagnosis of ß-thalassemia intermedia (ß-TI). Hemoglobin (Hb) high performance liquid chromatography (HPLC) analysis identified Hb A (64.4%), Hb F (12.3%) and Hb A2/E (15.9%) with small peaks of Hb Bart's (γ4) and Hb H (ß4). She was initially diagnosed as EA Bart's disease, which occurs from combination of Hb H disease and Hb E (HBB: c.79G > A) trait. However, the Hb analysis using capillary electrophoresis (CE) demonstrated no Hb E, 68.5% Hb A, 15.5% Hb F and 16.0% Hb A2. DNA analysis showed a compound heterozygosity for (ß(+)) -31 (A > G) (HBB: c.-81A > G) and (ß(0)) codon 17 (A > T) (HBB: c.52A > T) mutations and deletional Hb H (- -(SEA)/-α(3.7)). Thus, she was finally diagnosed with a combination of Hb H disease and compound heterozygosity of ß(+)/ß(0)-thalassemia (ß(+)/ß(0)-thal). The ß-globin mutations could affect not only hematological parameters but also elevate the Hb A2 levels. These effects could not be ameliorated by the coinheritance of Hb H disease. Therefore, a better understanding of the effects of this combination on hematological analysis data will be useful for providing accurate diagnosis, genetic counseling, prevention and control programs of ß-thalassemia major (ß-TM).

Synthesis of three alpha 7 agonists in labeled form.

In support of a program to develop an alpha 7 agonist as a treatment for Alzheimer's disease, three drug candidates, 1, 2, and 3, were prepared in labeled forms. Compound 1 was prepared in C-14 labeled form by lithiation of [2,6-(14)C2]2-chloropyridine and subsequent coupling with spirooxirane-2,3'-quinuclidine. When this same coupling was attempted using [3,4,5,6-(2)H4]2-chloropyridine, alcohol [(2)H6]-6 was the major product indicating that the primary isotope effect for the lithiation step was significant enough to shift the reaction pathway. Therefore, an alternate site of labeling was used to prepare [(2)H4]-1. [(13)C5]-2 was prepared in five steps from [(13)C5 ]2-furoic acid, but the C-14 labeled compound used [(14)C2]-1 as the starting material instead. [(14)C2]-3 was prepared in two steps from [carbonyl-(14)C]nicotinic acid.

The prognostic value of peak oxygen uptake in obstructive hypertrophic cardiomyopathy: a literature review to inform economic model development.

AIMS: Patients with obstructive hypertrophic cardiomyopathy (oHCM) experience significant clinical burden which is associated with a high economic burden. Peak oxygen uptake (pVO2), measured by cardiopulmonary exercise testing, is used to quantify functional capacity, and has been studied as a primary endpoint in recent clinical trials. This study aimed to gather evidence to consolidate the prognostic value of pVO2 in oHCM and to assess whether it is feasible to predict health outcomes in an economic model based on changes in pVO2. METHODS: A targeted literature review was conducted in MEDLINE (via PubMed) and Embase databases to identify evidence on the prognostic value of pVO2 as a surrogate health outcome to support future oHCM economic model development. Following screening, study characteristics, population characteristics, and pVO2 prognostic association data were extracted. RESULTS: A total of 4,687 studies were identified. In total, 3,531 and 538 studies underwent title/abstract and full-text screening, respectively, of which 151 were included and nine of these were in hypertrophic cardiomyopathy (HCM); only three studies focused on oHCM. The nine HCM studies consisted of one systematic literature review and eight primary studies reporting on 27 potentially predictive relationships from a pVO2-based metric with clinical outcomes including all-cause mortality, cardiovascular mortality, sudden cardiac death, transplant, paroxysmal, and permanent atrial fibrillation. pVO2 was described as a predictor of single and composite endpoints, in three and six studies, respectively, with one study reporting on both. LIMITATIONS: This study primarily uses systemic literature review methods but does not qualify as one due to not entailing parallel reviewers during title-abstract and full-text stages of review. CONCLUSION: The findings of this study suggest pVO2 is predictive of multiple health outcomes, providing a rationale to use pVO2 in the development of an economic model.

Obstructive hypertrophy cardiomyopathy (oHCM) is a condition where the heart muscle thickens, obstructing blood flow and potentially impacting health. Peak oxygen uptake (pVO2) measures the highest amount of oxygen consumption during peak exercise and serves as an indicator of fitness. pVO2 can be used to assess heart health and predict severe conditions and death, acting as a surrogate endpoint. Surrogate endpoints are valuable in drug investigations since they allow earlier decisions on drug approval and funding before longer-term patient follow-up is available.This study reviewed evidence on the relationship between pVO2 values in patients with heart disease and the risk of becoming sicker or dying. Our goal was to assess if these relationships had been established and whether it is feasible to use them to predict future treatment benefits and support economic evaluations of new treatments. Our review found that most studies reported on patients with heart failure, with only nine focusing on HCM. Evidence indicates that low pVO2 values in patients with heart disease are linked to an increased risk of developing other heart conditions, needing a heart transplant, or dying.

Cost-effectiveness analysis of sodium zirconium cyclosilicate for hyperkalemia among patients with chronic kidney disease or heart failure in Kuwait.

INTRODUCTION: Our model was conducted from Kuwaiti payer's perspective to provide evidence on the cost-effectiveness of Sodium zirconium cyclosilicate (SZC) versus patiromer to correct and maintain serum potassium (K+) in combination with renin-angiotensin-aldosterone system inhibitors (RAASis) with different dose titration in patients with chronic kidney disease/heart failure (CKD/HF) with/without renal replacement therapy (RRT). METHODOLOGY: The model was developed as a patient-level, fixed-time increment stochastic simulation to simulate the complexity of disease, including multiple coexisting and competing conditional risks. This model was established to compare SZC versus patiromer as a treatment for hyperkalemia (HK) among adult populations with underlying conditions of advanced CKD stages 3a-5 or HF to correct and maintain serum K + over a lifetime horizon. The clinical outcomes of SZC and patiromer were demonstrated through arm-specific K + trajectories extracted from the HARMONIZE trial and OPAL-HK trial, respectively. The utility data was captured from different studies. Direct medical cost was captured from local data from Kuwaiti hospitals. Sensitivity analyses were conducted to assess the uncertainty in the model. RESULTS: Within different scenarios of CKD/HF, SZC was a cost-saving option, with/without RRT, whether one-off administration or repeated administration, except for one-off treatment administration among the HF cohort, which generated an incremental cost effectiveness ratio of KWD 331/quality adjusted life year (QALY). The incremental QALY of SZC ranged from 0.007 to 0.202. In addition, the savings observed with SZC fall within a range of KWD -60 to KWD -1,235 at serum K+ ≥ 5.1 mmol/L. CONCLUSION: The evidence generated by our model recommends the inclusion of SZC as a treatment option to correct HK and maintain normal serum K + level for CKD/HF patients within the Kuwaiti healthcare system. The costs saved from reducing frequent HK episodes, RAASis discontinuation/down titration, major cardiovascular events, and hospitalization offset the drug acquisition cost of SZC.

Validity and measurement equivalence of EQ-5D-5L questionnaire among heart failure patients in Malaysia: a cohort study.

AIM: This study aimed to examine the validity of EQ-5D-5L among HFrEF patients in Malaysia, and to explore the measurement equivalence of three main language versions. METHODS: We surveyed HFrEF patients from two hospitals in Malaysia, using Malay, English or Chinese versions of EQ-5D-5L. EQ-5D-5L dimensional scores were converted to utility scores using the Malaysian value set. A confirmatory factor analysis longitudinal model was constructed. The utility and visual analog scale (VAS) scores were evaluated for validity (convergent, known-group, responsiveness), and measurement equivalence of the three language versions. RESULTS: 200 HFrEF patients (mean age = 61 years), predominantly male (74%) of Malay ethnicity (55%), completed the admission and discharge EQ-5D-5L questionnaire in Malay (49%), English (26%) or Chinese (25%) languages. 173 patients (86.5%) were followed up at 1-month post-discharge (1MPD). The standardized factor loadings and average variance extracted were ≥ 0.5 while composite reliability was ≥ 0.7, suggesting convergent validity. Patients with older age and higher New York Heart Association (NYHA) class reported significantly lower utility and VAS scores. The change in utility and VAS scores between admission and discharge was large, while the change between discharge and 1MPD was minimal. The minimal clinically important difference for utility and VAS scores was ±0.19 and ±11.01, respectively. Malay and English questionnaire were equivalent while the equivalence of Malay and Chinese questionnaire was inconclusive. LIMITATION: This study only sampled HFrEF patients from two teaching hospitals, thus limiting the generalizability of results to the entire heart failure population. CONCLUSION: EQ-5D-5L is a valid questionnaire to measure health-related quality of life and estimate utility values among HFrEF patients in Malaysia. The Malay and English versions of EQ-5D-5L appear equivalent for clinical and economic assessments.

EQ-5D is the most commonly used questionnaire to measure patients' health-related quality of life in clinical trials and health technology assessments. To increase confidence over clinical trial findings that heart failure interventions improve health-related quality of life and quality-adjusted life years (number of years alive with equivalence health-related quality of life), the questionnaire used to measure health-related quality of life needs to be validated in the specific population. Since EQ-5D-5L has not been validated in Malaysia's heart failure with reduced ejection fraction (HFrEF) population, this study evaluated the psychometric properties (validity) of EQ-5D-5L among HFrEF patients in Malaysia and the equivalence of different versions of languages (i.e. Malay, Chinese and English) of EQ-5D-5L in measuring the health-related quality of life. The findings suggested that EQ-5D-5L is a valid questionnaire to measure the health-related quality of life in HFrEF patients and estimate the quality-adjusted life years. The Malay and English versions of EQ-5D-5L appear to be equivalent for use in clinical trials and health technology assessments.

Cost-effectiveness analysis of upadacitinib as a treatment option for patients with rheumatoid arthritis in the Kingdom of Saudi Arabia.

AIM: To evaluate cost-effectiveness of upadacitinib (targeted synthetic-disease modifying anti-rheumatic drug [ts-DMARD]) as first-line (1 L) treatment versus current treatment among patients with rheumatoid arthritis (RA) in the Kingdom of Saudi Arabia (KSA), who had an inadequate response to prior conventional-synthetic (csDMARDs) and/or biologic-DMARDs (bDMARDs). METHODS: This Excel-based model included patients with moderate (Disease Activity Score [DAS28]: >3.2 to ≤5.1) or severe RA (DAS28 > 5.1). Cost-effectiveness of current treatment (1 L: adalimumab-originator/biosimilar; second-line (2 L): other bDMARDs/tofacitinib) was compared against a new treatment involving two scenarios (1 L: upadacitinib, 2 L: adalimumab-biosimilar [scenario-1]/adalimumab-originator [scenario-2]) for a 10-year time-horizon from societal perspective. Model outcomes included direct and indirect costs, quality-adjusted life-years (QALYs), hospitalization days, number of orthopedic surgeries, and incremental cost-utility ratio (ICUR) per QALY. RESULTS: With the current pathway, estimated total societal costs for 100 RA patients over 10-year period were Saudi Riyal (SAR) 50,450,354 (United States dollars [USD] 13,453,428) (moderate RA) and SAR50,013,945 (USD13,337,052) (severe RA). New pathway (scenario-1) showed that in patients with moderate-to-severe RA, upadacitinib led to higher QALY gain (+8.99 and +15.63) at lower societal cost (cost difference: -SAR2,023,522 [-USD539,606] and -SAR3,373,029 [-USD899,474], respectively). Thus, as 1 L, upadacitinib projects "dominant" ICUR per QALY over current pathway. Moreover, in alternate pathway (scenario-2), upadacitinib also projects "dominant" ICUR per QALY for patient with severe RA (QALY gain: +15.63; cost difference: -SAR 164,536 [-USD43,876]). However, moderate RA was associated with additional cost of SAR1,255,696 (USD334,852) for improved QALY (+8.99) over current pathway (ICUR per QALY: SAR139,742 [USD37,264]). Both scenarios resulted in reduced hospitalization days (scenario-1: -14.83 days; scenario-2: -11.41 days) and number of orthopedic surgeries (scenario-1: -8.36; scenario-2: -6.54) for moderate-to-severe RA over the current treatment pathway. CONCLUSION: Upadacitinib as 1 L treatment in moderate-to-severe RA can considerably reduce healthcare resource burden in KSA, majorly due to reduced drug administration/monitoring/hospitalization/surgical and indirect costs.

Income and democracy: a bivariate copula approach.

We propose a new approach for exploring the relationship between income and democracy by modeling the two most popular discrete democracy indexes, Polity IV and Freedom House, as a joint random variable by means of a copula function. Joint modeling is crucial for eliciting complementarity and/or substitutability amongst these indexes claiming to measure similar things, i.e. a country's degree of democratization. We find strong evidence supporting both the existence of the relationship and the positive dependence between the two democracy indexes, suggesting that they are complements to each other. Our findings are robust to different samples and model specifications.

Transarterial therapies in patients with hepatocellular carcinoma eligible for transarterial embolization: a US cost-effectiveness analysis.

OBJECTIVES: To assess the cost-effectiveness of transarterial radioembolization (TARE) versus conventional transarterial chemoembolization (cTACE) and drug-eluting beads chemoembolization (DEE-TACE) for patients with unresectable early- to intermediate-stage hepatocellular carcinoma (HCC). DESIGN: A cohort-based Markov model with a five-year time horizon was developed to evaluate the cost-effectiveness of the three embolization treatments. Upon entering the model, patients with HCC received either TARE or one of the two other embolization treatments. Patients remained in a "watch and wait" state for tumor downstaging that allowed them to move to health states such as liver transplant, resection, systemic therapies, or cure. Clinical input parameters were retrieved from the published literature, and where values could not be sourced, assumptions were made and validated by clinical experts. Health benefits were quantified using quality-adjusted life years (QALYs). Cost input parameters were obtained from various sources, including the Medicare Cost Report, IBM® Micromedex RED BOOK, and published literature. RESULTS: At five years, TARE was found to be cost-saving (saving $15,779 per person compared to cTACE) and produced 0.33 more QALYs per person than cTACE. TARE cost $13,696 more but produced 0.33 more QALYs than DEE-TACE, with an incremental cost-effectiveness ratio of $41,474 per QALY gained at five years. After accounting for parameter uncertainty, the likelihood of TARE being cost-effective was at least 90% against all comparators at a cost-effectiveness threshold of $100,000 per QALY gained. CONCLUSIONS: TARE produces more QALYs than cTACE and DEE-TACE, with a high probability of being cost-effective against both comparators.

The Barcelona Clinic Liver Cancer guideline recommends the use of transarterial radioembolization (TARE), conventional (cTACE), or drug-eluting bead transarterial chemoembolization (DEE-TACE) for treating hepatocellular carcinoma (HCC). This study evaluated the cost-effectiveness of TARE versus two alternative embolization treatments (cTACE and DEE-TACE) in treating patients with unresectable early- to intermediate-stage HCC.A cohort-based Markov model was developed to analyze the costs and benefits of these treatments from a US healthcare perspective within a 5-year time horizon. A 20-year time horizon was assessed as a scenario. In the model, patients were assigned to receive TARE, cTACE, or DEE-TACE and remained in the "watch and wait" stage for tumor downstaging. Data used in the model was taken from previous studies and in consultation with clinical experts. The benefits of the treatments were measured by considering the impact on the patient's quality of life. The costs associated with the treatments were obtained from various sources, including reports, publicly available databases, and published literature.The findings show that TARE is not only cost-saving compared to cTACE but also results in a higher number of quality-adjusted life years (QALYs) per person. While TARE was more expensive than DEE-TACE, it produced more QALYs, further indicating more favorable patient outcomes and overall treatment effectiveness. These findings could potentially impact resource allocation and decision-making for the treatment of HCC.

Attention based dynamic graph neural network for asset pricing.

Recent studies suggest that networks among firms (sectors) play a vital role in asset pricing. This paper investigates these implications and develops a novel end-to-end graph neural network model for asset pricing by combining and modifying two state-of-the-art machine learning techniques. First, we apply the graph attention mechanism to learn dynamic network structures of the equity market over time and then use a recurrent convolutional neural network to diffuse and propagate firms' information into the learned networks. This novel approach allows us to model the implications of networks along with the characteristics of the dynamic comovement of asset prices. The results demonstrate the effectiveness of our proposed model in both predicting returns and improving portfolio performance. Our approach demonstrates persistent performance in different sensitivity tests and simulated data. We also show that the dynamic network learned from our proposed model captures major market events over time. Our model is highly effective in recognizing the network structure in the market and predicting equity returns and provides valuable market information to regulators and investors.

Quantification of model risk that is caused by model misspecification.

In this paper, we suggest a technique to quantify model risk, particularly model misspecification for binary response regression problems found in financial risk management, such as in credit risk modelling. We choose the probability of default model as one instance of many other credit risk models that may be misspecified in a financial institution. By way of illustrating the model misspecification for probability of default, we carry out quantification of two specific statistical predictive response techniques, namely the binary logistic regression and complementary log-log. The maximum likelihood estimation technique is employed for parameter estimation. The statistical inference, precisely the goodness of fit and model performance measurements, are assessed. Using the simulation dataset and Taiwan credit card default dataset, our finding reveals that with the same sample size and very small simulation iterations, the two techniques produce similar goodness-of-fit results but completely different performance measures. However, when the iterations increase, the binary logistic regression technique for balanced dataset reveals prominent goodness of fit and performance measures as opposed to the complementary log-log technique for both simulated and real datasets.

Modification of treatment-sequence model with a customizable number of treatments to better reflect contemporary and future clinical practice in moderate to severe psoriasis.

AIMS: Existing treatment-sequence models for psoriasis are limited by lines of treatments included. We sought to more accurately capture the patient experience with an increasing number of treatments while maintaining the complexity and transparency of current models. MATERIALS AND METHODS: We adapted a standard treatment-sequence model for psoriasis with two lines of active treatments followed by best supportive care (BSC). The first line was used to model the targeted treatments for comparison (Biologic A or B). The second line was used potentially to model all treatments (excluding the first-line treatment) before BSC, termed the basket of biologics (BoB). First-line treatment and the BoB were modeled with an induction and maintenance phase. The BoB efficacy was assumed to be the average of all treatments included and the BoB annual discontinuation rate was based on the number of treatments included and their individual annual discontinuation rate. A varying number of treatments in the BoB were tested (1, 5, 10). Model inputs were from published literature. RESULTS: In our example, when the number of treatments in the BoB increased from 1 to 10, the annual discontinuation rate of the BoB dropped from 16.5% to 1.2%. Time on BoB increased from 4.16 to 19.16 years and the time on BSC decreased from 28.28 to 13.29 years. Total costs and quality-adjusted life years increased with an increasing number of treatments in the BoB. LIMITATIONS: The properties of the BoB were simplified in order to maintain the transparency of the model. Results may differ if individual treatments in the BoB are modeled line by line. CONCLUSIONS: Modification with the BoB allows a greater number of treatments within the model, providing a closer reflection of clinical reality, and has implications for evaluation of the long-term cost-effectiveness of psoriasis treatments.

Psoriasis is a chronic skin disease with no cure that causes itchy and painful plaques and scales, most commonly found on the scalp, trunk, elbows, and knees. A variety of treatments are available that can improve the signs and symptoms of psoriasis. Healthcare payers are interested in the costs, benefits, and risks of treatments for all diseases, including those for psoriasis. These payers often use mathematical models to better understand and compare the value of various treatments. With psoriasis, these models usually assume three lines of active therapy and then a final supportive therapy over a patient's lifetime. However, the average number of therapies patients with psoriasis receive is often greater than three, resulting in them spending most of their time on, and switching among, treatments rather than on best supportive care. Therefore, instead of modeling each line of treatment individually, the researchers proposed a modification to the existing model framework, whereby all subsequent treatments are combined into a single basket. This modification allowed for many treatments to be considered over the lifetime of patients with psoriasis and also maintained the model's complexity. The researchers found that as the amount of time on active therapy increased, the amount of time on supportive therapy decreased, treatment costs increased, and patients spent more time with better quality-of-life. The researchers concluded that the proposed model modification more closely resembles clinical practice than the previous model and would be very useful to healthcare payers in better estimating the value of psoriasis treatments.

Cost-effectiveness of vibegron for the treatment of overactive bladder in the United States.

AIMS: To evaluate the cost-effectiveness of vibegron compared with other oral pharmacologic therapies as treatment for overactive bladder (OAB). METHODS: A semi-Markov model with monthly cycles was developed to support a lifetime horizon of vibegron 75 mg from a US commercial payor or Medicare perspective. The model incorporated efficacy (reductions in daily micturitions and urinary incontinence episodes), adverse events, OAB-related comorbidities, drug-drug interactions, anticholinergic burden, and treatment persistence. Direct costs and quality-adjusted life years (QALY) were accumulated over time. The primary outcome was the cost per QALY incremental cost-effectiveness ratio (ICER). One-way (OWSA) and probabilistic sensitivity analyses (PSA) were performed. RESULTS: For commercial payors, vibegron was cost-effective at a willingness-to-pay (WTP) threshold of $50,000/QALY versus mirabegron 50 mg (ICER, $9,311) and at a WTP threshold of $150,000/QALY versus mirabegron 25 mg (ICER, $141,957) and versus an anticholinergic basket based on market share (ICER, $118,121). For Medicare, vibegron was cost-effective at a WTP threshold of $50,000/QALY versus mirabegron 50 mg (ICER, $12,154) and at a WTP threshold of $100,000/QALY versus mirabegron 25 mg (ICER, $99,150) and versus an anticholinergic market basket (ICER, $60,756). For commercial payors and Medicare, OWSAs for vibegron versus mirabegron indicated cost-effectiveness was most sensitive to vibegron persistence at 1 and 12 months. PSAs indicated that vibegron was cost-effective versus mirabegron 50 mg 98.6% and 100% of the time at $50,000/QALY for commercial payors and Medicare payors, respectively. LIMITATIONS: Due to lack of real-world data available on persistence, vibegron was assumed to have the same persistence as mirabegron 50 mg. Long-term efficacy was assumed to be sustained beyond 52 weeks in the absence of clinical trials longer than 52 weeks. CONCLUSIONS: Vibegron is cost-effective from a commercial payor (WTP threshold $150,000/QALY) and Medicare (WTP threshold $100,000/QALY) perspective when compared with other oral pharmacologic treatments for OAB.

Overactive bladder (OAB) affects more than 30 million adults in the United States. OAB is a condition associated with frequent and sudden urges to urinate. Drugs for treating OAB may improve symptoms for patients. Anticholinergic drugs are one type of drug available for treating OAB. Anticholinergic drugs may cause side effects such as dry mouth and constipation. Newer types of drugs called ß₃-adrenergic receptor agonists are available for treating OAB symptoms. Vibegron is a member of the ß₃-adrenergic receptor agonist class of drugs. Vibegron does not cause the same side effects related to anticholinergic drugs such as dry mouth and constipation. ß₃-adrenergic receptor agonists work well for OAB symptoms but may be more expensive than anticholinergic drugs. It is important to choose drugs that work well and that are a reasonable price. This study assessed if vibegron is cost-effective for people enrolled in US private insurance and Medicare plans. Compared with other common drugs such as anticholinergic drugs for OAB, vibegron is cost-effective for people enrolled in private insurance and Medicare plans. This was in part because vibegron works better for longer and causes fewer adverse effects than other drugs. Vibegron may be considered "good value for money" for patients with OAB.

How accurate are the longer-term projections of overall survival for cancer immunotherapy for standard versus more flexible parametric extrapolation methods?

AIMS: To assess the accuracy of standard parametric survival models, spline models, and mixture cure models (MCMs) fitted to overall survival (OS) data available at the time of submission in the NICE HTA process compared with data subsequently made available. METHODS: Standard parametric distributions, spline models, and MCMs were fitted to OS data presented in single technology appraisals (TAs) for immune-checkpoint inhibitors (ICIs) in cancer. For each TA, the estimated survival from the fitted models was compared with Kaplan-Meier (KM) data that were made available following the HTA submission using differences between point estimates and restricted area under the curve (AUC) at both the midpoint and the end of additional follow-up. Differences in interval AUC values (calculated for each 6-month period) were also assessed. RESULTS: Standard parametric survival models and spline models were more likely to underestimate longer-term survival, irrespective of the measure used to assess model accuracy. MCMs were more likely to overestimate survival; however, this was improved in some cases by applying an additional hazard of mortality for "statistically cured" patients. LIMITATIONS: The accuracy of the models was assessed based on much shorter OS data than the period for which extrapolation is needed, which may impact conclusions regarding the most accurate models. The most recent TAs for ICIs have not been captured. CONCLUSIONS: There are no definitive findings that unquestionably support the use of one specific extrapolation technique. Rather, each has the potential to provide accurate or inaccurate extrapolation to longer-term data in certain circumstances, but the added flexibility of more complex models can be justified for treatments, like ICIs, that have extended survival for patients across disease areas. The use of mortality adjustments for "statistically cured" patients allows decision-makers to explore more conservative scenarios in the face of high decision uncertainty.

Phylogenetic analysis of PP2C proteins and interactive proteins analyze of BjuPP2C52 in Brassica juncea.

Brassica juncea var. tumida Tsen et Lee (Tumorous stem mustard) is an unique vegetable in China. Its enlarged tumorous stem was used as main raw material to produce pickle (Zhacai). In practice, early-bolting happens around 15% of planting area all year and inhibits its production. Here, about 209 PP2C proteins were identified through HMMER software and divided into 13 sub-families in B. juncea. BjuPP2C52 belongs to E sub-family, was up-regulated at reproductive growth stages and interacts with BjuFKF1, a key protein in regulating plant photoperiod flowering, in vitro and in vivo. To explore interactive proteins, BjuPP2C52 was used as bait, 12 potential interactive proteins were screened from yeast library, and they are BjuCOL3, BjuCOL5, BjuAP2, BjuAP2-1, BjuSVP-1, BjuFLC-2, BjuSKP1f, BjuA014572, BjuA008686, BjuO002119, BjuB036787 and BjuA019268. Further study verified that 10 out of the 12 screened proteins interacted with BjuPP2C52 in vivo. qRT-PCR was conducted to understand the expression pattern of those 10 interactive proteins in different tissues and development stages in B. juncea. The results showed that BjuCOL3, BjuCOL5, BjuB036787 and BjuA019268 were significantly up-regulated, while BjuA008686 and BjuO002119 were down-regulated in flowers compared with other four tissues. In developmental stages, BjuCOL5, BjuAP2, BjuAP2-1, BjuA014572, BjuB036787 and BjuA019268 were significantly up-regulated, while BjuSVP-1, BjuA008686 and BjuO002119 were down-regulated at reproductive stages. Based on the results, BjuCOL5, BjuAP2, BjuAP2-1, BjuSVP-1, BjuA014572, BjuB036787 and BjuA019268 may function in regulating flowering time in B. juncea.

Public health impact of booster vaccination against COVID-19 in the UK during Delta variant dominance in autumn 2021.

AIM: To evaluate the public health impact of the UK COVID-19 booster vaccination program in autumn 2021, during a period of SARS-CoV-2 Delta variant predominance. MATERIALS AND METHODS: A compartmental Susceptible-Exposed-Infectious-Recovered model was used to compare age-stratified health outcomes for adult booster vaccination versus no booster vaccination in the UK over a time horizon of September-December 2021, when boosters were introduced in the UK and the SARS-CoV-2 Delta variant was predominant. Model input data were sourced from targeted literature reviews and publicly available data. Outcomes were predicted COVID-19 cases, hospitalizations, post-acute sequelae of COVID-19 (PASC) cases, deaths, and productivity losses averted, and predicted healthcare resources saved. Scenario analyses varied booster coverage, virus infectivity and severity, and time horizon parameters. RESULTS: Booster vaccination was estimated to have averted approximately 547,000 COVID-19 cases, 36,000 hospitalizations, 147,000 PASC cases, and 4,200 deaths in the UK between September and December 2021. It saved over 316,000 hospital bed-days and prevented the loss of approximately 16.5 million paid and unpaid patient work days. In a scenario of accelerated uptake, the booster rollout would have averted approximately 3,400 additional deaths and 25,500 additional hospitalizations versus the base case. A scenario analysis assuming four-fold greater virus infectivity and lower severity estimated that booster vaccination would have averted over 105,000 deaths and over 41,000 hospitalizations versus the base case. A scenario analysis assuming pediatric primary series vaccination prior to adult booster vaccination estimated that expanding vaccination to children aged ≥5 years would have averted approximately 51,000 additional hospitalizations and 5,400 additional deaths relative to adult booster vaccination only. LIMITATIONS: The model did not include the wider economic burden of COVID-19, hospital capacity constraints, booster implementation costs, or non-pharmaceutical interventions. CONCLUSIONS: Booster vaccination during Delta variant predominance reduced the health burden of SARS-CoV-2 in the UK, releasing substantial NHS capacity.

Identifying chronic disease patients using predictive algorithms in pharmacy administrative claims: an application in rheumatoid arthritis.

OBJECTIVE: To evaluate the predictive performance of logistic and linear regression versus machine learning (ML) algorithms to identify patients with rheumatoid arthritis (RA) treated with target immunomodulators (TIMs) using only pharmacy administrative claims. METHODS: Adults aged 18-64 years with ≥1 TIM claim in the IBM MarketScan commercial database were included in this retrospective analysis. The predictive ability of logistic regression to identify RA patients was compared with supervised ML classification algorithms including random forest (RF), decision trees, linear support vector machines (SVMs), neural networks, naïve Bayes classifier, linear discriminant analysis (LDA), quadratic discriminant analysis (QDA), and K-nearest neighbors (k-NN). Model performance was evaluated using F1 score, accuracy, precision, sensitivity, area under the receiver operating characteristic curve (AUROC), and Matthews correlation coefficient (MCC). Analyses were conducted in all-patient and etanercept-only samples. RESULTS: In the all-patients sample, ML approaches did not outperform logistic regression. RF showed small improvements versus logistic regression that were not considered remarkable, respectively: F1 score (84.55% vs 83.96%), accuracy (84.05% vs 83.79%), sensitivity (84.53% vs 82.20%), AUROC (84.04% vs 83.85%), and MCC (68.07% vs 67.66%). Findings were similar in the etanercept samples. CONCLUSION: Logistic regression and ML approaches successfully identified patients with RA in a large pharmacy administrative claims database. The ML algorithms were no better than logistic regression at prediction. RF, SVMs, LDA, and ridge classifier showed comparable performance, while neural networks, decision trees, naïve Bayes classifier, and QDA underperformed compared with logistic regression in identifying patients with RA.

Estimating Engel curves: a new way to improve the SILC-HBS matching process using GLM methods.

Microdata are required to evaluate the distributive impact of the taxation system as a whole (direct and indirect taxes) on individuals or households. However, in European Union countries this information is usually distributed into two separate surveys: the Household Budget Surveys (HBS), including total household expenditure and its composition, and EU Statistics on Income and Living Conditions (EU-SILC), including detailed information about households' income and direct (but not indirect) taxes paid. We present a parametric statistical matching procedure to merge both surveys. For the first stage of matching, we propose estimating total household expenditure in HBS (Engel curves) using a GLM estimator, instead of the traditionally used OLS method. It is a better alternative, insofar as it can deal with the heteroskedasticity problem of the OLS estimates, while making it unnecessary to retransform the regressors estimated in logarithms. To evaluate these advantages of the GLM estimator, we conducted a computational Monte Carlo simulation. In addition, when an error term is added to the deterministic imputation of expenditure in the EU-SILC, we propose replacing the usual Normal distribution of the error with a Chi-square type, which allows a better approximation to the original expenditures variance in the HBS. An empirical analysis is provided using Spanish surveys for years 2012-2016. In addition, we extend the empirical analysis to the rest of the European Union countries, using the surveys provided by Eurostat (EU-SILC, 2011; HBS, 2010).

Oil prices and agricultural commodity markets: Evidence from pre and during COVID-19 outbreak.

This paper represents an analysis of the spillover effects and time-frequency connectedness between crude oil prices and agricultural commodity markets using both the spillover index of Diebold and Yilmaz (2012) and the wavelet coherence model to evaluate whether the time-varying return spillover index exhibited the intensity and direction of transmission during the Covid-19 outbreak. Overall, the current results shed light on that in comparison with the pre-Covid-19 period, and the return spillover is more apparent during the Covid-19 crisis. However, levels of the intensity of this relationship vary through the period of research, with several intervals witnessing both negative and positive interactions. Further, our findings indicate significant heterogeneity among agriculture commodity markets in the degree of spillover to crude oil prices over time, amplifying our understanding of the economic channels through which the agriculture commodity markets are correlated. More importantly, there exist significant dependent patterns about the information spillovers across the crude oil and agriculture commodity markets might provide prominent implications for portfolio managers, investors, and government agencies.