Association of severity and prognosis with elevated blood pressure and heart rate levels in patients with intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) has a high mortality and morbidity in the world. Elevated blood pressure (BP) and heart rate (HR) have been identified as independent risk factors, with potential to predict prognosis and recurrence of cardiovascular diseases. Our study aimed to elucidate the association between BP and HR levels and the severity, as well as prognosis, of patients diagnosed with ICH. METHODS: The basic characteristics of patients and laboratory examination results, inclusive of BP and HR levels upon admission, were recorded as baseline data. The modified Rankin Scale and living status were taken into account for all patients at a 1-year follow-up. The relationship between various BP and HR levels and clinical outcome was analyzed using logistic regression and the Kaplan-Meier survival method. RESULTS: A total of 1,416 patients with acute ICH from 13 hospitals in Beijing were enrolled in our study. Logistic regression analysis indicated that patients with higher HR and BP (group 4), along with those with higher HR but lower BP (group 2), exhibited a poorer prognosis compared to those with lower BP and HR (group 1). This result was particularly pronounced in younger, male subgroups (OR (95% CI) = 4.379(2.946-6.508), P < 0.0001 for group 4; OR (95% CI) = 1.819 (1.219-2.714), P = 0.0034 for group 2). At the 1-year follow-up, group 4 patients demonstrated a significantly higher rate of fatal incidence compared to other groups (P < 0.01). CONCLUSIONS: Higher HR and BP levels, suggestive of an autonomic dysfunction, were independently associated with a poorer 1-year prognosis and reduced survival rate in ICH patients. Our findings underscore the need for early intervention to modulate these physiological parameters in patients with ICH.

Subarachnoid extension and unfavorable outcomes in patients with supratentorial intracerebral hemorrhage.

OBJECTIVE: Our study aimed to investigate the association between the subarachnoid extension of intracranial hemorrhage (SAHE) and clinical outcomes in patients with supratentorial intracerebral hemorrhage (ICH). METHODS: We analyzed the data from a prospective, multi-center, and registry-based database. Two experienced investigators independently assessed ICH imaging data. We compared baseline characteristics and follow-up outcomes. Multivariable logistic regression analysis was used to evaluate the association between SAHE and poor clinical outcomes. We also performed Kaplan-Meier curves and Cox proportional hazards regression analyses to analyze whether SAHE was relevant to a higher mortality rate. RESULTS: A total of 931 patients were included in this study (SAHE vs. no SAHE, 121 [13.0%] vs. 810 [87.0%]). Patients with SAHE had more severe neurological deficits, higher scores of the mRS, and more remarkable mortality rates at follow-up (all p values < 0.05). In multivariable-adjusted models, SAHE was independently associated with a higher risk of poor outcomes (adjusted OR [95%CI]: 2.030 [1.142-3.608] at 3 months; 2.348 [1.337-4.123] at 1 year). In addition, SAHE remained an independent association with an increased death rate at 1 year (adjusted HR [95%CI], 1.314[1.057-1.635]). In the subgroup analysis, the correlation between SAHE and prognosis exists in patients with lobar or deep ICH. CONCLUSIONS: SAHE is independently associated with poor outcomes in patients with supratentorial ICH. It may provide a promising target for developing new predictive tools targeting ICH.

EQ-5D-5L measurement properties are superior to EQ-5D-3L across the continuum of health using US value sets.

OBJECTIVE: The objective of this study was to compare the measurement properties of the US EQ-5D-3L, EQ-5D-5L, and -5L to -3L crosswalk value sets (3L; 5L; 5L > 3L) across the spectrum of health. METHODS: The three scoring approaches were compared in terms of range of scale, percent of worse-than-dead health states, and mean single-level transitions. Discriminative ability was compared by leveraging two cross-sectional datasets. A novel method was used to visualize and compare the responsiveness of 3L and 5L scoring approaches across EQ VAS values. RESULTS: The US 5L value set had the broadest range of scale at 1.573 (vs. 1.109 for 3L and crosswalk). The crosswalk had the smallest mean single-level transition of 0.061 (vs. 0.078 for 5L and 0.111 for 3L). The 5L value set tended to be more discriminative/greater statistical efficiency than the crosswalk (F-statistic ratio: 1.111, 95% CI 0.989-1.240) and 3L (F-statistic ratio: 1.102 95% CI 0.861-1.383) across levels of general health. The 5L was the most responsive value set between EQ VAS values of 25 and 75. CONCLUSION: These results imply greater sensitivity of the 5L to health changes and potentially lower incremental cost-utility ratios compared to the 3L.

Real-world clinical outcomes of patients with stage IIB or IIC cutaneous melanoma treated at US community oncology clinics.

Aim: To describe clinical outcomes after complete surgical resection of stage IIB and IIC melanoma. Methods: Adult patients (n = 567) with stage IIB or IIC cutaneous melanoma initially diagnosed and completely resected from 2008-2017 were identified using data from a US community-based oncology network. Results: Median patient follow-up was 38.8 months from melanoma resection to death, last visit or data cut-off (31 December 2020). For stage IIB (n = 375; 66%), Kaplan-Meier median real-world recurrence-free survival (rwRFS) was 58.6 months (95% CI, 48.6-69.5). For stage IIC (n = 192; 34%), median rwRFS was 29.9 months (24.9-45.5). Overall, 44% of patients had melanoma recurrence or died; 30% developed distant metastases. Conclusion: Melanoma recurrence was common, highlighting the need for effective adjuvant therapy for stage IIB and IIC melanoma.

New treatments are now available that decrease tumor recurrence when administered after surgery to remove melanoma skin tumors that are graded as stage IIB or IIC (i.e., with no cancer spread to the local lymph nodes). We studied 567 'real-world' patients at clinics in the USA who had stage IIB or IIC melanoma tumors removed in 2008­2017, before these new postsurgical treatments were widely available, to evaluate their survival and tumor recurrence. We found that almost half of these patients (44%) had melanoma recurrence or had died, and a third (30%) had tumor spread beyond the original site, by the end of 2020. These findings highlight the need for more effective treatments after surgical removal of stage IIB and IIC melanoma.

Combining EQ-5D-5L items into a level summary score: demonstrating feasibility using non-parametric item response theory using an international dataset.

BACKGROUND: The EQ-5D-5L is a well-established health questionnaire that estimates health utilities by applying preference-based weights. Limited work has been done to examine alternative scoring approaches when utility weights are unavailable or inapplicable. We examined whether the Mokken scaling approach can elucidate 1) if the level summary score is appropriate for the EQ-5D-5L and 2) an interpretation of such a score. METHODS: The R package "mokken" was used to assess monotonicity (scaling coefficients H, automated item selection procedure) and manifest invariant item ordering (MIIO: paired item response functions [IRF], HT). We used a rich dataset (the Multiple Instrument Comparison, MIC) which includes EQ-5D-5L data from six Western countries. RESULTS: While all EQ-5D-5L items demonstrated monotonicity, the anxiety/depression (AD) item had weak scalability (Hi = 0.377). Without AD, scalability improved from Hs = 0.559 to Hs = 0.714. MIIO revealed that the 5 items can be ordered, and the ordering is moderately accurate in the MIC data (HT = 0.463). Excluding AD, HT improves to 0.743. Results were largely consistent across disease and country subgroups. DISCUSSION: The 5 items of the EQ-5D-5L form a moderate to strong Mokken scale, enabling persons to be ordered using the level summary score. Item ordering suggests that the lower range of the score represents mainly problems with pain and anxiety/depression, the mid-range indicates additional problems with mobility and usual activities, and middle to higher range of scores reveals additional limitations with self-care. Scalability and item ordering are even stronger when the anxiety/depression item is not included in the scale.

Lower low-density lipoprotein cholesterol levels are associated with an increased risk of hematoma expansion and ensuing mortality in acute ICH patients.

BACKGROUND AND PURPOSE: The relationship between lipid levels and the prognosis of acute intracerebral hemorrhage (ICH) remains controversial. Thus, we aimed to investigate whether lower low-density lipoprotein cholesterol (LDL-C) levels increased the risk of adverse outcomes, as well as the current situation of statin treatment in acute ICH patients with premorbid lipid-lowering therapy. METHODS: From August 1, 2015, to July 31, 2019, a total of 73,098 ICH patients were included in our study from the Chinese Stroke Center Alliance program. Patients were grouped by LDL-C levels of < 1.4 mmol/L, 1.4-1.8 mmol/L, 1.8-2.6 mmol/L, and > 2.6 mmol/L. Logistic regression was used to assess the association between LDL-C levels and the composite risk of hematoma expansion (HE) or in-hospital death. Moreover, statin treatment in ICH patients with cardio-cerebrovascular diseases was analyzed. RESULTS: In total, 6368 (8.7%) patients were identified as a composite of HE or in-hospital death with a mean LDL-C level of 2.9 ± 1.7 mmol/L. In the univariate analysis, patients who achieved lower LDL-C concentrations under 1.4 mmol/L had a 36% higher risk of adverse outcomes compared with the ≥ 2.6 mmol/L group (OR 1.36, 95%CI 1.23-1.51). Similar results were obtained in multivariate analyses, especially for patients with GCS scores of 9-15. For acute ICH patients with concomitant atherosclerotic disease, statin treatment was discontinued in the majority of Chinese population. CONCLUSIONS: Lower LDL-C levels (< 1.4 mmol/L) are associated with an increased risk of HE and ensuing mortality in acute ICH patients. Maintaining an optimal LDL-C range may have therapeutic potential against HE which merits further investigation.

US population norms for the EQ-5D-5L and comparison of norms from face-to-face and online samples.

PURPOSE: Normative scores (norms) allow for comparisons between population(s) of interest and the general population, which is useful for burden of disease studies and cost-effectiveness analysis. The primary aim of this study was to estimate US visual analogue scale (EQ VAS) and utility-based norms for the EQ-5D-5L using the face-to-face sample. The secondary aim was to compare norms estimated in the face-to-face and online populations. METHODS: This study estimated population norms from two general population surveys: (a) face-to-face and (b) online. In these surveys, respondents provided their health state using the EQ-5D-5L health classifier and the EQ VAS. Descriptive statistics, including mean, standard deviation (SD), 95% confidence interval, and median for the 5L utility and EQ VAS were estimated for each sample and across relevant respondent characteristics to serve as the basis for US EQ-5D-5L norms RESULTS: Face-to-face sample respondents (n = 1134) were representative of the US adult general population. In this sample, mean (SD) utility decreased with increasing age until age 45 or greater (age 45-54: 0.816 (0.249) age 55-64: 0.815 (0.243) age 65-74: 0.824 (0.217) age 75 + : 0.811 (0.218)). With increasing age, more problems were reported on all dimensions except anxiety/depression; a smaller proportion of respondents age 65 and older reported problems with anxiety/depression (23.8%) as compared to the youngest respondents (42.1%). Online (n = 2018) mean utility and EQ VAS values were consistently lower than the face-to-face sample. CONCLUSIONS: The availability of US EQ-5D-5L norms facilitates interpretation and understanding of general population and patient health.

Comparison of online and face-to-face valuation of the EQ-5D-5L using composite time trade-off.

OBJECTIVE: The aim of this study was to compare online, unsupervised and face-to-face (F2F), supervised valuation of EQ-5D-5L health states using composite time trade-off (cTTO) tasks. METHODS: The official EuroQol experimental design and valuation protocol for the EQ-5D-5L of 86 health states were implemented in interviewer-assisted, F2F and unsupervised, online studies. Validity of preferences was assessed using prevalence of inconsistent valuations and expected patterns of TTO values. Respondent task engagement was measured using number of trade-offs and time per task. Trading patterns such as better-than-dead only was compared between modes. Value sets were generated using linear regression with a random intercept (RILR). Value set characteristics such as range of scale and dimension ranking were evaluated between modes. RESULTS: Five hundred one online and 1,134 F2F respondents completed the surveys. Mean elicited TTO values were higher online than F2F when compared by health state severity. Compared to F2F, a larger proportion of online respondents did not assign the poorest EQ-5D-5L health state (i.e., 55555) the lowest TTO value ([Online] 41.3% [F2F] 12.2%) (p < 0.001). A higher percentage of online cTTO tasks were completed in 3 trade-offs or fewer ([Online] 15.8% [F2F] 3.7%), (p < 0.001). When modeled using the RILR, the F2F range of scale was larger than online ([Online] 0.600 [F2F] 1.307) and the respective dimension rankings differed. CONCLUSIONS: Compared to F2F data, TTO tasks conducted online had more inconsistencies and decreased engagement, which contributed to compromised data quality. This study illustrates the challenges of conducting online valuation studies using the TTO approach.

Exploring the Internal Structure of the EQ-5D Using Non-Preference-Based Methods.

BACKGROUND: When the EuroQol EQ-5D is applied in settings other than resource allocation, a non-preference-based score may be more appropriate than societal, preference-weighted utility. To develop a psychometric score for the EQ-5D, its structural relationship, ie, how the 5 items/dimensions interrelate, must be understood to inform appropriate methods of summarizing the instrument. OBJECTIVES: To explore psychometrically derived approaches of elucidating the 5-level EQ-5D (EQ-5D-5L) item structure. METHODS: Three measurement models were assessed. All 5 items were modeled as reflective indicators using confirmatory factor analysis. EQ-5D-5L items were conceptualized as formative indicators, and other health scales (eg, the short form 36 health survey) were conceptualized as reflective indicators in Multiple Indicators Multiple Causes models (external MIMIC). The EQ-5D-5L items were modeled as a combination of formative and reflective indicators in internal MIMIC models. Results across 9 data sets from various countries and patient groups were examined to determine their robustness. RESULTS: All items loaded well (0.63-0.96) in the confirmatory factor analysis except for anxiety/depression (0.20-0.66, excluding 1 outlier). The model fit statistics of the external MIMIC models were poor, and the coefficients of the Self-Care dimension were small. The internal MIMIC model with Mobility, Pain/Discomfort, and Anxiety/Depression as formative indicators and Self-Care and Usual Activities as reflective indicators fit best. The model results of the Spanish valuation data set were outliers. CONCLUSIONS: Although there were some variations in results across subgroups, the relationship between the items remained robust. The evidence calls for testing of formative/reflective combination approaches to summarize the EQ-5D-5L.

United States Valuation of EQ-5D-5L Health States Using an International Protocol.

OBJECTIVE: To derive a US-based value set for the EQ-5D-5L questionnaire using an international, standardized protocol developed by the EuroQol Group. METHODS: Respondents from the US adult population were quota-sampled on the basis of age, sex, ethnicity, and race. Trained interviewers guided participants in completing composite time trade-off (cTTO) and discrete choice experiment (DCE) tasks using the EuroQol Valuation Technology software and routine quality control measures. Data were modeled using a Tobit model for cTTO data, a mixed logit model for DCE data, and a hybrid model that combined cTTO and DCE data. Model performance was compared on the basis of logical ordering of coefficients, statistical significance, parsimony, and theoretical considerations. RESULTS: Of 1134 respondents, 1062, 1099, and 1102 respondents provided useable cTTO, DCE, and cTTO or DCE responses, respectively, on the basis of quality control criteria and interviewer judgment. Respondent demographic characteristics and health status were similar to the 2015 US Census. The Tobit model was selected as the preferred model to generate the value set. Values ranged from -0.573 (55 555) to 1 (11 111), with 20% of all predicted health states scores less than 0 (ie, worse than dead). CONCLUSIONS: A societal value set for the EQ-5D-5L was developed that can be used for economic evaluations and decision making in US health systems. The internationally established, standardized protocol used to develop this US-based value set was recommended by the EuroQol Group and can facilitate cross-country comparisons.

How work stress influence turnover intention among Chinese local undergraduate university teachers: the mediating effect of job burnout and the moderating effect of self-efficacy.

Background: Turnover intention is one of the common disturbances that affect the career development and management of university teachers. With an aim to solve this thorny issue, the study examined the associations between turnover intention and work stress among local undergraduate university teachers in China. Methods: A questionnaire survey was carried out on 7,565 local university teachers. Initially, confirmatory factor analysis was employed to validate the reliability and validity of the scale. Subsequently, descriptive statistics and correlation analyses were conducted. Following this, a latent moderated structural equation (LMS) was used to explore the relationship among work stress, job burnout, self-efficacy, and turnover intention. Moreover, the bias-corrected Bootstrap method was applied to further examine the mediating effects, moderating effects, and moderated mediating effects in the model. Results: The hypothesized moderated mediation model was verified significant. Work stress directly and positively predicted job burnout and turnover intention, with job burnout serving a partial mediating role between work stress and turnover intention. Additionally, self-efficacy negatively moderated the direct impact of work stress on job burnout, as well as the mediating effect of job burnout. As the self-efficacy of university teachers increased, the direct effect of work stress on job burnout and the mediating effect of job burnout decreased. Conclusion: This study expanded the research on the antecedent variables of university teachers' turnover intention and revealed the individual contingency mechanism by which work stress affected turnover intention: the negative moderating effect of self-efficacy. Work stress induced university teachers' turnover intention, and this phenomenon was more obvious for faculties with low self-efficacy. Administrators of local undergraduate universities need to rationalize the allocation of teachers' job responsibilities and pay attention to the negative consequences of work stress in order to reduce turnover intentions. Particular attention should be paid to enhance teachers' self-efficacy. The findings of this study can provide in-depth recommendations for university faculty management and policy making, which can help shape a working atmosphere more conducive to teaching and research, thus enhancing the overall quality and competitiveness of faculty members within universities.

The economic burden of recurrence in elderly patients with completely resected, stage IIB/IIC or III melanoma: an analysis of the Surveillance, Epidemiology, and End Results-Medicare linked database.

AIMS: To compare healthcare resource utilization (HRU) and costs between patients with or without melanoma recurrence and between patients with distant or locoregional melanoma recurrence. METHODS: Patients aged ≥65 years with completely resected, stage IIB/IIC or III melanoma were identified from Surveillance, Epidemiology, and End Results-Medicare data and stratified based on whether they experienced a recurrence, and whether it was distant or locoregional (separately for each stage). The index date was the date of recurrence (recurrence group) or a randomly assigned date (non-recurrence group). Patients in the recurrence and non-recurrence groups were propensity score-matched 1:1 based on patient characteristics; HRU and healthcare costs were compared between the 2 groups and between patients with distant or locoregional recurrence during the ≤24 months following index. RESULTS: After matching, 507 pairs of patients with recurrent or non-recurrent stage IIB/IIC melanoma (236 patients with distant recurrence, 271 with locoregional) and 141 pairs of patients with recurrent or non-recurrent stage III melanoma (50 patients with distant recurrence, 91 with locoregional) were included. During the first year following recurrence, unadjusted HRU was generally higher in patients with versus without recurrence and patients with distant versus locoregional recurrence among both stage IIB/IIC and III cohorts. Patients who experienced recurrence incurred $6,474 (stage IIB/IIC) or $6,112 (stage III) per patient per month (PPPM) more in unadjusted, all-cause, total healthcare costs than patients without recurrence (both p < 0.001). Patients with distant recurrence incurred $7,292 (stage IIB/IIC) or $5,436 (stage III) PPPM more in unadjusted, all-cause, total healthcare costs than patients with locoregional recurrence (both p < 0.05). LIMITATIONS: Melanoma recurrence was identified using a claims-based algorithm. CONCLUSIONS: Economic burden is higher in patients with versus without melanoma recurrence and patients with distant versus locoregional recurrence. There is a high unmet need for adjuvant therapies that may help to prevent or delay recurrence.

Relationships between survival and real-world recurrence-free survival or distant metastasis-free survival among patients with completely resected stage IIB or IIC melanoma.

Long follow-up time is needed for overall survival (OS) data to mature for early-stage melanoma. This retrospective study aimed to describe the relationships between OS and two intermediate endpoints - real-world recurrence-free survival (rwRFS) and real-world distant metastasis-free survival (rwDMFS) - for patients with stage IIB or IIC melanoma that was completely resected from 1 January 2008 to 31 December 2017, with follow-up to 31 December 2020. We used three different approaches to describe the relationships: estimates of correlation using Kendall τ rank correlation; comparisons of all-cause survival with/without recurrence or distant metastasis using adjusted Cox proportional hazard models; and landmark analyses of all-cause survival stratified by recurrence status at 1-5 years. During a 39-month median follow-up from surgical resection, 223/567 patients (39%) experienced recurrence, among whom 171/567 patients (30%) developed distant metastasis. Median OS from surgical resection was 117.6 months [95% confidence interval (CI), 104.7-not reached], median rwRFS was 49.8 months (95% CI, 39.6-61.0), and median rwDMFS was 70.9 months (95% CI, 58.4-89.1). We observed strong correlations between rwRFS and OS, and between rwDMFS and OS (Kendall τ of 0.73 and 0.82, respectively). Risk of death was significantly greater after recurrence (all-cause survival adjusted hazard ratio [HR], 7.48; 95% CI, 4.55-12.29) or distant metastasis (adjusted HR, 11.00; 95% CI, 6.92-17.49). Risk of death remained significantly elevated with recurrence or distant metastasis by landmark years 1, 3, and 5 after surgical resection. These findings support the use of recurrence/rwRFS and distant metastasis/rwDMFS as surrogate endpoints for OS after complete resection of stage IIB or IIC melanoma.

Quercetin ameliorates bone loss in OVX rats by modulating the intestinal flora-SCFAs-inflammatory signaling axis.

BACKGROUND: Osteoporosis (OP) is a common systemic skeletal disorder characterized by an imbalance in bone homeostasis, involving increased osteoclastic bone formation and decreased osteoblastic bone resorption. Quercetin is a plant polyphenol that has been found to exhibit various biological activities, including antioxidant, anti-inflammatory, and antimicrobial effects. Previous studies have demonstrated its potential to improve postmenopausal OP, although the exact mechanism remains unclear. This study aims to investigate the anti-osteoporotic mechanism of quercetin based on the "intestinal flora - short-chain fatty acids (SCFAs) - inflammatory" signaling axis. METHODS: In this study, we established an ovariectomized (OVX)-induced rat model, quercetin intervention and evaluated the effects on rats following antibiotic (ABX) treatment and fecal microbiota transplantation (FMT). After 6 weeks of intervention, the rats were euthanized, and samples from their femur, tibia, lumbar spine, serum, colon and feces were collected, and bone strength, intestinal flora structure, SCFAs levels and cytokine levels were assessed. RESULTS: Quercetin modulates the intestinal flora by increasing potentially probiotic bacteria (i.e., Lactobacillales, Prevotellaceae, and Blautia) and decreasing potentially pathogenic bacteria (Desulfobacterota, Erysipelotrichales, Romboutsia, and Butyricoccaceae). It also increases SCFAs content and reduces colonic permeability by enhancing tight junction proteins (ZO-1, Occludin). Furthermore, quercetin lowers proinflammatory cytokine levels (LPS, IL-1ß, and TNF-α), which enhances bone strength and prevents OVX-induced bone loss. CONCLUSIONS: Quercetin may effectively reduce bone loss in OVX rats via the "intestinal flora - SCFAs - inflammatory" signaling pathway.

Eye Movement Abnormalities During Different Periods in Patients with Vestibular Migraine.

Purpose: The aim of this study was to assess abnormal eye movement signs during different periods, namely, ictal periods and symptom-free intervals, in patients with vestibular migraine. Patients and Methods: We assessed oculomotor signs using videonystagmography in 90 patients with VM (40 during ictal periods and 50 during symptom-free intervals) according to validated diagnostic criteria. Results: Abnormal saccades, smooth pursuit and optokinetic test results; spontaneous nystagmus; and positional nystagmus were all observed in vestibular migraine patients, and there was no significant difference between different periods. Positional nystagmus was the most common in both the ictal and asymptomatic periods (60% and 36%, respectively). Positional nystagmus was induced in a variety of positions during both periods, and the slow-phase velocity ranged from <2 to 10°/s. The duration of positional nystagmus was over 60s in most cases. Overall, central oculomotor dysfunctions occurred in 27.5% of patients during VM attacks and 4% of patients during symptom-free intervals; this difference was statistically significant (p = 0.002). Conclusion: In patients with VM, abnormal oculomotor signs can be found during both vertigo attacks and asymptomatic intervals. Positional nystagmus is the most common of these abnormalities and can be induced in different positions. The amplitude of these patients' positional nystagmus tends to be low, and the duration tends to be long. Observing changes in eye movements by videonystagmography may be helpful in the diagnosis of VM.

Cost-effectiveness of pembrolizumab as an adjuvant treatment for patients with resected stage IIB or IIC melanoma in Switzerland.

AIM: To assess the cost-effectiveness of adjuvant pembrolizumab versus observation for patients with resected stage IIB/IIC melanoma from a third-party payers' perspective in Switzerland over a lifetime horizon. MATERIALS AND METHODS: A Markov state transition model with four health states (recurrence-free [RF], locoregional recurrence, distant metastases [DM], and death) was developed to determine the cost-effectiveness of pembrolizumab versus observation as an adjuvant treatment in patients with stage IIB/IIC melanoma who have undergone complete resection. The model utilized data from the KEYNOTE-716 randomized controlled trial (ClinicalTrials.gov, NCT03553836). The incremental cost-effectiveness ratio (ICER) (Swiss Franc [CHF] per life year or quality-adjusted life years [QALYs] gained) was calculated. A probabilistic sensitivity analysis and deterministic sensitivity analysis were conducted to assess the robustness of the base case results. RESULTS: Model results demonstrated that pembrolizumab is highly cost-effective as an adjuvant treatment for resected stage IIB/IIC melanoma versus observation in Switzerland. Base case results showed an ICER of CHF 27,424/QALY (EUR 27,342/QALY; exchange rate: 1 CHF = 0.997 EUR) for pembrolizumab versus observation. Results were most sensitive to changes to transition probabilities from the RF state. Most sensitivity and scenario analyses resulted in ICERs below the willingness-to-pay threshold (WTP) of CHF 100,000. At this WTP, pembrolizumab had a 78.9% probability of being cost-effective versus observation. LIMITATIONS: Due to a limited follow-up period in the KEYNOTE-716 trial, data from other clinical trials in the advanced melanoma setting were synthesized in a network meta-analysis and used to inform transition probabilities from DM to death in the cost-effectiveness model, to overcome the absence of these data from the trial. CONCLUSION: The model demonstrated that pembrolizumab is highly cost-effective versus observation in patients with resected stage IIB/IIC melanoma in Switzerland. The ICER was below the WTP threshold of CHF 100,000, commonly used for cost-effectiveness models in Switzerland.

Cost-Effectiveness Analysis of Pembrolizumab as an Adjuvant Treatment of Resected Stage IIB or IIC Melanoma in the United States.

INTRODUCTION: Pembrolizumab was approved in the US as adjuvant treatment of patients with stage IIB or IIC melanoma post-complete resection, based on prolonged recurrence-free survival vs. placebo in the Phase 3 KEYNOTE-716 trial. This study aimed to evaluate the cost-effectiveness of pembrolizumab vs. observation as adjuvant treatment of stage IIB or IIC melanoma from a US health sector perspective. METHODS: A Markov cohort model was constructed to simulate patient transitions among recurrence-free, locoregional recurrence, distant metastasis, and death. Transition probabilities from recurrence-free and locoregional recurrence were estimated via multistate parametric modeling based on patient-level data from an interim analysis (data cutoff date: 04-Jan-2022). Transition probabilities from distant metastasis were based on KEYNOTE-006 data and network meta-analysis. Costs were estimated in 2022 US dollars. Utilities were based on applying US value set to EQ-5D-5L data collected in trial and literature. RESULTS: Compared to observation, pembrolizumab increased total costs by $80,423 and provided gains of 1.17 quality-adjusted life years (QALYs) and 1.24 life years (LYs) over lifetime, resulting in incremental cost-effectiveness ratios of $68,736/QALY and $65,059/LY. The higher upfront costs of adjuvant treatment were largely offset by reductions in costs of subsequent treatment, downstream disease management, and terminal care, reflecting the lower risk of recurrence with pembrolizumab. Results were robust in one-way sensitivity and scenario analyses. At a $150,000/QALY threshold, pembrolizumab was cost-effective vs. observation in 73.9% of probabilistic simulations that considered parameter uncertainty. CONCLUSION: As an adjuvant treatment of stage IIB or IIC melanoma, pembrolizumab was estimated to reduce recurrence, extend patients' life and QALYs, and be cost-effective versus observation at a US willingness-to-pay threshold.

Comparison of Preferences and Data Quality between Discrete Choice Experiments Conducted in Online and Face-to-Face Respondents.

INTRODUCTION: Discrete choice experiments (DCE) are increasingly being conducted using online panels. However, the comparability of such DCE-based preferences to traditional modes of data collection (e.g., in-person) is not well established. In this study, supervised, face-to-face DCE was compared with its unsupervised, online facsimile on face validity, respondent behavior, and modeled preferences. METHODS: Data from face-to-face and online EQ-5D-5L health state valuation studies were compared, in which each used the same experimental design and quota sampling procedure. Respondents completed 7 binary DCE tasks comparing 2 EQ-5D-5L health states presented side by side (health states A and B). Data face validity was assessed by comparing preference patterns as a function of the severity difference between 2 health states within a task. The prevalence of potentially suspicious choice patterns (i.e., all As, all Bs, and alternating As/Bs) was compared between studies. Preference data were modeled using multinomial logit regression and compared based on dimensional contribution to overall scale and importance ranking of dimension-levels. RESULTS: One thousand five Online respondents and 1,099 face-to-face screened (F2FS) respondents were included in the main comparison of DCE tasks. Online respondents reported more problems on all EQ-5D dimensions except for Mobility. The face validity of the data was similar between comparators. Online respondents had a greater prevalence of potentially suspicious DCE choice patterns ([Online]: 5.3% [F2FS] 2.9%, P = 0.005). When modeled, the relative contribution of each EQ-5D dimension differed between modes of administration. Online respondents weighed Mobility more importantly and Anxiety/Depression less importantly. DISCUSSION: Although assessments of face validity were similar between Online and F2FS, modeled preferences differed. Future analyses are needed to clarify whether differences are attributable to preference or data quality variation between modes of data collection.

Low-Cost Fabrication of Efficient Perovskite Photovoltaics Using Low-Purity Lead Iodide via Powder Engineering.

Low cost is the eternal theme for any commercial production. Numerous efforts have been explored to realize low-cost, high-efficiency perovskite solar cells (PSCs), such as replacing the traditional spin-coating method with an economical printing strategy, simplifying the device structure, reducing the number of functional layers, etc. However, there are few reports on the use of low-cost precursors. Herein, we enable the low-cost fabrication of efficient PSCs based on a very cheaper low-purity PbI2 via powder engineering. The low-purity PbI2 is blended with formamidinium iodide followed by dissolving in a 2-methoxyethanol solvent, and then, the high-quality FAPbI3 powders are formed via an inverse temperature crystallization process and solvent washing after several simple processes to reduce the impurities. As a result, the devices fabricated using the as-synthesized black powders based on the low-purity PbI2 exhibit a champion power conversion efficiency (PCE) of 23.9% and retained ∼95% of the initial PCE after ∼400 h of storage in the conditions of 25 ± 5 °C and 25 ± 5 RH% without encapsulation. In addition, the upscaling fabrication of a 5 cm × 5 cm solar minimodule also demonstrates an impressive efficiency of 19.5%. Our findings demonstrate an economic strategy for the commercialization of PSCs from the perspective of low-cost production.