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.

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.

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.

Cost-Effectiveness of Pembrolizumab as an Adjuvant Treatment in Colombia for Melanoma Patients with Lymph Node Involvement After Complete Resection.

INTRODUCTION: The KEYNOTE-054 trial found that adjuvant treatment with pembrolizumab improved recurrence-free survival versus placebo in completely resected high-risk stage III melanoma patients. We assessed the cost-effectiveness of adjuvant pembrolizumab in Colombia compared with watchful waiting, a widely used strategy despite the high risk of recurrence with surgery alone. METHODS: A four-health state [recurrence-free (RF), locoregional recurrence (LR), distant metastases (DM), and death) Markov model was developed to assess the lifetime medical costs and outcomes (3% annual discount), along with cost-effectiveness ratios (ICERs). The transitions from the RF and LR states were modeled using KEYNOTE-054 data, and those from the DM state were modeled using data from the KEYNOTE-006 trial and a network meta-analysis of advanced treatments received after adjuvant pembrolizumab and watchful waiting. The health state utilities were derived from KEYNOTE-054 Euro-QoL data and literature. Costs are expressed in 2021 Colombian pesos (COP). RESULTS: Over a 46-year time horizon, patients on adjuvant pembrolizumab and watchful waiting were estimated to gain 9.69 and 7.56 quality-adjusted life-years (QALYs), 10.83 and 8.65 life-years (LYs), and incur costs of COP 663,595,726 and COP 563,237,206, respectively. The proportion of LYs spent in RF state was 84.63% for pembrolizumab and 72.13% for watchful waiting, yielding lower subsequent treatment, disease management, and terminal care costs for pembrolizumab. Adjuvant pembrolizumab improved survival by 2.18 LYs and 2.13 QALYs versus watchful waiting. The ICER per QALY was COP 47,081,917, primarily driven by recurrence rates and advanced melanoma treatments. The deterministic sensitivity analysis results were robust and consistent across various reasonable inputs and alternative scenarios. At a willingness-to-pay threshold of COP 69,150,201 per QALY, the probability of pembrolizumab being cost-effective was 65.70%. CONCLUSION: Pembrolizumab is cost-effective as an adjuvant treatment compared to watchful waiting among patients with high-risk stage III melanoma after complete resection in Colombia.

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.

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.

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.

Systematic literature review and meta-analysis of clinical outcomes and prognostic factors for melanoma brain metastases.

Background: More than 60% of all stage IV melanoma patients develop brain metastases, while melanoma brain metastases (MBM) is historically difficult to treat with poor prognosis. Objectives: To summarize clinical outcomes and prognostic factors in MBM patients. Methods: A systematic review with meta-analysis was conducted, and a literature search for relevant studies was performed on November 1, 2020. Weighted average of median overall survival (OS) was calculated by treatments. The random-effects model in conducting meta-analyses was applied. Results: A total of 41 observational studies and 12 clinical trials with our clinical outcomes of interest, and 31 observational studies addressing prognostic factors were selected. The most common treatments for MBM were immunotherapy (IO), MAP kinase inhibitor (MAPKi), stereotactic radiosurgery (SRS), SRS+MAPKi, and SRS+IO, with median OS from treatment start of 7.2, 8.6, 7.3, 7.3, and 14.1 months, respectively. Improved OS was observed for IO and SRS with the addition of IO and/or MAPKi, compared to no IO and SRS alone, respectively. Several prognostic factors were found to be significantly associated with OS in MBM. Conclusion: This study summarizes pertinent information regarding clinical outcomes and the association between patient characteristics and MBM prognosis.

Burden and Risk Factors of Brain Metastases in Melanoma: A Systematic Literature Review.

Melanoma can frequently metastasize to the brain with severe consequences. However, variation of melanoma brain metastases (MBM) development among populations is not well studied, and underlying mechanisms and risk factors for MBM development are not consistently documented. We conducted a systematic literature review (SLR) including a total of 39 articles to evaluate the proportion of melanoma patients who are diagnosed with, or develop, brain metastases, and summarize the risk factors of MBM. The average proportion of MBM was calculated and weighted by the sample size of each study. Meta-analyses were conducted for the selected risk factors using a random-effects model. The proportion of MBM at diagnosis was 33% (975 with MBM out of 2948 patients) among patients with cutaneous melanoma (excluding acral) and 23% (651/2875) among patients with cutaneous mixed with other types of melanoma. The proportion at diagnosis was lower among populations with mucosal (9/96, 9%) or uveal (4/184, 2%) melanoma and among populations outside the United States and Europe. Meta-analysis demonstrated that male vs. female gender and left-sided tumors vs. right-sided were significantly associated with increased risk of melanoma brain metastases. These data may help clinicians to assess an individual patient's risk of developing melanoma brain metastases.

Association between non-HDLC and 1-year prognosis in patients with spontaneous intracerebral haemorrhage: a prospective cohort study from 13 hospitals in Beijing.

OBJECTIVES: Previous studies suggested an inverse association between lipoprotein cholesterols and bleeding risk, while limited data were available about the predictive value of lipoproteins on intracerebral haemorrhage (ICH). Our recent research series showed that higher non-high-density lipoprotein cholesterol (non-HDLC) was an independent predictor of favourable 3-month outcome in ICH patients, we thus aimed to further investigate the association between non-HDLC levels and 1-year functional outcomes after ICH. DESIGN: Prospective multicentre cohort study. SETTING: 13 hospitals in Beijing, China. PARTICIPANTS: A total of 666 ICH patients were included between December 2014 and September 2016. METHODS: Non-HDLC was calculated by subtracting HDL-C from total cholesterol. Patients were then grouped by non-HDLC levels into three categories: <3.4 mmol/L, 3.4-4.2 mmol/L and ≥4.2 mmol/L. Both the univariate and multivariate logistic regressions were used to assess the association between non-HDLC levels and 1-year unfavourable functional outcomes (modified Rankin Scale ≥3) in ICH patients. Moreover, sensitivity analysis was performed in ICH patients without statin use after admission. RESULTS: There were 33.5% (223/666) ICH patients identified with unfavourable functional outcomes at 1-year follow-up. In the univariate analysis, patients who achieved non-HDLC levels above 4.2 mmol/L had a 49% decreased risk of 1-year poor prognosis (OR 0.51, 95% CI 0.33 to 0.81). However, non-HDLC did not retain its independent prognostic value in multivariate analysis, the fully adjusted OR values were 1.00 (reference), 1.06 (0.63, 1.79) and 0.83 (0.45, 1.54) from the lowest to the highest non-HDLC group. Moreover, statin use after ICH onset made no difference to the long-term prognosis. CONCLUSIONS: Non-HDLC was not an independent predictor for 1-year functional outcome in ICH patients, irrespective of poststroke statin use. The predictive value of well-recognised confounding factors was more dominant than non-HDLC on long-term prognosis.

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.

A novel risk score to predict deep vein thrombosis after spontaneous intracerebral hemorrhage.

Background and purpose: Studies showed that patients with hemorrhagic stroke are at a higher risk of developing deep vein thrombosis (DVT) than those with ischemic stroke. We aimed to develop a risk score (intracerebral hemorrhage-associated deep vein thrombosis score, ICH-DVT) for predicting in-hospital DVT after ICH. Methods: The ICH-DVT was developed based on the Beijing Registration of Intracerebral Hemorrhage, in which eligible patients were randomly divided into derivation (60%) and internal validation cohorts (40%). External validation was performed using the iMCAS study (In-hospital Medical Complication after Acute Stroke). Independent predictors of in-hospital DVT after ICH were obtained using multivariable logistic regression, and ß-coefficients were used to generate a scoring system of the ICH-DVT. The area under the receiver operating characteristic curve (AUROC) and the Hosmer-Lemeshow goodness-of-fit test were used to assess model discrimination and calibration, respectively. Results: The overall in-hospital DVT after ICH was 6.3%, 6.0%, and 5.7% in the derivation (n = 1,309), internal validation (n = 655), and external validation (n = 314) cohorts, respectively. A 31-point ICH-DVT was developed from the set of independent predictors including age, hematoma volume, subarachnoid extension, pneumonia, gastrointestinal bleeding, and length of hospitalization. The ICH-DVT showed good discrimination (AUROC) in the derivation (0.81; 95%CI = 0.79-0.83), internal validation (0.83, 95%CI = 0.80-0.86), and external validation (0.88; 95%CI = 0.84-0.92) cohorts. The ICH-DVT was well calibrated (Hosmer-Lemeshow test) in the derivation (P = 0.53), internal validation (P = 0.38), and external validation (P = 0.06) cohorts. Conclusion: The ICH-DVT is a valid grading scale for predicting in-hospital DVT after ICH. Further studies on the effect of the ICH-DVT on clinical outcomes after ICH are warranted.

Adjuvant pembrolizumab versus placebo in resected high-risk stage II melanoma: Health-related quality of life from the randomized phase 3 KEYNOTE-716 study.

BACKGROUND: Adjuvant pembrolizumab significantly improved recurrence-free survival (RFS) versus placebo in resected stage IIB and IIC melanoma in the phase 3 KEYNOTE-716 study. Health-related quality of life (HRQoL) results are reported. METHODS: Patients were randomly assigned 1:1 to pembrolizumab 200 mg (2 mg/kg, patients ≥12 to <18 years) Q3W or placebo for ≤17 cycles or until disease recurrence, unacceptable toxicity, or withdrawal. Change from baseline in EORTC QLQ-C30 global health status (GHS)/quality of life (QoL) was a prespecified exploratory end point. Change in EORTC QLQ-C30 functioning, symptom, and single-item scales, and EQ-5D-5L visual analog scale (VAS) were also summarized. Primary analyses were performed at week 48 to ensure adequate completion/compliance. The HRQoL population comprised patients who received ≥1 dose of treatment and completed ≥1 assessment. RESULTS: The HRQoL population included 969 patients (pembrolizumab, n = 483; placebo, n = 486). Compliance at week 48 was ≥80% for both instruments. EORTC QLQ-C30 GHS/QoL, physical functioning, role functioning, and EQ-5D-5L VAS scores were stable from baseline to week 48 in both arms, with no clinically meaningful decline observed. Scores did not differ significantly between pembrolizumab and placebo. EORTC QLQ-C30 GHS/QoL, physical functioning, role functioning, and EQ-5D-5L VAS scores remained stable through week 96 in both arms. CONCLUSIONS: HRQoL was stable with adjuvant pembrolizumab, with no clinically meaningful decline observed. Change from baseline in HRQoL was similar between arms. These results, in conjunction with the improved RFS and manageable safety previously reported, support the use of adjuvant pembrolizumab for high-risk stage II melanoma.

Liver Fibrosis is Associated with Clinical Outcomes in Patients with Intracerebral Hemorrhage.

Background: Recent studies have reported the predictive value of liver fibrosis indices for hematoma enlargement in patients with intracerebral hemorrhage (ICH). However, little is known about the precise association between fibrosis and ICH prognosis. Thus, our study was designed to investigate the relevance of liver fibrosis, as evaluated by fibrosis-4 (FIB-4) score and poor outcomes after ICH. Methods: We used data from a prospective, multi-center and registry-based database. In this study, patients were stratified by the higher cut-off value of a FIB-4 score ≥2.67. The two groups of patients were then compared with regard to baseline characteristics, ICH severity and follow-up outcomes. We performed univariable and multivariable logistic regression analysis to determine the prognostic value of a FIB-4 score ≥2.67 for major disability or death. Kaplan-Meier survival curves were used to analyze the association between different FIB-4 scores and survival rate. Results: Our present study included 839 patients from 13 hospitals in Beijing. Participants with FIB-4 scores ≥2.67 had a larger baseline hematoma volume and a higher score on the modified Rankin Scale at follow-up (all p values <0.05). In the logistic regression analysis, liver fibrosis defined by a FIB-4 score ≥2.67 was independently associated with poor clinical outcomes at discharge and at 1 year (at discharge: adjusted odds ratio [95% CI] = 1.894 [1.120-3.202], p = 0.0172; at 1 year: adjusted odds ratio [95% CI] = 1.694 [1.021-2.809], p = 0.0412). However, this association was not observed at 3 months. During the follow-up period, patients with a FIB-4 score ≥2.67 also had a significantly lower survival rate according to Kaplan-Meier survival analysis. Conclusion: Our study suggests that liver fibrosis defined by a FIB-4 score ≥2.67 is associated with poor clinical outcomes and lower survival rates in patients with mild to moderate ICH. These data provide reliable evidence for detecting fibrosis and managing related risk factors to improve prognosis after 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.

Comparison of clinical scores for predicting stroke-associated pneumonia after intracerebral hemorrhage (ICH): potential tools for personalized care and clinical trials for ICH.

Background: This study aimed to systematically compare the discrimination and calibration of 5 clinical scores for stroke-associated pneumonia (SAP) after intracerebral hemorrhage (ICH). Methods: We derived a validation cohort from the Beijing Registration of Intracerebral Hemorrhage. SAP was then diagnosed according to the Center for Disease Control and Prevention's criteria for hospital-acquired pneumonia. The area under the receiver operating characteristic curve (AUROC) and Hosmer-Lemeshow goodness-of-fit test were used to assess model discrimination and calibration. Results: A total of 1964 patients were enrolled in the study. The mean age was 56.8±14.4 years, and 67.6% were male. The median National Institutes of Health Stroke Scale (NIHSS) score at admission was 11 [interquartile range (IQR), 3-21], while the median length of stay (LOS) was 16 days (IQR, 8-22 days). A total of 575 (29.2%) patients were diagnosed with in-hospital SAP after ICH. The AUROC of the 5 clinical scores ranged from 0.732 to 0.800. In comparing these scores, we found that the ICH-associated pneumonia score-B (ICH-APS-B 0.800; 95% CI: 0.780-0.820; P<0.001) showed a statistically better discrimination than did the other risk models (all P<0.001). Furthermore, all clinical scores performed better in patients with an LOS >72 h. The ICH-APS-B (0.827; 95% CI: 0.806-0.848; P<0.001) still showed statistically better discrimination than did the other risk models in patients with an LOS longer than 72 hours. The Hosmer-Lemeshow test also revealed that the ICH-APS-B. had the largest Cox and Snell R2 result for in-hospital SAP after ICH. Conclusions: Among the 5 models for predicting SAP after ICH, the ICH-APS-B showed the best predictive performance, suggests it may be a useful tool for implementing the personalized care of patients and conducting clinical trials of SAP after ICH.

Current Treatment Approaches and Global Consensus Guidelines for Brain Metastases in Melanoma.

Background: Up to 60% of melanoma patients develop melanoma brain metastases (MBM), which traditionally have a poor diagnosis. Current treatment strategies include immunotherapies (IO), targeted therapies (TT), and stereotactic radiosurgery (SRS), but there is considerable heterogeneity across worldwide consensus guidelines. Objective: To summarize current treatments and compare worldwide guidelines for the treatment of MBM. Methods: Review of global consensus treatment guidelines for MBM patients. Results: Substantial evidence supported that concurrent IO or TT plus SRS improves progression-free survival (PFS) and overall survival (OS). Guidelines are inconsistent with regards to recommendations for surgical resection of MBM, since surgical resection of symptomatic lesions alleviates neurological symptoms but does not improve OS. Whole-brain radiation therapy is not recommended by all guidelines due to negative effects on neurocognition but can be offered in rare palliative scenarios. Conclusion: Worldwide consensus guidelines consistently recommend up-front combination IO or TT with or without SRS for the treatment of MBM.

Real-World Therapy with Pembrolizumab: Outcomes and Surrogate Endpoints for Predicting Survival in Advanced Melanoma Patients in Germany.

Knowledge on the real-world characteristics and outcomes of pembrolizumab-treated advanced melanoma patients in Germany and on the value of different real-world endpoints as surrogates for overall survival (OS) is limited. A sample of 664 pembrolizumab-treated patients with advanced melanoma from the German registry ADOReg was used. We examined OS, real-world progression-free survival (rwPFS), real-world time to next treatment (rwTtNT), and real-world time on treatment (rwToT). Spearman's rank and iterative multiple imputation (IMI)-based correlation coefficients were computed between the OS and the rwPFS, rwTtNT, and rwToT and reported for the first line of therapy and the overall sample. The median OS was 30.5 (95%CI 25.0-35.4) months, the rwPFS was 3.9 months (95%CI 3.5-4.9), the rwTtNT was 10.7 months (95%CI 9.0-12.9), and the rwToT was 6.2 months (95%CI 5.1-6.8). The rwTtNT showed the highest correlation with the OS based on the IMI (rIMI = 0.83), Spearman rank correlations (rs = 0.74), followed by the rwToT (rIMI = 0.74 and rs = 0.65) and rwPFS (rIMI = 0.69 and rs = 0.56). The estimates for the outcomes and correlations were similar for the overall sample and those in first-line therapy. The median OS was higher compared to recent real-world studies, supporting the effectiveness of pembrolizumab in regular clinical practice. The rwTtNT may be a valuable OS surrogate, considering the highest correlation was observed with the OS among the investigated real-world endpoints.