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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Patients with type 2 diabetes mellitus (T2DM) are clinically heterogeneous in terms of disease severity, treatment, and comorbidities, potentially resulting in differential diabetic nephropathy (DN) progression courses. In this exploratory study we used latent class analysis (LCA) to identify patient groups with distinct clinical profiles of T2DM severity and explored the association between disease severity, DN progression or reversal, and healthcare resource use (HRU) and costs.Methods: Latent class analysis was used to group adults with ≥  2 medical claims with a diagnosis of T2DM and ≥ 2 urine albumin tests within the Truven MarketScan database (2004-2014), based on T2DM-related complications, comorbidities, and therapies. DN severity categories (normoalbuminuria, moderately increased albuminuria, and severely increased albuminuria) were determined based on urine albumin measure. The risks of DN progression and reversal (change to a more/less severe DN category) were compared among all identified latent classes using Kaplan-Meier analyses and log-rank tests. All-cause and DN-related costs and HRU were assessed and compared during the study period among the identified latent classes.Results: Four clinically distinct profiles were identified among the 23,235 eligible patients: low comorbidity/low treatment (46.5%), low comorbidity/high treatment (29.0%), moderate comorbidity/high insulin use (9.7%), and high comorbidity/moderate treatment (14.8%). The 5-year DN progression rates for these clinically distinct profiles were 11.8, 18, 16.5, and 27.7%, respectively. Compared with the low comorbidity/low treatment group, all other groups were associated with an increased risk of DN progression (all p < 0.001). Increasing comorbidity was significantly associated with higher all-cause and DN-related HRU and costs, primarily driven by higher pharmacy and inpatient costs.Conclusion: Patients with T2DM who have more comorbidities experienced higher rates of DN progression and HRU and incurred higher healthcare costs compared with patients with low comorbidity profiles. Future prospective studies are needed to confirm the significance of these groups on DN progression, HRU, and costs.Funding: Takeda Development Center Americas, Inc. [ABSTRACT FROM AUTHOR]

Objective: Heroin use in the United States has reached epidemic proportions. The objective of this paper is to estimate the annual societal cost of heroin use disorder in the United States in 2015 US dollars. Methods: An analytic model was created that included incarceration and crime; treatment for heroin use disorder; chronic infectious diseases (HIV, Hepatitis B, Hepatitis C, and Tuberculosis) and their treatments; treatment of neonatal abstinence syndrome; lost productivity; and death by heroin overdose. Results: Using literature-based estimates to populate the model, the cost of heroin use disorder was estimated to be $51.2 billion in 2015 US dollars ($50,799 per heroin user). One-way sensitivity analyses showed that overall cost estimates were sensitive to the number of heroin users, cost of HCV treatment, and cost of incarcerating heroin users. Conclusion: The annual cost of heroin use disorder to society in the United States emphasizes the need for sustained investment in healthcare and non-healthcare related strategies that reduce the likelihood of abuse and provide care and support for users to overcome the disorder. [ABSTRACT FROM AUTHOR]

Background and aims Given the recognized links between atherosclerosis and cognitive impairment, the aim of this study was to examine the association between the ankle-brachial index (ABI) and cognitive impairment in a cross-sectional setting of a Chinese population. Methods Participants (n = 3,048, aged ≥40 years, 1727 men and 1321 women) were recruited from the ongoing community-based Asymptomatic Polyvascular Abnormalities Community Study. ABI was measured and a low ABI was defined as <0.9. Cognition status was evaluated via the Mini-Mental Status Exam. Multivariate logistic regression models and linear regression models were used to assess the association between ABI and cognitive impairment. Results A low ABI was associated with cognitive impairment (odds ratio, OR = 1.983; 95% confidence interval, CI: 1.150–3.419), independent of the potential confounders. In addition, a decreasing ABI (per standard deviation) was significantly associated with cognitive impairment in fully adjusted models (OR = 1.156; CI: 1.013–1.319) and with a significant trend of decreasing MMSE scores (β = 0.703, 95% CI 0.189–1.218, p = 0.0074). Furthermore, the odds of a low ABI associated with cognitive impairment in participants without hypertension and participants with diabetes were 4.924 (CI: 1.860–13.035) and 6.393 (CI: 2.431–16.810), respectively. Conclusions A low ABI is associated with cognitive impairment, especially in non-hypertensive and diabetic patients. [ABSTRACT FROM AUTHOR]

Purpose The objective of this study was to compare the health-related quality of life (HRQL) burden across different types of advanced cancer with the use of 2 widely used patient-reported outcome measures, the generic EQ-5D and the cancer-specific Functional Assessment of Cancer Therapy-General (FACT-G). Methods Patients with advanced cancer of the bladder, brain, breast, colon/rectum, head/neck, hepatobiliary tract/pancreas, kidney, lung, lymphoma, ovary, or prostate completed the EQ-5D and FACT-G. HRQL domains and summary scores were compared across types of cancer, using regression models to adjust for age and sex. Findings Approximately 50 patients with each type of cancer were recruited (total, 534 patients). According to EQ-5D dimensions, the highest proportion of problems was associated with prostate (mobility); prostate and kidney (self-care); head/neck, bladder, and lung (usual activities); breast, head/neck, and lung (pain/discomfort); and lymphoma and lung (anxiety/depression) cancers. EQ-5D visual analogue scale scores were lowest for breast and head/neck cancers; US index-based scores were lowest for breast and lung cancers and highest for brain cancer. For the FACT-G, physical well-being scores were lowest for head/neck, hepatobiliary, and kidney cancers; emotional well-being scores were lowest for hepatobiliary cancer, and functional well-being scores were lowest for head/neck, hepatobiliary, and bladder cancers. Implications The overall and dimension-specific HRQL burden of advanced cancer depended on the type of cancer. Such results may aid clinicians and patients in better understanding of how cancer site can affect HRQL and functioning in different ways. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Converting PbI2 residues into low‐dimensional perovskites through post‐treatment with ammonium‐based large cations can passivate 3D perovskites, thus has emerged as an effective strategy to improve the performance of perovskite solar cells (PSCs). Herein, a dramatically improved efficiency is demonstrated for PSCs based on a two‐step‐processed FAPbI3 perovskite via post‐treatment with formamidinium (FA)‐based benzamidine hydrochloride (PFACl), outperforming the commonly used methylamine (MA)‐based benzylamine hydrochloride (PMACl). With an in‐depth exploration of the crystal structures and morphology changes of the FAPbI3 perovskite upon the PFACl post‐treatment, the preferential formation of 1D rather than 2D structures on the 3D perovskite film is identified. In contrast to the 2D counterpart, the more energetically favorable 1D structure enables a more effective elimination of PbI2 residues. As a consequence, the PFACl‐induced 1D/3D perovskite film is endowed with smoother morphology, more uniform surface potential distribution, lower trap density, faster charge transfer, and better film stability than the PMACl‐induced 2D/3D perovskite and control films, demonstrating champion efficiencies of 24.9% for a small‐size PSC, 23.6% for a 1 cm2 large‐size PSC, and 21.2% for a 5 × 5 cm2 mini‐module, which is the highest among the perovskite solar mini‐modules using the two‐step deposition method. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: Brain metastases are common with severe consequences in patients with melanoma. We conducted a systematic literature review to evaluate the proportion of melanoma patients diagnosed with brain metastases and to summarize risk factors of melanoma brain metastases. These results may contribute to our understanding of the risk and associated factors of brain metastases in melanoma patients. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

[Display omitted] • Quercetin ameliorates osteoporosis by modulating intestinal flora in OVX rats. • The anti-osteoporotic effect of quercetin disappears after the depletion of gut flora by antibiotics. • Transplantation of quercetin-modulated intestinal flora also exerts anti-osteoporotic effects. • Quercetin improves colonic barrier and fecal SCFAs. • Quercetin ameliorates OVX-induced inflammatory response. 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. 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. 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-1β, and TNF-α), which enhances bone strength and prevents OVX-induced bone loss. Quercetin may effectively reduce bone loss in OVX rats via the "intestinal flora − SCFAs − inflammatory" signaling pathway. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: Knowledge on the real-world outcomes of patients with advanced melanoma and the value of different endpoints for evaluating survival benefits is limited. We investigated the outcomes and different surrogate endpoints for overall survival (OS) in 664 pembrolizumab-treated patients with advanced melanoma in Germany. Our findings support the effectiveness of pembrolizumab in real-world clinical practice. The real-world time to next treatment was most strongly correlated with OS, suggesting it as a valuable surrogate endpoint to assess treatment effectiveness. Real-world studies assessing time to next treatment could support clinical and payer decision making. 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. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic nephropathy (DN) is a progressive kidney disease resulting as a complication of diabetes mellitus. This study evaluated the disease progression and economic burden of DN among commercially insured patients with type 2 diabetes in the USA. Methods: The research design was a retrospective observational study based on healthcare claims data. The Truven MarketScan Databases (2004-2014) were queried for adults with type 2 diabetes with at least one urine albumin test (index, randomly selected) after diagnosis and at least one test after the index. On the basis of the index test, patients were classified into normoalbuminuria, microalbuminuria, or macroalbuminuria groups. Nephropathy-related treatment use was measured in the 6 months after the index, disease progression was assessed from the index to the end of data availability, and annual all-cause and nephropathy-related costs and healthcare resource use (HRU) were assessed up to 2 years from the index. Outcomes were compared between any two groups, controlling for baseline demographics. Results: A total of 23,235 patients were identified and classified into normoalbuminuria ( N = 18,409), microalbuminuria ( N = 3863), or macroalbuminuria ( N = 963) groups. Patients with albuminuria were more likely to be older, male, and have a higher burden of baseline comorbidities and HRU. Within 6 months following the index, 12-20% of patients with albuminuria were not treated with any relevant recommended treatment. Compared to the normoalbuminuria group, patients with macroalbuminuria had a significantly greater risk of disease progression (hazard ratio [HR] = 1.44), and both albuminuria groups were more likely to require dialysis (HR = 4.23 and 40.14 for micro- and macroalbuminuria, respectively; all p < 0.05). Annual all-cause (2016 US dollars, $3580 and $12,830 higher for micro- and macroalbuminuria vs. normoalbuminuria, respectively) and nephropathy-related ($362 and $3716) costs increased significantly with increasing nephropathy severity, consistent with the trend in increased HRU. Conclusions: Diabetic nephropathy may be undertreated or inappropriately treated. It was also associated with significantly higher costs, HRU, and risk of disease progression among commercially insured patients with type 2 diabetes in the USA. Funding: Takeda Development Center Americas, Inc. [ABSTRACT FROM AUTHOR]

The relationship between atherosclerosis and cognitive function is less well studied in Chinese populations. In addition, the results among middle-aged adults have been mixed. We aimed to investigate the association of atherosclerosis measured by carotid intima-media thickness (CIMT) and cognitive function in middle-aged and older adults from a Chinese community. Participants in the Asymptomatic Polyvascular Abnormalities in Community study (APAC) who had completed the CIMT detection and cognitive function measurements in 2012/2013 were included. Cognitive function was measured using the Mini-Mental State Examination (MMSE). Multivariate linear regression analysis was used to analyze the association between CIMT and MMSE. Then, a stratified analysis was performed separately in middle-aged and older adults. A total of 3227 participants were included in this study (mean age 57.9 years, range 43-93 years); 56.6 % of them were men, 66.0 % were middle-aged adults. After adjusting for potential confounders, larger CIMT was associated with lower MMSE scores, with a 0.75-point decrease in MMSE score for every 1-mm increase in CIMT ( β = − 0.75, P = 0.0020). The association remained statistically significant in middle-aged adults ( β = − 0.57, P = 0.0390), and was stronger in older adults and adults with low education levels. There is a significant association between CIMT and cognitive function among middle-aged and older adults sampled from a Chinese population. This association was stronger in older adults and adults with low education levels. [ABSTRACT FROM AUTHOR]

Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Correction to: Lower low-density lipoprotein cholesterol levels are associated with an increased risk of hematoma expansion and ensuing mortality in acute ICH patients B Correction to: Neurological Sciences (2022) b https://doi.org/10.1007/s10072-021-05742-w Affiliation 1 should be revised to: "China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China". [Extracted from the article]