Estimating individualized treatment rules by optimizing the adjusted probability of a longer survival.

Individualized treatment rules inform tailored treatment decisions based on the patient's information, where the goal is to optimize clinical benefit for the population. When the clinical outcome of interest is survival time, most of current approaches typically aim to maximize the expected time of survival. We propose a new criterion for constructing Individualized treatment rules that optimize the clinical benefit with survival outcomes, termed as the adjusted probability of a longer survival. This objective captures the likelihood of living longer with being on treatment, compared to the alternative, which provides an alternative and often straightforward interpretation to communicate with clinicians and patients. We view it as an alternative to the survival analysis standard of the hazard ratio and the increasingly used restricted mean survival time. We develop a new method to construct the optimal Individualized treatment rule by maximizing a nonparametric estimator of the adjusted probability of a longer survival for a decision rule. Simulation studies demonstrate the reliability of the proposed method across a range of different scenarios. We further perform data analysis using data collected from a randomized Phase III clinical trial (SWOG S0819).

Gender differences in symptom burden among people living with HIV/AIDS receiving antiretroviral therapy in Yunnan, China.

ABSTRACTLittle is known about gender differences in the symptom burden of people living with HIV/AIDS (PLWHA) on antiretroviral therapy in China. This study was conducted based on a biopsychosocial-medical model to describe gender differences in symptom burden among 1035 PLWHA in Yunnan Province, China. After propensity score matching, 798 PLWHA were included in this analysis. Feeling stressed, poor sleep, and memory loss were the most burdensome symptoms among men, while feeling stressed, memory loss, and dizziness were the most burdensome symptoms among women. Among men PLWHA, factors associated with symptom burden were being of the ethnic minority, CD4 count ≥ 500 cells/mm3, physical functioning, and social support. Among women PLWHA, factors associated with symptom burden were being an inpatient, physical functioning, psychological functioning, and social support. Our findings suggest that healthcare providers need to take into account gender differences when developing optimal prevention, treatment, and care programs that provide individualized care to reduce patients' symptom burden.

Measuring care-related regret intensity: Reliability and validation of a 10-item scale among Chinese nursing interns.

AIM: The 10-item care-related regret intensity scale (RIS-10) assesses the experience and intensity of care-related regrets. The aim of this study was to validate a Chinese version of the RIS and examine its reliability and validity when applied to Chinese nursing interns. BACKGROUND: Nursing students, the future healthcare workforce, often face clinical errors and adverse events due to limited knowledge and experience. Assessing care-related regret during their internships is crucial for their development. METHODS: Through a process involving translation, back-translation and cross-cultural adaptation, a Chinese version of the RIS-10 was developed. A convenience sampling method was employed to survey 529 nursing interns to validate the reliability and validity of the scale. RESULTS: The Chinese version of the scale, consisting of 10 items, demonstrated a single dimension, explaining 66.77% of the total variance according to exploratory factor analysis. Content validity for the 10 items ranged from 0.800 to 1.000, with a scale-level content validity of 0.980. Confirmatory factor analysis indicated a well-fitting model (CFI = 0.968, GFI = 0.921, NFI = 0.952, IFI = 0.969, TLI = 0.957, RMSEA = 0.088). Convergent validity was supported by an Average Variance Extracted of 0.636 and a Composite Reliability of 0.946. The scale also exhibited strong reliability with a Cronbach's α coefficient of 0.945, a split-half reliability coefficient of 0.903 and a test-retest reliability of 0.901. CONCLUSIONS: This comprehensive translation and validation process confirms the suitability of the Chinese version of the RIS-10 for use among Chinese nursing interns.

Restricted survival benefit with right-censored data.

The hazard ratio is widely used to quantify treatment effects. However, it may be difficult to interpret for patients and practitioners, especially when the hazard ratio is not constant over time. Alternative measures of the treatment effects have been proposed such as the difference of the restricted mean survival times, the difference in survival proportions at some fixed follow-up time, or the net chance of a longer survival. In this paper, we propose the restricted survival benefit (RSB), a quantity that can incorporate multiple useful measurements of treatment effects. Hence, it provides a framework for a comprehensive assessment of the treatment effects. We provide estimation and inference procedures for the RSB that accommodate censored survival outcomes, using methods of the inverse-probability-censoring-weighted U$U$ -statistic and the jackknife empirical likelihood. We conduct extensive simulation studies to examine the numerical performance of the proposed method, and we analyze data from a randomized Phase III clinical trial (SWOG S0777) using the proposed method.

[Spatiotemporal variability characteristics and driving forces of land use in the Pan-Pearl River Basin, China]. / æ³›ç æ±ŸæµåŸŸåœŸåœ°åˆ©ç”¨æ—¶ç©ºå˜åŒ–ç‰¹å¾åŠé©±åŠ¨å› å­.

The Pan-Pearl River Basin is a bridgehead for China's reform and opening-up and the construction of the Belt and Road at Sea, with vital strategic significance in Chinese overall development. Land use data and climate and socio-economic indicators were integrated to probe the spatiotemporal change and its driving forces of land use in the Pan-Pearl River basin with ArcGIS spatial analysis tool and SPSS factor analysis tool. Results showed that land use in the Pan-Pearl River Basin significantly changed between 1990 and 2015, with decreases of the area of paddy field and woodland and rapid increases of urban land and other construction land. Outflow of grassland occurred in the northwestern part of the basin. Reduction of cultivated field was mainly concentrated in the central part of the basin and coastal areas. Increases in urban and rural land, industrial and mining land, and residential land were centrally distributed in the Guangdong-Hong Kong-Marco Greater Bay Area. The prominent change areas were Guangdong-Hong Kong-Marco Greater Bay Area : central and southeast of Guangxi Province : northern Hainan Province. Land use changes during 1990-2000 were most obvious in the basin. The main driving factor of spatiotemporal variation of land use was the rapid development of social economy and industry and the improvement of residents' consumption level.

Chronic Intermittent Hypobaric Hypoxia Pretreatment Ameliorates Ischemia-Induced Cognitive Dysfunction Through Activation of ERK1/2-CREB-BDNF Pathway in Anesthetized Mice.

Chronic intermittent hypobaric hypoxia (CIHH) has protective effects on heart and brain against ischemia injury through mobilizing endogenous adaptive mechanisms. However, whether CIHH prevents against cognitive impairment was not elucidated. The present study aimed to investigate the effect and mechanism of CIHH treatment on ischemia/reperfusion (IR)-induced cognitive dysfunction. Mice were randomly divided into 8 groups: Control, Sham, CIHH (simulating 5000 m high-altitude for 28 days, 6 h per day), IR (three 16-min occlusions of bilateral common carotid arteries interrupted by two 10-min intervals), CIHH + IR, PD98059 (inhibitor of MEK1/2) + CIHH + IR, PD98059 + Sham and PD98059 + IR group. Morris water maze and step-down passive avoidance tests were performed to evaluate the capability of learning and memory 1 month after ischemia. Thionine dyeing was to examine histological manifestations of pyramidal neurons in hippocampus CA1 region. Western blotting assay was for measurement of the protein expressions in ERK1/2-CREB-BDNF signaling pathway. There were a shorter escape latency and a longer percentage of time retaining in the target quadrant in Morris water maze test, fewer times of errors in the step-down avoidance test and a higher neuronal density of the hippocampal CA1 subfield in CIHH + IR group than in IR group. CIHH upregulated the expressions of BDNF, phosphorylated CREB, ERK1/2 and TrkB with or without ischemia. The protective effects of CIHH were abolished by PD98059 administration 15 min before ischemia. CIHH ameliorated ischemia-induced cognitive dysfunction through activation of ERK1/2-CREB-BDNF signaling pathway.

Chronic intermittent hybobaric hypoxia protects against cerebral ischemia via modulation of mitoKATP.

OBJECTIVE: Providing adequate protection against cerebral ischemia remains an unrealized goal. The present study was aimed at testing whether chronic intermittent hypobaric hypoxia (CIHH) would have protective effects against cerebral ischemia and investigating the potential role of mitochondrial membrane ATP-sensitive potassium channel (mitoKATP) in this effect. METHODS: Ischemia was induced in rats by occlusion of bilateral common carotid arteries for 8min on day 2 after bilateral vertebral arteries were permanently electrocauterized and CIHH was simulated in a hypoxic chamber. Learning and memory impairments were analyzed using the Morris water maze. The delay neuronal death (DND) in the hippocampus CA1 was observed by thionine staining. The expression of the two subunits of mitoKATP, SUR1 and Kir 6.2, and the concentration of cytochrome c (Cyt c) were observed by Western blotting. The mitochondrial membrane potential (Δym) was determined by flow cytometry. Morphological changes of the mitochondria were investigated by electron microscopy. The antagonist of mitoKATP, 5-hydroxydecanoate (5-HD), was used to demonstrate the involvement of mitoKATP. RESULTS: CIHH pretreatment ameliorated the learning and memory impairments produced by ischemia, concomitant with reduced DND in the hippocampus CA1 area. Expression levels of SUR1 and Kir6.2 both increased for at least one week after CIHH pretreatment. Levels of the two subunits were higher in the CIHH pretreatment combined with ischemia group than the ischemia only group at 2 d and 7 d after ischemia. Furthermore, the concentration of Cyt c was decreased in mitochondria and increased in the cytoplasm after ischemia which was prevented by CIHH. The decrease of Δψm and the destruction of mitochondrial ultrastructure were both rescued by CIHH pretreatment. The above protective effects of CIHH were blocked by 5-HD intraperitoneal injection 30min before ischemia. CONCLUSION: CIHH pretreatment can reduce cerebral ischemic injury, which is mediated by upregulating the expression and activity of mitoKATP.