Evaluation of prognostic staging systems of multiple myeloma in the era of novel agents.

This study aimed to evaluate the existing staging systems for multiple myeloma (MM) in the real world. From January 2010 to June 2019, we retrospectively analyzed 859 newly diagnosed MM patients from two institutions. Clinical data including laboratory findings, imaging examinations and staging system were obtained by reviewing medical records. Survival distributions were estimated using the Kaplan-Meier curve analysis, and Cox proportional hazards model were used to identified risk factors. The overall survival (OS) of eligible patients was 61.0 months. The Revised International Staging System (R-ISS) had a larger receiver operating characteristic curve area (0.603) than both the International Staging System (0.573) and the Durie Salmon staging system (0.567). In the group receiving immunomodulatory agents-based regimens, the median OS was 92.0 months in R-ISS I, 63.0 months in R-ISS II and 18.0 months in R-ISS III (p < 0.0001). In the group receiving proteasome inhibitors-based regimens, the median OS was 102.0 months in R-ISS I, 63.0 months in R-ISS II and 22.0 months in R-ISS III (p < 0.0001). In different subgroups grouped according to age, hemoglobin (HGB), creatinine, and Ca, R-ISS also had a good stratification effect. Patients in R-ISS II, which accounted for 69.9% of all patients, were further analyzed. Univariate and multivariate Cox analyses revealed that age >65 years (p = 0.001), HGB < 100 g/L (p < 0.001), elevated LDH (p = 0.001), and Ca (p = 0.010) were independent predictors of worse prognosis within R-ISS II. To conclusion, R-ISS remains a valuable staging system in the real world of the novel drug era. However, patients classified as R-ISS II still have great heterogeneity.

Development and Local Contextualization of Mobile Health Messages for Enhancing Disease Management Among Community-Dwelling Stroke Patients in Rural China: Multimethod Study.

BACKGROUND: Rural China has experienced an increasing health burden because of stroke. Stroke patients in rural communities have relatively poor awareness of and adherence to evidence-based secondary prevention and self-management of stroke. Mobile technology represents an innovative way to influence patient behaviors and improve their self-management. OBJECTIVE: This study is part of the System-Integrated Technology-Enabled Model of Care (the SINEMA trial) to improve the health of stroke patients in resource-poor settings in China. This study aimed to develop and pilot-test a mobile phone message-based package, as a component of the SINEMA intervention. METHODS: The SINEMA trial was conducted in Nanhe County, Hebei Province, China. A total of 4 villages were selected for pretrial contextual research and pilot study. The 5 stages for developing the mobile phone messages were as follows: (1) conducting literature review on existing message banks and analyzing the characteristics of these banks; (2) interviewing stroke patients and caregivers to identify their needs; (3) drafting message contents and designing dispatching algorithms for a 3-month pilot testing; (4) collecting feedback from pilot participants through questionnaire survey and in-depth interviews on facilitators and barriers related to their acceptance and understanding of messages; and (5) finalizing the message-based intervention based on participants' feedback for the SINEMA trial. RESULTS: On the basis of 5 existing message banks screened out of 120 papers and patients' needs identified from 32 in-depth interviews among stroke patients and caregivers, we developed a message bank containing 224 messages for a pilot study among 54 community-dwelling stroke patients from 4 villages. Of 54 participants, 51 (response rate: 94.4%) completed the feedback survey after receiving daily messages for 3 months. Participants' mean age was 68 years (SD 9.2), and about half had never been to school. We observed a higher proportion of participants who were in favor of voice messages (23/42, 54%) than text messages (14/40, 35%). Among participants who received voice messages (n=43) and text messages (n=40), 41 and 30, respectively, self-reported a full or partial understanding of the contents, and 39 (39/43, 91%) and 32 (32/40, 80%), respectively, rated the messages as helpful. Analyses of the 32 interviews further revealed that voice messages containing simple and single-theme content, in plain language, with a repeated structure, a slow playback speed, and recorded in local dialect, were preferred by rural stroke patients. In addition, the dispatching algorithm and tools may also influence the acceptance of message-based interventions. CONCLUSIONS: By applying multiple methodologies and conducting a pilot study, we designed and fine-tuned a voice message-based intervention package for promoting secondary prevention among community-dwelling stroke patients in rural China. Design of the content and dispatching algorithm should engage both experts and end users and adequately consider the needs and preferences of recipients.

Amygdalar Endothelin-1 Regulates Pyramidal Neuron Excitability and Affects Anxiety.

An abnormal neuronal activity in the amygdala is involved in the pathogenesis of anxiety disorders. However, little is known about the mechanisms. High-anxiety mice and low-anxiety mice, representing the innate extremes of anxiety-related behaviors, were first grouped according to their anxiety levels in the elevated plus maze test. We found that the mRNA for endothelin-1 (ET1) and ET1 B-type receptors (ETBRs) in the amygdala was down-regulated in high-anxiety mice compared with low-anxiety mice. Knocking down basolateral amygdala (BLA) ET1 expression enhanced anxiety-like behaviors, whereas over-expressing ETBRs, but not A-type receptors (ETARs), had an anxiolytic effect. The combined down-regulation of ETBR and ET1 had no additional anxiogenic effect compared to knocking down the ETBR gene alone, suggesting that BLA ET1 acts through ETBRs to regulate anxiety-like behaviors. To explore the mechanism underlying this phenomenon further, we verified that most of the ET1 and the ET1 receptors in the BLA were expressed in pyramidal neurons. The ET1-ETBR signaling pathway decreased the firing frequencies and threshold currents for the action potentials of BLA pyramidal neurons but did not alter BLA synaptic neurotransmission. Together, these results indicate that amygdalar ET1-ETBR signaling could attenuate anxiety-like behaviors by directly decreasing the excitability of glutamatergic neurons.