Early intervention in myelofibrosis and impact on outcomes: A pooled analysis of the COMFORT-I and COMFORT-II studies

Background

In a pooled analysis of the phase 3 Controlled Myelofibrosis Study With Oral JAK Inhibitor Treatment I (COMFORT-I) and COMFORT-II clinical trials, adult patients with intermediate-2 or high-risk myelofibrosis who received oral ruxolitinib at randomization or after crossover from placebo or best available therapy (BAT) had improved overall survival (OS).

Methods

This post hoc analysis of pooled COMFORT data examined relevant disease outcomes based on the disease duration (≤12 or >12 months from diagnosis) before ruxolitinib initiation.

Results

The analysis included 525 patients (ruxolitinib: ≤12 months, n = 84; >12 months, n = 216; placebo/BAT: ≤12 months, n = 66; >12 months, n = 159); the median age was 65.0–70.0 years. Fewer thrombocytopenia and anemia events were observed among patients who initiated ruxolitinib treatment earlier. At Weeks 24 and 48, the spleen volume response (SVR) was higher for patients who initiated ruxolitinib earlier (47.6% vs. 32.9% at Week 24, p = .0610; 44.0% vs. 26.9% at Week 48, p = .0149). In a multivariable analysis of factors associated with spleen volume reduction, a logistic regression model that controlled for confounding factors found that a significantly greater binary reduction was observed among patients with shorter versus longer disease duration (p = .022). At Week 240, OS was significantly improved among patients who initiated ruxolitinib earlier (63% [95% CI, 51%‒73%] vs. 57% [95% CI, 49%‒64%]; hazard ratio, 1.53; 95% CI, 1.01‒2.31; p = .0430). Regardless of disease duration, a longer OS was observed for patients who received ruxolitinib versus those who received placebo/BAT.

Conclusions

These findings suggest that earlier ruxolitinib initiation for adult patients with intermediate-2 and high-risk myelofibrosis may improve clinical outcomes, including fewer cytopenia events, durable SVR, and prolonged OS.

Plain Language Summary

• Patients with myelofibrosis, a bone marrow cancer, often do not live as long as the general population. These patients may also have an enlarged spleen and difficult symptoms such as fatigue.
• Two large clinical trials showed that patients treated with the drug ruxolitinib lived longer and had improved symptoms compared to those treated with placebo or other standard treatments.
• Here it was examined whether starting treatment with ruxolitinib earlier (i.e., within a year of diagnosis) provided benefits versus delaying treatment.
• Patients who received ruxolitinib within a year of diagnosis lived longer and experienced fewer disease symptoms than those whose treatment was delayed.

     

皮肤瘙痒神经传导介质的研究进展

瘙痒是皮肤科的一种常见症状,是多因素相互作用的结果,其发生受到中枢和外周机制的双重调控,但具体发生机制尚不十分清楚。近年来随着研究的不断深入,多种物质如组胺、乙酰胆碱、5-羟色胺、蛋白酶和蛋白酶相关受体、细胞因子、阿片样肽等介质在瘙痒产生过程中起重要作用,这些介质通过刺激C类神经纤维或直接与皮肤感觉神经纤维受体相结合来介导瘙痒。本文就将皮肤瘙痒的神经传导及传导介质作一综述。     

South African abortion attitudes from 2007-2016: the roles of religiosity and attitudes toward sexuality and gender equality

ABSTRACT

Abortion is legal in South Africa, but negative abortion attitudes remain common and are poorly understood. We used nationally representative South African Social Attitudes Survey data to analyze abortion attitudes in the case of fetal anomaly and in the case of poverty from 2007 to 2016 (n = 20,711; ages = 16+). We measured correlations between abortion attitudes and these important predictors: religiosity, attitudes about premarital sex, attitudes about preferential hiring and promotion of women, and attitudes toward family gender roles. Abortion acceptability for poverty increased over time (b = 0.05, p < .001), but not for fetal anomaly (b = ?0.008, p = .284). Highly religious South Africans reported lower abortion acceptability in both cases (Odds Ratio (OR)_anomaly = 0.85, p = .015; OR_poverty = 0.84, p = .02). Premarital sex acceptability strongly and positively predicted abortion acceptability (OR_anomaly = 2.63, p < .001; OR_poverty = 2.46, p < .001). Attitudes about preferential hiring and promotion of women were not associated with abortion attitudes, but favorable attitudes about working mothers were positively associated with abortion acceptability for fetal anomaly ((OR_anomaly = 1.09, p = .01; OR_poverty = 1.02, p = .641)). Results suggest negative abortion attitudes remain common in South Africa and are closely tied to religiosity, traditional ideologies about sexuality, and gender role expectations about motherhood.     

聪耳通窍汤联合耳针对老年神经性耳鸣近远期疗效观察

目的探讨聪耳通窍汤联合耳针治疗老年神经性耳鸣患者的近远期疗效。方法选取耳鼻喉科门诊收治的老年神经性耳鸣患者136例,按随机数字表法分组,对照组68例予以耳针治疗,研究组68例在对照组基础上予以聪耳通窍汤治疗。检测比较两组间近、远期临床疗效、甲襞微循环指标、血液流变学指标以及不良反应发生率。结果治疗后,对照组总有效率为67.64%(46/68)低于研究组总有效率83.82%(57/68),具有统计学意义(P<0.05);随访6个月后,对照组总有效率64.71%(44/68)低于研究组总有效率89.71%(61/68),具有统计学意义(P<0.05);与对照组比较,研究组治疗后甲襞微循环襻周积分、管襻积分、流态积分及总积分较低,治疗后血浆黏度、高切全血黏度、低切全血黏度及红细胞压积较低,差异具有统计学意义(P<0.05);治疗中出现的不良反应为恶心、腹胀、针刺部位疼痛,两组间不良反应发生率无统计学差异(P>0.05)。结论聪耳通窍汤联合耳针治疗老年神经性耳鸣患者的近远期疗效均较好,能明显改善患者微循环状态及血液流变学指标,减轻内耳循环障碍,具有较高安全性。     

H型高血压患者舌面诊图像颜色特征参数分析＊

目的 分析H型高血压患者的舌面诊图像颜色参数特征，探讨H型高血压患者的舌诊、面诊变化规律。方法 运用上海中医药大学自行研制的Smart TCM-1型中医舌面一体仪，采集高血压患者舌面诊图像，提取特征参数，分析健康对照组、H型高血压组与非H型高血压组患者舌面颜色参数特征。结果 ①在舌色各项参数中，H型高血压组舌尖部R值、B值、V值均显著小于健康对照组（P < 0.01）；非H型高血压组舌尖部B值显著小于健康对照组（P < 0.01），S值较健康对照组显著增大（P < 0.05）；H型高血压组舌尖部R、V值均明显小于非H型高血压组（P < 0.05）。在舌苔各项参数中，H型高血压组舌中H值、V值均明显小于健康对照组（P < 0.05）；非H型高血压组舌中V值、舌右V值均显著小于健康对照组（P < 0.01）；H型高血压组舌中H值明显小于非H型高血压组（P < 0.05），右侧舌苔S值明显大于非H型高血压组（P < 0.05）。②H型高血压组面色参数鼻G值、下颌G值、口唇R值、口唇V值均明显小于健康对照组（P < 0.05）；非H型高血压组前额H值、目眶H值、脸颊H值、鼻H值、下颌H值、整体H值均明显大于健康对照组（P < 0.05）；H型高血压组前额H值、目眶G值、目眶H值、脸颊H值、鼻G值、鼻H值、下颌R值、下颌G值、下颌H值、下颌V值、口唇R值、口唇G值、口唇V值、整体R值、整体G值、整体H值、整体V值均明显小于非H型高血压组（P < 0.05）。结论 H型高血压患者苔色偏黄，以舌中部为主，且舌右侧黄苔积聚较明显；H型高血压患者面色为黄中带红，口唇、下颌部更为晦暗。H型高血压患者的舌、面诊特征参数的变化，与高血压病阳亢湿盛病机相符。