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Srdan Verstovsek MD PhD Jean-Jacques Kiladjian MD PhD Alessandro M. Vannucchi MD Ruben A. Mesa MD FACP Peg Squier MD PhD J. E. Hamer-Maansson MSPH Claire Harrison MD 《Cancer》2023,129(11):1681-1690
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.
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Elizabeth A. Mosley PhD MPH Amy J. Schulz PhD MPH MSW Lisa H. Harris MD PhD Barbara A. Anderson PhD 《Women & health》2020,60(7):806-820
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; ORpoverty = 0.84, p = .02). Premarital sex acceptability strongly and positively predicted abortion acceptability (ORanomaly = 2.63, p < .001; ORpoverty = 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 ((ORanomaly = 1.09, p = .01; ORpoverty = 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. 相似文献
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Takaharu Negoro Kanami Orihara Tomoko Irahara Hiroshi Nishiyama Kanae Hagiwara Risa Nishida Hiroki Takagi Kazue Satoh Yoshiki Yamamoto Shunichi Shimizu Tamio Hagiwara Masakazu Ishii Toshihiro Tanioka Yasuko Nakano Ken Takeda Isao Yoshimura Yoji Iikura Takashi Tobe 《Pediatric allergy and immunology》2006,17(8):583-590
Although many single nucleotide polymorphism (SNP) studies have reported an association of atopy, allergic diseases and total serum immunoglobulin E (IgE) levels, almost all of these studies sought risk factors for the onset of these allergic diseases. Furthermore, many studies have analyzed a single gene and hardly any have analyzed environmental factors. In these analyses, the results could be masked and the effects of other genes and environmental factors may be decreased. Here, we described the correlation between four genes [interleukin (IL)-4 (C-590T), IL-4 receptor (A1652G), FCER1B (G6842A) and STAT6 (G2964A)] in connection with IgE production; the role of IL-10 (C-627A) as a regulatory cytokine of allergy; and the severity of food allergy (FA) and atopic eczema (AE) in 220 Japanese allergic children. In addition to these SNPs, environmental factors, i.e., patient's attitude, indoor environment, and so on, were also investigated in this study. Our study was retrospective, and the correlation was analyzed by our defined clinical scores divided into three terms: worst symptoms, recent symptoms and general amelioration at the most recent examination during the disease course. Our results indicated that IL-10 AA, the genotype with lower IL-10 production, is associated with higher IgE levels in the serum (p < 0.0001, estimate; 0.912). Marginal liver abnormalities were observed in the subject group with both FA and AE (p < 0.1191, estimate; 0.1490). Our defined clinical scores enabled evaluation of various aspects of disease severity. Based on the scores, while no single SNP selected in this study determined severity, the combination of the SNP with laboratory data and environmental factors appeared to determine severity. 相似文献
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