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.

     

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.     

Priming sentence comprehension in aphasia: effects of lexically independent and specific structural priming

Background & Aims: Impaired message-structure mapping results in deficits in both sentence production and comprehension in aphasia. Structural priming has been shown to facilitate syntactic production for persons with aphasia (PWA). However, it remains unknown if structural priming is also effective in sentence comprehension. We examined if PWA show preserved and lasting structural priming effects during interpretation of syntactically ambiguous sentences and if the priming effects occur independently of or in conjunction with lexical (verb) information.

Methods & Procedures: Eighteen PWA and 20 healthy older adults (HOA) completed a written sentence-picture matching task involving the interpretation of prepositional phrases (PP; the chef is poking the solider with an umbrella) that were ambiguous between high (verb modifier) and low attachment (object noun modifier). Only one interpretation was possible for prime sentences, while both interpretations were possible for target sentences. In Experiment 1, the target was presented immediately after the prime (0-lag). In Experiment 2, two filler items intervened between the prime and the target (2-lag). Within each experiment, the verb was repeated for half of the prime-target pairs, while different verbs were used for the other half. Participants’ off-line picture matching choices and response times were measured.

Results: After reading a prime sentence with a particular interpretation, HOA and PWA tended to interpret an ambiguous PP in a target sentence in the same way and with faster response times. Importantly, both groups continued to show this priming effect over a lag (Experiment 2), although the effect was not as reliable in response times. However, neither group showed lexical (verb-specific) boost on priming, deviating from robust lexical boost seen in the young adults of prior studies.

Conclusions: PWA demonstrate abstract (lexically-independent) structural priming in the absence of a lexically-specific boost. Abstract priming is preserved in aphasia, effectively facilitating not only immediate but also longer-lasting structure-message mapping during sentence comprehension.