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Background Chronic or gestational hypertension complicates approximately 7% of pregnancies, half of which reach 37 weeks' gestation. Early term birth (at 37 to 38 weeks) may reduce maternal complications, cesareans, stillbirths, and costs but may increase neonatal morbidity. In the WILL Trial (When to Induce Labour to Limit risk in pregnancy hypertension), we aimed to establish optimal timing of birth for women with chronic or gestational hypertension who reach term and remain well. Methods and findings This 50-centre, open-label, randomised trial in the United Kingdom included an economic analysis. WILL randomised women with chronic or gestational hypertension at 36 to 37 weeks and a singleton fetus, and who provided documented informed consent to 'Planned early term birth at 38.sup.+0-3 weeks' (intervention) or 'usual care at term' (control). The coprimary outcomes were 'poor maternal outcome' (composite of severe hypertension, maternal death, or maternal morbidity; superiority hypothesis) and 'neonatal care unit admission for [greater than or equal to]4 hours' (noninferiority hypothesis). The key secondary was cesarean. Follow-up was to 6 weeks postpartum. The planned sample size was 540/group. Analysis was by intention-to-treat. A total of 403 participants (37.3% of target) were randomised to the intervention (n = 201) or control group (n = 202), from 3 June 2019 to 19 December 2022, when the funder stopped the trial for delayed recruitment. In the intervention (versus control) group, losses to follow-up were 18/201 (9%) versus 15/202 (7%). In each group, maternal age was about 30 years, about one-fifth of women were from ethnic minorities, over half had obesity, approximately half had chronic hypertension, and most were on antihypertensives with normal blood pressure. In the intervention (versus control) group, birth was a median of 0.9 weeks earlier (38.4 [38.3 to 38.6] versus 39.3 [38.7 to 39.9] weeks). There was no evidence of a difference in 'poor maternal outcome' (27/201 [13%] versus 24/202 [12%], respectively; adjusted risk ratio [aRR] 1.16, 95% confidence interval [CI] 0.72 to 1.87). For 'neonatal care unit admission for [greater than or equal to]4 hours,' the intervention was considered noninferior to the control as the adjusted risk difference (aRD) 95% CI upper bound did not cross the 8% prespecified noninferiority margin (14/201 [7%] versus 14/202 [7%], respectively; aRD 0.003, 95% CI -0.05 to +0.06), although event rates were lower-than-estimated. The intervention (versus control) was associated with no difference in cesarean (58/201 [29%] versus 72/202 [36%], respectively; aRR 0.81, 95% CI 0.61 to 1.08. There were no serious adverse events. Limitations include our smaller-than-planned sample size, and lower-than-anticipated event rates, so the findings may not be generalisable to where hypertension is not treated with antihypertensive therapy. Conclusions In this study, we observed that most women with chronic or gestational hypertension required labour induction, and planned birth at 38.sup.+0-3 weeks (versus usual care) resulted in birth an average of 6 days earlier, and no differences in poor maternal outcome or neonatal morbidity. Our findings provide reassurance about planned birth at 38.sup.+0-3 weeks as a clinical option for these women. Trial registration isrctn.com ISRCTN77258279., Author(s): Laura A. Magee 1,2,*, Katie Kirkham 3, Sue Tohill 4, Eleni Gkini 3, Catherine A. Moakes 3, Jon Dorling 5, Marcus Green 6, Jennifer A. Hutcheon 7, Mishal Javed [...]

Introduction: Autologous blood products like Platelet Rich Plasma (PRP) and Leukocyte and Platelets Rich Fibrin (L-PRF) have been used for many years across many types of skin ulcers. However, the effectiveness of autologous blood products on wound healing is not well established. Methods: We evaluated the 'second generation' autologous product- Leukocyte and Platelet- Rich Fibrin (L-PRF). Our trial was undertaken on patients suffering from neuropathic leprosy ulcers at the Anandaban hospital which serves the entire country of Nepal. We conducted a 1:1 (n = 130) individually randomised trial of L-PRF (intervention) vs. normal saline dressing (control) to compare rate of healing and time to complete healing. Rate of healing was estimated using blind assessments of ulcer areas based on three different measurement methods. Time to complete healing was measured by the local unblinded clinicians and by blind assessment of ulcer images. Results: The point estimates for both outcomes were favourable to L-PRF but the effect sizes were small. Unadjusted mean differences (intervention vs control) in mean daily healing rates (cm2) were respectively 0.012 (95% confidence interval 0.001 to 0.023, p = 0.027); 0.016 (0.004 to 0.027, p = 0.008) and 0.005 (-0.005 to 0.016, p = 0.313) across the three measurement methods. Time to complete healing at 42 days yielded Hazard Ratios (unadjusted) of 1.3 (0.8 to 2.1, p = 0.300) assessed by unblinded local clinicians and 1.2 (0.7 to 2.0, p = 0.462) on blind assessment. Conclusion: Any benefit from L-PRF appears insufficient to justify routine use in care of neuropathic ulcers in leprosy. Trial registration: ISRCTN14933421. Date of trial registration: 16 June 2020. Author summary: Autologous Blood Products such as Leucocyte and Platelets Rich Fibrin (L-PRF) gel have been widely used in the treatment of skin ulcers, including Leprosy ulcers. L-PRF gel contains a high concentration of platelets and leucocytes rich in growth factors that might promote wound healing. However, our systematic review showed that there is a lack of high-quality trial evidence for the effectiveness of L-PRF. To evaluate the efficacy of L-PRF we conducted an individual randomised controlled trial (n = 130) of L-PRF gel vs conventional normal saline dressings. Photographs were taken during twice weekly dressing changes in both intervention and control groups. The ulcer photographs were assessed by blinded assessors using three different ulcer area measurement methods. Outcomes were rate of healing and time to complete epithelialisation. Point estimates for intervention effects across outcomes and measurement methods, intervention vs control was favorable to L-PRF but the effect sizes were small and mostly not statistically significant. [ABSTRACT FROM AUTHOR]

Background: The cisplatin-pemetrexed and cisplatin-gemcitabine combinations are considered the standard treatment for malignant pleural mesothelioma. The purpose of this study was to examine the efficacy of gemcitabine plus docetaxel in the first-line setting, as this combination has not been investigated in mesothelioma before., Patients and Methods: Twenty-five consecutive patients with malignant pleural mesothelioma were enrolled. They received 80 mg/m(2) of docetaxel and 1,000 mg/m(2) of gemcitabine on days 1 and 14 of a 28-day cycle. The treatment was scheduled for a maximum of 6 cycles or until disease progression or unacceptable toxicity., Results: A total of 7 out of our 25 patients (28%) responded to treatment. In 14 patients (56%), the disease remained stable, while in 4 (16%) it progressed. The median time to progression was 7 months (range: 5.4-8.6 months) and the median overall survival was 15 months (range: 12.4-17.5 months)., Conclusion: The administration of gemcitabine and doctaxel appears to be promising first-line therapy for patients with mesothelioma, as it is well tolerated and appears to improve survival.