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Various home blood pressure monitors (HBPMs) are available to the public for purchase but only some are validated against standardised protocols. This study aimed to assess whether HBPMs owned by participants taking part in a clinical trial were validated models. The TIME study is a decentralised randomised trial investigating the effect of antihypertensive medication dosing time on cardiovascular outcomes in adults with hypertension. No HBPMs were provided to participants in this trial but patients were asked to report if they already owned one. We identified the model of HBPM reported by participants, then cross-referenced this against lists of validated HBPMs produced by dabl Educational Trust and the British and Irish Hypertension Society (BIHS). Of 21,104 participants, 10,464 (49.6%) reported their model of HBPM. 7464 (71.3%) of these participants owned a monitor that could be identified from the participants' entry. Of these, 6066 (81.3%) participants owned a monitor listed as validated by either dabl (n = 5903) or BIHS (n = 5491). Some were listed as validated by both. 1398 (18.7%) participants owned an identifiable HBPM that lacked clear evidence of validation. 6963 (93.3%) participants owned an upper arm HBPM and 501 (6.7%) owned a wrist HBPM. Validated HBPMs had a higher median online retail price of £45.00 compared to £20.00 for HBPMs lacking clear evidence of validation. A significant number of participants own HBPMs lacking evidence of validation.To investigate the optimal blood pressure (BP) in patients with coronary artery disease (CAD), we conducted subgroup analysis using SPRINT data. The study sample included 1206 participants with CAD (of whom 692 underwent coronary revascularization) and 8127 participants without CAD. Participants were randomized into two groups (systolic BP target of 140 mm Hg vs. 120 mm Hg). The primary outcome was a composite of cardiovascular events. https://www.selleckchem.com/products/gsk-2837808A.html After a median follow-up of 3.9 years, the hazard ratios (HRs) for the primary outcome were 0.65 (95% confidence interval (CI) 0.53-0.79) and 1.05 (95% CI 0.76-1.46) among those in the non-CAD and CAD subgroups, respectively (P value for interaction 0.02). Intensive BP treatment was a protective factor for all-cause death (HR 0.60, 95% CI 0.37-0.96) in the CAD subgroup, compared with standard BP treatment. The HRs (95% CI) for stroke were 3.57 (1.17-10.85) and 1.03 (0.29-3.62) among those in the coronary revascularization and non-revascularization subgroups, respectively (P value for interaction 0.13). For safety events, intensive BP treatment increased the risk of hypotension (HR 2.00, 95% CI 1.06-3.79) and electrolyte abnormalities (HR 2.38, 95% CI 1.25-4.56) in the CAD subgroup, while the risk of serious adverse events did not increase (HR 1.03, 95% CI 0.88-1.20). These results suggest that positive benefits from intensive BP treatment might be attenuated in patients with CAD who are under better secondary prevention. The risk of stroke might increase at the systolic BP target of 120 mm Hg in case of coronary revascularization, although the confidence interval was wide.Carfilzomib (CFZ) improves survival in relapsed/refractory multiple myeloma but is associated with cardiovascular adverse events (CVAEs). We prospectively investigated the effect of CFZ on endothelial function and associations with CVAEs. Forty-eight patients treated with Kd (CFZ 20/56 mg/m2 and dexamethasone) underwent serial endothelial function evaluation, using brachial artery flow-mediated dilatation (FMD) and 26S proteasome activity (PrA) measurement in PBMCs; patients were followed until disease progression or cycle 6 for a median of 10 months. FMD and PrA decreased acutely after the first dose (p 40% at the end of first cycle was also independently associated with CVAEs (HR = 3.91, 95% CI 1.29-11.83). Kd treatment impairs endothelial function which is associated with PrA inhibition and recovery. Both pre- and posttreatment FMD predicted CFZ-related CVAEs supporting its role as a possible cardiovascular toxicity biomarker.Myeloid leukemia of Down syndrome (ML-DS) is associated with good response to chemotherapy, resulting in favorable outcomes. However, no universal prognostic factors have been identified to date. To clarify a subgroup with high risk of relapse, the role of minimal residual disease (MRD) was explored in the AML-D11 trial by the Japanese Pediatric Leukemia/Lymphoma Study Group. MRD was prospectively evaluated at after induction therapy and at the end of all chemotherapy, using flow cytometry (FCM-MRD) and GATA1-targeted deep sequencing (GATA1-MRD). A total of 78 patients were eligible and 76 patients were stratified to the standard risk (SR) group by morphology. In SR patients, FCM-MRD and GATA1-MRD after induction were positive in 5/65 and 7/59 patients, respectively. Three-year event-free survival (EFS) and overall survival (OS) rates were 95.0% and 96.7% in the FCM-MRD-negative population, and 60.0% and 80.0% in the positive population. Three-year EFS and OS rates were both 98.1% in the GATA1-MRD-negative population, and 57.1% and 71.4% in the positive population. Adjusted hazard ratios for associations of FCM-MRD with EFS were 14.67 (p = 0.01). Detection of MRD by either FCM or GATA1 after initial induction therapy represents a significant prognostic factor for predicting ML-DS relapse.Precision medicine is gaining importance in the treatment of acute myeloid leukemia (AML). Objectively reviewing past and current knowledge aids guiding future research. Therefore, we provide a complete overview of all phase II and phase III trials investigating targeted therapies in AML and their primary endpoints over the past two decades in perspective of their clinical benefit. We assessed whether drugs were primarily designed to treat AML or were repurposed and how successful they were based on progression of distinct drugs from phase II to phase III to FDA-approval. Between January 2000 and September 2020, 167 agents with 96 targets were investigated in 397 phase II trials. Twenty-eight agents were steered towards phase III, after three phase II trials on average. Repurposed drugs less often advanced in clinical development than drugs primarily developed for AML. Composite responses were the most prevalent primary endpoints in phase II. Of the eight FDA-approved drugs, none investigated quality of life at time of approval, and three out of eight have yet to show benefit in overall survival.
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