EPZ011989, A Potent,Orally-Available EZH2 Inhibitor with Robust in Vivo Activity

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Discovery of Benzimidazole Oxazolidinediones as Novel and Selective Nonsteroidal Mineralocorticoid Receptor Antagonists

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Changes in Burnout and Satisfaction With Work-Life Integration in Physicians and the General US Working Population Between 2011 and 2017

ObjectiveTo evaluate the prevalence of burnout and satisfaction with work-life integration among physicians and other US workers in 2017 compared with 2011 and 2014.Participants and MethodsBetween October 12, 2017, and March 15, 2018, we surveyed US physicians and a probability-based sample of the US working population using methods similar to our 2011 and 2014 studies. A secondary survey with intensive follow-up was conducted in a sample of nonresponders to evaluate response bias. Burnout and work-life integration were measured using standard tools.ResultsOf 30,456 physicians who received an invitation to participate, 5197 (17.1%) completed surveys. Among the 476 physicians in the secondary survey of nonresponders, 248 (52.1%) responded. A comparison of responders in the 2 surveys revealed no significant differences in burnout scores (P=.66), suggesting that participants were representative of US physicians. When assessed using the Maslach Burnout Inventory, 43.9% (2147 of 4893) of the physicians who completed the MBI reported at least one symptom of burnout in 2017 compared with 54.4% (3680 of 6767) in 2014 (P<.001) and 45.5% (3310 of 7227) in 2011 (P=.04). Satisfaction with work-life integration was more favorable in 2017 (42.7% [2056 of 4809]) than in 2014 (40.9% [2718 of 6651]; P<.001) but less favorable than in 2011 (48.5% [3512 of 7244]; P<.001). On multivariate analysis adjusting for age, sex, relationship status, and hours worked per week, physicians were at increased risk for burnout (odds ratio, 1.39; 95% CI, 1.26-1.54; P<.001) and were less likely to be satisfied with work-life integration (odds ratio, 0.77; 95% CI, 0.70-0.85; P<.001) than other working US adults.ConclusionBurnout and satisfaction with work-life integration among US physicians improved between 2014 and 2017, with burnout currently near 2011 levels. Physicians remain at increased risk for burnout relative to workers in other fields.     

The effects of unimanual and bimanual massed practice on upper limb function in adults with cervical spinal cord injury: a systematic review

BackgroundIndividuals with cervical spinal cord injury (cSCI) have identified improving upper limb function as their most important rehabilitation goal. Unimanual massed practice (UMP) and bimanual massed practice (BMP) may help achieve this.ObjectivesTo evaluate and compare the effects of UMP and BMP on upper limb function in adults with cSCI.Data sourcesCochrane Central Register of Controlled Trials, PubMed, CINAHL, Web of Science and PEDro until April 2016.Study selectionStudies investigating the effects of UMP and/or BMP on upper limb function in adults with cSCI.Data extraction and synthesisData was extracted using a standardised form. Studies were appraised using a modified version of the Cochrane risk of bias tool. The findings were qualitatively synthesised.ResultsFive randomised controlled trials and two case studies were included. Six studies included UMP, three included BMP, and two compared these approaches. Overall the studies reported that UMP and BMP improved upper limb function, particularly when combined with electrical stimulation, with no clear differences between UMP and BMP. These findings should be interpreted with caution however, as six studies presented a high or unclear risk of bias for all functional upper limb outcome measures included, and the remaining study was a small pilot study with no control group.ConclusionAlthough the findings of the included studies support the use of UMP and BMP in adults with cSCI, only seven studies, all with significant limitations, were included; hence robust conclusions cannot be drawn and further research is warranted.PROSPERO registration number: CRD42016037365     

Nodular regenerative hyperplasia: a deleterious consequence of chemotherapy for colorectal liver metastases?

AIMS: This report describes three patients suffering from nodular regenerative hyperplasia (NRH). METHODS: These patients have received six, 16 and 20 cycles of neoadjuvant 5-fluorouracil and oxaliplatin-based chemotherapy before planned extended hepatectomy. Two patients underwent uneventful portal vein embolization to hypertrophy the future remnant liver. RESULTS: At the end of chemotherapy, liver function tests deteriorated and portal hypertension appeared in two patients, including ascites, splenomegaly and oesophageal varices. Liver biopsy was performed through a percutaneous (two patients) or a transjugular approach (one patient) and allowed the diagnosis of NRH, which was considered to be a contraindication for major liver resection in all three patients, associated with extrahepatic disease progression in one patient. All patients died from neoplastic disease progression despite further chemotherapy at 6, 17 and 31 months following the diagnosis of NRH. One patient developed liver failure and ascites at the time of death. CONCLUSIONS: Physicians should be aware of the potential occurrence and therapeutic impact of NRH in patients suffering from CRLM and treated by neoadjuvant 5FU-oxaliplatin-based chemotherapy before major liver surgery.