The novel dihydroorotate dehydrogenase (DHODH) inhibitor BAY 2402234 triggers differentiation and is effective in the treatment of myeloid malignancies.

Acute myeloid leukemia (AML) is a devastating disease, with the majority of patients dying within a year of diagnosis. For patients with relapsed/refractory AML, the prognosis is particularly poor with currently available treatments. Although genetically heterogeneous, AML subtypes share a common differentiation arrest at hematopoietic progenitor stages. Overcoming this differentiation arrest has the potential to improve the long-term survival of patients, as is the case in acute promyelocytic leukemia (APL), which is characterized by a chromosomal translocation involving the retinoic acid receptor alpha gene. Treatment of APL with all-trans retinoic acid (ATRA) induces terminal differentiation and apoptosis of leukemic promyelocytes, resulting in cure rates of over 80%. Unfortunately, similarly efficacious differentiation therapies have, to date, been lacking outside of APL. Inhibition of dihydroorotate dehydrogenase (DHODH), a key enzyme in the de novo pyrimidine synthesis pathway, was recently reported to induce differentiation of diverse AML subtypes. In this report we describe the discovery and characterization of BAY 2402234 - a novel, potent, selective and orally bioavailable DHODH inhibitor that shows monotherapy efficacy and differentiation induction across multiple AML subtypes. Herein, we present the preclinical data that led to initiation of a phase I evaluation of this inhibitor in myeloid malignancies.

Omega-3 supplementation in patients with sepsis: a systematic review and meta-analysis of randomized trials.

BACKGROUND: Nutritional supplementation of omega-3 fatty acids has been proposed to modulate the balance of pro- and anti-inflammatory mediators in sepsis. If proved to improve clinical outcomes in critically ill patients with sepsis, this intervention would be easy to implement. However, the cumulative evidence from several randomized clinical trials (RCTs) remains unclear. METHODS: We searched the Cochrane Library, MEDLINE, and EMBASE through December 2016 for RCTs on parenteral or enteral omega-3 supplementation in adult critically ill patients diagnosed with sepsis or septic shock. We analysed the included studies for mortality, intensive care unit (ICU) length of stay, and duration of mechanical ventilation, and used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the quality of the evidence for each outcome. RESULTS: A total of 17 RCTs enrolling 1239 patients met our inclusion criteria. Omega-3 supplementation compared to no supplementation or placebo had no significant effect on mortality [relative risk (RR) 0.85; 95% confidence interval (CI) 0.71, 1.03; P = 0.10; I 2 = 0%; moderate quality], but significantly reduced ICU length of stay [mean difference (MD) -3.79 days; 95% CI -5.49, -2.09; P < 0.0001, I 2 = 82%; very low quality] and duration of mechanical ventilation (MD -2.27 days; 95% CI -4.27, -0.27; P = 0.03, I 2 = 60%; very low quality). However, sensitivity analyses challenged the robustness of these results. CONCLUSION: Omega-3 nutritional supplementation may reduce ICU length of stay and duration of mechanical ventilation without significantly affecting mortality, but the very low quality of overall evidence is insufficient to justify the routine use of omega-3 fatty acids in the management of sepsis.

Truck Drivers' Experiences and Perspectives Regarding Factors Influencing Traffic Accidents: A Qualitative Study.

Traffic accidents are a major public health problem, leading to death and disability. Although pertinent studies have been conducted, little data are available in Iran. This study explored the experiences of truck drivers and their perspectives regarding factors contributing to traffic accidents. Eighteen truck drivers, purposively sampled, participated in semi-structured interviews. Data were analyzed using qualitative content analysis. A main theme, lack of ability to control stress, emerged as a factor influencing the incidence of traffic accidents. This main theme was found to have three subthemes: poor organization of the job, lack of workplace facilities and proper equipment, and unsupportive environment. Although several factors were found to contribute to traffic accidents, their effects were not independent, and all were considered significant. Identifying factors that contribute to traffic accidents requires a systematic and holistic approach. Findings could be used by the transportation industry and community health centers to prevent traffic accidents.

A study of Iranian nurses' and midwives' knowledge, attitudes, and implementation of evidence-based practice: the time for change has arrived.

BACKGROUND: Evidence-based practice (EBP) leads to enhanced quality of care, and the individual and professional development of nurses and midwives. Therefore, it is important for nurses and midwives as well as all other healthcare providers and stakeholders to inform clinical decision-making and implement EBP. AIM: This study aimed to determine the EBP knowledge, attitudes, and practice of clinical nurses and midwives in Mashhad public hospitals in Iran. METHODS: The descriptive cross-sectional study was conducted with a stratified cluster, random sample of 240 employed nurses and midwives (response rate of 96%) in Mashhad, who held a Bachelor of Science degree and had at least 1 year of clinical experience. Two valid and reliable questionnaires were used to collect demographic and EBP data. Data were analyzed using SPSS version 11.5 software and descriptive and inferential statistics calculated. RESULTS: Participants' mean age was 31.0 (SD = 5.5) years and 80% (n = 194) were female. Most participants reported low knowledge or skills and practice of EBP, but moderate attitudes toward EBP. Significant differences between the mean scores on knowledge or skills, attitudes, and practice were identified by field of study. Nurses reported higher knowledge or skills and practice of EBP than midwives (p < .001). Nurses and midwives with master-s degrees displayed greater knowledge or skills and practice of EBP, and more positive attitudes than nurses with bachelor-s degrees (p < .001). LINKING EVIDENCE TO ACTION: Although clinical nurses and midwives apply EBP in clinical settings, it is necessary to develop their knowledge or skills and practice. The results of this study can be applied by educational planners, educational managers, and authorities to enhance the quality and consistency of EBP implementation. The results provide a base for future studies in this field.

Folic acid supplementation in younger and older nonpregnant women of reproductive age: findings from the Central Pennsylvania Women's Health Study (CePAWHS).

INTRODUCTION AND BACKGROUND: This study explores variables associated with daily folic acid supplementation among nonpregnant women ages 18-24, in comparison with women ages 25-45. Health-related behaviors, reproductive status, health care access, and sociodemographic variables are included. METHODS: Data are from a cross-sectional population-based survey of 2,002 women ages 18-45 in the Central Pennsylvania Women's Health Study. The analytic sample included 246 women ages 18-24 and 1,636 women ages 25-45 who were not pregnant at the time of survey. RESULTS: Seventeen percent of women ages 18-24 and 27% of women ages 24-45 used daily folic acid supplements. In multiple logistic regression analysis, folic acid use was significantly associated with only two variables among younger women: fruit consumption at least daily and regular physical activity levels meeting recommended guidelines. Among older women, folic acid use was associated with these same two health-related behaviors in addition to not smoking, seeing an obstetrician-gynecologist, receiving diet/nutrition counseling, being married or living with a partner, and no prior pregnancy. Folic acid use was not associated with pregnancy intention in either age group. CONCLUSIONS AND DISCUSSION: Women ages 18-24 have significantly lower rates of folic acid supplementation compared with older women of reproductive age, but fewer variables are associated with folic acid use among younger women. Missed opportunities to educate younger women about the benefits of folic acid supplementation are identified.