Strategies for improving outcomes in the acute management of ischemic stroke in rural emergency departments: a quality improvement initiative in the Stroke Belt.

BACKGROUND: The timely evaluation and initiation of treatment for acute ischemic stroke (AIS) is critical to optimal patient outcomes. However, clinical practice often falls short of guideline-established goals. Hospitals in rural regions of the USA, and notably those in the Stroke Belt, are particularly challenged to meet timing goals since the vast majority of primary stroke centers (PSCs) are concentrated in urban academic institutions. METHODS: Between May 2015 and May 2017, emergency department (ED) teams from 5 non-PSC hospitals in the Stroke Belt participated in a quality improvement (QI) initiative. The intervention included a baseline practice assessment survey, repeat audit-and-feedback cycles with patient data on AIS treatment timing, personalized Continuing Medical Education/Continuing Education-certified grand rounds sessions at each participating site with expert study faculty, targeted reinforcement of best practices, and follow-up to evaluate the benefits and limitations of the intervention. RESULTS: At the start of the initiative, clinical staff from participating EDs overestimated the proportion of patients with AIS who received alteplase within the guideline-recommended 60-minute door-to-needle window at their facility. At the end of the 6-month intervention period, significantly more patients were treated with alteplase within 60 minutes of ED arrival compared to baseline across the entire sample (1.9% of patients at baseline vs. 5.2% at 6 months; P < 0.01). Similarly, there was a trend toward a decrease in the percentage of patients whose alteplase treatment was initiated more than 60 minutes after their arrival at the ED (67.3% at baseline vs. 22.2% at 6 months). CONCLUSION: Structured QI interventions that engage ED care teams to reflect on processes related to AIS diagnosis and treatment and deploy repeat audit-and-feedback cycles with real-time patient data have the potential to support an increase in the number of patients who receive alteplase within the guideline-recommended timeframe of 60 minutes from hospital arrival.

A performance improvement initiative for enhancing the care of patients with depression.

BACKGROUND: Depression is a common and potentially disabling condition, yet many patients remain undiagnosed, and many more fail to receive adequate treatment. To address this gap, clinicians must routinely evaluate patient care practices. The purpose of this study was to evaluate the effectiveness of a three-stage performance improvement (PI) continuing medical education (CME) initiative to strengthen evidence-based psychiatric practices for the screening and management of patients with depression. METHODS: A total of 492 physician participants voluntarily registered to complete a three-stage initiative consisting of self-evaluation, improvement, and reevaluation. Participants were recruited through a series of faxes, e-mails, and direct-mail invitations. RESULTS: Approximately 20% (n=86) of the registrants completed the three-stage initiative. Completers provided chart data on 2,122 patients encountered before and 2,130 patients encountered after engaging in the PI CME activity. Large gains were made in the percentage of patients screened using standardized criteria to assess depression status, particularly the Patient Health Questionnaire-2 (PHQ-2) and the PHQ-9 (26% of 1,378 patients at Stage A vs.68% of 1,711 patients at Stage C; p<0.001). Physicians were also more likely to rescreen patients 4 to 8 weeks after initial screening (48% of 1,961 patients at Stage A vs. 75% of 2,028 patients at Stage C; p<0.001) and to assess patient adherence to antidepressants using standardized measures (10% of 1,909 patients at Stage A vs. 45% of 1,740 patients at Stage C; p<0.001). CONCLUSIONS: PI CME provides insight into and aids in improving evidence-based patient care in psychiatric practices.

Release of methyl CpG binding proteins and histone deacetylase 1 from the Estrogen receptor alpha (ER) promoter upon reactivation in ER-negative human breast cancer cells.

Estrogen receptor alpha (ER) is an epigenetically regulated gene. Inhibitors of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) synergistically activate the methylated ER gene promoter in ER-negative MDA-MB-231 human breast cancer cells. Chromatin immunoprecipitation was used to examine the chromatin status and repressor complex associated with silenced ER and changes in the key regulatory factors during reactivation by inhibitors of DNMT (5-aza-2'-deoxycytidine) and HDAC (trichostatin A). The silencing of ER due to CpG hypermethylation correlates with binding of specific methyl-binding proteins, DNMTs, and HDAC proteins. Inhibition of HDAC activity by trichostatin A results in the accumulation of hyperacetylated core histones. The activation of ER gene expression by 5-aza-2'-deoxycytidine also involves the release of the repressor complex involving various methyl-binding proteins, DNMTs, and HDAC1. HDAC and DNMT inhibitors modulate histone methylation at H3-K9 and H3-K4 to form a more open chromatin structure necessary for reactivation of silenced ER transcription. Together these results impart a better understanding of molecular mechanisms of chromatin remodeling during ER reactivation by DNMT and HDAC inhibitors. These findings will aid in the application of agents targeting epigenetic changes in the treatment of breast cancer.