A Progressive Early Mobilization Program Is Significantly Associated With Clinical and Economic Improvement: A Single-Center Quality Comparison Study.

OBJECTIVES: To determine whether a progressive early mobilization protocol improves patient outcomes, including in-hospital mortality and total hospital costs. DESIGN: Retrospective preintervention and postintervention quality comparison study. SETTINGS: Single tertiary community hospital with a 12-bed closed-mixed ICU. PATIENTS: All consecutive patients 18 years old or older were eligible. Patients who met exclusion criteria or were discharged from the ICU within 48 hours were excluded. Patients from January 2014 to May 2015 were defined as the preintervention group (group A) and from June 2015 to December 2016 was the postintervention group (group B). INTERVENTION: Maebashi early mobilization protocol. MEASUREMENTS AND MAIN RESULTS: Group A included 204 patients and group B included 187 patients. Baseline characteristics evaluated include age, severity, mechanical ventilation, and extracorporeal membrane oxygenation, and in group B additional comorbidities and use of steroids. Hospital mortality was reduced in group B (adjusted hazard ratio, 0.25; 95% CI, 0.13-0.49; p < 0.01). This early mobilization protocol is significantly associated with decreased mortality, even after adjusting for baseline characteristics such as sedation. Total hospital costs decreased from $29,220 to $22,706. The decrease occurred soon after initiating the intervention and this effect was sustained. The estimated effect was $-5,167 per patient, a 27% reduction. Reductions in ICU and hospital lengths of stay, time on mechanical ventilation, and improvement in physical function at hospital discharge were also seen. The change in Sequential Organ Failure Assessment score and Sequential Organ Failure Assessment score at ICU discharge were significantly reduced after the intervention, despite a similar Sequential Organ Failure Assessment score at admission and at maximum. CONCLUSIONS: In-hospital mortality and total hospital costs are reduced after the introduction of a progressive early mobilization program, which is significantly associated with decreased mortality. Cost savings were realized early after the intervention and sustained. Further prospective studies to investigate causality are warranted.

The safety of a novel early mobilization protocol conducted by ICU physicians: a prospective observational study.

BACKGROUND: There are numerous barriers to early mobilization (EM) in a resource-limited intensive care unit (ICU) without a specialized team or an EM culture, regarding patient stability while critically ill or in the presence of medical devices. We hypothesized that ICU physicians can overcome these barriers. The aim of this study was to investigate the safety of EM according to the Maebashi EM protocol conducted by ICU physicians. METHODS: This was a single-center prospective observational study. All consecutive patients with an unplanned emergency admission were included in this study, according to the exclusion criteria. The observation period was from June 2015 to June 2016. Data regarding adverse events, medical devices in place during rehabilitation, protocol adherence, and rehabilitation outcomes were collected. The primary outcome was safety. RESULTS: A total of 232 consecutively enrolled patients underwent 587 rehabilitation sessions. Thirteen adverse events occurred (2.2%; 95% confidence interval, 1.2-3.8%) and no specific treatment was needed. There were no instances of dislodgement or obstruction of medical devices, tubes, or lines. The incidence of adverse events associated with mechanical ventilation or extracorporeal membrane oxygenation (ECMO) was 2.4 and 3.6%, respectively. Of 587 sessions, 387 (66%) sessions were performed at the active rehabilitation level, including sitting out of the bed, active transfer to a chair, standing, marching, and ambulating. ICU physicians attended over 95% of these active rehabilitation sessions. Of all patients, 143 (62%) got out of bed within 2 days (median 1.2 days; interquartile range 0.1-2.0). CONCLUSIONS: EM according to the Maebashi EM protocol conducted by ICU physicians, without a specialized team or EM culture, was performed at a level of safety similar to previous studies performed by specialized teams, even with medical devices in place, including mechanical ventilation or ECMO. Protocolized EM led by ICU physicians can be initiated in the acute phase of critical illness without serious adverse events requiring additional treatment.

A mutant PSEN1 causes dementia with Lewy bodies and variant Alzheimer's disease.

We report early-onset parkinsonism and dementia of 18 years' duration in a 52-year-old man whose grandfather and father had suffered from a similar neurological disease. In this patient, we found neuronal loss in various brain regions including the substantia nigra and cerebral cortex, Lewy bodies, cotton wool plaques, corticospinal tract degeneration, cerebral amyloid angiopathy, and a novel three-base pair deletion in exon 12 of the presenilin-1 (PSEN1) gene. We considered that the mutant PSEN1 might play an important role in the pathogenetic process of both aggregation of alpha-synuclein into Lewy bodies and deposition of beta-amyloid into cotton wool plaques.

Discovery of a novel, potent and selective human beta3-adrenergic receptor agonist.

The discovery of a novel, potent and selective beta(3)-adrenergic receptor (AR) agonist is described. SAR studies demonstrated the structural requirements for activity and selectivity. Compound 1c, which showed good beta(3)-AR activity and selectivity, was identified and pharmacokinetics were investigated.