A state-wide implementation of a whole of hospital sepsis pathway with a mortality based cost-effectiveness analysis from a healthcare sector perspective.

With global estimates of 15 million cases of sepsis annually, together with a 24% in-hospital mortality rate, this condition comes at a high cost to both the patient and to the health services delivering care. This translational research determined the cost-effectiveness of state-wide implementation of a whole of hospital Sepsis Pathway in reducing mortality and/or hospital admission costs from a healthcare sector perspective, and report the cost of implementation over 12-months. A non-randomised stepped wedge cluster implementation study design was used to implement an existing Sepsis Pathway ("Think sepsis. Act fast") across 10 of Victoria's public health services, comprising 23 hospitals, which provide hospital care to 63% of the State's population, or 15% of the Australian population. The pathway utilised a nurse led model with early warning and severity criteria, and actions to be initiated within 60 minutes of sepsis recognition. Pathway elements included oxygen administration; blood cultures (x2); venous blood lactate; fluid resuscitation; intravenous antibiotics, and increased monitoring. At baseline there were 876 participants (392 female (44.7%), mean 68.4 years); and during the intervention, there were 1,476 participants (684 female (46.3%), mean 66.8 years). Mortality significantly reduced from 11.4% (100/876) at baseline to 5.8% (85/1,476) during implementation (p>0.001). Respectively, at baseline and intervention the average length of stay was 9.1 (SD 10.3) and 6.2 (SD 7.9) days, and cost was $AUD22,107 (SD $26,937) and $14,203 (SD $17,611) per patient, with a significant 2.9 day reduction in length of stay (-2.9; 95%CI -3.7 to -2.2, p<0.01) and $7,904 reduction in cost (-$7,904; 95%CI -$9,707 to -$6,100, p<0.01). The Sepsis Pathway was a dominant cost-effective intervention due to reduced cost and reduced mortality. Cost of implementation was $1,845,230. In conclusion, a well-resourced state-wide Sepsis Pathway implementation initiative can save lives and dramatically reduce the health service cost per admission.

An Ai Chi-based aquatic group improves balance and reduces falls in community-dwelling adults: A pilot observational cohort study.

BACKGROUND: Falls are associated with morbidity, loss of independence, and mortality. While land-based group exercise and Tai Chi programs reduce the risk of falls, aquatic therapy may allow patients to complete balance exercises with less pain and fear of falling; however, limited data exist. OBJECTIVE: The objective of the study was to pilot the implementation of an aquatic group based on Ai Chi principles (Aquabalance) and to evaluate the safety, intervention acceptability, and intervention effect sizes. DESIGN: Pilot observational cohort study. METHODS: Forty-two outpatients underwent a single 45-minute weekly group aquatic Ai Chi-based session for eight weeks (Aquabalance). Safety was monitored using organizational reporting systems. Patient attendance, satisfaction, and self-reported falls were also recorded. Balance measures included the Timed Up and Go (TUG) test, the Four Square Step Test (FSST), and the unilateral Step Tests. RESULTS: Forty-two patients completed the program. It was feasible to deliver Aquabalance, as evidenced by the median (IQR) attendance rate of 8.0 (7.8, 8.0) out of 8. No adverse events occurred and participants reported high satisfaction levels. Improvements were noted on the TUG, 10-meter walk test, the Functional Reach Test, the FSST, and the unilateral step tests (p < 0.05). The proportion of patients defined as high falls risk reduced from 38% to 21%. The study was limited by its small sample size, single-center nature, and the absence of a control group. CONCLUSIONS: Aquabalance was safe, well-attended, and acceptable to participants. A randomized controlled assessor-blinded trial is required.

Sterol-induced dislocation of 3-hydroxy-3-methylglutaryl coenzyme A reductase from membranes of permeabilized cells.

The polytopic endoplasmic reticulum (ER)-localized enzyme 3-hydroxy-3-methylglutaryl CoA reductase catalyzes a rate-limiting step in the synthesis of cholesterol and nonsterol isoprenoids. Excess sterols cause the reductase to bind to ER membrane proteins called Insig-1 and Insig-2, which are carriers for the ubiquitin ligases gp78 and Trc8. The resulting gp78/Trc8-mediated ubiquitination of reductase marks it for recognition by VCP/p97, an ATPase that mediates subsequent dislocation of reductase from ER membranes into the cytosol for proteasomal degradation. Here we report that in vitro additions of the oxysterol 25-hydroxycholesterol (25-HC), exogenous cytosol, and ATP trigger dislocation of ubiquitinated and full-length forms of reductase from membranes of permeabilized cells. In addition, the sterol-regulated reaction requires the action of Insigs, is stimulated by reagents that replace 25-HC in accelerating reductase degradation in intact cells, and is augmented by the nonsterol isoprenoid geranylgeraniol. Finally, pharmacologic inhibition of deubiquitinating enzymes markedly enhances sterol-dependent ubiquitination of reductase in membranes of permeabilized cells, leading to enhanced dislocation of the enzyme. Considered together, these results establish permeabilized cells as a viable system in which to elucidate mechanisms for postubiquitination steps in sterol-accelerated degradation of reductase.