Implementation of a multicomponent intervention to optimise patient safety through improved oxygen prescription in a rural hospital.

OBJECTIVE: To rationalise oxygen procedures in adult medical and surgical inpatients with a view to improving patient safety. DESIGN: Prospective pre- and post-intervention audit. SETTING: Manning Hospital, a rural referral hospital in Taree NSW. PARTICIPANTS: Pre-intervention: 82 patients aged 72.7 ± 14.7 years. Post-intervention: 77 patients aged 73.6 ± 12.4 years. INTERVENTION: A multicomponent intervention composed of implementation of a local hospital oxygen policy, introduction of a specific oxygen prescription chart and targeted staff education. MAIN OUTCOME MEASURES: Satisfactory oxygen prescription, monitoring and titration. RESULTS: Only 2/82 (2.4%) patients had satisfactory oxygen prescription specifying target saturation, device and initial flow rate before the intervention compared with 26/77 (34%) patients post-intervention (χ(2) = 56.88, df = 5, P < 0.0001). Percentage of patients with conditions predisposing to hypercapnic respiratory failure who were overtreated with oxygen dropped from 9/19 (47%) to 4/22 (18%) following the study intervention (χ(2) = 4.011, df = 1, P = 0.04). Oxygen therapy monitoring was satisfactory during the audit period, but oxygen titration was unsatisfactory and did not significantly improve following the intervention. CONCLUSIONS: A multicomponent intervention can achieve a significantly increased rate of satisfactory oxygen prescriptions specifying target saturation, including in those who are at risk of hypercapnic respiratory failure.

Filaggrin deficiency confers a paracellular barrier abnormality that reduces inflammatory thresholds to irritants and haptens.

BACKGROUND: Mutations in the human filaggrin gene (FLG) are associated with atopic dermatitis (AD) and are presumed to provoke a barrier abnormality. Yet additional acquired stressors might be necessary because the same mutations can result in a noninflammatory disorder, ichthyosis vulgaris. OBJECTIVE: We examined here whether FLG deficiency alone suffices to produce a barrier abnormality, the basis for the putative abnormality, and its proinflammatory consequences. METHODS: By using the flaky-tail mouse, which lacks processed murine filaggrin because of a frameshift mutation in the gene encoding profilaggrin that mimics some mutations in human AD, we assessed whether FLG deficiency provokes a barrier abnormality, further localized the defect, identified its subcellular basis, and assessed thresholds to irritant- and hapten-induced dermatitis. RESULTS: Flaky-tail mice exhibit low-grade inflammation with increased bidirectional, paracellular permeability of water-soluble xenobiotes caused by impaired lamellar body secretion and altered stratum corneum extracellular membranes. This barrier abnormality correlates with reduced inflammatory thresholds to both topical irritants and haptens. Moreover, when exposed repeatedly to topical haptens at doses that produce no inflammation in wild-type mice, flaky-tail mice experience a severe AD-like dermatosis with a further deterioration in barrier function and features of a T(H)2 immunophenotype (increased CRTH levels plus inflammation, increased serum IgE levels, and reduced antimicrobial peptide [mBD3] expression). CONCLUSIONS: FLG deficiency alone provokes a paracellular barrier abnormality in mice that reduces inflammatory thresholds to topical irritants/haptens, likely accounting for enhanced antigen penetration in FLG-associated AD.

Epidermal vascular endothelial growth factor production is required for permeability barrier homeostasis, dermal angiogenesis, and the development of epidermal hyperplasia: implications for the pathogenesis of psoriasis.

Primary abnormalities in permeability barrier function appear to underlie atopic dermatitis and epidermal trauma; a concomitant barrier dysfunction could also drive other inflammatory dermatoses, including psoriasis. Central to this outside-inside view of disease pathogenesis is the epidermal generation of cytokines/growth factors, which in turn signal downstream epidermal repair mechanisms. Yet, this cascade, if sustained, signals downstream epidermal hyperplasia and inflammation. We found here that acute barrier disruption rapidly stimulates mRNA and protein expression of epidermal vascular endothelial growth factor-A (VEGF-A) in normal hairless mice, a specific response to permeability barrier requirements because up-regulation is blocked by application of a vapor-impermeable membrane. Moreover, epidermal vegf(-/-) mice display abnormal permeability barrier homeostasis, attributable to decreased VEGF signaling of epidermal lamellar body production; a paucity of dermal capillaries with reduced vascular permeability; and neither angiogenesis nor epidermal hyperplasia in response to repeated tape stripping (a model of psoriasiform hyperplasia). These results support a central role for epidermal VEGF in the maintenance of epidermal permeability barrier homeostasis and a link between epidermal VEGF production and both dermal angiogenesis and the development of epidermal hyperplasia. Because psoriasis is commonly induced by external trauma [isomorphic (Koebner) phenomenon] and is associated with a prominent permeability barrier abnormality, excess VEGF production, prominent angiogenesis, and epidermal hyperplasia, these results could provide a potential outside-inside mechanistic basis for the development of psoriasis.

The Association Between Obesity and Cognitive Function in Older Persons: How Much Is Mediated by Inflammation, Fasting Plasma Glucose, and Hypertriglyceridemia?

BACKGROUND: The aim of the study was to determine how much of the association between obesity, measured by body mass index (BMI), and cognition in older persons is mediated through inflammation, fasting plasma glucose, and hypertriglyceridemia. METHODS: Anthropometrics, high-sensitivity C-reactive protein (CRP), fasting plasma glucose, and serum triglycerides were measured in 3,256 community-dwelling individuals aged 55-85 years residing in Newcastle, New South Wales, Australia. Audio recorded cognitive screen (ARCS) was used to assess multiple cognitive domains. RESULTS: Mediation analyses showed very modest but significant direct mediation effects, whereby obesity was associated with better cognitive function after adjusting for potential confounders (controlled direct effect ≈ 1/500 point increase in the total ARCS score per 1.0-kg/m2 increase in BMI). There were significant indirect negative mediation effects from BMI to cognition mediated through CRP, that is, increased BMI was associated with increased CRP which was associated with decreased cognition (natural indirect effect -0.20 unit; 95% confidence interval [CI] -0.39, -0.02), and through fasting plasma glucose, that is, increased BMI was associated with increased fasting plasma glucose which was associated with decreased cognition (natural indirect effect -0.12 unit; 95% CI -0.24, -0.01], but not through serum triglycerides. CONCLUSIONS: There is a weak positive association between obesity and cognitive performance in older persons, which is partially antagonized by inflammation and elevated fasting plasma glucose, but not hypertriglyceridemia. Further studies are needed to elucidate whether this is due to selection bias, or truly reflects biologically complex and counter balancing pathways involved in obesity.

The Human Epidermal Antimicrobial Barrier: Current Knowledge, Clinical Relevance and Therapeutic Implications.

Most of the defensive functions of the human skin are localized to the stratum corneum (SC), the outermost layer of the epidermis consisting of several layers of cornified keratinocytes embedded in a lipid matrix. Included in the armamentarium of the epidermal barrier against microbial invasion are surface pH, SC lipids, specialized antimicrobial peptides such as defensins and cathelicidins, enzymes and enzyme inhibitors, chemokines, and epidermal Toll-like receptors. Multiple epidermal defensive mechanisms are co-localized, coregulated, and intertwined. The purpose of this review is to discuss patents and to describe the current knowledge that concerns the role of the epidermis as an antimicrobial barrier, outlining potential clinical and therapeutic implications.

Pasteurella Multocida Peritonitis After Cat Scratch in a Patient with Cirrhotic Ascites.

Pasteurella multocida, a zoonotic agent transmitted by canines and felines, has been very rarely reported to cause bacterial peritonitis in humans. Pasteurella multocida peritonitis is associated with high mortality even with appropriate treatment, therefore its early recognition is essential. We report a case of Pasteurella multocida peritonitis following cat scratch in a patient with Child Pugh Class C alcoholic cirrhosis, culminating in multiple organ failure and death.

pH-regulated mechanisms account for pigment-type differences in epidermal barrier function.

To determine whether pigment type determines differences in epidermal function, we studied stratum corneum (SC) pH, permeability barrier homeostasis, and SC integrity in three geographically disparate populations with pigment type I-II versus IV-V skin (Fitzpatrick I-VI scale). Type IV-V subjects showed: (i) lower surface pH (approximately 0.5 U); (ii) enhanced SC integrity (transepidermal water loss change with sequential tape strippings); and (iii) more rapid barrier recovery than type I-II subjects. Enhanced barrier function could be ascribed to increased epidermal lipid content, increased lamellar body production, and reduced acidity, leading to enhanced lipid processing. Compromised SC integrity in type I-II subjects could be ascribed to increased serine protease activity, resulting in accelerated desmoglein-1 (DSG-1)/corneodesmosome degradation. In contrast, DSG-1-positive CDs persisted in type IV-V subjects, but due to enhanced cathepsin-D activity, SC thickness did not increase. Adjustment of pH of type I-II SC to type IV-V levels improved epidermal function. Finally, dendrites from type IV-V melanocytes were more acidic than those from type I-II subjects, and they transfer more melanosomes to the SC, suggesting that melanosome secretion could contribute to the more acidic pH of type IV-V skin. These studies show marked pigment-type differences in epidermal structure and function that are pH driven.