The skin safety model: Reconceptualizing skin vulnerability in older patients

Purpose: To develop a unique skin safety model (SSM) that offers a new and uni���ed perspective on the diverse yet interconnected antecedents that contribute to a spectrum of potential iatrogenic skin injuries in older hospitalized adults. Organizing Construct: Discussion paper. Methods: A literature search of electronic databases was conducted for published articles written in English addressing skin integrity and iatrogenic skin injury in elderly hospital patients between 1960 and 2014. Findings: There is a multiplicity of literature outlining the etiology, prevention, and management of speci���c iatrogenic skin injuries. Complex and interrelated factors contribute to iatrogenic skin injury in the older adult, including multiple comorbidities, factors in���uencing healthcare delivery, and acute situational stressors. A range of injuries can result when these factors are com- plicated by skin irritants, pressure, shear, or friction; however, despite skin injuries sharing multiple ntecedents, no uni���ed overarching skin safety conceptual model has been published. Conclusions: The SSM presented in this article offers a new, uni���ed framework that encompasses the spectrum of antecedents to skin vulnerability as well as the spectrum of iatrogenic skin injuries that may be sustained by older acute care patients. Current skin integrity frameworks address prevention and management of speci���c skin injuries. In contrast, the SSM recognizes the complex interplay of patient and system factors that may result in a range of iatrogenic skin injuries. Skin safety is reconceptualized into a single model that has the potential for application at the individual patient level, as well as health-care systems and governance levels. Clinical Relevance: Skin safety is concerned with keeping skin safe from any iatrogenic skin injury, and remains an ongoing challenge for healthcare providers. A conceptual framework that encompasses all of the factors that may contribute to a range of iatrogenic skin injuries is essential, and guides the clinician in maintaining skin integrity in the vulnerable older patient.

Pharmacogenetics of SLCO1B1: Population genetics and effect on statins

Kohonneiden kolesterolipitoisuuksien alentamisessa k��ytett��vien statiinien hy��dyt syd��n- ja verisuonisairauksien estossa on vahvasti osoitettu ja niiden k��ytt�� on niin Suomessa kuin muuallakin maailmassa kasvanut voimakkaasti ��� Suomessa statiinink��ytt��ji�� on noin 600 000. Statiinil����kitys on pitk��aikaisessakin k��yt��ss�� melko hyvin siedetty, mutta yleisimpin�� haittavaikutuksina voi ilmet�� lihasheikkoutta, -kipua ja -kramppeja, jotka voivat edet�� jopa henke�� uhkaavaksi lihasvaurioksi. Lihashaittariski suurenee suhteessa statiiniannokseen ja plasman statiinipitoisuuksiin. Statiinien plasmapitoisuuksissa, tehossa ja haittavaikutusten ilmenemisess�� on suuria potilaskohtaisia eroja. SLCO1B1-geenin koodaama OATP1B1-kuljetusproteiini kuljettaa monia elimist��n omia aineita ja l����keaineita verenkierrosta solukalvon l��pi maksasoluun, mm. statiineja, joiden kolesterolia alentava vaikutus ja poistuminen elimist��st�� tapahtuvat p����osin maksassa. Er����n SLCO1B1-geenin nukleotidimuutoksen (c.521T>C) tiedet����n heikent��v��n OATP1B1:n kuljetustehoa. T��ss�� v��it��skirjaty��ss�� selvitettiin SLCO1B1-geenin perinn��llist�� muuntelua suomalaisilla ja eri v��est��iss�� maailmanlaajuisesti. Lis��ksi selvitettiin SLCO1B1:n muunnosten vaikutusta eri statiinien pitoisuuksiin (farmakokinetiikka) ja vaikutuksiin (farmakodynamiikka) sek�� kolesteroliaineenvaihduntaan. N��ihin tutkimuksiin valittiin SLCO1B1-genotyypin perusteella terveit�� vapaaehtoisia koehenkil��it��, joille annettiin eri p��ivin�� kerta-annos kutakin tutkittavaa statiinia: fluvastatiinia, pravastatiinia, simvastatiinia, rosuvastatiinia ja atorvastatiinia. Verin��ytteist�� m����ritettiin plasman statiinien ja niiden aineenvaihduntatuotteiden sek�� kolesterolin ja sen muodostumista ja imeytymist�� kuvaavien merkkiaineiden pitoisuuksia. Toiminnallisesti merkitt��vien SLCO1B1-geenimuunnosten esiintyvyydess�� todettiin suuria eroja eri v��est��jen v��lill��. Suomalaisilla SLCO1B1 c.521TC-genotyypin (geenimuunnos toisessa vastinkromosomissa) esiintyvyys oli noin 32 % ja SLCO1B1 c.521CC-genotyypin (geenimuunnos molemmissa vastinkromosomeissa) esiintyvyys noin 4 %. Globaalisti geenimuunnosten esiintyvyys korreloi maapallon leveyspiirien kanssa siten, ett�� matalaan transportteriaktiivisuuteen johtavat muunnokset olivat yleisimpi�� pohjoisessa ja korkeaan aktiivisuuteen johtavat p��iv��ntasaajan l��hell�� asuvilla v��est��ill��. SLCO1B1-genotyypill�� oli merkitt��v�� vaikutus statiinien plasmapitoisuksiin lukuun ottamatta fluvastatiinia. Simvastatiinihapon plasmapitoisuudet olivat keskim����rin 220 %, atorvastatiinin 140 %, pravastatiinin 90 % ja rosuvastatiinin 70 % suuremmat c.521CC-genotyypin omaavilla koehenkil��ill�� verrattuna normaalin c.521TT-genotyypin omaaviin. Genotyypill�� ei ollut merkitt��v���� vaikutusta mink����n statiinin tehoon t��ss�� kerta-annostutkimuksessa, mutta geenimuunnoksen kantajilla perustason kolesterolisynteesinopeus oli suurempi. Tulokset osoittavat, ett�� SLCO1B1 c.521T>C geenimuunnos on varsin yleinen suomalaisilla ja muilla ei-afrikkalaisilla v��est��ill��. T��m�� geenimuunnos voi altistaa erityisesti simvastatiinin, mutta my��s atorvastatiinin, pravastatiinin ja rosuvastatiinin, aiheuttamille lihashaitoille suurentamalla niiden plasmapitoisuuksia. SLCO1B1:n geenimuunnoksen testaamista voidaan tulevaisuudessa k��ytt���� apuna valittaessa sopivaa statiinil����kityst�� ja -annosta potilaalle, ja n��in parantaa sek�� statiinihoidon turvallisuutta ett�� tehoa.

Myoblast transplantation and adenoviral VEGF-C transfer in porcine model of coronary artery disease

Heart failure is a common and highly challenging medical disorder. The progressive increase of elderly population is expected to further reflect in heart failure incidence. Recent progress in cell transplantation therapy has provided a conceptual alternative for treatment of heart failure. Despite improved medical treatment and operative possibilities, end-stage coronary artery disease present a great medical challenge. It has been estimated that therapeutic angiogenesis would be the next major advance in the treatment of ischaemic heart disease. Gene transfer to augment neovascularization could be beneficial for such patients. We employed a porcine model to evaluate the angiogenic effect of vascular endothelial growth factor (VEGF)-C gene transfer. Ameroid-generated myocardial ischemia was produced and adenovirus encoding (ad)VEGF-C or ��-galactosidase (LacZ) gene therapy was given intramyocardially during progressive coronary stenosis. Angiography, positron emission tomography (PET), single photon emission computed tomography (SPECT) and histology evidenced beneficial affects of the adVEGF-C gene transfer compared to adLacZ. The myocardial deterioration during progressive coronary stenosis seen in the control group was restrained in the treatment group. We observed an uneven occlusion rate of the coronary vessels with Ameroid constrictor. We developed a simple methodological improvement of Ameroid model by ligating of the Ameroid���stenosed coronary vessel. Improvement of the model was seen by a more reliable occlusion rate of the vessel concerned and a formation of a rather constant myocardial infarction. We assessed the spontaneous healing of the left ventricle (LV) in this new model by SPECT, PET, MRI, and angiography. Significant spontaneous improvement of myocardial perfusion and function was seen as well as diminishment of scar volume. Histologically more microvessels were seen in the border area of the lesion. Double staining of the myocytes in mitosis indicated more cardiomyocyte regeneration at the remote area of the lesion. The potential of autologous myoblast transplantation after ischaemia and infarction of porcine heart was evaluated. After ligation of stenosed coronary artery, autologous myoblast transplantation or control medium was directly injected into the myocardium at the lesion area. Assessed by MRI, improvement of diastolic function was seen in the myoblast-transplanted animals, but not in the control animals. Systolic function remained unchanged in both groups.

Soy supplementation and role of equol production capability in postmenopausal women using tibolone: effects on cardiovascular risk markers

Tibolone, a synthetic steroid, is effective in the treatment of postmenopausal symptoms. Its cardiovascular safety profile has been questioned, because tibolone reduces the levels of high-density lipoprotein (HDL) cholesterol. Soy-derived isoflavones may offer health benefits, particularly as regards lipids and also other cardiovascular disease (CVD) risk factors. The soy-isoflavone metabolite equol is thought to be the key as regards soy-related beneficial effects. We studied the effects of soy supplementation on various CVD risk factors in postmenopausal monkeys and postmenopausal women using tibolone. In addition, the impact of equol production capability was studied. A total of 18 monkeys received casein/lactalbumin (C/L) (placebo), tibolone, soy (a woman s equivalent dose of 138 mg of isoflavones), or soy with tibolone in a randomized order for 14 weeks periods, and there was a 4-week washout (C/L) in between treatments. Postmenopausal women using tibolone (N=110) were screened by means of a one-week soy challenge to find 20 women with equol production capability (4-fold elevation from baseline equol level) and 20 control women, and treated in a randomized cross-over trial with a soy powder (52 g of soy protein containing 112 mg of isoflavones) or placebo for 8 weeks. Before and after the treatments lipids and lipoproteins were assessed in both monkeys and women. In addition, blood pressure, arterial stiffness, endothelial function, sex steroids, sex hormone-binding globulin (SHBG), and vascular inflammation markers were assessed. A 14% increase in plasma low-density lipoprotein (LDL) + very low-density lipoprotein (VLDL) cholesterol was observed in tibolone-treated monkeys vs. placebo. Soy treatment resulted in a 18% decrease in LDL+VLDL cholesterol, and concomitant supplementation with tibolone did not negate the LDL+VLDL cholesterol-lowering effect of soy. A 30% increase in HDL cholesterol was observed in monkeys fed with soy, whereas HDL cholesterol levels were reduced (48%) after tibolone. Interestingly, Soy+Tibolone diet conserved HDL cholesterol levels. Tibolone alone increased the total cholesterol (TC):HDL cholesterol ratio, whereas it was reduced by Soy or Soy+Tibolone. In postmenopausal women using tibolone, reductions in the levels of total cholesterol and LDL cholesterol were seen after soy supplementation compared with placebo, but there was no effect on HDL cholesterol, blood pressure, arterial stiffness or endothelial function. Soy supplementation decreased the levels of estrone in equol producers, and those of testosterone in the entire study population. No changes were seen in the levels of androstenedione, dehydroepiandrosterone sulfate, or SHBG. The levels of vascular cell adhesion molecule-1 increased, and platelet-selectin decreased after soy treatment, whereas C-reactive protein and intercellular adhesion molecule-1 remained unchanged. At baseline and unrelated to soy treatment, equol producers had lower systolic, diastolic and mean arterial pressures, less arterial stiffness and better endothelial function than non-producers. To conclude, soy supplementation reversed the tibolone-induced fall in HDL cholesterol in postmenopausal monkeys, but this effect was not seen in women taking tibolone. Equol production capability was associated with beneficial cardiovascular changes and thus, this characteristic may offer cardiovascular benefits, at least in women using tibolone.

Stabilization of an All-Metal Antiaromatic Molecule (Al4Li4) Using BH and C as Caps

It has been reported by Pati et al. (J. Am. Chem. Soc. 2005, 127, 3496) that coordination with a transition metal can stabilize the ���antiaromatic���, all-metal compound Al4Li4. Here, we report that it can also be stabilized by capping with a main group element like C and its isoelectronic species BH. Our calculations of binding energy, nuclear independent chemical shift, energy decomposition analysis, and molecular orbital analysis support the capping-induced stability, reduction of bond length alternation, and increase of aromaticity of these BH/C-capped Al4Li4 systems. The interaction between px and py orbitals of BH/C and the HOMO and LUMO of Al4Li4 is responsible for the stabilization. Our calculations suggest that capping can introduce fluxionality at room temperature.

General Practitioner Antimicrobial Stewardship Programme Study (GAPS): protocol for a cluster randomised controlled trial

Background There is a strong link between antibiotic consumption and the rate of antibiotic resistance. In Australia, the vast majority of antibiotics are prescribed by general practitioners, and the most common indication is for acute respiratory infections. The aim of this study is to assess if implementing a package of integrated, multifaceted interventions reduces antibiotic prescribing for acute respiratory infections in general practice. Methods/design This is a cluster randomised trial comparing two parallel groups of general practitioners in 28 urban general practices in Queensland, Australia: 14 intervention and 14 control practices. The protocol was peer-reviewed by content experts who were nominated by the funding organization. This study evaluates an integrated, multifaceted evidence-based package of interventions implemented over a six month period. The included interventions, which have previously been demonstrated to be effective at reducing antibiotic prescribing for acute respiratory infections, are: delayed prescribing; patient decision aids; communication training; commitment to a practice prescribing policy for antibiotics; patient information leaflet; and near patient testing with C-reactive protein. In addition, two sub-studies are nested in the main study: (1) point prevalence estimation carriage of bacterial upper respiratory pathogens in practice staff and asymptomatic patients; (2) feasibility of direct measures of antibiotic resistance by nose/throat swabbing. The main outcome data are from Australia���s national health insurance scheme, Medicare, which will be accessed after the completion of the intervention phase. They include the number of antibiotic prescriptions and the number of patient visits per general practitioner for periods before and during the intervention. The incidence of antibiotic prescriptions will be modelled using the numbers of patients as the denominator and seasonal and other factors as explanatory variables. Results will compare the change in prescription rates before and during the intervention in the two groups of practices. Semi-structured interviews will be conducted with the general practitioners and practice staff (practice nurse and/or practice manager) from the intervention practices on conclusion of the intervention phase to assess the feasibility and uptake of the interventions. An economic evaluation will be conducted to estimate the costs of implementing the package, and its cost-effectiveness in terms of cost per unit reduction in prescribing. Discussion The results on the effectiveness, cost-effectiveness, acceptability and feasibility of this package of interventions will inform the policy for any national implementation.

Leading Digital Transformation: Building Technology and Information Governance Capability in Boards of Directors and the C-Suite

Information and technology and its use in organisation transformation presents unprecedented opportunities and risks. Increasingly, the Governance of Enterprise Information and Technology (GEIT) competency in the board room and executive is needed. Whether your organization is small or large, public, private or not for profit or whether your industry is not considered high-tech, IT is impacting your sector ��� no exceptions. But there is a skill shortage in boards: GEIT capability is concerningly low. This capability is urgently needed across the board, including those directors who come from finance, legal, marketing, operations and HR backgrounds. Digital disruption also affects all occupations. Putting in place a vision will help ensure emergency responses will meet technology-related duty of care responsibilities. When GEIT-related forward thinking and planning is carried out at the same time that you put your business strategy and plan in place, your organization has a significantly increased chance of not only surviving, but thriving into the future. Those organizations that don���t build GEIT capability risk joining the growing list of once-leading firms left behind in the digital ���cloud of smoke���. Those organizations that do will be better placed to reap the benefits and hedge against the risks of a digital world. This chapter provides actionable, research-based considerations and processes for boards to use, to build awareness, knowledge and skills in governing technology-related organization strategy, risk and value creation.

Conformationally restricted formyl methionyl tripeptide chemoattractants: a three-dimensional structure-activity study of analogs incorporating a C alpha,alpha-dialkylated glycine at position 2

The conformationally restricted CHO-L-Met-Xxx-L-Phe-OY (where Xxx = Aib, Ac3c, Ac5c, Ac6c, and Ac7c; Y = H, Me) tripeptides, analogs of the chemoattractant CHO-L-Met-L-Leu-L-Phe-OH, have been synthesized in solution by classical methods and fully characterized. Compounds were compared to determine the combined effect of backbone conformational preferences and side-chain bulkiness on the relation of three-dimensional structure to biological activity. Each peptide was tested for its ability to induce granule enzyme secretion from rabbit peritoneal polymorphonuclear leukocytes. In parallel, a conformational analysis on the CHO-blocked peptide and their tertbutyloxycarbonylated synthetic precursors was performed in the crystal state and in solution using X-ray diffraction, infrared absorption, and 1H nuclear magnetic resonance. The biological and conformational data are discussed in relation to the proposed model of the chemotactic peptide receptor of rabbit neutrophils.

Stereochemistry of peptides containing 1-aminocycloheptane-1-carboxylic acid (Ac-c)

The crystal structures of four peptides incorporating 1-aminocycloheptane-1-carboxylic acid (Ac7c) are described. Boc-Aib-Ac7c-NHMe and Boc-Pro-Ac7c-Ala-OMe adopt beta-turn conformations stabilized by an intramolecular 4----1 hydrogen bond, the former folding into a type-I/III beta-turn and the latter into a type-II beta-turn. In the dipeptide esters, Boc-Aib-Ac7c-OMe and Boc-Pro-Ac7c-OMe, the Ac7c and Aib residues adopt helical conformations, while the Pro residue remains semi-extended in both the molecules of Boc-Pro-Ac7c-OMe found in the asymmetric unit. The cycloheptane ring of Ac7c residues adopts a twist-chair conformation in all the peptides studied. 1H-NMR studies in CDCl3 and (CD3)2SO and IR studies in CDCl3 suggest that Boc-Aib-Ac7c-NHMe and Boc-Pro-Ac7c-Ala-OMe maintain the beta-turn conformations in solution.