Implementing a cirrhosis order set in a tertiary healthcare system: a theory-informed formative evaluation.

BACKGROUND: Standardized order sets are a means of increasing adherence to clinical practice guidelines and improving the quality of patient care. Implementation of novel quality improvement initiatives like order sets can be challenging. Before the COVID-19 pandemic, we conducted a formative evaluation to understand healthcare providers' perspectives on implementing clinical changes and the individual, collective and organizational contextual factors that might impact implementation at eight hospital sites in Alberta, Canada. METHODS: We utilized concepts from the Consolidated Framework for Implementation Research (CFIR) and Normalisation Process Theory (NPT) to understand the context, past implementation experiences, and perceptions of the cirrhosis order set. Eight focus groups were held with healthcare professionals caring for patients with cirrhosis. Data were coded deductively using relevant constructs of NPT and CFIR. A total of 54 healthcare professionals, including physicians, nurses, nurse practitioners, social workers and pharmacists and a physiotherapist, participated in the focus groups. RESULTS: Key findings revealed that participants recognized the value of the cirrhosis order set and its potential to improve the quality of care. Participants highlighted potential implementation challenges, including multiple competing quality improvement initiatives, feelings of burnout, lack of communication between healthcare provider groups, and a lack of dedicated resources to support implementation. CONCLUSIONS: Implementing a complex improvement initiative across clinician groups and acute care sites presents challenges. This work yielded insights into the significant influence of past implementation of similar interventions and highlighted the importance of communication between clinician groups and resources to support implementation. However, by using multiple theoretical lenses to illuminate what and how contextual and social processes will influence uptake, we can better anticipate challenges during the implementation process.

A thromboxane effect of a hydroxytyrosol-rich olive oil wastewater extract in patients with uncomplicated type I diabetes.

OBJECTIVE: To assess the antioxidant/non-antioxidant effects of a hydroxytyrosol (HT)-rich phenolic extract from olive mill wastewaters administered with a breakfast. DESIGN, SETTING AND SUBJECTS: Five type I diabetic patients received 25 mg of HT the first day and 12.5 mg/day the following 3 days. Blood sampling was carried out at T(0) (baseline) and T(4d) just before the breakfast + HT administration and at time points 1, 2, 3 and 4 h after T(0). Urines (24-h) were collected from T(0) to T(4d). Baseline HbA1c was generally inferior to 10%, glycemia was within the range 6-24 mmol/l, whereas total cholesterol, HDL-chol and triglycerides were normal. RESULTS: The major finding was the 46% decrease in the serum TXB(2) production after blood clotting at T(4d). Plasma vitamin A, E, beta-carotene were not changed. Vitamin C tended to increase (P = 0.075). Plasma antioxidant capacity was enhanced at T(0)+1 h only, whereas its main determinants (albumin, bilirubin, uric acid) were not modified. Urinary 8-isoPGF(2alpha) levels were highly variable and were not affected significantly by HT administration. CONCLUSION: The major effect of HT accounts for an antiaggregating platelet action, leading to a possible prevention of thrombotic and microthrombotic processes.

Lipoperoxidation in plasma and red blood cells of patients undergoing haemodialysis: vitamins A, E, and iron status.

In 14 patients undergoing haemodialysis, lipoperoxidation (LPO) processes were determined in plasma and red blood cells (RBC) before and after a dialysis session by determining (a) the direct substrate, polyunsaturated fatty acids (PUFA); (b) the end product of LPO, malondialdehyde (MDA); and (c) the hydrophobic antioxidant systems, vitamins A and E. In plasma before dialysis, linoleic and arachidonic acid, and the antioxidant vitamin E, were significantly lowered as compared to the healthy controls (p < 0.05). On the contrary, the free MDA level was enhanced (p < 0.05). These results were emphasized by a dialysis session. In RBC of these patients, no difference in linoleic acid, free MDA, or vitamin E level were observed before or after dialysis when compared to controls. However, only vitamin A was significantly higher in haemodialysis patients (before and after dialysis) and in renal failure patients (p < 0.05) than in the healthy control group. The present results suggest that increased RBC vitamin A may offer some degree of protection against oxidative stress in erythrocytes, but not in plasma where LPO is demonstrated.

Fatty acids and carbohydrate-containing lipids in four Micrococcaceae strains.

Fatty acid composition and lipidic carbohydrate to lipidic phosphorus molar ratio of yellow pigmented micrococci are compared to red pigmented ones and may be summarized by three indexes. These bacteria show wide differences in their fatty acid composition: three strains possess saturated branched chain fatty acids and one has unsaturated straight chain ones. A significant increase in 'anteiso/iso indexes' is observed between pink (M. roseus) and yellow colored bacteria (M. lysodeikticus, S. lutea). There is no significant difference (P greater than 0.05) between the 'unsaturation indexes' of the red pigmented parental D. radiodurans strain and its colorless mutant. Radioresistant strains exhibit a higher 'carbohydrate/phosphorus index' than other strains. There seems to be a relationship between a high carbohydrate-containing lipid content and a high resistance to physical and chemical agents, in particular to radiations. These differences observed in the lipid composition have implications in taxonomy and in establishing an evolutionary scheme.

Polar lipids from the radiation resistant bacterium Deinococcus radiodurans: structural investigations on glucosaminyl and N-acetyl glucosaminyl lipids.

Deinococcus radiodurans, although a gram-positive bacterium, has a complex cell wall with multiple layers and associates to this structural particularity, a quite unusual lipid composition for gram-positive bacteria. The conventional phospholipids (phosphatidyl ethanolamine, phosphatidyl choline, phosphatidyl glycerol...) are absent. Among the nine polar lipids detected in the R1 Anderson strain, three are glycolipids only one is a phospholipid, the other ones are glycophospholipids. One of the latter compounds contains one free amino group. Analysis by aminoacid autoanalyser enables to identify glucosamine in one glycolipid and in two glycophospholipids. Sugar analysis by gas-liquid chromatography after acid methanolysis and trifluoroacetylation, reveals the occurrence of N-acetyl glucosaminyl residues in one glycolipid and in one phospholipid. The following identification for the two lipids of D. radiodurans is proposed: phosphatidyl glucosaminyl glycerol and phosphatidyl N-acetyl glucosaminyl glycerol.

Lipid composition, lipid fluidity and radioresistance of Deinococcus radiodurans and two mutant strains.

The lipid composition of D. radiodurans strain R1 and of two mutant strains has been studied in relation to membrane fluidity and sensitivity to X-ray radiation. No significant difference in the unsaturation degree of fatty acids was found between parental and mutant strains. An important decrease of carbohydrate-containing lipids was observed in the radiosensitive mutant strain. We also observed a higher fluidity in both mutant strains than in the parental one. Modification of membrane lipid fluidity by growing the parental strain at 39 degrees C did not lead to modified radioresistance. These results suggest that a particular chemical composition of the membrane leading to a special lipid phase may be an important parameter in controlling radiosensitivity.

Supplementation with wine phenolic compounds increases the antioxidant capacity of plasma and vitamin E of low-density lipoprotein without changing the lipoprotein Cu(2+)-oxidizability: possible explanation by phenolic location.

OBJECTIVES: To evaluate the effect of the red wine phenolic compound (RWPC) dietary supplementation without alcohol interference on: (1) some of the biochemical characteristics of LDL, (2) the oxidative susceptibility of LDL and (3) the antioxidant capacity of total plasma (Pl-AOC). In order to account for discrepancies between the three series of data, the in vitro stability of the association of phenolic compounds and LDL was tested. DESIGN: An intervention study with 20 volunteers. Each served as his own control. Cu(2+)-oxidizability of LDL and Pl-AOC were tested on blood samples before and after dietary supplementation. Cu(2+)-oxidizability of LDL was also tested by co-incubation in the presence of RWPC or phenolic acids with or without extensive dialysis. SETTING: The Laboratory of Lipid Biochemistry and Biology, School of Medicine, and the Laboratory of Metabolic Diseases, Lapeyronie Hospital, University of Montpellier, France. SUBJECTS: Healthy males, nonsmokers and moderate drinkers, submitted to a dietary regimen deprived of vitamin E and C for a period of 10 d before supplementation. They also abstained from alcohol, wine, fruit juices, coffee, tea and cola beverages during this period. INTERVENTION: Six 0.33 g capsules/d (namely two capsules at each meal) of a preparation of red wine phenolic compounds in a dry powder form were given to the volunteers over a period of two weeks. Blood samples were drawn in fasting conditions at day 0 and day 14 of the supplementation period. RESULTS: Supplementation led to: (1) in LDL, a significant increase in vitamin E content (n = 20, P = 0.01) or vitamin E/total fatty acid bis-allylic carbon number ratio (n = 20, P = 0.006) without modification in the other biochemical characteristics or Cu(2+)-oxidizability; (2) in plasma, a significant increase in the antioxidant capacity (n = 11, P = 0.01). In vitro studies showed that RWPC or sinapic, caffeic or ferulic acids incubated in the presence of LDL increased the protection of the lipoparticle against oxidation (caffeic > sinapic > ferulic). This effect, however, was totally lost after extensive dialysis. CONCLUSIONS: The enhancing effect of the RWPC supplementation on Pl-AOC may be due to a phenolic-compound action both in the aqueous phase of plasma and at the surface of lipoprotein particles. Surface location possibly explains the enhancing-sparing effect of supplementation on LDL vitamin E and the absence of effect on dialysed-LDL oxidizability.

[The impact of a food service in the school milieu on the quality of nutrition in children]. / L'impact d'un service alimentaire en milieu scolaire sur la qualité de l'alimentation des enfants.

The food service at the Le Tremplin school (QC), which is managed by a non-profit organization including parents and members of the community, was evaluated in terms of its impact on the nutritional quality of the meals consumed by the students from the point of view of the prevention of cardiovascular diseases (CVDs) in children. This was done by comparing it with a traditional food service operated by a concessionnaire. On the nutritional level, the menus offered in the two schools were comparable: in both cases, they fell far short of meeting nutritional recommendations related to the prevention of CVDs. In other respects, the nutritional value of the meals consumed by the children differed according to the school. It was closer to meeting recommendations in the case of the Le Tremplin school. The results obtained show that the organization of the food service at the Le Tremplin school appears to favour a more adequate consumption of lipids and carbohydrates, as well as a more appropriate distribution of the different fatty acids in the food.

[Demonstration of the anti-lipid peroxidation effect of 3',5,7-trihydroxy-4'-methoxy flavone rutinoside: in vitro study]. / Mise en évidence de l'effet antilipoperoxydant du 7 rutinoside de la 3',5,7-trihydroxy-4'-methoxy flavone: étude in vitro.

Diosmin (DI) 3'5,7-trihydroxy-4'-methoxy flavone rutinoside is a member of the flavonoid family, some of whom have antioxidant or free radical scavenger properties. Paw oedema induced by doxorubicin in rats is reduced by DI as observed by SAUVAIRE et al (1989). This suggests a free radical scavenger activity for DI. In this work we demonstrate that such activity is able to protect isolated human LDL from oxidation in vitro. The study of the electrophoretic mobility of oxidized LDL and of total-MDA values as lipoperoxidation-marker indicates an oxidation inhibiting effect higher than 70% for 0.16 mM DI in LDL mixtures containing 50 mM Cu2+ or 4.3 mU/ml xanthine-oxidase and incubated during 20 and 6 hours respectively. Owing to the high level of the oxidizing conditions and the vitamin E (48 mM), vitamin A (1.4 mM) and beta-carotene (2.4 mM) content of the LDL mixtures, it is concluded that DI is clearly able to complement the antioxidant effect of isoprenoids which are naturally present in LDL mixtures.

[First observations on the main plasma parameters of oxidative stress in homozygous sickle cell disease]. / Premières observations sur les principaux paramètres plasmatiques du stress oxydatif chez le drépanocytaire homozygote.

The present study report 7 cases of sickle homozygous disease which have been analysed using markers of the oxidative-stress, 26 african male subjects were studied: 7 Hb SS subjects (age: m = 20) and 19 control subjects (Hb AA, age: m = 40). Plasma concentrations of F-MDA, T-MDA, TBARS, alpha tocopherol, retinol and beta carotene were measured. Plasma MDA and TBARS mean levels increased in sickle homozygous patients more than in controls. However, only TBARS mean concentrations were significantly increased between patients and controls: TBARS: 4.14 +/- 1.49 nMol/ml for Hb SS versus 2.10 +/- 1.21 nMol/ml for Hb AA (P less than 0.005). Vitamin A and vitamin E concentrations were significantly lower in Hb SS than in Hb AA. Beta carotene was significantly increased in patients vs controls. The significant increase of TBARS explains the great importance of the oxidative damage, whereas the significant decrease of vitamins A and E, may contribute, at least for a part, to maintain the autoxidation process or reveals its intensity in these patients.

[In vivo study of the antilipoperoxidant effect of 3',5,7-trihydroxy-4'-methoxy flavone 7 rutinoside]. / Etude in vivo de l'effet antilipoperoxydant du 7 rutinoside de la 3',5,7-trihydroxy-4'-méthoxy flavone.

In 3-month-old Wistar rats carrageenan and CCl4 injected intraperitoneally induce an acute phase reaction which is characterized by a marked increase in alpha 1, alpha 2, beta serum globulins. This reaction corresponds to a large increase in these globulins in the first case and a smaller one in the second. A lipoperoxidant effect is demonstrated by the serum lipoprotein mobility as the lipoperoxidation index (in MDA units) or the decrease in serum vitamin A and E concentrations. This effect is also greater in the first case than in the second one. In the same way the lipoperoxidant effect is shown in liver microsomes but with a lower amplitude in the first case than in the second one. The treatment of rats by intraperitoneal injection of diosmine (150 mg/kg per week) during the 8 weeks which precede the injection of carrageenan or CCl4 results in: i) a marked decrease in the acute-phase reaction and a lower one in the lipoperoxidant effect, in serum; ii) a decrease in the CCl4 induced lipoperoxidant effect in liver microsomes. It may be concluded that diosmine, not injected at the same time as carrageenan or CCl4, but during the previous 8 weeks is sufficiently well distributed in the whole body to produce a marked inhibition of the acute phase reaction and a perceptible effect on lipoperoxidation. It may be considered an effective complement to the natural antioxidant defences of the organism (vitamins A and E).

[Markers of lipid peroxidation, inflammatory proteins and plasma tocopherols in homozygotic and heterozygotic sickle cell anemia]. / Marqueurs de la lipoperoxydation (LPO), protéines inflammatoires et tocophérols plasmatiques dans les drépanocytoses homozygote et hétérozygote.

Lipoperoxidation final products represented by the TBARS (substances reacting with the Thiobarbituric acid), inflammatory reaction proteins and sera tocopherol have been studied in homozygous forms as well as in heterozygous forms of sickle cell diseases. The significant increase of TBARS (P < 0.001) measured by spectrofluorimetry, the considerable decrease of the sera alpha gamma tocopherol, measured by HPLC (P < 0.005) in all sickle cell patients, especially in crisis homozygous form, reinforce our previous study (22, 23, 24). The absence of links between the TBARS and the tocopherols (fig. 1) suggests that other defence mechanisms occur without vitamin E. The collapse of haptoglobinemia in homozygous sickle cell patients associated with the fall of hemoglobinemia indicates a severe tissue and intravascular hemolysis as a consequence of LPO. Furthermore, the simultaneous decrease of cholesterolemia seems to indicate important lipoperoxide activity detected in sickle cell patients.

Influenza and pneumococcal vaccination in long term care facilities in two regions of Quebec.

OBJECTIVES: To evaluate the use of influenza and pneumococcal vaccines in long term care facilities. DESIGN: Cross-sectional survey in a random sample of 30 facilities in two regions of Quebec. Information was collected from the general manager or the chief of nursing, all consultant physicians and a random sample of 20 residents in each facility. RESULTS: Twenty-nine centres agreed to participate. The mean influenza vaccination rate was 70%, and was not influenced by differences in the types of facilities or the organization of the programs for immunization. The main obstacle to influenza vaccination reported by physicians was nonacceptance by a significant proportion of residents. Of the residents who did not initially request influenza vaccine, only 64% accepted vaccination when it was offered. The vast majority of residents were satisfied with the information they had received and the respect shown for their freedom of choice. Forty per cent of residents were unfit to provide a valid consent and the vaccination rate was 76% in this group. Only one-third of the physicians regularly obtained authorization from a relative or the legal guardian before prescribing vaccination for incompetent residents. None of the facilities studied had an effective program for pneumococcal vaccination, only 43% of the physicians reported any use of pneumococcal vaccine and 98% of residents had never heard of the vaccine. CONCLUSIONS: The national objective of 95% coverage with influenza vaccine will be difficult to achieve in long term care facilities, mainly because a minority of residents are not likely to be convinced of the benefit of immunization. Much remains to be done to promote and administer pneumococcal vaccine in this setting.

Effects of positive and negative music on performance of a karate drill.

Although athletes frequently report using music while training or before an event, laboratory studies have not detected a beneficial effect, so the influence of positive and negative music on performance of a selected karate drill was investigated in this double-blind study using 14 volunteers from two Shotokan karate schools. Each subject performed a preselected drill three times following positive and negative music and white noise in a random order. Performance of the drill was rated on a 7-item, 5-point scale by 2 rates. Differences among conditions were assessed via a with-in-subject t test for paired scores. The subjects' self-evaluation of their performance was also examined. Enhancement of performance for both types of music over white noise was significant.

Metabolic intervention on lipid synthesis converging pathways abrogates prostate cancer growth.

One of the most conserved features of all cancers is a profound reprogramming of cellular metabolism, favoring biosynthetic processes and limiting catalytic processes. With the acquired knowledge of some of these important changes, we have designed a combination therapy in order to force cancer cells to use a particular metabolic pathway that ultimately results in the accumulation of toxic products. This innovative approach consists of blocking lipid synthesis, at the same time that we force the cell, through the inhibition of AMP-activated kinase, to accumulate toxic intermediates, such as malonyl-coenzyme A (malonyl-CoA) or nicotinamide adenine dinucleotide phosphate. This results in excess of oxidative stress and cancer cell death. Our new therapeutic strategy, based on the manipulation of metabolic pathways, will certainly set up the basis for new upcoming studies defining a new paradigm of cancer treatment.

Protective effects of high-density lipoprotein against oxidative stress are impaired in haemodialysis patients.

INTRODUCTION: Cardiovascular diseases represent the major cause of mortality in haemodialysis (HD) patients. Oxidized low-density lipoprotein (Ox-LDL) is a major cardiovascular risk factor, implicated in atherosclerotic plaque formation. It has been suggested that high-density lipoprotein (HD) has the capacity to reduce the oxidative modifications of LDL. The aim of this study is to analyse the protective effects of HDL in HD patients. METHODS: In vitro copper-induced LDL oxidation was evaluated in 12 patients with chronic renal failure (mean age 61.0+/-12.8 years) and compared to 25 healthy subjects (mean age 57.3+/-19.2 years). LDL were incubated in oxygen-saturated PBS, LDL oxidation was initiated by Cu (II) in the presence and absence of HDL and assessed by measuring the absorbance (abs) increase at 234 nm due to conjugated diene formation. Duration of lag time, maximum velocity (V(max.)) of lipid peroxidation, oxidation slope and half-time of maximum diene formation (T (1/2)) were obtained by kinetic modelling analysis. RESULTS: HDL (1.06+/-0.31 vs 1.23+/-0.39 mmol/l) and Apo AI (1. 17+/-0.39 vs 1.49+/-0.20 g/l) levels were decreased in HD patients. In the absence of HDL, LDL obtained from HD patients showed an enhanced susceptibility to oxidation in vitro as demonstrated by the significant decrease in lag time (54.5+/-22.2 vs 79.4+/-37.8 min) and a significant increase in V(max.) (0.026+/-0.006 vs 0.017+/-0. 005 abs/min). In all cases, HDL (from 0.1 to 2 microM) prevented LDL oxidation in vitro; however, this effect was significantly reduced in HD patients: increase in lag time 54.2% vs 150.4% in HD vs controls; increase in T (1/2) 52.2% vs 124.6% in HD vs controls; decrease in V(max). 13.5% vs 38.5% in HD vs controls. CONCLUSIONS: These results suggest that qualitative abnormalities such as an impairment of HDL-associated enzymes are associated with a decrease of HDL levels during HD. Hence, in addition to the known impairment of reverse cholesterol transport, the reduction of HDL protective capacity against oxidative stress could be involved in the development of HD-induced atherosclerosis.

Polyacrylamide gradient gel electrophoresis of cytosolic retinol- and retinoic acid-binding proteins: application to rat testis and liver.

Distribution and cellular levels of retinol-binding protein and retinoic acid-binding protein, involved in the molecular action of retinoids, were analyzed in rat testis and liver. Both binding proteins of cytosolic extracts were separated by linear-polyacrylamide gradient gel electrophoresis and following electrophoretic separation, could be visualized by complementary identification tests such as autoradiography and marker proteins. The concentration of the binding proteins were evaluated by scanning the polyacrylamide gradient gels and the resulting data were found to be in accordance with those obtained by counting radioactivities. Polyacrylamide gradient gel electrophoresis appears suitable to detect and quantitatively evaluate cytosolic retinol- and retinoic acid-binding proteins.

The action of free radicals on Deinococcus radiodurans carotenoids.

The possible role of carotenoids as free radical scavengers has not been completely elucidated. To gain further insight into the quenching of OH radicals by carotenoids, we used a feasible bacterial model, Deinococcus radiodurans, a red pigmented bacterium. We compared the action of H2O2 which produces in vivo OH radicals by a Fenton-type reaction on the parental and two mutant strains, i.e., a red pigmented and a colorless one. While the red pigmented bacteria were resistant to H2O2 action, the colorless strain was significantly more sensitive and its sensitivity was dose-dependent. In the red pigmented strains, H2O2 induced a significant decrease in one carotenoid (X5), which could be responsible for the antioxidant activity.

Free and bound malondialdehyde measured as thiobarbituric acid adduct by HPLC in serum and plasma.

Assay of free and total malondialdehyde (MDA) in human serum and plasma from healthy subjects and from patients with high risk of lipoperoxidation was performed as follows: (a) acidic (HClO4, pH 1, at 20 degrees C) or basic (NaOH, pH 13, at 60 degrees C) treatments for 30 min; (b) reaction of the protein-free extract (obtained by acid precipitation) with thiobarbituric acid (TBA); (c) HPLC separation on C18 columns with an eluting solution of methanol/phosphate buffer, 10 mmol/L, pH 5.8 (40/60, by vol), at a flow rate of 1.5 mL/min. Free MDA averaged 0.042 (SEM 0.008) and 0.043 (SEM 0.007) mumol/L, respectively, in serum and plasma from healthy subjects. Free (+/- SEM) MDA increased significantly in the plasma from cancer patients (0.270 +/- 0.047 mumol/L) and from hemodialyzed patients (0.214 +/- 0.035 mumol/L). In serum of hemodialyzed patients, analyses for total MDA were unsuitable because of interfering peaks. MDA bound to NH2 groups constituted 83.2% and 83.5% of total MDA in serum and plasma of healthy subjects, respectively, and only 58% in plasma of hemodialyzed patients.