Modeling the antimicrobial effects of olive mill waste extract, rich in hydroxytyrosol, on the growth of lactic acid bacteria using response surface methodology.

The objective of this study is to assess the inhibitory effects of an aqueous extract from olive oil mill waste (alperujo) on the growth of a lactic acid bacteria (LAB) cocktail consisting of various strains of Lactiplantibacillus pentosus and Lactiplantibacillus plantarum species. For this purpose, response surface methodology was employed using two independent variables (pH levels 3.5-5.55; hydroxytyrosol concentration ranging from 0.93-2990 ppm). The response variable was the average inhibition per treatment on the LAB cocktail (expressed as a percentage). The developed model identified significant terms, including the linear effect of hydroxytyrosol and pH, their interaction, and the quadratic effect of pH. Maximum inhibition of the LAB cocktail was observed at progressively higher concentrations of hydroxytyrosol and lower pH values. Therefore, complete inhibition of LAB in the synthetic culture medium could only be achieved for concentrations of 2984 ppm hydroxytyrosol at a pH of 3.95. These findings suggest that extracts derived from "alperujo" could be utilized as a natural preservative in acidified foods with a bitter flavor and antioxidant requirements.

The Effect of the Extra Virgin Olive Oil Minor Phenolic Compound 3',4'-Dihydroxyphenylglycol in Experimental Diabetic Kidney Disease.

The aim of this study was to analyze the possible nephroprotective effect of 3',4'-dihydroxyphenylglycol (DHPG), a polyphenolic compound of extra virgin olive oil (EVOO), on renal lesions in an experimental model of type 1 diabetes. Rats were distributed as follows: healthy normoglycemic rats (NDR), diabetic rats treated with saline (DR), and DR treated with 0.5 mg/kg/day or 1 mg/kg/day of DHPG. DR showed a significantly higher serum and renal oxidative and nitrosative stress profile than NDR, as well as reduced prostacyclin production and renal damage (defined as urinary protein excretion, reduced creatinine clearance, increased glomerular volume, and increased glomerulosclerosis index). DHPG reduced the oxidative and nitrosative stress and increased prostacyclin production (a 59.2% reduction in DR and 34.7-7.8% reduction in DHPG-treated rats), as well as 38-56% reduction in urinary protein excretion and 22-46% reduction in glomerular morphological parameters (after the treatment with 0.5 or 1 mg/kg/day, respectively). Conclusions: DHPG administration to type 1-like diabetic rats exerts a nephroprotective effect probably due to the sum of its antioxidant (Pearson's coefficient 0.68-0.74), antinitrosative (Pearson's coefficient 0.83), and prostacyclin production regulator (Pearson's coefficient 0.75) effects.

Using Metal-Organic Framework HKUST-1 for the Preparation of High-Conductive Hybrid Membranes Based on Multiblock Copolymers for Fuel Cells.

Novel proton-conducting hybrid membranes consisting of sulfonated multiblock copolymer of polysulfone and polyphenylsulfone (SPES) reinforced with a HKUST-1 metal-organic framework (MOF) (5, 10, and 20 wt. %) were prepared and characterized for fuel cell applications. The presence of the MOF in the copolymer was confirmed by means of FE-SEM and EDS. The hybrid membranes show a lower contact angle value than the pure SPES, in agreement with the water uptake (WU%), i.e., by adding 5 wt. % of the MOF, this parameter increases by 20% and 40% at 30 °C and 60 °C, respectively. Additionally, the presence of the MOF increases the ion exchange capacity (IEC) from 1.62 to 1.93 mequivH+ g−1. Thermogravimetric analysis reveals that the hybrid membranes demonstrate high thermal stability in the fuel cell operation temperature range (<100 °C). The addition of the MOF maintains the mechanical stability of the membranes (TS > 85 MPa in the Na+ form). Proton conductivity was analyzed using EIS, achieving the highest value with a 5 wt. % load of the HKUST-1. This value is lower than that observed for the HKUST-1/Nafion system. However, polarization and power density curves show a remarkably better performance of the hybrid membranes in comparison to both the pure SPES and the pure Nafion membranes.

Perampanel as adjuvant treatment in epileptic encephalopathies: A multicenter study in routine clinical practice.

OBJECTIVE: Developmental and epileptic encephalopathies (DEEs) are a heterogeneous group of syndromes, including Lennox-Gastaut syndrome (LGS), which are refractory to multiple therapies. Perampanel efficacy has been reported in LGS but further real-world evidence is needed in DEEs. METHODS: A multicenter, retrospective, 1-year observational study in patients with DEEs on adjuvant perampanel treatment was conducted to assess perampanel safety and effectiveness in this type of patients in a real-world setting. Seizure types [focal onset seizures (FOS), generalized tonic-clonic seizures (GTCS), tonic seizures (TS), atonic seizures (AtS), atypical absences (AA), and myoclonic seizures (MS)] and seizure clusters were divided in different frequency groups: daily, weekly, and monthly seizures, and absent or seizure freedom. Patients could have more than one seizure type. For each frequency group, group change and seizure freedom were analyzed. RESULTS: Eighty-seven patients diagnosed with DEEs (45 males) of median age 22 [1-70] years were included. The most frequent DEEs were LGS (35.6%) and Lennox-like syndrome (37.9%). At baseline 20 patients had three to five types of seizures, 36 patients had two types of seizures and 31 patients had one predominant type of seizure. The mean number of seizure types per patient at baseline was 2.12 ± 0.97 which was reduced to 1.62 ± 0.91 at 12 months (p < 0.001). Overall, 51.7% of patients had a significant improvement in at least one seizure type. At baseline, 45 patients had GTCS, 42 FOS, 41 TS, 18 AA, 16 AtS, 11 MS, and 30 seizures clusters. Seizure freedom for each specific type at 12 months was significantly achieved by 35% of patients with GTCS (p < 0.001), 17% (p = 0.016) with TS and 37% with seizure clusters (p < 0.001). Patients achieved seizure freedom from other seizure types but with no statistical significance: 7% FOS-free, 28% AA-free, 6% Ats-free, and 18% MS-free. Regarding changes of group at 12 months, 22% of TS and 19% of FOS improved significantly to a group with lower seizure frequency (p = 0.004 and p = 0.02, respectively). In remaining groups (4% of GTCS, 11% of AA, 18% of Ats, 18% of MS, and 13% of seizure clusters), the improvement was not statistically significant. Twenty-nine patients discontinued perampanel: 18 (21%) due to AEs, 8 (9%) due to lack of efficacy, and 3 (3%) due to seizure worsening. Adverse events, mostly mild or moderate, were reported in 53% of patients, and irritability/mood changes (22%) and somnolence (17%) were the most frequent. CONCLUSION: This is the first large-scale real-world study with perampanel across different seizure types in patients with DEEs. Perampanel was effective, especially in GTCS, TS, and FOS, as well as in seizure clusters. Perampanel was generally well-tolerated without unexpected AEs.

Characterization and Modeling of Free Volume and Ionic Conduction in Multiblock Copolymer Proton Exchange Membranes.

Free volume plays a key role on transport in proton exchange membranes (PEMs), including ionic conduction, species permeation, and diffusion. Positron annihilation lifetime spectroscopy and electrochemical impedance spectroscopy are used to characterize the pore size distribution and ionic conductivity of synthesized PEMs from polysulfone/polyphenylsulfone multiblock copolymers with different degrees of sulfonation (SPES). The experimental data are combined with a bundle-of-tubes model at the cluster-network scale to examine water uptake and proton conduction. The results show that the free pore size changes little with temperature in agreement with the good thermo-mechanical properties of SPES. However, the free volume is significantly lower than that of Nafion®, leading to lower ionic conductivity. This is explained by the reduction of the bulk space available for proton transfer where the activation free energy is lower, as well as an increase in the tortuosity of the ionic network.

Neuroprotective Effect of 3',4'-Dihydroxyphenylglycol in Type-1-like Diabetic Rats-Influence of the Hydroxytyrosol/3',4'-dihydroxyphenylglycol Ratio.

The aim of this study was to assess the possible neuroprotective effect of 3',4'-dihydroxyphenylglycol (DHPG), a polyphenol from extra virgin olive oil (EVOO), in an experimental model of diabetes and whether this effect is modified by the presence of another EVOO polyphenol, hydroxytyrosol (HT). The neuroprotective effect was assessed in a hypoxia-reoxygenation model in brain slices and by quantifying retinal nerve cells. The animals were distributed as follows: (1) normoglycemic rats (NDR), (2) diabetic rats (DR), (3) DR treated with HT (5 mg/kg/day p.o.), (4) DR treated with DHPG (0.5 mg/kg/day), or (5) with 1 mg/kg/day, (6) DR treated with HT plus DHPG 0.5 mg/kg/day, or (7) HT plus 1 mg/kg/day p.o. DHPG. Diabetic animals presented higher levels of oxidative stress variables and lower numbers of neuronal cells in retinal tissue. The administration of DHPG or HT reduced most of the oxidative stress variables and brain lactate dehydrogenase efflux (LDH) as an indirect index of cellular death and also reduced the loss of retinal cells. The association of DHPG+HT in the same proportions, as found in EVOO, improved the neuroprotective and antioxidant effects of both polyphenols.

Synergistic Effect of 3',4'-Dihidroxifenilglicol and Hydroxytyrosol on Oxidative and Nitrosative Stress and Some Cardiovascular Biomarkers in an Experimental Model of Type 1 Diabetes Mellitus.

The objective of this study was to assess a possible synergistic effect of two extra-virgin olive oil polyphenols, 3,4,-dyhydroxyphenylglycol (DHPG) and hydroxytyrosol (HT), in an experimental model of type 1 diabetes. Seven groups of animals were studied: (1) Nondiabetic rats (NDR), (2) 2-month-old diabetic rats (DR), (3) DR treated with 5 mg/kg/day p.o. HT, (4) DR treated with 0.5 mg/kg/day p.o. DHPG, (5) DR treated with 1 mg/kg/day p.o. DHPG, (6) DR treated with HT + DHPG (0.5), (7) DR treated with HT + DHPG (1). Oxidative stress variables (lipid peroxidation, glutathione, total antioxidant activity, 8-isoprostanes, 8-hydroxy-2-deoxyguanosine, and oxidized LDL), nitrosative stress (3-nitrotyrosine), and some cardiovascular biomarkers (platelet aggregation, thromboxane B2, prostacyclin, myeloperoxidase, and vascular cell adhesion protein 1 (VCAM-1)) were analyzed. The diabetic animals showed an imbalance in all of the analyzed variables. HT exerted an antioxidant and downregulatory effect on prothrombotic biomarkers while reducing the fall of prostacyclin. DHPG presented a similar, but quantitatively lower, profile. HT plus DHPG showed a synergistic effect in the reduction of oxidative and nitrosative stress, platelet aggregation, production of prostacyclin, myeloperoxidase, and VCAM-1. This synergism could be important for the development of functional oils enriched in these two polyphenols in the proportion used in this study.

Extra Virgin Oil Polyphenols Improve the Protective Effects of Hydroxytyrosol in an In Vitro Model of Hypoxia-Reoxygenation of Rat Brain.

Hydroxytyrosol (HT) is the component primarily responsible for the neuroprotective effect of extra virgin olive oil (EVOO). However, it is less effective on its own than the demonstrated neuroprotective effect of EVOO, and for this reason, it can be postulated that there is an interaction between several of the polyphenols of EVOO. The objective of the study was to assess the possible interaction of four EVOO polyphenols (HT, tyrosol, dihydroxyphenylglycol, and oleocanthal) in an experimental model of hypoxia-reoxygenation in rat brain slices. The lactate dehydrogenase (LDH) efflux, lipid peroxidation, and peroxynitrite production were determined as measures of cell death, oxidative stress, and nitrosative stress, respectively. First, the polyphenols were incubated with the brain slices in the same proportions that exist in EVOO, comparing their effects with those of HT. In all cases, the cytoprotective and antioxidant effects of the combination were greater than those of HT alone. Second, we calculated the concentration-effect curves for HT in the absence or presence of each polyphenol. Tyrosol did not significantly modify any of the variables inhibited by HT. Dihydroxyphenylglycol only increased the cytoprotective effect of HT at 10 µM, while it increased its antioxidant effect at 50 and 100 µM and its inhibitory effect on peroxynitrite formation at all the concentrations tested. Oleocanthal increased the cytoprotective and antioxidant effects of HT but did not modify its inhibitory effect on nitrosative stress. The results of this study show that the EVOO polyphenols DHPG and OLC increase the cytoprotective effect of HT in an experimental model of hypoxia-reoxygenation in rat brain slices, mainly due to a possibly synergistic effect on HT's antioxidant action. These results could explain the greater neuroprotective effect of EVOO than of the polyphenols alone.

Sulfonated Polysulfone/TiO2(B) Nanowires Composite Membranes as Polymer Electrolytes in Fuel Cells.

New proton conducting membranes based on sulfonated polysulfone (sPSU) reinforced with TiO2(B) nanowires (1, 2, 5 and 10 wt.%) were synthesized and characterized. TiO2(B) nanowires were synthesized by means of a hydrothermal method by mixing TiO2 precursor in aqueous solution of NaOH as solvent. The presence of the TiO2(B) nanowires into the polymer were confirmed by means of Field Emission Scanning Electron Microscopy, Fourier transform infrared and X-ray diffraction. The thermal study showed an increase of almost 20 °C in the maximum temperature of sPSU backbone decomposition due to the presence of 10 wt.% TiO2(B) nanowires. Water uptake also is improved with the presence of hydrophilic TiO2(B) nanowires. Proton conductivity of sPSU with 10 wt.% TiO2(B) nanowires was 21 mS cm-1 (at 85 °C and 100% RH). Under these experimental conditions the power density was 350 mW cm-2 similar to the value obtained for Nafion 117. Considering all these obtained results, the composite membrane doped with 10 wt.% TiO2(B) nanowires is a promising candidate as proton exchange electrolyte in fuel cells (PEMFCs), especially those operating at high temperatures.

Synthesis and Characterization of Novel Anion Exchange Membranes Based on Semi-Interpenetrating Networks of Functionalized Polysulfone: Effect of Ionic Crosslinking.

In this work, anion exchange membranes based on polymer semi-interpenetrating networks were synthesized and characterized for the first time. The networks are composed of sulfonated polysulfone and 1-methylimidazolium-functionalized polysulfone crosslinked covalently with N,N,N',N'-tetramethylethylenediamine (degree of crosslinking of 5%). In these membranes, sulfonic groups interact electrostatically with cationic groups to form an ionic crosslinking structure with improved alkaline stability. The effect of the ionic crosslinking on the thermal, chemical, mechanical, and electrochemical behavior of membranes was studied. These crosslinked membranes containing sulfonated polysulfone showed higher thermal stability, with a delay of around 20 °C in the onset decomposition temperature value of the functional groups than the crosslinked membranes containing free polysulfone. The tensile strength values were maintained above 44 MPa in all membranes with a degree of chloromethylation (DC) below 100%. The maximum ionic conductivity value is reached with the membrane with the highest degree of chloromethylation. The chemical stability in alkaline medium of the conducting membranes also improved. Thus, the ionic conductivity variation of the membranes after 96 h in a 1 M potassium hydroxide (KOH) solution is less pronounced when polysulfone is replaced by sulfonated polysulfone. So, the ionic crosslinking which joins both components of the blends together, improves the material's properties making progress in the development of new solid electrolyte for polymeric fuel cells.

Antioxidant Capacity and Phenolic and Sugar Profiles of Date Fruits Extracts from Six Different Algerian Cultivars as Influenced by Ripening Stages and Extraction Systems.

The study investigated the phenols, sugar and the antioxidant capacities of date fruit extracts obtained by organic solvents and by hydrothermal treatment from six different Algerian cultivars at two ripening stages for the first time. The analyzed cultivars exhibited potent antioxidant properties (ferric reducing antioxidant power (FRAP), 1,1-Diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) scavenging capacities) and different phenols regardless of the solvents and the maturity stages. About 18 phenols were identified and quantified, mainly in the hydrothermal extracts. The earlier stages were characterized by high amounts of o-coumaric acid, cinnamic acid and luteolin, with a noticeable absence of quercetin. The tamr stage presented the highest sugar content (78.15-86.85 mg/100 mg dry weight (DW)) with an abundance of glucose. Galactose was present only in some cultivars from the kimri stage (tamjouhert). Uronic acids were mostly detected at the tamr stage (4.02-8.82 mg gallic acid equivalent/100 mg dried weight). The obtained results highlight the potential of using date fruit extracts as natural antioxidants, especially at industrial scales that tend use hydrothermal extraction.

From Green Technology to Functional Olive Oils: Assessing the Best Combination of Olive Tree-Related Extracts with Complementary Bioactivities.

Our aim was to assess the combination of olive tree-related extracts with the most favorable profile of in vitro bioactive properties. We tested the antioxidant (increment of low-density lipoprotein resistance against oxidation), vasoactive (promotion of nitric oxide release and decrease of endothelin-1 production in human umbilical vein endothelial cells), anti-inflammatory (decrease of the endothelial production of vascular cell adhesion molecule-1), and antithrombotic (reduction of the endothelial release of plasminogen activator inhibitor-1) capacities of six phenolic extracts and three triterpenic acid solutions (Ps and Ts, respectively). We tested extracts alone and in combination, at nutritional (Ps: 0.05-0.5 µmol/L; Ts: 0.001-0.1 µmol/L) and nutraceutical doses (Ps: 1-10 µmol/L; Ts: 0.25-10 µmol/L). The combination of Ps rich in 3,4-dihydroxyphenylglycol (76%, P2), hydroxytyrosol (95%, P3), and oleuropein (70%, P4) (final nutritional concentration: 0.15 µmol/L; final nutraceutical concentration: 3 µmol/L) was the best in order to prepare functional products and nutraceuticals with cardioprotective properties, despite the fact that the isolated extract with the greatest in vitro properties was P5 (75% oleocanthal), suggesting a potential synergistic effect among different olive components.

New Liquid Source of Antioxidant Phenolic Compounds in the Olive Oil Industry: Alperujo Water.

The current management of alperujo as the main solid by-product from the two-phase olive oil extraction system has led to the appearance of a new liquid effluent that until now was treated together with the alperujo itself. The composition and antioxidant properties of its bioactive components at different depths of the pond were studied using colorimetric and HPLC with UV and MS detectors, DPPH, reducing power and rancimat. The concentration of suspended solids varied between 1.71 and 8.49 g/L, total fat was between 0.74 and 1.47 g/L, and total phenols were found between 3.74 and 4.11 g/L, which included hydroxytyrosol, 3,4-dihydroxyphenylglycol and tyrosol as the main phenols. Two types of extracts were obtained through two industrial systems with ethyl acetate and by chromotography, with an average content in total sugars of 2.1% and 3.16%, total phenols of 17.9% and 28.6% and hydroxytyrosol of 51.5 and 79.0 mg/g of extract, respectively. The activity presented by the chromatographic extract was higher in terms of free radical sequestering capacity, reducing power and the inhibition of lipid oxidation. Obtaining bioactive extracts would improve the formulation of food with natural components and at the same time would be the first step in a biorefinery to improve the management of the new effluent.

Effectiveness and safety of perampanel monotherapy for focal and generalized tonic-clonic seizures: Experience from a national multicenter registry.

OBJECTIVE: To assess the effectiveness and tolerability of perampanel (PER) monotherapy in routine clinical practice for the treatment of focal onset and generalized tonic-clonic seizures (GTCS). METHODS: This multicenter, retrospective, observational study was conducted in patients aged ≥12 years treated with PER as primary monotherapy or converted to PER monotherapy by progressive reduction of background antiepileptic drugs. Outcomes included retention, responder, and seizure-free rate after 3, 6, and 12 months and tolerability throughout the follow-up. RESULTS: A total of 98 patients (mean age = 49.6 ± 21.7 years, 51% female) with focal seizures and/or GTCS were treated with PER monotherapy for a median exposure of 14 months (range = 1-57) with a median dose of 4 mg (range = 2-10). The retention rates at 3, 6, and 12 months and last follow-up were 93.8%, 89.3%, 80.9%, and 71.4%, respectively. The retention rates according to the type of monotherapy (primary vs conversion) did not differ (log-rank P value = .57). Among the 98 patients, 61.2% patients had seizures throughout the baseline period, with a median seizure frequency of 0.6 seizures per month (range = 0.3-26). Responder rates at 3, 6, and 12 months were 79.6%, 70.1%, and 52.8%, respectively, and seizure freedom rates at the same points were 62.7%, 56.1%, and 41.5%. Regarding the 33 patients who had GTCS in the baseline period, 87.8% were seizure-free at 3 months, 78.1% at 6 months, and 55.1% at 12 months. Over the entire follow-up, PER monotherapy was generally well tolerated, and only 16% of patients discontinued PER due to adverse events (AEs). Female patients were found to be at a higher risk of psychiatric AEs (female vs male odds ratio = 2.85, 95% confidence interval = 1-8.33, P = .046). SIGNIFICANCE: PER demonstrated good effectiveness and a good safety profile when used as primary therapy or conversion to monotherapy at relatively low doses, in a clinical setting with patients with focal seizures and GTCS.

Areas for improvement in community optometry: flashes and floaters take priority.

PURPOSE: A common response to rising demand for healthcare is to extend the role of health professionals and the range of their service provision. Community optometry in Scotland is a recent example of this. Within this context of innovation and change there are challenges to ensuring quality in optometry practice. The purpose of this research is to establish what the priorities are for practice improvement within community optometry and to start a programme to inform strategies to improve practice. METHODS: A four stage study was conducted: (1) a service-driven topic prioritisation exercise to identify priorities for optometry practice improvement; (2) a review of national and international guidance and UK protocols relating to the identified priority topic; (3) a national theory-based survey identifying current practice and the barriers and facilitators to the target behaviour; and (4) the identification of theory-based intervention options to improve practice. The Behaviour Change Wheel approach to behaviour change intervention development and Theoretical Domains Framework (TDF) provided the underlying theoretical framework. RESULTS: Stakeholders identified 'patients presenting with flashes and floaters' as an important priority for practice improvement. The decision about whether or not to refer patients on to secondary care for further examination is the target behaviour. Guidance for optometrists on this topic is lacking. Six TDF domains were related to the decision about whether or not to refer patients with flashes and floaters to secondary care - 'social influences', 'emotion', 'beliefs about capabilities', 'beliefs about consequences', 'behavioural regulation' and 'reinforcement'. CONCLUSIONS: This study has examined current practice in relation to the management of patients with flashes and floaters, identified the most salient targets for future strategies to improve optometry practice and highlighted what form these strategies may take. It demonstrates the use of a flexible, theory-informed approach, which can be used to engage with stakeholders and professionals to inform the design and development of efforts to improve practice in a variety of healthcare settings.

Efficacy and safety of eslicarbazepine acetate monotherapy for partial-onset seizures: Experience from a multicenter, observational study.

Eslicarbazepine acetate (ESL, Aptiom™) is a once-daily anticonvulsant, approved as adjunctive treatment of partial-onset seizures (POS). Historical-controlled trials investigating the use of ESL as monotherapy have demonstrated a favorable efficacy and tolerability profile in patients with POS. This prospective, non-interventional study recruited POS patients in 17 hospitals in Spain. After a 3-month baseline period, ESL therapy was initiated as 400mg QD and up-titrated to an optimal maintenance dose based on clinical response and tolerance. The incidence of seizures was assessed via seizure calendars and the nature and severity of adverse events (AEs) were also recorded. A total of 117 patients (aged 9-87years) enrolled in the study and were treated with ESL at either 400mg/day (3.4% patients), 800mg/day (61% patients), 1200mg/day (27.1% patients) or 1600mg/day (8.5% patients). At 3months, 82.0% (n=72) of patients achieved a ≥50% reduction in seizure frequency, compared to 79.7% (n=67) of patients at 6months and 83.0% (n=49) at 12months. Patients who suffered secondary generalized tonic-clonic (SGTC) seizures had seizure-free rates of 71% (n=27), 69.6% (n=29), and 72.7% (n=16) at 3, 6, and 12months, respectively. Overall, 18 patients (15.3%) reported AEs of instability and dizziness (n=9), somnolence (n=3), mild hyponatremia (n=3), headache (n=1), hypertriglyceridemia (n=1), and allergic reaction (n=1), which caused ESL discontinuation of ESL treatment. ESL is effective and well tolerated as monotherapy for patients with POS, which supports previous findings. Early use is supported by its frequent use as monotherapy in this study and lack of severe side effects.

Barriers and facilitators of evidence-based management of patients with bacterial infections among general dental practitioners: a theory-informed interview study.

BACKGROUND: General dental practitioners (GDPs) regularly prescribe antibiotics to manage dental infections although most infections can be treated successfully by local measures. Published guidance to support GDPs to make appropriate prescribing decisions exists but there continues to be wide variation in dental antibiotic prescribing. An interview study was conducted as part of the Reducing Antibiotic Prescribing in Dentistry (RAPiD) trial to understand the barriers and facilitators of using local measures instead of prescribing antibiotics to manage bacterial infections. METHODS: Thirty semi-structured one-to-one telephone interviews were conducted using the Theoretical Domains Framework (TDF). Responses were coded into domains of the TDF and sub-themes. Priority domains (high frequency: ≥50 % interviewees discussed) relevant to behaviour change were identified as targets for future intervention efforts and mapped onto 'intervention functions' of the Behaviour Change Wheel system. RESULTS: Five domains (behavioural regulation, social influences, reinforcement, environmental context and resources, and beliefs about consequences) with seven sub-themes were identified as targets for future intervention. All participants had knowledge about the evidence-based management of bacterial infections, but they reported difficulties in following this due to patient factors and time management. Lack of time was found to significantly influence their decision processes with regard to performing local measures. Beliefs about their capabilities to overcome patient influence, beliefs that performing local measures would impact on subsequent appointment times as well as there being no incentives for performing local measures were also featured. Though no knowledge or basic skills issues were identified, the participants suggested some continuous professional development programmes (e.g. time management, an overview of published guidance) to address some of the barriers. The domain results suggest a number of intervention functions through which future interventions could change GDPs' antibiotic prescribing for bacterial infections: imparting skills through training, providing an example for GDPs to imitate (i.e. modelling) or creating the expectation of a reward (i.e. incentivisation). CONCLUSIONS: This is the first theoretically informed study to identify barriers and facilitators of evidence-based management of patients with bacterial infections among GDPs. A pragmatic approach is needed to address the modifiable barriers in future interventions intended to change dentists' inappropriate prescribing behaviour.

Clinical effectiveness and cost-effectiveness of foam sclerotherapy, endovenous laser ablation and surgery for varicose veins: results from the Comparison of LAser, Surgery and foam Sclerotherapy (CLASS) randomised controlled trial.

BACKGROUND: Foam sclerotherapy (foam) and endovenous laser ablation (EVLA) have emerged as alternative treatments to surgery for patients with varicose veins, but uncertainty exists regarding their effectiveness in the medium to longer term. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of foam, EVLA and surgery for the treatment of varicose veins. DESIGN: A parallel-group randomised controlled trial (RCT) without blinding, and economic modelling evaluation. SETTING: Eleven UK specialist vascular centres. PARTICIPANTS: Seven hundred and ninety-eight patients with primary varicose veins (foam, n = 292; surgery, n = 294; EVLA, n = 212). INTERVENTIONS: Patients were randomised between all three treatment options (eight centres) or between foam and surgery (three centres). PRIMARY OUTCOME MEASURES: Disease-specific [Aberdeen Varicose Vein Questionnaire (AVVQ)] and generic [European Quality of Life-5 Dimensions (EQ-5D), Short Form questionnaire-36 items (SF-36) physical and mental component scores] quality of life (QoL) at 6 months. Cost-effectiveness as cost per quality-adjusted life-year (QALY) gained. SECONDARY OUTCOME MEASURES: Quality of life at 6 weeks; residual varicose veins; Venous Clinical Severity Score (VCSS); complication rates; return to normal activity; truncal vein ablation rates; and costs. RESULTS: The results appear generalisable in that participants' baseline characteristics (apart from a lower-than-expected proportion of females) and post-treatment improvement in outcomes were comparable with those in other RCTs. The health gain achieved in the AVVQ with foam was significantly lower than with surgery at 6 months [effect size -1.74, 95% confidence interval (CI) -2.97 to -0.50; p = 0.006], but was similar to that achieved with EVLA. The health gain in SF-36 mental component score for foam was worse than that for EVLA (effect size 1.54, 95% CI 0.01 to 3.06; p = 0.048) but similar to that for surgery. There were no differences in EQ-5D or SF-36 component scores in the surgery versus foam or surgery versus EVLA comparisons at 6 months. The trial-based cost-effectiveness analysis showed that, at 6 months, foam had the highest probability of being considered cost-effective at a ceiling willingness-to-pay ratio of £20,000 per QALY. EVLA was found to cost £26,107 per QALY gained versus foam, and was less costly and generated slightly more QALYs than surgery. Markov modelling using trial costs and the limited recurrence data available suggested that, at 5 years, EVLA had the highest probability (≈ 79%) of being cost-effective at conventional thresholds, followed by foam (≈ 17%) and surgery (≈ 5%). With regard to secondary outcomes, health gains at 6 weeks (p < 0.005) were greater for EVLA than for foam (EQ-5D, p = 0.004). There were fewer procedural complications in the EVLA group (1%) than after foam (7%) and surgery (8%) (p < 0.001). Participants returned to a wide range of behaviours more quickly following foam or EVLA than following surgery (p < 0.05). There were no differences in VCSS between the three treatments. Truncal ablation rates were higher for surgery (p < 0.001) and EVLA (p < 0.001) than for foam, and were similar for surgery and EVLA. CONCLUSIONS: Considerations of both the 6-month clinical outcomes and the estimated 5-year cost-effectiveness suggest that EVLA should be considered as the treatment of choice for suitable patients. FUTURE WORK: Five-year trial results are currently being evaluated to compare the cost-effectiveness of foam, surgery and EVLA, and to determine the recurrence rates following each treatment. This trial has highlighted the need for long-term outcome data from RCTs on QoL, recurrence rates and costs for foam sclerotherapy and other endovenous techniques compared against each other and against surgery. TRIAL REGISTRATION: Current Controlled Trials ISRCTN51995477. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 27. See the NIHR Journals Library website for further project information.

Fertilization failure after IVF in 304 couples--a case-control study on predictors and long-term prognosis.

OBJECTIVES: To identify predictors of total fertilization failure (TFF) and thereby optimize the primary allocation of patients with no well-defined male factor to either IVF or intracytoplasmatic sperm injection (ICSI). Further, to evaluate the long-term fertility prognosis of couples experiencing TFF. STUDY DESIGN: A retrospective case-control study including 304 couples with TFF and 304 controls with fertilization after IVF during a 10-year period from year 2000-2010. The controls were the patients with minimum one fertilized oocyte just prior to the cases. Multiple logistic regression analysis was used to evaluate the predictors of TFF. RESULTS: The multiple regression analysis identified the following independent predictors of TFF: female smoking, adjusted odds ratio (AOR) 1.7 (95% CI 1.1-2.3), non-tubal factor AOR 2.2 (95% CI 1.5-3.4), progressive motile spermatozoa after preparation × 10(6)/ml (Log2 scale) AOR 1.4 (95% CI 1.2-1.6). For every oocyte, decreasing from four to one oocytes, the risk of TFF increased with AOR 2.0 (95% CI: 1.5-2.9) and from seven to four oocytes with AOR 1.2 (95%CI: 1.0-1.3), respectively. In case of more than seven oocytes the risk of TFF did not vary significantly by the number of oocytes. Female age, BMI, duration of infertility, earlier natural or IUI conceptions were not predictors of TFF. After a minimum of 30 months of follow-up from the index cycle, 50% of the TFF patients succeeded in a live childbirth compared with 70% of the controls. Only thirty five percent of the total number of births in the TFF patients was after ICSI. CONCLUSION: The risk of TFF is associated with the number of available oocytes for fertilization, female smoking, non-tubal factor infertility and an apparently minor sperm factor. However, anticipated predictors like advanced female age, duration of infertility and earlier conceptions proved not to have any predictive value. Couples experiencing TFF have a significantly reduced overall long-term chance of live birth compared with controls.

Application of theory to enhance audit and feedback interventions to increase the uptake of evidence-based transfusion practice: an intervention development protocol.

BACKGROUND: Audits of blood transfusion demonstrate around 20% transfusions are outside national recommendations and guidelines. Audit and feedback is a widely used quality improvement intervention but effects on clinical practice are variable, suggesting potential for enhancement. Behavioural theory, theoretical frameworks of behaviour change and behaviour change techniques provide systematic processes to enhance intervention. This study is part of a larger programme of work to promote the uptake of evidence-based transfusion practice. OBJECTIVES: The objectives of this study are to design two theoretically enhanced audit and feedback interventions; one focused on content and one on delivery, and investigate the feasibility and acceptability. METHODS: Study A (Content): A coding framework based on current evidence regarding audit and feedback, and behaviour change theory and frameworks will be developed and applied as part of a structured content analysis to specify the key components of existing feedback documents. Prototype feedback documents with enhanced content and also a protocol, describing principles for enhancing feedback content, will be developed. Study B (Delivery): Individual semi-structured interviews with healthcare professionals and observations of team meetings in four hospitals will be used to specify, and identify views about, current audit and feedback practice. Interviews will be based on a topic guide developed using the Theoretical Domains Framework and the Consolidated Framework for Implementation Research. Analysis of transcripts based on these frameworks will form the evidence base for developing a protocol describing an enhanced intervention that focuses on feedback delivery. Study C (Feasibility and Acceptability): Enhanced interventions will be piloted in four hospitals. Semi-structured interviews, questionnaires and observations will be used to assess feasibility and acceptability. DISCUSSION: This intervention development work reflects the UK Medical Research Council's guidance on development of complex interventions, which emphasises the importance of a robust theoretical basis for intervention design and recommends systematic assessment of feasibility and acceptability prior to taking interventions to evaluation in a full-scale randomised study. The work-up includes specification of current practice so that, in the trials to be conducted later in this programme, there will be a clear distinction between the control (usual practice) conditions and the interventions to be evaluated.