University Hospital Ayr

Background: Sodium-glucose cotransporter 2 inhibitors reduce the risk of heart failure hospitalization and cardiovascular death in patients with heart failure and reduced ejection fraction (HFrEF). However, their effects on cardiac structure and function in HFrEF are uncertain. Methods: We designed a multicenter, randomized, double-blind, placebo-controlled trial (the SUGAR-DM-HF trial [Studies of Empagliflozin and Its Cardiovascular, Renal and Metabolic Effects in Patients With Diabetes Mellitus, or Prediabetes, and Heart Failure]) to investigate the cardiac effects of empagliflozin in patients in New York Heart Association functional class II to IV with a left ventricular (LV) ejection fraction ≤40% and type 2 diabetes or prediabetes. Patients were randomly assigned 1:1 to empagliflozin 10 mg once daily or placebo, stratified by age (<65 and ≥65 years) and glycemic status (diabetes or prediabetes). The coprimary outcomes were change from baseline to 36 weeks in LV end-systolic volume indexed to body surface area and LV global longitudinal strain both measured using cardiovascular magnetic resonance. Secondary efficacy outcomes included other cardiovascular magnetic resonance measures (LV end-diastolic volume index, LV ejection fraction), diuretic intensification, symptoms (Kansas City Cardiomyopathy Questionnaire Total Symptom Score, 6-minute walk distance, B-lines on lung ultrasound, and biomarkers (including N-terminal pro-B-type natriuretic peptide). Results: From April 2018 to August 2019, 105 patients were randomly assigned: mean age 68.7 (SD, 11.1) years, 77 (73.3%) male, 82 (78.1%) diabetes and 23 (21.9%) prediabetes, mean LV ejection fraction 32.5% (9.8%), and 81 (77.1%) New York Heart Association II and 24 (22.9%) New York Heart Association III. Patients received standard treatment for HFrEF. In comparison with placebo, empagliflozin reduced LV end-systolic volume index by 6.0 (95% CI, –10.8 to –1.2) mL/m 2 ( P =0.015). There was no difference in LV global longitudinal strain. Empagliflozin reduced LV end-diastolic volume index by 8.2 (95% CI, –13.7 to –2.6) mL/m 2 ( P =0.0042) and reduced N-terminal pro-B-type natriuretic peptide by 28% (2%–47%), P =0.038. There were no between-group differences in other cardiovascular magnetic resonance measures, diuretic intensification, Kansas City Cardiomyopathy Questionnaire Total Symptom Score, 6-minute walk distance, or B-lines. Conclusions: The sodium-glucose cotransporter 2 inhibitor empagliflozin reduced LV volumes in patients with HFrEF and type 2 diabetes or prediabetes. Favorable reverse LV remodeling may be a mechanism by which sodium-glucose cotransporter 2 inhibitors reduce heart failure hospitalization and mortality in HFrEF. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03485092.

Patient assessment of disease activity in rheumatoid arthritis (RA) may be useful in clinical practice, offering a patient-friendly, location independent, and a time-efficient and cost-efficient means of monitoring the disease. The objective of this study was to identify patient-reported outcome measures (PROMs) to assess disease activity in RA and to evaluate the measurement properties of these measures. Systematic literature searches were performed in the PubMed and EMBASE databases to identify articles reporting on clinimetric development or evaluation of PROM-based instruments to monitor disease activity in patients with RA. 2 reviewers independently selected articles for review and assessed their methodological quality based on the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) recommendations. A total of 424 abstracts were retrieved for review. Of these abstracts, 56 were selected for reviewing the full article and 34 articles, presenting 17 different PROMs, were finally included. Identified were: Rheumatoid Arthritis Disease Activity Index (RADAI), RADAI-5, Patient-based Disease Activity Score (PDAS) I & II, Patient-derived Disease Activity Score with 28-joint counts (Pt-DAS28), Patient-derived Simplified Disease Activity Index (Pt-SDAI), Global Arthritis Score (GAS), Patient Activity Score (PAS) I & II, Routine Assessment of Patient Index Data (RAPID) 2–5, Patient Reported Outcome-index (PRO-index) continuous (C) & majority (M), Patient Reported Outcome CLinical ARthritis Activity (PRO-CLARA). The quality of reports varied from poor to good. Typically 5 out of 10 clinimetric domains were covered in the validations of the different instruments. The quality and extent of clinimetric validation varied among PROMs of RA disease activity. The Pt-DAS28, RADAI, RADAI-5 and RAPID 3 had the strongest and most extensive validation. The measurement properties least reported and in need of more evidence were: reliability, measurement error, cross-cultural validity and interpretability of measures.

We included six new studies (624 participants) for this update, which now includes a total of 23 trials that randomised a total of 2890 participants undergoing cardiac rehabilitation. Participants had an acute myocardial infarction, revascularisation or heart failure. A number of studies provided insufficient detail to enable assessment of potential risk of bias, in particular, details of generation and concealment of random allocation sequencing and blinding of outcome assessment were poorly reported.

Phytophthora infestans, the causal agent of late blight, is a major threat to potato production in northwestern Europe. Before 1980, the worldwide population of P. infestans outside Mexico appeared to be asexual and to consist of a single clonal lineage of A1 mating type characterized by a single genotype. It is widely believed that new strains migrated into Europe in 1976 and that this led to subsequent population changes including the introduction of the A2 mating type. The population characteristics of recently collected isolates in NW Europe show a diverse population including both mating types, sexual reproduction and oospores, although differences are observed between regions. Although it is difficult to find direct evidence that new strains are more aggressive, there are several indications from experiments and field epidemics that the aggressiveness of P. infestans has increased in the past 20 years. The relative importance of the different primary inoculum sources and specific measures for reducing their role, such as covering dumps with plastic and preventing seed tubers from becoming infected, is described for the different regions. In NW Europe, varieties with greater resistance tend not to be grown on a large scale. From the grower’s perspective, the savings in fungicide input that can be achieved with these varieties are not compensated by the higher (perceived) risk of blight. Fungicides play a crucial role in the integrated control of late blight. The spray strategies in NW Europe and a table of the specific attributes of the most important fungicides in Europe are presented. The development and use of decision support systems (DSSs) in NW Europe are described. In The Netherlands, it is estimated that almost 40% of potato growers use recommendations based on commercially available DSS. In the Nordic countries, a new DSS concept with a fixed 7-day spray interval and a variable dose rate is being tested. In the UK, commercially available DSSs are used for c. 8% of the area. The validity of Smith Periods for the new population of P. infestans in the UK is currently being evaluated.

The effect of the ingestion of myo-inositol hexaphosphate (IP6) and phytase (EC 3.1.3.26) on the digestibility of casein was investigated using growing broiler chickens. A total of 64 female Ross broilers were used in a precision feeding study. One group of 8 birds was fed a solution of glucose to estimate endogenous losses. Seven groups, each of 8 birds, were fed either casein, casein + 1,000 units of phytase activity (FTU), casein + 2,000 FTU, casein + 0.5 g of IP6, casein + 0.5 g of IP6 + 1,000 FTU, casein + 1 g of IP6, or casein + 1 g of IP6 + 1,000 FTU. The excretion of DM, amino acids, nitrogen, minerals, and phytate-phosphorus was determined over a 48-h period and nutrient digestibility coefficients were calculated. Casein was found to be highly digestible, with true coefficients of DM, N, and amino acid digestibility of between 0.85 and 1.0. However, the ingestion of IP6 reduced (P < 0.05) the digestibility coefficients of amino acids, N, and DM of casein compared with birds fed casein alone. Supplementation of the mixture of casein and IP6 with phytase improved (P < 0.05) the digestibility coefficients of amino acids compared with birds fed on casein and IP6 with no supplemental phytase. The excretion of endogenous minerals was increased (P < 0.05) by the ingestion of IP6 and reduced (P < 0.05) by the supplementation of IP6 with phytase. In the absence of exogenous phytase, the recovery of phytate-P in excreta was approximately 80%. However, the recovery of phytate-P was significantly reduced by the addition of exogenous phytase to the IP6/casein mixture. It can be concluded that the ingestion of IP6 reduces the digestibility coefficients of amino acids and the metabolizability of nitrogen of casein. This is likely to be mediated partially through increased endogenous losses. However, the addition of phytase can partially ameliorate the detrimental effects of IP6 on protein utilization.

BACKGROUND: Peripheral nerve blocks can be performed using ultrasound guidance. It is not yet clear whether this method of nerve location has benefits over other existing methods. This review was originally published in 2009 and was updated in 2014. OBJECTIVES: The objective of this review was to assess whether the use of ultrasound to guide peripheral nerve blockade has any advantages over other methods of peripheral nerve location. Specifically, we have asked whether the use of ultrasound guidance:1. improves success rates and effectiveness of regional anaesthetic blocks, by increasing the number of blocks that are assessed as adequate2. reduces the complications, such as cardiorespiratory arrest, pneumothorax or vascular puncture, associated with the performance of regional anaesthetic blocks SEARCH METHODS: In the 2014 update we searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 8); MEDLINE (July 2008 to August 2014); EMBASE (July 2008 to August 2014); ISI Web of Science (2008 to April 2013); CINAHL (July 2014); and LILACS (July 2008 to August 2014). We completed forward and backward citation and clinical trials register searches.The original search was to July 2008. We reran the search in May 2015. We have added 11 potential new studies of interest to the list of 'Studies awaiting classification' and will incorporate them into the formal review findings during future review updates. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing ultrasound-guided peripheral nerve block of the upper and lower limbs, alone or combined, with at least one other method of nerve location. In the 2014 update, we excluded studies that had given general anaesthetic, spinal, epidural or other nerve blocks to all participants, as well as those measuring the minimum effective dose of anaesthetic drug. This resulted in the exclusion of five studies from the original review. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We used standard Cochrane methodological procedures, including an assessment of risk of bias and degree of practitioner experience for all studies. MAIN RESULTS: We included 32 RCTs with 2844 adult participants. Twenty-six assessed upper-limb and six assessed lower-limb blocks. Seventeen compared ultrasound with peripheral nerve stimulation (PNS), and nine compared ultrasound combined with nerve stimulation (US + NS) against PNS alone. Two studies compared ultrasound with anatomical landmark technique, one with a transarterial approach, and three were three-arm designs that included US, US + PNS and PNS.There were variations in the quality of evidence, with a lack of detail in many of the studies to judge whether randomization, allocation concealment and blinding of outcome assessors was sufficient. It was not possible to blind practitioners and there was therefore a high risk of performance bias across all studies, leading us to downgrade the evidence for study limitations using GRADE. There was insufficient detail on the experience and expertise of practitioners and whether experience was equivalent between intervention and control.We performed meta-analysis for our main outcomes. We found that ultrasound guidance produces superior peripheral nerve block success rates, with more blocks being assessed as sufficient for surgery following sensory or motor testing (Mantel-Haenszel (M-H) odds ratio (OR), fixed-effect 2.94 (95% confidence interval (CI) 2.14 to 4.04); 1346 participants), and fewer blocks requiring supplementation or conversion to general anaesthetic (M-H OR, fixed-effect 0.28 (95% CI 0.20 to 0.39); 1807 participants) compared with the use of PNS, anatomical landmark techniques or a transarterial approach. We were not concerned by risks of indirectness, imprecision or inconsistency for these outcomes and used GRADE to assess these outcomes as being of moderate quality. Results were similarly advantageous for studies comparing US + PNS with NS alone for the above outcomes (M-H OR, fixed-effect 3.33 (95% CI 2.13 to 5.20); 719 participants, and M-H OR, fixed-effect 0.34 (95% CI 0.21 to 0.56); 712 participants respectively). There were lower incidences of paraesthesia in both the ultrasound comparison groups (M-H OR, fixed-effect 0.42 (95% CI 0.23 to 0.76); 471 participants, and M-H OR, fixed-effect 0.97 (95% CI 0.30 to 3.12); 178 participants respectively) and lower incidences of vascular puncture in both groups (M-H OR, fixed-effect 0.19 (95% CI 0.07 to 0.57); 387 participants, and M-H OR, fixed-effect 0.22 (95% CI 0.05 to 0.90); 143 participants). There were fewer studies for these outcomes and we therefore downgraded both for imprecision and paraesthesia for potential publication bias. This gave an overall GRADE assessment of very low and low for these two outcomes respectively. Our analysis showed that it took less time to perform nerve blocks in the ultrasound group (mean difference (MD), IV, fixed-effect -1.06 (95% CI -1.41 to -0.72); 690 participants) but more time to perform the block when ultrasound was combined with a PNS technique (MD, IV, fixed-effect 0.76 (95% CI 0.55 to 0.98); 587 participants). With high levels of unexplained statistical heterogeneity, we graded this outcome as very low quality. We did not combine data for other outcomes as study results had been reported using differing scales or with a combination of mean and median data, but our interpretation of individual study data favoured ultrasound for a reduction in other minor complications and reduction in onset time of block and number of attempts to perform block. AUTHORS' CONCLUSIONS: There is evidence that peripheral nerve blocks performed by ultrasound guidance alone, or in combination with PNS, are superior in terms of improved sensory and motor block, reduced need for supplementation and fewer minor complications reported. Using ultrasound alone shortens performance time when compared with nerve stimulation, but when used in combination with PNS it increases performance time.We were unable to determine whether these findings reflect the use of ultrasound in experienced hands and it was beyond the scope of this review to consider the learning curve associated with peripheral nerve blocks by ultrasound technique compared with other methods.

Abstract This paper evaluates current issues surrounding the role and development of rural tourism in southeastern Europe (SEE) (Romania, Bulgaria, Albania and much of former Yugoslavia), setting this within the wider context of change in post‐communist central and eastern Europe (CEE). It examines local and global factors of development and change, particularly within the context of aspirations towards sustainability. The paper concludes that the impacts of EU membership — both of the 2004 enlargement, and later potentially for the countries of southeastern Europe themselves — is likely to be crucial in market and product development for rural tourism. Copyright © 2004 John Wiley &amp; Sons, Ltd.

BACKGROUND: Cardiovascular disease is the most common cause of death globally. Traditionally, centre-based cardiac rehabilitation programmes are offered to individuals after cardiac events to aid recovery and prevent further cardiac illness. Home-based cardiac rehabilitation programmes have been introduced in an attempt to widen access and participation. This is an update of a review originally published in 2009. OBJECTIVES: To compare the effect of home-based and supervised centre-based cardiac rehabilitation on mortality and morbidity, health-related quality of life, and modifiable cardiac risk factors in patients with heart disease. SEARCH METHODS: To update searches from the previous Cochrane review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 9, 2014), MEDLINE (Ovid, 1946 to October week 1 2014), EMBASE (Ovid, 1980 to 2014 week 41), PsycINFO (Ovid, 1806 to October week 2 2014), and CINAHL (EBSCO, to October 2014). We checked reference lists of included trials and recent systematic reviews. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared centre-based cardiac rehabilitation (e.g. hospital, gymnasium, sports centre) with home-based programmes in adults with myocardial infarction (MI), angina, heart failure or who had undergone revascularisation. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the eligibility of the identified trials and data were extracted by a single author and checked by a second. Authors were contacted where possible to obtain missing information. MAIN RESULTS: Seventeen trials included a total of 2172 participants undergoing cardiac rehabilitation following an acute MI or revascularisation, or with heart failure. This update included an additional five trials on 345 patients with heart failure. Authors of a number of included trials failed to give sufficient detail to assess their potential risk of bias, and details of generation and concealment of random allocation sequence were particularly poorly reported. In the main, no difference was seen between home- and centre-based cardiac rehabilitation in outcomes up to 12 months of follow up: mortality (relative risk (RR) = 0.79, 95% confidence interval (CI) 0.43 to 1.47, P = 0.46, fixed-effect), cardiac events (data not poolable), exercise capacity (standardised mean difference (SMD) = -0.10, 95% CI -0.29 to 0.08, P = 0.29, random-effects), modifiable risk factors (total cholesterol: mean difference (MD) = 0.07 mmol/L, 95% CI -0.24 to 0.11, P = 0.47, random-effects; low density lipoprotein cholesterol: MD = -0.06 mmol/L, 95% CI -0.27 to 0.15, P = 0.55, random-effects; systolic blood pressure: mean difference (MD) = 0.19 mmHg, 95% CI -3.37 to 3.75, P = 0.92, random-effects; proportion of smokers at follow up (RR = 0.98, 95% CI 0.79 to 1.21, P = 0.83, fixed-effect), or health-related quality of life (not poolable). Small outcome differences in favour of centre-based participants were seen in high density lipoprotein cholesterol (MD = -0.07 mmol/L, 95% CI -0.11 to -0.03, P = 0.001, fixed-effect), and triglycerides (MD = -0.18 mmol/L, 95% CI -0.34 to -0.02, P = 0.03, fixed-effect, diastolic blood pressure (MD = -1.86 mmHg; 95% CI -0.76 to -2.95, P = 0.0009, fixed-effect). In contrast, in home-based participants, there was evidence of a marginally higher levels of programme completion (RR = 1.04, 95% CI 1.01 to 1.07, P = 0.009, fixed-effect) and adherence to the programme (not poolable). No consistent difference was seen in healthcare costs between the two forms of cardiac rehabilitation. AUTHORS' CONCLUSIONS: This updated review supports the conclusions of the previous version of this review that home- and centre-based forms of cardiac rehabilitation seem to be equally effective for improving the clinical and health-related quality of life outcomes in low risk patients after MI or revascularisation, or with heart failure. This finding, together with the absence of evidence of important differences in healthcare costs between the two approaches, supports the continued expansion of evidence-based, home-based cardiac rehabilitation programmes. The choice of participating in a more traditional and supervised centre-based programme or a home-based programme should reflect the preference of the individual patient. Further data are needed to determine whether the effects of home- and centre-based cardiac rehabilitation reported in these short-term trials can be confirmed in the longer term. A number of studies failed to give sufficient detail to assess their risk of bias.

BACKGROUND: Since the early 1980s, it has become more and more common to carry out surgical procedures on a day case basis. Many patients are anxious before surgery yet there is sometimes a reluctance to provide sedative medication because it is believed to delay discharge from hospital.This is an updated version of the review first published in 2000 (previous updates 2003; 2006). OBJECTIVES: To assess the effect of anxiolytic premedication on time to discharge in adult patients undergoing day case surgery under general anaesthesia. SEARCH STRATEGY: We identified trials by computerized searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2009 Issue 1 ); MEDLINE (1980 to January 2009); EMBASE (1980 to January 2009). We also checked the reference lists of trials and review articles and handsearched three main anaesthesia journals. SELECTION CRITERIA: We included all identified randomized controlled trials comparing anxiolytic drug(s) with placebo before general anaesthesia in adult day case surgical patients. DATA COLLECTION AND ANALYSIS: We collected data on anaesthetic drugs used; results of psychomotor function tests where these were used to assess residual effect of premedication; and on times from end of anaesthesia to ability to walk unaided or readiness for discharge from hospital. Formal statistical synthesis of individual trials was not performed in view of the variety of drugs studied. MAIN RESULTS: We included 17 studies. Methodological quality of included studies was poor. Of these 17, only seven studies specifically addressed the discharge question; none found any delay in premedicated patients. Two other studies used clinical criteria to assess fitness for discharge, though times were not given. Again, there was no difference from placebo. Eleven studies used tests of psychomotor function with or without clinical measures as indicators of recovery from anaesthesia. In none of these studies did the premedication appear to delay discharge, although performance on tests of psychomotor function was sometimes still impaired. Three studies showed no impairment in psychomotor function, six showed some impairment which had resolved by three hours or time of discharge and two showed significant impairment. AUTHORS' CONCLUSIONS: We found no evidence of a difference in time to discharge from hospital, assessed by clinical criteria, in patients who received anxiolytic premedication. However, in view of the age and variety of anaesthetic techniques used and clinical heterogeneity between studies, inferences for current day case practice should be made with caution.

Abstract Excessive gambling is recognized with dopamine agonist therapy, but the prevalence is unknown. We assessed the prevalence of excess gambling by specific prospective enquiry in Parkinson's disease patients attending six West Scotland movement disorder clinics. Of 388 patients taking anti‐Parkinson medication, 17 (4.4%) developed pathological gambling, all of whom were prescribed dopamine agonists. Thus, 8% of patients taking dopamine agonists had pathological gambling. Pathological gambling is not uncommon, and patients should be made aware of this potential adverse effect. © 2006 Movement Disorder Society

Plant uptake is one of the major pathways by which sludge-borne potentially toxic metals enter the food chain. This study examined the accumulation of Cd, Cu, Ni, Pb and Zn in wheat, carrots and spinach grown on soils from 13 sites previously amended with sewage sludge. Winter wheat, carrots and spinach were grown consecutively under field like conditions. The results showed that plant availability of heavy metals differed widely among the crop species. The accumulation of Cd, Ni and Zn in the plants showed the greatest increases compared to their background levels. The Cu and Pb accumulation in the plants grown on sludge-amended soils showed only small increases compared to those grown on uncontaminated soils. Multiple regression analysis of various soil properties showed that the surest way to control the accumulation of metals in food plants is by controlling their concentrations in the soils. Furthermore, soils with a non-acidic pH and a clayey texture tended to achieve better control of metal accumulation in food plants compared to those with an acidic reaction and a coarse texture. Metal concentrations in the plants generally correlated well with those extracted from soils in 0·005 M DTPA, 0·05 M EDTA-(Na)2, 1 M NH4NO3 and 0·05 M CaCl2. The EDTA, however, proved to be a more reliable and consistent test in predicting the accumulation of metals in the plants. The results also showed that liming soils to pH 7 effectively reduced the metal contents in carrots and spinach, but liming to pH 6·5 had little effect on metal concentrations in wheat grain. © 1997 SCI.

Background Pragmatic trials compare the effects of different decisions in usual clinical practice. Objectives To develop and evaluate methods to implement simple pragmatic trials using routinely collected electronic health records (EHRs) and recruiting patients at the point of care; to identify the barriers and facilitators for general practitioners (GPs) and patients and the experiences of trial participants. Design Two exemplar randomised trials (Retropro and eLung) with qualitative evaluations. Setting Four hundred and fifty-nine English and Scottish general practices contributing EHRs to a research database, of which 17 participated in the trials. Participants Retropro aimed to recruit 300 patients with hypercholesterolaemia and high cardiovascular risk and eLung aimed to recruit 150 patients with a chronic obstructive pulmonary disease exacerbation. Interventions Retropro randomised between simvastatin and atorvastatin and eLung between immediate antibiotics and deferred or non-use. eLung recruited during an unscheduled consultation using EHR flagging. Main outcome measure Successful trial completion with implementation of information technology (IT) system for flagging and data processing and documentation of operational and scientific experiences. Data sources EHR research database. Results The governance approval process took over 3 years. A total of 58.8% of the practices (n = 270) expressed interest in participating. The number of interested practices dropped substantially with each stage of the governance process. In Retropro, 6.5% of the practices (n = 30) were eventually approved and 3.7% (n = 17) recruited patients; in eLung, these numbers were 6.8% (n = 31) and 1.3% (n = 6) respectively. Retropro successfully completed recruitment (301 patients) whereas eLung recruited 31 patients. Retropro recruited 20.6% of all statin starters in recruiting practices and 1.1% in the EHR database; the comparable numbers for eLung were 32.3% and 0.9% respectively. The IT system allowed for complex eligibility criteria with central on and off control of recruitment and flagging at a practice. Good Clinical Practice guidelines, governance and consent procedures were found to have substantially affected the intended simple nature of the trials. One qualitative study of 13 clinicians found that clinicians were generally positive about the principle of computerised trial recruitment (flagging during consultation). However, trials which did not include patients with acute illness were favoured. The second qualitative process evaluation interviewed 27 GPs about their actual experiences, including declining, recruiting and non-recruiting GPs. Opportunistic patient recruitment during a routine GP consultation was found to be the most controversial element. The actual experiences of recruiting patients during unscheduled consultation were generally more positive than the hypothetical views of GPs. Several of the recruiting GPs reported the process took 5 minutes and was straightforward and feasible on most occasions. Almost all GPs expressed their strong support for the use of EHRs for trials. Ten eLung participants were interviewed, all of whom considered it acceptable to be recruited during a consultation and to use EHRs for trials. Conclusions EHR point-of-care trials are feasible, although the recruitment of clinicians is a major challenge owing to the complexity of trial approvals. These trials will provide substantial evidence on clinical effectiveness only if trial interventions and participating clinicians and patients are typical of usual clinical care and trials are simple to initiate and conduct. Recommendations for research include the development of evidence and implementation of risk proportionality in trial governance and conduct. Trial registration Current Controlled Trials ISRCTN33113202 and ISRCTN72035428. Funding This project was funded by the NIHR Health Technology Assessment programme and the Wellcome Trust and will be published in full in Health Technology Assessment; Vol. 18, No. 43. See the NIHR Journals Library website for further project information.

Objective To update the Cochrane review comparing the effects of home-based and supervised centre-based cardiac rehabilitation (CR) on mortality and morbidity, quality of life, and modifiable cardiac risk factors in patients with heart disease. Methods Systematic review and meta-analysis. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and CINAHL were searched up to October 2014, without language restriction. Randomised trials comparing home-based and centre-based CR programmes in adults with myocardial infarction, angina, heart failure or who had undergone coronary revascularisation were included. Results 17 studies with 2172 patients were included. No difference was seen between home-based and centre-based CR in terms of: mortality (relative risk (RR) 0.79, 95% CI 0.43 to 1.47); cardiac events; exercise capacity (mean difference (MD) −0.10, −0.29 to 0.08); total cholesterol (MD 0.07 mmol/L, −0.24 to 0.11); low-density lipoprotein cholesterol (MD −0.06 mmol/L, −0.27 to 0.15); triglycerides (MD −0.16 mmol/L, −0.38 to 0.07); systolic blood pressure (MD 0.2 mm Hg, −3.4 to 3.8); smoking (RR 0.98, 0.79 to 1.21); health-related quality of life and healthcare costs. Lower high-density lipoprotein cholesterol (MD −0.07 mmol/L, −0.11 to −0.03, p=0.001) and lower diastolic blood pressure (MD −1.9 mm Hg, −0.8 to −3.0, p=0.009) were observed in centre-based participants. Home-based CR was associated with slightly higher adherence (RR 1.04, 95% CI 1.01 to 1.07). Conclusions Home-based and centre-based CR provide similar benefits in terms of clinical and health-related quality of life outcomes at equivalent cost for those with heart failure and following myocardial infarction and revascularisation.

The aim of this study was to characterise the microbiome of new and recurrent diabetic foot ulcers using 16S amplicon sequencing (16S AS), allowing the identification of a wider range of bacterial species that may be important in the development of chronicity in these debilitating wounds. Twenty patients not receiving antibiotics for the past three months were selected, with swabs taken from each individual for culture and 16S AS. DNA was isolated using a combination of bead beating and kit extraction. Samples were sequenced on the Illumina Hiseq 2500 platform. Conventional laboratory culture showed positive growth from only 55 % of the patients, whereas 16S AS was positive for 75 % of the patients (41 unique genera, representing 82 different operational taxonomic units (OTU’s). S. aureus was isolated in 72 % of culture-positive samples, whereas the most commonly detected bacteria in all ulcers were Peptoniphilus spp., Anaerococcus spp. and Corynebacterium spp., with the addition of Staphylococcus spp. in new ulcers. The majority of OTU’s residing in both new and recurrent ulcers (over 67 %) were identified as facultative or strict anaerobic Gram-positive organisms. Principal component analysis (PCA) showed no difference in clustering between the two groups (new and recurrent ulcers). The abundance of anaerobic bacteria has important implications for treatment as it suggests that the microbiome of each ulcer “starts afresh” and that, although diverse, are not distinctly different from one another with respect to new or recurrent ulcers. Therefore, when considering antibiotic therapy the duration of current ulceration may be a more important consideration than a history of healed ulcer.

INTRODUCTION: The obstructed, infected kidney is a urological emergency. It has been accepted that the management of infected hydronephrosis secondary to ureteric stones is through prompt decompression of the collecting system. However, the optimal method of decompression has yet to be established. MATERIALS AND METHODS: A PubMed and Medline search was performed of all English-language articles from 1960 using key words "sepsis," "urosepsis," "obstruction," "obstructive pyelonephritis," "pyonephrosis," "infection and hydronephrosis" "decompression," "stent," "nephrostomy," and "management." The Cochrane database and National Institute for Clinical Effectiveness guidelines were searched using the terms "sepsis," "urosepsis," "stent," "nephrostomy," or "obstruction." Scottish intercollegiate guidelines were reviewed and no relevant guidance was identified. RESULTS: Two randomised trials have compared retrograde stent insertion with percutaneous nephrostomy with one trial reporting specifically on patients with acute sepsis and obstruction. Neither trial showed one superior modality of decompression in effecting decompression and resolution of sepsis. A further literature search regarding the complications of percutaneous nephrostomy and stent insertion was carried out. An overall major complication rate from percutaneous nephrostomy insertion was found to be 4%, although the complication rates from stent insertion are less consistently reported. DISCUSSION: There appears little evidence to suggest that retrograde stent insertion leads to increased bacteraemia or is significantly more hazardous in the setting of acute obstruction. Further region-wide discussion between urologists and interventional radiologists is required to establish management protocols for these acutely unwell patients.

. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children.

Transcranial Doppler sonography is a non-invasive, non-ionising, inexpensive, portable and safe technique that uses a pulsed Doppler transducer for assessment of intracerebral blood flow. This article deals with the principles and technique of transcranial Doppler sonography. It gives a brief overview of its use in evaluation of intracranial steno-occlusive disease, subarachnoid haemorrhage, and extracranial diseases (including carotid artery disease and subclavian steal syndrome). The role of transcranial Doppler in detection of microembolic signals and evaluation of right to left shunts is also dealt with. Finally, its use in acute stroke is briefly outlined.

Abstract The antifungal and fungicidal effects of two chemotypes of basil ( Ocimum basilicum ) oil and its major individual components were studied in a series of in vitro and in vivo experiments. Mycelial growth of the plant pathogenic fungus Botrytis fabae was reduced significantly by both the methyl chavicol chemotype oil and the linalol chemotype oil, and the major individual components of the oils all reduced fungal growth, with methyl chavicol, linalol, eugenol and eucalyptol reducing growth significantly. Combining the pure oil components in the same proportions as found in the whole oil led to very similar reductions in fungal growth, suggesting that the antifungal effects of the whole oils were due primarily to the major components. When the fungus was exposed to the oils in liquid culture, growth was reduced by concentrations considerably smaller than those used in the Petri dish studies. Botrytis fabae and the rust fungus Uromyces fabae were also controlled in vivo , with the whole oils of both chemotypes, as well as pure methyl chavicol and linalol, reducing infection of broad bean leaves significantly. Most effective control of fungal infection was achieved if the treatments were applied 3 h postinoculation.

AIMS: To compare the degree of conjunctival autograft inflammation, subconjunctival haemorrhage (SCH) and graft stability following the use of sutures or fibrin glue (FG) during pterygium surgery. METHODS: Prospective, observer masked, clinical trial. 40 eyes of 40 patients undergoing primary pterygium surgery with conjunctival autograft were allocated into two groups. Group 1 (n = 20) had FG (Tisseel) for attaching the conjunctival autograft, whereas group 2 (n = 20) had sutures. Standardised digital slit-lamp photographs were taken at 1 week, 1 month and 3 months postoperatively. Sutures were masked using commercially available photo-editing software. Two masked observers objectively graded the digital photographs for degree of inflammation, SCH and graft stability. RESULTS: 34 of the 40 patients completed the study. When using FG, the degree of inflammation was significantly less than with sutures at 1 month (p = 0.019) and 3 months (p = 0.001) postoperatively. No significant difference was found for inflammation at 1 week postoperatively (p = 0.518). Conjunctival grafts secured with FG were as stable as those secured with sutures (p = 0.258, p = 0.076 and p = 0.624, at 1 week, 1 month and 3 months, respectively). No significant difference was found in degree of postoperative SCH between the groups (p = 0.417, p = 1 and p = 1, at 1 week, 1 month and 3 months, respectively). CONCLUSION: This is the first prospective clinical trial confirming that conjunctival grafts secured with FG during pterygium surgery not only are as stable as those secured with sutures, but also produce significantly less inflammation.