Intravenous magnesium sulfate for treating adults with acute asthma in the emergency department.

BACKGROUND: Asthma is a chronic respiratory condition characterised by airways inflammation, constriction of airway smooth muscle and structural alteration of the airways that is at least partially reversible. Exacerbations of asthma can be life threatening and place a significant burden on healthcare services. Various guidelines have been published to inform management personnel in the acute setting; several include the use of a single bolus of intravenous magnesium sulfate (IV MgSO4) in cases that do not respond to first-line treatment. However, the effectiveness of this approach remains unclear, particularly in less severe cases. OBJECTIVES: To assess the safety and efficacy of IV MgSO4 in adults treated for acute asthma in the emergency department. SEARCH METHODS: We identified trials from the Cochrane Airways Review Group Specialised Register (CAGR) up to 2 May 2014. We also searched www.ClinicalTrials.gov and reference lists of other reviews, and we contacted trial authors to ask for additional information. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of adults treated in the emergency department (ED) for exacerbations of asthma if they compared any dose of IV MgSO4 with placebo. DATA COLLECTION AND ANALYSIS: All review authors screened titles and abstracts for inclusion, and at least two review authors independently extracted study characteristics, risk of bias and numerical data. Disagreements were resolved by consensus, and we contacted trial investigators to obtain missing information.We analysed dichotomous data as odds ratios using study participants as the unit of analysis, and we analysed continuous data as mean differences or standardised mean differences using fixed-effect models. We rated all outcomes using GRADE and presented results in Summary of findings table 1.We carried out subgroup analyses on the primary outcome for baseline severity of exacerbations and whether or not ipratropium bromide was given as a co-medication. Unpublished data and studies at high risk of bias for blinding were removed from the main analysis in sensitivity analyses. MAIN RESULTS: Fourteen studies met the inclusion criteria, randomly assigning 2313 people with acute asthma to the comparisons of interest in this review.Most studies were double-blinded trials comparing a single infusion of 1.2 g or 2 g IV MgSO4 over 15 to 30 minutes versus a matching placebo. Eleven were conducted at a single centre, and three were multi-centre trials. Participants in almost all of the studies had already been given at least oxygen, nebulised short-acting beta2-agonists and IV corticosteroids in the ED; in some studies, investigators also administered ipratropium bromide. Ten studies included only adults, and four included both adults and children; these were included because the mean age of participants was over 18 years.Intravenous MgSO4 reduced hospital admissions compared with placebo (odds ratio (OR) 0.75, 95% confidence interval (CI) 0.60 to 0.92; I(2) = 28%, P value 0.18; n = 972; high-quality evidence). In absolute terms, this odds ratio translates into a reduction of seven hospital admissions for every 100 adults treated with IV MgSO4 (95% CI two to 13 fewer). The test for subgroup differences revealed no statistical heterogeneity between the three severity subgroups (I(2) = 0%, P value 0.73) or between the four studies that administered nebulised ipratropium bromide as a co-medication and those that did not (I(2) = 0%, P value 0.82). Sensitivity analyses in which unpublished data and studies at high risk for blinding were removed from the primary analysis did not change conclusions.Within the secondary outcomes, high- and moderate-quality evidence across three spirometric indices suggests some improvement in lung function with IV MgSO4. No difference was found between IV MgSO4and placebo for most of the non-spirometric secondary outcomes, all of which were rated as low or moderate quality (intensive care admissions, ED treatment duration, length of hospital stay, readmission, respiration rate, systolic blood pressure).Adverse events were inconsistently reported and were not meta-analysed. The most commonly cited adverse events in the IV MgSO4 groups were flushing, fatigue, nausea and headache and hypotension (low blood pressure). AUTHORS' CONCLUSIONS: This review provides evidence that a single infusion of 1.2 g or 2 g IV MgSO4 over 15 to 30 minutes reduces hospital admissions and improves lung function in adults with acute asthma who have not responded sufficiently to oxygen, nebulised short-acting beta2-agonists and IV corticosteroids. Differences in the ways the trials were conducted made it difficult for the review authors to assess whether severity of the exacerbation or additional co-medications altered the treatment effect of IV MgSO4. Limited evidence was found for other measures of benefit and safety.Studies conducted in these populations should clearly define baseline severity parameters and systematically record adverse events. Studies recruiting participants with exacerbations of varying severity should consider subgrouping results on the basis of accepted severity classifications

Robust assessment of future changes in extreme precipitation over the Rhine basin using a GCM

Estimates of future changes in extremes of multiday precipitation sums are critical for estimates of future discharge extremes of large river basins. Here we use a large ensemble of global climate model SRES A1b scenario simulations to estimate changes in extremes of 1–20 day precipitation sums over the Rhine basin, projected for the period 2071–2100 with reference to 1961–1990. We find that in winter, an increase of order 10%, for the 99th percentile precipitation sum, is approximately fixed across the selected range of multiday sums, whereas in summer, the changes become increasingly negative as the summation time lengthens. Explanations for these results are presented that have implications for simple scaling methods for creating time series of a future climate. We show that the dependence of quantile changes on summation time is sensitive to the ensemble size and indicate that currently available discharge estimates from previous studies are based on insufficiently long time series

Combination formoterol and budesonide as maintenance and reliever therapy versus combination inhaler maintenance for chronic asthma in adults and children.

BACKGROUND: Asthma is characterised by chronic inflammation of the airways and recurrent exacerbations with wheezing, chest tightness and cough. Treatment with inhaled steroids and bronchodilators often results in good control of symptoms, prevention of further morbidity and mortality and improved quality of life. Several steroids and beta2-agonists (long- and short-acting) as well as combinations of these treatments are available in a single inhaler to be used once or twice a day, with a separate inhaler for relief of symptoms when needed (for patients in Step three or higher, according to Global Initiative for Asthma (GINA) guidelines). Budesonide/formoterol is also licenced for use as maintenance and reliever therapy from a single inhaler (SiT; sometimes referred to as SMART therapy). SiT can be prescribed at a lower dose than other combination therapy because of the additional steroid doses being received as reliever therapy. It has been suggested that using SiT improves compliance and hence reduces symptoms and exacerbations, but it is unclear whether it increases side effects associated with the use of inhaled steroids. OBJECTIVES: To assess the efficacy and safety of budesonide/formoterol in a single inhaler (SiT) to be used for both maintenance and reliever therapy in asthma in comparison with maintenance treatment provided through combination inhalers with a higher maintenance steroid dose (either fluticasone/salmeterol or budesonide/formoterol), along with additional fast-acting beta2-agonists for relief of symptoms. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register of trials, online trial registries and drug company websites. The most recent search was conducted in November 2013. SELECTION CRITERIA: We included parallel-group, randomised controlled trials of at least 12 weeks' duration. Studies were included if they compared single-inhaler therapy with budesonide/formoterol (SiT) versus combination inhalers at a higher maintenance dose of steroids than was given in the SiT arm (either salmeterol/fluticasone or budesonide/formoterol). DATA COLLECTION AND ANALYSIS: We used standard methods expected by The Cochrane Collaboration. Primary outcomes were exacerbations requiring hospitalisation, exacerbations requiring oral corticosteroids and serious adverse events (including mortality). MAIN RESULTS: Four studies randomly assigning 9130 people with asthma were included; two were six-month double-blind studies, and two were 12-month open-label studies. No trials included children younger than age 12. Trials included more women than men, with mean age ranging from 38 to 45, and mean baseline steroid dose (inhaled beclomethasone (BDP) equivalent) from 636 to 888 μg. Mean baseline forced expiratory volume in one second (FEV1) percentage predicted was between 70% and 73% in three of the trials, and 96% in another. All studies were funded by AstraZeneca and were generally free from methodological biases, although the two open-label studies were rated as having high risk for blinding, and some evidence of selective outcome reporting was found. These possible sources of bias did not lead us to downgrade the quality of the evidence. The quantity of inhaled steroids, including puffs taken for relief from symptoms, was consistently lower for SiT than for the comparison groups.Separate data for exacerbations leading to hospitalisations, to emergency room (ER) visits or to a course of oral steroids could not be obtained. Compared with higher fixed-dose combination inhalers, fewer people using SiT had exacerbations requiring hospitalisation or a visit to the ER (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.57 to 0.90; I(2) = 0%, P = 0.66), and fewer had exacerbations requiring a course of oral corticosteroids (OR 0.75, 95% CI 0.65 to 0.87; I(2) = 0%, P = 0.82). This translates to one less person admitted to hospital or visiting the ER (95% CI 0 to 2 fewer) and two fewer people needing oral steroids (95% CI 1 to 3 fewer) compared with fixed-dose combination treatment with a short-acting beta-agonist (SABA) reliever (per 100 treated over eight months). No statistical heterogeneity was observed in either outcome, and the evidence was rated of high quality. Although issues with blinding were evident in two of the studies, and one study recruited a less severe population, sensitivity analyses did not change the main results, so quality was not downgraded.We could not rule out the possibility that SiT increased rates of serious adverse events (OR 0.92, 95% CI 0.74 to 1.13; I(2) = 0%, P = 0.98; moderate-quality evidence, downgraded owing to imprecision).We were unable to say whether SiT improved results for several secondary outcomes (morning and evening peak expiratory flow (PEF), rescue medication use, symptoms scales), and in cases where results were significant, the effect sizes were not considered clinically meaningful (predose FEV1, nocturnal awakenings and quality of life). AUTHORS' CONCLUSIONS: SiT reduces the number of people having asthma exacerbations requiring oral steroids and the number requiring hospitalisation or an ER visit compared with fixed-dose combination inhalers. Evidence for serious adverse events was unclear. The mean daily dose of inhaled corticosteroids (ICS) in SiT, including the total dose administered with reliever use, was always lower than that of the other combination groups. This suggests that the flexibility in steroid administration that is possible with SiT might be more effective than a standard fixed-dose combination by increasing the dose only when needed and keeping it low during stable stages of the disease. Data for hospitalisations alone could not be obtained, and no studies have yet addressed this question in children younger than age 12

Confidence Intervals for Policy Reforms in Behavioural Tax Microsimulation Modelling

This paper addresses the need for a measure of the uncertainty that is associated with the results calculated through tax policy behavioural microsimulation modelling. Deriving the analytical measure would be extremely complicated, therefore, a simulated approach is proposed which generates a pseudo sampling distribution of aggregate measures based on the sampling distribution of the estimated labour supply parameters. This approach, which is very computer intensive, is compared to a more time-efficient approach where the functional form of the sampling distribution is assumed to be normal. The results show that in many instances the results from the two approaches are quite similar. The exception is when aggregate measures for minor types of payments, involving relatively small groups of the population, are examined.

Fearsome truths : the challenge of animal liberation.

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN029281 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

An Exploration of Organisational Culture's Contribution to Job Stress in Cape Town Non-Profit Organisations, using the Culture-Work-Health Model

Organisational culture plays an essential role in the aetiology of job stress. Job stress has numerous negative effects including lower work performance and effectiveness, health problems and increased absenteeism. The direct and indirect costs associated with stress-related conditions, such as burnout, can result in reduced organisational commitment and engagement. Such situations require urgent attention from the management of any organisation, and it is essential that organisations take appropriate steps to avoid excessive stress of employees if they are to continue their vital work. The study uses the Culture-Work-Health Model as a framework to understand organisational culture and its contribution to job stress in Cape Town non-profit organisations (NPOs) working in the discipline of mental health and mental disability. An exploratory, qualitative research design was selected to develop an understanding of organisational culture in Cape Town NPOs. Seven employees from three NPOs, making up the total sample of 21 participants, were selected through non-probability, purposive sampling. From each organisation of seven employees, four were selected from management/leadership positions and three were selected from non-management in order to gain rich insightful data from both management and non-management perspectives. Data collection was done through semistructured, face-to-face interviews with the participants. The data was analysed through the use of Tesch's (1990) stages of analysis. Finally, a framework for analysis was developed based on the themes, categories and sub-categories that emerged. This study contributes to enhancing understanding of Cape Town NPO organisational culture, NPO management practices and job stress as well as providing a springboard for further research into these areas. A number of significant findings were made including: NPOs described a clan organisation-type culture with a committed and passionate staff; NPO management were perceived as unsupportive due to lack of transparency, which was exasperated by their inability to pay higher salaries; NPOs where management incorporate supervision and regular staff meetings were perceived more positively and reported fewer issues of miscommunication; and individuals who were able to incorporate a healthy work and non-work life balance thrived in the NPO setting. Based on these findings, a number of recommendations were made including: the development of an organisational mental health policy; mandatory regular staff meetings attended by all levels of staff to discuss general administrative issues; the communicated availability of support structures to staff, such as on-site counselling; and - very importantly - regular supervision for all staff members working directly with vulnerable clients

Compact/micro heat exchangers – Their role in heat pumping equipment

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.Compact and micro-heat exchangers have many advantages over their larger counterparts, particularly when used to handle clean fluid streams, either single- or two-phase. Probably the most exciting feature of such heat exchangers is their ability to operate with close approach temperatures, leading to high effectiveness. This can be particularly beneficial when the exchangers are used in power-producing or power-consuming systems, where the improved heat exchanger effectiveness can be immediately realised in higher power outputs or reduced power consumption. In the case of heat pumping equipment – the most common examples being air-water or air-air vapour compression cycle heat pumps for domestic heating – this manifests itself in an increased Coefficient of Performance (COP) that reduces CO2 emissions due to a lower energy input needed to drive the compressor. This paper discusses some of the work carried out in five countries, Austria, Japan, Sweden, USA and the UK, within the IEA Heat Pump Implementing Agreement Annex 33 to identify the heat exchangers that can most benefit heat pump cycles, with a strong emphasis on micro-channel heat transfer. It also presents data on other research relevant to the subject, with an emphasis on the ‘micro’ size range

Boiling in narrow channels

An experimental and theoretical study of the phenomena involved during boiling in narrow channels is presented. The channels are of a small size typical of those in the new micro-compact heat exchangers. Correlations and design methods used in the design of conventionally sized evaporators are summarised and the literature covering boiling in confined spaces is reviewed. It is shown that the published data are insufficient to allow the design of novel compact evaporators incorporating narrow channels to be undertaken with confidence. A dimensionless criterion for determining the channel size at which the effects of confinement are likely to be significant for different fluids has been derived. It has been demonstrated that the flow in narrow channels can be divided into three flow regimes; Isolated Bubble, Confined Bubble and Annular-Slug Flow. A new model has been proposed which allows the prediction of evaporative heat transfer coefficients in each regime and this model has been tested against the Author's and other measured data. A fair degree of corroboration was achieved and it is argued that the model yields a thermal design methodology for narrow channel evaporators