Factors that impact on the use of mechanical ventilation weaning protocols in critically ill adults and children: a qualitative-evidence synthesis

Background:
Prolonged mechanical ventilation is associated with a longer intensive care unit (ICU) length of stay and higher mortality. Consequently, methods to improve ventilator weaning processes have been sought. Two recent Cochrane systematic reviews in ICU adult and paediatric populations concluded that protocols can be effective in reducing the duration of mechanical ventilation, but there was significant heterogeneity in study findings. Growing awareness of the benefits of understanding the contextual factors impacting on effectiveness has encouraged the integration of qualitative evidence syntheses with effectiveness reviews, which has delivered important insights into the reasons underpinning (differential) effectiveness of healthcare interventions.

Objectives:
1. To locate, appraise and synthesize qualitative evidence concerning the barriers and facilitators of the use of protocols for weaning critically-ill adults and children from mechanical ventilation;

2. To integrate this synthesis with two Cochrane effectiveness reviews of protocolized weaning to help explain observed heterogeneity by identifying contextual factors that impact on the use of protocols for weaning critically-ill adults and children from mechanical ventilation;

3. To use the integrated body of evidence to suggest the circumstances in which weaning protocols are most likely to be used.

Search methods:
We used a range of search terms identified with the help of the SPICE (Setting, Perspective, Intervention, Comparison, Evaluation) mnemonic. Where available, we used appropriate methodological filters for specific databases. We searched the following databases: Ovid MEDLINE, Embase, OVID, PsycINFO, CINAHL Plus, EBSCOHost, Web of Science Core Collection, ASSIA, IBSS, Sociological Abstracts, ProQuest and LILACS on the 26th February 2015. In addition, we searched: the grey literature; the websites of professional associations for relevant publications; and the reference lists of all publications reviewed. We also contacted authors of the trials included in the effectiveness reviews as well as of studies (potentially) included in the qualitative synthesis, conducted citation searches of the publications reporting these studies, and contacted content experts.

We reran the search on 3rd July 2016 and found three studies, which are awaiting classification.

Selection criteria:
We included qualitative studies that described: the circumstances in which protocols are designed, implemented or used, or both, and the views and experiences of healthcare professionals either involved in the design, implementation or use of weaning protocols or involved in the weaning of critically-ill adults and children from mechanical ventilation not using protocols. We included studies that: reflected on any aspect of the use of protocols, explored contextual factors relevant to the development, implementation or use of weaning protocols, and reported contextual phenomena and outcomes identified as relevant to the effectiveness of protocolized weaning from mechanical ventilation.

Data collection and analysis:
At each stage, two review authors undertook designated tasks, with the results shared amongst the wider team for discussion and final development. We independently reviewed all retrieved titles, abstracts and full papers for inclusion, and independently extracted selected data from included studies. We used the findings of the included studies to develop a new set of analytic themes focused on the barriers and facilitators to the use of protocols, and further refined them to produce a set of summary statements. We used the Confidence in the Evidence from Reviews of Qualitative Research (CERQual) framework to arrive at a final assessment of the overall confidence of the evidence used in the synthesis. We included all studies but undertook two sensitivity analyses to determine how the removal of certain bodies of evidence impacted on the content and confidence of the synthesis. We deployed a logic model to integrate the findings of the qualitative evidence synthesis with those of the Cochrane effectiveness reviews.

Main results:
We included 11 studies in our synthesis, involving 267 participants (one study did not report the number of participants). Five more studies are awaiting classification and will be dealt with when we update the review.

The quality of the evidence was mixed; of the 35 summary statements, we assessed 17 as ‘low’, 13 as ‘moderate’ and five as ‘high’ confidence. Our synthesis produced nine analytical themes, which report potential barriers and facilitators to the use of protocols. The themes are: the need for continual staff training and development; clinical experience as this promotes felt and perceived competence and confidence to wean; the vulnerability of weaning to disparate interprofessional working; an understanding of protocols as militating against a necessary proactivity in clinical practice; perceived nursing scope of practice and professional risk; ICU structure and processes of care; the ability of protocols to act as a prompt for shared care and consistency in weaning practice; maximizing the use of protocols through visibility and ease of implementation; and the ability of protocols to act as a framework for communication with parents.

Authors' conclusions:
There is a clear need for weaning protocols to take account of the social and cultural environment in which they are to be implemented. Irrespective of its inherent strengths, a protocol will not be used if it does not accommodate these complexities. In terms of protocol development, comprehensive interprofessional input will help to ensure broad-based understanding and a sense of ‘ownership’. In terms of implementation, all relevant ICU staff will benefit from general weaning as well as protocol-specific training; not only will this help secure a relevant clinical knowledge base and operational understanding, but will also demonstrate to others that this knowledge and understanding is in place. In order to maximize relevance and acceptability, protocols should be designed with the patient profile and requirements of the target ICU in mind. Predictably, an under-resourced ICU will impact adversely on protocol implementation, as staff will prioritize management of acutely deteriorating and critically-ill patients.

The effectiveness of disaster risk communication: a systematic review of intervention studies

INTRODUCTION: A disaster is a serious disruption to the functioning of a community that exceeds its capacity to cope within its own resources. Risk communication in disasters aims to prevent and mitigate harm from disasters, prepare the population before a disaster, disseminate information during disasters and aid subsequent recovery. The aim of this systematic review is to identify, appraise and synthesise the findings of studies of the effects of risk communication interventions during four stages of the disaster cycle.

METHODS: We searched the Cochrane Central Register of Controlled Trials, Embase, MEDLINE, PsycInfo, Sociological Abstracts, Web of Science and grey literature sources for randomised trials, cluster randomised trials, controlled and uncontrolled before and after studies, interrupted time series studies and qualitative studies of any method of disaster risk communication to at-risk populations. Outcome criteria were disaster-related knowledge and behaviour, and health outcomes.

RESULTS: Searches yielded 5,224 unique articles, of which 100 were judged to be potentially relevant. Twenty-five studies met the inclusion criteria, and two additional studies were identified from other searching. The studies evaluated interventions in all four stages of the disaster cycle, included a variety of man-made, natural and infectious disease disasters, and were conducted in many disparate settings. Only one randomised trial and one cluster randomised trial were identified, with less robust designs used in the other studies. Several studies reported improvements in disaster-related knowledge and behaviour.

DISCUSSION: We identified and appraised intervention studies of disaster risk communication and present an overview of the contemporary literature. Most studies used non-randomised designs that make interpretation challenging. We do not make specific recommendations for practice but highlight the need for high-quality randomised trials and appropriately-analysed cluster randomised trials in the field of disaster risk communication where these can be conducted within an appropriate research ethics framework.

Review of survey techniques used in urban freight studies

Report produced as part of the Green Logistics project (EPSRC and Department for Transport funded). This report is based on a review of studies in which data has been collected to obtain an understanding of road-based urban freight transport activities and patterns of operation. Studies from the UK and other countries have been included in this review. While it may be thought that relatively few such studies have been conducted, approximately 60 such studies have been identified as taking place in the UK and approximately 100 elsewhere since the 1960s. In addition, other studies have been carried out in order to assess industry and policy maker opinions about urban freight transport , however this type of study and survey work is not the focus of this report. Gaining an understanding of road-based urban freight transport activities is an important element in determining the current sustainability of such activity (in economic, social and environmental terms) and how best to go about enhancing its sustainability. By reviewing the existing survey work in this subject it has been possible to draw together the methodologies developed and implemented. This should therefore be of help in understanding which techniques are most commonly used, the strengths and limitations of the various techniques, and in assessing the most suitable urban freight survey techniques for a given study.

Review of UK urban freight studies

Report produced as part of the Green Logistics project (EPSRC and Department for Transport funded). This report is based on a review of UK studies in which data has been collected to obtain an understanding of road-based urban freight transport activities and patterns of operation. Urban freight remains relatively under researched by comparison with passenger transport both in the UK and worldwide. However, in the UK there have been a number of studies that have attempted to investigate road-based freight operations since the 1960s. But no attempt has been made to draw together the results of these various studies and compare them. This is what is presented in this report. The report has studied the results of 30 UK urban freight studies carried out in the last decade in order to attempt to provide insight into urban freight activities in our towns and cities. It presents this current knowledge about urban freight transport activities in the UK from these studies, and compares the similarities and differences between study findings.

Analysing the results of UK urban freight studies

The paper is based on work carried out as part of the Green Logistics project1. The paper provides a review of urban freight studies that have taken place in the UK over approximately a thirty year period from the early 1970 s to the present (this is the first attempt at such a review in the UK as far as the authors are aware). Coverage of both goods collection and delivery vehicle activity and service vehicle activity is included. This review covers the survey techniques used, as well as the survey results obtained. Comparisons are made between the results of studies from the 1970 s and those carried out in the last decade in order to gain insight to changes in urban freight transport operations. The data provided in the studies reviewed is extremely important as it provides insight into urban freight operations that is unavailable from any other data source, including national freight surveys conducted by government. However, until now, the results of these studies have not been widely disseminated or compared.

Comprehensive treatments for social cognitive deficits in schizophrenia: A critical review and effect-size analysis of controlled studies

Recent advances in psychosocial treatments for schizophrenia have targeted social cognitive deficits. A critical literature review and effect-size (ES) analysis was conducted to investigate the efficacy of comprehensive programs of social cognitive training in schizophrenia. Results revealed 16 controlled studies consisting of seven models of comprehensive treatment with only three of these treatment models investigated in more than one study. The effects of social cognitive training were reported in 11/15 studies that included facial affect recognition skills (ES=.84) and 10/13 studies that included theory-of-mind (ES=.70) as outcomes. Less than half (4/9) of studies that measured attributional style as an outcome reported effects of treatment, but effect sizes across studies were significant (ESs=.30-.52). The effect sizes for symptoms were modest, but, with the exception of positive symptoms, significant (ESs=.32-.40). The majority of trials were randomized (13/16), selected active control conditions (11/16) and included at least 30 participants (12/16). Concerns for this area of research include the absence of blinded outcome raters in more than 50% of trials and low rates of utilization of procedures for maintaining treatment fidelity. These findings provide preliminary support for the broader use of comprehensive social cognitive training procedures as a psychosocial intervention for schizophrenia.

Studies in the mass spectra of perfluoroaromatic derivatives of phosphorus and some selected transition metals

The mass spectra and fragmentation of a variety of fluoroaromatic compounds of Group V and some selected transition elements are discussed in some detail, aided by data from metastable defocussed experiments. Results of ,studies on the coupling reaction using unstable organotitanium chloride intermediate species are reported. The preparation of some 5-substituted octafluorodibenzophospho1es is also discussed. Rearrangements under electron bombardment resulting in the loss of heteroatom-fluoride fragments are discussed in the light of presently accepted mechanisms for these processes as are rearrangements observed in compounds involving thionophosphoryl bonds ( p=s ).

A Longitudinal Examination of Bidirectional Associations between Subjective Sleep Characteristics and Psychosocial Functioning among University Students

A number of studies have found a significant link between sleep and psychosocial functioning among university students. A critical examination of this literature, however, indicates that one important gap within the literature is the need for longitudinal studies that specifically test for bidirectional associations between these two constructs. The main purpose of my dissertation was to address this gap by conducting three studies that examined bidirectional associations between sleep and psychosocial functioning among a sample of university students. Participants were 942 (71.5% female) undergraduate students enrolled at a Canadian university, who completed survey assessments annually for three consecutive years, beginning in their first year of university. In the first study, I assessed bidirectional associations between two sleep characteristics (sleep quality and sleep duration) and three psychosocial functioning variables (academics, friendship quality, and intrapersonal adjustment). Results based on cross-lagged models indicated a significant bidirectional association between sleep quality and intrapersonal adjustment, such that more sleep problems predicted more negative intrapersonal adjustment over time, and vice versa. Unidirectional associations indicated that both higher academic achievement and more positive friendship quality were significant predictors of less sleep problems over time. In the second study, in which I examined bidirectional associations between sleep and media use, results provided support only for unidirectional associations; such that more sleep problems predicted increases in both time spent watching television and time spent engaged in online social networking. In the third study of my dissertation, in which I examined social ties at university and sleep quality, results indicated a significant bidirectional association, such that more positive social ties predicted less sleep problems over time, and vice versa. Importantly, emotion regulation was a significant mediator of this association. Findings across the three studies, highlight the importance of determining the direction of effects between different sleep characteristics and various aspects of university students’ psychosocial functioning, as such findings have important implications for both methodology and practice. A better understanding of the nature of the associations between sleep and psychosocial functioning will equip students, parents and university administrators with the tools necessary to facilitate successful adjustment across the university years.

Studies on the littoral processes in relation to stability of beaches around Cchin

The coastal and nearshore areas have played vital role in the trade and economic development of coastal nations since ancient times. In recent years, the demands for utilization of these areas have increased for purposes of navigation, setting up of offshore structures for oil industry, exploitation of the available fishery and mineral resources, and to provide recreational facilities along the coast as a part of the coastal zone management. It is in this context the studies on nearshore processes receive greater priorities. Stability of beaches is controlled by the interaction of various physical parameters such as winds, waves, currents, tides and the nature and constituents of the beaches. The results of studies carried out by the author on the dynamical effects of these environmental parameters on the shoreline processes along the beaches around Cochin are presented in this thesis. The section of the coast investigated is about 57 km of shore from Azhikode to Anthakaranazhi situated on the central Kerala coast. Four regions namely Narakkal, Malipuram, Fort Cochin and Anthakaranazhi were chosen for detailed study

Oestrogenic activity of p-hydroxybenzoic acid (common metabolite of paraben esters) and methylparaben in human breast cancer cell lines

This paper addresses the question of whether p-hydroxybenzoic acid, the common metabolite of parabens, possesses oestrogenic activity in human breast cancer cell lines. The alkyl esters of p-hydroxybenzoic acid (parabens) are used widely as preservatives in consumer products to which the human population is exposed and have been shown previously to possess oestrogenic activity and to be present in human breast tumour tissue, which is an oestrogen-responsive tissue. Recent work has shown p-hydroxybenzoic acid to give an oestrogenic response in the rodent uterotrophic assay. We report here that p-hydroxybenzoic acid possesses oestrogenic activity in a panel of assays in human breast cancer cell lines. p-Hydroxybenzoic acid was able to displace [H-3]oestradiol from cytosolic oestrogen receptor of MCF7 human breast cancer cells by 54% at 5 x 10(6)-fold molar excess and by 99% at 10(7)-fold molar excess. It was able to increase the expression of a stably integrated oestrogen responsive reporter gene (ERE-CAT) at a concentration of 5 x 10(-4) M in MCF7 cells after 24 h and 7 days, which could be inhibited by the anti-oestrogen ICI 182 780 (Faslodex, fulvestrant). Proliferation of two human breast cancer cell lines (MCF7, ZR-75-1) could be increased by 10(-5) M p-hydroxybenzoic acid. Following on from previous studies showing a decrease in oestrogenic activity of parabens with shortening of the linear alkyl chain length, this study has compared the oestrogenic activity of p-hydroxybenzoic acid where the alkyl grouping is no longer present with methylparaben, which has the shortest alkyl group. Intrinsic oestrogenic activity of p-hydroxybenzoic acid was similar to that of methylparaben in terms of relative binding to the oestrogen receptor but its oestrogenic activity on gene expression and cell proliferation was lower than that of methylparaben. It can be concluded that removal of the ester group from parabens does not abrogate its oestrogenic activity and that p-hydroxybenzoic acid can give oestrogenic responses in human breast cancer cells. Copyright (C) 2005 John Wiley & Sons, Ltd.

Time-resolved gas-phase kinetic and quantum chemical studies of reactions of silylene with chlorine-containing species. 2. CH3Cl

Time-resolved kinetic studies of the reaction of silylene, SiH2, generated by laser flash photolysis of both silacyclopent-3-ene and phenylsilane, have been carried out to obtain second-order rate constants for its reaction with CH3Cl. The reaction was studied in the gas phase at six temperatures in the range 294-606 K. The second-order rate constants gave a curved Arrhenius plot with a minimum value at T approximate to 370 K. The reaction showed no pressure dependence in the presence of up to 100 Torr SF6. The rate constants, however, showed a weak dependence on laser pulse energy. This suggests an interpretation requiring more than one contributing reaction pathway to SiH2 removal. Apart from a direct reaction of SiH2 with CH3Cl, reaction of SiH2 with CH3 (formed by photodissociation of CH3Cl) seems probable, with contributions of up to 30% to the rates. Ab initio calculations (G3 level) show that the initial step of reaction of SiH2 with CH3Cl is formation of a zwitterionic complex (ylid), but a high-energy barrier rules out the subsequent insertion step. On the other hand, the Cl-abstraction reaction leading to CH3 + ClSiH2 has a low barrier, and therefore, this seems the most likely candidate for the main reaction pathway of SiH2 with CH3Cl. RRKM calculations on the abstraction pathway show that this process alone cannot account for the observed temperature dependence of the rate constants. The data are discussed in light of studies of other silylene reactions with haloalkanes.

Fruit polyphenols and CVD risk: a review of human intervention studies.

Epidemiological evidence suggests that polyphenols may, in part, explain the cardioprotective properties of fruits. This review aims to summarise the evidence for the effects of fruit polyphenols on four risk factors of CVD: platelet function, blood pressure, vascular function and blood lipids. This review includes human dietary intervention studies investigating fruits and their polyphenols. There was some evidence to suggest that fruits containing relatively high concentrations of flavonols, anthocyanins and procyanindins, such as pomegranate, purple grapes and berries, were effective at reducing CVD risk factors, particularly with respect to anti-hypertensive effects, inhibition of platelet aggregation and increasing endothelial-dependent vasodilation than other fruits investigated. Flavanone-rich fruits, such as oranges and grapefruits, were reported to have hypocholesterolaemic effects, with little impact on other risk factors being examined. However, the evidence was limited, inconsistent and often inconclusive. This is in part due to the heterogeneity in the design of studies, the lack of controls, the relatively short intervention periods and low power in several studies. Details of the polyphenol content of the fruits investigated were also omitted in some studies, negating comparison of data. It is recommended that large, well-powered, long-term human dietary intervention studies investigating a wider range of fruits are required to confirm these observations. Investigations into the potential synergistic effects of polyphenols on a combination of CVD risk markers, dose–response relationships and standardisation in methodology would facilitate the comparison of studies and also provide valuable information on the types of fruits which could confer protection against CVD.

Effects of beverage alcohol taxes and prices on drinking: a meta-analysis of 1003 estimates from 112 studies

Aims: We conducted a systematic review of studies examining relationships between measures of beverage alcohol tax or price levels and alcohol sales or self-reported drinking. A total of 112 studies of alcohol tax or price effects were found, containing 1003 estimates of the tax/price–consumption relationship. Design: Studies included analyses of alternative outcome measures, varying subgroups of the population, several statistical models, and using different units of analysis. Multiple estimates were coded from each study, along with numerous study characteristics. Using reported estimates, standard errors, t-ratios, sample sizes and other statistics, we calculated the partial correlation for the relationship between alcohol price or tax and sales or drinking measures for each major model or subgroup reported within each study. Random-effects models were used to combine studies for inverse variance weighted overall estimates of the magnitude and significance of the relationship between alcohol tax/price and drinking. Findings: Simple means of reported elasticities are -0.46 for beer, -0.69 for wine and -0.80 for spirits. Meta-analytical results document the highly significant relationships (P < 0.001) between alcohol tax or price measures and indices of sales or consumption of alcohol (aggregate-level r = -0.17 for beer, -0.30 for wine, -0.29 for spirits and -0.44 for total alcohol). Price/tax also affects heavy drinking significantly (mean reported elasticity = -0.28, individual-level r = -0.01, P < 0.01), but the magnitude of effect is smaller than effects on overall drinking. Conclusions: A large literature establishes that beverage alcohol prices and taxes are related inversely to drinking. Effects are large compared to other prevention policies and programs. Public policies that raise prices of alcohol are an effective means to reduce drinking.

Modulation of vaccine response by concomitant probiotic administration

Evidence suggests that probiotic bacteria modulate both innate and adaptive immunity in the host, and in some situations can result in reduced severity of common illnesses, such as acute rotavirus infection and respiratory infections. Responses to vaccination are increasingly being used to provide high quality information on the immunomodulatory effects of dietary components in humans. The present review focuses on the effect of probiotic administration upon vaccination response. The majority of studies investigating the impact of probiotics on responses to vaccination have been conducted in healthy adults, and at best they show modest effects of probiotics on serum or salivary IgA titres. Studies in infants and in elderly subjects are very limited, and it is too early to draw any firm conclusions regarding the potential for probiotics to act as adjuvants in vaccination. Although some studies are comparable in terms of duration of the intervention and age and characteristics of the subjects, most differ in terms of the probiotic selected. Further well designed, randomized, placebo-controlled studies are needed to fully understand the immunomodulatory properties of probiotics, whether the effects exerted are strain-dependent and age-dependent, and their clinical relevance in enhancing immune protection following vaccination.

Use of simulated intestinal fluids with Caco-2 cells and rat ileum

In most in vitro studies of oral drug permeability, little attempt is made to reproduce the gastrointestinal lumenal environment. The aim of this study was to evaluate the compatibility of simulated intestinal fluid (SIF) solutions with Caco-2 cell monolayers and Ussing chamber-mounted rat ileum under standard permeability experiment protocols. In preliminary experiments, fasted-state simulated intestinal fluid (FaSSIF) and fed-state simulated intestinal fluid (FeSSIF) solutions based on the dissolution medium formulae of Dressman and co-workers (1998) were modified for compatibility with Caco-2 cells to produce FaS-SIF and FeSSIF "transport" solutions for use with in vitro permeability models. For Caco-2 cells exposed to FaSSIF and FESSIF transport solutions, the transepithelial electrical resistance was maintained for over 4 h and mannitol permeability was equivalent to that in control (Hank's Balanced Salt Solution-treated) cell layers. Scanning electron microscopy revealed that microvilli generally maintained a normal distribution, although some shortening of microvilli and occasional small areas of denudation were observed. For rat ileum in the Ussing chambers, the potential difference (PD) collapsed to zero over 120 min when exposed to the FaSSIF transport solution and an even faster collapse of the PD was observed when the FeSSIF transport solution was used. Electron micrographs revealed erosion of the villi tips and substantial denudation of the microvilli after exposure of ileal tissue to FaSSIF and FeSSIF solutions, and permeability to mannitol was increased by almost two-fold. This study indicated that FaSSIF and FeSSIF transport solutions can be used with Caco-2 monolayers to evaluate drug permeability, but rat ileum in Ussing chambers is adversely affected by these solutions. Metoprolol permeability in Caco-2 experiments was reduced by 33% using the FaSSIF and 75% using the FeSSIF compared to permeability measured using HBSS. This illustrates that using physiological solutions can influence permeability measurements.