Dapagliflozin – do we need it registered for type 2 diabetes?

INTRODUCTION: Inhibitors of the sodium-glucose co-transporter 2 (SGLT2) promote the excretion of glucose to reduce glycated hemoglobin (HbA1c) levels. Canagliflozin was the first SGLT2 inhibitor to be approved by the US FDA for use in the treatment of type 2 diabetes, and recently dapagliflozin has also been approved. AREAS COVERED: We evaluated a recent Phase III clinical trial with dapagliflozin. EXPERT OPINION: Dapagliflozin was studied as add-on therapy to sitagliptin with or without metformin, and was shown to lower HbA1c levels and body weight. The incidence of hypoglycaemia was low with dapagliflozin, but it did increase the incidence of urogenital infections. As no clear benefits have been identified for dapagliflozin over canagliflozin, which was the first gliflozin registered by the FDA, we do not fully understand why it was necessary to register dapagliflozin. Given that there are no completed cardiovascular/clinical outcome studies with dapagliflozin, and therefore no evidence of beneficial effect, it also seems premature to be using it extensively or considering it as an alternative to the clinically proven metformin.

Long-term outcomes following Medtronic Open Pivot valved conduit

Aortic root replacement is a complex procedure, though subsequent modifications of the original Bentall procedure have made surgery more reproducible. The study aim was to examine the outcomes of a modified Bentall procedure, using the Medtronic Open PivotTM valved conduit. Whilst short-term data on the conduit and long-term data on the valve itself are available, little is known of the long-term results with the valved conduit. Patients undergoing aortic root replacement between February 1999 and February 2010, using the Medtronic Open Pivot valved conduit were identified from the prospectively collected Cardiothoracic Register at The Prince Charles Hospital, Brisbane, Australia. All patients were followed up echocardiographically and clinically. The primary end-point was death, and a Cox proportional model was used to identify factors associated.with survival. Secondary end-points were valve-related morbidity (as defined by STS guidelines) and postoperative morbidity. Predictors of morbidity were identified using logistic regression. A total of 246 patients (mean age 50 years) was included in the study. The overall mortality was 12%, with actuarial 10-year survival 79% and a 10-year estimate of valve-related death of 0.04 (95% CI: 0.004, 0.07). Preoperative myocardial infarction (p = 0.004, HR 4.74), urgency of operation (p = 0.038, HR 2.8) and 10% incremental decreases in ejection fraction (p = 0.046, HR 0.69) were predictive of mortality. Survival was also affected by the valve gradients, with a unit increase in peak gradient reducing mortality (p = 0.021, HR 0.93). Valve-related morbidity occurred in 11 patients. Urgent surgery (p <0.001, OR 4.12), aortic dissection (p = 0.015, OR 3.35), calcific aortic stenosis (p = 0.016, OR 2.35) and Marfan syndrome (p 0.009, OR 3.75) were predictive of postoperative morbidity. The reoperation rate was 1.2%. The Medtronic Open Pivot valved conduit is a safe and durable option for aortic root replacement, and is associated with low morbidity and 10-year survival of 79%. However, further studies are required to determine the effect of valve gradient on survival.

Community wide interventions for increasing physical activity

Background Multi-strategic community wide interventions for physical activity are increasingly popular but their ability to achieve population level improvements is unknown. Objectives To evaluate the effects of community wide, multi-strategic interventions upon population levels of physical activity. Search methods We searched the Cochrane Public Health Group Segment of the Cochrane Register of Studies,The Cochrane Library, MEDLINE, MEDLINE in Process, EMBASE, CINAHL, LILACS, PsycINFO, ASSIA, the British Nursing Index, Chinese CNKI databases, EPPI Centre (DoPHER, TRoPHI), ERIC, HMIC, Sociological Abstracts, SPORTDiscus, Transport Database and Web of Science (Science Citation Index, Social Sciences Citation Index, Conference Proceedings Citation Index). We also scanned websites of the EU Platform on Diet, Physical Activity and Health; Health-Evidence.org; the International Union for Health Promotion and Education; the NIHR Coordinating Centre for Health Technology (NCCHTA); the US Centre for Disease Control and Prevention (CDC) and NICE and SIGN guidelines. Reference lists of all relevant systematic reviews, guidelines and primary studies were searched and we contacted experts in the field. The searches were updated to 16 January 2014, unrestricted by language or publication status. Selection criteria Cluster randomised controlled trials, randomised controlled trials, quasi-experimental designs which used a control population for comparison, interrupted time-series studies, and prospective controlled cohort studies were included. Only studies with a minimum six-month follow up from the start of the intervention to measurement of outcomes were included. Community wide interventions had to comprise at least two broad strategies aimed at physical activity for the whole population. Studies which randomised individuals from the same community were excluded. Data collection and analysis At least two review authors independently extracted the data and assessed the risk of bias. Each study was assessed for the setting, the number of included components and their intensity. The primary outcome measures were grouped according to whether they were dichotomous (per cent physically active, per cent physically active during leisure time, and per cent physically inactive) or continuous (leisure time physical activity time (time spent)), walking (time spent), energy expenditure (as metabolic equivalents or METS)). For dichotomous measures we calculated the unadjusted and adjusted risk difference, and the unadjusted and adjusted relative risk. For continuous measures we calculated percentage change from baseline, unadjusted and adjusted. Main results After the selection process had been completed, 33 studies were included. A total of 267 communities were included in the review (populations between 500 and 1.9 million). Of the included studies, 25 were set in high income countries and eight were in low income countries. The interventions varied by the number of strategies included and their intensity. Almost all of the interventions included a component of building partnerships with local governments or non-governmental organisations (NGOs) (29 studies). None of the studies provided results by socio-economic disadvantage or other markers of equity. However, of those included studies undertaken in high income countries, 14 studies were described as being provided to deprived, disadvantaged or low socio-economic communities. Nineteen studies were identified as having a high risk of bias, 10 studies were unclear, and four studies had a low risk of bias. Selection bias was a major concern with these studies, with only five studies using randomisation to allocate communities. Four studies were judged as being at low risk of selection bias although 19 studies were considered to have an unclear risk of bias. Twelve studies had a high risk of detection bias, 13 an unclear risk and four a low risk of bias. Generally, the better designed studies showed no improvement in the primary outcome measure of physical activity at a population level. All four of the newly included, and judged to be at low risk of bias, studies (conducted in Japan, United Kingdom and USA) used randomisation to allocate the intervention to the communities. Three studies used a cluster randomised design and one study used a stepped wedge design. The approach to measuring the primary outcome of physical activity was better in these four studies than in many of the earlier studies. One study obtained objective population representative measurements of physical activity by accelerometers, while the remaining three low-risk studies used validated self-reported measures. The study using accelerometry, conducted in low income, high crime communities of USA, emphasised social marketing, partnership with police and environmental improvements. No change in the seven-day average daily minutes of moderate to vigorous physical activity was observed during the two years of operation. Some program level effect was observed with more people walking in the intervention community, however this result was not evident in the whole community. Similarly, the two studies conducted in the United Kingdom (one in rural villages and the other in urban London; both using communication, partnership and environmental strategies) found no improvement in the mean levels of energy expenditure per person per week, measured from one to four years from baseline. None of the three low risk studies reporting a dichotomous outcome of physical activity found improvements associated with the intervention. Overall, there was a noticeable absence of reporting of benefit in physical activity for community wide interventions in the included studies. However, as a group, the interventions undertaken in China appeared to have the greatest possibility of success with high participation rates reported. Reporting bias was evident with two studies failing to report physical activity measured at follow up. No adverse events were reported.The data pertaining to cost and sustainability of the interventions were limited and varied. Authors' conclusions Although numerous studies have been undertaken, there is a noticeable inconsistency of the findings in the available studies and this is confounded by serious methodological issues within the included studies. The body of evidence in this review does not support the hypothesis that the multi-component community wide interventions studied effectively increased physical activity for the population, although some studies with environmental components observed more people walking. Plain language summary Community wide interventions for increasing physical activity Not having enough physical activity leads to poorer health. Regular physical activity can reduce the risk of chronic disease and improve one's health and wellbeing. The lack of physical activity is a common and in some cases a growing health problem. To address this, 33 studies have used improvement activities directed at communities, using more than one approach in a single program. When we first looked at the available research in 2011 we observed that there was a lack of good studies which could show whether this approach was beneficial or not. Some studies claimed that community wide programs improved physical activities and other studies did not. In this update we found four new studies that were of good quality; however none of these four studies increased physical activity levels for the population. Some studies reported program level effects such as observing more people walking, however the population level of physical activity had not increased. This review found that community wide interventions are very difficult to undertake, and it appears that they usually fail to provide a measurable benefit in physical activity for a population. It is apparent that many of the interventions failed to reach a substantial portion of the community, and we speculate that some single strategies included in the combination may lack individual effectiveness. Laički sažetak Intervencije u zajednici za povećanje tjelesne aktivnosti Nedostatna tjelesna aktivnost povezana je s lošijim zdravljem.Redovita tjelesna aktivnost može umanjiti rizik od kroničnih bolesti te poboljšati zdravlje i kvalitetu života pojedinca.Manjak tjelesne aktivnosti čest je problem, a učestalost tog problema se povećava.Cochrane sustavni pregled je analizirao 33 studije koje su istražile programe za povećanje tjelesne aktivnosti u zajednici, u kojima se koristilo više od jednog pristupa.Kad su prvi put pregledani dokazi iz istraživanja koja su bila dostupna 2011. godine, utvrđeno je da nema dovoljno dobrih studija koje bi mogle pokazati je li takav pristup koristan ili ne.Primjerice, neke studije tvrde da programi za povećanje tjelesne aktivnosti u zajednici poboljšavaju tjelesnu aktivnost pojedinaca u zajednici, a druge studije tvrde suprotno.U ovom obnovljenom sustavnom pregledu pronađene su 4 nove studije koje su bile visoke kvalitete, ail nijedna od tih studija nije pokazala da je istraživana intervencija dovela do povećanja tjelesne aktivnosti u zajednici.Neke su studije opisale učinak na način da je opisano da je uočeno da više ljudi u zajednici hoda, međutim, ukupna razina tjelesne aktivnosti u promatranoj populaciji nije se povećala.Ovaj sustavni pregled je utvrdio da je intervencije za povećanje tjelesne aktivnosti u zajednici teško provesti i čini se da one obično ne uspijevaju u svojoj namjeri da na mjerljiv način povećaju tjelesnu aktivnost u populaciji.Čini se da mnoge intervencije nisu uspjele doseći veći broj stanovnika u zajednici pa se može smatrati da neke od strategija uključene u analizirane kombinacije nisu zasebno učinkovite.

Family-based programmes for preventing smoking by children and adolescents (Review)

Background There is evidence that family and friends influence children's decisions to smoke. Objectives To assess the effectiveness of interventions to help families stop children starting smoking. Search methods We searched 14 electronic bibliographic databases, including the Cochrane Tobacco Addiction Group specialized register, MEDLINE, EMBASE, PsycINFO, CINAHL unpublished material, and key articles' reference lists. We performed free-text internet searches and targeted searches of appropriate websites, and hand-searched key journals not available electronically. We consulted authors and experts in the field. The most recent search was 3 April 2014. There were no date or language limitations. Selection criteria Randomised controlled trials (RCTs) of interventions with children (aged 5-12) or adolescents (aged 13-18) and families to deter tobacco use. The primary outcome was the effect of the intervention on the smoking status of children who reported no use of tobacco at baseline. Included trials had to report outcomes measured at least six months from the start of the intervention. Data collection and analysis We reviewed all potentially relevant citations and retrieved the full text to determine whether the study was an RCT and matched our inclusion criteria. Two authors independently extracted study data for each RCT and assessed them for risk of bias. We pooled risk ratios using a Mantel-Haenszel fixed effect model. Main results Twenty-seven RCTs were included. The interventions were very heterogeneous in the components of the family intervention, the other risk behaviours targeted alongside tobacco, the age of children at baseline and the length of follow-up. Two interventions were tested by two RCTs, one was tested by three RCTs and the remaining 20 distinct interventions were tested only by one RCT. Twenty-three interventions were tested in the USA, two in Europe, one in Australia and one in India. The control conditions fell into two main groups: no intervention or usual care; or school-based interventions provided to all participants. These two groups of studies were considered separately. Most studies had a judgement of 'unclear' for at least one risk of bias criteria, so the quality of evidence was downgraded to moderate. Although there was heterogeneity between studies there was little evidence of statistical heterogeneity in the results. We were unable to extract data from all studies in a format that allowed inclusion in a meta-analysis. There was moderate quality evidence family-based interventions had a positive impact on preventing smoking when compared to a no intervention control. Nine studies (4810 participants) reporting smoking uptake amongst baseline non-smokers could be pooled, but eight studies with about 5000 participants could not be pooled because of insufficient data. The pooled estimate detected a significant reduction in smoking behaviour in the intervention arms (risk ratio [RR] 0.76, 95% confidence interval [CI] 0.68 to 0.84). Most of these studies used intensive interventions. Estimates for the medium and low intensity subgroups were similar but confidence intervals were wide. Two studies in which some of the 4487 participants already had smoking experience at baseline did not detect evidence of effect (RR 1.04, 95% CI 0.93 to 1.17). Eight RCTs compared a combined family plus school intervention to a school intervention only. Of the three studies with data, two RCTS with outcomes for 2301 baseline never smokers detected evidence of an effect (RR 0.85, 95% CI 0.75 to 0.96) and one study with data for 1096 participants not restricted to never users at baseline also detected a benefit (RR 0.60, 95% CI 0.38 to 0.94). The other five studies with about 18,500 participants did not report data in a format allowing meta-analysis. One RCT also compared a family intervention to a school 'good behaviour' intervention and did not detect a difference between the two types of programme (RR 1.05, 95% CI 0.80 to 1.38, n = 388). No studies identified any adverse effects of intervention. Authors' conclusions There is moderate quality evidence to suggest that family-based interventions can have a positive effect on preventing children and adolescents from starting to smoke. There were more studies of high intensity programmes compared to a control group receiving no intervention, than there were for other compairsons. The evidence is therefore strongest for high intensity programmes used independently of school interventions. Programmes typically addressed family functioning, and were introduced when children were between 11 and 14 years old. Based on this moderate quality evidence a family intervention might reduce uptake or experimentation with smoking by between 16 and 32%. However, these findings should be interpreted cautiously because effect estimates could not include data from all studies. Our interpretation is that the common feature of the effective high intensity interventions was encouraging authoritative parenting (which is usually defined as showing strong interest in and care for the adolescent, often with rule setting). This is different from authoritarian parenting (do as I say) or neglectful or unsupervised parenting.

Understanding classroom trouble through regulative gravity and instructional elasticity

This paper aims to develop a more nuanced analytic vocabulary to typify how and where classroom trouble can manifest in pedagogic discourse. It draws on classroom ethnographies conducted in non-academic secondary school pathways and alternative programs in Australian communities with high youth unemployment, where the policy of ‘earning or learning’ till age 17 has effectively extended compulsory schooling. Three concepts are developed and exemplified: ‘regulative flares’, being moments when teachers resort to explicitly reasserting the lesson’s social order; ‘moral gravity’ to describe the degree to which the moral order underpinning the regulative discourse is tied to the immediate context or beyond; and ‘instructional elasticity’ to account for trouble originating in the instructional register.

How does Australian diabetic foot screening rate on an international Stage?

Background From the conservative estimates of registrants with the National Diabetes Supply Scheme, we will be soon passing 1.1 Million Australians affected by all types of diabetes. The diabetes complications of foot ulceration and amputation are costly to all. These costs can be reduced with appropriate prevention strategies, starting with identifying people at risk through primary care diabetic foot screening. However, levels of diabetic foot screening in Australia are difficult to quantify. Methods This presentation reports on foot screening rates as recorded in the academic literature, national health surveys and national database reports. The focus is on type 1 and type 2 diabetes in adults, and not gestational diabetes or children. Literature searches included diabetic foot screening that occurred in the primary care setting for populations over 2000 people from 2002 to 2014. Searches were performed using Medline and CINAHL as well as internet searches of OECD health databases. The primary outcome measure was foot -screening rates as a percentage of adult diabetic population. Results The lack of a national diabetes database and register hampers efforts to analyse diabetic foot screening levels. The most recent and accurate level for Australian population review was in the AUSDIAB (Australian Diabetes and lifestyle survey) from 2004. This survey reported screening in primary care to be as low as 50%. Countries such as the United Kingdom and United States of America report much higher rates of foot screening (67-88%) using national databases and web based initiatives that involve patients and clinicians. Conclusions Australian rates of diabetic foot screening in primary care centres is ambiguous. Uptake of national registers, incentives and web based systems improve levels of diabetic foot assessment which are the first steps to a healthier diabetic population.

Preoperative bathing or showering with skin antiseptics to prevent surgical site infection

Background Surgical site infections (SSIs) are wound infections that occur after invasive (surgical) procedures. Preoperative bathing or showering with an antiseptic skin wash product is a well-accepted procedure for reducing skin bacteria (microflora). It is less clear whether reducing skin microflora leads to a lower incidence of surgical site infection. Objectives To review the evidence for preoperative bathing or showering with antiseptics for preventing hospital-acquired (nosocomial) surgical site infections. Search methods For this fifth update we searched the Cochrane Wounds Group Specialised Register (searched 18 December 2014); the Cochrane Central Register of Controlled Trials (The Cochrane Library 2014 Issue 11); Ovid MEDLINE (2012 to December Week 4 2014), Ovid MEDLINE (In-Process & Other Non-Indexed Citations December 18, 2014); Ovid EMBASE (2012 to 2014 Week 51), EBSCO CINAHL (2012 to December 18 2014) and reference lists of articles. Selection criteria Randomised controlled trials comparing any antiseptic preparation used for preoperative full-body bathing or showering with non-antiseptic preparations in people undergoing surgery. Data collection and analysis Two review authors independently assessed studies for selection, risk of bias and extracted data. Study authors were contacted for additional information. Main results We did not identify any new trials for inclusion in this fifth update. Seven trials involving a total of 10,157 participants were included. Four of the included trials had three comparison groups. The antiseptic used in all trials was 4% chlorhexidine gluconate (Hibiscrub/Riohex). Three trials involving 7791 participants compared chlorhexidine with a placebo. Bathing with chlorhexidine compared with placebo did not result in a statistically significant reduction in SSIs; the relative risk of SSI (RR) was 0.91 (95% confidence interval (CI) 0.80 to 1.04). When only trials of high quality were included in this comparison, the RR of SSI was 0.95 (95%CI 0.82 to 1.10). Three trials of 1443 participants compared bar soap with chlorhexidine; when combined there was no difference in the risk of SSIs (RR 1.02, 95% CI 0.57 to 1.84). Three trials of 1192 patients compared bathing with chlorhexidine with no washing, one large study found a statistically significant difference in favour of bathing with chlorhexidine (RR 0.36, 95%CI 0.17 to 0.79). The smaller studies found no difference between patients who washed with chlorhexidine and those who did not wash preoperatively. Authors' conclusions This review provides no clear evidence of benefit for preoperative showering or bathing with chlorhexidine over other wash products, to reduce surgical site infection. Efforts to reduce the incidence of nosocomial surgical site infection should focus on interventions where effect has been demonstrated.

Predicting people’s intention to donate their body to medical science and research

Predictors of people’s intention to register with a body bequest program for donating their deceased body to medical science and research were examined using standard theory of planned behavior (TPB) predictors (attitude, subjective norm, perceived behavioral control) and adding moral norm, altruism, and knowledge. Australian students (N = 221) at a university with a recently established body bequest program completed measures of the TPB’s underlying beliefs (behavioral, normative, and control beliefs) and standard and extended TPB predictors, with a sub-sample reporting their registration-related behavior 2 months later. The standard TPB accounted for 43.6%, and the extended predictors an additional 15.1% of variance in intention. The significant predictors were attitude, subjective norm, and moral norm, partially supporting an extended TPB in understanding people’s body donation intentions. Further, important underlying beliefs can inform strategies to target prospective donors.

A kinematic and electromyographic study of grip force

Background The hand is an element of great importance to humans, as it enables us to have different grips. Its analysis, based on an accelerometer and electromyography, is critical in order to determine its operation. The processing and analysis of variables obtained by these devices offer a different approach in functional assessment. Therefore, knowledge of the muscles and elements of the hand in the grip force will offer a better approach for different interventions. Method The functionality of the hand of seven healthy subjects was parameterized and synchronized in real time based on grip force. The AcceleGlove was used to register accelerometric (fingers and palm) values and the Mega ME6000 was used for the surface electromyography and maximum voluntary contraction for the hand and forearm muscles. A computer script based on “R” and MATLAB software was developed to enable the correct interpretation of the main variables (variation of acceleration and maximum peak value of electromyography). Results The muscles of greater activity in grip was found in the hypothenar region (0.313 ± 0.148%) and the flexor ulnaris carpi (0.360 ± 0.118%), based on maximum voluntary contraction. Reference values in the module vector of the palm have proved an essential element for the identification of the movement phases. The ring and index fingers were the elements with the greatest variation of acceleration in the movement phases. Conclusion: Parameterization of the force grip and fragmentation of the registered data has been made possible due to the development of a technical procedure.

Whole-body cryotherapy (extreme cold air exposure) for preventing and treating muscle soreness after exercise in adults

Background Recovery strategies are often usedwith the intention of preventing orminimisingmuscle soreness after exercise. Whole-body cryotherapy, which involves a single or repeated exposure(s) to extremely cold dry air (below -100 °C) in a specialised chamber or cabin for two to four minutes per exposure, is currently being advocated as an effective intervention to reduce muscle soreness after exercise. Objectives To assess the effects (benefits and harms) of whole-body cryotherapy (extreme cold air exposure) for preventing and treating muscle soreness after exercise in adults. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, the British Nursing Index and the Physiotherapy Evidence Database. We also searched the reference lists of articles, trial registers and conference proceedings, handsearched journals and contacted experts. The searches were run in August 2015. Selection criteria We aimed to include randomised and quasi-randomised trials that compared the use of whole-body cryotherapy (WBC) versus a passive or control intervention (rest, no treatment or placebo treatment) or active interventions including cold or contrast water immersion, active recovery and infrared therapy for preventing or treating muscle soreness after exercise in adults. We also aimed to include randomised trials that compared different durations or dosages of WBC. Our prespecified primary outcomes were muscle soreness, subjective recovery (e.g. tiredness, well-being) and adverse effects. Data collection and analysis Two review authors independently screened search results, selected studies, assessed risk of bias and extracted and cross-checked data. Where appropriate, we pooled results of comparable trials. The random-effects model was used for pooling where there was substantial heterogeneity.We assessed the quality of the evidence using GRADE. Main results Four laboratory-based randomised controlled trials were included. These reported results for 64 physically active predominantly young adults (mean age 23 years). All but four participants were male. Two trials were parallel group trials (44 participants) and two were cross-over trials (20 participants). The trials were heterogeneous, including the type, temperature, duration and frequency of WBC, and the type of preceding exercise. None of the trials reported active surveillance of predefined adverse events. All four trials had design features that carried a high risk of bias, potentially limiting the reliability of their findings. The evidence for all outcomes was classified as ’very low’ quality based on the GRADE criteria. Two comparisons were tested: WBC versus control (rest or no WBC), tested in four studies; and WBC versus far-infrared therapy, also tested in one study. No studies compared WBC with other active interventions, such as cold water immersion, or different types and applications of WBC. All four trials compared WBC with rest or no WBC. There was very low quality evidence for lower self-reported muscle soreness (pain at rest) scores after WBC at 1 hour (standardised mean difference (SMD) -0.77, 95% confidence interval (CI) -1.42 to -0.12; 20 participants, 2 cross-over trials); 24 hours (SMD -0.57, 95%CI -1.48 to 0.33) and 48 hours (SMD -0.58, 95% CI -1.37 to 0.21), both with 38 participants, 2 cross-over studies, 1 parallel group study; and 72 hours (SMD -0.65, 95% CI -2.54 to 1.24; 29 participants, 1 cross-over study, 1 parallel group study). Of note is that the 95% CIs also included either no between-group differences or a benefit in favour of the control group. One small cross-over trial (9 participants) found no difference in tiredness but better well-being after WBC at 24 hours post exercise. There was no report of adverse events. One small cross-over trial involving nine well-trained runners provided very low quality evidence of lower levels of muscle soreness after WBC, when compared with infrared therapy, at 1 hour follow-up, but not at 24 or 48 hours. The same trial found no difference in well-being but less tiredness after WBC at 24 hours post exercise. There was no report of adverse events. Authors’ conclusions There is insufficient evidence to determine whether whole-body cryotherapy (WBC) reduces self-reportedmuscle soreness, or improves subjective recovery, after exercise compared with passive rest or no WBC in physically active young adult males. There is no evidence on the use of this intervention in females or elite athletes. The lack of evidence on adverse events is important given that the exposure to extreme temperature presents a potential hazard. Further high-quality, well-reported research in this area is required and must provide detailed reporting of adverse events.

Clinical pathways for chronic cough in children

Background Chronic cough (a cough lasting longer than four weeks) is a common problem internationally. Chronic cough has associated economic costs and is distressing to the child and to parents; ignoring cough may lead to delayed diagnosis and progression of serious underlying respiratory disease. Clinical guidelines have been shown to lead to efficient and effective patient care and can facilitate clinical decision making. Cough guidelines have been designed to facilitate the management of chronic cough. However, treatment recommendations vary, and specific clinical pathways for the treatment of chronic cough in children are important, as causes of and treatments for cough vary significantly from those in adults. Therefore, systematic evaluation of the use of evidence-based clinical pathways for the management of chronic cough in children would be beneficial for clinical practice and for patient care. Use of a management algorithm can improve clinical outcomes; such management guidelines can be found in the guidelines for cough provided by the American College of Chest Physicians (ACCP) and the British Thoracic Society (BTS). Objectives To evaluate the effectiveness of using a clinical pathway in the management of children with chronic cough. Search methods The Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register, MEDLINE, EMBASE, review articles and reference lists of re levant articles were searched. The latest search was conducted in January 2014. Selection criteria All randomised controlled trials of parallel-group design comparing use versus non-use of a clinical pathway for treatment of chronic cough in children (< 18 years of age). Data collection and analysis Results of searches were reviewed against predetermined cr iteria for inclusion. Two review authors independently selected studies and performed data extraction in duplicate. Main results One study was included in the review. This multi-centre trial was based in five Australian hospitals and recruited 272 children with chronic cough. Children were randomly assigned to early (two weeks) or delayed (six weeks) referral to respiratory specialists who used a cough management pathway. When an intention-to-treat analysis was performed, clinical failure at six wee ks post randomisation (defined as < 75% improvement in cough score, or total resolution for fewer than three consecutive days) was significantly less in the early pathway arm compared with the control arm (odds ratio (OR) 0.35, 95% confidence interval (CI) 0.21 to 0.58). These results indicate that one additional child will be cured for e very five children treated via th e cough pathway (number needed to treat for an additional beneficial outcome (NNTB) = 5, 95% CI 3 to 9) at six weeks. Cough-specific parent-reported quality of life scores were significantly better in th e early-pathway group; the mean difference (MD) between groups was 0.60 (95% CI 0.19 to 1.01). Duration of cough post randomisation was significantly shorter in the intervention group (early-pathway arm) compared with the control group (delayed-pathway arm) (MD -2.70 weeks, 95% CI -4.26 to -1.14). Authors’ conclusions. Current evidence suggests that using a clinical algorithm for the management of children with ch r onic cough in h ospital outpatient settings is more effective than providing wait-list care. Futher high-quality randomised controlled trials are needed to perform ongoing evaluation of cough management pathways in general practitioner and other primary care settings.

Combination inhaled corticosteroids and long-acting beta2-agonists for children and adults with bronchiectasis

BACKGROUND Bronchiectasis is a major contributor to chronic respiratory morbidity and mortality worldwide. Wheeze and other asthma-like symptoms and bronchial hyperreactivity may occur in people with bronchiectasis. Physicians often use asthma treatments in patients with bronchiectasis. OBJECTIVES To assess the effects of inhaled long-acting beta2-agonists (LABA) combined with inhaled corticosteroids (ICS) in children and adults with bronchiectasis during (1) acute exacerbations and (2) stable state. SEARCH METHODS The Cochrane Airways Group searched the the Cochrane Airways Group Specialised Register of Trials, which includes records identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and other databases. The Cochrane Airways Group performed the latest searches in October 2013. SELECTION CRITERIA All randomised controlled trials (RCTs) of combined ICS and LABA compared with a control (placebo, no treatment, ICS as monotherapy) in children and adults with bronchiectasis not related to cystic fibrosis (CF). DATA COLLECTION AND ANALYSIS Two review authors extracted data independently using standard methodological procedures as expected by The Cochrane Collaboration. MAIN RESULTS We found no RCTs comparing ICS and LABA combination with either placebo or usual care. We included one RCT that compared combined ICS and LABA with high-dose ICS in 40 adults with non-CF bronchiectasis without co-existent asthma. All participants received three months of high-dose budesonide dipropionate treatment (1600 micrograms). After three months, participants were randomly assigned to receive either high-dose budesonide dipropionate (1600 micrograms per day) or a combination of budesonide with formoterol (640 micrograms of budesonide and 18 micrograms of formoterol) for three months. The study was not blinded. We assessed it to be an RCT with overall high risk of bias. Data analysed in this review showed that those who received combined ICS-LABA (in stable state) had a significantly better transition dyspnoea index (mean difference (MD) 1.29, 95% confidence interval (CI) 0.40 to 2.18) and cough-free days (MD 12.30, 95% CI 2.38 to 22.2) compared with those receiving ICS after three months of treatment. No significant difference was noted between groups in quality of life (MD -4.57, 95% CI -12.38 to 3.24), number of hospitalisations (odds ratio (OR) 0.26, 95% CI 0.02 to 2.79) or lung function (forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)). Investigators reported 37 adverse events in the ICS group versus 12 events in the ICS-LABA group but did not mention the number of individuals experiencing adverse events. Hence differences between groups were not included in the analyses. We assessed the overall evidence to be low quality. AUTHORS' CONCLUSIONS In adults with bronchiectasis without co-existent asthma, during stable state, a small single trial with a high risk of bias suggests that combined ICS-LABA may improve dyspnoea and increase cough-free days in comparison with high-dose ICS. No data are provided for or against, the use of combined ICS-LABA in adults with bronchiectasis during an acute exacerbation, or in children with bronchiectasis in a stable or acute state. The absence of high quality evidence means that decisions to use or discontinue combined ICS-LABA in people with bronchiectasis may need to take account of the presence or absence of co-existing airway hyper-responsiveness and consideration of adverse events associated with combined ICS-LABA.

Borders, belonging, beyond: New curriculum history

For Iain Chambers, understanding the redefinition of social life and hence of social theories is not aided by splitting the analytical register simply between global and local. This is especially problematic if global is taken to mean the dispersal of an already-dominant or privileged version of the local within wider coordinates that ensure the continuation of forms of representation and frames of reference that are familiar and over-exposed. The chapters in New Curriculum History take up the challenge posed by Chambers, collectively confronting the dread of a rationality confronted with what exceeds and slips its grasp. Finding purchase and continually slipping away from the strictures of the taken-for-granted and of fixity, New Curriculum History embodies the dueling reverberations of its non-localizable domains – in some ways, a shaping by its pasts and in others, contributions irreducible to dominant narratives about the field of education and “its” histories...

Themes in landscape architecture publishing: Past trends, future needs

Many scholars acknowledge the need for rigorous research in landscape architecture to improve practice and teaching, and several recent studies have explored research trends in the discipline. This study continues this exploration by reviewing the articles published in the three prominent English- language landscape architecture journals: Landscape Journal, Landscape Review, and the Journal of Landscape Architecture. Specifically, this study analyzes the abstracts from 441 research articles to determine specific themes and publishing trends over 31 years (1982–2013). Findings indicate that “history” is by far the most prominent research theme, followed by “social and cultural processes and issues” and “aesthetics.” Several themes—such as “sustainability and green infrastructure,” “participation and collaboration,” and “research methods and methodologies”—have become more prominent in recent years. However, topics of current social and political concern—such as “climate change,” “active living,” “energy,” and “health”—are not yet prominent themes in the research literature, and could be key areas for future contribution. With the exception of a few themes, findings also suggest a moderate degree of alignment between research and practice. The article concludes with recommendations for future areas of research that will better position landscape architecture as a research- oriented profession with broad social relevance.

Mechanism of foetal wastage following immunoneutralization of riboflavin carrier protein in the pregnant rat: disturbances in flavin coenzyme levels

Immunoneutralization of maternal RCP results in a >90% decrease in the content and the incorporation of [2-14C]riboflavin into embryonic FAD as well as a percentage redistribution of both embryonic FMN and riboflavin. This is unaccompanied by any discernible changes in flavin distribution pattern in the maternal liver. Embryonic α-glycerophosphate dehydrogenase and NADPH-cytochrome c reductase register significant decreases in activities in the RCP antiserum-treated rats. These alterations readily explain the arrest of foetal growth culminating in pregnancy termination in the antiserum-treated animals.