Recommendations for the appropriate use of anti-inflammatory drugs in the era of the coxibs: Defining the role of gastroprotective agents

Treatment with anti-inflammatory drugs and the analgesic efficacy of conventional nonsteroidal anti-inflammatory drugs (NSAIDs) are compromised by a two-to fourfold increased risk of gastrointestinal complications. This increased risk has resulted in an increasing use of the new selective cyclooxygenase-2 inhibitors or coxibs, which, in clinical trials and outcomes studies, reduced gastrointestinal adverse events by 50% to 65% compared with conventional NSAIDs. However, the coxibs are not available to all patients who need them, and NSAIDs are still widely used. Moreover, treatment with a coxib cannot heal preexisting gastrointestinal lesions, and cotherapy with an antisecretory drug or mucosal protective agent may be required. This paper addresses the management of patients with risk factors for gastrointestinal complications who are taking NSAIDs and makes recommendations for the appropriate use of 'gastroproteccontinued on next pag

Ambulatory teaching: Do approaches to learning predict the site and preceptor characteristics valued by clerks and residents in the ambulatory setting?

BACKGROUND: In a study to determine the site and preceptor characteristics most valued by clerks and residents in the ambulatory setting we wished to confirm whether these would support effective learning. The deep approach to learning is thought to be more effective for learning than surface approaches. In this study we determined how the approaches to learning of clerks and residents predicted the valued site and preceptor characteristics in the ambulatory setting. METHODS: Postal survey of all medical residents and clerks in training in Ontario determining the site and preceptor characteristics most valued in the ambulatory setting. Participants also completed the Workplace Learning questionnaire that includes 3 approaches to learning scales and 3 workplace climate scales. Multiple regression analysis was used to predict the preferred site and preceptor characteristics as the dependent variables by the average scores of the approaches to learning and perception of workplace climate scales as the independent variables. RESULTS: There were 1642 respondents, yielding a 47.3% response rate. Factor analysis revealed 7 preceptor characteristics and 6 site characteristics valued in the ambulatory setting. The Deep approach to learning scale predicted all of the learners' preferred preceptor characteristics (β = 0.076 to β = 0.234, p < .001). Valuing preceptor Direction was more strongly associated with the Surface Rational approach (β = .252, p < .001) and with the Surface Disorganized approach to learning (β = .154, p < 001) than with the Deep approach. The Deep approach to learning scale predicted valued site characteristics of Office Management, Patient Logistics, Objectives and Preceptor Interaction (p < .001). The Surface Rational approach to learning predicted valuing Learning Resources and Clinic Set-up (β = .09, p = .001; β = .197, p < .001). The Surface Disorganized approach to learning weakly negatively predicted Patient Logistics (β = -.082, p = .003) and positively the Learning Resources (β = .088, p = .003). Climate factors were not strongly predictive for any studied characteristics. Role Modeling and Patient Logistics were predicted by Supportive Receptive climate (β = .135, p < .001, β = .118, p < .001). CONCLUSION: Most site and preceptor characteristics valued by clerks and residents were predicted by their Deep approach to learning scores. Some characteristics reflecting the need for good organization and clear direction are predicted by learners' scores on less effective approaches to learning

Dressings and securements for the prevention of peripheral intravenous catheter failure in adults (SAVE): a pragmatic, randomised controlled, superiority trial

Background: Two billion peripheral intravenous catheters (PIVCs) are used globally each year, but optimal dressing and securement methods are not well established. We aimed to compare the efficacy and costs of three alternative approaches to standard non-bordered polyurethane dressings. Methods: We did a pragmatic, randomised controlled, parallel-group superiority trial at two hospitals in Queensland, Australia. Eligible patients were aged 18 years or older and required PIVC insertion for clinical treatment, which was expected to be required for longer than 24 h. Patients were randomly assigned (1:1:1:1) via a centralised web-based randomisation service using random block sizes, stratified by hospital, to receive tissue adhesive with polyurethane dressing, bordered polyurethane dressing, a securement device with polyurethane dressing, or polyurethane dressing (control). Randomisation was concealed before allocation. Patients, clinicians, and research staff were not masked because of the nature of the intervention, but infections were adjudicated by a physician who was masked to treatment allocation. The primary outcome was all-cause PIVC failure (as a composite of complete dislodgement, occlusion, phlebitis, and infection [primary bloodstream infection or local infection]). Analysis was by modified intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12611000769987. Findings: Between March 18, 2013, and Sept 9, 2014, we randomly assigned 1807 patients to receive tissue adhesive with polyurethane (n=446), bordered polyurethane (n=454), securement device with polyurethane (n=453), or polyurethane (n=454); 1697 patients comprised the modified intention-to-treat population. 163 (38%) of 427 patients in the tissue adhesive with polyurethane group (absolute risk difference −4·5% [95% CI −11·1 to 2·1%], p=0·19), 169 (40%) of 423 of patients in the bordered polyurethane group (–2·7% [–9·3 to 3·9%] p=0·44), 176 (41%) of 425 patients in the securement device with poplyurethane group (–1·2% [–7·9% to 5·4%], p=0·73), and 180 (43%) of 422 patients in the polyurethane group had PIVC failure. 17 patients in the tissue adhesive with polyurethane group, two patients in the bordered polyurethane group, eight patients in the securement device with polyurethane group, and seven patients in the polyurethane group had skin adverse events. Total costs of the trial interventions did not differ significantly between groups. Interpretation: Current dressing and securement methods are commonly associated with PIVC failure and poor durability, with simultaneous use of multiple products commonly required. Cost is currently the main factor that determines product choice. Innovations to achieve effective, durable dressings and securements, and randomised controlled trials assessing their effectiveness are urgently needed

Elevated O-GlcNAc-dependent signaling through inducible mOGT expression selectively triggers apoptosis

O-linked N-acetylglucosamine transferase (OGT) catalyzes O-GlcNAc addition to numerous cellular proteins including transcription and nuclear pore complexes and plays a key role in cellular signaling. One differentially spliced isoform of OGT is normally targeted to mitochondria (mOGT) but is quite cytotoxic when expressed in cells compared with the ncOGT isoform. To understand the basis of this selective cytotoxicity, we constructed a fully functional ecdysone-inducible GFP–OGT. Elevated GFP–OGT expression induced a dramatic increase in intracellular O-GlcNAcylated proteins. Furthermore, enhanced OGT expression efficiently triggered programmed cell death. Apoptosis was dependent upon the unique N-terminus of mOGT, and its catalytic activity. Induction of mOGT expression triggered programmed cell death in every cell type tested including INS-1, an insulin-secreting cell line. These studies suggest that deregulated activity of the mitochondrially targeted mOGT may play a role in triggering the programmed cell death observed with diseases such as diabetes mellitus and neurodegeneration

The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis

Objective: The Surviving Sepsis Campaign (SSC or “the Campaign”) developed guidelines for management of severe sepsis and septic shock. A performance improvement initiative targeted changing clinical behavior (process improvement) via bundles based on key SSC guideline recommendations on process improvement and patient outcomes. Design and setting: A multifaceted intervention to facilitate compliance with selected guideline recommendations in the ICU, ED, and wards of individual hospitals and regional hospital networks was implemented voluntarily in the US, Europe, and South America. Elements of the guidelines were “bundled” into two sets of targets to be completed within 6 h and within 24 h. An analysis was conducted on data submitted from January 2005 through March 2008. Main results: Data from 15,022 subjects at 165 sites were analyzed to determine the compliance with bundle targets and association with hospital mortality. Compliance with the entire resuscitation bundle increased linearly from 10.9% in the first site quarter to 31.3% by the end of 2 years (P < 0.0001). Compliance with the entire management bundle started at 18.4% in the first quarter and increased to 36.1% by the end of 2 years (P = 0.008). Compliance with all bundle elements increased significantly, except for inspiratory plateau pressure, which was high at baseline. Unadjusted hospital mortality decreased from 37 to 30.8% over 2 years (P = 0.001). The adjusted odds ratio for mortality improved the longer a site was in the Campaign, resulting in an adjusted absolute drop of 0.8% per quarter and 5.4% over 2 years (95% CI, 2.5–8.4%). Conclusions: The Campaign was associated with sustained, continuous quality improvement in sepsis care. Although not necessarily cause and effect, a reduction in reported hospital mortality rates was associated with participation. The implications of this study may serve as an impetus for similar improvement efforts.Electronic supplementary material The online version of this article (doi:10.1007/s00134-009-1738-3) contains supplementary material, which is available to authorized users

Plant Identity Influences Decomposition through More Than One Mechanism

Plant litter decomposition is a critical ecosystem process representing a major pathway for carbon flux, but little is known about how it is affected by changes in plant composition and diversity. Single plant functional groups (graminoids, legumes, non-leguminous forbs) were removed from a grassland in northern Canada to examine the impacts of functional group identity on decomposition. Removals were conducted within two different environmental contexts (fertilization and fungicide application) to examine the context-dependency of these identity effects. We examined two different mechanisms by which the loss of plant functional groups may impact decomposition: effects of the living plant community on the decomposition microenvironment, and changes in the species composition of the decomposing litter, as well as the interaction between these mechanisms. We show that the identity of the plant functional group removed affects decomposition through both mechanisms. Removal of both graminoids and forbs slowed decomposition through changes in the decomposition microenvironment. We found non-additive effects of litter mixing, with both the direction and identity of the functional group responsible depending on year; in 2004 graminoids positively influenced decomposition whereas in 2006 forbs negatively influenced decomposition rate. Although these two mechanisms act independently, their effects may be additive if both mechanisms are considered simultaneously. It is essential to understand the variety of mechanisms through which even a single ecosystem property is affected if we are to predict the future consequences of biodiversity loss

Dystropathology increases energy expenditure and protein turnover in the mdx mouse model of Duchenne muscular dystrophy

The skeletal muscles in Duchenne muscular dystrophy and the mdx mouse model lack functional dystrophin and undergo repeated bouts of necrosis, regeneration, and growth. These processes have a high metabolic cost. However, the consequences for whole body energy and protein metabolism, and on the dietary requirements for these macronutrients at different stages of the disease, are not well-understood. This study used juvenile (4- to 5- wk-old) and adult (12- to 14-wk-old) male dystrophic C57BL/10ScSn-mdx/J and age-matched C57BL/10ScSn/J control male mice to measure total and resting energy expenditure, food intake, spontaneous activity, body composition, whole body protein turnover, and muscle protein synthesis rates. In juvenile mdx mice that have extensive muscle damage, energy expenditure, muscle protein synthesis, and whole body protein turnover rates were higher than in age-matched controls. Adaptations in food intake and decreased activity were insufficient to meet the increased energy and protein needs of juvenile mdx mice and resulted in stunted growth. In (non-growing) adult mdx mice with less severe dystropathology, energy expenditure, muscle protein synthesis, and whole body protein turnover rates were also higher than in age-matched controls. Food intake was sufficient to meet their protein and energy needs, but insufficient to result in fat deposition. These data show that dystropathology impacts the protein and energy needs of mdx mice and that tailored dietary interventions are necessary to redress this imbalance. If not met, the resultant imbalance blunts growth, and may limit the benefits of therapies designed to protect and repair dystrophic muscles

Global warming and recurrent mass bleaching of corals

During 2015–2016, record temperatures triggered a pan-tropical episode of coral bleaching, the third global-scale event since mass bleaching was first documented in the 1980s. Here we examine how and why the severity of recurrent major bleaching events has varied at multiple scales, using aerial and underwater surveys of Australian reefs combined with satellite-derived sea surface temperatures. The distinctive geographic footprints of recurrent bleaching on the Great Barrier Reef in 1998, 2002 and 2016 were determined by the spatial pattern of sea temperatures in each year. Water quality and fishing pressure had minimal effect on the unprecedented bleaching in 2016, suggesting that local protection of reefs affords little or no resistance to extreme heat. Similarly, past exposure to bleaching in 1998 and 2002 did not lessen the severity of bleaching in 2016. Consequently, immediate global action to curb future warming is essential to secure a future for coral reefs

Association between neighborhood socioeconomic status and screen time among pre-school children: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Sedentary behavior is considered a separate construct from physical activity and engaging in sedentary behaviors results in health effects independent of physical activity levels. A major source of sedentary behavior in children is time spent viewing TV or movies, playing video games, and using computers. To date no study has examined the impact of neighborhood socioeconomic status (SES) on pre-school children's screen time behavior.</p> <p>Methods</p> <p>Proxy reports of weekday and weekend screen time (TV/movies, video games, and computer use) were completed by 1633 parents on their 4-5 year-old children in Edmonton, Alberta between November, 2005 and August, 2007. Postal codes were used to classified neighborhoods into low, medium or high SES. Multiple linear and logistic regression models were conducted to examine relationships between screen time and neighborhood SES.</p> <p>Results</p> <p>Girls living in low SES neighborhoods engaged in significantly more weekly overall screen time and TV/movie minutes compared to girls living in high SES neighborhoods. The same relationship was not observed in boys. Children living in low SES neighborhoods were significantly more likely to be video game users and less likely to be computer users compared to children living in high SES neighborhoods. Also, children living in medium SES neighborhoods were significantly less likely to be computer users compared to children living in high SES neighborhoods.</p> <p>Conclusions</p> <p>Some consideration should be given to providing alternative activity opportunities for children, especially girls who live in lower SES neighborhoods. Also, future research should continue to investigate the independent effects of neighborhood SES on screen time as well as the potential mediating variables for this relationship.</p