Timing of onset of gastrointestinal bleeding in the ICU: Protocol for a preplanned observational study.

BACKGROUND: Critically ill patients are at risk of gastrointestinal bleeding, but clinically important gastrointestinal bleeding is rare. The majority of intensive care unit (ICU) patients receive stress ulcer prophylaxis (SUP), despite uncertainty concerning the balance between benefit and harm. For approximately half of ICU patients with gastrointestinal bleeding, onset is early, ie within the first two days of the ICU stay. The aetiology of gastrointestinal bleeding and consequently the balance between benefit and harm of SUP may differ between patients with early vs late gastrointestinal bleeding. METHODS: This is a protocol and statistical analysis plan for a preplanned exploratory substudy of the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) randomized clinical trial, comparing intravenous pantoprazole (40 mg once daily) with placebo in 3350 acutely ill adult ICU patients. We will describe baseline characteristics and assess the time to onset of the first clinically important episode of GI bleeding accounting for survival status and allocation to SUP or placebo. In addition, we will describe differences in therapeutic and diagnostic procedures used in patients with clinically important gastrointestinal bleeding according to early vs late bleeding and 90-day vital status. CONCLUSIONS: The study outlined in this protocol will provide detailed information on patient characteristics and the timing of onset of gastrointestinal bleeding in the patients enrolled in the SUP-ICU trial. This may provide additional knowledge and incentives for future studies on which patients benefit from SUP.

Stress ulcer prophylaxis in the intensive care unit trial: detailed statistical analysis plan.

BACKGROUND: In this statistical analysis plan, we aim to provide details of the pre-defined statistical analyses of the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial. The aim of the SUP-ICU trial is to assess benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in adult patients in the intensive care unit (ICU). METHODS: The SUP-ICU trial is an investigator-initiated, international, multicentre, randomised, blinded, parallel-group trial of intravenously pantoprazole 40 mg once daily vs. placebo in 3350 acutely ill adult ICU patients at risk of gastrointestinal bleeding. The primary outcome measure is 90-day mortality. Secondary outcomes include the proportion of patients with clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection or myocardial ischaemia, days alive without life support, serious adverse reactions, 1-year mortality, and a health economic analysis. Two formal interim analyses will be performed. The statistical analyses will be conducted according to the outlined pre-defined statistical analysis plan. The primary analysis will be a logistic regression analysis adjusted for stratification variables comparing the two intervention groups in the intention-to-treat population. In a secondary analysis, we will additionally adjust the primary outcome for potential random differences in baseline characteristics. The conclusion will be based on the intention-to-treat population. CONCLUSION: Stress ulcer prophylaxis is standard of care in ICUs worldwide, but has never been tested in large high-quality randomised placebo-controlled trials. The SUP-ICU trial will provide important high-quality data on the balance between the benefits and harms of stress ulcer prophylaxis in adult critically ill patients.

Pharmacist's review and outcomes: Treatment-enhancing contributions tallied, evaluated, and documented (PROTECTED-UK).

PURPOSE: The purpose was to describe clinical pharmacist interventions across a range of critical care units (CCUs) throughout the United Kingdom, to identify CCU medication error rate and prescription optimization, and to identify the type and impact of each intervention in the prevention of harm and improvement of patient therapy. MATERIALS AND METHODS: A prospective observational study was undertaken in 21 UK CCUs from November 5 to 18, 2012. A data collection web portal was designed where the specialist critical care pharmacist reported all interventions at their site. Each intervention was classified as medication error, optimization, or consult. In addition, a clinical impact scale was used to code the interventions. Interventions were scored as low impact, moderate impact, high impact, and life saving. The final coding was moderated by blinded independent multidisciplinary trialists. RESULTS: A total of 20517 prescriptions were reviewed with 3294 interventions recorded during the weekdays. This resulted in an overall intervention rate of 16.1%: 6.8% were classified as medication errors, 8.3% optimizations, and 1.0% consults. The interventions were classified as low impact (34.0%), moderate impact (46.7%), and high impact (19.3%); and 1 case was life saving. Almost three quarters of interventions were to optimize the effectiveness of and improve safety of pharmacotherapy. CONCLUSIONS: This observational study demonstrated that both medication error resolution and pharmacist-led optimization rates were substantial. Almost 1 in 6 prescriptions required an intervention from the clinical pharmacist. The error rate was slightly lower than an earlier UK prescribing error study (EQUIP). Two thirds of the interventions were of moderate to high impact.

Stress ulcer prophylaxis in the intensive care unit: an international survey of 97 units in 11 countries.

BACKGROUND: Stress ulcer prophylaxis (SUP) may decrease the incidence of gastrointestinal bleeding in patients in the intensive care unit (ICU), but the risk of infection may be increased. In this study, we aimed to describe SUP practices in adult ICUs. We hypothesised that patient selection for SUP varies both within and between countries. METHODS: Adult ICUs were invited to participate in the survey. We registered country, type of hospital, type and size of ICU, preferred SUP agent, presence of local guideline, reported indications for SUP, criteria for discontinuing SUP, and concerns about adverse effects. Fisher's exact test was used to assess differences between groups. RESULTS: Ninety-seven adult ICUs in 11 countries participated (eight European). All but one ICU used SUP, and 64% (62/97) reported having a guideline for the use of SUP. Proton pump inhibitors were the most common SUP agent, used in 66% of ICUs (64/97), and H2-receptor antagonists were used 31% (30/97) of the units. Twenty-three different indications for SUP were reported, the most frequent being mechanical ventilation. All patients were prescribed SUP in 26% (25/97) of the ICUs. Adequate enteral feeding was the most frequent reason for discontinuing SUP, but 19% (18/97) continued SUP upon ICU discharge. The majority expressed concern about nosocomial pneumonia and Clostridium difficile infection with the use of SUP. CONCLUSIONS: In this international survey, most participating ICUs reported using SUP, primarily proton pump inhibitors, but many did not have a guideline; indications varied considerably and concern existed about infectious complications.

Psoriasis: snapshots of the unspoken: using novel methods to explore patients' personal models of psoriasis and the impact on well-being.

BACKGROUND: People with psoriasis report high levels of undermanaged distress. This is compounded by the problem that some patients find it difficult to discuss their emotions. Distress prevents optimal self-management, which may exacerbate psoriasis flares, thereby creating a vicious cycle. OBJECTIVES: To offer people with psoriasis a novel way of expressing their personal models of psoriasis in order to gain a better understanding of their experiences of living with the condition. METHODS: We used a qualitative technique - asking people with psoriasis to complete a postcard entitled 'Dear Psoriasis...' - to collect survey data on their personal models of psoriasis. RESULTS: One hundred and four returned postcards provided new insights into the extent of and reasons for distress in psoriasis. Seven dominant themes emerged: identity and relationships; battleground; control; emotional consequences; hypervigilance; coping; treatment burden. CONCLUSIONS: Reports of distress were common, and for many it was long-standing. Some reported low self-esteem and self-denigration bordering on self-loathing, and described being hypervigilant and in a constant battle with their skin. Many people did not expect to have intimate relationships, resulting in reduced social support for patients in the future. This research underscores the need for patient support and psychological treatment to be made available as part of routine care.

Crossover from stretched to compressed exponential relaxations in a polymer-based sponge phase.

X-ray photon correlation spectroscopy was used to characterize the wave vector- and temperature-dependent dynamics of spontaneous thermal fluctuations in a sponge (L3) phase that occurs in a blend of a symmetric poly(styrene-ethylene/butylene-styrene) triblock copolymer with a polystyrene homopolymer. Measurements of the intermediate scattering function reveal a crossover from stretched- to compressed-exponential relaxations as the temperature is lowered from 180 to 120 degrees C.

Fluctuation dynamics of block copolymer vesicles.

X-ray photon correlation spectroscopy was used to characterize the wave-vector- and temperature-dependent dynamics of spontaneous thermal fluctuations in a vesicle (L4) phase that occurs in a blend of a symmetric poly(styrene-ethylene/butylene-styrene) triblock copolymer with a polystyrene homopolymer. Measurements of the intermediate scattering function reveal stretched-exponential behavior versus time, with a stretching exponent slightly larger than 2/3. The corresponding relaxation rates show an approximate q(3) dependence versus wave vector. Overall, the experimental measurements are well described by theories that treat the dynamics of independent membrane plaquettes.

Evolution of particle-scale dynamics in an aging clay suspension.

Multispeckle x-ray photon correlation spectroscopy was employed to characterize the slow dynamics of a suspension of highly charged, nanometer-sized disks. At wave vectors q corresponding to interparticle length scales, the dynamic structure factor follows a form f(q,t) approximately exp([-(t/tau)(beta)], where beta approximately 1.5. The relaxation time tau increases with the sample age t(a) approximately as tau approximately t(1.8)(a) and decreases with q as tau approximately q(-1). Such behavior is consistent with models that describe the dynamics in disordered elastic media in terms of strain from random, local structural rearrangements. The measured amplitude of f(q,t) varies with q in a manner that implies caged particle motion. The decrease in the range of this motion and an increase in suspension conductivity with increasing t(a) indicate a growth in interparticle repulsion as the mechanism for internal stress development implied by these models.

Symmetric-to-asymmetric transition in triblock copolymer-homopolymer blends.

In blends of a symmetric poly(styrene-ethylene/butylene-styrene) tri-block-copolymer with a polystyrene homopolymer, small-angle x-ray scattering and cryotransmission electron microscopy measurements reveal a microstructure consisting of a disordered arrangement of poly(ethylene/butylene) membranes suspended in polystyrene. For triblock volume fractions less than 0.22, the membranes form an asymmetric sponge or L4 phase, consisting predominantly of equilibrium vesicles. For volume fractions greater than 0.22, they form a symmetric sponge-phase (L3 phase), separated from the L4 phase by a first-order transition.

Equilibrium dynamics in the nondiffusive regime of an entangled polymer blend.

The dynamics of compositional fluctuations in a miscible, entangled homopolymer blend of poly(ethylene oxide) and poly(methyl methacrylate) were studied on length scales smaller than the polymer radii of gyration, and for times comparable to the polymers' disentanglement time. The measured relaxation rates are consistent with predictions of the reptation model, as expressed via the dynamic random-phase approximation. Moreover, the observed mode amplitudes allow for an estimate of the entanglement length in the blend.

Absence of scaling for the intermediate scattering function of a hard-sphere suspension: static and dynamic x-ray scattering from concentrated polystyrene latex spheres.

X-ray photon correlation spectroscopy and small-angle scattering measurements are presented of the dynamics and structure of concentrated suspensions of charge-stabilized polystyrene latex spheres dispersed in glycerol, for volume fractions from 3% to 52%. The static structures of the suspensions show essentially hard-sphere behavior, and the short-time dynamics shows good agreement with predictions for the wave-vector-dependent collective diffusion coefficient. However, the intermediate scattering function is found to violate a scaling behavior found previously for a sterically stabilized hard-sphere suspension.

Tactile short-term memory revisited.

In each of three experiments subjects were required to point to the location of a discrete tactile stimulus applied to the underside of the forearm after delays of 10, 15, 20, & 30 seconds. Experiment 1 showed that recall accuracy was impaired independently by both concurrent articulatory suppression and increased delay between stimulation and recall. Experiment 2 compared two types of articulatory suppression task (repeating "the" continuously and counting backwards in threes) and showed that both exert the same effect on recall accuracy. Experiment 3 showed that, in comparison to a quiet condition, recall accuracy was impaired equally by: concurrent articulatory suppression; additional tactile interference; and both applied in combination. It is argued that articulatory suppression and tactile interference operate on separate mechanisms to impair recall accuracy for a tactile stimulus. In particular, tactile interference reduces the discriminability of the target tactile location, whereas articulatory suppression results in a depletion of central processing resources concerned with memorisation of the original location of the tactile stimulus. Such memorisation is not necessarily underpinned by an articulatory code.