Development of process control methodology for tracking the quality and safety of pain, agitation and sedation management in critical care units

Objective: To develop sedation, pain, and agitation quality measures using process control methodology and evaluate their properties in clinical practice. Design: A Sedation Quality Assessment Tool was developed and validated to capture data for 12-hour periods of nursing care. Domains included pain/discomfort and sedation-agitation behaviors; sedative, analgesic, and neuromuscular blocking drug administration; ventilation status; and conditions potentially justifying deep sedation. Predefined sedation-related adverse events were recorded daily. Using an iterative process, algorithms were developed to describe the proportion of care periods with poor limb relaxation, poor ventilator synchronization, unnecessary deep sedation, agitation, and an overall optimum sedation metric. Proportion charts described processes over time (2 monthly intervals) for each ICU. The numbers of patients treated between sedation-related adverse events were described with G charts. Automated algorithms generated charts for 12 months of sequential data. Mean values for each process were calculated, and variation within and between ICUs explored qualitatively. Setting: Eight Scottish ICUs over a 12-month period. Patients: Mechanically ventilated patients. Interventions: None. Measurements and Main Results: The Sedation Quality Assessment Tool agitation-sedation domains correlated with the Richmond Sedation Agitation Scale score (Spearman [rho] = 0.75) and were reliable in clinician-clinician (weighted kappa; [kappa] = 0.66) and clinician-researcher ([kappa] = 0.82) comparisons. The limb movement domain had fair correlation with Behavioral Pain Scale ([rho] = 0.24) and was reliable in clinician-clinician ([kappa] = 0.58) and clinician-researcher ([kappa] = 0.45) comparisons. Ventilator synchronization correlated with Behavioral Pain Scale ([rho] = 0.54), and reliability in clinician-clinician ([kappa] = 0.29) and clinician-researcher ([kappa] = 0.42) comparisons was fair-moderate. Eight hundred twenty-five patients were enrolled (range, 59-235 across ICUs), providing 12,385 care periods for evaluation (range 655-3,481 across ICUs). The mean proportion of care periods with each quality metric varied between ICUs: excessive sedation 12-38%; agitation 4-17%; poor relaxation 13-21%; poor ventilator synchronization 8-17%; and overall optimum sedation 45-70%. Mean adverse event intervals ranged from 1.5 to 10.3 patients treated. The quality measures appeared relatively stable during the observation period. Conclusions: Process control methodology can be used to simultaneously monitor multiple aspects of pain-sedation-agitation management within ICUs. Variation within and between ICUs could be used as triggers to explore practice variation, improve quality, and monitor this over time

Muscle signaling in exercise intolerance: Insights from the McArdle mouse model

We recently generated a knock-in mouse model (PYGM p.R50X/p.R50X) of McArdle disease (myophosphorylase deficiency). One mechanistic approach to unveil the molecular alterations caused by myophosphorylase deficiency, which is arguably the paradigm of 'exercise intolerance', is to compare the skeletal-muscle tissue of McArdle, heterozygous, and healthy (wild type (wt)) mice. We analyzed in quadriceps muscle of p.R50X/p.R50X (n=4), p.R50X/wt (n=6) and wt/wt mice (n=5) (all male, 8 wk-old) molecular markers of energy-sensing pathways, oxidative phosphorylation (OXPHOS) and autophagy/proteasome systems, oxidative damage and sarcoplamic reticulum (SR) Ca handling. We found a significant group effect for total AMPK (tAMPK) and ratio of phosphorylated (pAMPK)/tAMPK (P=0.012 and 0.033), with higher mean values in p.R50X/p.R50X mice vs. the other two groups. The absence of massive accumulation of ubiquitinated proteins, autophagosomes or lysosomes in p.R50X/p.R50X mice suggested no major alterations in autophagy/proteasome systems. Citrate synthase activity was lower in p.R50X/p.R50X mice vs. the other two groups (P=0.036) but no statistical effect existed for respiratory chain complexes. We found higher levels of 4-hydroxy-2-nonenal-modified proteins in p.R50X/p.R50X and p.R50X/wt mice compared with the wt/wt group (P=0.011). Sarco(endo)plasmic reticulum ATPase 1 (SERCA1) levels detected at 110kDa tended to be higher in p.R50X/p.R50X and p.R50X/wt mice compared with wt/wt animals (P=0.076), but their enzyme activity was normal. We also found an accumulation of phosphorylated SERCA1 in p.R50X/p.R50X animals. Myophosphorylase deficiency causes alterations in sensory energetic pathways together with some evidence of oxidative damage and alterations in Ca handling but with no major alterations in OXPHOS capacity or autophagy/ubiquitination pathways, which suggests that the muscle tissue of patients is likely to adapt overall favorably to exercise training interventions.

Body image and body satisfaction differ by race in overweight postpartum mothers.

BACKGROUND: Body image (BI) and body satisfaction may be important in understanding weight loss behaviors, particularly during the postpartum period. We assessed these constructs among African American and white overweight postpartum women. METHODS: The sample included 162 women (73 African American and 89 white) in the intervention arm 6 months into the Active Mothers Postpartum (AMP) Study, a nutritional and physical activity weight loss intervention. BIs, self-reported using the Stunkard figure rating scale, were compared assessing mean values by race. Body satisfaction was measured using body discrepancy (BD), calculated as perceived current image minus ideal image (BD<0: desire to be heavier; BD>0: desire to be lighter). BD was assessed by race for: BD(Ideal) (current image minus the ideal image) and BD(Ideal Mother) (current image minus ideal mother image). RESULTS: Compared with white women, African American women were younger and were less likely to report being married, having any college education, or residing in households with annual incomes >$30,000 (all p < 0.01). They also had a higher mean body mass index (BMI) (p = 0.04), although perceived current BI did not differ by race (p = 0.21). African Americans had higher mean ideal (p = 0.07) and ideal mother (p = 0.001) BIs compared with whites. African Americans' mean BDs (adjusting for age, BMI, education, income, marital status, and interaction terms) were significantly lower than those of whites, indicating greater body satisfaction among African Americans (BD(Ideal): 1.7 vs. 2.3, p = 0.005; BD(Ideal Mother): 1.1 vs. 1.8, p = 0.0002). CONCLUSIONS: Racial differences exist in postpartum weight, ideal images, and body satisfaction. Healthcare providers should consider tailored messaging that accounts for these racially different perceptions and factors when designing weight loss programs for overweight mothers.

Daily intake of antioxidants in relation to survival among adult patients diagnosed with malignant glioma.

BACKGROUND: Malignant glioma is a rare cancer with poor survival. The influence of diet and antioxidant intake on glioma survival is not well understood. The current study examines the association between antioxidant intake and survival after glioma diagnosis. METHODS: Adult patients diagnosed with malignant glioma during 1991-1994 and 1997-2001 were enrolled in a population-based study. Diagnosis was confirmed by review of pathology specimens. A modified food-frequency questionnaire interview was completed by each glioma patient or a designated proxy. Intake of each food item was converted to grams consumed/day. From this nutrient database, 16 antioxidants, calcium, a total antioxidant index and 3 macronutrients were available for survival analysis. Cox regression estimated mortality hazard ratios associated with each nutrient and the antioxidant index adjusting for potential confounders. Nutrient values were categorized into tertiles. Models were stratified by histology (Grades II, III, and IV) and conducted for all (including proxy) subjects and for a subset of self-reported subjects. RESULTS: Geometric mean values for 11 fat-soluble and 6 water-soluble individual antioxidants, antioxidant index and 3 macronutrients were virtually the same when comparing all cases (n=748) to self-reported cases only (n=450). For patients diagnosed with Grade II and Grade III histology, moderate (915.8-2118.3 mcg) intake of fat-soluble lycopene was associated with poorer survival when compared to low intake (0.0-914.8 mcg), for self-reported cases only. High intake of vitamin E and moderate/high intake of secoisolariciresinol among Grade III patients indicated greater survival for all cases. In Grade IV patients, moderate/high intake of cryptoxanthin and high intake of secoisolariciresinol were associated with poorer survival among all cases. Among Grade II patients, moderate intake of water-soluble folate was associated with greater survival for all cases; high intake of vitamin C and genistein and the highest level of the antioxidant index were associated with poorer survival for all cases. CONCLUSIONS: The associations observed in our study suggest that the influence of some antioxidants on survival following a diagnosis of malignant glioma are inconsistent and vary by histology group. Further research in a large sample of glioma patients is needed to confirm/refute our results.

Cross-cultural variability of component processes in autobiographical remembering: Japan, Turkey, and the USA.

Although the underlying mechanics of autobiographical memory may be identical across cultures, the processing of information differs. Undergraduates from Japan, Turkey, and the USA rated 30 autobiographical memories on 15 phenomenological and cognitive properties. Mean values were similar across cultures, with means from the Japanese sample being lower on most measures but higher on belief in the accuracy of their memories. Correlations within individuals were also similar across cultures, with correlations from the Turkish sample being higher between measures of language and measures of recollection and belief. For all three cultures, in multiple regression analyses, measures of recollection were predicted by visual imagery, auditory imagery, and emotions, whereas measures of belief were predicted by knowledge of the setting. These results show subtle cultural differences in the experience of remembering.

Effects Of Preservation On Wet Weight Dry-Weight Nitrogen And Carbon Contents Of Calanus-Helgolandicus (Crustacea Copepoda)

The lengths, wet and dry weights, nitrogen and carbon contents of fresh, frozen and formaldehyde-fixed specimens of Calanus helgolandicus (Claus) were determined. Samples were collected during May 1980 in the Celtic Sea. Individual Copepodite Stages 3, 4, 5, and Adult Male and Female Stage 6 were measured and analysed, and 36 linear regression equations derived for these variables together with mean values, standard deviations and 95% confidence limits. The range of nitrogen values in the fresh material, expressed as a percentage of dry weight, ranged from 8.08%±0.80 (Copepodite Stage 3) to 10.89%±0.27 (adult female); carbon values changed from 41.6%±3.05 (mean ±95% confidence limits) for Copepodite Stage 3 to 50.97%±2.63 in Copepodite Stage 5. The adult females had a high nitrogen and relatively low carbon content, while the converse was true for Stage 5 copepodites. There was a loss of dry weight from the frozen samples (57%) and the fixed samples (38%) compared with the mean of the fresh dry weight of all stages. The material lost from the copepods was rich in nitrogen, thus, artificially high percentage carbon values were determined from the frozen and fixed samples (52.0 to 60.3% and 44.7 to 58.5%, respectively).

Calorific Ash Carbon And Nitrogen-Content In Relation To Length And Dry-Weight Of Parathemisto-Gaudichaudi (Amphipoda Hyperiidea) In The North-East Atlantic Ocean

The calorific, ash, carbon and nitrogen content, length and dry weight were determined for the hyperiid Parathemisto gaudichaudi (Guerin). Regression equations for all these variables were determined so that they can be estimated by calculation from measurements of length of the hyperiid. Mean values for total nitrogen and carbon were 7.79±0.85% and 36.80±4.18% of the dry weight, respectively. The carbon to calorific equivalent for P. gaudichaudi was 10.37 kcal g-1 carbon (9.13 kcal g-1 when corrected for nitrogen). The calorific value for ash-free adult P. gaudichaudi was 5.138 kcal g-1±1.309 (4.510 kcal g-1 when corrected for nitrogen). This large variation in the calorific content (coefficient of variation of 25.84%) can be accounted for largely by variation in the ash content (coefficient of variation of 21.84%). The calorific value determined for P. gaudichaudi is similar to that measured for other carnivorous crustaceans and adds support to the hypothesis that animals with high calorific content have a low fecundity and an energy-rich store which can be used as a buffer during unfavourable periods in their life.

Columnar aerosol properties in a northeastern atlantic site (plymouth united kingdom) by means of ground based skyradiometer data during years 2000-2008.

Between 2000 and 2008, columnar optical and radiative properties were measured at the Plymouth Marine Laboratory (PML), UK (50° 21.95′N, 4° 8.85′W) using an automatic Prede POM01L sun–sky photometer. The database was analyzed for aerosol optical properties using the SKYRAD radiative inversion algorithm and calibrated using the in situ SKYIL calibration method. Retrievals include aerosol optical depth, Ångström wavelength exponent, aerosol volume distribution, refractive index and single scattering albedo. The results show that the Plymouth site is characterized by low values of aerosol optical depth with low variability (0.18 ± 0.08 at 500 nm) and a mean annual Ångström exponent of 1.03 ± 0.21. The annual mean of the single scattering albedo is 0.97, indicative of non-absorbing aerosols. The aerosol properties were classified in terms of air mass back trajectories: the area is mainly affected by Atlantic air masses and the dominant aerosol type is a mixture of maritime particles, present in low burdens with variable size. The maritime air masses were defined by annual mean values for the AOD (at 500 nm) of 0.13–0.14 and a wavelength exponent of 0.96–1.03. Episodic anthropogenic and mineral dust intrusions occasionally occur, but they are sporadic and dilute (AOD at 500 nm about 0.20). Tropical continental air masses were characterized by the highest AOD at 500 nm (0.34) and the lowest wavelength exponent (0.83), although they were the least represented in the analysis.

Coccolithophore species as indicators of surface oceanographic conditions in the vicinity of Azores islands

During summer 2008 and spring 2009, surface oceanographic surveys were carried out around three islands of the Azores archipelago (Terceira, Sao Miguel and Santa Maria) to assess the phytoplankton distribution and associated physico-chemical processes. The Azores archipelago is a major feature in the biogeochemical North Atlantic Subtropical Gyre (NAST) province although its influence on the productivity of the surrounding ocean is poorly known. Surface phytoplankton was studied by microscopy and HPLC (High Precision Liquid Chromatography). The mean values for biomass proxy Chlorophyll a (Chla) ranged from 0.04 to 0.55 mu g L-1 (Chla maximum = 0.86 mu g L-1) and coccolithophores were the most abundant group, followed by small flagellates, Cyanobacteria, diatoms and dinoflagellates being the least abundant group. The distribution of phytoplankton and coccolithophore species in particular presented seasonal differences and was consistent with the nearshore influence of warm subtropical waters from the south Azores current and colder subpolar waters from the north. The satellite-derived circulation patterns showed southward cold water intrusions off Terceira and northward warm water intrusions off Santa Maria. The warmer waters signal was confirmed by the subtropical coccolithophore assemblage, being Discosphaera tubifera a constant presence under these conditions. The regions of enhanced biomass, either resulting from northern cooler waters or from island induced processes, were characterized by the presence of Emiliania huxleyi. Diatoms and dinoflagellates indicated coastal and regional processes of nutrient enrichment and areas of physical stability, respectively.

Coccolithophore surface distributions in the North Atlantic and their modulation of the air-sea flux of CO2 from 10 years of satellite Earth observation data

Coccolithophores are the primary oceanic phytoplankton responsible for the production of calcium carbonate (CaCO3). These climatically important plankton play a key role in the oceanic carbon cycle as a major contributor of carbon to the open ocean 5 carbonate pump (�50%) and their formation can affect the atmosphere-to-ocean (airsea) uptake of carbon dioxide (CO2) through increasing the seawater partial pressure of CO2 (pCO2). Here we document variations in the areal extent of surface blooms of the globally important coccolithophore, Emiliania huxleyi, in the North Atlantic over a 10-year period (1998–2007), using Earth observation data from the Sea-viewing Wide 10 Field of view Sensor (SeaWiFS).We calculate the annual mean surface areal coverage of E. huxleyi in the North Atlantic to be 474 000±119 000km2 yr−1, which results in a net CaCO3 production of 0.62±0.15 Tg CaCO3 carbon per year. However, this surface coverage and net production can fluctuate by −54/+81% about these mean values and are strongly correlated with the El Ni˜no/Southern Oscillation (ENSO) climate os15 cillation index (r =0.75, p<0.02). Our analysis evaluates the spatial extent over which the E. huxleyi blooms in the North Atlantic can increase the pCO2 and thus decrease the localised sink of atmospheric CO2. In regions where the blooms are prevalent, the average reduction in the monthly CO2 sink can reach 12 %. The maximum reduction of the monthly CO2 sink in the time series is 32 %. This work suggests that the high 20 variability, frequency and distribution of these calcifying plankton and their impact on pCO2 should be considered within modelling studies of the North Atlantic if we are to fully understand the variability of its air-to-sea CO2 flux.

Family-level AMBI is valid for use in the north-eastern Atlantic but not for assessing the health of microtidal Australian estuaries

Analysis of benthic macroinvertebrate samples at a higher taxonomic level than species, e.g. family, potentially provides a more cost-effective protocol for environmental impact assessments and monitoring as it requires less time, funds and taxonomic expertise. Using the AMBI database, species ecological group scores are shown to be coherent within families. Faunal data from a wide range of environmental impact scenarios in the north-eastern Atlantic demonstrate that AMBI, calculated from mean values for families, exhibits a strong linear relationship with species-level AMBI, the correlation improving by using square-root transformed rather than untransformed abundances. In many regions of the world, however, the sensitivity of benthic macroinvertebrates to environmental perturbations is unknown, precluding the use of AMBI for environmental assessments. Yet the families are essentially the same as in the AMBI database. The utility of family-level AMBI is tested using data for four south-western Australian estuaries previously subjected to environmental quality assessments, but where only 17 species of the 144 taxa are included in the AMBI database. Although family-level AMBI scores reflect differences in environmental quality spatially and temporally within an estuary, they do not follow variations in environmental quality among estuaries. Indeed, south-western Australia estuaries are numerically dominated by families with high AMBI scores, probably due to the detrimental effects of natural accumulations of organic material in estuaries with long residence times. As taxonomic distinctness follows trends in environmental quality among estuaries, as well as temporally and spatially within a system, it provides an appropriate substitute for assessing the 'heath' of microtidal estuaries.

Multiwavelength observations of the M15 intermediate-velocity cloud

We present Westerbork Synthesis Radio Telescope HI images, Lovell telescope multibeam H I wide-field mapping, William Herschel Telescope long-slit echelle Ca II observations, Wisconsin Halpha Mapper (WHAM) facility images, and IRAS ISSA 60- and 100-mum co-added images towards the intermediate- velocity cloud (IVC) at + 70 km s(-1), located in the general direction of the M15 globular cluster. When combined with previously published Arecibo data, the H I gas in the IVC is found to be clumpy, with a peak H I column density of similar to1.5 x 10(20) cm(-2), inferred volume density (assuming spherical symmetry) of similar to24 cm(-3)/D (kpc) and a maximum brightness temperature at a resolution of 81 x 14 arcsec(2) of 14 K. The major axis of this part of the IVC lies approximately parallel to the Galactic plane, as does the low- velocity H I gas and IRAS emission. The H I gas in the cloud is warm, with a minimum value of the full width at half-maximum velocity width of 5 km s(-1) corresponding to a kinetic temperature, in the absence of turbulence, of similar to540 K. From the H I data, there are indications of two-component velocity structure. Similarly, the Ca II spectra, of resolution 7 km s(-1), also show tentative evidence of velocity structure, perhaps indicative of cloudlets. Assuming that there are no unresolved narrow-velocity components, the mean values of log(10)[N(Ca II K) cm(2)] similar to 12.0 and Ca II/H I similar to2 5 x 10(-8) are typical of observations of high Galactic latitude clouds. This compares with a value of Ca II/H I>10(-6) for IVC absorption towards HD 203664, a halo star of distance 3 kpc, some 3.degrees1 from the main M15 IVC condensation. The main IVC condensation is detected by WHAM in Halpha with central local-standard-of-rest velocities of similar to60-70 km s(-1), and intensities uncorrected for Galactic extinction of up to 1.3 R, indicating that the gas is partially ionized. The FWHM values of the Halpha IVC component, at a resolution of 1degrees, exceed 30 km s(-1). This is some 10 km s(-1) larger than the corresponding H I value at a similar resolution, and indicates that the two components may not be mixed. However, the spatial and velocity coincidence of the Halpha and H I peaks in emission towards the main IVC component is qualitatively good. If the Halpha emission is caused solely by photoionization, the Lyman continuum flux towards the main IVC condensation is similar to2.7 x 10(6) photon cm(-2) s(-1). There is not a corresponding IVC Halpha detection towards the halo star HD 203664 at velocities exceeding similar to60 km s(- 1). Finally, both the 60- and 100-mum IRAS images show spatial coincidence, over a 0.675 x 0 625 deg(2) field, with both low- and intermediate-velocity H I gas (previously observed with the Arecibo telescope), indicating that the IVC may contain dust. Both the Halpha and tentative IRAS detections discriminate this IVC from high-velocity clouds, although the H I properties do not. When combined with the H I and optical results, these data point to a Galactic origin for at least parts of this IVC.

Variation in shell morphology of Calliostoma zizyphinum (Gastropoda : Trochidae)

Differences in shell morphology in the intertidal prosobranch mollusc Calliostoma zizyphinum were studied from a number of sites within four geographical reo ions of the British Isles with varying exposures to wave action and crab predation. Mean values of damage scarring were highest in shells sampled from Strangford Lough, Northern Ireland, and lowe;t in individuals from the Atlantic Coast. Shells collected front the Isle of Man were smaller than those from either the Atlantic coast of Ireland or Strangford Lough. Shells front Strangford Lough had taller shells (higher aspect ratio) than shells from the County Down and Atlantic Coast and shells from the County Down coast were more squat (lower aspect ratio) than those from all other areas. Shells from Strangford Lough were significantly thinner than shells from all other geographical areas. The relationships between shell damage scarring and shell size and tallness were not consistent among areas. Shells from Strangford Lough are notable in showing a steep, positive relationship between shell size and scarring and a steep, negative relationship between scarring and tallness. The unusual shell phenotypes observed in shells from Strangford 1,Lough may be explained by rapid shell growth, which would not only allow Calliostoma to attain a size refuge from crab predators but also to recover successfully from repeated crab attacks on the shell lip. Such a strategy would result in larger, thinner shells with a high number of damage scars.

Performing meta-analysis with incomplete statistical information in clinical trials

Background: Results from clinical trials are usually summarized in the form of sampling distributions. When full information (mean, SEM) about these distributions is given, performing meta-analysis is straightforward. However, when some of the sampling distributions only have mean values, a challenging issue is to decide how to use such distributions in meta-analysis. Currently, the most common approaches are either ignoring such trials or for each trial with a missing SEM, finding a similar trial and taking its SEM value as the missing SEM. Both approaches have drawbacks. As an alternative, this paper develops and tests two new methods, the first being the prognostic method and the second being the interval method, to estimate any missing SEMs from a set of sampling distributions with full information. A merging method is also proposed to handle clinical trials with partial information to simulate meta-analysis.

The developmental character of cardiac autonomic responses to an acute noxious event in 4- and 8-month-old healthy infants

Heart rate (HR) has been widely studied as a measure of an individual's response to painful stimuli. It remains unclear whether changes in mean HR or the variability of HR are specifically related to the noxious stimulus (i.e. pain). Neither is it well understood how such changes reflect underlying neurologic control mechanisms that produce these responses, or how these mechanisms change during the first year of life. To study the changes in cardiac autonomic modulation that occur with acute pain and with age during early infancy, the relationship between respiratory activity and short-term variations of HR (i.e. respiratory sinus arrhythmia) was quantified in a longitudinal study of term born healthy infants who underwent a finger lance blood collection at 4 months of age (n = 24) and again at 8 months of age (n = 20). Quantitative respiratory activity and HR were obtained during baseline, lance, and recovery periods. Time and frequency domain analyses from 2.2-min epochs of data yielded mean values, spectral measures of low (0.04-0.15 Hz) and high (0.15-0.80 Hz) frequency power (LF and HF), and the LF/HF ratio. To determine sympathetic and parasympathetic cardiac activity, the transfer relation between respiration and HR was used. At both 4 and 8 months, mean HR increased significantly with the noxious event (p > 0.01). There were age-related differences in the pattern of LF, HF, and LF/HF ratio changes. Although these parameters all decreased (p > 0.01) at 4 months, LF and LF/HF increased at 8 months and at 8 months HF remained stable in response to the noxious stimulus. Transfer gain changes with the lance demonstrated a change from predominant vagal baseline to a sympathetic condition at both ages. The primary finding of this study is that a response to an acute noxious stimulus appears to produce an increase in respiratory-related sympathetic HR control and a significant decrease in respiratory-related parasympathetic control at both 4 and 8 months. Furthermore, with increasing age, the sympathetic and parasympathetic changes appear to be less intense, but more sustained.