Entropy and bispectral index for assessment of sedation, analgesia and the effects of unpleasant stimuli in critically ill patients: an observational study

INTRODUCTION: Sedative and analgesic drugs are frequently used in critically ill patients. Their overuse may prolong mechanical ventilation and length of stay in the intensive care unit. Guidelines recommend use of sedation protocols that include sedation scores and trials of sedation cessation to minimize drug use. We evaluated processed electroencephalography (response and state entropy and bispectral index) as an adjunct to monitoring effects of commonly used sedative and analgesic drugs and intratracheal suctioning. METHODS: Electrodes for monitoring bispectral index and entropy were placed on the foreheads of 44 critically ill patients requiring mechanical ventilation and who previously had no brain dysfunction. Sedation was targeted individually using the Ramsay Sedation Scale, recorded every 2 hours or more frequently. Use of and indications for sedative and analgesic drugs and intratracheal suctioning were recorded manually and using a camera. At the end of the study, processed electroencephalographical and haemodynamic variables collected before and after each drug application and tracheal suctioning were analyzed. Ramsay score was used for comparison with processed electroencephalography when assessed within 15 minutes of an intervention. RESULTS: The indications for boli of sedative drugs exhibited statistically significant, albeit clinically irrelevant, differences in terms of their association with processed electroencephalographical parameters. Electroencephalographical variables decreased significantly after bolus, but a specific pattern in electroencephalographical variables before drug administration was not identified. The same was true for opiate administration. At both 30 minutes and 2 minutes before intratracheal suctioning, there was no difference in electroencephalographical or clinical signs in patients who had or had not received drugs 10 minutes before suctioning. Among patients who received drugs, electroencephalographical parameters returned to baseline more rapidly. In those cases in which Ramsay score was assessed before the event, processed electroencephalography exhibited high variation. CONCLUSIONS: Unpleasant or painful stimuli and sedative and analgesic drugs are associated with significant changes in processed electroencephalographical parameters. However, clinical indications for drug administration were not reflected by these electroencephalographical parameters, and barely by sedation level before drug administration or tracheal suction. This precludes incorporation of entropy and bispectral index as target variables for sedation and analgesia protocols in critically ill patients.

Systematic review of the empirical evidence of study publication bias and outcome reporting bias

BACKGROUND: The increased use of meta-analysis in systematic reviews of healthcare interventions has highlighted several types of bias that can arise during the completion of a randomised controlled trial. Study publication bias has been recognised as a potential threat to the validity of meta-analysis and can make the readily available evidence unreliable for decision making. Until recently, outcome reporting bias has received less attention. METHODOLOGY/PRINCIPAL FINDINGS: We review and summarise the evidence from a series of cohort studies that have assessed study publication bias and outcome reporting bias in randomised controlled trials. Sixteen studies were eligible of which only two followed the cohort all the way through from protocol approval to information regarding publication of outcomes. Eleven of the studies investigated study publication bias and five investigated outcome reporting bias. Three studies have found that statistically significant outcomes had a higher odds of being fully reported compared to non-significant outcomes (range of odds ratios: 2.2 to 4.7). In comparing trial publications to protocols, we found that 40-62% of studies had at least one primary outcome that was changed, introduced, or omitted. We decided not to undertake meta-analysis due to the differences between studies. CONCLUSIONS: Recent work provides direct empirical evidence for the existence of study publication bias and outcome reporting bias. There is strong evidence of an association between significant results and publication; studies that report positive or significant results are more likely to be published and outcomes that are statistically significant have higher odds of being fully reported. Publications have been found to be inconsistent with their protocols. Researchers need to be aware of the problems of both types of bias and efforts should be concentrated on improving the reporting of trials.

AN ASSESSMENT OF BALLAST SOURCE'S QUALITY AND LOCATIONS WITH RESPECT TO MDOT'S UPGRADE OF THE WOLVERINE RAILROAD LINE FOR HIGH SPEED RAIL USEAGE

The Michigan Department of Transportation is evaluating upgrading their portion of the Wolverine Line between Chicago and Detroit to accommodate high speed rail. This will entail upgrading the track to allow trains to run at speeds in excess of 110 miles per hour (mph). An important component of this upgrade will be to assess the requirement for ballast material for high speed rail. In the event that the existing ballast materials do not meet specifications for higher speed train, additional ballast will be required. The purpose of this study, therefore, is to investigate the current MDOT railroad ballast quality specifications and compare them to both the national and international specifications for use on high speed rail lines. The study found that while MDOT has quality specifications for railroad ballast it does not have any for high speed rail. In addition, the American Railway Engineering and Maintenance-of-Way Association (AREMA), while also having specifications for railroad ballast, does not have specific specifications for high speed rail lines. The AREMA aggregate specifications for ballast include the following tests: (1) LA Abrasion, (2) Percent Moisture Absorption, (3) Flat and Elongated Particles, (4) Sulfate Soundness test. Internationally, some countries do require a highly standard for high speed rail such as the Los Angeles (LA) Abrasion test, which is uses a higher standard performance and the Micro Duval test, which is used to determine the maximum speed that a high speed can operate at. Since there are no existing MDOT ballast specification for high speed rail, it is assumed that aggregate ballast specifications for the Wolverine Line will use the higher international specifications. The Wolverine line, however, is located in southern Michigan is a region of sedimentary rocks which generally do not meet the existing MDOT ballast specifications. The investigation found that there were only 12 quarries in the Michigan that meet the MDOT specification. Of these 12 quarries, six were igneous or metamorphic rock quarries, while six were carbonate quarries. Of the six carbonate quarries four were locate in the Lower Peninsula and two in the Upper Peninsula. Two of the carbonate quarries were located in near proximity to the Wolverine Line, while the remaining quarries were at a significant haulage distance. In either case, the cost of haulage becomes an important consideration. In this regard, four of the quarries were located with lake terminals allowing water transportation to down state ports. The Upper Peninsula also has a significant amount of metal based mining in both igneous and metamorphic rock that generate significant amount of waste rock that could be used as a ballast material. The main drawback, however, is the distance to the Wolverine rail line. One potential source is the Cliffs Natural Resources that operates two large surface mines in the Marquette area with rail and water transportation to both Lake Superior and Lake Michigan. Both mines mine rock with a very high compressive strength far in excess of most ballast materials used in the United States and would make an excellent ballast materials. Discussions with Cliffs, however, indicated that due to environmental concerns that they would most likely not be interested in producing a ballast material. In the United States carbonate aggregates, while used for ballast, many times don't meet the ballast specifications in addition to the problem of particle degradation that can lead to fouling and cementation issues. Thus, many carbonate aggregate quarries in close proximity to railroads are not used. Since Michigan has a significant amount of carbonate quarries, the research also investigated using the dynamic properties of aggregate as a possible additional test for aggregate ballast quality. The dynamic strength of a material can be assessed using a split Hopkinson Pressure Bar (SHPB). The SHPB has been traditionally used to assess the dynamic properties of metal but over the past 20 years it is now being used to assess the dynamic properties of brittle materials such as ceramics and rock. In addition, the wear properties of metals have been related to their dynamic properties. Wear or breakdown of railroad ballast materials is one of the main problems with ballast material due to the dynamic loading generated by trains and which will be significantly higher for high speed rails. Previous research has indicated that the Port Inland quarry along Lake Michigan in the Southern Upper Peninsula has significant dynamic properties that might make it potentially useable as an aggregate for high speed rail. The dynamic strength testing conducted in this research indicate that the Port Inland limestone in fact has a dynamic strength close to igneous rocks and much higher than other carbonate rocks in the Great Lakes region. It is recommended that further research be conducted to investigate the Port Inland limestone as a high speed ballast material.

Routine vaccination against pertussis and the risk of childhood asthma: a population-based cohort study

BACKGROUND: In industrialized countries vaccination coverage remains suboptimal, partly because of perception of an increased risk of asthma. Epidemiologic studies of the association between childhood vaccinations and asthma have provided conflicting results, possibly for methodologic reasons such as unreliable vaccination data, biased reporting, and reverse causation. A recent review stressed the need for additional, adequately controlled large-scale studies. OBJECTIVE: Our goal was to determine if routine childhood vaccination against pertussis was associated with subsequent development of childhood wheezing disorders and asthma in a large population-based cohort study. METHODS: In 6811 children from the general population born between 1993 and 1997 in Leicestershire, United Kingdom, respiratory symptom data from repeated questionnaire surveys up to 2003 were linked to independently collected vaccination data from the National Health Service database. We compared incident wheeze and asthma between children of different vaccination status (complete, partial, and no vaccination against pertussis) by computing hazard ratios. Analyses were based on 6048 children, 23 201 person-years of follow-up, and 2426 cases of new-onset wheeze. RESULTS: There was no evidence for an increased risk of wheeze or asthma in children vaccinated against pertussis compared with nonvaccinated children. Adjusted hazard ratios comparing fully and partially vaccinated with nonvaccinated children were close to one for both incident wheeze and asthma. CONCLUSION: This study provides no evidence of an association between vaccination against pertussis in infancy and an increased risk of later wheeze or asthma and does not support claims that vaccination against pertussis might significantly increase the risk of childhood asthma.

Expanding the spectrum of mutations in GH1 and GHRHR: genetic screening in a large cohort of patients with congenital isolated growth hormone deficiency

CONTEXT: It is estimated that 3-30% of cases with isolated GH deficiency (IGHD) have a genetic etiology, with a number of mutations being reported in GH1 and GHRHR. The aim of our study was to genetically characterize a cohort of patients with congenital IGHD and analyze their characteristics. PATIENTS AND METHODS: A total of 224 patients (190 pedigrees) with IGHD and a eutopic posterior pituitary were screened for mutations in GH1 and GHRHR. To explore the possibility of an association of GH1 abnormalities with multiple pituitary hormone deficiencies, we have screened 62 patients with either multiple pituitary hormone deficiencies (42 pedigrees), or IGHD with an ectopic posterior pituitary (21 pedigrees). RESULTS: Mutations in GH1 and GHRHR were identified in 41 patients from 21 pedigrees (11.1%), with a higher prevalence in familial cases (38.6%). These included previously described and novel mutations in GH1 (C182X, G120V, R178H, IVS3+4nt, a>t) and GHRHR (W273S, R94L, R162W). Autosomal dominant, type II IGHD was the commonest form (52.4%), followed by type IB (42.8%) and type IA (4.8%). Patients with type II IGHD had highly variable phenotypes. There was no difference in the endocrinology or magnetic resonance imaging appearance between patients with and without mutations, although those with mutations presented with more significant growth failure (height, -4.7 +/- 1.6 SDS vs. -3.4 +/- 1.7 SDS) (P = 0.001). There was no apparent difference between patients with mutations in GH1 and GHRHR. CONCLUSIONS: IGHD patients with severe growth failure and a positive family history should be screened for genetic mutations; the evolving endocrinopathy observed in some of these patients suggests the need for long-term follow-up.

[Sternocostoclavicular hyperostosis. Association with pustular psoriasis and systemic vasculitis]

A female patient with sternocostoclavicular hyperostosis has been followed for 14 years. The case merits special attention because of its association with psoriasis and with an episode of systemic vasculitis. Although patients with sternocostoclavicular hyperostosis usually lack the tissue type antigen HLA-B27, there are grounds for suspicion that the disease is related to the group of seronegative spondylo-arthritides.

Dental injuries in association with facial fractures

PURPOSE: The aim of the study was to investigate the association between dental injuries and facial fractures. MATERIALS AND METHODS: We performed a prospective study of 273 patients examined at a level 1 trauma center in Switzerland from September 2005 until August 2006 who had facial fractures. Medical history and clinical and radiologic examination findings were recorded to evaluate demographics, etiology, presentation, and type of facial fracture, as well as its relationship to dental injury site and type. RESULTS: In 273 patients with dentition, we recorded 339 different facial fractures. Of these patients, 130 (47.5%) sustained a fracture in the non-tooth-bearing region, 44 (16%) had a fractured maxilla, and 65 (24%) had a fractured mandible. Among 224 patients with dentition who had a facial fracture in only 1 compartment, 140 injured teeth were found in 50 patients. Of 122 patients with an injury limited to the non-tooth-bearing facial skeleton, 12 sustained dental trauma (10%). In patients with fractures limited to the maxilla (n = 41), 6 patients had dental injuries (14.5%). In patients with fractures to the mandible (n = 61), 24 sustained dental injuries (39%). When we compared the type of tooth lesion and the location, simple crown fractures prevailed in both jaws. Patients with a fracture of the mandible were most likely to have a dental injury (39.3%). The highest incidence of dental lesions was found in the maxilla in combination with fractures of the lower jaw (39%). This incidence was even higher than the incidence of dental lesions in the lower jaw in combination with fractures of the mandible (24%). CONCLUSIONS: Knowledge of the association of dental injuries and maxillofacial fractures is a basic tool for their prevention. Our study showed that in cases of trauma with mandibular fracture, the teeth in the upper jaw might be at higher risk than the teeth in the lower jaw. Further larger-scale studies on this topic could clarify this finding and may provide suggestions for the amelioration of safety devices (such as modified bicycle helmets).

Hierarchical modeling gave plausible estimates of associations between metabolic syndrome and components of antiretroviral therapy

OBJECTIVE: Hierarchical modeling has been proposed as a solution to the multiple exposure problem. We estimate associations between metabolic syndrome and different components of antiretroviral therapy using both conventional and hierarchical models. STUDY DESIGN AND SETTING: We use discrete time survival analysis to estimate the association between metabolic syndrome and cumulative exposure to 16 antiretrovirals from four drug classes. We fit a hierarchical model where the drug class provides a prior model of the association between metabolic syndrome and exposure to each antiretroviral. RESULTS: One thousand two hundred and eighteen patients were followed for a median of 27 months, with 242 cases of metabolic syndrome (20%) at a rate of 7.5 cases per 100 patient years. Metabolic syndrome was more likely to develop in patients exposed to stavudine, but was less likely to develop in those exposed to atazanavir. The estimate for exposure to atazanavir increased from hazard ratio of 0.06 per 6 months' use in the conventional model to 0.37 in the hierarchical model (or from 0.57 to 0.81 when using spline-based covariate adjustment). CONCLUSION: These results are consistent with trials that show the disadvantage of stavudine and advantage of atazanavir relative to other drugs in their respective classes. The hierarchical model gave more plausible results than the equivalent conventional model.

Impact of unlinked deaths and coding changes on mortality trends in the Swiss National Cohort

BACKGROUND Results of epidemiological studies linking census with mortality records may be affected by unlinked deaths and changes in cause of death classification. We examined these issues in the Swiss National Cohort (SNC). METHODS The SNC is a longitudinal study of the entire Swiss population, based on the 1990 (6.8 million persons) and 2000 (7.3 million persons) censuses. Among 1,053,393 deaths recorded 1991-2007 5.4% could not be linked using stringent probabilistic linkage. We included the unlinked deaths using pragmatic linkages and compared mortality rates for selected causes with official mortality rates. We also examined the impact of the 1995 change in cause of death coding from version 8 (with some additional rules) to version 10 of the International Classification of Diseases (ICD), using Poisson regression models with restricted cubic splines. Finally, we compared results from Cox models including and excluding unlinked deaths of the association of education, marital status, and nationality with selected causes of death. RESULTS SNC mortality rates underestimated all cause mortality by 9.6% (range 2.4%-17.9%) in the 85+ population. Underestimation was less pronounced in years nearer the censuses and in the 75-84 age group. After including 99.7% of unlinked deaths, annual all cause SNC mortality rates were reflecting official rates (relative difference between -1.4% and +1.8%). In the 85+ population the rates for prostate and breast cancer dropped, by 16% and 21% respectively, between 1994 and 1995 coincident with the change in cause of death coding policy. For suicide in males almost no change was observed. Hazard ratios were only negligibly affected by including the unlinked deaths. A sudden decrease in breast (21% less, 95% confidence interval: 12%-28%) and prostate (16% less, 95% confidence interval: 7%-23%) cancer mortality rates in the 85+ population coincided with the 1995 change in cause of death coding policy. CONCLUSIONS Unlinked deaths bias analyses of absolute mortality rates downwards but have little effect on relative mortality. To describe time trends of cause-specific mortality in the SNC, accounting for the unlinked deaths and for the possible effect of change in death certificate coding was necessary.

Ranking of tests for pain hypersensitivity according to their discriminative ability in chronic neck pain

BACKGROUND AND OBJECTIVES Quantitative sensory testing (QST) is widely used to investigate peripheral and central sensitization. However, the comparative performance of different QST for diagnostic or prognostic purposes is unclear. We explored the discriminative ability of different quantitative sensory tests in distinguishing between patients with chronic neck pain and pain-free control subjects and ranked these tests according to the extent of their association with pain hypersensitivity. METHODS We performed a case-control study in 40 patients and 300 control subjects. Twenty-six tests, including different modalities of pressure, heat, cold, and electrical stimulation, were used. As measures of discrimination, we estimated receiver operating characteristic curves and likelihood ratios. RESULTS The following quantitative sensory tests displayed the best discriminative value: (1) pressure pain threshold at the site of the most severe neck pain (fitted area under the receiver operating characteristic curve, 0.92), (2) reflex threshold to single electrical stimulation (0.90), (3) pain threshold to single electrical stimulation (0.89), (4) pain threshold to repeated electrical stimulation (0.87), and (5) pressure pain tolerance threshold at the site of the most severe neck pain (0.86). Only the first 3 could be used for both ruling in and out pain hypersensitivity. CONCLUSIONS Pressure stimulation at the site of the most severe pain and parameters of electrical stimulation were the most appropriate QST to distinguish between patients with chronic neck pain and asymptomatic control subjects. These findings may be used to select the tests in future diagnostic and longitudinal prognostic studies on patients with neck pain and to optimize the assessment of localized and spreading sensitization in chronic pain patients.

Systemic Determinants of the Information Systems Outsourcing Decision: A Comparative Study of German and United States Firms

The practice of information systems (IS) outsourcing is widely established among organizations. Nonetheless, evidence suggests that organizations differ considerably in the extent to which they deploy IS outsourcing. This variation has motivated research into the determinants of the IS outsourcing decision. Most of this research is based on the assumption that a decision on the outsourcing of a particular IS function is made independently of other IS functions. This modular view ignores the systemic nature of the IS function, which posits that IS effectiveness depends on how the various IS functions work together effectively. This study proposes that systemic influences are important criteria in evaluating the outsourcing option. It further proposes that the recognition of systemic influences in outsourcing decisions is culturally sensitive. Specifically, we provide evidence that systemic effects are factored into the IS outsourcing decision differently in more individualist cultures than in collectivist ones. Our results of a survey of United States and German firms indicate that perceived in-house advantages in the systemic impact of an IS function are, indeed, a significant determinant of IS outsourcing in a moderately individualist country (i.e., Germany), whereas insignificant in a strongly individualist country (i.e., the United States). The country differences are even stronger with regard to perceived in-house advantages in the systemic view of IS professionals. In fact, the direction of this impact is reversed in the United States sample. Other IS outsourcing determinants that were included as controls, such as cost efficiency, did not show significant country differences.