Baseline hospital performance and the impact of medical emergency teams: Modelling vs. conventional subgroup analysis

<p>Abstract</p> <p>Background</p> <p>To compare two approaches to the statistical analysis of the relationship between the baseline incidence of adverse events and the effect of medical emergency teams (METs).</p> <p>Methods</p> <p>Using data from a cluster randomized controlled trial (the MERIT study), we analysed the relationship between the baseline incidence of adverse events and its change from baseline to the MET activation phase using quadratic modelling techniques. We compared the findings with those obtained with conventional subgroup analysis.</p> <p>Results</p> <p>Using linear and quadratic modelling techniques, we found that each unit increase in the baseline incidence of adverse events in MET hospitals was associated with a 0.59 unit subsequent reduction in adverse events (95%CI: 0.33 to 0.86) after MET implementation and activation. This applied to cardiac arrests (0.74; 95%CI: 0.52 to 0.95), unplanned ICU admissions (0.56; 95%CI: 0.26 to 0.85) and unexpected deaths (0.68; 95%CI: 0.45 to 0.90). Control hospitals showed a similar reduction only for cardiac arrests (0.95; 95%CI: 0.56 to 1.32). Comparison using conventional subgroup analysis, on the other hand, detected no significant difference between MET and control hospitals.</p> <p>Conclusions</p> <p>Our study showed that, in the MERIT study, when there was dependence of treatment effect on baseline performance, an approach based on regression modelling helped illustrate the nature and magnitude of such dependence while sub-group analysis did not. The ability to assess the nature and magnitude of such dependence may have policy implications. Regression technique may thus prove useful in analysing data when there is a conditional treatment effect.</p

The ENCODE Project at UC Santa Cruz

The goal of the Encyclopedia Of DNA Elements (ENCODE) Project is to identify all functional elements in the human genome. The pilot phase is for comparison of existing methods and for the development of new methods to rigorously analyze a defined 1% of the human genome sequence. Experimental datasets are focused on the origin of replication, DNase I hypersensitivity, chromatin immunoprecipitation, promoter function, gene structure, pseudogenes, non-protein-coding RNAs, transcribed RNAs, multiple sequence alignment and evolutionarily constrained elements. The ENCODE project at UCSC website () is the primary portal for the sequence-based data produced as part of the ENCODE project. In the pilot phase of the project, over 30 labs provided experimental results for a total of 56 browser tracks supported by 385 database tables. The site provides researchers with a number of tools that allow them to visualize and analyze the data as well as download data for local analyses. This paper describes the portal to the data, highlights the data that has been made available, and presents the tools that have been developed within the ENCODE project. Access to the data and types of interactive analysis that are possible are illustrated through supplemental examples

Effects of intraoperative hypothermia on neuropsychological outcomes after intracranial aneurysm surgery

Objective Subarachnoid hemorrhage and surgical obliteration of ruptured intracranial aneurysms are frequently associated with neurological and neuropsychological abnormalities. We reported that intraoperative cooling did not improve neurological outcome in good-grade surgical subarachnoid hemorrhage patients, as assessed by the Glasgow Outcome Scale score or other neurological and functional measures (National Institutes of Health Stroke Scale, Rankin Disability Scale, Barthel Activities of Daily Living). We now report the results of neuropsychological testing in these patients. Methods A total of 1,001 patients who bled ≤14 days before surgery were randomly assigned to intraoperative hypothermia (t = 33°C) or normothermia (37°C). Outcome was assessed approximately 3 months after surgery. Patients underwent the Benton Visual Retention, Controlled Oral Word Association, Rey–Osterrieth Complex Figure, Grooved Pegboard, and the Trail Making tests. T -scores for each test were calculated from normative data. T -scores were averaged to calculate a Composite Score. A test result (or the Composite Score) was considered “impaired” if the T -score was two or more standard deviations below the norm. A Mini-Mental State Examination was also performed. Results Neurological outcome data were available in 1,000 patients. Sixty-one patients died. Of the 939 survivors, 873 completed 3 or more tests (exclusive of the Mini-Mental State Examination). Patients with poor neurological outcomes were less likely to complete testing; only 3.9% of Good Outcome (Glasgow Outcome Scale score = 1) patients were untested, compared with 38.6% of patients with Glasgow Outcome Scale scores of 3 and 4. There were no prerandomization demographic differences between the two treatment groups. For hypothermic patients, 16.8% were impaired from their Composite Score versus 20.0% of patients in the normothermic group ( p = 0.317). For patients in the hypothermic group, 54.5% were impaired on at least one test, compared with 55.5% of patients in the normothermic group ( p = 0.865). Similar results were seen in patients with baseline WFNS scores = I. Mini-Mental State Examination scores in the hypothermic and normothermic groups were 27.4 ± 3.8 and 26.8 ± 4.5, respectively. Interpretation This is the largest prospective evaluation of neuropsychological function after subarachnoid hemorrhage to date. Testing was completed in a high fraction of patients, demonstrating the feasibility of such testing in a large trial. However, the frequent inability to complete testing in poor-outcome patients suggests that testing may be best used to refine outcome assessments in good-grade patients. Many patients showed impairment on at least one test, with global impairment present in 17 to 20% of patients (18–21% of survivors). This was true even among the patients with the best preoperative condition (WFNS = 1). There was no difference in the incidence of impairment between hypothermic and normothermic groups. Ann Neurol 2006;60:518–527Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55889/1/21018_ftp.pd

Experiences of a long-term randomized controlled prevention trial in a maiden environment: Estonian Postmenopausal Hormone Therapy trial

<p>Abstract</p> <p>Background</p> <p>Preventive drugs require long-term trials to show their effectiveness or harms and often a lot of changes occur during post-marketing studies. The purpose of this article is to describe the research process in a long-term randomized controlled trial and discuss the impact and consequences of changes in the research environment.</p> <p>Methods</p> <p>The Estonian Postmenopausal Hormone Therapy trial (EPHT), originally planned to continue for five years, was planned in co-operation with the Women's International Study of Long-Duration Oestrogen after Menopause (WISDOM) in the UK. In addition to health outcomes, EPHT was specifically designed to study the impact of postmenopausal hormone therapy (HT) on health services utilization.</p> <p>Results</p> <p>After EPHT recruited in 1999–2001 the Women's Health Initiative (WHI) in the USA decided to stop the estrogen-progestin trial after a mean of 5.2 years in July 2002 because of increased risk of breast cancer and later in 2004 the estrogen-only trial because HT increased the risk of stroke, decreased the risk of hip fracture, and did not affect coronary heart disease incidence. WISDOM was halted in autumn 2002. These decisions had a major influence on EPHT.</p> <p>Conclusion</p> <p>Changes in Estonian society challenged EPHT to find a balance between the needs of achieving responses to the trial aims with a limited budget and simultaneously maintaining the safety of trial participants. Flexibility was the main key for success. Rapid changes are not limited only to transiting societies but are true also in developed countries and the risk must be included in planning all long-term trials.</p> <p>The role of ethical and data monitoring committees in situations with emerging new data from other studies needs specification. Longer funding for preventive trials and more flexibility in budgeting are mandatory. Who should prove the effectiveness of an (old) drug for a new preventive indication? In preventive drug trials companies may donate drugs but they take a financial risk, especially with licensed drugs. Public funding is crucial to avoid commercial biases. Legislation to share the costs of large post-marketing trials as well as regulation of manufacturer's participation is needed. [ISRCTN35338757]</p

The UCSC Genome Browser database: update 2010

The University of California, Santa Cruz (UCSC) Genome Browser website (http://genome.ucsc.edu/) provides a large database of publicly available sequence and annotation data along with an integrated tool set for examining and comparing the genomes of organisms, aligning sequence to genomes, and displaying and sharing users’ own annotation data. As of September 2009, genomic sequence and a basic set of annotation ‘tracks’ are provided for 47 organisms, including 14 mammals, 10 non-mammal vertebrates, 3 invertebrate deuterostomes, 13 insects, 6 worms and a yeast. New data highlights this year include an updated human genome browser, a 44-species multiple sequence alignment track, improved variation and phenotype tracks and 16 new genome-wide ENCODE tracks. New features include drag-and-zoom navigation, a Wiki track for user-added annotations, new custom track formats for large datasets (bigBed and bigWig), a new multiple alignment output tool, links to variation and protein structure tools, in silico PCR utility enhancements, and improved track configuration tools

The role of nominating committees and director reputation in shaping the labor market for directors: an empirical assessment

Research Question/Issue: Do the presence and independence of nominating committees within boards of directors affect the extent of rewards and sanctions provided by the labor market to directors with a reputation for being active in monitoring management? Research Findings/Insights: Results drawn from a longitudinal sample of directors sitting on the board of 200 public French firms suggest that the stronger a director's reputation for being active in increasing control over management, the larger the number of his/her subsequent appointments to (1) boards with a nominating committee, (2) to boards with a nominating committee which excludes the CEO and (3) to boards with a nominating committee dominated by non-executive directors. In contrast, we found that a director's reputation of being active in increasing control over management does not impact the number of his/her subsequent appointments (1) to boards without a nominating committee, (2) to boards with a nominating committee which includes the CEO and (3) to boards with a nominating committee dominated by executive directors. Theoretical/Academic Implications: This study shows that the outcome of the power struggle between the CEO and incumbent directors during the candidate selection process determines the profile of directors who will ultimately obtain the board appointment. On the one hand, independent nominating committees are likely to reduce the influence of CEOs over the process of a director's appointment, and therefore are likely to increase the recruitment of directors with reputations for being active in exercising control over managers. On the other hand, nonexistence of nominating committees or presence of weak nominating committees under the influence of the CEO decouple directors' reputations for being active in controlling management from the likelihood of obtaining new appointments. Practitioner/Policy Implications: This study offers insights to policy makers interested in increasing the efficiency of the labor market for directors. More specifically, it highlights the conditions under which directors with a reputation of being active in increasing control over management are likely to be rewarded by the labor market for directors. These conditions include (1) the creation of a nominating committee; (2) exclusion of the CEO from this committee and (3) domination of this committee by outside directors

Injuries at a Canadian National Taekwondo Championships: a prospective study

BACKGROUND: The purpose of this prospective study was to assess the injury rates in male and female adult Canadian Taekwondo athletes relative to total number of injuries, type and body part injured. METHODS: Subjects (219 males, 99 females) participated in the 1997 Canadian National Taekwondo Championships in Toronto, Canada. Injuries were recorded on an injury form to documents any injury seen and treatment provided by the health care team. These data were later used for this study. The injury form describes the athlete and nature, site, severity and mechanism of the injury. RESULTS: The overall rate of injuries was 62.9/1,000 athlete-exposures (A-E). The males (79.9/1,000 A-E) sustained significantly more injuries than the females (25.3/1,000 A-E). The lower extremities were the most commonly injured body region in the men (32.0 /1,000 A-E), followed by the head and neck (18.3/1,000 A-E). Injuries to the spine (neck, upper back, low back and coccyx) were the third most often injured body region in males (13.8/1,000 A-E). All injuries to the women were sustained to the lower extremities. The most common type of injury in women was the contusion (15.2/1,000 A-E). However, men's most common type of injury was the sprain (22.8/1,000 A-E) followed by joint dysfunction (13.7/1,000A-E). Concussions were only reported in males (6.9/1,000 A-E). Compared to international counterparts, the Canadian men and women recorded lower total injury rates. However, the males incurred more cerebral concussions than their American colleagues (4.7/1,000 A-E). CONCLUSIONS: Similar to what was found in previous studies, the current investigation seems to suggest that areas of particular concern for preventive measures involve the head and neck as well as the lower extremities. This is the first paper to identify spinal joint dysfunction

Missing domesticated plant forms: can artificial selection fill the gap?

In the course of their evolution, the angiosperms have radiated into most known plant forms and life histories. Their adaptation to a recently created habitat, the crop field, produced a novel form: the plant that allocates an unprecedented 30–60% of its net productivity to sexual structures. Long-lived trees, shrubs and vines of this form evolved, as did annual herbs. Perennial herb forms with increased allocation to asexual reproduction evolved, but there are no examples of perennial herbs with high sexual effort. We suggest that sowing seed into annually tilled fields favored shorter-lived herbs because of trade-offs between first-year seed production and relative growth rate and/or persistence. By propagating cuttings, people quickly domesticated tuber crops and large woody plants. Perennial herbs were too small to be efficiently propagated by cuttings, and the association between longevity, allogamy and genetic load made rapid domestication by sexual cycles unlikely. Perennial grain crops do not exist because they could not have evolved under the original set of conditions; however, they can be deliberately developed today through artificial phenotypic and genotypic selection

Performances in cerebellar and neuromuscular transmission tests are correlated in migraine with aura

In previous studies, we described subclinical abnormalities of neuromuscular transmission and cerebellar functions in migraineurs. The aim of this study was to search if these two functions are correlated in the same patient. Thirteen migraineurs [five without aura (MO) and eight with aura (MA)] underwent both stimulation-SFEMG and 3D-movement analysis. Single fiber EMG (SFEMG) results were expressed as the “mean value of consecutive differences” (mean MCD). Precision of arm-reaching movements (measured with an infrared optoelectronic tracking system) was expressed as the average deviation in the horizontal plane. Median values of mean MCD and mean horizontal deviation were not different between MO and MA. However, in MA, but not in MO, both variables were positively correlated. Thus, we conclude that neuromuscular transmission and cerebellar functions are correlated in the same patient when affected by migraine with aura. We suggest that this correlation might be due to a common molecular abnormality