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The Hospital Standardised Mortality Ratio (HSMR) is a commonly used measure of hospital mortality that is standardised for age, comorbidities and other factors. By tradition, this statistic has always excluded patients classified as 'palliative'. The HSMR has never been validated as a reliable measure of quality of care, and it can be very hard to interpret, partly due to difficulties with defining and applying the term 'palliative'. In this paper, we review the Canadian experience with the palliative status flag, and explain why it is so difficult to define and apply consistently. We also highlight some potential concerns about clinicians labelling inpatients as 'palliative' during their admission. Finally, we propose an organisational ethics framework, and six specific suggestions for hospitals to use when publishing statistics such as the HSMR.

Objective: Neuroimaging techniques are increasingly important in psychiatric research and clinical practice, but few postgraduate psychiatry programs offer formal training in neuroimaging. To address this need, the authors developed a course to prepare psychiatric residents to use neuroimaging techniques effectively in independent practice., Methods: The authors present the format and curriculum of a highly interactive, 5-day intensive neuroimaging course, taught by psychiatry, neurology, radiology, nuclear medicine, and sleep medicine staff, covering psychiatrically oriented neuroanatomy; neuroimaging techniques and principles; clinical skills, including interpretation of computed tomography and MRI in neuropsychiatric cases; and formal approaches to critiquing neuroimaging research and applying its findings to clinical practice. Detailed questionnaires assessed the subjective and objective impact of the course on residents' knowledge of, and attitudes toward, neuroimaging in psychiatry before and after the course., Results: Twenty-five first-year residents completed the questionnaires. Participants were enthusiastic about the content and interested in improving their skills in interpreting clinical neuroimaging studies. By the end of the course, residents also reported large gains in subjective comfort level with neuroimaging literature appraisal and functional neuroanatomy and believed that the course was effective in meeting their own specific learning objectives. Objective measures showed significant gains in most areas of the curriculum., Conclusion: This short, intensive course effectively teaches clinically oriented neuroimaging principles to psychiatric residents and can be readily adapted to other postgraduate programs or continuing medical education.

Background: Patients and clinicians often find it difficult to discuss wishes regarding cardiopulmonary resuscitation (CPR) or "code status." Some authors have published effective communication styles, but there are currently no published guidelines for the content of a discussion about resuscitation or goals of care., Methods: We identified a group of physicians with expertise in end-of-life care and communication, and used the Delphi method to develop a series of consensus statements about the ideal content of a discussion of CPR and goals of care., Results: Twelve physicians agreed to participate in the study, generating nine consensus statements. These statements addressed the following topics: timing the discussion; framing the discussion in terms of "goals of care"; distinguishing between life-sustaining therapy (LST) and CPR; describing a cardiac arrest, LST, CPR, and palliative care; describing what happens after a cardiac arrest; how to modify the discussion to respect a patient's medical condition or beliefs; offering a prognosis; making a recommendation; and the importance of trust and rapport. There was consensus for each statement after the second Delphi round., Interpretation: Physicians with expertise in end-of-life care and communication were able to develop consensus statements for the ideal content of a discussion of CPR and goals of care. These statements can serve as guidelines for physicians who feel uncomfortable with these discussions, in order to facilitate effective, informed, and ethically sound decision making.

In the event of an overwhelming influenza pandemic, many health care systems will implement a triage system that would potentially deny critical care treatment to some seriously ill patients. Although all triage systems have guaranteed palliative care for those who are denied critical care, no jurisdiction has yet developed a plan to accommodate the anticipated "surge" in demand for palliative care. The authors present a mathematical and ethical justification for a palliative care surge plan and outline some of the key elements that should be included in such a plan., (Copyright 2010 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)

You have recently heard reports that synthetic colloids may be associated with renal failure and other morbidities in certain populations of critically ill patients. You have been asked by the hospital chief of staff whether there should be a suspension of the use of synthetic colloids until further information is available. You need to make a decision.

Physicians are biased and imprecise, but we are better at predicting mortality in the intensive care unit than any mathematical model currently available. But even if we were flawless prognosticators, we would still be left with the larger ethical problem of what to do with prognostic information. In order to translate prognosis into recommendation, we need to know about patient values.

Background: End-of-life care is suboptimally taught in undergraduate and postgraduate education in Canada. Previous interventions to improve residents' knowledge and comfort have involved lengthy comprehensive educational modules or dedicated palliative care rotations., Objective: To determine the effectiveness of a cheap, portable, and easily implemented pocket reference for improving residents' knowledge and comfort level in dealing with pain and symptom management on the medical ward., Design: Cluster-randomized controlled trial conducted from August 2005 to June 2006., Setting: Medical clinical teaching units (CTUs) in 3 academic hospitals in Toronto, Canada., Participants: All residents rotating through the medical CTUs who consented to participate in the study., Intervention: Residents at 1 hospital received a pocket reference including information about pain and symptom control, as well as 1-2 didactic end-of-life teaching sessions per month normally given as part of the rotation. Residents at the other 2 hospitals received only the didactic sessions., Main Outcome Measures: A 10-question survey assessing knowledge and comfort level providing end-of-life care to medical inpatients, as well as focus group interviews., Results: One hundred thirty-six residents participated on 3 CTUs for a participation rate of approximately 75%. Comfort levels improved in both control (p < .01) and intervention groups (p < .01), but the increase in comfort level was significantly higher in the intervention group (z = 2.57, p < .01). Knowledge was not significantly improved in the control group (p = .06), but was significantly improved in the intervention group (p = .01). Greater than 90% of residents in the intervention group used the card at least once per week, and feedback from the focus groups was very positive., Conclusions: Our pocket card is a feasible, economical, and educational intervention that improves resident comfort level and knowledge in delivering end-of-life care on CTUs.

Background: Many caregivers in intensive care units (ICUs) feel that they sometimes provide inappropriate or excessive care, but little is known about their definition of "futile care" or how they attempt to limit its impact. We sought to explore how ICU staff define medically futile care, why they provide it and what strategies might promote a more effective use of ICU resources., Methods: Using semi-structured interviews, we surveyed 14 physician directors, 16 nurse managers and 14 respiratory therapists from 16 ICUs across Ontario. We analyzed the transcripts using a modified grounded-theory approach., Results: From the interviews, we generated a working definition of medically futile care to mean the use of considerable resources without a reasonable hope that the patient would recover to a state of relative independence or be interactive with his or her environment. Respondents felt that futile care was provided because of family demands, a lack of timely or skilled communication, or a lack of consensus among the treating team. Respondents said they were able to resolve cases of futile care most effectively by improving communication and by allowing time for families to accept the reality of the situation. Respondents felt that further efforts to limit futile care should focus on educating the public and health care professionals about the role of the ICU and about alternatives such as palliative care; mandating early and skilled discussion of resuscitation status; establishing guidelines for admission to the ICU; and providing legal and ethical support for physicians who encounter difficulties. There was a broad consistency in responses among all disciplines., Interpretation: ICU physicians, nurses and respiratory therapists have similar and well-formed opinions about how to define and resolve medically futile care and where to focus future efforts to limit the impact of futile care in the ICU.

Serial passage of a clinical isolate of Streptococcus pneumoniae, in the presence of moxifloxacin, gatifloxacin or gemifloxacin, gave rise to resistant isolates. Non-susceptibility as defined by Clinical and Laboratory Standards Institute (CLSI, formerly NCCLS) breakpoints arose on Days 10, 11, and 12 with gatifloxacin, gemifloxacin, and moxifloxacin respectively. Moxifloxacin and gatifloxacin selected for a single step quinolone-resistant-determining-region (QRDR) mutation in DNA gyrase (GyrA) on Day 4 and 7 respectively, whereas gemifloxacin selected simultaneously for multi-step mutations in gyrase and topoisomerase IV (ParC) on Day 17 and activated a non-reserpine inhibited efflux mechanism by Day 4. As found in clinical isolates, mutations included Ser-81-Phe and Glu-85-Lys in GyrA and Ser-79-Phe or Asp-83-Tyr in ParC. At high MICs, moxifloxacin showed a previously unreported 4 amino-acid deletion in GyrB as well as a more unusual substitution Ser-79-Leu/Ile in ParC. Gemifloxacin showed a 2- to 16-fold greater activity than moxifloxacin or gatifloxacin against strains with two or more QRDR mutations, however, its potency did not translate to nonsusceptibility and gemifloxacin MIC values were either at or well above the CLSI nonsusceptible breakpoint concentration.

Mechanical ventilation is the cornerstone of therapy for patients with acute respiratory distress syndrome (ARDS). Paradoxically, mechanical ventilation can exacerbate lung damage--a phenomenon known as ventilator-induced lung injury. While new ventilation strategies have reduced the mortality rate in patients with ARDS, this mortality rate still remains high. High-frequency oscillatory ventilation (HFOV) is an unconventional form of ventilation that may improve oxygenation in patients with ARDS, while limiting further lung injury associated with high ventilatory pressures and volumes delivered during conventional ventilation. HFOV has been used for almost two decades in the neonatal population, but there is more limited experience with HFOV in the adult population. In adults, the majority of the published literature is in the form of small observational studies in which HFOV was used as 'rescue' therapy for patients with very severe ARDS who were failing conventional ventilation. Two prospective randomized controlled trials, however, while showing no mortality benefit, have suggested that HFOV, compared with conventional ventilation, is a safe and effective ventilation strategy for adults with ARDS. Several studies suggest that HFOV may improve outcomes if used early in the course of ARDS, or if used in certain populations. This review will summarize the evidence supporting the use of HFOV in adults with ARDS.

The importance of myocardial bridging of a coronary artery in the setting of hypertrophic cardiomyopathy is controversial, although we have previously reported an association with myocardial ischemia and sudden death in children. We report five symptomatic children in whom symptoms or evidence of myocardial ischemia resolved or improved after supraarterial myotomy alone.

Pain is a unique class of sensory experience from the perspective of salience. Nonpainful somatosensory stimuli usually require behavioral relevance or voluntary attention to maintain salience. In contrast, painful stimuli tend to have sustained salience even without explicit behavioral relevance or voluntary attention. We have previously identified a frontal-parietal-cingulate network of regions responding transiently to nonpainful sensory events. This network is sensitive to the task relevance and novelty of sensory events and likely represents the salience of events in the sensory environment. Since pain can remain salient for a prolonged period, we hypothesized that this network should show transient responses to the onset or offset of a nonpainful stimulus, but sustained responses throughout the duration of a painful stimulus. To test this hypothesis, we used functional MRI to examine the response of these regions to sustained (60-s) periods of painful and nonpainful transcutaneous electrical nerve stimulation. As predicted, the temporoparietal, inferior frontal, and anterior cingulate cortex showed only transient responses to the onset or offset of nonpainful stimulation, but a sustained response throughout the duration of painful stimulation. These regions therefore show tonic responses to stimuli with tonic salience, supporting a general role for these areas in representing stimulus salience. The thalamus and putamen also responded tonically throughout painful but not nonpainful stimulation. Previous studies have implicated the basal ganglia in supporting voluntary sustained attention. Our findings suggest that the basal ganglia may play a more general role in supporting sustained salience, whether through voluntary or involuntary mechanisms.

Objective: The authors hypothesized that central factors may underlie sensory deficits in patients with nondermatomal somatosensory deficits (NDSD) and that functional brain imaging would reveal altered responses in supraspinal nuclei., Background: Patients with chronic pain frequently present with NDSD, ranging from hypoesthesia to complete anesthesia in the absence of substantial pathology and often in association with motor weakness and occasional paralysis. Patients with pain and such pseudoneurologic symptoms can be classified as having both a pain disorder and a conversion disorder (Diagnostic and Statistical Manual of Mental Disorders-IV classification)., Methods: The authors tested their hypothesis with functional MRI (fMRI) of brush and noxious stimulation-evoked brain responses in four patients with chronic pain and NDSD., Results: The fMRI findings revealed altered somatosensory-evoked responses in specific forebrain areas. Unperceived stimuli failed to activate areas that were activated with perceived touch and pain: notably, the thalamus, posterior region of the anterior cingulate cortex (ACC), and Brodmann area 44/45. Furthermore, unperceived stimuli were associated with deactivations in primary and secondary somatosensory cortex (S1, S2), posterior parietal cortex, and prefrontal cortex. Finally, unperceived (but not perceived) stimuli activated the rostral ACC., Conclusions: Diminished perception of innocuous and noxious stimuli is associated with altered activity in many parts of the somatosensory pathway or other supraspinal areas. The cortical findings indicate a neurobiological component for at least part of the symptoms in patients presenting with nondermatomal somatosensory deficits.

Stimulus salience depends both on behavioral context and on other factors such as novelty and frequency of occurrence. The temporo-parietal junction (TPJ) responds preferentially to behaviorally relevant stimuli and is thought to play a general role in detecting salient stimuli. If so, it should respond preferentially to novel or infrequent events, even in a neutral behavioral context. To test this hypothesis, we used event-related functional magnetic resonance imaging (fMRI) to identify brain regions sensitive to the novelty of visual, auditory, and tactile stimuli during passive observation. Cortical regions with a greater response to novel than familiar stimuli across all modalities were identified at two sites in the TPJ region: the supramarginal gyrus (SMG) and superior temporal gyrus. The right inferior frontal gyrus (IFG), right anterior insula, left anterior cingulate cortex (ACC), and left inferior temporal gyrus also showed sensitivity to novelty. The novelty-sensitive TPJ activation in SMG overlaps a region previously identified as sensitive behavioral context. This region may play a general role in identifying salient stimuli, whether the salience is due to the current behavioral context or not. The IFG activation overlaps regions previously identified as responsive to nonnovel sensory events regardless of behavioral context. The IFG may therefore play a general role in stimulus evaluation rather than a specific role in identifying novel stimuli. The ACC activation lies in a region active during complex response-selection tasks, suggesting a general role in detecting and/or planning responses to salient events. A frontal-parietal-cingulate network may serve to identify and evaluate salient sensory stimuli in general.

Attention is, in part, a mechanism for identifying features of the sensory environment of potential relevance to behavior. The network of brain areas sensitive to the behavioral relevance of multimodal sensory events has not been fully characterized. We used event-related fMRI to identify brain regions responsive to changes in both visual and auditory stimuli when those changes were either behaviorally relevant or behaviorally irrelevant. A widespread network of "context-dependent" activations responded to both task-irrelevant and task-relevant events but responded more strongly to task-relevant events. The most extensive activations in this network were located in right and left temporoparietal junction (TPJ), with smaller activations in left precuneus, left anterior insula, left anterior cingulate cortex, and right thalamus. Another network of "context-independent" activations responded similarly to all events, regardless of task relevance. This network featured a large activation encompassing left supplementary and cingulate motor areas (SMA/CMA) as well as right IFG, right/left precuneus, and right anterior insula, with smaller activations in right/left inferior temporal gyrus and left posterior cingulate cortex. Distinct context-dependent and context-independent subregions of activation were also found within the left and right TPJ, left anterior insula, and left SMA/CMA. In the right TPJ, a subregion in the supramarginal gyrus showed sensitivity to the behavioral context (i.e., relevance) of stimulus changes, while two subregions in the superior temporal gyrus did not. The results indicate a role for the TPJ in detecting behaviorally relevant events in the sensory environment. The TPJ may serve to identify salient events in the sensory environment both within and independent of the current behavioral context., (Copyright 2001 Academic Press.)

We report a case of group C streptococcal meningitis in a woman with a history of close animal contact as well as head trauma as a result of a kick by a horse. Blood and cerebrospinal fluid cultures grew Streptococcus equi subsp. zooepidemicus, as did a throat culture taken from the colt that had kicked her 2 weeks prior to admission.

Novel approaches to the development of analytical procedures for monitoring incoming starting material in support of chemical/pharmaceutical processes are described. High technology solutions were utilized for timely process development and preparation of high quality clinical supplies. A single robust HPLC method was developed and characterized for the analysis of the key starting material from three suppliers. Each supplier used a different process for the preparation of this material and, therefore, each suppliers' material exhibited a unique impurity profile. The HPLC method utilized standard techniques acceptable for release testing in a QC/manufacturing environment. An automated experimental design protocol was used to characterize the robustness of the HPLC method. The method was evaluated for linearity, limit of quantitation, solution stability, and precision of replicate injections. An LC-MS method that emulated the release HPLC method was developed and the identities of impurities were mapped between the two methods.

Sensory stimuli undergoing sudden changes draw attention and preferentially enter our awareness. We used event-related functional magnetic-resonance imaging (fMRI) to identify brain regions responsive to changes in visual, auditory and tactile stimuli. Unimodally responsive areas included visual, auditory and somatosensory association cortex. Multimodally responsive areas comprised a right-lateralized network including the temporoparietal junction, inferior frontal gyrus, insula and left cingulate and supplementary motor areas. These results reveal a distributed, multimodal network for involuntary attention to events in the sensory environment. This network contains areas thought to underlie the P300 event-related potential and closely corresponds to the set of cortical regions damaged in patients with hemineglect syndromes.