Lions Gate Hospital

BACKGROUND: Low-molecular-weight heparin has a high bioavailability and a prolonged half-life in comparison with conventional unfractionated heparin. Limited data are available for low-molecular-weight heparin as compared with unfractionated heparin for the treatment of deep-vein thrombosis. METHODS: In a multicenter, double-blind clinical trial, we compared fixed-dose subcutaneous low-molecular-weight heparin given once daily with adjusted-dose intravenous heparin given by continuous infusion for the initial treatment of patients with proximal-vein thrombosis, using objective documentation of clinical outcomes. RESULTS: Six of 213 patients who received low-molecular-weight heparin (2.8 percent) and 15 of 219 patients who received intravenous heparin (6.9 percent) had new episodes of venous thromboembolism (P = 0.07; 95 percent confidence interval for the difference, 0.02 percent to 8.1 percent). Major bleeding associated with initial therapy occurred in 1 patient receiving low-molecular-weight heparin (0.5 percent) and in 11 patients receiving intravenous heparin (5.0 percent), a reduction in risk of 91 percent (P = 0.006). This apparent protection against major bleeding was lost during long-term therapy. Minor hemorrhagic complications were infrequent. Ten patients receiving low-molecular-weight heparin (4.7 percent) died, as compared with 21 patients receiving intravenous heparin (9.6 percent), a risk reduction of 51 percent (P = 0.049). CONCLUSIONS: Low-molecular-weight heparin is at least as effective and as safe as classic intravenous heparin therapy under the conditions of this study and more convenient to administer. The simplified therapy provided by low-molecular-weight heparin may allow patients with uncomplicated proximal deep-vein thrombosis to be cared for in an outpatient setting.

OBJECTIVE: To evaluate the long-term efficacy of acarbose, an alpha-glucosidase inhibitor, in improving glycemic control in patients with non-insulin-dependent diabetes mellitus. DESIGN: A 1-year, multicenter, randomized, double-blind, placebo-controlled study. SETTING: Seven university-affiliated, community-based, tertiary care diabetes clinics. PATIENTS: 354 patients with non-insulin-dependent diabetes mellitus were recruited; 77 were being treated with diet alone, 83 with diet and metformin, 103 with diet and sulfonylurea, and 91 with diet and insulin. Patients in each treatment group were randomly assigned to either acarbose or placebo for 1 year. Eighty-seven percent of patients receiving acarbose and 92% of those receiving placebo were included in the efficacy analysis (n = 316). MEASUREMENTS: At baseline and at 3-month intervals, levels of hemoglobin A1c (HbA1c), fasting and postprandial plasma glucose, fasting and postprandial serum C-peptide, and fasting serum lipids were measured. RESULTS: Compared with placebo, acarbose treatment caused a significant decrease in the mean postprandial plasma glucose peak (90 minutes) in all four groups (19.0 +/- 0.4 mmol/L to 15.5 +/- 0.4 mmol/L; P < 0.001). Analysis of the postprandial plasma glucose incremental area under the curve showed that the change from baseline to the end of the treatment period differed for placebo and acarbose recipients by 4.73 mmol.h/L in the diet alone group (P < 0.001), 2.06 mmol.h/L in the metformin group (P = 0.01), 2.65 mmol.h/L in the sulfonylurea group (P < 0.001), and 3.13 mmol.h/L in the insulin group (P = 0.001). Corresponding decreases in HbA1c levels occurred; these were 0.9% in the diet alone group (P = 0.005), 0.8% in the metformin group (P = 0.011), 0.9% in the sulfonylurea group (P = 0.002), and 0.4% in the insulin group (P = 0.077). Acarbose did not significantly affect mean serum C-peptide or mean serum lipid levels. CONCLUSIONS: Acarbose improved long-term glycemic control in patients with non-insulin-dependent diabetes mellitus regardless of concomitant antidiabetic medication.

BACKGROUND AND PURPOSE: This systematic review analyzed studies examining the effectiveness of various physical therapy interventions for temporomandibular disorder. METHODS: Studies met 4 criteria: (1) subjects were from 1 of 3 groups identified in the first axis of the Research Diagnostic Criteria for Temporomandibular Disorders, (2) the intervention was within the realm of physical therapist practice, (3) an experimental design was used, and (4) outcome measures assessed one or more primary presenting symptoms. Thirty studies were evaluated using Sackett's rules of evidence and 10 scientific rigor criteria. Four randomly selected articles were classified independently by 2 raters (interrater agreement of 100% for levels of evidence and 73.5% for methodological rigor). RESULTS: The following recommendations arose from the 30 studies: (1) active exercises and manual mobilizations may be effective; (2) postural training may be used in combination with other interventions, as independent effects of postural training are unknown; (3) mid-laser therapy may be more effective than other electrotherapy modalities; (4) programs involving relaxation techniques and biofeedback, electromyography training, and proprioceptive re-education may be more effective than placebo treatment or occlusal splints; and (5) combinations of active exercises, manual therapy, postural correction, and relaxation techniques may be effective. DISCUSSION AND CONCLUSION: These recommendations should be viewed cautiously. Consensus on defining temporomandibular joint disorder, inclusion and exclusion criteria, and use of reliable and valid outcome measures would yield more rigorous research.

Foot drop is a common and distressing problem that can lead to falls and injury. Although the most frequent cause is a (common) peroneal neuropathy at the neck of the fibula, other causes include anterior horn cell disease, lumbar plexopathies, L5 radiculopathy and partial sciatic neuropathy. And even when the nerve lesion is clearly at the fibular neck there are a variety of causes that may not be immediately obvious; habitual leg crossing may well be the most frequent cause and most patients improve when they stop this habit. A meticulous neurological evaluation goes a long way to ascertain the site of the lesion. Nerve conduction and electromyographic studies are useful adjuncts in localising the site of injury, establishing the degree of damage and predicting the degree of recovery. Imaging is important in establishing the cause of foot drop be it at the level of the spine, along the course of the sciatic nerve or in the popliteal fossa; ultrasonography, CT and MR imaging are all useful. For patients with a severe foot drop of any cause, an ankle foot orthosis is a helpful device that enables them to walk better and more safely.

Background: Administering antimicrobial agents before obtaining blood cultures could potentially decrease time to treatment and improve outcomes, but it is unclear how this strategy affects diagnostic sensitivity. Objective: To determine the sensitivity of blood cultures obtained shortly after initiation of antimicrobial therapy in patients with severe manifestations of sepsis. Design: Patient-level, single-group, diagnostic study. (ClinicalTrials.gov: NCT01867905). Setting: 7 emergency departments in North America. Participants: Adults with severe manifestations of sepsis, including systolic blood pressure less than 90 mm Hg or a serum lactate level of 4 mmol/L or more. Intervention: Blood cultures were obtained before and within 120 minutes after initiation of antimicrobial treatment. Measurements: Sensitivity of blood cultures obtained after initiation of antimicrobial therapy. Results: Of 3164 participants screened, 325 were included in the study (mean age, 65.6 years; 62.8% men) and had repeated blood cultures drawn after initiation of antimicrobial therapy (median time, 70 minutes [interquartile range, 50 to 110 minutes]). Preantimicrobial blood cultures were positive for 1 or more microbial pathogens in 102 of 325 (31.4%) patients. Postantimicrobial blood cultures were positive for 1 or more microbial pathogens in 63 of 325 (19.4%) patients. The absolute difference in the proportion of positive blood cultures between pre- and postantimicrobial testing was 12.0% (95% CI, 5.4% to 18.6%; P < 0.001). Sensitivity of postantimicrobial culture was 52.9% (CI, 42.8% to 62.9%). When the results of other microbiological cultures were included, microbial pathogens were found in 69 of 102 (67.6% [CI, 57.7% to 76.6%]) patients. Limitation: Only a proportion of screened patients were recruited. Conclusion: Among patients with severe manifestations of sepsis, initiation of empirical antimicrobial therapy significantly reduces the sensitivity of blood cultures drawn shortly after treatment initiation. Primary Funding Source: Vancouver Coastal Health, St. Paul's Hospital Foundation Emergency Department Support Fund, the Fonds de recherche Santé-Québec, and the Maricopa Medical Foundation.

RATIONALE: Small studies have suggested that inhaled corticosteroids can suppress systemic inflammation in chronic obstructive pulmonary disease (COPD). OBJECTIVES: To determine the effect of inhaled corticosteroids with or without long-acting beta(2)-adrenergic agonist on systemic biomarkers of inflammation. METHODS: We conducted a double-blind randomized placebo-controlled trial across 11 centers (n = 289 patients with FEV(1) of 47.8 +/- 16.2% of predicted) to compare the effects of inhaled fluticasone alone or in combination with salmeterol against placebo on circulating biomarkers of systemic inflammation over 4 weeks. The primary endpoint was C-reactive protein (CRP) level. Secondary molecules of interest were IL-6 and surfactant protein D (SP-D). MEASUREMENTS AND MAIN RESULTS: Neither fluticasone nor the combination of fluticasone/salmeterol had a significant effect on CRP or IL-6 levels. There was, however, a significant reduction in SP-D levels with fluticasone and fluticasone/salmeterol compared with placebo (P = 0.002). Health status also improved significantly in both the fluticasone and fluticasone/salmeterol groups compared with placebo, driven mostly by improvements in the symptom scores. Changes in the circulating SP-D levels were related to changes in health status scores. FEV(1) improved significantly only in the fluticasone/salmeterol group compared with placebo. CONCLUSIONS: ICS in conjunction with long-acting beta(2)-adrenergic agonist do not reduce CRP or IL-6 levels in serum of patients with COPD over 4 weeks. They do, however, significantly reduce serum SP-D levels. These data suggest that these drugs reduce lung-specific but not generalized biomarkers of systemic inflammation in COPD.

BACKGROUND: Chronic noncancer pain (CNCP) is a global issue, not only affecting individual suffering, but also impacting the delivery of health care and the strength of local economies. OBJECTIVES: The current study (the Canadian Chronic Pain Study II [CCPSII]) was designed to assess any changes in the prevalence and treatment of CNCP, as well as in attitudes toward the use of strong analgesics, compared with a 2001 study (the CCPSI), and to provide a snapshot of the current standards of care for pain management in Canada. METHODS: Standard, computer-assisted telephone interview survey methodology was applied in two segments, ie, a general population survey and a survey targeting randomly selected primary care physicians (PCPs) who treat moderate to severe CNCP. RESULTS AND DISCUSSION: The patient-reported prevalence of CNCP within Canada has not markedly changed since 2001 but the duration of suffering has decreased. There have been minor changes in regional distribution and generally more patients receive medical treatment, which includes prescription analgesics. Physicians continue to demonstrate opiophobia in their prescribing practices; however, although this is lessened relating to addiction, abuse remains an important concern to PCPs. Canadian PCPs, in general, are implementing standard assessments, treatment approaches, evaluation of treatment success and tools to prevent abuse and diversion, in accordance with guidelines from the Canadian Pain Society and other pain societies globally, although there remains room for improvement and standardization.

The multidisciplinary International Committee for the Advancement of Procedural Sedation presents the first fasting and aspiration prevention recommendations specific to procedural sedation, based on an extensive review of the literature. These were developed using Delphi methodology and assessment of the robustness of the available evidence. The literature evidence is clear that fasting, as currently practiced, often substantially exceeds recommended time thresholds and has known adverse consequences, for example, irritability, dehydration and hypoglycaemia. Fasting does not guarantee an empty stomach, and there is no observed association between aspiration and compliance with common fasting guidelines. The probability of clinically important aspiration during procedural sedation is negligible. In the post-1984 literature there are no published reports of aspiration-associated mortality in children, no reports of death in healthy adults (ASA physical status 1 or 2) and just nine reported deaths in adults of ASA physical status 3 or above. Current concerns about aspiration are out of proportion to the actual risk. Given the lower observed frequency of aspiration and mortality than during general anaesthesia, and the theoretical basis for assuming a lesser risk, fasting strategies in procedural sedation can reasonably be less restrictive. We present a consensus-derived algorithm in which each patient is first risk-stratified during their pre-sedation assessment, using evidence-based factors relating to patient characteristics, comorbidities, the nature of the procedure and the nature of the anticipated sedation technique. Graded fasting precautions for liquids and solids are then recommended for elective procedures based upon this categorisation of negligible, mild or moderate aspiration risk. This consensus statement can serve as a resource to practitioners and policymakers who perform and oversee procedural sedation in patients of all ages, worldwide.

The role of ketamine anesthesia in the prehospital, emergency department and operating theater settings is not well defined. A nonsystematic review of ketamine was performed by authors from Australia, Europe, and North America. Results were discussed among authors and the final manuscript accepted. Ketamine is a useful agent for induction of anesthesia, procedural sedation, and analgesia. Its properties are appealing in many awkward clinical scenarios. Practitioners need to be cognizant of its side effects and limitations.

OBJECTIVE: To compare within-subject variability of plasma glucose measured 2 h after a glucose tolerance test (GTT) with that of plasma glucose measured 2 h after administration of a standardized test meal (diabetes screening product [DSP], Ceapro, Edmonton, Alberta, Canada) and to determine the relationship between the two sets of plasma glucose measurements. RESEARCH DESIGN AND METHODS: Plasma glucose and insulin responses of 36 overnight-fasted subjects (10 lean normal, 9 obese normal, 9 with impaired glucose tolerance [IGT], and 8 with mild diabetes) were studied on eight different mornings after they consumed 75 g oral glucose or 50 g carbohydrate from the DSP. Each test meal was repeated four times by each subject. Within-subject coefficients of variation (CVs) (CV = 100 x SD/mean) of plasma glucose concentrations 2 h after administration of the GTT and DSP were compared by repeated measures ANOVA and linear regression analysis. RESULTS: Mean plasma glucose 2 h after administration of the DSP (D) was linearly related to that 2 h after the GTT (G): G = 1.5 x D - 1.6 (r = 0.97, P < 0.0001). The CV of 2-h plasma glucose was significantly lower after administration of the DSP, 10.5 +/- 1.0%, than after the GTT, 12.7 +/- 1.18% (P = 0.025). The effect of test meal on CV differed in different groups of subjects (P = 0.018), with the largest difference found in IGT subjects, in whom the CV after DSP administration was 47% less than after the GTT (P = 0.0005). The DSP was significantly more palatable and produced fewer adverse symptoms than the GTT. CONCLUSIONS: Plasma glucose concentrations measured 2 h after DSP administration are closely related to those measured 2 h after the GTT but are more consistent than the 2-h post-GTT concentrations within the critical IGT range. This finding suggests that measurement of plasma glucose 2 h after administration of the DSP may allow more precise discrimination among normal glucose levels, IGT, and diabetes than measurement of plasma glucose 2 h after the GTT.

Standardization of controls, both positive and negative controls, is needed for diagnostic immunohistochemistry (dIHC). The use of IHC-negative controls, irrespective of type, although well established, is not standardized. As such, the relevance and applicability of negative controls continues to challenge both pathologists and laboratory budgets. Despite the clear theoretical notion that appropriate controls serve to demonstrate the sensitivity and specificity of the dIHC test, it remains unclear which types of positive and negative controls are applicable and/or useful in day-to-day clinical practice. There is a perceived need to provide "best practice recommendations" for the use of negative controls. This perception is driven not only by logistics and cost issues, but also by increased pressure for accurate IHC testing, especially when IHC is performed for predictive markers, the number of which is rising as personalized medicine continues to develop. Herein, an international ad hoc expert panel reviews classification of negative controls relevant to clinical practice, proposes standard terminology for negative controls, considers the total evidence of IHC specificity that is available to pathologists, and develops a set of recommendations for the use of negative controls in dIHC based on "fit-for-use" principles.

In Brief Objective: The major goal of this study was to examine differences in the middle ear mechano-acoustical properties of normal ears and ears with surgically confirmed otosclerosis using conventional and multifrequency tympanometry (MFT) as well as energy reflectance (ER). Second, we sought to compare ER, standard tympanometry, and MFT in their ability to distinguish healthy and otosclerotic ears examining both overall test performance (sensitivity and specificity) and receiver- operating characteristic analyses. Design: Sixty-two normal-hearing adults and 28 patients diagnosed with otosclerosis served as subjects. Tympanometric data were gathered on a clinical immittance machine, the Virtual 310 equipped with a high-frequency option. Two of the parameters, static admittance and tympanometric width, were measured automatically at a standard 226 Hz frequency. The remaining two parameters, resonant frequency and frequency corresponding to admittance phase angle of 45 degree (F45°), were derived from MFT, multicomponent tympanometry, using a mathematical approach similar to the method used in GSI Tympstar Version 2. ER data were gathered using Mimosa Acoustics (RMS-system v4.0.4.4) equipment. Results: Analyses of receiver-operating characteristic plots confirmed the advantage of MFT measures of resonant frequency and F45° over the standard low-frequency measures of static admittance and tympanometric width with respect to distinguishing otosclerotic ears from normal ears. The F45° measure was also found to be the best single index for making this distinction among tympanometric parameters. ER less than 1 kHz was significantly higher in otosclerotic ears than normal ears. This indicates that most of the incident energy below 1 kHz is reflected back into the ear canal in otosclerotic ears. ER patterns exceeding the 90th percentile of the normal ears across all frequencies correctly identify 82% of the otosclerotic ears while maintaining a low false alarm rate (17.2%); thus, this measure outperforms the other individual tympanometric parameters. Combination of ER and F45° were able to distinguish all otosclerotic ears. Correlations and the individual patterns of test performance revealed that information provided by ER is supplemental to the information provided by conventional and MFT with respect to distinguishing otosclerotic ears from normal ears. Conclusion: The present findings show that the overall changes of ER across frequencies can distinguish otosclerotic ears from normal ears and from other sources of conductive hearing loss. Incorporating ER in general practice will improve the identification of otosclerotic ears when conventional tympanometry and MFT may fail to do so. To further improve the false alarm rate, ER should be interpreted in conjunction with other audiologic test batteries because it is unlikely that signs of a conductive component, including abnormal middle ear muscle reflex and ER responses, would be observed in an ear with normal middle ear function. Sixty-two normal-hearing adults and 28 patients diagnosed with otosclerosis served as subjects. Overall, energy reflectance (ER) in the otosclerotic ears was statistically higher than ER in the normal ears between 400 and 1000 Hz. Analysis of receiver operating characteristic plots revealed that ER is potentially useful in differentiating otosclerotic ears from normal ears. More importantly, comparison of the test performance in individual otosclerotic ears between ER and tympanometric measures revealed that the information provided by ER is supplemental to the information provided by tympanometry. Therefore, combination of tympanometry and ER could potentially improve distinguishing otosclerotic ears from normal ears.

OBJECTIVES: The objective was to examine the feasibility, effectiveness, and adverse effect profile of intranasal ketamine for analgesia in emergency department (ED) patients. METHODS: This was a prospective observational study examining a convenience sample of patients aged older than 6 years experiencing moderate or severe pain, defined as a visual analog scale (VAS) score of 50 mm or greater. Patients received 0.5 to 0.75 mg/kg intranasal ketamine. Pain scores were recorded on a standard 100-mm VAS by trained investigators at baseline, then every 5 minutes for 30 minutes, and then every 10 minutes for an additional 30 minutes. The primary outcome was the number and proportion of patients experiencing clinically significant reductions in VAS pain scores, defined as VAS reductions of 13 mm or more, within 30 minutes. Secondary outcomes included the median reduction in VAS, the median time required to achieve a 13 mm reduction in VAS, vital sign changes, and adverse events. Continuous data are reported with medians and interquartile ranges (IQRs). The Wilcoxon signed-ranks test was used to assess changes in VAS scores. Adverse effects are reported with proportions and 95% confidence intervals (CIs). RESULTS: Forty patients were enrolled with a median age of 47 years (IQR = 36 to 57 years; range = 11 to 79 years) for primarily orthopedic injuries. A reduction in VAS of 13 mm or more within 30 minutes was achieved in 35 patients (88%). The median change in VAS at 30 minutes was 34 mm (44%). Median time required to achieve a 13 mm VAS reduction was 9.5 minutes (IQR = 5 to 13 minutes; range = 5 to 25 minutes). No serious adverse effects occurred. Minor adverse effects included dizziness (21 patients, 53%; 95% CI = 38% to 67%), feeling of unreality (14 patients, 35%; 95% CI = 22% to 50%), nausea (four patients, 10%; 95% CI = 4% to 23%), mood change (three patients, 8%; 95% CI = 3% to 20%), and changes in hearing (one patient, 3%; 95% CI = 0% to 13%). All adverse effects were transient and none required intervention. There were no changes in vital signs requiring clinical intervention. CONCLUSIONS: Intranasal ketamine reduced VAS pain scores to a clinically significant degree in 88% of ED patients in this series. Adverse effects were minor and transient. Intranasal ketamine may have a role in the provision of effective, expeditious analgesia to ED patients.

OBJECTIVES: This study evaluated the effectiveness, recovery time, and adverse event profile of intravenous (IV) ketofol (mixed 1:1 ketamine-propofol) for emergency department (ED) procedural sedation and analgesia (PSA) in children. METHODS: Prospective data were collected on all PSA events in a trauma-receiving, community teaching hospital over a 3.5-year period, from which data on all patients under 21 years of age were studied. Patients receiving a single-syringe 1:1 mixture of 10 mg/mL ketamine and 10 mg/mL propofol (ketofol) were analyzed. Patients received ketofol in titrated aliquots at the discretion of the treating physician. Effectiveness, recovery time, caregiver and patient satisfaction, drug doses, physiologic data, and adverse events were recorded. RESULTS: Ketofol PSA was performed in 219 patients with a median age of 13 years (range = 1 to 20 years; interquartile range [IQR] = 8 to 16 years) for primarily orthopedic procedures. The median dose of medication administered was 0.8 mg/kg each of ketamine and propofol (range = 0.2 to 3.0 mg/kg; IQR = 0.7 to 1.0 mg/kg). Sedation was effective in all patients. Three patients (1.4%; 95% confidence interval [CI] = 0.0% to 3.0%) had airway events requiring intervention, of which one (0.4%; 95% CI = 0.0% to 1.2%) required positive pressure ventilation. Two patients (0.9%; 95% CI = 0.0% to 2.2%) had unpleasant emergence requiring treatment. All other adverse events were minor. Median recovery time was 14 minutes (range = 3 to 41 minutes; IQR = 11 to 18 minutes). Median staff satisfaction was 10 on a 1-to-10 scale. CONCLUSIONS: Pediatric PSA using ketofol is highly effective. Recovery times were short; adverse events were few; and patients, caregivers, and staff were highly satisfied.

The persistent presence of pathogenic bacteria is one of the main obstacles to wound healing. Detection of wound bacteria relies on sampling methods, which delay confirmation by several days. However, a novel handheld fluorescence imaging device has recently enabled real-time detection of bacteria in wounds based on their intrinsic fluorescence characteristics, which differ from those of background tissues. This device illuminates the wound with violet (405 nm) light, causing tissues and bacteria to produce endogenous, characteristic fluorescence signals that are filtered and displayed on the device screen in real-time. The resulting images allow for rapid assessment and documentation of the presence, location, and extent of fluorescent bacteria at moderate-to-heavy loads. This information has been shown to assist in wound assessment and guide patient-specific treatment plans. However, proper image interpretation is essential to assessing this information. To properly identify regions of bacterial fluorescence, users must understand: (1) Fluorescence signals from tissues (e.g., wound tissues, tendon, bone) and fluids (e.g., blood, pus); (2) fluorescence signals from bacteria (red or cyan); (3) the rationale for varying hues of both tissue and bacterial fluorescence; (4) image artifacts that can occur; and (5) some potentially confounding signals from non-biological materials (e.g., fluorescent cleansing solutions). Therefore, this tutorial provides clinicians with a rationale for identifying common wound fluorescence characteristics. Clinical examples are intended to help clinicians with image interpretation-with a focus on image artifacts and potential confounders of image interpretation-and suggestions of how to overcome such challenges when imaging wounds in clinical practice.

OBJECTIVES: The objective was to evaluate the effectiveness, recovery time, and adverse event profile of intravenous (IV) mixed 1:1 ketamine-propofol (ketofol) for adult procedural sedation and analgesia (PSA) in the emergency department (ED). METHODS: Prospective data were collected on all PSA events over a 4.5-year period in a trauma-receiving suburban teaching hospital. PSAs using a 1:1 single-syringe mixture of 10 mg/mL ketamine and 10 mg/mL propofol in patients over 21 years of age were analyzed. Physiologic data, drug doses, adverse events, recovery time, patient satisfaction, and staff satisfaction were recorded. RESULTS: Ketofol PSA was used in 728 patients for primarily orthopedic procedures. Median patient age was 53 years (range = 21 to 99 years, interquartile range [IQR] = 36-70 years). The median dose of ketamine and propofol was 0.7 mg/kg each (range =0.2 to 2.7 mg/kg, IQR = 0.5-0.9 mg/kg), and median recovery time was 14 minutes (range = 3 to 50 minutes, IQR = 10-17 minutes). PSA was effective in 717 cases (98%). Bag-mask ventilation occurred in 15 patients (2.1%; 95% confidence interval [CI] = 1.0% to 3.1%). Recovery agitation occurred in 26 patients (3.6%; 95% CI = 2.2% to 4.9%), of whom 13 (1.8%; 95% CI = 0.8% to 2.7%) required treatment. One patient experienced vomiting and one patient was admitted to the hospital for monitoring of transient dysrhythmia and hypotension. No sequelae were identified. The median staff satisfaction scores were 10 (IQR = 9-10) on a scale of 1 to 10, and 97% of patients would have chosen the same method of PSA in the future. CONCLUSIONS: Ketofol is an effective PSA agent in adult ED patients. Recovery times are short and adverse events are few. Patients and ED staff were highly satisfied.

PURPOSE: This systematic review evaluated the clinical utility of single photon emission computed tomography (SPECT) in traumatic brain injury (TBI). METHODS: After defining a PICO Statement (Population, Intervention, Comparison and Outcome Statement), PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria were applied to identify 1600 articles. After screening, 374 articles were eligible for review. Inclusion for review was focus on SPECT in the setting of mild, moderate, or severe TBI with cerebral lobar specificity of SPECT findings. Other inclusion criteria were comparison modalities in the same subjects and articles in English. Foreign language articles, SPECT studies that did not include comparison modalities, and case reports were not included for review. RESULTS: We identified 19 longitudinal and 52 cross-sectional studies meeting inclusion criteria. Three longitudinal studies examined diagnostic predictive value. The first showed positive predictive value increases from initial SPECT scan shortly after trauma to one year follow up scans, from 59% to 95%. Subsequent work replicated these results in a larger cohort. Longitudinal and cross sectional studies demonstrated SPECT lesion localization not detected by CT or MRI. The most commonly abnormal regions revealed by SPECT in cross-sectional studies were frontal (94%) and temporal (77%) lobes. SPECT was found to outperform both CT and MRI in both acute and chronic imaging of TBI, particularly mild TBI. It was also found to have a near 100% negative predictive value. CONCLUSIONS: This review demonstrates Level IIA evidence (at least one non-randomized controlled trial) for the value of SPECT in TBI. Given its advantages over CT and MRI in the detection of mild TBI in numerous studies of adequate quality, and given its excellent negative predictive value, it may be an important second test in settings where CT or MRI are negative after a closed head injury with post-injury neurological or psychiatric symptoms.

OBJECTIVE: To determine whether a forced titration of acarbose (from 50 to 300 mg three times daily) administered over a 24-week period, in conjunction with diet and insulin therapy, improves glycemic control and reduces daily insulin requirements in insulin-requiring type II diabetes. RESEARCH DESIGN AND METHODS: This multicenter, randomized, double-blind, placebo-controlled trial was 36 weeks in duration. The trial consisted of a 6-week pretreatment period, a 24-week double-blind treatment period, and a 6-week post-treatment follow-up period. The primary efficacy variables were the mean change from baseline in HbA1c levels and the mean percentage change from baseline in total daily insulin dose. RESULTS: Treatment with acarbose was associated with significant reductions in HbA1c levels of 0.40% (P = 0.0001) and in total daily insulin dose of 8.3% (P = 0.0015). There were also significant reductions in all plasma glucose variables measured, including a 0.9 mmol/l reduction in fasting glucose (P = 0.0440), a 2.6 mmol/l reduction in glucose Cmax (P = 0.0001) and a 270 mmol.min-1.l-1 reduction in glucose area under the curve (P = 0.0002). Although acarbose treatment was associated with a greater incidence of adverse events than was placebo treatment, primarily flatulence and diarrhea, these events did not generally prevent patients from completing the study. CONCLUSIONS: The results of this study suggest that acarbose is a safe and effective adjunct to diet and insulin therapy for the management of insulin-requiring type II diabetes.

BACKGROUND: Malignant melanoma is resistant to almost all conventional forms of chemotherapy. Recent evidence suggests that anti-apoptotic proteins of the Bcl-2 family are overexpressed in melanoma and may contribute to melanoma's striking resistance to apoptosis. ABT-737, a small-molecule inhibitor of Bcl-2, Bcl-xl and Bcl-w, has demonstrated efficacy in several forms of leukemia, lymphoma as well as solid tumors. However, overexpression of Mcl-1, a frequent observance in melanoma, is known to confer ABT-737 resistance. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that knockdown of Mcl-1 greatly reduces cell viability in combination with ABT-737 in six different melanoma cell lines. We demonstrate that the cytotoxic effect of this combination treatment is due to apoptotic cell death involving not only caspase-9 activation but also activation of caspase-8, caspase-10 and Bid, which are normally associated with the extrinsic pathway of apoptosis. Caspase-8 (and caspase-10) activation is abrogated by inhibition of caspase-9 but not by inhibitors of the death receptor pathways. Furthermore, while caspase-8/-10 activity is required for the full induction of cell death with treatment, the death receptor pathways are not. Finally, we demonstrate that basal levels of caspase-8 and Bid correlate with treatment sensitivity. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that the combination of ABT-737 and Mcl-1 knockdown represents a promising, new treatment strategy for malignant melanoma. We also report a death receptor-independent role for extrinsic pathway proteins in treatment response and suggest that caspase-8 and Bid may represent potential markers of treatment sensitivity.

A significantly lower proportion of the patients in the Jay group (25%) experienced pressure ulcer formation during the three months of observation as compared to the foam group (41%). No statistically significant differences were found between groups on the location, severity, or healing duration of the pressure ulcers. Most lesions (65%) were limited to persistent erythema of intact skin, and healed in three to four weeks. Significantly higher proportions of patients in the Jay groups (7%) rejected their cushion because of discomfort as compared to foam (1%). The incidence of pressure ulcers was significantly higher among those patients who experienced peak interface pressures recorded at 60 mmHg or higher, had low Norton scores (< or = 11), or were malnourished.