Hubert Wong

Safety and efficiency of emergency department assessment of chest discomfort

Background: Most Canadian emergency departments use an unstructured, individualized approach to patients with chest pain, without data to support the safety and efficiency of this practice. We sought to determine the proportions of patients with chest discomfort in emergency departments who either had acute coronary syndrome (ACS) and were inappropriately discharged from the emergency department or did not have ACS and were held for investigation. Methods: Consecutive consenting patients aged 25 years or older presenting with chest discomfort to 2 urban tertiary care emergency departments between June 2000 and April 2001 were prospectively enrolled unless they had a terminal illness, an obvious traumatic cause, a radiographically identifiable cause, severe communication problems or no fixed address in British Columbia or they would not be available for follow-up by telephone. At 30 days we assigned predefined explicit outcome diagnoses: definite ACS (acute myocardial infarction [AMI] or definite unstable angina) or no ACS. Results: Of 1819 patients, 241 (13.2%) were assigned a 30-day diagnosis of AMI and 157 (8.6%), definite unstable angina. Of these 398 patients, 21 (5.3%) were discharged from the emergency department without a diagnosis of ACS and without plans for further investigation. The clinical sensitivity for detecting ACS was 94.7% (95% confidence interval [CI] 92.5%– 96.9%) and the specificity 73.8% (95% CI 71.5%– 76.0%). Of the patients without ACS or an adverse event, 71.1% were admitted to hospital or held in the emergency department for more than 3 hours. Interpretation: The current individualized approach to evaluation and disposition of patients with chest discomfort in 2 Canadian tertiary care emergency departments misses 5.3% of cases of ACS while consuming considerable health care resources for patients without coronary disease. Opportunities exist to improve both safety and efficiency.

Intermediate-Term Results of Total Ankle Replacement and Ankle Arthrodesis

BACKGROUND Surgical treatments for end-stage ankle arthritis include total ankle replacement and ankle arthrodesis. Although arthrodesis is a reliable procedure, ankle replacement is often preferred by patients. This prospective study evaluated intermediate-term outcomes of ankle replacement and arthrodesis in a large cohort at multiple centers, with variability in ankle arthritis type, prosthesis type, surgeon, and surgical technique. We hypothesized that patient-reported clinical outcomes would be similar for both procedures. METHODS Patients in the Canadian Orthopaedic Foot and Ankle Society (COFAS) Prospective Ankle Reconstruction Database were treated with total ankle replacement (involving Agility, STAR, Mobility, or HINTEGRA prostheses) or ankle arthrodesis by six subspecialty-trained orthopaedic surgeons at four centers between 2001 and 2007. Data collection included demographics, comorbidities, and the Ankle Osteoarthritis Scale (AOS) and Short Form-36 (SF-36) scores. The preoperative and latest follow-up scores for patients with at least four years of follow-up were analyzed. Sensitivity analyses excluded ankles that had undergone revision. A linear mixed-effects regression model compared scores between the groups, adjusting for age, sex, side, smoking status, body mass index, inflammatory arthritis diagnosis, baseline score, and surgeon. RESULTS Of the 388 ankles (281 in the ankle replacement group and 107 in the arthrodesis group), 321 (83%; 232 ankle replacements and eighty-nine arthrodeses) were reviewed at a mean follow-up of 5.5 ± 1.2 years. Patients treated with arthrodesis were younger, more likely to be diabetic, less likely to have inflammatory arthritis, and more likely to be smokers. Seven (7%) of the arthrodeses and forty-eight (17%) of the ankle replacements underwent revision. The major complications rate was 7% for arthrodesis and 19% for ankle replacement. The AOS total, pain, and disability scores and SF-36 physical component summary score improved between the preoperative and final follow-up time points in both groups. The mean AOS total score improved from 53.4 points preoperatively to 33.6 points at the time of follow-up in the arthrodesis group and from 51.9 to 26.4 points in the ankle replacement group. Differences in AOS and SF-36 scores between the arthrodesis and ankle replacement groups at follow-up were minimal after adjustment for baseline characteristics and surgeon. CONCLUSIONS Intermediate-term clinical outcomes of total ankle replacement and ankle arthrodesis were comparable in a diverse cohort in which treatment was tailored to patient presentation; rates of reoperation and major complications were higher after ankle replacement.

Association of Biomarkers With Pre-Radiographically Defined and Radiographically Defined Knee Osteoarthritis in a Population-Based Study

OBJECTIVE To evaluate 10 biomarkers in magnetic resonance imaging (MRI)-determined, pre-radiographically defined osteoarthritis (pre-ROA) and radiographically defined OA (ROA) in a population-based cohort of subjects with symptomatic knee pain. METHODS Two hundred one white subjects with knee pain, ages 40-79 years, were classified into OA subgroups according to MRI-based cartilage (MRC) scores (range 0-4) and Kellgren/Lawrence (K/L) grades of radiographic severity (range 0-4): no OA (MRC score 0, K/L grade<2), pre-ROA (MRC score>or=1, K/L grade<2), or ROA (MRC score>or=1, K/L grade>or=2). Urine and serum samples were assessed for levels of the following biomarkers: urinary biomarkers C-telopeptide of type II collagen (uCTX-II), type II and types I and II collagen cleavage neoepitopes (uC2C and uC1,2C, respectively), and N-telopeptide of type I collagen, and serum biomarkers sC1,2C, sC2C, C-propeptide of type II procollagen (sCPII), chondroitin sulfate 846 epitope, cartilage oligomeric matrix protein, and hyaluronic acid. Multicategory logistic regression was performed to evaluate the association of OA subgroup with individual biomarker levels and biomarker ratios, adjusted for age, sex, and body mass index. RESULTS The risk of ROA versus no OA increased with increasing levels of uCTX-II (odds ratio [OR] 3.12, 95% confidence interval [95% CI] 1.35-7.21), uC2C (OR 2.13, 95% CI 1.04-4.37), and uC1,2C (OR 2.07, 95% CI 1.06-4.04), and was reduced in association with high levels of sCPII (OR 0.53, 95% CI 0.30-0.94). The risk of pre-ROA versus no OA increased with increasing levels of uC2C (OR 2.06, 95% CI 1.05-4.01) and uC1,2C (OR 2.06, 95% CI 1.12-3.77). The ratios of type II collagen degradation markers to collagen synthesis markers were better than individual biomarkers at differentiating the OA subgroups, e.g., the ratio of [uCTX-II][uC1,2C] to sCPII was associated with a risk of ROA versus no OA of 3.47 (95% CI 1.34-9.03) and a risk of pre-ROA versus no OA of 2.56 (95% CI 1.03-6.40). CONCLUSION Different cartilage degradation markers are associated with pre-ROA than are associated with ROA, indicating that their use as diagnostic markers depends on the stage of OA. Biomarker ratios contrasting cartilage degradation with cartilage synthesis are better able to differentiate OA stages compared with levels of the individual markers.

Variation in length of intensive care unit stay after cardiac arrest: where you are is as important as who you are.

Objective:To determine whether hospital site is independently associated with length of intensive care unit (ICU) stay in those patients who die in hospital after experiencing a cardiac arrest. Design:Retrospective cohort study. Setting:Thirty-one Canadian ICUs, all but one being members of the Critical Care Research Network. Patients:All patients admitted to these ICUs after resuscitation from a cardiac arrest. Interventions:None. Measurements and Main Results:Retrospective analysis of prospectively collected clinical data. Using gamma regression with ICU length of stay as the dependent variable, we found the following variables to be independently associated with ICU length of stay: age, gender, Acute Physiology and Chronic Health Evaluation II score, Glasgow Coma Scale score, hospital size, and hospital site. Conclusions:In this cohort of patients admitted to ICU after cardiac arrest, hospital site was strongly associated with ICU length of stay after controlling for patient-specific factors. Variation in processes of care among ICUs may point to opportunities for improvement.

Association between Source of Infection and Hospital Mortality in Patients Who Have Septic Shock

RATIONALE Mortality caused by septic shock may be determined by a systemic inflammatory response, independent of the inciting infection, but it may also be influenced by the anatomic source of infection. OBJECTIVES To determine the association between the anatomic source of infection and hospital mortality in critically ill patients who have septic shock. METHODS This was a retrospective, multicenter cohort study of 7,974 patients who had septic shock in 29 academic and community intensive care units in Canada, the United States, and Saudi Arabia from January 1989 to May 2008. MEASUREMENTS AND MAIN RESULTS Subjects were assigned 1 of 20 anatomic sources of infection based on clinical diagnosis and/or isolation of pathogens. The primary outcome was hospital mortality. Overall crude hospital mortality was 52% (21-85% across sources of infection). Variation in mortality remained after adjusting for year of admission, geographic source of admission, age, sex, comorbidities, community- versus hospital-acquired infection, and organism type. The source of infection with the highest standardized hospital mortality was ischemic bowel (75%); the lowest was obstructive uropathy-associated urinary tract infection (26%). Residual variation in adjusted hospital mortality was not explained by Acute Physiology and Chronic Health Evaluation II score, number of Day 1 organ failures, bacteremia, appropriateness of empiric antimicrobials, or adjunct therapies. In patients who received appropriate antimicrobials after onset of hypotension, source of infection was associated with death after adjustment for both predisposing and downstream factors. CONCLUSIONS Anatomic source of infection should be considered in future trial designs and analyses, and in development of prognostic scoring systems.

Validation of the Berg Balance Scale as a predictor of length of stay and discharge destination in stroke rehabilitation.

OBJECTIVE To validate the utility of the Berg Balance Scale (BBS) in predicting length of stay (LOS) and discharge destination for patients admitted to a stroke rehabilitation unit. DESIGN Prospective study. SETTING Provincial tertiary inpatient stroke unit for a primarily geriatric population. PARTICIPANTS A total of 313 of the 325 patients admitted consecutively between April 1998 and August 2000. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES LOS and discharge destination. RESULTS Admission BBS scores correlated negatively with LOS (r=-.53, controlling for age). Logistic regression confirmed that the following were independent predictors of being discharged home rather than to an institution (adjusted odds ratio, 95% confidence interval): admission BBS (1.09, 1.06-1.12) and the presence of family supports (15.0, 7.2-31.3). These results generally concur with previously published results, obtained at a different stroke rehabilitation setting. CONCLUSIONS This study validates the use of the BBS scores in assisting to estimate approximate LOS and eventual discharge destination. Age did not correlate significantly with the outcomes measured in this study, which was conducted in a geriatric population.

CAUSALITY, MEASUREMENT ERROR AND MULTICOLLINEARITY IN EPIDEMIOLOGY

SUMMARY This paper demonstrates that measurement error can conspire with multicollinearity among explanatory variables to mislead an investigator. A causal variable measured with error may be overlooked and its significance transferred to a surrogate. The latter’s significance can then be entirely spurious, in that controlling it will not predictably change the response variable. In epidemiological research, such a response may be a health outcome. The phenomenon we study is demonstrated through simulation experiments involving nonlinear regression models. Also, the paper presents the measurement error problem in a theoretical setting. The paper concludes by echoing the familiar warning against making conclusions about causality from a multiple regression analysis, in this case because of the phenomenon presented in the paper.

Endotracheal intubation and esophageal tracheal Combitube insertion by regular ambulance attendants: a comparative trial.

Objective. Recent cardiac arrest resuscitation guidelines have recommended the esophageal tracheal Combitube (ETC) as an advanced airway management alternative for individuals who infrequently perform endotracheal intubation (ETI). This study attempted to analyze basic (nonparamedic) ambulance attendant success rates at ETI and ETC insertion as well as their continuing skill competency over time and whether ongoing practice on mannequins improved skill performance. Methods. Three hundred fifty-seven adult patients in cardiorespiratory arrest were treated by 81 basic ambulance attendants. Original study design called for the analysis of two treatment options in three patient groups: ETC insertion, ETI insertion with mannequin practice (ETI-MP), and ETI insertion without mannequin practice (ETI-NMP). The main outcome measures were: (1) successful insertion and ventilation with ETC or ETI, assessed by receiving physicians; and (2) differences in successful insertion/ventilation between the MP and NMP groups. Results. Successful insertion (intent-to-treat) for the ETI-NMP group was 70 of 111 (63%; 95% confidence interval [CI], 54–73%); ETI-MP success was 105 of 139 (76%; 95% CI, 67–84%); ETC-NMP success was 26 of 42 (62%; 95% CI, 49–75%); and ETC-MP success was 36 of 53 (68%; 95% CI, 54–82%). Continuing mannequin practice appeared to improve ETI success (as-treated): MP 75% versus NMP 61% (odds ratio, 2.1; 95% CI, 1.11–3.94). Conclusions. There were similar rates of successful insertion/ventilation with the ETC and ETI. ETI insertion success was lower without mannequin practice. ETI skill erosion was partially mitigated by additional field experience.

Incidence of medication errors and adverse drug events in the ICU: a systematic review

Background Medication errors (MEs) and adverse drug events (ADEs) are both common and under-reported in the intensive care setting. The definitions of these terms vary substantially in the literature. Many methods have been used to estimate their incidence. Methods A systematic review was done to assess methods used for tracking unintended drug events in intensive care units (ICUs). Studies published up to 22 June 2007 were identified by searching eight online databases, including Medline. In total, 613 studies were evaluated for inclusion by two reviewers. Results The authors selected 29 papers to analyse; all studies took place in an ICU, were reproducible and reported ICU-specific rates of events. Rates of MEs varied from 8.1 to 2344 per 1000 patient-days, and ADEs from 5.1 to 87.5 per 1000 patient-days. The definitions of ADE and ME in the studies varied widely. Conclusions Much variation exists in reported rates and definitions of ADEs and MEs in ICUs. Some of this variation may be due to a lack of standard definitions for ADEs and MEs, and methods for detecting them. Further standardisation is needed before these methods can be used to evaluate process improvements.

A Novel Mechanism and Treatment Target for Presynaptic Abnormalities in Specific Striatal Regions in Schizophrenia

Abnormalities of amount and function of presynaptic terminals may have an important role in the mechanism of illness in schizophrenia. The SNARE proteins (SNAP-25, syntaxin, and VAMP) are enriched in presynaptic terminals, where they interact to form a functional complex to facilitate vesicle fusion. SNARE protein amounts are altered in the cortical regions in schizophrenia, but studies of protein–protein interactions are limited. We extended these investigations to the striatal regions (such as the nucleus accumbens, ventromedial caudate (VMC), and dorsal caudate) relevant to disease symptoms. In addition to measuring SNARE protein levels, we studied SNARE protein–protein interactions using a novel ELISA method. The possible effect of antipsychotic treatment was investigated in parallel in the striatum of rodents that were administered haloperidol and clozapine. In schizophrenia samples, compared with controls, SNAP-25 was 32% lower (P=0.015) and syntaxin was 26% lower (P=0.006) in the VMC. In contrast, in the same region, SNARE protein–protein interactions were higher in schizophrenia (P=0.008). Confocal microscopy of schizophrenia and control VMC showed qualitatively similar SNARE protein immunostaining. Haloperidol treatment of rats increased levels of SNAP-25 (mean 24%, P=0.003), syntaxin (mean 18%, P=0.010), and VAMP (mean 16%, P=0.001), whereas clozapine increased only the VAMP level (mean 13%, P=0.004). Neither drug altered SNARE protein–protein interactions. These results indicate abnormalities of amount and interactions of proteins directly related to presynaptic function in the VMC in schizophrenia. SNARE proteins and their interactions may be a novel target for the development of therapeutics.