Screening tools to identify patients with unmet palliative care needs in the emergency department: A systematic review.

OBJECTIVES: This systematic review identified and assessed psychometric properties of the available screening tools to identify patients with unmet palliative care (PC) needs in the emergency department (ED). METHODS: A comprehensive search of electronic databases and the gray literature was conducted. Two independent reviewers completed study screening and inclusion, data extraction, and quality assessment. A descriptive summary of the results was reported using median of medians and interquartile ranges (IQRs). RESULTS: A total of 35 studies were included, involving the assessment of 14 unique screening tools. The most commonly used screening tool was the surprise question (SQ; n = 12 studies), followed by the Palliative Care and Rapid Emergency Screening (P-CaRES) tool (n = 8), and the screening for palliative and end-of-life care needs in the emergency department (SPEED) instrument (n = 4). Twelve of the included studies reported on the psychometric properties of the screening tools, of which eight of these studies assessed the performance of the SQ to predict patient mortality. Overall, the median sensitivity (63%, IQR 38%-78%) and specificity (75%, IQR 57%-84%) of the SQ to predict mortality at 1 or 12 months was moderate. While the median positive predictive value of the SQ was low (32%, IQR 16%-40%), the median negative predictive value was high (91%, IQR 88%-95%). Across the studies, the proportion of patients identified as having unmet PC based on the criteria of the screening tools ranged from 5% to 83%. CONCLUSIONS: This review identified 14 unique screening tools used to identify adult patients with unmet PC needs in the ED. One screening tool, the SQ, was found to have moderate sensitivity and specificity to accurately predict future patient mortality. Additional research is needed to better understand the clinical value of this and the other available tools prior to their widespread implementation.

Comparison of the Management and Short-Term Outcomes between Patients with Advanced Cancer and Other End-of-Life Conditions Presenting to Two Canadian Emergency Departments.

Background: An increasing number of patients with end-of-life (EOL) conditions, particularly those with advanced cancer, are presenting to the emergency department (ED). Objectives: To assess the characteristics, management and short-term outcomes of ED patients with advanced cancer compared to patients with other EOL conditions. Methodology/Design: A secondary analysis of a prospective cohort study. Setting/Participants: Volunteer emergency physicians in two Canadian EDs identified presentations for advanced cancer and other EOL conditions with the aid of a modified screening tool March-August 2018. Results: Among the 663 presentations by patients with EOL conditions, 272 (41%) presented with advanced cancer. The majority of presentations for advanced cancer (81%) or other EOL conditions (77%) were by patients with unmet palliative care (PC) needs. Patients with advanced cancer were significantly less likely to have active goals of care (GOC) documented on their charts (53% vs. 75%; p < 0.001). While no significant differences were found between the groups, the majority of presentations involved imaging, investigations, consultations, and hospitalization. Presentations for advanced cancer were more likely to receive a postdischarge referral (38% vs. 23%; p < 0.001). Referrals to PC consultations or postdischarge referrals were infrequent. Regression analysis found that patients with advanced cancer were associated with shorter length of stay (LOS). Conclusions: The majority of presentations for advanced cancer or other EOL conditions involved significant resource use. Patients with cancer experienced shorter LOS; however, had less documentation of GOC and gaps in referrals to PC services were identified. Interventions should be explored to promote early GOC discussions and PC referrals in this patient group.

Comparison of characteristics and management of emergency department presentations between patients with met and unmet palliative care needs.

INTRODUCTION: This study examined emergency department (ED) presentations of patients with end of life (EOL) conditions and patients having met and unmet palliative care needs were compared. METHODS: Presentations for EOL conditions were prospectively identified and screened for palliative care needs. Descriptive data were reported as proportions, means or medians. Bi-variable analysis for dichotomous and continuous variables were performed by chi-squared and T-tests (p≤0.01), respectively. A multivariable logistic regression model identified factors associated with having unmet palliative needs and reported adjusted odds ratios (aOR) with 95% confidence intervals (CI). RESULTS: Overall, 663 presentations for EOL conditions were identified; 518 (78%) involved patients with unmet palliative care needs. Presentations by patients with unmet palliative needs were more likely to involve consultations (80% vs. 67%, p = 0.001) and result in hospitalization (69% vs. 51%, p<0.001) compared to patients whose palliative needs were met. Patients with unmet palliative care needs were more likely to have previous ED visits (73% unmet vs. 48% met; p<0.001). While medication, procedures, investigations and imaging ordering were high across all patients with EOL conditions, there were no significant differences between the groups. Consultations with palliative specialists in the ED (6% unmet vs. 1% met) and following discharge (29% unmet vs. 18% met) were similarly uncommon. Patients having two or more EOL conditions (aOR = 2.41; 95% CI: 1.16, 5.00), requiring hospitalization (aOR = 1.93; 95% CI: 1.30, 2.87), and dying during the ED visit (aOR = 2.15; 95% CI: 1.02, 4.53) were strongly associated with having unmet palliative care needs. CONCLUSIONS: Most ED presentations for EOL conditions were made by patients with unmet palliative care needs, who were significantly more likely to require consultation, hospitalization, and to die. Referrals to palliative care services during and after the ED visit were infrequent, indicating important opportunities to promote these services.

An Assessment of the Management of Patients with Advanced End-Stage Illness in the Emergency Department: An Observational Cohort Study.

Background: Presentations to the emergency department (ED) by patients with end-of-life (EOL) conditions for their acute care needs are common. Objectives: The objective of this study was to identify and describe the ED management across presentations to the ED for EOL conditions. Design: Prospective observational cohort study. Settings/Subjects: Emergency physicians in two Canadian ED's were asked to identify presentations by adult patients with EOL conditions using a modified screening tool. Measurements: Patient characteristics and ED management for each presentation were collected through chart review by trained research assistants. Descriptive analyses were conducted as appropriate and bivariate comparisons of dichotomous and continuous variables were completed using χ2 tests and using t test or Wilcoxon rank-sum test, respectively. Results: Physicians identified 663 ED presentations for EOL conditions, with advanced cancer (41%), dementia (23%), and chronic obstructive pulmonary disease (16%) being the most common EOL conditions. The majority of presentations involved consultations (77%), hospitalization (65%), and numerous investigations (97%), including blood work (97%) and imaging (92%). The majority of patients with EOL conditions had a history of ED visits (68%). Using a modified screening tool, 78% of presentations involved patients with unmet palliative care needs, but only 1% of presentations involved a palliative consultation or admission to a palliative care unit. Conclusion: Presentations to the ED for EOL conditions involve significant ED resources; however, only a handful of patients are referred to palliative services. Patients with EOL conditions are appropriate targets for palliative services and community support outside the ED.

Increased Private Healthcare for Canada: Is That the Right Solution?

Medicare is a publicly funded healthcare system that is a source of national pride in Canada; however, Canadians are increasingly concerned about its performance and sustainability. One proposed solution is private financing (including both private for-profit insurance and private out-of-pocket financing) that would fundamentally change medicare. We investigate international experiences to determine if associations exist between the degree of private spending and two of the core values of medicare - universality and accessibility - as well as the values of equity and quality. We further investigate the impact of private spending on overall health system performance, health outcomes and health expenditure growth rates. Private financing (both private for-profit insurance and private out-of-pocket financing) was found to negatively affect universality, equity, accessibility and quality of care. Increased private financing was not associated with improved health outcomes, nor did it reduce health expenditure growth. Therefore, increased private financing is not the panacea proposed for improving quality or sustainability. The debate over the future of medicare should not be rooted in the source of its funding but rather in the values Canadians deem essential for their healthcare system.

An Assessment of Emergency Department-Based Interventions for Patients with Advanced or End-Stage Illness: A Systematic Review.

Background and Objective: With the increase of visits among patients with end-of-life needs, palliative care (PC) interventions delivered in the emergency department (ED) have become increasingly important. The objective of this systematic review was to examine the effectiveness of ED-based PC interventions. Methods: A comprehensive search of the literature was conducted to identify any comparative studies assessing the effectiveness of ED-based PC interventions. Two independent reviewers completed study selection, quality assessment, and data extraction. Relative risks (RR) with 95% confidence intervals (CIs) were calculated using a random effects model and heterogeneity (I2) was reported. Results: A total of 18 unique studies were included. Two studies reported no difference in return visits to the ED (RR = 1.31; 95% CI: 0.73-2.35; I2 = 47%). Two randomized trials reported no difference in mortality (RR = 0.89; 95% CI: 0.71-1.13; I2 = 0%), while one cohort study reported an increased mortality among patients referred to PC in the ED (RR = 1.89; 95% CI: 1.58-2.27). Overall, six out of eight studies reported a decrease in hospital length of stay (LOS) among patients undergoing an ED-based PC intervention compared with usual care. Conclusions: While there is compelling evidence to suggest that ED-based PC interventions can reduce hospital LOS, the evidence for the impact of these interventions on other outcomes is less robust. More high-quality comparative studies are needed to better understand the overall impact of ED-based PC interventions on improving patient outcomes as well as improving throughput and other quality of service-related outcomes.

Who Doesn't Come Home? Factors Influencing Mortality Among Long-Term Care Residents Transitioning to and From Emergency Departments in Two Canadian Cities.

Residents of long-term care (LTC) whose deaths are imminent are likely to trigger a transfer to the emergency department (ED), which may not be appropriate. Using data from an observational study, we employed structural equation modeling to examine relationships among organizational and resident variables and death during transitions between LTC and ED. We identified 524 residents involved in 637 transfers from 38 LTC facilities and 2 EDs. Our model fit the data, (χ2 = 72.91, df = 56, p = .064), explaining 15% variance in resident death. Sustained shortness of breath (SOB), persistent decreased level of consciousness (LOC) and high triage acuity at ED presentation were direct and significant predictors of death. The estimated model can be used as a framework for future research. Standardized reporting of SOB and changes in LOC, scoring of resident acuity in LTC and timely palliative care consultation for families in the ED, when they are present, warrant further investigation.

Comparative efficacy of glucocorticoid receptor agonists on Th2 cell function and attenuation by progesterone.

BACKGROUND: Corticosteroids (CS)s suppress cytokine production and induce apoptosis of inflammatory cells. Prednisone and dexamethasone are oral CSs prescribed for treating asthma exacerbations. While prednisone is more commonly prescribed, dexamethasone is long acting and a more potent glucocorticoid receptor (GR) agonist. It can be administered as a one or two dose regime, unlike the five to seven days required for prednisone, a feature that increases compliance. We compared the relative ability of these two oral CSs to suppress type 2 inflammation. Since progesterone has affinity for the GR and women are more likely to relapse following an asthma exacerbation, we assessed its influence on CS action. RESULTS: Dexamethasone suppressed the level of IL-5 and IL-13 mRNA within Th2 cells with ~ 10-fold higher potency than prednisolone (the active form of prednisone). Dexamethasone induced a higher proportion of apoptotic and dying cells than prednisolone, at all concentrations examined. Addition of progesterone reduced the capacity of both CS to drive cell death, though dexamethasone maintained significantly more killing activity. Progesterone blunted dexamethasone-induction of FKBP5 mRNA, indicating that the mechanism of action was by interference of the CS:GR complex. CONCLUSIONS: Dexamethasone is both more potent and effective than prednisolone in suppressing type 2 cytokine levels and mediating apoptosis. Progesterone attenuated these anti-inflammatory effects, indicating its potential influence on CS responses in vivo. Collectively, our data suggest that when oral CS is required, dexamethasone may be better able to control type 2 inflammation, eliminate Th2 cells and ultimately lead to improved long-term outcomes. Further research in asthmatics is needed.

Correction to: Preventing emergency department visits among patients with cancer: a scoping review.

Table 2 is incorrect in the original manuscript. The correct table 2 is shown below.

Preventing emergency department visits among patients with cancer: a scoping review.

PURPOSE: The objective of this scoping review was to examine the effectiveness of supportive care interventions designed to reduce ED visits among patients receiving active cancer treatment. METHODS: Literature search involving nine electronic databases and grey literature. Inclusion criteria considered studies assessing the impact of any intervention to reduce ED utilization among patients with active cancer. Dichotomous and continuous outcomes were summarized as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CIs) using a random-effects model, wherever appropriate. RESULTS: A total of 25 studies were included. Interventions identified in these studies comprised the following: routine and symptom-based patient follow-up, oncology outpatient clinics, early symptom detection, comprehensive inpatient management, hospital at home, and patient navigators. Six out of eight studies assessing oncology outpatient clinics reported a decrease in the proportion of patients presenting to the ED. A meta-analysis of three of these studies did not demonstrate reduction in ED utilization (RR 0.78; 95% CI 0.56 to 1.08; I2 = 77%) when comparing oncology outpatient clinics with standard care; however, sensitivity analysis supported a decrease in ED visits (RR 0.86; 95% CI 0.74 to 0.99; I2 = 47%). Three studies assessing patient follow-up interventions showed no difference in ED utilization (RR 0.69; 95% CI 0.38 to 1.25; I2 = 86%). CONCLUSION: A variety of supportive care interventions designed to mitigate ED presentations by patients receiving active cancer treatment have been developed and evaluated. Limited evidence suggests that an oncology outpatient clinic may be an effective strategy to reduce ED utilization; however, additional high-quality studies are needed.

Special topic section: linkages among cerebrovascular, cardiovascular, and cognitive disorders: Preventing dementia by preventing stroke: The Berlin Manifesto.

The incidence of stroke and dementia are diverging across the world, rising for those in low-and middle-income countries and falling in those in high-income countries. This suggests that whatever factors cause these trends are potentially modifiable. At the population level, neurological disorders as a group account for the largest proportion of disability-adjusted life years globally (10%). Among neurological disorders, stroke (42%) and dementia (10%) dominate. Stroke and dementia confer risks for each other and share some of the same, largely modifiable, risk and protective factors. In principle, 90% of strokes and 35% of dementias have been estimated to be preventable. Because a stroke doubles the chance of developing dementia and stroke is more common than dementia, more than a third of dementias could be prevented by preventing stroke. Developments at the pathological, pathophysiological, and clinical level also point to new directions. Growing understanding of brain pathophysiology has unveiled the reciprocal interaction of cerebrovascular disease and neurodegeneration identifying new therapeutic targets to include protection of the endothelium, the blood-brain barrier, and other components of the neurovascular unit. In addition, targeting amyloid angiopathy aspects of inflammation and genetic manipulation hold new testable promise. In the meantime, accumulating evidence suggests that whole populations experiencing improved education, and lower vascular risk factor profiles (e.g., reduced prevalence of smoking) and vascular disease, including stroke, have better cognitive function and lower dementia rates. At the individual levels, trials have demonstrated that anticoagulation of atrial fibrillation can reduce the risk of dementia by 48% and that systolic blood pressure lower than 140 mmHg may be better for the brain. Based on these considerations, the World Stroke Organization has issued a proclamation, endorsed by all the major international organizations focused on global brain and cardiovascular health, calling for the joint prevention of stroke and dementia. This article summarizes the evidence for translation into action. © 2019 the Alzheimer's Association and the World Stroke Organisation. Published by Elsevier Inc. All rights reserved.

Preventing dementia by preventing stroke: The Berlin Manifesto.

The incidence of stroke and dementia are diverging across the world, rising for those in low- and middle-income countries and falling in those in high-income countries. This suggests that whatever factors cause these trends are potentially modifiable. At the population level, neurological disorders as a group account for the largest proportion of disability-adjusted life years globally (10%). Among neurological disorders, stroke (42%) and dementia (10%) dominate. Stroke and dementia confer risks for each other and share some of the same, largely modifiable, risk and protective factors. In principle, 90% of strokes and 35% of dementias have been estimated to be preventable. Because a stroke doubles the chance of developing dementia and stroke is more common than dementia, more than a third of dementias could be prevented by preventing stroke. Developments at the pathological, pathophysiological, and clinical level also point to new directions. Growing understanding of brain pathophysiology has unveiled the reciprocal interaction of cerebrovascular disease and neurodegeneration identifying new therapeutic targets to include protection of the endothelium, the blood-brain barrier, and other components of the neurovascular unit. In addition, targeting amyloid angiopathy aspects of inflammation and genetic manipulation hold new testable promise. In the meantime, accumulating evidence suggests that whole populations experiencing improved education, and lower vascular risk factor profiles (e.g., reduced prevalence of smoking) and vascular disease, including stroke, have better cognitive function and lower dementia rates. At the individual levels, trials have demonstrated that anticoagulation of atrial fibrillation can reduce the risk of dementia by 48% and that systolic blood pressure lower than 140 mmHg may be better for the brain. Based on these considerations, the World Stroke Organization has issued a proclamation, endorsed by all the major international organizations focused on global brain and cardiovascular health, calling for the joint prevention of stroke and dementia. This article summarizes the evidence for translation into action.

Stroke Mimics Transported by Emergency Medical Services to a Comprehensive Stroke Center: The Magnitude of the Problem.

BACKGROUND: Despite the use of validated prehospital stroke scales, stroke mimics are frequent among patients transported by Emergency Medical Services to the Emergency Department. We aimed to describe the frequency and characteristics of neurological and non-neurological mimics transported to a comprehensive stroke center for acute stroke evaluation. METHODS: This was a retrospective analysis of a database consisting of all consecutive patients with suspected stroke transported to the Emergency Department of a comprehensive stroke center during an 18-month period. Hospital charts and neuroimaging were utilized to adjudicate the final diagnosis (acute stroke, stroke mimic, and specific underlying diagnoses). RESULTS: Nine hundred fifty patients were transported with suspected stroke, among whom 405 (42.6%) were stroke mimics (age 66.9 ± 17.1 years; 54% male). Neurological mimics were diagnosed in 223 (55.1%) patients and mimics were non-neurological in 182. The most common neurological diagnoses were seizures (19.7%), migraines (18.8%), and peripheral neuropathies (11.2%). Cardiovascular (14.6%) and psychiatric (11.9%) diagnoses were common non-neurological mimics. Patients with neurological mimics were younger (64.1 ± 17.3 years versus 70.5 ± 16.1 years, P < .001) and had less vascular risk factors than non-neurological mimics. The proportion of non-neurological mimics remained high (38%) despite the use of a prehospital stroke identification scale. CONCLUSIONS: Stroke mimics are common among patients transported by Emergency Medical Services to a comprehensive stroke center for suspected stroke, with a considerable proportion being non-neurological in origin. Studies refining triage and transport of suspected acute stroke may be warranted to minimize the number of mimics transported by to a comprehensive stroke center for acute stroke evaluation.

Development of a patient-centred, evidence-based and consensus-based discharge care bundle for patients with acute exacerbation of chronic obstructive pulmonary disease.

INTRODUCTION: Hospital and emergency department discharge for patients with chronic obstructive pulmonary disease (COPD) is often poorly organised. We developed a patient-centred, evidence-based and consensus-based discharge care bundle for patients with acute exacerbations of COPD. METHODS: A purposeful sample of clinicians and patients were invited to participate in a two-round Delphi study (July-November 2015). In round 1, participants rated on a seven-point Likert scale (1=not at all important; 7=extremely important) the importance of 29 unique COPD care actions. Round 2 comprised items selected from round 1 based on consensus (>80% endorsement for Likert values 5-7). A list of 18 care items from round 2 was discussed in a face-to-face nominal group meeting. RESULTS: Seven care items were included in the COPD discharge bundle based on clinician and patient input: (1) ensure adequate inhaler technique is demonstrated; (2) send discharge summary to family physician and arrange follow-up; (3) optimise and reconcile prescription of respiratory medications; (4) provide a written discharge management plan and assess patient's and caregiver's comprehension of discharge instructions; (5) refer to pulmonary rehabilitation; (6) screen for frailty and comorbidities; and (7) assess smoking status, provide counselling and refer to smoking cessation programme. CONCLUSION: We present a seven-item, patient-centred, evidence-based and consensus-based discharge bundle for patients with acute exacerbations of COPD. Alignment with clinical practice guidelines and feasibility of local adaptations of the bundle should be explored to facilitate wide applicability and evaluation of the effectiveness of the COPD discharge bundle.

Effectiveness of Interventions to Decrease Image Ordering for Low Back Pain Presentations in the Emergency Department: A Systematic Review.

BACKGROUND: Low back pain (LBP) is an extremely frequent reason for patients to present to an emergency department (ED). Despite evidence against the utility of imaging, simple and advanced imaging (i.e., computed tomography [CT], magnetic resonance imaging) for patients with LBP has become increasingly frequent in the ED. The objective of this review was to identify and examine the effectiveness of interventions aimed at reducing image ordering in the ED for LBP patients. METHODS: A protocol was developed a priori, following the PRISMA guidelines, and registered with PROSPERO. Six bibliographic databases (including MEDLINE, EMBASE, EBM Reviews, SCOPUS, CINAHL, and Dissertation Abstracts) and the gray literature were searched. Comparative studies assessing interventions that targeted image ordering in the ED for adult patients with LBP were eligible for inclusion. Two reviewers independently screened study eligibility and completed data extraction. Study quality was completed independently by two reviewers using the before-after quality assessment checklist, with a third-party mediator resolving any differences. Due to a limited number of studies and significant heterogeneity, only a descriptive analysis was performed. RESULTS: The search yielded 603 unique citations of which a total of five before-after studies were included. Quality assessment identified potential biases relating to comparability between the pre- and postintervention groups, reliable assessment of outcomes, and an overall lack of information on the intervention (i.e., time point, description, intervention data collection). The type of interventions utilized included clinical decision support tools, clinical practice guidelines, a knowledge translation initiative, and multidisciplinary protocols. Overall, four studies reported a decrease in the relative percentage change in imaging in a specific image modality (22.7%-47.4%) following implementation of the interventions; however, one study reported a 35% increase in patient referrals to radiography, while another study reported a subsequent 15.4% increase in referrals to CT and myelography after implementing an intervention which reduced referrals for simple radiography. DISCUSSION: While imaging of LBP has been identified as a key area of imaging overuse (e.g., Choosing Wisely recommendation), evidence on interventions to reduce image ordering for ED patients with LBP is sparse. There is some evidence to suggest that interventions can reduce the use of simple imaging in LBP in the ED; however, a shift in imaging modality has also been demonstrated. Additional studies employing higher-quality methods and measuring intervention fidelity are strongly recommended to further explore the potential of ED-based interventions to reduce image ordering for this patient population.

Effectiveness of Implementing Evidence-based Interventions to Reduce C-spine Image Ordering in the Emergency Department: A Systematic Review.

OBJECTIVES: Appropriate use of imaging for adult patients with cervical spine (C-spine) injuries in the emergency department (ED) is a longstanding issue. Guidance for C-spine ordering exists; however, the effectiveness of the decision support implementation in the ED is not well studied. This systematic review examines the implementation and effectiveness of evidence-based interventions aimed at reducing C-spine imaging in adults presenting to the ED with neck trauma. METHODS: Six electronic databases and the gray literature were searched. Comparative intervention studies were eligible for inclusion. Two independent reviewers screened for study eligibility, study quality, and extracted data. The change in imaging was reported using individual odds ratios (ORs) with 95% confidence intervals (CIs) using random effects. RESULTS: A total of 990 unique citations were screened for relevance of which six before-after studies and one randomized controlled trial were included. None of the studies were assessed as high quality. Interventions consisted primarily of locally developed guidelines or established clinical decision rules such as the NEXUS or the Canadian C-spine rule. Overall, implementation of interventions aimed at reducing C-spine image ordering resulted in a statistically significant reduction in imaging (OR = 0.69, 95% CI = 0.51-0.93); however, heterogeneity was high (I2  = 82%). Subgroup analysis revealed no differences between studies that specified enrolling alert and stable patients compared to unspecified trauma (p = 0.81) or between studies employing multifaceted versus nonmultifaceted interventions (p = 0.66). While studies generally provided details on implementation strategies (e.g., teaching sessions, pocket cards, posters, computerized decision support) the effectiveness of these implementation strategies were frequently not reported. CONCLUSION: There is moderate evidence regarding the effectiveness of interventions to reduce C-spine image ordering in adult patients seen in the ED with neck trauma. Given the national and international focus on improving appropriateness and reducing unnecessary C-spine imaging through campaigns such as Choosing Wisely, additional interventional research in this field is warranted.

Descriptive analysis of cochrane child-relevant systematic reviews: an update and comparison between 2009 and 2013.

BACKGROUND: Systematic reviews support health systems and clinical decision-making by identifying and summarizing all existing studies on a particular topic. In 2009, a comprehensive description of child-relevant systematic reviews published in the Cochrane Database of Systematic Reviews was compiled. This study aims to provide an update, and to describe these systematic reviews according to their content and methodological approaches. METHODS: All child-relevant systematic reviews published by the Cochrane Collaboration in the Cochrane Database of Systematic Reviews (CDSR) as of March, 2013 were identified and described in relation to their content and methodological approaches. This step equated to an update of the Child Health Field Review Register (CHFRR). The content of the updated CHFRR was compared to the published 2009 CHFRR description regarding clinical and methodological characteristics, using bivariate analyses. As the Cochrane Collaboration has recognized that disease burden should guide research prioritization, we extracted data from the Global and National Burden of Diseases and Injuries Among Children and Adolescents Between 1990 and 2013 study in order to map the distribution of the burden of disease in child health to the distribution of evidence across Review Groups in the CHFRR. RESULTS: Of the 5,520 potential Cochrane systematic reviews identified, 1,293 (23.4%) were child-relevant (an increase of 24% since 2009). Overall, these reviews included 16,738 primary studies. The most commonly represented Review Groups were Airways (11.5%), Cystic Fibrosis and Genetic Diseases (7.9%), Acute Respiratory Infections (7.8%), Developmental, Psychological and Learning Problems (6.7%), and Infectious Diseases (6.2%). Corresponding authors were most often from Europe (51%), North America (15%), and Australia (15%). The majority of systematic reviews examined pharmacological interventions alone (52% compared to 59% in 2009). Out of 611 reviews that were assessed as up-to-date, GRADE was used in 204 (35%) reviews to assess the overall quality of the evidence, which was often moderate (35.6%) or low (37.8%) for primary outcomes. Ninety percent of reviews that were assessed as up to date used the Cochrane Risk of Bias tool, or a modified version, to assess methodological quality. Most reviews conducted one or more meta-analyses (73%). Among the 25 leading causes of death globally, the Review Groups associated with the largest number of causes were: 1) Infectious Diseases, 2) Anaesthesia, Critical, and Emergency Care, 3) Injuries, 4) Pregnancy and Childbirth (PC), and 5) Neonatal. There were large discrepancies between the number of causes of mortality that each Review Group was associated with and the total amount of evidence each Review Group contributed to the CHFRR. Ninety-eight percent of the causes of mortality in 2013 were from developing nations, but only 224 (17.3%) reviews had corresponding authors from developing countries. CONCLUSION: The content and methodological characteristics of child-relevant systematic reviews in the Cochrane CHFRR have been described in detail. There were modest advances in methods between 2009 and 2013. Systematic reviews contained in the CDSR offer an important resource for researcher's, clinicians and policy makers by synthesizing an extensive body of primary research. Further content analysis will allow the identification of clinical topics of greatest priority for future systematic reviews in child health.

Resting and Post-Exercise Ankle-Brachial Index Measurements to Diagnose Asymptomatic Peripheral Arterial Disease in Middle Aged and Elderly Chronic Obstructive Pulmonary Disease Patients: A Pilot Study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients are at risk for asymptomatic peripheral arterial disease (PAD) because smoking is a risk factor for COPD and PAD. The objectives of this study were to determine the proportion of COPD patients with asymptomatic PAD and to investigate whether the estimated risk of asymptomatic PAD in subjects with COPD differs using resting and exercise ankle-brachial index (ABI) in smokers. METHODS: Using a cross-sectional study design, consecutive smokers > 50 years old were recruited over 2 months from the inpatient units and the outpatient clinics. Subjects previously diagnosed with PAD, unstable angina, recent (< 3 months) myocardial infarction or abdominal, intracranial, eye or lung surgery, and palliative care patients were excluded. Vascular risk factors, ABI (supine and post-3-minute walk supine), self-reported PAD symptoms, and spirometry were obtained. Two measurements of systolic blood pressure on all limbs were obtained using a sphygmomanometer and a Doppler ultrasound, and the ABI was calculated. Data were expressed as means ± standard deviation (SD). Dichotomous outcomes were assessed using Chi-square statistics; P-values of < 0.05 were considered significant. RESULTS: Thirty patients with no previous diagnosis of PAD were recruited. Mean age was 67.7 years (SD: 10.5). Overall, 21 subjects (70%) had spirometry-proven COPD. Significant ABI for PAD (< 0.9) was seen in 7/21 COPD (33.5%) and 0/9 non-COPD subjects in the supine resting position (P = 0.07), and in 9/21 COPD (42.9%) vs. 0/9 non-COPD subjects after exercise (P = 0.03). CONCLUSIONS: A significant proportion of patients with spirometry-proven COPD screened positive for asymptomatic PAD after exercise. Resting ABI may not be very sensitive to diagnose asymptomatic PAD in COPD subjects. ABI may be a reliable, sensitive and practical screening tool to assess cardiovascular risk in COPD patients. Future large-scale studies are required to confirm this finding.

Metabolomic profiling of asthma and chronic obstructive pulmonary disease: A pilot study differentiating diseases.

BACKGROUND: Differentiating asthma from other causes of chronic airflow limitation, such as chronic obstructive pulmonary disease (COPD), can be difficult in a typical outpatient setting. The inflammation of asthma typically is different than that of COPD, and the degree of inflammation and cellular damage varies with asthma severity. Metabolomics is the study of molecules created by cellular metabolic pathways. OBJECTIVES: We hypothesized that the metabolic activity of adults with asthma would differ from that of adults with COPD. Furthermore, we hypothesized that nuclear magnetic resonance spectroscopy (NMR) would measure such differences in urine samples. METHODS: Clinical and urine-based NMR data were collected on adults meeting the criteria of asthma and COPD before and after an exacerbation (n = 133 and 38, respectively) and from patients with stable asthma or COPD (n = 54 and 23, respectively). Partial least-squares discriminant analysis was performed on the NMR data to create models of separation (86 metabolites were measured per urine sample). Some subjects' metabolomic data were withheld from modeling to be run blindly to determine diagnostic accuracy. RESULTS: Partial least-squares discriminant analysis of the urine NMR data found unique differences in select metabolites between patients with asthma and those with COPD seen in the emergency department and even in follow-up after exacerbation. By using these select metabolomic profiles, the model could correctly diagnose blinded asthma and COPD with greater than 90% accuracy. CONCLUSION: This is the first report showing that metabolomic analysis of human urine samples could become a useful clinical tool to differentiate asthma from COPD.