Limited utility of exercise stress testing in the evaluation of suspected acute coronary syndrome in patients aged less than 40 years with intermediate risk features

Objective National guidelines for management of intermediate risk patients with suspected acute coronary syndrome, in whom AMI has been excluded, advocate provocative testing to final risk stratify these patients into low risk (negative testing) or high risk (positive testing suggestive of unstable angina). Adults less than 40 years have a low pretest probability of acute coronary syndrome. The utility of exercise stress testing in young adults with chest pain suspected of acute coronary syndrome who have National Heart Foundation intermediate risk features was evaluated Methods A retrospective analysis of exercise stress testing performed on patients less than 40 years was evaluated. Patients were enrolled on a chest pain pathway and had negative serial ECGs and cardiac biomarkers before exercise stress testing to rule-out acute coronary syndrome. Chart review was completed on patients with positive stress tests. Results The 3987 patients with suspected intermediate risk acute coronary syndrome underwent exercise stress testing. One thousand and twenty-seven (25.8%) were aged less than 40 years (age 33.3 ± 4.8 years). Four of these 1027 patients had a positive exercise stress test (0.4% incidence of positive exercise stress testing). Of those, three patients had subsequent non-invasive functional testing that yielded a negative result. One patient declined further investigations. Assuming this was a true positive exercise stress test, the incidence of true positive exercise stress testing would have been 0.097% (95% confidence interval: 0.079–0.115%) (one of 1027 patients). Conclusions Routine exercise stress testing has limited value in the risk stratification of adults less than 40 years with suspected intermediate risk of acute coronary syndrome

The new Vancouver Chest Pain Rule using troponin as the only biomarker: An external validation study

Objectives To externally evaluate the accuracy of the new Vancouver Chest Pain Rule and to assess the diagnostic accuracy using either sensitive or highly sensitive troponin assays. Methods Prospectively collected data from 2 emergency departments (EDs) in Australia and New Zealand were analysed. Based on the new Vancouver Chest Pain Rule, low-risk patients were identified using electrocardiogram results, cardiac history, nitrate use, age, pain characteristics and troponin results at 2 hours after presentation. The primary outcome was 30-day diagnosis of acute coronary syndrome (ACS), including acute myocardial infarction, and unstable angina. Sensitivity, specificity, positive predictive values and negative predictive values were calculated to assess the accuracy of the new Vancouver Chest Pain Rule using either sensitive or highly sensitive troponin assay results. Results Of the 1635 patients, 20.4% had an ACS diagnosis at 30 days. Using the highly sensitive troponin assay, 212 (13.0%) patients were eligible for early discharge with 3 patients (1.4%) diagnosed with ACS. Sensitivity was 99.1% (95% CI 97.4-99.7), specificity was 16.1 (95% CI 14.2-18.2), positive predictive values was 23.3 (95% CI 21.1-25.5) and negative predictive values was 98.6 (95% CI 95.9-99.5). The diagnostic accuracy of the rule was similar using the sensitive troponin assay. Conclusions The new Vancouver Chest Pain Rule should be used for the identification of low risk patients presenting to EDs with symptoms of possible ACS, and will reduce the proportion of patients requiring lengthy assessment; however we recommend further outpatient investigation for coronary artery disease in patients identified as low risk.

Use of observed within-person variation of cardiac troponin in emergency department patients for determination of biological variation and percentage and absolute reference change values

BACKGROUND Many patients presenting to the emergency department (ED) for assessment of possible acute coronary syndrome (ACS) have low cardiac troponin concentrations that change very little on repeat blood draw. It is unclear if a lack of change in cardiac troponin concentration can be used to identify acutely presenting patients at low risk of ACS. METHODS We used the hs-cTnI assay from Abbott Diagnostics, which can detect cTnI in the blood of nearly all people. We identified a population of ED patients being assessed for ACS with repeat cTnI measurement who ultimately were proven to have no acute cardiac disease at the time of presentation. We used data from the repeat sampling to calculate total within-person CV (CV(T)) and, knowing the assay analytical CV (CV(A)), we could calculate within-person biological variation (CV(i)), reference change values (RCVs), and absolute RCV delta cTnI concentrations. RESULTS We had data sets on 283 patients. Men and women had similar CV(i) values of approximately 14%, which was similar at all concentrations <40 ng/L. The biological variation was not dependent on the time interval between sample collections (t = 1.5-17 h). The absolute delta critical reference change value was similar no matter what the initial cTnI concentration was. More than 90% of subjects had a critical reference change value <5 ng/L, and 97% had values of <10 ng/L. CONCLUSIONS With this hs-cTnI assay, delta cTnI seems to be a useful tool for rapidly identifying ED patients at low risk for possible ACS.

A 2-hour diagnostic protocol for possible cardiac chest pain in the emergency department: A randomized clinical trial

IMPORTANCE Patients with chest pain represent a high health care burden, but it may be possible to identify a patient group with a low short-term risk of adverse cardiac events who are suitable for early discharge. OBJECTIVE To compare the effectiveness of a rapid diagnostic pathway with a standard-care diagnostic pathway for the assessment of patients with possible cardiac chest pain in a usual clinical practice setting. DESIGN, SETTING, AND PARTICIPANTS A single-center, randomized parallel-group trial with blinded outcome assessments was conducted in an academic general and tertiary hospital. Participants included adults with acute chest pain consistent with acute coronary syndrome for whom the attending physician planned further observation and troponin testing. Patient recruitment occurred from October 11, 2010, to July 4, 2012, with a 30-day follow-up. INTERVENTIONS An experimental pathway using an accelerated diagnostic protocol (Thrombolysis in Myocardial Infarction score, 0; electrocardiography; and 0- and 2-hour troponin tests) or a standard-care pathway (troponin test on arrival at hospital, prolonged observation, and a second troponin test 6-12 hours after onset of pain) serving as the control. MAIN OUTCOMES AND MEASURES Discharge from the hospital within 6 hours without a major adverse cardiac event occurring within 30 days. RESULTS Fifty-two of 270 patients in the experimental group were successfully discharged within 6 hours compared with 30 of 272 patients in the control group (19.3% vs 11.0%; odds ratio, 1.92; 95% CI, 1.18-3.13; P = .008). It required 20 hours to discharge the same proportion of patients from the control group as achieved in the experimental group within 6 hours. In the experimental group, 35 additional patients (12.9%) were classified as low risk but admitted to an inpatient ward for cardiac investigation. None of the 35 patients received a diagnosis of acute coronary syndrome after inpatient evaluation. CONCLUSIONS AND RELEVANCE Using the accelerated diagnostic protocol in the experimental pathway almost doubled the proportion of patients with chest pain discharged early. Clinicians could discharge approximately 1 of 5 patients with chest pain to outpatient follow-up monitoring in less than 6 hours. This diagnostic strategy could be easily replicated in other centers because no extra resources are required.

Implementation of a chest pain management service improves patient care and reduces length of stay

Objective Chest pain is one of the most common complaints in patients presenting to an emergency department. Delays in management due to a lack of readily available objective tests to risk stratify patients with possible acute coronary syndromes can lead to an unnecessarily lengthy admission placing pressure on hospital beds or inappropriate discharge. The need for a co-ordinated system of clinical management based on enhanced communication between departments, timely and appropriate triage, clinical investigation, diagnosis, and treatment was identified. Methods An evidence-based Chest Pain Management Service and clinical pathway were developed and implemented, including the introduction of after-hours exercise stress testing. Results Between November 2005 and March 2013, 5662 patients were managed according to a Chest Pain Management pathway resulting in a reduction of 5181 admission nights by more timely identification of patients at low risk who could then be discharged. In addition, 1360 days were avoided in high-risk patients who received earlier diagnosis and treatment. Conclusions The creation of a Chest Pain Management pathway and the extended exercise stress testing service resulted in earlier discharge for low-risk patients; and timely treatment for patients with positive and equivocal exercise stress test results. This service demonstrated a significant saving in overnight admissions.

Development and validation of the Emergency Department Assessment of Chest pain Score and 2h accelerated diagnostic protocol

Objective Risk scores and accelerated diagnostic protocols can identify chest pain patients with low risk of major adverse cardiac event who could be discharged early from the ED, saving time and costs. We aimed to derive and validate a chest pain score and accelerated diagnostic protocol (ADP) that could safely increase the proportion of patients suitable for early discharge. Methods Logistic regression identified statistical predictors for major adverse cardiac events in a derivation cohort. Statistical coefficients were converted to whole numbers to create a score. Clinician feedback was used to improve the clinical plausibility and the usability of the final score (Emergency Department Assessment of Chest pain Score [EDACS]). EDACS was combined with electrocardiogram results and troponin results at 0 and 2 h to develop an ADP (EDACS-ADP). The score and EDACS-ADP were validated and tested for reproducibility in separate cohorts of patients. Results In the derivation (n = 1974) and validation (n = 608) cohorts, the EDACS-ADP classified 42.2% (sensitivity 99.0%, specificity 49.9%) and 51.3% (sensitivity 100.0%, specificity 59.0%) as low risk of major adverse cardiac events, respectively. The intra-class correlation coefficient for categorisation of patients as low risk was 0.87. Conclusion The EDACS-ADP identified approximately half of the patients presenting to the ED with possible cardiac chest pain as having low risk of short-term major adverse cardiac events, with high sensitivity. This is a significant improvement on similar, previously reported protocols. The EDACS-ADP is reproducible and has the potential to make considerable cost reductions to health systems.

The literacy curriculum: A critical review

This is a critical review of the scope of the literacy curriculum in the twenty-first century, uncovering the strengths, controversies, and silences that have divided literacy researchers and educators. It conceptualizes the literacy curriculum as a particular set of socially organized symbolic practices that are always selective, and which are inextricably connected to the function and organization of schooling. We trace the political, historical, and ideological antecedents of literacy curriculum and schooling as a form of cultural apparatus of the nation-state, before tracing some of the major interpretive paradigms that have influenced the shape of the literacy curriculum in many parts of the world. These include debates about skills-based approaches, whole language, systemic functional grammar, and critical literacy. It then draws attention to noteworthy advances and shifts in the field over recent decades: debates about the role of orality in the literacy curriculum, home-school community literacy practices, teacher and student knowledge of language and grammar, and the role of curriculum area literacies. It anticipates the future of the literacy curriculum in online textual environments and the changing sensorial and material nature of literacy practices, while acknowledging that curriculum innovation is always limited in complex ways by historically established pedagogic discourses of schooling.

Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1

Ankylosing spondylitis (AS) is a common, highly heritable, inflammatory arthritis for which HLA-B*27 is the major genetic risk factor, although its role in the aetiology of AS remains elusive. To better understand the genetic basis of the MHC susceptibility loci, we genotyped 7,264 MHC SNPs in 22,647 AS cases and controls of European descent. We impute SNPs, classical HLA alleles and amino-acid residues within HLA proteins, and tested these for association to AS status. Here we show that in addition to effects due to HLA-B*27 alleles, several other HLA-B alleles also affect susceptibility. After controlling for the associated haplotypes in HLA-B, we observe independent associations with variants in the HLA-A, HLA-DPB1 and HLA-DRB1 loci. We also demonstrate that the ERAP1 SNP rs30187 association is not restricted only to carriers of HLA-B*27 but also found in HLA-B*40:01 carriers independently of HLA-B*27 genotype.

Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013. Methods Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refi nements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries. Findings Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2∙4 billion and 1∙6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537∙6 million in 1990 to 764∙8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114∙87 per 1000 people to 110∙31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21·1% in 1990 to 31·2% in 2013. Interpretation Ageing of the world’s population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to nonfatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries.

Factors potentiating the risk of sudden infant death syndrome associated with the prone position

Background. In several studies the sudden infant death syndrome (SIDS) has been significantly associated with sleeping in the prone position. It is not known how the prone position increases the risk of SIDS. Methods. We analyzed data from a case-control study (58 infants with SIDS and 120 control infants) and a prospective cohort study (22 infants with SIDS and 213 control infants) in Tasmania. Interactions were examined in matched analyses with a multiplicative model of interaction. Results. In the case-control study, SIDS was significantly associated with sleeping in the prone position, as compared with other positions (unadjusted odds ratio, 4.5; 95 percent confidence interval, 2.1 to 9.6). The strength of this association was increased among infants who slept on natural-fiber mattresses (P = 0.05), infants who were swaddled (P = 0.09), infants who slept in heated rooms (P = 0.006), and infants who had had a recent illness (P = 0.02). These variables had no significant effect on infants who did not sleep in the prone position. A history of recent illness was significantly associated with SIDS among infants who slept prone (odds ratio, 5.7; 95 percent confidence interval, 1.8 to 19) but not among infants who slept in other positions (odds ratio, 0.83). In the cohort study, the risk of SIDS was greater among infants who slept prone on natural-fiber mattresses (odds ratio, 6.6; 95 percent confidence interval, 1.3 to 33) than among infants who slept prone on other types of mattresses (odds ratio, 1.8). Conclusions. When infants sleep prone, the elevated risk of SIDS is increased by each of four factors: the use of natural-fiber mattresses, swaddling, recent illness, and the use of heating in bedrooms.

Understanding the determinants of Australian hospital nurses' hand hygiene decisions following the implementation of a national hand hygiene initiative

Hand hygiene is the primary measure in hospitals to reduce the spread of infections, with nurses experiencing the greatest frequency of patient contact. The ‘5 critical moments’ of hand hygiene initiative has been implemented in hospitals across Australia, accompanied by awareness-raising, staff training and auditing. The aim of this study was to understand the determinants of nurses’ hand hygiene decisions, using an extension of a common health decision-making model, the theory of planned behaviour (TPB), to inform future health education strategies to increase compliance. Nurses from 50 Australian hospitals (n = 2378) completed standard TPB measures (attitude, subjective norm, perceived behavioural control [PBC], intention) and the extended variables of group norm, risk perceptions (susceptibility, severity) and knowledge (subjective, objective) at Time 1, while a sub-sample (n = 797) reported their hand hygiene behaviour 2 weeks later. Regression analyses identified subjective norm, PBC, group norm, subjective knowledge and risk susceptibility as the significant predictors of nurses’ hand hygiene intentions, with intention and PBC predicting their compliance behaviour. Rather than targeting attitudes which are already very favourable among nurses, health education strategies should focus on normative influences and perceptions of control and risk in efforts to encourage hand hygiene adherence.

Development of a vaccine for Chlamydia trachomatis: Challenges and current progress

Chlamydia trachomatis remains an enigmatic bacterial pathogen with no vaccine yet available to treat human ocular and genital tract infections caused by tissue-tropic serovars of the organism. Globally, it is the leading cause of preventable blindness as well as the leading cause of bacterial sexually transmitted infections. The pathogen has a range of virulence factors that enable it to successfully evade both the innate and adaptive immune system of the host. The host immune system, although protective, paradoxically is also associated closely with the pathologies of trachoma and pelvic inflammatory disease – disease sequelae of some chlamydial infections and reinfections in some genetically susceptible hosts. In this review, we focus on what is known currently about the pathogenesis of ocular and genital infections caused by this mucosal pathogen. We also discuss novel insights into the pathogenesis of infections caused by the genital and ocular serovars of C. trachomatis, including a discussion of both pathogen and host factors, such as the human microbiota at these mucosal sites as well as the current immunological challenges facing vaccine development. Finally, we discuss the current progress toward development of a vaccine against C. trachomatis. A wide range of recombinant protein antigens are being identified and, hence, are available for vaccine trials. A plasmid-free live strain has recently been produced and evaluated in the mouse (Chlamydia muridarum) and monkey (C. trachomatis) models. The data for ocular infections in the monkey model was particularly encouraging, although the path to regulatory approval of a live vaccine is still uncertain. While still a major challenge, vaccines for ocular and genital C. trachomatis infections are looking more promising.

Staphylococcus epidermidis as a cause of bacteremia

Staphylococcus epidermidis is a biofilm-producing commensal organism found ubiquitously on human skin and mucous membranes, as well as on animals and in the environment. Biofilm formation enables this organism to evade the host immune system. Colonization of percutaneous devices or implanted medical devices allows bacteria access to the bloodstream. Isolation of this organism from blood cultures may represent either contamination during the blood collection procedure or true bacteremia. S. epidermidis bloodstream infections may be indolent compared with other bacteria. Isolation of S. epidermidis from a blood culture may present a management quandary for clinicians. Over-treatment may lead to patient harm and increases in healthcare costs. There are numerous reports indicating the difficulty of predicting clinical infection in patients with positive blood cultures with this organism. No reliable phenotypic or genotypic algorithms currently exist to predict the pathogenicity of a S. epidermidis bloodstream infection. This review will discuss the latest advances in identification methods, global population structure, pathogenicity, biofilm formation, antimicrobial resistance and clinical significance of the detection of S. epidermidis in blood cultures. Previous studies that have attempted to discriminate between invasive and contaminating strains of S. epidermidis in blood cultures will be analyzed.

Aboriginal and Torres Strait Islander Health

The chapter introduces Aboriginal and Torres Strait Islander health and discusses the important role that Indigenous and non-Indigenous peoples can play in ‘closing the gap’ in health disparities as experienced by Aboriginal and Torres Strait Islander peoples.