An assessment and characterization of pharmaceuticals and personal care products (PPCPs) within the Great Lakes Basin: Mussel Watch Program (2013-2018).

Defining the environmental occurrence and distribution of chemicals of emerging concern (CECs), including pharmaceuticals and personal care products (PPCPs) in coastal aquatic systems, is often difficult and complex. In this study, 70 compounds representing several classes of pharmaceuticals, including antibiotics, anti-inflammatories, insect repellant, antibacterial, antidepressants, chemotherapy drugs, and X-ray contrast media compounds, were found in dreissenid mussel (zebra/quagga; Dreissena spp.) tissue samples. Overall concentration and detection frequencies varied significantly among sampling locations, site land-use categories, and sites sampled proximate and downstream of point source discharge. Verapamil, triclocarban, etoposide, citalopram, diphenhydramine, sertraline, amitriptyline, and DEET (N,N-diethyl-meta-toluamide) comprised the most ubiquitous PPCPs (> 50%) detected in dreissenid mussels. Among those compounds quantified in mussel tissue, sertraline, metformin, methylprednisolone, hydrocortisone, 1,7-dimethylxanthine, theophylline, zidovudine, prednisone, clonidine, 2-hydroxy-ibuprofen, iopamidol, and melphalan were detected at concentrations up to 475 ng/g (wet weight). Antihypertensives, antibiotics, and antidepressants accounted for the majority of the compounds quantified in mussel tissue. The results showed that PPCPs quantified in dreissenid mussels are occurring as complex mixtures, with 4 to 28 compounds detected at one or more sampling locations. The magnitude and composition of PPCPs detected were highest for sites not influenced by either WWTP or CSO discharge (i.e., non-WWTPs), strongly supporting non-point sources as important drivers and pathways for PPCPs detected in this study. As these compounds are detected at inshore and offshore locations, the findings of this study indicate that their persistence and potential risks are largely unknown, thus warranting further assessment and prioritization of these emerging contaminants in the Great Lakes Basin.

Effects of light intensity and reduction of starter diet digestible lysine and metabolizable energy on broiler chicken growth performance, breast meat yield, and meat quality defects.

The etiology of Wooden Breast (WB) is unknown; therefore, it is difficult to produce broiler flocks with similar proportions of WB-affected and unaffected birds. Because WB has been detected as early as 15 d posthatch, the objective of this randomized complete block experiment with a 2 × 2 factorial treatment arrangement was to determine whether combining the effects of light intensity (LI) and early nutrient reduction strategies could reliably produce WB-affected and normal broilers to further investigate the physiological mechanisms underlying WB. On day of hatch, male, Ross 708 × Yield Plus broilers (n = 384; 16 birds per pen; 3 replicate blocks) were randomly allotted to floor pens in the same facility and exposed to either 2 (LOWLI) or 30 (HIGHLI) lux of light from d 0 to 35. Birds were fed either a commercial starter diet (CON) or the CON diet with a 10% reduction in both ME and digestible lysine (dLys; RED) from d 0 to 14 and then a common grower diet from d 15 to 35. Broiler growth performance, breast yield, and incidence and severity of WB and White Striping (WS) were assessed. Data were analyzed as a 2-way ANOVA with SAS PROC GLIMMIX and means separated at P < 0.05 with PDIFF. No interaction among LI and diet was observed (P > 0.05). Broilers reared with HIGHLI were heavier on d 35 and consumed more feed in all phases compared with broilers reared under LOWLI (P ≤ 0.0096). Broilers reared under LOWLI gained less BW from d 15 to 35 and d 0 to 35 compared with broilers reared under HIGHLI (P = 0.0073). Broilers fed the RED starter diet consumed more feed and had higher FCR from d 0 to 14 compared with broilers fed the CON diet (P ≤ 0.0012). In conclusion, combining reductions in LI and starter diet ME and dLys did not produce the hypothesized reductions in breast yield and incidence and severity of WB or WS.

Evaluation of crystallization patterns in oral potentially malignant disorders and oral malignancies: A prospective study.

Background: Oral cancers are often detected at late stages, and patients usually had a 50% chance of a 5-year survival rate. Oral cancer usually has an early precancerous stage before its actual malignant transformation. Although there are various approaches to diagnose the early stages of cancer, there is one less explored, cost-effective, and simple technique known as the crystallization test. The aim of the study was to evaluate the crystallization patterns in tobacco users, oral potentially malignant disorders (OPMDs), and oral malignancies. Materials and Methods: Fifteen patients with oral malignancies, 15 patients with oral potentially malignant disorders, 15 tobacco users, and 15 healthy individuals participated in the crystallization test. Single blood drop was used to perform this test and the obtained crystal patterns were analyzed. Results: This test had a sensitivity of 93.3%, 80.0%, and 20.0% for oral malignancies, oral Potentially Malignant Disorders (PMDs), and tobacco users, respectively. Chi-square analysis revealed a highly significant transverse form between OPMDs and oral malignancies (P < 0.05). Conclusion: Crystallization test was found to be a sensitive, reliable, economical, and less invasive procedure for screening of oral PMDs and oral malignancies under strictly maintained physical conditions.

A novel role for MLC1 in regulating astrocyte-synapse interactions.

Loss of function of the astrocyte membrane protein MLC1 is the primary genetic cause of the rare white matter disease Megalencephalic Leukoencephalopathy with subcortical Cysts (MLC), which is characterized by disrupted brain ion and water homeostasis. MLC1 is prominently present around fluid barriers in the brain, such as in astrocyte endfeet contacting blood vessels and in processes contacting the meninges. Whether the protein plays a role in other astrocyte domains is unknown. Here, we show that MLC1 is present in distal astrocyte processes, also known as perisynaptic astrocyte processes (PAPs) or astrocyte leaflets, which closely interact with excitatory synapses in the CA1 region of the hippocampus. We find that the PAP tip extending toward excitatory synapses is shortened in Mlc1-null mice. This affects glutamatergic synaptic transmission, resulting in a reduced rate of spontaneous release events and slower glutamate re-uptake under challenging conditions. Moreover, while PAPs in wildtype mice retract from the synapse upon fear conditioning, we reveal that this structural plasticity is disturbed in Mlc1-null mice, where PAPs are already shorter. Finally, Mlc1-null mice show reduced contextual fear memory. In conclusion, our study uncovers an unexpected role for the astrocyte protein MLC1 in regulating the structure of PAPs. Loss of MLC1 alters excitatory synaptic transmission, prevents normal PAP remodeling induced by fear conditioning and disrupts contextual fear memory expression. Thus, MLC1 is a new player in the regulation of astrocyte-synapse interactions.

Student pharmacist practice-based interprofessional education in Scotland: a qualitative study of stakeholders' views and experiences.

Scottish Government funding supports practice-based experiential learning (EL) for student pharmacists. We explored views and experiences of key stakeholders on current practice and future development of interprofessional education (IPE) in EL including barriers and enablers. A pre-piloted schedule was used for online qualitative semi-structured interviews. eMail invitations were sent to 37 stakeholders with an information sheet and consent process. Interviews were analyzed thematically by two researchers independently. Recruitment continued until data saturation and wide representation were achieved. Twenty interviews were conducted with eight EL facilitators, seven faculty and five policy stakeholders. "Nature and experience of current IPE in EL activities" and "Future developments" were the two main themes. Barriers and enablers were also identified at macro, meso, and micro socio-institutional levels. The essence of the analysis highlighted stakeholders' views of the importance of building on current IPE while challenging the ethos and culture of EL practices. All stakeholders should be involved in co-production, training, piloting, and evaluation of curricular developments to overcome logistic barriers and enhanced enablers. Finally, the importance of workload management strategies and continuity of funding for success was also stressed by those interviewed. Future research could include designing frameworks for developing and implementing IPE within EL.

Basal cell adenocarcinoma of the minor salivary gland - A rare case report involving the upper lip.

Minor salivary gland neoplasms constitute up to approximately 25% of all salivary gland tumors. The incidence of malignancy of these tumors is slightly greater than half. Basal cell adenocarcinoma (BCAC) is a rare salivary gland malignancy that occurs most commonly in the parotid gland. In this report, we describe a case of an older woman presenting with BCAC of the upper lip arising from the minor salivary gland.

Dietary Protein Source and Litter Condition Alter Broiler Chicken Intestinal Macrophage and Mitotically Active Cell Populations.

As antibiotic-free (ABF) broiler production continues to increase, understanding the development and local immune response in the intestines of ABF broilers is essential. Mitotically active cells, the majority of which will become enterocytes, help maintain the intestinal epithelial barrier. Macrophages prevent pathogen invasion by their phagocytic activity, functioning as immune response amplifying cells to aid in the recruitment of additional immune cells, and stimulating cytokine production in other adjacent cells. The objective of this experiment was to evaluate commonly used practical production practices on intestinal cell mitotic activity and local intestinal immunological responses. A randomized complete block design experiment with a 3 × 2 factorial treatment structure was conducted. The 3 dietary protein sources were: soybean meal (SBM), a mix of 50% poultry by-product meal and 50% feather meal (PFM), and porcine meat and bone meal (MBM) and broilers were reared on either new litter (NL) or used litter (UL). On d 3, 8, 11, 15, and 21, 6 birds per treatment from 6 blocks (total n = 36 per d) were randomly selected for sampling. Broilers were injected intraperitoneally with 5'-bromo-2'-deoxyuridine (BrdU) 1 h prior to sampling to label mitotically active cells. Samples were analyzed using cryohistology and immunofluorescence to determine the density of mitotically active cells and macrophages. Mitotically active cell and macrophage densities changed in both the duodenum and ileum over time. Neither dietary protein source nor litter condition affected mitotically active cell or macrophage densities in the duodenum on d 11 and 21 or in the ileum on d 3, 8, 11, and 15. However, on d 3 and 15 in the duodenum (P ≤ 0.0126) and d 21 in the ileum (P ≤ 0.0009), broilers reared on UL had greater mitotically active cell densities than those reared on NL. On d 8 in the duodenum, broilers fed MBM had increased macrophage density compared with those fed PFM and SBM (P ≤ 0.0401). These results indicate dietary protein source and litter condition may impact the physiology of the broiler small intestine, though additional work with this model is necessary to understand the underlying mechanisms.

Evaluation of effects of essential oil vapors on the bacterial count in bioaerosols.

Background: The aerosols generated during dental treatments contain bacteria and other microorganisms that penetrate the body through the respiratory system of dental surgeons and cause infectious diseases. Several studies have been done to reduce these hazards. The aim of the present study is to evaluate the effects of the plant extract essential oil (EO) vapors of Neem, Clove, Cinnamon bark, Thyme, Lemon Grass, and Eucalyptus on the bacterial count in bioaerosols near dental units. Materials and Methods: Sampling was taken on nutrient blood agar plates by placing them open near dental units using passive air sampling method, before commencement of treatment for 1 h, during treatments for 2 h, and after introducing EO vapors for 2 h. The collected samples were taken for incubation at 37°C for 48 h. The colonies formed were counted in colony-forming units per cubic meter and taken for statistical analysis. Results: After comparing the obtained results, it was found that there was a significant reduction (P < 0.05) in the bacterial count for about 43% near the dental units after the introduction of the EO vapours. Conclusion: It is concluded that natural extracts like EOs can reduce bacterial contamination near dental units in the vapourized state, thereby reducing the health hazards in Dental Health Professionals.

Modeling Site-Specific Nucleotide Biases Affecting Himar1 Transposon Insertion Frequencies in TnSeq Data Sets.

TnSeq is a widely used methodology for determining gene essentiality, conditional fitness, and genetic interactions in bacteria. The Himar1 transposon is restricted to insertions at TA dinucleotides, but otherwise, few site-specific biases have been identified. As a result, most analytical approaches assume that insertions are expected to be randomly distributed among TA sites in nonessential regions. However, through analysis of Himar1 transposon libraries in Mycobacterium tuberculosis, we demonstrate that there are site-specific biases that affect the frequency of insertion of the Himar1 transposon at different TA sites. We use machine learning and statistical models to characterize patterns in the nucleotides surrounding TA sites that correlate with high or low insertion counts. We then develop a quantitative model based on these patterns that can be used to predict the expected counts at each TA site based on nucleotide context, which can explain up to half of the variance in insertion counts. We show that these insertion preferences exist in Himar1 TnSeq data sets from other mycobacterial and nonmycobacterial species. We present an improved method for identification of essential genes, called TTN-Fitness, that can better distinguish true biological fitness effects by comparing observed counts to expected counts based on our site-specific model of insertion preferences. Compared to previous essentiality methods, TTN-Fitness can make finer distinctions among genes whose disruption causes a fitness defect (or advantage), separating them out from the large pool of nonessentials, and is able to classify many smaller genes (with few TA sites) that were previously characterized as uncertain. IMPORTANCE When using the Himar1 transposon to create transposon insertion mutant libraries, it is known that the transposon is restricted to insertions at TA dinucleotide sites throughout the genome, and the absence of insertions is used to infer which genes are essential (or conditionally essential) in a bacterial organism. It is widely assumed that insertions in nonessential regions are otherwise random, and this assumption is used as the basis of several methods for statistical analysis of TnSeq data. In this paper, we show that the nucleotide sequence surrounding TA sites influences the magnitude of insertions, and these Himar1 insertion preferences (sequence biases) can partially explain why some sites have higher counts than others. We use this predictive model to make improved estimates of the fitness effects of genes, which help make finer distinctions of the phenotype and biological consequences of disruption of nonessential genes.

Evaluation of Adiponectin and Resistin Levels in Gingival Crevicular Fluid in Patients with Chronic Periodontitis Before and After Treatment: A Clinico-Biochemical Study.

AIM: The aim of this study was to find out the association of adiponectin and resistin levels in gingival crevicular fluid (GCF) with the clinical parameters before and after scaling and root planing in periodontitis patients. METHODS: A total of 50 patients were recruited from the Outpatient Department of Periodontics, JKK Nattraja Dental College and Hospital, Komarapalayam, Tamil Nadu, India. The protocol was reviewed and approved by the institutional ethical board. Informed consent was obtained from the patients and the study-related procedures were explained. Patients were divided into two groups. Group I (25 patients) consisted of healthy patients. Group II (25 patients) consisted of periodontitis patients. The periodontitis patients after treatment were considered as Group III. GCF samples were collected before treatment and 21 days after treatment. The levels of adiponectin and resistin were evaluated using Immunotag™ Human RETN enzyme-linked immunosorbent assay (ELISA) kit (ITEH0269) and Immunotag™ Human ADP (adiponectin) ELISA kit (ITEH2593). The levels were correlated with the clinical parameters. RESULTS: There were an increase in the mean adiponectin level and a decrease in the mean resistin level at the end of periodontal therapy. CONCLUSIONS: Adiponectin which is an anti-inflammatory component was found to increase after periodontal therapy, and resistin which is an inflammatory component has been decreased after periodontal therapy.

Value of Repeated Troponin Measurements to Improve the Safety of the HEART Score for Chest Pain Patients at the Emergency Department.

OBJECTIVE: The HEART score is a clinical decision support tool for physicians to stratify the risk of major adverse cardiac events (MACE) in patients presenting with chest pain at the emergency department. The score includes 5 elements, including troponin level. Our aim was to compare safety and efficiency of the HEART scores calculated by using the first representative troponin (ie, based on time since symptom onset) compared to the original HEART score, where calculation was based on the first available troponin measurement, irrespective of duration of symptoms. METHODS: We performed a secondary analysis on patients from the HEART-impact trial (2013-2014, the Netherlands). Two HEART scores were calculated for all patients: a HEART score with a T (troponin) element score based on the first available troponin (HEART-first) and 1 with a T element score based on the first representative troponin (ie, at least 3 hours after symptom onset; HEART-representative). We compared all patients' scores and risk categories between HEART-first and HEART-representative. Furthermore, we compared safety (proportion of patients with MACE receiving a low score) and efficiency (proportion of patients with a low score) between HEART-first and HEART-representative. RESULTS: We included 1222 patients. In 882 (72%) patients, the first troponin was representative, resulting in the same HEART-first and HEART-representative score. In the remaining 340 patients the use of HEART-representative led to a different score than HEART-first in 43 patients (3.5%). Out of the 222 patients with MACE, 11 patients (5.0%) received a low score by using HEART-first compared with 10 patients (4.5%) when using HEART-representative (P = 0.83). The number of patients with a low score was similar (P = 0.93) when using the HEART-first (464/1222; 38%) or HEART-representative score (462/1222; 38%). CONCLUSIONS: Using a representative troponin measurement changed the value of the HEART score in only 3.5% of patients and had no impact on safety and efficiency of the HEART score. These results suggest there is no need to wait for a representative troponin measurement and should encourage physicians to adhere to the original HEART score guidelines.

Ameloblastic fibro-odontoma in a 14 year old girl: A case report.

Ameloblastic fibro-odontoma (AFO) is a benign, epithelial odontogenic tumor with odontogenic mesenchyme having the histologic characteristics of both ameloblastic fibroma and complex odontoma. This report describes the case of a 14-year-old girl with AFO on the right posterior mandibular region that mimics complex odontoma on incisional biopsy due to the presence of atypical dentin- and cementum-like areas. On histological examination, sections of excisional biopsy showed odontogenic epithelial islands with embryonic connective tissue and decalcified sections showed atypical dentin with dentinal tubules and islands of cementum. These features led to the diagnosis of AFO.

Effect of Using the HEART Score in Patients With Chest Pain in the Emergency Department: A Stepped-Wedge, Cluster Randomized Trial.

BACKGROUND: The HEART (History, Electrocardiogram, Age, Risk factors, and initial Troponin) score is an easy-to-apply instrument to stratify patients with chest pain according to their short-term risk for major adverse cardiac events (MACEs), but its effect on daily practice is unknown. OBJECTIVE: To measure the effect of use of the HEART score on patient outcomes and use of health care resources. DESIGN: Stepped-wedge, cluster randomized trial. (ClinicalTrials.gov: NCT01756846). SETTING: Emergency departments in 9 Dutch hospitals. PATIENTS: Unselected patients with chest pain presenting at emergency departments in 2013 and 2014. INTERVENTION: All hospitals started with usual care. Every 6 weeks, 1 hospital was randomly assigned to switch to "HEART care," during which physicians calculated the HEART score to guide patient management. MEASUREMENTS: For safety, a noninferiority margin of a 3.0% absolute increase in MACEs within 6 weeks was set. Other outcomes included use of health care resources, quality of life, and cost-effectiveness. RESULTS: A total of 3648 patients were included (1827 receiving usual care and 1821 receiving HEART care). Six-week incidence of MACEs during HEART care was 1.3% lower than during usual care (upper limit of the 1-sided 95% CI, 2.1% [within the noninferiority margin of 3.0%]). In low-risk patients, incidence of MACEs was 2.0% (95% CI, 1.2% to 3.3%). No statistically significant differences in early discharge, readmissions, recurrent emergency department visits, outpatient visits, or visits to general practitioners were observed. LIMITATION: Physicians were hesitant to refrain from admission and diagnostic tests in patients classified as low risk by the HEART score. CONCLUSION: Using the HEART score during initial assessment of patients with chest pain is safe, but the effect on health care resources is limited, possibly due to nonadherence to management recommendations. PRIMARY FUNDING SOURCE: Netherlands Organisation for Health Research and Development.

Prognostic Factors in Chest Pain Patients: A Quantitative Analysis of the HEART Score.

OBJECTIVES: Risk stratification for chest pain patients at the emergency department is recommended in several guidelines. The history, ECG, age, risk factors, and troponin (HEART) score is based on medical literature and expert opinion to estimate the risk of a major adverse cardiac event. We aimed to assess the predictive effects of the 5 HEART components and to compare performances of the original HEART score and a model based on regression analysis. METHODS: We analyzed prospectively collected data from 2388 patients, of whom 407 (17%) had a major adverse cardiac event within 6 weeks (acute myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, significant stenosis with conservative treatment and death due to any cause). RESULTS: Univariate regression analysis showed the same ordering of predictive effects as used in the HEART score. Based on multivariable logistic regression analysis, an adjusted score showed slightly better calibration and discrimination (c statistic HEART, 0.83, HEART-adj, 0.85). In comparison to HEART, HEART-adj proved in a decision curve analysis clinically useful for decision thresholds over 25%. Nevertheless, the original HEART classified patients better than HEART-adj (net reclassification improvement = 14.1%). CONCLUSION: The previously chosen weights of the 5 elements of the HEART score are supported by multivariable statistical analyses, although some improvement in calibration and discrimination is possible by adapting the score. The gain in clinical usefulness is relatively small and supports the use of either the original or adjusted HEART score in daily practice.

The canonical equation of adaptive dynamics for life histories: from fitness-returns to selection gradients and Pontryagin's maximum principle.

This paper should be read as addendum to Dieckmann et al. (J Theor Biol 241:370-389, 2006) and Parvinen et al. (J Math Biol 67: 509-533, 2013). Our goal is, using little more than high-school calculus, to (1) exhibit the form of the canonical equation of adaptive dynamics for classical life history problems, where the examples in Dieckmann et al. (J Theor Biol 241:370-389, 2006) and Parvinen et al. (J Math Biol 67: 509-533, 2013) are chosen such that they avoid a number of the problems that one gets in this most relevant of applications, (2) derive the fitness gradient occurring in the CE from simple fitness return arguments, (3) show explicitly that setting said fitness gradient equal to zero results in the classical marginal value principle from evolutionary ecology, (4) show that the latter in turn is equivalent to Pontryagin's maximum principle, a well known equivalence that however in the literature is given either ex cathedra or is proven with more advanced tools, (5) connect the classical optimisation arguments of life history theory a little better to real biology (Mendelian populations with separate sexes subject to an environmental feedback loop), (6) make a minor improvement to the form of the CE for the examples in Dieckmann et al. and Parvinen et al.

Serum Trimethylamine-N-Oxide is Elevated in CKD and Correlates with Coronary Atherosclerosis Burden.

Trimethlyamine-N-oxide (TMAO) was recently identified as a promoter of atherosclerosis. Patients with CKD exhibit accelerated development of atherosclerosis; however, no studies have explored the relationship between TMAO and atherosclerosis formation in this group. This study measured serum concentrations and urinary excretion of TMAO in a CKD cohort (n=104), identified the effect of renal transplant on serum TMAO concentration in a subset of these patients (n=6), and explored the cross-sectional relationship between serum TMAO and coronary atherosclerosis burden in a separate CKD cohort (n=220) undergoing coronary angiography. Additional exploratory analyses examined the relationship between baseline serum TMAO and long-term survival after coronary angiography. Serum TMAO concentrations demonstrated a strong inverse association with eGFR (r(2)=0.31, P<0.001). TMAO concentrations were markedly higher in patients receiving dialysis (median [interquartile range], 94.4 µM [54.8-133.0 µM] for dialysis-dependent patients versus 3.3 µM [3.1-6.0 µM] for healthy controls; P<0.001); whereas renal transplantation resulted in substantial reductions in TMAO concentrations (median [min-max] 71.2 µM [29.2-189.7 µM] pretransplant versus 11.4 µM [8.9-20.2 µM] post-transplant; P=0.03). TMAO concentration was an independent predictor for coronary atherosclerosis burden (P=0.02) and predicted long-term mortality independent of traditional cardiac risk factors (hazard ratio, 1.26 per 10 µM increment in TMAO concentration; 95% confidence interval, 1.13 to 1.40; P<0.001). In conclusion, serum TMAO concentrations substantially increase with decrements in kidney function, and this effect is reversed by renal transplantation. Increased TMAO concentrations correlate with coronary atherosclerosis burden and may associate with long-term mortality in patients with CKD undergoing coronary angiography.

The diagnostic value of clinical symptoms in women and men presenting with chest pain at the emergency department, a prospective cohort study.

BACKGROUND: Previous studies suggested that diagnosing coronary artery disease (CAD) is more difficult in women than in men. Studies investigating the predictive value of clinical signs and symptoms and compare its combined diagnostic value between women and men are lacking. METHODOLOGY: Data from a large multicenter prospective study was used. Patients admitted to the emergency department (ED) with chest pain but without ST-elevation were eligible. The endpoint was proven CAD, defined as a significant stenosis at angiography or the diagnosis of a non-ST-elevation myocardial infarction or cardiovascular death within six weeks after presentation at the ED. Twelve clinical symptoms and seven cardiovascular risk factors were collected. Potential predictors of CAD with a p-value <0.15 in the univariable analysis were included in a multivariable model. The diagnostic value of clinical symptoms and cardiovascular risk factors was quantified in women and men separately and areas under the curve (AUC) were compared between sexes. RESULTS: A total of 2433 patients were included. We excluded 102 patients (4%) with either an incomplete follow up or ST-elevation. Of the remaining 2331 patients 43% (1003) were women. CAD was present in 111 (11%) women and 278 (21%) men. In women 11 out of 12 and in men 10 out of 12 clinical symptoms were univariably associated with CAD. The AUC of symptoms alone was 0.74 (95%CI: 0.69-0.79) in women and 0.71 (95%CI: 0.68-0.75) in men and increased to respectively 0.79 (95%CI: 0.74-0.83) in women versus 0.75 (95%CI: 0.72-0.78) in men after adding cardiovascular risk factors. The AUCs of women and men were not significantly different (p-value symptoms alone: 0.45, after adding cardiovascular risk factors: 0.11). CONCLUSION: The diagnostic value of clinical symptoms and cardiovascular risk factors for the diagnosis of CAD in chest pain patients presenting on the ED was high in women and men. No significant differences were found between sexes.

The value of clinical and laboratory diagnostics for chest pain patients at the emergency department.

BACKGROUND: The focus during the diagnostic process for patients with acute chest pain is to discriminate patients who can be safely discharged from those who are at risk for an acute coronary syndrome (ACS). In this study the diagnostic value of the clinical examination is compared with laboratory testing of troponin. METHODS: This study included 710 chest pain patients who presented at the ED of two hospitals in the Netherlands. Clinical examination and laboratory testing were combined in the recently developed HEART-score. The diagnostic values of clinical presentation, troponin and the HEART-score for a major adverse coronary event (MACE) and an ACS within 6 weeks were assessed. Furthermore, the improvement of HEART with the second troponin measurement after 6 h was assessed using the net reclassification improvement (NRI). RESULTS: The use of HEART (AUCMACE: 0.77; AUCACS: 0.82) obtains a higher diagnostic value than troponin (AUCMACE: 0.72; AUCACS: 0.74) or clinical evaluation (AUCMACE: 0.69; AUCACS: 0.74). Statistical significant different AUCs were obtained when HEART is compared to troponin or clinical evaluation (p<0.01). The use of the second troponin test (after 6 h of admission) within HEART resulted in an improvement of 8.0%. CONCLUSIONS: The HEART-score combines clinical evaluation and results from laboratory testing, which should be used together, to discriminate patients at risk of a cardiac event from patients who can be safely discharged. In addition, it is shown that a second troponin measurement slightly improves the discriminative ability of the HEART-score.

The impact of the HEART risk score in the early assessment of patients with acute chest pain: design of a stepped wedge, cluster randomised trial.

BACKGROUND: Chest pain remains a diagnostic challenge: physicians do not want to miss an acute coronary syndrome (ACS), but, they also wish to avoid unnecessary additional diagnostic procedures. In approximately 75% of the patients presenting with chest pain at the emergency department (ED) there is no underlying cardiac cause. Therefore, diagnostic strategies focus on identifying patients in whom an ACS can be safely ruled out based on findings from history, physical examination and early cardiac marker measurement. The HEART score, a clinical prediction rule, was developed to provide the clinician with a simple, early and reliable predictor of cardiac risk. We set out to quantify the impact of the use of the HEART score in daily practice on patient outcomes and costs. METHODS/DESIGN: We designed a prospective, multi-centre, stepped wedge, cluster randomised trial. Our aim is to include a total of 6600 unselected chest pain patients presenting at the ED in 10 Dutch hospitals during an 11-month period. All clusters (i.e. hospitals) start with a period of 'usual care' and are randomised in their timing when to switch to 'intervention care'. The latter involves the calculation of the HEART score in each patient to guide clinical decision; notably reassurance and discharge of patients with low scores and intensive monitoring and early intervention in patients with high HEART scores. Primary outcome is occurrence of major adverse cardiac events (MACE), including acute myocardial infarction, revascularisation or death within 6 weeks after presentation. Secondary outcomes include occurrence of MACE in low-risk patients, quality of life, use of health care resources and costs. DISCUSSION: Stepped wedge designs are increasingly used to evaluate the real-life effectiveness of non-pharmacological interventions because of the following potential advantages: (a) each hospital has both a usual care and an intervention period, therefore, outcomes can be compared within and across hospitals; (b) each hospital will have an intervention period which enhances participation in case of a promising intervention; (c) all hospitals generate data about potential implementation problems. This large impact trial will generate evidence whether the anticipated benefits (in terms of safety and cost-effectiveness) of using the HEART score will indeed be achieved in real-life clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov 80-82310-97-12154.

The HEART score for the assessment of patients with chest pain in the emergency department: a multinational validation study.

OBJECTIVE: The HEART score for the early risk stratification of patients presenting to the emergency department with chest pain contains 5 elements: history, electrocardiogram, age, risk factors, and troponin. It has been validated in The Netherlands. The purpose of this investigation was to perform an external validation of the HEART score in an Asia-Pacific population. METHODS: Data were used from 2906 patients presenting with chest pain to the emergency departments of 14 hospitals. HEART scores were determined retrospectively. Three risk groups were composed based on previous research. The predictive values for the occurrence of 30-day major adverse coronary events (MACE) were assessed. A comparison was made with the Thrombolysis in Myocardial Infarction (TIMI) score in terms of the value of C-statistics. RESULTS: The low-risk group, HEART score ≤ 3, consisted of 820/2906 patients (28.2%). Fourteen (1.7%) patients were incorrectly defined as low risk (false negatives). The high-risk population, HEART score 7-10, consisted of 464 patients (16%) with a risk of MACE of 43.1%. The C-statistics were 0.83 (0.81-0.85) for HEART and 0.75 (0.72-0.77) for TIMI (P < 0.01). CONCLUSIONS: Utilization of the HEART score provided excellent determination of risk for 30-day MACE, comparing well with the Thrombolysis in Myocardial Infarction score. This study externally validates previous findings that HEART is a powerful clinical tool in this setting. It quickly identifies both a large proportion of low-risk patients, in whom early discharge without additional testing goes with a risk of MACE of only 1.7%, and high-risk patients who are potential candidates for early invasive strategies.