Ruling out coronary heart disease in primary care patients with chest pain: a clinical prediction score.

ABSTRACT: BACKGROUND: Chest pain raises concern for the possibility of coronary heart disease. Scoring methods have been developed to identify coronary heart disease in emergency settings, but not in primary care. METHODS: Data were collected from a multicenter Swiss clinical cohort study including 672 consecutive patients with chest pain, who had visited one of 59 family practitioners' offices. Using delayed diagnosis we derived a prediction rule to rule out coronary heart disease by means of a logistic regression model. Known cardiovascular risk factors, pain characteristics, and physical signs associated with coronary heart disease were explored to develop a clinical score. Patients diagnosed with angina or acute myocardial infarction within the year following their initial visit comprised the coronary heart disease group. RESULTS: The coronary heart disease score was derived from eight variables: age, gender, duration of chest pain from 1 to 60 minutes, substernal chest pain location, pain increases with exertion, absence of tenderness point at palpation, cardiovascular risks factors, and personal history of cardiovascular disease. Area under the receiver operating characteristics curve was of 0.95 with a 95% confidence interval of 0.92; 0.97. From this score, 413 patients were considered as low risk for values of percentile 5 of the coronary heart disease patients. Internal validity was confirmed by bootstrapping. External validation using data from a German cohort (Marburg, n = 774) revealed a receiver operating characteristics curve of 0.75 (95% confidence interval, 0.72; 0.81) with a sensitivity of 85.6% and a specificity of 47.2%. CONCLUSIONS: This score, based only on history and physical examination, is a complementary tool for ruling out coronary heart disease in primary care patients complaining of chest pain.

Bias related to body mass index in pediatric echocardiographic z scores.

In pediatric echocardiography, cardiac dimensions are often normalized for weight, height, or body surface area (BSA). The combined influence of height and weight on cardiac size is complex and likely varies with age. We hypothesized that increasing weight for height, as represented by body mass index (BMI) adjusted for age, is poorly accounted for in Z scores normalized for weight, height, or BSA. We aimed to evaluate whether a bias related to BMI was introduced when proximal aorta diameter Z scores are derived from bivariate models (only one normalizing variable), and whether such a bias was reduced when multivariable models are used. We analyzed 1,422 echocardiograms read as normal in children ≤18 years. We computed Z scores of the proximal aorta using allometric, polynomial, and multivariable models with four body size variables. We then assessed the level of residual association of Z scores and BMI adjusted for age and sex. In children ≥6 years, we found a significant residual linear association with BMI-for-age and Z scores for most regression models. Only a multivariable model including weight and height as independent predictors produced a Z score free of linear association with BMI. We concluded that a bias related to BMI was present in Z scores of proximal aorta diameter when normalization was done using bivariate models, regardless of the regression model or the normalizing variable. The use of multivariable models with weight and height as independent predictors should be explored to reduce this potential pitfall when pediatric echocardiography reference values are evaluated.

Predicting Adverse Events in Children with Fever and Chemotherapy-Induced Neutropenia. Results of the Prospective Multicenter SPOG 2003 FN Study

PURPOSE To develop a score predicting the risk of adverse events (AEs) in pediatric patients with cancer who experience fever and neutropenia (FN) and to evaluate its performance. PATIENTS AND METHODS Pediatric patients with cancer presenting with FN induced by nonmyeloablative chemotherapy were observed in a prospective multicenter study. A score predicting the risk of future AEs (ie, serious medical complication, microbiologically defined infection, radiologically confirmed pneumonia) was developed from a multivariate mixed logistic regression model. Its cross-validated predictive performance was compared with that of published risk prediction rules. Results An AE was reported in 122 (29%) of 423 FN episodes. In 57 episodes (13%), the first AE was known only after reassessment after 8 to 24 hours of inpatient management. Predicting AE at reassessment was better than prediction at presentation with FN. A differential leukocyte count did not increase the predictive performance. The score predicting future AE in 358 episodes without known AE at reassessment used the following four variables: preceding chemotherapy more intensive than acute lymphoblastic leukemia maintenance (weight = 4), hemoglobin > or = 90 g/L (weight = 5), leukocyte count less than 0.3 G/L (weight = 3), and platelet count less than 50 G/L (weight = 3). A score (sum of weights) > or = 9 predicted future AEs. The cross-validated performance of this score exceeded the performance of published risk prediction rules. At an overall sensitivity of 92%, 35% of the episodes were classified as low risk, with a specificity of 45% and a negative predictive value of 93%. CONCLUSION This score, based on four routinely accessible characteristics, accurately identifies pediatric patients with cancer with FN at risk for AEs after reassessment.

Comparison of the glomerular filtration rate in children by the new revised Schwartz formula and a new generalized formula.

The most widely used formula for estimating glomerular filtration rate (eGFR) in children is the Schwartz formula. It was revised in 2009 using iohexol clearances with measured GFR (mGFR) ranging between 15 and 75 ml/min × 1.73 m(2). Here we assessed the accuracy of the Schwartz formula using the inulin clearance (iGFR) method to evaluate its accuracy for children with less renal impairment comparing 551 iGFRs of 392 children with their Schwartz eGFRs. Serum creatinine was measured using the compensated Jaffe method. In order to find the best relationship between iGFR and eGFR, a linear quadratic regression model was fitted and a more accurate formula was derived. This quadratic formula was: 0.68 × (Height (cm)/serum creatinine (mg/dl))-0.0008 × (height (cm)/serum creatinine (mg/dl))(2)+0.48 × age (years)-(21.53 in males or 25.68 in females). This formula was validated using a split-half cross-validation technique and also externally validated with a new cohort of 127 children. Results show that the Schwartz formula is accurate until a height (Ht)/serum creatinine value of 251, corresponding to an iGFR of 103 ml/min × 1.73 m(2), but significantly unreliable for higher values. For an accuracy of 20 percent, the quadratic formula was significantly better than the Schwartz formula for all patients and for patients with a Ht/serum creatinine of 251 or greater. Thus, the new quadratic formula could replace the revised Schwartz formula, which is accurate for children with moderate renal failure but not for those with less renal impairment or hyperfiltration.

Diagnostic Performances of 18F-FDG Positron Emission Tomography in Large Vessels Vasculitis: Meta-analysis

Toperform a meta-analysis of FDG-PET performances in the diagnosis of largevessels vasculitis (Giant Cell Arteritis (GCA) associated or not withPolymyalgia Rheumatica(PMR), Takayasu). Materials and methods : The MEDLINE,Cochrane Library, Embase were searched for relevant original articlesdescribing FDG-PET for vasculitis assessment, using MesH terms ("GiantCell Arteritis or Vasculitis" AND "PET"). Criteria for inclusionwere:(1)FDG-PET for diagnosis of vasculitis(2)American College of Rheumatologycriteria as reference standard(3)control group. After data extraction, analyseswere performed using a random-effects model. Results : Of 184 citations(database search and references screening),70 articles were reviewed of which12 eligible studies were extracted (sensitivity range from 32% to 97%). 7studies fulfilled all inclusion criteria. Owing to overlapping population, 1study was excluded. Statistical heterogeneity justified the random-effectsmodel. Pooled 6 studies analysis(116 vasculitis,224 controls) showed a 81%sensitivity (95%CI:70-89%);a 89% specificity (95%CI:77-95%);a 85%PPV(95%CI:63-95%); a 90% NPV(95%CI:79-95%);a 7.1 positive LR(95%CI:3.4-14.9); a0.2 negative LR(95%CI:0.14-0.35) and 90.1 DOR(95%CI: 18.6-437). Conclusion :FDG-PET has good diagnostic performances in the detection of large vesselsvasculitis. Its promising role could be extended to follow up patients undertreatment, but further studies are needed to confirm this possibility.

Risk factors for survival after lung metastasectomy in colorectal cancer patients: a systematic review and meta-analysis.

BACKGROUND: Resection of lung metastases (LM) from colorectal cancer (CRC) is increasingly performed with a curative intent. It is currently not possible to identify those CRC patients who may benefit the most from this surgical strategy. The aim of this study was to perform a systematic review of risk factors for survival after lung metastasectomy for CRC. METHODS: We performed a meta-analysis of series published between 2000 and 2011, which focused on surgical management of LM from CRC and included more than 40 patients each. Pooled hazard ratios (HR) were calculated by using random effects model for parameters considered as potential prognostic factors. RESULTS: Twenty-five studies including a total of 2925 patients were considered in this analysis. Four parameters were associated with poor survival: (1) a short disease-free interval between primary tumor resection and development of LM (HR 1.59, 95 % confidence interval [CI] 1.27-1.98); (2) multiple LM (HR 2.04, 95 % CI 1.72-2.41); (3) positive hilar and/or mediastinal lymph nodes (HR 1.65, 95 % CI 1.35-2.02); and (4) elevated prethoracotomy carcinoembryonic antigen (HR 1.91, 95 % CI 1.57-2.32). By comparison, a history of resected liver metastases (HR 1.22, 95 % CI 0.91-1.64) did not achieve statistical significance. CONCLUSIONS: Clinical variables associated with prolonged survival after surgery for LM in CRC patients include prolonged disease-free interval between primary tumor and metastatic spread, normal prethoracotomy carcinoembryonic antigen, absence of thoracic node involvement, and a single pulmonary lesion.

Modifiable and nonmodifiable risk factors for postoperative delirium after cardiac surgery with cardiopulmonary bypass.

Postoperative delirium after cardiac surgery is associated with increased morbidity and mortality as well as prolonged stay in both the intensive care unit and the hospital. The authors sought to identify modifiable risk factors associated with the development of postoperative delirium in elderly patients after elective cardiac surgery in order to be able to design follow-up studies aimed at the prevention of delirium by optimizing perioperative management. A post hoc analysis of data from patients enrolled in a randomized controlled trial was performed. A single university hospital. One hundred thirteen patients aged 65 or older undergoing elective cardiac surgery with cardiopulmonary bypass. None. MEASUREMENTS AND MAINS RESULTS: Screening for delirium was performed using the Confusion Assessment Method (CAM) on the first 6 postoperative days. A multivariable logistic regression model was developed to identify significant risk factors and to control for confounders. Delirium developed in 35 of 113 patients (30%). The multivariable model showed the maximum value of C-reactive protein measured postoperatively, the dose of fentanyl per kilogram of body weight administered intraoperatively, and the duration of mechanical ventilation to be independently associated with delirium. In this post hoc analysis, larger doses of fentanyl administered intraoperatively and longer duration of mechanical ventilation were associated with postoperative delirium in the elderly after cardiac surgery. Prospective randomized trials should be performed to test the hypotheses that a reduced dose of fentanyl administered intraoperatively, the use of a different opioid, or weaning protocols aimed at early extubation prevent delirium in these patients.

The relationship between a short measure of health status and physical activity in a workplace population.

Many interventions promoting physical activity (PA) are effective in preventing disease onset, and although studies have found a positive relationship between health-related quality of life (HRQL) and PA, most of these studies have focused on older adults and those with chronic conditions. Less is known regarding the association between PA level and HRQL among healthy adults. Our objective was to analyse the relationship between PA level and HRQL among a sample of 573 employees aged 20-68 taking part in a workplace intervention to promote PA. Measures included HRQL (using a single item) and PA (i.e. Godin Leisure-Time Questionnaire). The Modified Canadian Aerobic Fitness Test (MCAFT) was also completed by 10% of the employees. MET-minute scores (assessing energy expenditure over one week) were compared across HRQL categories using ANOVA. A multiple linear regression analysis was conducted to further examine the relationship between HRQL and PA, controlling for potential covariates. Participants in the higher health status categories were found to report higher levels of energy expenditure (one-way ANOVA, p < 0.001). In the multiple linear regression model, each unit increase in health status level translated in a mean increase of 356 MET-minutes in energy expenditure (p < 0.001). This single-item assessment of health status explained six percent of the variance in energy expenditure. The study concludes that higher energy expenditure through PA among an adult workplace population is positively associated with increased health status, and it also suggests that a single-item HRQL measure is suitable for community- and population-based studies, reducing response burden and research costs.

Individual patient data systematic review and meta-analysis of optic nerve sheath diameter ultrasonography for detecting raised intracranial pressure: protocol of the ONSD research group.

BACKGROUND: The purpose of the optic nerve sheath diameter (ONSD) research group project is to establish an individual patient-level database from high quality studies of ONSD ultrasonography for the detection of raised intracranial pressure (ICP), and to perform a systematic review and an individual patient data meta-analysis (IPDMA), which will provide a cutoff value to help physicians making decisions and encourage further research. Previous meta-analyses were able to assess the diagnostic accuracy of ONSD ultrasonography in detecting raised ICP but failed to determine a precise cutoff value. Thus, the ONSD research group was founded to synthesize data from several recent studies on the subject and to provide evidence on the diagnostic accuracy of ONSD ultrasonography in detecting raised ICP. METHODS: This IPDMA will be conducted in different phases. First, we will systematically search for eligible studies. To be eligible, studies must have compared ONSD ultrasonography to invasive intracranial devices, the current reference standard for diagnosing raised ICP. Subsequently, we will assess the quality of studies included based on the QUADAS-2 tool, and then collect and validate individual patient data. The objectives of the primary analyses will be to assess the diagnostic accuracy of ONSD ultrasonography and to determine a precise cutoff value for detecting raised ICP. Secondly, we will construct a logistic regression model to assess whether patient and study characteristics influence diagnostic accuracy. DISCUSSION: We believe that this IPD MA will provide the most reliable basis for the assessment of diagnostic accuracy of ONSD ultrasonography for detecting raised ICP and to provide a cutoff value. We also hope that the creation of the ONSD research group will encourage further study. TRIAL REGISTRATION: PROSPERO registration number: CRD42012003072.

Cervical cancer: incidence and survival in migrants within Spain

This study examined the incidence of cervical cancer and survival rates according to migrant experience of women from different regions of Spain to Girona, Catalonia (Spain). DESIGN--Using data from the population based cancer registry of Girona for the period 1980-89, crude and age adjusted incidence rates were calculated for local-born and first generation migrants from other Spanish regions. The age standardised rate ratio (SRR) was calculated and Cox's regression model was used to adjust survival according to migrant status for age and stage at diagnosis. MAIN RESULTS--The incidence of cervical cancer was significantly higher in first generation Spanish migrants compared with locally born women (SRR: 2.02; 95% CI 1.40:2.92). The stage at diagnosis was more advanced among migrants. Survival probability was significantly associated with stage at diagnosis, but age and region of birth were not. CONCLUSIONS--Migrants from the southern Spanish regions show a twofold excess in the incidence of cervical cancer compared with the Girona-born female population. Cases of cervical cancer in migrants are diagnosed at a more advanced stage and as a consequence have a poorer prognosis.

Climate oscillations and species interactions: large-scale congruence but regional differences in the phylogeographic structures of an alpine plant and its monophagous insect

Aim. To predict the fate of alpine interactions involving specialized species, using a monophagous beetle and its host-plant as a case study. Location. The Alps. Methods. We investigated genetic structuring of the herbivorous beetle Oreina gloriosa and its specific host-plant Peucedanum ostruthium. We used genome fingerprinting (in the insect and the plant) and sequence data (in the insect) to compare the distribution of the main gene pools in the two associated species and to estimate divergence time in the insect, a proxy for the temporal origin of the interaction. We quantified the similarity in spatial genetic structures by performing a Procrustes analysis, a tool from the shape theory. Finally, we simulated recolonization of an empty space analogous to the deglaciated Alps just after ice retreat by two lineages from two species showing unbalanced dependence, to examine how timing of the recolonization process, as well as dispersal capacities of associated species, could explain the observed pattern. Results. Contrasting with expectations based on their asymmetrical dependence, patterns in the beetle and plant were congruent at a large scale. Exceptions occurred at a regional scale in areas of admixture, matching known suture zones in Alpine plants. Simulations using a lattice-based model suggested these empirical patterns arose during or soon after recolonization, long after the estimated origin of the interaction c. 0.5 million years ago. Main conclusions. Species-specific interactions are scarce in alpine habitats because glacial cycles have limited opportunities for coevolution. Their fate, however, remains uncertain under climate change. Here we show that whereas most dispersal routes are paralleled at large scale, regional incongruence implies that the destinies of the species might differ under changing climate. This may be a consequence of the host-dependence of the beetle that locally limits the establishment of dispersing insects.

Success of a general school-based physical activity intervention on bone mineral content depends on pubertal stage but not on gender

Aims: We performed a randomised controlled trial in children of both gender and different pubertal stages to determine whether a school-based physical activity (PA) program during a full schoolyear influences bone mineral content (BMC) and whether there are differences in response for boys and girls before and during puberty. Methods: Twenty-eight 1st and 5th grade classes were cluster randomised to an intervention (INT, 16 classes, n=297) and control (CON; 12 classes, n=205) group. The intervention consisted of a multi-component PA intervention including daily physical education during a full school year. Each lesson was predetermined, included about ten minutes of jumping or strength training exercises of various intensity and was the same for all children. Measurements included anthropometry (height and weight), tanner stages (by self-assessment), PA (by accelerometry) and BMC for total body, femoral neck, total hip and lumbar spine using dualenergy X-ray absorptiometry (DXA). Bone parameters were normalized for gender and tanner stage (pre- vs. puberty). Analyses were performed by a regression model adjusted for gender, baseline height, baseline weight, baseline PA, post-intervention tanner stage, baseline BMC, and cluster. Researchers were blinded to group allocation. Children in the control group did not know about the intervention arm. Results: 217 (57%) of 380 children who initially agreed to have DXA measurements had also post-intervention DXA and PA data. Mean age of prepubertal and pubertal children at baseline was 9.0±2.1 and 11.2±0.6 years, respectively. 47/114 girls and 68/103 boys were prepubertal at the end of the intervention. Compared to CON, children in INT showed statistically significant increases in BMC of total body (adjusted z-score differences: 0.123; 95%>CI 0.035 to 0.212), femoral neck (0.155; 95%>CI 0.007 to 0.302), and lumbar spine (0.127; 95%>CI 0.026 to 0.228). Importantly, there was no gender*group, but a tanner*group interaction consistently favoring prepubertal children. Conclusions: Our findings show that a general, but stringent school-based PA intervention can improve BMC in elementary school children. Pubertal stage, but not gender seems to determine bone sensitivity to physical activity loading.

Herramientas estadísticas para el estudio de perfiles de riesgo

En este documento se ilustra de un modo práctico, el empleo de tres instrumentos que permiten al actuario definir grupos arancelarios y estimar premios de riesgo en el proceso que tasa la clase para el seguro de no vida. El primero es el análisis de segmentación (CHAID y XAID) usado en primer lugar en 1997 por UNESPA en su cartera común de coches. El segundo es un proceso de selección gradual con el modelo de regresión a base de distancia. Y el tercero es un proceso con el modelo conocido y generalizado de regresión linear, que representa la técnica más moderna en la bibliografía actuarial. De estos últimos, si combinamos funciones de eslabón diferentes y distribuciones de error, podemos obtener el aditivo clásico y modelos multiplicativos

Estimating the time since discharge of spent cartridges: a logical approach fro interpreting the evidence

Estimating the time since discharge of a spent cartridge or a firearm can be useful in criminal situa-tions involving firearms. The analysis of volatile gunshot residue remaining after shooting using solid-phase microextraction (SPME) followed by gas chromatography (GC) was proposed to meet this objective. However, current interpretative models suffer from several conceptual drawbacks which render them inadequate to assess the evidential value of a given measurement. This paper aims to fill this gap by proposing a logical approach based on the assessment of likelihood ratios. A probabilistic model was thus developed and applied to a hypothetical scenario where alternative hy-potheses about the discharge time of a spent cartridge found on a crime scene were forwarded. In order to estimate the parameters required to implement this solution, a non-linear regression model was proposed and applied to real published data. The proposed approach proved to be a valuable method for interpreting aging-related data.

Impacts of deforestation on water balance components of a watershed on the Brazilian East Coast

The Brazilian East coast was intensely affected by deforestation, which drastically cut back the original biome. The possible impacts of this process on water resources are still unknown. The purpose of this study was an evaluation of the impacts of deforestation on the main water balance components of the Galo creek watershed, in the State of Espírito Santo, on the East coast of Brazil. Considering the real conditions of the watershed, the SWAT model was calibrated with data from 1997 to 2000 and validated for the period between 2001 and 2003. The calibration and validation processes were evaluated by the Nash-Sutcliffe efficiency coefficient and by the statistical parameters (determination coefficient, slope coefficient and F test) of the regression model adjusted for estimated and measured flow data. After calibration and validation of the model, new simulations were carried out for three different land use scenarios: a scenario in compliance with the law (C1), assuming the preservation of PPAs (permanent preservation areas); an optimistic scenario (C2), which considers the watershed to be almost entirely covered by native vegetation; and a pessimistic scenario (C3), in which the watershed would be almost entirely covered by pasture. The scenarios C1, C2 and C3 represent a soil cover of native forest of 76, 97 and 0 %, respectively. The results were compared with the simulation, considering the real scenario (C0) with 54 % forest cover. The Nash-Sutcliffe coefficients were 0.65 and 0.70 for calibration and validation, respectively, indicating satisfactory results in the flow simulation. A mean reduction of 10 % of the native forest cover would cause a mean annual increase of approximately 11.5 mm in total runoff at the watershed outlet. Reforestation would ensure minimum flows in the dry period and regulate the maximum flow of the main watercourse of the watershed.