Individual Clinical Risk Factors Research Articles

Clinical risk factors associated with cardiac events in children with BrS-SCN5A

Abstract Introduction between 20-30% of patients with Brugada syndrome (BrS) are carriers of deleterious genetic variants in the SCN5A gene. However, the risk factors for cardiac events in these patients remain under consideration, especially in the paediatric population, with many risk factors being still undetermined. Objectives to investigate and evaluate individual clinical risk factors associated with cardiac events in children with BrS-SCN5A. Methods a Spanish retrospective single-centre paediatric cohort study was conducted including 41 BrS patients under 21 years of age carrying rare variants in the SCN5A gene. Demographic, clinical, genetic, and therapeutic variables were collected. Descriptive and univariate analyses were performed to identify independent risk factors for cardiac events. Outcomes were defined as cardiac syncope, ventricular tachycardia/fibrillation (VT/VF), sudden cardiac death (SCD), and appropriate shock in ICD. Results Nearly 20% of BrS-SCN5A patients presented with cardiac events. Five patients showing cardiogenic syncope, 4-SCD, 3-VT and 2 appropriate shocks in the ICD. The presence of bradycardia and bradyarrhythmia in baseline EKG (P<0.05), AV block type 1 (P<0.02), type 1 Brugada pattern in fever EKG (P<0.02), atrial fibrillation(P<0.05), arrhythmias in febrile episodes (P<0.05), progressive cardiac conduction defect (PCCD; P<0.001), sick sinus syndrome (SSS; P=0.001) and overlap phenotype (P<0.001) were predictor of cardiac events in this cohort. Conclusions We have identified several statistically significant independent risk factors associated with cardiac events and worse phenotype severity in BrS-SCN5A children from a single-centre Spanish cohort. These results may help to improve prognosis assessment, establish accurate risk stratification, and prevent SCD in children with BrS-SCN5A. Future studies in large cohorts of different ethnicities are crucial to strengthen our risk factors in paediatric cohorts at high risk of malignant arrhythmias.

Correlation of Clinical Risk Scores for Unstable Angina with the Angiographic Extent and Severity of Coronary Artery Disease

Objective: In patients presenting with Unstable Angina the correlation of clinical risk predictors and clinical risk scores with angiographic extent of Coronary Artery Disease (CAD) is less well understood. The objective is to assess the correlation of various clinical risk scores for unstable angina and individual clinical risk factors with the extent and severity of coronary artery disease as assessed by coronary angiography. Materials and Methods: The present study was a single centre, hospital based, observational, cross-sectional, descriptive study conducted at a tertiary care teaching and research institute in South India. One hundred and fifty patients presenting with chest pain consistent with unstable angina were assessed for existence of independent clinical predictors and calculations were done for their 5 clinical risk scores. Coronary angiography was performed in all the patients leading to the generation of Modified Gensini score and its correlation with the various clinical risk scores was done. Results: Presence of dyslipidemia and diabetes were stronger predictors of Modified Gensini score. TIMI, GRACE& HEART risk scores had moderate correlation with angiographic severity while FRISC and PURSUIT scoring systems had a weak correlation. Conclusion: Presence of dyslipidemia and diabetes significantly affect the extent of CAD. Thus their presence in patients presenting with unstable angina assign them to the high risk category. Angiographic extent of CAD was strongly correlated with TIMI, GRACE and HEART risk scores, thus emphasizing on their use in risk stratification and in identifying the category of patients likely to make the most out of an early invasive strategy.

Pre-Existing and Pragmatically-Derived Immunohematologic Phenotypes Predict All-Cause and COVID-19-Specific Mortality: A 'Population Immunology' Approach

Background: Dysregulation of immunohematologic function (IHF) promotes cardiovascular disease and impairs protective responses to cancer and infection. A pragmatic method to identify those as risk due to IHF could improve the precision of preventive interventions and provide insight into the heterogeneity of immunologic capacity. We developed and validated a method to distill complete blood cell count data into distinct IHF profiles of prognostic relevance. Methods: We adapted latent profile analysis methods to simultaneously identify distinct groups of patients with respect to 10 immunohematologic indicators and regress time to all-cause mortality on this latent IHF profile. The model was developed using data from 30274 National Health and Nutrition Examination Survey participants and externally validated in 49851 outpatients in the Veterans Heath Administration (VHA) system and 44142 SARS-CoV-2 positive VHA patients.Findings: Ten distinct IHF profiles were identified. Profile 1, with relative mild pan-leukopenia in absence of red cell abnormalities, was associated with the best long term survival in each setting. Profiles 8-10, featuring anemia/anisocytosis especially in the setting of lymphopenia (Profiles 9-10) were associated with adjusted hazard ratio (HR) estimates of 1.76-2.62 for mortality across the three cohorts, compared to Profile 1. Profiles 6-7, featuring relative neutrophilia, were less common but also independently associated with mortality risk, especially after COVID-19 infection (Profile 7 HR [95% CI]: 2.51 [1.63 – 3.86]). The magnitude of adjusted risk conveyed by IHF profiles was greater than individual clinical risk factors (i.e., smoking, diabetes) or prevalent co-morbidities.Interpretation: Distinct immunohematologic endotypes can be identified during routine blood panels which project to mortality risk on par with a decade of life, additive to demographic and clinical factors. Applications that consider immunohematologic dysfunction may improve prevention of common fatal diseases, including COVID-19.Funding Information:This study was funded in part by The National Institute on Aging (R01AG055480; Dalton and Perzynski), the National Cancer Institute (U01CA260513; Zidar and Chan), and the United States Veteran Administration (COVID19-8900-05; Zidar). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veteran Affairs or the National Institutes of Health.Declaration of Interests: No conflict of interest exists between any of the authors and the contents of this paper.Ethics Approval Statement: The study was approved by the Institutional Review Board of the Louis Stokes Cleveland VAMC.

Biomarkers' ability to predict cardiac toxicity in oncological patients undergoing to antineoplastic treatment: 5-year follow-up

Abstract Background It is known that anticancer treatment can cause adverse cardiovascular (CV) events, influencing patients' survival and quality of life regardless of their cancer prognosis; today there are no defined protocols for the early identification of cardiotoxicity (CTX). Purpose To evaluate the ability of biomarkers, cardiac TnI and NT-proBNP, to predict CTX induced by antineoplastic therapy. Methods We have enrolled women with non-metastatic breast cancer who had to start a treatment with Anthracycline (ANT), in the patients (pts) with HER2+ cancer, Trastuzumab (TRZ) could also be introduced. The presence of a known heart disease, a previous mediastinal irradiation and a previous treatment with ANT, were the main exclusion criteria. All pts underwent complete cardiological evaluation (ECG, Echo) before the beginning of the therapy (T0), after each ANT cycle and every 3 months up to 1 year of follow-up after the end of therapy with ANT. During each visit, a venous sampling was performed for the determination of biomarkers. We collected the data of the routine cardiological visits carried out by the pts in the following 5 years. Results 179pts finished the follow-up,7pts (21%) were hypertensive, 9pts (5%) diabetic, 32pts (18%) dyslipidemics. 53pts (30%) (“TnI+ group”) showed a significant increase in TnI (>0.04ng/mL) or less than this cut-off but persistently >0.015ng/mL in at least 2 measurements; comparing the LVEF of the two groups detected at 1 year follow-up it was observed a significant difference: 60±6.5% in the “TnI+ group” and 63±4.1% in the “TnI− group” (p=0.005); a tendency to significance was observed from the comparison between LVEF measured at baseline compared to that of 1-year follow-up in the “TnI+ group” (62±4.2% vs 60±6.5%, p=0.06); furthermore 7 patients of the “TnI+ group” developed LV systolic dysfunction (according to the definition of the CREC) early in the first year of follow-up (vs 1 pts of the “TnI− group”, p=0.001), with recovery after the introduction of specific cardiology therapy. 76/179 pts (43%) showed NT-proBNP values ≥125 ng/L in at least two consecutive determinations (“NT-proBNP+ group”), in this group 25% of the pts had more than 3 CV risk factors, compared to 11% in the “NT-proBNP− group” (p=0.011), 3/8 pts that showed LV systolic dysfunction were included in the “NT-proBNP+ group”. Conclusion(s) In a homogeneous group of patients with a low CV risk profile, anticancer treatment with low doses of ANT and with TRZ can induce significant changes in plasma TnI levels that can be correlated with early alterations in LV systolic function, but not with major CV events after 5 years. Significant increases in NT-proBNP have also been reported, but there has been no significant correlation with the progressive development of LV dysfunction and HF. The combination of individual clinical risk factors and biomarkers, especially TnI, in a predictive model could allow early identification of CTX. Funding Acknowledgement Type of funding source: None

New Developments in Fracture Risk Assessment for Current Osteoporosis Reports.

Identifying individuals at high fracture risk can be used to target those likely to derive the greatest benefit from treatment. This narrative review examines recent developments in using specific risk factors used to assess fracture risk, with a focus on publications in the last 3years. There is expanding evidence for the recognition of individual clinical risk factors and clinical use of composite scores in the general population. Unfortunately, enthusiasm is dampened by three pragmatic randomized trials that raise questions about the effectiveness of widespread population screening using clinical fracture prediction tools given suboptimal participation and adherence. There have been refinements in risk assessment in special populations: men, patients with diabetes, and secondary causes of osteoporosis. New evidence supports the value of vertebral fracture assessment (VFA), high resolution peripheral quantitative CT (HR-pQCT), opportunistic screening using CT, skeletal strength assessment with finite element analysis (FEA), and trabecular bone score (TBS). The last 3years have seen important developments in the area of fracture risk assessment, both in the research setting and translation to clinical practice. The next challenge will be incorporating these advances into routine work flows that can improve the identification of high risk individuals at the population level and meaningfully impact the ongoing crisis in osteoporosis management.

Volumetric Bone Mineral Density and Failure Load of Distal Limbs Predict Incident Clinical Fracture Independent HR-pQCT BMD and Failure Load Predicts Incident Clinical Fracture of FRAX and Clinical Risk Factors Among Older Men.

Our objective was to determine the associations of peripheral bone strength and microarchitecture with incident clinical and major osteoporotic fracture among older men after adjusting for major clinical risk factors. We used a prospective cohort study design with data from 1794 men (mean age 84.4 years) in the Osteoporotic Fractures in Men (MrOS) study. Eligible men attended the year 14 visit, had high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and distal or diaphyseal tibia, DXA measured BMD, and were followed for mean 1.7 years for incident fracture. Failure load was estimated using finite element analysis. We used Cox proportional hazards models with standardized HR-pQCT parameters as exposure variables. Primary outcome was clinical fracture (n = 108). Covariates included either Fracture Risk Assessment Tool (FRAX) major osteoporotic fracture probability calculated with BMD (FRAX-BMD), or individual clinical risk factors (CRF) including age, total hip BMD, race, falls, and prevalent fracture after age 50 years. Lower failure load was associated with higher risk of incident clinical fracture and incident major osteoporotic fracture. For clinical fracture with FRAX-BMD adjustment, the associations ranged from hazard ratio (HR) 1.58 (95% CI, 1.25 to 2.01) to 2.06 (95% CI, 1.60 to 2.66) per SD lower failure load at the diaphyseal tibia and distal radius. These associations were attenuated after adjustment for individual CRFs, but remained significant at the distal sites. Associations of volumetric BMD with these outcomes were similar to those for failure load. At the distal radius, lower trabecular BMD, number, and thickness, and lower cortical BMD, thickness, and area were all associated with higher risk of clinical fracture, but cortical porosity was not. Among community-dwelling older men, HR-pQCT measures including failure load, volumetric BMD, and microstructure parameters at peripheral sites (particularly distal radius) are robust independent predictors of clinical and major osteoporotic fracture. © 2018 American Society for Bone and Mineral Research.

Prediction Model of In-Hospital Mortality After Hip Fracture Surgery

Mortality in elderly patients after the surgical treatment of hip fractures remains high. Although individual clinical risk factors have been widely studied, there has been limited research on prediction models in this population. The purpose of this study was to develop a prediction model for in-hospital mortality after hip fracture surgery and to evaluate the performance of this model. Using the National Inpatient Sample database from 2012 to 2013, we collected data on 535,475 patients older than 50 years who had hip fracture surgery. Patient characteristics, surgery-specific factors, and Elixhauser comorbidities were used as candidate variables. The patients were randomly divided into training and testing cohorts. The Lasso (least absolute shrinkage and selection operator) method was used to select predictor variables, and points were assigned to each variable based on its coefficient. We identified 8 essential predictors (age, timing of surgery, male sex, congestive heart failure, pulmonary circulation disease, renal failure, weight loss, and fluid and electrolyte disorders) for mortality, with a maximum prediction score of 20. The model's area under the curve was 0.74, and the Hosmer-Lemeshow test P value was 0.59 on the testing set. With the application of cutoff values (scores 0-5, 6-9, and 10-20), the observed in-hospital postoperative mortality was 0.6%, 2.5%, and 7.5%, respectively. We built a simple prediction model with 8 essential clinical factors that predict in-hospital mortality after hip fracture surgery. This model may assist in counseling patients and families and measuring hospital quality of care. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Intrapartum Antibiotic Chemoprophylaxis Policies for the Prevention of Group B Streptococcal Disease Worldwide: Systematic Review.

Intrapartum antibiotic chemoprophylaxis (IAP) prevents most early-onset group B streptococcal (GBS) disease. However, there is no description of how IAP is used around the world. This article is the sixth in a series estimating the burden of GBS disease. Here we aimed to review GBS screening policies and IAP implementation worldwide. We identified data through (1) systematic literature reviews (PubMed/Medline, Embase, Literature in the Health Sciences in Latin America and the Caribbean [LILACS], World Health Organization library database [WHOLIS], and Scopus) and unpublished data from professional societies and (2) an online survey and searches of policies from medical societies and professionals. We included data on whether an IAP policy was in use, and if so whether it was based on microbiological or clinical risk factors and how these were applied, as well as the estimated coverage (percentage of women receiving IAP where indicated). We received policy information from 95 of 195 (49%) countries. Of these, 60 of 95 (63%) had an IAP policy; 35 of 60 (58%) used microbiological screening, 25 of 60 (42%) used clinical risk factors. Two of 15 (13%) low-income, 4 of 16 (25%) lower-middle-income, 14 of 20 (70%) upper-middle-income, and 40 of 44 (91%) high-income countries had any IAP policy. The remaining 35 of 95 (37%) had no national policy (25/33 from low-income and lower-middle-income countries). Coverage varied considerably; for microbiological screening, median coverage was 80% (range, 20%-95%); for clinical risk factor-based screening, coverage was 29% (range, 10%-50%). Although there were differences in the microbiological screening methods employed, the individual clinical risk factors used were similar. There is considerable heterogeneity in IAP screening policies and coverage worldwide. Alternative global strategies, such as maternal vaccination, are needed to enhance the scope of global prevention of GBS disease.

Duration of Bisphosphonate Treatment

Large, randomized, controlled trials have demonstrated the efficacy of bisphosphonates (BP) in terms of improving bone mineral density (BMD) and reducing fracture risk. Consequently, bisphosphonates are used widely in the treatment of osteoporosis. Recently, however, several safety issues regarding the long-term use of BP, especially BP-related osteonecrosis of the jaws and atypical fractures, have been noted and have emerged as a limitation of their clinical use. Although the absolute risk is very small, the risks could increase with the long-term use of BP. The anti-fracture efficacy of BP is not sustained after treatment for 5-10 years. Therefore, recommendations suggest that a drug holiday be considered after 5 years of treatment for patients at low risk of fracture. However, as the individual fracture risk varies, the treatment duration should be based on individual clinical risk factors and bone metabolism status. Moreover, recommendations regarding monitoring after discontinuing and reinitiating BP await further studies. (Korean J Med 2014;87:151-155)

Stop Light: Mortality Risk In Adult Sickle Cell Disease and Criteria For Hematopoietic Stem Cell Transplant

▪ IntroductionThe integration of prognostic information into the clinical care of adults with sickle cell disease (SCD) assumes greater importance as more intensive therapeutic strategies are being developed, including hematopoietic stem cell transplantation (HSCT). In addition, more high-risk alternate donor options predominate in SCD, since allogeneic HSCT candidates seldom have matched sibling donors (MSD). We wanted to integrate individual clinical risk factors for death, such as white blood cell count (Platt, NEJM, 1994) or Tricuspid Regurgitant Jet Velocity (TRV), (Gladwin, NEJM, 2004) into eligibility criteria for HSCT. MethodsBaseline demographics, laboratory values, high-risk TRV (greater than 3.0 m/s), and 2-year mortality data on adults with SCD, available from the multi-centered Walk-PHaSST study (n=468 HbSS, 19 deaths), were used to estimate one- and two-variable positive predictive values (PPVs) for short-term mortality (Figure 1A). Using these data, we suggest the basis for a graded (‘stop light') HSCT eligibility schema in which patients with morbid disease and <10% 2-year mortality (green light, ‘low risk' disease) could be considered for standard-risk HSCT (e.g. reduced-intensity MSD) (Figure 1B). 10-15% mortality (yellow light, ‘moderate risk') or highly morbid disease could be considered for alternate donor transplants in which there is published experience in adults (e.g. reduced intensity haploidentical, Bolanos-Meade, Blood 2012). >15% mortality (red light, ‘high risk' disease) could be considered for high-risk alternate donor transplants (without published experience in adults, e.g. cord blood). We then applied this method for estimating HSCT eligibility to HbSS adults followed at University Hospitals Case Medical Center in Cleveland, Ohio (n=122), and contrasted this with criteria based on published recommendations (Hseih, NEJM, 2009), (STRIDE trial: http://clinicaltrials.gov/show/NCT01565616). ResultsWe developed a simple mortality-based prognostic scale with which to estimate SCD severity prior to referring for HSCT. In Walk-PHASST, multiple clinical variables contributed to high risk SCD (red boxes, Figure 1A). The Cleveland population is young (median age 28 years). Nonetheless, 23% (28 of 122) were high risk (red) patients, and 52% (64 of 122) were moderate risk (yellow) or had highly morbid disease. 12% (15 of 122) had low risk (green) SCD and morbid disease, based on our proposed ‘stop light' eligibility schema. Published eligibility criteria, which do not stratify based on SCD prognosis, identify 75-86% of adults in our center as having ≥1 indications for HSCT. [Display omitted] ConclusionsAlthough estimation of risk from transplant is evolving, we believe the proposed ‘stop light' graded eligibility may aid in the selection of appropriate patients and in risk-benefit counseling. We recognize the limitations of a scale based on a modest number of deaths. Nonetheless our simple mortality based prognostic scale is a tool with which to approach the integration of disease severity and HSCT risk in SCD.Yellow: Patients at moderate risk for 2-year (10-15%) mortality (yellow boxes, Figure 1A) or with highly morbid disease (>5 hospitalizations per year, h/o CVA, h/o silent infarct, estimated GFR <90 mL/min, macroalbuminuria, ≥2 ACS within 5 years, or sickle hepatopathy) are eligible for alternate donors with which there is published experience in adults (e.g. haploidentical as well as MSD).Green: Patients with 2-year mortality (<10%) but with morbid disease (>2 hospitalizations per year for two or more years, or acute chest within the past five years) are eligible for standard-risk HSCT (MSD only). Disclosures:No relevant conflicts of interest to declare.

Associations Between Conventional Cardiovascular Risk Factors and Risk of Peripheral Artery Disease in Men

Previous studies have examined the associations of individual clinical risk factors with risk of peripheral artery disease (PAD), but the combined effects of these risk factors are largely unknown. To estimate the degree to which the 4 conventional cardiovascular risk factors of smoking, hypertension, hypercholesterolemia, and type 2 diabetes are associated with the risk of PAD among men. Prospective study of 44,985 men in the United States without a history of cardiovascular disease at baseline in 1986; participants in the Health Professionals Follow-up Study were followed up for 25 years until January 2011. The presence of risk factors was updated biennially during follow-up. Clinically significant PAD defined as limb amputation or revascularization, angiogram reporting vascular obstruction of 50% or greater, ankle-brachial index of less than 0.90, or physician-diagnosed PAD. During a median follow-up of 24.2 years (interquartile range, 20.8-24.7 years), there were 537 cases of incident PAD. Each risk factor was significantly and independently associated with a higher risk of PAD after adjustment for the other 3 risk factors and confounders. The age-adjusted incidence rates were 9 (95% CI, 6-14) cases/100,000 person-years (n = 19 incident cases) for 0 risk factors, 23 (95% CI, 18-28) cases/100,000 person-years (n = 99 incident cases) for 1 risk factor, 47 (95% CI, 39-56) cases/100,000 person-years (n = 176 incident cases) for 2 risk factors, 92 (95% CI, 76-111) cases/100,000 person-years (n = 180 incident cases) for 3 risk factors, and 186 (95% CI, 141-246) cases/100,000 person-years (n = 63 incident cases) for 4 risk factors. The multivariable-adjusted hazard ratio for each additional risk factor was 2.06 (95% CI, 1.88-2.26). Men without any of the 4 risk factors had a hazard ratio of PAD of 0.23 (95% CI, 0.14-0.36) compared with all other men in the cohort. In 96% of PAD cases (95% CI, 94%-98%), at least 1 of the 4 risk factors was present at the time of PAD diagnosis. The population-attributable risk associated with these 4 risk factors was 75% (95% CI, 64%-87%). The absolute incidence of PAD among men with all 4 risk factors was 3.5/1000 person-years. Among men in this cohort, smoking, hypertension, hypercholesterolemia, and type 2 diabetes account for the majority of risk associated with development of clinically significant PAD.

Association of Left Atrial Fibrosis Detected by Delayed-Enhancement Magnetic Resonance Imaging and the Risk of Stroke in Patients With Atrial Fibrillation

This study tried to determine the association between left atrial (LA) fibrosis, detected using delayed-enhanced magnetic resonance imaging (DE-MRI), and the CHADS(2) score (point system based on individual clinical risk factors including congestive heart failure, hypertension, age, diabetes, and prior stroke) variables, specifically stroke. In patients with atrial fibrillation (AF), conventional markers for the risk of stroke base their higher predictive effect on clinical features, particularly previous stroke history, and not individual LA pathophysiological properties. We aimed to determine the association between LA fibrosis, detected using DE-MRI, and the CHADS(2) score variables, specifically stroke. Patients with AF who presented to the AF clinic and received a DE-MRI of the LA were evaluated. Their risk factor profiles, including a CHADS(2) score, were catalogued. The degree of LA fibrosis was determined as a percentage of the LA area. Any history of previous strokes, warfarin use, or cerebrovascular disease was recorded. A total of 387 patients, having a mean age of 65 ± 12 years, 36.8% female, were included in this study. A history of previous stroke was present in 36 (9.3%) patients. Those patients with previous strokes had a significantly higher percentage of LA fibrosis (24.4 ± 12.4% vs. 16.2 ± 9.9%, p < 0.01). A larger amount of LA fibrosis was also seen in those patients with a higher CHADS(2) score (≥ 2: 18.7 ± 11.4 vs. <2: 14.7 ± 9.2, p < 0.01). A logistic regression analysis of all variables except strokes (CHAD score) demonstrated that LA fibrosis independently predicted cerebrovascular events (p = 0.002) and significantly increased the predictive performance of the score (area under the curve = 0.77). Our preliminary, multicenter results suggest DE-MRI-based detection of LA fibrosis is independently associated with prior history of strokes. We propose that the amount of DE-MRI-determined LA fibrosis could represent a marker for stroke and a possible therapeutic target with potential applicability for clinical treatment for patients with AF.

New Treatment Approach for Osteopenia

Nearly 44 million persons in the United States have osteoporosis or osteopenia, most of whom are osteopenic. Because of sheer numbers, an increased number of fractures occur in the osteopenic group. Bone mineral density alone, based on dual energy X-ray absorptiometry scan results, is not enough to identify persons at increased risk for fracture. The World Health Organization (WHO) Working Group On Osteoporosis has developed an online tool, known as FRAX, to calculate future hip fracture probability based on individual clinical risk factors. Determining the risk of hip fracture is critical because it is the most devastating osteoporosis complication. The FRAX model was developed from population-based cohort studies in Europe, North America, Asia, and Australia. In 2008, the National Osteoporosis Foundation (NOF) adopted the WHO approach in the treatment of osteopenia. This article presents a clinical scenario to demonstrate the application of the WHO FRAX tool and the new NOF guidelines.

Gene Expression Profiling for Survival Prediction in Pediatric Rhabdomyosarcomas: A Report From the Children's Oncology Group

We investigated whether tumors from diagnostic biopsies of primary rhabdomyosarcoma (RMS) contain relevant prognostic information in the form of gene expression signatures that can be used to model and predict outcome of patients. A 22,000-probe set microarray was used to evaluate 120 RMS specimens and correlate gene expression patterns to survival. Multivariate gene expression models or metagenes were developed using cross-validated Cox regression proportional hazards modeling and were evaluated using Kaplan-Meier analysis. A 34-metagene, based on expression patterns of 34 genes, was highly predictive of outcome. It was not highly correlated with individual clinical risk factors such as patient age, stage, tumor size, or histology. However, it was correlated with a risk classification used by the Children's Oncology Group and the biologic subsets of alveolar histology tumors. These data support further evaluation of RMS metagenes to discriminate patients with good prognosis from those with poor prognosis, with the potential to direct risk-adapted therapy.

An administrative data merging solution for dealing with missing data in a clinical registry: adaptation from ICD-9 to ICD-10

BackgroundWe have previously described a method for dealing with missing data in a prospective cardiac registry initiative. The method involves merging registry data to corresponding ICD-9-CM administrative data to fill in missing data 'holes'. Here, we describe the process of translating our data merging solution to ICD-10, and then validating its performance.MethodsA multi-step translation process was undertaken to produce an ICD-10 algorithm, and merging was then implemented to produce complete datasets for 1995–2001 based on the ICD-9-CM coding algorithm, and for 2002–2005 based on the ICD-10 algorithm. We used cardiac registry data for patients undergoing cardiac catheterization in fiscal years 1995–2005. The corresponding administrative data records were coded in ICD-9-CM for 1995–2001 and in ICD-10 for 2002–2005. The resulting datasets were then evaluated for their ability to predict death at one year.ResultsThe prevalence of the individual clinical risk factors increased gradually across years. There was, however, no evidence of either an abrupt drop or rise in prevalence of any of the risk factors. The performance of the new data merging model was comparable to that of our previously reported methodology: c-statistic = 0.788 (95% CI 0.775, 0.802) for the ICD-10 model versus c-statistic = 0.784 (95% CI 0.780, 0.790) for the ICD-9-CM model. The two models also exhibited similar goodness-of-fit.ConclusionThe ICD-10 implementation of our data merging method performs as well as the previously-validated ICD-9-CM method. Such methodological research is an essential prerequisite for research with administrative data now that most health systems are transitioning to ICD-10.

Traitement substitutif de la ménopause et risque thrombotique veineux

Venous thromboemboembolism is a multigenic and a multifactorial disease. Several genetic risk factors have been identified: antithrombin, protein C and protein S deficiencies, and molecular defects in factor V gene (factor V Leiden) or factor II gene (G 20210A transition). Retrospective and prospective studies have demonstrated that hormone replacement therapy (HRT) in women is associated with a 2–3-fold increase of venous thromboembolism events. To minimize this risk, it seems desirable to carefully evaluate the individual clinical risk factors. Prescribing HRT should clearly be avoided in women with previous thromboembolic events. In case of familial thrombophilia, HRT should probably be prescribed with caution. Recent data suggest that transdermal HRT would induce a lower increase in thrombotic risk, but additional studies are needed to determine whether they can be safely used in women at risk. In each case, the net balance of risk and benefit of HRT use must consider the potential beneficial health effects, the most evident being the relief of climacteric symptoms.

Risk factors and risk assessment tools for falls in hospital in-patients: a systematic review.

To identify all published papers on risk factors and risk assessment tools for falls in hospital inpatients. To identify clinical risk assessment tools or individual clinical risk factors predictive of falls, with the ultimate aim of informing the design of effective fall prevention strategies. Systematic literature review (Cochrane methodology). Independent assessment of quality against agreed criteria. Calculation of odds ratios and 95% confidence intervals for risk factors and of sensitivity, specificity, negative and positive predictive value for risk assessment tools (with odds ratios and confidence intervals), where published data sufficient. 28 papers on risk factors were identified, with 15 excluded from further analysis. Despite the identification of 47 papers purporting to describe falls risk assessment tools, only six papers were identified where risk assessment tools had been subjected to prospective validation, and only two where validation had been performed in two or more patient cohorts. A small number of significant falls risk factors emerged consistently, despite the heterogeneity of settings namely gait instability, agitated confusion, urinary incontinence/frequency, falls history and prescription of 'culprit' drugs (especially sedative/hypnotics). Simple risk assessment tools constructed of similar variables have been shown to predict falls with sensitivity and specificity in excess of 70%, although validation in a variety of settings and in routine clinical use is lacking. Effective falls interventions in this population may require the use of better-validated risk assessment tools, or alternatively, attention to common reversible falls risk factors in all patients.

Thromboembolic complications after arthroscopic knee surgery. Incidence and risk factors in 101 patients.

Deep venous thrombosis (DVT) and pulmonary embolism (PE) are less common after knee arthroscopy than after elective hip and knee arthroplasties. There is no consensus on the optimal prophylaxis. In this prospective cohort study, we used ultrasound, phlebography and lung scan pre- and postoperatively to assess the incidence of thromboembolic complications in 101 consecutive patients who underwent knee arthroscopy. Preoperatively, patients were screened for typical risk factors for DVT such as age, obesity, varicose veins, contraceptive pills and nicotine abuse. All patients received a once-daily injection of 5000 IU of low molecular weight heparin, at least 12 hours prior to surgery. 5 weeks after surgery, the same screening tests were repeated. In 12 of the 101 patients either DVT or PE was diagnosed. DVT occurred in 8 cases, 4 of which were silent and 4 symptomatic. The number of PEs was 9, 8 silent and 1 symptomatic. We found no correlation between DVT or PE and individual clinical risk factors, but there was a tendency towards the development of DVT and PE, with a higher number of risk factors. We found no correlation between DVT and intraoperative risk factors such as use of a tourniquet, type of anesthesia or duration of surgery. The relatively high rate of thromboembolic events after knee arthroscopy in our study suggests the need of all patients for routine use of thromboprophylaxis, probably in a higher dose than given.