Head position angles to open the upper airway differ less with the head positioned on a support.

INTRODUCTION: The aim of the study was to assess the effects of positioning the head on a support on "head position angles" to optimally open the upper airway during bag-valve mask ventilation. METHODS: We ventilated the lungs of anesthetized adults with a bag-valve mask and the head positioned with (n = 30) or without a support (n = 30). In both groups, head position angles and ventilation parameters were measured with the head positioned in (1) neutral position, (2) in a position deemed optimal for ventilation by the investigator, and (3) in maximal extension. RESULTS: Between groups ("head with/without a support") and between head positions within each group, head position angles and ventilation parameters differed (P < .0001, respectively). However, head position angles and ventilation parameters between head positions differed less "with a support" (P < .001), and ventilation parameters improved with a support compared with the head-without-a-support group (P < .001). CONCLUSIONS: In the head-with-a-support group, when compared with the head-without-a-support group, head position angles differed less, indicating a decreased potential for failure during bag-valve mask ventilation with the head on a support. Moreover, in the head-with-a-support group, ventilation parameters differed less between head positions, and ventilation improved. These findings suggest a potential benefit of positioning the head on a support during bag-valve mask ventilation.

Mobile phone-assisted basic life support augmented with a metronome.

BACKGROUND: Basic life support (BLS) performed by lay rescuers is poor. We developed software for mobile phones augmented with a metronome to improve BLS. STUDY OBJECTIVES: To assess BLS in lay rescuers with or without software assistance. METHODS: Medically untrained volunteers were randomized to run through a cardiac arrest scenario with ("assisted BLS") or without ("non-assisted BLS") the aid of a BLS software program installed on a mobile phone. RESULTS: Sixty-four lay rescuers were enrolled in the "assisted BLS" and 77 in the "non-assisted BLS" group. The "assisted BLS" when compared to the "non-assisted BLS" group, achieved a higher overall score (19.2 ± 7.5 vs. 12.9 ± 5.7 credits; p < 0.001). Moreover, the "assisted BLS" when compared to the "non-assisted" group checked (64% vs. 27%) and protected themselves more often from environmental risks (70% vs. 39%); this group also called more often for help (56% vs. 27%), opened the upper airway (78% vs. 16%), and had more correct chest compressions rates (44% ± 38% vs. 14% ± 28%; all p < 0.001). However, the "assisted BLS" when compared to the "non-assisted BLS" group, was slower in calling the dispatch center (113.6 ± 86.4 vs. 54.1 ± 45.1 s; p < 0.001) and starting chest compressions (165.3 ± 93.3 vs. 87.1 ± 53.2 s; p < 0.001). CONCLUSIONS: "Assisted BLS" augmented by a metronome resulted in a higher overall score and a better chest compression rate when compared to "non-assisted BLS." However, in the "assisted BLS" group, time to call the dispatch center and to start chest compressions was longer. In both groups, lay persons did not ventilate satisfactorily during this cardiac arrest scenario.

Suctioning via the tube during endotracheal intubation in a model of severe upper airway haemorrhage: is there an advantage vs. suctioning with a separate catheter?

INTRODUCTION: In a model of severe simulated upper airway haemorrhage, we compared two techniques of performing endotracheal intubation: (1) suctioning via the endotracheal tube during laryngoscopy with subsequently advancing the endotracheal tube, and (2) the standard intubation strategy with performing laryngoscopy, and performing suction with subsequently advancing the endotracheal tube. METHODS: Forty-one emergency medical technicians intubated the trachea of a manikin with severe simulated airway haemorrhage using each technique in random order. RESULTS: There was no significant difference in the number of oesophageal intubations between suctioning via the tube and the standard intubation strategy [8/41 (20%) vs. 6/41 (15%); P = 0.688], but suctioning via the endotracheal tube needed significantly more time [median (IQR, CI 95%): 42 (20, 39-60) vs. 33 (15, 35-48)s; P = 0.015]. CONCLUSIONS: Suctioning via the endotracheal tube showed no benefit regarding the number of oesophageal intubations and needed more time when compared to the standard intubation strategy.

Antibody dynamics and spontaneous viral clearance in patients with acute hepatitis C infection in Rio de Janeiro, Brazil.

BACKGROUND: The anti-HCV antibody response has not been well characterized during the early phase of HCV infection and little is known about its relationship to the clinical course during this period. METHODS: We analyzed serial anti-HCV antibodies longitudinally obtained from a prospective cohort of 65 patients with acute HCV infection by using a microparticle enzyme immunoassay AxSYM HCV 3.0 (Abbott Diagnostics) during the first 12 months from HCV acquisition in Rio de Janeiro, Brazil. Spontaneous viral clearance (SVC) was defined as undetectable HCV RNA in serum, in the absence of treatment, for three consecutive HCV PCR tests within 12-months of follow-up. RESULTS: Baseline antibody values were similar among patient groups with self-limiting HCV evolution (n = 34) and persistent viremia (n = 31) [median (interquartile range) signal/cut-off ratio (s/co) 78.7 (60.7-93.8) vs. 93.9 (67.8-111.9), p = 0.26]. During 12-months follow-up, patients with acute spontaneous resolving HCV infection showed significantly lower serial antibody response in comparison to individuals progressing to chronic infection [median (interquartile range) s/co 62.7 (35.2-85.0) vs. 98.4 (70.4-127.4), p < 0.0001]. In addition, patients with self-limiting HCV evolution exhibited an expeditious, sharp decline of serial antibody values after SVC in comparison to those measured before SVC [median (interquartile range) s/co 56.0 (25.4-79.3) vs. 79.4 (66.3-103.0), p < 0.0001]. CONCLUSION: Our findings indicate a rapid short-term decline of antibody values in patients with acute spontaneous resolving HCV infection.

Prospective study of the association of serum gamma-glutamyltransferase with cervical intraepithelial neoplasia III and invasive cervical cancer.

Epidemiologic studies indicate that elevated levels of gamma-glutamyltransferase (GGT), a key enzyme of glutathione metabolism, might be associated with increased cancer risk. Furthermore, preclinical studies support a role for GGT in tumor invasion and progression. However, the relationship between GGT and risks of cervical intraepithelial neoplasia III (CIN-III) and invasive cervical cancer (ICC) have not been evaluated. We investigated the association of enzymatically determined GGT in blood serum with subsequent incidence of CIN-III and ICC in a prospective population-based cohort of 92,843 women ages 18 to 95, of whom 79% had at least one gynecologic examination including Pap smear testing during follow-up. Cox regression was used to compute adjusted hazard ratios (HR) with 95% confidence intervals for the association of GGT with CIN-III and ICC. During median follow-up of 13.8 years, 702 CIN-III and 117 ICC diagnoses were observed. Compared with normal low GGT (<17.99 units/L), risk of ICC was significantly elevated for all other baseline GGT categories, with adjusted HRs of 2.31 (1.49-3.59) for normal high GGT (18.00-35.99 units/L), 2.76 (1.52-5.02) for elevated GGT (36.00-71.99 units/L), and 3.38 (1.63-7.00) for highly elevated GGT [>72.00 units/L; P trend < 0.0001, HR log unit increase 3.45 (1.92-6.19)]. In contrast, associations between GGT serum levels and CIN-III risk were not statistically significant in the main analysis. Exclusion of the first 2 or 5 years of follow-up did not change the results. Effects did not differ by age, body mass index, or socioeconomic status. Our findings implicate GGT in the progression of premalignant cervical lesions to invasive cancer.

Prospective follow-up of patients with acute hepatitis C virus infection in Brazil.

BACKGROUND: The natural outcome of infection with hepatitis C virus (HCV) varies substantially among individuals. However, little is known about host and viral factors associated with a self-limiting or chronic evolution of HCV infection. METHODS: From 1 January 2001 through 31 December 2008, a consecutive series of 65 patients from Rio de Janeiro, Brazil, with a well-documented diagnosis of acute HCV infection, acquired via various routes, were enrolled in this study. Patients were prospectively followed up for a median of 40 months after the estimated date of HCV infection with serial measurements of serum alanine aminotransferase, HCV RNA, and anti-HCV antibodies. Spontaneous viral clearance (SVC) was defined as undetectable levels of HCV RNA in serum, in the absence of treatment, for 3 consecutive HCV polymerase chain reaction tests within the first 6 months of follow-up. Cox proportional hazards regression was used to identify host and viral predictors of SVC. RESULTS: The cumulative rate of SVC was 44.6% (95% confidence interval, 32.3%-57.5%). Compared with chronic HCV evolution, patients with self-limiting disease had significantly lower peak levels of anti-HCV antibodies (median, 109.0 vs 86.7 optical density-to-cutoff ratio [od/co]; P<.02), experienced disease symptoms more frequently (69.4% vs 100%; P<.001), and had lower viral load at first clinical presentation (median, 4.3 vs 0.0 log copies; P=.01). In multivariate analyses, low peak anti-HCV level (<93.5 od/co) was the only independent predictor for SVC; the hazard ratio compared with high anti-HCV levels (> or =93.5 od/co) was 2.62 (95% confidence interval, 1.11-6.19; P=.03). CONCLUSION: Our data suggest that low levels of anti-HCV antibodies during the acute phase of HCV infection are independently related to spontaneous viral clearance.

Gender differences in the accuracy of time-dependent blood pressure indices for predicting coronary heart disease: A random-effects modeling approach.

BACKGROUND: Previous studies on blood pressure (BP) indices as a predictor of coronary heart disease (CHD) have provided equivocal results and generally relied on Cox proportional hazards regression methodology, with age and sex accounting for most of the predictive capability of the model. OBJECTIVE: The aim of the present study was to use serially collected BP measurements to examine age-and gender-related differences in BP indices for predicting CHD. METHODS: The predictive accuracy of time-dependent BP indices for CHD was investigated using a method of risk prediction based on posterior probabilities calculated from mixed-effects regression to utilize intraindividual differences in serial BP measurements according to age changes within gender groups. Data were collected prospectively from 2 community-dwelling cohort studies in the United States (Baltimore Longitudinal Study of Aging [BLSA]) and Europe (Vorarlberg Health Monitoring and Promotion Program [VHM&PP]). RESULTS: The study comprised 152,633 participants (aged 30-74 years) and 610,061 BP measurements. During mean follow-up of 7.5 years, 2457 nonfatal and fatal CHD events were observed. In both study populations, pulse pressure (PP) and systolic blood pressure (SBP) performed best as individual predictors of CHD in women (area under the receiver operating characteristic curve [AUC(ROC)] was between 0.83 and 0.85 for PP, and between 0.77 and 0.81 for SBP). Mean arterial pressure (MAP) and diastolic blood pressure (DBP) performed better for men (AUC(ROC) = 0.67 and 0.65 for MAP and DBP, respectively, in the BLSA; AUC(ROC) = 0.77 and 0.75 in the VHM&PP) than for women (AUC(ROC) = 0.60 for both MAP and DBP in the BLSA; AUC(ROC) = 0.75 and 0.52, respectively, in the VHM&PP). The degree of discrimination in both populations was overall greater but more varied for all BP indices for women (AUC(ROC) estimates between 0.85 [PP in the VHM&PP] and 0.52 [DBP in the VHM&PP]) than for men (AUC(ROC) estimates between 0.78 [MAP + PP in the VHM&PP] and 0.63 [PP in the BLSA]). CONCLUSION: Our findings indicate differences in discrimination between women and men in the accuracy of longitudinally collected BP measurements for predicting CHD, implicating the usefulness of gender-specific BP indices to assess individual CHD risk.

A suction laryngoscope facilitates intubation for physicians with occasional emergency medical service experience--a manikin study with severe simulated airway haemorrhage.

INTRODUCTION: We developed a suction laryngoscope, which enables simultaneous suction and laryngoscopy in cases of airway haemorrhage and evaluated its potential benefits in physicians with varying emergency medical service experience. METHODS: Eighteen physicians with regular and 24 physicians with occasional emergency medical service experience intubated the trachea of a manikin with severe simulated airway haemorrhage using the suction laryngoscope and the Macintosh laryngoscope in random order. RESULTS: In physicians with regular emergency medical service experience, there was neither a difference in time needed for intubation [median (IQR, CI 95%)]: 34 (18, 30-46) vs. 34 (22, 30-52) s; P=0.52, nor in the number of oesophageal intubations [0/18 (0%) vs. 3/18 (16.7%); P=NS] when using the suction vs. the Macintosh laryngoscope. In physicians with occasional emergency medical service experience, there was no difference in time needed for intubation [median (IQR, CI 95%)]: 42 (25, 41-57) vs. 45 (33, 41-65) s; P=0.56, but the number of oesophageal intubations was significantly lower when using the suction laryngoscope [4/24 (16.7%) vs. 12/24 (50.0%); P=0.04]. CONCLUSIONS: In a model of severe simulated airway haemorrhage, employing a suction laryngoscope significantly decreased the likelihood of oesophageal intubations in physicians with occasional emergency medical service experience.

Use of penalized splines in extended Cox-type additive hazard regression to flexibly estimate the effect of time-varying serum uric acid on risk of cancer incidence: a prospective, population-based study in 78,850 men.

PURPOSE: We sought to investigate the effect of serum uric acid (SUA) levels on risk of cancer incidence in men and to flexibly determine the shape of this association by using a novel analytical approach. METHODS: A population-based cohort of 78,850 Austrian men who received 264,347 serial SUA measurements was prospectively followed-up for a median of 12.4 years. Data were collected between 1985 and 2003. Penalized splines (P-splines) in extended Cox-type additive hazard regression were used to flexibly model the association between SUA, as a time-dependent covariate, and risk of overall and site-specific cancer incidence and to calculate adjusted hazard ratios with their 95% confidence intervals. RESULTS: During follow-up 5189 incident cancers were observed. Restricted maximum-likelihood optimizing P-spline models revealed a moderately J-shaped effect of SUA on risk of overall cancer incidence, with statistically significantly increased hazard ratios in the upper third of the SUA distribution. Increased SUA (>/=8.00 mg/dL) further significantly increased risk for several site-specific malignancies, with P-spline analyses providing detailed insight about the shape of the association with these outcomes. CONCLUSIONS: Our study is the first to demonstrate a dose-response association between SUA and cancer incidence in men, simultaneously reporting on the usefulness of a novel methodological framework in epidemiologic research.

Prospective study of the association of gamma-glutamyltransferase with cancer incidence in women.

Although several epidemiologic studies have shown that gamma-glutamyltransferase (GGT) is associated with cardiovascular disease and all-cause mortality, its relationship with cancer incidence remains widely unexplored. In experimental models the ability of cellular GGT to modulate crucial redox-sensitive functions has been established, and it may thus play a role in tumor progression. In the present study, we investigated the association of GGT with overall and site-specific cancer incidence in a population-based cohort of 92,843 Austrian women with 349,674 serial GGT measurements, prospectively followed-up for a median of 13.5 years. The relationship between GGT and cancer incidence was analyzed using adjusted Cox regression models with age as underlying time metric with age as underlying time metric including GGT concentrations at baseline and incorporating repeated GGT measurements as a time-dependent variable. During follow-up, 4,884 incidence cancers were observed. Compared to normal low GGT (<17.99 U/L), cancer risk was elevated for all other GGT categories (p for trend < 0.0001), with adjusted hazard ratios (95% confidence intervals) of 1.06 (0.99-1.13) for GGT levels between 18.00 and 35.99 U/L (normal high), 1.12 (1.02-1.22) for GGT levels between 36.00 and 71.99 U/L (elevated) and 1.43 (1.28-1.61) for highly elevated GGT (>72.00 U/L). Very similar results were seen when GGT was analyzed as a time-dependent variable. In cancer-site specific models, elevated GGT statistically significantly increased the risk for malignant neoplasms of digestive organs, the respiratory system/intrathoracic organs, breast and female genital organs and lymphoid and haematopoietic cancers (all, p < 0.006). Our study is the first to demonstrate in a large population-based cohort that high GGT levels significantly increased cancer risk in women.

A set of SAS macros for calculating and displaying adjusted odds ratios (with confidence intervals) for continuous covariates in logistic B-spline regression models.

In clinical and epidemiologic research to investigate dose-response associations, non-parametric spline regression has long been proposed as a powerful alternative to conventional parametric regression approaches, since no underlying assumptions of linearity have to be fulfilled. For logistic spline models, however, to date, little standard statistical software is available to estimate any measure of risk, typically of interest when quantifying the effects of one or more continuous explanatory variable(s) on a binary disease outcome. In the present paper, we propose a set of SAS macros which perform non-parametric logistic regression analysis with B-spline expansions of an arbitrary number of continuous covariates, estimating adjusted odds ratios with respective confidence intervals for any given value with respect to a supplied reference value. Our SAS codes further allow to graphically visualize the shape of the association, retaining the exposure variable under consideration in its initial, continuous form while concurrently adjusting for multiple confounding factors. The macros are easily to use and can be implemented quickly by the clinical or epidemiological researcher to flexibly investigate any dose-response association of continuous exposures with the risk of binary disease outcomes. We illustrate the application of our SAS codes by investigating the effect of body-mass index on risk of cancer incidence in a large, population-based male cohort.

Longitudinal change in serum gamma-glutamyltransferase and cardiovascular disease mortality: a prospective population-based study in 76,113 Austrian adults.

OBJECTIVE: The purpose of this study was to investigate the association of longitudinal change in serum gamma-glutamyltransferase (GGT) with mortality from cardiovascular disease (CVD). METHODS AND RESULTS: A population-based cohort of 76,113 Austrian men and women with 455,331 serial GGT measurements was prospectively followed-up for a median of 10.2 years after assessment of longitudinal GGT change during an average period of 6.9 years. Cox proportional hazards regression with time-varying covariates was used to evaluate GGT change as an independent predictor for CVD death. Independently of baseline GGT and other classical CVD risk factors, a pronounced increase in GGT (7-year change >9.2 U/L) was significantly associated with increased total CVD mortality in men (P=0.005); the adjusted hazard ratio (95% confidence interval) in comparison to stable GGT (7-year change -0.7 to 1.3 U/L) was 1.40 (1.09 to 1.81). Similarly, total CVD risk was elevated for increasing GGT in women, although effects were less pronounced and statistically significant only in subanalyses regarding coronary heart disease. Age of participants significantly modified the relation between GGT change and CVD mortality, with markedly stronger associations to be observable for younger individuals. CONCLUSIONS: Our study is the first to demonstrate that a longitudinal increase in GGT, independently of baseline GGT and even within its normal range, significantly increases risk of fatal CVD.

Premature aging of the immune system in children with juvenile idiopathic arthritis.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is an autoimmune disease of the young. The pathogenesis is not completely understood. Premature aging, associated thymic involution, and compensatory autoproliferation could play important roles in the pathogenesis of autoimmunity. We undertook this study to determine whether patients with JIA demonstrate premature immunosenescence. METHODS: To test this hypothesis, we measured 3 indicators of aging: the percentages and total counts of peripheral blood naive T cells, the frequency of T cell receptor excision circles (TRECs) in naive T cells, and telomeric erosion and Ki-67 expression as estimates of the replicative history of homeostatic proliferation. RESULTS: JIA patients showed an accelerated loss of CD4+,CD45RA+,CD62L+ naive T cells with advancing age and a compensatory increase in the number of CD4+,CD45RO+ memory T cells. JIA patients demonstrated a significantly decreased frequency of TRECs in CD4+,CD45RA+ naive T cells compared with age-matched healthy donors (P = 0.002). TREC numbers correlated with age only in healthy donors (P = 0.0001). Telomeric erosion in CD4+,CD45RA+ naive T cells was increased in JIA patients (P = 0.01). The percentages of Ki-67-positive CD4+,CD45RA+ naive T cells were increased in JIA patients (P = 0.001) and correlated with disease duration (P = 0.003), which was also an independent factor contributing to telomeric erosion (P = 0.04). CONCLUSION: Our findings suggest that age-inappropriate T cell senescence and disturbed T cell homeostasis may contribute to the development of JIA. In patients with JIA, dysfunction in the ability to reconstitute the T cell compartment should be considered when exploring new therapeutic strategies.

Association of gamma-glutamyltransferase and risk of cancer incidence in men: a prospective study.

Although several epidemiologic studies have shown that gamma-glutamyltransferase (GGT) is independently associated with cardiovascular disease and all-cause mortality, its relationship with cancer incidence remains widely unexplored. In several experimental models, the ability of cellular GGT to modulate crucial redox-sensitive functions has been established, and it thus may play a role in tumor progression, as has been repeatedly suggested. We prospectively investigated the association between GGT and risk of overall and site-specific cancer incidence in a large population-based cohort of 79,279 healthy Austrian men with serial GGT measurements. Median follow-up was 12.5 years. Adjusted Cox proportional hazards models were calculated to evaluate GGT as an independent predictor for cancer incidence, and nonparametric regression splines were fitted to flexibly capture the dose-response relationship. Elevated GGT significantly increased overall cancer risk, showing a clear dose-response relationship (P for GGT log-unit increase < 0.0001; P for trend < 0.0001). In comparison with the reference GGT concentration (25 units/L), we found adjusted relative risks (95% confidence intervals) equalling 1.19 (1.15-1.22) for GGT concentrations of 60 units/L, 1.32 (1.28-1.36) for 100 units/L, 1.67 (1.60-1.75) for 200 units/L, and 2.30 (2.14-2.47) for 400 units/L. In cancer site-specific models, GGT was significantly associated with malignant neoplasms of digestive organs, the respiratory system/intrathoracic organs, and urinary organs (all P < 0.0001). Age of participants significantly modified the association of GGT and cancer risk (P < 0.001), revealing markedly stronger associations in participants ages

Prognostic value of admission C-reactive protein in stroke patients undergoing iv thrombolysis.

OBJECTIVE: To test the hypothesis that pre-treatment Creactive protein (CRP) predicts outcome in stroke patients undergoing intravenous thrombolysis (IVT) treatment. METHODS: We analyzed the data of 111 consecutive patients with IVT within 6 hours of stroke onset for stroke involving the middle cerebral artery territory and admission CRP < or = 6 mg/dl. RESULTS: CRP levels were consistently, yet non-significantly lower in patients with unfavourable outcome definitions. Median (range) CRP levels were 0.3 (0-5.9) mg/dl vs. 0.4 (0-5.7) mg/dl (p = 0.13) in patients dependent or dead after 3 months (modified Rankin Scale score > 2; n = 59) vs. independent patients (n = 52); 0.2 (0.1-1.5) mg/dl vs. 0.4 (0-5.9) mg/dl (p = 0.28) in patients dead after 3 months (n = 14) versus survivors (n = 97); and 0.2 (0.1-0.7) mg/dl vs. 0.4 (0-5.9) mg/dl (p = 0.09) in patients with significant neurological deterioration within 24 hours (increase in > or = 4 points on National Institute of Health Stroke scale; n = 9) vs. patients without early deterioration (n = 102). Independent predictors of dependency/death after 3 months, identified by multivariate logistic regression analyses, were baseline NIHSS score (OR = 1.31, 95 % CI 1.16-1.48, p < 0.001), time from onset to treatment (OR = 1.01, 95 % CI 1.0-1.02, p = 0.024), and presence of diabetes (OR = 8.16, 95 % CI 1.18-56.5, p = 0.033). CONCLUSION: Pre-treatment CRP clearly failed to predict outcome in stroke patients treated with IVT. Our findings contradict previously published work and highlight the need for further research on this topic.

Serum uric acid is an independent predictor for all major forms of cardiovascular death in 28,613 elderly women: a prospective 21-year follow-up study.

BACKGROUND: The role of serum uric acid (SUA) as a risk factor for cardiovascular disease (CVD) remains controversial. Little is known about its predictive value for mortality from congestive heart failure (CHF) and stroke, particularly in elderly, post-menopausal women. METHODS: The relation of SUA to risk of death from total CVD, CHF, stroke and coronary heart disease (CHD) was examined prospectively in a large cohort of 28613 elderly Austrian women (mean age 62.3 years), followed-up for a median of 15.2 years. Adjusted Cox proportional hazards models were calculated to evaluate SUA as an independent predictor for fatal CVD events. RESULTS: SUA in the highest quartile (>or=5.41 mg/dL) was significantly associated with mortality from total CVD (p<0.0001), showing a clear dose-response relationship; the adjusted hazard ratio (95%CI) in comparison to the lowest SUA quartile was 1.35 (1.20-1.52). In subgroup analyses SUA was independently predictive for deaths from acute and subacute (p<0.0001) and chronic forms (p=0.035) of CHD, yielding adjusted hazard ratios for the highest versus lowest SUA quartile of 1.58 (1.19-2.10) and 1.25 (1.01-1.56), respectively. SUA was further significantly related to fatal CHF (p<0.0001) and stroke (p=0.018); the adjusted hazard ratios for the highest versus lowest SUA quartile were 1.50 (1.04-2.17) and 1.37 (1.09-1.74), respectively. CONCLUSIONS: These findings, for the first time, demonstrate that SUA is an independent predictor for all major forms of death from CVD including acute, subacute and chronic forms of CHD, CHF and stroke in elderly, post-menopausal women.

Comparison of low-molecular-weight heparin and antithrombin versus antithrombin alone for the prevention of symptomatic venous thromboembolism in children with acute lymphoblastic leukemia.

BACKGROUND: Children with acute lymphoblastic leukemia (ALL) have a substantial risk for thromboembolism (TE) that is related to L-asparaginase-induced antithrombin (AT) deficiency and placement of central venous lines. Recent in vitro studies showed that the anticoagulant effects of low-molecular-weight heparin were profoundly affected by endogenous AT levels in children undergoing ALL therapy. METHODS: A total of 112 consecutively recruited children with newly diagnosed ALL treated according to BFM 95/2000 protocols were enrolled in this trial. This prospective cohort study was carried out to determine the influence of combined low molecular weight heparin-prophylaxis (enoxaparin 1 mg/kg/ per day) and AT supplementation versus AT alone (noncontemporaneous control group) on the incidence of symptomatic TE during a follow-up of 240 days. RESULTS: To maintain AT plasma levels above 50%, nearly 60% of all children needed at least one, most children two or three AT supplementations during induction therapy. 12.7% of the children that did receive only AT-prophylaxis (n = 71) (95% CI = 6.0-22.7) developed objectively confirmed symptomatic TE, as compared with no TE in children after combined prophylaxis (n = 41) (95% CI = 0.0-8.6, P < 0.05). Thromboses were located in the sinovenous system in the brain (n = 3), the lower deep veins (n = 3), the upper deep veins (n = 2) and in an upper deep vein combined with pulmonary embolism (n = 1). CONCLUSION: Prophylaxis with enoxaparin was safe and effective in preventing TE. Although our data are encouraging, the in vivo efficacy of combined enoxaparin and AT prophylaxis to prevent symptomatic venous TE in children with ALL should be evaluated in a prospective randomized clinical trial.

Serum uric acid and risk of cancer mortality in a large prospective male cohort.

OBJECTIVE: To examine the prognostic role of serum uric acid (SUA) for cancer mortality in apparently healthy men across a wide age range. METHODS: Prospective data from a large cohort of 83,683 male Austrian adults with a median follow-up of 13.6 years was analyzed. Cox proportional hazards models, adjusted for established risk factors, were calculated to evaluate SUA as a predictive marker for fatal cancer events. RESULTS: High SUA (>6.71 mg/dl) was independently associated with increased risk of mortality from all cancers, showing a clear dose-response relationship (p for trend < 0.0001); the adjusted hazard ratio for the highest versus lowest quintile of SUA was 1.41 (1.22-1.62). In subgroup analyses this hazard ratio increased to 1.53 (1.29-1.80) for participants aged <65 years. When considering the time interval between baseline SUA measurement and subsequent death, SUA levels were more predictive for "late deaths", occurring 10 or more years after screening (HR 1.65 [1.35-2.03], p < 0.0001), in comparison to deaths within 10 years after SUA measurement. In cancer site-specific analyses, SUA was significantly associated with deaths from malignant neoplasms of digestive organs (p = 0.03) and respiratory system and intrathoracic organs (p < 0.0001). Elevated SUA was further independently related to an increased risk of all-cause mortality (p < 0.0001). CONCLUSIONS: Our results are contrary to the proposed antioxidant, inhibitory effect of SUA against cancer and rather suggest high SUA to be a valuable long-term surrogate parameter, indicative for a life-style at increased risk for the development of cancer.

Statistical errors in medical research - a review of common pitfalls.

BACKGROUND: Standards in the use of statistics in medical research are generally low. A growing body of literature points to persistent statistical errors, flaws and deficiencies in most medical journals. METHODS: In this paper we present a comprehensive review of common statistical pitfalls which can occur at different stages in the scientific research process, ranging from planning a study, through conducting statistical data analysis and documenting statistical methods applied, to the presentation of study data and interpretation of study results. RESULTS: 47 potential statistical errors and shortcomings, differentiated for the distinct phases of medical research are presented and discussed. CONCLUSIONS: Statisticians should be involved early in study design, as mistakes at this point can have major repercussions, negatively affecting all subsequent stages of medical research. Consideration of issues discussed in this paper, when planning, conducting and preparing medical research manuscripts, should help further enhance statistical quality in medical journals.