Predicting perceived vulnerability for breast cancer among women with an average breast cancer risk

OBJECTIVES: The purpose of the present study was to investigate predictors of perceived vulnerability for breast cancer in women with an average risk for breast cancer. On the basis of empirical findings that suggested which variables might be associated with perceived vulnerability for breast cancer, we investigated whether knowledge of breast cancer risk factors, cancer worry, intrusions about breast cancer, optimism about not getting cancer and perceived health status have a predictive value for perceived breast cancer vulnerability. DESIGN: In a 3-step approach, we recruited 292 women from the general public in Germany who had neither a family history of breast cancer nor breast cancer themselves. After receiving an initial informational letter about study objectives, the women were interviewed by telephone and then asked to fill in a self-administered questionnaire. METHODS: We used structural equation modelling and hypothesized that each of the included variables has a direct influence on perceived vulnerability for breast cancer. RESULTS: We found a valid model with acceptable fit indices. Optimism about not getting cancer, intrusions about breast cancer and women's perceived health status explained 32% of the variance of perceived vulnerability for breast cancer. Cancer worry and knowledge about breast cancer did not influence perceived vulnerability for breast cancer. CONCLUSION: Perceived vulnerability for breast cancer is associated with health-related variables more than with knowledge about breast cancer risk factors.

First trimester markers for pre-eclampsia: placental vs. non-placental protein serum levels

BACKGROUND/AIM: Parallel investigation, in a matched case-control study, of the association of different first-trimester markers with the risk of subsequent pre-eclampsia (PE). METHOD: The levels of different first trimester serum markers and fetal nuchal translucency thickness were compared between 52 cases of PE and 104 control women by non-parametric two-group comparisons and by calculating matched odds ratios. RESULTS: In univariable analysis increased concentrations of inhibin A and activin A were associated with subsequent PE (p < 0.02). Multivariable conditional logistic regression models revealed an association between increased risk of PE and increased inhibin A and translucency thickness and respectively reduced pregnancy-associated plasma protein A (PAPP-A) and placental lactogen . However, these associations varied with the gestational age at sample collection. For blood samples taken in pregnancy weeks 12 and 13 only, increased levels of activin A, inhibin A and nuchal translucency thickness, and lower levels of placenta growth factor and PAPP-A were associated with an increased risk of PE. CONCLUSIONS: Members of the inhibin family and to some extent PAPP-A and placental growth factor are superior to other serum markers, and the predictive value of these depends on the gestational age at blood sampling. The availability of a single, early pregnancy 'miracle' serum marker for PE risk assessment seems unlikely in the near future.

Choosing Smoothness Parameters for Smoothing Splines by Minimizing and Estimate of Risk

Smoothing splines are a popular approach for non-parametric regression problems. We use periodic smoothing splines to fit a periodic signal plus noise model to data for which we assume there are underlying circadian patterns. In the smoothing spline methodology, choosing an appropriate smoothness parameter is an important step in practice. In this paper, we draw a connection between smoothing splines and REACT estimators that provides motivation for the creation of criteria for choosing the smoothness parameter. The new criteria are compared to three existing methods, namely cross-validation, generalized cross-validation, and generalization of maximum likelihood criteria, by a Monte Carlo simulation and by an application to the study of circadian patterns. For most of the situations presented in the simulations, including the practical example, the new criteria out-perform the three existing criteria.

Multicentre study on peri- and postoperative central venous oxygen saturation in high-risk surgical patients

Introduction Low central venous oxygen saturation (ScvO2) has been associated with increased risk of postoperative complications in high-risk surgery. Whether this association is centre-specific or more generalisable is not known. The aim of this study was to assess the association between peri- and postoperative ScvO2 and outcome in high-risk surgical patients in a multicentre setting. Methods Three large European university hospitals (two in Finland, one in Switzerland) participated. In 60 patients with intra-abdominal surgery lasting more than 90 minutes, the presence of at least two of Shoemaker's criteria, and ASA (American Society of Anesthesiologists) class greater than 2, ScvO2 was determined preoperatively and at two hour intervals during the operation until 12 hours postoperatively. Hospital length of stay (LOS) mortality, and predefined postoperative complications were recorded. Results The age of the patients was 72 ± 10 years (mean ± standard deviation), and simplified acute physiology score (SAPS II) was 32 ± 12. Hospital LOS was 10.5 (8 to 14) days, and 28-day hospital mortality was 10.0%. Preoperative ScvO2 decreased from 77% ± 10% to 70% ± 11% (p < 0.001) immediately after surgery and remained unchanged 12 hours later. A total of 67 postoperative complications were recorded in 32 patients. After multivariate analysis, mean ScvO2 value (odds ratio [OR] 1.23 [95% confidence interval (CI) 1.01 to 1.50], p = 0.037), hospital LOS (OR 0.75 [95% CI 0.59 to 0.94], p = 0.012), and SAPS II (OR 0.90 [95% CI 0.82 to 0.99], p = 0.029) were independently associated with postoperative complications. The optimal value of mean ScvO2 to discriminate between patients who did or did not develop complications was 73% (sensitivity 72%, specificity 61%). Conclusion Low ScvO2 perioperatively is related to increased risk of postoperative complications in high-risk surgery. This warrants trials with goal-directed therapy using ScvO2 as a target in high-risk surgery patients.

A coronary heart disease risk model for predicting the effect of potent antiretroviral therapy in HIV-1 infected men

BACKGROUND: Many HIV-infected patients on highly active antiretroviral therapy (HAART) experience metabolic complications including dyslipidaemia and insulin resistance, which may increase their coronary heart disease (CHD) risk. We developed a prognostic model for CHD tailored to the changes in risk factors observed in patients starting HAART. METHODS: Data from five cohort studies (British Regional Heart Study, Caerphilly and Speedwell Studies, Framingham Offspring Study, Whitehall II) on 13,100 men aged 40-70 and 114,443 years of follow up were used. CHD was defined as myocardial infarction or death from CHD. Model fit was assessed using the Akaike Information Criterion; generalizability across cohorts was examined using internal-external cross-validation. RESULTS: A parametric model based on the Gompertz distribution generalized best. Variables included in the model were systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, triglyceride, glucose, diabetes mellitus, body mass index and smoking status. Compared with patients not on HAART, the estimated CHD hazard ratio (HR) for patients on HAART was 1.46 (95% CI 1.15-1.86) for moderate and 2.48 (95% CI 1.76-3.51) for severe metabolic complications. CONCLUSIONS: The change in the risk of CHD in HIV-infected men starting HAART can be estimated based on typical changes in risk factors, assuming that HRs estimated using data from non-infected men are applicable to HIV-infected men. Based on this model the risk of CHD is likely to increase, but increases may often be modest, and could be offset by lifestyle changes.

Hypothetical mortality risk associated with spiral tomography of the maxilla and mandible prior to endosseous implant treatment

Radiation dose delivered from the SCANORA radiography unit during the cross-sectional mode for dentotangential projections was determined. With regard to oral implantology, patient situations of an edentulous maxilla and mandible as well as a single tooth gap in regions 16 and 46 were simulated. Radiation doses were measured between 0.2 and 22.5 mGy to organs and tissues in the head and neck region when the complete maxilla or mandible was examined. When examining a single tooth gap, only 8% to 40% of that radiation dose was generally observed. Based on these results, the mortality risk was estimated according to a calculation model recommended by the Committee on the Biological Effects of Ionizing Radiations. The mortality risk ranged from 31.4 x 10(-6) for 20-year-old men to 4.8 x 10(-6) for 65-year-old women when cross-sectional imaging of the complete maxilla was performed. The values decreased by 70% when a single tooth gap in the molar region of the maxilla was radiographed. The figures for the mortality risk for examinations of the complete mandible were similar to those for the complete maxilla, but the mortality risk decreased by 80% if only a single tooth gap in the molar region of the mandible was examined. Calculations according to the International Commission on Radiological Protection carried out for comparison did not reveal the decrease of the mortality risk with age and resulted in a higher risk value in comparison to the group of 35-year old individuals in calculations according to the Committee on the Biological Effects of Ionizing Radiations.

The value of conservative treatment in ruptures of the anterior cruciate ligament (ACL)

BACKGROUND: Thirty-eight of the 73 consecutive acute ruptures of the anterior cruciate ligament (ACL) proven by a magnetic resonance imaging scan (MRI) in skeletally mature patients (16-55 years old) were classified as suitable for primarily conservative treatment. Patient selection was performed using a preoperative screening protocol based on the structural damage, clinical symptoms, compliance, sportive activity, and the consent of a well-informed patient. METHODS: In 12 of the 38 treated patients, the conservative protocol showed a good to very good outcome, 2 patients had persistent giving-way and were considering ACL reconstruction, 14 patients had a secondary ACL reconstruction in our clinic (average 5.3 months after injury), 9 patients were operated on in other hospitals (average 13.3 months after injury), and 1 patient was lost to follow-up. RESULTS: All patients with successful conservative treatment were able to perform low-risk pivoting sports and two patients are practicing high-risk pivoting sports. The average International Knee Documentation Committee (IKDC) score was 92.5 (82.8-98.9); the subjective overall knee function was 93% (60% to 100%). Of the 12 patients with good and very good results, 6 continued playing the same sports at an unreduced intensity, 4 patients reduced their activities slightly, and 1 patient played more sports than before. CONCLUSIONS: Although the authors performed a preoperative screening to select patients suitable for conservative treatment, almost two-thirds of the primarily conservatively treated ACL ruptures needed an operative reconstruction in the long term. In one-third of the patients, conservative treatment led to a good or very good result. At the endpoint of the study only 12 (16%) of a total of 73 patients with acute injuries of the ACL had successful conservative treatment. Therefore, patients must be comprehensively instructed about the treatment program and the chances of success of conservative ACL treatment.

Predictive value of known and novel alleles of CYP2B6 for efavirenz plasma concentrations in HIV-infected individuals

To assess the association of CYP2B6 allelic diversity with efavirenz (EFV) pharmacokinetics, we performed extensive genotyping of 15 relevant single nucleotide polymorphism in 169 study participants, and full resequencing of CYP2B6 in individuals with abnormal EFV plasma levels. Seventy-seven (45.5%) individuals carried a known (CYP2B6*6, *11, *15, or *18) or new loss/diminished-function alleles. Resequencing defined two new loss-of-function alleles: allele *27 (marked by 593T>C [M198T]), that results in 85% decrease in enzyme activity and allele *28 (marked by 1132C>T), that results in protein truncation at arginine 378. Median AUC levels were 188.5 microg h/ml for individuals homozygous for a loss/diminished-function allele, 58.6 microg h/ml for carriers, and 43.7 microg h/ml for noncarriers (P<0.0001). Individuals with a poor metabolizer genotype had a likelihood ratio of 35 (95% CI, 11-110) of presenting very high EFV plasma levels. CYP2B6 poor metabolizer genotypes explain to a large extent EFV pharmacokinetics and identify individuals at risk of extremely elevated EFV plasma levels.

Early prognostic value of the medical emergency team calling criteria in patients admitted to intensive care from the emergency department

OBJECTIVES: To evaluate the early prognostic value of the medical emergency team (MET) calling criteria in patients admitted to intensive care from the emergency department. DESIGN: Retrospective cohort study. SETTING: Emergency department and department of intensive care medicine of a 960-bed tertiary referral hospital. PATIENTS: A total of 452 consecutive adult patients admitted to intensive care from the emergency department from January 1, 2004, to December 31, 2004. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: MET calling criteria were retrospectively extracted from patient records, and the sum of positive criteria was calculated for the first hour in the emergency department (METinitial) and subsequently until admission to the intensive care unit in a series of time periods. The maximum number of positive MET calling criteria during any time period was defined (METmax). Logistic regression analysis revealed METinitial (odds ratio [OR] 3.392, 95% confidence interval [CI] 2.534-4.540) and METmax (OR 3.867, 95% CI 2.816-5.312) to be significant predictors of hospital mortality, the need for mechanical ventilation (METinitial: OR 4.151, 95% CI 3.53-4.652; METmax: OR 4.292, 95% CI 3.151-5.846), and occurrence of hemodynamic instability (METinitial: OR 1.548, 95% CI 1.258-1.905; METmax: OR 1.685, 95% CI 1.355-2.094) (all p < .0001). CONCLUSIONS: MET scores collected early after admission or throughout the stay in the emergency department allow for simple identification of patients at risk of unfavorable outcome during the subsequent intensive care unit stay.

Blood donor screening: how to decrease the risk of transfusion-transmitted hepatitis B virus?

QUESTIONS UNDER STUDY: The risk of transfusion-transmitted HBV remains significant in Switzerland, where routine screening for hepatitis B virus (HBV) in blood donations relies solely on serological hepatitis B surface antigen (HBsAg) testing. This study was designed to determine the prevalence of anti-hepatitis B core (anti-HBc) and HBV nucleic acid testing (NAT) positive donations in two different Swiss donor populations, to help in deciding whether supplemental testing may bring additional safety to blood products. METHODS: In a first population of donors, 18143 consecutive donations were screened initially for HBsAg, anti-HBc (with one EIA assay) and with HBV NAT in minipools of 24 donations. The screening repeatedly reactive anti-HBc donations were then "confirmed" with two supplemental anti-HBc assays, an anti-hepatitis B surface assay (anti-HBs) and with single donation HBV NAT. In a second population of donors, 4186 consecutive donations were screened initially with two different anti-HBc assays in addition to the mandatory HBsAg screening test. The screening repeatedly reactive donations with at least one anti-HBc assay were tested for anti-HBs. RESULTS: In the first subset of 18143 donations, 17593 (97.0%) were negative for HBsAg, anti-HBc and HBV NAT in minipools. 549 (3.0%) were HBsAg and HBV NAT negative, but repeatedly reactive for anti-HBc. Of these 549 donations, 287 could not be "confirmed" with two additional anti-HBc assays and were negative with an anti-HBs assay, as well as with single donation HBV NAT. Only 211 (1.2% of the total screened donations) were "confirmed" positive with at least one of two supplemental anti-HBc assays. One repeatedly reactive HBsAg donation, from a first-time donor, was confirmed positive for HBsAg and anti-HBc, as well as with single donation HBV NAT. In the second subset of 4186 donations, 4014 (95.9%) were screened negative for HBsAg and for anti-HBc, tested with two independent anti-HBc assays. 172 donations (4.1%) were HBsAg negative but repeatedly reactive with at least one of the two anti-HBc assays. Of these 172 samples, 86 were reactive with the first anti-HBc assay only, 13 were reactive with the second anti-HBc assay only and 73 (1.7% of the total screened donations) were "confirmed" positive with both anti-HBc assays. CONCLUSION: The prevalence of anti-HBc "confirmed" positive donations in the two Swiss blood donor populations studied was low (<2%) and we found only one HBV NAT positive (HBsAg positive) donation among more than 18000. Concerning blood product safety, an increase in the deferral rate of less than 2% of anti-HBc positive, potentially infectious donors, would in our opinion make routine anti-HBc testing of blood donations cost-effective. There is however still a need for more specific assays to avoid an unacceptably high deferral rate of "false" positive donors. In contrast, the introduction of HBV NAT in minipools gives minimal benefit due to the inadequate sensitivity of the assay. It remains to evaluate more extensively the value of individual donation NAT, alone or in addition to anti-HBc, as supplemental testing in the context of several Swiss blood donor populations.

Prognostic value of early exercise testing after coronary stent implantation

The clinical value of early exercise stress testing (EST) after coronary stenting to predict long-term clinical outcomes is unknown. Of 1,000 unselected patients who underwent coronary stenting, 446 random patients underwent early EST the day after intervention. Clinical long-term outcomes (41 +/- 20 months) were correlated with normal (n = 314 [70%]) or positive (n = 102 [23%]) EST results. Patients with inconclusive test results (n = 30 [7%]) were excluded from the analysis. Overall mortality was significantly higher in patients with positive EST results (9.3% vs 3.9%, p = 0.04). Major adverse cardiac events and cardiac mortality also tended to be higher in patients with positive stress test results (45.4% vs 35.4%, p = 0.08, and 4.1% vs 1.1%, p = 0.05, respectively). Patients with the combination of positive stress test results and incomplete revascularization appeared to be the group at highest risk for major adverse cardiac events (47.1% vs 33.3% for patients with normal stress test results and complete revascularization, p = NS). Negative stress test results reduced (odds ratio 0.329, 95% confidence interval 0.120 to 0.905, p = 0.031) and a lower ejection fraction increased (odds ratio 0.942, 95% confidence interval 0.897 to 0.989, p = 0.017) the risk for death. In conclusion, an early stress test after coronary stenting provides important prognostic information. Positive stress test results, especially in combination with incomplete revascularization, are associated with higher mortality, a trend toward more repeat revascularization procedures, and higher risk for major adverse cardiac events.

Performance of Interleukin-6 and Interleukin-8 serum levels in pediatric oncology patients with neutropenia and fever for the assessment of low-risk

BACKGROUND: Patients with chemotherapy-related neutropenia and fever are usually hospitalized and treated on empirical intravenous broad-spectrum antibiotic regimens. Early diagnosis of sepsis in children with febrile neutropenia remains difficult due to non-specific clinical and laboratory signs of infection. We aimed to analyze whether IL-6 and IL-8 could define a group of patients at low risk of septicemia. METHODS: A prospective study was performed to assess the potential value of IL-6, IL-8 and C-reactive protein serum levels to predict severe bacterial infection or bacteremia in febrile neutropenic children with cancer during chemotherapy. Statistical test used: Friedman test, Wilcoxon-Test, Kruskal-Wallis H test, Mann-Whitney U-Test and Receiver Operating Characteristics. RESULTS: The analysis of cytokine levels measured at the onset of fever indicated that IL-6 and IL-8 are useful to define a possible group of patients with low risk of sepsis. In predicting bacteremia or severe bacterial infection, IL-6 was the best predictor with the optimum IL-6 cut-off level of 42 pg/ml showing a high sensitivity (90%) and specificity (85%). CONCLUSION: These findings may have clinical implications for risk-based antimicrobial treatment strategies.

Parametric estimation of pulse arrival time: a robust approach to pulse wave velocity

Pulse wave velocity (PWV) is a surrogate of arterial stiffness and represents a non-invasive marker of cardiovascular risk. The non-invasive measurement of PWV requires tracking the arrival time of pressure pulses recorded in vivo, commonly referred to as pulse arrival time (PAT). In the state of the art, PAT is estimated by identifying a characteristic point of the pressure pulse waveform. This paper demonstrates that for ambulatory scenarios, where signal-to-noise ratios are below 10 dB, the performance in terms of repeatability of PAT measurements through characteristic points identification degrades drastically. Hence, we introduce a novel family of PAT estimators based on the parametric modeling of the anacrotic phase of a pressure pulse. In particular, we propose a parametric PAT estimator (TANH) that depicts high correlation with the Complior(R) characteristic point D1 (CC = 0.99), increases noise robustness and reduces by a five-fold factor the number of heartbeats required to obtain reliable PAT measurements.

Whole-body vibration exposure study in U.S. railroad locomotives--an ergonomic risk assessment

Whole-body vibration exposure of locomotive engineers and the vibration attenuation of seats in 22 U.S. locomotives (built between 1959 and 2000) was studied during normal revenue service and following international measurement guidelines. Triaxial vibration measurements (duration mean 155 min, range 84-383 min) on the seat and on the floor were compared. In addition to the basic vibration evaluation (aw rms), the vector sum (av), the maximum transient vibration value (MTVV/aw), the vibration dose value (VDV/(aw T1/4)), and the vibration seat effective transmissibility factor (SEAT) were calculated. The power spectral densities are also reported. The mean basic vibration level (aw rms) was for the fore-aft axis x = 0.18 m/sec2, the lateral axis y = 0.28 m/sec2, and the vertical axis z = 0.32 m/sec2. The mean vector sum was 0.59 m/sec2 (range 0.27 to 1.44). The crest factors were generally at or above 9 in the horizontal and vertical axis. The mean MTVV/aw was 5.3 (x), 5.1 (y), and 4.8 (z), and the VDV/(aw T1/4) values ranged from 1.32 to 2.3 (x-axis), 1.33 to 1.7 (y-axis), and 1.38 to 1.86 (z-axis), generally indicating high levels of shocks. The mean seat transmissibility factor (SEAT) was 1.4 (x) and 1.2 (y) and 1 (z), demonstrating a general ineffectiveness of any of the seat suspension systems. In conclusion, these data indicate that locomotive rides are characterized by relatively high shock content (acceleration peaks) of the vibration signal in all directions. Locomotive vertical and lateral vibrations are similar, which appears to be characteristic for rail vehicles compared with many road/off-road vehicles. Tested locomotive cab seats currently in use (new or old) appear inadequate to reduce potentially harmful vibration and shocks transmitted to the seated operator, and older seats particularly lack basic ergonomic features regarding adjustability and postural support.

Prevalence and risk factors for carriage of multi-drug resistant Staphylococci in healthy cats and dogs

We investigated the distribution of commensal staphylococcal species and determined the prevalence of multi-drug resistance in healthy cats and dogs. Risk factors associated with the carriage of multi-drug resistant strains were explored. Isolates from 256 dogs and 277 cats were identified at the species level using matrix-assisted laser desorption ionisation-time of flight mass spectrometry. The diversity of coagulase-negative Staphylococci (CNS) was high, with 22 species in dogs and 24 in cats. Multi-drug resistance was frequent (17%) and not always associated with the presence of the mecA gene. A stay in a veterinary clinic in the last year was associated with an increased risk of colonisation by multi-drug resistant Staphylococci (OR = 2.4, 95% CI: 1.1˜5.2, p value LRT = 0.04). When identifying efficient control strategies against antibiotic resistance, the presence of mechanisms other than methicillin resistance and the possible role of CNS in the spread of resistance determinants should be considered.