Predicting smear negative pulmonary tuberculosis with classification trees and logistic regression: a cross-sectional study

Abstract Background Smear negative pulmonary tuberculosis (SNPT) accounts for 30% of pulmonary tuberculosis cases reported yearly in Brazil. This study aimed to develop a prediction model for SNPT for outpatients in areas with scarce resources. Methods The study enrolled 551 patients with clinical-radiological suspicion of SNPT, in Rio de Janeiro, Brazil. The original data was divided into two equivalent samples for generation and validation of the prediction models. Symptoms, physical signs and chest X-rays were used for constructing logistic regression and classification and regression tree models. From the logistic regression, we generated a clinical and radiological prediction score. The area under the receiver operator characteristic curve, sensitivity, and specificity were used to evaluate the model's performance in both generation and validation samples. Results It was possible to generate predictive models for SNPT with sensitivity ranging from 64% to 71% and specificity ranging from 58% to 76%. Conclusion The results suggest that those models might be useful as screening tools for estimating the risk of SNPT, optimizing the utilization of more expensive tests, and avoiding costs of unnecessary anti-tuberculosis treatment. Those models might be cost-effective tools in a health care network with hierarchical distribution of scarce resources.

Low sclerostin levels: a predictive marker of persistent inflammation in ankylosing spondylitis during anti-tumor necrosis factor therapy?

Abstract Introduction Sclerostin levels have been reported to be low in ankylosing spondylitis (AS), but there is no data regarding the possible role of this Wnt inhibitor during anti-tumor necrosis factor (TNF) therapy. The present study longitudinally evaluated sclerostin levels, inflammatory markers and bone mineral density (BMD) in AS patients under anti-TNF therapy. Methods Thirty active AS patients were assessed at baseline, 6 and 12 months after anti-TNF therapy regarding clinical parameters, inflammatory markers, BMD and baseline radiographic damage (mSASSS). Thirty age- and sex-matched healthy individuals comprised the control group. Patients' sclerostin levels, sclerostin binding low-density lipoprotein receptor-related protein 6 (LRP6) and BMD were evaluated at the same time points and compared to controls. Results At baseline, AS patients had lower sclerostin levels (60.5 ± 32.7 vs. 96.7 ± 52.9 pmol/L, P = 0.002) and comparable sclerostin binding to LRP6 (P = 0.387) than controls. Improvement of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Ankylosing Spondylitis quality of life (ASQoL) was observed at baseline vs. 6 vs. 12 months (P < 0.01). Concomitantly, a gradual increase in spine BMD (P < 0.001) and a positive correlation between baseline mSASSS and spine BMD was found (r = 0.468, P < 0.01). Inflammatory parameters reduction was observed comparing baseline vs. 6 vs. 12 months (P <0.01). Sclerostin levels progressively increased [baseline (60.5 ± 32.7) vs. 6 months (67.1 ± 31.9) vs. 12 months (72.7 ± 32.3) pmol/L, P <0.001]. At 12 months, the sclerostin levels remained significantly lower in patients compared to controls (72.7 ± 32.3 vs. 96.70 ± 52.85 pmol/L, P = 0.038). Moreover, sclerostin serum levels at 12 months were lower in the 10 patients with high C reactive protein (CRP) (≥ 5 mg/l) compared to the other 20 patients with normal CRP (P = 0.004). Of note, these 10 patients with persistent inflammation also had lower sclerostin serum levels at baseline compared to the other patients (P = 0.023). Univariate logistic regression analysis demonstrated that AS patients with lower sclerostin serum levels had an increased risk to have high CRP at 12 months (odds ratio = 7.43, 95% CI 1.23 to 45.01, P = 0.020) than those with higher sclerostin values. Conclusions Persistent low sclerostin levels may underlie continuous inflammation in AS patients under anti-TNF therapy.

Validation of the Asthma Predictive Index and comparison with simpler clinical prediction rules

Background The loose and stringent Asthma Predictive Indices (API), developed in Tucson, are popular rules to predict asthma in preschool children. To be clinically useful, they require validation in different settings. Objective To assess the predictive performance of the API in an independent population and compare it with simpler rules based only on preschool wheeze. Methods We studied 1954 children of the population-based Leicester Respiratory Cohort, followed up from age 1 to 10 years. The API and frequency of wheeze were assessed at age 3 years, and we determined their association with asthma at ages 7 and 10 years by using logistic regression. We computed test characteristics and measures of predictive performance to validate the API and compare it with simpler rules. Results The ability of the API to predict asthma in Leicester was comparable to Tucson: for the loose API, odds ratios for asthma at age 7 years were 5.2 in Leicester (5.5 in Tucson), and positive predictive values were 26% (26%). For the stringent API, these values were 8.2 (9.8) and 40% (48%). For the simpler rule early wheeze, corresponding values were 5.4 and 21%; for early frequent wheeze, 6.7 and 36%. The discriminative ability of all prediction rules was moderate (c statistic ≤ 0.7) and overall predictive performance low (scaled Brier score < 20%). Conclusion Predictive performance of the API in Leicester, although comparable to the original study, was modest and similar to prediction based only on preschool wheeze. This highlights the need for better prediction rules.

Concordance Probability and Discriminatory Power in Proportional Hazards Regression

The concordance probability is used to evaluate the discriminatory power and the predictive accuracy of nonlinear statistical models. We derive an analytic expression for the concordance probability in the Cox proportional hazards model. The proposed estimator is a function of the regression parameters and the covariate distribution only and does not use the observed event and censoring times. For this reason it is asymptotically unbiased, unlike Harrell's c-index based on informative pairs. The asymptotic distribution of the concordance probability estimate is derived using U-statistic theory and the methodology is applied to a predictive model in lung cancer.

Evaluating Prediction Rules for t-Year Survivors With Censored Regression Models

Suppose that we are interested in establishing simple, but reliable rules for predicting future t-year survivors via censored regression models. In this article, we present inference procedures for evaluating such binary classification rules based on various prediction precision measures quantified by the overall misclassification rate, sensitivity and specificity, and positive and negative predictive values. Specifically, under various working models we derive consistent estimators for the above measures via substitution and cross validation estimation procedures. Furthermore, we provide large sample approximations to the distributions of these nonsmooth estimators without assuming that the working model is correctly specified. Confidence intervals, for example, for the difference of the precision measures between two competing rules can then be constructed. All the proposals are illustrated with two real examples and their finite sample properties are evaluated via a simulation study.

Bloodstream infections in pediatric ECLS: usefulness of daily blood culture monitoring and predictive value of biological markers. The British Columbia experience

INTRODUCTION: The incidence of bloodstream infection (BSI) in extracorporeal life support (ECLS) is reported between 0.9 and 19.5%. In January 2006, the Extracorporeal Life Support Organization (ELSO) reported an overall incidence of 8.78% distributed as follows: respiratory: 6.5% (neonatal), 20.8% (pediatric); cardiac: 8.2% (neonatal) and 12.6% (pediatric). METHOD: At BC Children's Hospital (BCCH) daily surveillance blood cultures (BC) are performed and antibiotic prophylaxis is not routinely recommended. Positive BC (BC+) were reviewed, including resistance profiles, collection time of BC+, time to positivity and mortality. White blood cell count, absolute neutrophile count, immature/total ratio, platelet count, fibrinogen and lactate were analyzed 48, 24 and 0 h prior to BSI. A univariate linear regression analysis was performed. RESULTS: From 1999 to 2005, 89 patients underwent ECLS. After exclusion, 84 patients were reviewed. The attack rate was 22.6% (19 BSI) and 13.1% after exclusion of coagulase-negative staphylococci (n = 8). BSI patients were significantly longer on ECLS (157 h) compared to the no-BSI group (127 h, 95% CI: 106-148). Six BSI patients died on ECLS (35%; 4 congenital diaphragmatic hernias, 1 hypoplastic left heart syndrome and 1 after a tetralogy repair). BCCH survival on ECLS was 71 and 58% at discharge, which is comparable to previous reports. No patient died primarily because of BSI. No BSI predictor was identified, although lactate may show a decreasing trend before BSI (P = 0.102). CONCLUSION: Compared with ELSO, the studied BSI incidence was higher with a comparable mortality. We speculate that our BSI rate is explained by underreporting of "contaminants" in the literature, the use of broad-spectrum antibiotic prophylaxis and a higher yield with daily monitoring BC. We support daily surveillance blood cultures as an alternative to antibiotic prophylaxis in the management of patients on ECLS.

DEVELOPMENT OF A PREDICTIVE COMBUSTION MODEL OF A SPARK IGNITED ENGINE WITH GASOLINE DIRECT INJECTION, VARIABLE VALVE TIMING, DURATION AND LIFT TECHNOLOGIES

There is a need by engine manufactures for computationally efficient and accurate predictive combustion modeling tools for integration in engine simulation software for the assessment of combustion system hardware designs and early development of engine calibrations. This thesis discusses the process for the development and validation of a combustion modeling tool for Gasoline Direct Injected Spark Ignited Engine with variable valve timing, lift and duration valvetrain hardware from experimental data. Data was correlated and regressed from accepted methods for calculating the turbulent flow and flame propagation characteristics for an internal combustion engine. A non-linear regression modeling method was utilized to develop a combustion model to determine the fuel mass burn rate at multiple points during the combustion process. The computational fluid dynamic software Converge ©, was used to simulate and correlate the 3-D combustion system, port and piston geometry to the turbulent flow development within the cylinder to properly predict the experimental data turbulent flow parameters through the intake, compression and expansion processes. The engine simulation software GT-Power © is then used to determine the 1-D flow characteristics of the engine hardware being tested to correlate the regressed combustion modeling tool to experimental data to determine accuracy. The results of the combustion modeling tool show accurate trends capturing the combustion sensitivities to turbulent flow, thermodynamic and internal residual effects with changes in intake and exhaust valve timing, lift and duration.

Admission blood glucose is an independent predictive factor for hospital mortality in polytraumatised patients

PURPOSE: The goal of this study was to analyse a possible association of admission blood glucose with hospital mortality of polytraumatised patients and to develop an outcome prediction model for this patient group. METHODS: The outcome of adult polytraumatised patients admitted to the University Hospital of Berne, Switzerland, between 2002 and 2004 with an ISS > or = 17, and more than one severely injured organ system was retrospectively analysed. RESULTS: The inclusion criteria were met by 555 patients, of which 108 (19.5%) died. Hyperglycaemia proved to be an independent predictor for hospital mortality (P < 0.0001), following multiple regression analysis. After inclusion of admission blood glucose, the calculated mortality prediction model performed better than currently described models (P < 0.0001, AUC 0.924). CONCLUSION: In this retrospective, single-centre study in polytraumatised patients, admission blood glucose proved to be an independent predictor of hospital mortality following regression analysis controlling for age, gender, injury severity and other laboratory parameters. A reliable admission blood glucose-based mortality prediction model for polytraumatised patients could be established. This observation may be helpful in improving the precision of future outcome prediction models for polytraumatised patients. These observations warrant further prospective evaluation.

Limited predictive value of FDG-PET for response assessment in the preoperative treatment of esophageal cancer: results of a prospective multi-center trial (SAKK 75/02)

BACKGROUND: Only responding patients benefit from preoperative therapy for locally advanced esophageal carcinoma. Early detection of non-responders may avoid futile treatment and delayed surgery. PATIENTS AND METHODS: In a multi-center phase ll trial, patients with resectable, locally advanced esophageal carcinoma were treated with 2 cycles of induction chemotherapy followed by chemoradiotherapy (CRT) and surgery. Positron emission tomography with 2[fluorine-18]fluoro-2-deoxy-d-glucose (FDG-PET) was performed at baseline and after induction chemotherapy. The metabolic response was correlated with tumor regression grade (TRG). A decrease in FDG tumor uptake of less than 40% was prospectively hypothesized as a predictor for histopathological non-response (TRG > 2) after CRT. RESULTS: 45 patients were included. The median decrease in FDG tumor uptake after chemotherapy correlated well with TRG after completion of CRT (p = 0.021). For an individual patient, less than 40% decrease in FDG tumor uptake after induction chemotherapy predicted histopathological non-response after completion of CRT, with a sensitivity of 68% and a specificity of 52% (positive predictive value 58%, negative predictive value 63%). CONCLUSIONS: Metabolic response correlated with histopathology after preoperative therapy. However, FDG-PET did not predict non-response after induction chemotherapy with sufficient clinical accuracy to justify withdrawal of subsequent CRT and selection of patients to proceed directly to surgery.

Mid-term results in relation to age and analysis of predictive factors after fixation of acetabular fractures using the modified Stoppa approach.

INTRODUCTION Data concerning outcome after management of acetabular fractures by anterior approaches with focus on age and fractures associated with roof impaction, central dislocation and/or quadrilateral plate displacement are rare. METHODS Between October 2005 and April 2009 a series of 59 patients (mean age 57 years, range 13-91) with fractures involving the anterior column was treated using the modified Stoppa approach alone or for reduction of displaced iliac wing or low anterior column fractures in combination with the 1st window of the ilioinguinal approach or the modified Smith-Petersen approach, respectively. Surgical data, accuracy of reduction, clinical and radiographic outcome at mid-term and the need for endoprosthetic replacement in the postoperative course (defined as failure) were assessed; uni- and multivariate regression analysis were performed to identify independent predictive factors (e.g. age, nonanatomical reduction, acetabular roof impaction, central dislocation, quadrilateral plate displacement) for a failure. Outcome was assessed for all patients in general and in accordance to age in particular; patients were subdivided into two groups according to their age (group "<60yrs", group "≥60yrs"). RESULTS Forty-three of 59 patients (mean age 54yrs, 13-89) were available for evaluation. Of these, anatomic reduction was achieved in 72% of cases. Nonanatomical reduction was identified as being the only multivariate predictor for subsequent total hip replacement (Adjusted Hazard Ratio 23.5; p<0.01). A statistically significant higher rate of nonanatomical reduction was observed in the presence of acetabular roof impaction (p=0.01). In 16% of all patients, total hip replacement was performed and in 69% of patients with preserved hips the clinical results were excellent or good at a mean follow up of 35±10 months (range: 24-55). No statistical significant differences were observed between both groups. CONCLUSION Nonanatomical reconstruction of the articular surfaces is at risk for failure of joint-preserving management of acetabular fractures through an isolated or combined modified Stoppa approach resulting in total joint replacement at mid-term. In the elderly, joint-preserving surgery is worth considering as promising clinical and radiographic results might be obtained at mid-term.

Clinical signs of deformed wing virus infection are predictive markers for honey bee colony losses.

The ectoparasitic mite Varroa destructor acting as a virus vector constitutes a central mechanism for losses of managed honey bee, Apis mellifera, colonies. This creates demand for an easy, accurate and cheap diagnostic tool to estimate the impact of viruliferous mites in the field. Here we evaluated whether the clinical signs of the ubiquitous and mite-transmitted deformed wing virus (DWV) can be predictive markers of winter losses. In fall and winter 2007/2008, A.m. carnica workers with apparent wing deformities were counted daily in traps installed on 29 queenright colonies. The data show that colonies which later died had a significantly higher proportion of workers with wing deformities than did those which survived. There was a significant positive correlation between V. destructor infestation levels and the number of workers displaying DWV clinical signs, further supporting the mite's impact on virus infections at the colony level. A logistic regression model suggests that colony size, the number of workers with wing deformities and V. destructor infestation levels constitute predictive markers for winter colony losses in this order of importance and ease of evaluation.

Tumor regression grade of urothelial bladder cancer after neoadjuvant chemotherapy: a novel and successful strategy to predict survival.

Histopathologic tumor regression grades (TRGs) after neoadjuvant chemotherapy predict survival in different cancers. In bladder cancer, corresponding studies have not been conducted. Fifty-six patients with advanced invasive urothelial bladder cancer received neoadjuvant chemotherapy before cystectomy and lymphadenectomy. TRGs were defined as follows: TRG1: complete tumor regression; TRG2: >50% tumor regression; TRG3: 50% or less tumor regression. Separate TRGs were assigned for primary tumors and corresponding lymph nodes. The prognostic impact of these 2 TRGs, the highest (dominant) TRG per patient, and competing tumor features reflecting tumor regression (ypT/ypN stage, maximum diameter of the residual tumor) were determined. Tumor characteristics in initial transurethral resection of the bladder specimens were tested for response prediction. The frequency of TRGs 1, 2, and 3 in the primary tumors were n=16, n=19, and n=21; corresponding data from the lymph nodes were n=31, n=9, and n=16. Interobserver agreement in determination of the TRG was strong (κ=0.8). Univariately, all evaluated parameters were significantly (P≤0.001) related to overall survival; however, the segregation of the Kaplan-Meier curves was best for the dominant TRG. In multivariate analysis, only dominant TRG predicted overall survival independently (P=0.035). In transurethral resection specimens of the chemotherapy-naive bladder cancer, the only tumor feature with significant (P<0.03) predictive value for therapy response was a high proliferation rate. In conclusion, among all parameters reflecting tumor regression, the dominant TRG was the only independent risk factor. A favorable chemotherapy response is associated with a high proliferation rate in the initial chemotherapy-naive bladder cancer. This feature might help personalize neoadjuvant chemotherapy.

Predictive Margins and Marginal Effects in Stata

Tables of estimated regression coefficients, usually accompanied by additional information such as standard errors, t-statistics, p-values, confidence intervals or significance stars, have long been the preferred way of communicating results from statistical models. In recent years, however, the limits of this form of exposition have been increasingly recognized. For example, interpretation of regression tables can be very challenging in the presence of complications such as interaction effects, categorical variables, or nonlinear functional forms. Furthermore, while these issues might still be manageable in the case of linear regression, interpretational difficulties can be overwhelming in nonlinear models such as logistic regression. To facilitate sensible interpretation of such models it is often necessary to compute additional results such as marginal effects, predictive margins, or contrasts. Moreover, smart graphical displays of results can be very valuable in making complex relations accessible. A number of helpful commands geared at supporting these tasks have been recently introduced in Stata, making elaborate interpretation and communication of regression results possible without much extra effort. Examples of such commands are -margins-, -contrasts-, and -marginsplot-. In my talk, I will discuss the capabilities of these commands and present a range of examples illustrating their use.

Vancomycin: Predictive risk factors for nephrotoxicity and implication for monitoring

The increased use of vancomycin in hospitals has resulted in a standard practice to monitor serum vancomycin levels because of possible nephrotoxicity. However, the routine monitoring of vancomycin serum concentration is under criticism and the cost effectiveness of such routine monitoring is in question because frequent monitoring neither results in increase efficacy nor decrease nephrotoxicity. The purpose of the present study is to determine factors that may place patients at increased risk of developing vancomycin induced nephrotoxicity and for whom monitoring may be most beneficial.^ From September to December 1992, 752 consecutive in patients at The University of Texas M. D. Anderson Cancer Center, Houston, were prospectively evaluated for nephrotoxicity in order to describe predictive risk factors for developing vancomycin related nephrotoxicity. Ninety-five patients (13 percent) developed nephrotoxicity. A total of 299 patients (40 percent) were considered monitored (vancomycin serum levels determined during the course of therapy), and 346 patients (46 percent) were receiving concurrent moderate to highly nephrotoxic drugs.^ Factors that were found to be significantly associated with nephrotoxicity in univariate analysis were: gender, base serum creatinine greater than 1.5mg/dl, monitor, leukemia, concurrent moderate to highly nephrotoxic drugs, and APACHE III scores of 40 or more. Significant factors in the univariate analysis were then entered into a stepwise logistic regression analysis to determine independent predictive risk factors for vancomycin induced nephrotoxicity.^ Factors, with their corresponding odds ratios and 95% confidence limits, selected by stepwise logistic regression analysis to be predictive of vancomycin induced nephrotoxicity were: Concurrent therapy with moderate to highly nephrotoxic drugs (2.89; 1.76-4.74), APACHE III scores of 40 or more (1.98; 1.16-3.38), and male gender (1.98; 1.04-2.71).^ Subgroup (monitor and non-monitor) analysis showed that male (OR = 1.87; 95% CI = 1.01, 3.45) and moderate to highly nephrotoxic drugs (OR = 4.58; 95% CI = 2.11, 9.94) were significant for nephrotoxicity in monitored patients. However, only APACHE III score (OR = 2.67; 95% CI = 1.13,6.29) was significant for nephrotoxicity in non-monitored patients.^ The conclusion drawn from this study is that not every patient receiving vancomycin therapy needs frequent monitoring of vancomycin serum levels. Such routine monitoring may be appropriate in patients with one or more of the identified risk factors and low risk patients do not need to be subjected to the discomfort and added cost of multiple blood sampling. Such prudent selection of patients to monitor may decrease cost to patients and hospital. ^

PREDICTIVE VARIABLES FOR WEIGHT CHANGE 2 YEARS FOLLOWING PARTICIPATION IN A WEIGHT LOSS INTERVENTION PROGRAM

A historical prospective study was designed to assess the man weight status of subjects who participated in a behavioral weight reduction program in 1983 and to determine whether there was an association between the dependent variable weight change and any of 31 independent variables after a 2 year follow-up period. Data was obtained by abstracting the subjects records and from a follow-up questionnaire administered 2 years following program participation. Five hundred nine subjects (386 females and 123 males) of 1460 subjects who participated in the program, completed and returned the questionnaire. Results showed that mean weight was significantly different (p < 0.001) between the measurement at baseline and after a 2 year follow-up period. The mean weight loss of the group was 5.8 pounds, 10.7 pounds for males and 4.2 pounds for females after a 2 year follow-up period. A total of 63.9% of the group, 69.9% of males and 61.9% of females were still below their initial weight after the 2 year follow-up period. Sixteen of the 31 variables assessed utilizing bivariate analyses were found to be significantly (p (LESSTHEQ) 0.05) associated with weight change after a 2 year follow-up period. These variables were then entered into a multivariate linear regression model. A total of 37.9% of the variance of the dependent variable, weight change, was accounted for by all 16 variables. Eight of these variables were found to be significantly (p (LESSTHEQ) 0.05) predictive of weight change in the stepwise multivariate process accounting for 37.1% of the variance. These variables included: Two baseline variables (percent over ideal body weight at enrollment and occupation) and six follow-up variables (feeling in control of eating habits, percent of body weight lost during treatment, frequency of weight measurement, physical activity, eating in response to emotions, and number of pounds of weight gain needed to resume a diet). It was concluded that a greater amount of emphasis should be placed on the six follow-up variables by clinicians involved in the treatment of obesity, and by the subjects themselves to enhance their chances of success at long-term weight loss. ^