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Predicting the risk of mobility difficulty in older women with screening nomograms: the Women's Health and Aging Study II.

BACKGROUND: A major obstacle to screening for early mobility disability (ie, mobility difficulty), a major public health concern, is the lack of a method that identifies those who are at high risk. The goal of this study was to develop easy-to-use clinical nomograms for estimation of the probability of incident mobility difficulty. METHODS: We conducted a population-based prospective study using data from 266 high physically and cognitively functioning older women, aged 70 to 80 years, who were free of mobility disability at the baseline evaluation of the Women's Health and Aging Study II. The outcome measure was incident mobility disability within 18 months, defined as self-reported difficulty walking 0.8 km, climbing 10 steps, or transferring from or into a car or bus. Logistic regression and receiver operating characteristic curve analyses were used for evaluation of the optimal combination of self-reported and performance-based mobility measures. Bootstrap sampling and estimation was used for validation. RESULTS: Predictive nomograms were developed based on a final model that included 3 simple-to-obtain measures of preclinical disability: self-report of modification in mobility tasks without having difficulty with them, one-leg stance balance, and time to walk 1 m at a usual pace. Final model accuracy (as estimated by the area under the receiver operating characteristic curve) was 73% (SE = 0.04). Validation analysis confirmed the high accuracy of these nomograms. CONCLUSIONS: An original tool was developed for assessment of the risk of mobility difficulty in older women that can be used to assist physicians and researchers in deciding which women to target for preventive interventions.

Aged↗

Crucial role of telomere maintenance-related genes in survival prediction and subtype identification in colorectal cancer.

BACKGROUND: Telomere maintenance-related genes (TMRGs) are implicated in Colorectal cancer (CRC) development, but their prognostic value and clinical relevance remain insufficiently explored. This study aims to develop a TMRG-based prognostic model and elucidate its clinical utility in CRC management. METHODS: The Cancer Genome Atlas database was utilized to download RNA-seq data from 638 CRC and 51 control samples. Differential expressed genes were screened and intersected with 2086 TMRGs, resulting in the identification of 976 TMRGs. Through univariate and multivariate Cox regression analysis, a prognostic model comprising three telomere maintenance-related biomarkers (PDE1B, TFAP2B, and HSPA1A) was developed and validated using an external dataset. By integrating the model risk score with clinical features, a nomogram was constructed to predict the survival outcomes of CRC patients. Additionally, an in-depth investigation of the immuno-infiltration, functional variation and drug sensitivity analysis were performed in two risk subgroups defined by the prognostic model. Finally, the functional significance of PDE1B in CRC cell lines was investigated through MTT assays, cell colony formation assays, transwell assays and flow cytometry. RESULTS: A total of 976 DE-TMRGs were enriched in telomere/DNA replication pathways. A three-gene signature (PDE1B, TFAP2B, and HSPA1A) stratified patients into high- and low-risk groups with divergent survival (AUC >0.60, validated externally). High-risk patients had advanced N/M stages, elevated M0/M2 macrophages, reduced CD4+ memory T cells, and upregulated immune checkpoints. Nomogram integrating risk score, age, and N/M stage accurately predicted 1-/3-/5-year survival. Low-risk patients showed greater 5-fluorouracil sensitivity. PDE1B expression was significantly reduced in CRC tissues and correlated with advanced stages. Functional assays confirmed PDE1B overexpression suppressed proliferation, migration, invasion, and induced apoptosis in CRC cells. CONCLUSION: This study identifies a moderately predictive telomere maintenance-related gene signature as an independent prognostic predictor in CRC. The risk stratification model effectively discriminates patients with distinct survival patterns, tumor microenvironments, and therapeutic responses, while the integrated nomogram offers additional reference information for survival analysis, albeit with only moderate predictive accuracy. These findings indicate telomere maintenance-related gene signature could serve as a preliminary auxiliary risk stratification tool for postoperative CRC patients, PDE1B may also serve as a potential epithelial tumor-suppressor target for future preclinical studies.

PDE1B↗

Exercise versus recovery electrocardiography in predicting mortality in patients with uncomplicated myocardial infarction.

BACKGROUND: Exercise testing after acute myocardial infarction has limited prognostic accuracy. We prospectively used stress-recovery, heart rate-adjusted, ST-segment analysis to predict cardiac death in this clinical setting. METHODS: The stress-recovery index, defined as the difference in absolute values of the areas designated by ST depression in the heart-rate domain during exercise and recovery, was derived in 708 survivors of a first myocardial infarction. To assess whether it contributed additional prognostic information to routinely obtained information, clinical data, resting ejection fraction, and exercise testing data were entered into a sequential Cox model; the stress-recovery index was entered last. Model validation was performed by bootstrapping adjusted for the degree of optimism in estimates. Survival curves were set up using Kaplan-Meier analysis and compared by the log-rank test. RESULTS: Hypertension (OR 1.3, 95%CI 0.9-4.6), exercise capacity (OR 0.6, 95%CI 0.3-1.1 for the interquartile difference in kilopounds per minute), and the stress-recovery index (OR 0.7, 95%CI 0.5-0.9 for the interquartile difference) were independent predictors of cardiac death at a median follow-up of 32 months. However, the stress-recovery index enhanced the prognostic power of the model on top of clinical and exercise testing variables in all diagnostic subgroups according to ST-segment analysis and significantly discriminated survival. A simple nomogram was generated from the fitted Cox model to estimate risk in individual patients. CONCLUSIONS: Stress-recovery, heart rate-adjusted, ST-segment analysis predicts cardiac death after acute myocardial infarction and provides additional prognostic information over clinical and exercise testing data.

Cohort Studies↗

A regional blood circulation alternative to in-series two compartment urea kinetic modeling.

Assuming that the clearance of urea from total body water (TBW) is flow limited, the authors developed a parallel flow model using physiologic data. Organ systems with a blood flow to water volume ratio of greater than 0.2 min-1 were allocated to the high flow system. Remaining organs were represented in the low flow system. In end-stage renal disease patients with minimal renal blood flow, the high flow system contained 20% TBW and received 70% of the systemic blood flow. The authors used this flow heterogeneity to predict the post-dialysis urea rebound (R) in 12 patients after 1 hr of hemodialysis. Dialyzer clearance was 248 +/- 14.5 ml/min (mean +/- SEM) Access recirculation was obviated by returning cleared blood into a central vein. In these patients, R at 1, 3, 5, 7, 10, and 15 minutes. after slowing dialyzer blood flow (Qb) from 383 +/- 18 to 50 ml/min was 3.8 +/- 2.9, 6.2 +/- 3.4, 7.6 +/- 3.1, 8.8 +/- 3.9, 9.0 +/- 4.1, and 9.9 +/- 4.4%, respectively. CO and QAc were modeled with values of 5.5 and 0.5 L/min, respectively. The modeled TBW was 35 L. Total body water derived by nomogram was 38.1 +/- 2.0 L. Our results suggest that the parallel-flow model for urea transport can be used to explain the amount and time course of post dialysis R on a physiologic basis.

Blood Flow Velocity↗

Development and validation of a nomogram predicting the outcome of prostate biopsy based on patient age, digital rectal examination and serum prostate specific antigen.

PURPOSE: We developed and validated a nomogram which predicts presence of prostate cancer (PCa) on needle biopsy. MATERIALS AND METHODS: We used 3 cohorts of men who were evaluated with sextant biopsy of the prostate and whose presenting prostate specific antigen (PSA) was not greater than 50 ng/ml. Data from 4,193 men from Montreal, Canada were used to develop a nomogram based on age, digital rectal examination (DRE) and serum PSA. External validation was performed on 1,762 men from Hamburg, Germany. Data from these men were subsequently used to develop a second nomogram in which percent free PSA (%fPSA) was added as a predictor. External validation was performed using 514 men from Montreal. Both nomograms were based on multivariate logistic regression models. Predictive accuracy was evaluated with areas under the receiver operating characteristic curve and graphically with loess smoothing plots. RESULTS: PCa was detected in 1,477 (35.2%) men from Montreal, 739 (41.9%) men from Hamburg and 189 (36.8%) men from Montreal. In all models all predictors were significant at 0.05. Using age, DRE and PSA external validation AUC was 0.69. Using age, DRE, PSA and %fPSA external validation AUC was 0.77. CONCLUSIONS: A nomogram based on age, DRE, PSA and %fPSA can highly accurately predict the outcome of prostate biopsy in men at risk for PCa.

Adolescent↗

Population pharmacokinetics of gentamicin in patients with cancer.

AIMS: The purpose of this study was to describe the population pharmacokinetics of gentamicin in patients with cancer, to identify possible relationships between clinical covariates and population pharmacokinetic parameter estimates and to examine the relevance of existing dosage nomograms in light of the population model developed in these patients. METHODS: Data were collected prospectively from 210 patients with cancer and were analysed with package NONMEM. Data were split into two sets: a population data set and an evaluation set. Creatinine clearance was estimated using measured creatinine concentrations and using 'low' creatinines set to a minimum of 60 micromol l(-1), 70 micromol l(-1) or 88.4 micromol l(-1) RESULTS: A two compartment model was fitted to the concentration-time curve. Two best models were obtained, one that related clearance to estimated creatinine clearance (minimum creatinine value 60 micromol l(-1)) and the other that related clearance to age, creatinine concentration and body surface area. Volume of the central compartment was influenced by body surface area and albumin concentration. For both models 90% of measured concentrations lay within the 95% confidence interval of the simulated concentrations and the mean prediction errors were -7.2% and -6.6%, respectively. A final analysis performed in all patients identified the following relationship CL (1 h(-1))=0.88 x (1 + 0.043 x creatinine clearance) and central volume of distribution V1 (1)=8.59 x body surface area x (albumin/34)(-0.39). The mean population estimate of intercompartmental clearance (Q) was 1.301 h(-1) and peripheral volume of distribution (V2) was 9.801. Coefficient of variation was 18.5% on clearance and 28.2% on Q. Residual error expressed as a standard deviation was 0.36 mg l(-1) at 1.0 mg l(-1) and 1.32 mg l(-1) at 8.0 mg l(-1). The mean population estimate of clearance was 4.21 h(-1) and volume of distribution (Vss) was 24.61 (0.381 kg(-1)). The mean population estimates of half-lives were 1.8 h and 8.0 h. CONCLUSIONS: In the context of published nomograms this analysis indicated that both the traditional approach and the new, 'once daily' approach should achieve satisfactory concentrations in cancer patients although serum concentration monitoring is required to confirm optimal dosing in individual patients.

Adolescent↗

Maximal oxygen consumption in patients with lung disease.

A theoretical model for oxygen transport assuming a series linkage of ventilation, diffusion, oxygen uptake by erythrocytes, cardiac output, and oxygen release was used to calculate expected values for maximal oxygen intake (VO2max) of patients with various pulmonary disorders 22 patients with either restrictive or obstructive ventilatory impairment were studied at rest and maximal exercise. When exercise measurements of maximal pulmonary blood flow (QCmax), oxygen capacity, membrane diffusing capacity for CO, pulmonary capillary blood volume, alveolar ventilation, and mixed venous oxygen saturation were employed as input values, predictions of VO2max from the model correlated closely with measured values (r = 0.978). Measured VO2max was 976+/-389 ml/min (45.3+/-13% of predicted normal), and VO2max predicted from the model was 1,111+/-427 ml/min. The discrepancy may in part reflect uneven matching of alveolar ventilation, pulmonary capillary blood flow, and membrane diffusing capacity for CO within the lung; uniform matching is assumed in the model so that mismatching will impair gas exchange beyond our predictions. Although QCmax was less than predicted in most patients (63.6+/-19.6% of predicted) the model suggests that raising QCmax to normal could have raised VO2max only 11.6+/-8.8% in the face of existent impairment of intrapulmonary gas exchange. Since pulmonary functions measured at rest correlated well with exercise parameters needed in the model to predict VO2max we developed a nomogram for predicting VO2max from resting CO diffusing capacity, the forced one second expired volume, and the resting ratio of dead space to tidal volume. The correlation coefficient between measured and predicted VO2max, by using this nomogram, was 0.942.

Adolescent↗

Identifying newborns at risk of significant hyperbilirubinaemia: a comparison of two recommended approaches.

AIMS: To compare the predictive performance of clinical risk factor assessment and pre-discharge bilirubin measurement as screening tools for identifying infants at risk of developing significant neonatal hyperbilirubinaemia (post-discharge total serum bilirubin (TSB) >95th centile). METHODS: Retrospective cohort study of term and near term infants born in an urban community teaching hospital in Pennsylvania (1993-97). A clinical risk factor scoring system was developed and its predictive performance compared to a pre-discharge TSB expressed as a risk zone on a bilirubin nomogram. Main outcome measures were prediction model discrimination, range of predicted probabilities, and sensitivity, specificity, positive and negative predictive values, and likelihood ratios for various positivity criteria. RESULTS: The clinical risk factor scoring system developed included birth weight, gestational age <38 weeks, oxytocin use during delivery, vacuum extraction, breast feeding, and combination breast and bottle feeding. The pre-discharge bilirubin risk zone had better discrimination (c = 0.83; 95% CI 0.80 to 0.86) than the clinical risk factor score (c = 0.71; 95% CI 0.66 to 0.76) and predicted risk of significant hyperbilirubinaemia as high as 59% compared with a maximum of 44% for the clinical risk factor score. Neither the risk score nor the pre-discharge TSB risk zone predicted the outcome with > or =0.98 sensitivity without significantly compromising specificity (0.13 and 0.21, respectively). Multi-level clinical risk factor scores and TSB risk zones produced likelihood ratios of 0.15-3.25 and 0.05-9.43, respectively. CONCLUSIONS: The pre-discharge bilirubin expressed as a risk zone on an hour specific bilirubin nomogram is more accurate and generates wider risk stratification than a clinical risk factor score.

Cohort Studies↗

Predicting the presence and side of extracapsular extension: a nomogram for staging prostate cancer.

PURPOSE: We developed a model to predict the side specific probability of extracapsular extension (ECE) in radical prostatectomy (RP) specimens based on the clinical features of the cancer. MATERIALS AND METHODS: We studied 763 patients with clinical stage T1c-T3 prostate cancer who were diagnosed by systematic needle biopsy and subsequently treated with RP. Candidate predictor variables associated with ECE were clinical T stage, the highest Gleason sum in any core, percent positive cores, percent cancer in the cores from each side and serum prostate specific antigen (PSA). Receiver operating characteristic (ROC) analyses were performed to assess the predictive value of each variable alone and in combination. We constructed and internally validated nomograms to predict the side specific probability of ECE based on logistic regression analysis. RESULTS: Overall 30% of the patients and 17% of 1,526 prostate lobes (left or right) had ECE. The areas under the ROC curves (AUC) of the standard features in predicting side specific probability of ECE were 0.627 for PSA, 0.695 for clinical T stage on each side and 0.727 for Gleason sum on each side. When these features were combined predictive accuracy increased to 0.788. The highest value (0.806) was achieved by adding the percent positive cores and the percent cancer in the biopsy specimen to the standard features. The resulting nomograms were internally validated and had excellent calibration and discrimination accuracy. CONCLUSIONS: Standard clinical features of prostate cancer in each lobe-PSA, palpable induration and biopsy Gleason sum-can be used to predict the side specific probability of ECE in RP specimens. The predictive accuracy is increased by adding information from systematic biopsy results. The predictive nomograms are sufficiently accurate for use in clinical practice in decisions such as wide versus close dissection of the cavernous nerves from the prostate.

Adult↗

Pharmacodynamic optimization of warfarin therapy II.

A pharmacodynamic (E(max)) model for optimizing warfarin initiation had previously been reported. This study assessed the validity of this model, adjusted further for age in both the initial cohort and another cohort distinct from that used for the formulation of the model. Thirty-one patients undergoing oral anticoagulation for mainly cardiac indications were recruited from Kuala Lumpur. Thirty-four patients undergoing oral anticoagulation for deep vein thrombosis were recruited from Cambridge. They were studied for their anticoagulant response to the initiation of warfarin. The former were intuitively dosed after a 2-day loading of 10 mg warfarin/d. The latter all were commenced on warfarin via a standard 4-day induction protocol of Fennerty et al that allows early estimation of the required maintenance dose. The actual maintenance doses in both cohorts were compared with their predicted doses on the initiation of therapy that was calculated both from this model and from the induction protocol of Fennerty et al. The third day's international normalized ratio and age combination was additive in terms of their influence on the maintenance dose. The predictive model in both cohorts returned similar results and explained at least two thirds of the interindividual variability in warfarin maintenance dose requirements, whereas the induction protocol of Fennerty et al explained only one third of this interindividual variability. Use of this model in the form of the included nomogram should be able to decrease both the occurrence of either under- or overanticoagulation as well as the time taken to initiate treatment and decide the correct maintenance dose during the initiation of oral anticoagulation with warfarin in hospitals. A prospective evaluation of the nomogram is recommended.

Administration, Oral↗

Alzheimer's disease risk factors as related to cerebral blood flow: additional evidence.

In a previous report, Alzheimer's disease risk factors, including alcohol abuse, depression, Down's syndrome, cerebral glucose metabolism defect, head trauma, old age, Parkinson's disease, sleep disturbance, and underactivity, were shown to have an association with reduced cerebral blood flow. In this report an attempt is made to strengthen a hypothesis that reduced cerebral blood flow may be a required cofactor in the cause of Alzheimer's disease with examples of additional putative risks, including aluminum, ApoE 4 alleles, estrogen deficiency, family history of dementia, low education-attainment, olfactory deficit, and underactivity coupled with gender, considered to have a relationship or potential relationship with reduced cerebral blood flow. Factors, believed to ameliorate Alzheimer's disease, associated with improved or stabilized cerebral blood flow are tabulated. A tentative cerebral blood flow nomogram is shown as a potential model to possibly help predict Alzheimer's disease susceptibility.

Alleles↗

A comparative study of intraplacental villous arteries by latex cast model in vitro and color Doppler flow imaging in vivo.

OBJECTIVE: The purpose of this study was to determine whether color Doppler sonogram can accurately depict the placental vascular structures using a latex cast model of the placental vessels, and to make a nomogram of several blood flow parameters according to the vascular structures. METHODS: First, we made 9 latex cast models of placental arteries and performed morphologic observation and measurement. Second, the comparative anatomical observation of placental vessels by color flow mapping was performed for all 9 patients from whom the latex models were made. Third, a total of 102 uncomplicated pregnant women between 18 and 40 weeks gestation were examined by color Doppler imaging. The resistance indices (RI) and peak systolic velocity (PSV) were measured. RESULTS: In the latex cast model of placentas, cotyledons could be differentiated by the presence of independent vascular structure units. First, second, third and fourth branches were noted in one cotyledon. Cotyledons were easily identified and counted by color Doppler imaging. Each cotyledon contained only one first branch of the intraplacental villous artery (IPVA). The number of IPVA-1 on color Doppler imaging was equal to the number of the cotyledon calculated from the latex model. RI exhibited a negative, and PSV a positive correlation with gestational age (p < 0.05 in both cases). At any given gestational age, both RI and PSV in the peripheral arteries were significantly lower (p < 0.01) than those in the upstream arteries. CONCLUSIONS: Color Doppler flow sonography is a valuable tool for detecting the blood flow of intraplacental villous arteries in vivo and the images agree with the vascular anatomy of placenta in vitro. These results may also provide the basic parameters for future studies of some complicated pregnancies.

Adolescent↗

Evaluation of a model to predict poor survival in patients undergoing elective TIPS procedures.

PURPOSE: To validate a previously published model to predict the probability of patient death within 3 months after an elective transjugular intrahepatic portosystemic shunt (TIPS) procedure. The model is implemented with use of a nomogram or a formula. MATERIALS AND METHODS: Patients who underwent an elective TIPS procedure between May 1, 1999, and May 1, 2001, were selected. Patients who underwent emergency TIPS creation and patients with serum creatinine levels greater than 3.0 mg/dL were excluded. A total of 72 patients met the inclusion criteria. The patients were divided into two groups: group A (ethanol-induced cirrhosis; n = 23) and group B (non-ethanol-induced cirrhosis; n = 49). The model was applied and the predicted probability of death was compared to actual patient survival. A high risk score (R > or = 1.8) is associated with a high risk of death within 3 months after TIPS creation. Survival curves were estimated with use of Kaplan-Meier product limit estimates and were compared with use of the log-rank test. The model's accuracy was evaluated with use of the c-statistic. P values lower than.05 indicated statistical significance. RESULTS: The technical success rate was 98.7%. The 3-month survival rate for the whole group was 79.7%. The predicted mortality rate was higher than the observed mortality rate. The c-statistic was 0.65 for the formula and 0.66 for the nomogram. Patients with a risk score of at least 1.8 had a 3-month survival rate of 54.6% and patients with a risk score lower than 1.8 had a 3-month survival rate of 84.9% (P =.037). CONCLUSION: These results confirm that, after an elective TIPS procedure, patients with risk scores of at least 1.8 have a significantly lower 3-month survival rate than patients with risk scores lower than 1.8.

Elective Surgical Procedures↗

Errors involved in instantaneous intravascular input assumptions.

A comparative evaluation of a zero-order input and the generally accepted instantaneous intravascular input assumption is made for two- and three-compartment open model systems. Equations are derived and a nomogram is prepared to calculate the magnitude of error involved in instantaneous input assumptions. It is suggested that all intravascular administrations be considered as zero-order inputs.

Injections, Intra-Arterial↗

Fat-free mass qualitative assessment with bioelectric impedance analysis (BIA).

Body composition studies, when based on two-compartment volumetric estimates, can hardly assess nutritional states. Phase-sensitive impedance analysis can be used to reflect directly the proportions between intra- and extracellular spaces (ECM/BCM), which is one of the most sensitive indexes of malnutrition. Resistance and reactance values actually measured with BIA are referred to as the series RC model; however, due to the morphology of the FFM, which is composed of cells surrounded by interstitial fluids, in reality this should be modeled as a parallel RC circuit. A nomogram developed with series-to-parallel transformations of resistance and reactance measured with commercial BIA on controls and patients shows interesting gender and disease sensitivity and specificity.

Anorexia Nervosa↗

Postoperative nomogram for disease recurrence after radical prostatectomy for prostate cancer.

PURPOSE: Although models exist that place patients into discrete groups at various risks for disease recurrence after surgery for prostate cancer, we know of no published work that combines pathologic factors to predict an individual's probability of disease recurrence. Because clinical stage and biopsy Gleason grade only approximate pathologic stage and Gleason grade in the prostatectomy specimen, prediction of prognosis should be more accurate when postoperative information is added to preoperative variables. Therefore, we developed a postoperative nomogram that allows more accurate prediction of probability for disease recurrence for patients who have received radical prostatectomy as treatment for prostate cancer, compared with the preoperative nomogram we previously published. PATIENTS AND METHODS: By Cox proportional hazards regression analysis, we modeled the clinical and pathologic data and disease follow-up for 996 men with clinical stage T1a-T3c NXM0 prostate cancer who were treated with radical prostatectomy by a single surgeon at our institution. Prognostic variables included pretreatment serum prostate-specific antigen level, specimen Gleason sum, prostatic capsular invasion, surgical margin status, seminal vesicle invasion, and lymph node status. Treatment failure was recorded when there was either clinical evidence of disease recurrence, a rising serum prostate-specific antigen level (two measurements of 0.4 ng/mL or greater and rising), or initiation of adjuvant therapy. Validation was performed on this set of men and a separate sample of 322 men from five other surgeons' practices from our institution. RESULTS: Cancer recurrence was noted in 189 of the 996 men, and the recurrence-free group had a median follow-up period of 37 months (range, 1 to 168 months). The 7-year recurrence-free probability for the cohort was 73% (95% confidence interval, 68% to 76%). The predictions from the nomogram appeared to be accurate and discriminating, with a validation sample area under the receiver operating characteristic curve (ie, a comparison of the predicted probability with the actual outcome) of 0.89. CONCLUSION: A postoperative nomogram has been developed that can be used to predict the 7-year probability of disease recurrence among men treated with radical prostatectomy.

Adult↗

Predicting the insertion distance for placing gastric tubes.

Approximately 1 million enteral tubes are placed through the nose or mouth in adults and children in the United States annually. Previous studies found gastric tube placement errors to be common. A primary issue in ensuring safe and effective gastric feeding by tube is achieving optimal tube position on insertion. The purpose of this study is to use 24 variables to develop a clinical prediction rule for gastric tube insertion distance in adults, using the internal-nares-to-distal-lower esophageal-sphincter distance. A three-variable model using gender, weight, and nose-umbilicus-flat was selected. This new model, validated using nonparametric bootstrap cross-validation, correctly predicted gastric tube insertion distance 85.3% of the time. This new model is compared to two other methods, one evidence based and one commonly used in practice, and was found to be superior. Two nomograms, one for each gender, are drawn to make this new model easier to use.

Adolescent↗