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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↗

Methods of clinical prediction.

The ability to predict clinical outcomes is of great importance to physicians and patients alike. Accordingly, multiple different methods have been used in an effort to accurately predict these outcomes. These methods include the development of scoring systems based on univariable and multivariable analysis, as well as models involving the use of neural network, nomograms, and classification and regression trees. The principles of these types of methods, as well as their advantages and disadvantages will be presented.

Forecasting↗

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↗

Prediction of indolent prostate cancer: validation and updating of a prognostic nomogram.

PURPOSE: Screening with serum prostate specific antigen testing leads to the detection of many prostate cancers early in their natural history. Statistical models have been proposed to predict indolent cancer. We validated and updated model predictions for a screening setting. MATERIALS AND METHODS: We selected 247 patients with clinical stage T1C or T2A from the European Randomized Study on Screening for Prostate Cancer who were treated with radical prostatectomy. We validated a nomogram that had previously been developed in a clinical setting. Predictive characteristics were serum prostate specific antigen, ultrasound prostate volume, clinical stage, prostate biopsy Gleason grade, and total length of cancer and noncancer tissue in biopsy cores. Indolent cancer was defined as pathologically organ confined cancer 0.5 cc or less in volume without poorly differentiated elements. Logistic regression was used to update the previous model and examine the contribution of other potential predictors. RESULTS: Overall 121 of 247 patients (49%) had indolent cancer, while the average predicted probability was around 20% (p <0.001). Effects of individual variables were similar to those found before and discriminative ability was adequate (AUC 0.76). An updated model was constructed, which merely recalibrated the nomogram and did not apply additional predictors. CONCLUSIONS: Prostate cancers identified in a screening setting have a substantially higher likelihood of being indolent than those predicted by a previously proposed nomogram. However, an updated model can support patients and clinicians when the various treatment options for prostate cancer are considered.

Aged↗

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↗

A nomogram for predicting the likelihood of additional nodal metastases in breast cancer patients with a positive sentinel node biopsy.

BACKGROUND: The standard of care for breast cancer patients with sentinel lymph node (SLN) metastases includes complete axillary lymph node dissection (ALND). However, many question the need for complete ALND in every patient with detectable SLN metastases, particularly those perceived to have a low risk of non-SLN metastases. Accurate estimates of the likelihood of additional disease in the axilla could assist greatly in decision-making regarding further treatment. METHODS: Pathological features of the primary tumor and SLN metastases of 702 patients who underwent complete ALND were assessed with multivariable logistic regression to predict the presence of additional disease in the non-SLNs of these patients. A nomogram was created using pathological size, tumor type and nuclear grade, lymphovascular invasion, multifocality, and estrogen-receptor status of the primary tumor; method of detection of SLN metastases; number of positive SLNs; and number of negative SLNs. The model was subsequently applied prospectively to 373 patients. RESULTS: The nomogram for the retrospective population was accurate and discriminating, with an area under the receiver operating characteristic (ROC) curve of 0.76. When applied to the prospective group, the model accurately predicted likelihood of non-SLN disease (ROC, 0.77). CONCLUSIONS: We have developed a user-friendly nomogram that uses information commonly available to the surgeon to easily and accurately calculate the likelihood of having additional, non-SLN metastases for an individual patient.

Adult↗

Preoperative nomogram predicting the 10-year probability of prostate cancer recurrence after radical prostatectomy.

An existing preoperative nomogram predicts the probability of prostate cancer recurrence, defined by prostate-specific antigen (PSA), at 5 years after radical prostatectomy based on clinical stage, serum PSA, and biopsy Gleason grade. In an updated and enhanced nomogram, we have extended the predictions to 10 years, added the prognostic information of systematic biopsy results, and enabled the predictions to be adjusted for the year of surgery. Cox regression analysis was used to model the clinical information for 1978 patients treated by two high-volume surgeons from our institution. The nomogram was externally validated on an independent cohort of 1545 patients with a concordance index of 0.79 and was well calibrated with respect to observed outcome. The inclusion of the number of positive and negative biopsy cores enhanced the predictive accuracy of the model. Thus, a new preoperative nomogram provides robust predictions of prostate cancer recurrence up to 10 years after radical prostatectomy.

Aged↗

Role of surgery in treatment of locally advanced prostate cancer.

The proportion of prostate cancer diagnosed at localized stages increased from 56.7% to 74. 0% between 1973 and 1993 ("stage migration"). A corresponding increase in the number of radical prostatectomies performed each year was also noted. Nomograms are mathematical algorithms derived from statistical models that are used to predict outcomes for an individual patient, or for groups of patients. In fact, careful pre-operative patient and tumor selection before radical prostatectomy is mandatory. Locally advanced prostate cancer is defined as tumor that has extended clinically beyond the prostatic capsule, with invasion of the pericapsular tissue, apex, bladder neck or seminal vescicle, but without lymph node involvement or distant metastasis. It is estimated that 12-15% of prostate cancer are stage T3. Overstaging or understaging of this cancer is common. Correct staging of clinical T3 disease is even more difficult and both overstaging pT2 and understaging pT4 or pN+ are common. The goals of treatment for T3 tumors are to cure the disease, prolong survival or metastasis-free survival and improve the quality of life. The authors reviewed the most important studies, investigated radical prostatectomy as monotherapy for locally advanced prostate cancer and the integration of surgery with hormonal treatment. The EAU guidelines on prostate cancer state that radical prostatectomy in locally advanced disease is an option for selected patients with small T3, PSA <20 ng/ml, Gleason score <8 and a life expectancy > 10 years. Ten to 15% of clinical T3 are overstaged as pT2. This may lead to the possibility of curing these patients with surgery as the monotherapy. The increased use of nomograms and increased knowledge of recognized prognostic factors could lead to the selection of a large number of patients, often with a long life expectancy, who could benefit from surgical treatment.

Aged↗

Postoperative nomogram for disease-specific survival after an R0 resection for gastric carcinoma.

PURPOSE: Few published studies have addressed individual patient risk after R0 resection for gastric cancer. We developed and internally validated a nomogram that combines these factors to predict the probability of 5-year gastric cancer-specific survival on the basis of 1,039 patients treated at a single institution. METHODS: Nomogram predictor variables included age, sex, primary site (distal one-third, middle one-third, gastroesophageal junction, and proximal one-third), Lauren histotype (diffuse, intestinal, mixed), number of positive lymph nodes resected, number of negative lymph nodes resected, and depth of invasion. Death as a result of gastric cancer was the predicted end point. The concordance index was used as an accuracy measure, with bootstrapping to correct for optimistic bias. Calibration plots were constructed. RESULTS: Gastric cancer-specific survival at 5 years was 50%. A nomogram was constructed on the basis of a Cox regression model. The bootstrap-corrected concordance index was 0.80. When compared with the predictive ability of American Joint Committee on Cancer stage, the nomogram discrimination was superior (P <.001). Nomogram calibration appeared to be excellent. CONCLUSION: A nomogram was developed to predict 5-year disease-specific survival after R0 resection for gastric cancer. This tool should be useful for patient counseling, follow-up scheduling, and clinical trial eligibility determination.

Adult↗

High incidence of prostate cancer detected by saturation biopsy after previous negative biopsy series.

OBJECTIVES: We explored the yield of saturation biopsy and developed a nomogram predicting the probability of prostate cancer (PCa) on the basis of saturation biopsy. MATERIALS AND METHODS: Between 2001 and 2004, saturation biopsies (average of 24 cores) were performed in 161 men with persistently elevated prostate specific antigen (PSA) level (median, 9 ng/ml). All had at least two previously negative, eight-core biopsy sessions. PCa predictors on saturation biopsy were integrated within multivariate nomograms. RESULTS: PCa detection was 41% (n=66 of 161). PSA density and transition zone volume were the most significant predictors of PCa on saturation biopsy. The accuracy of the nomogram with the best performance characteristics was 72%. CONCLUSIONS: Saturation biopsy may be indicated in men with a persistent suspicion of PCa. High-risk individuals can be identified accurately with our nomogram.

Adult↗

Nomograms for precise determination of birth weight for dates.

We have derived a mathematical model (Altman and Coles, 1980) that matches closely the birth weight standards derived from the large Aberdeen survey (Thomson et al, 1968). From this, we have drawn nomograms that can be used to assess an infant's position in relation to these standards. The nomograms are easy to use and give adequate precision.

Birth Weight↗

Selection of thrombolytic therapy for individual patients: development of a clinical model. GUSTO-I Investigators.

We developed a logistic regression model with data from the GUSTO-I trial to predict mortality rate differences in individual patients who received accelerated tissue plasminogen activator (TPA) versus streptokinase treatment for acute myocardial infarction. A nomogram was developed from a reduced version of this model that approximated the underlying risk of patients treated with streptokinase, and thus the benefit of TPA. The 30-day mortality rate with accelerated TPA was 0.063 versus 0.073 with streptokinase and subcutaneously administered heparin and 0.074 with streptokinase and intravenously administered heparin. No baseline patient characteristics were significantly associated with a different relative effect of TPA. Older patients and those with anterior infarction, higher Killip classification (except Killip class IV), lower blood pressure, and increased heart rate had the greatest absolute benefit with accelerated TPA. Patients with acute myocardial infarction who had more high-risk characteristics derived a greater absolute benefit from treatment with accelerated TPA versus streptokinase.

Age Factors↗