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A nomogram for predicting lifetime hip fracture risk from radius bone mineral density and age.

A statistical model for predicting a woman's lifetime risk of hip fracture using her bone mineral density at menopause has been proposed by Black et al. (1992b). We made an additional assumption concerning the correlation of bone mineral density between any two ages among postmenopausal women and applied the modified model to baseline ages between 50 and 85 years and any bone mineral density level likely to be observed in the population. The results are displayed in a form more convenient for application of this model in the clinical setting.

Aged↗

Dose response explorer: an integrated open-source tool for exploring and modelling radiotherapy dose-volume outcome relationships.

Radiotherapy treatment outcome models are a complicated function of treatment, clinical and biological factors. Our objective is to provide clinicians and scientists with an accurate, flexible and user-friendly software tool to explore radiotherapy outcomes data and build statistical tumour control or normal tissue complications models. The software tool, called the dose response explorer system (DREES), is based on Matlab, and uses a named-field structure array data type. DREES/Matlab in combination with another open-source tool (CERR) provides an environment for analysing treatment outcomes. DREES provides many radiotherapy outcome modelling features, including (1) fitting of analytical normal tissue complication probability (NTCP) and tumour control probability (TCP) models, (2) combined modelling of multiple dose-volume variables (e.g., mean dose, max dose, etc) and clinical factors (age, gender, stage, etc) using multi-term regression modelling, (3) manual or automated selection of logistic or actuarial model variables using bootstrap statistical resampling, (4) estimation of uncertainty in model parameters, (5) performance assessment of univariate and multivariate analyses using Spearman's rank correlation and chi-square statistics, boxplots, nomograms, Kaplan-Meier survival plots, and receiver operating characteristics curves, and (6) graphical capabilities to visualize NTCP or TCP prediction versus selected variable models using various plots. DREES provides clinical researchers with a tool customized for radiotherapy outcome modelling. DREES is freely distributed. We expect to continue developing DREES based on user feedback.

Computer Simulation↗

The addition of interleukin-6 soluble receptor and transforming growth factor beta1 improves a preoperative nomogram for predicting biochemical progression in patients with clinically localized prostate cancer.

PURPOSE: Several preoperative prostate cancer nomograms have been developed that predict risk of progression using pretreatment prostate-specific antigen (PSA) level, clinical stage, and biopsy Gleason grade. We describe the development and performance of a new nomogram. The nomogram adds new markers to the standard clinical predictors that reflect the biologic behavior of prostate cancer: pretreatment plasma levels of interleukin-6 soluble receptor (IL6SR) and transforming growth factor beta1 (TGF-beta1). PATIENTS AND METHODS: Between November 7, 1994 and December 22, 1997, 714 patients with stage cT1c to cT3a prostate cancer and no prior therapy were treated with radical prostatectomy at the Methodist Hospital, Houston TX. Plasma levels of IL6SR and TGF-beta1 were measured in banked preoperative plasma. With these data, a nomogram was developed to predict the probability of PSA progression within 5 years of surgery. The nomogram was validated with bootstrapping to assess its discrimination and calibration performance. RESULTS: In the multivariable Cox model, PSA (P =.004), IL6SR (P <.001), TGF-beta1 (P <.001), primary Gleason grade (P <.002), and secondary Gleason grade (P =.029) were associated with PSA progression, whereas clinical stage (P =.696) was not. The nomogram seemed to be well calibrated and had a bootstrap-corrected area under the receiver operating characteristic curve (ie, concordance index) of 0.83. For comparison, a nomogram that omitted IL6SR and TGF-beta1 achieved a concordance index of only 0.75. CONCLUSION: We found that pretreatment plasma levels of IL6SR and TGF-beta1 improved the ability to predict biochemical progression by a prognostically substantial margin. A nomogram including the pretreatment levels of these molecular markers, along with standard clinical markers, has been developed and internally validated.

Adult↗

Adverse cardiac events after surgery: assessing risk in a veteran population.

OBJECTIVE: To establish rates of and risk factors for cardiac complications after noncardiac surgery in veterans. DESIGN: Prospective cohort study. SETTING: A large urban veterans affairs hospital. PARTICIPANTS: One thousand patients with known or suspected cardiac problems undergoing 1,121 noncardiac procedures. MEASUREMENTS: Patients were assessed preoperatively for important clinical variables. Postoperative evaluation was done by an assessor blinded to preoperative status with a daily physical examination, electrocardiogram, and creatine kinase with MB fraction until postoperative day 6, day of discharge, death, or reoperation (whichever occurred earliest). Serial electrocardiograms, enzymes, and chest radiographs were obtained as indicated. Severe cardiac complications included cardiac death, cardiac arrest, myocardial infarction, ventricular tachycardia, and fibrillation and pulmonary edema. Serious cardiac complications included the above, heart failure, and unstable angina. MAIN RESULTS: Severe and serious complications were seen in 24% and 32% of aortic, 8.3% and 10% of carotid, 11.8% and 14.7% of peripheral vascular, 9.0% and 13.1% of intraabdominal/intrathoracic, 2.9% and 3.3% of intermediate-risk (head and neck and major orthopedic procedures), and 0.27% and 1.1% of low-risk procedures respectively. The five associated patient-specific risk factors identified by logistic regression are: myocardial infarction < 6 months (odds ratio [OR], 4.5; 95% confidence interval [CI], 1.9 to 12.9), emergency surgery (OR, 2.6; 95% CI, 1.2 to 5.6), myocardial infarction > 6 months (OR, 2.2; 95% CI, 1.4 to 3.5), heart failure ever (OR, 1.9; 95% CI, 1.2 to 3.0), and rhythm other than sinus (OR, 1.7; 95% CI, 0.9 to 3.2). Inclusion of the planned operative procedure significantly improves the predictive ability of our risk model. CONCLUSIONS: Five patient-specific risk factors are associated with high risk for cardiac complications in the perioperative period of noncardiac surgery in veterans. Inclusion of the operative procedure significantly improves the predictive ability of the risk model. Overall cardiac complication rates (pretest probabilities) are established for these patients. A simple nomogram is presented for calculation of post-test probabilities by incorporating the operative procedure.

Adult↗

A postoperative prognostic nomogram for renal cell carcinoma.

PURPOSE: Few published studies have combined prognostic factors to predict the likelihood of recurrence after surgery for renal cell carcinoma. We developed a nomogram for this purpose. MATERIALS AND METHODS: With Cox proportional hazards regression analysis, we modeled pathological data and disease followup for 601 patients with renal cell carcinoma who were treated with nephrectomy. Predictor variables were patient symptoms, including incidental, local or systemic, histology, including chromophobe, papillary or conventional, tumor size, and pathological stage. Treatment failure was recorded when there was either clinical evidence of disease recurrence or death from disease. Validation was performed with a statistical (bootstrapping) technique. RESULTS: Disease recurrence was noted in 66 of the 601 patients, and those in whom treatment was successful had a median and maximum followup of 40 and 123 months, respectively. The 5-year probability of freedom from failure for the patient cohort was 86% (95% confidence interval 82 to 89). With statistical validation, predictions by the nomogram appeared accurate and discriminating with an area under the receiver operating characteristic curve, that is a comparison of the predicted probability with the actual outcome of 0.74. CONCLUSIONS: A nomogram has been developed that can be used to predict the 5-year probability of treatment failure among patients with newly diagnosed renal cell carcinoma. The nomogram may be useful for patient counseling, clinical trial design and patient followup planning.

Carcinoma, Renal Cell↗

Relationship between body fat and anthropometric variables in a large sample of young males.

To establish the relationship between fat mass (FM) and other anthropometric variables, 2152 males of mid-European extract aged between 18 and 24 years were examined. Based on these data, three models for either fat percent (FP) or FM prediction were calculated from body mass (BM), body height (BH) and body mass index (BMI = BM/BH2). The best models for fat percent prediction both explained only 51% of the variance (FP = 0.02711.BMI2.042 (0.043 SE); and FP = 720310.BM2.05 (0.043).BH-3.76 (0.155), R2 = 0.51 for both models). There was a remarkable increase in R2 when FP was replaced by FM. The best model explained 70% of the variance for FM prediction (FM = 7207.BM3.05 (0.043).BH-3.76 (0.155), R2 = 0.70). We have incorporated these data into a nomogram applicable to an active, young male mid-European population. From this study we conclude that for the estimation of body fat, models based upon FM (absolute value) are preferred over models for prediction of FP (relative value).

Adipose Tissue↗

[Selection criteria for the expected management of localised prostate cancer].

Prostate cancer harbours the possibility of overtreatment more than any other malignant disease. Due to its slow growth, expected management is an established therapeutic option in newly diagnosed carcinomas. Improved diagnostic methods and the widespread use of PSA lead to earlier diagnosis of cancers that would not adversely affect the life expectancy of the patient, even when they were left untreated. Several statistical models have been published to identify such insignificant cancers; however, all such nomograms suffer from limited sensitivity and specificity. For the indication of expected management, comorbidity and life expectancy must be considered using risk scores and life tables. In general, expected management is a suitable option for elderly patients with low grade cancers. Young patients and those with intermediate or high-grade cancers are most likely to benefit from active local treatment.

Decision Support Systems, Clinical↗

Combination of the preoperative PSA level, biopsy gleason score, percentage of positive biopsies, and MRI T-stage to predict early PSA failure in men with clinically localized prostate cancer.

OBJECTIVES: Early (2 years or less) prostate-specific antigen (PSA) failure has been shown to predict for distant failure. The independent clinical predictors of time to postoperative PSA failure were used to identify prostate cancer patients at high risk for early PSA failure. METHODS: A Cox regression multivariable analysis was used to determine whether additional predictive information was provided by the endorectal coil magnetic resonance imaging (erMRI) T-stage when controlling for the established prognostic factors in predicting the time to postoperative PSA failure in 977 men with palpable (T2) or PSA-detected (T1c) prostate cancer. RESULTS: Preoperative PSA (P = 0.0001), percentage of positive prostate biopsies (P= 0.0001), erMRI T-stage (P = 0.0001), biopsy Gleason score (P = 0.0015), and clinical stage T2c disease (P = 0.004) were independent predictors of time to postoperative PSA failure. Two-year PSA failure rates derived from the Cox regression model and bootstrap estimates of the 95% confidence intervals are presented in nomogram format stratified by the preoperative PSA, percentage of positive prostate biopsies, erMRI T-stage, and the biopsy Gleason score. CONCLUSIONS: Patients at high risk for early PSA failure and subsequent distant progression include men with erMRI T3 disease and 3 or more of 6 cores positive for a Gleason score 6 or higher disease when the PSA is more than 10 but not more than 20 ng/mL and any Gleason score when the PSA is more than 20 ng/mL. Men with erMRI T2 disease and 3 or more of 6 cores positive for a Gleason score 8 or higher disease and who have a PSA more than 20 ng/mL are also at high risk. Neoadjuvant therapy trials in these select patients may be justified.

Biomarkers, Tumor↗

Validation of the Kattan preoperative nomogram for prostate cancer recurrence using a community based cohort: results from cancer of the prostate strategic urological research endeavor (capsure).

PURPOSE: The Kattan preoperative nomogram combines preoperative prostate specific antigen (PSA), biopsy Gleason grade and clinical stage to estimate disease recurrence after radical prostatectomy. Several studies using patient data from academic centers have validated the nomogram. We assessed the performance of the Kattan nomogram using the Cancer of the Prostate Strategic Urological Research Endeavor database, a national, largely community based observational disease registry. MATERIALS AND METHODS: From the Cancer of the Prostate Strategic Urological Research Endeavor database we identified 1701 men with clinically localized prostate cancer undergoing radical prostatectomy with sufficient pretreatment information and PSA followup after surgery. Disease recurrence was defined as 2 consecutive PSA values 0.2 ng/ml or greater, or a second cancer treatment more than 6 months after prostatectomy. A concordance index was used to evaluate the performance of the nomogram compared to observed 5-year recurrence-free survival (Kaplan-Meier). Kattan nomogram scores were calculated for each patient and stratified into 6 groups for analysis. RESULTS: In our cohort of 1701 men 413 (24%) had evidence of disease recurrence. Median followup in these patients was 2.3 years. Kattan nomogram scores were 17% to 99% (mean 79%). The overall concordance index was 0.68. Varying the definition of recurrent disease and excluding patients with imputed data did not substantially alter nomogram performance (concordance index 0.65 to 0.70). The Kattan nomogram tended to overestimate 5-year freedom from recurrence in patients with scores of 65% and higher. CONCLUSIONS: We noted the reasonable performance of the Kattan nomogram for predicting cancer outcomes after radical prostatectomy using a community based population. Although concordance is lower than in previous validation studies and the nomogram overestimates recurrence-free survival in patients at lower risk, the model is fairly robust and it provides important information when counseling patients regarding treatment options in the community setting. Further refinements in pretreatment estimation of disease-free survival and ultimately overall survival are needed.

Cohort Studies↗

Predicting survival using simple clinical variables: a case study in traumatic brain injury.

OBJECTIVES: Prediction of patient outcome can be useful as an aid to clinical decision making, to explore possible biological mechanisms, and as part of the clinical audit process. Many studies have constructed predictive models for survival after traumatic brain injury, but these have often used expensive, time consuming, or highly specialised measurements. The aim of this study was to develop a simple easy to use model involving only variables which are rapidly and easily clinically achievable in routine practice. METHODS: All consecutive patients admitted to a regional trauma centre with moderate or severe head injury were enrolled in the study. Basic demographic, injury, and CT characteristics were recorded. Patient survival at 1 year was used to construct a simple predictive model which was then validated on a very similar patient group. RESULTS: 372 patients were included in the study, of whom 365 (98%) were followed up for survival at 1 year. Multiple logistic regression resulted in a model containing age (p<0.001), Glasgow coma scale score (p<0.001), injury severity score (p<0.001), pupil reactivity (p=0.004), and presence of haematoma on CT (p=0.004) as independently significant predictors of survival. The model was validated on an independent set of 520 patients, showing good discrimination and adequate calibration, but with a tendency to be pessimistic about very severely injured patients. It is presented as an easy to use nomogram. CONCLUSIONS: All five variables have previously been shown to be related to survival. All variables in the model are clinically simple and easy to measure rapidly in a centre with access to 24 hour CT, resulting in a model that is both well validated and clinically useful.

Adolescent↗

[Multifactor analysis of parameters of immunity under the combined action of doxycycline and a low molecular weight immunomodulator of microbial origin].

The effect of doxycycline combination with a low molecular immunomodulator of microbial origin on the primary immune response to the vaccine EV antigens was studied in multifactor experiments. Mathematical processing of the data provided construction of polynomial statistic models of the second order describing increased delayed type hypersensitivity (IDTH) and the antibody titer. Analysis of the quasimonofactor models revealed different character of regulation of the cellular and humoral response. Nomograms were plotted for precise quantitative estimation of the dose-time parameters of the regimens for combined use of the antibiotic and immunomodulator providing the required levels of IDTH and the antibody titer.

Adjuvants, Immunologic↗

New method to predict patients' intravenous heparin dose requirements.

OBJECTIVE: To predict intravenous heparin dose requirements of patients treated for thromboembolic disorders. DESIGN: A retrospective cohort study in which we used simple linear regression to predict patients' effective maintenance dose (EMD) of heparin (units/kg/hour needed to achieve and maintain APTT therapeutic range) from patients' "heparin responsiveness" (the APTT increase after the initial 6 hours of heparin treatment per units/kg/hour received). SETTING/PATIENTS: The model was derived from 46 patients treated at one hospital (Hospital A) and then tested in 42 patients treated at another hospital (Hospital B). MEASUREMENTS AND MAIN RESULTS: Among Hospital A patients, there was a strong linear correlation (r = -.880; p < .001) between EMD (mean 16.02 units/kg/hour; 95% CI 14.9, 17.15) and "heparin responsiveness" (HR): EMD = 25.651 - [95.118 x HR]. This model accurately predicted Hospital B patients' EMD: 97% (37/38) fell within the model's 95% prediction interval; the mean absolute difference between predicted and actual EMD was 1.73 units/kg/hour (95% CI 1.39, 2.08); and only 16% of patients had EMD's more than 3 units/kg/hour different from that predicted by the regression model. The model's accuracy was comparable to that of our gold standard, the weight-based heparin dosing nomogram. CONCLUSION: The infusion dose of intravenous heparin effective for an individual patient can be predicted accurately from the patient's body weight and APTT response to the initial 6 hours of treatment. Especially in hospitals where validated heparin dosing nomograms are not used, clinicians may find this simple technique useful in achieving timely therapeutic anticoagulation.

Anticoagulants↗

Transurethral needle ablation (TUNA): thermal gradient mapping and comparison of lesion size in a tissue model and in patients with benign prostatic hyperplasia.

A new device has been development for treating benign prostatic hyperplasia (BPH) that is performed as an outpatient procedure. the device (transurethral needle ablation or TUNA) employs needles that deliver low-level radiofrequency (RF) power locally at high temperature to ablate hyperplastic prostate tissue. During the TUNA procedure the temperature proximal to the needle tips is measured with thermocouples within the needle's protective shields and urethral temperature is measured via a thermocouple contained within the catheter tip. Tissue impedance is also measured by the TUNA catheter since it is well known from other thermal treatment methods that thermal destruction of prostatic tissue depends upon a particular prostate's tissue composition and thermoregulation. Because of this variation in prostates, a nomogram guide for setting the TUNA device was created using a turkey breast tissue model. Lesion sizes created at particular settings in the turkey breast model were similar to those created at the same settings in patients with BPH. In addition, local thermal gradients within the TUNA lesions were visualized and mapped using an infrared thermal imaging system which demonstrated that central lesion temperature with the device is approximately 80-100 degrees C.

Catheter Ablation↗

Empirical modeling of particle deposition in the alveolar region of the lungs: a basis for interspecies extrapolation.

Different species exposed to the same particle atmosphere may not receive identical initial doses in comparable respiratory tract regions, and the selection of a certain species for toxicologic evaluation of inhaled particles may, thus, influence the estimated human lung, or systemic, dose, as well as its relationship to potential adverse health effects. Estimating regional particle deposition patterns is important for establishing the comparability of animal models, for understanding interspecies differences in the expression of chemical toxicities, and, ultimately, for the human risk assessment process. A method is described which offers a strategy for summarizing published data on regional deposition of particles of different diameters and calculating a deposited fraction for a particular particle size distribution. This involved the construction of nomograms to allow estimation of alveolar deposition fractions in three species, namely the human, monkey, and rat. A regression model was then developed to permit the calculation of more exact deposition fractions. Although this paper describes the procedure for one region of the lungs, the same technique can be applied to other regions of the respiratory tract or to the total system for which deposition data are available. While this technique may facilitate the interpretation of available experimental results and their application to human health risk assessment, appropriate caution should be exercised in applying the developed nomograms given limitations of the deposition database upon which it is based.

Animals↗

Predictors of Efficacy Maintenance After Vunakizumab Discontinuation in Patients With Moderate-to-Severe Plaque Psoriasis: A Post Hoc Analysis of a Randomized Controlled Trial.

BACKGROUND: Efficacy cannot be maintained in some psoriasis patients after biological discontinuation. This study aimed to explore predictors of efficacy maintenance after vunakizumab discontinuation in patients with moderate-to-severe plaque psoriasis. METHODS: This post hoc analysis used data from a phase III trial (NCT04839016); 291 patients with moderate-to-severe plaque psoriasis who achieved 100% improvement in Psoriasis Area and Severity Index (PASI) score at Week 52 were enrolled. Efficacy maintenance was defined as patients who maintained PASI 90 or PASI 100 after 20&#x2009;weeks of vunakizumab discontinuation. RESULTS: There were 44.7% and 72.5% of patients with PASI 100 and PASI 90 maintenance, respectively. In the multivariate logistic regression model, body mass index (BMI) (odds ratio [OR]&#x2009;=&#x2009;0.922, p&#x2009;=&#x2009;0.024) and treatment interruption (OR&#x2009;=&#x2009;0.550, p&#x2009;=&#x2009;0.020) were independently associated with a lower possibility of PASI 100 maintenance; however, the association of family history of psoriasis and the first time of PASI 100 achievement with PASI 100 maintenance did not achieve statistical significance. Duration of psoriasis (OR&#x2009;=&#x2009;0.972, p&#x2009;=&#x2009;0.049) and treatment interruption (OR&#x2009;=&#x2009;0.257, p&#x2009;<&#x2009;0.001) were independently associated with a lower possibility of PASI 90 maintenance. Two nomograms for predicting PASI 90 and PASI 100 maintenance were constructed based on the multivariate models, which disclosed good calibration performance. CONCLUSIONS: PASI 90 and PASI 100 maintenance rates are 72.5% and 44.7% after 20&#x2009;weeks of vunakizumab discontinuation in patients with moderate-to-severe plaque psoriasis. BMI, treatment interruption, and duration of psoriasis predict a lower possibility of efficacy maintenance after vunakizumab discontinuation.

Humans↗

A nomogram to predict seminal vesicle invasion by the extent and location of cancer in systematic biopsy results.

PURPOSE: We determined whether systematic biopsy results increases the accuracy of standard clinical information in predicting seminal vesicle invasion (SVI). MATERIALS AND METHODS: We analyzed a retrospective cohort of 763 patients with clinical stages T1c-T3 prostate cancer who were diagnosed by systematic biopsy and treated with radical prostatectomy. We recorded the location of each biopsy core and measured the length of cancer and total length of each core. Using logistic regression analysis we constructed and internally validated a nomogram to predict SVI. RESULTS: A total of 60 patients (7.9%) had SVI. Cancer was present in a biopsy core from the base in 437 patients, of whom 12.8% had SVI compared with only 1.2% of the 326 without cancer at the base. None of the 275 patients with prostate specific antigen (PSA) 10 ng/ml or less and no cancer at the base had SVI. On multivariate analysis serum PSA (p <0.0005), primary Gleason grade (p = 0.028) and percent cancer at the base (p <0.005) were the only significant predictors of SVI. The predictive accuracy of a standard model that included only stage, grade and PSA was maximally enhanced by including the percent cancer at the base (p = 0.0013). A nomogram that incorporated this variable produced probabilities of SVI that differed from the standard model by +/- 10% in 68% of the cases. CONCLUSIONS: The presence and amount of cancer in systematic needle biopsy cores from the base of the prostate strongly predicts the presence of SVI. Systematic biopsy results enhance the accuracy of nomograms to predict SVI.

Adult↗

Individualized adjustment of vancomycin dosage: comparison with two dosage nomograms.

An individualized method of vancomycin dosage adjustment using steady-state serum concentrations was assessed in 50 patients (86 sets of vancomycin serum concentrations). The predictive accuracy of this method was compared with that of two published nomograms (Moellering, Matzke). Peak and trough serum concentrations predicted from previously drawn vancomycin serum concentrations (individualized method) using a one-compartment pharmacokinetic model were compared with measured steady-state peak and trough serum concentrations. Predicted peak and trough serum concentrations were also generated for both the Moellering and Matzke nomograms by using the elimination rate constant derived from each of the respective nomograms and the fixed volume of distribution (0.9 L/kg) assumed by the nomograms, and the actual administered vancomycin dose and dosage interval. These predicted concentrations were also compared with the measured peak and trough concentrations. Statistical measures of bias and precision indicated that the individualized method of dosage adjustment more closely predicted vancomycin serum concentrations following a dosage change than did either of the nomograms. Overall, the Moellering nomogram was the least accurate of the three methods in predicting vancomycin serum concentrations, and this nomogram should not be used to titrate vancomycin dosages in a clinical setting. Adjustment of vancomycin dosages should be individualized based on pharmacokinetic data derived from measured serum concentrations. In situations where quantitative analysis of vancomycin concentrations is not available, the Matzke nomogram appears to be a reasonable method of adjusting vancomycin dosages.

Adult↗

Evaluation of a nomogram for estimating the rate of phenytoin accumulation.

This study evaluated a nomogram designed to identify a subgroup of the patients whose serum phenytoin concentrations are near steady state at a given time after initiation of therapy. A sample of 95 adult subjects with reported values of Vmax and Km was pooled from the literature, and computer simulations of phenytoin accumulation for 15 days after initiation of phenytoin acid at 300 mg/day were performed. Simulated serum concentrations on days 5, 10, and 15 were used to identify subjects who were predicted by the nomogram to be at greater than or equal to 83% of steady state, and these results were compared with those expected from the Michaelis-Menten model. In the simulations, 42, 62, and 66 subjects reached greater than or equal to 83% of steady state by days 5, 10, and 15, respectively. The nomogram correctly identified 13 (31.0%), 33 (53.2%), and 43 (65.2%) of these individuals, respectively. The frequency of erroneous predictions was low, even in subjects whose Km and volume of distribution were outside the limits set in the development of the nomogram. Use of a nomogram such as this would help a subgroup of patients to attain a desired serum phenytoin concentration earlier in therapy and with fewer serum phenytoin determinations than would otherwise be required. It would also prevent premature increases in phenytoin dose in patients whose serum concentration is still rising.

Adult↗