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Nomogram for dosing warfarin at steady state.

The predictive performance of a nomogram for dosing warfarin was compared with that of a computer program. The nomogram and the computer program were developed from the log-linear model describing warfarin pharmacodynamics at steady state. The nomogram's dose-response curves were generated by using previously reported pharmacodynamic and pharmacokinetic values for an outpatient population receiving warfarin. The series of dose-response curves were plotted by altering the pharmacodynamic values over a range of 3 standard deviations. The ability of the nomogram to predict the steady-state prothrombin time ratio (PTR) after an adjustment in the dosage of warfarin was evaluated, and the results were compared with those of a commercially available program involving Bayesian regression. Data for 65 outpatients were evaluated. The mean +/- S.D. nomogram-predicted, computer-predicted, and measured PTRs were 1.63 +/- 0.27, 1.64 +/- 0.24, and 1.66 +/- 0.23, respectively. The mean prediction errors for the nomogram and the computer program were -0.037 and -0.026, respectively, and the mean percent absolute prediction errors were 11.6% and 11.0%, respectively. Neither method was biased, and differences between the results for the two methods were not significant. The predictive performance of the warfarin dosing nomogram was comparable to that of the computer program.

Bayes Theorem↗

Diagnostic X-ray shielding design based on an empirical model of photon attenuation.

A series of nomograms that simplify determination of diagnostic X-ray shielding requirements with lead are presented. All recommendations of the NCRP, except that to "add one half value layer" in determining secondary barriers, were followed in the production of these curves. For secondary barriers, the shielding required to reduce the weekly exposure to the applicable MPD has been determined. This eliminates the over-shielding inherent in the "add one HVL" approximation and allows a variety of more cost effective materials to be considered for secondary barriers.

Hospital Departments↗

Apnea testing in suspected brain dead children--physiological and mathematical modelling.

OBJECTIVE: To study the validity and safety of the traditional apnea test in children, and to evaluate a mathematical equation estimating the hemodynamic response to the apnea test. DESIGN: A prospective clinical study. SETTING: Pediatric ICU. PATIENTS AND PARTICIPANTS: 38 pediatric patients suffering severe brain injury aged 2 months to 17 years, undergoing apnea testing for brain death. MEASUREMENTS AND RESULTS: Apnea tests were performed 61 times (once in 19 patients, twice in 15, and 3 times in 4 patients). Mean PaCO2 was 41.1 +/- 10.6 mmHg before apnea and increased to 68.0 +/- 17.6 at 5 min. PaCO2 increased to 81.8 +/- 20.1 and 86.0 +/- 25.6 at 10 and 15 min, respectively. There was a mean PaCO2 increase by 5.38 +/- 1.4 mmHg/min in the first 5 min, and 2.75 +/- 0.5 mmHg/min during the next 5 min. We found a statistically significant (p < 0.05) linear relationship between the natural logarithm of PaCO2, time, and the logarithm of the initial level of PaCO2. An inverse linear relationship (p < 0.05) was found between systemic mean arterial pressure (MAP) and initial level of PaCO2 presented as mathematical correlations and nomograms. CONCLUSIONS: By using our model for predicting MAP and PCO2 prior to apnea testing, hemodynamic embarrassment can be anticipated and prevented, thus allowing a safer procedure in the detection of brain death. Despite the fact that continuous cardiorespiratory monitoring is important, hemodynamic disturbances can be estimated before the apnea test, thus allowing a safer approach to brain death detection.

Adolescent↗

[A nomogram of duplex ultrasound quantification of peripheral arterial stenoses. Studies of the cardiovascular model and in angiography patients].

BACKGROUND AND METHODS: Blood flow velocity measurements were performed with duplex ultrasound in vitro (flow phantom) and in 62 patients who underwent angiography due to peripheral vascular disease. RESULTS: Intrastenotic peak systolic velocity (PSV) divided by proximally recorded PSV (peak velocity ratio, PVR) exhibited a strong correlation with percent diameter reduction: r2 = 0.86; N = 106 stenoses. A PVR value > or = 2.4 indicated a more than 50% stenosis with a sensitivity of 87% and a specificity of 94%. Calculation of PVR may normalize for patient variation and allow noninvasive quantification of lumen narrowing with high sensitivity and specificity. The intraobserver variability (95% CI) of stenosis quantification using PVR values was 10%. A nomogram simplifies estimation of lumen narrowing after measurement of intrastenotic and proximal PSV values. CONCLUSION: Quantification of peripheral artery stenoses can be performed easily and noninvasively with duplex ultrasound using the peak velocity ratio (PVR).

Aged↗

Prediction of 1-year survival after thrombolysis for acute myocardial infarction in the global utilization of streptokinase and TPA for occluded coronary arteries trial.

BACKGROUND: When a patient survives thrombolysis for acute myocardial infarction, little information from large studies exists from which to estimate prognosis during follow-up visits. METHODS AND RESULTS: Baseline, in-hospital, and later survival data were collected from 41 021 patients enrolled in Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries, a randomized trial of 4 thrombolytic-heparin regimens with standard aspirin and beta-blockade. Cox proportional hazards models were developed to predict 1-year survival in 30-day survivors (n=37 869) from baseline clinical and ECG factors and in-hospital factors; a combined model then was developed (C-index 0.800). The model was simplified into a nomogram to predict individual outcomes (C-index 0.754). Factors reflecting demographics (advanced age, lighter weight), larger infarctions (higher Killip class, lower blood pressure, faster heart rate, longer QRS duration), cardiac risk (smoking, hypertension, prior cerebrovascular disease), and arrhythmia were important predictors of death between 30 days and 1 year. Black race was associated with a substantial increase in risk after considering other factors. Revascularization was associated with reduced risk between 30 days and 1 year. CONCLUSIONS: When evaluating a patient who has survived acute infarction treated with thrombolysis, clinicians can estimate the likelihood of survival from factors easily measured during admission. Although many risk factors clearly relate to age, left ventricular dysfunction, or clinical instability, black race is an unexplained risk factor requiring further examination.

Aged↗

The prognostic significance of ubiquitination-related genes in multiple myeloma by bioinformatics analysis.

BACKGROUND: Immunoregulatory drugs regulate the ubiquitin-proteasome system, which is the main treatment for multiple myeloma (MM) at present. In this study, bioinformatics analysis was used to construct the risk model and evaluate the prognostic value of ubiquitination-related genes in MM. METHODS AND RESULTS: The data on ubiquitination-related genes and MM samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The consistent cluster analysis and ESTIMATE algorithm were used to create distinct clusters. The MM prognostic risk model was constructed through single-factor and multiple-factor analysis. The ROC curve was plotted to compare the survival difference between high- and low-risk groups. The nomogram was used to validate the predictive capability of the risk model. A total of 87 ubiquitination-related genes were obtained, with 47 genes showing high expression in the MM group. According to the consistent cluster analysis, 4 clusters were determined. The immune infiltration, survival, and prognosis differed significantly among the 4 clusters. The tumor purity was higher in clusters 1 and 3 than in clusters 2 and 4, while the immune score and stromal score were lower in clusters 1 and 3. The proportion of B cells memory, plasma cells, and T cells CD4 na&#xef;ve was the lowest in cluster 4. The model genes KLHL24, HERC6, USP3, TNIP1, and CISH were highly expressed in the high-risk group. AICAr and BMS.754,807 exhibited higher drug sensitivity in the low-risk group, whereas Bleomycin showed higher drug sensitivity in the high-risk group. The nomogram of the risk model demonstrated good efficacy in predicting the survival of MM patients using TCGA and GEO datasets. CONCLUSIONS: The risk model constructed by ubiquitination-related genes can be effectively used to predict the prognosis of MM patients. KLHL24, HERC6, USP3, TNIP1, and CISH genes in MM warrant further investigation as therapeutic targets and to combat drug resistance.

Humans↗

Spirometric nomograms for normal children and adolescents in Puerto Rico.

OBJECTIVE: The use of spirometric reference values specific to the population being tested is preferable. A study carried out in Puerto Rico is used here to develop nomograms for normal children and adolescents based on age and height, two variables that have been found to be good predictors of pulmonary function. MATERIAL AND METHODS: The data for healthy individuals aged 5 to 18 were extracted (108 girls and 107 boys) from a larger study of spirometric measurements collected on 4527 individuals attending medical services in Puerto Rico. Several models were tested for the prediction of FEV1, FVC and the ratio FEV1/FVC. The best models were selected for each gender, and nomograms were developed showing the fifth, twenty-fifth, fiftieth, seventy-fifth, and ninety-fifth percentile of the predicted values according to age and height separately. RESULTS: The best models were those using the logarithm of the pulmonary function and the cube of height (R2 = 0.79-0.81), and age without transformation (R2 = 0.73-0.77). Corresponding nomograms were developed based on these models. The ratio showed little variation for different ages and heights. CONCLUSIONS: Pulmonary function can be efficiently predicted by age and height. Nomograms provide a simple way to use spirometric references that can be incorporated to clinical practice.

Adolescent↗

Prognostic significance of the initial electrocardiogram in patients with acute myocardial infarction. GUSTO-I Investigators. Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries.

CONTEXT: Early risk stratification of patients with myocardial infarction is critical to determine optimum treatment strategies and enhance outcomes, but knowledge of the prognostic importance of the initial electrocardiogram (ECG) is limited. OBJECTIVE: To assess the independent value of the initial ECG for short-term risk stratification after acute myocardial infarction. DESIGN: Retrospective analysis of the Global Utilization of Streptokinase and t-PA (alteplase) for Occluded Coronary Arteries (GUSTO-I) clinical trial database. SETTING: A total of 1081 hospitals in 15 countries. PATIENTS: From the 41 021 patients enrolled in the overall study, we selected those who presented within 6 hours of chest pain onset with ST-segment elevation and no confounding factors (paced rhythms, ventricular rhythms, or left bundle-branch block) on the ECG performed before thrombolysis was administered (n=34 166). MAIN OUTCOME MEASURE: Ability of initial ECG to predict all-cause mortality at 30 days. RESULTS: Most ECG variables were associated with 30-day mortality in a univariable analysis. In a multivariable analysis combining the initial ECG variables and clinical predictors of mortality, the sum of the absolute ST-segment deviation (both ST elevation and ST depression: odds ratio [OR], 1.53; 95% confidence interval [CI], 1.38-1.69), ECG, heart rate (OR, 1.49; 95% CI, 1.41-1.59), QRS duration (for anterior infarct: OR, 1.55; 95% CI, 1.43-1.68), and ECG evidence of prior infarction (for new inferior infarct: OR, 2.47; 95% CI, 2.02-3.00) were the strongest ECG predictors of mortality. A nomogram based on the multivariable model produced excellent discrimination of 30-day mortality (C-index, 0.830). CONCLUSIONS: In patients presenting with myocardial infarction accompanied by ST-segment elevation, components of the initial ECG help predict 30-day mortality. This information should be valuable in early risk stratification, when the opportunity to reduce mortality is greatest, and may help in assessing outcomes adjusted for patient risk.

Aged↗

Estimation of vulnerable zones due to accidental release of toxic materials resulting in dense gas clouds.

Heavy gas dispersion models have been developed at IIT (hereinafter referred as IIT heavy gas models I and II) with a view to estimate vulnerable zones due to accidental (both instantaneous and continuous, respectively) release of dense toxic material in the atmosphere. The results obtained from IIT heavy gas models have been compared with those obtained from the DEGADIS model [Dense Gas Dispersion Model, developed by Havens and Spicer (1985) for the U.S. Coast Guard] as well as with the observed data collected during the Burro Series, Maplin Sands, and Thorney Island field trials. Both of these models include relevant features of dense gas dispersion, viz., gravity slumping, air entrainment, cloud heating, and transition to the passive phase, etc. The DEGADIS model has been considered for comparing the performance of IIT heavy gas models in this study because it incorporates most of the physical processes of dense gas dispersion in an elaborate manner, and has also been satisfactorily tested against field observations. The predictions from IIT heavy gas models indicate a fairly similar trend to the observed values from Thorney Island, Burro Series, and Maplin experiments with a tendency toward overprediction. There is a good agreement between the prediction of IIT Heavy Gas models I and II with those from DEGADIS, except for the simulations of IIT heavy gas model-I pertaining to very large release quantities under highly stable atmospheric conditions. In summary, the performance of IIT heavy gas models have been found to be reasonably good both with respect to the limited field data available and various simulations (selected on the basis of relevant storages in the industries and prevalent meteorological conditions performed with DEGADIS). However, there is a scope of improvement in the IIT heavy gas models (viz., better formulation for entrainment, modification of coefficients, transition criteria, etc.). Further, isotons (nomograms) have been prepared by using IIT heavy gas models for chlorine, which provide safe distance for various storage amounts for 24 meteorological scenarios prevalent in the entire year. These nomograms are prepared such that a nonspecialist can use them easily for control and management in case of an emergency requiring the evacuation of people in the affected region. These results can also be useful for siting and limiting the storage quantities.

Accidents, Occupational↗

scRNA-seq and bulk RNA-seq reveal the characteristics of macrophage copper metabolism and establish a risk signature in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a prevalent malignancy with an urgent need for improved prognostic stratification and treatment-response prediction. This study aimed to explore a macrophage copper metabolism-associated prognostic model and to investigate the relationship between this risk model and the tumor immune microenvironment. METHODS: The FindClusters function was used to analyze cell clusters, and CellChat and CellPhoneDB/LIANA were employed for cell-cell communication analysis. Copper metabolism-related genes were sourced from the MSigDB database. A prognostic risk model was established using least absolute shrinkage and selection operator (LASSO) analysis and multivariate Cox regression analysis, and a nomogram was constructed by integrating the prognostic model with clinicopathological factors. Additional analyses were performed to map the seven model genes in single-cell data, assess model uncertainty and robustness, evaluate macrophage/copper/cuproptosis-related transcriptional programs, and examine the correlations between risk score, immune infiltration and predicted drug sensitivity. RESULTS: Using single-cell RNA sequencing (scRNA-seq) data, we identified four macrophage subpopulations. Macrophages with high SPP1 expression showed close interaction with T cell populations and were associated with copper ion metabolism. By incorporating 141 copper metabolism-related genes and using The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort, we constructed a seven-gene risk prediction model. Additional single-cell mapping showed that the model genes were detectable in the HCC single-cell dataset and showed a macrophage-associated expression pattern. The model showed moderate prognostic discrimination in TCGA-LIHC, whereas its external performance was heterogeneous and remained evaluable across external cohorts, with performance varying among datasets. Immune and mechanism-related analyses suggested that the risk signature was associated with macrophage-related infiltration, copper metabolism and cuproptosis-related transcriptional programs. Drug sensitivity analysis nominated Daporinad as a computationally predicted candidate compound, supporting Daporinad as a pharmacogenomic candidate for follow-up investigation. CONCLUSIONS: By integrating scRNA-seq and bulk RNA sequencing (RNA-seq) data, we constructed a macrophage copper metabolism-associated prognostic signature for HCC. The risk score was associated with survival, immune microenvironment features and predicted drug response, providing a transcriptomic framework for risk stratification and therapeutic hypothesis generation.

Hepatocellular carcinoma (HCC)↗

Development and validation of a comprehensive prognostic model for 28-day ICU mortality in non-traumatic subarachnoid hemorrhage: an analysis based on the MIMIC-IV database.

BACKGROUND: Due to the complex pathophysiology of non-traumatic subarachnoid hemorrhage (SAH), accurate risk prediction remains a challenge. Our aim is to develop and validate a comprehensive prognostic model that integrates demographic characteristics, vital signs, laboratory parameters, and more, to provide clinical decision-making support in real-world practice. METHODS: We conducted a retrospective cohort study of 785 Non-traumatic subarachnoid hemorrhage patients. The cohort was randomly divided into a training set (n&#xa0;=&#xa0;549) and a validation set (n&#xa0;=&#xa0;236). Feature selection was performed using LASSO regression, followed by backward stepwise Cox regression for optimization. A nomogram was constructed based on independent predictive factors, and model performance was assessed using discrimination, calibration, and decision curve analysis. To prevent immortal-time bias, all predictors were anchored to a fixed early (first-24-hour) measurement window, treatment variables were modelled as binary indicators rather than cumulative exposures, and a five-model sensitivity analysis with baseline-severity adjustment was performed. RESULTS: The development of our model followed a systematic approach: first, 15 potential predictive factors were selected via LASSO regression, which were then refined to 12 independent predictors using backward stepwise Cox regression. The final predictive factors included: Ventilation, AHT, Nimodipine 60&#xa0;mg, Age, SAPS.II, Input amount, Calcium total, Platelet count, White blood cells, Anion gap, pH, and Chloride. The integrated model demonstrated excellent predictive ability for 7-day, 14-day, and 21-day mortality in both the training set (AUC: 0.972, 0.934, 0.898) and the validation set (AUC: 0.968, 0.948, 0.911). Calibration curves and decision curve analysis confirmed the model's reliability and clinical utility across different time points. We constructed a nomogram for individualized risk prediction. Univariate Kaplan-Meier survival analysis demonstrated significant stratification of survival outcomes by each predictor, while restricted cubic spline analysis revealed non-linear relationships between continuous variables and mortality risk. Random survival forest analysis identified the top three predictive factors (Nimodipine 60&#xa0;mg, Ventilation, AHT) and compared them with our full 12-variable model, confirming superior performance of the integrated model at all time points. At the 28-day primary endpoint, the model achieved a time-dependent AUC of 0.898 (training) and 0.904 (validation); after restricting predictors to the early baseline window, the leakage-controlled model retained good discrimination (validation C-index 0.803). CONCLUSIONS: Our ICU 28-day mortality prognosis model demonstrated robust performance in predicting ICU 28-day mortality in non-traumatic subarachnoid hemorrhage. The model, through the nomogram, provides individualized risk assessment, aiding clinical decision-making and patient stratification.

Humans↗

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↗

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↗

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↗

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↗