Predicting Addiction Severity Index (ASI) interviewer severity ratings for a computer-administered ASI.

The Addiction Severity Index (ASI) is a reliable and valid measure of problem severity among addicted patients. Concerns have been raised about the reliability of the Interviewer Severity Rating (ISR), a summary score for each of 7 domains. As part of an effort to build a computer-administered ASI, regression equations were developed to predict the ISR. Repeated resampling of a large dataset, consisting of 1,124 ASIs conducted by trained interviewers, permitted derivation of stable regression equations predicting the ISR for each ASI domain from patients' answers to preselected interview items. The resulting 7 Predicted Severity Ratings (PSRs) were tested on 8, standardized vignettes, with "gold standard," expert-generated ISRs. Reliabilities compared well with those of intensively trained interviewers. The PSRs could provide an alternative to potentially unreliable interviewer ratings, enhancing the ASI's role in treatment planning and treatment matching and make possible a computer-administered version of the ASI. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Design of robust gain-scheduled PI controllers for nonlinear processes

Gain-scheduling has proven to be a successful design methodology in many engineering applications. However, in the absence of a sound theoretical analysis, these designs come with no guarantees of robust stability, performance or even nominal stability of the overall gain-scheduled deign.This paper presents such an analysis for one type of nonlinear gain-scheduled control system based on the process input for nonlinear chemical processes. A methodology is also proposed for the design and optimization of the robust gain-scheduled PI controller. Conditions which guarantee robust stability and performance are formulated as a finite set of linear matrix inequalities (LMIs) and hence, the resulting problem is numerically tractable. Issues of modeling error and input-saturation are explicitly incorporated into the analysis. A simulation study of a nonlinear continuous stirred tank reactor (CSTR) process indicates that this approach can produce efficient sub-optimal robust gain-scheduled controllers.     

Amplification of Periodic Temperature Disturbances in a Packed‐Bed Reactor: CO Oxidation over a CuO/Al2O3 Catalyst

Amplification of periodic variations of input temperature in a product‐inhibited reaction — CO oxidation over CuO‐γ‐Al₂O₃ — was investigated experimentally in an insulated packed‐bed reactor. At steady state the temperature profile was elongated compared with that of a reactant‐inhibited CO oxidation over Pt/Al₂O₃, studied elsewhere. Under periodic operation, amplitudes of the resulting travelling temperature waves, monitored downstream from the reaction front, were amplified to a greater extent than those in the reactant‐inhibited CO oxidation over Pt/Al₂O₃. The magnitude of the amplification depended on the perturbation frequency and showed resonance behaviour. The magnitude decreased monotonically with increasing perturbation amplitude.     

Fluorescence‐based fouling prediction and optimization of a membrane filtration process for drinking water treatment

A novel fluorescence‐based approach is proposed for modeling, predicting, and optimizing different fouling dynamics in an ultrafiltration (UF) process for drinking water treatment. Principal component analysis (PCA) was used to extract information in terms of principal components (PCs), related to major membrane foulant groups, from fluorescence excitation–emission matrix measurements captured during UF of natural river water. The evolution of PC scores during the filtration process was then related to membrane fouling using dynamic balances of latent variable values (PC scores). This approach was found suitable for forecasting fouling behaviors with good accuracy based solely on fluorescence data collected 15 min from the start of the filtration. The proposed approach was tested experimentally through model‐based optimization of backwashing times with the objective of minimizing the energy consumption per unit amount of water produced during the filtration process. This approach was also useful for identifying fouling groups contributing to reversible and irreversible fouling. © 2011 American Institute of Chemical Engineers AIChE J, 2012     

Hypertension and renal disease in systemic lupus erythematosus

A retrospective analysis of 235 patients at the National Institutes of Health who met at least five criteria for systemic lupus erythematosus (SLE) indicated that 45% were hypertensive. Approximately two thirds of these hypertensive patients had creatinine clearances of more than 60 ml/min and nonnephrotic range proteinuria. Only 16% of normotensive patients had creatinine clearances of less than 60 ml/m9n. A subgroup of 36 patients with SLE and with biopsy-proved diffuse renal disease were studied. For these patients, the presence of hypertension could not be correlated with the degree of proteinuria or hematuria, with the level of serum complement, or with the presence of casts, focal necrosis, crescent formation, or interstitial inflammation. Hypertensive patients had a median age of 24.5 years; the majority had creatinine clearances of more than 60 ml/min. In SLE, hypertension is not necessarily associated with advanced renal disease, and high blood pressure may occur relatively early in the course of the disease.     

Development and preliminary experience with an ease of extractability rating system for prescription opioids

One important factor in the abuse potential of an opioid product is the ease with which active drug can be extracted. There are currently no standards for testing or reporting extractability. This article describes the development of an Extractability Rating System for use by the pharmaceutical industry and regulators. Despite several limitations, this effort serves as a call for standardized testing and reporting so that products can be accurately rated, and should help establish goals for drug developers who wish to develop “abuse-resistant” opioid products.     

Treatment delay, outcome, and satisfaction in time-limited group and individual psychotherapy.

As part of a randomized clinical trial in which we compared outcome in time-limited individual and time-limited group psychotherapy, patients were interviewed and completed a battery of assessment measures. All participants in the study were then randomly assigned to one or the other treatment modality. There were inevitable delays before patients began their assigned therapies. Group treatment patients waited an appreciably longer period of time, on average, than did individual treatment patients (48 days vs. 31 days). Nonetheless, it was only for individual therapy patients that we found a highly significant relationship between this delay and treatment satisfaction at the completion of therapy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer. The Cancer and Leukemia Group B

BACKGROUND: Both total dose and dose intensity of adjuvant chemotherapy are postulated to be important variables in the outcome for patients with operable breast cancer. The Cancer and Leukemia Group B study 8541 examined the effects of adjuvant treatment using conventional-range dose and dose intensity in female patients with stage II (axillary lymph node-positive) breast cancer. METHODS: Within 6 weeks of surgery (radical mastectomy, modified radical mastectomy, or lumpectomy), 1550 patients with unilateral breast cancer were randomly assigned to one of three treatment arms: high-, moderate-, or low-dose intensity. The patients received cyclophosphamide, doxorubicin, and 5-fluorouracil on day 1 of each chemotherapy cycle, with 5-fluorouracil administration repeated on day 8. The high-dose arm had twice the dose intensity and twice the drug dose as the low-dose arm. The moderate-dose arm had two thirds the dose intensity as the high-dose arm but the same total drug dose. Disease-free survival and overall survival were primary end points of the study. RESULTS: At a median follow-up of 9 years, disease-free survival and overall survival for patients on the moderate- and high-dose arms are superior to the corresponding survival measures for patients on the low-dose arm (two-sided P<.0001 and two-sided P = .004, respectively), with no difference in disease-free or overall survival between the moderate- and the high-dose arms. At 5 years, overall survival (average +/- standard error) is 79% +/- 2% for patients on the high-dose arm, 77% +/- 2% for the patients on the moderate-dose arm, and 72% +/- 2% for patients on the low-dose arm; disease-free survival is 66% +/- 2%, 61% +/- 2%, and 56% +/- 2%, respectively. CONCLUSION: Within the conventional dose range for this chemotherapy regimen, a higher dose is associated with better disease-free survival and overall survival.     

erbB-2, p53, and efficacy of adjuvant therapy in lymph node-positive breast cancer

BACKGROUND: We have previously reported that high expression of the erbB-2 gene (also known as HER-2/neu and ERBB2) in breast cancer is associated with patient response to dose-intensive treatment with cyclophosphamide, doxorubicin (Adriamycin), and 5-flurouracil (CAF) on the basis of short-term follow-up of 397 patients (set A) with axillary lymph node-positive tumors who were enrolled in Cancer and Leukemia Group B (CALGB) protocol 8541. METHODS: To validate those findings, we conducted immunohistochemical analyses of erbB-2 and p53 protein expression in an additional cohort of 595 patients (set B) from CALGB 8541, as well as a molecular analysis of erbB-2 gene amplification in tumors from all patients (sets A and B). Marker data were compared with clinical, histologic, treatment, and outcome data. RESULTS: Updated analyses of data from set A (median follow-up, 10.4 years) showed an even stronger interaction between erbB-2 expression and CAF dose, by use of either immunohistochemical or molecular data. A similar interaction between erbB-2 expression and CAF dose was observed in all 992 patients, analyzed as a single group. However, for set B alone (median follow-up, 8.2 years), results varied with the method of statistical analysis. By use of a proportional hazards model, the erbB-2 expression-CAF dose interaction was not significant for all patients. However, in the subgroups of patients randomly assigned to the high- or the moderate-dose arms, significance was achieved. When patient data were adjusted for differences by use of a prognostic index (to balance an apparent failure of randomization in the low-dose arm), the erbB-2 expression-CAF dose interaction was significant in all patients from the validation set B as well. An interaction was also observed between p53 immunopositivity and CAF dose. CONCLUSIONS: The hypothesis that patients whose breast tumors exhibit high erbB-2 expression benefit from dose-intensive CAF should be further validated before clinical implementation. Interactions between erbB-2 expression, p53 expression, and CAF dose underscore the complexities of predictive markers where multiple interactions may confound the outcome.     

Development and Preliminary Experience with an Ease of Extractability Rating System for Prescription Opioids

Abstract

One important factor in the abuse potential of an opioid product is the ease with which active drug can be extracted. There are currently no standards for testing or reporting extractability. This article describes the development of an Extractability Rating System for use by the pharmaceutical industry and regulators. Despite several limitations, this effort serves as a call for standardized testing and reporting so that products can be accurately rated, and should help establish goals for drug developers who wish to develop “abuse-resistant” opioid products.