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HIV risk behaviors during pharmacologic treatment for opioid dependence: a comparison of levomethadyl acetate [corrected] buprenorphine, and methadone.

The efficacies of three opioid substitution medications for reducing HIV risk behaviors in opioid-dependent patients were assessed in a randomized double-blind clinical trial comparing levomethadyl acetate [corrected] (LAAM), buprenorphine (BUP), and methadone (METH). Individually optimized flexible dosing was used for each group, with weekly possible doses of 255-391 mg of LAAM, 56-112 mg of BUP, and 420-700 mg of METH. An interview regarding specific HIV risk behaviors, including injecting, equipment sharing, and sexual activity, yielded data for pretreatment and four in-study time points for 137 subjects. Declines in risk behaviors during treatment were evident in all groups for most measures of injecting and equipment sharing. Only the METH group showed consistent declines in measures of sexual behaviors. These results demonstrate that all three medications can be highly effective in decreasing HIV risk behaviors when the dose is optimized. Reductions in sexual behaviors for the METH group are consistent with known METH side effects.

Adult↗

Coexisting thyroid and gastric autoimmune diseases are not due to cross-reactive autoantibodies.

Some autoimmune diseases tend to cluster within families, patients with one such disease showing an increased tendency to develop certain other autoimmune diseases within the same group. We have investigated the possibility that this clustering arises because some patients produce autoantibodies which cross-react with antigenic determinants which are shared by diverse tissues. Our data indicate that this is not the case, at least so far as thyroid and gastric autoimmune diseases are concerned. This observation increases the likelihood that the real explanation for such clustering concerns sharing of idiotypic determinants by the different pathogenic clones involved or by their precursors.

Anemia, Pernicious↗

PLUNC: a novel family of candidate host defence proteins expressed in the upper airways and nasopharynx.

The upper respiratory tract, including the nasal and oral cavities, is the major route of entry of pathogens into the body, and early recognition of bacterial products in this region is critical for host defence. A well-established family of four proteins involved in this process are bactericidal/permeability-increasing protein (BPI) and lipopolysaccharide-binding protein (LBP), which are central to the host defence against bacteria, and cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP), which have also been implicated in this response. In this paper, we demonstrate the existence of a related family of seven human proteins, which we designate PLUNC proteins. The PLUNC proteins are encoded by adjacent genes found within a 300 kb region of chromosome 20, suggesting that they may be under transcriptional control of shared genomic elements, and expression data shows that these proteins are found in overlapping regions of the pulmonary, nasopharyngeal and oral epithelium, sites where the previously described BPI family members are not expressed. Whereas the BPI family are predicted to share very closely similar three-dimensional structures, the PLUNC family is predicted to have much greater variability in the N-terminal domain, corresponding to the active domain of BPI, thus creating the notion of a BPI/PLUNC structural superfamily. We suggest that members of the PLUNC family may function in the innate immune response in regions of the mouth, nose and lungs, which are sites of significant bacterial exposure.

Amino Acid Sequence↗

The Second Sheffield Psychotherapy Project: rationale, design and preliminary outcome data.

The cost-efficiency of psychotherapy research can be enhanced by (a) dissemination of the rationale and design of large-scale investigations whilst still under way, (b) incorporation of process measures within comparative outcome studies, (c) cumulative development of a series of related studies, and (d) sharing of recordings and other data with other investigators. We present the rationale and design, including full details of process and outcome measures, of the second Sheffield psychotherapy project, in which 120 white-collar, professional and managerial employees presenting with major depressive disorder receive either eight or 16 sessions of either prescriptive (cognitive/behavioural) or exploratory (relationship-oriented) therapy in a 2 x 2 design. Ethical considerations prompted the analysis of preliminary outcome data on 48 clients. Results suggested substantial clinical improvement, of similar magnitude for both methods and both durations of treatment, except that exploratory therapy appeared more effective than prescriptive in relation to interpersonal difficulties. Other workers are invited to build collaboratively on this research by making their own process analyses of recordings available from this study, relating these analyses to the existing impact and outcome data, and developing comparable data sets based on the design and initial results of this project.

Depressive Disorder↗

Three perspectives on integrated clinical databases.

The dramatic transformation of health care organizations from independent local entities into regional and national integrated health care delivery enterprises has forced a reevaluation of the role of information systems. Until recently, nearly all clinical information systems were acquired to support financial and administrative services within single facilities. When independent facilities merge to form an integrated health system (IHS), they find that their unique computer systems do not allow for the sharing or combining of clinical data. However, new technologies are beginning to enable patient-specific data scattered among many information systems in many different hospitals and ambulatory care settings to be unified into a single database called a clinical data repository. The hope is that comprehensive electronic clinical records can enable IHSs to meet their goals of improving the quality and reducing the cost of health care. As the number of technological impediments to forming integrated clinical information systems rapidly decreases, nontechnologic issues surrounding the sharing of patient information become more prominent. The author focuses on the clinician's, the administrator's, and the patient's unique perspectives on the benefits and possible problems associated with clinical data repositories. He then describes how one IHS, together with an academic medical institution, has begun to grapple with many of these concerns through an effort called Project Spectrum. The goal of the project is the successful implementation of a comprehensive clinical data repository.

Clinical Medicine↗

Garner and congruence effects in the speeded classification of bimodal signals.

The role of attention in speeded Garner classification of concurrently presented auditory and visual signals was examined in 4 experiments. Within-trial interference (i.e., congruence effects) occurred regardless of the attentional demands of the task. Between-trials interference (i.e., Garner interference) occurred only under conditions of divided attention when making judgments about auditory signals. Of importance, the data show congruence effects in the absence of Garner interference. Such a pattern has been rarely reported in studies of the classification of purely visual stimuli and contradicts theoretical accounts asserting that the effects share a common locus. The data question the notion that Garner classification reveals fundamental insights about the nature of the perceptual processing of bimodal stimuli.

Attention↗

Kinetochore structure and its role in chromosome orientation during the first meiotic division in male D. melanogaster.

An electron microscopic investigation of kinetochore structure during the first meiotic division in male Drosophila melanogaster is presented. The data suggest that the structure that is responsible for initial microtubule attachment and chromosome orientation is a single, bilaminar hemisphere on each half-bivalent. Following the initial attachment this structure undergoes morphogenesis to a double-disc structure that reflects the underlying duality of sister chromatids in the half-bivalent. Thus these data support Darlington's idea that sister chromatids disjoin to the same spindle pole because they share a single kinetochore. Additionally, these data suggest that the meiotic mutations ord and mel-S332 sometimes cause premature "doubling" of the kinetochore region though, as discussed, possibly for a trivial reason.

Anaphase↗

Methods for quantifying variability and uncertainty in AP-42 emission factors: case studies for natural gas-fueled engines.

Quantitative methods for characterizing variability and uncertainty were applied to case studies of oxides of nitrogen and total organic carbon emission factors for lean-burn natural gas-fueled internal combustion engines. Parametric probability distributions were fit to represent inter-engine variability in specific emission factors. Bootstrap simulation was used to quantify uncertainty in the fitted cumulative distribution function and in the mean emission factor. Some methodological challenges were encountered in analyzing the data. For example, in one instance, five data points were available, with each data point representing a different market share. Therefore, an approach was developed in which parametric distributions were fitted to population-weighted data. The uncertainty in mean emission factors ranges from as little as approximately +/-10% to as much as -90 to +180%. The wide range of uncertainty in some emission factors emphasizes the importance of recognizing and accounting for uncertainty in emissions estimates. The skewness in some uncertainty estimates illustrates the importance of using numerical simulation approaches that do not impose restrictive symmetry assumptions on the confidence interval for the mean. In this paper, the quantitative method, the analysis results, and key findings are presented.

Air Pollutants↗

The National Program of Cancer Registries: explaining state variations in average cost per case reported.

INTRODUCTION: The Centers for Disease Control and Prevention's National Program of Cancer Registries is a federally funded surveillance program that provides support and assistance to state and territorial health departments for the operation of cancer registries. The objective of this study was to identify factors associated with the Centers for Disease Control and Prevention's costs to report cancer cases during the first 5 years of the National Program of Cancer Registries. METHODS: Information on expenditures and number of cases reported through the National Program of Cancer Registries was used to estimate the average cost per case reported for each state program. Additional information was obtained from other sources, and regression analyses were used to assess the contribution of each factor. RESULTS: Average costs of the National Program of Cancer Registries differed substantially among programs and were inversely associated with the number of cases reported (P < .001). The geographic area of the state was positively associated with the cost (P = .01), as was the regional cost of living (P = .08), whereas the program type (i.e., enhancement or planning) was inversely associated with cost (P = .08). CONCLUSION: The apparent existence of economies of scale suggests that contiguous state programs might benefit from sharing infrastructure and other fixed costs, such as database management resources, depending on the geographic area and population size served. Sharing database management resources might also promote uniform data collection and quality control practices, reduce the information-sharing burden among states, and allow more resources to be used for other cancer prevention and control activities.

Centers for Disease Control and Prevention, U.S.↗

A concept of humoral immunity among ruminants and an approach to its investigation.

My goal has been to piece together bits of information, both old and new, so as to provide you with some concepts of humoral immune function. Specifically I have described concepts of secretory immunity in two different organ systems, the lower respiratory tract and the mammary gland. Should these concepts not even survive this meeting or be proven incorrect by future research, I hope I have at least stimulated your thinking with an alternative view and challenged you to saw off the limb I have put myself on with the concepts I have presented. More than mere conjectural hypotheses, I have presented some data on the ELISA out of my belief that one approach to establishing concepts in humoral immunity depends on the ability to accurately and quantitatively measure the distribution of antibodies among isotypes. I have also shared with you some preliminary data on the transport of SIgA into bile and other secretion which will hopefully encourage others to finally establish the quantitative significance of locally synthesized versus serum-derived IgA in the various exocrine secretions of ruminants. Finally, I have dared to take ruminant immunoglobulin homology "back to sea"; perhaps this last topic will stimulate your palate if not your mind.

Animals↗

Multiinstitutional validation of the UCSF cancer of the prostate risk assessment for prediction of recurrence after radical prostatectomy.

BACKGROUND: The University of California, San Francisco (UCSF) Cancer of the Prostate Risk Assessment (CAPRA) is a novel preoperative index which predicts the risk of biochemical recurrence after radical prostatectomy. The performance of the index is at least as good as the best available instruments based on clinical variables, and the 0 to 10 score is simple to calculate for both clinical and research purposes. This study used a large external dataset to validate CAPRA. METHODS: Data were abstracted from the Shared Equal Access Regional Cancer Hospital (SEARCH) database, a registry of men who underwent radical prostatectomy at 4 Veterans Affairs and 1 active military medical center. Of 2096 men in the database, 1346 (64%) had full data available to calculate the CAPRA score. Performance of the CAPRA score was assessed with proportional hazards regression, survival analysis, and the concordance (c) index. RESULTS: Of the studied patients, 41% were non-Caucasian, and their mean age was 62 years. Twenty-six percent suffered recurrence; median follow-up among patients who did not recur was 34 months. The hazard ratio (HR) for each 1-point increase in CAPRA was 1.39 (95% CI [confidence interval], 1.31-1.46). The 5-year recurrence-free survival rate ranged from 86% for CAPRA 0-1 patients to 21% for CAPRA 7-10 patients. Increasing CAPRA scores were significantly associated with increasing risk of adverse pathologic outcomes. The c-index for CAPRA for the validation set was 0.68, compared with 0.66 for the original development set. CONCLUSIONS: The UCSF-CAPRA accurately predicted both biochemical and pathologic outcomes after radical prostatectomy among a large, diverse, cohort of men. These results validated the effectiveness of this powerful and straightforward instrument.

Adult↗

CERR: a computational environment for radiotherapy research.

A software environment is described, called the computational environment for radiotherapy research (CERR, pronounced "sir"). CERR partially addresses four broad needs in treatment planning research: (a) it provides a convenient and powerful software environment to develop and prototype treatment planning concepts, (b) it serves as a software integration environment to combine treatment planning software written in multiple languages (MATLAB, FORTRAN, C/C++, JAVA, etc.), together with treatment plan information (computed tomography scans, outlined structures, dose distributions, digital films, etc.), (c) it provides the ability to extract treatment plans from disparate planning systems using the widely available AAPM/RTOG archiving mechanism, and (d) it provides a convenient and powerful tool for sharing and reproducing treatment planning research results. The functional components currently being distributed, including source code, include: (1) an import program which converts the widely available AAPM/RTOG treatment planning format into a MATLAB cell-array data object, facilitating manipulation; (2) viewers which display axial, coronal, and sagittal computed tomography images, structure contours, digital films, and isodose lines or dose colorwash, (3) a suite of contouring tools to edit and/or create anatomical structures, (4) dose-volume and dose-surface histogram calculation and display tools, and (5) various predefined commands. CERR allows the user to retrieve any AAPM/RTOG key word information about the treatment plan archive. The code is relatively self-describing, because it relies on MATLAB structure field name definitions based on the AAPM/RTOG standard. New structure field names can be added dynamically or permanently. New components of arbitrary data type can be stored and accessed without disturbing system operation. CERR has been applied to aid research in dose-volume-outcome modeling, Monte Carlo dose calculation, and treatment planning optimization. In summary, CERR provides a powerful, convenient, and common framework which allows researchers to use common patient data sets, and compare and share research results.

Biomedical Research↗

High-performance clinical patient data review and consultation system.

Primary care physicians rely on specialists. Specialists are too expensive to be located at every clinical site requiring a practical means for specialists to help without requiring patients or specialists to travel for consultation. To address the challenge of providing primary care physician access to specialists, we are developing a clinical prototype system for the high-speed access and transfer of patient data and images within Radiology Departments, Medical Centers and Health Care Networks. The key components of the system are: a high-bandwidth network (100 Mbit/s upgradeable to ATM); an image server system with a 30-60 day patient image on-line archive ( < 10 sec. recall) coupled with a long term archive; viewing consoles matching existing film display paradigms located within the medical center and clinics providing rapid access to patient data and diagnostic images for house staff (OR/ER/ICU); clinician access to the image archive on a consultation basis in office computers; and image review applications which closely follow the established paradigms used by clinicians. Using our system primary care physicians can rapidly review patient data locally obtaining additional consultation from tertiary sites while the patient is present. Clinics and outlying medical centers gain rapid access to specialists with physicians in different cities discussing patient diagnostic and management issues in a shared environment leading to instantaneous data analysis and diagnosis further reducing health care costs and enhancing patient care.

Computer Communication Networks↗

Why more cost-sharing won't slow Medicare spending.

In considering ways to slow the growth in Medicare expenditures, policymakers have concluded that increasing point-of-service cost-sharing for patients will reduce demand for health services. Under the current system, Medicare beneficiaries faced with increased cost-sharing can reduce their demand for services or purchase additional private insurance. New data from the 1991 Medicare Current Beneficiary Survey show that high-income persons protect themselves from out-of-pocket costs by purchasing private supplemental insurance. Surprisingly, the data also reveal that many low-income persons also purchase private insurance, demonstrating that the elderly--whatever their income level--consider supplementary insurance more of a necessity than a luxury. Thus, it appears that increased beneficiary cost-sharing would have a limited effect on Medicare spending growth.

Aged↗