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PubMed1995

Quality improvement guidelines for the treatment of acute pain and cancer pain. American Pain Society Quality of Care Committee.

OBJECTIVE: To develop quality improvement (QI) guidelines and programs to improve treatment outcomes for patients with acute pain and cancer pain. PARTICIPANTS: Twenty-four members of the American Pain Society (APS) participated in preparing the statement, including 15 nurses (oncology, general medical-surgical nursing, pediatrics, and QI research), seven physicians (clinical pharmacology, neurology, anesthesiology, radiation oncology, and physiatry), one psychologist, and one statistician. Participants were self-selected from the 3000 members of the APS, which supported the process and held annual open committee meetings and scientific symposia beginning in 1988. EVIDENCE: MEDLINE was searched (1980 to 1995) to identify all articles on pain assessment, treatment of acute pain or cancer pain, and QI or education related to pain. CONSENSUS PROCESS: Following panel discussions, one member (M.B.M.) prepared successive drafts and circulated them to the panel and APS membership for comments. After publication of a prototype version in 1991, 14 panelists carried out formal studies of implementation of the guidelines at three medical centers. This article was prepared based on this research, a new literature review, and suggestions from 50 pain clinicians and researchers. CONCLUSIONS: Quality improvement programs to improve treatment of acute pain and cancer pain should include five key elements: (1) Assuring that a report of unrelieved pain raises a "red flag" that attracts clinicians' attention; (2) making information about analgesics convenient where orders are written; (3) promising patients responsive analgesic care and urging them to communicate pain; (4) implementing policies and safeguards for the use of modern analgesic technologies; and (5) coordinating and assessing implementation of these measures. Several short-term studies suggest that this QI approach may improve patient satisfaction and facilitate recognition of institutional obstacles to optimal pain treatment, but it is not a panacea for undertreated pain. By making the magnitude of the problem apparent and committing the institution to change, pain treatment QI programs can provide a foundation for a multifaceted approach that includes education of clinicians and patients, design of informational tools to minimize errors in prescribing, and improved coordination of the process of assessing and treating pain.

Humans↗

PubMed1998

Are physicians' office laboratory results of comparable quality to those produced in other laboratory settings?

CONTEXT: In 1995, California adopted a bill that brought laboratory laws in line with the 1988 Clinical Laboratory Improvement Amendments' standards for clinical laboratories and mandated a study comparing results in physicians' office laboratories (POLs) with other settings. OBJECTIVE: To determine whether persons conducting tests in POLs produce accurate and reliable test results comparable to those produced by non-POLs. DESIGN: Survey of clinical laboratories using proficiency testing data. SETTING: All California clinical laboratories participating in the American Association of Bioanalysts proficiency testing program in 1996 (n=1110). MAIN OUTCOME MEASURES: "Unsatisfactory" (single testing event failure) and "unsuccessful" (repeated testing event failure) on proficiency testing samples. RESULTS: The unsatisfactory failure rate for POLs was nearly 3 times (21.5% vs 8.1%) the rate for the non-POLs and about 1.5 times (21.5% vs 14.0%) for POLs that used laboratory professionals as testing or supervisory personnel (P<.001). The POL unsuccessful rate was more than 4 times (4.4% vs 0.9%) the rate for non-POLs and more than twice (4.4% vs 1.8%) the rate for the POLs using laboratory professionals (P<.001). CONCLUSIONS: Significant differences exist among POLs, POLs using licensed clinical laboratory scientists (medical technologists), and non-POLs. Testing personnel in many POLs might lack the necessary education, training, and oversight common to larger facilities. We must better understand the contributing factors that result in the poorer results of POLs relative to non-POLs. In the meantime, patients should be aware that preliminary findings suggest that differences in quality of laboratory tests based on testing site may exist. Laboratory directors at all testing sites must ensure that they understand laboratory practice sufficiently to minimize errors and maximize accuracy and reliability. Directors must understand their obligation when they elect to oversee those assigned testing responsibility. Legislators may wish to reconsider the wisdom of further easing restrictions on those to whom we entrust our laboratory specimens.

California↗

PubMed2002

Cognitive and behavioral outcomes of school-aged children who were born preterm: a meta-analysis.

CONTEXT: The cognitive and behavioral outcomes of school-aged children who were born preterm have been reported extensively. Many of these studies have methodological flaws that preclude an accurate estimate of the long-term outcomes of prematurity. OBJECTIVE: To estimate the effect of preterm birth on cognition and behavior in school-aged children. DATA SOURCES: MEDLINE search (1980 to November 2001) for English-language articles, supplemented by a manual search of personal files maintained by 2 of the authors. STUDY SELECTION: We included case-control studies reporting cognitive and/or behavioral data of children who were born preterm and who were evaluated after their fifth birthday if the attrition rate was less than 30%. From the 227 reviewed studies, cognitive data from 15 studies and behavioral data from 16 studies were selected. DATA EXTRACTION: Data on population demographics, study characteristics, and cognitive and behavioral outcomes were extracted from each study, entered in a customized database, and reviewed twice to minimize error. Differences between the mean cognitive scores of cases and controls were pooled. Homogeneity across studies was formally tested using a general variance-based method and graphically using Galbraith plots. Linear meta-analysis regression models were fitted to explore the impact of birth weight and gestational age on cognitive outcomes. Study-specific relative risks (RRs) were calculated for the incidence of attention-deficit/hyperactivity disorder (ADHD) and pooled. Quality assessment of the studies was performed based on a 10-point scale. Publication bias was examined using Begg modified funnel plots and formally tested using the Egger weighted-linear regression method. DATA SYNTHESIS: Among 1556 cases and 1720 controls, controls had significantly higher cognitive scores compared with children who were born preterm (weighted mean difference, 10.9; 95% confidence interval [CI], 9.2-12.5). The mean cognitive scores of preterm-born cases and term-born controls were directly proportional to their birth weight (R(2) = 0.51; P<.001) and gestational age (R(2) = 0.49; P<.001). Age at evaluation had no significant correlation with mean difference in cognitive scores (R(2) = 0.12; P =.20). Preterm-born children showed increases in externalizing and internalizing behaviors in 81% of studies and had more than twice the RR for developing ADHD (pooled RR, 2.64; 95% CI, 1.85-3.78). No differences were noted in cognition and behaviors based on the quality of the study. CONCLUSIONS: Children who were born preterm are at risk for reduced cognitive test scores and their immaturity at birth is directly proportional to the mean cognitive scores at school age. Preterm-born children also show an increased incidence of ADHD and other behaviors.

Attention Deficit Disorder with Hyperactivity↗

PubMed1999

Fine-needle aspiration biopsy using a newly-developed pencil-grip syringe holder.

Until now, commercially available syringe holders for fine-needle aspiration (FNA) were designed to be held in a pistol-grip manner. A newly developed, pencil-grip syringe holder, the Tao Aspirator, was tested. The device is equipped with a release button for automatically drawing back the syringe plunger and a regulating knob for adjusting negative pressure for the aspiration. After direct smears were made for on-site examination, the remaining aspirated material was collected by rinsing the needle and syringe with CytoRich red fixative. Hettich cytocentrifuge preparations were then prepared. The quality of the first 150 FNA specimens procured by this device and prepared with liquid fixation was evaluated in terms of adequacy of specimen, amount of obscuring blood, preservation of cells, and ease of screening and interpretation. These 150 specimens included 32 from thyroids; 34 from breasts; 40 from lymph nodes; 24 from subcutaneous nodules; and 20 from salivary glands. There were no unsatisfactory specimens. In Hettich preparations, red blood cells were lysed, making interpretation easier. All cellular elements and tissue fragments were adequately fixed, showing excellent cellular morphology. Specimens fixed in liquid fixative yielded uniform cell suspensions, resulting in cytocentrifuge preparations with evenly distributed cells, and so the screening was also easier. The aspiration techniques using pistol-grip and pencil-grip FNA syringe holders were also compared in terms of control in tissue sampling, ease of use, and safety. The pencil-grip syringe holder allowed greater tactile sensation of the texture of the lesion, and enabled the operator to use a single hand to place a needle into a target lesion with minimal error. This device placed the hand relatively close to the needle tip while the hand was in a position of natural function, imparting more control in tissue sampling. It was more easily manipulated, and could prevent dripping when cystic fluid was aspirated. Specimen collection using the Tao Aspirator and processing with liquid fixation in addition to direct smear preparations allowed the laboratory to consistently produce adequate cytologic preparations and cell blocks.

Biopsy, Needle↗

PubMed1999

An overlapping subzone technique for MR-based elastic property reconstruction.

A finite element-based nonlinear inversion scheme for magnetic resonance (MR) elastography is detailed. The algorithm operates on small overlapping subzones of the total region of interest, processed in a hierarchical order as determined by progressive error minimization. This zoned approach allows for a high degree of spatial discretization, taking advantage of the data-rich environment afforded by the MR. The inversion technique is tested in simulation under high-noise conditions (15% random noise applied to the displacement data) with both complicated user-defined stiffness distributions and realistic tissue geometries obtained by thresholding MR image slices. In both cases the process has proved successful and has been capable of discerning small inclusions near 4 mm in diameter. Magn Reson Med 42:779-786, 1999.

Algorithms↗

PubMed2001

A flow cytometry assay simultaneously detects independent apoptotic parameters.

BACKGROUND: Apoptosis regulation is of fundamental importance in tissue homeostasis and in the pathogenesis of a variety of diseases. Different cytofluorometric methods are used to investigate apoptotic events. We set up a method to simultaneously evaluate mitochondria depolarization, cell morphology changes, and loss of plasma membrane asymmetry and integrity, thus increasing the information and minimizing errors in the analysis of the apoptotic process. METHODS: Jurkat T cells were induced to undergo apoptosis with different agents. They were labeled with (1) the mitochondrion-selective probes tetramethylrhodamine methyl ester (TMRM) or chloromethyl X-rosamine (CMXRos), which do not accumulate in depolarized mitochondria; (2) Annexin V-fluorescein isothyocianate (FITC) to detect phosphatidylserine (PS) exposure on the cell surface; and (3) propidium iodide (PI) to assess loss of plasma membrane integrity. Cell morphology changes were studied following variations in light scatter parameters. RESULTS: This is a fast, reliable, and reproducible technique to detect simultaneously independent apoptotic changes by cytofluorometric inspection. TMRM is more effective than CMXRos in responding to variations in the electrochemical gradient of mitochondria. CONCLUSIONS: This technique allows us to integrate the analysis and to follow the kinetics of different apoptotic cell changes.

Annexin A5↗

PubMed2005

Speculations on the pathogenesis of CHARGE syndrome.

To be seriously considered, a theory about the pathogenesis of a multiple congenital anomaly syndrome should meet three criteria: (1) it should explain all of the anomalies associated with the syndrome; (2) it should explain why certain anomalies are not associated with the syndrome; and (3) it should predict anomalies that could be associated with the syndrome, but have not yet been described. The theory must eventually pass the ultimate test, that is, molecular confirmation of the proposed mechanism. Several theories about the pathogenesis of CHARGE syndrome have been proposed, but none of these meet the three criteria stated above. In this study, the author proposes that CHARGE syndrome is due to a disruption of mesenchymal-epithelial interaction (epithelial includes ectoderm and endoderm). The theory is tested against the major, minor, and occasional anomalies that are used to make the clinical diagnosis of CHARGE syndrome. Review of the known embryology of the organs and tissues involved in CHARGE syndrome confirms that mesenchymal-epithelial interactions are necessary for proper formation of these organs and tissues. The presence of limb anomalies in approximately one-third of CHARGE syndrome patients fulfills criteria #3 above, in that limb anomalies were not felt to be a part of CHARGE syndrome until relatively recently. It is known that some patients with chromosomal abnormalities have a phenotype that overlaps with CHARGE syndrome. Given that critical developmental pathways must be robust and redundant in order to minimize errors, it may be that disruption of more than one gene is necessary to generate the CHARGE phenotype, as has been proposed for the holoprosencephaly sequence. Mutations and deletions of CHD7 have recently been identified as causing CHARGE syndrome in more than 50% of tested patients. Given this gene classes' putative role as a general controller of developmental gene expression as well as mesodermal patterning, it would fit the hypothesized mechanisms discussed in the study.

Abnormalities, Multiple↗

PubMed2005

Coevolution theory of the genetic code at age thirty.

The coevolution theory of the genetic code, which postulates that prebiotic synthesis was an inadequate source of all twenty protein amino acids, and therefore some of them had to be derived from the coevolving pathways of amino acid biosynthesis, has been assessed in the light of the discoveries of the past three decades. Its four fundamental tenets regarding the essentiality of amino acid biosynthesis, role of pretran synthesis, biosynthetic imprint on codon allocations and mutability of the encoded amino acids are proven by the new knowledge. Of the factors that guided the evolutionary selection of the universal code, the relative contributions of Amino Acid Biosynthesis: Error Minimization: Stereochemical Interaction are estimated to first approximation as 40,000,000:400:1, which suggests that amino acid biosynthesis represents the dominant factor shaping the code. The utility of the coevolution theory is demonstrated by its opening up experimental expansions of the code and providing a basis for locating the root of life.

Amino Acids↗

PubMed2003

Quantification of central metabolic fluxes in the facultative methylotroph methylobacterium extorquens AM1 using 13C-label tracing and mass spectrometry.

The metabolic fluxes of central carbon metabolism were measured in chemostat-grown cultures of Methylobacterium extorquens AM1 with methanol as the sole organic carbon and energy source and growth-limiting substrate. Label tracing experiments were carried out using 70% (13)C-methanol in the feed, and the steady-state mass isotopomer distributions of amino acids derived from total cell protein were measured by gas chromatography coupled to mass spectrometry. Fluxes were calculated from the isotopomer distribution data using an isotopomer balance model and evolutionary error minimization algorithm. The combination of labeled methanol with unlabeled CO(2), which enters central metabolism in two different reactions, provided the discriminatory power necessary to allow quantification of the unknown fluxes within a reasonably small confidence interval. In wild-type M. extorquens AM1, no measurable flux was detected through pyruvate dehydrogenase or malic enzyme, and very little flux through alpha-ketoglutarate dehydrogenase (1.4% of total carbon). In contrast, the alpha-ketoglutarate dehydrogenase flux was 25.5% of total carbon in the regulatory mutant strain phaR, while the pyruvate dehydrogenase and malic enzyme fluxes remained insignificant. The success of this technique with growth on C(1) compounds suggests that it can be applied to help characterize the effects of other regulatory mutations, and serve as a diagnostic tool in the metabolic engineering of methylotrophic bacteria.

Amino Acids↗

PubMed1980

A method for the analysis of catecholamines by selected ion monitoring and 14C isotope dilution in adrenal medullary cell culture.

Extracts have been made from culture medium of rat medullar adrenal cells developed in tissue culture in this laboratory. After pentafluorobenzylimine-trimethylsilyl ether formation the catecholamine derivatives were characterized by gas-liquid chromatography chemical ionization mass spectrometry. In order to assess the catecholamine production capabilities of the cells in culture, a mass spectrometric method with isotope dilution has been devised. Chemical ionization selected ion monitoring allows specific detection at the nanogram level in a higher mass range (400-600 amu) than in the electron impact mode. The isotopic dilution method with 14C catecholamines gives rise to accurate measurements and linear response in the picomole range. The use of the [M-15]+ ion for monitoring m/z values minimizes errors in selected ion monitoring analysis. The results obtained are computerized and treated by the data system for fine background subtraction when high sensitivity and accuracy are required.

Adrenal Medulla↗

PubMed1981

Quantitative mass spectrometry.

The basic principle in quantitative analysis by mass spectrometry is the measurement of a signal representative of the mass of the analyte relative to a known amount of an internal mass standard. To ensure that the signal is representative of the particular substance to be measured and not a result of some other substance in the biological matrix, a range of analytical methods have been employed. Combination of mass spectrometry with chromatographic (gas or liquid) separations and selective chemical derivatization frequently allows quantification of substances at the ppm and ppb level. Below the ppb level, new problems arise due to mass spectrometric sensitivity and chromatographic separation resolution with resulting debate regarding the specificity and significance of quantitative data. Successful high sensitivity (ppt) plasma analysis of the pineal hormone melatonin is described and critically compared with conflicting analytical data. A second area of application of quantitative mass spectrometry is the establishment of absolute or definitive reference measurements which require rigorous error minimization. Conflicting results published by two laboratories regarding methods for the definitive measurement of serum cholesterol are compared.

Cholesterol↗

PubMed1979

Screening methods using sulfamethazine for determining acetylator phenotype.

Analysis of sulfamethazine (SMZ) kinetics in man has revealed complexities including wide intersubject variability. In our study, an attempt was made to assess the potential influence of changes in nonmetabolic parameters (absorption and urinary elimination rate constants) on the markers of acetylation capacity normally used in clinical screening procedures to determine phenotype. Seven normal subjects were classified as slow (SA) or fast acetylators (FA) according to their metabolic rate constant for SMZ (Km), plasma SMZ half-life, and percentage of N-acetyl SMZ in a 6-hr blood sample (PI6), a 5- to 6-hr urine collection (UI5--6), or a 6-hr total urine collection (UI6). Computer simulations were applied to baseline SMZ kinetic data from these subjects, varying nonmetabolic kinetic parameters over experimentally defined ranges singly, or in parallel with 1 or more of the other parameters. The simulations indicate that all the usual phenotyping procedures were sensitive to changes in absorption and urinary elimination rate constants. While these predictions require experimental confirmation, results show that the PI6 method is least sensitive to such changes, suggesting this method may minimize errors in phenotyping screening.

Absorption↗

PubMed1978

Postweaning environmental stimulation and somesthetic performance in rats sustaining cortical lesions at maturity.

Rats were enucleated at 28 days of age and were assigned to complex or relatively barren tactile environments for the duration of the experiment. Approximately half of the animals in each group received large, bilateral lesions of the somatosensory cortex when they were 60 days of age, and the remainder underwent sham operations. Twenty days later all groups were tested for the ability to master a series of tactile discriminations. Statistical tests revealed a highly significant lesion effect, but no environment or lesion x environment interaction effects. These sensory discriminative findings stand in contrast to some earlier reports which have shown that environmental complexity provided prior to or following other forebrain lesions can minimize error scores on simple learning tasks.

Animals↗

PubMed2006

The UMD TP53 database and website: update and revisions.

Mutation of the p53 gene is the most frequent genetic alteration found in human cancer, but it is also the most frequently reported with more than 22,000 mutations published in 2,000 papers. In 1991, we developed a database and software to handle and analyze all this information. The database has been widely used for clinical analysis and molecular epidemiology. We have expanded the scope of the database by integrating structural, phylogenetic and biological information on wild-type (wt) and mutant TP53. Integration of the TP53 mutant activity database provides unique information that will be useful to both clinicians and scientists. All of this information is available from a new website (www.umd.be:2072/) that will generate a detailed informative page for every TP53 mutant in the database. New tools to check TP53 mutations and minimize errors found in the literature are also available.

DNA Mutational Analysis↗

PubMed1981

Selective determination of elemental mercury in blood and urine exposed to mercury vapor in vitro.

A method is described to ensure quantitative measurement of dissolved mercury vapor (Hg0) in blood and urine. Room air passed through samples of blood and urine carries with it all the dissolved Hg0 but leaves behind all the ionic mercury (Hg++). Oxidation of Hg0 to Hg++ in blood samples is completely inhibited by addition of ethanol (0.5% v/v). To minimize error due to evaporation of Hg0, it is suggested that samples should be stored at 0 degree C and Hg0 should be determined within 60 min of collection of blood samples and within 10 min of urine samples.

Ethanol↗

PubMed2001

Accurate estimation of pharmacokinetic contrast-enhanced dynamic MRI parameters of the prostate.

Quantitative analysis of contrast-enhanced dynamic MR images has potential for diagnosing prostate cancer. Contemporary fast acquisition techniques can give sufficiently high temporal resolution to sample the fast dynamics observed in the prostate. Data reduction for parametric visualization requires automatic curve fitting to a pharmacokinetic model, which to date has been performed using least-squares error minimization methods. We observed that these methods often produce unexpectedly noisy estimates, especially for the typically fast, intermediate parameters time-to-peak and start-of-enhancement, resulting in inaccurate pharmacokinetic parameter estimates. We developed a new curve fit method that focuses on the most probable slope. A set of 10 patients annotated using histopathology was used to compare the conventional and new methods. The results show that our new method is significantly more accurate, especially in the relatively less-enhancing peripheral zone. We conclude that estimation accuracy depends on the curve fit method, which is especially important when evaluating the peripheral zone of the prostate.

Aged↗

PubMed2006

Determination of the abduction-adduction axis of rotation at the human knee: helical axis representation.

This study used a finite helical axes representation to derive the axis of rotation of the human knee in the frontal plane for the neutral flexion/extension posture during resting and no load-bearing conditions. The three-dimensional finite helical axis pathway of the tibia relative to the femur was computed by passively adducting/abducting the lower limb via a servomotor system. Knee joint movements as a result of the positional perturbations were captured with an active marker kinematic tracking system. Contrary to traditional assumptions used in studies conducted under a similar experimental paradigm, our results indicated that the knee joint center, defined as the intercept point between the finite helical axis and the mid-coronal plane of the distal femur, was located within the femoral notch for a wide range of abduction and adduction angles (6 degrees abduction to 6 degrees adduction angles). Our data also indicated that at the neutral posture of the knee, the helical axes directions change as a function of the abduction/adduction perturbation angle. These findings are not only essential to error minimization during joint moment calculations, but can also facilitate new biomechanical interpretations of, for example, the functional role of the quadriceps and patellofemoral joint mechanics to overall knee stability in the medial-lateral direction.

Adult↗

PubMed1993

Feature-recognizing MRI.

We describe a new theory of MR imaging that utilizes prior information in the form of a set of "training" images thought to be similar to the "unknown" objects to be scanned. First, the training images are processed to find an orthonormal series representation of these images that is more convergent than the usual Fourier series. The coefficients in this new series can be calculated from a subset of the phase-encoded signals needed to construct the Fourier image representation. The characteristics of the training images also determine exactly which phase-encoded signals should be measured in order to minimize error in the image reconstruction. The optimal phase-encodings are usually scattered nonuniformly in kappa-space. Good results were obtained when this theory was applied to imaging data from simulated objects and to experimental data from phantom scans. This theory provides the basis for developing efficient scanning and image reconstruction techniques that are "tailored" to each body part or to particular disease states.

Algorithms↗