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Should endomyocardial biopsy be performed for detection of myocarditis? A decision analytic approach.

BACKGROUND: Performance of endomyocardial biopsy (EMB) to diagnose myocarditis in patients with dilated cardiomyopathy is controversial because of a lack of evidence favoring immunosuppressive therapy. In spite of advances in heart failure treatment, dilated cardiomyopathy carries a poor prognosis, and myocardial inflammation and viral infection are potential therapeutic targets. METHODS: We used decision analysis to determine the efficacy (5-year risk reduction in mortality or transplantation) that a treatment for myocarditis would require to favor a biopsy-guided approach over conventional therapy. Literature-based estimates included prevalence of myocarditis among patients with dilated cardiomyopathy with or without borderline myocarditis (16% and 11%, respectively); probability of 5-year transplantation-free survival (55%); sensitivity (50% and 63%, respectively), specificity (95.4%), and mortality rate (0.4%) of EMB; side effects resulting in withdrawal of immunosuppressive treatment (4%); and a 6-month mortality rate for immunosuppressive treatment (0.1%). All estimates were varied to determine impact on model results (sensitivity analysis). RESULTS: A therapy that decreased the rate of death or transplantation by 12.7% and 7.1% for patients without or with borderline myocarditis, respectively, favored EMB. Sensitivity analysis indicated that therapeutic efficacy was influenced by myocarditis prevalence and biopsy-related death, but not by accuracy of biopsy or probability of immunosuppressive therapy side effects. Randomized trials powered to detect 7% and 25% reductions in death and transplantation would require 5790 and 380 end points, respectively. CONCLUSION: Decreasing the rate of death or transplantation by 7.1% offsets therapy side effects, EMB-related death, and inaccuracies in histologic diagnosis. Prospective randomized trials of treatments for myocarditis may be more feasible during periods of high prevalence or with more sensitive diagnostic techniques.

Biopsy↗

rHuEpo for the treatment of anemia in myelofibrosis with myeloid metaplasia. Experience in 6 patients and meta-analytical approach.

BACKGROUND AND OBJECTIVE: Experience with recombinant human erythropoietin (rHuEPO) in the treatment of the anemia secondary to myelofibrosis with myeloid metaplasia (MMM) is slight up to now. We present our results of the treatment of 6 patients and a review of the literature in search of possible parameters predicting response to this treatment. DESIGN AND METHODS: From January 1994 to June 1996 all transfusion-dependent patients with MMM diagnosed in our hospital were included in this study. We established a minimum period of 4 weeks of treatment and a maximum of 12 if no response was observed. Initial dosages used were 100 U/kg s.c. 3 times weekly, increasing by 50 U/kg every 4 weeks where no response was observed. Response was defined as a reduction > or = 30% of the previous transfusional needs. The review of the literature was made using a MEDLINE search (January 1990-December 1996) on the keywords erythropoietin, myelofibrosis, and agnogenic myeloid metaplasia. A statistical study was made in search of possible parameters to predict response. The parameters studied include age, sex, hemoglobin, serum erythropoietin (sEPO) levels, transfusional dependency, transfusional requirements per month prior to treatment, maximum dosages used and dosage at which response was obtained. RESULTS: Only 2 of our 6 patients responded, both at a dosage of 600 U/kg/week (200 U/kg 3 times weekly s.c.). In addition to our 6 patients we have found only 28 other patients in the literature. For statistical calculation 2 of our patients were not considered as they did not complete the period of study. The overall rate of response was 17/32 (53.1%). In the univariate analysis comparing responders and non-responders we found a tendency to significance with respect to sex (p = 0.07), sEPO (p = 0.07) and transfusional needs in units of packed red blood cells per month (PRBC/m) (p = 0.13). In this way patients with low sEPO, females and those with low transfusional needs (< 3 PRBC/m) respond better. This better response in females could be explained by the fact that their disease situation was more stable (with both lower sEPO levels and transfusional dependency). The best cut-off point in the sEPO to predict response was 123 mU/mL. No important side-effects have been observed except three cases of aggravation of splenomegaly. In two cases this condition improved when the rHuEPO was discontinued. The association of rHuEPO with hydroxyurea or interferon does not seem to affect the response. INTERPRETATION AND CONCLUSIONS: Though the number of patients is low, our data suggest that some MMM patients, in particular females and individuals with low sEPO levels and with low transfusional needs, might benefit from rHuEPO in terms of elevation of hemoglobin levels. Unfortunately, transfusion dependent-patients, i.e. those in whom a beneficial effect of rHuEPO would be most welcome, are unlikely to respond, and more generally, treatment is not cost effective in medically responsive patients.

Aged↗

Goals for clinical biochemistry analytical imprecision: a graphic approach.

Analytical performance standards for the imprecision of commonly requested clinical biochemistry tests are proposed in the form of goal graphs. The goals delineated in graphic form are a consensus of published performance standards. The graphs define acceptable and unacceptable performance standards for levels of analyte commonly encountered in clinical laboratory practice. The graphic approach allows a flexible presentation of goals that is easy to interpret. The disadvantage of goal graphs is their necessarily empirical foundation.

Bilirubin↗

[Burning mouth syndromes and depression. A psychoanalytic approach].

1. Analytical approaches to Burning Mouth Syndrome permit the suggestion that it is a symptom of hidden depression, where the depressive process and its two major indicators (vital sadness and psycho-motor slowing down) are totally or partially concealed by a somatic symptomatology which can strike down any system: vaso-vegetative, cardio-vascular, gastro-intestinal, genito-urinary, muscles and skeleton. 2. Depression is a mental process, part of normal psychic development, which must be overcome at least once in a lifetime in order to reach the status of an autonomous being. Hidden depression is one form of pathological depression, which expresses an inability to (i) mentalize depression, separation, and (ii) become an autonomous being. 3. Burning mouth is a symptom resulting from complex dynamics, from hysterical conversion to the inability to mentalize separation, both with underlying fault in the "narcissistic nucleus" (a term meaning the sense of identity originating in the motherly holding, in the skin to skin touch). 4. Treatment will be a combination of anti-depressive drugs and psychotherapy, drugs being prescribed by the practitioner, and psychotherapy conducted by a therapist with an analytical background.

Adult↗

A Bayesian aggregate meta-analytic evaluation approach.

The Bayesian inferential process is modified to be used as an approach to an aggregate meta-analytic evaluation. Comparisons of the Bayesian approach with the traditional average effect size meta-analytic approach indicated that the Bayesian approach was more sensitive to differences between studies. The approaches to derive descriptive and inferential statistics were more consistent in the Bayesian approach. Because of its ability to account for all available information, the Bayesian approach was statistically more powerful. It is recommended that this approach be used for combining evaluation results when primary data are not available and when all evaluations involve comparisons of two independent samples.

Evaluation Studies as Topic↗

Quantitation of endogenous analytes in biofluid without a true blank matrix.

A method is presented that describes a reliable and practical procedure for quantitation of an analyte present at relatively high background levels in blank (untreated) biological matrixes. Using a "surrogate analyte" approach, an endogenous analyte was quantitated in a variety of biological matrixes containing both very low (<10 ng/mL) and high (>2000 ng/mL) background levels of the desired analyte. This quantitative "surrogate analyte" approach was applied during the development of an HPLC/MS method for alpha-ketoisocaproic acid (KIC), which was identified as a potential biomarker for branched chain amino acid transferase inhibitor activity. Using deuterium-labeled KIC (d(3)) as a surrogate analyte, not an internal standard, to generate the calibration curve, the concentration of KIC in biofluid could be back-calculated based on the regression equation and response factor of KIC to KIC-d(3). In particular, this approach made it possible to prepare standards in control biofluid such as plasma, which greatly facilitated the process of method development. For the validated method, a linear range of 10-5000 ng/mL for KIC-d(3) was observed. Intraday and interday experimental accuracy, calculated as percent error, were in the range of < or =10% for KIC-d(3). This method is simple, rapid, and reliable for the quantitation of KIC in plasma, brain homogenate, cerebrospinal fluid, and other biological samples from discovery and pharmacological studies.

Journal Article↗

Point-of-care immunotesting: approaching the analytical performance of central laboratory methods.

The use of point-of-care (POC) immunoassays has increased significantly and the menu of analytes continues to expand. Most of the rapid immunoassays are currently based on simple manual assay devices such as the immunochromatographic, agglutination, and immunofiltration assays. Although automated readers have recently been introduced at an increasing pace, the major benefit of these genuinely hand-portable assay devices is that they do not usually necessitate instrumentation but can be performed anywhere. Significant advances in assay and detection technologies have, however, recently facilitated the introduction of truly quantitative, sophisticated immunoassay methods to POC settings as well, with the analytical performance characteristics approaching those of conventional laboratory assays. Furthermore, innovative assay technologies such as those based on immunosensors have been introduced to POC testing (POCT) without ever being employed in clinical laboratories. However, further simplification of the assay procedures and analyzers is still feasible, and strong efforts are directed towards the development of miniaturized and simple, yet sensitive and quantitative, novel assay technologies to keep up with the increasing expectations set on future POC immunotesting.

Clinical Laboratory Techniques↗

Dose rate constant and energy spectrum of interstitial brachytherapy sources.

In the past two years, several new manufacturers have begun to market low-energy interstitial brachytherapy seeds containing 125I and 103Pd. Parallel to this development, the National Institute of Standards and Technology (NIST) has implemented a modification to the air-kerma strength (S(K)) standard for 125I seeds and has also established an S(K) standard for 103Pd seeds. These events have generated a considerable number of investigations on the determination of the dose rate constants (inverted V) of interstitial brachytherapy seeds. The aim of this work is to study the general properties underlying the determination of dose rate constant and to develop a simple method for a quick and accurate estimation of dose rate constant. As the dose rate constant of clinical seeds is defined at a fixed reference point, we postulated that dose rate constant may be calculated by treating the seed as an effective point source when the seed's source strength is specified in S(K) and its source characteristics are specified by the photon energy spectrum measured in air at the reference point. Using a semi-analytic approach, an analytic expression for dose rate constant was derived for point sources with known photon energy spectra. This approach enabled a systematic study of dose rate constant as a function of energy. Using the measured energy spectra, the calculated dose rate constant for 125I model 6711 and 6702 seeds and for 192Ir seed agreed with the AAPM recommended values within +/-1%. For the 103Pd model 200 seed, the agreement was 5% with a recently measured value (within the +/-7% experimental uncertainty) and was within 1% with the Monte Carlo simulations. The analytic expression for dose rate constant proposed here can be evaluated using a programmable calculator or a simple spreadsheet and it provides an efficient method for checking the measured dose rate constant for any interstitial brachytherapy seed once the energy spectrum of the seed is known.

Biophysical Phenomena↗

Holistic approach to health education on AIDS.

OBJECTIVE: To identify a method for health education using the example of an educational seminar on AIDS prevention and control at Hebei Medical University in China, 1994. METHODS: Our goal is the theoretical formulation of a unified community approach for problem solving through the combination of the self regulative approach and the case analytical approach. "Quality improvement", "essential quality" and "human ecosystems" provide the basic ideas for better understanding the integration of culture, science and technology within the "cultural norm". RESULTS: The present seminar was successfully organized for Chinese medical students based on the theme of "living with AIDS". Through this program, we identified that self regulative and case analytical approach were major issues for holistic approach to health education. We also identified that a community approach provides the scientific basis for health education in the community. CONCLUSIONS: The present paper generates a healthcare paradigm for surveillance in health/medical education. Through a better understanding of community approach, we related "community care" (emphasizing self, mutual, professional and institutional care) to the "practical norm"; and "preventive epidemiology" (emphasizing the unification of quality and quantity, as well as systems and population) to the "research norm".

Acquired Immunodeficiency Syndrome↗

Measuring Coping Strategies in Daily Life: A Systematic Review of Experience Sampling Methodology and Daily Diary Studies.

Advances in daily diary methods and experience sampling method (ESM) have improved the study of coping strategies in daily life and their role in shaping health and well-being. In this review, we examine study designs, measurement approaches, and analytical practices used to investigate coping in natural contexts. We performed a systematic review of studies published before 5 December 2025 that used daily diary or ESM to measure coping strategies over multiple days or moments. Studies were examined with regard to sampling schemes, assessment frequency and duration, measurement of coping strategies, incorporation of stressor appraisals, and analytic techniques used to model coping processes. Fifty-five studies met the inclusion criteria. Results indicated that 80% employed end-of-day diary designs, generally lasting 1-3 weeks, whereas higher-frequency ESM protocols were less common and ranged 2-14&#xa0;days. Coping strategies were often assessed using abbreviated or single-item measures, frequently adapted from established questionnaires. Many studies incorporated appraisals such as perceived stressor intensity or controllability, enabling tests of coping flexibility. Multilevel modelling was the dominant analytic approach, allowing researchers to distinguish within-person dynamics from between-person differences. However, analyses were predominantly concurrent, and temporally ordered models remained comparatively rare. Overall, the literature demonstrates substantial progress in capturing coping in everyday contexts, yet heterogeneity in measurement and limited use of temporal modelling constrain cumulative knowledge about the temporal links between coping and psychological and physiological health outcomes. Future research would benefit from greater alignment between theoretical assumptions, assessment strategies, and analytic methods.

Humans↗

Using decision analytic methods to assess the utility of family history tools.

Family history may be a useful tool for identifying people at increased risk of disease and for developing targeted interventions for individuals at higher-than-average risk. This article addresses the issue of how to examine the utility of a family history tool for public health and preventive medicine. We propose the use of a decision analytic framework for the assessment of a family history tool and outline the major elements of a decision analytic approach, including analytic perspective, costs, outcome measurements, and data needed to assess the value of a family history tool. We describe the use of sensitivity analysis to address uncertainty in parameter values and imperfect information. To illustrate the use of decision analytic methods to assess the value of family history, we present an example analysis based on using family history of colorectal cancer to improve rates of colorectal cancer screening.

Colorectal Neoplasms↗

Examples of the role of analytical chemistry in environmental risk management research.

Analytical chemistry is an important tier of environmental protection and has been traditionally linked to compliance and/or exposure monitoring activities for environmental contaminants. The adoption of the risk management paradigm has led to special challenges for analytical chemistry applied to environmental risk analysis. Namely, methods developed for regulated contaminants may not be appropriate and/or applicable to risk management scenarios. This paper contains examples of analytical chemistry applied to risk management challenges broken down by the analytical approach and analyte for some selected work in our laboratory. Specific techniques discussed include stable association complex electrospray mass spectrometry (cESI-MS), gas chromatography-mass spectrometry (GC-MS), split-flow thin cell (SPLITT) fractionation and matrix-assisted laser desorption time of flight mass spectrometry (MALDI-ToF-MS). Specific analytes include haloacetic acids (HAA9), perchlorate, bromate, triazine degradation products, metal-contaminated colloids and Cryptosporidium parvum oocysts.

Acetates↗

Circular asymmetric Helmholtz resonators

A three-dimensional (3D) analytical approach is developed to account for the nonplanar wave propagation in the cavity and neck of "piston-driven" circular asymmetric Helmholtz resonators. The present 3D analytical results are compared with (1) the numerical predictions from the boundary element method (BEM) to evaluate the analytical approach; and (2) the one-dimensional (1D) solution to examine the effect of nonplanar waves at area discontinuity between the neck and the cavity. In order to improve the 1D solution, the end correction is also determined by using the 3D analytical approach. The effect of neck offset on the resonance frequency of circular asymmetric Helmholtz resonators is investigated. Predictions of resonance frequency and transmission loss from the present 3D and corrected 1D analytical approaches are, respectively, identical and close to the BEM results, while the corrected 1D approach provides a better accuracy compared to the 1D solutions with Ingard's correction. Finally, the boundary element method is employed to determine the wave attenuation performance of the "pipe-mounted" Helmholtz resonators to examine the effect of multidimensional waves in the vicinity of the main duct and neck junction.

Journal Article↗

On meta-analytic assessment of surrogate outcomes.

We discuss the strengths and weaknesses of the meta-analytic approach to estimating the effect of a new treatment on a true clinical outcome measure, T, from the effect of treatment on a surrogate response, S. The meta-analytic approach (see Daniels and Hughes (1997) 16, 1965-1982) uses data from a series of previous studies of interventions similar to the new treatment. The data are used to estimate relationships between summary measures of treatment effects on T and S that can be used to infer the magnitude of the effect of the new treatment on T from its effects on S. We extend the class of models to cover a broad range of applications in which the parameters define features of the marginal distribution of (T, S). We present a new bootstrap procedure to allow for the variability in estimating the distribution that governs the between-study variation. Ignoring this variability can lead to confidence intervals that are much too narrow. The meta-analytic approach relies on quite different data and assumptions than procedures that depend, for example, on the conditional independence, at the individual level, of treatment and T, given S (see Prentice (1989) 8, 431-440). Meta-analytic calculations in this paper can be used to determine whether a new study, based only on S, will yield estimates of the treatment effect on T that are precise enough to be useful. Compared to direct measurement on T, the meta-analytic approach has a number of limitations, including likely serious loss of precision and difficulties in defining the class of previous studies to be used to predict the effects on T for a new intervention.

Journal Article↗

A Process Analytical Technology approach to near-infrared process control of pharmaceutical powder blending. Part I: D-optimal design for characterization of powder mixing and preliminary spectral data evaluation.

Experimental design, multivariate data acquisition, and analysis in addition to real time monitoring and control through process analyzers, represent an integrated approach for implementation of Process Analytical Technology (PAT) in the pharmaceutical industry. This study, which is the first in a series of three parts, uses an experimental design approach to identify critical factors affecting powder blending. Powder mixtures composed of salicylic acid and lactose were mixed in an 8 qt. V-blender. D-optimal design was employed to characterize the blending process, by studying the effect of humidity, component concentration, and blender speed on mixing end point. Additionally, changes in particle size and density of powder mixtures were examined. A near-infrared (NIR) fiber-optic probe was used to monitor mixing, through multiple optical ports on the blender. Humidity, component concentration, and blender speed were shown to have a significant impact on the blending process. Furthermore, humidity and concentration had a significant effect on particle size and density of powder mixtures. NIRS was sensitive to changes in physicochemical properties of the mixtures, resulting from process variables. Proper selection of NIR spectral preprocessing is of ultimate importance for successful implementation of this technology in the monitoring and control of powder blending and is discussed.

Chemistry, Pharmaceutical↗

Some considerations in selecting interactive and analytical decision approaches for EMS councils.

The application of analytical and interactive decision models to decisions, in EMS councils, with various levels of uncertainty is described. Uncertainty is defined as having temporal, procedural, quantifiability, and environmental attributes. Highly uncertain decisions are unique, with unknown decision procedures. Decision premises, like available funds or demands for services, are constantly shifting in uncertain environments. Low uncertainty occurs when decisions are repeatable and follow known procedures. Past practice can be used as templates when uncertainty is "low" because funding levels and use rates are predictable. The results (e.g., validity, risk of omission, etc.) of applying interactive and analytical decision models under varying levels of uncertainty are discussed.

Conflict, Psychological↗

Protein interaction with immobilized ligands: quantitative analyses of equilibrium partition data and comparison with analytical chromatographic approaches using immobilized metal affinity adsorbents.

Quantitative or analytical affinity chromatography has been successful primarily for the analysis of biologically determined macromolecular affinity relationships. Quantitative approaches are also needed to better characterize simpler, chemically defined immobilized ligands with potential for selective interaction with specific, predetermined protein surface groups. Protein interaction with immobilized metal is a rather selective and versatile, high-affinity adsorption technique for which there is little quantitative information. Using model protein interactions with immobilized Cu2+ ions, we have compared analytical frontal affinity chromatographic methods to a simple, nonchromatographic protocol for the rapid determination of quantitative affinity relationships. Values obtained for the equilibrium dissociation constant (Kd) and binding capacity (Lt) characterizing the interaction of lysozyme with immobilized Cu2+ were quite similar by frontal analysis (Kd = 37-42 X 10(-6) M; Lt = 6.8-7.4 X 10(-6) mol protein/ml gel) and by equilibrium binding analyses (Kd = 33 +/- 4.7 X 10(-6) M; Lt = 5.8-6.1 X 10(-6) mol protein/ml gel; 14 determinations). The interaction of ovalbumin with immobilized Cu2+ was characterized by an affinity (Kd = 4.2-4.8 X 10(-6) M) and capacity (Lt = 1.5-2.1 X 10(-6) mol protein/ml gel) which were also the same regardless of the method for affinity analysis. These values indicate that the total protein bound at saturation corresponds to as much as 17% of the total immobilized Cu2+ ions (approximately 40 X 10(-6) mol/ml gel). Thus, depending on the fraction of total immobilized Cu2+ available for interaction with a given protein (e.g., lysozyme), the number of individual immobilized ligands actively participating as well as those rendered unavailable upon individual protein binding events may be greater than 1. Linear Scatchard plots obtained for both lysozyme and ovalbumin (purified) suggest the presence of only a single type of immobilized Cu2+-protein interaction operative under the experimental conditions employed. However, Scatchard analyses of data obtained by the nonchromatographic equilibrium binding method also demonstrated the ability to simultaneously resolve the contribution of two components whose presence was predicted by frontal chromatography. Our results support the validity and utility of equilibrium binding data analyzed according to the equations outlined by Scatchard and others as an alternative to analytical chromatographic methods.

Chromatography, Affinity↗

Differential diagnosis between thyroid follicular adenoma and carcinoma. Analytic morphometric approach.

In this study some nuclear dimensional and analytical parameters were evaluated in order to distinguish follicular atypical adenoma from follicular carcinoma of the thyroid. Eighty nuclei from carcinomas, 80 from adenomas and 80 from normal thyroid were studied. Analytical parameters obtained by the nuclear shape study (by S.A.M. system) as well as dimensional parameters were submitted to univariate statistical analysis. On the ground of our results atypical adenoma could be considered as an intermediate aspect of a progressive change from benign to malignant even if they are closer to normal thyroid than to carcinoma.

Adenocarcinoma↗