Multilevel modeling in psychosomatic medicine research.

The primary purpose of this study is to provide an overview of multilevel modeling for Psychosomatic Medicine readers and contributors. The article begins with a general introduction to multilevel modeling. Multilevel regression modeling at two levels is emphasized because of its prevalence in psychosomatic medicine research. Simulated data sets based on some core ideas from the Familias Unidas effectiveness study are used to illustrate key concepts including communication of model specification, parameter interpretation, sample size and power, and missing data. Input and key output files from Mplus and SAS are provided. A cluster randomized trial with repeated measures (i.e., three-level regression model) is then briefly presented with simulated data based on some core ideas from a cognitive-behavioral stress management intervention in prostate cancer.

An examination of personality characteristics related to acquiescence.

Acquiescence, the tendency to agree with statements regardless of content, is often a concern when administering self-report instruments. While there is evidence to support acquiescence as a response style, this reporting tendency may be related to personality factors of individuals. Using a sample of 757 adults, we investigated the Rosenberg Self-Esteem Scale for acquiescence response tendencies by applying the Rasch partial credit model. Results suggested that favorable (i.e., Agree or Strongly Agree) responses were more frequent for the positively worded items than for negatively worded items. Second, the relationship between acquiescence and seven additional personality measures was examined overall and by sex. Among females, acquiescence was correlated with personality measures measuring perceptions by others, whereas acquiescence among males was related to exhibition types of behaviors.

Multi-factor scale consolidation when theory is weak.

As a practical matter, Spirituality and Quality of Life in the health sciences are usually measured separately. Theoretical foundations for this distinction, however, are not strong. In this research, an empirical investigation was conducted into their joint calibration with a Rasch model. Functional Assessment of Cancer Therapy-General (28 items), a cancer health-related quality of life measure (HRQOL), and Functional Assessment of Chronic Illness - Spiritual Well-Being (12 items), a measure of religious and existential well-being (Spirituality), were co-calibrated with a Rasch model implemented with WINSTEPS software for ratings from 545 breast cancer patients. The results show a hierarchical integration of QOL and Spirituality items on a common variable, and both patient separation (2.66) and reliability (.88) improve after co-calibration. Principal Component Analysis of co-calibrated item residuals did not show major threats to dimensionality, and joint calibration explains item variance comparable to separate calibrations (51.9%). Although patient measures (logits) based on separate and co-calibration are within two standard errors, ethnic and racial group values shift after co-calibration.

The interpretation of speech reception threshold data in normal-hearing and hearing-impaired listeners: steady-state noise.

Speech-in-noise-measurements are important in clinical practice and have been the subject of research for a long time. The results of these measurements are often described in terms of the speech reception threshold (SRT) and SNR loss. Using the basic concepts that underlie several models of speech recognition in steady-state noise, the present study shows that these measures are ill-defined, most importantly because the slope of the speech recognition functions for hearing-impaired listeners always decreases with hearing loss. This slope can be determined from the slope of the normal-hearing speech recognition function when the SRT for the hearing-impaired listener is known. The SII-function (i.e., the speech intelligibility index (SII) against SNR) is important and provides insights into many potential pitfalls when interpreting SRT data. Standardized SNR loss, sSNR loss, is introduced as a universal measure of hearing loss for speech in steady-state noise. Experimental data demonstrates that, unlike the SRT or SNR loss, sSNR loss is invariant to the target point chosen, the scoring method or the type of speech material.

[Effectiveness of biological treatments based on ACR70 response in rheumatoid arthritis: indirect comparison and meta-regression using Bayes-model]. / A rheumatoid arthritisben alkalmazott biológiai kezelések hatásossága az ACR70-végpont szerint: indirekt összehasonlítás és metaregresszió Bayes-modell alkalmazásával.

UNLABELLED: The therapy of rheumatoid arthritis has been changed by biological treatments. Their efficacy was evaluated in several randomized controlled trials. These trials were different in patient characteristics and the administration regimen. Placebo was the control and direct comparison of biological treatments is missing. OBJECTIVES: In the present study the efficacy of biological treatments in patients with rheumatoid arthritis was compared based on the randomized controlled trials available in the literature. A meta-analysis was conducted and meta-regression was used to explore the relationship between disease characteristic variables and observed efficacy. RESULTS: The related scientific literature is broad. Thirty two trials involving 18,500 patients were included into the current meta-analysis. The relative odds ratios of biological treatments compared to placebo varied between 3.6 and 20.0, and between 6.4 and 35.5 in case of monotherapy and combination with non-biological therapy, respectively. Disease duration and added non-biological therapy were in positive relationship with relative efficacy. More severe disease resulted smaller relative effect. CONCLUSIONS: The results show that the efficacy of biological treatments is similar. The relative efficacy worsens with more severe disease and improves with disease duration.

The cell cycle profile test is a prognostic indicator for breast cancer patients treated with postoperative 5-fluorouracil-based chemotherapy.

OBJECTIVE: The cell cycle profile test is suggested to be an independent prognostic indicator for breast cancer patients. To further clarify the prognostic value, we applied this to breast cancer patients treated with postoperative 5-fluorouracil-based chemotherapy. METHODS: A total of 153 breast cancer patients, who were treated with postoperative 5-fluorouracil-based chemotherapies, were randomly selected. Specific activities of cyclin-dependent kinases 1 and 2 in the tumor samples were analyzed. Patients were divided into three categories (low, intermediate or high risk) based on cell cycle profile analysis. RESULTS: The proportions of the cell cycle profile categories were 39% for low risk, 10% for intermediate risk and 45% for high risk, respectively. Although the cell cycle profile test did not show a significant predictive power for relapse-free survival (high vs. low risk; P = 0.052), the cell cycle profile categories were significant prognostic factors in a subgroup of 98 patients with fewer than three involved nodes (high vs. low risk, P = 0.004). Multivariate analyses also indicated that a cell cycle profile parameter (high vs. low risk) was an independent prognostic indicator from the number of involved nodes and clinical stage in this subgroup (hazard ratio = 2.46, P = 0.01). Interestingly, the prognostic power of the cell cycle profile test was significant in 75 patients treated with oral 5-fluorouracil derivatives alone (hazard ratio = 6.29 for high vs. low risk, P = 0.02). CONCLUSIONS: These findings suggest that the cell cycle profile test is useful for predicting a higher risk of relapse in patients treated with postoperative 5-fluorouracil-based chemotherapy.

How to appropriately choose and arrange research factors.

Research factors are a very important element in any research design. Research factors include experimental and non-experimental factors. The former is the general term used to describe the similar experimental conditions that researchers are interested in, while the latter are other factors that researchers have little interest in but may influence the result. This article mainly focuses on the following issues: the definition of research factors, the selection and arrangement of experimental factors and non-experimental factors, the interaction between research factors, the standardization of research factors and the common mistakes frequently made by researchers.

Prediction of human renal clearance from preclinical species for a diverse set of drugs that exhibit both active secretion and net reabsorption.

Identifying any extrahepatic excretion phenomenon in preclinical species is crucial for an accurate prediction of the pharmacokinetics in man. This understanding is particularly key for drugs with a small volume of distribution, because they require an especially low total clearance to be suitable for a once-a-day dosing regimen in man. In this study, three animal scaling techniques were applied for the prediction of the human renal clearance of 36 diverse drugs that show active secretion or net reabsorption: 1) direct correlations between renal clearance in man and each of the two main preclinical species (rat and dog); 2) simple allometry; and 3) Mahmood's renal clearance scaling method. The results show clearly that the predictions to man for the methods are improved significantly when corrections are made for species differences in plasma protein binding. Overall, the most accurate predictions were obtained by using a direct correlation with the dog renal clearance after correcting for differences in plasma protein binding and kidney blood flow (r² = 0.84), where predictions, on average, were within 2-fold of the observed renal clearance values in human.

[Cancer survival analysis in Germany--heading towards representative and comparable findings]. / Überlebenschancen von Krebspatienten in Deutschland--auf dem Weg zu repräsentativen, vergleichbaren Aussagen.

Cancer is an important issue within the German health care system with an estimated annual number of 435 000 incident cases and almost 210 000 deaths. Data of population-based cancer registries enable us to identify improvements of survival in oncological patients due to progress in therapeutic care and secondary prevention, as well as to investigate regional and international differences of this outcome. Comparing cancer survival rates, however, requires considering the impact of both methodical approaches and data quality. Potential factors of influence like algorithms, reference population, completeness of case ascertainment and quality of follow-up are discussed. For the first time harmonized proceedings are recommended in order to achieve comparability of population-based cancer survival rates in Germany.

Assessing instantaneous synchrony of nonlinear nonstationary oscillators in the brain.

Neuronal populations throughout the brain achieve levels of synchronous electrophysiological activity as a consequence of both normal brain function as well as during pathological states such as in epileptic seizures. Understanding this synchrony and being able to quantitatively assess the dynamics with which neuronal oscillators across the brain couple their activity is a critical component toward decoding such complex behavior. Commonly applied techniques to resolve relationships between oscillators typically make assumptions of linearity and stationarity that are likely not to be valid for complex neural signals. In this study, intracranial electroencephalographic activity was recorded bilaterally in both hippocampi and in anteromedial thalamus of rat under normal conditions and during hypersynchronous seizure activity induced by focal injection of the epileptogenic agent kainic acid. Nonlinear oscillators were first extracted using empirical mode decomposition. The technique of eigenvalue decomposition was used to assess global phase synchrony of the highest energy oscillators. The Hilbert analytical technique was then used to measure instantaneous phase synchrony of these oscillators as they evolved in time. To test the reliability of this method, we first applied it to a system of two coupled Rössler attractors under varying levels of coupling with small frequency mismatch. The application of these analytical techniques to intracranially recorded brain signals provides a means for assessing how complex oscillatory behavior in the brain evolves and changes during both normal activity and as a consequence of diseased states without making restrictive and possibly erroneous assumptions of the linearity and stationarity of the underlying oscillatory activity.

Washout filter aided mean field feedback desynchronization in an ensemble of globally coupled neural oscillators.

We propose an approach for desynchronization in an ensemble of globally coupled neural oscillators. The impact of washout filter aided mean field feedback on population synchronization process is investigated. By blocking the Hopf bifurcation of the mean field, the controller desynchronizes the ensemble. The technique is generally demand-controlled. It is robust and can be easily implemented practically. We suggest it for effective deep brain stimulation in neurological diseases characterized by pathological synchronization.

Use of complementary and alternative medicine in departments of obstetrics in Germany.

BACKGROUND: This nationwide study aimed to assess the use of complementary and alternative medicine (CAM) methods in German departments of obstetrics. METHODS: All German departments of obstetrics were identified and were sent a questionnaire designed to assess which CAM methods, if any, they used during childbirth, how frequently, and why. SPSS software was used for statistical analyses (Spearman's bivariate correlation, cross-tabulation, and Pearson's chi-square test). RESULTS: The questionnaires were returned by 40.3% (381/946) of the identified departments. The most commonly used CAM therapy was acupuncture (available in 97.3% (366/376) of departments) followed by homeopathy (offered in 93.4%) and aromatherapy (available in 76.6%). Most decisions regarding CAM use were made by midwives; only decisions on acupuncture were taken by obstetricians and midwives. Reasons given for using CAM were patient demand and perceived efficacy of CAM, particularly by midwives. Obstetricians were only partly convinced of the efficacy of CAM methods and their conviction varied with the type of unit they worked in. CONCLUSIONS: CAM methods are widely used in German departments of obstetrics despite lacking evidence of effectiveness. Efficacy, side effects and consequences of CAM use should be assessed using the mandatory German quality assurance measures and birth surveys. CAM use elsewhere also merits further study.

Aqueous solubility calculation for petroleum mixtures in soil using comprehensive two-dimensional gas chromatography analysis data.

An assessment of aqueous solubility (leaching potential) of soil contaminations with petroleum hydrocarbons (TPH) is important in the context of the evaluation of (migration) risks and soil/groundwater remediation. Field measurements using monitoring wells often overestimate real TPH concentrations in case of presence of pure oil in the screened interval of the well. This paper presents a method to calculate TPH equilibrium concentrations in groundwater using soil analysis by high-performance liquid chromatography followed by comprehensive two-dimensional gas chromatography (HPLC-GCXGC). The oil in the soil sample is divided into 79 defined hydrocarbon fractions on two GCXGC color plots. To each of these fractions a representative water solubility is assigned. Overall equilibrium water solubility of the non-aqueous phase liquid (NAPL) present in the sample and the water phase's chemical composition (in terms of the 79 fractions defined) are then calculated using Raoult's law. The calculation method was validated using soil spiked with 13 different TPH mixtures and 1 field-contaminated soil. Measured water solubilities using a column recirculation equilibration experiment agreed well to calculated equilibrium concentrations and water phase TPH composition.

Combination of dynamic time warping and multivariate analysis for the comparison of comprehensive two-dimensional gas chromatograms: application to plant extracts.

Comprehensive two-dimensional gas chromatography (GC x GC) is now recognized as the preferred technique for the detailed analysis and characterization of complex mixtures of volatile compounds. However, for comparison purposes, taking into account all the information contained in the chromatogram is far from trivial. In this paper, it is shown that the combination of peak alignment by dynamic time warping and multivariate analysis facilitated the comparison of complex chromatograms of tobacco extracts. The comparison is shown to be efficient enough to provide a clear discrimination among three types of tobacco. A tentative interpretation of loadings is presented in order to give access to the compounds which differ from one sample to another. Once located, mass spectrometry was used to identify markers of tobacco type.

[Role of computerised programs for the evaluation, diagnosis and treatment of partially edendulous patients]. / Aportul programelor computerizate in evaluare, diagnostic si tratament la pacientul edentat partial.

UNLABELLED: In order to elaborate a correct plan of diagnosis and find the correct therapeutic solution of election in partial edentulous it would be necessary to use a Support System for Clinical Decisions (SSCD). This may bring many benefits both to the private medical assistance,and to institutions with wider therapeutic, educational and scientific objectives. MATERIALS AND METHODS: Using as starting point the ProDent platform of application existing at the Faculty of Dental Medicine from The University of Medicine and Pharmacy Gr.T. Popa Iasi we have developed an expert system for clinical case evaluation and for providing a reliable therapeutic solution. In this respect we have used the ProDent application database--a complete and complex database which records information about patients. RESULTS: At the same time the application generates a table recording a clinico-biological data hierarchy, highlighting the categories which may require intervention during the specific preparation stage. The use of bayes inference also indicates the most reliable therapeutic solution, the initial plan of treatment, the reliability score and the oral rehabilitation predictions. By adding the patient initial score and the oral rehabilitation predictions provided by the application, we obtain the patient initial therapeutic score. CONCLUSIONS: The simulation programs and the electronic format of the observation paper are efficient tools that provide an integrative holistic approach of patients with different forms of oral pathology, under the incidence of local, loco-regional and general complications.

Statistical validation of strategies for Zang-Fu single pattern differentiation.

OBJECTIVE: To propose and validate a method to aid traditional Chinese medicine (TCM) physicians in differentiation of Zang-Fu single patterns. METHODS: The procedure started with data collection and search on a knowledge database. Candidate patterns were selected and ranked according to the relative amount of explained exam's manifestations. Diagnosis identification was performed on a list of diagnostic hypotheses. Validation was conducted with 96,600 simulations of manifestation profiles obtained from database. Statistical performance based on confusion matrices was assessed for individual methods including inspection, auscultation and olfaction, inquiry, and palpation. Combined methods (inspection+auscultation and olfaction, inspection+auscultation and olfaction+inquiry) and four methods (inspection+auscultation and olfaction+inquiry+palpation) were also tested. RESULTS: The highest accuracy was obtained with the inquiry method (89.7%), followed by inspection (70.7%), auscultation and olfaction (59.9%), and palpation (56.1%). The same sequence was found for both sensitivity and negative predictive values. Specificity and positive predictive values were almost equal and high (>99%) among individual exam methods. The combination of all methods provided the highest accuracy (93.2%), sensitivity (86.5%), and negative predictive value (88.1%), while sustained high specificity (99.9%) and positive predictive value (99.8%). The four methods presented the higher performance compared to combination of two or three exam methods as well as all single exam methods. CONCLUSION: The proposed strategies present statistical evidence of its diagnostic performance and can be used to aid TCM physicians in making single pattern diagnosis according to Zang-Fu theory.

Model-based imaging of cardiac apparent conductivity and local conduction velocity for diagnosis and planning of therapy.

We present an adaptive algorithm which uses a fast electrophysiological (EP) model to estimate apparent electrical conductivity and local conduction velocity from noncontact mapping of the endocardial surface potential. Development of such functional imaging revealing hidden parameters of the heart can be instrumental for improved diagnosis and planning of therapy for cardiac arrhythmia and heart failure, for example during procedures such as radio-frequency ablation and cardiac resynchronisation therapy. The proposed model is validated on synthetic data and applied to clinical data derived using hybrid X-ray/magnetic resonance imaging. We demonstrate a qualitative match between the estimated conductivity parameter and pathology locations in the human left ventricle. We also present a proof of concept for an electrophysiological model which utilizes the estimated apparent conductivity parameter to simulate the effect of pacing different ventricular sites. This approach opens up possibilities to directly integrate modelling in the cardiac EP laboratory.

Applications of natural orbitals for chemical valence in a description of bonding in conjugated molecules.

Natural orbitals for chemical valence (NOCV) were used to describe bonding in conjugated pi-electron molecules. The 'single' C-C bond in trans-1,3-butadiene, 1,3-butadiene-1,1,4,4-tetra-carboxilic acid, 1,3,5,7-octatetraene, and 11-cis-retinal was characterized. In the NOCV framework, the formation of the sigma-bond appears as the sum of two complementary charge transfer processes from each vinyl fragment to the bond region, and partially to the other fragment. The formation of the pi-component of the bond is described by two pairs of NOCV representing the transfer of charge density from the neighboring 'double' C-C bonds. The NOCV eigenvalues and the related fragment-fragment bond multiplicities were used as quantitative measures of the sigma- and pi- contributions. The sigma-component of the 'single' C-C bonds appears to be practically constant in the systems analyzed, whereas the pi-contributions increase from butadiene (ca. 7.5%) to retinal (ca. 14%).

A 3-factor model for the FACIT-Sp.

OBJECTIVE: The 12-item Functional Assessment of Chronic Illness Therapy-Spiritual Well-being Scale (FACIT-Sp) is a popular measure of the religious/spiritual (R/S) components of quality of life (QoL) in patients with cancer. The original factor analyses of the FACIT-Sp supported two factors: Meaning/Peace and Faith. Because Meaning suggests a cognitive aspect of R/S and Peace an affective component, we hypothesized a 3-factor solution: Meaning, Peace, and Faith. METHODS: Participants were 240 long-term female survivors of cancer who completed the FACIT-Sp, the SF-12, and the BSI 18. We used confirmatory factor analysis to compare the 2- and 3-factor models of the FACIT-Sp and subsequently assessed associations between the resulting solutions and QoL domains. RESULTS: Survivors averaged 44 years of age and 10 years post-diagnosis. A 3-factor solution of the FACIT-Sp significantly improved the fit of the model to the data over the original 2-factor structure (Delta chi(2)=72.36, df=2, p<0.001). Further adjustments to the 3-factor model resulted in a final solution with even better goodness-of-fit indices (chi(2)=59.11, df=1, p=0.13, CFI=1.00, SMRM=0.05).The original Meaning/Peace factor controlling for Faith was associated with mental (r=0.63, p<0.000) and physical (r=0.22, p<0.01) health on the SF-12, and the original Faith factor controlling for Meaning/Peace was negatively associated with mental health (r=-0.15, p<0.05). The 3-factor model was more informative. Specifically, using partial correlations, the Peace factor was only related to mental health (r=0.53, p<0.001); Meaning was related to both physical (r=0.18, p<0.01) and mental (r=0.17, p<0.01) health; and Faith was negatively associated with mental health (r=-0.17, p<0.05). CONCLUSION: The results of this study support a 3-factor solution of the FACIT-Sp. The new solution not only represents a psychometric improvement over the original, but also enables a more detailed examination of the contribution of different dimensions of R/S to QoL.