Transconvolution and the virtual positron emission tomograph--a new method for cross calibration in quantitative PET∕CT imaging

PURPOSE Positron emission tomography (PET)∕computed tomography (CT) measurements on small lesions are impaired by the partial volume effect, which is intrinsically tied to the point spread function of the actual imaging system, including the reconstruction algorithms. The variability resulting from different point spread functions hinders the assessment of quantitative measurements in clinical routine and especially degrades comparability within multicenter trials. To improve quantitative comparability there is a need for methods to match different PET∕CT systems through elimination of this systemic variability. Consequently, a new method was developed and tested that transforms the image of an object as produced by one tomograph to another image of the same object as it would have been seen by a different tomograph. The proposed new method, termed Transconvolution, compensates for differing imaging properties of different tomographs and particularly aims at quantitative comparability of PET∕CT in the context of multicenter trials. METHODS To solve the problem of image normalization, the theory of Transconvolution was mathematically established together with new methods to handle point spread functions of different PET∕CT systems. Knowing the point spread functions of two different imaging systems allows determining a Transconvolution function to convert one image into the other. This function is calculated by convolving one point spread function with the inverse of the other point spread function which, when adhering to certain boundary conditions such as the use of linear acquisition and image reconstruction methods, is a numerically accessible operation. For reliable measurement of such point spread functions characterizing different PET∕CT systems, a dedicated solid-state phantom incorporating (68)Ge∕(68)Ga filled spheres was developed. To iteratively determine and represent such point spread functions, exponential density functions in combination with a Gaussian distribution were introduced. Furthermore, simulation of a virtual PET system provided a standard imaging system with clearly defined properties to which the real PET systems were to be matched. A Hann window served as the modulation transfer function for the virtual PET. The Hann's apodization properties suppressed high spatial frequencies above a certain critical frequency, thereby fulfilling the above-mentioned boundary conditions. The determined point spread functions were subsequently used by the novel Transconvolution algorithm to match different PET∕CT systems onto the virtual PET system. Finally, the theoretically elaborated Transconvolution method was validated transforming phantom images acquired on two different PET systems to nearly identical data sets, as they would be imaged by the virtual PET system. RESULTS The proposed Transconvolution method matched different PET∕CT-systems for an improved and reproducible determination of a normalized activity concentration. The highest difference in measured activity concentration between the two different PET systems of 18.2% was found in spheres of 2 ml volume. Transconvolution reduced this difference down to 1.6%. In addition to reestablishing comparability the new method with its parameterization of point spread functions allowed a full characterization of imaging properties of the examined tomographs. CONCLUSIONS By matching different tomographs to a virtual standardized imaging system, Transconvolution opens a new comprehensive method for cross calibration in quantitative PET imaging. The use of a virtual PET system restores comparability between data sets from different PET systems by exerting a common, reproducible, and defined partial volume effect.

Benefits and challenges in practice-oriented psychotherapy research in Germany: The TK and the QS-PSY-BAY projects of quality assurance in outpatient psychotherapy

Objective: Two patient-focused long-term research projects performed in the German outpatient psychotherapy system are focused on in this article. The TK (Techniker Krankenkasse) project is the first study to evaluate a quality assurance and feedback system with regard to its practical feasibility in German routine care. The other study (“Quality Assurance in Outpatient Psychotherapy in Bavaria”; QS-PSY-BAY) was designed to test a new approach for quality assurance in outpatient psychotherapy using electronic documentation of patient characteristics and outcome parameters. In addition this project provides the opportunity to analyze data on health-related costs for the patients undergoing outpatient psychotherapy. Method: Both projects and their results indicating high effect sizes are briefly described. Results: From the perspectives of the research teams, advisory boards and other stakeholders, the experiences with these projects are discussed focusing on obstacles, challenges, difficulties, and benefits in developing and implementing the studies. The triangle collaboration of therapists, researchers, and health insurance companies/health service institutions turned out to be fruitful in both studies. Conclusions: Despite some controversies between the partners the experiences indicate the importance of practiced-research collaborations to provide relevant information about the delivery of outpatient psychotherapy in the health system

Comparative evaluation of the My5-FU™ immunoassay and LC-MS/MS in monitoring the 5-fluorouracil plasma levels in cancer patients

BACKGROUND: Chemotherapies of solid tumors commonly include 5-fluorouracil (5-FU). With standard doses of 5-FU, substantial inter-patient variability has been observed in exposure levels and treatment response. Recently, improved outcomes in colorectal cancer patients due to pharmacokinetically guided 5-FU dosing were reported. We aimed at establishing a rapid and sensitive method for monitoring 5-FU plasma levels in cancer patients in our routine clinical practice. METHODS: Performance of the Saladax My5-FU™ immunoassay was evaluated on the Roche Cobas® Integra 800 analyzer. Subsequently, 5-FU concentrations of 247 clinical plasma samples obtained with this assay were compared to the results obtained by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and other commonly used clinical analyzers (Olympus AU400, Roche Cobas c6000, and Thermo Fisher CDx90). RESULTS: The My-FU assay was successfully validated on the Cobas Integra 800 analyzer in terms of linearity, precision, accuracy, recovery, interference, sample carryover, and dilution integrity. Method comparison between the Cobas Integra 800 and LC-MS/MS revealed a proportional bias of 7% towards higher values measured with the My5-FU assay. However, when the Cobas Integra 800 was compared to three other clinical analyzers in addition to LC-MS/MS including 50 samples representing the typical clinical range of 5-FU plasma concentrations, only a small proportional bias (≤1.6%) and a constant bias below the limit of detection was observed. CONCLUSIONS: The My5-FU assay demonstrated robust and highly comparable performance on different analyzers. Therefore, the assay is suitable for monitoring 5-FU plasma levels in routine clinical practice and may contribute to improved efficacy and safety of commonly used 5-FU-based chemotherapies.

Multiprofessional collaboration in teaching practices in all-day-schools in Switzerland

Multiprofessional collaboration in settings of extended education has been an important research topic in the past 40 years and has been discussed as a means to improve educational achievement, foster professional development, and support teachers in their everyday work. Several recent studies in multiprofessional settings found that collaboration practices often remain on a student-centered, time-limited, and superficial level of exchange, whereas higher forms of collaboration are very rare (Dizinger, Fussangel, Kasper, 2011). Furthermore there exists an obvious research gap on collaboration in Swiss all-day schools (Jutzi&Thomann, 2012). In this study we analyzed practices of multiprofessional collaboration in school-based and community-based extracurricular activities of all-day schools in Switzerland. The aim of this qualitative study of 10 all-day schools was to answer the following questions: (a) What forms of collaboration (informal/formal) are used between the different professionals? and (b) Are there different types of all-day schools with regard to distinctive and consistent types of collaboration? We conducted 18 problem-centered interviews (with the principals/heads of the all-day schools) and 10 focus group discussions (teams). In the process of data evaluation, we applied the method of qualitative content analysis. The results show that multiprofessional collabo ration is taking place in all of the all-day schools examined in the study. However, the collaborative practices differ in their level of intensity, design, and purpose.

Sleepwalking, REM sleep behaviour disorder and overlap parasomnia in patients with Parkinson's disease

BACKGROUND/AIMS In a questionnaire survey, we identified 36 (9%) of 417 Parkinson's disease (PD) patients with sleepwalking (SW); 72% of them also had a history of REM sleep behaviour disorder (RBD). We aimed to assess the clinical and polysomnographic characteristics of SW in PD and to compare them to patients with PD with and without a history of RBD. METHODS We performed video-polysomnography and detailed clinical examination in 30 PD patients from the above-mentioned survey: 10 patients with a history of SW, 10 patients with a history of RBD, and 10 patients with no history of either SW or RBD. RESULTS PD patients with SW had higher depression, anxiety and Hoehn & Yahr scores and lower activities of daily living scores than patients without a history of RBD but did not differ from patients with RBD. Patients with SW and RBD also had more often dyskinesia and hallucinations. By polysomnography, RBD was observed in 8 patients with SW and in all patients with a history of RBD. A total of 5 patients without a history of either SW or RBD had REM sleep without atonia without behavioural peculiarities. CONCLUSION SW in PD is associated with depression, higher disease severity and functional disability. The simultaneous occurrence of SW and RBD (overlap parasomnia) in most patients suggests a common underlying disturbance of motor control during sleep in PD, with variable manifestations in different sleep stages.

Determination of genetic transferrin variants in human serum by high-resolution capillary zone electrophoresis(†)

High-resolution capillary zone electrophoresis in the routine arena with stringent quality assurance is employed for the determination of carbohydrate-deficient transferrin in human serum. The assay comprises mixing of human serum with a Fe(III) -containing solution prior to analysis of the iron-saturated mixture in a dynamically double-coated capillary using a commercial buffer at alkaline pH. In contrast to other assays, it provides sufficient resolution for proper recognition of genetic transferrin variants. Analysis of 7290 patient sera revealed 166 isoform patterns that could be assigned to genetic variants, namely, 109 BC, 53 CD, one BD and three CC variants. Several subtypes of transferrin D can be distinguished as they have large enough differences in pI values. Subtypes of transferrin C and B cannot be resolved. However, analysis of the detection time ratios of tetrasialo isoforms of transferrin BC and transferrin CD variants revealed multimodal frequency histograms, indicating the presence of subtypes of transferrin C, B and D. The data gathered over 11 years demonstrate the robustness of the high-resolution capillary zone electrophoresis assay. This is the first account of a capillary zone electrophoresis based carbohydrate-deficient transferrin assay with a broad overview on transferrin isoform patterns associated with genetic transferrin variants.

Delay of cortical thinning in very preterm born children

BACKGROUND: Cortical gray matter thinning occurs during childhood due to pruning of inefficient synaptic connections and an increase in myelination. Preterms show alterations in brain structure, with prolonged maturation of the frontal lobes, smaller cortical volumes and reduced white matter volume. These findings give rise to the question if there is a differential influence of age on cortical thinning in preterms compared to controls. AIMS: To investigate the relationship between age and cortical thinning in school-aged preterms compared to controls. STUDY DESIGN AND OUTCOME MEASURES: The automated surface reconstruction software FreeSurfer was applied to obtain measurements of cortical thickness based on T1-weighted MRI images. SUBJECTS: Forty-one preterms (<32weeks gestational age and/or <1500g birth weight) and 30 controls were included in the study (7-12years). RESULTS: In preterms, age correlated negatively with cortical thickness in right frontal, parietal and inferior temporal regions. Furthermore, young preterms showed a thicker cortex compared to old preterms in bilateral frontal, parietal and temporal regions. In controls, age was not associated with cortical thickness. CONCLUSION: In preterms, cortical thinning still seems to occur between the age of 7 and 12years, mainly in frontal and parietal areas whereas in controls, a substantial part of cortical thinning appears to be completed before they reach the age of 7years. These data indicate slower cortical thinning in preterms than in controls.

Effectiveness of integrated care including therapeutic assertive community treatment in severe schizophrenia spectrum and bipolar I disorders: the 24-month follow-up ACCESS II study

OBJECTIVE The ACCESS treatment model offers assertive community treatment embedded in an integrated care program to patients with psychoses. Compared to standard care and within a controlled study, it proved to be more effective in terms of service disengagement and illness outcomes in patients with schizophrenia spectrum disorders over 12 months. ACCESS was implemented into clinical routine and its effectiveness assessed over 24 months in severe schizophrenia spectrum disorders and bipolar I disorder with psychotic features (DSM-IV) in a cohort study. METHOD All 115 patients treated in ACCESS (from May 2007 to October 2009) were included in the ACCESS II study. The primary outcome was rate of service disengagement. Secondary outcomes were change of psychopathology, severity of illness, psychosocial functioning, quality of life, satisfaction with care, medication nonadherence, length of hospital stay, and rates of involuntary hospitalization. RESULTS Only 4 patients (3.4%) disengaged with the service. Another 11 (9.6%) left because they moved outside the catchment area. Patients received a mean of 1.6 outpatient contacts per week. Involuntary admissions decreased from 34.8% in the 2 previous years to 7.8% during ACCESS (P < .001). Mixed models repeated-measures analyses revealed significant improvements among all patients in psychopathology (effect size d = 0.64, P < .001), illness severity (d = 0.84, P = .03), functioning level (d = 0.65, P < .001), quality of life (d = 0.50, P < .001), and client satisfaction (d = 0.11, P < .001). At 24 months, 78.3% were fully adherent to medication, compared to 25.2% at baseline (P = .002). CONCLUSIONS ACCESS was successfully implemented in clinical routine and maintained excellent rates of service engagement and other outcomes in patients with schizophrenia spectrum disorders or bipolar I disorder with psychotic features over 24 months. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01888627.

Psychometric and biohormonal indices of dental anxiety in children. A prospective cohort study.

The stress of dental treatment often elicits negative emotions in children, expressed as dental fear or anxiety. Highly anxious children obstruct treatment and avoid therapy, further amplifying oral health problems. The aim of this study was to examine the neuroendocrine and autonomic nervous system responses to dental treatment and their possible interactions and associations with psychometric indices of anxiety, caries, previous dental experience, anesthesia, age and gender in school children. Upon informed consent, saliva was obtained from 97 children (59% males, mean age ±  SD: 89.73 ± 15 months) in the Clinic of pediatric dentistry before treatment, immediately post-treatment and at the recall visit to determine cortisol and salivary alpha-amylase (sAA) levels. Dental and general anxiety was assessed through specific questionnaires completed by the children. Compared to pre-treatment, cortisol levels were increased following treatment, while sAA levels were higher at the recall. Pre- and post-treatment cortisol and sAA responses were positively correlated. Dental and general anxiety questionnaire scores were also significantly correlated with each other. The integrated autonomic and neuroendocrine responses prior to treatment were correlated with state anxiety and those following treatment with dental anxiety. However, univariable and multivariable linear regression analysis associated post-treatment cortisol, but not sAA, levels with dental anxiety. No associations of cortisol or sAA responses with caries, age, gender, previous dental experience or anesthesia were detected. These data provide some evidence that both sAA and cortisol levels are altered in children in anticipation or during dental treatment, but only cortisol levels are associated to dental anxiety.

Assessment of patient setup errors in IGRT in combination with a six degrees of freedom couch

PURPOSE The range of patient setup errors in six dimensions detected in clinical routine for cranial as well as for extracranial treatments, were analyzed while performing linear accelerator based stereotactic treatments with frameless patient setup systems. Additionally, the need for re-verification of the patient setup for situations where couch rotations are involved was analyzed for patients treated in the cranial region. METHODS AND MATERIALS A total of 2185 initial (i.e. after pre-positioning the patient with the infrared system but before image guidance) patient setup errors (1705 in the cranial and 480 in the extracranial region) obtained by using ExacTrac (BrainLAB AG, Feldkirchen, Germany) were analyzed. Additionally, the patient setup errors as a function of the couch rotation angle were obtained by analyzing 242 setup errors in the cranial region. Before the couch was rotated, the patient setup error was corrected at couch rotation angle 0° with the aid of image guidance and the six degrees of freedom (6DoF) couch. For both situations attainment rates for two different tolerances (tolerance A: ± 0.5mm, ± 0.5°; tolerance B: ± 1.0 mm, ± 1.0°) were calculated. RESULTS The mean (± one standard deviation) initial patient setup errors for the cranial cases were -0.24 ± 1.21°, -0.23 ± 0.91° and -0.03 ± 1.07° for the pitch, roll and couch rotation axes and 0.10 ± 1.17 mm, 0.10 ± 1.62 mm and 0.11 ± 1.29 mm for the lateral, longitudinal and vertical axes, respectively. Attainment rate (all six axes simultaneously) for tolerance A was 0.6% and 13.1% for tolerance B, respectively. For the extracranial cases the corresponding values were -0.21 ± 0.95°, -0.05 ± 1.08° and -0.14 ± 1.02° for the pitch, roll and couch rotation axes and 0.15 ± 1.77 mm, 0.62 ± 1.94 mm and -0.40 ± 2.15 mm for the lateral, longitudinal and vertical axes. Attainment rate (all six axes simultaneously) for tolerance A was 0.0% and 3.1% for tolerance B, respectively. After initial setup correction and rotation of the couch to treatment position a re-correction has to be performed in 77.4% of all cases to fulfill tolerance A and in 15.6% of all cases to fulfill tolerance B. CONCLUSION The analysis of the data shows that all six axes of a 6DoF couch are used extensively for patient setup in clinical routine. In order to fulfill high patient setup accuracies (e.g. for stereotactic treatments), a 6DoF couch is recommended. Moreover, re-verification of the patient setup after rotating the couch is required in clinical routine.

Comprehensive validation of published immunohistochemical prognostic biomarkers of prostate cancer-what has gone wrong? A blueprint for the way forward in biomarker studies

BACKGROUND Treatment planning of localised prostate cancer remains challenging. Besides conventional parameters, a wealth of prognostic biomarkers has been proposed so far. None of which, however, have successfully been implemented in a routine setting so far. The aim of our study was to systematically verify a set of published prognostic markers for prostate cancer. METHODS Following an in-depth PubMed search, 28 markers were selected that have been proposed as multivariate prognostic markers for primary prostate cancer. Their prognostic validity was examined in a radical prostatectomy cohort of 238 patients with a median follow-up of 60 months and biochemical progression as endpoint of the analysis. Immunohistochemical evaluation was performed using previously published cut-off values, but allowing for optimisation if necessary. Univariate and multivariate Cox regression were used to determine the prognostic value of biomarkers included in this study. RESULTS Despite the application of various cut-offs in the analysis, only four (14%) markers were verified as independently prognostic (AKT1, stromal AR, EZH2, and PSMA) for PSA relapse following radical prostatectomy. CONCLUSIONS Apparently, many immunohistochemistry-based studies on prognostic markers seem to be over-optimistic. Codes of best practice, such as the REMARK guidelines, may facilitate the performance of conclusive and transparent future studies.

Ultrasound evaluation of synovitis in RA: correlation with clinical disease activity and sensitivity to change in an observational cohort study.

OBJECTIVE To evaluate the correlation between clinical measures of disease activity and a ultrasound (US) scoring system for synovitis applied by many different ultrasonographers in a daily routine care setting within the Swiss registry for RA (SCQM) and further to determine the sensitivity to change of this US Score. METHODS One hundred and eight Swiss rheumatologists were trained in performing the Swiss Sonography in Arthritis and Rheumatism (SONAR) score. US B-mode and Power Doppler (PwD) scores were correlated with DAS28 and compared between the clinical categories in a cross-sectional cohort of patients. In patients with a second US (longitudinal cohort), we investigated if change in US score correlated with change in DAS and evaluated the responsiveness of both methods. RESULTS In the cross-sectional cohort with 536 patients, correlation between the B-mode score and DAS28 was significant but modest (Pearson coefficient r = 0.41, P < 0.0001). The same was true for the PwD score (r = 0.41, P < 0.0001). In the longitudinal cohort with 183 patients we also found a significant correlation between change in B-mode and in PwD score with change in DAS28 (r = 0.54, P < 0.0001 and r = 0.46, P < 0.0001, respectively). Both methods of evaluation (DAS and US) showed similar responsiveness according to standardized response mean (SRM). CONCLUSIONS The SONAR Score is practicable and was applied by many rheumatologists in daily routine care after initial training. It demonstrates significant correlations with the degree of as well as change in disease activity as measured by DAS. On the level of the individual, the US score shows many discrepancies and overlapping results exist.

Complementary Medicine in Nursing Homes - Results of a Mixed Methods Pilot Study

Background ‘Kneipp Therapy’ (KT) is a form of Complementary and Alternative Medicine (CAM) that includes a combination of hydrotherapy, herbal medicine, mind-body medicine, physical activities, and healthy eating. Since 2007, some nursing homes for older adults in Germany began to integrate CAM in the form of KT in care. The study investigated how KT is used in daily routine care and explored the health status of residents and caregivers involved in KT. Methods We performed a cross-sectional pilot study with a mixed methods approach that collected both quantitative and qualitative data in four German nursing homes in 2011. Assessments in the quantitative component included the Quality of Life in Dementia (QUALIDEM), the Short Form 12 Health Survey (SF-12), the Barthel-Index for residents and the Work Ability Index (WAI) and SF-12 for caregivers. The qualitative component addressed the residents’ and caregivers’ subjectively experienced changes after integration of KT. It was conceptualized as an ethnographic rapid appraisal by conducting participant observation and semi-structured interviews in two of the four nursing homes. Results The quantitative component included 64 residents (53 female, 83.2 ± 8.1 years (mean and SD)) and 29 caregivers (all female, 42.0 ± 11.7 years). Residents were multimorbid (8 ± 3 diagnoses), and activities of daily living were restricted (Barthel-Index 60.6 ± 24.4). The caregivers’ results indicated good work ability (WAI 37.4 ± 5.1), health related quality of life was superior to the German sample (SF-12 physical CSS 49.2 ± 8.0; mental CSS 54.1 ± 6.6). Among both caregivers and residents, 89% considered KT to be positive for well-being. The qualitative analysis showed that caregivers perceived emotional and functional benefits from more content and calmer residents, a larger variety in basic care practices, and a more self-determined scope of action. Residents reported gains in attention and caring, and recognition of their lay knowledge. Conclusion Residents showed typical characteristics of nursing home inhabitants. Caregivers demonstrated good work ability. Both reported to have benefits from KT. The results provide a good basis for future projects, e.g. controlled studies to evaluate the effects of CAM in nursing homes.