Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 84-90).

<u>Introduction:</u> the area of process research has identified differences in the process of CB and PI therapy and has highlighted factors which contribute to outcome. The present research aimed to explore three factors, therapist focus, client experiencing and client cognitive change, in very brief 2+1 therapy, and explore their relation to immediate outcome as measured by the assimilation scale. <u>Method:</u> intensive quantitative analyses of eight cases receiving 2+1 therapy was carried out. Four cases received CB therapy, four received PI therapy. Two of each showed 'good' and 'poor' outcome. Ten excerpts, rated in a previous project as significant, were used as items of analysis. <u>Results:</u> PI therapists focused more than CB therapists on 'Constructing Meaning' (CM). Good outcome PI therapy showed a greater emphasis than poor outcome PI therapy on CM. PI therapy clients had higher levels of experiencing, which increased over therapy. Good outcome PI therapy was associated with higher EXP levels, good outcome CB therapy with lower levels of EXP. Good outcome CB clients had fewer negative selfstatements. Movement on the assimilation model was associated with increased EXP levels in PI and fewer negative self-statements in CB therapy. <u>Discussion:</u> results supported previous findings of differences in the process of CB and PI therapy. The mechanism of change in very brief CB and PI therapy are discussed, followed by implications for clinical practice and future research. Overall, findings suggest a picture of the process of therapy which may contribute to the clarification of the complex nature of change in psychotherapy and what is meant by therapeutic change.

Acceptance and commitment therapy (ACT) was developed to specifically target experiential avoidance (EA) rather than any specific diagnostic category. A functional ACT manual was presented and used to treat diagnostically diverse clients in a large sliding fee-for-service training clinic. A multiple baseline across participants and behaviors research design was used to evaluate session-by-session changes in EA, values identification, valued action, and clinical distress. The Acceptance and Action Questionnaire-2 (AAQ2), Valued Living Questionnaire (VLQ), and Outcome Questionnaire (OQ-45) were given to measure processes and outcomes given the functional ACT model presented in the introduction to the paper. Baseline included the Structured Clinical Interview for DSM-IV Axis I and II Disorders given across 2-5 50- minute sessions. The treatment phase consisted of 7-10 50-minute sessions. Participants were 10 clients. Four participants completed sufficient treatment sessions (4-9) to test the study hypotheses. Participants generally improved across time, but most improvements could not be attributed to the functional application of ACT due to changes during baseline for AAQ, VLQ-Consistency, and OQ-45. VLQ-Importance significantly improved for all participants given ACT.

Outcomes measurement is an important component of routine hemophilia care, clinical trials and economic evaluations. Assessing outcomes in patients living with hemophilia is challenging due to a lack of validated outcome measures. Conventional clinical outcomes, for instance, bleeding rate, structural changes of joints or functional joint scores may be less relevant for the decision-making process. Patient reported outcomes measures has been increasingly interested in routine medical care and clinical research. However, the available validated patients reported outcome measures for patients with hemophilia are not generally implemented in routine care or clinical trials. The Patent Reported Outcomes, Burdens, and Experiences (PROBE) study aims to develop a validated patient reported outcome measure for patients living with hemophilia. The PROBE questionnaire is organized in 4 sections, comprising 29 questions. Section I contains questions pertaining to demographic data. Section II contains questions pertaining to patient reported outcomes. Section III contains questions pertaining to hemophilia specific problems and treatments. Section IV contains the EuroQol five dimension 5-level instrument (EQ-5D-5L). The psychometric analysis of revealed that the PROBE questionnaire has a good internal consistency (Cronbach’s alpha coefficient=0.84). PROBE items showed moderate to strong correlations with corresponding EQ-5D-5L domains. The PROBE Score has a known group validity among known groups. The psychometric properties of the PROBE questionnaire demonstrated the validity of the instrument in both patients living with hemophilia and control population (participants without bleeding disorder). The test-retest reliability analysis demonstrated that the PROBE questionnaire has a substantial agreement when the questionnaire was repeatedly administrated. There were acceptable reliability properties between the paper-based and web-based questionnaires. The reliability properties of the PROBE questionnaire were established in both patients living with hemophilia and control population. The PROBE questionnaire was cross-cultural implemented in 21 countries. The results showed that the regions of participant contributed a trivial variability of the PROBE score, indicating that the PROBE questionnaire is valid for assessing the health status among hemophilia patients and participants without bleeding disorder across regions. Sexual health of patients living with hemophilia was evaluated using the PROBE questionnaire. The results showed that sexual difficulty was more prevalent in patients with hemophilia and associated with markers of disease severity. This finding warrants the sexual health assessment in routine hemophilia care. / Thesis / Doctor of Philosophy (PhD)

Background Research on the optimal management of deceased organ donors poses unique challenges including the fact that one deceased donor may provide up to 8 organs for transplantation. Measuring the post-transplant function of these organs – good or bad – represents an attractive way of deciding whether treatment of deceased donors is working well, or not so well. Function, however, is organ-specific. Therefore, to conduct the most efficient and informative research on deceased donor management, we need an outcome measure that works well in all organs. The new outcome measure is called Generic Rating of Allograft Function post-Transplantation (GRAFT). Methods In this thesis, I highlight the methods for developing the cardiac-specific version of the GRAFT instrument. The same methods, however, have and will be applied to other organ-specific versions. The work comprised various study designs and developed novel research tools, all of which have advanced the development of the GRAFT instrument. At first, we developed a simple conceptualization for the instrument. Through regular consultation with research methodologists, biostatisticians and clinical experts, we refined the fundamental conceptualization and then refined the generic instrument, itself. One key concept is that GRAFT ratings should correlate with one-year graft function. To maximize its utility, I developed a heart--specific guide for applying GRAFT in future studies, and other organ-specific guides are underway. Specifically, we developed these guides by identifying the most robust predictors of one-year graft function through the conduct of organ-specific systematic reviews and meta-analyses of prognostic factors. The evidence from these reviews, in consultation with a focus group of organ-specific transplant physicians, lead to refinements of our guides. We subsequently conducted a mixed-methods user testing to assess reliability and usability of the organ-specific guides. In appraising the evidence informing the guides, we developed GRADE guidance and a novel absolute risk calculator to assess our certainty in the body of evidence on prognostic factors informing our guides. Results We developed a 6-point generic rating instrument for classification of graft function to be applied post-transplant across all major solid organs. We designed GRAFT to be applied at the time of discharge, 1-month post-transplant, or at the time of death (whichever occurs first). We classify function as 1) normal, 2A) impaired but likely to gain normal function, 2B) impaired and unlikely to gain normal function, 3A) severely impaired but likely to gain some function, 3B) severely impaired and unlikely to gain some function, and 4) irreversible graft failure. Clinical expert collaborators for each organ type confirmed face validity of the GRAFT instrument. For all organs, we identified a number of prognostic factors that can guide users in classifying organ function post-transplant. In consultation with clinical experts, we determined that the most important factor is graft function as measured by left ventricular ejection fraction (LVEF) or right atrial pressure (RAP). Due to limitations with the quality and quantity of the evidence, however, the heart transplant experts did not rely on the results of their organ group’s systematic review. In turn, we conducted a retrospective cohort study to calculate the best estimate of association between LVEF, RAP, and overall mortality post heart transplant. For the cardiac version of GRAFT, user testing demonstrated high reliability (Kappa of 0.87, 95% CI 0.62 – 1.00) and acceptable usability (system usability score of 75, inter-quartile range of 72.5 – 80). In the process, we developed and published GRADE guidance for assessing certainty in the body of evidence addressing prognostic factors and devised a calculator to transform relative effect of each prognostic factor to absolute risks (http://hiru.mcmaster.ca/AbsoluteRiskCalculator/). Conclusion In this thesis, I advanced the development of an innovative generic instrument for the classification of graft function specifically for the purpose of application in clinical trials of deceased donor interventions. This work is ongoing, but very advanced for heart-specific components, for which I have ensured face validity, and demonstrated reliability and usability. The GRAFT instrument may better facilitate the conduct of future research to improve care of deceased organ donors with a view to improving quality and quantity of organs for transplantation. / Thesis / Candidate in Philosophy

No description available.

Few authors report comprehensive psychometric data for their acquired brain injury (ABI) outcome indices (e.g., items analyses, test-retest reliability, survivor-proxy agreement, internal consistency, convergent validity). Even fewer authors submit their indices to modern psychometric analyses, like Rasch analysis. The purpose of this dissertation was to evaluate the traditional and modern psychometric properties of a new index of brain injury outcome: the Functional Outcome Profile (FOP). One hundred and thirteen mixed (estimated mild, moderate, and severe injury) ABI survivors and 22 significant others participated in the study. Items analyses (n = 113) revealed that all items were endorsed by at least one ABI survivor, suggesting that the FOP assessed areas relevant to ABI survivors. However most items, composite scores, and the total score had distributions that were negatively skewed. One-week test-retest reliability correlations for the total score, composites, and items (n = 25) were generally in the moderate to strong range (r > 0.7), while survivor-proxy agreement correlations for the items (n = 22) were generally in the moderate range (r = 0.5 to 0.7). The internal consistency scores (n = 113) for 5 of the 8 composite scales and for the full FOP were good (Cronbach α > 0.7). Concurrent-convergent validity analyses revealed that the FOP correlated moderately well with the Mayo-Portland Adaptability Index (MPAI-4) (r = -0.75), but that it did not correlate with injury-related information (e.g., age at injury, time since injury, estimated severity). Rasch calibration of the FOP resulted in a 62-item index that fit the Rasch model well and that demonstrated good reliability and separation. Overall, the results suggest that the FOP has good traditional and modern psychometric properties when used with community-based outpatient ABI survivors. Future studies with the FOP should focus on improving the FOP’s clinical utility and further verifying its convergent and divergent validity.

Caffeine is used for the treatment of apnea of prematurity. The objective of this study was to determine the long term neuropathological and neurobehavioral effects of caffeine on the immature rat brain. Newborn rats were injected with either caffeine, or normal saline from postnatal days 3 to 7, equivalent to the human premature infant of 28-36 weeks. Behavioral tests revealed no abnormality in caffeine treated animals compared to controls. Fluro-Jade B stain of P4 rat brains showed that caffeine caused significant neuronal cell death in some areas of the brain, compared to controls, but this alteration was transient and not present at P8. Anti-NeuN stain at P21 showed significant neuronal cell loss in CA1 and hypothalamus regions in the caffeine group, but not at P160. Anti-Neurofilament M stain at P8, P21 and P160 showed no differences between the control and caffeine groups. We conclude that use of caffeine has no significant effect on the behavioral tests measured in our newborn rat pups. While caffeine caused neuronal cell death at P4, and neuronal cell loss in CA1 and hypothalamus regions at P21, there was no long-lasting effect on neuropathological outcome. However, given these latter findings, the use of caffeine in the premature infant must still be done with caution. / Medical Sciences

Hintergrund: Weltweit berichteten zahlreiche Studien von einer steigenden Inzidenz von Patienten mit angeborenen Bauchwanddefekten. Besonders die Zahl der Gastroschisis-Kinder hat deutlich zugenommen. Auch die Neonatologen der Universitätsklinik Leipzig beschrieben ein gehäuftes Auftreten von Patienten mit Gastroschisis und Omphalocele. Aufgabe der vorliegenden Arbeit war es, die Inzidenz dieser beiden Fehlbildungen am Universitätsklinikum Leipzig zu ermitteln und zu untersuchen, wie sich die Fallzahlen während des Untersuchungszeitraumes (1998-2008) entwickelt hatten. Zudem sollten Parameter identifiziert werden, die die Prognose der betroffenen Kinder bis zur Entlassung beeinflussten. Ein weiteres Anliegen dieser Studie war es, mithilfe einer ausführlichen Literaturrecherche, einen Überblick über die aktuelle Behandlung und Prognose der beiden Fehlbildungen zu geben. Methoden: Im Rahmen einer retrospektiven Untersuchung erfolgte die Erhebung und Auswertung der Daten von 27 Kindern mit Gastroschisis sowie 19 Kindern mit Omphalocele, die zwischen 1998 und 2008 in der Universitätsklinik Leipzig behandelt wurden. Mithilfe des Mann-U-Whitney-Tests sowie des exakten Tests nach Fisher wurden zahlreiche Merkmale hinsichtlich ihrer Auswirkungen auf das Outcome überprüft. Als Parameter, die das Outcome widerspiegelten, galten der Beginn des enteralen Kostaufbaus mit Tee-Glucose-Lösung und Milch, die Dauer der parenteralen Nährstoffzufuhr und des Krankenhausaufenthaltes, sowie Nachoperationen, Komplikationen und die Letalität während des stationären Aufenthaltes. Ergebnisse: An der Universitätsklinik Leipzig betrug die Inzidenz von Gastroschisis 14 pro 10 000 Lebendgeburten und von Omphalocele 9 pro 10 000 Lebendgeburten. Die Inzidenz blieb während des elfjährigen Beobachtungszeitraumes konstant. Der Vergleich früh- und reifgeborener Gastroschisis-Patienten zeigte, dass eine Frühgeburt weder mit einem früheren Beginn der oralen Ernährung mit Tee-Glucose-Lösung (11 d vs. 14 d; p nicht signifikant) und Milch (17 d vs. 17 d; p nicht signifikant), noch mit einer Verkürzung der parenteralen Ernährung (36 d vs. 37 d; p nicht signifikant) und stationären Behandlung (48 d vs. 50 d; p nicht signifikant) einherging. Häufig verkomplizierten Infektionen (12/27) und sekundäre Darmverschlüsse (9/27) mit der Notwendigkeit einer zusätzlichen Operation den postoperativen Verlauf der Gastroschisis-Patienten. Letztgenannte Komplikation führte zu einer erheblich protrahierten parenteralen Ernährung (79 d vs. 31 d; p < 0,05) und stationären Behandlung (101 d vs. 38 d; p < 0,05), während Infektionen kaum Auswirkungen auf das Outcome hatten. Es zeigte sich, dass vorrangig Kinder mit kleinem Defekt (<= 4 cm) sowie mit prolabiertem Magen einen Ileus entwickelten. Neben Darmverschlüssen führten intestinale Begleitfehlbildungen tendenziell zu einer Verlängerung der Hospitalisierungszeit (73 d vs. 48,5 d; p nicht signifikant). Gelang die orale Zufuhr von Milch innerhalb der ersten 14 Lebenstage, so verringerte sich die Dauer der parenteralen Ernährung (30 d vs. 37 d; p < 0,05) und der stationären Behandlung (41 d vs. 67 d; p nicht signifikant). Bei Patienten mit Omphalocele bestimmten vor allem die Größe der Omphalocele, der Inhalt des Bruchsackes sowie der Zeitpunkt des oralen Ernährungsbeginns die Prognose. Ein großer (> 4 cm) Bauchwanddefekt ging mit einer erhöhten Infektionsrate (4/7 vs. 1/11; p < 0,05), prolongierten parenteralen Nahrungszufuhr (26 d vs. 17 d; p < 0,05) sowie stationären Behandlung (46 d vs. 24 d; p nicht signifikant) einher. Extraintestinale Begleitanomalien zeigten sich jedoch häufiger bei Patienten mit kleinem Defekt (5/11 vs. 1/7; p nicht signifikant). Befand sich die Leber außerhalb der Abdominalhöhle, waren zusätzliche Fehlbildungen seltener (3/11 vs. 5/7; p < 0,05). Eine prolabierte Leber verzögerte tendenziell die parenterale Ernährung (24 d vs. 18 d; p nicht signifikant) und die Krankenhausverweildauer (46 d vs. 21 d; p nicht signifikant). Ein frühzeitiger Beginn des enteralen Kostaufbaus mit Milch innerhalb der ersten zehn Lebenstage führte hingegen zu einer Verkürzung der parenteralen Ernährung (17 d vs. 27 d; p < 0,05) und stationären Behandlung (22,5 d vs. 49 d; p nicht signifikant). Schlussfolgerung: Die Inzidenz von Gastroschisis und Omphalocele blieb während des Beobachtungszeitraumes konstant. Die Prognose der Gastroschisis-Patienten wurde durch eine Frühgeburt nicht verbessert, so dass eine Termingeburt angestrebt werden sollte. Die Daten der vorliegenden Arbeit legen nahe, dass ein frühzeitiger Nahrungsaufbau mit der oralen Zufuhr von Tee ab dem achten Lebenstag sowie Milch ab dem zehnten Lebenstag günstig für das Outcome hinsichtlich der Dauer der parenteralen Ernährung und des stationären Aufenthaltes ist. Darmverschlüsse stellten schwerwiegende Komplikationen dar und verschlechterten das Outcome maßgeblich. Eine große Omphalocele sowie eine ausgetretene Leber erhöhten die Morbidität. Ebenso wie bei Gastroschisis-Kindern scheint ein frühzeitiger Beginn der enteralen Ernährung das Outcome der Omphalocele-Patienten hinsichtlich der Dauer der parenteralen Ernährung und Krankenhausbehandlung zu verbessern. Deshalb empfehlen wir ab dem fünften sowie siebten Lebenstag die enterale Ernährung mit Tee sowie Milch zu beginnen. Ein großes Manko der vorliegenden Studie ist die kleine Fallzahl dieser retrospektiven, monozentrischen Erhebung. Zur besseren Erfassung der Patienten mit angeborenen Bauchwanddefekten und um aussagekräftige epidemiologische und prognostische Ergebnisse zu erhalten, bedarf es eines Fehlbildungsregisters in Sachsen, so wie es bereits in anderen Bundesländern angewandt wird.

Few authors report comprehensive psychometric data for their acquired brain injury (ABI) outcome indices (e.g., items analyses, test-retest reliability, survivor-proxy agreement, internal consistency, convergent validity). Even fewer authors submit their indices to modern psychometric analyses, like Rasch analysis. The purpose of this dissertation was to evaluate the traditional and modern psychometric properties of a new index of brain injury outcome: the Functional Outcome Profile (FOP). One hundred and thirteen mixed (estimated mild, moderate, and severe injury) ABI survivors and 22 significant others participated in the study. Items analyses (n = 113) revealed that all items were endorsed by at least one ABI survivor, suggesting that the FOP assessed areas relevant to ABI survivors. However most items, composite scores, and the total score had distributions that were negatively skewed. One-week test-retest reliability correlations for the total score, composites, and items (n = 25) were generally in the moderate to strong range (r > 0.7), while survivor-proxy agreement correlations for the items (n = 22) were generally in the moderate range (r = 0.5 to 0.7). The internal consistency scores (n = 113) for 5 of the 8 composite scales and for the full FOP were good (Cronbach α > 0.7). Concurrent-convergent validity analyses revealed that the FOP correlated moderately well with the Mayo-Portland Adaptability Index (MPAI-4) (r = -0.75), but that it did not correlate with injury-related information (e.g., age at injury, time since injury, estimated severity). Rasch calibration of the FOP resulted in a 62-item index that fit the Rasch model well and that demonstrated good reliability and separation. Overall, the results suggest that the FOP has good traditional and modern psychometric properties when used with community-based outpatient ABI survivors. Future studies with the FOP should focus on improving the FOP’s clinical utility and further verifying its convergent and divergent validity.